A modified technique for arteriovenous fistula anastomosis: Preserving the surrounding tissue of the vein without the use of vascular clamps.

BACKGROUND: This pilot study describes a new technique for creating an arteriovenous fistula (AVF) and presents the preliminary outcomes after 1 year of follow-up. METHODS: The study included 19 patients (10 males, 9 females) with a mean age of 62 years (range 26-88 years). All patients received an AVF using a modified technique in which the surrounding tissues were not removed from the veins and no elastic loops or vascular clamps were used. RESULTS: Immediate patency was obtained for all patients. The proportion of patients experiencing primary patency at 30 days and 6 months was 89.5% and 83.1%, respectively, and cumulative patency at 30 days and 6 months was 100%. At 1 year of follow-up, primary patency was 83.1% and cumulative patency was 100%. CONCLUSIONS: Complete preservation of the surrounding venous tissue in the absence of vascular clamps successfully established AVF, with a high surgical success rate.

Epidemic characteristics and prediction of varicella in Chongqing in 2014-2020 / 公共卫生与预防医学

Objective To analyze the epidemic characteristics of varicella in Chongqing from 2014 to 2020, and to provide evidence for the development of scientific and effective varicella control strategies. Methods Data on the outbreak of varicella and vaccination in Chongqing from 2014 to 2020 were collected through the China Disease Prevention and Control Information System, and descriptive epidemiological methods were used for statistical analysis. Results A total of 181 551 cases of varicella were reported in Chongqing from 2014 to 2020, with an average annual incidence rate of 83.79 per 100 000. The incidence rate of varicella increased from 39.95 per 100 000 in 2014 to 81.88 per 100 000 in 2020 (P < 0.001). The incidence of varicella was seasonal, with the peak periods occurring from May to June and from October to December each year. The average annual incidence rate in municipal districts was 88.90/100 000, higher than 67.42/100 000 in counties and 82.50/100 000 in autonomous counties. The average annual incidence rate of varicella in males (87.13/100 000) was higher than that in females (80.38/100 000). The incidence of varicella was mainly distributed in people under 15 years old, with 143 508 cases (79.10%) reported, and the highest incidence age was 5-9 years old (37.00%). Among the affected occupations , 133 733 cases (62.6%) were students , 39 274 cases (18.40%) were children in nursery care, and 17 963 cases (8.4%) were scattered children. The actual number of doses of varicella vaccine from 2014 to 2020 was 2 302 522 doses, with the coverage rates of one-dose and two-dose vaccines being 75.56% and 32.17%, respectively. ARIMA predicted that there would be 2 604, 811, 756, 1 226, 2 405, 3 904, 2 410, 1 211, 2 034, 6 878, 10 887, and 8 955 cases of varicella from January to December 2021. Conclusion The incidence of varicella in Chongqing is on the rise, with obvious seasonal, regional and population distribution characteristics. It is necessary to strengthen the prevention and control of varicella epidemic, strengthen the prevention and control measures of key groups and key institutions in the high incidence season, strengthen the publicity of varicella vaccine, and improve the vaccination rate of two-doses of varicella vaccine for eligible children.

Immunostimulatory gene therapy combined with checkpoint blockade reshapes tumor microenvironment and enhances ovarian cancer immunotherapy

Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor (iPDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of pIL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation, macrophage polarization and DC maturation. The F-DPC/pIL-12/iPDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/pIL-12/iPDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.

First Report of Cladosporium scabrellum Causing Stipe Spot Disease of Morchella importuna in China.

Morchella is a genus of edible and medicinal fungi with a global distribution and economic value. Artificial cultivation of Morchella has risen to 8,000 hectares in China in last 5 years (Zhao et al. 2020). In the early March of 2021, a peculiar stipe spot disease was first detected on Morchella importuna at a manufacturing base in Yangxian county (33°02' N, 108°11' E), Shaanxi, China. Several dark brown patches were observed on the surface of M. importuna fruiting bodies, with approximately 40% of the fruiting bodies infected at a late stage of production. This symptom typically manifests in March to May each year during the growing season of M. importuna. Following infection of the fruiting body, a light brown spot (2 to 4 mm) appears at the base of the stipe when the fruiting body is about 3 cm long. The spot progressively darkens and proceeds to cover the large stipe of the fruiting body. At 5 to 7 days after the appearance of the first spot, infected young fruiting bodies soften and decay. Temperature (>20℃) or humidity (80 to 90%) increases the likelihood of disease. To isolate the causal agent, the edge of a lesion was carefully scraped, inoculated into potato dextrose agar (PDA), and then incubated in the dark at 24±2°C (Bensch et al. 2010). The colonies were grayish-green in front, green to black on the reverse, and grew as concentric rings after 14 days of culture. The conidiophore was thin, branched with warty ramoconidia, and 2.5 to 4.7 µm long by 1.5 to 2.0 µm wide (length×width, mean=0.72, n=150). The ramoconidia were cylindrical and long at 14.3 to 28.7 µm by 6.4 to 10.7 µm (length×width, mean=2.52, n=150); the secondary ramoconidia were narrower and rod-shaped at 3.8 to 4.9 µm by 2.4 to 3.6 µm (length×width, mean=0.19, n=150). These morphological features were consistent with Cladosporium scabrellum (Bensch et al. 2012). Genomic DNA was extracted from mycelia of the pathogen using an Ezup column fungal genomic DNA extraction kit (Sangon Biotech, Shanghai, China). To confirm the identity of the pathogen (C. scabrellum), the genomic fragments for the internal transcribed spacer (ITS), translation elongation factor 1 alpha (EF-1α) and actin (ACT) gene of the isolate were amplified by PCR (Carbone et al. 1999; Walker et al. 2016; Xu et al. 2021). The resultant sequence was uploaded to the GenBank database with accession number (GeneBank ID of gene ITS, EF-1α, ACT are MZ736660, OQ982380, OQ982381, respectively). BLAST results showed >99% identity with those of C. scabrellum(GeneBank ID of gene ITS, EF-1α, ACT are HM148195, HM148440, HM148685, respectively). Phylogenetic analysis was performed using the maximum-likelihood (ML) method and Bayesian phylogenetic inference (BI) analyses in MEGA7 software (Kumar et al., 2018). For pathogenicity testing, 20 naturally occurring M. importuna fruiting bodies in an artificial climate chamber were randomly selected, inoculated by spraying with a conidial suspension of the pathogen (1×106 conidia/ml sterile water), and incubated at 20°C and 90 to 95% humidity. On the third day after inoculation, a yellow-brown spot appeared around the grafting sites, the spot gradually darkened and began to cover the stipe; the infection rate was 80 to 85%. Ten control fruiting bodies of M. importuna sprayed with sterile water grew normally and were symptomless. The pathogen was reisolated from infected fruiting bodies and confirmed as C. scabrellum by morphology and ITS, EF-1α, ACT sequence. To our knowledge, this is the first report of M. importuna stipe spot disease caused by C. scabrellum. According to a farmer in Yangxian, these spots rapidly spread every year, drastically reducing the production and market value of Morchella. This is a major problem for producers of this edible mushroom.

Analysis of genetic variant in a child with Pitt-Hopkins syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child featuring facial dysmorphism, single palmar crease, motor and language delay, and hypoplasia of corpus callosum.@*METHODS@#A child who had visited the Affiliated Hospital of Binzhou Medical College on March 16, 2021 was selected as the study subject. Peripheral blood samples of the child and his parents were collected, and the genomic DNA was extracted for whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#WES revealed that the child has harbored a heterozygous c.607delT (p.S203Pfs*31) variant in exon 9 of the TCF4 gene, for which both of his parents were of the wild-type. Based on guidelines from the American College of Medical Genetics and Genomics, the variant was classified as pathogenic (PVS1+PM2_Supporting+PM6).@*CONCLUSION@#The heterozygous c.607delT (p.S203Pfs*31) variant of the TCF4 gene probably underlay the Pitt-Hopkins syndrome in this child. Genetic testing has enabled the definite diagnosis.

Longitudinal analysis of immune reconstitution and metabolic changes in women living with HIV: A real-world observational study / 中华医学杂志(英文版)

BACKGROUND@#Women comprise more than half of people living with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) worldwide and incomplete immune recovery and metabolic abnormalities affect them deeply. Studies of HIV antiretroviral therapy (ART) have a low female representation in China. We aimed to investigate immune reconstitution and metabolic changes of female HIV-positive cohort in China longitudinally.@*METHODS@#HIV-positive women who initiated ART from January 2005 to June 2021 and were followed up regularly at least once a year were included in this study. Immunological indicators (cluster of differentiation 4 [CD4] counts and CD8 counts), viral load (VL), and metabolic indicators were collected at follow-up. All data were collected from the China Disease Prevention and Control Information System (CDPCIS). VL was tested half a year, 1 year after receiving ART, and every other year subsequently according to local policy. CD4/CD8 ratio normalization was considered as the primary outcome and defined as a value ≥1. Incidence rate and probability of CD4/CD8 ratio normalization were estimated through per 100 person-years follow-up (PYFU) and Kaplan-Meier curve, respectively. Multivariate Cox regression was used to identify independent risk factors associated with CD4/CD8 ratio normalization. We further studied the rate of dyslipidemia, hyperuricemia, diabetes, liver injury, and renal injury after ART initiation with the chi-squared tests or Fisher's exact probability tests, and a generalized estimating equation model was used to analyze factors of dyslipidemia and hyperuricemia.@*RESULTS@#A total of 494 female patients with HIV/AIDS started ART within 16 years from January 2005 to June 2021, out of which 301 women were enrolled with a median duration of ART for 4.1 years (interquartile range, 2.3-7.0 years). The overall incidence rate of CD4/CD8 ratio normalization was 8.9 (95% confidence interval [CI], 7.4-10.6) per 100 PYFU, and probabilities of CD4/CD8 normalization after initiating ART at 1 year, 2 years, 5 years, and 10 years follow-up were 11.7%, 23.2%, 44.0%, and 59.0%, respectively. Independent risk factors associated with CD4/CD8 normalization were baseline CD4 cell counts <200 cells/μL, CD8 counts >1000 cells/μL, and more than 6 months from the start of combined ART (cART) to first virological suppression. Longitudinally, the rate of hypercholesterolemia (total cholesterol [TC]) and high triglyceride (TG) showed an increasing trend, while the rate of low high-density lipoprotein cholesterol (HDL) showed a decreasing trend. The rate of hyperuricemia presented a downtrend at follow-up. Although liver and renal injury and diabetes persisted during ART, the rate was not statistically significant. Older age and protease inhibitors were independent risk factors for increase of TC and TG, and ART duration was an independent factor for elevation of TC and recovery of HDL-C.@*CONCLUSIONS@#This study showed that women were more likely to normalize CD4/CD8 ratio in comparison with findings reported in the literature even though immune reconstruction was incomplete.

Mediating role of family function between coping strategies and emotional behavior in children with chronic superficial gastritis / 四川精神卫生

BackgroundChronic superficial gastritis （CSG） is a common clinical disease in children. The emotional behavior of CSG children is susceptible due to them suffering from such disease at young age. ObjectiveTo explore the impact of coping strategies on emotional behavior and the effect of family function in children with CSG， and to provide references for clinical intervention in CSG children with emotional behavior problems. MethodsA total of 177 children with CSG admitted to Anhui Children's Hospital from June 2019 to January 2023 were selected as the research subjects. Investigation on family function， emotional and behavioral problems and coping strategies of children was conducted by employing the Family APGAR index （APGAR）， the Strengths and Difficulties Questionnaire （SDQ） and Coping Strategies Questionnaire （CSQ）. The structural equation model was used to test the mediating effect of family function between coping strategies and emotional behaviors. ResultsThe APGAR score was negatively correlated with both SDQ score and negative coping strategies score （r=-0.507， -0.551， P<0.01）， but was positively correlated with positive coping strategy score （r=0.579， P<0.01）. The positive coping strategy score was negatively correlated with SDQ score （r=-0.539， P<0.01）， while the negative coping strategy score was positively correlated with SDQ score （r=0.543， P<0.01）. The result showed that family function played a partial mediating role between positive coping strategies and emotional behavior ［indirect effect was -0.133 （95% CI： -0.256~-0.079， P<0.01）， accounting for 29.40% of the total effect］. The same mediating effect happened between negative coping strategies and emotional behavior ［indirect effect was 0.093 （95% CI： 0.198~0.045， P<0.01）， accounting for 28.50% of the total effect］. ConclusionCoping strategies of CSG children can affect emotional behavior directly and indirectly with family function playing a partial intermediary effect.

Effects of Gegen Qinlian Decoction on NLRP3 inflammatome signaling pathway in liver of mice with type 2 diabetes mellitus / 国际中医中药杂志

Objective:To observe the effects of different doses of Gegen Qinlian Decoction on nucleotide oligomeric domain-like receptor protein 3 (NLRP3)/Caspase-1/IL1β inflammatory signaling pathway in liver of db/db mice with type 2 diabetes mellitus (T2DM).Methods:Totally 75 SPF male db/db mice were randomly divided into model group, metformin group (0.2 g/kg), Gegen Qinlian Decoction high-, medium-, and low-dosage groups (61.80, 30.90, 15.45 g/kg), with 15 mice in each group. Another 15 db/m male mice were selected as blank control group. Each administration group was given relevant medicine for gavage, while the blank group and model group were given 0.9% sodium chloride solution for gavage, once a day, for 12 weeks. The body weight, fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) contents of each group were measured after treatment. The mRNA expression levels of NLRP3, Caspase-1 and interleukin-1β (IL-1β) in liver were detected by real-time quantitative PCR. The expression levels of NLRP3, Caspase-1, IL-1β and IL-18 in liver tissues were detected by Western Blot. HE staining was used to observe the morphology of liver tissues.Results:Compared with model group, body weight, fasting blood glucose and HbA1c contents of mice in Gegen Qinlian Decoction high- and medium-dosage groups and metformin groups decreased ( P<0.05), the body weight and fasting blood glucose levels of mice in Gegen Qinlian Decoction low-dosage group decreased ( P<0.05); the mRNA levels of NLRP3 and IL-1β in liver tissues of all treatment groups decreased ( P<0.05), the mRNA level of Caspase-1 in liver tissue decreased in Gegen Qinlian Decoction high- and medium-dosage groups ( P<0.05); the expression of NLRP3, Caspase-1, and IL-18 in liver tissue of each treatment group decreased ( P<0.05), while the expression of IL-1β in Gegen Qinlian Decoction high- and medium-dosage groups and the metformin group decreased ( P<0.05); compared with the metformin group, the body weight and fasting blood glucose of mice in the Gegen Qinlian Decoction high-dosage decreased ( P<0.05), while the HbA1c levels in the Qinlian Decoction high- and medium-dosage decreased ( P<0.05); the expressions of NLRP3, Caspase-1 and IL-18 in liver tissues of Gegen Qinlian Decoction high-dosage group decreased ( P<0.05), the expression of IL-1β, NLRP3, Caspase-1, IL-1β, and IL-18 decreased ( P<0.05); HE staining showed that the pathological changes of liver tissue were reduced in all treatment groups. Conclusion:Gegen Qinlian Decoction may reduce blood sugar by inhibiting the activation of NLRP3/Caspase-1/IL-1β inflammatory signaling pathway in liver of db/db mice, thereby improving the inflammatory damage of T2DM.

Asymptomatic cerebral artery stenosis and cognitive impairment / 国际脑血管病杂志

Asymptomatic cerebral artery stenosis (aCAS) is closely associated with cognitive impairment, which can lead to multiple cognitive domain impairments, thereby affecting the behavior and daily life of patients. This article reviews the main involved cognitive domains, injury mechanisms, and treatment in different types of aCAS, with the aim of increasing attention to aCAS, early clinical intervention, and delaying cognitive deterioration.

Mechanism of Gegen Qinliantang in Improving Ectopic Lipid Accumulation in Liver of db/db Mice with Type 2 Diabetes Mellitus by Regulating AMPK-FoxO3a Autophagy Axis / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Gegen Qinliantang （GQT） in improving ectopic lipid accumulation in the liver of db/db mice with type 2 diabetes mellitus （T2DM） by regulating the adenosine monophosphate-activated protein kinase （AMPK）-forkhead box O3a （FoxO3a） autophagy axis， to provide a scientific basis for clarifying the hypoglycemic mechanism of GQT and its clinical application. MethodSeventy-five spontaneous T2DM db/db mice and 15 normal db/m mice were selected and maintained on a regular diet for one week， followed by the measurement of blood glucose. They were then randomly divided into six groups， with 15 mice in each group， including normal group （0.2 g·kg-1 saline）， metformin group （0.2 g·kg-1）， high-， medium， and low-dose GQT group （31.9， 19.1， 6.9 g·kg-1）， and model group （0.2 g·kg-1 saline）. The mice were orally administered the corresponding drugs once daily for 12 weeks. Fasting blood glucose （FBG） and glycated hemoglobin （HbA1c） were detected. Fasting insulin （FINS） and free fatty acid （FFA） levels were measured by enzyme-linked immunosorbent assay （ELISA）. Pathological changes in liver tissues were observed by hematoxylin-eosin （HE） staining. The protein expression levels of phosphorylated （p）-AMPK， p-FoxO3a， and autophagy-related proteins microtubule-associated protein 1 light chain 3 Ⅱ （LC3Ⅱ） and p62 were detected using Western blot. Immunofluorescence was used to detect the expression of hypoxia-inducible factor-1α （HIF-1α） in liver tissues. Real-time polymerase chain reaction （Real-time PCR） was performed to detect the mRNA expression of AMPK， FoxO3a， and LC3 in liver tissues. ResultCompared with the normal group， the model group showed pathological changes in liver tissues， increased FBG， HbA1c， FINS， and FFA levels （P<0.01）， increased protein expression levels of p-AMPK， p62， and HIF-1α， decreased protein expression levels of p-FoxO3a and LC3Ⅱ in liver tissues （P<0.01）， decreased mRNA expression of AMPK， and increased expression of FoxO3a （P<0.01）. Compared with the model group， the treatment groups showed relieved liver tissue lesions and decreased FBG， HbA1c， FINS， and FFA levels （P<0.01）. The expression of p-AMPK， p62， and HIF-1α increased， while the expression of p-FoxO3a showed a dose-dependent decrease in the high-dose GQT group. The expression of LC3Ⅱ increased in the metformin group and the high-dose GQT group （P<0.01）. The mRNA expression of AMPK showed a dose-dependent increase， and the expression of FoxO3a showed a dose-dependent decrease in the treatment groups （P<0.01）. ConclusionGQT can improve ectopic lipid accumulation in the liver of T2DM db/db mice， which may be related to the regulation of the AMPK-FoxO3a autophagy axis.

Emotional and behavioral effects of after-school tutoring on school-age children in a district in Shanghai / 上海预防医学

ObjectiveTo explore the effects of after-school tutoring for school-age children on their emotions and behaviors， and to provide a basis for developing after-school tutoring and psychological support strategies for school-age children. MethodsFour elementary schools in a district of Shanghai were selected by simple random sampling method. Whole group sampling was conducted by class， and parents of students were surveyed by general questionnaire and the scale of strengths and difficulties. Information was collected on the basic conditions of children and families and the results were compared and analyzed. ResultsThis study showed that 88.26% of children attended extracurricular classes， of which 26.16% attended 3 or more classes， 42.5% attended cultural classes， 28.3% attended sports classes， and 59.8% attended art classes. Children who did not attend classes had higher pro-social scores. Children who attended reading class had lower scores for emotional problems that was a protective factor for emotional problems. Children who chose extracurricular programs in sports and reading also had lower overall scores for difficulties. Excessive use of electronic devices by school-age children on weekdays or weekends had a negative effect on emotional and conduct problem scores regardless of whether they chose extracurricular programs. It appeared that the choice of cultural programs， art programs and different levels of exercise intensity had no effect on children's emotions and behaviors. ConclusionFor children with low pro-social level， extracurricular classes should be carefully selected. For extracurricular classes， more reading and sports-related courses can be considered， which have positive effects on school-age children’s emotions and behaviors. Regardless of the choice of extracurricular classes， try to avoid excessive online classes.

Evaluation on the effect of teacher simulate standardized patient consultation training in pediatric practical teaching / 中华医学教育探索杂志

Objective:To evaluate the effect of teacher simulate standardized patient (TSSP) consultation training in pediatric practical teaching.Methods:A total of 120 interns from the five-year clinical medicine major of Batch 2015 were randomly divided into experimental group and control group. In the experimental group, 60 interns were trained by TSSP for consultation after admission. After the training, the clinical parents of the children were consulted and the children were physically examined under the guidance of teachers. In the control group, 60 interns were trained according to the same requirements, but TSSP consultation training was not included. At the end of the practice, the performance, operation skills and medical record writing ability of the interns were compared, and the satisfaction of the experimental group was investigated. SPSS 25.0 software was used for t test and chi-square test. Results:The medical record writing results of the experimental group were (96.15±3.00) points, significantly higher than that of the control group [(81.02±3.29) points], and the differences were statistically significant ( t = 26.38; P < 0.001). In the mini-clinical evaluation exercise (Mini-CEX), the scores of medical history collection, communication skills, humanistic care and physical examination were significantly higher than those of the control group ( t= 15.41, 17.67, 15.39 respectively; all P < 0.001). The experimental group had high satisfaction with the teaching method of TSSP consultation training. Conclusion:TSSP consultation training improves the intern medical record writing ability, doctor-patient communication ability, clinical operation ability, stimulates the learning interest of interns, trains the trainee doctors humanistic consciousness, integrates into the ideological and political education, effectively ensures the quality of practical teaching of pediatrics, and obtains recognition from intern, which is worth promoting.

Experience of caesarean section women participating in skin-to-skin contact: Meta-integration qualitative study / 中国实用护理杂志

Objective:To systematically review qualitative research on maternal participation in skin-to-skin contact experience during cesarean delivery, the promotion of skin-to-skin contact in cesarean section.Methods:We searched databases including the PubMed, Embase, Web of Science, Cochrane Library, Ebsco, SinoMed, Wan Fang, CNKI, VIP. All of the qualitative research on the real experience of skin-to-skin contact from the participation of caesarean section women were collected. The search time limit was from the establishment of the databases to May 2022. The JBI Critical Appraisal Tool for qualitative studies from Australia was used to evaluate the methodology quality of the included research, and the meta-aggregation was used to conduct the synthesis.Results:Totally 11 qualified studies were included and integrated into 49 valuable findings. Similar results were summarized into 12 groups, and 4 integrated results were synthesized, including the needs of cesarean section mothers; positive experience after skin-to-skin contact in caesarean section; skin-to-skin contact practice strengthen the role of mothers and promotes breastfeeding; difficulties and challenges of skin-to-skin contact during cesarean section.Conclusions:Skin-to-skin contact positively affects mother and infant delivered by cesarean section. Medical staff need to pay attention to the feelings and needs of cesarean section women participating in skin-to-skin contact, optimize information, environment, and humanistic support, and improve skin-to-skin contact practices. Medical institutions should rationally allocate obstetric resources to alleviate the difficulties faced by skin-to-skin contact practices.

Mechanism of Modified Zhenwutang in Delaying Progression of Chronic Renal Failure Based on Network Pharmacology， Molecular Docking， and Experimental Verification / 中国实验方剂学杂志

ObjectiveTo preliminarily predict the active ingredients， targets， and signaling pathways of modified Zhenwutang in the treatment of chronic renal failure （CRF） based on network pharmacology and explore its potential mechanism for delaying disease progression through molecular docking and animal experiments. MethodThe effective ingredients and targets of modified Zhenwutang were obtained from the HERB database. The targets related to CRF were obtained from the GeneCards. The intersection target genes were obtained using Venny 2.1 software and a protein-protein interaction （PPI） network was constructed using the STRING. The core targets for treating CRF with modified Zhenwutang were screened using Cytoscape 3.9.1 software. The intersection genes were analyzed using Metascape database for gene ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. Molecular docking validation was performed using AutoDockTools 1.5.6 software for the key targets and active ingredients. An experimental CRF model was established in rats by administering adenine via gavage for 12 weeks， followed by intervention with modified Zhenwutang and benazepril hydrochloride for four weeks. After treatment， the rats were euthanized， and immunohistochemistry （IHC）， immunofluorescence （IF）， real-time quantitative polymerase chain reaction （Real-time PCR）， and western blot were performed to detect the expression levels of prolyl hydroxylase domain-containing proteins 1 （PHD1）， prolyl hydroxylase domain-containing proteins 2 （PHD2）， hypoxia-inducible factor-1α （HIF-1α）， and α-smooth muscle actin （α-SMA） in the renal tissues of the rats. ResultA total of 426 drug target genes of modified Zhenwutang were obtained from the HERB database. A total of 2 698 target genes related to CRF were obtained from the GeneCards database. There were 154 intersection genes between the drug and the disease. Eight core targets were identified， including albumin （ALB）， protein kinase B1 （Akt1）， tumor necrosis factor （TNF）， interleukin-6 （IL-6）， insulin （INS）， vascular endothelial growth factor A （VEGFA）， tumor protein p53 （TP53）， and interleukin-1β （IL-1β）， which might be closely related to the treatment of CRF with modified Zhenwutang. KEGG enrichment analysis predicted that the main mechanism of modified Zhenwutang in treating CRF involved lipid and atherosclerosis， HIF-1 signaling pathway， cell apoptosis， and nuclear factor kappa B （NF-κB） signaling pathway. Molecular docking results showed that the ingredients of modified Zhenwutang had stable binding activity with the core targets ALB， Akt1， TNF， IL-6， INS， VEGFA， TP53， and IL-1β， which may regulate inflammation and cell apoptosis by affecting the target proteins. The animal model validation results demonstrated that modified Zhenwutang could reduce the expression levels of HIF-1α and α-SMA in the renal tissues of CRF rats， increase the expression levels of PHD1 and PHD2， alleviate renal tissue hypoxia injury， reduce myofibroblast formation， and slow down the progression of CRF in rats. ConclusionModified Zhenwutang may improve renal tissue hypoxia， inhibit cell transdifferentiation， cell apoptosis/necroptosis， and inflammation by affecting the expression of target proteins such as ALB， Akt1， TNF， IL-6， INS， VEGFA， TP53， and IL-1β， as well as regulating the HIF-1 signaling pathway， thus delaying the progression of CRF.

Effect of Modified Zhenwutang on Interstitial Fibrosis in Rats with Chronic Renal Failure Based on IL-6/MMP-9/COL-Ⅳ Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the modulatory effect of modified Zhenwutang on the interleukin-6 （IL-6）， matrix metallopeptidase-9（MMP-9）， type Ⅳ collagen（COL-Ⅳ） in rats with chronic renal failure （CRF） and to investigate the potential mechanism of its treatment of CRF. MethodFifty male SD rats were randomly divided into a modeling group of 40 rats and a normal group of 10 rats， and the modeling group was prepared by continuous adenine gavage for 12 weeks. After successful modelling， the modelling group was divided into the model group， the low dose （7.2 g·kg-1·d-1） group， the medium dose （14.4 g·kg-1·d-1） group， the high dose （28.8 g·kg-1·d-1） group and the Benadryl hydrochloride （10 mg·kg-1·d-1） group for gavage according to the random number table method， In the normal group and the model group， equal volume of distilled water was administered by gavage for 4 weeks. After the administration， the levels of blood creatinine （SCr）， blood urea nitrogen （BUN） and 24 h urine protein （24 h-UTP） were measured， the levels of serum IL-6 were measured by enzyme linked immunosorbent assay（ELISA）. Immunohistochemistry （IHC） was used to detect intercellular cell adhesion molecule-1 （ICAM-1）， IL-6， MMP-9， and other molecules in the rat kidney. The expression of ICAM-1 mRNA， IL-6 mRNA， MMP-9 mRNA and COL-Ⅳ mRNA in rat kidney tissues was measured by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expression levels of ICAM-1， IL-6， MMP-9 and COL-Ⅳ in rat kidney tissues were measured by Western blot. ResultCompared with the normal group， the levels of SCr， BUN and 24 h-UTP were significantly increased in the model group （P<0.01）； the serum IL-6 level was significantly increased （P<0.01）， the tubular lumen was dilated with atrophy， the tubular epithelial cells were necrotic， swollen and vacuolated， the interstitium was infiltrated by a large number of inflammatory cells and collagen fibers were deposited， the levels of IL-6， ICAM-1 and COL-Ⅳ were strongly positive in the tubular interstitium of the model group （P<0.01）， The levels of ICAM-1 mRNA， IL-6 mRNA and COL-Ⅳ mRNA were significantly increased （P<0.01） and MMP-9 mRNA was significantly decreased （P<0.05） in the model rats. ICAM-1， IL-6 and COL-Ⅳ protein expression was significantly increased （P<0.01） and MMP-9 protein expression was significantly increased （P<0.01） in the renal tissue， and MMP-9 protein expression was significantly decreased （P<0.01）. Compared with the model group， the 24 h-UTP， SCr and BUN levels of rats were significantly reduced after treatment with modified Zhenwutang （P<0.01）， the serum IL-6 level was significantly decreased （P<0.01）， the renal lesions of rats were significantly improved and collagen fiber deposition was reduced； the expression of IL-6， ICAM-1 and COL-Ⅳ in renal tubules and interstitium was weakened， and MMP-9 in ICAM-1 mRNA， IL-6 mRNA and COL-Ⅳ mRNA levels were significantly reduced （P<0.01） and MMP-9 mRNA levels were significantly increased （P<0.05）， ICAM-1， IL-6 and COL-Ⅳ protein expression was significantly reduced （P<0.01） and MMP-9 protein expression was significantly The expression of ICAM-1， IL-6 and COL-Ⅳ proteins was significantly decreased （P<0.01） and MMP-9 protein expression was significantly increased （P<0.01）. ConclusionModified Zhenwutang may regulate the IL-6/MMP-9/COL-Ⅳ signaling pathway， thereby reducing proteinuria， improving renal function， reducing renal pathological damage and delaying the progression of CRF interstitial fibrosis.

Based on Oxidative Stress/NF-κB Exploration of Mechanism of Modified Zhenwutang in Delaying Progression of Chronic Renal Failure Complicated with Cardiac Disease by Inflammatory Factors / 中国实验方剂学杂志

ObjectiveBy observing the effect of modified Zhenwutang on the expression of superoxide dismutase 1（SOD1）， malondialdehyde（MDA）， advanced oxidation protein product（AOPP）， nuclear factor kappa-B（NF-κB） p65，p-p65，IL-1β， TNF-α in serum and renal tissue of adenine-induced chronic renal failure rats and the pathology of heart and kidney tissue， the possible mechanism of modified Zhenwutang delaying the progression of chronic renal failure complicated with heart disease was discussed. MethodFifty SPF male SD rats were divided into normal group 10 and model group 40 according to the random number table method. After one week of adaptive feeding， the experimental chronic renal failure complicated with cardiovascular disease rat model was established by intragastric administration of adenine 150 mg·kg-1·d-1. After the model was completed， 3 rats in the normal group and the model group were randomly selected to detect whether the model was successful. After successful modeling， the rats in the model group were divided into model group ， modified Zhenwutang low-dose group ， modified Zhenwutang medium-dose group， modified Zhenwutang high-dose group and Benazepril hydrochloride group according to the random number table method， with 6 rats in each group. Drugs were administered once a day for 4 weeks. At the end of the 17th week of the experiment， 24-hour urinary total protein（24 h-UTP） and urine creatinine（UCr）were detected. At the end of the 17th week， the rats in each group were anesthetized and the abdominal aorta was taken. After centrifugation， the supernatant was taken to detect triglyceride（TG）， total cholesterol（TC）， serum calcium（Ca）， serum potassium， serum phosphate， serum creatinine（Scr）， blood urea nitrogen（BUN）； the expression levels of serum AOPP， IL-1β and TNF-α were detected by enzyme linked immunosorbent assay（ELISA）. The pathological changes of heart and kidney tissues were observed by hematoxylin-eosin（HE）/Masson method. The ultrastructural changes of proximal renal tubules were observed by transmission electron microscopy . The kidney tissue expressions of SOD1， MDA， AOPP， NF-κB p65，p-p65，IL-1β and TNF-α were observed by immunohistochemistry. The kidney tissue expression levels of SOD1， NF-κB p65， IL-1β and TNF-α mRNA were observed by real-time polymerase chain reaction（Real-time PCR）. The kidney tissue expression levels of SOD1， MDA， NF-κB p65 and p-p65 were detected by Western blot. Result①Compared with the normal group， the experimental rats in the model group showed an increase in 24-hour UTP （P<0.01）and a decrease in UCr（P<0.01）. The experimental rats in the model group showed an increase in Cr， BUN， TG， TC， serum phosphate， and serum potassium（P<0.01）.The levels of AOPP， IL-1β and TNF-α in serum of rats in the model group were significantly increased（P<0.01）. In the model group， the glomerular balloon space was significantly widened， the renal interstitium was significantly widened with a large number of inflammatory cell infiltration， a large number of renal tubular lumens were blocked by brown deposits， and there were a large number of collagen fiber deposition in the renal interstitium. The collagen fibers around the renal vessels， outside the capsule wall of the renal capsule wall， glomerular basement membrane and renal tubular basement membrane were significantly increased， and the cardiac muscle fibers were significantly thickened. There was a small amount of inflammatory cell infiltration around the blood vessels， and a large number of collagen fibers around the cardiac vessels and between the myocardial cells. In the model group， high-density diamond-shaped needle-like crystals were observed in the proximal renal tubular epithelial cells of rats， with increased lysosomes， mitochondrial proliferation， mitochondrial cristae and dense mitochondrial outer membrane. The left ventricular diastolic wall thickness and systolic wall thickness of the experimental rats in the model group was increased in proximal renal tubular epithelial cells and their nuclei.In the model group， the expression of MDA， AOPP， NF-κB p65，p-p65 IL-1β and TNF-α in proximal renal tubular epithelial cells was significantly increased（P<0.01）， the expression of p-p65 in the nucleus of proximal renal tubular epithelial cells was significantly increased（P<0.01）， and the expression of SOD1 in proximal renal tubular epithelial cells was significantly decreased（P<0.01）. The kidney tissue expression of NF-κB p65， IL-1β and TNF-α mRNA in the model group was increased（P<0.01）， and the expression of SOD1 mRNA was decreased（P<0.01）. The kidney tissue expression of SOD1 protein in the model group was significantly decreased（P<0.01）. The kidney tissue expression of MDA， NF-κB p65 and p-p65 protein was increased （P<0.01）. ② Compared with the model group， after the intervention of modified Zhenwutang， 24 h-UTP was decreased （P<0.01）and UCr was increased（P<0.01）. Cr， BUN， TG， TC， serum phosphate， serum potassium was decreased （P<0.01）. Serum AOPP， IL-1β and TNF-α levels were decreased（P<0.01）. Cardiac and Renal pathological damage was reduced； mitochondrial damage in proximal renal tubules was reduced； the expression of MDA， AOPP， NF-κB p65， IL-1β， TNF-α in proximal renal tubular epithelial cells was decreased （P<0.01）， the expression of p-p65 in the nucleus of proximal renal tubular epithelial cells was significantly decreased （P<0.01）， and the expression of SOD1 in proximal renal tubular epithelial cells was significantly increased （P<0.01）. The kidney tissue expression of NF-κB p65， IL-1β， TNF-α mRNA was decreased （P<0.01）， and the expression of SOD1 mRNA was increased（P<0.01）. The kidney tissue expression of SOD1 protein was significantly increased （P<0.01）， and the expression of MDA， NF-κB p65 and p-p65 protein was decreased （P<0.01）. The Chinese medicine group showed a significant dose-effect trend. ConclusionModified Zhenwutang may reduce the production of oxidative stress and mitochondrial damage in proximal renal tubular epithelial cells， thereby reducing oxidative stress products and inhibiting the release of inflammatory factors caused by the activation of NF-κB signaling pathway， reducing the damage to heart and kidney tissues and functions， and delaying the progression of chronic renal failure complicated with heart disease， and the traditional Chinese medicine group has a dose-effect trend.

Mechanism of Modified Zhenwutang in Delaying Renal Interstitial Fibrosis in Chronic Renal Failure Based on Ang Ⅱ/AT1R/NOX4 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the underlying mechanism of modified Zhenwutang in delaying renal interstitial fibrosis in chronic renal failure （CRF） by observing the effects of modified Zhenwutang on the expression of angiotensin Ⅱ （Ang Ⅱ）， angiotensin Ⅱ type 1 receptor （AT1R）， nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4）， transforming growth factor-β1 （TGF-β1）， type I collagen （COL1A1）， and type Ⅲ collagen （COL3A1） in the serum and renal tissues of adenine-induced CRF rats. MethodFifty male SPF-grade SD rats were randomly divided into a normal group （n=10） and an experimental group （n=40） using a random number table. After one week of adaptive feeding， the experimental CRF model was established in rats by administering adenine at 150 mg·kg-1·d-1 orally. Three rats from each group were randomly selected to evaluate the model induction. After successful modeling， rats in the experimental group were randomly divided into a model group， low-， medium， and high-dose modified Zhenwutang groups， and a benazepril hydrochloride group， with six rats in each group. The rats were orally administered the corresponding drugs once daily for four weeks. At the end of the first week， 13th week， and 17th week of the experiment， 24 hour urinary protein quantification （24 h-UTP） was measured. At the end of the 17th week， the rats were euthanized， and blood samples were collected from the abdominal aorta for the measurement of total protein （TP）， albumin （ALB）， creatinine （Cr）， and blood urea nitrogen （BUN） in the serum. Enzyme-linked immunosorbent assay （ELISA） was used to measure the expression levels of serum Ang Ⅱ. Hematoxylin-eosin （HE） staining and Masson's trichrome staining were performed to observe the pathological changes in renal tissues. Immunohistochemistry （IHC） was performed to observe the expression of AT1R， NOX4， TGF-β1， COL1A1， and COL3A1. Real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR） was used to observe the mRNA expression levels of AT1R， NOX4， and TGF-β1. Western blot was conducted to measure the protein expression levels of AT1R， NOX4， and TGF-β1. Result① Compared with the normal group， the model group showed a significant increase in 24 h-UTP （P<0.01）. The levels of Cr and BUN in the model group were significantly higher （P<0.01）， while the levels of TP and ALB were significantly lower （P<0.01）. The serum Ang Ⅱ level in the model group was significantly elevated （P<0.01）. The model group exhibited widening of the renal glomerular mesangial space， necrotic glomeruli， increased interstitial width with extensive inflammatory cell infiltration， brownish precipitates blocking the renal tubular lumens， irregular renal tubules， and significant deposition of collagen fibers in the renal interstitium. Additionally， the collagen fibers around the renal vessels， outside the parietal layer of the renal sacs， glomerular basement membrane， and tubular basement membrane increased significantly. The expression of AT1R and NOX4 in the glomeruli and renal tubules of the model group was significantly enhanced， and TGF-β1 expression also significantly increased in the renal tubules. The expression of COL1A1 and COL3A1 in the renal interstitium significantly increased. The mRNA expression of AT1R and TGF-β1 in the model group significantly increased （P<0.01）， while NOX4 mRNA expression significantly decreased （P<0.01）. The protein expression of AT1R， NOX4， and TGF-β1 was significantly enhanced （P<0.01）. ② Compared with the model group， modified Zhenwutang significantly reduced 24h-UTP （P<0.01）， decreased levels of Cr and BUN （P<0.01）， increased levels of TP and ALB （P<0.01）， reduced serum Ang Ⅱ level （P<0.01）， alleviated renal pathological damage， reduced expression of AT1R， NOX4， TGF-β1， COL1A1， and COL3A1 in the glomeruli， renal tubules， and renal interstitium， reduced mRNA expression of AT1R and TGF-β1 （P<0.01）， increased NOX4 mRNA expression （P<0.01）， and weakened protein expression of AT1R， NOX4， and TGF-β1 （P<0.01）. The modified Zhenwutang groups showed a significant dose-effect trend. ConclusionModified Zhenwutang may delay renal interstitial fibrosis in CRF rats by reducing the expression of Ang Ⅱ， AT1R， NOX4， and TGF-β1 in the serum and renal tissues， thereby alleviating renal pathological damage， reducing proteinuria， protecting renal function， and delaying the progression of CRF. The modified Zhenwutang group exhibited a dose-effect trend.

A Rat Model of Adenine-induced Chronic Renal Failure Complicated with Cardiovascular Disease / 中国实验方剂学杂志

ObjectiveTo explore the preparation method of a rat model of adenine-induced chronic renal failure complicated with cardiovascular disease by investigating the effect of different time points of adenine gastric lavage on general vital signs， biochemical indicators， and cardiac and renal tissue structure and function of model rats. MethodRats in the model group were administered adenine at 150 mg·kg-1·d-1 by gavage for 16 weeks， while those in the normal group were given an equal volume of 0.5% carboxymethyl cellulose sodium solution by gavage. At weeks 5， 13， 17， 24-hour urinary protein quantification （24 h-UTP）， biochemical indicators， cardiac ultrasound， and changes in cardiac and renal tissue structure and function were measured in both the model and normal groups. Blood pressure was measured at weeks 5 and 13 in both groups. Weekly changes in body weight were recorded， and general conditions of the rats were observed daily. Result① Compared with the normal group， the model group showed a significant decrease in body weight （P<0.05）. ② Rats in the model group exhibited a significant increase in urine volume， and proteinuria appeared at week 13. ③ Compared with the normal group， the model group showed significant differences in triglyceride （TG）， total cholesterol （TC）， creatinine （Cr）， blood urea nitrogen （BUN）， blood potassium， and blood phosphorus at week 5 （P<0.05）， which increased gradually over time. At week 17， uric acid levels were significantly elevated （P<0.05）， and blood calcium levels were reduced at the end of week 17 （P<0.01）. ④ Compared with the normal group， the model group showed a significant increase in blood pressure at week 5 （P<0.05）， which progressively worsened. ⑤ There was no statistically significant difference in left ventricular wall thickness between the model and normal groups at week 5， but a significant difference was observed at week 13 （P<0.05）. ⑥ Fibrosis appeared in the kidneys of rats in the model group at week 5 and gradually worsened， while obvious fibrosis occurred around the cardiovascular system at week 13 as compared with the results in the normal group. ⑦ In the proximal tubular epithelial cells of the model group， there was an increasing presence of high-density rhomboid needle-shaped crystals， damaged cell membrane integrity， increased cell spacing， increased lysosomes， increased mitochondrial proliferation， denser mitochondrial cristae， and outer mitochondrial membrane. ⑧ Compared with the rats in the normal group， rats in the model group exhibited depressed spirits， significantly reduced activity， hunched posture， dry fur， pale ears and toes， swollen cheeks， increased nocturnal urination， and dark and viscous blood. ConclusionAdenine by gavage at 150 mg·kg-1·d-1 for 12 weeks can be used to establish a rat model of chronic renal failure complicated with cardiovascular disease， which can be used for the prevention and treatment research on chronic renal failure and its associated cardiovascular complications. The syndrome of adenine-induced rat model of chronic renal failure belongs to the deficiency of spleen and kidney， turbidity and stasis obstruction， and can be used to study the mechanisms of warming and tonifying the spleen and kidney， resolving stasis， and eliminating turbidity in the treatment of chronic renal failure.

Implementation and revision of the Measures for the Management of Radiation Workers’ Occupational Health / 中国辐射卫生

Since the implementation of the Measures for the Management of Radiation Workers’ Occupational Health in November 2007, it has played an extremely important role in protecting the occupational health of radiation workers. There are more than 700 000 radiation workers in about 100 000 workplaces with potential radiation exposure, as well as a large number of miners exposed to high levels of radon. As the radiation health monitoring project suggests, measures of occupational health management such as personal dose monitoring and occupational health examination of radiation workers have been widely implemented and achieved good results in the protection of radiation workers. However, the risks of chromosomal aberration and specific turbidity of the eye lens of radiation workers have increased in high-risk positions such as interventional radiology, nuclear medicine, and industrial flaw detection. The control of high radon exposure in miners needs to be strengthened. It is necessary to adapt to the new situation in view of new challenges and actively promote the revision of the Measures for the Management of Radiation Workers’ Occupational Health, so as to further improve the occupational health management of radiation workers in China.

Investigation and analysis of radiation doses to CT examinees in 11 medical institutions in Shijiazhuang, China / 中国辐射卫生

Objective To investigate radiation doses to examinees undergoing computed tomography (CT) scanning of different body parts (the head, chest, and abdomen) in medical institutions of Shijiazhuang, China, and to provide a reference for optimizing radiation protection for examinees in medical institutions. Methods March 2021 to March 2022, eleven medical institutions of radiation monitoring in Shijiazhuang were surveyed for the basic information, scanning parameters, and dosimetric data of a total of 930 adults and children who received CT examinations. The dosimetric data of the subjects were analyzed and compared with the domestic and international diagnostic reference levels and the results of other cities in China. Results In the above hospitals, the CTDIvol(P50) of CT subjects in children's group were 17.42-50.45 mGy, 2.13-14.01 mGy and 3.58-28.20 mGy, respectively. DLP(P50) ranges from 228.87 to 966.97 mGy·cm, 33.20 to 296.03 mGy·cm, and 74.90 to 926.53 mGy·cm, respectively. In the adult group, the CTDIvol(P50) in the head, chest and abdomen of CT subjects were 37.28-54.05 mGy, 6.43-14.99 mGy and 8.28-18.75 mGy, respectively. DLP(P50) ranges from 372.81 to 630.56 mGy·cm, from 219.77 to 467.93 mGy·cm, and from 313.86 to 689.87 mGy·cm, respectively. The distribution of radiation doses in different-grade hospitals varied greatly. The abdomen dose of the children's hospital was higher than other hospitals. Especially the primary hospitals were significantly higher than the recommended diagnostic reference level (DRL). Conclusion In some secondary and primary hospitals, the setting of CT scanning parameters was simplified, not specific to the subjects’ age and body types. They should strictly comply with the principal of optimizing radiation protection to strengthen radiation dose optimization and supervision, reducing the radiation dose of examinees in future examinations .