Biosensor analysis technology and its research progress in drug development of Alzheimer's disease / 药学学报

Biosensor analysis technology is a kind of technology with high specificity that can convert biological reactions into optical and electrical signals. In the development of drugs for Alzheimer's disease (AD), according to different disease hypotheses and targets, this technology plays an important role in confirming targets and screening active compounds. This paper briefly describes the pathogenesis of AD and the current situation of therapeutic drugs, introduces three biosensor analysis techniques commonly used in the discovery of AD drugs, such as surface plasmon resonance (SPR), biolayer interferometry (BLI) and fluorescence analysis technology, explains its basic principle and application progress, and summarizes their advantages and limitations respectively.

Effect of safflower yellow on learning and memory ability of APP/PS1 at different months based on TLR4/NF-KB signaling pathway / 中国药理学通报

Aim To investigate the effect of safflower yellow (SY) on learning and memory ability of APP/ PS1 mice at different disease stages, and to explore the mechanism of SY anti- Alzheimer's disease by using 3-,6- and 9-month-old APP/PS 1 transgenic mice as experimental animal models. Methods Behavioral experiments were conducted to observe the effects of SY on learning and memory of APP/PS1 mice of different months. ELISA was used to detect the effect of SY on the expression of inflammatory factors in cortex of mice of different months. Western blot was used to detect the microglia activation marker protein, and its mechanism of action was further analyzed. Results SY could enhance the learning and memory ability of mice aged 3, 6 and 9 months, reduce the content of IL-6 and increase the content of TGF-β1 in brain tissue, up-regulate the expression levels of arginase-1 (arg-1) and triggering receptor expressed on myeloid cells 2 (tREM2) in brain tissue of mice of different months, and down-regulate the expression levels of inducible nitric oxide synthase (iNOS), Toll-like receptors 4 (tlr4) and nuclear factor-kappa B (nf-KB). Conclusions Compared with 3- and 9-month-old mice, SY is the most effective in improving learning memory in 6-month-old APP/PS1 mice. SY inhibits TLR4/NF-KB pathway activation by inducing TREM2 expression in brain tissue of APP/PS 1 transgenic mice, promotes microglia phenotype shift to anti-inflammatory phenotype, reduces chronic neuroinflammatory response, and improves learning memory in APP/PS1 mice at all months of age.

Tripterine promotes pyroptosis of liver cancer cells by regulating ATF4/caspase-3/GSDME signaling pathway / 中国药理学通报

Aim To explore the new mechanism of triptolide (TRI) inhibiting the progression of hepatocellular carcinoma (HCC) . Methods Different concentrations (0, 0 . 5, 2, and 8 jjunol • L~) of TRI were administered to act on liver cancer cells, and then the cell phenotypes and possible mechanisms were explored using experimental methods such as CCK-8, cell cloning, Transwell, and protein immunoblotting; siRNA was used to interfere with the target gene GSDME and its role was determined. Finally, the mechanism of TRI inhibiting the growth of HCC cells in vivo was validated using a transplanted tumor model. Results TRI could inhibit the proliferation, cloning, and invasion of HCC cells, and promote cell apoptosis. Immunoblotting results showed that the expression of GSDME was significantly upregulated in HepG2 or He-pal-6 hepatocellular carcinoma after TRI treatment, while the expression of cleaved caspase-3 and PARP also significantly increased. Knocking out GSDME could partially reverse TRI-induced cell apoptosis. At the same time, cells knocked down by GSDME had stronger cloning and migration abilities, and the apoptosis rate was reduced compared to the TRI treatment group alone. In vivo experiments showed that TRI inhibited HCC tumor growth, and the TRI + siGSDME group had a faster tumor growth rate than the TRI treatment group alone did. In addition, after TRI stimulation, p-eIF2a and ATF4 in HepG2 and Hepal-6 cells significantly increased. The immunofluorescence results showed a dose-dependent increase in the number of ATF4 positive cells in HepG2 and Hepal-6 cells after TRI stimulation. Conclusion The inhibitory effect of TRI on the growth and invasion of liver cancer cells may be related to its regulation of the ATF4/caspase-3/GSDME signaling pathway and promotion of liver cancer cell apoptosis.

Mechanism and experimental validation of Zukamu granules in treatment of bronchial asthma based on network pharmacology and molecular docking / 中国药理学通报

Aim To anticipate the mechanism of zuka- mu granules (ZKMG) in the treatment of bronchial asthma, and to confirm the projected outcomes through in vivo tests via using network pharmacology and molecular docking technology. Methods The database was examined for ZKMG targets, active substances, and prospective targets for bronchial asthma. The protein protein interaction network diagram (PPI) and the medication component target network were created using ZKMG and the intersection targets of bronchial asthma. The Kyoto Encyclopedia of Genes and Genomics (KEGG) and gene ontology (GO) were used for enrichment analysis, and network pharmacology findings were used for molecular docking, ovalbumin (OVA) intraperitoneal injection was used to create a bronchial asthma model, and in vivo tests were used to confirm how ZKMG affected bronchial asthma. Results There were 176 key targets for ZKMG's treatment of bronchial asthma, most of which involved biological processes like signal transduction, negative regulation of apoptotic processes, and angiogenesis. ZKMG contained 194 potentially active components, including quercetin, kaempferol, luteolin, and other important components. Via signaling pathways such TNF, vascular endothelial growth factor A (VEGFA), cancer pathway, and MAPK, they had therapeutic effects on bronchial asthma. Conclusion Key components had strong binding activity with appropriate targets, according to molecular docking data. In vivo tests showed that ZKMG could reduce p-p38, p-ERKl/2, and p-I

Effect of LAG3 deficiency on natural killer cell function and hepatic fibrosis in mice infected with Echinococcus multilocularis / 中国血吸虫病防治杂志

Objective To investigate the effect of LAG-3 deficiency (LAG3-/-) on natural killer (NK) cell function and hepatic fibrosis in mice infected with Echinococcus multilocularis. Methods C57BL/6 mice, each weighing (20 ± 2) g, were divided into the LAG3-/- and wild type (WT) groups, and each mouse in both groups was inoculated with 3 000 E. multilocularis protoscoleces via the hepatic portal vein. Mouse liver and spleen specimens were collected 12 weeks post-infection, sectioned and stained with sirius red, and the hepatic lesions and fibrosis were observed. Mouse hepatic and splenic lymphocytes were isolated, and flow cytometry was performed to detect the proportions of hepatic and splenic NK cells, the expression of CD44, CD25 and CD69 molecules on NK cell surface, and the secretion of interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin (IL)-4, IL-10 and IL-17A. Results Sirius red staining showed widening of inflammatory cell bands and hyperplasia of fibrotic connective tissues around mouse hepatic lesions, as well as increased deposition of collagen fibers in the LAG3-/-group relative to the WT group. Flow cytometry revealed lower proportions of mouse hepatic (6.29% ± 1.06% vs. 11.91% ± 1.85%, P < 0.000 1) and splenic NK cells (4.44% ± 1.22% vs. 5.85% ± 1.10%, P > 0.05) in the LAG3-/- group than in the WT group, and the mean fluorescence intensity of CD44 was higher on the surface of mouse hepatic NK cells in the LAG3-/- group than in the WT group (t = −3.234, P < 0.01), while no significant differences were found in the mean fluorescence intensity of CD25 or CD69 on the surface of mouse hepaticNK cells between the LAG3-/- and WT groups (both P values > 0.05). There were significant differences between the LAG3-/- and WT groups in terms of the percentages of IFN-γ (t = −0.723, P > 0.05), TNF-α (t = −0.659, P > 0.05), IL-4 (t = −0.263, P > 0.05), IL-10 (t = −0.455, P > 0.05) or IL-17A secreted by mouse hepatic NK cells (t = 0.091, P > 0.05), and the percentage of IFN-γ secreted by mouse splenic NK cells was higher in the LAG3-/- group than in the WT group (58.40% ± 1.64% vs. 50.40% ± 4.13%; t = −4.042, P < 0.01); however, there were no significant differences between the two groups in terms of the proportions of TNF-α (t = −1.902, P > 0.05), IL-4 (t = −1.333, P > 0.05), IL-10 (t = −1.356, P > 0.05) or IL-17A secreted by mouse splenic NK cells (t = 0.529, P > 0.05). Conclusions During the course of E. multilocularis infections, LAG3-/- promotes high-level secretion of IFN-γ by splenic NK cells, which may participate in the reversal the immune function of NK cells, resulting in aggravation of hepatic fibrosis.

Re-understanding of the mechanism of coagulation disorder in liver cirrhosis / 临床肝胆病杂志

The liver plays an important regulatory role in maintaining the dynamic balance of coagulation and anticoagulation in the body. Such dynamic balance is fragile in patients with liver cirrhosis， and the risk of bleeding can be increased due to reductions in coagulation factors and platelet count and excessive fibrinolysis； meanwhile， thrombus can be formed due to the increases in von Willebrand factor and coagulation factor Ⅷ， the reductions in anticoagulant protein C and anticoagulant protein S， the increase in thrombin-generating potential， and alterations in antifibrinolytic components. This article reviews the mechanisms of coagulation disorder in liver cirrhosis， so as to help clinicians with the prevention and treatment of bleeding or thrombotic disorders in patients with liver cirrhosis.

Therapeutic Effect of Gandou Decoction on Wilson's Disease with Dampness Heat Accumulation Accompanied by Rapid Eye Movement Sleep Behavior Disorder / 中国实验方剂学杂志

ObjectiveTo explore the clinical efficacy of Gandou decoction in treating Wilson's disease （WD） with dampness heat accumulation accompanied by rapid eye movement （REM） sleep behavior disorder （RBD）. MethodFrom April 2019 to August 2023，62 patients with dampness heat accumulation type WD accompanied by RBD who met the inclusion criteria were selected from the Department of Encephalopathy at the First Affiliated Hospital of Anhui University of Chinese Medicine. They were randomly divided into a control group and an observation group with 31 cases each using a computer distributor. The control group received routine copper removal treatment，while the observation group received additional treatment with Gandou decoction on the basis of the control group. Eight days was one course of treatment，totaling three courses. The scores of traditional Chinese medicine syndromes，RBD screening questionnaire （RBDSQ） scores，RBD questionnaire-Hong Kong （RBDQ-HK） scores，polysomnography （PSG） parameters，24-hour urine copper （24 h U-Cu） levels，and non-ceruloplasmin-bound copper （NCC） levels between the two groups before and after treatment were compared，and adverse reactions were observed. ResultSixty trial cases were ultimately completed，with 30 cases in each group. Before treatment，there was no statistically significant difference in various indicators between the two groups， and thus they were comparable. Compared with those before treatment，the traditional Chinese medicine syndrome scores，RBDSQ scores and RBDQ-HK scores of the two groups were significantly reduced，the 24 h U-Cu levels were significantly increased，and the NCC levels were significantly reduced （P<0.05，P<0.01）. Compared with the control group， the observation group showed better improvement in traditional Chinese medicine syndrome scores， RBDSQ scores， RBDQ-HK scores， and NCC levels （P<0.05，P<0.01）. Compared with those before treatment，the total sleep time （TST），sleep efficiency （SE），sleep/REM latency，the proportion of N1/N2/REM stages，arousal index （ARI），and proportion of phasic electromyographic activity （P-EMG-A） were significantly improved in both groups （P<0.05）. Compared with the control group after treatment，the observation group showed more significant improvements in the proportion of TST，SE，REM stages，ARI，and P-EMG-A proportion （P<0.05）. ConclusionGandou decoction can not only improve the traditional Chinese medicine syndrome of WD patients with dampness heat accumulation accompanied by RBD but also alleviate their RBD symptoms.

Swyer syndrome with gonadal non-dysgerminoma malignant germ cell tumors: a report of 15 cases in a national medical center / 中华妇产科杂志

Objective: To evaluate the incidence, treatment, and survival outcomes of Swyer syndrome with gonadal non-dysgerminoma malignant germ cell tumor (MGCT-NDG). Methods: A retrospective study was performed on Swyer syndrome patients with MGCT-NDG between January 2011 and December 2022 in Peking Union Medical College Hospital to investigate their characteristics and outcomes. Results: A total of 15 patients (4.9%, 15/307) with Swyer syndrome were identified in 307 MGCT-NDG patients. The average age at diagnosis of MGCT-NDG and Swyer syndrome were (16.8±6.7) and (16.7±6.6) years, respectively. Six cases were preoperatively diagnosed as Swyer syndrome, of which 4 cases received bilateral gonadectomy with or without hysterectomy, while the other 2 cases underwent removal of gonadal tumor and unilateral gonadectomy with hysterectomy, respectively. Of the 9 patients postoperatively diagnosed as Swyer syndrome, unilateral gonadectomy, removal of gonadal tumor, and unilateral gonadectomy with hysterectomy were performed in 6 patients, 2 patients, and 1 patient, respectively. Mixed malignant germ cell tumor (MGCT;10 cases), yolk sac tumor (4 cases), and immature teratoma (1 case) were the pathological subtypes, in the descending order. There were International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ in 6 cases, stage Ⅱ in 3 cases, stage Ⅲ in 5 cases, and stage Ⅳ in 1 case, respectively. Eleven patients received reoperation for residual gonadectomy after a average delay of (7.9±6.2) months, including 8 MGCT-NDG patients and 1 gonadoblastoma patient, no tumor involved was seen in the remaining gonads in the other 2 cases. Ten patients experienced at least one recurrence, with a median event free survival of 9 months (5, 30 months), of which 2 patients received surgery only at the time of initial treatment. All patients with recurrence received surgery and combined with postoperative chemotherapy. After a median follow-up of 25 months (15, 42 months), 10 patients were disease-free, 3 patients died of the tumor, 1 died of side effects of leukemia chemotherapy, and 1 survived with disease. Conclusion: The incidence rate of Swyer syndrome in patients with MGCT-NDG is about 4.9%; timely diagnosis and bilateral gonadectomy should be emphasized to reduce the risk of reoperation and second carcinogenesis in this population.

Study on gene therapy for DPOAE and ABR threshold changes in adult Otof-/- mice / 临床耳鼻咽喉头颈外科杂志

Objective:This study aims to analyze the threshold changes in distortion product otoacoustic emissions（DPOAE） and auditory brainstem response（ABR） in adult Otof-/- mice before and after gene therapy, evaluating its effectiveness and exploring methods for assessing hearing recovery post-treatment. Methods:At the age of 4 weeks, adult Otof-/- mice received an inner ear injection of a therapeutic agent containing intein-mediated recombination of the OTOF gene, delivered via dual AAV vectors through the round window membrane（RWM）. Immunofluorescence staining assessed the proportion of inner ear hair cells with restored otoferlin expression and the number of synapses.Statistical analysis was performed to compare the DPOAE and ABR thresholds before and after the treatment. Results:AAV-PHP. eB demonstrates high transduction efficiency in inner ear hair cells. The therapeutic regimen corrected hearing loss in adult Otof-/- mice without impacting auditory function in wild-type mice. The changes in DPOAE and ABR thresholds after gene therapy are significantly correlated at 16 kHz. Post-treatment,a slight increase in DPOAE was observeds,followed by a recovery trend at 2 months post-treatment. Conclusion:Gene therapy significantly restored hearing in adult Otof-/- mice, though the surgical delivery may cause transient hearing damage. Precise and gentle surgical techniques are essential to maximize gene therapy's efficacy.

Development and application of in vitro intestinal absorption model based on microfluidic chips / 药学实践杂志

The intestine is the main site of oral drug absorption, and the epithelial cells of the intestine contain villi and microvilli, which promote secretion, cell adhesion, and absorption by increasing surface area and other factors. Traditional two-dimensional/three-dimensional (2D/3D) cell culture models and animal models have played an important role in studying drug absorption, but their application is limited due to the lack of sufficient predictability of human pharmacokinetics or ethical issues, etc. Therefore, mimicking the core structure and key functions of the human intestine based on in vitro live cells has been the focus of research on constructing a microfluidic chip-based intestinal model. The model is a microfluidic chip bionic system that simulates the complex microstructure, microenvironment, and physiological functions of the human intestine using microfabrication technology. Compared with 2D cell culture and animal experiments, the intestinal microarray model can effectively simulate the human in vivo environment and is more specific in drug screening. The research progress and applications in disease modeling, drug absorption and transport of intestinal microarray models and intestine-related multi-organ coupled microarray models at home and abroad were reviewed in this paper. The current challenges of intestinal chip simulating intestinal homeostasis and diseases were summarized，in order to provide reference for the further establishment of a more reliable in vitro intestinal chip model.

Specific DNA barcodes screening, germplasm resource identification, and genetic diversity analysis of Platycodon grandiflorum / 药学学报

Platycodonis Radix is the dry root of Platycodon grandiflorum of Campanulaceae, which has a variety of pharmacological effects and is a commonly used bulk Chinese medicine. In this study, the chloroplast genome sequences of six P. grandiflorum from different producing areas has been sequenced with Illumina HiSeq X Ten platform. The specific DNA barcodes were screened, and the germplasm resources and genetic diversity were analyzed according to the specific barcodes. The total length of the chloroplast genome of 6 P. grandiflorum samples was 172 260-172 275 bp, and all chloroplast genomes showed a typical circular tetrad structure and encoded 141 genes. The comparative genomics analysis and results of amplification efficiency demonstrated that trnG-UCC and ndhG_ndhF were the potential specific DNA barcodes for identification the germplasm resources of P. grandiflorum. A total of 305 P. grandiflorum samples were collected from 15 production areas in 9 provinces, for which the fragments of trnG-UCC and ndhG_ndhF were amplificated and the sequences were analyzed. The results showed that trnG-UCC and ndhG_ndhF have 5 and 11 mutation sites, respectively, and 5 and 7 haplotypes were identified, respectively. The combined analysis of the two sequences formed 13 haplotypes (named Hap1-Hap13), and Hap4 is the main genotype, followed by Hap1. The unique haplotypes possessed by the three producing areas can be used as DNA molecular tags in this area to distinguish from the germplasm resources of P. grandiflorum from other areas. The haplotype diversity, nucleotide diversity and genetic distance were 0.94, 4.79×10-3 and 0.000 0-0.020 3, respectively, suggesting that the genetic diversity was abundant and intraspecific kinship was relatively close. This study laid a foundation for the identification of P. grandiflorum, the protection and utilization of germplasm resources, and molecular breeding.

Identification and expression analysis of cellulose synthase family genes in Aquilaria sinensis / 药学学报

Cellulose synthase (CesA), one of the key enzymes in the biosynthesis of cellulose in plants, plays an important role in plant growth and plant resistance. In this study, a total of 21 AsCesA genes from Aquilaria sinensis were systematically identified and the physico-chemical characteristics were analyzed based on genome database and bioinformatical methods. The phylogenetic tree was constructed and the gene location on chromosome, cis-acting elements in the 2 000 basepairs upstream regulatory regions and conservative motifs were analyzed. The AsCesA proteins were mainly located on the plasma membrane. The number of amino acids of the proteins ranged from 390 to 1 261. The isoelectric point distributed from 5.67 to 8.86. All of the 21 AsCesA proteins possessed the transmembrane domains, the number of which was from 6 to 8. The genes were classified into 3 groups according to the phylogenetic relationship. Obvious differences were observed in motif composition in genes from different groups. However, motif2, motif6, motif7 and motif10 were observed in all of AsCesA proteins. Analysis of cis-acting elements indicated that AsCesA genes family has cis-acting elements related to plant hormones, abiotic stresses, and biological processes. Seven AsCesA genes with differential expression were selected according to the calli transcriptome data induced by NaCl at different times and their expression levels under different abiotic stresses were analyzed by quantitative real-time PCR. The results indicated that salt, low temperature, drought, and heavy metal stresses could affect the expression level of AsCesA genes, and the abundance of AsCesA1, AsCesA3 and AsCesA20 showed a significant change, implying their potential important roles to the abiotic stresses. The accumulation pattern of cellulose content under different abiotic stresses was similar to the expression trend of AsCesA genes. Our results provide valuable insights into the role of cellulose synthase in A.sinensis in plant defense.

Impacts of resistance training on physical fitness and injury prevention in children and adolescents / Impactos do treinamento de resistência sob a aptidão física e prevenção de lesões em crianças e adolescentes / Impactos del entrenamiento de resistencia en la aptitud física y la prevención de lesiones en niños y adolescentes

ABSTRACT Introduction: An adequate physical intervention program can improve the physical level of adolescents, promoting their interest in sports learning and socialization, factors that indirectly contribute to academic performance. Despite having a positive impact on athlete performance, cardiopulmonary resistance training has received few studies related to its benefits in children and adolescents. Objective: Explore the effect of resistance training on the physical fitness of children and adolescents and the prevention of their sports injuries. Methods: The statistical method was used in a situational analysis of injuries in different sports of 455 young people. In a second moment, 20 volunteers divided into groups by sex were submitted to resistance training exercises involving aerobic (30 minutes) and anaerobic (15 minutes) activity, under 45 minutes daily, three times a week, for ten weeks. Pertinent data were collected before, during, and after the intervention. They were submitted for analysis and consideration and performed statistical treatment on the data. Results: The frequency of sports injuries in adolescents was high, especially the mild injuries related to the characteristics of adolescents. Under the same intensity of resistance training, there was an improvement in running performance. There was a significant improvement in lung capacity, with relatively small differences between males and females. Conclusion: Resistance training can effectively improve the fitness level of children and adolescents, and its promotion is strongly recommended. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: Um programa de intervenção física adequado pode melhorar o nível físico dos adolescentes, promovendo seu interesse na aprendizagem esportiva e socialização, fatores que contribuem indiretamente para o desempenho acadêmico. O treinamento de resistência cardiopulmonar, apesar de impactar positivamente na performance de atletas, recebeu poucos estudos relacionados aos benefícios desempenhados em crianças e adolescentes. Objetivo: Explorar o efeito do treinamento de resistência sob a aptidão física de crianças e adolescentes, bem como na prevenção de suas lesões esportivas. Métodos: O método estatístico foi empregado na análise situacional de lesões em diferentes esportes de 455 jovens. Num segundo momento, 20 voluntários divididos em grupos por sexo foram submetidos à exercícios de treinamento de resistência envolvendo atividade aeróbica (30 minutos) e anaeróbica (15 minutos), sob 45 minutos diários, três vezes por semana, durante 10 semanas. Os dados pertinentes foram coletados antes, durante e após a intervenção. Efetuada a estatística de tratamento nos dados, foram submetidos para análise e consideração. Resultados: A frequência das lesões esportivas em adolescentes foi alta, principalmente as lesões leves, relacionadas às características dos adolescentes. Sob a mesma intensidade do treinamento de resistência, houve melhora no desempenho da corrida. Houve melhora significativa na capacidade pulmonar, com diferenças relativamente pequenas entre homens e mulheres. Conclusão: O treinamento de resistência pode melhorar efetivamente o nível físico de crianças e adolescentes, e sua promoção é fortemente recomendada. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: Un adecuado programa de intervención física puede mejorar el nivel físico de los adolescentes, promoviendo su interés por el aprendizaje deportivo y la socialización, factores que contribuyen indirectamente al rendimiento académico. El entrenamiento de resistencia cardiopulmonar, a pesar de tener un impacto positivo en el rendimiento de los deportistas, ha recibido pocos estudios relacionados con los beneficios realizados en niños y adolescentes. Objetivo: Explorar el efecto del entrenamiento de resistencia en la condición física de niños y adolescentes, así como en la prevención de sus lesiones deportivas. Métodos: Se empleó el método estadístico en el análisis situacional de las lesiones en diferentes deportes de 455 jóvenes. En un segundo momento, 20 voluntarios divididos en grupos por sexo fueron sometidos a ejercicios de entrenamiento de resistencia que incluían actividad aeróbica (30 minutos) y anaeróbica (15 minutos), bajo 45 minutos diarios, tres veces por semana, durante 10 semanas. Los datos pertinentes se recogieron antes, durante y después de la intervención. Realizado el tratamiento estadístico de los datos, éstos fueron sometidos a análisis y consideración. Resultados: La frecuencia de las lesiones deportivas en los adolescentes fue alta, principalmente las lesiones leves, relacionadas con las características de los adolescentes. Con la misma intensidad de entrenamiento de resistencia, se produjo una mejora en el rendimiento de la carrera. Hubo una mejora significativa en la capacidad pulmonar, con diferencias relativamente pequeñas entre hombres y mujeres. Conclusión: El entrenamiento de resistencia puede mejorar eficazmente el nivel físico de los niños y adolescentes, y su promoción es muy recomendable. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Establishment of treatment center for peritoneal metastasis in colorectal cancer / 中华胃肠外科杂志

The prognosis of patients with peritoneal metastasis from colorectal cancer is poor. At present, the comprehensive treatment system based on cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has significantly improved the survival of these patients. However, CRS and HIPEC have strict indications, high procedural difficulty, and high morbidity and mortality. If CRS+HIPEC is performed in an inexperienced center, overall survival and quality of life of patients may bo compromised. The establishment of specialized diagnosis and treatment centers can provide a guarantee for standardized clinical diagnosis and treatment. In this review, we first introduced the necessity of establishing a colorectal cancer peritoneal metastasis treatment center and the construction situation of the diagnosis and treatment center for peritoneal surface malignancies at home and abroad. Then we focused on introducing our construction experience of the colorectal peritoneal metastasis treatment center, and emphasized that the construction of the center must be done well in two aspects: firstly, the clinical optimization should be realized and the specialization of the whole workflow should be strengthened; secondly, we should ensure the quality of patient care and the rights, well-being and health of every patient.

Combined effect of PNPLA3 rs738409 and UGT1A1 rs10929303 gene polymorphisms on nonalcoholic fatty liver disease in children / 中华肝脏病杂志

Objective: To investigate the combined effects of patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 (C > G) and uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) rs10929303 (C > T) on nonalcoholic fatty liver disease (NAFLD) in children and adolescents so as to provide scientific evidence for NAFLD genetic research. Methods: 1 027 children and adolescents aged 7-18 were selected as the research subjects. The general situation, past medical history, height and body weight measurements, and B- mode ultrasound test of the liver were investigated by dedicated full-time personnel. In addition, the morning fasting venous blood was collected to measure the blood biochemical indicators. DNA was extracted and genotyped for PNPLA3 rs738409 and UGT1A1 rs10929303. Logistic regression analysis was used to analyze the association and combined effect of the two gene polymorphisms and NAFLD. Statistical analysis was performed by t-test, Mann-Whitney U test, or c2 test according to different data. Results: The GG genotype of PNPLA3 rs738409 and the CC genotype of UGT1A1 rs10929303 were associated with an increased risk of developing NAFLD in children by 89% (OR = 1.89, 95% CI: 1.11-3.23, P = 0.019) and 96% (OR = 1.96, 95% CI: 1.21-3.17, P = 0.006), respectively, while the concurrent risk of NAFLD in those who carried the above two genotypes increased by 306% compared with those who did not carry both genotypes (OR = 4.06, 95% CI: 1.90 ~ 8.66, P < 0.001). Conclusion: The combined effect of PNPLA3 and UGT1A1 gene polymorphisms can significantly increase the risk of NAFLD in children, providing new evidence for elucidating the genetic susceptibility to NAFLD.

Establishment and validation of clinical prediction model for steroid-resistant nephrotic syndrome in children / 中华儿科杂志

Objective: To identify the clinically relevant factors of steroid-resistant nephrotic syndrome (SSNS) in children and establish a predictive model followed by verifying its feasibility. Methods: A retrospective analysis was performed in a total of 111 children with nephrotic syndrome admitted to Children's Hospital of ShanXi from January 2016 to December 2021. The clinical data of general conditions, manifestations, laboratory tests, treatment, and prognosis were collected. According to the steroid response, patients were divided into SSNS and steroid resistant nephrotic syndrome (SRNS) group. Single factor Logistic regression analysis was used for comparison between the 2 groups, and variables with statistically significant differences were included in multivariate Logistic regression analysis. The multivariate Logistic regression analysis was used to identify the related variables of children with SRNS. The area under the receiver operating characteristic curve (ROC), the calibration curve and the clinical decision curve were used to evaluate its effectiveness of the variables. Results: Totally 111 children with nephrotic syndrome was composed of 66 boys and 45 girls, aged 3.2 (2.0, 6.6) years. There were 65 patients in the SSNS group and 46 in the SRNS group.Univariate Logistic regression analysis showed that the 6 variables, including erythrocyte sedimentation rate, 25-hydroxyvitamin D, suppressor T cells, D-dimer, fibrin degradation products, β2-microglobulin, had statistically significant differences between SSNS and SRNS groups (85 (52, 104) vs. 105 (85, 120) mm/1 h, 18 (12, 39) vs. 16 (12, 25) nmol/L, 0.23 (0.19, 0.27) vs. 0.25 (0.20, 0.31), 0.7 (0.6, 1.1) vs. 1.1 (0.9, 1.7) g/L, 3.1 (2.3, 4.1) vs. 3.3 (2.7, 5.8) g/L, 2.3 (1.9,2.8) vs. 3.0 (2.5, 3.7) g/L, χ2=3.73, -2.42, 2.24, 3.38, 2.24,3.93,all P<0.05), were included in the multivariate Logistic regression analysis. Finally, we found that 4 variables including erythrocyte sedimentation rate, suppressor T cells, D-dimer and β2-microglobulin (OR=1.02, 1.12, 25.61, 3.38, 95%CI 1.00-1.04, 1.03-1.22, 1.92-341.04, 1.65-6.94, all P<0.05) had significant correlation with SRNS. The optimal prediction model was selected. The ROC curve cut-off=0.38, with the sensitivity of 0.83, the specificity of 0.77 and area under curve of 0.87. The calibration curve showed that the predicted probability of SRNS group occurrence was in good agreement with the actual occurrence probability, χ2=9.12, P=0.426. The clinical decision curve showed good clinical applicability. The net benefit is up to 0.2. Make the nomogram. Conclusions: The prediction model based on the 4 identified risk factors including erythrocyte sedimentation rate, suppressor T cells, D-dimer and β2-microglobulin was suitable for the early diagnosis and prediction of SRNS in children. The prediction effect was promising in clinical application.

Clinical characteristics of patients with colon complications after necrotizing pancreatitis: a retrospective cohort study / 中华外科杂志

Objective: To investigate the clinical characteristics of colon complications in patients with necrotizing pancreatitis(NP). Methods: The clinical data of 403 patients with NP admitted to the Department of General Surgery,Xuanwu Hospital, Capital Medical University from January 2014 to December 2021 were retrospectively analyzed. There were 273 males and 130 females,aged (49.4±15.4) years(range: 18 to 90 years). Among them,there were 199 cases of biliary pancreatitis,110 cases of hyperlipidemic pancreatitis,and 94 cases of pancreatitis caused by other causes. A multidisciplinary diagnosis and treatment model was used to diagnose and treat patients. Depending on whether the patients had colon complications,they were divided into colon complications group and noncolon complications group. Patients with colon complications were treated with anti-infection therapy,parental nutritional support,keeping the drainage tube unobstructed,and terminal ileostomy. The clinical results of the two groups were compared and analyzed using a 1∶1 propensity score match(PSM) method. The t test,χ2 test, or rank-sum test was used to analyze data between groups,respectively. Results: The incidence of colon complications was 13.2%(53/403),including 15 cases of colon obstruction,23 cases of colon fistula,and 21 cases of colon hemorrhage. After PSM,the baseline and clinical characteristics at admission of the two groups of patients were comparable (all P>0.05). In terms of clinical outcome,compared to patients with NP without colon complications,the number of patients with colon complications who received minimally invasive intervention(88.7%(47/53) vs. 69.8%(37/53),χ2=5.736,P=0.030),the number of minimally invasive interventions (M(IQR))(2(2) vs. 1(1), Z=4.638,P=0.034),the number of patients with multiple organ failure(45.3%(24/53) vs. 32.1%(17/53),χ2=4.826,P=0.041),and the number of extrapancreatic infections(79.2%(42/53) vs. 60.4%(32/53),χ2=4.476,P=0.034) increased significantly. The time required for enteral nutrition support(8(30)days vs. 2(10) days, Z=-3.048, P=0.002), parental nutritional support(32(37)days vs. 17(19)days, Z=-2.592, P=0.009),the length of stay in the ICU(24(51)days vs. 18(31)days, Z=-2.268, P=0.002),and the total length of stay (43(52)days vs. 30(40)days, Z=-2.589, P=0.013) were also significantly prolonged. However,mortality rates in the two groups were similar(37.7%(20/53) vs. 34.0%(18/53),χ2=0.164,P=0.840). Conclusions: Colonic complications in NP patients are not rare,which can lead to prolonged hospitalization and increased surgical intervention. Active surgical intervention can help improve the prognosis of these patients.

Performance of screening of contacts of COVID-19 cases in same flight / 中华流行病学杂志

Objective: To understand the performance of 2019-nCoV nucleic acid detection in screening of contacts of COVID-19 cases in same flights and provide evidence for the effective screening of persons at high risk for the infection in domestic flights. Methods: The information of passengers who took same domestic flights with COVID-19 cases in China from April 1, 2020 to April 30, 2022 were retrospectively collected,and χ2 test was used to analyze positive nucleic acid detection rates in the passengers in different times before the onsets of the index cases, in different seat rows and in epidemic periods of different 2019-nCoV variants. Results: During the study period, a total of 433 index cases were identified among 23 548 passengers in 370 flights. Subsequently, 72 positive cases of 2019-nCoV nucleic acid were detected in the passengers, in whom 57 were accompanying persons of the index cases. Further analysis of the another 15 passengers who tested positive for the nucleic acid showed that 86.67% of them had onsets or positive detections within 3 days after the diagnosis of the index cases, and the boarding times were all within 4 days before the onsets of the index cases. The positive detection rate in the passengers who seated in first three rows before and after the index cases was 0.15% (95%CI: 0.08%-0.27%), significantly higher than in the passengers in other rows (0.04%, 95%CI: 0.02%-0.10%, P=0.007),and there was no significant difference in the positive detection rate among the passengers in each of the 3 rows before and after the index cases (P=0.577). No significant differences were found in the positive detection rate in the passengers, except the accompanying persons, among the epidemics caused by different 2019-nCoV variants (P=0.565). During the Omicron epidemic period, all the positive detections in the passengers, except the accompanying persons, were within 3 days before the onset of the index cases. Conclusions: The screening test of 2019-nCoV nucleic acid can be conducted in the passengers took the same flights within 4 days before the onsets of the index cases on board. Passengers who seated within 3 rows from the index cases can considered as the close contacts at high risk for 2019-nCoV, for whom screening should be conducted first and special managements are needed. The passengers in other rows can be classified as general risk persons for screening and management.

Depression status of elderly patients with metabolic syndrome in three provinces of China / 中华流行病学杂志

Objective: To understand the depression status and its influencing factors in elderly patients with MS in China and to explore the correlation between various components of elderly MS and depression. Methods: This study is based on the "Prevention and Intervention of Key Diseases in Elderly" project. We used a multi-stage stratified cluster random sampling method to complete 16 199 elderly aged 60 years and above in 16 counties (districts) in Liaoning, Henan, and Guangdong Provinces in 2019, excluding 1 001 missing variables. Finally, 15 198 valid samples were included for analysis. The respondents' MS disease was obtained through questionnaires and physical examinations, and the respondents' depression status within the past half month was assessed using the PHQ-9 Depression Screening Scale. The correlation between elderly MS and its components and depression and its influencing factors were analyzed by logistic regression. Results: A total of 15 198 elderly aged 60 years and above were included in this study, with the prevalence of MS at 10.84% and the detection rate of depressive symptoms in MS patients at 25.49%. The detection rates of depressive symptoms in patients with 0, 1, 2, 3, and 4 MS abnormal group scores were 14.56%, 15.17%, 18.01%, 25.21%, and 26.65%, respectively. The number of abnormal components of MS was positively correlated with the detection rate of depressive symptoms, and the difference between groups was statistically significant (P<0.05). The risk of depression symptoms in patients with MS, overweight/obesity, hypertension, diabetes, and dyslipidemia was 1.73 times (OR=1.73, 95%CI:1.51-1.97), 1.13 times (OR=1.13, 95%CI:1.03-1.24), 1.25 times (OR=1.25, 95%CI:1.14-1.38), 1.41 times (OR=1.41, 95%CI:1.24-1.60), 1.81 times (OR=1.81,95%CI:1.61-2.04), respectively, more than those without the disease. Multivariate logistic regression analysis showed that the detection rate of depressive symptoms in patients with sleep disorders was higher than that with normal sleep (OR=4.89, 95%CI: 3.79-6.32). The detection rate of depressive symptoms in patients with cognitive dysfunction was 2.12 times higher than that in the average population (OR=2.12, 95%CI: 1.56-2.89). The detection rate of depressive symptoms in patients with impaired instrumental activities of daily living (IADL) was 2.31 times (OR=2.31, 95%CI: 1.64-3.26) higher than that in the average population. Tea drinking (OR=0.73, 95%CI: 0.54-0.98) and physical exercise (OR=0.67, 95%CI: 0.49-0.90) seemed to be protective factors for depression in elderly MS patients (P<0.05). Conclusions: Older patients with MS and its component abnormalities have a higher risk of depression than the average population. Sleep disorders, cognitive impairment, and IADL impairment are important influencing factors for depression in elderly MS patients, while tea drinking and physical exercise may help to reduce the risk of the disease.

Health risk assessment of chemical substances in drinking water in Shijiazhuang from 2014 to 2021 / 环境与职业医学

Background A variety of substances in drinking water are hazardous to human health and there are health risks associated with ingestion of these substances via drinking water. Objective To assess the carcinogenic and non-carcinogenic health risks of drinking water in Shijiazhuang from 2014 to 2021. Methods The collection, preservation, and testing of 10529 drinking water samples (including finished water and tap water) in Shijiazhuang were conducted from 2014 to 2021 and followed the Standard examination methods for drinking water (GB/T 5750—2006). The health risks of 15 chemicals in drinking water by oral exposure were assessed using the US Environmental Protection Agency's four-step method combined with Monte Carlo simulation. Results Among the 15 chemicals in drinking water assessed for their health risks at general exposure levels and high exposure levels via oral route in Shijiazhuang from 2014 to 2021, the leading three chemicals and related values of carcinogenic risks for adults were cadmium (1.11×10−4, 2.98×10−4), arsenic (5.88×10−5, 1.56×10−4), and chromium (5.48×10−5, 2.41×10−4), and the leading three chemicals and related values of non-carcinogenic risks were fluoride (3.57×10−1, 6.57×10−1), arsenic (1.31×10−1, 3.47×10−1), and nitrate (1.14×10−1, 5.98×10−1). The health risk values of trichloromethane and aluminum were elevated but still in acceptable ranges. Drinking water-associated health risk values were higher in males than in females, such as the cancer risk for general exposure levels of arsenic in men was 5.76×10−5, compared to 5.72×10−5 in women. The health risk values of cadmium, chromium, fluoride, nitrate, and other chemicals in ground water were higher than those of surface water, and the health risk values of trichloromethane and carbon tetrachloride were lower than those in surface water, such as the non-carcinogenic risk value for general exposure levels of fluoride in groundwater was 3.61×10−1, compared to 2.27×10−1 in surface water. Factors such as water transmission and distribution links, water period, and season affected the health risks of drinking water. The general exposure levels of trichloromethane in tap water had a higher carcinogenic risk of 1.75×10−7 compared with 8.17×10−8 in finished water. The general levels of arsenic exposure was higher in the dry season at 1.36×10−1, compared with 1.26×10−1 in the wet season. Conclusion Except that the carcinogenic risk of cadmium at general exposure levels in Shijiazhuang exceeds the maximum acceptable range recommended by US Environmental Protection Agency, the health risk values of the remaining 14 chemicals are below the maximum acceptable risk. The carcinogenic risk values of arsenic and chromium and the non-carcinogenic risk values of fluoride, arsenic, and nitrate are relatively high, but do not exceed the maximum acceptable ranges. The emphasis should be on the management of drinking water in highly exposed areas and populations.