The role of innate immunity in diabetic nephropathy and their therapeutic consequences / 药物分析学报

Diabetic nephropathy(DN)is an enduring condition that leads to inflammation and affects a substantial number of individuals with diabetes worldwide.A gradual reduction in glomerular filtration and emergence of proteins in the urine are typical aspects of DN,ultimately resulting in renal failure.Mounting evidence suggests that immunological and inflammatory factors are crucial for the develop-ment of DN.Therefore,the activation of innate immunity by resident renal and immune cells is critical for initiating and perpetuating inflammation.Toll-like receptors(TLRs)are an important group of re-ceptors that identify patterns and activate immune responses and inflammation.Meanwhile,inflam-matory responses in the liver,pancreatic islets,and kidneys involve inflammasomes and chemokines that generate pro-inflammatory cytokines.Moreover,the activation of the complement cascade can be triggered by glycated proteins.This review highlights recent findings elucidating how the innate immune system contributes to tissue fibrosis and organ dysfunction,ultimately leading to renal failure.This re-view also discusses innovative approaches that can be utilized to modulate the innate immune responses in DN for therapeutic purposes.

Effects of Yishen Gujing Kangyan Prescription on the Levels of Interleukin 18,Transforming Growth Factor β1,Anti-ds-DNA Antibody and Complement C3 in Patients with Lupus Nephritis of Qiand Yin Deficiency Type / 广州中医药大学学报

Objective To investigate the clinical value of Yishen Gujing Kangyan Prescription(with the actions of benefiting the kidneys,consolidating essence and anti-inflammatory,mainly composed of Imperatae Rhizoma,Codonopsis Radix,Corni Fructus,Moutan Cortex,Lycii Fructus,Cuscutae Semen,Dioscoreae Rhizoma,honey-roasted Astragali Radix,Poria,Rehmanniae Radix Praeparata,etc.)in the treatment of lupus nephritis(LN)of qi and yin deficiency type.Methods A total of 116 patients with LN of qi and yin deficiency type were randomly divided into observation group and control group,58 cases in each group.The control group was given conventional western medicine treatment,and the observation group was treated with the combination of Yishen Gujing Kangyan Prescription on the basis of treatment for the control group.Both groups were treated for a period of 6 months.The changes of traditional Chinese medicine(TCM)syndrome scores,renal function parameters,immune function indicators,serum interleukin 18(IL-18),homocysteine(Hcy),transforming growth factor β1(TGF-β1),cystatin C(Cys C)levels in the two groups were observed before and after the treatment.After treatment,the clinical efficacy and the negative-conversion of anti-double-stranded DNA(ds-DNA)antibody were compared between the two groups.Results(1)After 6 months of treatment,the total effective rate of the observation group was 94.83%(55/58),and that of the control group was 75.86%(44/58).The intergroup comparison showed that the therapeutic effect of the observation group was significantly superior to that of the control group(χ2 = 5.453,P＜0.05).(2)After treatment,the scores of primary symptoms(edema,fatigue)and secondary symptoms(lumbar and knee soreness,loose stools)in the two groups were lower than those before treatment(P＜0.05),and the effect on lowering the scores in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the levels of renal function parameters of blood urea nitrogen(BUN),serum creatinine(Scr),and 24-hour urine protein quantification of the two groups were all lower than those before treatment(P＜0.05),and the effect on lowering renal function parameters in the observation group was significantly superior to that in the control group(P＜0.01).(4)After treatment,serum IL-18,TGF-β1,Hcy and Cys C levels of the two groups of patients were all reduced compared with those before treatment(P＜0.05),and the effect on lowering the levels of inflammatory factors and fibrosis parameters in the observation group was significantly superior to that in the control group(P＜0.01).(5)After treatment,the levels of immune function indicators of T cell subsets CD4+,CD4+/CD8+ and complement C3 in the two groups were increased compared with those before treatment(P＜0.05),and the increase in the observation group was significantly superior to that in the control group,and the differences were all statistically significant(P＜0.05 or P＜0.01).(6)The negative-conversion rate of anti-ds-DNA antibody in the observation group was 77.59%(45/58),which was significantly higher than that in the control group(55.17%,32/58),and the difference was statistically significant between the two groups(P＜0.05).Conclusion For the treatment of patients with LN of qi and yin deficiency type,Yishen Gujing Kangyan Prescription exerts synergistic effect on reducing inflammatory response,regulating immune function,promoting the recovery of renal function,and enhancing clinical efficacy.

Research Progress on the Anti-tumor Activity and Mechanism of Narciclasine / 昆明医科大学学报

Narciclasine(NCS),a hymenocallis littoralis alkaloid extracted from the bulbs of the genus Narcissus in the Lycoriaceae family,has been proven to have significant anti-tumor activity against a variety of tumor cells.The antitumor mechanisms of NCS are diverse and NCS exhibits antitumor effects through different pathways,which adapts to the current trend of developing multi-target anti-tumor drugs.This review introduces the research progress of the anti-tumor activity and mechanism of NCS in recent years based on the inhibitory effect of NCS on gastric cancer cells,oral cancer cells,polymorphous glioblastoma cells,colon cancer cells,breast cancer cells,melanoma cells and primary exudative lymphoma cells,aiming to provide ideas and references for the research and development,and design of NCS type anti-tumor drugs in the future.

Effects of high-efficiency centering pregnancy care combined with information-knowledge-attitude-practice health education on cesarean delivery on maternal request rate, maternal and neonatal health status and breastfeeding in primiparas / 中国实用护理杂志

Objective:To explore the effects of high-efficiency centering pregnancy care (CPC) combined with information-knowledge-attitude-practice (IKAP) health education on cesarean delivery on maternal request (CDMR) rate, maternal and neonatal health status so as to provide referential significance for reducing CDMR rate and improving postpartum maternal and neonatal health status and breastfeeding rate.Methods:In the prospective, single-center and controlled study, a total of 82 primiparas undergoing antenatal examination and delivery in South Binhu Hospital of Hefei First People′s Hospital were enrolled as the research objects between January 2020 and December 2021 by convenience sampling method, including 41 cases given routine health care in routine group between January and December 2020 and 41 cases given high-efficiency CPC combined with IKAP health education on basis of routine group in combination group between January and December 2021. The cognition of cesarean section, delivery modes, incidence of postpartum complications, neonatal complications and breastfeeding between the two groups were compared.Results:The age of the routine group was (26.71 ± 2.18) years old, and the age of the combination group was (27.16 ± 1.79) years old. The proportions of correct cognition, partially correct cognition and incorrect cognition to cesarean section in combination group were 73.17% (30/41), 21.95% (9/41), 4.88% (2/41), and 53.66% (22/41), 26.83% (11/41), 19.51% (8/41) in routine group, and the difference between the two groups was statistically significant ( Z = 4.22, P<0.05). The incidence of cesarean section and CDMR in combination group was 24.39% (10/41) and 1/10, lower than that in routine group [46.34% (19/41), 10/19], and the difference between the two groups was statistically significant ( χ2 = 4.32, P<0.05; Fisher′s exact test, P = 0.049 ). The total incidence rates of postpartum complications of primiparas and neonatal complications in the combination group were 4.88%(2/41) and 7.32%(3/41), lower than 12.20%(5/41) and 12.20%(5/41) in the routine group, and the differences between the two groups were not statistically significant (Fisher′s exact test, P = 0.432, 0.712). The scores of functional health literacy, communicative health literacy and critical health literacy in combination group were (85.73 ± 4.09), (51.93 ± 4.72) and (58.63 ± 4.32) points, higher than those in routine group [(80.17 ± 5.26), (46.37 ± 5.11) , (52.71 ± 5.07) points], and the difference between the two groups was statistically significant ( t = 5.34, 5.12, 5.69, all P<0.01). At 3 months after delivery, exclusive breastfeeding rate, milk powder feeding rate and mixed feeding rate in combination group were 58.54% (24/41), 7.32%(3/41), 34.15(14/41), higher than 26.83% (11/41), 29.27(12/41), 43.90%(18/41) in routine group, and the difference between the two groups was statistically significant ( χ2 = 10.73, P<0.05). Conclusions:High-efficiency CPC combined with IKAP health education can reduce incidence of CDMR, decrease maternal and neonatal complications, enhance maternal postpartum health literacy and improve breastfeeding rate in primiparas by improving correct cognition to cesarean section. It is worthy of clinical application.

Low intramuscular adipose tissue index is a protective factor of all-cause mortality in maintenance dialysis patients / 中华肾脏病杂志

Objective:To investigate the relationship between intramuscular adipose tissue index (IATI) calculated from computed tomography images at transverse process of the first lumbar and all-cause mortality in maintenance dialysis patients, and to provide a reference for improving the prognosis in these patients.Methods:It was a multicenter retrospective cohort study. The clinical data of patients who received maintenance hemodialysis or peritoneal dialysis treatment from January 1, 2017 to December 31, 2019 in 4 grade Ⅲ hospitals including Zhongda Hospital Affiliated to Southeast University, Taizhou People's Hospital Affiliated to Nanjing Medical University, Affiliated Hospital of Yangzhou University, and the Third Affiliated Hospital of Soochow University were retrospectively collected. IATI was calculated by low attenuation muscle (LAM) density/skeletal muscle density. The receiver-operating characteristic curve was used to determine the optimal cut-off value of IATI, and the patients were divided into high IATI group and low IATI group according to the optimal cut-off value. The differences of baseline clinical data and measurement parameters of the first lumbar level between the two groups were compared. The follow-up ended on December 23, 2022. The endpoint event was defined as all-cause mortality within 3 years. Kaplan-Meier survival curve and log-rank test were used to analyze the survival rates and the differences between the two groups. Multivariate Cox regression analysis models were used to analyze the association between IATI and the risk of all-cause mortality in maintenance dialysis patients. Multivariate logistic regression analysis model was used to analyze the influencing factors of high IATI.Results:A total of 478 patients were eligibly recruited in this study, with age of (53.55±13.19) years old and 319 (66.7%) males, including 365 (76.4%) hemodialysis patients and 113 (23.6%) peritoneal dialysis patients. There were 376 (78.7%) patients in low IATI (<0.42) group and 102 (21.3%) patients in high IATI (≥0.42) group. The proportion of age ≥ 60 years old ( χ2=24.746, P<0.001), proportion of diabetes mellitus ( χ2=5.570, P=0.018), fasting blood glucose ( t=-2.145, P=0.032), LAM density ( t=-3.735, P<0.001), LAM index ( t=-7.072, P<0.001), and LAM area/skeletal muscle area ratio ( Z=-9.630, P<0.001) in high IATI group were all higher than those in low IATI group, while proportion of males ( χ2=11.116, P<0.001), serum albumin ( Z=2.708, P=0.007) and skeletal muscle density ( t=12.380, P<0.001) were lower than those in low IATI group. Kaplan-Meier survival analysis showed that the 3-years overall survival rate of low IATI group was significantly higher than that in high IATI group (Log-rank χ2=19.188, P<0.001). Multivariate Cox regression analysis showed that IATI<0.42 [<0.42/≥0.42, HR(95% CI): 0.50 (0.31-0.83), P=0.007] was an independent protective factor of all-cause mortality, and age ≥60 years old [ HR (95% CI): 2.61 (1.60-4.23), P<0.001], diabetes mellitus [ HR (95% CI): 1.71 (1.06-2.78), P=0.029] and high blood neutrophil/lymphocyte ratio [ HR (95% CI): 1.04 (1.00-1.07), P=0.049] were the independent risk factors of all-cause mortality in maintenance dialysis patients. Stepwise Cox regression analysis showed that IATI<0.42 was still an independent protective factor of all-cause mortality in maintenance dialysis patients [<0.42/≥0.42, HR (95% CI): 0.45 (0.27-0.76), P=0.003]. Multivariate logistic regression analysis showed that low skeletal muscle density [ OR (95% CI): 0.84 (0.81-0.88), P<0.001] and high serum triglyceride [ OR (95% CI): 1.39 (1.07-1.82), P=0.015] were the independent influencing factors of IATI≥0.42. Conclusion:IATI<0.42 of the first lumbar level is an independent protective factor of all-cause mortality in maintenance dialysis patients. Localized myosteatosis within high-quality skeletal muscle may reduce the risk of all-cause mortality in these patients.

Correlation between Content of Active Ingredients of Aurantii Fructus and Soil Factor / 中国实验方剂学杂志

ObjectiveTo study the correlation between the content of active ingredients of Aurantii Fructus in different main production areas and soil factors， so as to provide a theoretical basis for implementing ecological regulation of soil， improving the quality of Aurantii Fructus， and revealing the origin of genuine medicinal materials. MethodThe content of naringin， neohesperidin， total flavonoids， volatile oil， total nitrogen， total phosphorus， total potassium， and 17 soil factor-related indicators in 25 batches of Aurantii Fructus from different production areas were determined. The main soil factors affecting the content of active ingredients of Aurantii Fructus were analyzed by Pearson correlation analysis， principal component analysis， and grey correlation analysis. ResultThe pH value of the soil is between 4.83 and 8.21， and the soil is weakly acidic and neutral in general. Soil fertility exceeds the average. Pearson correlation analysis shows that the soil factors most related to the four active ingredients of Aurantii Fructus are total phosphorus， available copper， available zinc， exchangeable magnesium， available sulfur， available phosphorus， and available molybdenum. Principal component analysis shows that total nitrogen， alkali-hydrolyzable nitrogen， organic matter， available phosphorus， and available zinc are the main characteristic factors in soil. Grey correlation analysis shows that the main soil factors affecting the active ingredients of Aurantii Fructus are total phosphorus， total nitrogen， available zinc， available copper， exchangeable magnesium， and pH. ConclusionIn the cultivation of Aurantii Fructus， the medicinal material quality of Aurantii Fructus could be improved by adjusting the level of beneficial factors in the soil and improving the soil texture.

Analysis of occupational health literacy level and its influencing factors among drivers in transportation industry / 中国职业医学

ObjectiveTo analyze the current occupational health literacy (OHL) level and its influencing factors among drivers in transportation industry. Methods A total of 880 drivers of taxi companies, passenger transport companies, freight companies and online booking companies were selected as the research subjects using the judgment sampling method. The Occupational Health Literacy Questionnaire of National Key Populations was used to conduct a survey on their OHL levels via online questionnaires, and the influencing factors of OHL were analyzed. Results The OHL level of the research subjects was 54.32% (478/880). The OHL levels in the dimensions of occupational health legal knowledge, basic knowledge of occupational health protection, basic skills of occupational health protection, healthy working style and behavior were 55.34%, 79.55%, 58.30% and 46.25%, respectively. The results of the multivariate logistic regression analysis showed that the OHL levels of drivers in passenger transport and freight companies were higher than that in taxi companies (all P<0.01). The OHL levels of drivers in private enterprises, foreign-funded enterprises, and other enterprises were lower than those in state-owned enterprises (all P<0.05). The OHL levels of drivers in large enterprises were lower than that of drivers in micro-enterprises (P<0.05). The OHL levels of drivers worked >5-10 years and >10 years were lower than that of drivers working 1-5 years (all P<0.05). Conclusion There is a considerable room for improvement in the OHL levels of drivers in the transportation industry. The category, economic type, and scale of the employing unit and driving work year of the current position are the main influencing factors of OHL levels.

Pollution status and distribution characteristics of indoor air bacteria in subway stations and compartments in a city of Central South China / 环境与职业医学

Background Bacteria are the most diverse and widely sourced microorganisms in the indoor air of subway stations, where pathogenic bacteria can spread through the air, leading to increased health risks. Objective To understand the status and distribution characteristics of indoor air bacterial pollution in subway stations and compartments in a city of Central South China, and to provide a scientific basis for formulating intervention measures to address indoor air bacteria pollution in subways. Methods Three subway stations and the compartments of trains parking there in a city in Central South China were selected according to passenger flow for synchronous air sampling and monitoring. Temperature, humidity, wind speed, carbon dioxide (CO2), fine particulate matter (PM2.5), and inhalable particulate matter (PM10) were measured by direct reading method. In accordance with the requirements of Examination methods for public places-Part 3: Airborne microorganisms (GB/T 18204.3-2013), air samples were collected at a flow rate of 28.3 L·min−1, and total bacterial count was estimated. Bacterial microbial species were identified with a mass spectrometer and pathogenic bacteria were distinguished from non-pathogenic bacteria according to the Catalogue of pathogenic microorganisms transmitted to human beings issued by National Health Commission. Kruskal-Wallis H test was used to compare the subway hygiene indicators in different regions and time periods, and Bonferroni test was used for pairwise comparison. Spearman correlation test was used to evaluate the correlation between CO2 concentration and total bacterial count. Results The pass rates were 100.0% for airborne total bacteria count, PM2.5, and PM10 in the subway stations and train compartments, 94.4% for temperature and wind speed, 98.6% for CO2, but 0% for humidity. The overall median (P25, P75) total bacteria count was 177 (138,262) CFU·m−3. Specifically, the total bacteria count was higher in station halls than in platforms, and higher during morning peak hours than during evening peak hours (P<0.05). A total of 874 strains and 82 species were identified by automatic microbial mass spectrometry. The results of identification were all over 9 points, and the predominant bacteria in the air were Micrococcus luteus (52.2%) and Staphylococcus hominis (9.8%). Three pathogens, Acinetobacter baumannii (0.3%), Corynebacterium striatum (0.1%), and Staphylococcus epidermidis bacilli (2.2%) were detected in 23 samples (2.6%), and the associated locations were mainly distributed in train compartments during evening rush hours. Conclusion The total bacteria count in indoor air varies by monitoring sites of subway stations and time periods, and there is a risk of opportunistic bacterial infection. Attention should be paid to cleaning and disinfection during peak passenger flow hours in all areas.

Association Between Objective Social Isolation and Unmet Medical Needs: A Nationwide Cross-sectional Study in Korea / 예방의학회지

Objectives@#The aim of this study was to analyze the relationship between objective social isolation (SI) and unmet medical needs (UMN) in adults aged 19 and older. @*Methods@#A cross-sectional analysis was conducted of 208 619 adults aged 19 and older, excluding missing data, using the 2019 Korea Community Health Survey. To analyze the association between objective SI and UMN, the chi-square test and logistic regression analysis were performed. @*Results@#The prevalence of UMN was 1.14 times higher (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.06 to 1.23) among those with SI than among those without SI, and the OR for groups with 5 SI types was 2.77 (95% CI, 1.86 to 4.12) compared to those with no SI types. In addition, a stratified analysis by age group showed that the association between SI and UMN existed even in groups under 64 years old. However, among those aged 65 and older, SI was associated with an OR of 1.53 (95% CI, 1.37 to 1.71) for UMN compared to non-SI. As the number of SI types increased, the prevalence of UMN also increased, indicating a strong association between SI and UMN in older adults. @*Conclusions@#This study found that individuals with SI experienced UMN due to fear and anxiety about interpersonal relationships. Therefore, based on the results of this cross-sectional study, it is necessary to investigate the causal relationship between SI and UMN through future longitudinal data.

Curcumin plays an anti-osteoporosis role by inhibiting NF-κB signaling pathway to reduce oxidative stress damage to osteogenesis / 中国药理学通报

Aim To investigate the mechanism of curcumin inhibition of oxidative stress on osteogenic differentiation and its dose-dependent anti-osteoporosis effect. Methods Cellular oxidative stress models were used, different concentrations of curcumin were added to determinethebone formation markers, and the potential signaling pathways involvedwere detected. Meanwhile, the mouse model of osteoporosis ( ovariecto- mized, 0VX) was used to confirm its effect against osteoporosis. Results In vitro experiments found that low concentrations of curcumin (1-10 μmol · L

Multi-center Randomized Controlled Clinical Trial of Huangqi Injection Combined with Buzhong Yiqi Acupuncture in Treatment of Chronic Fatigue Syndrome with Qi Deficiency / 中国实验方剂学杂志

ObjectiveTo investigate the clinical efficacy of Huangqi injection combined with Buzhong Yiqi acupuncture in the treatment of chronic fatigue syndrome （CFS） with Qi deficiency and its effects on TCM syndromes， fatigue symptoms， serum superoxide dismutase （SOD）， malondialdehyde （MDA）， and oxidized low-density lipoprotein （ox-LDL） levels. MethodA total of 200 patients with CFS of Qi deficiency were randomly divided into a control group （100 cases） and an observation group （100 cases）. The control group was treated with vitamin B compounds， and the observation group was treated with Huangqi injection combined with Buzhong Yiqi acupuncture for two weeks. The scores of TCM syndromes， fatigue symptoms， levels of serum SOD， MDA， and ox-LDL and the incidence of adverse reactions were observed and compared before and after treatment in two groups. ResultAfter treatment， the total effective rate of the control group was 54.34% （50/92）， while that of the observation group was 88.54% （85/96）. The total effective rate of the observation group was higher than that of the control group （χ2=27.13，P<0.05）. Compared with those in the two groups before treatment， scores of fatigue self-assessment scale （FSAS）， physical fatigue and mental fatigue， and sleep/rest response scores of fatigue in the two groups after treatment were significantly decreased （P<0.05）. After treatment， scores of FSAS， physical fatigue and mental fatigue， and sleep/rest response scores of fatigue in the observation group were significantly decreased compared with those in the control group （P<0.05）. Compared with those in the two groups before treatment， TCM syndrome scores in the two groups after treatment were significantly decreased （P<0.05）. After treatment， TCM syndrome scores in the observation group were significantly decreased compared with those in the control group （P<0.05）. Compared with those in the two groups before treatment， MDA levels in the two groups were significantly decreased （P<0.05）， ox-LDL levels in the observation group were significantly decreased （P<0.05）， and SOD levels were significantly increased （P<0.05）. After treatment， compared with those in the control group， the serum MDA and ox-LDL levels in the observation group were significantly decreased （P<0.05）， and the serum SOD was significantly increased （P<0.05）. No serious adverse events or adverse reactions occurred during this clinical trial. ConclusionHuangqi injection combined with Buzhong Yiqi acupuncture has a good clinical curative effect in the treatment of CFS with Qi deficiency， which can effectively improve the fatigue symptoms of patients， increase the level of SOD， and reduce the level of serum MDA and ox-LDL. It is related to the production of antioxidants， inhibiting the production of lipid peroxides， and improving the body's ability to resist oxidative stress.

Levofloxacin combined with cellulase can eradicate bacille Calmette-Guerin biofilm infection / 南方医科大学学报

OBJECTIVE@#To investigate the inhibitory effects of levofloxacin (LEV) combined with cellulase against bacille CalmetteGuerin (BCG) biofilms in vitro.@*METHODS@#The mature growth cycle of BCG biofilms was determined using the XTT method and crystal violet staining. BCG planktonic bacteria and BCG biofilms were treated with different concentrations of LEV and cellulose alone or jointly, and the changes in biofilm biomass were quantified with crystal violet staining. The mature BCG biofilm was then treated with cellulase alone for 24 h, and after staining with SYTO 9 and Calcofluor White Stain, the number of viable bacteria and the change in cellulose content in the biofilm were observed with confocal laser scanning microscopy. The structural changes of the treated biofilm were observed under scanning electron microscopy.@*RESULTS@#The MIC, MBC and MBEC values of LEV determined by broth microdilution method were 4 μg/mL, 8 μg/mL and 1024 μg/mL, respectively. The combined treatment with 1/4×MIC LEV and 2.56, 5.12 or 10.24 U/mL cellulase resulted in a significant reduction in biofilm biomass (P < 0.001). Cellulase treatments at the concentrations of 10.24, 5.12 and 2.56 U/mL all produced significant dispersion effects on mature BCG biofilms (P < 0.001).@*CONCLUSION@#LEV combined with cellulose can effectively eradicate BCG biofilm infections, suggesting the potential of glycoside hydrolase therapy for improving the efficacy of antibiotics against biofilmassociated infections caused by Mycobacterium tuberculosis.

Advances in Diagnosis and Treatment of Transplant-Associated Thrombotic Microangiopathy --Review / 中国实验血液学杂志

Transplantation-associated thrombotic microangiopathy (TA-TMA) is one of the serious complications mostly occurring within 100 days after hematopoietic stem cell transplantation (HSCT). Risk factors of TA-TMA include genetic predispositions, GVHD, and infections. The pathophysiological mechanisms of TA-TMA start with endothelial injury caused by complement activation, which leads to microvascular thrombosis, and microvascular hemolysis, ultimately resulting in multi-organ dysfunction. In recent years, the development of complement inhibitors has markedly improved the prognosis of TA-TMA patients. This review will give an update on risk factors, clinical manifestations, diagnosis, and treatment of TA-TMA, so as to provide references for clinical practice.

Monoclonal antibody targeting mu-opioid receptor attenuates morphine tolerance via enhancing morphine-induced receptor endocytosis / 药物分析学报

Morphine is a frequently used analgesic that activates the mu-opioid receptor(MOR),which has prominent side effects of tolerance.Although the inefficiency of morphine in inducing the endocytosis of MOR underlies the development of morphine tolerance,currently,there is no effective therapy to treat morphine tolerance.In the current study,we aimed to develop a monoclonal antibody(mAb)precisely targeting MOR and to determine its therapeutic efficacy on morphine tolerance and the underlying molecular mechanisms.We successfully prepared a mAb targeting MOR,named 3A5C7,by hybridoma technique using a strategy of deoxyribonucleic acid immunization combined with cell immunization,and identified it as an immunoglobulin G mAb with high specificity and affinity for MOR and binding ability to antigens with spatial conformation.Treatment of two cell lines,HEK293T and SH-SY5Y,with 3A5C7 enhanced morphine-induced MOR endocytosis via a G protein-coupled receptor kinase 2(GRK2)/β-arrestin2-dependent mechanism,as demonstrated by immunofluorescence staining,flow cytometry,Western blotting,coimmunoprecipitation,and small interfering ribonucleic acid(siRNA)-based knock-down.This mAb also allowed MOR recycling from cytoplasm to plasma membrane and attenuated morphine-induced phosphorylation of MOR.We established an in vitro morphine tolerance model using differentiated SH-SY5Y cells induced by retinoic acid.Western blot,enzyme-linked immunosorbent assays,and siRNA-based knockdown revealed that 3A5C7 mAb diminished hyperactivation of adenylate cyclase,the in vitro biomarker of morphine tolerance,via the GRK2/β-arrestin2 pathway.Furthermore,in vivo hotplate test demonstrated that chronic intrathecal administration of 3A5C7 significantly alle-viated morphine tolerance in mice,and withdrawal jumping test revealed that both chronic and acute 3A5C7 intrathecal administration attenuated morphine dependence.Finally,intrathecal electroporation of silencing short hairpin RNA illustrated that the in vivo anti-tolerance and anti-dependence efficacy of 3A5C7 was mediated by enhanced morphine-induced MOR endocytosis via GRK2/β-arrestin2 pathway.Collectively,our study provided a therapeutic mAb,3A5C7,targeting MOR to treat morphine tolerance,mediated by enhancing morphine-induced MOR endocytosis.The mAb 3A5C7 demonstrates promising translational value to treat clinical morphine tolerance.

Impact of Target Lesion Calcification Evaluated by Coronary Angiography on Immediate Procedure Success Rate and Long-term Prognosis in Patients Underwent Percutaneous Coronary Intervention / 中国循环杂志

Objectives:To analyze the impact of target lesion calcification evaluated by coronary angiography on immediate procedure success rate and long-term clinical outcome in patients underwent percutaneous coronary intervention(PCI). Methods:Consecutive patients received angiographic calcification evaluation and underwent PCI in Fuwai Hospital,Chinese Academy of Medical Sciences from January 2017 to December 2018 were prospectively enrolled in this study.Patients are divided into 4 groups,including non-calcification group(n=14 387),mild calcification group(n=8 231),moderate calcification group(n=3 208)and severe calcification group(n=886).The primary endpoint was immediate post-PCI procedure success rate,which was defined as residual stenosis<50%without major operational complications(including coronary artery perforation,coronary artery dissection,intraoperative stent thrombosis)and failure to cross the lesion.The long-term clinical endpoint was the 3-year major adverse cardiovascular events(MACE),which included composite endpoint events such as all cause death,myocardial infarction(MI),and revascularization. Results:The severe calcification group had a lower success rate of interventional therapy(80.59%vs.94.23%vs.94.29%vs.91.49%),a higher incidence of residual stenosis≥50%(17.72%vs.5.03%vs.4.84%vs.7.29%),a higher incidence of coronary artery dissection(1.81%vs.0.66%vs.0.78%vs.1.25%),and a higher incidence of coronary artery perforation(2.14%vs.0.51%vs.0.38%vs.0.69%),and a higher incidence of failure to cross the lesion(0.23%vs.0.12%vs.0.04%vs.0.16%)compared to the non-calcification group,mild calcification group,and moderate calcification group(all P<0.05).Multivariate Cox regression analysis showed that patients with severe calcification had a higher risk of MACE(12.98%vs.9.35%,HR=1.21,95%CI:1.00-1.47,P=0.046),all-cause mortality(4.29%vs.1.80%,HR=1.55,95%CI:1.10-2.18,P=0.013),and MI(2.14%vs.0.97%,HR=1.97,95%CI:1.21-3.20,P=0.006)compared to patients without calcification. Conclusions:Patients with angiographic-detected severe calcification after PCI treatment face higher risk of PCI procedure failure,MACE,all-cause death,and MI compared to patients without,with mild,and moderate calcification.

The value of non-invasive prenatal testing for the identification of numerical and structural chromosomal abnormalities and copy number variations in the fetuses / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of non-invasive prenatal testing (NIPT) for the identification of numerical and structural chromosomal abnormalities and copy number variations (CNVs) in fetuses.@*METHODS@#46 197 pregnant women undergoing NIPT at the Prenatal Diagnosis Center of Chenzhou First People's Hospital from January 2018 to December 2021 were selected as the study subjects. Positive cases were subjected to chromosomal karyotyping and copy number variation sequencing (CNV-seq) following amniocentesis.@*RESULTS@#Nearly 50% of common chromosomal aneuploidies were found in the elder pregnant women. Among these, sex chromosome aneuploidies were mainly found in pregnant women with advanced age as well as borderline risks by serological screening. Rare autosomal aneuploidies and CNVs were mainly found in those with borderline or high risks by serological screening. The positive predictive values (PPV) for fetal chromosomal abnormalities indicated by NIPT were as follows: T21 (92.37%, 109/118), T18 (53.85%, 14/26), sex chromosome aneuploidies (45.04%, 59/131), T13 (34.62%, 9/26), CNVs (29.17%, 14/48), and rare autosomal aneuploidies (2.60%, 2/77).@*CONCLUSION@#NIPT has a high detection rate for T21, T18, T13 and sex chromosome aneuploidies. It can also detect rare autosomal aneuploidies and CNVs, including some rare structural abnormalities, though verification is required by analyzing amniotic fluid samples.

Enhanced nitrogen removal by bioelectrochemical coupling anammox and characteristics of microbial communities / 生物工程学报

To investigate the bioelectrochemical enhanced anaerobic ammonia oxidation (anammox) nitrogen removal process, a bioelectrochemical system with coupled anammox cathode was constructed using a dual-chamber microbial electrolysis cell (MEC). Specifically, a dark incubation batch experiment was conducted at 30 ℃ with different influent total nitrogen concentrations under an applied voltage of 0.2 V, and the enhanced denitrification mechanism was investigated by combining various characterization methods such as cyclic voltammetry, electrochemical impedance spectroscopy and high-throughput sequencing methods. The results showed that the total nitrogen removal rates of 96.9%±0.3%, 97.3%±0.4% and 99.0%±0.3% were obtained when the initial total nitrogen concentration was 200, 300 and 400 mg/L, respectively. In addition, the cathode electrode biofilm showed good electrochemical activity. High-throughput sequencing results showed that the applied voltage enriched other denitrifying functional groups, including Denitratisoma, Limnobacter, and ammonia oxidizing bacteria SM1A02 and Anaerolineaceae, Nitrosomonas europaea and Nitrospira, besides the anammox bacteria. These electrochemically active microorganisms comprised of ammonium oxidizing exoelectrogens (AOE) and denitrifying electrotrophs (DNE). Together with anammox bacteria Candidatus Brocadia, they constituted the microbial community structure of denitrification system. Enhanced direct interspecies electron transfer between AOE and DNE was the fundamental reason for the further improvement of the total nitrogen removal rate of the system.

Prediction of internal fixation failure of femoral trochanteric fracture by external wall morphology / 中国骨伤

OBJECTIVE@#To investigate the relationship between the shape of the lateral wall and the early failure of internal fixation in the fracture of the femoral trochanteric region(FFT).@*METHODS@#Total 295 patients with femoral trochanteric fracture underwent internal fixation from January 2015 to January 2020 were selected. The patients were divided into two groups according to whether there was early internal fixation failure after surgery, 19 patients in the failure group and 276 patients in the normal group. Gender, affected side, age, AO classification, body mass index(BMI), preoperative hemoglobin, X-ray measurement of lower lateral wall thickness, preoperative internal diseases, intraoperative blood loss, postoperative tip apex distance(TAD), postoperative neck shaft angle, operation time and other data were compared between two groups. The shape of the lateral wall was compared between two groups, and the correlation between the shape of the lateral wall and the early internal fixation failure of femoral trochanteric fracture was analyzed.@*RESULTS@#All patients were followed up for more than 1 year. There was no significant difference between two groups in terms of intraoperative blood loss, operation time, postoperative TAD, and postoperative neck shaft angle(P>0.05). At the latest follow-up, the visual anaglue scale (VAS) of the failure group was higher than that of the normal group(P<0.01), and the Harris score of the failure group was lower than that of normal group(P<0.05). The receiver operator characteristic (ROC) curve between shape of lateral wall and failure of early internal fixation of femoral trochanteric fracture was drawn. The critical value of the midpoint lateral wall thickness was 16.5 mm, and the area under the ROC curve was 0.845;The critical value of average sidewall thickness was 16.5 mm, and the area under ROC curve was 0.838;The critical value of the axial area of the sidewall was 7.5 mm, and the area under the ROC curve was 0.826.@*CONCLUSION@#The shape of the lateral femoral wall measured by CT could be used as a predictive factor for the early failure of internal fixation of femoral trochanteric fractures. For patients at risk, more reasonable surgical plans and postoperative preventive measures should be developed.

Perinatal risk factors for the occurrence of singleton apparently stillborn infants / 中国当代儿科杂志

OBJECTIVES@#To identify the perinatal risk factors for the occurrence of singleton apparently stillborn infants.@*METHODS@#This was a case-control study. A total of 154 singleton neonates with gestational age ≥28 weeks and Apgar score of 0-1 who were subsequently successfully resuscitated in the Obstetrics and Gynecology Hospital of Fudan University from January 2006 to December 2015 were enrolled as the case group (apparently stillborn group). A total of 616 singleton infants born from January 2006 to December 2015 (1-minute Apgar score >1) were randomly selected in a 1:4 ratio as the control group. Univariate analysis and multivariate logistic regression were used to analyze the perinatal risk factors for the occurrence of apparently stillborn infants.@*RESULTS@#The gestational age and birth weight in the apparently stillborn group were significantly lower than those in the control group (P<0.05). The incidences of fetal hydrops, cord prolapse, grade III meconium-stained amniotic fluid, placental abruption, breech presentation, severe pre-eclampsia, maternal general anesthesia at delivery, abnormal antenatal fetal heart monitoring and decreased fetal movement were significantly higher in the apparently stillborn group than those in the control group (P<0.05). The multivariate logistic analysis showed that the mother had general anesthesia at delivery (OR=34.520), decreased antenatal fetal movement (OR=28.168),placental abruption (OR=15.641), grade III meconium-stained amniotic fluid (OR=6.365), abnormal antenatal fetal heart monitoring (OR=5.739), and breech presentation (OR=2.614) were risk factors for the occurrence of apparently stillborn infants (P<0.05), while higher gestational age was a protective factor (OR=0.686, P<0.05).@*CONCLUSIONS@#Attention needs to be paid to mothers with abnormal prenatal fetal heart monitoring, decreased fetal movement, preterm labor, placental abruption, breech presentation, grade III meconium-stained amniotic fluid, and general anesthesia. Preparations for resuscitation should be done to rescue apparently stillborn infants.

Research on the establishment of standard limits for perfluorooctanoic acid and perfluorooctane sulfonate in the "Standards for Drinking Water Quality（GB5749-2022）"in China / 中华预防医学杂志

Perfluorinated compounds, especially Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), are widely detected in water environments in China. Considering the potential health risks of drinking water exposure routes, PFOA and PFOS have been added to the water quality reference index of the newly issued "Standards for Drinking Water Quality (GB5749-2022)", with limit values of 40 and 80 ng/L, respectively. This study analyzed and discussed the relevant technical contents for determining the limits of the hygiene standard, including the environmental existence level and exposure status of PFOA and PFOS, health effects, derivation of safety reference values, and determination of hygiene standard limits. It also proposed prospects for the future direction of formulating drinking water standards.