BACKGROUND:Studies have shown that patients with premature ovarian failure have changes in the structure of intestinal flora and that imbalance of intestinal microbiota may be one of the important mechanisms in the development of premature ovarian failure. OBJECTIVE:To investigate the effect of Liuwei Dihuang Wan on oxidative stress and intestinal microbiota in premature ovarian failure mice induced by cyclophosphamide. METHODS:Forty-five female ICR mice were randomized into three groups:blank group(normal mice),model group(premature ovarian failure mice),and Liuwei Dihuang Wan group.A mouse model of premature ovarian failure was prepared by one-time intraperitoneal injection of cyclophosphamide(120 mg/kg)in the latter two groups.After successful modeling,the Liuwei Dihuang Wan group was intragastrically administered for 28 continuous days,and the other two groups were intragastrically administered with the same amount of normal saline for 28 days.Mouse body mass was recorded weekly and ovarian index was calculated.The development of mouse follicles was observed using hematoxylin-eosin staining.ELISA method was used to detect serum levels of anti-Mullerian hormone,estradiol,follicle stimulating hormone,superoxide dismutase,glutathione peroxidase,and malondialdehyde.Meanwhile,the gut microbiome of all mice was detected through 16S rDNA sequencing. RESULTS AND CONCLUSION:The mice in the model group had loose hair,decreased vigor and grip strength,almost no increase in body mass,and decreased ovarian index.Whereas,the mouse body mass and ovarian index were increased after treatment with Liuwei Dihuang Wan(P<0.05).The estrous cycle of mice in the model group was disorganized;Liuwei Dihuang Wan could restore the estrous cycle and reduce the number of atretic follicles in mice with premature ovarian failure.The serum levels of follicle stimulating hormone and malondialdehyde in the model group significantly increased(P<0.01),while the levels of estradiol,anti-Mullerian hormone,superoxide dismutase,and glutathione peroxidase significantly decreased(P<0.01).Liuwei Dihuang Wan could significantly decrease the serum levels of follicle stimulating hormone and malondialdehyde(P<0.01),and increase the levels of estradiol,anti-Mullerian hormone,superoxide dismutase,and glutathione peroxidase.According to the 16S rDNA sequencing results,Liuwei Dihuang Wan could regulate the abundance and diversity of intestinal microbiota,and increase the relative abundance of beneficial bacteria.KEGG pathway analysis showed that the intestinal microbiota and metabolic pathways,biosynthesis of secondary metabolites,microbial metabolism in different environments,and biosynthesis of amino acids were regulated by Liuwei Dihuang Wan.To conclude,the changes in the structure of intestinal microbiome may be one of the potential mechanisms of Liuwei Dihuang Wan in treating premature ovarian failure.Liuwei Dihuang Wan can regulate the structure of intestinal microbiome,increase the number of beneficial bacteria,reduce the number of harmful bacteria,and thus improve the balance of intestinal microbiota.This regulatory effect helps to reduce oxidative stress levels and further inhibit ovarian oxidative stress in mice with premature ovarian failure.

Objective To explore the comparative application of phase and diaphragmatic navigation in three-dimensional magnetic resonance cholangiopancreatography(3D-MRCP)thin-layer scanning in elderly patients.Methods A total of 180 elderly patients were scanned by phase and diaphragmatic navigation via Siemens Aera1.5T superconducting MR scanner.The acquired images were reconstructed by 3D reconstruction.The anatomical structure,image quality and disease diagnosis were compared between the phase and diaphragmatic navigation groups.Results In liver of anatomy,the liver of primary bile duct,the superior,middle and inferior extrahepatic bile duct and the gallbladder could be well displayed,and the difference was not statistically significant between the two groups(P＞0.05).The display of pancreatic duct and the liver of secondary bile duct of diaphragmatic navigation was significantly better than those of phase navigation(P＜0.05).In terms of image quality,the excellent rate of diaphragmatic navigation was significantly higher than that of phase navigation,and the difference was statistically significant(P＜0.05).There were no statistically significant differences in the detection rate of pancreatobiliary system diseases,the diagnostic rate of cholelithiasis,common bile duct stones,common bile duct dilatation and pancreatic duct dilatation between the two groups(P＞0.05).Conclusion Diaphragmatic navigation is signifi-cantly better than phase navigation in the display of the anatomical structure of the pancreatic duct,the liver of secondary bile duct,and the excellent rate of image quality.Diaphragmatic navigation is more suitable for thin-layer 3D-MRCP scanning in elderly patients.

BACKGROUND:Most of the formulas for the clinical treatment of premature ovarian insufficiency have evolved from the basic formula of Liuwei Dihuang Pills,and have achieved good therapeutic efficacy.Currently,most of the experimental studies on Liuwei Dihuang Pills focus on morphological observations and physiological and biochemical detection of in vivo animal models,while fewer studies on molecular mechanisms have been reported. OBJECTIVE:To explore the molecular mechanism of Liuwei Dihuang Pills in the treatment of premature ovarian insufficiency based on the receptor gamma coactivator-1 alpha/mitochondrial transcription factor A/reactive oxygen species pathway. METHODS:Premature ovarian insufficiency model was established in mice by intraperitoneal injection of cyclophosphamide 120 mg/kg combined with busulfan 12 mg/kg,and then Liuwei Dihuang Pill suspension was used to intervene in premature ovarian insufficiency mice.After 12 weeks of intervention,the levels of follicle-stimulating hormone,luteinizing hormone,estradiol,anti-Mullerian hormone,8-hydroxydeoxyguanosine,total antioxidant capacity and reactive oxygen species in serum of mice were detected by ELISA method.The morphological changes in mouse ovaries were observed by hematoxylin-eosin staining.The ultrastructure of mouse follicular granulosa cells and the apoptosis of granulosa cell mitochondria were observed by transmission electron microscopy.The expression levels of receptor gamma coactivator-1 alpha and mitochondrial transcription factor A in mouse ovarian granulosa cells were detected by immunohistochemistry. RESULTS AND CONCLUSION:Compared with the model group,serum levels of follicle-stimulating hormone,luteinizing hormone,reactive oxygen species,and 8-hydroxydeoxyguanosine were decreased in the experimental group(P＜0.05),and the levels of estradiol,anti-Mullerian hormone,and total antioxidant capacity were increased(P＜0.05).Hematoxylin-eosin staining showed that in the model group,there were more atretic follicles and corpus luteum forms,some secondary follicles,and interstitial fibrosis and hyperplasia;in the experimental group,a large number of atretic follicles,few corpus luteum forms,primordial follicles were observed at the edges but there were few secondary follicles and no mature follicles.Transmission electron microscopy showed that the organelles in ovarian granulosa cells of mice in the experimental groups were relatively intact.Immunohistochemical results showed that compared with the model group,the expression level of receptor gamma coactivator-1 alpha in the ovarian tissue of mice increased slightly in the experimental group at the 4th week,and there was no significant change at the 8th and 12th weeks.The expression level of mitochondrial transcription factor A in the ovarian tissues of mice in the experimental group was transiently increased at the 4th week,and then slightly decreased,which were all significantly different from those of the model group.To conclude,Liuwei Dihuang Pills inhibit ovarian granulosa cell apoptosis in mice with premature ovarian insufficiency to a certain extent through the receptor gamma coactivator-1 alpha/mitochondrial transcription factor A/reactive oxygen species signaling pathway,thereby improving the endocrine function of the ovary,enhancing the antioxidant capacity,and attenuating the degree of oxidative stress damage.

The neurovascular unit (NVU) is highly responsible for cerebral homeostasis and its dysfunction emerges as a critical contributor to Alzheimer's disease (AD) pathology. Hence, rescuing NVU dysfunction might be a viable approach to AD treatments. Here, we fabricated a self-regulated muti-functional nano-modulator (siR/PIO@RP) that can intelligently navigate to damaged blood-brain barrier and release therapeutical cargoes for synergetic AD therapy. The resulting siR/PIO@RP enables self-regulation of its distribution in accordance with the physio/pathological state (low/high RAGE expression) of the target site via a feedback loop. siR/PIO@RP is capable of performing intricate tasks and goes beyond the capabilities of single-target therapeutic agents utilized in AD therapy, such as reducing cerebral Aβ load, relieving neuroinflammation, and alleviating the dysfunction of NVU. Overall, the current study provides proof of concept that normalizing NVU holds promise as a means of alleviating AD symptoms.

Objective:To explore the risk factors for postoperative delirium in colorectal cancer patients based on Meta-analysis.Methods:A computer search was conducted on PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang, VIP and China Biology Medicine disc, and literatures on influencing factors of postoperative delirium of colorectal cancer published by each database until April 6, 2022 were selected. Two researchers independently screened the literature, extracted the data, and evaluated the quality of the literature using Newcastle-Ottawa Scale (NOS) . Stata 15.0 statistical software was used to conduct a Meta-analysis of the included literatures.Results:A total of 19 articles were included, including 5 295 patients. The Meta-analysis results showed that the combined odds ratio ( OR) values and 95% confidence interval (95% CI) of various factors for postoperative delirium in colorectal cancer patients were advanced age [1.10 (1.06-1.14) ] , male [2.29 (1.81-4.44) ] , alcohol abuse [3.14 (1.63-6.06) ] , preoperative physical condition grading (≥level 3) [1.47 (1.13-1.91) ] , comorbidities [1.59 (1.16-2.17) ] , history of mental illness [7.86 (4.57-13.54) ] , history of cerebrovascular disease [5.74 (3.78-8.72) ] , cognitive impairment [3.31 (1.20-9.08) ] , albumin [0.81 (0.66-0.99) ] , perioperative blood transfusion [2.29 (1.41-3.69) ] and C-reactive protein [2.24 (1.11-4.53) ] , all P<0.05. Conclusions:The risk factors for delirium in colorectal cancer patients after operation are old age, male, alcoholism, preoperative physical condition grading≥level 3, combined diabetes and other basic diseases, history of mental disease, history of cerebrovascular disease, cognitive dysfunction, low albumin, perioperative blood transfusion and elevated C-reactive protein.

Macrophages, as important immune cells, are involved in the key processes that maintain the homeostasis of intrahepatic microenvironment. Recent studies have shown that different liver diseases can induce macrophage polarization (MPP) and form M1 and M2 phenotypes with mutual antagonism. The former promotes the clearance of pathogens and inhibits tumor progression, while the latter exerts an anti-inflammatory effect and promotes tissue repair. However, there are significant differences in the mechanism of action and phenotypic switching of MPP in different liver diseases or at different pathological stages of the disease. This article focuses on the origin and polarization characteristics of intrahepatic macrophages and summarizes the research advances in the role of MPP in the pathogenesis and therapeutic drugs of non-neoplastic liver diseases such as viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, and liver fibrosis, in order to explore the potential of MPP in regulating the immune response and inflammatory response of liver diseases.

Antibody-drug conjugates(ADCs)are commonly heterogeneous and require extensive assessment of exposure-efficacy and exposure-safety relationships in preclinical and clinical studies.In this study,we report the generation of a monoclonal antibody against monomethyl auristatin E(MMAE)and the development,validation,and application of sensitive and high-throughput enzyme-linked immunosor-bent assays(ELISA)to measure the concentrations of MMAE-conjugated ADCs and total antibodies(tAb,antibodies in ADC plus unconjugated antibodies)in cynomolgus monkey sera.These assays were suc-cessfully applied to in vitro plasma stability and pharmacokinetic(PK)studies of SMADC001,an MMAE-conjugated ADC against trophoblast cell surface antigen 2(TROP-2).The plasma stability of SMADC001 was better than that of similar ADCs coupled with PEG4-Val-Cit,Lys(m-dPEG24)-Cit,and Val-Cit linkers.The developed ELISA methods for the calibration standards of ADC and tAb revealed a correlation be-tween serum concentrations and the OD450 values,with R2 at 1.000,and the dynamic range was 0.3-35.0 ng/mL and 0.2-22.0 ng/mL,respectively;the intra-and inter-assay accuracy bias％ranged from-12.2％to-5.2％,precision ranged from-12.4％to-1.4％,and the relative standard deviation(RSD)was less than 6.6％and 8.7％,respectively.The total error was less than 20.4％.The development and validation steps of these two assays met the acceptance criteria for all addressed validation parameters,which suggested that these can be applied to quantify MMAE-conjugated ADCs,as well as in PK studies.Furthermore,these assays can be easily adopted for development of other similar immunoassays.

ObjectiveTo analyze the management and treatment for patients with severe mental disorders in Chengdu from 2016 to 2020， in order to provide references for the relevant authorities to formulate policies and improving the mental health service system. MethodsData relating to 22 districts （cities） and counties in Chengdu from January 1， 2016 to December 31， 2020 were extracted from the National Information System for Severe Mental Disorders. Indicators such as reported prevalence rate， management rate， standardized management rate， medication rate， regular medication rate and stable condition rate of patients with severe mental disorders were analyzed on a yearly basis. ResultsBy the end of 2020， there were 71 899 registered cases of severe mental disorders in Chengdu， with a reported prevalence rate of 0.34%， a standardized management rate of 95.53%， and a regular medication rate of 72.50%. From 2016 to 2020， except the reported prevalence rate （χ²=269.566， P<0.01）， management rate （χ²=384.030， P<0.01）， standardized management rate （χ²=309.742， P<0.01）， medication rate （χ²=414.252， P<0.01）， regular medication rate （χ²=316.172， P<0.01） and stable condition rate （χ²=288.335， P<0.01） had linear trends of increasing with the annual increase. ConclusionFrom 2016 to 2020， the management rate， treatment rate and regular medication rate of patients with severe mental disorders have been increased year by year in Chengdu. Nevertheless， the increase in reported prevalence rate should be accompanied by strengthened management and follow-up to increase the regular medication rate to maintain the stability of patients' conditions.

Objective:To describe the status and influencing factors of nurse-related empowerment perception in inpatients with chronic diseases.Methods:Totally 586 inpatients with chronic diseases from 6 class A hospitals in Shanghai from November 2019 to September 2020 were investigated by the Chinese version of Patient Perception of Patient-empowering Nurses Behaviors (PPPNBS), Self-Efficacy of Chronic Diseases (SECD6), Nurse-patient Trust Scale (NPTS), Chinese version of Chronic Illness Resource Survey (CV-CIRS) and a general information questionnaire which was designed by researchers.Results:The total score of PPPNBS was (134.98 ± 59.60) points, and the average score for each item was (6.14 ± 2.71) points. The total score of SECD6 was (38.81 ± 9.28) points. The total score of NPTS was (141.94 ± 11.42) points, and the total score of CV-CIRS was (57.90 ± 15.24) points, which were positively correlated with empowerment perception through Pearson correlation analysis. Multiple Linear Regression showed that the degree of education, the number of forms and compliance of health education, the times of admission, participation intention in medical decision-making, the dimension of Symptom Management in Self-efficacy, three dimensions of consistency, respect, and confidence in knowledge and technology in Nurse-Patient Trust degree and four dimensions of medical staff support, organization support, family and friends support, media and government support in Chronic Illness Resource were influencing factors of patients ′ empowerment perception (adjusted R 2 value was 0.636, F value was 79.441, P<0.01). Conclusions:Compared with the foreign level, the perception of nurses ′ empowerment of inpatients with chronic diseases is at a lower level, and self-efficacy, nurse-patient trust and chronic disease resource support are all at a medium level, which still need to be improved. Nurses should allow them to participate in their treatment, improve the control of life and reduce their anxiety.