Effect of Direct-acting Antivirals Treatment on Renal Function Among HCV-infected Patients / 中山大学学报(医学科学版)

； ObjectiveTo explore the effect of direct-acting antiviral treatment on renal function in patients with chronic hepatitis C. MethodsA total of 123 HCV-infected patients receiving DAAs treatment at the Third Affiliated Hospital of Sun Yat-sen University from January 2017 to December 2021 were included in this study. To explore the renal function in patients with chronic hepatitis C treated with direct-acting antivirals， serum creatinine values were collected before， during and after the treatment， which were used to estimate the eGFR by the MDRD equation to assess the changes in renal function. ResultsOf the 123 patients enrolled， 67.5%（n=83）were male， and the mean age of participants was （50±11） years old. The mean follow-up period was 24 weeks . Comorbidities included cirrhosis in 26.8%， and diabetes in 10.6%. Meanwhile， 11.4% of the cohort had eGFR < 60 mL/（min ·1.73 m2）， 33.3% of the cohort had eGFR 60 to 90 mL/（min ·1.73 m2）， and 55.3% had eGFR≥90 mL/（min ·1.73 m2）. No decrease in renal function was seen among all the HCV-infected patients at the end of treatment or the follow-up period after treatment. However， compared with the eGFR at the baseline， eGFR in CKD2 patients in the follow-up period was improved 【（88.65±15.52） mL/（min ·1.73 m2）vs （78.12 ±7.60） mL/（min ·1.73 m2）， P< 0.001】. And 14.6% （n=18） of patients experienced progressive deterioration of renal function. Logistic regression analysis showed that diabetes could predict the deterioration of renal function （OR=4.663， P=0.016）. ConclusionsOur study shows renal function is not impair among HCV-infected patients following DAAs treatment， and renal function in CKD2 patients have improvements. However， HCV-infected patients with diabetes mellitus are at a high risk of renal impairment and closely monitoring of renal function is still needed.

Mechanism of Yiqi Jiedu Formula Against Ischemic Stroke Based on Microbial-gut-brain Axis / 中国实验方剂学杂志

ObjectiveTo explore the possible mechanism of the Yiqi Jiedu formula （YQ） in treating ischemic stroke （IS） from the perspective of the microbial-gut-brain axis （MGBA）. MethodRats were randomly divided into five groups， with six in each group， including sham surgery group， model group， and low， medium， and high dose YQ groups （1， 5， and 25 mg·kg-1）. Except for the sham surgery group， all other groups were established with a middle cerebral artery occlusion （MCAO） model using the thread occlusion method. The success of modeling was determined through neurobehavioral scoring， and the protective effect of YQ on IS was evaluated. Then， the changes in gut microbiota before and after MCAO modeling and YQ administration were compared using 16S rDNA sequencing technology， and the possible biological pathways related to the effect of this formula were analyzed. The expression of inflammatory factors such as interleukin-6 （IL-6）， interleukin-17A （IL-17A）， and interleukin-10 （IL-10） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the expression of tight junction proteins ZO-1 and Occludin in brain and intestinal tissue， and hematoxylin-eosin staining （HE） was used to observe pathological changes in the cerebral cortex and colon， so as to validate the possible mechanism of action. ResultYQ significantly improved the neurobehavioral score of MCAO rats （P<0.01） and played a good regulatory role in intestinal microbial disorders caused by enriched pathogens and opportunistic pathogens during the acute phase. Among them， significantly changed microorganisms include Morgentia， Escherichia Shigella， Adlercreutzia， and Androbacter. Bioinformatics analysis found that these bacteria may be related to the regulation of inflammation in the brain. Compared with the blank group， the detection of inflammatory factors in the serum of IS model rats showed an increase in inflammatory factors IL-6 and IL-17A （P<0.01） and a decrease in the content of anti-inflammatory factor IL-10 （P<0.01）. Compared with the model group， the content of inflammatory factors IL-6 and IL-17A in the serum of the treatment group decreased （P<0.05）， and that of anti-inflammatory factor IL-10 increased （P<0.01）. The expression results of barrier proteins ZO-1 and Occludin in brain and intestinal tissue showed that the expression levels of both decreased in IS model rats （P<0.05）， while the expression levels of both increased in the treatment group （P<0.05）. ConclusionAcute cerebral ischemia can lead to an imbalance of intestinal microbiota and damage to the intestinal barrier， and it can increase intestinal permeability. YQ can regulate intestinal microbiota imbalance caused by ischemia， inhibit systemic inflammatory response， and improve the disruption of the gut-blood brain barrier， preventing secondary cascade damage to brain tissue caused by inflammation. The MGBA may be an important mechanism against the IS.

Recent advances in small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase / 药学学报

Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.

Establishment and validation of bioactivity measurement method for recombinant human midkine / 药学学报

To establish and optimize a method for the detection of recombinant human midkine (rhMK) activity and verify its methodology, cell counting kit-8 (cck-8) method was used to measure the proliferation activity of rat knee chondrocytes. The specificity, accuracy, precision, linearity and robustness of the method were also verified in this study. The established method was proven to have good specificity because the buffer of rhMK and recombinant human interleukin-1 receptor antagonist have no obvious active effect; the recoveries of the samples with relative activities of 50%, 75%, 100%, 125%, 150% were in the range of 80.0% to 124.0% by statistical analysis, the relative standard deviations (RSD) of relative potency were all within 20%, the linear correlation coefficient, R2 ≥ 0.98, suggesting that the accuracy, precision and linearity of the method were good; the robustness correlation coefficient, R2 ≥ 0.92 and the ratio of maximum to minimum of sigmoidal dose-response were no less than 1.5, indicating that robustness of the methods was good. In conclusion, a bioactivity measurement method for rhMK was established and fully validated in this study and it provides a reliable method for the bioactivity analysis of rhMK routine samples during the development. This study was approved by the Animal Care and Use Committee of Shanghai Model Organisms Center, Inc. (approval number: 2019-0008-06).

Identification, expression and protein interaction analysis of Aux/IAA and ARF gene family in Senna tora L / 药学学报

The early response of plant auxin gene family Aux/IAA (auxin/indole-3-acetic acid) and its interaction with auxin response factor (ARF) are important pattern to regulate plant growth and development. This work identified 28 StoIAA and 24 StoARF members based on the whole genome data of the medicinal plant Senna tora L., which were classified into 10 and 8 subfamilies, respectively. Phylogenetic tree and collinearity analysis showed that S. tora has close evolutionary relationship with the IAA and ARF homologous genes of Glycine max, Medicago truncatula, and the segment duplication events dominate the expansion of StoIAA and StoARF. Gene structure analysis showed that the vast majority of StoIAA and StoARF contain characteristic conserved domain. Transcriptome data showed that StoIAAs and StoARFs were expressed in leaves, roots and seeds, some members had tissue specific expression. The StoIAA and StoARF promoter region most contain functional elements related to stress response, growth and development, hormone induction and secondary metabolism. In addition, gene expression analysis showed that many StoIAAs and StoARFs can quickly respond to drought and salt stress and exhibited same expression patterns under both stress condition. The yeast two-hybrid experiment confirmed that StoARF8 and StoARF10 exhibit varying degrees of interaction with multiple StoIAA proteins, respectively. The above results provide a basis for further biological functional analysis of the Aux/IAA and ARF gene family of S. tora.

Factors influencing the development of executive function in adolescents / 中国学校卫生

Abstract@#Executive function is an advanced cognitive process aimed at the flexible coordination, optimization, and control of the cognitive processes of task solving in order to accomplish a specific task, ensuring that the individual produces effective behaviors, including inhibitory control, working memory, and cognitive flexibility. Given the sensitivities and specificities that characterize an individual s physical and mental development during adolescence, this period is critical for the development of executive function in adolescents. In the paper, the influencing factors of adolescents executive function development are systematically described from three dimensions, namely, biology, environment and lifestyle; by analyzing the mechanisms and differences in the effects of different influencing factors, this editorial provides a scientific basis for adolescents executive function improvement and intervention.

A new strategy for evaluating antitumor activity in vitro with time-dimensional characteristics of RTCA technology / 中国药理学通报

Aim To analyze the anti-A549 and HI299 lung ade-nocarcinoma activities via using examples of baicalin, astragalo-side, hesperidin and cisplatin based on real time cellular analysis (RTCA) technology, and to build a new strategy for EC50 e-valuation reflecting the time-dimensional characteristic. Methods Using RTCA Software Pro for data analysis and GraphPad Prism and Origin Pro plotting, the in vitro anti-A549 and H1299 lung adenocarcinoma activities of baicalin, astragaloside, hesperidin, and cisplatin were characterized using the endpoint method and time dimension, respectively. Results (X) There were significant differences in EC50 values of A549 and H1299 cells at 24 h and 48 h endpoint methods. (2) The correlation coefficient of the curve fitted with the four-parameter equation was > 0. 9, and the dynamic change of EC50 remained relatively stable (the linear fitting of EC50 at adjacent 4 points I slope 1

A case-crossover study on association between short-term atmospheric NO2 exposure and outpatient visits due to pediatric neurological system conditions in Shijiazhuang / 环境与职业医学

Background Nitrogen dioxide (NO2), a crucial component of traffic pollutants, has been shown in studies to exert toxic effects on the nervous system. However, there is a limited body of research examining the relationship between NO2 exposure and neurological disorders in children. Objective To explore the impact of short-term NO2 exposure on the outpatient visits due to pediatric neurological diseases in Shijiazhuang. Methods From 2013 to 2021, we collected outpatient data related to neurological diseases at the Children's Hospital in Shijiazhuang, Hebei Province. We also collected air pollution data and meteorological data of the same city. The air pollution data included daily average concentrations of inhalable particles (PM10), fine particulate matter (PM2.5), sulfur dioxide (SO2), NO2, carbon monoxide (CO), and daily maximum 8-hour average concentration of ozone (O3). The meteorological data comprised daily average atmospheric pressure, temperature, relative humidity, wind speed, and sunshine duration. Employing a time-stratified case-crossover design, we used conditional logistic regression models to analyze the association between NO2 and pediatric outpatient visits for neurological diseases. Stratification analyses were conducted based on gender (male, female) and age groups (0-6 years, 7-14 years). Results The study included a total of 154348 valid pediatric outpatient visits for neurological diseases. The daily average concentration of NO2 was 49.3 μg·m−3 for the study period. The results from the single-pollutant model indicated that NO2 increased the risk of pediatric neurological outpatient visits, with the highest association observed at lag0. Specifically, for every 10 μg·m⁻³ increase in atmospheric NO2 exposure, there was a 1.40% increase (95%CI: 1.05%, 1.74%) in pediatric neurological outpatient visits. The stratification analyses revealed that increased atmospheric NO2 exposure was associated with an elevated risk of neurological outpatient visits for girls (ER=1.54, 95%CI: 1.01, 2.08) and children aged 7-14 years (ER=2.35, 95%CI: 1.68, 3.02). Even after introducing PM2.5 (ER=1.96, 95%CI: 1.49, 2.43), SO2 (ER=2.09, 95%CI: 1.62, 2.55), and O3 (ER=1.40, 95%CI: 1.06, 1.74) to the models, the impact of NO2 exposure on pediatric neurological outpatient visits remained statistically significant. The results of the multi-pollutant model also indicated a significant association (ER=2.53, 95%CI: 1.97, 3.08). Conclusion The effect of short-term exposure to atmospheric NO2 on the outpatient visits of children with neurological diseases in Shijiazhuang is acute and independent, especially for children aged 7-14.

Development of enzyme immobilization systems for CO2 bioconversion: advances and challenges / 生物工程学报

Enzyme-catalyzed CO2 reduction to value-added commodities is important for alleviating the global environmental issues and energy crises due to high selectivity and mild conditions. Owing to high energy density, formic acid or methanol produced from CO2 using formate dehydrogenase (FDH) or multi-enzyme cascades are promising target chemicals for CO2 utilization. However, the low activity, poor stability and low reusability of key enzymes involved in such process hampered its large-scale application. Enzyme immobilization provides an effective solution to these problems and significant progress have been made in immobilization carriers. Moreover, integration of enzyme immobilization with other catalysis techniques have been explored extensively. This review summarized the recent advances in the immobilization of enzymes using membranes, inorganic materials, metal-organic frameworks, covalent organic frameworks and other carriers, and illustrated the characteristics and advantages of different immobilization materials and immobilization methods. The synergistic effects and applications of immobilized enzymes and electrocatalytic or photocatalytic coupling reaction systems for CO2 reduction were further summarized. Finally, the current challenges of enzyme immobilization technology and coupling reaction systems were pointed out and their development prospects were presented.

Research progress of celastrol on the prevention and treatment of metabolic associated fatty liver disease / 生理学报

Metabolic associated fatty liver disease (MAFLD) is a liver disease with hepatocyte steatosis caused by metabolic disorders, which is closely related to obesity, diabetes, metabolic dysfunction, and other factors. Its pathological process changes from simple steatosis, liver inflammation to non-alcoholic steatohepatitis (NASH), and then leads to liver fibrosis, cirrhosis, and liver cancer. At present, no specific therapeutics are available for treatment of MAFLD targeting its etiology. Celastrol is the main active component of the traditional Chinese medicine Celastrus orbiculatus Thunb. In recent years, it has been found that celastrol shows important medicinal value in regulating lipid metabolism, reducing fat and weight, and protecting liver, and then ameliorates MAFLD. This article reviews the related research progress of celastrol in the prevention and treatment of MAFLD, so as to provide a reference for the comprehensive development and utilization of celastrol.

Residual coronary artery tree description and lesion EvaluaTion (CatLet) score, clinical variables, and their associations with outcome predictions in patients with acute myocardial infarction / 中华医学杂志(英文版)

BACKGROUND@#We have recently developed a new Coronary Artery Tree description and Lesion EvaluaTion (CatLet) angiographic scoring system. Our preliminary studies have demonstrated its superiority over the the Synergy between percutaneous coronary intervention (PCI) with Taxus and Cardiac Surgery (SYNTAX) score with respect to outcome predictions for acute myocardial infarction (AMI) patients. The current study hypothesized that the residual CatLet (rCatLet) score predicts clinical outcomes for AMI patients and that a combination with the three clinical variables (CVs)-age, creatinine, and ejection fraction, will enhance its predicting values.@*METHODS@#The rCatLet score was calculated retrospectively in 308 consecutively enrolled patients with AMI. Primary endpoint, major adverse cardiac or cerebrovascular events (MACCE) including all-cause mortality, non-fatal AMI, transient ischemic attack/stroke, and ischemia-driven repeat revascularization, was stratified according to rCatLet score tertiles: rCatLet_low ≤3, rCatLet_mid 4-11, and rCatLet_top ≥12, respectively. Cross-validation confirmed a reasonably good agreement between the observed and predicted risks.@*RESULTS@#Of 308 patients analyzed, the rates of MACCE, all-cause death, and cardiac death were 20.8%, 18.2%, and 15.3%, respectively. Kaplan-Meier curves for all endpoints showed increasing outcome events with the increasing tertiles of the rCatLet score, with P values <0.001 on trend test. For MACCE, all-cause death, and cardiac death, the area under the curves (AUCs) of the rCatLet score were 0.70 (95% confidence intervals [CI]: 0.63-0.78), 0.69 (95% CI: 0.61-0.77), and 0.71 (95% CI: 0.63-0.79), respectively; the AUCs of the CVs-adjusted rCatLet score models were 0.83 (95% CI: 0.78-0.89), 0.87 (95% CI: 0.82-0.92), and 0.89 (95% CI: 0.84-0.94), respectively. The performance of CVs-adjusted rCatLet score was significantly better than the stand-alone rCatLet score in terms of outcome predictions.@*CONCLUSION@#The rCatLet score has a predicting value for clinical outcomes for AMI patients and the incorporation of the three CVs into the rCatLet score will enhance its predicting ability.@*TRIAL REGISTRATION@#http://www.chictr.org.cn , ChiCTR-POC-17013536.

The expression of GSTM5 in prostate cancer and its potential mechanism for the progress of prostate cancer / 西安交通大学学报(医学版)

【Objective】 To explore the differentially expressed genes in normal prostate and prostate cancer (PCa) tissues based on bioinformatics and screen out potential biomarkers for PCa, so as to provide scientific basis for later clinical medicine. 【Methods】 Three gene chip datasets of GSE55945, GSE46602 and GSE69223 were downloaded from GEO database, and differentially expressed genes (DEGs) were screened by the OmicStudio tools, and protein-protein interaction network (PPI) of DEGs was constructed by STRING. After Cytoscape was imported, CytoHubba plug-in was used to screen the top 30 genes in MCC score as key genes (Hub gene). DAVID was used for GO and KEGG enrichment analysis of Hub gene, and GraphPad Prism software was used to draw ROC curve. GEPIA database was used to verify the key genes, and survival analysis was further carried out. UALCAN was used to verify the correlation between the expression of key genes and Gleason grade of PCa. 【Results】 Three data sets (GSE55945, GSE46602 and GSE69223) obtained 428, 727 and 1285 differentially expressed genes, respectively. The Venn diagram shows that the three datasets contain 105 DEGs. Among 105 PPI networks corresponding to DEGs, the top 30 genes with MCC score were selected as Hub genes. The biological processes involved mainly include the positive regulation of protein kinase B signal, cell differentiation, positive regulation of transcription, negative regulation of transforming growth factor β receptor signaling pathway, positive regulation of cell migration, etc. The pathways involved are adhesion plaque, estrogen signaling pathway, etc. ROC curve results showed that the diagnostic ability of 9 genes in 3 data sets was statistically significant, and 9 Hub genes were CAV1, KDR, CAV2, TGFBR1, SLC7A11, GSTM2, GSTM3, GSTM5 and MYO6. Nine Hub genes were verified by GEPIA website, among which CAV1, KDR, CAV2, TGFBR1, GSTM2, GSTM3 and GSTM5 showed low expression in PCa, while SLC7A11 and MYO6 showed high expression in PCa. Survival analysis suggested that high GSTM5 expression prolonged OS in PCa patients. UALCAN results showed that the expression of GSTM5 gene was significantly correlated with Gleason grade, and the expression of GSTM5 gene decreased with the increase of Gleason score. 【Conclusion】 Hub genes CAV1, KDR, CAV2, TGFBR1, GSTM2, GSTM3 and GSTM5 are low expression in PCa, while SLC7A11 and MYO6 are high expression in PCa. GSTM5 gene is related to the survival rate of PCa. The expression of GSTM5 decreased with the increase of Gleason score, which indicated that GSTM5 may be a potential biomarker for PCa.

Analysis and enlightenment of the current situation of medical psychology undergraduate education in China and foreign countries / 西安交通大学学报(医学版)

With the economic development of China and transformation of medical model, people pay more attention to their spiritual world and psychological health, and medical psychology has become a major in urgent need of construction. Foreign medical/clinical psychology education was established earlier and has become relatively mature, thus making its experience valuable for reference. This paper compares and analyzes the current situation of undergraduate medical psychology education, and puts forward optimization strategies from the aspects of college planning, curriculum training scheme and teachers’ teaching philosophy, hoping to provide some ideas for the construction of undergraduate medical psychology education in China.

HBsAg non-reactive but HBV DNA reactive blood donors in Wuhu area: infection status and tracing results / 中国输血杂志

【Objective】 To detect and analyze the infection status of HBsAg non-reactive /HBV DNA reactive blood donors by individual donor-NAT (ID-NAT) and chemiluminescence technology, and to explore the feasibility and potential risks of reentry. 【Methods】 The blood screening results of blood donors in Wuhu from January 2018 to October 2021 were queried by blood station information management software. The blood donation information of all HBsAg non-reactive /HBV DNA reactive blood donors was collected and then recalled by telephone. After informed consent, samples were taken for HBV DNA nucleic acid single test, enzyme-linked immunoassay for HBsAg, chemiluminescence assay for HBV seromarkers(including HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc), and alanine aminotransferase (ALT) test. All the results were statistically analyzed. 【Results】 From January 2018 to October 2021, there were 142 051 donations, and the positive rate of sole HBV DNA was 0.06% (91/142 051), and 33 people (37 person-times) were successfully followed up. The yield rates of HBsAg, anti-HBs and anti-HBc were 6.06% (2/33), 39.39% (13/33) and 96.97% (32/33), respectively; None HBeAg was yielded. After two times of ID-NAT, 8 patients remained non-reactive to both systems, with a negative conversion rate of 24.24% (8/33). Meanwhile, 25 patients were at least once reactive to ID-NAT, and 23 of them were occult HBV infection with serologically reactivity. There were 2(6.25%) patients with HBsAg positive conversion and HBV DNA persistent reactivity, which were window period infection. One person was confirmed as false reactivity (no HBV infection) as he remained unreactive to both repeated ID-NAT and serological tests. 【Conclusion】 Chemiluminescence assay is more sensitive than ELISA in detecting HBV serum markers, which is beneficial to early detection of HBV samples in window period. The yielding rate of anti-HBc among HBsAg non-reactive/HBV DNA reactive blood donors detected by blood screening in this region is very high, and most of them are occulting infection, so the ID-NAT should be no less than 2 times in the reentry strategy.

Schisandrin B Improves the Hypothermic Preservation of Celsior Solution in Human Umbilical Cord Mesenchymal Stem Cells

BACKGROUND@#Human umbilical cord mesenchymal stem cells (hUCMSCs) have emerged as promising therapy for immune and inflammatory diseases. However, how to maintain the activity and unique properties during cold storage and transportation is one of the key factors affecting the therapeutic efficiency of hUCMSCs. Schisandrin B (SchB) has many functions in cell protection as a natural medicine. In this study, we investigated the protective effects of SchB on the hypothermic preservation of hUCMSCs. @*METHODS@#hUCMSCs were isolated from Wharton’s jelly. Subsequently, hUCMSCs were exposed to cold storage (4 °C) and 24-h re-warming. After that, cells viability, surface markers, immunomodulatory effects, reactive oxygen species (ROS), mitochondrial integrity, apoptosis-related and antioxidant proteins expression level were evaluated. @*RESULTS@#SchB significantly alleviated the cells injury and maintained unique properties such as differentiation potential, level of surface markers and immunomodulatory effects of hUCMSCs. The protective effects of SchB on hUCMSCs after hypothermic storage seemed associated with its inhibition of apoptosis and the anti-oxidative stress effect mediated by nuclear factor erythroid 2–related factor 2 signaling. @*CONCLUSION@#These results demonstrate SchB could be used as an agent for hypothermic preservation of hUCMSCs.

Six-week Aerobic Exercise Improves Oxidative Damage of Skeletal Muscles and Promotes Myokine Production in Atherosclerotic Mice / 中国生物化学与分子生物学报

Atherosclerosis involving peripheral arteries can cause skeletal muscle lesions, in which oxidative damage is an important manifestation, and atherosclerosis also reduces the production and secretion of beneficial myokines. Irisin, musclin and β-aminoisobutyric acid (BAIBA) are thought to be involved in improving atherosclerosis. However, the molecular mechanism of atherosclerosis-induced skeletal muscle lesions and the effects of aerobic exercise training on the oxidative damage of skeletal muscle and myokine production remain unclear. In this study, apolipoprotein E knockout (ApoE

Effect of a novel phosphodiesterase type 5 inhibitor, CPD1, on carbon tetrachloride-induced liver fibrosis in mice / 中国药理学通报

Aim To investigate the effects of CPD1, a novel phosphodiesterase 5 inhibitor, on liver pathological phenotype and hepatic stellate cells (HSCs) activation in hepatic fibrosis model mice caused by carbon tetrachloride ( CCl

Effect of chemogenetic manipulation of PVN corticotropin-releasing factor-expressing neurons on excitability of presympathetic neurons in SHR / 中国药理学通报

Aim To observe the effect of corticotropin-releasing factor ( CRF) -expressing neurons on presympathetic neurons in hypothalamic paraventricular nucleus ( PVN) of normotensive Wistar Kyoto ( WKY) rats or spontaneously hypertensive rats (SHR) , and to elucidate the underlying neuronal circuit mechanism of central sympathetic hyperexcitability. Methods The expression levels of CRF protein in WKY rats and SHR PVN were determined by Western blot. Meanwhile, the WKY and SHR PVN CRF-expressing neurons and presympathetic neurons were observed by immunofluo-rescent staining. Adult WKY rats and SHR were used in this study. By microinjection of Cre-dependent ade-no-associated viruses ( AAV) that specifically recognized the CRF promoter and AAV of chemogenetics into the PVN, CRF-expressing neurons expressed designer receptors exclusively activated by designer drugs (DREADDs). Human M3 muscarinic DREADD coupled to Gq receptor ( hM3 Dq) was specifically expressed in PVN CRF-expressing neurons in WKY rats, while human M4 muscarinic DREADD coupled to Gi receptor ( hM4Di) was specifically expressed in PVN CRF-expressing neurons in SHR. Clozapine-N-oxide (CNO) , as a designer ligand, would couple to excitatory hM3Dq or inhibitory hM4Di to regulate the excitability of PVN CRF-expressing neurons. Then the PVN presympathetic neurons were retrogradely labeled by microinjection of fluosecent tracer into the intermedio-lateral column (IML) of spinal cord. Lastly, whole cell patch clamp was used to determine the effect of CNO (10 jjumol L~ ) on spontaneous excitatory postsynaptic currents ( sEPSCs) and current-evoked firing of PVN presympathtic neurons of WKY rats and SHR. Results The expression of CRF protein in the PVN of SHR was significantly higher than that of WKY rats, and the activity and number of CRF-expressing neurons in the PVN of SHR were increased. PVN CRF-expressing neurons were expressed with chemogenetic DREADDs and PVN presympathetic neurons were retrogradely labeled with fluorescent tracer in WKY rats and SHR. In SHR expressed with chemogenetic inhibitory hM4Di-mCherry of PVN CRF-expressing neurons, bath application of CNO to the brain slices resulted in a significant decrease in sEPSCs frequency, but no change in their amplitude of labeled PVN presympathetic neurons. In contrast, in WKY rats expressed with excitatory hM3Dq-eGFP of PVN CRF-expressing neurons, CNO had no obvious effect on the sEPSCs frequency and amplitude in PVN presympathetic neurons. Furthermore, bath application of CNO had no significant effect on current-evoked firing of PVN presympathetic neurons of either WKY rats with hM3Dq-eGFP expression in CRF neurons or SHR with hM4Di-mCherry expression in CRF neurons. Conclusions The activity and number of PVN CRF-expressing neurons are increased in SHR, and CRF-expressing neurons enhance the excitability of presympathetic neurons, which acts as a regulatory neuronal microcircuit between CRF neurons and presympathetic neurons in the PVN.

Effect of Liuwei Dihuang decoction on β-catenin and EMT in kidney tissue of UUO rats / 中国药理学通报

Aim To explore the effect of Liuwei Dihuang decoction ( LWDHD) on the expression of β-catenin, E-cadherin,α-SMA, the pathological changes of renal tissue, and the changes of an epithelial-mesen-chymal transformation ( EMT) in renal tissue of rats with unilateral ureteral obstruction ( UUO ) . Methods Forty-eight SPF grade SD rats were randomly divided into sham group ( Sham), model group ( UUO), Liuwei Dihuang decoction low, medium, and high groups ( LWDHD 3. 375, 6. 75, 13. 5 g · kg

Clinicopathological analysis of benign mammary ductal cystic papillomatosis with loss of myoepithelial cells / 中华病理学杂志

Objective: To investigate the histopathological and immunohistochemical characteristics of benign apocrine cystic papillary hyperplasia of the breast with loss of myoepithelial cell layer. Methods: The clinical data, histopathological features and immunohistochemical profile of patients with benign apocrine cystic papillary hyperplasia of breast with loss of myoepithelial cell layer from January 2016 to December 2021 were examined, in which six patients were identified. Results: All six patients were female, aged 36-61 years (median 46 years), who presented with a breast mass; three cases were from the left breast and three cases were from the right breast. Microscopic examination of all cases showed breast hyperplasia with apocrine cysts, accompanied by different degrees of micropapillary and papillary hyperplasia of apocrine cells. One case was associated with lobular carcinoma in situ, and one case was associated with apocrine ductal carcinoma in situ with intraductal dissemination in adenosis. Immunohistochemical staining of CK5/6, p63, SMA, SMMHC, Calponin and CD10 showed complete absence of myoepithelial cell layer surrounding ducts in apocrine cystic papillary hyperplasia. Conclusions: The myoepithelial cells of apocrine cystic papillary hyperplasia of the breast may undergo abnormal changes and may even be completely lost. The diagnosis should be comprehensively considered along with cytomorphological and histological features to avoid overdiagnosis.