ObjectiveTo investigate the mechanism of salvianolic acid F （Sal F） in repairing the high glucose-induced injury in human kidney-2 （HK-2） cells via the B-cell lymphoma-2 （Bcl-2）-associated X protein （Bax）/cysteinyl aspartate-specific proteinase 3 （Caspase-3）/gasdermin-E （GSDME） pathway. MethodThe cell counting kit-8 （CCK-8） was used to measure the relative viability of HK-2 cells exposed to high glucose and different concentrations （2.5， 5， 10， 20 μmol·L^-1） of Sal F and the relative viability of HK-2 cells treated with Sal F for different time periods. The levels of lactate dehydrogenase （LDH） and interleukin-1β （IL-1β） in the supernatant of the cell culture were measured by the LDH assay kit and enzyme-linked immunosorbent assay （ELISA） kit， respectively. Flow cytometry combined with Annexin V-FITC/propidium iodide （PI） and Hoechst 33342/PI staining was employed to reveal the proportion of PI-positive HK-2 cells exposed to high glucose. Western blotting was employed to determine the protein levels of Bax， Bcl-2， cytochrome C， cysteinyl aspartate-specific proteinase （Caspase）-9， Caspase-3， and GSDME in the HK-2 cells exposed to high glucose and treated with Sal F. The 2，7-dichlorodihydrofluorescein diacetate fluorescence probe （DCFH-DA） and mitochondrial membrane potential assay kit （JC-1） were used to determine the production of reactive oxygen species （ROS） and the mitochondrial membrane potential in the HK-2 cells exposed to high glucose and treated with Sal F. ResultCompared with the blank group， the model group showed decreased cell viability （P<0.01）， elevated levels LDH and IL-1β， increased proportion of PI-positive cells （P<0.01）， up-regulated protein levels of Bax， cytochrome C， Caspase-9， Caspase-3， and GSDME （P<0.01）， down-regulated protein level of Bcl-2 （P<0.01）， decreased mitochondrial membrane potential， and excessive ROS accumulation. Compared with the model group， Sal F repaired the high glucose-induced injury in HK-2 cells （P<0.05）， lowered the levels of LDH and IL-1β （P<0.05， P<0.01）， and decreased the proportion of PI-positive cells （P<0.01）. In addition， Sal F down-regulated the protein levels of Bax， cytochrome C， Caspase-9， Caspase-3， and GSDME and up-regulated the protein level of Bcl-2 （P<0.05， P<0.01）， increased the mitochondrial membrane potential， and decreased the accumulation of ROS in HK-2 cells. ConclusionSal F can reduce the production of ROS， restore the balance of mitochondrial membrane potential， and inhibit pyroptosis via the Bax/Caspase-3/GSDME signaling pathway to repair the high glucose-induced injury in HK-2 cells.

ObjectiveTo investigate the antidepressant effect of Sinisan （SNS） by regulating glycogen aynthase kinase-3β （GSK-3β）/tumor necrosis factor alpha-induced protein 3（A20）/CCAAT enhancer binding protein β（C/EBPβ） to inhibit the activation of microglia. MethodA total of 72 male C57/6J mice were randomly divided into the normal group， model group， fluoxetine group （5.0 mg·kg^-1）， low-dose Sinisan group （4.9 g·kg^-1）， medium-dose Sinisan group （9.8 g·kg^-1）， and high-dose Sinisan group （19.6 g·kg^-1）， with 12 mice in each group. After one week of adaptive feeding， chronic unpredictable mild stress （CUMS） was performed to establish the depression model. In the fifth week， drug treatment was conducted for four weeks. In the ninth week， behavioral tests were performed， including sucrose preference test （SPT）， open field test （OPT）， elevated plus maze （EPM） test， and forced swimming test （FST）. Western blot was used to detect the expression levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， nitric oxide synthase （iNOS）， GSK-3β， A20， and C/EBPβ in the cortex. The expression of M1-polarized ionized calcium-binding adapter molecule 1 （Iba1） and cluster of differentiation 68 （CD68） in microglia was detected by immunofluorescence. ResultAfter eight weeks of CUMS， compared with the normal group， the mice in the model group had a significantly reduced sucrose preference rate （P<0.01）， and the activity in the central area of the OPT was significantly reduced （P<0.01）. The activity in the open arm area of the EPM test was significantly reduced （P<0.05）， and the immobility time of FST was increased （P<0.01）. The expression levels of inflammatory proteins IL-1β， IL-6， and iNOS were increased （P<0.01）， and the fluorescence co-localization index of Iba1 and CD68 was increased （P<0.05）. The protein expression levels of GSK-3β and C/EBPβ were significantly increased （P<0.05， P<0.01）. After four weeks of SNS intervention， compared with the model group， the mice in the SNS group had significantly increased sucrose preference rate （P<0.01）， significantly increased activities in the central area and the open arm area in the OPT and the EPM test （P<0.05）， and significantly reduced immobility time in the FST （P< 0.01）. The protein expression levels of IL-1β， IL-6， and iNOS were significantly decreased （P<0.05）， and the fluorescence co-localization index of Iba1 and CD68 was decreased in the high-dose SNS group （P<0.05）. The protein expression levels of GSK-3β and C/EBPβ in the medium-dose and high-dose SNS groups were significantly decreased （P<0.01）， and that of A20 was significantly increased （P<0.01）. ConclusionThe antidepressant effect of SNS is related to the regulation of GSK-3β/A20/C/EBPβ protein expression and the inhibition of M1-type activation of microglia.

Pulmonary fibrosis， chronic obstructive pulmonary disease， acute lung injury， asthma， and infectious pneumonia are common pulmonary inflammatory diseases worldwide. There is evidence that mitochondria produce a large amount of reactive oxygen species （ROS） when stimulated by inflammation， leading to oxidative stress that affects the onset and progression of pulmonary inflammatory diseases. With in-depth research， traditional Chinese medicine （TCM） has made significant progress in the treatment of pulmonary inflammatory diseases. An increasing amount of evidence indicates that single TCM and their active components， as well as TCM compound formulas， can improve mitochondrial oxidative stress status through multi-target and multi-pathway mechanisms， thereby effectively treating pulmonary inflammatory diseases. Currently， there is a lack of systematic review and summary of TCM research in this field both domestically and internationally. Therefore， this article aims to summarize and conclude the mechanisms by which TCM regulates mitochondrial oxidative stress to intervene in pulmonary inflammatory diseases， providing a scientific basis for its clinical application and offering new ideas and references for in-depth research on the prevention and treatment of pulmonary inflammatory diseases with TCM.

Objective To investigate the mechanism of astragaloside Ⅰ,the active constituent of milkvetch root,in inhibiting podocyte injury and improving diabetic kidney disease.Methods According to the body weight,60 male db/db mice were randomly divided into the model group,astragaloside Ⅰ low-dose group(10 mg/kg),astragaloside Ⅰ medium-dose group(20 mg/kg),astragaloside Ⅰ high-dose group(40 mg/kg),and valsartan group(10mg/kg),with 12 mice per group.Twelve db/db littermate control db/m mice were used as the control group.The drug was administered by gavage for 8 weeks.Transmission electron microscope was used to observe the ultrastructure of the kidney;immunohistochemistry and Western blotting were used to detect the expression of nephrotic protein(nephrin),a marker of renal podocytes;enzyme-linked immunosorbent assay was used to detect the contents of interleukin-1β(IL-1β)and interleukin-18(IL-18)in the serum of mice;Western blotting was used to detect the protein expressions of NOD-like receptor thermoprotein domain-related protein 3(NLRP3),cysteinyl aspartate specific proteinase 1(Caspase-1),and Gasdermin D(GSDMD)in kidney tissue.Results Compared with the control group,the glomeruli of the model group showed obvious podocyte loss and foot process fusion;the protein expression of nephrin was decreased(P＜0.05);the contents of IL-1 β and IL-18 in serum were increased(P＜0.05);the protein expressions of NLRP3,Cleaved-Caspase-1,and GSDMD-N were increased(P＜0.05).Compared with the model group,the renal pathological damage in the astragaloside Ⅰ administration groups were alleviated;the protein expression of nephrin was increased(P＜0.05);the contents of IL-1β and IL-18 in serum were decreased(P＜0.05);the protein expressions of NLRP3,Cleaved-Caspase-1,and GSDMD-N were decreased(P＜0.05).Conclusion Astragaloside Ⅰ may play a role in intervening diabetic kidney disease by inhibiting pyroptosis and improving podocyte injury.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

In recent 20 years, the incidence of thyroid cancer has shown an obvious upward trend, especially in female patients. As the second most common molecular marker of thyroid cancer, RAS mutation affects the occurrence and development of thyroid cancer mainly through RAS-RAF-MEK-ERK and PI3K-Akt signaling pathways. However, the effect of RAS mutation on the invasive characteristics, prognosis and survival rate of thyroid cancer is still controversial. This article reviews the research progress of RAS gene mutation in thyroid cancer.

Objective To investigate the therapeutic effect of three-line anchors combined with modified Mason-Allen technique in repair of moderate to massive rotator cuff tear under arthroscopy. Methods The clinical data of 48 patients (repair of moderate to massive rotator cuff tear using modified Mason-Allen technique) were analyzed retrospectively. According to the anchors used, patients were divided into control group (double-wire anchors, n=23) and observation group (three-wire anchors, n=25). Age, gender, operation time, the number of anchors used during operation and postoperative complications were recorded in the two groups. American shoulder and elbow surgeon (ASES) scores, Constant-Murley shoulder function scores and Visual Analogue Scale (VAS) scores were compared between the two groups before and after surgery (last follow-up). During follow-up, magnetic resonance imaging(MRI)was used to evaluate rotator cuff retear. Results At the last follow-up, VAS score of the shoulder in the two groups was significantly lower than before surgery, constant-Murley shoulder function score and ASES score were significantly higher than before surgery (P < 0.05). The number of anchors used in the control group was significantly higher than that in the observation group (P < 0.05). Conclusion The clinical effect of three-line anchor combined with the modified Mason-Allen technique in repair of moderate to massive rotator cuff tear is better, which is consistent with the traditional two-wire anchors, but the amount of anchors is less.

OBJECTIVE To mine and analyze adverse drug event （ADE） signals after the marketing of pazopanib and provide references for clinically safe medication. METHODS OpenVigil 2.1 data platform was used to mine ADE signals from the US FDA adverse event reporting system （FAERS） database. ADE reports of pazopanib from October 2009 to June 2022 were collected， and ADE signals were analyzed using proportional reporting ratio （PRR） method and reporting odds ratio （ROR） method in the proportional imbalance method. RESULTS A total of 16 655 ADE reports were identified with pazopanib as the primary suspect drug. Through ROR and PRR analysis， 220 ADE signals involving 19 system organ classes were identified. The top 10 ADE signals by frequency were recorded in the drug instruction. Additionally， 88 new ADE signals were discovered， mainly related to the gastrointestinal system， various investigations， and the renal and urinary system. Decreased basophil count， nail bed hemorrhage， tumor rupture， and vaginal fistula were both new ADE signals and the top 10 ADE signals by strength. CONCLUSIONS The occurrence of common ADEs （diarrhea， hair color changes， hypertension， etc.） during the use of pazopanib after marketing is generally consistent with its drug instruction； the number of reported cases for new suspected risk signals （decreased basophil count， nail bed hemorrhage， tumor rupture， and vaginal fistula， etc.） is limited， and continuous monitoring is required.

OBJECTIVE：To overview the systematic review on the effectiveness of indomethacin in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis （PEP），and to provide reliable evidence-based reference for the prevention of PEP. METHODS ：Retrieved from PubMed ，the Cochrane Library ，Embase，CBM，CNKI，Wanfang database and VIP，systematic review on indomethacin in the prevention of PEP were collected during the inception to Nov. 2020. The methodological quality ，report quality and evidence quality of the included studies were evaluated by AMSTAR 2 scale，PRISMA statement and GRADE method. The effectiveness of PEP prevention was described. RESULTS ：Finally，23 systematic reviews were obtained ，including 12 in Chinese and 11 in English. Tweenty-two systematic reviews showed that compared with placebo ， indomethacin could effectively reduce the incidence of PEP. Eight systematic reviews showed that indomethacin significantly reduced the incidence of moderate and severe PEP compared with placebo. Five systematic reviews showed that indomethacin could reduce the incidence of postoperative hyperamylasemia compared with placebo. Three systematic reviews showed that indomethacin also had a good preventive effect on people with high risk of PEP. PRISMA score of included systematic reviews ranged from 15 to 25. The quality evaluation of AMSTAR 2 methodology included in systematic reviews was low ，and the key items of complete report were 4，9，11 and 13. The GRADE evidence quality evaluation of the included systematic reviews showed that the quality of the evidence was concentrated in the low level. CONCLUSIONS ：Indomethacin has a certain effect in the prevention of PEP ，but the overall evidence quality of the included literatures is generally not high. It needs to be further validated by high-quality clinical research.

Objective:To investigate the clinical efficacy of early pancreatic duct stenting in the treatment of acute pancreatitis.Methods:The retrospective and descriptive study was conducted. The clinical data of 201 patients with acute pancreatitis who were admitted to General Hospital of Ningxia Medical University from October 2011 to December 2017 were collected. There were 106 males and 95 females, aged from 18 to 90 years, with a median age of 62 years. Of 201 patients, there were 178 cases with moderate severe acute pancreatitis and 23 cases with serious severe acute pancreatitis. Patients were treated with pancreatic duct stenting within 48 hours after admission. Observation indicators: (1) treatment; (2) follow-up. Follow-up was conducted using outpatient examination and telephone interview to detect recurrence of acute pancreatitis after surgery up to June 2019. Measurement data with normal distribution were represented by Mean± SD, and the independent sample t test was used for comparison between groups, and the matched samples t test was used for comparison between before and after. Measurement data with skewed distribution were represented by M( P25 ,P75) or M(range), and the Mann-Whitney U test was used for comparison between groups, and the Wilcoxon signed rank sum test was used for comparison between before and after. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test . Results:(1) Treatment: 201 patients received pancreatic duct stenting successfully, 63 of which were detected pancreatic obstruction with white-floc. The interval time from admission to surgery , operation time, time for initial oral intake, duration of hospital stay and hospital expenses of 201 patients were 10 hours(4 hours,22 hours), (35±15)minutes, 3 days(2 days,5 days), 6 days(5 days,10 days) and 3.8×10 4 yuan (3.0×10 4 yuan,4.9×10 4 yuan). Of 201 patients, 22 patients were transferred to intensive care unit, including 1 case with serious severe underwent inhospital death and 1 case with moderate severe and 7 cases with serious severe underwent auto-discharge from hospital. There were 25 cases with local complications, including 17 cases with pancreatic infectious necrosis, 7 cases with pancreatic walled-off necrosis and 1 case with spleen infarction. All 25 patients were cured after surgical inter-vention or conservative treatment. Further analysis showed that cases being transferred to intensive care unit, cases undergoing surgical treatment, the time for initial oral intake, duration of hospital stay and cases undergoing auto-discharge from hospital were 6, 11, 3 days(2 days,5 days), 6 days(5 days,10 days) and 1 for the 178 moderate severe cases, versus 16, 5, 7 days(4 days,9 days), 9 days (7 days,17 days) and 7 for the 23 serious severe cases, showing significant differences ( χ2=91.561, 6.730, Z=6.485, 5.463, χ2=47.561, P<0.05). The white blood cell count, serum amylase indexes and chronic health evaluation Ⅱ score of 201 patients were (14±6)×10 9/L, 928 U/L(411 U/L,1 588 U/L), 9±5 before admission, versus (10±4)×10 9/L, 132 U/L(72 U/L,275 U/L), 6±4 at 48 hours after admission, respectively, showing significant differences ( t=12.219, Z=11.639, t=16.016, P<0.05). (2) Follow-up: of 201 patients, 153 cases were followed up for 40 months (27 months,55 months). During the follow-up, 32 of the 153 cases had recurrence of acute pancreatitis. Conclusion:Early pancreatic duct stenting is safe and feasible in the treatment of acute pancreatitis.