ObjectiveTo compare the hepatic bile acid profile between a mouse model of metabolic-associated steatohepatitis （MASH） induced by a high-fat， high-sugar， and high-cholesterol diet combined with intraperitoneal injection of 10% carbon tetrachloride （CCl₄） and MASH cases in clinical practice， and to investigate the feasibility of this model in studying drug interventions on bile acid profile in MASH. MethodsA total of 30 male C57BL/6J mice were randomly divided into control group and model group， with 15 mice in each group. The mice in the control group were given normal diet and drinking water and weekly injections of olive oil， and those in the model group were given a high-fat， high-sugar， and high-cholesterol diet， high-sugar drinking water， and weekly injections of CCl₄+olive oil. At the end of weeks 8， 12， and 16， 5 mice were selected from each group to collect samples. Behavioral assessments were performed， and body weight and liver wet weight were measured； liver pathology and lipid deposition were evaluated by HE staining， SAF scoring， oil Red O staining， the semi-quantitative analysis of stained area， the serum levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST）， and liver triglyceride （TG） content； Sirius Red staining was performed for liver tissue to assess liver fibrosis； ultra-performance liquid chromatography-tandem mass spectrometry and targeted metabolomics were used to measure the hepatic bile acid profile， including cholic acid （CA）， glycocholic acid （GCA）， chenodeoxycholic acid （CDCA）， glycochenodeoxycholic acid （GCDCA）， ursodeoxycholic acid （UDCA）， tauroursodeoxycholic acid （TUDCA）， hyodeoxycholic acid （HDCA）， and glycodeoxycholic acid （GDCA）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups. ResultsCompared with the control group at the same time point， the model group had disheveled and dull fur， reduced activity， and relatively slow reactions at weeks 8， 12， and 16， as well as significant increases in liver wet weight （P<0.05）， the serum level of ALT （P<0.05）， the content of TG in the liver （P<0.05）， and SAF score （P<0.05）. As for the differentially expressed bile acids in liver tissue， compared with the control group at week 8， the model group had significantly higher levels of CA and CDCA and significantly lower levels of UDCA， TUDCA， HDCA， and GDCA （all P<0.05）； compared with the control group at week 12， the model group had significantly higher levels of CA， GCA， CDCA， and GCDCA and significantly lower levels of UDCA and HDCA （all P<0.05）； compared with the control group at week 16， the model group had significantly higher levels of CA， GCA， CDCA， GCDCA， and TUDCA and significantly lower levels of UDCA， HDCA， and GDCA （all P<0.05）. As for the differentially expressed bile acids in the bile acid pool of liver tissue， compared with the control group at week 8， the model group had significantly higher levels of CA and CDCA and significantly lower levels of UDCA， TUDCA， GDCA， and HDCA （all P<0.05）； compared with the control group at weeks 12 and 16， the model group had significantly higher levels of GCA and GCDCA and significantly lower levels of UDCA， GDCA， and HDCA （all P<0.05）. ConclusionThere are significant changes in the hepatic bile acid profile in a mouse model of MASH induced by a high-fat， high-sugar， and high-cholesterol diet combined with CCl₄， which are similar to the changes in bile acids in MASH cases in clinical practice， suggesting that this model can be used to explore the interventional effect of drugs on the bile acid profile in MASH.

ObjectivesTo investigate the effect of the Bioinformatics Infrared Liver Therapeutic （BILT） instrument on portal vein blood flow， liver stiffness， and spleen stiffness in patients with liver cirrhosis， and to preliminarily explore the therapeutic effect and mechanism of the BILT instrument. MethodsA total of 78 patients with compensated liver cirrhosis who attended the outpatient service or were hospitalized in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from October 2017 to December 2021 were enrolled， among whom 68 patients completed the 12-week treatment and were randomly divided into BILT group and simulated instrument group， with 34 patients in each group. In addition to basic treatment， the patients in the BILT group received irradiation with the BILT instrument， while those in the simulated instrument group received irradiation with the simulated instrument， for 30 minutes each time， twice a day； the course of treatment was 12 weeks for both groups. The two groups were compared in terms of laboratory markers （liver function， renal function， and routine blood test results）， liver and spleen ultrasound morphology， color Doppler blood flow detection （portal vein diameter， portal vein cross-sectional area， mean portal vein velocity， peak portal vein velocity， and mean portal vein flow）， and liver/spleen stiffness measurement before and after treatment. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the non-parametric Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between groups. The paired samples correlation test was performed for the data before and after treatment within each group， and the paired samples t-test or the non-parametric Wilcoxon signed-rank test was performed for data with significant correlations. ResultsThe paired samples correlation test showed no correlation in spleen attenuation parameter before and after treatment， suggesting that the results of spleen fat measured by FibroTouch could not be used for statistical analysis. After 12 weeks of treatment， compared with the control group， the treatment group had significantly greater increases in portal vein diameter， portal vein cross-sectional area， and mean portal vein flow and a significantly greater reduction in liver stiffness measurement （all P0.05）. At week 0 before treatment and after 12 weeks of treatment， comparison of the immediate effect after 30 minutes of BILT irradiation showed that the treatment group had significant increases in portal vein diameter， portal vein cross-sectional area， mean portal vein velocity， and mean portal vein flow （all P0.05）， while the control group showed no significant changes after irradiation （all P0.05）； compared with the control group， the treatment group had significantly greater changes in all indicators except peak portal vein flow at week 0 （all P0.05）. No adverse events were observed in either group. ConclusionThe BILT instrument can improve portal vein blood flow in the liver and alleviate liver stiffness/fibrosis in patients with liver cirrhosis.

Hepatic steatosis can be observed in chronic liver diseases of different etiologies. The main predisposing factors for hepatic steatosis include chronic viral hepatitis， cholestatic liver disease， alcoholic liver disease， and nonalcoholic fatty liver disease. Simple fatty liver disease is the initial manifestation of hepatic steatosis， followed by steatohepatitis， liver fibrosis， liver cirrhosis， and even hepatocellular carcinoma. With the development of medical imaging technology， magnetic resonance imaging-proton density fat fraction （MRI-PDFF） has been widely used in the diagnosis of fatty liver disease （FLD） in clinical practice. MRI-PDFF is gradually becoming the gold standard for the noninvasive diagnosis of FLD due to its high accuracy and good repeatability. This article reviews the clinical application of MRI-PDFF in liver fat quantification and related research advances.

ObjectiveTo investigate the effect of transplantation of bone marrow mesenchymal stem cells （BMSCs） co-cultured with bone marrow-derived M2 macrophages （M2-BMDMs）， named as BMSC^M2， on a rat model of liver cirrhosis induced by carbon tetrachloride （CCl₄）/2-acetaminofluorene （2-AAF）. MethodsRat BMDMs were isolated and polarized into M2 phenotype， and rat BMSCs were isolated and co-cultured with M2-BMDMs at the third generation to obtain BMSC^M2. The rats were given subcutaneous injection of CCl₄ for 6 weeks to establish a model of liver cirrhosis， and then they were randomly divided into model group （M group）， BMSC group， and BMSC^M2 group， with 6 rats in each group. A normal group （N group） with 6 rats was also established. Since week 7， the model rats were given 2-AAF by gavage in addition to the subcutaneous injection of CCl₄. Samples were collected at the end of week 10 to observe liver function， liver histopathology， and hydroxyproline （Hyp） content in liver tissue， as well as changes in the markers for hepatic stellate cells， hepatic progenitor cells， cholangiocytes， and hepatocytes. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the N group， the M group had significant increases in the activities of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in ALT and AST （P<0.01）， and the BMSC^M2 group had significantly better activities than the BMSC group （P<0.05）. Compared with the N group， the M group had significant increases in Hyp content and the mRNA and protein expression levels of alpha-smooth muscle actin （α-SMA） in the liver （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in Hyp content and the expression of α-SMA （P<0.05）， and the BMSC^M2 group had a significantly lower level of α-SMA than the BMSC group （P<0.01）. Compared with the N group， the M group had significant increases in the mRNA expression levels of the hepatic progenitor cell markers EpCam and Sox9 and the cholangiocyte markers CK7 and CK19 （P<0.01） and significant reductions in the expression levels of the hepatocyte markers HNF-4α and Alb （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in the mRNA expression levels of EpCam， Sox9， CK7， and CK19 （P<0.05） and significant increases in the mRNA expression levels of HNF-4α and Alb （P<0.05）， and compared with the BMSC group， the BMSC^M2 group had significant reductions in the mRNA expression levels of EpCam and CK19 （P<0.05） and significant increase in the expression level of HNF-4α （P<0.05）. ConclusionM2-BMDMs can enhance the therapeutic effect of BMSCs on CCl₄/2-AAF-induced liver cirrhosis in rats， which provides new ideas for further improving the therapeutic effect of BMSCs on liver cirrhosis.

Background Nonylphenol (NP) is a typical phenolic endocrine disruptor, and there are significant differences in NP concentration in different regions and water types. Objective To investigate the concentration of NP in three types (river, lake, and reservoir) of water sources in Hubei Province, and assess its ecological risk and population health risk. Methods Fifteen sampling points were set up at four river water sources (Liangtingshan Waterworks, Baishazhou Waterworks, Dijiao Waterworks, and Zongguan Waterworks), one lake water source (Liangzi Lake), and one reservoir water source (Fushui Reservoir). Water samples were collected from the 15 sampling points in June 2019 (wet season), October 2019 (level season), and December 2019 (dry season), respectively. The NP concentration in water samples was detected using ultra-high-performance liquid chromatography-tandem mass spectrometry, and the differences in NP concentration among groups were compared using variance analysis. The ecological risk and the health risk of NP were evaluated using risk quotient (RQ) and non-carcinogenic risk index (NCRI), respectively. Results The detection rate of NP was 100%, with an average concentration of (18.10±15.00) ng·L⁻¹ (5.45-92.71 ng·L⁻¹). The average concentrations of NP during the level, wet, and dry seasons were (11.52±5.31) ng·L⁻¹, (23.86±22.08) ng·L⁻¹, and (18.93±9.51) ng·L⁻¹, respectively, and the maximum concentrations were 24.62 ng·L⁻¹, 92.71 ng·L⁻¹, and 42.38 ng·L⁻¹, respectively. The variance analysis showed no statistical difference in the NP concentration in the samples from rivers, lakes, and reservoirs in different periods (P>0.05). Only the water samples from the water source serving the Zongguan Waterworks showed an RQ (0.19) greater than 0.1 during the wet season, indicating a moderate risk. The RQ values of other water samples were all less than 0.1, indicating an overall relatively low ecological risk. The highest NCRI values during the level, wet, and dry seasons were 0.1459, 0.5492, and 0.2511, respectively, all less than 1, indicating an acceptable health risk level. Conclusion The NP concentrations in all water sources in this study are at a relatively low level, which poses an acceptable risk level to human health.

ObjectiveTo investigate the role of traditional Chinese medicine （TCM） constitution in the progression of abnormal glucose metabolism among community population. MethodsA total of 393 community residents who participated in community diabetes screening from 2019 to 2021 and had complete physical examination data at baseline and at the 2nd year follow-up were selected. According to the results of glucose tolerance tests， community residents were divided into the abnormal glucose metabolism progression group and non-progression group， and were matched at the ratio of 1∶2 using the propensity score matching. The influencing factors related to diabetes at baseline were collected for both groups. The traditional Chinese medicine constitution was determined among population in two groups. The differences of influencing factors and traditional Chinese medicine constitution between the two groups were compared. Logistic regression analysis was used to analyze the risk factors for the progression of abnormal glucose metabolism. ResultsFinally， 131 patients were included in the progression group and 262 patients in the non-progression group. Compared to the non-progression group， the progression group had significantly higher proportion of hyperlipidemia history ， hyperglycemia history， phlegm-dampness constitution， and blood stasis constitution （P＜0.05 or P＜0.01）. Univariate logistic regression analysis revealed that the history of hyperlipidemia （P=0.011）， history of hyperglycemia （P＜0.001）， the family history of diabetes （P＜0.001）， yin-deficiency constitution （P=0.047）， phlegm-dampness constitution （P=0.011） and blood-stasis constitution （P=0.008） were risk factors for the progression of abnormal glucose metabolism. Multivariate logistic regression analysis indicated that the history of hyperglycemia （P＜0.001）， yin-deficiency constitution （P=0.026） and blood-stasis constitution （P=0.032） were independent risk factors for the progression of abnormal glucose metabolism. ConclusionThe history of hyperglycemia， yin-deficiency constitution and blood-stasis constitution may be the risk factors for the progression of abnormal glucose metabolism.

ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan（RYZBW）in the treatment of initial and early knee osteoarthritis （KOA） through a prospective multicenter，randomized，double-blind，and placebo-parallel controlled trial. MethodFrom October 13^th， 2021 to December 25^th， 2021， 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital， Chinese Academy of Chinese Medical Sciences， and they were randomly divided into observation group and control group， with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education， and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks， and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score （WOMAC score）， and the secondary outcome measures were the response rate of visual scale （VAS） pain score， WOMAC sub item scores （joint pain， joint stiffness， and joint function）， quality of life （SF-12） score， and traditional Chinese medicine （TCM） syndrome score. Result（1） Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW， and the difference was statistically significant （P<0.05）. There was no significant difference between the two groups in improving VAS score response rate， WOMAC function score， WOMAC stiffness score， SF12-PCS （quality of life-physical health） score， SF12-MCS （quality of life-mental health） score， and TCM syndrome score. （2） Subgroup analysis. ① In terms of VAS score response rate， the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of （4， 5］， and the difference was statistically significant （P<0.05）. ② In terms of TCM syndrome score， for subjects aged ［56， 60］ and ［61， 65］， the decrease in total TCM syndrome score in the observation group was better than that in the control group， and the difference was statistically significant （P<0.05）. ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score， VAS score response rate， WOMAC pain score， WOMAC function score， and TCM syndrome score for patients with initial and early KOA， which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.

Objective:To investigate the spectrum and antimicrobial resistance of major pathogens causing nosocomial infections in China during 2020-2021.Methods:A total of 1 311 non-duplicated nosocomial pathogens causing bloodstream infections (BSI, n=670), hospital-acquired pneumonia (HAP, n=394) and intra-abdominal infections (IAI, n=297) were collected from 10 teaching hospitals across China. The minimum inhibitory concentrations (MICs) of clinical common strains were determined using agar dilution or broth microdilution method. Interpretation of reults followed the CLSI M100-Ed33 criteria, with data analysis conducted using WHONET-5.6 software. The Chi-square test was used to compare rates. Results:The most prevalent pathogens causing BSI were Escherichia coli (21.2%, 142/670), Klebsiella pneumoniae (14.9%, 100/670) and Staphylococcus aureus (11.5%, 77/670); the most prevalent pathogens causing HAP were K. pneumoniae (27.7%, 109/394), Acinetobacter baumanii (22.1%, 87/394) and Pseudomonas aeruginosa (18.3%, 72/394). IN IAI, E. coli (24.3%, 60/247), Enterococcus faecium and K. pneumoniae (both 14.6%, 36/247) were dominated. All S. aureus strains were susceptible to tigecycline, linezolid, daptomycin and glycopeptides. Rates of methicillin-resistant S. aureus (MRSA) and coagulase-negative Staphylococcus (MRCNS) were 36.5% (42/115) and 74.5% (38/51), respectively. The rate of vancomycin-resistant E. faecium and E. faecalis was 3.3% (3/90) and 1.9% (1/53), respectively. The prevalence of extended-spectrum β-lactamase (ESBL) was 23.7% (58/245) in K. pneumonia and 60.5% (130/215) in E. coli.The rate of carbapenem-resistant K. pneumonia and E. coli was 29.8% (73/245) and 4.2% (9/215), respectively; the percentage of tigecycline-resistant K. pneumonia and E. coli was 1.6% (4/245) and 0, respectively; the rate of colistin-resistant K. pneumonia and E. coli was 1.6% (4/245) and 2.8% (6/215), respectively; the percentage of ceftazidime/avibactam-resistant K. pneumonia and E. coli was 2.0% (5/245) and 2.3% (5/215), respectively. The rate of carbapenem-resistant A. baumanii and P. aeruginosa was 76.7% (125/163) and 28.4% (33/116), respectively. A. baumanii showed low susceptibility to most antimicrobial agents except colistin (98.8%, 161/163) and tigecycline (89.6%, 146/163). Colistin, amikacin and ceftazidime/avibactam demonstrated high antibacterial activity against P. aeruginosa with susceptility rates of 99.1% (115/116), 94.0% (109/116) and 83.6% (97/116), respectively. Conclusions:The major pathogens of nosocomial infections were K. pneumonia, E. coli, A. baumanii, P. aeruginosa and S. aureus. Nosocomial Gram-negative pathogens exhibited high susceptibilities to tigecycline, colistin and ceftazidime/avibactam. Antimicrobial resistance in A. baumannii remains a significant challenge. The increasing prevalence of carbapenem-resistant Enterobacterales underscores the urgency of antibiotics rational applications and hospital infection controls.

ObjectiveTo observe the clinical efficacy of compound Huangbai liquid fomentation on diabetic foot ulcer of Wagner grade 1-2. MethodPatients were classified into the observation group and control group， with 41 cases in either group. The observation group received routine therapy and compound Huangbai liquid fomentation， while the control group was treated by routine therapy and medical silver nanoparticles-containing dressing. Ulcer area， ulcer depth， traditional Chinese medicine （TCM） syndrome score， ankle-brachial index， transcutaneous oxygen pressure， vascular endothelial growth factor， epidermal growth factor， advanced glycation end product， high-sensitivity C-reactive protein， interleukin-6， erythrocyte sedimentation rate， and adverse events were observed before and after treatment in two groups. ResultAfter treatment， the ulcer area， ulcer depth， TCM syndrome score， vascular endothelial growth factor， epidermal growth factor， advanced glycation end product， high-sensitivity C-reactive protein， interleukin-6（IL-6）， and erythrocyte sedimentation rate were lower than those before treatment in two groups （P<0.05）， and ankle-brachial index， transcutaneous oxygen pressure， vascular endothelial growth factor， and epidermal growth factor were higher than those before treatment in two groups （P<0.05）. After treatment， the ulcer area， ulcer depth， TCM syndrome score， advanced glycation end product， high-sensitivity C-reactive protein， IL-6， and erythrocyte sedimentation rate were lower in the observation group than in the control group （P<0.05）， and ankle-brachial index， transcutaneous oxygen pressure， vascular endothelial growth factor， and epidermal growth factor were higher in the observation group than in the control group （P<0.05）. The clinical efficacy of observation group was better than that of the control group （P<0.05）. There was no significant difference in the incidence of adverse events and endpoint events between two groups. ConclusionCompound Huangbai liquid fomentation is effective for diabetic foot ulcer of Wagner grade 1-2， as it is beneficial to the healing of the ulcer. This study provides clinical evidence for the further promotion of Chinese medicine fomentation.

ObjectiveTo explore the amelioration of cognitive dysfunction in diabetes mellitus （DM） by Jianpi Qinghua prescription （JPQH） based on type 2 diabetes （T2DM） model rats. MethodFifty healthy male Wistar rats of SPF grade were randomly divided into control group （n=10） and experimental group （n=40）. The rats in the control group were fed conventionally， while those in the experimental group were fed on a high-sugar， high-fat diet for six weeks and administered with streptozotocin （STZ） for the induction of the DM model. The model rats were randomly divided into model group， sitagliptin group （1.2 g·L^-1）， pioglitazone group （0.8 g·L^-1）， and JPQH group （1.3 g·mL^-1）， with 10 rats in each group. After six weeks of drug intervention， the changes in body weight， blood glucose， and other related indexes of each group were recorded. Enzyme-linked immunosorbent assay （ELISA） was performed to detect the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the peripheral blood and brain. The Morris water maze test was used to evaluate the cognitive function in rats. Hematoxylin-eosin （HE） staining was used to observe the pathological morphology of the hippocampal CA region. The amyloid β-protein 40 （Aβ₄₀） level was detected by immunohistochemistry. The protein expression of t-tau and p-tau in hippocampal neurons of rats was detected by Western blot. ResultCompared with blank group， the body weight of model group was significantly decreased （P<0.05）， blood glucose level was significantly increased （P<0.01）， inflammatory cytokines TNF-α and IL-1β were increased （P<0.05）， learning and spatial ability were significantly decreased （P<0.01）， the arrangement of hippocampal cells was loose and disordered， and the intercellular space was significantly increased. The number of cells decreased significantly， and the expression of Aβ₄₀ increased significantly. and increased t-tau and p-tau protein content in the hippocampus （P<0.01）. Compared with model group， the JPQH group showed reduced blood glucose （P<0.01）， decreased TNF-α and IL-1β levels in the peripheral blood and cerebrospinal fluid （P<0.05）， a downward trend of IL-6 without a statistical difference， improved learning and spatial memory ability （P<0.01）， densely arranged cells in the hippocampal CA1 area， increased cell number， reduced Aβ₄₀ expression， and decreased p-tau protein expression （P<0.05）. ConclusionJPQH can prevent cognitive dysfunction in DM by reducing inflammatory factor levels， decreasing neurotoxicity caused by Aβ₄₀ deposition， and inhibiting hyperphosphorylation of tau protein in DM rats.