Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

Objective To address personnel management challenges in large comprehensive hospitals by developing a comprehensive personnel information management system for refined multi-campus administration.Methods A centralized data-base was employed to construct a personnel information management system compatible with both"interactive management"and"independent management"modes.The system progressively implemented functions including personnel information manage-ment,meal card and subsidy administration,and shift scheduling.Results The system achieved effective interconnections be-tween subsystems,significantly improving personnel management efficiency,data governance,risk prevention capabilities,and operational decision-making.Personnel data were efficiently utilized across multiple scenarios.Conclusion The multi-campus comprehensive personnel information management system meets the refined requirements of multi-campus personnel administration and provides valuable experience for the development and expansion of subsequent hospital operation management information sys-tems.

Objective To address personnel management challenges in large comprehensive hospitals by developing a comprehensive personnel information management system for refined multi-campus administration.Methods A centralized data-base was employed to construct a personnel information management system compatible with both"interactive management"and"independent management"modes.The system progressively implemented functions including personnel information manage-ment,meal card and subsidy administration,and shift scheduling.Results The system achieved effective interconnections be-tween subsystems,significantly improving personnel management efficiency,data governance,risk prevention capabilities,and operational decision-making.Personnel data were efficiently utilized across multiple scenarios.Conclusion The multi-campus comprehensive personnel information management system meets the refined requirements of multi-campus personnel administration and provides valuable experience for the development and expansion of subsequent hospital operation management information sys-tems.

Objective To investigate the therapeutic effect and mechanism of astragaloside Ⅳ on systemic lupus erythematosus(SLE)mice.Methods A total of 40 female spontaneous MRL/lpr SLE model mice were randomly divided into five groups:model group,Prednisone group,astragaloside Ⅳ group,astragaloside Ⅳ+CHPG[nuclear factor KappaB(NF-κB)pathway activator]group and astragaloside Ⅳ+Nigerian[NOD-like receptor family pyrin domain containing protein 3(NLRP3)activator]group,with eight mice in each group.Eight female MRL/MpJ mice were used as normal group.During the administration,the body mass was weighted.After administration,the spleen,thymus and kidney were weighted,and the organ index was calculated.The 24-hour urinary protein level in urine samples,the biochemical indexes of creatinine(SCr),blood urea nitrogen(BUN),autoantibodies[antinuclear antibody(ANA),anti-double-stranded DNA(dsDNA)antibody,anti-snRNP/Sm antibody]and inflammatory mediators[interleukin(IL)-1β,IL-18]in blood samples were detected.The pathological damage of renal tissue was observed by hematoxylin-eosin(HE)staining,and the fibrosis of renal tissue was observed by Masson staining.The expressions of NF-κB/NLRP3 inflammasome pathway-related proteins in kidney and spleen tissues were detected by Western Blot.Results Compared with the model group,the body mass of mice in prednisone group and astragaloside Ⅳ group increased,the spleen index,thymus index and kidney index were decreased,the serum levels of ANA antibody,anti-dsDNA antibody and anti-snRNP/Sm antibody were decreased,the levels of SCr,BUN and 24-hour urine protein were decreased,the levels of IL-1 βand IL-18 wrere decreased,the ratios of p-p65/p65,p-IKBα/IKBα,cleaved caspase-1/pro caspase-1 and the relative expression of NLRP3 protein in kidney and spleen tissues were decreased(all P＜0.05),and the pathological damage and fibrosis of renal tissue in SLE mice were alleviated,there being no significant difference between the two administration groups(P＞0.05).NF-κB activator and NLRP3 inflammasome activator eliminated the improvement of astragaloside Ⅳ on the above indexes in SLE mice to a certain extent.Conclusion Astragaloside Ⅳ can improve the immune function of SLE mice,reduce renal injury and inflammatory response,and its mechanism may be related to its inhibition of the activation of NF-κB/NLRP3 inflammasome pathway.

Objective To establish a method based on high performance liquid chromatography for the determination of 3-demethylcolchicine(3 DMC)in rat plasma and to study its pharmacokinetic behavior in rats.Methods The concentration of 3 DMC in rat plasma was determined by high performance liquid chromatography(HPLC).Plasma samples were precipitated by acetonitrile and supernatant was centrifuged for analysis.The determination conditions were as follows:The chromatography was performed on Alphasil VC-C18 column(4.6 mm × 150.0 mm,5.0 μm)with mobile phase consisted of water-acetonitrile-methanol(79∶16∶5),iso-elution at the flow rate of 0.8 mL·min-1.The detection wavelength was set at 240 nm,with polydacryin as the internal standard.The specificity,standard curve and lower limit of quantitation,precision and recovery,matrix effect and stability of the method were investigated.The rats were randomly divided into low,medium and high dose groups(1,2 and 4 mg·kg-1 3DMC were injected into the tail vein,respectively),and blood was collected from orbital venous plexus.The concentration of 3DMC in plasma samples was measured;the pharmacokinetic parameters were calculated using Drug And Statistics(DAS)2.0.Results 3DMC has a good linear relationship between 0.39 and 25.00 μg·mL-1,and its standard curve is y=5.96 × 10-2x+7.60 × 10-3(r=0.999 5).The lower limit of quantitation was 0.39 μg·mL-1,the intra-day and inter-day relative standard deviations were-5.08％to 0.75％,the recovery was 93.23％to 108.90％,the matrix effect was 94.88％to 104.00％,and the stability relative standard deviation(RSD)was less than 8.72％.All the results met the requirements.Pharmacokinetic parameters of low,medium and high dose groups:Cmax were(1.66±0.24),(4.36±0.78)and(9.73±1.42)mg·L-1,respectively;t1/2 were(0.31±0.02),(0.32±0.11)and(0.48±0.06)h,respectively;AUC0-t were(0.50±0.09),(1.53±0.16)and(2.67±0.11)mg·L-1·h,respectively.Conclusion The established method for the determination of 3DMC concentration in rat plasma is simple,specific and sensitive,and is suitable for the determination of 3DMC concentration and pharmacokinetic study in rat plasma.

Objective To establish a method based on high performance liquid chromatography for the determination of 3-demethylcolchicine(3 DMC)in rat plasma and to study its pharmacokinetic behavior in rats.Methods The concentration of 3 DMC in rat plasma was determined by high performance liquid chromatography(HPLC).Plasma samples were precipitated by acetonitrile and supernatant was centrifuged for analysis.The determination conditions were as follows:The chromatography was performed on Alphasil VC-C18 column(4.6 mm × 150.0 mm,5.0 μm)with mobile phase consisted of water-acetonitrile-methanol(79∶16∶5),iso-elution at the flow rate of 0.8 mL·min-1.The detection wavelength was set at 240 nm,with polydacryin as the internal standard.The specificity,standard curve and lower limit of quantitation,precision and recovery,matrix effect and stability of the method were investigated.The rats were randomly divided into low,medium and high dose groups(1,2 and 4 mg·kg-1 3DMC were injected into the tail vein,respectively),and blood was collected from orbital venous plexus.The concentration of 3DMC in plasma samples was measured;the pharmacokinetic parameters were calculated using Drug And Statistics(DAS)2.0.Results 3DMC has a good linear relationship between 0.39 and 25.00 μg·mL-1,and its standard curve is y=5.96 × 10-2x+7.60 × 10-3(r=0.999 5).The lower limit of quantitation was 0.39 μg·mL-1,the intra-day and inter-day relative standard deviations were-5.08％to 0.75％,the recovery was 93.23％to 108.90％,the matrix effect was 94.88％to 104.00％,and the stability relative standard deviation(RSD)was less than 8.72％.All the results met the requirements.Pharmacokinetic parameters of low,medium and high dose groups:Cmax were(1.66±0.24),(4.36±0.78)and(9.73±1.42)mg·L-1,respectively;t1/2 were(0.31±0.02),(0.32±0.11)and(0.48±0.06)h,respectively;AUC0-t were(0.50±0.09),(1.53±0.16)and(2.67±0.11)mg·L-1·h,respectively.Conclusion The established method for the determination of 3DMC concentration in rat plasma is simple,specific and sensitive,and is suitable for the determination of 3DMC concentration and pharmacokinetic study in rat plasma.

BACKGROUND: The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). METHODS: A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated. RESULTS: A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98). CONCLUSIONS Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

OBJECTIVE: To investigate the distribution and antimicrobial susceptibility of causative microorganisms recovered from patients with intra-abdominal infections (IAIs). METHODS: A total of 2,926 bacterial and fungal strains were identified in samples collected from 1,679 patients with IAIs at the Peking Union Medical College Hospital between 2011 and 2021. Pathogenic bacteria and fungi were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Antimicrobial susceptibility testing (AST) was performed using the VITEK 2 compact system and the Kirby-Bauer method. AST results were interpreted based on the M100-Ed31 clinical breakpoints of the Clinical and Laboratory Standards Institute. RESULTS: Of the 2,926 strains identified, 49.2%, 40.8%, and 9.5% were gram-negative bacteria, gram-positive bacteria, and fungi, respectively. Escherichia coli was the most prevalent pathogen in intensive care unit (ICU) and non-ICU patients; however, a significant decrease was observed in the isolation of E. coli between 2011 and 2021. Specifically, significant decreases were observed between 2011 and 2021 in the levels of extended-spectrum β-lactamase (ESBL)-producing E. coli (from 76.9% to 14.3%) and Klebsiella pneumoniae (from 45.8% to 4.8%). Polymicrobial infections, particularly those involving co-infection with gram-positive and gram-negative bacteria, were commonly observed in IAI patients. Moreover, Candida albicans was more commonly isolated from hospital-associated IAI samples, while Staphylococcus epidermidis had a higher ratio in community-associated IAIs. Additionally, AST results revealed that most antimicrobial agents performed better in non-ESBL-producers than in ESBL-producers, while the overall resistance rates (56.9%-76.8%) of Acinetobacter baumanmii were higher against all antimicrobial agents than those of other common gram-negative bacteria. Indeed, Enterococcus faecium, Enterococcus faecalis, S. epidermidis, and S. aureus were consistently found to be susceptible to vancomycin, teicoplanin, and linezolid. Similarly, C. albicans exhibited high susceptibility to all the tested antifungal drugs. CONCLUSION The distribution and antimicrobial susceptibility of the causative microorganisms from patients with IAIs were altered between 2011 and 2021. This finding is valuable for the implementation of evidence-based antimicrobial therapy and provides guidance for the control of hospital infections.
Humans ; Anti-Bacterial Agents ; Escherichia coli ; Gram-Negative Bacteria ; Gram-Positive Bacteria ; Retrospective Studies ; Staphylococcus aureus ; Intraabdominal Infections/epidemiology* ; Candida albicans ; Coinfection

ObjectiveTo explore the mechanism of Wutou Chishizhi Wan in regulating autophagy and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/glycogen synthase kinase-3β （GSK-3β） signaling pathway in rats with myocardial ischemia-reperfusion injury （MIRI）. MethodSixty male SD rats were randomly assigned into the normal group （normal saline）， model group （normal saline）， positive control （trimetazidine， 5.4 mg·kg^-1） group， and low-， medium-， and high-dose （1.63， 4.9， 14.7 g·kg^-1， respectively） Wutou Chishizhi Wan groups， with 10 rats in each group. The rats in other groups except the normal group underwent left anterior descending coronary artery ligation for modeling. Electrocardiogram was employed to detect the ST-segment elevation to evaluate the modeling. Hematoxylin-eosin （HE） staining was performed to reveal the damage of myocardial tissue. The levels of aspartate aminotransferase （AST） and creatine kinase （CK） were determined by colorimetry， and those of cardiac troponin T （cTnT） and myoglobin （MYO） by enzyme-linked immunosorbent assay （ELISA）. Western blot was carried out to determine the protein levels of microtubule-associated proteins 1 light chain 3 （LC3）， autophagy-related gene Beclin-1， PI3K， Akt， GSK-3β， p-GSK-3β， and p-Akt. ResultCompared with the normal group， the modeling elevated the serum levels of AST， CK， cTnT， and MYO （P<0.01）， destroyed the arrangement of myocardial cells abd nucle， twisted and broken myocardial fibers， up-regulated the protein levels of LC3Ⅱ/Ⅰ and Beclin-1 （P<0.01）， and down-regulated the protein levels of PI3K， p-Akt， and p-GSK-3β （P<0.01）. Compared with the model group， trimetazidine and Wutou Chishizhi Wan （all the doses） lowered the levels of AST， CK， cTnT， and MYO in serum （P<0.01）， restored the arrangement of myocardial cells and muscle fibers， reduced necrosis， down-regulated the protein level of Beclin-1 （P<0.01）， and up-regulated the protein levels of PI3K， p-Akt， and p-GSK-3β （P<0.01）. Additionally， Wutou Chishizhi Wan （all the doses） down-regulated the protein level of LC3Ⅱ/Ⅰ （P<0.05， P<0.01）. Compared with those in the trimetazidine group， the serum AST level rose in the low-dose Wutou Chishizhi Wan group （P<0.05） and declined in the high-dose group （P<0.01）， and the protein level of Beclin-1 was down-regulated in the medium-dose group （P<0.01）. Additionally， the trimetazidine group had higher protein level of LC3Ⅱ/Ⅰ than medium- and high-dose Wutou Chishizhi Wan groups （P<0.05， P<0.01）， higher protein level of PI3K than low-， medium-， and high-dose groups （P<0.01）， lower protein level of p-Akt than low- and medium-dose groups （P<0.01）， and higher p-GSK-3β protein level than the medium-dose group （P<0.01）. ConclusionDifferent doses of Wutou Chishizhi Wan can ameliorate MIRI， and the high dose has the best effect. Wutou Chishizhi Wan can reduce the activity of myocardial injury markers AST， CK， cTnT， and MYO， and alleviate the pathological damage of myocardial tissue. It can down-regulate the protein levels of beclin-1， LC3Ⅱ/Ⅰ， and up-regulate those of PI3K， p-Akt， and p-GSK-3β. In summary， Wutou Chishizhi Wan may inhibit excessive autophagy and regulate the PI3K/Akt/GSK-3β signaling pathway to exert protective effect on MIRI rats.

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases