ObjectiveTo investigate the effects of Erchentang （ECD） on the body weight of the mouse model of simple obesity induced by a high-fat diet （HFD） and decipher the underlying mechanisms. MethodsFirstly， single-cell transcriptomics （Sc-RNAseq） was employed to analyze the transcriptional changes in the ileum tissue of mice in the normal group and model group. Then， a mouse model of simple obesity was established with a high-fat diet. The successfully modeled mice were randomly allocated into the following four groups （n=8）： model， low-dose （7.5 g·kg^-1） ECD， medium-dose （15 g·kg^-1） ECD， and high-dose （30 g·kg^-1） ECD. Additionally， 8 mice of the same age were selected as the normal group. The body weight was measured at fixed time points during the 4-week gavage period. The overall efficacy of ECD in alleviating obesity was evaluated through glucose tolerance testing， behavioral analysis， hematoxylin-eosin （HE） staining， and biochemical testing. Protein docking was employed to predict the degree of binding between corresponding proteins. Molecular docking was employed to predict the binding degree between key components of ECD and target proteins. Real-time PCR was employed to determine the mRNA levels of tumor necrosis factor-α （TNF-α）， inducible nitric oxide synthase （iNOS）， interleukin-1β （IL-1β）， CD68， CD206， zonula occludens-1 （ZO-1）， and Claudin-5 in the ileum. Immunofluorescence staining was used to observe the expression and distribution of Claudin-5 and ZO-1. ResultsThe Sc-RNAseq results indicated that the differentially expressed genes of immune cells in the model group in comparison with the normal group were primarily enriched in biological functions related to lipid metabolism and inflammatory metabolism. Additionally， these genes were associated with the janus kinases（JAK）/signal transducers and activators of transcription （STAT） signaling pathway， an inflammation-related pathway. Compared with the normal group， the model group showed increases in body weight （P<0.01） and blood glucose level （P<0.01）， a decrease in limb strength （P<0.01）， an increase in liver weight （P<0.05）， and elevated serum alanine amino-transferase （ALT） and aspartate transferase （AST） levels （P<0.05， P<0.01）. Additionally， the model group exhibited increased hepatic fat vacuoles， notably enlarged adipocytes in the epididymal and inguinal white adipose tissue， and increased inflammation. Compared with the model group， ECD groups showed reduced body weights （P<0.01） and blood glucose levels （P<0.01）， increased limb strength （P<0.05， P<0.01）， decreased liver weights （P<0.05， P<0.01）， and declined serum ALT and AST levels （P<0.05， P<0.01）. Additionally， ECD reduced hepatic fat vacuoles and the adipocyte volume in the epididymal and inguinal white adipose tissue， and alleviated inflammation. Potential interactions existed between CD68 and ZO-1/Claudin-5， as well as between CD206 and ZO-1/Claudin-5. The key components of ECD， nobiletin， diosmetin， and naringenin， all demonstrated strong binding affinity with the target proteins ZO-1 and Claudin-5. Compared with the normal group， the model group exhibited up-regulated mRNA levels of the pro-inflammatory cytokines TNF-α， iNOS， IL-1β， and CD68 （P<0.05， P<0.01） and down-regulated mRNA levels of the anti-inflammatory cytokine CD206 （P<0.01） and the tight junction proteins Claudin-5 and ZO-1 （P<0.05， P<0.01）. In comparison with the model group， the ECD groups showed down-regulated mRNA levels of TNF-α， iNOS， IL-1β， and CD68 （P<0.05， P<0.01） and up-regulated mRNA levels of CD206， Claudin-5， and ZO-1 （P<0.05， P<0.01）. Compared with the normal group， the model group exhibited down-regulated expression of tight junction proteins Claudin-5 and ZO-1 （P<0.01）. Compared with the model group， ECD groups showed up-regulated expression of Claudin-5 and ZO-1 （P<0.05， P<0.01）. ConclusionECD can significantly ameliorate HFD-induced obesity and excessive body weight gain in mice by improving the inflammatory microenvironment in the ileum and further restoring the integrity of the impaired ileal barrier.

Alzheimer's disease (AD), a progressive dementia, is one of the most common neurodegenerative diseases. Clinical trial results of amyloid-β (Aβ) and tau regulators based on the pretext of straightforward amyloid and tau immunotherapy were disappointing. There are currently no effective strategies for slowing the progression of AD. Herein, we spotlight the dysregulation of lipid metabolism, particularly the elevation of ceramides (Cers), as a critical yet underexplored facet of AD pathogenesis. Our study delineates the role of Cers in promoting microglial pyroptosis, a form of programmed cell death distinct from apoptosis and necroptosis, characterized by cellular swelling, and membrane rupture mediated by the NLRP3 inflammasome pathway. Utilizing both in vivo experiments with amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice and in vitro assays with BV-2 microglial cells, we investigate the activation of microglial pyroptosis by Cers and its inhibition by icariin (ICA), a flavonoid with known antioxidant and anti-inflammatory properties. Our findings reveal a significant increase in Cers levels and pyroptosis markers (NOD-like receptor family, pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain, caspase-1, gasdermin D (gasdermin D (GSDMD)), and interleukin-18 (IL-18)) in the brains of AD model mice, indicating a direct involvement of Cers in AD pathology through the induction of microglial pyroptosis. Conversely, ICA treatment effectively reduces these pyroptotic markers and Cer levels, thereby attenuating microglial pyroptosis and suggesting a novel therapeutic mechanism of action against AD. This study not only advances our understanding of the pathogenic role of Cers in AD but also introduces ICA as a promising candidate for AD therapy, capable of mitigating neuroinflammation and pyroptosis through the cyclooxygenase-2 (COX-2)-NLRP3 inflammasome-gasdermin D (GSDMD) axis. Our results pave the way for further exploration of Cer metabolism disorders in neurodegenerative diseases and highlight the therapeutic potential of targeting microglial pyroptosis in AD.

Alzheimer's disease(AD),a progressive dementia,is one of the most common neurodegenerative dis-eases.Clinical trial results of amyloid-β(Aβ)and tau regulators based on the pretext of straightforward amyloid and tau immunotherapy were disappointing.There are currently no effective strategies for slowing the progression of AD.Herein,we spotlight the dysregulation of lipid metabolism,particularly the elevation of ceramides(Cers),as a critical yet underexplored facet of AD pathogenesis.Our study delineates the role of Cers in promoting microglial pyroptosis,a form of programmed cell death distinct from apoptosis and necroptosis,characterized by cellular swelling,and membrane rupture mediated by the NLRP3 inflammasome pathway.Utilizing both in vivo experiments with amyloid precursor protein(APP)/presenilin 1(PS1)transgenic mice and in vitro assays with BV-2 microglial cells,we investigate the activation of microglial pyroptosis by Cers and its inhibition by icariin(ICA),a flavonoid with known antioxidant and anti-inflammatory properties.Our findings reveal a significant increase in Cers levels and pyroptosis markers(NOD-like receptor family,pyrin domain containing 3(NLRP3),apoptosis-associated speck-like protein containing a caspase recruitment domain,caspase-1,gasdermin D(GSDMD),and interleukin-18(IL-18))in the brains of AD model mice,indicating a direct involvement of Cers in AD pathology through the induction of microglial pyroptosis.Conversely,ICA treatment effec-tively reduces these pyroptotic markers and Cer levels,thereby attenuating microglial pyroptosis and suggesting a novel therapeutic mechanism of action against AD.This study not only advances our un-derstanding of the pathogenic role of Cers in AD but also introduces ICA as a promising candidate for AD therapy,capable of mitigating neuroinflammation and pyroptosis through the cyclooxygenase-2(COX-2)-NLRP3 inflammasome-gasdermin D(GSDMD)axis.Our results pave the way for further exploration of Cer metabolism disorders in neurodegenerative diseases and highlight the therapeutic potential of tar-geting microglial pyroptosis in AD.

Objective:The study retrospectively analyzed the etiology, clinical manifestations, emergency treatment and etiological treatment of a large sample of cases with hypercalcemic crisis.Methods:The clincial data of patients with hypercalcaemia cirisis who were administered in First Medical Center of Chinese PLA General Hospital from January 2009 to July 2022 were analyzed, inculding the general data, clinical manifestations, etiology, photographic examination, emergency treatment, etiological treatment, serological examination before and after treatment, pathological immunohistochemical findings and prognosis.Results:A total of 143 hypercalcaemia crisis patients(84 males and 59 females) with a mean age of 53.51±16.60 were enrolled. The most common disease was hyperparathyroidism(62/143), followed by solid malignancy(57/143) and multiple myeloma(12/143). Patients presented with digestive system symptoms at 76.91%, followed by neurological symptoms at 63.60%, urinary system symptoms at 58.76%, musculoskeletal symptoms at 55.23%, and cardiovascular system symptoms at 32.91%. After emergency calcium-lowering treatment, the remission rate of hypercalcemic crisis in 143 patients was 100%(143/143), and after etiological treatment, the remission rate of hypercalcemia was 85.31%(122/143).Conclusion:Early identification, emergency treatment and etiology treatment of hypercalcaemia crisis are essential. Effective treament with comprehensive calcium reduction can quickly relieve clinical symptoms and create opportunities for treatment for the cause. Targeted etiological interventions can lead to the correction or long-term remission of hypercalcemia.

Effective referral management of health and clinical services in maternal and child health hospitals plays an important role in enhancing patients′ medical experience, improving the efficiency and quality of maternal and child health services. A tertiary grade A maternal and child health hospital has carried out a practice of health and clinical service referral management based on information technology construction. A referral information module embedded in the hospital information system has been designed and constructed, and started to be applied in outpatient clinics in July 2021. At the same time, corresponding system and process construction, as well as quality control management and continuous improvement, have been carried out. The outpatient referral rate from July to December 2021 was 2.8% (11 466/412 808), from January to June 2022 it was 5.6% (22 705/402 586), from July to December 2022 it was 5.5% (22 233/402 959), and from January to June 2023 it was 6.7% (23 373/347 898). The referral rate has continued to improve and can provide reference for the referral management of other maternal and child health institutions.

African swine fever virus(ASFV)I177L gene deletion vaccine is one of the key directions of African swine fever(ASF)live attenuated vaccine research and development.In order to effec-tively distinguish between the wild-type ASFV strain and the I177L gene-deleted strain,specific primers and probes were designed based on ASFV B646L and I177L genes,respectively.After screening and optimization,a duplex real-time PCR method was developed that can simultaneously detect these two genes.The results showed that ASFV B646L and I177L genes were detected spe-cifically and simultaneously by the method developed without cross-reactions with porcine circovir-us type 2,Seneca virus A,classical swine fever virus,foot-and-mouth disease virus,porcine respira-tory and reproductive syndrome virus.The detection limits of the duplex real-time PCR for recom-binant plasmids pUC57-B646L and pUC57-I177L were 1×103 copies/mL.The intra-and inter-as-say coefficients of variation were less than 4％,respectively.Detection of 122 pork and pork prod-ucts using the duplex real-time PCR developed and the real-time PCR recommended by WOAH showed that the coincidence rates of the two methods for B646L gene detection was 100％with two amplification curves appeared in the positive results of the established methods.The method established in this study can be used for the detection of ASFV I177L gene deletion strains,which provides technical support for ASF surveillance and epidemiological investigation.

Objective:To actively monitor and analyze the safety of levofloxacin and sodium chloride injection produced by Guangzhou Green Cross Pharmaceutical Co., Ltd (generic drug). and levofloxacin and sodium chloride injection produced by Daiichi Sankyo (Beijing) Pharmaceutical Co., Ltd (original drug).Methods:The data in this study came from the adverse drug reaction reports on levofloxacin and sodium chloride injection voluntarily monitored and reported to the National Adverse Drug Reaction Monitoring System Database by the First Affiliated Hospital of Sun Yat-sen University, Guangdong Provincial People′s Hospital, and the First Affiliated Hospital of Ji'nan University from October 1, 2022, to September 30, 2023. The information on patients′age, gender, medication use, primary disease, time from medication to the occurrence of adverse reactions, clinical manifestations, treatment and prognosis of adverse reactions, and the occurrence of serious adverse reactions were collected. The incidence of adverse reactions was calculated.Results:A total of 30 adverse reaction reports involving levofloxacin and sodium chloride injection were collected, involving 30 patients. In the generic drug group, there were 21 cases, including 8 males and 13 females, aged from 20 to 91 years with a median age of 43 years; 2 cases of serious adverse reactions were reported. In the original drug group, there were 9 cases, including 3 males and 6 females, aged from 20 to 96 years with a median age of 56 years; no serious adverse reactions were reported. In the generic drug group, a total of 36 adverse reactions occurred in 21 patients, while in the original drug group, a total of 13 adverse reactions occurred in 9 patients. These adverse reactions involved the skin and appendages, digestive system, nervous system, musculoskeletal system, urinary system, and medication site, with skin itching and rash being the most common allergic reactions (15 case time in the generic drug group, accounting for 41.7%; 6 case time in the original drug group, accounting for 46.2%). Two cases of serious adverse reactions occurred in the generic drug group, and both were anaphylactic shock. After discontinuation of the drug, switching to other antibiotics, and symptomatic treatments, 5 cases in the generic drug group were cured, 15 cases were improved, and 1 case was unknown. In the original research drug group, 2 cases were cured and 7 cases were improved. There were no deaths in either the generic or original drug groups. The incidence of adverse reactions in outpatients and/or inpatients in the generic drug group was 0.07% (21/29 557), while that in the original research drug group was 0.08% (9/10 686). There was no statistically significant difference between the 2 groups ( χ2=0.183, P=0.669). Conclusion:The results of active monitoring show that there is no significant difference in safety between the generic and original drugs of levofloxacin and sodium chloride injection.

Objective:To actively monitor and analyze the safety of levofloxacin and sodium chloride injection produced by Guangzhou Green Cross Pharmaceutical Co., Ltd (generic drug). and levofloxacin and sodium chloride injection produced by Daiichi Sankyo (Beijing) Pharmaceutical Co., Ltd (original drug).Methods:The data in this study came from the adverse drug reaction reports on levofloxacin and sodium chloride injection voluntarily monitored and reported to the National Adverse Drug Reaction Monitoring System Database by the First Affiliated Hospital of Sun Yat-sen University, Guangdong Provincial People′s Hospital, and the First Affiliated Hospital of Ji'nan University from October 1, 2022, to September 30, 2023. The information on patients′age, gender, medication use, primary disease, time from medication to the occurrence of adverse reactions, clinical manifestations, treatment and prognosis of adverse reactions, and the occurrence of serious adverse reactions were collected. The incidence of adverse reactions was calculated.Results:A total of 30 adverse reaction reports involving levofloxacin and sodium chloride injection were collected, involving 30 patients. In the generic drug group, there were 21 cases, including 8 males and 13 females, aged from 20 to 91 years with a median age of 43 years; 2 cases of serious adverse reactions were reported. In the original drug group, there were 9 cases, including 3 males and 6 females, aged from 20 to 96 years with a median age of 56 years; no serious adverse reactions were reported. In the generic drug group, a total of 36 adverse reactions occurred in 21 patients, while in the original drug group, a total of 13 adverse reactions occurred in 9 patients. These adverse reactions involved the skin and appendages, digestive system, nervous system, musculoskeletal system, urinary system, and medication site, with skin itching and rash being the most common allergic reactions (15 case time in the generic drug group, accounting for 41.7%; 6 case time in the original drug group, accounting for 46.2%). Two cases of serious adverse reactions occurred in the generic drug group, and both were anaphylactic shock. After discontinuation of the drug, switching to other antibiotics, and symptomatic treatments, 5 cases in the generic drug group were cured, 15 cases were improved, and 1 case was unknown. In the original research drug group, 2 cases were cured and 7 cases were improved. There were no deaths in either the generic or original drug groups. The incidence of adverse reactions in outpatients and/or inpatients in the generic drug group was 0.07% (21/29 557), while that in the original research drug group was 0.08% (9/10 686). There was no statistically significant difference between the 2 groups ( χ2=0.183, P=0.669). Conclusion:The results of active monitoring show that there is no significant difference in safety between the generic and original drugs of levofloxacin and sodium chloride injection.

Objective:Development and validation of a nomogram for predicting the 4-year incidence of type-2 diabetes mellitus (T2DM) in a Chinese population was attempted.Methods:This prospective cohort study was conducted in Shijingshan District Pingguoyuan Community (Beijing, China) from December 2011 to April 2012 among adults aged≥40 years not suffering from T2DM. Finally, 8 058 adults free of T2DM were included with a median duration of follow-up of 4 years. Participants were divided into a modeling group and verification group using simple random sampling at a ratio of 7∶3. Univariate and multivariate Cox proportional risk models were applied to identify the independent risk predictors in the modeling group. A nomogram was constructed to predict the 4-year incidence of T2DM based on the results of multivariate analysis. The Concordance Index and calibration plots were used to evaluate the differentiation and calibration of the nomogram in both groups.Results:A total of 5 641 individuals were in the modeling group and 2 417 people were in the validation group, of which 265 and 106 had T2DM, respectively, at 4-year follow-up. In the modeling group, age ( HR=1.349, 95% CI 1.011-1.800), body mass index ( HR=1.347, 95% CI 1.038-1.746), hyperlipidemia ( HR=1.504, 95% CI 1.133-1.996), fasting blood glucose ( HR=4.189, 95% CI 3.010-5.830), 2-h blood glucose level according to the oral glucose tolerance test ( HR=3.005, 95% CI 2.129-4.241), level of glycosylated hemoglobin ( HR=3.162, 95% CI 2.283-4.380), and level of γ-glutamyl transferase ( HR=1.920, 95% CI 1.385-2.661) were independent risk factors for T2DM. Validation of the nomogram revealed the Concordance Index of the modeling group and validation group to be 0.906 (95% CI 0.888-0.925) and 0.844 (95% CI 0.796-0.892), respectively. Calibration plots showed good calibration in both groups. Conclusion:These data suggest that our nomogram could be a simple and reliable tool for predicting the 4-year risk of developing T2DM in a high-risk Chinese population.

Objective:To explore the characteristics of the association between the triglyceride glucose (TyG) index and nonfatal cardio-cerebrovascular disease risk in a community population.Method:This was a prospective cohort study. From December 2011 to April 2012, the first investigation was conducted among subjects with more than 40-year old who were from Shijingshan district and Pingguoyuan community in Beijing. The second investigation was conducted from April to October 2015. All the subjects were divided into three groups according to the tertile of the TyG index at baseline. The multivariate Cox proportional risk regression model was established to explore the correlation between the TyG index and nonfatal cardio-cerebrovascular disease risk and the Kaplan-Meier survival curve of the TyG index group was drawn. Subgroup analyses were performed according to age, gender, body mass index, type 2 diabetes mellitus (T2DM), hypertension, and hyperlipidemia to determine the correlation characteristics between the TyG index and nonfatal cardio-cerebrovascular disease among subgroups.Results:A total of 9 577 subjects were finally included to analyze. The mean follow-up time of this study was (34.14±3.84) months. During the follow-up, 363 subjects (3.8%) occurred nonfatal cardio-cerebrovascular disease. The multivariate Cox regression analysis results showed that the hazard ratio ( HR) of nonfatal cardio-cerebrovascular disease in the high TyG index group was 1.54 (95% CI 1.19-1.98), 1.60 (95% CI 1.23-2.10), and 1.57 (95% CI 1.20-2.05) in the three models, compared with the low TyG index group. The Kaplan-Meier analysis showed that the risk of nonfatal cardio-cerebrovascular disease increased from the low-TyG index group to the high-TyG index group ( P=0.015). In the six subgroups analysis, only gender was shown to have a significant interaction effect with the TyG index and nonfatal cardio-cerebrovascular disease risk. In the female population, the risk of nonfatal cardio-cerebrovascular disease is significantly increased with the increase in the TyG index level ( P<0.001). Conclusions:A high TyG index is independently related to the increased risk of nonfatal cardio-cerebrovascular disease in the Beijing community population. Gender has a significant interaction with the TyG index and nonfatal cardio-cerebrovascular disease risk. Therefore, the TyG index may be a useful marker to predict the nonfatal cardio-cerebrovascular disease risk of a community population.