ObjectiveTo explore the effects of Kaixuan Jiedu core prescription （KXJD） on sphingolipid metabolism in the mouse model of imiquimod-induced psoriasis-like skin lesions. MethodsThirty-seven male C57BL/6J mice were randomly assigned into five groups： healthy control （n=11）， model （n=11）， methotrexate （MTX， n=5）， low-dose （15.21 g·kg^-1） KXJD （n=5）， and high-dose （30.42 g·kg^-1） KXJD （n=5）. Psoriasis-like skin lesions were induced in mice with 62.5 mg 5% imiquimod cream applied on the back. The KXJD groups and MTX group were treated with 0.2 mL corresponding decoction and MTX， respectively， by gavage daily， while the other groups were given an equal volume of normal saline by the same way. After 5 days of treatment， back skin lesions were collected. Firstly， healthy control and model mice were selected for tandem mass tag （TMT） quantitative proteomics （control vs model=3 vs 3） and targeted lipid metabolomics （control vs model=11 vs 11）. Then， the binding degree between core components and target proteins was predicted via network pharmacology and molecular docking. Finally， an animal experiment was performed to decipher the specific regulation mechanism of KXJD on sphingolipid metabolism. Immunohistochemistry was employed to determine the expression level of sphingosine-1-phosphate （S1P）， and Western blot was employed to determine the expression levels of sphingosine kinase 2 （SPHK2） and monocyte chemotactic protein-1 （MCP-1）. ResultsTMT proteomics and targeted lipid metabolomics suggested that sphingolipid metabolism was active in the psoriatic skin， and key proteases ［serine palmitoyltransferase， long chain base subunit 2 （SPTLC2）， SPHK2， delta（4）-desaturase sphingolipid 1 （Degs1）， and ceramide synthase 4 （CerS4）］ and 8 sphingolipid metabolites （including ceramides， sphingol， sphingomyelin， and glycosphingolipid） expressed abnormally （P<0.05） compared with those in the healthy skin. The molecular docking results indicated that the binding energy between the active components （quercetin， kaempferol， and luteolin） in KXJD and key proteins involved in sphingolipid metabolism was less than-8 kal·mol^-1. Further experimental verification showed elevated expression levels of SPHK2， S1P， and MCP-1 in psoriatic skin compared with healthy skin （P<0.05）， and KXJD down-regulated the expression levels of SPHK2， S1P， and MCP-1 compared with the model group （P<0.05）. ConclusionThis study indicates that there is an imbalance in sphingolipid metabolism in psoriatic skin lesions. KXJD may reduce psoriasis-like lesions in mice by regulating sphingolipid metabolism via the SPHK2/S1P/MCP-1 pathway.

ObjectiveTo explore the effects of Kaixuan Jiedu core prescription （KXJD） on sphingolipid metabolism in the mouse model of imiquimod-induced psoriasis-like skin lesions. MethodsThirty-seven male C57BL/6J mice were randomly assigned into five groups： healthy control （n=11）， model （n=11）， methotrexate （MTX， n=5）， low-dose （15.21 g·kg^-1） KXJD （n=5）， and high-dose （30.42 g·kg^-1） KXJD （n=5）. Psoriasis-like skin lesions were induced in mice with 62.5 mg 5% imiquimod cream applied on the back. The KXJD groups and MTX group were treated with 0.2 mL corresponding decoction and MTX， respectively， by gavage daily， while the other groups were given an equal volume of normal saline by the same way. After 5 days of treatment， back skin lesions were collected. Firstly， healthy control and model mice were selected for tandem mass tag （TMT） quantitative proteomics （control vs model=3 vs 3） and targeted lipid metabolomics （control vs model=11 vs 11）. Then， the binding degree between core components and target proteins was predicted via network pharmacology and molecular docking. Finally， an animal experiment was performed to decipher the specific regulation mechanism of KXJD on sphingolipid metabolism. Immunohistochemistry was employed to determine the expression level of sphingosine-1-phosphate （S1P）， and Western blot was employed to determine the expression levels of sphingosine kinase 2 （SPHK2） and monocyte chemotactic protein-1 （MCP-1）. ResultsTMT proteomics and targeted lipid metabolomics suggested that sphingolipid metabolism was active in the psoriatic skin， and key proteases ［serine palmitoyltransferase， long chain base subunit 2 （SPTLC2）， SPHK2， delta（4）-desaturase sphingolipid 1 （Degs1）， and ceramide synthase 4 （CerS4）］ and 8 sphingolipid metabolites （including ceramides， sphingol， sphingomyelin， and glycosphingolipid） expressed abnormally （P<0.05） compared with those in the healthy skin. The molecular docking results indicated that the binding energy between the active components （quercetin， kaempferol， and luteolin） in KXJD and key proteins involved in sphingolipid metabolism was less than-8 kal·mol^-1. Further experimental verification showed elevated expression levels of SPHK2， S1P， and MCP-1 in psoriatic skin compared with healthy skin （P<0.05）， and KXJD down-regulated the expression levels of SPHK2， S1P， and MCP-1 compared with the model group （P<0.05）. ConclusionThis study indicates that there is an imbalance in sphingolipid metabolism in psoriatic skin lesions. KXJD may reduce psoriasis-like lesions in mice by regulating sphingolipid metabolism via the SPHK2/S1P/MCP-1 pathway.

Objective: To investigate the urban and rural differences in adverse outcomes of pulmonary tuberculosis (PTB) in patients with pulmonary tuberculosis-diabetes mellitus comorbidity (PTB-DM), so as to provide insights into improving the prevention and treatment measures for PTB-DM. Methods: Patients with PTB-DM who were admitted and discharged from 14 designated tuberculosis hospitals in Hangzhou City from 2018 to 2022 were selected. Basic information, and history of diagnosis and treatment were collected through hospital information systems. The adverse outcomes of PTB were defined as endpoints, and the proportions of adverse outcomes of PTB in urban and rural patients with PTB-DM were analyzed. Factors affecting the adverse outcomes of PTB were identified using a multivariable Cox proportional hazards regression model. Results: A total of 823 patients with PTB-DM were enrolled, including 354 (43.01%) urban and 469 (56.99%) rural patients. There were 112 (13.61%) patients with adverse outcomes of PTB. The proportions of adverse outcomes of PTB in urban and rural patients were 14.41% and 13.01%, respectively, with no statistically significant difference (P>0.05). Multivariable Cox proportional hazards regression analysis identified first diagnosed in county-level hospitals or above (HR=2.107, 95%CI: 1.181-3.758) and drug resistance (HR=3.303, 95%CI: 1.653-6.600) as the risk factors for adverse outcomes of PTB in urban patients with PTB-DM, while the treatment/observed management throughout the process (HR=0.470, 95%CI: 0.274-0.803) and fixed-dose combinations throughout the process (HR=0.331, 95%CI: 0.151-0.729) as the protective factors for adverse outcomes in rural patients with PTB-DM. Conclusions There are differences in influencing factors for adverse outcomes of PTB in urban and rural patients with PTB-DM. The adverse outcomes of PTB are associated with first diagnosed hospitals and drug resistance in urban patients, and are associated with the treatment/observed management and fixed-dose combinations throughout the process in rural patients.

ObjectiveTo investigate a suspected outbreak of healthcare-associated infection with carbapenem-resistant Klebsiella pneumoniae (CRKP) in a geriatric emergency ward, and to provide references for the prevention and control of multidrug-resistant bacteria in a hospital in Shanghai. MethodsOn-site epidemiological investigation, combined with environmental hygiene monitoring and pulsed field gel electrophoresis (PFGE) molecular typing method, were adopted to investigate a suspected outbreak of CRKP infection in the geriatric emergency ward of a hospital from October to November 2022, aiming at finding out factors caused the outbreak before taking corresponding control measures. ResultsA total of 3 cases of healthcare-associated CRKP infection were identified, of which 2 cases were homologous to a previous case of community-associated CRKP infection. What’s more, the 2 cases lived in the same ward with the latter and with adjacent beds, but the third case was non-homologous to the community-associated infection case. A total of 46 samples were collected from the environmental surfaces and the hands of healthcare workers, of which 7 samples tested positive for CRKP and were identical to the strains from the 2 healthcare-associated infection cases and the 1 community-associated infection case, originating from the bedrails, bedside tables, surface of non-invasive ventilator, bed curtains and panels of monitoring equipment, with a detection rate of 15.22%. But none of the 11 samples from the hands of healthcare workers tested positive for CRKP. The outbreak was effectively controlled after taking specific prevention and control measures such as strengthening personnel management, intensifying environmental cleaning and disinfection and strictly enforcing hand hygiene among healthcare workers. Subsequently, no similar new cases were reported during the 14-day follow-up period. ConclusionIncomplete environmental cleaning and disinfection, as well as inadequate enforcement of hand hygiene among heatheare workers may have contributed to the suspected outbreak of CRKP in the geriatric emergency ward. Early warning and timely investigation of suspected outbreaks of multidrug-resistant bacteria are crucial for preventing and controlling such outbreaks in hospitals.

ObjectiveTo investigate the value of Fried Frailty Phenotype （FFP）， liver frailty index （LFI）， and Short Physical Performance Battery （SPPB） in predicting 2-year all-cause mortality and decompensation events in patients with liver cirrhosis. MethodsA total of 277 patients with liver cirrhosis who were hospitalized in Beijing Friendship Hospital， Capital Medical University， from December 2020 to December 2021 were enrolled， and FFP， LFI， and SPPB were used to assess the state of frailty. Based on the scores of each tool， these patients were divided into frail and non-frail groups. These three tools were compared in terms of consistency and independent predictive performance. The primary endpoints were 2-year all-cause mortality rate and composite endpoints （death+decompensation events）， and the Cox regression analysis， the receiver operating characteristic （ROC） curve， net reclassification index （NRI）， and integrated discrimination improvement （IDI） index were used to analyze the predictive value of the three tools. Normally distributed continuous data were compared between two groups using the independent samples t-test， while non-normally distributed continuous data were compared using the Mann-Whitney U test. Categorical data were compared between groups using the chi-square test or Fisher’s exact test. The agreement among different frailty tools was evaluated using Cohen’s Kappa statistic. The Kaplan-Meier survival curve was plotted， and a survival analysis was performed using the log-rank test. ResultsThe prevalence rate of frailty assessed by FFP， LFI， and SPPB was 37.2%， 22.4%， and 20.2%， respectively， with a moderate consistency between FFP and LFI/SPPB （κ=0.57， 95% confidence interval ［CI］： 0.47 — 0.67； κ=0.51， 95%CI： 0.41 — 0.62） and a relatively high consistency between LFI and SPPB （κ=0.87， 95%CI： 0.80 — 0.94）. Compared with the non-frailty group， the frailty group had significantly higher all-cause mortality rate and incidence rate of composite endpoints （P0.001）. After multivariate adjustment， FFP， LFI， and SPPB had a hazard ratio of 2.42（95%CI： 1.51 — 5.11）， 2.21（95%CI： 1.11 — 4.42）， and 2.21（95%CI： 1.14 — 4.30）， respectively， in predicting all-cause mortality， as well as a hazard ratio of 2.51（95%CI： 1.61 — 3.91）， 2.40（95%CI： 1.51 — 3.80）， and 2.20（95%CI： 1.39 — 3.47）， respectively， in predicting composite endpoints. Compared with Child-Pugh score， FFP had a significantly greater area under the ROC curve （AUC） in predicting all-cause mortality （0.79 vs 0.69， P=0.032） and composite endpoints （0.75 vs 0.68， P=0.044）. Frailty assessment tools combined with Child-Pugh score significantly improved the performance in predicting all-cause mortality and composite endpoints， with an AUC of 0.81 — 0.82 and 0.77 — 0.78， respectively （P0.05）. NRI and IDI analyses further confirmed the improvement of the combined model in classification （all P0.001）. ConclusionFFP， LFI， and SPPB can independently predict adverse outcomes in patients with liver cirrhosis， among which FFP has the best predictive performance， and the combination of frailty assessment tools with Child-Pugh score can significantly enhance the accuracy of prognostic evaluation.

ObjectiveTo investigate the influence of triglyceride （TG）/high-density lipoprotein cholesterol （HDL-C） ratio on the onset of primary liver cancer. MethodsA prospective cohort study was conducted. Physical examination data were collected from 99 750 cases of on-the-job and retired employees of Kailuan Group who participated health examination from July 2006 to December 2007， and they were followed up till December 31， 2021 to observe the onset of primary liver cancer. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the Kruskal-Wallis H test was used for comparison of continuous data with skewed distribution between multiple groups； the chi-square test was used for comparison of categorical data between groups. According to the tertiles of TG/HDL-C ratio， the subjects were divided into Q1， Q2， and Q3 groups， and the incidence density of primary liver cancer was calculated for each group. The Kaplan-Meier method was used to calculate the cumulative incidence rate of primary liver cancer in each group， and the log-rank test was used to compare the difference in cumulative incidence rate between groups. The Cox proportional hazards model was used to analyze the influence of TG/HDL-C ratio on the onset of primary liver cancer. ResultsThere were significant differences between the three groups in age， proportion of male subjects， waist circumference， body mass index， fasting blood glucose， systolic pressure， diastolic pressure， triglyceride， total cholesterol， HDL-C， low-density lipoprotein cholesterol， alanine aminotransferase， high-sensitivity C-reactive protein， chronic liver diseases， hypertension， diabetes， the family history of malignant tumor， drinking， smoking， physical exercise， and educational level （P<0.05）. During the mean follow-up time of 14.06±2.71 years， there were 484 cases of new-onset liver cancer， among whom there were 446 male subjects and 38 female subjects. The incidence density of primary liver cancer was 0.39/1 000 person-years in the Q1 group， 0.35/1 000 person-years in the Q2 group， and 0.30/1 000 person-years in the Q3 group， and the cumulative incidence rates of primary liver cancer in the three groups were 6.03‰， 5.28‰， and 4.49‰， respectively， with a significant difference between the three groups based on the long-rank test （χ²=6.06， P=0.048）. After adjustment for the confounding factors considered， the Cox proportional hazards model showed that compared with the Q3 group， the Q1 group had a hazard ratio of 2.04 （95% confidence interval ［CI］： 1.61‍ ‍—‍ ‍2.58， P_{for trend}<0.05）， and the Q2 group had a hazard ratio of 1.53 （95%CI： 1.21‍ ‍—‍ ‍1.92， P_{for trend}<0.05）. ConclusionThe reduction in TG/HDL-C ratio is associated with an increase in the rask of primary liver cancer， especially in people with chronic liver diseases.

ObjectiveTo explore the therapeutic effect and mechanism of Guipitang on rats with myocardial ischemia. MethodFifty SD rats were divided into five groups： a control group， a model group， low and high-dose Guipitang （7.52， 15.04 g·kg^-1） groups， and a trimetazidine group （0.002 g·kg^-1）. By intragastric administration of vitamin D₃ and feeding rats with high-fat forage and injecting isoproterenol， the rat model of myocardial ischemia was established. After drug treatment of 15 d， an electrocardiogram （ECG） was performed to analyze the degree of myocardial injury. A fully automatic biochemical analyzer was used to detect the changes in the serum levels of total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C）. Hematoxylin-eosin （HE） staining and Masson staining were used to observe myocardial histopathological changes. TdT-mediated dUTP nick end labeling （TUNEL） staining was used to detect cardiomyocyte apoptosis. Western blot was adopted to detect the protein levels of extracellular signal-regulated kinase 1/2 （ERK1/2）， phospho-ERK1/2 （p-ERK1/2）， p38 mitogen-activated protein kinase （p38 MAPK）， phospho-p38 MAPK （p-p38 MAPK）， B-cell lymphoma-2 （Bcl-2）-associated X （Bax）， Bcl-2， and cleaved cysteine aspartate proteolytic enzyme （cleaved Caspase-3）. ResultCompared with the control group， the ECG S-T segment decreased in the model group. The serum levels of TC， TG， and LDL-C were increased significantly （P<0.05）. The arrangement of myocardial tissue was disordered， and the proportion of cardiomyocyte apoptosis increased. The protein levels of cleaved Caspase-3， Bax， and p-p38 MAPK in the heart were increased， and the Bcl-2 expression was decreased （P<0.05）. Compared with the model group， the S-T segment downward shift was restored in the low and high-dose Guipitang groups and trimetazidine group， and the levels of TC， TG， and LDL-C were decreased. The protein expression of cleaved Caspase-3 and Bax in the heart dropped， and p-p38 MAPK and p-ERK1/2 protein expressions increased significantly （P<0.05）. The degree of myocardial injury was alleviated， and the proportion of cardiomyocyte apoptosis decreased. Bcl-2 protein expression was increased significantly in the low-dose Guipitang group （P<0.05）. ERK1/2 and p38 MAPK proteins had no significant difference among different groups. ConclusionGuipitang could alleviate myocardial injury and inhibit cardiomyocyte apoptosis in rats by activating the expression of ERK1/2 and p38 MAPK.

Objective:To explore the therapeutic law of moxibustion in Professor Zhou Meisheng's medical manuscripts for epidemic hemorrhagic fever (EHF) based on data mining and knowledge map technology.Methods:The manuscript data of Professor Zhou Meisheng's moxibustion treatment of EHFwere collected from Infectious Diseases Department of Dangshan County People's Hospital from December 16, 1985 to December 25, 1987. Graphpad Grism 8.0 software was used for descriptive analysis. PHP 5.4 program code was used for association rule analysis. SPSS Statistics 26.0 was used for clustering analysis. Neo4j Community 3.5.25 database was used to analyze the syndrome-weight graph.Results:205 prescriptions were included. There were 21 symptoms with frequency>40, in which the frequency of aversion to cold, fever, rash and irritability was 100%. The main types of moxibustion methods used in the treatment included moxibustion frame fumigation moxibustion, Wanying acupoint moxibustion pen moxibustion, and fire needle instead of moxibustion. There were 29 acupoints with a frequency of >25, including Zhongwan (CV12), Shenshu (BL23) and Mingmen (DU4), etc. Association rules showed that Sanyinjiao (SP6)-Zhongwan (CV12)-Feishu (BL13)-Shenshu (BL23)-Zhiyang (DU9) had the highest correlation. Six effective clustering combinations of moxibustion for EHF were summarized by clustering analysis. The weight graph can obtained the first 30 relationships with high correlation of target syndromes.Conclusions:Professor Zhou applied the idea of "moxibustion for heat syndrome" to the treatment of EHF, and took the method of "acupoint selection according to symptoms" as the main acupoint selection idea for moxibustion treatment of EHF. In clinical practice, moxibustion combined with auxiliary operation of TCM is often used to treat EHF, which can achieve good results.

Objective To explore the relationship and internal path between activities of daily living(ADL),sleep quality and mental health of community elderly people in Shanghai.Methods A questionnaire survey was conducted among community residents aged 60 years and older seeing doctors in community health care center of five streets in Shanghai during Sept to Dec,2021 using convenience sampling.Activities of Daily Living(ADL),Pittsburgh Sleep Quality Index(PSQI)and 10-item Kessler Psychological Distress Scale(K10)were adopted in the survey.Single factor analysis,correlation analysis and multiple linear regression were used to analyze the data.The effect relationship between the variables was tested using Bootstrap's mediated effects test.Results A total of 1 864 participants were included in the study.The average score was 15.53±4.47 for ADL,5.60±3.71 for PSQI and 15.50±6.28 for K10.The rate of ADL impairment,poor sleep quality,poor and very poor mental health of the elderly were 23.6%,27.3%,11.9%and 4.9%,respectively.ADL and sleep quality were all positively correlated with mental health(r=0.321,P＜0.001;r=0.466,P＜0.001);ADL was positively correlated with sleep quality(r=0.294,P＜0.001).Multiple linear results of factors influencing mental health showed that ADL(β= 0.457,95%CI:0.341-0.573),sleep quality(β =0.667,95%CI:0.598-0.737)and mental health were positively correlated(P＜0.001).Sleep quality partially mediated the relationship between ADL and mental health(95%CI:0.078-0.124)with an effect size of 33.0%.Conclusion Sleep quality is a mediator between ADL and mental health among community elderly people.Improving ADL and sleep quality may improve mental health in the population.

Objective To explore the clinical characteristics and treatment scheme of patients with spinal infection caused by Prevotella intermedia(P.intermedia).Methods Clinical diagnosis and treatment processes of a patient with spinal infection caused by P.intermedia admitted to the spinal surgery department of a hospital were summa-rized,and relevant literature was retrieved from database for reviewing.Results The patient,a 50 year old male,was admitted to the hospital due to"lumbago pain complicated with pain in double lower extremities for 2 months".The lesion tissue was taken for metagenomic next-generation sequencing(mNGS)detection,which detected P.in-termedia,and the patient was diagnosed with P.intermedia spondylitis.After treatments with open lesion clea-rance,tube rinsing+autologous bone transplantation fusion internal fixation,intravenous drip of ceftriaxone sodium and metronidazole,as well as metronidazole rinsing,infection was under control.A total of 16 available papers were retrieved,together with this case,a total of 17 patients were included,with 7 males and 10 females.The main risk factors were diabetes and history of corticosteroid use(35.3％).The most common invasion sites were lumbar ver-tebra(n=12)and thoracic vertebra(n=6).13 cases were positive for pathogen culture,3 cases were positive for molecular detection,and 1 case was positive for staining microscopy.17 patients received anti-anaerobic bacteria treatment,with 14 cases receiving combined surgical treatment.One case died,with a mortality of 5.9％;5 cases had partial neurological impairment,with a disability rate of 29.4％.The survival rate of patients who received treatment of anti-anaerobic bacteria combined with surgery was 92.8％,3 patients only with anti-anaerobic bacteria treatment but without surgery were all cured.Conclusion P.intermedia is an opportunistic pathogeanic bacteria which often causes infection in immunocomprised individuals and is prone to be misdiagnosed.It is recommended to perform mNGS detection to identify the pathogen as early as possible and seize the opportunity for treatment to reduce mortality.