This study aims to explore the medication rules and mechanisms of treating chronic renal failure(CRF) by Jinling medical school based on data mining, network pharmacology, and experimental validation systematically and deeply. Firstly, the study selected the papers published by the inherited clinicians in Jinling medical school in Chinese journals using the subject headings named "traditional Chinese medicine(TCM) + chronic renal failure", "TCM + chronic renal inefficiency", or "TCM + consumptive disease" in China National Knowledge Infrastructure, Wanfang, and VIP Chinese Science and Technology Periodical Database and screened TCM formulas for treating CRF according to inclusion and exclusion criteria. The study analyzed the frequency of use of single TCM and the four properties, five tastes, channel tropism, and efficacy of TCM used with high frequency and performed association rule and clustering analysis, respectively. As a result, a total of 215 TCM formulas and 235 different single TCM were screened, respectively. The TCM used with high frequency included Astragali Radix, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Poria, and Atractylodis Macrocephalae Rhizoma(top 5). The single TCM characterized by "cold properties, sweet flavor, and restoring spleen channel" and the TCM with the efficacy of tonifying deficiency had the highest frequency of use, respectively. Then, the TCM with the rules of "blood-activating and stasis-removing" and "diuretic and dampness-penetrating" appeared. In addition, the core combination of TCM [(Hexin Formula, HXF)] included "Astragali Radix, Rhei Radix et Rhizoma, Poria, Salviae Miltiorrhizae Radix, and Angelicae Sinensis Radix". The network pharmacology analysis showed that HXF had 91 active compounds and 250 corresponding protein targets including prostaglandin-endoperoxide synthase 2(PTGS2), PTGS1, sodium voltage-gated channel alpha subunit 5(SCN5A), cholinergic receptor muscarinic 1(CHRM1), and heat shock protein 90 alpha family class A member 1(HSP90AA1)(top 5). Gene Ontology(GO) function analysis revealed that the core targets of HXF predominantly affected biological processes, cellular components, and molecular functions such as positive regulation of transcription by ribonucleic acid polymerase Ⅱ and DNA template transcription, formation of cytosol, nucleus, and plasma membrane, and identical protein binding and enzyme binding. Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis revealed that CRF-related genes were involved in a variety of signaling pathways and cellular metabolic pathways, primarily involving "phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt) pathway" and "advanced glycation end products-receptor for advanced glycation end products". Molecular docking results showed that the active components in HXF such as isomucronulatol 7-O-glucoside, betulinic acid, sitosterol, and przewaquinone B might be crucial in the treatment of CRF. Finally, a modified rat model with renal failure induced by adenine was used, and the in vivo experimental confirmation was performed based on the above-mentioned predictions. The results verify that HXF can regulate mitochondrial autophagy in the kidneys and the PI3K-Akt-mammalian target of rapamycin(mTOR) signaling pathway activation at upstream, so as to alleviate renal tubulointerstitial fibrosis and then delay the progression of CRF.
Data Mining ; Drugs, Chinese Herbal/chemistry* ; Network Pharmacology ; Humans ; Kidney Failure, Chronic/metabolism* ; Medicine, Chinese Traditional ; China

Sleep is an instinctive behavior alternating awakening state, sleep entails many active processes occurring at the cellular, circuit and organismal levels. The function of sleep is to restore cellular energy, enhance immunity, promote growth and development, consolidate learning and memory to ensure normal life activities. However, with the increasing of social pressure involved in work and life, the incidence of sleep disorders (SD) is increasing year by year. In the short term, sleep disorders lead to impaired memory and attention; in the longer term, it produces neurological dysfunction or even death. There are many ways to directly or indirectly contribute to sleep disorder and keep the hormones, including pharmacological alternative treatments, light therapy and stimulus control therapy. Exercise is also an effective and healthy therapeutic strategy for improving sleep. The intensities, time periods, and different types of exercise have different health benefits for sleep, which can be found through indicators such as sleep quality, sleep efficiency and total sleep time. So it is more and more important to analyze the mechanism and find effective regulation targets during sleep disorder through exercise. Dopamine (DA) is an important neurotransmitter in the nervous system, which not only participates in action initiation, movement regulation and emotion regulation, but also plays a key role in the steady-state remodeling of sleep-awakening state transition. Appreciable evidence shows that sleep disorder on humans and rodents evokes anomalies in the dopaminergic signaling, which are also implicated in the development of psychiatric illnesses such as schizophrenia or substance abuse. Experiments have shown that DA in different neural pathways plays different regulatory roles in sleep behavior, we found that increasing evidence from rodent studies revealed a role for ventral tegmental area DA neurons in regulating sleep-wake patterns. DA signal transduction and neurotransmitter release patterns have complex interactions with behavioral regulation. In addition, experiments have shown that exercise causes changes in DA homeostasis in the brain, which may regulate sleep through different mechanisms, including cAMP response element binding protein signal transduction, changes in the circadian rhythm of biological clock genes, and interactions with endogenous substances such as adenosine, which affect neuronal structure and play a neuroprotective role. This review aims to introduce the regulatory effects of exercise on sleep disorder, especially the regulatory mechanism of DA in this process. The analysis of intracerebral DA signals also requires support from neurophysiological and chemical techniques. Our laboratory has established and developed an in vivo brain neurochemical analysis platform, which provides support for future research on the regulation of sleep-wake cycles by movement. We hope it can provide theoretical reference for the formulation of exercise prescription for clinical sleep disorder and give some advice to the combined intervention of drugs and exercise.

Spinal cord injury(SCI)is a structural and functional disruption of the spinal cord caused by various factors,leading to neurological dysfunction.As a common central nervous system disorder in clinical practice,SCI poses significant risks to human life and health.Its pathological mechanism is exceedingly complex,involving multiple pathological processes.Given the irreversibility of primary injury,targeting secondary injury has gradually become the main direction for the clinical treatment of SCI in recent years.Recent studies have highlighted the crucial role of blood-spinal cord barrier damage and microvascular dysfunction in the progression of secondary injury following SCI.Therefore,investigating the pathological mechanisms of microcirculation and exploring targeted therapies could provide valuable insights for clinical SCI treatment.This paper aims to provide an objective review of the role of microcirculation in SCI,identify the critical regulators of microvascular function,and summarize strategies for treating SCI by targeting microcirculation.The findings of this study may offer novel references for the clinical management of SCI.

Spinal cord injury(SCI)is a central nervous system disease with high morbidity and disability rates,bringing serious economic and psychological burdens to families and society worldwide.AMP-activated protein kinase(AMPK)is an important sensor in the energy metabolism process in living organisms,which plays a central role in maintaining energy balance.It is currently considered a key target for the prevention and treatment of multiple diseases.Studies have shown that AMPK signaling can regulate autophagy,neuroinflammation,oxidative stress,mitochondrial function and other processes after SCI,thus affecting the pathological process of SCI.This review summarizes the research progress on AMPK signaling pathway involved in the regulation of SCI,in order to provide new ideas for the treatment and drug development of SCI.

OBJECTIVE To investigate the clinical distribution and dynamic change of drug resistance of K.pneu-moniae and carbapenem-resistant Klebsiella pneumoniae(CRKP)isolated from a three-A hospital of Suzhou so as to provide scientific bases for prevention and control of hospital-associated infections and reasonable application of antibiotics.METHODS The K.pneumoniae and CRKP strains that were isolated from the submitted specimens were collected from the patients who treated in the Affiliated Suzhou Hospital of Nanjing Medical University from 2019 to 2023.The clinical characteristics of the patients with infection and the trend of drug resistance were statis-tically analyzed.RESULTS Totally 5631 strains of K.pneumoniae were isolated,1205(21.40％)of which were CRKP,and the isolation rate of CRKP showed an upward trend in the five years(x2=236.352,P＜0.001).Among the K.pneumoniae isolates,51.59％were isolated from sputum,13.51％from urine;19.43％were isolated from intensive care unit(ICU),7.64％from emergency department,and 7.19％from respiratory department.There were significant differences in gender,age and season between the patients detected with CRKP and the patients detected with non-CRKP(P＜0.05).The drug resistance rates of the K.pneumoniae strains to cephalosporins,quinolones and carbapenems con-tinuously increased from 2019 to 2023(P＜0.001),the drug resistance rate to imipenem increased from 11.69％to 34.24％,meropenem from 10.92％to 34.24％.CONCLUSIONS The K.pneumoniae isolates show severe drug re-sistance from 2019 to 2023,and the isolation rate of CRKP strains rises increasingly.It is necessary for the hospi-tal to focus on the continuous monitoring of key populations and departments and optimize the management of an-tibiotics and infection control strategies so as to provide guidance for reasonable clinical use of antibiotics,effective control of transmission of drug-resistant strains and cope with the increasingly severe drug resistance.

OBJECTIVE To investigate the clinical distribution and dynamic change of drug resistance of K.pneu-moniae and carbapenem-resistant Klebsiella pneumoniae(CRKP)isolated from a three-A hospital of Suzhou so as to provide scientific bases for prevention and control of hospital-associated infections and reasonable application of antibiotics.METHODS The K.pneumoniae and CRKP strains that were isolated from the submitted specimens were collected from the patients who treated in the Affiliated Suzhou Hospital of Nanjing Medical University from 2019 to 2023.The clinical characteristics of the patients with infection and the trend of drug resistance were statis-tically analyzed.RESULTS Totally 5631 strains of K.pneumoniae were isolated,1205(21.40％)of which were CRKP,and the isolation rate of CRKP showed an upward trend in the five years(x2=236.352,P＜0.001).Among the K.pneumoniae isolates,51.59％were isolated from sputum,13.51％from urine;19.43％were isolated from intensive care unit(ICU),7.64％from emergency department,and 7.19％from respiratory department.There were significant differences in gender,age and season between the patients detected with CRKP and the patients detected with non-CRKP(P＜0.05).The drug resistance rates of the K.pneumoniae strains to cephalosporins,quinolones and carbapenems con-tinuously increased from 2019 to 2023(P＜0.001),the drug resistance rate to imipenem increased from 11.69％to 34.24％,meropenem from 10.92％to 34.24％.CONCLUSIONS The K.pneumoniae isolates show severe drug re-sistance from 2019 to 2023,and the isolation rate of CRKP strains rises increasingly.It is necessary for the hospi-tal to focus on the continuous monitoring of key populations and departments and optimize the management of an-tibiotics and infection control strategies so as to provide guidance for reasonable clinical use of antibiotics,effective control of transmission of drug-resistant strains and cope with the increasingly severe drug resistance.

Objective To investigate the implementation of surveillance,prevention and control measures for healthcare-associated infection(HAI)in maternal and child healthcare(MCH)institutions,and provide policy evi-dence for optimizing HAI prevention and control in MCH institutions.Methods Stratified sampling was conducted among the MCH institutions at provincial,municipal and county levels in 8 provinces/autonomous regions.A uni-fied questionnaire was designed and the online survey was conducted through"Questionnaire Star".Results The data from 123 MCH institutions were included in the analysis.90.24％of the MCH institutions carried out compre-hensive surveillance on HAI.The ratios of MCH institutions which implemented targeted surveillance on HAI in neonatal intensive care unit(NICU),surgical site infection,multidrug-resistant organisms(MDROs)and HAI in intensive care units(non-NICU excluded)were 89.66％,85.96％,80.77％,and 74.19％,respectively.51.22％MCH institutions adopted information surveillance system on HAI cases.94.31％MCH institutions carried out surveillance on hand hygiene compliance.Over 90％MCH institutions carried out surveillance on environment hy-giene in high-risk departments.71.54％MCH institutions conducted centralized cleaning,disinfection,sterilization and supply for reusable medical instruments in the central sterile supply department(CSSD).Over 90％MCH insti-tutions established three-level pre-examination triage systems.86.18％set up transitional wards.MCH institutions generally adopted a management model with established effective communication,full appointment visits,and sepa-rate visits for special medical groups,such as registered pregnant women,high-risk newborns,healthcare groups,and long-term rehabilitation patients.However,the ratio of institutions conducting on-line follow-up visits was less than 50％.Conclusion MCH institutions have generally carried out comprehensive and targeted surveillance on HAI.Information surveillance need to be facilitated.Hand hygiene and environmental hygiene surveillance has been popularized to a certain extent at all levels of MCH institutions.The cleaning,disinfection,sterilization,and supply processes of reusable medical devices in a few MCH institutions are not standardized.Special medical populations get effective management.On-line healthcare is to be further promoted.

Objective:To investigate the knowledge of Sixth Chinese national consensus report on the management of Helicobacter pylori infection ( treatment excluded) (hereinafter referred to as sixth national consensus) and 2022 Chinese national clinical practice guideline on Helicobacter pylori eradication treatment (hereinafter referred to as the guideline)among medical staff from general hospitals in Hainan. Methods:From February 20 to May 7, 2023, a questionnaire survey on the diagnosis and treatment of Helicobacter pylori ( H. pylori) infection was conducted among 1 463 medical staff from 15 general hospitals in Hainan Province. The questionnaire was drawn up according to the sixth national consensus and the guideline, covering knowledge of 6 sections, induding H. pylori related diseases, detection of H. pylori, eradication, prevention and influence factors of eradication of H. pylori, etc. Chi-square test was used for statistical analysis. Results:A total of 1 463 valid questionnaires were collected with the effective responsive rate of 100.00%.The 1 463 subjects included 225 gastroenterologists and 1 238 other medical staff(including 503 physicians from other departments, 264 surgeons and 471 medical technologists and pharmacists). About 78.67%(177/225)of gastroenterologists agreed that the overall infection rate of H. pylori in China was more than 20%, the awareness rate was higher than that of other medical staff (physicians from other departments 65.41%(329/503), surgeons 61.74%(163/264), medical technologists and pharmacists 60.30%(284/471); the following datas were sorted by this position), and the difference was statistically significant ( χ2=30.97, P<0.001). About 51.11%(115/225) of gastroenterologists considered that H. pylori serological antibody test could not be used as a diagnostic method for current infection, the awareness rate was higher than that of other medical staff(22.07%(111/503), 14.02%(37/264), 12.31%(58/471)), and the difference was statistically significant( χ2 =152.66, P<0.001). Proton pump inhibitor and potassium-competitive acid blocker should be discontinued for 2 weeks, and antibiotics and bismuth should be discontinued for 4 weeks before urea breath test, and the awareness rates of gastroenterologists were higher than those of other medical staff (38.67%(87/225) vs. 23.26%(117/503), 19.70%(52/264), 18.47%(87/471); 60.89%(137/225) vs. 26.64%(134/503), 25.76%(68/264), 23.78%(112/471)), and the differences were statistically significant ( χ2 =133.70 and 165.51, both P<0.001). For refractory H. pylori infection, 98.67%(222/225)of gastroenterologists agreed with the individualized diagnosis and treatment of H. pylori infection should be guided by bacterial culture, antibiotic susceptibility test or drug resistance gene test, and the awareness rate was higher than that of other medical staff (91.85%(462/503), 93.56%(247/264), 93.21%(439/471)), and the difference was statistically significant( χ2=20.55, P=0.002). About 70.67% (159/225) of gastroenterologists recommended a bismuth containing quadruple regimen, 80.44% (181/225) supported a 10 to 14 day H. pylori eradication course, and the awareness rates were higher than other medical staff (46.92%(236/503), 33.33%(88/264), 32.91%(155/471); 67.20%(338/503), 59.09%(156/264), 53.93%(254/471)), and the differences were statistically significant ( χ2=111.25 and 59.99, both P<0.001). The understanding rates of the sixth national consensus and the guideline in gastroenterologists was 85.33% (192/225), which was higher than that of other medical staff (64.21%(323/503), 66.67%(176/264), 57.96%(273/471)), and the difference was statistically significant ( χ2=85.47, P<0.001). Conclusions:Gastroenterologists from general hospitals in Hainan Province have a better understanding of the sixth national consensus and the guideline than other medical staff. However, there is still a lack of deep understanding of the sixth national consensus and the guideline, and it is necessary to further strengthen the learning and application of the sixth national consensus and the guideline.

Objective To describe the changing trend and related factors of prevalence rates of healthcare-associa-ted infection(HAI)in a tertiary hospital in the past 10 years,and analyze the influencing factors for HAI.Methods A cross-sectional survey on HAI was conducted for 10 consecutive years from 2013 to 2022(one day was selected as the survey day each year),data were collected.The distribution and related factors of prevalence rates of HAI were analyzed by trend-x2 test and Pearson correlation coefficient.Multivariate logistic regression and multilayer percep-tron(MLP)models were constructed to analyze the independent effect and significance of factors.Results From 2013 to 2022,the prevalence rates of HAI ranged from 4.66％to 8.07％in this hospital,showing a linear upward trend.The proportions of ICU patients and utilization rate of central venous catheters within 2 days before the sur-vey showed linear upward trends,while the proportion of patients with urinary catheters within 2 days before the survey and proportion of patients undergoing surgery within 30 days before the survey decreased.The MLP model revealed that the top 3 important factors for HAI were length of hospital stay＞10 days,admission in ICU,and in-dwelling central venous catheters within 2 days before the survey.Multivariate logistic regression model indicated that length of hospital stay＞10 days,indwelling central venous catheters or urinary catheters within 2 days before the survey,surgery within 30 days before the survey,and admission in ICU were independent influencing factors for HAI.Conclusion The incidence of HAI in this hospital presents a linear increase in recent 10 years,the causes should be further analyzed and the direction of intervention should be determined through targeted surveillance.Adopting trend test statistical analysis method,logistic regression,MLP multi-factor model can further explore the data value of HAI prevalence survey.

Objective:To evaluate the gene mutation profile and prognostic significance of adult cytogenetically normal acute myeloid leukemia (CN-AML) with CEBPA-bZIP mutation. Methods:Targeted sequencing was implemented on the diagnostic bone marrow DNA samples of 141 adult CN-AML subjects with CEBPA-bZIP mutation. The nomogram model for leukemia-free survival (LFS) rate was generated by combining genetic abnormalities and clinical data. Risk stratification was conducted based on prognostic variables and the effect of risk-adjusted consolidation therapy was investigated by Kaplan-Meier method. Results:Four variables were finally included in our nomogram model after multivariate Cox analysis,and an equation for risk score calculation was obtained,risk score=1.3002×white blood cell (WBC) (≥18.77×109/L)+1.4065×CSF3R mutation positive+2.6489×KMT2A mutation positive+1.0128×DNA methylation-related genes mutation positive. According to the nomogram model,patients were further divided into low-risk group (score=0,n=46) and high-risk group (score>0,n=95). Prognostic analysis showed that the 5-year LFS rate,5-year overall survival (OS) rate,and 5-year cumulative incidence of relapse (CIR) of patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the high-risk group were 93.5％,97.1％,and 3.5％,while those in patients who received maintenance chemotherapy were 32.9％,70.5％,and 63.4％,respectively. The differences were statistically significant (all P<0.05). Allo-HSCT could significantly improve the prognosis of patients in high-risk group. However,no corresponding benefit was observed in the low-risk group. Conclusion:Adult CN-AML with CEBPA-bZIP mutation has a complex co-mutation pattern. The nomogram model based on mutations of CFS3R,KMT2A and DNA methylation-related genes together with WBC count can further divide this subset of patients into a relatively low-risk group and a relatively high-risk group. For individuals in the high-risk group,allo-HSCT is proposed as post-remission therapy. The above data will benefit the prognosis estimation and treatment decision for adult CN-AML with CEBPA-bZIP mutation.