In the present study, a mouse model of coronary artery ligation was employed to evaluate the effects of Jiming Powder on mitophagy in the mouse model of myocardial infarction and elucidate its underlying mechanisms. A mouse model of myocardial infarction post heart failure was constructed by ligating the left anterior descending branch of the coronary artery. The therapeutic efficacy of Jiming Powder was assessed from multiple perspectives, including ultrasonographic imaging, hematoxylin-eosin(HE) staining, Masson staining, and serum cardiac enzyme profiling. Dihydroethidium(DHE) staining was employed to evaluate the oxidative stress levels in the hearts of mice from each group. Mitophagy levels were assessed by scanning electron microscopy and immunofluorescence co-localization. Western blot was employed to determine the levels of key proteins involved in mitophagy, including Bcl-2-interacting protein beclin 1(BECN1), sequestosome 1(SQSTM1), microtubule-associated protein 1 light chain 3 beta(LC3B), PTEN-induced putative kinase 1(PINK1), phospho-Parkinson disease protein(p-Parkin), and Parkinson disease protein(Parkin). The results demonstrated that compared with the model group, high and low doses of Jiming Powder significantly reduced the left ventricular internal diameter in systole(LVIDs) and left ventricular internal diameter in diastole(LVIDd) and markedly improved the left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), effectively improving the cardiac function in post-myocardial infarction mice. Jiming Powder effectively reduced the levels of myocardial injury markers such as creatine kinase(CK), creatine kinase isoenzyme(CK-MB), and lactate dehydrogenase(LDH), thereby protecting ischemic myocardium. HE staining revealed that Jiming Powder attenuated inflammatory cell infiltration after myocardial infarction. Masson staining indicated that Jiming Powder effectively inhibited ventricular remodeling. Western blot results showed that Jiming Powder activated the PINK1-Parkin pathway, up-regulated the protein level of BECN1, down-regulated the protein level of SQSTM1, and increased the LC3Ⅱ/LC3Ⅰ ratio to promote mitophagy. In conclusion, Jiming Powder exerts therapeutic effects on myocardial infarction by inhibiting ventricular remodeling. The findings pave the way for subsequent pharmacological studies on the active components of Jiming Powder.
Animals ; Myocardial Infarction/physiopathology* ; Mitophagy/drug effects* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Protein Kinases/genetics* ; Male ; Ubiquitin-Protein Ligases/genetics* ; Humans ; Disease Models, Animal ; Mice, Inbred C57BL ; Signal Transduction/drug effects*

This study employed a mouse model of coronary artery ligation to assess the effect and mechanism of Jiming Powder on mitochondrial autophagy in mice with myocardial infarction. The mouse model of heart failure post-myocardial infarction was established by ligating the left anterior descending coronary artery. The pharmacological efficacy of Jiming Powder was evaluated through echocardiographic imaging, hematoxylin-eosin(HE) staining, and Masson staining. The levels of malondialdehyde(MDA), Fe~(2+), reduced glutathione(GSH), and superoxide dismutase(SOD) in heart tissues, as well as MDA immunofluorescence of heart tissues, were measured to assess lipid peroxidation and Fe~(2+) levels in the hearts of mice in different groups. Ferroptosis levels in the groups were evaluated using scanning electron microscopy and Prussian blue staining. Western blot analysis was conducted to detect the levels of key ferroptosis-related proteins, including nuclear factor erythroid 2-related factor 2(NRF2), ferritin heavy chain(FTH), glutathione peroxidase 4(GPX4), solute carrier family 7 member 11(SLC7A11), heme oxygenase 1(HO-1), and Kelch-like ECH-associated protein 1(KEAP1). The results showed that compared with the model group, both the high-and low-dose Jiming Powder groups exhibited significantly reduced left ventricular internal diameter in systole(LVIDs) and left ventricular internal diameter in diastole(LVIDd), while the left ventricular ejection fraction(EF) and left ventricular fractional shortening(FS) were significantly improved, effectively enhancing cardiac function in mice post-myocardial infarction. HE staining revealed that Jiming Powder attenuated myocardial inflammatory cell infiltration post-infarction, and Masson staining indicated that Jiming Powder effectively reduced fibrosis in the infarct margin area. Treatment with Jiming Powder reduced the levels of MDA and Fe~(2+), indicators of lipid peroxidation post-myocardial infarction, while increasing GSH and SOD levels, thus protecting ischemic myocardium. Western blot results demonstrated that Jiming Powder reduced KEAP1 protein accumulation, activated the NRF2/HO-1/GPX4 pathway, and up-regulated the protein expression of FTH and SLC7A11, exerting an inhibitory effect on ferroptosis. This study reveals that Jiming Powder exerts a therapeutic effect on myocardial infarction by inhibiting ferroptosis through the NRF2/HO-1/GPX4 pathway, providing a foundation for subsequent research on the pharmacological effects of Jiming Powder.
Animals ; Ferroptosis/drug effects* ; Myocardial Infarction/physiopathology* ; NF-E2-Related Factor 2/genetics* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Heme Oxygenase-1/genetics* ; Phospholipid Hydroperoxide Glutathione Peroxidase/genetics* ; Humans ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Disease Models, Animal

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To understand the status of screen exposure in children with epilepsy and analyze the influencing factors for screen exposure time,providing a scientific basis for managing screen exposure in these children. Methods A convenience sampling method was used to select 275 children with epilepsy from outpatient clinics or those undergoing 24-hour electroencephalogram monitoring at two tertiary hospitals in Jinan from March to June 2023. Their parents (fathers or mothers) completed a questionnaire to collect data on screen exposure,parental screen regulation behaviors,and related information about the children and their families. The Wilcoxon rank-sum test or the Kruskal-Wallis H test was used to conduct a univariate analysis of the average screen exposure time of children on school days and weekends,as well as the daily average screen exposure time. A multivariate logistic regression analysis was used to identify the risk factors for children whose screen exposure time exceeded the recommended guidelines (average screen exposure time on school days>1 hour or average on weekends>2 hours). Results The median screen exposure duration on school days was 40 minutes,while on weekends it was 120 minutes. Among the children studied,23.1％ (63/273) had average screen exposure time exceeding 1 hour on school days,and 42.5％ (117/275) had average screen exposure time exceeding 2 hours on weekends. Four children experienced seizures while using screen devices. Multivariate logistic regression analysis indicated that using screen devices shortly before sleep,lower educational levels of parents,caregivers discussing screen content with children,and longer seizure durations in children were risk factors for exceeding recommended guidelines (P<0.05). Conclusions Some children with epilepsy have a screen exposure time exceeding the recommended guidelines. A longer seizure duration,lower parental education levels,and permissive digital parenting are closely associated with children's screen exposure time exceeding the recommended guidelines. Families and children exhibiting these characteristics should be prioritized for attention and health education.

Objective To understand the application of skin disinfectant in neonatal intensive care units(NICUs)nationwide.Methods From April to May 2023,application of skin disinfectant in 93 NICUs nationwide was sur-veyed with convenience sampling method by a self-designed questionnaire.Questionnaire contents included types of disinfectant,disinfection tools,cleaning and disinfection frequency,disinfectant drying status,removal of disinfec-tant,and adverse reactions caused by disinfectant.Results A total of 93 nursing units in 71 medical institutions from 25 provinces/municipalities were included in this study.In NICUs,three most commonly used disinfectants were ethanol(79.57％),iodophor(74.19％),and anerdian(62.37％).In nursing units for neonates＜2 months of age,chlorhexidine was prohibited in 28 units(30.11％),used with caution in 23 units(24.73％),allowed in 9 units(9.68％),and there was no unified requirement in 33 units(35.48％).When using ethanol,staff only wiped once in 13(17.57％)nursing units.In some nursing units,there was no unified requirements on the wiping fre-quency of disinfectant.As for the removal of residual iodine,saline was used in 29(42.03％)nursing units,ethanol in 8(11.59％),and 19(27.54％)did not have unified requirements.The adverse reactions of disinfectant mainly included rash and contact dermatitis.Disinfectants that caused adverse reactions included ethanol,iodophor,aner-dian,and chlorhexidine.Conclusion In clinical practice,unified standards for the use of neonatal skin disinfectant remain absent.Selection and use of neonatal skin disinfectant vary considerably.Neonatal skin disinfectants have common adverse reactions.It is necessary to strengthen the training of health care workers on the standardized use of disinfectant,as well as carry out large-scale and rigorous randomized controlled trial designs to provide scientific basis for the correct selection of disinfectant.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

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.

This study used kidney metabolomics to investigate the underlying mechanisms of Guilingji (GLJ) on mild cognitive impairment (MCI) rats. The rats were randomly divided into 6 groups (n = 8), i.e., control group, model group, positive drug (Ginkgo biloba tablet, donepezil) group, GLJ group (low and high dose group). The MCI rat model was replicated using subcutaneous injection of D-galactose into the back of the neck along with a semi-high-fat diet for a total of 8 weeks, and drug was administered from the 5th week for 4 weeks. The kidney function and renal pathological changes of each group of rats were tested. And LC-MS based kidney metabolomics coupled with multivariate data analysis were conducted to explore the potential biomarkers, and corresponding metabolic pathways were then determined. After administration of GLJ, the level of urea nitrogen was decreased compared with those of the model group, and the abnormalities of morphology in kidney tissues were improved. The positive drugs (ginkgo biloba tablet and donepezil) had no significant modulating effect on renal function indexes. Ginkgo biloba tablet can lessen the pathological injury of kidney tissue, and donepezil had no improvement on renal histopathology. A total of 23 MCI related differential metabolites were identified in kidney, and 17 metabolites were signifcantly restored by GLJ compared with those of the model group. Additionally, we found that the cysteine and methionine metabolism, nicotinate and nicotinamide metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism were significantly involved in the regulatory effect of GLJ. The results illuminate the "cong shen zhi nao" mechanism of GLJ, and also provide a research basis for the clinical use of GLJ for the treatment of MCI. The animal experiment of this study was approved by the Ethics Committee of Shanxi University (approval number: 2020DW121).

The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Objective To analyze the effect of tislelizumab combined with chemotherapy in the treatment of stage Ⅲb-Ⅳ non-small cell lung cancer(NSCLC)and its influence on T lymphocyte immunity and survival prognosis.Methods Patients with NSCLC were divided into control group and treatment group according to different treatment methods.The control group was treated with platinum-containing dual-drug combined chemotherapy regimen(PC regimen:intravenous drip of pemetrexed 500 mg·m-2 on the 1st day and intravenous drip of carboplatin with area under plasma concentration-time curve(AUC)=5 mg·mL-1·min-1 on the 1st day;TP regimen:intravenous drip of taxol 135 mg·m-2 on the 1st day,and intravenous drip of carboplatin with AUC=5 mg·mL-1·min-1 on the 1st day to 3rd day).The treatment group was given tislelizumab 200 mg intravenously once every 3 weeks on the basis of the control group.Both groups were treated for 2 cycles by taking 3 weeks as 1 treatment cycle.The clinical efficacy,serum tumor markers levels,T lymphocyte immune function,progression-free survival(PFS)and overall survival(OS)and occurrence of adverse drug reactions during treatment were compared between the two groups.Results There were 40 cases in control group and 40 cases in treatment group.After treatment,the total effective rates in control group and treatment group were 40.00％(16 cases/40 cases)and 62.50％(25 cases/40 cases),the disease control rates were 70.00％(28 cases/40 cases)and 90.00％(36 cases/40 cases),carcinoembryonic antigen(CEA)levels were(9.21±2.03)and(5.42±1.36)ng·mL-1,carbohydrate antigen 125(CA125)levels were(72.53±8.16)and(31.95±5.08)U·mL-1,carbohydrate antigen 19-9(CA19-9)levels were(25.79±3.31)and(10.38±2.04)U·mL-1,cytokeratin19 fragment antigen 21-1(CYFRA21-1)levels were(6.47±1.34)and(4.26±0.91)ng·mL-1,CD3+levels were(54.36±5.81)％and(61.85±4.96)％,CD4+levels were(31.28±2.93)％and(43.08±3.15)％,CD4+/CD8+were 1.43±0.40 and 1.91±0.46,survival rates were 47.37％(18 cases/38 cases)and 67.57％(25 cases/37 cases),PFS were 7.73 months(95％CI:6.42-9.03)and 9.75 months(95％CI:8.68-10.82),and OS were 8.96 months(95％CI:7.94-9.97)and 10.52 months(95％CI:9.78-11.27)respectively(all P＜0.05).There were no statistically significant differences in the incidence of gastrointestinal reactions,liver dysfunction,bone marrow suppression,hypothyroidism and non-infectious pneumonia between both groups(all P＞0.05).Conclusion Tislelizumab combined with chemotherapy has a good effect in the treatment of stage Ⅲb-Ⅳ NSCLC,and it can effectively reduce the levels of serum tumor markers,improve the T lymphocyte immune function,and prolong the survival time of patients,with good safety.