ObjectiveTo investigate the possible mechanism of Shufeng Jiedu capsules （SFJD） in alleviating influenza A （H1N1） virus pneumonia and focus on its effect on Toll-like receptor （TLR） signaling pathway in respiratory epithelial cells. MethodsA mouse model of viral pneumonia was established via the A/PR/8/34 （PR8） strain of influenza A virus. Mice were randomly divided into a normal group， a PR8 infection （PR8） group， and an SFJD group （8.4 g·kg^-1）， with 10 mice in each group. The day of infection was designated as day 1. The SFJD group was administered intragastrically at a volume of 20 mL·kg^-1 daily， while the normal and PR8 groups were given an equal volume of deionized water. Micro-computed tomography （Micro-CT） was performed on day 5， and the mice were dissected to collect their lungs， after which the lung index was calculated to verify the therapeutic effect of SFJD. Single-cell sequencing was used to analyze the differentially expressed genes in respiratory epithelial cells. Multiplex fluorescence immunohistochemistry was employed to detect the expression of TLR， tumor necrosis factor receptor-associated factor 6 （TRAF6）， and myeloid differentiation factor 88 （MyD88） proteins in epithelial cell adhesion molecule （EpCAM）-positive cells， and the proportion of respiratory epithelial cells expressing TLR pathway proteins was calculated. Respiratory epithelial cells were then sorted by flow cytometry， and Western blot was used to detect the expression of TLR， MyD88， TRAF6， Toll-interleukin receptor domain-containing adaptor inducing interferon-β （TRIF）， inhibitor of κB kinase α （IKKα）， and nuclear factor-κB （NF-κB） in the sorted epithelial cells. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in lung tissue. ResultsAt the transcriptional level， SFJD reversed the expression of TLR signaling pathway genes in respiratory epithelial cells， downregulating multiple TLR signaling pathway-related genes （P<0.01）. At the protein level， SFJD significantly reduced the proportion of respiratory epithelial cells expressing TLR3 （P<0.05）， the expression levels of TLR2， TLR3， TLR4， TRIF， TRAF6， IKKα， and NF-κB in epithelial cells（P<0.05， P<0.01）， as well as the levels of pro-inflammatory cytokines IL-1β and TNF-α in lung tissue （P<0.01）. ConclusionSFJD may alleviate viral pneumonia by suppressing the expression of TLR in respiratory epithelial cells and their subsequent signaling cascades.

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

Type 2 diabetes mellitus(T2DM)is a chronic metabolic disorder characterized primarily by pancreatic β-cell dysfunction and insulin resistance.Beyond impaired glucose homeostasis,the glucotox-icity resulting from dysregulated glucose metabolism can lead to complications such as diabetic nephropa-thy,diabetic coronary heart disease,and diabetic cognitive dysfunction,posing severe threats to patients' health.Therefore,enhancing glucose metabolism and improving insulin resistance are critical strategies for T2DM prevention and treatment.Currently,the primary therapeutic approaches for T2DM include oral hypoglycemic agents and exogenous insulin injections.However,these methods face challenges such as unclear diagnostic markers,suboptimal therapeutic efficacy,and drug-related side effects.Consequently,the development of more precise and effective treatment strategies remains a top priority in clinical re-search.MicroRNA(miRNA)is a short non-coding RNA that regulates gene transcription.It has been reported to exhibit significant alterations even before the onset of overt pathological features like hypergly-cemia,suggesting their potential as early diagnostic biomarkers for T2DM to address current issues like delayed diagnosis and disease progression due to missed optimal treatment windows.Moreover,miRNAs can modulate the expression of pathways involved in glucose metabolism,thereby improving insulin resist-ance and maintaining glucose homeostasis while avoiding side effects associated with conventional thera-pies,such as reduced bone density and localized fat accumulation.This positions miRNAs as a promising avenue for precise and efficient T2DM management.This article systematically elucidates the molecular mechanisms by which miRNAs regulate glucose metabolism-related pathways,providing a theoretical foundation and reference for future clinical research.

Type 2 diabetes mellitus(T2DM)is a chronic metabolic disorder characterized primarily by pancreatic β-cell dysfunction and insulin resistance.Beyond impaired glucose homeostasis,the glucotox-icity resulting from dysregulated glucose metabolism can lead to complications such as diabetic nephropa-thy,diabetic coronary heart disease,and diabetic cognitive dysfunction,posing severe threats to patients' health.Therefore,enhancing glucose metabolism and improving insulin resistance are critical strategies for T2DM prevention and treatment.Currently,the primary therapeutic approaches for T2DM include oral hypoglycemic agents and exogenous insulin injections.However,these methods face challenges such as unclear diagnostic markers,suboptimal therapeutic efficacy,and drug-related side effects.Consequently,the development of more precise and effective treatment strategies remains a top priority in clinical re-search.MicroRNA(miRNA)is a short non-coding RNA that regulates gene transcription.It has been reported to exhibit significant alterations even before the onset of overt pathological features like hypergly-cemia,suggesting their potential as early diagnostic biomarkers for T2DM to address current issues like delayed diagnosis and disease progression due to missed optimal treatment windows.Moreover,miRNAs can modulate the expression of pathways involved in glucose metabolism,thereby improving insulin resist-ance and maintaining glucose homeostasis while avoiding side effects associated with conventional thera-pies,such as reduced bone density and localized fat accumulation.This positions miRNAs as a promising avenue for precise and efficient T2DM management.This article systematically elucidates the molecular mechanisms by which miRNAs regulate glucose metabolism-related pathways,providing a theoretical foundation and reference for future clinical research.

Objective:To investigate lymph node metastasis(LNM)in the prostatic anterior fat pad(PAFP)of PCa patients after robot-assisted radical prostatectomy(RARP),and analyze the clinicopathological features and prognosis of LNM in the PAFP.Methods:We retrospectively analyzed the clinicopathological data on 1 003 cases of PCa treated by RARP in the Department of Urolo-gy of PLA General Hospital from January 2017 to December 2022.All the patients underwent routine removal of the PAFP during RARP and pathological examination,with the results of all the specimens examined and reported by pathologists.Based on the pres-ence and locations of LNM,we grouped the patients for statistical analysis,compared the clinicopathological features between different groups using the Student's t,Mann-Whitney U and Chi-square tests,and conducted survival analyses using the Kaplan-Meier and Log-rank methods and survival curves generated by Rstudio.Results:Lymph nodes were detected in 77(7.7％)of the 1 003 PAFP samples,and LNM in 11(14.3％)of the 77 cases,with a positive rate of 1.1％(11/1 003).Of the 11 positive cases,9 were found in the upgraded pathological N stage,and the other 2 complicated by pelvic LNM.The patients with postoperative pathological stage≥T3 constituted a significantly higher proportion in the PAFP LNM than in the non-PAFP LNM group(81.8％[9/11]vs 36.2％[359/992],P=0.005),and so did the cases with Gleason score ≥8(87.5％[7/8]vs 35.5％[279/786],P=0.009).No statisti-cally significant differences were observed in the clinicopathological features and biochemical recurrence-free survival between the pa-tients with PAFP LNM only and those with pelvic LNM only.Conclusion:The PAFP is a potential route to LNM,and patients with LNM in the PAFP are characterized by poor pathological features.There is no statistically significant difference in biochemical recur-rence-free survival between the patients with PAFP LNM only and those with pelvic LNM only.Routine removal of the PAFP and inde-pendent pathological examination of the specimen during RARP is of great clinical significance.

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

OBJECTIVE: To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study. METHODS: A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 community older adults. After the baseline survey, the last follow-up was March 31, 2021 with an average 8.13 years of follow-up. Cox proportional hazard model was used to estimate the hazard ratios (HR) with 95% CI for cardiovascular disease (CVD) death and all-cause death in associations with baseline lipid indicators. RESULTS: A total of 4499 participants were recruited, and the mean levels of uric acid, body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol (TC), triglyceride, and low-density lipoprotein cholesterol (LDL-C) showed an upward trend with the increasing remnant cholesterol (RC) quarters (P_trend < 0.05), while the downward trend was found in high-density lipoprotein cholesterol (HDL-C). During the total 36,596 person-years follow-up, the CVD mortality and all-cause mortality during an average 8.13 years of follow-up was 3.87% (95% CI: 3.30%-4.43%) and 14.83% (95% CI: 13.79%-15.86%) with 174 CVD death participants and 667 all-cause death participants. After adjusting for confounders, the higher level of TC (HR = 0.854, 95% CI: 0.730-0.997), LDL-C (HR = 0.817, 95% CI: 0.680-0.982) and HDL-C (HR = 0.443, 95% CI: 0.271-0.724) were associated with lower risk of CVD death, and the higher level of HDL-C (HR = 0.637, 95% CI: 0.501-0.810) were associated with lower risk of all-cause death. The higher level of RC (HR = 1.276, 95% CI: 1.010-1.613) increase the risk of CVD death. Compared with the normal lipid group, TC ≥ 6.20 mmol/L group and LDL-C ≥ 4.10 mmol/L group were no longer associated with lower risk of CVD death, while RC ≥ 0.80 mmol/L group was still associated with higher risk of CVD death. In normal lipid group, the higher levels of TC, LDL-C and HDL-C were related with lower CVD death. CONCLUSIONS In community older adults, higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range. Higher RC was associated with higher CVD mortality, which may be a better lipid indicator for estimating the CVD death risk in older adults.

BACKGROUND: The new emerging avian influenza A H7N9 virus, causing severe human infection with a mortality rate of around 41%. This study aims to provide a novel treatment option for the prevention and control of H7N9. METHODS: H7 hemagglutinin (HA)-specific B cells were isolated from peripheral blood plasma cells of the patients previously infected by H7N9 in Jiangsu Province, China. The human monoclonal antibodies (mAbs) were generated by amplification and cloning of these HA-specific B cells. First, all human mAbs were screened for binding activity by enzyme-linked immunosorbent assay. Then, those mAbs, exhibiting potent affinity to recognize H7 HAs were further evaluated by hemagglutination-inhibiting (HAI) and microneutralization in vitro assays. Finally, the lead mAb candidate was selected and tested against the lethal challenge of the H7N9 virus using murine models. RESULTS: The mAb 6-137 was able to recognize a panel of H7 HAs with high affinity but not HA of other subtypes, including H1N1 and H3N2. The mAb 6-137 can efficiently inhibit the HA activity in the inactivated H7N9 virus and neutralize 100 tissue culture infectious dose 50 (TCID50) of H7N9 virus (influenza A/Nanjing/1/2013) in vitro, with neutralizing activity as low as 78 ng/mL. In addition, the mAb 6-137 protected the mice against the lethal challenge of H7N9 prophylactically and therapeutically. CONCLUSION The mAb 6-137 could be an effective antibody as a prophylactic or therapeutic biological treatment for the H7N9 exposure or infection.
Animals ; Antibodies, Monoclonal/therapeutic use* ; Antibodies, Neutralizing/therapeutic use* ; Antibodies, Viral ; Hemagglutinins ; Humans ; Influenza A Virus, H1N1 Subtype ; Influenza A Virus, H3N2 Subtype ; Influenza A Virus, H7N9 Subtype ; Influenza Vaccines ; Influenza in Birds ; Influenza, Human/prevention & control* ; Mice

Objective: To investigate the incidence and trend of short-term outcomes among preterm infants born <34 weeks' gestation. Methods: A secondary analysis of data from the standardized database established by a multicenter cluster-randomized controlled study "reduction of infection in neonatal intensive care units (NICU) using the evidence-based practice for improving quality (REIN-EPIQ) study". This study was conducted in 25 tertiary NICU. A total of 27 192 infants with gestational age <34 weeks at birth and admitted to NICU within the first 7 days of life from May 2015 to April 2018 were enrolled. Infants with severe congenital malformation were excluded. Descriptive analyses were used to describe the mortality and major morbidities of preterm infants by gestational age groups and different admission year groups. Cochran-Armitage test and Jonckheere-Terpstra test were used to analyze the trend of incidences of mortality and morbidities in 3 study-years. Multiple Logistic regression model was constructed to analyze the differences of outcomes in 3 study-years adjusting for confounders. Results: A total of 27 192 preterm infants were enrolled with gestational age of (31.3±2.0) weeks at birth and weight of (1 617±415) g at birth. Overall, 9.5% (2 594/27 192) of infants were discharged against medical advice, and the overall mortality rate was 10.7% (2 907/27 192). Mortality for infants who received complete care was 4.7% (1 147/24 598), and mortality or any major morbidity was 26.2% (6 452/24 598). The incidences of moderate to severe bronchopulmonary dysplasia, sepsis, severe intraventricular hemorrhage or periventricular leukomalacia, proven necrotizing enterocolitis, and severe retinopathy of prematurity were 16.0% (4 342/27 192), 11.9% (3 225/27 192), 6.8% (1 641/24 206), 3.6% (939/25 762) and 1.5% (214/13 868), respectively. There was a decreasing of the overall mortality (P<0.001) during the 3 years. Also, the incidences for sepsis and severe retinopathy of prematurity both decreased (both P<0.001). However, there were no significant differences in the major morbidity in preterm infants who received complete care during the 3-year study period (P=0.230). After adjusting for confounders, infants admitted during the third study year showed significantly lower risk of overall mortality (adjust OR=0.62, 95%CI 0.55-0.69, P<0.001), mortality or major morbidity, moderate to severe bronchopulmonary dysplasia, sepsis and severe retinopathy of prematurity, compared to those admitted in the first study year (all P<0.05). Conclusions: From 2015 to 2018, the mortality and major morbidities among preterm infants in Chinese NICU decreased, but there is still space for further efforts. Further targeted quality improvement is needed to improve the overall outcome of preterm infants.
Bronchopulmonary Dysplasia/epidemiology* ; Gestational Age ; Humans ; Infant ; Infant Mortality/trends* ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases/epidemiology* ; Patient Discharge ; Retinopathy of Prematurity/epidemiology* ; Sepsis/epidemiology*

Abstract: Objective　To analyze the distribution and drug resistance evolution characteristics of pathogenic bacteria of bloodstream infection in nine tertiary hospitals in Yunnan Province from 2017 to 2021, so as to provide reliable basis for rational selection of antibiotics in clinic. Methods Using the drug sensitive paper method or instrument method, the bacteria identification and drug sensitivity test were carried out in nine tertiary hospitals in different regions according to the unified technical scheme. The results were judged according to the Clinical and Laboratory Standards Institute (CLSI) breakpoint standard in 2021, and use WHONET5.6 for data statistical analysis. Results A total of 12 003 strains of pathogenic bacteria were isolated from bloodstream infection samples in the past five years, including 7 442 strains of Gram-negative bacteria (62.0%) and 4562 strains of Gram-positive bacteria (38.0%), with an increasing trend in the number of isolated strains; of these, 163 strains (1.4%) were isolated from outpatients and 11 840 strains (98.6%) were isolated from inpatients. The top three gram-negative bacteria were Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii, of which 309 strains (4.2%) were carbapenem-resistant Klebsiella pneumoniae (CR-KPN), 29 strains (0.4%) carbapenem-resistant Escherichia coli and 19 strains (0.3%) carbapenem-resistant Enterobacter cloacae, and the number of CR-KPN was on the rise year by year. The top three Gram-positive bacteria were coagulase-negative staphylococci, Staphylococcus aureus and Enterococcus faecium, of which methicillin-resistant Staphylococcus aureus (MRSA) was detected for 213 strains, accounting for 27.7%, and decreased from 40.0% in 2017 to 23.4% in 2021, showing a downward trend year by year. No vancomycin-resistant staphylococci and enterococci were found. Conclusions The detection and composition of bloodstream infection pathogenic bacteria in multicenter have not changed much in the past five years, but each hospital has its own characteristics. The number of carbapenem resistant Enterobacteriaceae increased year by year, which should be paid more attention.