Objective To investigate the effect of sodium-glucose cotransporter 2 inhibitor (empagliflozin, EMPA) on myocardial remodeling in a mouse uremic cardiomyopathy (UCM) model induced by 5/6 nephrectomy, through the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (PKB/AKT)/p65 signaling pathway. Methods The animals were divided into three groups: Sham group (n=6), UCM group (n=8), and UCM＋EMPA group (n=8). A UCM model was established in C57BL/6N mice using the 5/6 nephrectomy. Starting from 5 weeks post-surgery, EMPA or a placebo was administered. After 16 weeks, blood pressure, serum creatinine, blood urea nitrogen, 24-hour urine glucose and urine sodium were measured. Cardiac structure and function were assessed by echocardiography. Hematoxylin-eosin (HE) staining and Masson trichrome staining were used to observe pathological changes in the heart and kidneys. Wheat germ agglutinin (WGA) staining was used to evaluate myocardial hypertrophy. The real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of myocardial hypertrophy- and fibrosis-related mRNAs. Western blotting was used to detect the expression levels of PI3K, AKT and p65 in myocardial tissues. Results After 16 weeks, UCM group exhibited significantly higher blood pressure, serum creatinine, blood urea nitrogen than sham group (P＜0.01); UCM＋EMPA group exhibited lower blood pressure, serum creatinine, blood urea nitrogen, and higher 24 h urine sodium and glucose than UCM group (P＜0.05). Echocardiographic results showed ventricular remodeling in the UCM group, evidenced by left ventricular wall thickening, left ventricular enlargement, increased left ventricular mass, and decreased systolic function (P＜0.05); ventricular remodeling was alleviated (P＜0.05), though there was no significant improvement in systolic function in UCM＋EMPA group. HE and Masson stainings revealed myocardial degeneration, necrosis, and interstitial fibrosis in UCM group (P＜0.01); the myocardial pathology improved with reduced collagen deposition in UCM＋EMPA group (P＜0.01). WGA staining confirmed myocardial hypertrophy in UCM group (P＜0.01), while myocardial hypertrophy was alleviated in UCM＋EMPA group (P＜0.01). RT-qPCR results showed myocardial hypertrophy- and fibrosis-related genes (NPPA, NPPB, MYH7, COL1A1, COL3A1, TGF-β1) were upregulated in UCM group (P＜0.05), but downregulated in UCM＋EMPA group. Western blotting showed PI3K, p-AKT/AKT ratio, and p-p65/p65 ratio were increased in UCM group, but decreased in UCM＋EMPA group (P＜0.05). Conclusion EMPA can improve myocardial hypertrophy and fibrosis in the UCM mouse model, and it may play the role through inhibiting the PI3K/AKT/p65 signaling pathway.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Healthy lifestyles and good living habits are effective strategies and important approaches to prevent chronic non-communicable diseases. With the development of evidence-based medicine, the evidence translation system has made some achievements in clinical practice. There is, however, no comprehensive, professional and efficient system for translating lifestyle evidence globally. Therefore, the Health Lifestyle Evidence (HLSE) Group of Lanzhou University constructed the HLSE Evidence Translation System (https://hlse.cn/), with the aim of synthesizing, evaluating, translating, and applying lifestyle-related evidence resources. This paper aims to introduce the functional module design of the evidence translation system, the system development process and testing, introduce the interface design and function demonstration, and explain the significance of constructing the HLSE.

Acute high altitude disease (AHAD) is a general term for a series of clinical reactions that occur when the body fails to adapt to the low-pressure hypoxic environment of high altitudes. Mild cases can cause symptoms such as headache, nausea and vomiting, while more severe cases can lead to life-threatening conditions such as pulmonary edema, cerebral edema and other critical conditions that can be fatal. With the increasing demand for high altitudes deployment, understanding the common preventive measures of AHAD can reduce its morbidity or mortality to a certain extent, which is of great benefit to those who reside temporarily at high altitudes. In recent years, as people's health awareness has improved, there has been a growing attention towards non-pharmacological methods of disease prevention. At the same time, non-pharmacological therapy has significant therapeutic effects in preventing and treating high-altitude diseases, which has attracted the attention of researchers in this field. This review summarizes the major non-pharmacological preventive components of modern medicine and outlines the current non-pharmacological approaches to AHAD from the perspective of traditional Chinese medicine, intending to serve clinical purposes and improve the onset and prognosis of AHAD.

Objective To investigate disease characteristics and hospitalization costs of children with Mycoplasma Pneumoniae pneumonia(MPP)admitted to Shanghai municipal medical hospitals from 2019 to 2023.Methods Depending on the Shanghai Municipal Hospital Pediatric Alliance,we retrospectively investigated community acquired MPP pediatric patients hospitalized in 22 municipal hospitals with pediatric qualifications(including 4 children's hospitals)in Shanghai from Jan 2019 to Dec 2023.We collected the patients'diagnosis codes,gender,age,length of hospital stay,hospitalization costs,and whether they progressed to severe Mycoplasma pneumoniae pneumonia(SMPP).Results From 2019 to 2023,a total of 29 045 hospitalized children with MPP were treated,with 6 035 cases(20.8%)identified as SMPP in the 22 hospitals.Trend analysis revealed a rising trend with years in the proportion of SMPP patients(χ2trend=365.498,P<0.001).Among the 4 children's hospitals,there were 18 710 cases with MPP,including 4 078 cases(21.8%)of SMPP.The proportion of SMPP patients also showed an increasing trend with years(χ2trend=14.548,P<0.001),and the proportion in 2023(23.0%)was higher than that in previous years with statistical significance.There were statistical differences in the seasonal distribution of MPP cases between different years,with higher proportions in summer and autumn overall.The age distribution of hospitalized MPP children varied among different years,with school-age children accounting for the majority(56.8%)in 2023.There was no difference in the distribution of severe cases between different genders,but there were differences in the proportion of severe cases among different age groups in different years,with a gradual increase in severe cases among children aged 1 to 3 years(χ2trend=191.567,P<0.001).The average length of hospital stay for MPP during the epidemic was higher than that during non-epidemic periods,and there were statistically significant differences in the average length of hospital stay between different years(P<0.001).The individual hospitalization costs during the epidemic were higher than in other years,and there were statistically significant differences in individual hospitalization costs between different years(P<0.001).The total hospitalization costs were still higher in 2019 and 2023.The individual hospitalization costs for SMPP were higher than for non-SMPP cases.Conclusion MPP outbreaks occurred in Shanghai in 2019 and 2023,with the higher proportions in summer and autumn overall.Compared to previous years,the number of hospitalized MPP children in Shanghai was higher in 2023,with a higher proportion of SMPP cases,especially among children under 3 years old.The individual per capita hospitalization expenses for SMPP cases were higher than for non-SMPP cases.

Objective To investigate the effect of Mex3c gene knockout on embryonic neural tube development and its possible mechanisms.Methods The NCBI database was used to analyze the expression of Mex3c gene in various tissues of mice.Fluorescence in situ hybridization(FISH)was employed to detect the expression of Mex3c in neural tubes of Mex3c+/+mice at different developmental stages(E12.5 d,E14.5 d).Sexual mature mice were mated at a ratio of Mex3c+/-male to female(1:1)in the same cage.Embryos were collected and genotyped using PCR.They were divided into 3 groups based on their genotype:wild-type group(Mex3c+/+,WT group),homozygous knockout group(Mex3c-/-,KO group),and heterozygous knockout group(Mex3c+/-).HE staining was employed to observe the development of neural tubes in the 3 groups of embryos.Immunofluorescence staining and Western blotting were performed to detect the proliferation and apoptosis of embryonic neural stem cells in the WT and KO groups.Transmission electron microscopy was used to observe the ultrastructure of the neural tubes and mitochondria in the WT and KO groups.RNA was extracted from the neural tubes of WT and KO groups for RNA-seq sequencing.The R.3.6.3 software was used to perform KEGG signaling pathway enrichment analysis on differentially expressed genes.RT-qPCR was used to validate the sequencing results.Results The NCBI database analysis and FISH detection results showed that the Mex3c gene was mainly expressed in the central nervous system of embryos.HE staining results showed that there was no significant difference in the development of embryonic neural tubes between KO group,WT group,and heterozygous knockout group at E12.5 d and E13.5 d.However,at E14.5 d,the embryonic neural tube development in KO group was delayed and the phenotype was significantly abnormal compared with those in WT group.Therefore,the embryonic neural tube tissues of KO group and WT group at E14.5 d were selected for subsequent experiments.The immunofluorescence staining results showed that the PCNA positive cell rate in KO group was significantly lower than that in WT group(P<0.001).The Western blotting results showed that the Bax/Bcl-2 ratio in KO group was higher than that in WT group(P<0.01).Transmission electron microscopy observation showed that compared with WT group,the synaptic gap in KO group disappeared,the mitochondrial of the embryonic neural tube in KO group were swollen,the mitochondrial cristae were disrupted,and the structure was significantly abnormal.The results of RNA-seq analysis showed that a total of 377 differentially expressed genes were obtained,including 101 up-regulated genes and 276 down-regulated genes.KEGG signaling pathway enrichment analysis revealed that the main signaling pathways of differentially expressed genes were enriched in the neuroactive ligand receptor interaction signaling pathways.The RT-qPCR validation results showed that the mRNA expression levels of Avpr1a,Drd1,Htr7,Sstr1,Oxtr and Gabra5 in this signaling pathway were down-regulated(P<0.05 or P<0.01),which was consistent with the RNA-seq results.Conclusion Mex3c plays an important role in the development of neural tubes in mouse embryos,which may participate in regulating the proliferation and apoptosis of neural stem cells through neural active ligand receptor interaction signaling pathways,thereby affecting the development of neural tubes.

In the treatment of persistent atrial fibrillation with radiofrequency ablation,it is often necessary to add the ablation of external trigger foci of pulmonary vein on the basis of annular pulmonary vein isolation,including linear ablation,BOX ablation and fragmentation potential ablation.The isthmus of mitral valve is the most important component of linear ablation,but it is difficult to reach the isthmus of mitral valve for complete blockade by conventional radiofrequency ablation.The guide catheter was transported through the inferior vena cava to the coronary sinus,and the injection of Marshall vein anhydrous ethanol for ablation could achieve epicardial and myocardial block in the mitral isthmus,and the ablation combined with the endocardial patch ablation in the mitral isthmus could significantly improve the ablation effect,but there were disadvantages such as Marshall vein and coronary vein injury,high surgical cost and long time.This paper reports a case of persistent atrial fibrillation treated by self-made perforated balloon with Marshall intravenous anhydrous ethanol combined with individualized ablation strategy.No major adverse cardiovascular events or recurrence of atrial fibrillation occurred during 6 months of follow-up after discharge.

Healthy lifestyles and good living habits are effective strategies and important approaches to prevent chronic non-communicable diseases. With the development of evidence-based medicine, the evidence translation system has made some achievements in clinical practice. There is, however, no comprehensive, professional and efficient system for translating lifestyle evidence globally. Therefore, the Health Lifestyle Evidence (HLSE) Group of Lanzhou University constructed the HLSE Evidence Translation System (https://hlse.cn/), with the aim of synthesizing, evaluating, translating, and applying lifestyle-related evidence resources. This paper aims to introduce the functional module design of the evidence translation system, the system development process and testing, introduce the interface design and function demonstration, and explain the significance of constructing the HLSE.

The pursuit of cosmetic effects in post-surgical wounds has led to the development of ultra-minimally invasive techniques in surgery. Minimal invasive surgery has replaced open surgery and has become the new gold-standard for treating diseases. One such technique is the single incision triangulated umbilicus surgery (SITUS), which offers several advantages over traditional laparoscopic and other scarless surgeries, including reduced trauma, faster recovery, and better cosmetic outcomes. SITUS also has a short learning curve, aligns with conventional instrumentation operating habits, and can be used for whole abdominal surgeries. Chinese scholars have made further improvements to the SITUS technology, including expanding its applicability in intra-abdominal surgery and refining its incision closure methods to achieve superior cosmetic results. Currently, SITUS technology is experiencing rapid development in urology applications and has demonstrated satisfactory results in both domestic and international reports. This review aims to discuss the effectiveness and development of the SITUS technique in urology.

The deubiquitinases (DUBs), as the crucial peptidohydrolases in the ubiquitin system, can reverse and strictly regulate ubiquitination and play key roles in various biological processes, including the regulation of protein stability, cell signal transduction. Ubiquitin-specific protease 28 (USP28) involves multiple cancer-related signaling pathways by enhancing the stability of various cancer-related proteins, and is closely associated with the progression of colorectal, breast cancer, lung carcinomas, and pancreatic cancer. USP28 has been considered as a promising drug target in anticancer therapy, and the development of USP28 inhibitors has made some progress. In this article, we review the structure of USP28 and its interaction with substrates, discuss the research progress of USP28 in cancers and summarize the development of USP28 inhibitors.