OBJECTIVE: To investigate the effect of Tongmai Hypoglycemic Capsule (THC) on myocardium injury in diabetic cardiomyopathy (DCM) rats. METHODS: A total of 24 Sprague Dawley rats were fed for 4 weeks with high-fat and high-sugar food and then injected with streptozotocin intraperitoneally for the establishment of the DCM model. In addition, 6 rats with normal diets were used as the control group. After modeling, 24 DCM rats were randomly divided into the model, L-THC, M-THC, and H-THC groups by computer generated random numbers, and 0, 0.16, 0.32, 0.64 g/kg of THC were adopted respectively by gavage, with 6 rats in each group. After 12 weeks of THC administration, echocardiography, histopathological staining, biochemical analysis, and Western blot were used to detect the changes in myocardial structure, oxidative stress (OS), biochemical indexes, protein expressions of myocardial fibrosis, and nuclear factor erythroid 2-related faactor 2 (Nrf2) element, respectively. RESULTS: Treatment with THC significantly decreased cardiac markers such as creatine kinase, lactate dehydrogenase, and creatine kinase-MB, etc., (P<0.01); enhanced cardiac function indicators including heart rate, ejection fraction, cardiac output, interventricular septal thickness at diastole, and others (P<0.05 or P<0.01); decreased levels of biochemical indicators such as fasting blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, aspartate transaminase, (P<0.05 or P<0.01); and decreased the levels of myocardial fibrosis markers α-smooth muscle actin (α-SMA), and collagen I (Col-1) protein (P<0.01), improved myocardial morphology and the status of myocardial interstitial fibrosis. THC significantly reduced malondialdehyde levels in model rats (P<0.01), increased levels of catalase, superoxide dismutase, and glutathione (P<0.01), and significantly increased the expression of Nrf2, NAD(P)H:quinone oxidoreductase 1, heme oxygenase-1, and superoxide dismutase 2 proteins in the left ventricle of rats (P<0.01). CONCLUSION THC activates the Nrf2 signaling pathway and plays a protective role in reducing OS injury and cardiac fibrosis in DCM rats.
Animals ; Diabetic Cardiomyopathies/physiopathology* ; Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Rats, Sprague-Dawley ; Myocardium/metabolism* ; Fibrosis ; Male ; Capsules ; Hypoglycemic Agents/therapeutic use* ; NF-E2-Related Factor 2/metabolism* ; Rats ; Diabetes Mellitus, Experimental/drug therapy*

Transfer-RNA derived small RNA(tsRNA),a re-cently discovered class of non-coding RNA,is produced by ma-ture tRNA or tRNA precursor through the mediation of specific endonucleases.By regulating gene expression at the transcrip-tional and post transcriptional levels and acting as an epigenetic regulator,tsRNA plays an important role in the physiological and pathological processes of many organisms.Therefore,it has gradually become a research hotspot in biomedicine and attracted widespread attention.Moreover,there is increasing evidence that tsRNA is involved in the occurrence and development of many neuropsychiatric diseases through participating in stress re-sponse,cell proliferation and apoptosis,neural development,synaptic plasticity,neuroinflammation and immune regulation,epigenetic regulation,RNA processing,and protein translation regulation.This article mainly discusses the generation,classifi-cation and biological functions of tsRNA,and elaborates on the role and possible mechanisms of tsRNA in neurodevelopment and neuropsychiatric disorders,thereby further revealing the poten-tial of tsRNA as a reliable biomarker and therapeutic target for neuropsychiatric disorders.

Abnormal expression of CMTM4 protein is closely related to tumour occurrence,development and prognosis.Although the important role of CMTM4 in tumours has been gradually manifested,its spe-cific mechanism of action in cervical cancer remains unclear.The aim of this study was to investigate the relationship between CMTM4 expression and clinicopathological features in cervical cancer and study its mechanism.Immunohistochemistry and Western blot were used to detect the expression level of CMTM4 in cancer tissues and paracancerous tissues,and it was found that CMTM4 was significantly under-ex-pressed in cervical cancer tissues(P＜0.001).The chi-square test analysed the relationship between high and low CMTM4 expression and the clinical and pathological characteristics of cervical cancer pa-tients and results found that CMTM4 expression was correlated with the number of births,HPV infection status,pathological type,FIGO stage and lymph node metastasis.Data from Western blot and RT-qPCR found that CMTM4 protein and mRNA levels in HaCaT cells were significantly higher than that of C-33A cells,HeLa cells,U14 cells,and HT-3 cells.Among them,the most significant change in CMTM4 ex-pression was observed in C-33A cells,so the C-33A cell line was selected for subsequent overexpression experiments.CCK-8 analysis found that the proliferation ability of C-33A cervical cancer cells in the pcDNA-CMTM4 group was significantly lower than that in the pcDNA-NC group(P＜0.001).Flow cy-tometry and Western blot results indicated that CMTM4 overexpression promoted apoptosis(P＜0.001),significantly increased Bax(P＜0.001)and cleaved caspase 3(P＜0.05)protein levels,and significant-ly decreased Bcl-2 protein level(P＜0.01).Western blot results further found that CMTM4 overexpres-sion significantly reduced the protein levels of p-PI3K(P＜0.001)and p-AKT(P＜0.01),but did not affect the protein levels of PI3K and AKT(P＞0.05).The above findings indicated that CMTM4 gene expression was down-regulated in cervical cancer,and CMTM4 overexpression inhibited cervical cancer cell proliferation and induced apoptosis by inhibiting the PI3K/AKT pathway.Therefore,CMTM4 may be used as a biological marker for screening cervical cancer.

Transfer-RNA derived small RNA(tsRNA),a re-cently discovered class of non-coding RNA,is produced by ma-ture tRNA or tRNA precursor through the mediation of specific endonucleases.By regulating gene expression at the transcrip-tional and post transcriptional levels and acting as an epigenetic regulator,tsRNA plays an important role in the physiological and pathological processes of many organisms.Therefore,it has gradually become a research hotspot in biomedicine and attracted widespread attention.Moreover,there is increasing evidence that tsRNA is involved in the occurrence and development of many neuropsychiatric diseases through participating in stress re-sponse,cell proliferation and apoptosis,neural development,synaptic plasticity,neuroinflammation and immune regulation,epigenetic regulation,RNA processing,and protein translation regulation.This article mainly discusses the generation,classifi-cation and biological functions of tsRNA,and elaborates on the role and possible mechanisms of tsRNA in neurodevelopment and neuropsychiatric disorders,thereby further revealing the poten-tial of tsRNA as a reliable biomarker and therapeutic target for neuropsychiatric disorders.

Abnormal expression of CMTM4 protein is closely related to tumour occurrence,development and prognosis.Although the important role of CMTM4 in tumours has been gradually manifested,its spe-cific mechanism of action in cervical cancer remains unclear.The aim of this study was to investigate the relationship between CMTM4 expression and clinicopathological features in cervical cancer and study its mechanism.Immunohistochemistry and Western blot were used to detect the expression level of CMTM4 in cancer tissues and paracancerous tissues,and it was found that CMTM4 was significantly under-ex-pressed in cervical cancer tissues(P＜0.001).The chi-square test analysed the relationship between high and low CMTM4 expression and the clinical and pathological characteristics of cervical cancer pa-tients and results found that CMTM4 expression was correlated with the number of births,HPV infection status,pathological type,FIGO stage and lymph node metastasis.Data from Western blot and RT-qPCR found that CMTM4 protein and mRNA levels in HaCaT cells were significantly higher than that of C-33A cells,HeLa cells,U14 cells,and HT-3 cells.Among them,the most significant change in CMTM4 ex-pression was observed in C-33A cells,so the C-33A cell line was selected for subsequent overexpression experiments.CCK-8 analysis found that the proliferation ability of C-33A cervical cancer cells in the pcDNA-CMTM4 group was significantly lower than that in the pcDNA-NC group(P＜0.001).Flow cy-tometry and Western blot results indicated that CMTM4 overexpression promoted apoptosis(P＜0.001),significantly increased Bax(P＜0.001)and cleaved caspase 3(P＜0.05)protein levels,and significant-ly decreased Bcl-2 protein level(P＜0.01).Western blot results further found that CMTM4 overexpres-sion significantly reduced the protein levels of p-PI3K(P＜0.001)and p-AKT(P＜0.01),but did not affect the protein levels of PI3K and AKT(P＞0.05).The above findings indicated that CMTM4 gene expression was down-regulated in cervical cancer,and CMTM4 overexpression inhibited cervical cancer cell proliferation and induced apoptosis by inhibiting the PI3K/AKT pathway.Therefore,CMTM4 may be used as a biological marker for screening cervical cancer.

Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates.Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity.This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes.The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes,and corresponding reference ranges will be established.The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance,with altitude gradients divided into 4 categories:800 m,1 900 m,2 400 m,and 3 500 m,with an anticipated sample size of 170 neonates per altitude gradient.This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.[Chinese Journal of Contemporary Pediatrics,2024,26(4):403-409]

A 5-year-old girl was admitted due to one episode of melena and one episode of hematemesis.Upon admission,gastroscopy revealed esophageal and gastric varices.Abdominal CT scan,MRI,and color Doppler ultrasound suggested cirrhosis,intrahepatic bile duct dilation,and bilateral kidney enlargement.Genetic testing identified compound heterozygous mutations in the PKHD1 gene:c.2264C>T(p.Pro755Leu)and c.1886T>C(p.Val629Ala).The c.2264C>T(p.Pro755Leu)mutation is a known pathogenic variant with previous reports,while c.1886T>C(p.Val629Ala)is a novel mutation predicted to have pathogenic potential according to Mutation Taster and PolyPhen2.The child was diagnosed with autosomal recessive polycystic kidney disease.In children presenting with gastrointestinal bleeding without obvious causes,particularly those with liver or kidney disease,consideration should be given to the possibility of autosomal recessive polycystic kidney disease,and genetic testing should be conducted for definitive diagnosis when necessary.

Objective To clarify the high-touch surface in oral diagnosis and treatment procedures,provide basis and guidance for cleaning and disinfection.Methods The direct observation method was used to investigate the tou-ch time and frequency of environmental surfaces in 7 outpatient departments of a tertiary stomatology hospitals in Beijing.The average touch frequency,95％confidence interval and cumulative touch rate were calculated.Results In oral diagnosis and treatment procedures,the average touch frequency of the environmental surface was 26.75 times per procedure,with the highest in endodontics(46.25 times per procedure)and the lowest in the oral mucosal specialty(10.19 times per procedure).The high-touch surface consisted of the shadowless lamp handle,manipula-tion panel and handle on dental unit(doctor's side),computer keyboard and mouse,handle and line front end of three way syringe,as well as dental high speed handpiece and line front end,with average touch frequencies of 3.99,3.85,2.65,1.86,and 1.40 times per procedure.The high-touch surface in all stomatology specialties in-cluded the manipulation panel and handle on dental unit(doctor's side),75％of specialties included computer key-board and mouse,and the shadowless lamp handle has the highest touch frequency in 50％of specialties.The ave-rage touch frequency of the environmental surface was highest(113.50 times per procedure)during crown prepara-tion procedure,and the lowest(8.50 times per procedure)during the orthodontic consultations.Conclusion The high-touch surface of different dental specialties and different diagnosis and treatment procedures are different.Me-dical institutions should take corresponding cleaning,disinfection and management measures according to the actual situation of high-touch surface in stomatology departments,so as to effectively improve the quality of environmental cleaning and disinfection.

The aberrant expression of CMTM4 protein has been implicated in tumorigenesis,develop-ment,and prognosis;however,its precise role and underlying mechanism in cervical cancer remain elu-sive.We aimed to investigate the expression level of CMTM4 in cervical cancer and its regulatory effect and molecular mechanism on MDSCs differentiation and immune cell function.Firstly,immunohisto-chemical (IHC) staining and Western blot analysis were employed to assess the expression level of CMTM4 in cervical cancer tumors and adjacent tissues.The results revealed a significant decrease in the expression level of CMTM4 in cervical cancer tissues compared to adjacent tissues (P<0.01) .Differenti-ation of MDSCs in tumor samples from cervical cancer patients was assessed using flow cytometry,with CD45,CD11b,and Ly6G used as markers for M-MDSCs,and CD45,CD11b,and Ly6C used as mark-ers for G-MDSCs.The percentage of M-MDSCs and G-MDSCs in the blood of cervical cancer patients was significantly higher than that observed in healthy volunteers (P<0.01) .Furthermore,flow cytometry a-nalysis demonstrated that high expression of CMTM4 increased the proportion of CD3+CD4+T cells and CD3+CD8+T cells in the blood of cervical cancer patients (P<0.01),while also promoting the activa-tion ratio of Th1 and Th17 cells (P<0.05) .Conversely,it inhibited the activation ratio of Th2 and Treg cells (P<0.05 or P<0.01) .The percentage of CD8+PD-1+T cells and CD8+PD-L1+T cells within tumor tissues was determined by flow cytometry analysis which showed that high expression levels of CMTM4 suppressed their presence within tumor tissues (P<0.05) .The in vitro studies demonstrated that overexpression of CMTM4 in HeLa cells significantly suppressed the generation of MDSCs (P<0.01),while overexpression of PD-1 in HeLa cells further enhanced the generation of MDSCs (P<0.05) .Additionally,ELISA was employed to measure the levels of Th1,Th2,Th17,and Treg cyto-kines.It was observed that CMTM4 overexpression in HeLa cells reduced IL-10 secretion by T cells (P<0.01),but increased IFN-γ and TNF-α secretion (P<0.01),both of which were reversed by PD-1 overexpression (P<0.05 or P<0.01) .In conclusion,low expression of CMTM4 in cervical cancer leads to abnormal differentiation of MDSCs and immune escape of tumors.CMTM4 influences the activation of tumor T cells by regulating the PD-1/PD-L1 pathway.Thus,CMTM4 may be a potential target for the treatment of cervical cancer.

The aberrant expression of CMTM4 protein has been implicated in tumorigenesis,develop-ment,and prognosis;however,its precise role and underlying mechanism in cervical cancer remain elu-sive.We aimed to investigate the expression level of CMTM4 in cervical cancer and its regulatory effect and molecular mechanism on MDSCs differentiation and immune cell function.Firstly,immunohisto-chemical (IHC) staining and Western blot analysis were employed to assess the expression level of CMTM4 in cervical cancer tumors and adjacent tissues.The results revealed a significant decrease in the expression level of CMTM4 in cervical cancer tissues compared to adjacent tissues (P<0.01) .Differenti-ation of MDSCs in tumor samples from cervical cancer patients was assessed using flow cytometry,with CD45,CD11b,and Ly6G used as markers for M-MDSCs,and CD45,CD11b,and Ly6C used as mark-ers for G-MDSCs.The percentage of M-MDSCs and G-MDSCs in the blood of cervical cancer patients was significantly higher than that observed in healthy volunteers (P<0.01) .Furthermore,flow cytometry a-nalysis demonstrated that high expression of CMTM4 increased the proportion of CD3+CD4+T cells and CD3+CD8+T cells in the blood of cervical cancer patients (P<0.01),while also promoting the activa-tion ratio of Th1 and Th17 cells (P<0.05) .Conversely,it inhibited the activation ratio of Th2 and Treg cells (P<0.05 or P<0.01) .The percentage of CD8+PD-1+T cells and CD8+PD-L1+T cells within tumor tissues was determined by flow cytometry analysis which showed that high expression levels of CMTM4 suppressed their presence within tumor tissues (P<0.05) .The in vitro studies demonstrated that overexpression of CMTM4 in HeLa cells significantly suppressed the generation of MDSCs (P<0.01),while overexpression of PD-1 in HeLa cells further enhanced the generation of MDSCs (P<0.05) .Additionally,ELISA was employed to measure the levels of Th1,Th2,Th17,and Treg cyto-kines.It was observed that CMTM4 overexpression in HeLa cells reduced IL-10 secretion by T cells (P<0.01),but increased IFN-γ and TNF-α secretion (P<0.01),both of which were reversed by PD-1 overexpression (P<0.05 or P<0.01) .In conclusion,low expression of CMTM4 in cervical cancer leads to abnormal differentiation of MDSCs and immune escape of tumors.CMTM4 influences the activation of tumor T cells by regulating the PD-1/PD-L1 pathway.Thus,CMTM4 may be a potential target for the treatment of cervical cancer.