ObjectiveTo explore the mechanism of Sangpi Zhike prescription in treating cough after respiratory syncytial virus （RSV） infection through the "lung-intestine co-treatment" approach using network pharmacology and animal experimental validation. MethodsActive ingredients and targets of Sangpi Zhike prescription were retrieved from the Traditional Chinese Medicine Systems Pharmacology （TCMSP） database. Disease targets were obtained from GeneCards and Online Mendelian Inheritance in Man（OMIM） databases. Protein-protein interaction （PPI） networks and drug-component-target networks were constructed using overlapping targets between drugs and diseases to identify core targets. Gene ontology（GO） and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analyses were performed on the overlapping targets. Sixty mouse models were established： 10 as the normal group， and the remaining mice were infected with RSV via slow nasal drip of RSV suspension， with cough induced using capsaicin solution. After modeling， mice were divided into a model group， a Montelukast Sodium group （1 mg·kg^-1·d^-1）， and low， medium， and high dose groups of Sangpi Zhike prescription （4.875，9.75，and 19.5 g·kg^-1·d^-1）， with 10 mice per group. From day 14 after RSV infection， the normal and model groups received saline via gavage， while other groups received corresponding drug treatments once daily for 5 d. Hematoxylin-eosin（HE） staining was used to observe pathological changes in lung and intestinal tissue. The protein content of extracellular signal-regulated kinase 1/2 （ERK1/2） and phosphorylated （p）-ERK1/2 in the lung and colon tissue of mice was detected by Western blot. Real-time polymerase chain reaction（Real-time PCR） detected ERK1/2 mRNA expression in lung and intestinal tissue. Immunohistochemistry assessed p-MEK1/2， p-ERK1/2， p-c-Fos protein levels， and inflammatory cytokines interleukin（IL）-4 and （TNF）-α in lung and colon tissue. ResultsNetwork pharmacology identified 184 active ingredients and 684 targets in Sangpi Zhike prescription， with 1 344 RSV-related disease targets and 209 overlapping targets. Core targets included TNF， Fos， and Jun. KEGG enrichment revealed 179 pathways， primarily mitogen-activated protein kinase（MAPK）， cancer， TNF， and IL-17 signaling pathways. Animal experiments showed that， compared to those of the normal group， the lung tissue sections of the model group showed typical inflammatory damage， infiltration of inflammatory cells， rupture of alveolar septa， extensive alveolar fusion， and disruption of tight junctions between single-layer columnar epithelial cells in the intestinal tissue. The values of p-ERK1/2 and ERK1/2 in lung and intestinal tissue were significantly increased （P<0.01）， and the expression level of ERK1/2 mRNA was significantly elevated （P<0.01）. The levels of ERK1/2， p-MEK1/2， p-ERK1/2， p-c-Fos， IL-4， and TNF-α along the ERK pathway were significantly increased （P<0.05， P<0.01）. Compared to the model group， Sangpi Zhike prescription groups showed reduced lung and intestinal inflammation， decreased p-ERK1/2/ERK1/2 ratios （P<0.05，P<0.01）， lower ERK1/2 mRNA levels， and downregulated ERK pathway proteins （P<0.05，P<0.01）. ConclusionSangpi Zhike prescription alleviates cough and intestinal symptoms after RSV infection via the "lung-intestine co-treatment" mechanism by suppressing expression levels of ERK1/2， p-MEK1/2， p-ERK1/2， p-c-Fos， IL-4， and TNF-α on ERK pathway components， thereby mitigating lung and intestinal pathological damage.

ObjectiveTo investigate the effect and mechanism of simvastatin pretreatment on kidney ischemia reperfusion injury （IRI） in mice. MethodsFifteen male C57BL/6 mice aged 6-8 weeks were divided into three groups： Sham operation group （Sham group）， kidney IRI group （IR group）， and simvastatin pretreatment+kidney IRI group （SIM group）. Hematoxylin-eosin （HE） staining of kidney tissue and detection of serum creatinine （SCr） and lactate dehydrogenase （LDH） were used to evaluate kidney injury. The levels of superoxide dismutase （SOD）， reduced glutathione （GSH）， malondialdehyde （MDA） and reactive oxygen species （ROS） were detected to evaluate oxidative stress. The contents of ferrous iron （Fe²⁺） and ferric iron （Fe³⁺） in kidney tissue were detected， and the morphological changes of mitochondria were observed by transmission electron microscope. The relative expression levels of Kruppel-like factor 2 （KLF2）， glutathione peroxidase 4 （GPX4）， solute carrier family 7 member 11 （SLC7A11）， and acyl-coa synthetase long chain family member 4 （ACSL4） protein in kidney tissue were detected. ResultsCompared with the IR group， the SIM group had significantly reduced renal tubular injury and decreased contents of Scr and LDH in serum （P < 0.001）. It also showed increased expression of SOD and GSH and decreased expression of MDA and ROS （P < 0.01）. Simvastatin pretreatment reduced the contents of Fe²⁺ and Fe³⁺ in the tissues （P < 0.01） and alleviated mitochondrial damage. It also promoted the expression of KLF2 （P < 0.01）， up-regulated the expression of ferroptosis-related protective proteins GPX4 and SLC7A11， and down-regulated the expression of ferroptosis-related damage protein ACSL4 （P < 0.05）. ConclusionSimvastatin pretreatment may inhibit kidney ferroptosis by promoting the expression of KLF2 to alleviate kidney IRI.

Atherosclerotic plaques arise within the vessels， yet their morphological evolution parallels that of carbuncles and abscesses. Drawing on the pathomechanism progression of carbuncles and abscesses， this paper proposes a dynamic pathogenesis model of "constraint-putrefaction-ulceration" for atherosclerotic plaques. The formation of atherosclerotic plaque begins with phlegm-turbidity obstruction and qi-blood stagnation （constraint stage）； prolonged constraint transforms into heat that scorches the vessels and forms plaques （putrefaction stage）； ultimately， toxin invades inward and ruptures the vessels， injuring the heart （ulceration stage）. Accordingly， staged differentiation and treatments are proposed. During the constraint stage， the focus is venting constraint and unblocking collaterals， clearing and relieving constraint-heat， for which Yue Jyu Pills （越鞠丸） and Danzhi Xiaoyao Powder （丹栀逍遥散） with modifications can be used. During the putrefaction stage， the method is clearing heat and dispelling abscesses， resolving stasis and dissipating knot， with modified Wuwei Xiaodu Beverage （五味消毒饮） and Xuefu Zhuyu Decoction （血府逐瘀汤）. During the ulceration stage， it is suggested to expell toxin and stasis， benefit qi and nourish yin using modified Gualou Xiebai Banxia Decoction （瓜蒌薤白半夏汤） and Sheng Mai Powder （生脉散）. This framework offers new perspectives for the differentiation and treatment of atherosclerotic plaques in traditional Chinese medicine.

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, characterized by poor prognosis due to its high proliferative and invasive potential. Tumor metabolic reprogramming, particularly involving glucose metabolism, is essential for tumor survival. This study investigates the role of the Hippo pathway effector transcriptional co-activator with PDZ-binding motif (TAZ) in regulating gluconeogenesis and promoting tumorigenesis in HCC. Methods: TAZ expression in HCC was analyzed using The Cancer Genome Atlas data and validated in clinical samples and cell lines. TAZ was overexpressed or silenced in HCC cell lines to evaluate its effects on cell proliferation, apoptosis, migration, and invasion. The expression and prognostic relevance of the gluconeogenesis-related genes phosphoenolpyruvate carboxykinase 1 (PCK1) and glucose-6-phosphatase (G6PC) were examined, along with their correlation with TAZ expression. Tumor growth was assessed in nude mice. Interactions between TAZ and the glucocorticoid receptor (GR) were investigated using co-immunoprecipitation, immunofluorescence, and chromatin immunoprecipitation assays. Results: TAZ was significantly upregulated in HCC tissues and cell lines. TAZ overexpression enhanced proliferation, reduced apoptosis, and promoted migration and invasion. In contrast, PCK1 and G6PC were downregulated in HCC and showed a negative correlation with TAZ expression. Conclusion TAZ modulates gluconeogenesis and accelerates tumor growth, whereas its knockdown attenuates tumor progression. TAZ interacts with GR, suppressing its transcriptional activity on gluconeogenic gene promoters.

[Objective] To investigate the factors influencing the detection of HLA-C expression by flow cytometry. [Methods] A total of 12 hematopoietic stem cell suspension samples from peripheral hematopoietic stem cell volunteer donors were randomly collected after CD34⁺ cell counting detection. The influence of detecting different number of nucleated cell (500 000, 50 000 and 5 000), sequential order of red blood cell lysis and antibody incubation, and the HLA-C antibody with varied remaining time from the expiration date on the detection results of HLA-C expression by flow cytometry were investigated, respectively. The significance of differences between different groups was analyzed through Student t test. [Results] There was no significant difference in the proportion of HLA-C positive cells and mean fluorescence intensity (MFI) among the three groups with different nucleated cell numbers detected (500 000, 50 000 and 5 000) (P>0.05). The sequential order of red blood cell lysis and antibody incubation had no influence on the proportion of HLA-C positive cells (P>0.05), but HLA-C MFI value was significantly lower when antibody incubation was performed after red blood cell lysis than that when antibody incubation was performed before red blood cell lysis (P<0.05). The proportion of HLA-C positive cells and MFI value detected by HLA-C antibody remaining 24 months from the expiration date were significantly higher than those detected by HLA-C antibody remaining only 5 months from the expiration date (P<0.05). [Conclusion] The present study has investigated the factors of influencing HLA-C expression level by flow cytometry, the results have important reference and application value for standardizing the experimental operation of HLA-C expression and improving the accuracy and comparability of detection results.

OBJECTIVE: To investigate the clinical phenotype and genetic characteristics of a family with Dentinogenesis imperfecta type Ⅰ(DGI-Ⅰ). METHODS: Clinical data were collected from a patient with DGI-Ⅰ admitted to the Reproductive Medicine Department of the Affiliated Hospital of Jining Medical University in March 2024. Clinical and familial data were retrospectively collected. Peripheral blood samples (5 mL each) were obtained from the proband and her family members for genomic DNA extraction, followed by whole-exome sequencing (WES) and Sanger sequencing validation. The pathogenicity of the detected variants was assessed according to the Classification Standards and Guidelines for Genetic Variants formulated by the American Society of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the "ACMG Guidelines"). The study was approved by the Ethics Committee of the Affiliated Hospital of Jining Medical University (Ethics No. 2024-08-C012), and written informed consent for clinical research were obtained from all participants. RESULTS: The proband, a 35-year-old female, presented with translucent yellow primary teeth and progressive browning, darkening, and loss of permanent teeth, without skeletal abnormalities. Affected family members exhibited similar phenotypes. Genetic testing revealed a heterozygous COL1A2 variant (c.1503+1G>A) in the patient and other affected members, while unaffected family members all lacked this variant. Based on the ACMG Guidelines, this variant was classified as likely pathogenic (PM4 + PP1_Strong + PM2_Supporting). CONCLUSION The COL1A2 c.1503+1G>A heterozygous variant is the disease-causing mutation in this family. Above finding has expanded the mutational spectrum of the COL1A2 gene and provided a basis for genetic counseling and diagnosis in similar cases.
Humans ; Female ; Dentinogenesis Imperfecta/genetics* ; Collagen Type I/genetics* ; Adult ; Pedigree ; Mutation ; Male ; Phenotype ; Exome Sequencing

Objective To evaluate the therapeutic effect of Shenfu injection in shock patients by using bedside critical ultrasound.Methods A total of 80 shock patients admitted to First Hospital of Nanchang from January 2022 to May 2024 were selected and divided into Shenfu group(45 cases)and control group(35 cases)according to whether Shenfu injection was applied.Patients in control group were given conventional western medical treatment,while patients in Shenfu group were treated with Shenfu injection in addition to control group.The ultrasound measurement indicators and clinical results were recorded on the 1st,3rd,and 7th days of treatment respectively,and left ventricular end diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF),peak velocity of early diastolic flow of mitral valve(E)/peak velocity of early diastolic motion of mitral annulus(E'),tricuspid annular plane systolic excusion(TAPSE),right ventricular fractional area change(RVFAC),inferior vena cava variation rate(IVCV),heart rate(HR),mean arterial pressure(MAP),N-terminal pro-brain natriuretic peptide(NT-proBNP),lactic acid(Lac),sequential organ failure assessment(SOFA)score and 30-day survival status of two groups of patients was compared.Results After 1 day,3 days and 7 days of treatment,LVEDD and E/E'of two groups of patients gradually decreased,while LVEF,TAPSE,RVFAC and IVCV gradually increased significantly(P＜0.05).After 7 days of treatment,the LVEF,TAPSE,RVFAC and IVCV of patients in Shenfu group were significantly higher than those in control group(P＜0.05).After 7 days of treatment,the HR,NT-proBNP,Lac and SOFA scores of two groups of patients were significantly lower than those before treatment in same group,and the MAP was significantly higher than that before treatment in same group(P＜0.05).The HR,NT-proBNP,Lac and SOFA scores of patients in Shenfu group were significantly lower than those in control group,the MAP was significantly higher than that in control group,and the mechanical ventilation time and the length of stay in intensive care unit were significantly shorter than those in control group(P＜0.05).Kaplan-Meier survival analysis showed that 30-day survival rate of patients in Shenfu group was significantly higher than that in control group(82.22％vs.54.28％,P＜0.05).Conclusion Bedside critical ultrasound showed that Shenfu injection could effectively improve ventricular systolic and diastolic function in shock patients,providing a valuable real-time assessment tool for shock treatment.

Objective:To investigate the prevalence of cardiometabolic multimorbidity (CMM) in Chinese middle-aged and elderly population, and the associated factors of cognitive function in CMM patients.Methods:It was a cross-sectional study. Data of demographic characteristics, lifestyle, chronic disease, and cognitive function in middle-aged and elderly subjects were obtained from the Harmonized CHARLS D version 2015 database, subjects with emotional and psychiatric disorders and memory-related disorders, and those with missing chronic disease data were excluded. The factors associated with cognitive function in CMM patients were analyzed with generalized linear regression model.Results:A total of 15 007 respondents aged (61.07±9.70) years were included in the analysis, 7 338 (48.9%) of whom were males. There were 3 303 cases of CMM with a prevalence rate of 22.01%, and the proportion of females was 54.9% (1 814/3 033), and the proportion of males was 45.1% (1 489/3 033). Generalized linear regression analysis showed that age, educational level, place of residence, depressive symptoms were correlated with cognitive function scores of CMM patients (all P<0.05). Conclusion:The prevalence rate of CMM in middle-aged and elderly people in China is higher, and age, education level, place of residence, depressive symptoms are associated with cognitive function in CMM patients.

Objective:To understand the prevalence and related factors of three common chronic diseases, hyperlipidemia, hypertension and diabetes in HIV-infected persons.Methods:As of December 2023, HIV-infected persons >15 years old who are receiving antiviral therapy (ART) and follow-up in Henan Province were selected as the study objects. Questionnaires, physical examinations, and blood samples were collected to collect demographic information, ART, body weight, blood lipids, blood pressure, and blood sugar of HIV-infected persons. The logistic regression model was used to analyze the related factors of hyperlipidemia, hypertension and diabetes.Results:Among 4 023 HIV-infected patients, the prevalence rates of hyperlipidemia, hypertension, and diabetes were 64.47% (2 594/4 023), 16.80% (676/4 023), and 10.54% (424/4 023), respectively. Multivariate analysis showed that hyperlipidemia was positively associated with ≥40 years of age, overweight and obesity, two nucleoside reverse transcriptase inhibitors (NRTIs) + proteasome inhibitors (PIs) regimen and two NRTIs+ integrase inhibitor regimen, and negatively associated with low body weight. Hypertension was positively correlated with the age group ≥40 years old, family history of cardiovascular and cerebrovascular diseases, overweight and obesity, ART time ≥0.5 years, and negatively correlated with low body weight. Diabetes was positively associated with age group ≥40 years, family history of cardiovascular and cerebrovascular disease, overweight and obesity, and negatively associated with the use of two NRTIs+PIs treatment regimens.Conclusions:In 2023, the prevalence of hyperlipidemia, hypertension, and diabetes among HIV-infected people in Henan Province was relatively high, and the risk of common chronic diseases among those ≥40 years old, overweight and obese, and those with a family history of cardiovascular and cerebrovascular diseases was also relatively high. It is recommended to strengthen the prevention and management of common chronic diseases among HIV-infected people.

Objective:To investigate the clinical phenotype and genetic characteristics of a family with Dentinogenesis imperfecta type Ⅰ(DGI-Ⅰ).Methods:Clinical data were collected from a patient with DGI-Ⅰ admitted to the Reproductive Medicine Department of the Affiliated Hospital of Jining Medical University in March 2024. Clinical and familial data were retrospectively collected. Peripheral blood samples (5 mL each) were obtained from the proband and her family members for genomic DNA extraction, followed by whole-exome sequencing (WES) and Sanger sequencing validation. The pathogenicity of the detected variants was assessed according to the Classification Standards and Guidelines for Genetic Variants formulated by the American Society of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the " ACMG Guidelines" ). The study was approved by the Ethics Committee of the Affiliated Hospital of Jining Medical University (Ethics No. 2024-08-C012), and written informed consent for clinical research were obtained from all participants.Results:The proband, a 35-year-old female, presented with translucent yellow primary teeth and progressive browning, darkening, and loss of permanent teeth, without skeletal abnormalities. Affected family members exhibited similar phenotypes. Genetic testing revealed a heterozygous COL1A2 variant (c.1503+ 1G>A) in the patient and other members, while unaffected family all members lacked this variant. Based on the ACMG Guidelines, this variant was classified as likely pathogenic(PM4 + PP1_Strong + PM2_Supporting). Conclusion:The COL1A2 c. 1503+ 1G>A heterozygous variant is the disease-causing mutation in this family. Above finding has expanded the mutational spectrum of the COL1A2 gene and provided a basis for genetic counseling and diagnosis in similar cases.