Background::Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease (PD) risk factors; however, no comprehensive analyses of these genes in patients with PD have been undertaken. Therefore, we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD.Methods::Whole-exome sequencing (WES) was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls. Additionally, whole-genome sequencing (WGS) was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls.Results::We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts, respectively. Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD. However, the significance did not pass the Bonferroni correction. Meanwhile, 72 and 1730 common variants were found in the WES and WGS cohorts, respectively. Unfortunately, single-variant logistic association analyses did not identify significant associations between common variants and PD. Conclusions::Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients. However, we highlight the complexity of PD and the need for extensive research elucidating its etiology.

Objective:To screen the differentially expressed genes(DEGs)under high phosphate-induced calcification in the vascular smooth muscle cells(VSMCs)by mRNA high-throughput sequencing technology,and to analyze the key genes and signaling pathways involved in the VSMCs calcification.Methods:The human VSMCs were divided into control group and model group.The cells in model group was exposed to the high-phosphate medium,while the cells in control group were cultured in DMEM supplemented with 10%fetal bovine serum under the same conditions.The VSMCs in two groups,stably transfected,were cultured for 12 d.The morphology of the cells in two groups were observed and photographed under inverted microscope.The DEGs were selected by Hisat2 software,and Gene Ontology(GO)functional and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were performed by Stringtie software from three aspects,such as biological processes(BP),molecular functions(MF),and cellular components(CC).The calcification of the cells in two groups was observed by Von Kossa staining method.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to analyze the expression levels of alkaline phosphatase(ALP),bone morphogenetic protein 2(BMP2),alpha-smooth muscle actin(α-SMA),tumor protein 53(Tp53),glutathione peroxidase 4(GPX4),ferritin light chain 1(Ftl1),and glycosylphosphatidylinositol-specific phospholipase D1(GPLD1)mRNA in the cells in two groups.Results:Compared with control group,there were 2 524 DEGs in the cells in model group,and there were 1 368 upregulated DEGs and 1 156 downregulated DEGs.Clustering of DEGs between the cells in two groups was distinct.The GO functional and KEGG pathway enrichment analysis results showed that the upregulated DEGs were primarily involved in regulating the microtubule cytoskeleton,cell polarity,protein localization,and cell cycle regulation among BPs;in constructing cell membrane,microtubule organization,chromosomes,and kinetochore among CCs;and functioning in phosphatidylinositol phosphate,Rho GTPase protein binding,transmembrane transport,and protein kinase regulatory activity among MFs.Downregulated DEGs were mainly involved in cytoplasmic translation,protein membrane localization,mRNA metabolism,and protein endoplasmic reticulum localization among BPs;in forming ribosome subunits,cell membrane,and autophagy among CCs;and functioning in single-stranded DNA,ribonucleoprotein complex,growth factor binding,regulating protein kinase activity,and catalytic activity among MFs.Seven signaling pathways were significantly enriched in upregulated genes,most notably in the biosynthesis of glycosylphosphatidylinositol(GPI)anchors;whereas 18 signaling pathways were significantly enriched in the downregulated genes,most notably in ferroptosis.The RT-qPCR results showed that compared with control group,the expression levels of GPX4,Ftl1,and Tp53 mRNA in the cells in model group were significantly decreased(P<0.01),while the expression level of GPLD1 mRNA was significantly increased(P<0.01);compared with control group,the expression level of α-SMA mRNA in the cells in model group was significantly decreased(P<0.01),and the expression levels of ALP and BMP2 mRNA were significantly increased(P<0.01).Conclusion:The VSMCs underwent calcification and normal cells exhibit the DEGs.The key signaling pathways in the calcification induced by high phosphate in the VSMCs include ferroptosis and GPI anchor biosynthesis,mediated primarily through GPX4,Ftl1,Tp53,and GPLD1.

Objective To observe the interventional effects of complex probiotic powder on blood bio-chemical indices and vaginal flora in pregnant women with high risk of gestational diabetes mellitus(GDM). Methods One hundred and ten pregnant women with high risk of GDM recruited from the outpatient clinics of the obstetric department and nutrition department in this hospital were randomly divided into the probiotic intervention group (n=55) and the placebo control group (n=55).The intervention group was given 1 bag of complex probiotic powder per day,and the control group was given 1 bag of placebo powder.The colors,shapes,sizes and tastes of powders in the two groups remained the consistency.The intervention duration in this trial was 23 weeks.The questionnaire survey were conducted at baseline and at the intervention endpoint,and the blood biochemical indexes detections were performed at baseline,after 24-28 weeks of gestation,and after 34-38 weeks of gestation,respectively.In addition,the differences in the composition of the vaginal flora structure between the two groups of high risk pregnant women with GDM were detected at the intervention endpoint.Results A total of 97 cases were eventually included in the statistical analysis.Among them,there were 50 cases in the probiotic intervention group and 47 cases in the placebo control group.At the end of the 23 week intervention,there were no statistically significant differences in fasting blood glucose,red blood cells,hemoglobin,leukocytes,ferritin,total protein,albumin,glutamic transaminase,glutamic oxalate transam-inase and total bilirubin between the probiotic intervention group and placebo control group (P>0.05).In terms of vaginal flora,there was a significant difference in some indicators of α diversity between the probiotic group and placebo control group (P<0.05),and there was no significant difference in β diversity between the two groups (P>0.05).At the level of vaginal flora phyla,there were significant differences in the Firmicutes,Actinobacteria,Desulfobacterota,Deferribacterota,and δ-Myxococcota between the two groups (P<0.05).At the level of vaginal flora genera,the relative abundance of Lactobacillus spp.in the probiotic intervention group was significantly higher than that in the control group (P<0.05).Conclusion Complex probiotic pow-der supplementation may have a limited role in improving blood glucose and other related biochemical indica-tors in high-risk pregnant women with GDM.But it has a certain role in regulating the vaginal micro ecological balance in pregnant women with high risk of GDM.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

Objective:To systematically evaluate and Meta-synthesize qualitative studies on the home management needs of patients with spinal cord injury (SCI) to understand their actual self-management needs and improve the quality of home management for patients with SCI in China.Methods:A comprehensive search was conducted in databases including CNKI, Wanfang, CBM, PubMed, Embase, Web of Science, CINAHL, and Cochrane Library for qualitative research on the home management needs of patients with SCI, with a search timeframe up to November 30, 2023. The methodological quality of the included studies was evaluated using the Joanna Briggs Institute (JBI) Qualitative Assessment and Review Instrument (2016). Results were integrated and analyzed using Meta-synthesize methods.Results:A total of 15 studies were included, from which 58 distinct research findings were extracted. These were categorized into 10 new categories, which were further integrated into four main results: the need for positive emotional support, daily living-related needs, healthcare service needs, and social support needs.Conclusions:Healthcare providers should deeply understand the home management needs of patients with SCI. Utilizing artificial intelligence technology, an integrated support model encompassing hospital, home, and society can be constructed. Establishing a comprehensive home rehabilitation platform for patients with SCI can focus on psychological issues and enhance social support levels, thereby improving patients' quality of life.

Objective:To integrate qualitative research on the real experience of patients with spinal cord injury (SCI) returning to society after discharge, so as to provide a basis for developing transitional care intervention program, and promote patients' reintegration into society.Methods:Qualitative research on the real experience of patients with SCI returning to society after discharge was electronically retrieved on China National Knowledge Infrastructure, WanFang Data, VIP, China Biomedical Literature Service System, Cochrane Library, PubMed, Embase, Web of Science, CINAHL, and so on .The search period was from database establishment to August 30, 2023. The quality evaluation criteria for qualitative research of the JBI Evidence-Based Health Care Center (2016) was used to assess the quality of literature, and Meta-synthesis was used to integrate the results.Results:A total of 16 articles were included, and 51 research results were extracted. Similar research results were summarized and combined to form 12 new categories, which were then synthesized into four integrated results, including experiencing physical and mental discomfort following discharge, facing challenges in reintegrating into society, seeking social support, and adapting to social life through self-adjustment role changes.Conclusions:Patients with SCI have multiple psychological experiences in the process of reintegration into society. Medical and nursing staff should attach importance to their inner needs, help them overcome stress and challenges, provide them with personalized continuous care, and promote their role adaptation and reintegration into society.

Objective To construct a rehabilitation care platform for spinal cord injury patients,based on patient portrait technology and to validate its application effect.Methods Artificial intelligence technology was used to realize the fusion of data.We constructed a patient portrait rehabilitation nursing system that can provide systematic and personalized information support.By the convenience sampling method,53 perioperative patients with spinal cord injury from July 2023 to December 2023 were selected as the test group to implement the intelligent intervention based on patient portrait technology;53 perioperative patients with spinal cord injury who were hospitalized from January 2023 to June 2023 were selected as the control group to implement the conventional information support intervention.The self-efficacy,self-care ability,and quality of life were compared before the intervention,and 2 weeks,4 weeks,12 weeks after the intervention between the 2 groups.Results 45 cases in the experimental group and 43 cases in the control group reached the endpoint of the study after 12 weeks of intervention.The ANOVA of the 2 groups showed the test group having a greater advantage over the control group,with statistically significant differences in self-efficacy,ability to perform daily living tasks,and quality of life between groups,intergroup effect,and interaction effect(P＜0.05).Conclusion The rehabilitation care platform based on patient portraits has a positive effect on improving self-efficacy,self-care ability and quality of life for spinal cord injury patients.

BACKGROUND: Intrauterine growth restriction (IUGR) is associated with adverse metabolic outcomes during adulthood. Histone modifications and changes in DNA methylation-affected genes are important for fetal development. This study aimed to confirm the epigenetic mechanisms in IUGR. METHODS: IUGR models were established in Sprague-Dawley rats using a maternal nutritional restriction approach during pregnancy. The abundance of insulin-like growth factor 2 (IGF2), phosphoinositide 3-kinase (PI3K), AKT serine/threonine kinase 2 (AKT2), and PPAR gamma coactivator 1 alpha (PGC-1α) was examined by real-time polymerase chain reaction (RT-PCR) and Western blotting analysis. Chromatin immunoprecipitation RT-PCR was employed to analyze histone modification in CCCTC-binding factor (CTCF)1-4 binding sites of the IGF2/H19 imprinting control region (ICR). The methylation states of CTCF1-4 binding sites were studied by pyrosequencing. RESULTS: The IUGR models were constructed successfully. IGF2 mRNA abundance in the placenta, fetal liver, and newborn liver was decreased in the IUGR group (P <0.01). Meanwhile, as compared with the control group, the expression levels of AKT2, PI3K, and PGC-1α were lower in newborn and 8-week-old livers in the IUGR group (P <0.05). In addition, knocking down IGF2 reduced the protein expression levels of AKT2-P and PGC-1α (P <0.05). In CTCF binding sites 1-4 of the IGF2/H19 ICR, AcH3 enrichment was significantly lower in CTCF1-3 in newborn and 8-week-old IUGR rats. H3K4me3 enrichment was significantly lower in the CTCF1-4 of newborn and 8-week-old IUGR groups (P <0.01). H3K9me2 enrichment was significantly higher in the IUGR group (P <0.01). The CpG dinucleotide methylation levels of CTCF1 and CTCF3, but not those of CTCF2 and CTCF4 binding sites in IUGR rat fetal, 4-week old, and 8-week-old livers decreased significantly (P <0.05). CONCLUSION The methylation status and histone modification in the IGF2/H19 ICR are related to growth and lipid metabolism via the PGC-1α/PI3K/AKT2 pathway in IUGR rats.

Sepsis is an inflammatory disorder syndrome caused by the infection of pathogenic microorganisms, which organ dysfunction due to the dysregulated response of the body to the infection. Sepsis is a dangerous disease with a high fatality rate. The liver, an important organ involved in human biological transformation, energy metabolism, and cytokine production. Its role in sepsis is like a "double-edged sword" because the liver acts as not only an important defense line of the body against microorganisms but also a common target of inflammatory disorders and damage, making it one of the most vulnerable organs in sepsis. The liver contributes to pathogen clearance through immune responses, but the resulting inflammatory reactions can also lead to tissue and organ damage. Sepsis liver injury is an independent risk factor for poor prognosis in sepsis patients, and preventing its occurrence and promoting early recovery can partially inhibit disease progression and reduce mortality rates. However, the pathogenesis of sepsis liver injury is not yet fully understood, and there is a lack of early and effective means of diagnosis and treatment. In-depth research on its pathogenesis will provide a better understanding of its occurrence and development, further supporting the theoretical basis for the treatment of sepsis liver injury and identifying some new targets for sepsis treatment, ultimately reducing the mortality of sepsis.

OBJECTIVE: To assess the value of using flat-sided culture tubes for preparing chromosomes through chorionic villi (CV) and amniotic fluid (AF) cell cultures during prenatal diagnosis. METHODS: From February to March 2020, 157 CV samples and 147 AF samples subjected to prenatal diagnosis at the Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region were selected as the study subjects. For each sample, one flat-sided tube and one flask culture were set up by following the standard protocols. The methods were evaluated by comparing the cell growth, experimental process, quality of chromosome preparation and costs. RESULTS: The success rates for the culturing of CV and AF samples by the flat-sided culture tube method were 97.45% (153/157) and 97.96% (144/147), respectively. By contrast, the success rates for the conventional flask method were 98.72% (155/157) for CV and 98.64% (145/147) for AF samples. No significant difference was found between the two methods (P > 0.05). The average harvest time required by the flat-sided culture tube method was 8.45 days for CV and 9.43 days for AF cultures, whilst the average harvest time for conventional flask method was 9.05 days and 9.54 days, respectively. The flat-sided culture tube method for CV had required significantly shorter average harvest time than the conventional method (P < 0.001). No statistical significant difference was found in the average harvest time for AF by the two methods (P > 0.05). The conventional culturing method had required three containers with two sample transfers. By contrast, the flat-sided culture tube method was carried out in one tube without any sample transfer. The average total amount of medium used was 3.91 mL for each flat-sided culture tube and 6.26 mL for each conventional flask. CONCLUSION The flat-sided culture tube method can provide a simple, cost-effective and error-reducing procedure for the CV and AF samples culture during prenatal diagnosis.
Child ; Female ; Pregnancy ; Humans ; China ; Prenatal Diagnosis ; Chorionic Villi Sampling ; Amniotic Fluid ; Cell Proliferation