Over the past two decades, genome-wide association study(GWAS) has identified numerous genetic variants and loci associated with heritable diseases. With the gradual maturation and saturation of GWAS methodologies, transcriptome-wide association study(TWAS) offers a novel perspective by linkinggenetic phenotypes to gene expression levels. By integrating TWAS with other multi-omics analyses, researchers can gain a deeper understanding of heritable diseases. This article provides an overview of recent groundbreaking and representative TWAS methods and tools, analyzes their strengths and limitations, and discusses future trends in TWAS development.

ObjectiveTo explore the potential mechanism by which Huoxue Wentong prescription （HXWT） ameliorates post-myocardial infarction （MI） ventricular remodeling by regulating endothelial-to-mesenchymal transition （EndMT） via the hypoxia-inducible factor-1α （HIF-1α）/transforming growth factor-β₁ （TGF-β₁）/periostin （POSTN） signaling pathway. MethodsEighty SPF-grade male Sprague-Dawley rats were randomly assigned to a sham-operated group （n=10） and a modeling group （n=70）. The MI model was established by left anterior descending coronary artery ligation. Successfully modeled rats were further randomized into a model group， a sacubitril/valsartan （Entresto， 0.021 g·kg^-1） group， and low， medium， and high-dose （4.15， 8.30， and 16.60 g·kg^-1， respectively） HXWTF groups （n=10 per group）. From postoperative day 2， rats received HXWTF or sacubitril/valsartan by gavage once daily for 4 weeks， and those in sham and model groups received an equal volume of normal saline. After intervention， general conditions were assessed. Echocardiography was performed to measure the left ventricular ejection fraction （LVEF）， left ventricular fractional shortening （LVFS）， left ventricular end diastolic diameter （LVEDD）， and left ventricular end systolic diameter （LVESD）. Hematoxylin and eosin （HE） staining was employed to evaluate myocardial histopathology， and Masson's trichrome staining to assess myocardial fibrosis. Serum levels of B-type natriuretic peptide （BNP）， interleukin （IL）-6， IL-10， and matrix metalloproteinase-9 （MMP-9） were determined by enzyme-linked immunosorbent assay （ELISA）. Collagen type Ⅰ （ColⅠ） expression was assessed by immunohistochemistry. Immunofluorescence double staining was adopted to detect the expression of platelet endothelial cell adhesion molecule-1 （CD31） and α-smooth muscle actin （α-SMA）. Western blot was performed to quantify the expression of collagen type Ⅰ α2 （Col1A2）， VE-cadherin， CD31， α-SMA， HIF-1α， TGF-β₁， and POSTN. ResultsCompared with the sham group， the model group exhibited thinning and collapse of the left ventricular wall， decreased LVEF and LVFS and increased LVEDD and LVESD （P<0.01）， disrupted myocardial fibers with marked inflammatory cell infiltration， increased collagen deposition， enhanced ColⅠ immunoreactivity， elevate serum BNP， IL-6， and MMP-9 levels， a reduced IL-10 level （P<0.01）， downregulated expression of CD31 and VE-cadherin， and upregulated expression of α-SMA， Col1A2， HIF-1α， TGF-β₁， and POSTN （P<0.05，P<0.01）， accompanied by increased CD31/α-SMA co-localization. Compared with the model group， the sacubitril/valsartan group and all HXWTF groups showed improved ventricular wall structure， increased LVEF and LVFS， decreased LVEDD and LVESD， attenuated myocardial injury with reduced inflammatory infiltration and collagen deposition， declined serum BNP， IL-6， and MMP-9 levels， an elevated serum IL-10 level， upregulated expression of CD31 and VE-cadherin， downregulated expression of α-SMA， Col1A2， HIF-1α， TGF-β₁， and POSTN， and reduced CD31/α-SMA co-localization （P<0.05，P<0.01）. No significant differences were observed between the sacubitril/valsartan group and the medium- and high-dose HXWTF groups. ConclusionHXWTF may regulate the HIF-1α/TGF-β₁/POSTN pathway to inhibit EndMT， thereby ameliorating post-MI ventricular remodeling.

Objective:To investigate the clinical characteristics, treatment and prognosis of juvenile dermatomyositis (JDM) complicated by sever gastrointestinal hemorrhage in children.Methods:A retrospective analysis was conducted on 4 JDM patients with sever gastrointestinal hemorrhage admitted to our hospital, from January 2017 to January 2025. Data including demographics, clinical manifestations, laboratory and imaging findings, treatment courses, and outcomes were reviewed.Results:The cohort comprised 4 patients (2 males, 2 females), with onset ages of 6.1, 6.2, 10.0 and 8.0 years. All presented with rash and fatigue and were diagnosed with severe refractory JDM (strongly positive anti-NXP2 antibodies). Sever gastrointestinal hemorrhage occurred 18, 12, 51, and 2 months after JDM diagnosis. Two cases had confirmed gastrointestinal infections due to contaminated food. Abdominal pain was the initial gastrointestinal symptom and black stool was observed in all cases, hemoglobin levels dropped below 60 g/L (case 1-4 decreased to 38, 59, 60 and 43 g/L respectively). All patients exhibited intestinal wall thickening. Active bleeding sites included the duodenum (3 cases: 2 cases near the duodenal papilla, 1 cases with diffuse duodenal oozing). Emergency endoscopic hemostasis was performed in 3 cases. One patient with diffuse duodenal bleeding required additional glucocortieoid pulse therapy after failed interventional embolization. Three patients stabilized following aggressive treatment of JDM, while 1 case died due to duodenal perforation.Conclusions:Anti-NXP2 antibody-positive JDM patients are prone to gastrointestinal involvement, particularly in chronic cases. Duodenal bleeding is common, with vascular erosion and deep mucosal ulcers posing life-threatening risks. For children with positive anti-NXP2 antibodies who present with abdominal pain and thickened intestinal walls, early endoscopic examination should be conducted as soon as possible to detect digestive tract lesions and provide timely treatment. Patients with severe digestive tract bleeding usually require active treatment for the underlying disease combined with endoscopic hemostasis therapy. Under timely treatment, the prognosis is relatively favorable.

Objective:To explore the effects of combining APR-246 with irradiation for enhancing anti-tumor immune response against 4T1 breast cancer cells, and to develop multiple tumor treatment strategies.Methods:The control group, APR-246 group, irradiation group and irradiation combined APR-246 group were used both in the cell experiment and tumor-bearing mice experiment. The inhibitory effect of APR-246 on the proliferation of 4T1 cells was assessed by using Cell Counting Kit-8. The effect of APR-246 with irradiation on the survival rate of 4T1 cells using clone formation assay was measured. The levels of reactive oxygen species (ROS) and lipid peroxidation (LPO) in tumor cells using a 2’, 7’-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe and a lipid peroxidation sensor, the tumor inhibition rates of different groups of tumor bearing mice were compared, and the proportions of CD4+ and CD8+ T cells and the ratio of M1/M2 macrophages were determined in the tumor microenvironment by flow cytometry.Results:Compared with irradiation group, 2, 4, 6 Gy irradiation combined APR-246 group significantly reduced the survival rates of 4T1 cells ( t = 2.89, 4.15, 2.62, P < 0.05), the 6 Gy irradiation combined APR-246 group significantly increased the levels of ROS ( t = 16.95, P < 0.05) and LPO ( t = 6.09, P < 0.05) in 4T1 cells, and significantly increased the apoptosis rate of 4T1 cells ( t = 10.99, P < 0.05). Meanwhile, from the 16 th day of tumor inoculation, the 10 Gy irradiation combined APR-246 group showed significantly inhibited tumor growth ( t = 2.38-2.91, P < 0.05) and significantly increased proportions of CD4+ and CD8+ T cells ( t = 9.96, 6.28, P < 0.05) and M1/M2 ratio ( t = 15.30, P < 0.05) in tumor tissues. Conclusions:APR-246 combined with irradiation can effectively increase ROS and LPO levels in 4T1 cells, promote tumor cell apoptosis, and induce anti-tumor immune response, thus potentially inhibiting the growth of 4T1 cells.

Intestinal radiosensitivity makes radiation-induced intestinal injury (RIII) as a common complication among individuals exposed to accidental radiation and patients with abdominal or pelvic malignancies receiving radiotherapy. At present, there are no effective measures for the prevention and treatment of RIII. Developing novel prevention and treatment strategies is of great significance for improving the prognosis and quality of life for both individuals exposed to accidental radiation and cancer patients. Lactobacillus, a Gram-positive bacterium, is widely observed in humans and animals. It exhibits notable probiotic functions, including maintaining gut microbiota homeostasis, preserving intestinal barrier, and modulating immune responses. Substantial studies have demonstrated that Lactobacillus has remarkable protective and therapeutic effects against radiation-induced injury, specifically significantly alleviating RIII. These probiotic functions of Lactobacillus make it have high priority to become the chassis of genetically engineered strains. However, multiple factors influence the construction of a genetically engineered strain, limiting the application of Lactobacillus as a chassis. This review focuses on the probiotic functions of Lactobacillus, highlighting advances in research on Lactobacillus and its engineered probiotics in radiation protection and treatment. Furthermore, it summarizes key factors influencing the construction of genetically engineered strains based on the Lactobacillus chassis. It aims to provide insights for developing genetically engineered strains with radioprotective and therapeutic effects using Lactobacillus as the chassis.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objective:To analyze the clinical efficacy of the Schroth therapy in the treatment of adolescent idiopathic scoliosis.Methods:Relevant clinical studies on Schroth therapy for adolescent idiopathic scoliosis were retrieved from CNKI, Wanfang Data, SinoMed, Chinese Medical Journal Full-text Database, PubMed, Embase, Cochrane Library, and Web of Science. The search time was from the establishment of the database to November 2024. Two authors independently conducted the literature search and imported all potentially eligible studies into EndNote X9 to determine whether the studies met the inclusion criteria. If there was any disagreement, the two parties would discuss and solve it or add a third author for judgment. The scoliosis Cobb angle and the Scoliosis Research Society question-naires-22 (SRS-22) or SRS-23 were extracted from the scoliosis after treatment. The Schroth therapy was compared with other conservative treatment methods (functional exercise or no intervention). The modified Jadad scale was used to evaluate the quality of the included randomized controlled trials. When the heterogeneity between groups was small, the fixed-effect model was used for analysis, and when the heterogeneity between groups was large, the random-effect model was used for analysis. Sensitivity analysis was used to evaluate the stability of the meta-analysis results.Results:A total of 189 patients from 8 literatures were included in the meta-analysis, including 2 Chinese literatures and 6 English literatures, all of which were randomized controlled trials, with a modified Jadad score of 4-6 points. The results of meta-analysis showed that the Cobb angle of Schroth therapy in the treatment of adolescent idiopathic scoliosis was smaller than that of functional exercise or no intervention [ WMD=-3.63, 95% CI (-4.76, -2.51), P<0.001]. SRS-22 or SRS-23 was superior to functional exercise or no intervention [ WMD=0.23, 95% CI(0.14, 0.32), P<0.001], and the difference was statistically significant. The results of subgroup analysis showed that the Cobb angle of Schroth treatment was smaller than that of other conservative treatment methods such as functional exercise [ WMD=-3.48, 95% CI(-4.76, -2.20), P<0.001]. Conclusion:Compared with other conservative treatment methods and no intervention, Schroth therapy can effectively improve the Cobb angle and quality of life in the treatment of adolescent idiopathic scoliosis.

[Purpose]To analyze the trends of cervical cancer incidence in Qidong City of Jiangsu Province from 1977 to 2021.[Methods]Based on the cervical cancer registration database in Qi-dong City from 1977 to 2021,the crude incidence rate,the age-standardized rate by the standard Chinese standard population and the world standard population(ASRC and ASRW),the truncated rate of 35～64 years old,the cumulative rate of 0～74 years old,and the cumulative risk were cal-culated;the incidence rates of birth cohorts were analyzed.Joinpoint regression analysis was per-formed with Joinpoint 4.9.0.0 software to calculate the annual percentage change(APC)and the average annual percentage change(AAPC)of cervical cancer incidence.[Results]A total of 2 253 new cases of cervical cancer registered in Qidong City from 1977 to 2021,accounting for 1.62％of the total case numbers of cancer in the whole population,and for 4.03％of the total number of cancers in women.The crude incidence rate was 8.75/105,the ASRC was 4.54/105,the ASRW was 6.01/105,the truncated rate(35～64 years old)was 15.09/105,the cumulative rate(0～74 years old)was 0.63％,and the cumulative risk was 0.63％.The incidence of cervical cancer increased with age from 1977 to 2021.The average incident age was 55.36 years old,with the lowest age of 47.51 years old in 2010.Secular trend analysis showed that the AAPC of the crude incidence of cervical cancer was 6.010％(95％CI:4.951％～7.081％)(P＜0.001),among which the trend decreased from 1977 to 1999,with an APC of-2.507％;and then the trend increased from 1999 to 2017,with an APC of 14.436％(P＜0.001).The rising and falling trend curves of the AS-RC and ASRW were similar to that of the crude incidence.The age group and time period analysis showed that the peak incidence was in the older age groups before 2006,while the peak inci-dence appeared in the age groups of 45～54 years old from 2007 to 2021.The AAPCs in age groups of 25～64 years old demonstrated upward trends(all P＜0.05).The birth cohort analysis showed that the cervical cancer incidence in the 1937-1941 birth cohort was the lowest,and the birth cohort-specific rates in all age groups showed"V-shape"trends.[Conclusion]Long-term monitoring of cervical cancer incidence in Qidong has shown a trend of initially slow decline fol-lowed by a rapid increase,with the peak incident shifting towards younger ages.The rising trends of cervical cancer incidence in last two decades may be associated with the increased HPV infection,suggesting that measures to reduce HPV infection and enhance vaccination should be strengthened.

Adolescent idiopathic scoliosis(AIS)is a complex three-dimensional deformity involving coronal,sagittal,and axial planes,with a prevalence that should not be overlooked.With advancements in technology and in-depth research,an increasing number of hospitals and physicians are exploring standardized diagnostic and treatment approaches for AIS.Comprehensive and in-depth understanding is required for AIS,including its etiology,screening and diagnosis,classification,assessment and examination,treatment options,exploration of current focus,and evaluation of quality of life.Such understanding ensures that the diagnostic and treatment are scientific,standardized,and timely.Based on the principles of evidence-based medicine,a consensus on the diagnosis and treatment of AIS is reached after multiple discussions among spinal surgery experts,aiming to provide reference and guidance for clinical practice.

OBJECTIVES: To explore the association between GPSM2 expression level and gastric cancer progression and analyze the functional pathways and action mechanism of GPSM2. METHODS: We analyzed GPSM2 expression levels in gastric cancer tumors based on data from the GEPIA database and the clinical data of 109 patients. Public databases enrichment analysis were used to assess the impact of GPSM2 expression level on survival outcomes and the functional pathways and action mechanism of GPSM2. We further observed the effects of GPSM2 knockdown and overexpression on proliferation, migration and apoptosis of MGC803 cells using CCK-8 assay, colony formation assay, flow cytometry and immunoblotting and on the growth of MGC803 cell xenografts in nude mice. RESULTS: Bioinformatic analysis and immunohistochemical staining of the clinical specimens both revealed high GPSM2 expressions in gastric cancer (P<0.01). A high GPSM2 expression was significantly correlated with T3-4 stages, N2-3 stages, a carcinoembryonic antigen (CEA) level ≥5 μg/L, and a carbohydrate antigen (CA) 19-9 level ≥37 kU/L (P<0.05). Cox regression analysis identified high GPSM2 expression as an independent risk factor affecting 5-year survival of the patients (P<0.05). Gene ontology (GO) analysis suggested that GPSM2 was involved in cell cycle regulation. In MGC803 cells, GPSM2 overexpression significantly promoted cell proliferation and G1/S transition and xenograft growth in nude mice. KEGG pathway enrichment analysis indicated that GPSM2 executed its biological functions by regulating the p53 signaling pathway, which was confirmed by the results of immunoblotting experiments showing suppression of p53 signaling pathway activity in GPSM2-over expressing MGC803 cells. CONCLUSIONS GPSM2 is highly expressed in gastric cancer to affect patient prognosis by promoting tumor cell proliferation and G1/S transition possibly via inhibiting the p53 pathway.
Stomach Neoplasms/metabolism* ; Humans ; Cell Proliferation ; Prognosis ; Animals ; Mice, Nude ; Cell Line, Tumor ; Mice ; Apoptosis ; Tumor Suppressor Protein p53/metabolism* ; Cell Movement