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.

BACKGROUND:The most common complication of traumatic femoral neck fractures after internal fixation is femoral head necrosis.Currently,many studies have reported on the risk factors that affect the occurrence and development of postoperative femoral head necrosis,but there is still a lack of tools to predict the risk of femoral head necrosis after internal fixation of femoral neck fractures.OBJECTIVE:To develop a predictive model that estimates the risk of femoral head necrosis shortly after patients with femoral neck fractures receive cannulated screw internal fixation.METHODS:A retrospective analysis reviewed clinical records of 172 patients who underwent cannulated screw internal fixation for femoral neck fractures at Department of Orthopedics of Mianyang Central Hospital from January 2013 to June 2023.Patients were categorized into two groups based on the presence or absence of femoral head necrosis within one year post-operation:the necrosis group and the non-necrosis group.Univariate analysis,Lasso regression,and multivariate Logistic regression techniques were employed to identify the determinants of femoral head necrosis.A nomogram prediction model was constructed using R language's"rms"package,version 4.0.The receiver operating characteristic curve was used to evaluate the discriminatory ability of the model.The Hosmer-Lemeshow test was used to evaluate the goodness of fit of the model,and the decision curve analysis was used to determine its clinical application benefits.Internal validation of the study was conducted using the Bootstrap method,involving 1 000 repeated samplings.To delve deeper into the primary factors influencing femoral head necrosis post-internal fixation of the femoral neck,this paper employed the SHAP method for data set analysis.RESULTS AND CONCLUSION:(1)The risk factors leading to femoral head necrosis in the short term after cannulated screw fixation of femoral neck fractures include:smoking,diabetes,Garden classification,fracture line location,reduction quality,age,and operation time.(2)The prediction model demonstrated robust performance,evidenced by an area under the curve of 0.940(95％Confidence Interval:0.903 to 0.977),indicating a high level of prediction accuracy.The model achieved a sensitivity of 90.2％and a specificity of 87.6％,indicating that its diagnostic performance was stable.The Hosmer-Lemeshow goodness-of-fit test yielded a chi-square value of 6.593 with a P-value of 0.581,confirming that the model's predictions closely align with the observed outcomes.(3)The calibration curve of the model also performed well,and its overall trend was very close to the ideal curve,further proving the high accuracy of the model.(4)The internal validation was carried out by the Bootstrap method with 1 000 repeated samplings,and the area under the curve of the model internal validation was still as high as 0.939,proving that the model had good stability.(5)Through the decision curve,it is found that within the probability threshold range of 1％to 92％,the model can obtain the maximum net benefit value.(6)The SHAP analysis results show that among the risk factors analyzed in this study,the location of the fracture line serves as the most significant predictor of femoral head necrosis following internal fixation with cannulated screws in femoral neck fractures,and subcapital fractures are extremely prone to femoral head necrosis after surgery.(7)It is concluded that the validated prediction model demonstrates strong discriminative power and reliability,offering practical clinical utility.It serves as a useful reference tool for short-term risk assessment of femoral head necrosis following internal fixation of femoral neck fractures.

BACKGROUND:The most common complication of traumatic femoral neck fractures after internal fixation is femoral head necrosis.Currently,many studies have reported on the risk factors that affect the occurrence and development of postoperative femoral head necrosis,but there is still a lack of tools to predict the risk of femoral head necrosis after internal fixation of femoral neck fractures.OBJECTIVE:To develop a predictive model that estimates the risk of femoral head necrosis shortly after patients with femoral neck fractures receive cannulated screw internal fixation.METHODS:A retrospective analysis reviewed clinical records of 172 patients who underwent cannulated screw internal fixation for femoral neck fractures at Department of Orthopedics of Mianyang Central Hospital from January 2013 to June 2023.Patients were categorized into two groups based on the presence or absence of femoral head necrosis within one year post-operation:the necrosis group and the non-necrosis group.Univariate analysis,Lasso regression,and multivariate Logistic regression techniques were employed to identify the determinants of femoral head necrosis.A nomogram prediction model was constructed using R language's"rms"package,version 4.0.The receiver operating characteristic curve was used to evaluate the discriminatory ability of the model.The Hosmer-Lemeshow test was used to evaluate the goodness of fit of the model,and the decision curve analysis was used to determine its clinical application benefits.Internal validation of the study was conducted using the Bootstrap method,involving 1 000 repeated samplings.To delve deeper into the primary factors influencing femoral head necrosis post-internal fixation of the femoral neck,this paper employed the SHAP method for data set analysis.RESULTS AND CONCLUSION:(1)The risk factors leading to femoral head necrosis in the short term after cannulated screw fixation of femoral neck fractures include:smoking,diabetes,Garden classification,fracture line location,reduction quality,age,and operation time.(2)The prediction model demonstrated robust performance,evidenced by an area under the curve of 0.940(95％Confidence Interval:0.903 to 0.977),indicating a high level of prediction accuracy.The model achieved a sensitivity of 90.2％and a specificity of 87.6％,indicating that its diagnostic performance was stable.The Hosmer-Lemeshow goodness-of-fit test yielded a chi-square value of 6.593 with a P-value of 0.581,confirming that the model's predictions closely align with the observed outcomes.(3)The calibration curve of the model also performed well,and its overall trend was very close to the ideal curve,further proving the high accuracy of the model.(4)The internal validation was carried out by the Bootstrap method with 1 000 repeated samplings,and the area under the curve of the model internal validation was still as high as 0.939,proving that the model had good stability.(5)Through the decision curve,it is found that within the probability threshold range of 1％to 92％,the model can obtain the maximum net benefit value.(6)The SHAP analysis results show that among the risk factors analyzed in this study,the location of the fracture line serves as the most significant predictor of femoral head necrosis following internal fixation with cannulated screws in femoral neck fractures,and subcapital fractures are extremely prone to femoral head necrosis after surgery.(7)It is concluded that the validated prediction model demonstrates strong discriminative power and reliability,offering practical clinical utility.It serves as a useful reference tool for short-term risk assessment of femoral head necrosis following internal fixation of femoral neck fractures.

Objective To explore the efficacy and safety of blue laser vaporization in the treatment of large-volume (＞80 mL) benign prostatic hyperplasia (BPH). Methods A retrospective analysis was conducted on the clinical data of 149 BPH patients with prostate volume＞80 mL who underwent blue laser vaporization at our hospital during Aug. 2023 and Aug. 2025. The 1-month postoperative maximum urinary flow rate (Qmax) and international prostate symptom score (IPSS), operation time, postoperative hemoglobin drop, bladder irrigation volume, catheter indwelling time, and incidence of postoperative complications were recorded and analyzed. Results All operations were successfully completed, without conversion to other approaches. The operation time was (41.47±11.05) minutes, postoperative hemoglobin drop (2.78±1.19) g/L, bladder irrigation volume (9.97±1.49) bags, and catheter indwelling time (3.30±1.85) days. One month after surgery, the Qmax was significantly higher than the preoperative value [(20.19±3.39) mL/s vs. (2.39±2.17) mL/s], while the IPSS was significantly lower [(4.46±0.87) vs. (27.69±2.06)], with statistically significant differences (P＜0.001). Postoperative complications included 1 case of incontinence (0.67%), 2 cases of urethral stricture/bladder neck contracture (1.34%), and 1 case of secondary bleeding (0.67%), all of which improved with symptomatic treatment. Conclusion Blue laser vaporization is effective for treating large-volume BPH, with advantages such as minimal bleeding risk, short operation time, fast recovery and safety.

ObjectiveTo identify the direct target proteins for the anti-obesity effect of resveratrol （Res） via chemical proteomic analysis and systematically explore the molecular mechanisms by which Res inhibits lipid accumulation in adipocytes from mitochondrial function regulation， adipocyte browning， and inflammation inhibition， thus providing new targets and experimental evidence for the prevention and treatment of obesity and related metabolic diseases. MethodsThe cell counting kit-8 （CCK-8） assay was adopted to detect the safe and effective doses （7.5， 15， 30 μmol·L^-1） of Res for treating 3T3-L1 cells based on the cell survival rate. After being induced to differentiate into mature adipocytes， the cells were assigned into the blank ［treated with dimethyl sulfoxide （DMSO）］ group and the Res （7.5， 15， 30 μmol·L^-1） groups and treated for 48 h. Oil red O staining and total triglyceride （TG） content were assessed to measure lipid accumulation in adipocytes. Target protein identification of Res was conducted through IAA-P-based chemical proteomics combined with high-resolution mass spectrometry. Target proteins of Res were validated by cellular thermal shift assay （CETSA） combined with Western blot analysis. Furthermore， the expression of browning markers peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） and mitochondrial uncoupling protein 1 （UCP1）， as well as the target proteins NADH-ubiquinone oxidoreductase core subunit S8 （NDUFS8） and high-mobility group protein B1 （HMGB1） were determined by Western blot. The ATP assay kit was used to measure the ATP concentration. Mitochondrial biogenesis was characterized with MitoTracker Green， on the basis of which the regulatory effect of Res on mitochondrial function was analyzed. The level of the inflammatory cytokine tumor necrosis factor-α （TNF-α） was measured by enzyme-linked immunosorbent assay （ELISA）， on the basis of which the anti-inflammatory effect of Res on adipocytes was evaluated. ResultsCompared with the control group， Res demonstrated safety and efficacy within the range of 7.5-30 μmol·L^-1， without significantly affecting cell viability. Compared with the control group， different concentrations of Res reduced lipid accumulation in 3T3-L1 adipocytes （P<0.01）， promoted the expression of NDUFS8 （P<0.01）， increased the ATP concentration and the protein levels of UCP1 and PGC-1α， elevated the level of TNF-α （P<0.05， P<0.01）. ConclusionNDUFS8 and HMGB1were identified as the target proteins of Res in mitigating obesity. Res promotes mitochondrial biogenesis to induce the browning of 3T3-L1 adipocytes via targeting NDUFS8 and it inhibits the TNF-α-mediated inflammatory signaling via targeting HMGB1， thus inhibiting lipid accumulation and ameliorating obesity.

The herb pair Hedysari Radix-Angelicae Sinensis Radix is a classic combination embodying the theory of replenishing Qi and tonifying blood in traditional Chinese medicine. The two herbs are often used together to achieve the effects of replenishing Qi， tonifying blood， activating blood， and unblocking collaterals. Clinically， this herb pair is widely applied in the treatment of blood deficiency syndrome and hematopoietic dysfunction disorders such as myelosuppression induced by radiotherapy and chemotherapy. Modern research indicates that Hedysari Radix-Angelicae Sinensis Radix and their active components can synergistically promote hematopoiesis through multiple targets and pathways. At the cellular level， the active components directly activate hematopoietic stem cells （HSCs） and hematopoietic progenitor cells （HPCs）， promoting their proliferation and differentiation， while simultaneously stimulating the production and release of peripheral blood cells. Regarding molecular regulation， this herb pair can regulate the expression of various hematopoietic-related cytokines， such as stem cell factor and erythropoietin. Additionally， it modulates key signaling pathways， including phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） and Wnt/β-catenin， providing signal support for the hematopoietic process. Furthermore， Hedysari Radix-Angelicae Sinensis Radix can improve the hematopoietic microenvironment， protect bone marrow stromal cells， and eliminate free radicals through antioxidant effects， thereby reducing damage to hematopoietic cells. Furthermore， this herb pair regulates apoptosis-related proteins to inhibit excessive apoptosis of hematopoietic cells and increase their survival rate. Its material basis primarily includes active components such as Hedysarum polybotrys polysacchcrides and flavonoids， as well as Angelica sinensis polysaccharides and ferulic acid， which synergistically contribute to its hematopoietic-promoting effects. By elaborating on the active components and mechanisms of Hedysari Radix-Angelicae Sinensis Radix in promoting hematopoiesis， this paper aims to elucidate the molecular mechanisms underlying their hematopoietic effects and provide a reference for further research and clinical application.

Objective To investigate the nutritional quality characteristics of vitamin D3-fortified yogurt and explore its improving effect on vitamin D metabolism in the body under simulated weightlessness,thereby providing a theoretical basis for the development of functional foods.Methods Using reconstituted milk as the matrix and Vitamin D3(VD3)microcapsule powder as the fortifier,VD3-fortified yogurt was prepared.A systematic study was conducted to investigate the effects of different gradients(1.25 μg/100 mL,2.50 μg/100 mL,3.75 μg/100 mL,5.00 μg/100 mL,6.25 μg/100 mL)of VD3 microcapsule addition on its quality characteristics(titratable acidity,solid content,water-holding capacity,syneresis).In vivo assessments were conducted using a Sprague-Dawley(SD)rat tail-suspension model to simulate weightlessness.Levels in serum 25(OH)D3,1,25-(OH)2D3,calcium(Ca),and phosphorus(P)were detected using the enzyme-linked immunosorbent assay(ELISA)to evaluate its metabolic capacity.Results During fermentation(3 h),titratable acidity of VD?-fortified yogurt initially increased,then decreased,and eventually stabilized with rising microcapsule dosage,while total solid content remained consistent.WHC exhibited an initial increase followed by a decline,whereas syneresis showed an inverse trend.At an optimal dosage of 3.75 μg/100 mL,the yogurt displayed a dense and uniform network structure,characterized by non-Newtonian fluid behavior with shear-thinning properties.This formulation demonstrated robust structural stability under high-frequency mechanical stress,alongside desirable textural,flavor,and sensory attributes.Animal experiments revealed that the serum concentrations of 25(OH)D3,1,25-(OH)2D3,calcium,and phosphorus in the vitamin D?-fortified yogurt intervention group were significantly higher than those in the tail-suspended control group(P<0.05).Conclusion VD? microencapsulation technology effectively preserves and enhances the nutritional quality characteristics of yogurt and mitigates vitamin D metabolic dysregulation under simulated weightlessness.

Objective To evaluate the association of different obesity phenotypes and their components with the risk of cognitive impairment in older Chinese adults,and to assess the association between obesity and cognitive impairment in different cognition-related genetic backgrounds.Methods A cross-sectional study based on the West China Health and Aging Cohort was conducted.Logistic regression was applied to estimate the association of obesity phenotypes and components with cognitive impairment in older Chinese adults stratified by APOE gene and polygenic risk scores.Results A total of 7 316 participants were enrolled,of whom 1 820 had cognitive impairment.Weight gains were associated with a reduced risk of cognitive impairment(odds ratio[OR]=0.96,95%CI,0.95-0.97).Being overweight with a normal waist-to-hip ratio was a protective factor for cognition(OR=0.74,95%CI,0.61-0.90),whereas the coexistence of elevated waist-to-hip ratio and overweight did not increase the risk of cognitive impairment.Sarcopenia was associated with an elevated risk of cognitive impairment.This association was found in both overweight(OR=2.03,95%CI,1.71-2.41)and non-overweight older adults(OR=1.86,95%CI,1.58-2.20),and was significant across all polygenic risk score strata.Conclusion Increasing body mass may serve as a key protective factor against cognitive decline in older adults.Having sarcopenia and obesity is associated with an elevated risk of cognitive impairment,independent of genetic susceptibility.

Objective To investigate the protective effects of paeonol(PAE)on autophagy in human neuroblastoma cells(SH-SY5Y)induced by overexpression of α-synuclein(α-Syn),and to explore its related mechanism.Methods SH-SY5Y cells served as control group,while those induced with A53T-α-Syn mutation were used as model group.Additional groups included PAE(150 μg/ml)group,3-MA(1 mmol/L)group,and PAE(150 μg/ml)+3-MA(1 mmol/L)group.Cell viability was assessed using CCK-8 method,cell morphology was observed under an optical microscope,and protein expressions of α-Syn,LC3-Ⅱ,p62,Beclin-1,phosphorylated c-Jun N-terminal kinase(p-JNK),and p-Bcl-2 were determined by Western blotting.Results Compared with control group,model control exhibited decreased cell survival(P＜0.01),increased α-Syn expression(P＜0.001),reduced expression of autophagy-related proteins LC3-Ⅱ and Beclin-1(P＜0.01,P＜0.05),elevated autophagy substrate protein p62(P＜0.05),and decreased expression of autophagy pathway-related proteins p-JNK and Bcl-2(P＜0.05,P＜0.01).Compared with model group,PAE group showed increased cell survival(P＜0.01),decreased α-Syn and p62 protein expression(P＜0.01,P＜0.05),and increased expression of LC3-Ⅱ,Beclin-1,p-JNK and Bcl-2(P＜0.05).Compared with PAE group,3-MA+PAE group demonstrated increased α-Syn expression(P＜0.05).Conclusions PAE could attenuate the injury of SH-SY5Y cells induced by A53T-α-Syn and eliminate over-expressed α-Syn by activating autophagy pathway,which may be associated with the upregulation of JNK/Bcl-2 mediated autophagy pathway.

Objective To investigate the risk factors associated with recurrence of high-grade non-functioning pituitary neuroendocrine tumors(NF-PitNETs)following total resection.Methods A retrospective study was conducted on the clinical data of 252 patients with high-grade NF-PitNETs who underwent surgical treatment at the Department of Neurosurgery,Beijing Tiantan Hospital from January 2012 to December 2023,and met the inclusion criteria.High-grade NF-PitNETs included Knosp 3A,3B,and 4-grade subtypes.Kaplan-Meier curves and Log-rank tests were employed to compare the progression-free survival(PFS)of Knosp 3A,3B,and 4-grade patients.Cox regression analysis was applied to identify the risk factors associated with the recurrence of high-grade NF-PitNETs.Receiver operating characteristic(ROC)curve was used to calculate the area under the curve(AUC)of each recurrence-related factor to evaluate the diagnostic efficiency.Results Survival analysis revealed that there were significant differences in PFS among Knosp 3A,3B,and 4-grade patients(P<0.001).The PFS of Knosp 3A was significantly better than that of grade 3B and 4-grade(P<0.05),while there was no significant difference between Knosp 3B and 4-grade(P=0.118).After integrating the three groups into Knosp 3A group and 3B-4 group,there were significant differences in PFS and some clinical features between the two groups(P<0.05).Cox regression analysis indicated that age<55 years old(HR=2.883,95%CI 1.253-6.634;P=0.013),T2 heterogeneous signal(HR=1.842,95%CI 1.061-3.197;P=0.030),Knosp 3B-4(HR=2.190,95%CI 1.069-4.488;P=0.032),and Ki-67≥3%(HR=2.266,95%CI 1.265-4.061;P=0.006)were risk factors related to tumor recurrence.ROC curve analysis showed that the AUCs of the above-mentioned risk factors were 0.682,0.706,0.709 and 0.750,respectively,and the AUC of the multi-factor combined model(age+T2 signal+Knosp grade+Ki-67)was 0.838,which was significantly larger than that of each single risk factor(P<0.05).Conclusion High-grade NF-PitNETs patients with age<55 years old,T2 heterogeneous signal,Knosp 3B-4 and Ki-67≥3%have a higher recurrence risk.The combined application of multiple risk factors can improve the predictive value of recurrence.