Objective To explore whether there is a causal relationship between intestinal flora and esophageal cancer. Methods Summary statistics of intestinal flora and esophageal cancer were obtained from the Genome-wide Association Studies (GWAS) database. Five methods, including inverse variance weighted (IVW), weighted median estimation, Mendelian randomization (MR)-Egger regression, single mode, and weighted mode, were used for analysis, with IVW as the main analysis method. Sensitivity analysis was used to evaluate the reliability of MR results. Results In the IVW method, Oxalobacteraceae [OR=1.001, 95%CI (1.000, 1.002), P=0.023], Faecalibacterium [OR=1.001, 95%CI (1.000, 1.002), P=0.028], Senegalimassilia [OR=1.002, 95%CI (1.000, 1.003), P=0.006] and Veillonella [OR=1.001, 95%CI (1.000, 1.002), P=0.018] were positively correlated with esophageal cancer, while Burkholderiales [OR=0.999, 95%CI (0.998, 1.000), P=0.002], Eubacterium oxidoreducens [OR=0.998, 95%CI (0.997, 0.999), P=0.038], Romboutsia [OR=0.999, 95%CI (0.998, 1.000), P=0.048] and Turicibacter [OR=0.998, 95%CI (0.997, 0.999), P=0.013] were negatively correlated with esophageal cancer. Sensitivity analysis showed no evidence of heterogeneity, horizontal pleiotropy and reverse causality. Conclusion Oxalobacteraceae, Faecalibacterium, Senegalimassilia and Veillonella increase the risk of esophageal cancer, while Burkholderiales, Eubacterium oxidoreducens, Romboutsia and Turicibacter decrease the risk of esophageal cancer. Further studies are needed to explore how these bacteria affect the progression of esophageal cancer.

Objective To develop and validate a machine learning model based on preoperative clinical characteristics, laboratory indices, and radiological features for the non-invasive prediction of spread through air spaces (STAS) in patients with early-stage lung adenocarcinoma. Methods Preoperative data from patients with early-stage lung adenocarcinoma who underwent surgical resection at Northern Jiangsu People's Hospital between January 2020 and August 2025 were retrospectively collected. The data included clinical characteristics, laboratory indices, and radiological features. Patients were divided into a STAS-positive and a STAS-negative group based on postoperative pathological findings. The dataset was randomly split into a training set and a testing set at a 7 : 3 ratio. Feature variables were selected using the maximum relevance and minimum redundancy (mRMR) algorithm and the least absolute shrinkage and selection operator (LASSO) regression. Five machine learning models were constructed: logistic regression (LR), random forest (RF), support vector machine (SVM), light gradient boosting machine (LightGBM), and extreme gradient boosting (XGBoost). Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). The shapley additive explanations (SHAP) method was employed to interpret the optimal prediction model. Results A total of 377 patients were included, comprising 177 (46.9%) males and 200 (53.1%) females, with a mean age of (63.31±9.73) years. There were 261 patients in the training set and 116 patients in the testing set. In the training set, statistically significant differences were observed between the STAS-positive group (n=130) and STAS-negative group (n=131) across multiple features, including age, sex, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), clinical T stage, and maximum solid component diameter (P<0.05). A final set of 10 feature variables was selected by combining mRMR and LASSO regression, and five machine learning models (LR, RF, SVM, LightGBM, XGBoost) were developed. The XGBoost model demonstrated optimal performance in both the training and testing sets, achieving AUCs of 0.947 [95%CI (0.920, 0.975)] and 0.943 [95%CI (0.894, 0.993)], respectively. DCA indicated that the XGBoost model provided a high net clinical benefit across a wide range of threshold probabilities. SHAP analysis revealed that the vessel convergence sign, clinical T stage, age, consolidation-to-tumor ratio (CTR), and MLR were the features with the highest contributions to STAS prediction. Conclusion The XGBoost model effectively predicts preoperative STAS status in early-stage lung adenocarcinoma, exhibiting excellent discriminative performance and good clinical interpretability. Key predictors such as the vessel convergence sign, clinical T stage, age and CTR provide a crucial reference for preoperative risk assessment and the individualized selection of surgical strategies, ultimately benefiting patients.

Objective To analyze the relationship between neuroticism and gastroesophageal reflux disease (GERD) using the Mendelian randomization (MR) method. Methods Exposure and outcome data were downloaded from the Integrative Epidemiology Unit (IEU) database in August 2023, including summary statistics from genome-wide association studies (GWAS) for neuroticism (n=374 323) and GERD (n=602 604). MR was conducted using the weighted median method, MR-Egger method, inverse variance weighted method, weighted mode method, and simple mode method. The causal relationship between the two was assessed using odds ratio (OR), and sensitivity analyses were performed to ensure the accuracy of the results. Results Neuroticism was associated with an increased risk of GERD [OR=1.229, 95%CI (1.186, 1.274), P<0.001]. Similarly, GERD was associated with an increased risk of neuroticism [OR=1.786, 95%CI (1.623, 1.965), P<0.001]. Conclusion There is a bidirectional causal relationship between neuroticism and gastroesophageal reflux disease.

OBJECTIVE: To observe the effect of electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) on hippocampal neuronal ferritinophagy mediated by the nuclear receptor coactivator 4 (NCOA4)/ferritin heavy chain 1 (FTH1) signaling pathway in vascular dementia (VD) rats, and to explore the potential mechanisms of electroacupuncture for VD. METHODS: A total of 60 male rats of SPF grade were randomly divided into a blank group (12 rats), a sham surgery group (12 rats) and a modeling group (36 rats). In the modeling group, the modified 4-vessel occlusion method was used to establish the VD model. The 24 successfully modeled rats were randomly divided into a model group and an electroacupuncture group, with 12 rats in each group. In the electroacupuncture group, electroacupuncture was applied at left and right "Sishencong" (EX-HN1), and bilateral "Fengchi" (GB20), with continuous wave, in frequency of 2 Hz and current intensity of 1 mA, 30 min a time, once daily for 21 consecutive days. The learning and memory abilities were assessed using the Morris water maze test before modeling, after modeling and after intervention, as well as the novel object recognition test after intervention. After intervention, the neuronal morphology in the hippocampus was observed by Nissl staining; the iron deposition was observed by Prussian blue staining; the reactive oxygen species (ROS) level was detected by dihydroethidium (DHE) fluorescence staining; the levels of iron, malondialdehyde (MDA) and superoxide dismutase (SOD) in the hippocampal tissue were measured by the colorimetric assay, TBA method, and WST-1 method, respectively; the positive expression of NCOA4, FTH1 and glutathione peroxidase 4 (GPX4) was detected by immunohistochemistry; the protein expression of NCOA4, FTH1, GPX4, and the ratio of microtubule-associated protein 1 light chain 3B (LC3B) Ⅱ/Ⅰ in the hippocampus were detected by Western blot. RESULTS: Compared with the sham surgery group, in the model group, the escape latency was prolonged, and the number of platform crossings reduced (P<0.01), the recognition index (RI) was decreased (P<0.01); the hippocampal neurons displayed a blurred laminar structure, disorganized cellular arrangement, and the number of Nissl bodies was decreased (P<0.01); the percentage of iron deposition area in the hippocampus was increased (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were increased (P<0.01), the SOD level, and the protein expression of FTH1 and GPX4 were decreased (P<0.01). Compared with the model group, in the electroacupuncture group, the escape latency was shortened and the number of platform crossings was increased (P<0.01), the RI was increased (P<0.01); the hippocampal neurons exhibited more regular morphology, better-organized cellular structure, and the number of Nissl bodies was increased (P<0.05); the percentage of iron deposition area in the hippocampus reduced (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were decreased (P<0.01, P<0.05), the SOD level, and the protein expression of FTH1 and GPX4 were increased (P<0.01). CONCLUSION Electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) can improve learning and memory abilities in VD rats, and its mechanism may be associated with the regulation of the hippocampal NCOA4/FTH1 signaling pathway, inhibition of ferritinophagy, and alleviation of oxidative stress damage.
Animals ; Electroacupuncture ; Dementia, Vascular/genetics* ; Male ; Rats ; Signal Transduction ; Humans ; Memory ; Rats, Sprague-Dawley ; Nuclear Receptor Coactivators/genetics* ; Ferritins/genetics* ; Learning ; Hippocampus/metabolism* ; Acupuncture Points

The rationale for the design of control groups in tuina clinical trial is the foundation for rigorously validating the effectiveness and safety of this therapy. This article reviewed the current state of the design of tuina placebo in control groups of clinical trials， pointed out the necessity of setting up tuina placebo in clinical trials of tuina， analyzed the challenges in implementing blinding of tuina manipulation， and concluded that tuina placebo is still challenged by the placebo effect， the diversification of tuina manipulation but the lack of standardization， and the difficulty of implementing blinding due to the high level of public awareness of tuina. This article also summarized the design of placebo manipulation in three types of clinical trials， including spinal manipulation， acupressure， and paediatric tuina， and proposed four strategies for designing placebo tuina manipulation-controlling placebo effects， developing operational standards for placebo tuina manipulation， ensuring the rigor of blinding implementation， and applying new technologies to enhance the standardization and blinding capacity of placebo tuina methods. So the article is aimed at improving the methodological quality of tuina clinical trial designs， and promoting the standardization and scientificity of tuina clinical trial design.

Objective To explore the application effect of health education based on gain and loss message framing on the treatment behavior intention and self-management of patients with high-risk diabetic foot.Methods From July to September 2024,convenience sampling was used to select patients with high-risk diabetic foot who were hospitalized in the endocrinology department of a tertiary general hospital in Guiyang as the study subjects.They were divided into 3 groups according to the admission time,with 30 patients in each group.The experimental group adopted health education based on gain message framing or framing loss message,while in the control group,health education was provided in a conventional manner.Before and after intervention,the differences of intervention effects among the 3 groups were compared by using diabetic foot pre-hospital delay intention questionnaire,diabetic foot care knowledge questionnaire and Chinese version of Nottingham foot care assessment scale(CNAFF).Results Ultimately,29 cases in the gain framing group,29 cases in the loss framing group,and 29 cases in the control group completed the study.After intervention,the score of pre-hospital delay intention questionnaire of diabetic foot in the gain framing group was(21.48±4.32),and it was(24.31±2.49)in the loss framing group,and(17.76±5.03)in the control group.The difference among the 3 groups was statistically significant(F=18.725,P＜0.001);the loss framing group was superior to the gain framing group(P=0.01)and the control group(P＜0.001).After the intervention,the score of the CNAFF in the gain framing group was(55.83±3.06),and it was(59.14±2.90)in the loss framing group,and(48.66±2.58)in the control group.The difference between the 3 groups was statistically significant(F=102.245,P＜0.001).The loss framing group was superior to the gain framing group and the control group(all P＜0.001).Conclusion Health education based on the loss message framing is more conducive to improving patients' intention to delay diabetic foot visits,leading to good foot care behaviors,and may provide an effective means of pre-hospital prevention and control of diabetic foot.

AIM:To investigate the potential mechanisms by which cell division cycle protein 42(Cdc42)regulates endothelial-mesenchymal transition(EndMT)in pulmonary hypertension(PH).METHODS:The pulmonary hypertension(PH)model was established using Sugen-5416 combined with hypoxia.Twenty-four C57BL/6 mice were ran-domly divided into four groups:normoxia control(CON)group,normoxia+ML141(CON+ML141)group,Sugen-5416+hypoxia(SuHx)group,and SuHx+ML141 group,with 6 mice in each group.After 4 weeks,right ventricular systolic pressure(RVSP)and cardiac ultrasound parameters were measured,and lung tissues were collected for immunofluores-cence staining.Pulmonary microvascular endothelial cells(PMVECs)were isolated using magnetic bead sorting.Calcium imaging was performed to assess Ca2+signaling,and Western blot was used to detect EndMT-related proteins as well as stromal interaction molecule 1(STIM1)and Orai1 expression.RESULTS:In the SuHx group,mice exhibited signifi-cantly increased RVSP,Fulton index(right ventricle/left ventricle+septum),end-diastolic right ventricular free wall thick-ness(RVEDWT),and end-systolic right ventricular free wall thickness(RVESWT)(P<0.01).Conversely,pulmonary artery acceleration time/pulmonary artery ejection time(PAT/PET)and tricuspid annulus plane systolic excursion(TAPSE)were significantly reduced(P<0.01).The Cdc42 inhibitor ML141 ameliorated these changes.The SuHx group exhibited a significant decrease in CD31 fluorescence intensity in pulmonary vascular endothelial cells(P<0.01),a marked increase in α-smooth muscle actin(α-SMA)fluorescence intensity in smooth muscle cells(P<0.01),and the emergence of CD31/α-SMA co-localization.These alterations were reversed by ML141.Hypoxia induced EndMT in PM-VECs,characterized by decreased CD31 and vascular endothelial cadherin(VE-cadherin)along with increased α-SMA and vimentin(P<0.01),which was suppressed by ML141(P<0.01).Hypoxia activated store-operated calcium entry(SOCE),enhancing intracellular Ca2? release,extracellular Ca2? influx,and basal Ca2? levels(P<0.01),while upregulat-ing STIM1 and Orai1 expression(P<0.01).These changes were reversed by ML141.Furthermore,both ML141 and STIM1 knockdown inhibited the upregulation of EndMT-related transcription factors Snail and Twist(P<0.05).CON-CLUSION:Cdc42 may participate in EndMT in PH by regulating store-operated calcium channels in pulmonary microvas-cular endothelial cells.

Objective:To compare the clinical efficacy of a fixed exoskeleton robot with that of an exoskeleton walker in training the balance of stroke survivors in the subacute stage.Methods:Thirty persons with subacute stroke were divided at random into a fixed robot group (15 cases) and a walking robot group (15 cases). In addition to conventional rehabilitation treatment, the fixed robot group underwent daily 20-minute treadmill-based fixed exoskeleton robot training, 5 days a week for 2 weeks. The walking group was trained with an exoskeleton walking robot on the same schedule. Before and after the treatment, the Berg balance scale, the sitting modified functional stretch test (SMFRT), an isokinetic muscle strength test and the modified Barthel index (MBI) were used to evaluate the subjects′ global balance, self-dynamic balance, knee proprioception and ability in the activities of daily living (ADL).Results:After the treatment, both groups′ average Berg score, SMFRT extension difference, proprioceptive absolute error angle in the affected knee and MBI had improved significantly. The average SMFRT extension difference after treatment in the walker group was then significantly better than the fixed robot group′s average. However, the fixed robot group′s proprioception in the affected knee joint was then significantly better, on average, than among the walking robot group.Conclusions:Both fixed exoskeleton robot training and exoskeleton walker training can improve the balance, proprioception and ADL ability after a stroke. The former better improves dynamic balance; the latter better improves proprioception in the affected knee joint.

Acute lung injury(ALI)is a common critical illness caused by intrapulmonary or extra-pulmonary factors,which is accompanied by ex-tremely high morbidity and mortality.Its pathogen-esis is extremely complex and difficult to treat.Src homology 2 domain-containing protein tyrosine phosphatase(Shp2),a key cellular signal transduc-tion molecule,plays a pivotal role in the pathophys-iological processes of diverse diseases.Notably,in the context of pathogen infection,Shp2 regulates the functionality of cellular immunity,lung epitheli-al cells,and vascular endothelial cells.This review article highlights the significant role of Shp2 in the onset and progression of ALI,emphasizing its regu-lation of inflammatory response,apoptosis,and ox-idative stress.Shp2 could emerge as a novel thera-peutic target for ALI,offering valuable insights for the development of innovative drug candidates to treat this debilitating condition.

Objective:To observe and analyze the abnormal gait characteristics and lower limb kinematic chain in patients with bilateral moderate-to-severe hallux valgus(HV)during adaptive walking.Method:From September 2022 to August 2023,33 patients with moderate-and-severe HV were selected from the department of arthrology,Wangjing Hospital,Chinese Academy of Traditional Chinese Medicine and en-rolled in the observation group.A group of 29 healthy subjects were matched and enrolled in the control group.DC-G-150-F2 three-dimensional gait analysis system was used to collect gait characteristics and lower limb motion chain of two groups during a 10m adaptive walking test.Temporal-spatial gait parameters and ki-nematic changes in the hip,knee,and ankle joints were observed and analyzed.Result:The gait time-space parameters of left and right support phase,total double support phase,left lateral foot deviation angle,step length,stride length and pace in the observation group were significantly lower than those in the control group(P＜0.05).In contrast,the time-space parameters of left and right swing phase and stride frequency in the observation group were significantly higher than those in the control group(P＜0.05).The two groups had no significant difference in right lateral foot deviation angle and step width(P＞0.05).The range of flexion and extension of the right hip joint,rotation of the left hip joint,rotation of the left and right knee joint and flexion and extension of the left and right ankle joint in the observation group were significantly lower than those in the control group(P＜0.05).There were no significant differences be-tween the two groups in the range of motion of left hip flexion and extension,right hip rotation,left versus right hip spreading,left versus right knee flexion and extension,and left versus right ankle rotation(P＞0.05).However,the range of motion of right hip rotation and right knee flexion and extension was lower than that of the control subjects(P=0.084,P=0.093).Conclusion:Gait changes in patients with bilateral moderate-to-severe bunions are characterized by shortened sin-gle and double support phases,prolonged swing phase,increased step frequency,reduced step length and stride length,and a"broken stride and slow catching up"walking pattern.The range of motion of each lower limb joint in the sagittal plane and horizontal plane is reduced,resulting in a rigid and twisted state through-out the lower limb kinematic chain.