Objective To elucidate the changes in the gut microbiota and molecular mechanism of huaier in enhancing the efficacy of oxaliplatin (OXA) chemotherapy in gastric cancer (GC). Methods The effects of huaier on the gut microbiota structure and intestinal barrier function in MKN45-bearing mice were analyzed by using 16S rRNA sequencing, RT-qPCR, and IHC. UPLC-MS and network pharmacology, as well as in vivo experimental approaches, were employed to investigate the key bioactive constituents of huaier systematically and elucidate the underlying mechanisms by which huaier exerts therapeutic effects against GC. The expression of the PI3K/AKT/SREBP pathway was detected in cancer cells and tissues via Western blot analysis. The safety profile of huaier combined with OXA was verified through serum biochemistry and HE-stained tissue section analyses. Results Huaier inhibited the PI3K/AKT/SREBP pathway by increasing the abundance of Akkermansia muciniphila, reduced lipid droplet deposition, and ultimately enhanced the sensitivity to OXA in the treatment of GC. Conclusion This study demonstrates the value of huaier in gastric cancer treatment by enhancing chemosensitivity and provides novel insights into its systemic therapeutic effects through molecular mechanisms and gut microbiota modulation.

Ethanol (EtOH) is a common trigger for gastric mucosal diseases, and mitigating oxidative stress is essential for attenuating gastric mucosal damage. Capsaicin (CAP) has been identified as a potential agent to counteract oxidative damage in the gastric mucosa; however, its precise mechanism remains unclear. This study demonstrates that CAP alleviates EtOH-induced gastric mucosal injuries through two primary pathways: by suppressing the chemokine receptor 4 (CCR4)/Src/p47phox axis, thereby reducing oxidative stress, and by inhibiting the phosphorylation and nuclear translocation of nuclear factor-κB p65 (NF-κB) p65, resulting in diminished inflammatory responses. These findings elucidate the mechanistic pathways of CAP and provide a theoretical foundation for its potential therapeutic application in the treatment of gastric mucosal injuries.
Ethanol/toxicity* ; Animals ; Gastric Mucosa/metabolism* ; Signal Transduction/drug effects* ; Oxidative Stress/drug effects* ; Capsaicin/pharmacology* ; Male ; NADPH Oxidases/genetics* ; Mice ; Humans ; src-Family Kinases/genetics*

Objective To systematically review the efficacy and safety of the tislelizumab combined with anlotinib regimen for advanced non-small-cell lung cancer(NSCLC)patients.Methods PubMed,Embase,Cochrane Library,Web of Science,CNKI,WanFang Data databases were electronically searched to collect clinical studies on the combination of trastuzumab and anlotinib in the treatment of advanced NSCLC patients from inception to August 10,2024.Two reviewers independently screened literature,extracted data and assessed the risk of bias of the included studies.Meta-analysis was then performed by using RevMan 5.4.1 software.Results A total of 6 articles of 468 patients were included,involving 4 randomized controlled trials and 2 prospective cohort studies.Meta-analysis showed that the tislelizumab combined with anlotinib group had higher ORR[OR=2.53,95％CI(1.62,3.93),P＜0.001]and DCR[OR=4.45.95％CI(2.43,8.15),P＜0.001]than the anlotinib group.The CYFRA21-1 level in the combination group was significantly lower than that in the anlotinib group[SMD=-1.07,95％CI(-1.63,-0.51),P＜0.001].For safety,there were no significant differences in the incidence of adverse reaction of leukopenia[OR=0.91,95％CI(0.39,2.14),P=0.83],liver/kidney dysfunction[OR=1.16,95％CI(0.39,3.44)P=0.78].The descriptive analysis results indicated that there was no statistically significant difference in CEA levels between the two groups before treatment in each study(P＞0.05),and the CEA levels in the combination therapy group were lower than those in the anlotinib group after treatment(P＜0.05).Conclusion Compared to anlotinib alone,tislelizumab combined with anlotinib improves ORR,DCR,and reduces tumor markers in NSCLC patients,with comparable incidence of adverse reactions.Due to the limited quality and quantity of the included studies,more high quality studies are needed to verify the above conclusion.

Objective:To evaluate the effect of the degree of neuromuscular blockade on the intraoperative surgical conditions and postoperative recovery quality in patients undergoing lumbar interbody fusion.Methods:In this randomized controlled trial, 100 patients of either sex, aged 18-79 yr, with a body mass index of 18.5-35.0 kg/m 2, of American Society of Anesthesiologists Physical Status classification < Ⅳ, scheduled for elective lumbar interbody fusion at the Affiliated Hospital of Xuzhou Medical University from August to October 2024, were allocated into 2 groups ( n=50 each) using stratified randomization based on the number of lumbar segments: deep neuromuscular blockade group (group D) and moderate neuromuscular blockade group (group M). The intraoperative post-tetanic count was maintained at 1 or 2 in group D, and the intraoperative train-of-four was maintained at 1 or 2 in group M. The scores for surgical conditions, duration of operation, blood loss, length of incision, occurrence of severe hypoxemia after extubation, requirement for rescue analgesia in post-anesthesia care unit, 15-item Quality of Recovery scale score and length of stay were recorded. Results:Compared with group M, the scores for surgical conditions were significantly increased, the rate of rescue analgesia in post-anesthesia care unit was decreased, 15-item Quality of Recovery scale scores were increased at 3 days after surgery ( P<0.05), and no significant changes were found in the duration of operation, blood loss, length of incision, incidence of severe hypoxemia after extubation and length of hospital stay in group D ( P>0.05). Conclusions:Compared with moderate neuromuscular blockade, deep neuromuscular blockade can provide better surgical conditions and improve the quality of early postoperative recovery for patients undergoing lumbar interbody fusion.

Objective To analyze the situation of blood lipid and blood routine parameters in patients with pneumoconiosis,and construct a column chart diagnostic model to explore their diagnostic value for pneumo-coniosis.Methods A total of 456 patients with pneumoconiosis admitted to the First Affiliated Hospital of Chongqing Medical and Pharmaceutical College from January 2022 to January 2024 were selected as the pneu-moconiosis group,while 462 healthy subjects exposed to dust during the same period were chosen as the con-trol group.Serum lipids and blood routine parameters related to pneumoconiosis were measured and compared between two groups.Univariate and multivariate Logistic regression analyzes were conducted to examine ser-um lipids and blood routine parameters associated with pneumoconiosis.A risk prediction model was construc-ted using logistic regression in machine learning,and the diagnostic efficacy of the column chart diagnostic model was evaluated by calculating the C-index through receiver operating characteristic(ROC)curve and plotting the model calibration curve based on Hosmer Lemeshow goodness of fit.Decision curve analysis(DCA)was used to assess the clinical practicality of the column chart diagnostic model.Results The levels of serum high-density ester protein cholesterol(HDL-C),cholesterol(TC),red blood cell(RBC),hematocrit(HCT),hemoglobin concentration(HGB),lymphocyte number(LYM),and lymphocyte percentage(LYM％)in the pneumoconiosis group were lower than those in the control group(P＜0.05).The levels of neutrophil-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),and systemic immune inflammation index(SII)were higher than those in the control group(P＜0.05).Multivariate Logistic regression analysis showed that HDL-C,LYM％,PLR,and SII were independent influencing factors for pneumoconiosis(P＜0.05).A column chart diagnostic model for the occurrence of pneumoconiosis was constructed using HDL-C,TC,LYM％,PLR,and SII as diagnostic factors.The ROC curve C-index of the diagnostic model was 0.84(95％CI:0.81-0.86),with sensitivity for diagnosing pneumoconiosis of 75.29％,specificity of 77.51％,posi-tive predictive value of 83.25％,and negative predictive value of 67.88％.Internal validation was conducted on the constructed column chart diagnostic model,with a validation set ROC curve C-index of 0.84(95％CI:0.80-0.87),sensitivity of 80.91％,specificity of 72.62％,positive diagnostic value of 79.46％,and negative diagnostic value of 74.39％.The calibration positive curve slope of the diagnostic model was close to 1,and in the fit test P＞0.05.DCA analysis showed that the diagnostic model had clinical practical value for risk diag-nosis of pneumoconiosis.Conclusion HDL-C,TC,LYM％,PLR and SII are independent influencing factors for pneumoconiosis.A column chart diagnostic model for the occurrence of pneumoconiosis is successfully constructed based on machine learning principles,and it has been verified to have high diagnostic efficiency.

Objective To observe the clinical efficacy of electroacupuncture of bilateral Yifeng(SJ17)points penetrating Lianquan(RN23)points combined with electromyographic biofeedback therapy(shortened as EMG biofeedback)in the treatment of post-stroke dysphagia.Methods A total of 94 cases of patients admitted to the wards and outpatient clinics of Handan Mingren Hospital with a definitive diagnosis of post-stroke dysphagia from April 2022 to May 2023 were selected for the study.The patients were randomly divided into observation group and control group according to the random number table method,with 47 cases in each group.Both groups of patients were given basic treatment,the control group was treated with EMG biofeedback,and the observation group was treated with electroacupuncture of bilateral Yifeng points penetrating Lianquan points on the basis of the treatment of the control group.The course of treatment covered four consecutive weeks.After one month of treatment,the clinical efficacy of the two groups was evaluated,and the changes in traditional Chinese medicine(TCM)syndrome scores and Kubota Water Swallowing Test scores,Standardized Swallowing Assessment(SSA)scores,Functional Oral Intake Scale(FOIS)scores,and Swallowing-Quality of Life(SWAL-QOL)scores before and after treatment were observed in the patients of the two groups.The changes of tongue pressure before and after treatment were compared between the two groups.The safety and the incidence of adverse reactions in the two groups were evaluated.Results(1)The total effective rate was 95.74%(45/47)in the observation group and 76.60%(36/47)in the control group.The efficacy of the observation group was superior to that of the control group,the difference being statistically significant(P<0.05).(2)After treatment,the TCM syndrome scores and Kubota Water Swallowing Test scores of the patients in the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(3)After treatment,SSA and FOIS scores of patients in the two groups were significantly improved(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(4)After treatment,the peak tongue pressure,mean tongue pressure,duration of tongue pressure of the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(5)After treatment,the quality of life scores of patients in the two groups were significantly improved(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(6)No obvious adverse reactions occurred during the treatment of the two groups of patients,the difference in the incidence of adverse reactions between the two groups of patients being not statistically significant(P>0.05).Conclusion Electroacupuncture of bilateral Yifeng points penetrating Lianquan points combined with EMG biofeedback in the treatment of post-stroke dysphagia exerts certain efficacy,which can improve the swallowing function and tongue muscle strength,reduce TCM syndrome scores,and enhance patients'quality of life.

Objective Pre-packaged space scallion pancakes are prone to quality deterioration during storage due to starch retrogradation and lipid oxidation,which affects their food safety and sensory characteristics.Therefore,investigating their quality changes during storage and predicting shelf life are of great significance for ensuring the quality of space food.Methods study conducted accelerated shelf-life tests at(37±1)℃ and(47±1)℃ under simulated spacecraft food storage conditions.Comprehensive analyses were performed,including physicochemical properties(acid value,peroxide value,carbonyl value),microbiological indicators(total bacterial count,coliforms),color parameters(L*,a*,b*,c*,h°),and texture characteristics(hardness,adhesiveness,etc.).XRD and FTIR were employed to verify starch retrogradation and lipid oxidation.Results Physicochemical properties:The acid value gradually decreased and stabilized with prolonged storage.The peroxide value increased rapidly at 37℃and 47℃,with samples stored at 47℃approaching the safety limit(0.25 g/100 g)within 40 days,while the carbonyl value exhibited a decreasing trend.Microbiological indicators:All samples met the requirements of GJB 4992A-2012.No microbial contamination was detected initially,with only minor bacterial growth observed in later stages,and no coliforms were detected throughout the storage period.Color changes:During storage at 20℃,the a*value increased by 91.67%,while b* and c* values showed significant increases.Meanwhile,L* and h° values decreased by 7.42%and 8.75%,respectively.Texture deterioration:Overall texture characteristics declined,and XRD and FTIR analyses confirmed aggravated starch retrogradation.Shelf-life prediction:Correlation analysis identified peroxide value as the key factor.The established prediction model had an error margin of less than 10%,with predicted shelf lives of 236,121,and 57 days at 20℃,37℃,and 47℃,respectively.Conclusion This study reveals the quality change patterns of space scallion pancakes during storage.The established shelf-life prediction model provides theoretical and methodological support for quality monitoring of pre-packaged space foods.

Computational approaches,encompassing both physics-based and machine learning(ML)methodolo-gies,have gained substantial traction in drug repurposing efforts targeting specific therapeutic entities.The human dopamine(DA)transporter(hDAT)is the primary therapeutic target of numerous psychi-atric medications.However,traditional hDAT-targeting drugs,which interact with the primary binding site,encounter significant limitations,including addictive potential and stimulant effects.In this study,we propose an integrated workflow combining virtual screening based on weighted holistic atom localization and entity shape(WHALES)descriptors with in vitro experimental validation to repurpose novel hDAT-targeting drugs.Initially,WHALES descriptors facilitated a similarity search,employing four benztropine-like atypical inhibitors known to bind hDAT's allosteric site as templates.Consequently,from a compound library of 4,921 marketed and clinically tested drugs,we identified 27 candidate atypical inhibitors.Subsequently,ADMETlab was employed to predict the pharmacokinetic and toxi-cological properties of these candidates,while induced-fit docking(IFD)was performed to estimate their binding affinities.Six compounds were selected for in vitro assessments of neurotransmitter re-uptake inhibitory activities.Among these,three exhibited significant inhibitory potency,with half maximal inhibitory concentration(IC50)values of 0.753 μM,0.542 μM,and 1.210 μM,respectively.Finally,molecular dynamics(MD)simulations and end-point binding free energy analyses were con-ducted to elucidate and confirm the inhibitory mechanisms of the repurposed drugs against hDAT in its inward-open conformation.In conclusion,our study not only identifies promising active compounds as potential atypical inhibitors for novel therapeutic drug development targeting hDAT but also validates the effectiveness of our integrated computational and experimental workflow for drug repurposing.

Computational approaches, encompassing both physics-based and machine learning (ML) methodologies, have gained substantial traction in drug repurposing efforts targeting specific therapeutic entities. The human dopamine (DA) transporter (hDAT) is the primary therapeutic target of numerous psychiatric medications. However, traditional hDAT-targeting drugs, which interact with the primary binding site, encounter significant limitations, including addictive potential and stimulant effects. In this study, we propose an integrated workflow combining virtual screening based on weighted holistic atom localization and entity shape (WHALES) descriptors with in vitro experimental validation to repurpose novel hDAT-targeting drugs. Initially, WHALES descriptors facilitated a similarity search, employing four benztropine-like atypical inhibitors known to bind hDAT's allosteric site as templates. Consequently, from a compound library of 4,921 marketed and clinically tested drugs, we identified 27 candidate atypical inhibitors. Subsequently, ADMETlab was employed to predict the pharmacokinetic and toxicological properties of these candidates, while induced-fit docking (IFD) was performed to estimate their binding affinities. Six compounds were selected for in vitro assessments of neurotransmitter reuptake inhibitory activities. Among these, three exhibited significant inhibitory potency, with half maximal inhibitory concentration (IC₅₀) values of 0.753 μM, 0.542 μM, and 1.210 μM, respectively. Finally, molecular dynamics (MD) simulations and end-point binding free energy analyses were conducted to elucidate and confirm the inhibitory mechanisms of the repurposed drugs against hDAT in its inward-open conformation. In conclusion, our study not only identifies promising active compounds as potential atypical inhibitors for novel therapeutic drug development targeting hDAT but also validates the effectiveness of our integrated computational and experimental workflow for drug repurposing.

Methods:This study was a cross-sectional study. A prospective cohort study enrolled 42 patients with clinically suspected acute cerebrovascular disease and those undergoing follow-up examinations after intracranial vascular stenting at the First Affiliated Hospital of Zhengzhou University from June 2024 to May 2025. All patients underwent UHR PCD-CT examinations of the head and neck. Reconstructions were performed based on raw data, yielding conventional standard resolution (SR group) reconstructions and UHR images reconstructed using four distinct convolution kernels (Hv40, Hv48, Hv56, Hv64) in separate groups (Hv40 UHR group, Hv48 UHR group, Hv56 UHR group, Hv64 UHR group). Regions of interest were selected in the anterior cerebral artery, middle cerebral artery, posterior cerebral artery, posterior communicating artery, and anterior communicating artery. CT values and standard deviation (SD) values were measured for each artery, and signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Additionally, the sharpness of the vessel edges and the full-width-half-maximum (FWHM) of each artery were measured. One-way analysis of variance or the nonparametric Kruskal-Wallis test was used to compare the subjective and objective image quality metrics across the five groups. Pairwise comparisons were performed using the LSD test or Dunn method.Results:Statistically significant differences were observed in the overall comparison of vascular imaging SD, SNR, CNR, vascular edge sharpness, and FWHM among the SR group, Hv40 UHR group, Hv48 UHR group, Hv56 UHR group, and Hv64 UHR group ( P<0.05). No statistically significant differences in CT values were found ( P>0.05). Pairwise comparisons revealed statistically significant differences between all groups ( P<0.05), except that no significant differences were observed in image SD, SNR, CNR, vascular edge sharpness, or FWHM between the Hv56 UHR and Hv64 UHR groups ( P>0.05). Conclusions:UHR PCD-CT provides better image quality for neurovascular imaging. For the display of small intracranial vessels, the Hv64 provides sharper vessel walls and better subjective image quality compared to the less sharp convolutional cores.Objective:To explore the value of ultra-high resolution (UHR) photon-counting detector CT (PCD-CT) to improve the quality of neurovascular images.