Despite breakthroughs in immunotherapy for solid tumors, significant variations in treatment efficacy persist. Up to 80% of cancer patients suffer from malnutrition, which leads to: lymphoid atrophy and reduced T-cell reserves; deficiency of substrates required for T-cell activation and expansion; concurrent inflammation hindering T-cell infiltration into tumors; and cachexia accelerating PD-1 antibody clearance. Clinical studies confirm that severe malnutrition significantly impairs immune responses and increases the risk of treatment toxicity. Therefore, implementing standardized nutritional therapy is crucial for optimizing the reserve, activation, expansion, and infiltration capacity of immune cells, thereby providing a sound immune system foundation for immunotherapy. Immunonutrition therapy, by enhancing immunonutrients such as arginine, omega-3 polyunsaturated fatty acids, and nucleotides, reduces the secretion of pro-inflammatory mediators and promotes T-cell activation and proliferation. This enhances anti-tumor immune responses, prolongs survival, and advances cancer treatment towards multimodal combination and precision approaches.

OBJECTIVE To construct ensemble learning models for predicting high-use days of budesonide based on meteorological factors， thereby providing reference for hospital pharmacy management. METHODS Meteorological data for 2024 and outpatient budesonide usage data from the jurisdiction of Sanming Hospital of Integrated Traditional Chinese and Western Medicine were collected. High-use days were defined as the 75th percentile of outpatient budesonide usage， and a corresponding dataset was established. The prediction task was formulated as a classification problem， and three ensemble learning models were developed： Random Forest， Extreme Gradient Boosting （XGBoost）， and Histogram-based Gradient Boosting Classifier. Model performance was evaluated using accuracy， precision， recall， F1-score， and log-loss. Model interpretability was analyzed using Shapley Additive Explanations （SHAP）. RESULTS The Histogram-based Gradient Boosting Classifier achieved the best performance （accuracy＝0.75， F1-score＝0.48）， followed by XGBoost （accuracy＝0.74， F1-score＝0.43） and Random Forest （accuracy＝0.72， F1-score＝0.22）. SHAP results suggested that the prediction results of the last two models have the highest correction. CONCLUSIONS Ensemble learning models can effectively predict high-use days of budesonide， with the Histogram- based Gradient Boosting Classifier demonstrating the best predictive performance. Low temperature， high humidity， and low atmospheric pressure show significant positive impacts on the prediction of daily budesonide usage.

Objective: To analyze the monitoring results of key occupational hazard factors in workplaces across different industries in Aba Tibetan and Qiang Autonomous Prefecture (Aba Prefecture), Sichuan Province, so as to provide the basis for optimizing occupational disease prevention and control measures. Methods: Data of key occupational hazard factors in workplaces in Aba Prefecture from 2022 to 2024 were collected through the Workplace Occupational Hazard Monitoring System. Descriptive analyses were conducted on the over-standard rates of occupational hazard factors, completion rates of occupational health examinations, and participation rates in occupational health training. Results: From 2022 to 2024, 165 enterprise-times in Aba Prefecture were monitored, with 112 enterprise-times exceeding the standards, the over-standard rate of enterprises was 67.88%. A total of 1 005 worksite positions were monitored, with 302 exceeding the standards, the over-standard rate of worksite positions was 30.05%. The over-standard rates of enterprises and worksite positions showed upward trends from 2022 to 2024 (both P<0.05). The over-standard rates of enterprises in the ferrous metal mining and dressing industry and non-ferrous metal mining and dressing industry were both 100%. The top three over-standard rates of worksite positions were in the non-metallic mining and dressing industry, ferrous metal mining and dressing industry, and non-ferrous metal mining and dressing industry, at 62.50%, 56.00%, and 53.13%, respectively. Worksite positions exposed to silica dust, noise, and coal dust had relatively high over-standard rates, at 17.00%, 10.04%, and 7.27%, respectively. The actual numbers of physical examinations for personnel at worksite positions with dust, chemical factors, and physical factors were 9 398, 2 469, and 10 928 person-times, respectively, with completion rates of 95.78%, 81.03%, and 100.00%, respectively. The actual number of re-examinations were 428, 129, and 1 121 person-times, respectively, with re-examination rates of 64.26%, 27.27%, and 81.53%, respectively. Among the monitored enterprises, 102 enterprise-times participated in training for persons in charge, with a participation rate of 61.82%; 108 enterprise-times participated in training for occupational health management personnel, with a participation rate of 65.45%; and 10 489 person-times of workers exposed to hazards participated in occupational health training for workers, with a participation rate of 86.24%. Conclusions The over-standard rate of key occupational hazards factors in workplaces in Aba Prefecture was relatively high. The completion rate of occupational health examinations was good, but the re-examination rate was low. It is recommended to focus on strengthening the prevention and control of occupational hazard factors in the mining and dressing industry and promoting the effective implementation of occupational health examinations and occupational health training.

Environmental toxicants have been linked to aging and age-related diseases. The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice, Drosophila melanogaster, and Caenorhabditis elegans. Meanwhile, the resistance to toxicants was increased in long-lived animals. Here, we show that farnesoid X receptor (FXR) agonist obeticholic acid (OCA), a marketed drug for the treatment of cholestasis, may extend the lifespan and healthspan both in C. elegans and chemical-induced early senescent mice. Furthermore, OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C. elegans. The longevity effects of OCA were attenuated in Fxr ^-/- mice and Fxr homologous nhr-8 and daf-12 mutant C. elegans. In addition, metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor (PXR), a major nuclear receptor for detoxification regulation, in the liver of mice. Together, our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions, thus, targeting FXR may offer to promote longevity.

Objective: To assess the dynamic changes of microcirculation at acupoints in patients with primary dysmenorrhea and cold congelation and blood stasis syndrome using laser speckle blood flow imaging. Methods: Patients with primary dysmenorrhea and cold coagulation and blood stasis syndrome (primary dysmenorrhea group, n=53) and healthy female college students(control group, n=57) who met the inclusion and exclusion criteria from October 2020 to July 2022 were enrolled at Hebei University of Chinese Medicine. On the premenstrual and first day of menstruation, a laser speckle blood flow imaging system was used to measure the microcirculation blood flow perfusion on the surface of acupoints related to the conception, thoroughfare, and governor vessels, and stomach, spleen, and bladder meridians in the abdomen and lumbosacral regions. The dynamic changes in microcirculation were calculated based on the difference in average blood flow perfusion at each acupoint before and after menstruation. Receiver operating curve (ROC) analysis was used to analyze the diagnostic efficacy of dynamic changes in microcirculation on the surface of each acupoint. The microcirculation sensitization rate of acupoints was calculated. Results: Compared with the control group, the dynamic changes in microcirculation at the following acupoints in the primary dysmenorrhea group were increased (P<0.05): conception vessel (Yinjiao[CV7], Qihai[CV6], Shimen[CV5], Guanyuan[CV4]); left thoroughfare vessel (left Huangshu[KI16], left Zhongzhu[KI15], left Siman[KI14], left Qixue[KI13], left Dahe[KI12], left Henggu[KI11]); left stomach meridian (left Tianshu[ST25], left Wailing[ST26], left Qichong[ST30]); left spleen meridian (left Daheng[SP15], left Fujie[SP14]); right thoroughfare vessel (right Huangshu[KI16], right Zhongzhu[KI15], right Siman[KI14], right Qixue[KI13], right Dahe[KI12], right Henggu[KI11]); right stomach meridian (right Wailing[ST26], right Daju[ST27], right Shuidao[ST28], right Guilai[ST29], right Qichong[ST30]); and right spleen meridian (right Fujie[SP14]). The area under the ROC curve of conception vessel (Yinjiao[CV7], Qihai[CV6], Shimen[CV5], Guanyuan[CV4]), thoroughfare vessel (right Siman[KI14], left Huangshu[KI16], right Qixue[KI13], right Zhongzhu[KI15], right Dahe[KI12], left Zhongzhu[KI15], left Siman[KI14], right Huangshu[KI16], left Qixue[KI13], right Henggu[KI11], left Henggu[KI11], left Dahe[KI12]); stomach meridian (left Tianshu[ST25], right Guilai[ST29], left Wailing[ST26], right Shuidao[ST28], right Daju[ST27], right Wailing[ST26], right Qichong[ST30], left Qichong[ST30]), and spleen meridian (left Daheng[SP15], left Fujie[SP14], right Fujie[SP14]) was 0.610-0.682 (P<0.05). Compared with the control group, the sensitization rate of some acupoints in the primary dysmenorrhea group increased (P<0.05). Conclusion With the onset of menstruation, the blood flow perfusion of some acupoints in the abdomen (thoroughfare, and conception vessels, and stomach and spleen meridians) of patients with primary dysmenorrhea and cold blood coagulation and blood stasis syndrome increased, and the status of acupoints changed from a resting state to an active state. These acupoints are sensitive in patients with primary dysmenorrhea and cold blood coagulation and blood stasis syndrome and have a certain diagnostic efficacy, providing a basis for further analyzing the efficacy and mechanism of acupuncture and moxibustion to treat primary dysmenorrhea with cold blood coagulation and blood stasis syndrome.

Objective: To investigate the effect of auricular therapy on sleep improvement and the GABAergic system pathway in a rat model of insomnia and to explore its possible mechanism. Methods: According to the random number table, 60 male SD rats were randomly divided into blank control, model, auricular point sticking, auricular bloodletting, and auricular bloodletting combined with sticking groups, with 12 rats per group. Insomnia was induced by intraperitoneal injection of p-chlorophenylalanine. After establishing the insomnia model, 36 rats were treated once a day with auricular point sticking or bloodletting for 5 consecutive days. After the intervention, the general condition and body weight of rats were observed; the righting reflex test was used to detect the sleep latency and duration; HE staining was used to observe the morphology of hypothalamic neuron cells; and an enzyme-linked immunosorbent assay was used to detect the GABA and glutamate content in rat serum. Immunohistochemistry(IHC) and real-time fluorescence quantitative PCR were used to detect GABA ARα1 and GABA ARγ2 protein and mRNA expression in the hypothalamus of rats, and Western blotting(WB) was used to detect GABA ARα1, GABA ARγ2, GAD65/67, GAT-1, and GABA-T protein expression in the hypothalamus of rats. Results: Compared with the blank control group, the model group had a lower body weight, a significantly shorter sleep duration (P<0.05), severe damage to the morphological structure of hypothalamic neurons with disordered cell arrangement, larger intercellular gaps, enlarged cell bodies, and a vacuolated appearance. All the intervention groups had significantly higher body weight and longer sleep duration than the model group (P<0.05). Compared with the other intervention groups, the auricular point sticking group had a longer sleep duration (P<0.05), and the hypothalamic neuron cells in all intervention groups improved, with the auricular point sticking group showing more apparent improvement. The model group had a lower GABA and higher glutamate contents, and GABA ARα1, GABA ARγ2, and GAD65/67 protein expression in the hypothalamus were lower than in the blank control group. In contrast, GAT-1 and GABA-T protein expression was higher, and GABA ARα1 and GABA ARγ2 mRNA expression was lower (P<0.05). The serum GABA content in the auricular point sticking and auricular bloodletting groups was higher, and the serum glutamate content in the auricular point sticking and auricular bloodletting combined sticking groups was lower than in the model group. GABA ARα1 mRNA expression in the hypothalamus of each intervention group was significantly increased, and GABA ARγ2 mRNA expression in the hypothalamus of the auricular point sticking and auricular bloodletting combined sticking groups increased. GABA ARα1(IHC, WB), GABA ARγ2(WB), and GAD65/67 protein expression in the hypothalamus of the auricular point sticking group increased, whereas GAT-1 and GABA-T protein expression decreased. GABA ARα1 and GABA ARγ2 protein expression(IHC, WB) in the hypothalamus of the auricular bloodletting group increased, whereas GABA-T protein expression decreased. GABA ARγ1(IHC) and GABA ARγ2(WB) protein expression in the hypothalamus of the auricular bloodletting combined sticking group increased, whereas GAT-1 and GABA-T protein expression decreased (P<0.05). Compared with in the inventation groups, the serum GABA content in the auricular point sticking group increased, the serum glutamate content decreased, GABA ARα1 and GABA ARγ2 mRNA expression in the hypothalamus increased, and GABA ARα1(IHC), GAD65/67 protein expression increased. In contrast, GABA-T protein expression decreased (P<0.05), and GABA ARγ2 protein expression(IHC) in the hypothalamus of the auricular bloodletting group increased (P<0.05). Conclusion Auricular therapy, particularly auricular point sticking, may have modulated the GABAergic system pathway by upregulating hypothalamic GABA ARα1, GABA ARγ2, and GAD65/67 protein expression while downregulating GAT-1 and GABA-T protein expression to alleviate symptoms in an insomnia rat model.

Objective To investigate the safety and feasibility of the domestic SA-1000 single-port single-arm robot-assisted laparoscopic system in total hysterectomy.Methods Data from 16 patients who underwent total hysterectomy using the SA-1000 system at the Department of Obstetrics and Gynecology,The Second Affiliated Hospital of Naval Medical University,between Mar.2023 and Jan.2024 were retrospectively collected.Surgical parameters were analyzed.Postoperative pain was assessed using the visual analogue scale(VAS)at 24 h after surgery and before discharge.Incision cosmesis was evaluated 3-5 weeks postoperatively using the body image questionnaire(BIQ,score range 3-24).Results All 16 procedures were successfully completed using the SA-1000 system without conversion to open surgery,achieving a 100.0%procedural success rate.The mean whole surgery time was(234.40±56.24)min.The median robotic arm setup time was 8.0(4.0,13.5)min,and the median console operating time was 128.0(100.0,151.0)min.The median intraoperative blood loss was 100.0(100.0,200.0)mL.No perioperative complications,such as hemorrhage,infection,injury to adjacent organs(ureters,bladder,bowel),poor wound healing,or incisional hernia,were observed.The mean wound pain score at 24 h postoperatively was 3.81±1.64,decreasing to a median of 3.0(2.0,4.0)before discharge.The BIQ score assessed at 3-5 weeks postoperatively was 21.88±1.15.Conclusion The application of the domestic SA-1000 single-port single-arm robot-assisted laparoscopic system for total hysterectomy is safe and feasible,demonstrating favorable surgical outcomes.It holds promise for broader implementation and promotion in domestic medical centers.

Objective:To compare the performance of next-generation sequencing (NGS) and Sanger sequencing in investigating somatic hypermutation (SHM) status of immunoglobulin heavy chain variable region (IGHV) genes. It specifically focuses on identifying key factors contributing to discrepancies between the two methods, particularly under complex clonal backgrounds, to inform optimized strategies for clinical application.Methods:This retrospective analysis included 53 samples, comprising 43 identified as non-monoclonal and 10 as monoclonal using Sanger sequencing. All samples were further analyzed using NGS to assess IGHV SHM. The two methods were used for systematic comparison. For discordant cases, in-depth attribution analysis was conducted, considering factors, including clonal abundance quantification, differences in primer design, and interpretation criteria.Results:Among the 53 patients who underwent both Sanger and NGS testing, 36 were male and 17 were female, with a median age of 64 years (range: 33–88). Diagnoses included chronic lymphocytic leukemia (CLL) in 35 (66.0% ), diffuse large B-cell lymphoma in 9 (17.0% ), follicular lymphoma in 3 (5.7% ), mantle cell lymphoma in 3 (5.7% ), and other types in 3 (5.7% ) cases. In the 43 cases with non-monoclonal profiles using Sanger sequencing, NGS revealed 23 cases as biclonal or polyclonal, 17 as monoclonal, and 3 with no detectable clonality. The primary discrepancies between the two methods involved variations in clonality assessment, IGHV gene rearrangement types, and mutation rates. Among the 10 cases identified as monoclonal using Sanger sequencing, NGS detected biclonality and markedly different IGHV rearrangement types in 2 and 4 cases, respectively. Minor differences were observed in SHM percentage between the two methods; however, these did not substantially affect the overall determination of mutational status.Conclusion:Compared with Sanger sequencing, NGS exhibits superior performance in assessing IGHV SHM status under complex clonal conditions. It provides greater sensitivity and accuracy in detecting subclonal components and quantifying clonal proportions, thereby providing a more precise molecular basis for diagnosing and prognostically assessing lymphoid malignancies, including CLL.

Objective:This study aimed to explore the utility of transcutaneous electrical acupoint stimulation (TEAS) combined with skin sympathetic response (SSR) in assessing the effectiveness of perigastric autonomic nerve preservation during radical gastrectomy.Methods:A retrospective cohort analysis was conducted involving 221 patients who underwent laparoscopic radical gastrectomy at the Department of Gastric Surgery, Taizhou People's Hospital, affiliated with Nanjing Medical University, between June 2022 and September 2024. The cohort comprised 109 patients who underwent laparoscopic radical total gastrectomy without autonomic nerve preservation (total gastrectomy without nerve preservation group). Additionally, 112 patients underwent laparoscopic radical distal gastrectomy, including 34 patients who received autonomic nerve preservation (nerve preservation group) and 78 patients who did not (without nerve preservation group). TEAS was administered at the Zusanli and Tianshu acupoints one day before and one day after surgery, during which SSR latency and voltage amplitudes in the upper and lower extremities were recorded and compared across groups. Differences in SSR latency and voltage amplitude between the nerve preservation and non-nerve preservation groups of the distal gastrectomy cohort were also analyzed. Further, TEAS was applied at the same acupoints for 15 minutes on the 1st, 2nd, and 3rd postoperative days, and changes in intestinal sounds and intestinal functional recovery time were monitored. Surgical parameters, including operative duration, intraoperative blood loss, and harvested lymph node, were documented. Postoperative inflammatory indicators, including interleukin-6 (IL-6), C-reactive protein (CRP), procalcitonin (PCT), and the incidence of anastomotic leakage, were evaluated. At three months postoperatively, gastroscopy was performed to assess residual gastric food and bile reflux. Additionally, the prognostic nutritional index (PNI) was evaluated across all patient groups.Results:Following total gastrectomy, TEAS of Zusanli combined with arms' SSR revealed a latency of (23 59.71±410.55) ms and a voltage amplitude of (0.43±1.67) mV; for the legs, latency was (2 596.88±369.01) ms and voltage amplitude was (0.25±0.08) mV. TEAS of Tianshu combined with arms' SSR demonstrated a latency of (2 746.47±224.37) ms and a voltage amplitude of (0.31±0.14) mV; for the legs, latency was (2 891.90±193.61) ms and voltage amplitude was (0.19±0.72) mV. Postoperative latency was significantly prolonged, and voltage amplitude was markedly reduced (all P < 0.01). In the distal gastrectomy with nerve preservation group, TEAS of Zusanli combined with arms' SSR showed a latency of (1 668.04±261.91) ms and a voltage amplitude of (0.78±0.26) mV; for the legs, latency was (1 568.86±220.09) ms and voltage amplitude was (0.61±0.24) mV. TEAS of Tianshu combined with arms' SSR demonstrated a latency of (1 519.36±206.99) ms and a voltage amplitude of (0.66±0.34) mV; for the legs, latency was (2 004.80±508.53) ms and voltage amplitude was (0.55±0.28) mV. In the distal gastrectomy without nerve preservation group, TEAS of Zusanli combined with arms' SSR revealed a latency of (2 385.95±710.27) ms and a voltage amplitude of (0.23±0.11) mV; for the legs, latency was (2 506.81±779.37) ms and voltage amplitude was (0.26±1.29) mV. TEAS of Tianshu combined with arms' SSR indicated a latency of (2 697.78±385.55) ms and a voltage amplitude of (0.21±0.14) mV; for the legs, latency was (2 949.14±506.61) ms and voltage amplitude was (0.17±0.11) mV. The group without nerve preservation exhibited significantly prolonged latencies and reduced voltage amplitudes (all P<0.01). No statistically significant differences were observed between the groups in operative time, intraoperative bleeding, the number of dissected lymph nodes, inflammatory indicators (IL-6, CRP, PCT) at 3 days postoperatively, or anastomotic leakage rates (all P>0.05). In the group without nerve preservation, bowel sounds on postoperative days 1, 2, and 3 were (0.36±0.58), (1.04±0.97), and (1.74±1.10) times/min, respectively, with bowel function recovery time of (62.24±9.91) hours. The PNI at 3 months postoperatively was (37.42±3.01). Incidences of food residue in the residual stomach and bile reflux were 21.79% (17/78) and 29.49% (23/78), respectively. In the group with nerve preservation, bowel sounds on postoperative days 1, 2, and 3 were (0.76±0.82), (2.03±1.34), and (3.71±1.27) times/min, respectively, with bowel function recovery time of (44.94±8.05) hours. The PNI at 3 months postoperatively was (41.34±3.40). Incidences of food residue and bile reflux were 5.88% (2/34) and 11.76% (4/34), respectively. Statistically significant differences were observed between the groups (all P < 0.05). Conclusion:TEAS of Zusanli and Tianshu combined with SSR provides an objective measure for assessing the preservation of perigastric autonomic nerves during radical gastrectomy.

Objective To investigate the effects of long non coding RNA MAGI2 antisense chain RNA3(LncRNA MAGI2-AS3)on the migration,invasion,and epithelial mesenchymal transition(EMT)of gastric cancer(GCa)cells by regulating the miR-194-5 p/caveolin-1(CAV1)axis.Methods Fifty-two GCa patients who underwent surgical resection in our hospital from August 2022 to December 2023 were selected.Cancer and adjacent tissues were collected,and AGS,MKN45,HGC-27,and GES1 cells were cultured in vitro.The expression of MAGI2-AS3,miR-194-5p,and CAV1 in tissue samples and cell lines was analyzed.AGS cells were randomly separated into AGS group,sh-AGS group sh-MAGI2-AS3 group,miR-NC group,and in miR-194-5p group.The proliferation,apoptosis,migration,and invasion of cells in each group were compared.Immunoblotting was applied to analyze the expression of E-cadherin,CAV1,proliferating cell nuclear antigen(PCNA),N-cadherin,Bax,matrix metalloproteinase 2(MMP2),and vimentin of cells in each group.Dual luciferase assay was applied to analyze the relationship between MAGI2-AS3 and miR-194-5p,and between miR-194-5p and CAV1.Results The expression of MAGI2-AS3 mRNA,CAV1 mRNA,and positive expression rate of CAV1 protein in GCa tissue increased,while the expression of miR-194-5p mRNA decreased(P＜0.05).The expression of MAGI2-AS3 mRNA,CAV1 mRNA,and CAV1 protein in HGC-27,MKN45,and AGS cells was higher than that of GES1 cells,the expression of miR-194-5p mRNA was lower than that of GES1 cells(P＜0.05).Compared with the AGS and sh-AGS groups,the cell absorbance,number of clones,invasion and migration,expression of CAV1,PCNA,N-cadherin,MMP2,and vimentin in sh-MAGI2-AS3 group decreased,the apoptosis rate,expression of E-cadherin,and Bax increased(P＜0.05).Compared with the miR-NC group and sh-MAGI2-AS3 group,the cell absorbance,number of clones,invasion and migration,expression of CAV1,PCNA,N-cadherin,MMP2,and vimentin in in-miR-194-5p group increased,the apoptosis rate,expression of E-cadherin,and Bax reduced(P＜0.05).ENCORI database found that there were multiple binding sites between MAGI2-AS3 and miR-194-5p,and between miR-194-5p and CAV1.Compared with the WT-MAGI2-AS3+miR-NC group,the luciferase activity in the WT-MAGI2-AS3+miR-194-5p group decreased(P＜0.05),while compared with the WT-CAV1+miR-NC group,the luciferase activity in the WT-CAV1+miR-194-5p group decreased(P＜0.05).Conclusion LncRNA MAGI2-AS3 silencing can target miR-194-5p to downregulate CAV1,thereby inhibiting GCa cell migration,invasion,and EMT.