ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

This study assessed the role and mechanism of the recombinant Bacillus Calmette-Gue?rin vaccine(rBCG)with c-di-AMP adjuvant in regulating metabolism and immunity in epididymal white adipose(eWAT)in mice.Male C57BL/6 mice were intravenously immunized with BCG and rBCG,and their body weights were monitored.eWAT was isolated from the mice,and the stromal vascular fractions(SVFs)cell number was counted with a hemocytometer.Sections of mouse adipose tissue were prepared,and the size,number,and morphology of eWAT adipocytes and crown-like structure(CLS)formation were compared under a microscope after HE staining.The transcription levels of lipid metabolism-associated factors,cytokines and aging-associated genes in each group were determined with qRT-PCR.The body weights of mice gradually increased after immunization with BCG and rBCG.The proportions of eWAT increased,and the SVFs cell number decreased,in rBCG immunized mice.HE staining indicated that BCG immunization promoted hyperplasia,whereas rBCG immunization promoted hypertrophy of eWAT adipocytes;moreover,both BCG and rBCG immunization induced CLS formation in eWAT.The qRT-PCR results indicated that rBCG immunization inhibited the expression of genes associated with lipolysis and energy expenditure in eWAT.BCG immunization had little effect on cytokine transcription,whereas rBCG significantly induced the transcription of IFN-γ and IL-1Ra,and inhibited that of IL-15 and IL-2,but did not induce the expression of aging-associated genes.Thus,rBCG immunization induced eWAT adipocyte hypertrophy,which was associated with the inhibition of eWAT lipolysis and the regulation of cytokine expression.

This experiment was conducted to study the effects of replacing feed protein by Herme-tia illucens larvae meal on immune function,intestinal morphology and microflora of Sichuan white geese.A total of 64 healthy 1-day-old Sichuan white geese were randomly allocated into 4 groups with 4 replicates in each group and 4 geese in each replicate,namely the control group,the 2％HILM,4％HILM and 8％HILM groups fed diets contained 0％,2％,4％and 8％of HILM,re-spectively.The experimental period was 40 days.The results showed that compared with the con-trol group,8％HILM increased the levels of serum IgG1,IgG2a and complement C3,and the difference was statistically significant(P＜0.01).4％HILM significantly increased the expression level of CD4(P＜0.05),and 8％HILM significantly increased the expression level of IL-10(P＜0.05).The ratio of villus length to crypt depth(VH/CD)in the jejunum and ileum in 4％HILM group was significantly increased(P＜0.05).The SIgA level of jejunum was significantly increased in all HILM replacement groups(P＞0.05).The abundance of Bacteroides in 4％HILM group were extremely significantly increased(P＜0.01),and the abundance of Bilophila and Bilophila wadsworthia were significantly decreased in all HILM replacement groups(P＜0.05).In conclu-sion,HILM can enhance the immune function of Sichuan white geese,improve the intestinal mor-phology of jejunum and ileum,enhance the local mucosal immunity of jejunum,increase the abun-dance of beneficial bacteria in cecum and decrease the abundance of harmful bacteria in cecum,and protect intestinal health.

Objective:In this study, we aimed to investigate the short-term efficacy and safety of perioperative administration of the PD-1 inhibitor tislelizumab combined with the SOX regimen (oxaliplatin plus S-1) in patients with locally advanced gastric cancer, and to identify factors influencing therapeutic outcomes.Methods:In this retrospective cohort study, we analyzed clinical data of 166 patients who had undergone perioperative therapy and D2 radical gastrectomy in the Department of General Surgery, First Medical Center of Chinese PLA General Hospital between September 2021 and September 2023. The cohort comprised 140 men and 26 women, of median age 62 years (range: 30-75). The patients were allocated to two groups: 62 receiving tislelizumab plus SOX (combination therapy group), and 104 SOX alone (chemotherapy-only group). Primary outcomes included pathological complete response rate, treatment-related adverse events, and complications of surgery. Secondary outcomes comprised major pathological response rate, tumor regression grade (Grades 1-2 denoting favorable response, Grade 3 moderate, and Grades 4-5 poor response), R0 resection rate, and short-term survival outcomes (1-year disease-free and overall survivals). Risk factors associated with pCR in the combination group were also analyzed.Results:The combination therapy group exhibited significantly higher rates of pCR (25.8% vs. 8.7%, χ 2=8.93, P=0.003) and Grade 1 tumor regression (25.8% vs. 16.3%, χ 2=15.32, P=0.001) than the chemotherapy-only group. There were no statistically significant differences in major pathological response rates (41.9% vs. 39.4%), R0 resection rates (96.8% vs. 97.1%,), treatment- related adverse events (48.4% vs. 42.3%,), surgical complications (9.7% vs. 12.5%), 1-year disease-free survival (82.3% vs. 78.8%), or 1-year overall survival (93.5% vs. 91.3%), There were no statistically significant differences (all P>0.05). Multivariate logistic analysis identified neural invasion as an independent risk factor for reduced pCR in the combination group (OR=0.10, 95%CI:0.01-0.85, P=0.035). Conclusions:Perioperative tislelizumab combined with SOX chemotherapy improves pathological response rates in patients with locally advanced gastric cancer and has favorable short-term efficacy and safety profiles. Neural invasion may diminish the therapeutic efficacy of immunotherapy.

Objective To clarify the differences in the effects of bupivacaine liposome and ropivacaine on quadratus lumborum block in patients undergoing laparoscopic total hysterectomy.Methods A total of 70 patients who underwent laparoscopic total hysterectomy at Suqian First People's Hospital Affiliated to Nanjing Medical University from January 2023 to October 2024 were selected as the research subjects.The patients were randomly divided into the control group and the observation group,with 35 cases in each group.Before general anesthesia,patients of the control group were given ropivacaine quadratus lumborum block,while patients of the observation group were given bupivacaine liposome quadratus lumborum block.The general conditions before and after operation,visual analogue scale(VAS)scores at different time points after operation,rescue analgesia,mini-mental state examination(MMSE)scores at different time points after operation,postoperative rehabilitation and analgesic adverse reactions were compared between the two groups.Results There was no statistically significant difference in the general conditions of patients in the two groups before and after the operation(P>0.05).At 24 hours,48 hours,and 72 hours after surgery,the abdominal resting VAS scores of patients in the observation group were significantly lower than those in the control group(P<0.05).The time of the first self-controlled use of the intravenous analgesic pump after surgery in the observation group was significantly later than that in the control group(P<0.05).The number of analgesic pump compressions and the rate of oxycodone rescue analgesia in the observation group were significantly fewer/lower than those in the control group within 48 hours after surgery(P<0.05).At 24 hours,48 hours,and 72 hours after surgery,the MMSE scores of patients in the observation group were significantly higher than those in the control group(P<0.05).The time for patients to get out of bed and move around after surgery and the recovery time of anal exhaust in the observation group were significantly earlier than those in the control group(P<0.05).There was no statistically significant difference in the incidence of postoperative analgesic adverse reactions between the two groups of patients(P>0.05).Conclusion Compared with the use of ropivacaine for quadratus lumborum block in patients undergoing laparoscopic total hysterectomy,bupivacaine liposome can provide a longer-lasting analgesic effect,reduce patients'dependence on intravenous analgesia,be conducive to protecting patients'cognitive function,accelerate the recovery of patients without increasing the incidence of adverse reactions.

Objective:To study the incidence and epidemiological characteristics of tsutsugamushi disease in Ankang City, Shaanxi Province.Methods:From 2018 to 2023, data on tsutsugamushi disease cases reported by various medical institutions at all levels in Ankang City were collected through the China Disease Prevention and Control Information System. At the same time, individual epidemiological investigation of reported cases was carried out, and electronic medical records of patients were retrieved to verify their diagnosis. In 2023, the rodents and chigger mites were monitored in 3 townships with high incidence of tsutsugamushi disease in Ankang City by night clamping method, and the chigger mites rate and chigger mites index were calculated. Blood, liver, spleen and kidney samples of rodents were collected, DNA of blood and organ mixture was extracted, and quantitative real-time PCR was used to detect Orientia tsutsugamushi. Results:A total of 330 cases of tsutsugamushi disease were reported in Ankang City from 2018 to 2023, and the reported incidence rate increased from 0.56/100 000 in 2018 to 5.02/100 000 in 2023. Among them, 139 were males and 191 were females, with a sex ratio of 0.73∶1.00. The age was mainly 45 - 70 years old, accounting for 81.52% (269/330). The occupation was mainly farmers, accounting for 86.97% (287/330). The onset time was mainly concentrated from April to October, with a total of 317 cases, accounting for 96.06% (317/330). The main clinical manifestations were fever (93.20%, 274/294), ulcer or eschar (75.85%, 223/294), headache (44.56%, 131/294), and lymph node enlargement (44.22%, 130/294). The misdiagnosis rate at the first diagnosis was 73.81% (217/294). A total of 452 rodents were captured, of which 91 rodents carried chigger mites, and chigger mites rate was 20.13% (91/452). A total of 1 463 chigger mites were captured, and the chigger mites index was 3.24 (1 463/452). Quantitative real-time PCR was performed on blood and organ mixture samples collected from 452 rodents, and one of the organ mixture samples tested positive for Orientia tsutsugamushi. Conclusions:The incidence of tsutsugamushi disease in Ankang City is relatively high, and the overall incidence is on the rise. The cases are mainly female, middle-aged and elderly, and farmers, with a high misdiagnosis rate at the first diagnosis. There are chigger mites in rodents in townships with high incidence of tsutsugamushi disease.

To explore the effect of Macleaya cordata extract(MCE)on growth performance and serum biochemistry of Sichuan White Geese,and to analyze its mechanism of action by network pharmacology and molecular docking technology combined with animal experiments verification.A total of 90 1-day-old healthy goslings were randomly divided into 5 groups with 18 goslings per group after 5 d of adaptive feeding.The control group(CON)was fed with basal diet,the antibiotic group(CTC)was supplemented with 450 mg/kg chlortetracycline premix,and the low MCE group(MCEL),medium MCE group(MCEM)and high MCE group(MCEH)were supple-mented with 200,300 and 400 mg/kg MCE,respectively.The experimental period was 21 d.On the basis of the above experiments,Network pharmacology and molecular docking technology were used to predict the core targets and signaling pathways of MCE to promote geese growth from the levels of antioxidant,immune and apoptosis,and the expression levels of the core target genes were detected by Real-time fluorescence quantitative PCR.The results showed that compared with the CON group,MCE supplementation could increase the average daily weight gain,decrease the ratio of feed to gain,significantly increase the contents of serum GH,T3,T4,TP and ALB(P＜0.05),and significantly decrease the contents of serum AST and TG(P＜0.05).Network pharmacology analysis predicted 2 active ingredient and 237 active ingredient targets,and concluded that the mechanism of MCE promoting the growth of Sichuan White Geese may be related to the role of 5 key targets such as SRC,HSP90AA1,CASP3,ESR1 and MAPK14,and the action of MAPK,apop-tosis and other signaling pathways.Molecular docking results showed that the active ingredients of sanguinarine and chelerythrine in MCE could act through MAPK14.The validation results of core targets showed that MCE could significantly reduce the mRNA expression levels of CytC,CASP2,CASP3 and CASP9 in spleen(P＜0.05)and significantly increase the mRNA expression levels of Mcl-1(P＜0.05).These results indicated that MCE could promote the growth performance of Si-chuan White Geese by regulating apoptosis,promoting the secretion of serum growth-related hor-mones and improving biochemical indicators.

Objective:To explore the advantages of robotic-arm assisted total hip arthroplasty (rTHA) in acetabular component positioning and lower limb length assessment in patients with severe pelvic coronal tilt.Methods:A retrospective analysis was conducted on the data of 122 patients with unilateral end-stage hip disease and coronal pelvic tilt angle >3° who underwent total hip arthroplasty (THA) at the First Medical Center of PLA General Hospital from June 2022 to December 2023. Among them, 44 patients underwent rTHA, and 78 underwent manual THA (mTHA). The rTHA group included 18 males and 26 females, with an average age of 60.5±9.3 years; the mTHA group included 41 males and 37 females, with an average age of 58.5±8.4 years. Compare the differences in the anteversion angle, abduction angle, pelvic tilt angle, leg length discrepancy (LLD) of the acetabular prosthesis, and the proportions of patients with LLD>0.5 cm and >1 cm between the two groups of patients after surgery. Calculate the proportion of outlier rates of acetabular abduction angle (<30° or >45°), and proportions within Callanan's safe zone. The early efficacy of the hip joint was evaluated by using the modified Harris score and joint range of motion.Results:All patients were followed up for 6 to 12 months, with an average of 8 months. All the surgical incisions of the patients achieved primary healing. Postoperative comparisons showed no statistically significant differences in acetabular abduction angle (39.5°±3.3° vs. 38.4°±7.3°) or anteversion angle (20.7°±1.6° vs. 19.7°±1.6°) between rTHA and mTHA groups ( P>0.05). However, pelvic tilt angle [2.5° (1.1°, 3.6°) vs. 3.5° (2.3°, 5.9°)] showed a statistically significant difference ( U=4.371, P=0.008). The rTHA group exhibited smaller absolute LLD [0.2 (0.1, 0.4) cm vs. 0.5 (0.2, 0.5) cm] and lower proportions of LLD >0.5 cm [14% (6/44) vs. 49% (38/78)] and >1 cm [2% (1/44) vs. 18% (14/78)], with statistical significance ( P<0.05). The rTHA group had a lower outlier rate for acetabular abduction angle (<30°or >45°) compared to the mTHA group [2% (1/44) vs. 33% (26/78)], with statistical significance (χ 2=10.388, P<0.001). Taking the Callanan safety zone as the standard, the proportion of acetabular cups within the safe zone was significantly higher in the rTHA group (98%, 43/44) compared to the mTHA group (67%, 52/78), with a statistically significant difference (χ 2=13.998, P<0.001). The modified Harris score and hip joint range of motion in the mTHA group increased from 47.6±6.6 points and 83° (73°, 88°) before the operation to 83.5±11.2 points and 118° (110°, 122°) at the last follow-up, respectively. The rTHA group increased from 46.5±9.2 points and 79° (71°, 90°) before the operation to 85.0±12.5 points and 124° (116°, 130°) at the last follow-up. The differences in the modified Harris score and hip joint range of motion between the two groups before the operation and at the last follow-up were statistically significant ( P<0.05). However, there was no statistically significant difference between the groups at the last follow-up ( P>0.05). No THA-related complications occurred during follow-up period. Conclusion:For patients with end-stage hip joint diseases with coronal tilt exceeding 3°, robotic-assisted technology significantly improves the accuracy of acetabular component placement during THA and offers better control of postoperative LLD.

Objective To clarify the differences in the effects of bupivacaine liposome and ropivacaine on quadratus lumborum block in patients undergoing laparoscopic total hysterectomy.Methods A total of 70 patients who underwent laparoscopic total hysterectomy at Suqian First People's Hospital Affiliated to Nanjing Medical University from January 2023 to October 2024 were selected as the research subjects.The patients were randomly divided into the control group and the observation group,with 35 cases in each group.Before general anesthesia,patients of the control group were given ropivacaine quadratus lumborum block,while patients of the observation group were given bupivacaine liposome quadratus lumborum block.The general conditions before and after operation,visual analogue scale(VAS)scores at different time points after operation,rescue analgesia,mini-mental state examination(MMSE)scores at different time points after operation,postoperative rehabilitation and analgesic adverse reactions were compared between the two groups.Results There was no statistically significant difference in the general conditions of patients in the two groups before and after the operation(P>0.05).At 24 hours,48 hours,and 72 hours after surgery,the abdominal resting VAS scores of patients in the observation group were significantly lower than those in the control group(P<0.05).The time of the first self-controlled use of the intravenous analgesic pump after surgery in the observation group was significantly later than that in the control group(P<0.05).The number of analgesic pump compressions and the rate of oxycodone rescue analgesia in the observation group were significantly fewer/lower than those in the control group within 48 hours after surgery(P<0.05).At 24 hours,48 hours,and 72 hours after surgery,the MMSE scores of patients in the observation group were significantly higher than those in the control group(P<0.05).The time for patients to get out of bed and move around after surgery and the recovery time of anal exhaust in the observation group were significantly earlier than those in the control group(P<0.05).There was no statistically significant difference in the incidence of postoperative analgesic adverse reactions between the two groups of patients(P>0.05).Conclusion Compared with the use of ropivacaine for quadratus lumborum block in patients undergoing laparoscopic total hysterectomy,bupivacaine liposome can provide a longer-lasting analgesic effect,reduce patients'dependence on intravenous analgesia,be conducive to protecting patients'cognitive function,accelerate the recovery of patients without increasing the incidence of adverse reactions.

Objective:In this study, we aimed to investigate the short-term efficacy and safety of perioperative administration of the PD-1 inhibitor tislelizumab combined with the SOX regimen (oxaliplatin plus S-1) in patients with locally advanced gastric cancer, and to identify factors influencing therapeutic outcomes.Methods:In this retrospective cohort study, we analyzed clinical data of 166 patients who had undergone perioperative therapy and D2 radical gastrectomy in the Department of General Surgery, First Medical Center of Chinese PLA General Hospital between September 2021 and September 2023. The cohort comprised 140 men and 26 women, of median age 62 years (range: 30-75). The patients were allocated to two groups: 62 receiving tislelizumab plus SOX (combination therapy group), and 104 SOX alone (chemotherapy-only group). Primary outcomes included pathological complete response rate, treatment-related adverse events, and complications of surgery. Secondary outcomes comprised major pathological response rate, tumor regression grade (Grades 1-2 denoting favorable response, Grade 3 moderate, and Grades 4-5 poor response), R0 resection rate, and short-term survival outcomes (1-year disease-free and overall survivals). Risk factors associated with pCR in the combination group were also analyzed.Results:The combination therapy group exhibited significantly higher rates of pCR (25.8% vs. 8.7%, χ 2=8.93, P=0.003) and Grade 1 tumor regression (25.8% vs. 16.3%, χ 2=15.32, P=0.001) than the chemotherapy-only group. There were no statistically significant differences in major pathological response rates (41.9% vs. 39.4%), R0 resection rates (96.8% vs. 97.1%,), treatment- related adverse events (48.4% vs. 42.3%,), surgical complications (9.7% vs. 12.5%), 1-year disease-free survival (82.3% vs. 78.8%), or 1-year overall survival (93.5% vs. 91.3%), There were no statistically significant differences (all P>0.05). Multivariate logistic analysis identified neural invasion as an independent risk factor for reduced pCR in the combination group (OR=0.10, 95%CI:0.01-0.85, P=0.035). Conclusions:Perioperative tislelizumab combined with SOX chemotherapy improves pathological response rates in patients with locally advanced gastric cancer and has favorable short-term efficacy and safety profiles. Neural invasion may diminish the therapeutic efficacy of immunotherapy.