Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

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.

To analyze the distribution of serotypes and antimicrobial resistance of clinical Salmonella isolates from multiple centers across China.

Objective: To explore the influencing factors for implementation of weight management services in primary medical and healthcare institutions, so as to provide references for implementing sustainable services of weight management. Methods: From May to June 2025, Pinghu City, Zhejiang Province was selected as the survey site. Personnel responsible for weight management in primary medical and healthcare institutions were selected as the survey subjects using a combined method of purposive sampling and snowball sampling. Based on the five core domains of the consolidated framework for implementation research (CFIR), a semi-structured interview outline for weight management services in primary medical and healthcare institutions was designed. Original data was collected through face-to-face semi-structured interviews. Interview data was organized and analyzed using framework analysis. Factors affecting weight management services were quantitatively analyzed by referencing CFIR's structural rating criteria. Results: A total of 21 participants completed interviews, covering positions in nutrition, endocrinology, traditional Chinese medicine, general practice, maternal health, and public health. There were 9 males and 12 females. Fifteen participants (71.43%) were aged 35 years and above, 18 (85.71%) held a bachelor's degree or higher, and 15 (71.43%) were frontline medical staff. Fifteen factors affecting weight management services were identified across five domains: innovation, outer setting, inner setting, individuals, and implementation process. Six barrier factors were identified: difficulties in policy implementation, time-consuming interventions, limited incentive measures, lack of professional skills, unclear weight-loss plans and goal setting, and imperfect follow-up and evaluation mechanisms. Three neutral factors were identified: the development and refinement of policies and regulations, the implementation of weight management training, and the optimization of the referral process within integrated healthcare systems (medical alliances / communities). Six facilitating factors were identified: the relatively significant advantages of lifestyle interventions, collaboration and coordination across multiple departments, cooperative communication among different units within the institution, the inherent convenience of primary care settings, a strong sense of professional responsibility, and the establishment of multidisciplinary teams. Conclusions The delivery of weight management services in primary medical and healthcare institutions is influenced by a wide array of factors across multiple domains. It requires policy support, multi-department coordination, a practice-oriented training system, optimized team resource allocation, incentives, and improved professional skills of medical staff to jointly promote long-term implementation.

This study explored the potential therapeutic targets and mechanisms of Danggui Shaoyao San(DSS) in the prevention and treatment of Alzheimer's disease(AD) through transcriptomics and metabolomics, combined with animal experiments. Fifty male C57BL/6J mice, aged seven weeks, were randomly divided into the following five groups: control, model, positive drug, low-dose DSS, and high-dose DSS groups. After the intervention, the Morris water maze was used to assess learning and memory abilities of mice, and Nissl staining and hematoxylin-eosin(HE) staining were performed to observe pathological changes in the hippocampal tissue. Transcriptomics and metabolomics were employed to sequence brain tissue and identify differential metabolites, analyzing key genes and metabolites related to disease progression. Reverse transcription-quantitative polymerase chain reaction(RT-qPCR) was employed to validate the expression of key genes. The Morris water maze results indicated that DSS significantly improved learning and cognitive function in scopolamine(SCOP)-induced model mice, with the high-dose DSS group showing the best results. Pathological staining showed that DSS effectively reduced hippocampal neuronal damage, increased Nissl body numbers, and reduced nuclear pyknosis and neuronal loss. Transcriptomics identified seven key genes, including neurexin 1(Nrxn1) and sodium voltage-gated channel α subunit 1(Scn1a), and metabolomics revealed 113 differential metabolites, all of which were closely associated with synaptic function, oxidative stress, and metabolic regulation. RT-qPCR experiments confirmed that the expression of these seven key genes was consistent with the transcriptomics results. This study suggests that DSS significantly improves learning and memory in SCOP model mice and alleviates hippocampal neuronal pathological damage. The mechanisms likely involve the modulation of synaptic function, reduction of oxidative stress, and metabolic balance, with these seven key genes serving as important targets for DSS in the treatment of AD.
Animals ; Alzheimer Disease/genetics* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Mice, Inbred C57BL ; Metabolomics ; Transcriptome/drug effects* ; Maze Learning/drug effects* ; Hippocampus/metabolism* ; Humans ; Disease Models, Animal ; Memory/drug effects*

BACKGROUND: Acupuncture has shown potential therapeutic benefits for individuals with simple obesity. However, some researchers argue that some of the effectiveness of acupuncture may be due to the placebo response. OBJECTIVE: To understand the placebo response of acupuncture treatment in simple obesity, a systematic review and meta-analysis was designed based on the comparison between sham acupuncture before and after treatment. SEARCH STRATEGY: Eight databases (PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure, Wanfang Database, China Biology Medicine Database, and Chinese Scientific Journals Database) were searched from inception to August 1, 2023. The MeSH search terms comprised obesity and acupuncture. INCLUSION CRITERIA: Randomized controlled trials (RCTs) using sham or placebo acupuncture as a control in treating obesity were enrolled. DATA EXTRACTION AND ANALYSIS: Two researchers independently extracted data, and the results were cross-checked after completion. Each RCT's detailed sham/placebo acupuncture treatment protocol was assessed according to the SHam Acupuncture REporting guidelines. The revised Cochrane risk-of-bias tool for randomized trials and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system were used to determine the risk of bias and quality of evidence, respectively. Body mass index (BMI) was defined as the primary outcome. Anthropometric parameters and laboratory test parameters related to obesity were defined as secondary outcomes. We used standardized mean difference (SMD) with 95% confidence interval (CI) to calculate treatment effects of outcomes. RESULTS: Fifteen RCTs with a total of 1250 patients were included. The BMI significantly decreased after treatment in the sham acupuncture group compared to baseline (SMD 0.37, 95% CI 0.09-0.66; I² = 81%, random model; P < 0.01). Treatment duration (P = 0.02) and other interventions significantly impacted the placebo response rate (P = 0.00). CONCLUSION The placebo response of sham acupuncture was strong in the RCTs for simple obesity, and the effect sizes differed between various outcomes. The treatment duration and other interventions emerged as potential influencing factors for the placebo response of sham acupuncture. Please cite this article as: Liu KJ, Jiao RM, Ji J, Yao WW, Han CR, Zhao XY, Zhao JJ. Placebo response in sham acupuncture therapy trials for simple obesity: a systematic review and meta-analysis. J Integr Med. 2025; 23(3): 264-273.
Humans ; Acupuncture Therapy/methods* ; Obesity/therapy* ; Placebo Effect ; Placebos ; Randomized Controlled Trials as Topic

Photothermal therapy,as a novel anti-tumor treatment strategy,faces many challenges such as insufficient targeting,limited penetration ability,and inability to achieve long-term inhibition when used alone for anti-tumor treatment.Based on this,in this study,macrophage extracellular vesicles(MEVs)were modified onto the surface of a vector carrying CSF1R-siRNA and photothermal agents to form a multifunctional gene delivery vector MEVs@RNPs.It could induce the macrophages to reprogram from M2 type to M1 type,so as to achieve efficient photothermal and immunotherapy for triple negative breast cancer(TNBC).The basic physicochemical properties of each nanocarrier were characterized using nanoparticle size analyzer,UV-vis spectrometer,fluorescence spectrometer,thermal imaging instrument,etc.TNBC cells 4T1,endothelial cells Bend3,and macrophages 264.7 were used as in vitro experimental subjects for measurement of MEVs@RNPs.The ability to target tumor cells,kill tumor cells,and induce macrophage reprogramming in vitro was investigated.With Balb/c mice as the in vivo research object,a subcutaneous transplant tumor model was established in mice,and the changes in tumor volume and body weight of mice in different treatment groups were measured.In addition,further isolation of mouse blood and tumor tissue was performed,and hematoxylin-eosin(HE)staining,terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)method,and enzyme-linked immunosorbent assay(ELISA)method were used to determine the apoptosis and cytokine secretion of tumor cells for comprehensive evaluation of MEVs@RNPs.The results showed that the MEVs@RNPs could preferentially target tumor cells and induce stronger TNBC cell killing effect under photothermal conditions.Meanwhile,the results of flow cytometry and ELISA analysis showed that the MEVs@RNPs could promote the transformation of macrophages from M2 type to anti-tumor M1 type,significantly enhancing the secretion levels of anti-tumor cytokines tumor necrosis factor-α(TNF-α)and interleukin-12(IL-12).The in vivo anti-tumor treatment effect assessment of the MEVs@RNPs showed that under laser processing conditions,the MEVs@RNPs could significantly induce pathological necrosis and apoptosis of tumor cells,promote macrophage reprogramming and infiltration of CD4+/CD8+T cells into the tumor site,and enhance the secretion levels of TNF-α and IL-12,thereby comprehensively improving the therapeutic effect of TNBC.

Objective To investigate the regulation of macrophage polarization and foaminess by homocysteine(Hcy)and its potential underlying mechanisms.Methods ELISA and flow cytometry were used to detect the effect of Hcy treatment on the polarization of macrophages.The contents of various forms of intracellular cholesterol were detected,and the effects of Hcy on intracellular lipid accumulation and ox-LDL uptake were evaluated by oil red O staining and Dil-oxLDL.RT-qPCR and Western blot were used to detect mRNA and pro-tein expression of key genes modified by N6-methyladenosine(m6 A).Results Hcy promoted M1 polarization of macrophages and ox-LDL-induced foam macrophages and promoted ox-LDL uptake as well as intracellular lipid accumulation.In addition,Hcy upregulated methyltransferase like 3(METTL3)expression,and the tendency of Hcy to promote macrophage M1 polarization and foaminess was markedly reduced after inhibition or knockdown of METTL3 expression.Conclusions Hcy significantly promotes macrophage M1 polarization and foaminess,an effectthat may be attenuated by METTL3 silencing.

Objective To investigate the mechanism by which Senegenin(SEN)alleviates microglial inflammatory response through the nuclear factor erythroid 2-related factor 2(Nrf2)/NOD-like receptor protein 3(NLRP3)pathway.Methods BV2 mouse microglia cells were randomly divided into control group,model group,SEN group and MCC950 group.Cells in control group were not treated,and cells in model group were added with 1 μg/ml lipopolysaccharide(LPS);Cells in SEN group were added with 1 μg/ml LPS+4 μmol/L SEN,and cells in MCC950 group were added with 1 μg/ml LPS+10 μmol/L MCC950 for 24 hours.CCK-8 method was used to detect the effect of different concentrations of SEN on the viability of BV2 cells.Griess method was used to determine the release amount of nitric oxide(NO)in the supernatant.Real-time fluorescent quantitative PCR was used to determine the mRNA expression levels of NLRP3,lymphocyte apoptosis-associated spect-like protein containing a CARD(ASC),caspase-1,interleukin(IL)-1β and IL-18 mRNA.Immunofluorescence staining was used to detect the expression levels of ASC,IL-1β,Nrf2 and heme oxygenase-1(HO-1).Western blotting was used to detect the expression levels of NLRP3,caspase-1,ASC,IL-1β,IL-18,Nrf2,HO-1,nuclear factor kappa B(NF-κB)and inducible nitric oxide synthase(iNOS).Results The results of CCK-8 method showed that there was no significant difference in the viability of BV2 cells treated with 2～20 μmol/L SEN compared with control group(P>0.05).Compared with control group,the viability of BV2 cells in model group decreased significantly(P<0.05).Compared with model group,the viability of BV2 cells in 4 μmol/L SEN group was significantly restored(P<0.05).Compared with control group,the results of Griess method showed that the release amount of NO in cells of model group increased significantly(P<0.05);the results of real-time PCR showed that the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 mRNA in cells of model group increased significantly(P<0.05);the results of Western blotting showed that the protein expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 proteins in cells of model group increased significantly(P<0.05),and the immunofluorescence staining results showed that the expression levels of iNOS and NF-κB protein in cells of model group increased,and the expression levels of Nrf2 and HO-1 decreased,with statistically significant differences(P<0.05).Compared with model group,the release amount of NO in cells of SEN group and MCC950 group decreased,and the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 mRNA and proteins decreased,with statistically significant differences(P<0.05);in the SEN group,the expression levels of iNOS and NF-κB decreased,and immunofluorescence staining showed that Nrf2 was translocated into the nucleus,and the expression levels of Nrf2 and HO-1 proteins increased significantly,with statistically significant differences(P<0.05).Conclusions SEN could alleviate the inflammatory response of mouse microglia cells induced by LPS and inhibit the activation and expression of NLRP3 inflammasome,with an effect comparable to that of the inflammasome inhibitor MCC950.The mechanism may be related to the regulation of the expression of upstream factors Nrf2 and HO-1.