ObjectiveTo investigate the possible mechanism of Jishe Qushi Capsule （脊蛇祛湿胶囊， JQC） in treating rheumatoid arthritis （RA） from the perspective of macrophage polarization mediated by neutrophil extracellular traps （NETs）. MethodsTwenty-four female SD rats were randomly divided into four groups， blank control group， model group， JQC group， and peptidylarginine deiminase 4 （PAD4） inhibitor group with 6 rats in each group. All groups but the blank control group were subjected to the induction of collagen-induced arthritis （CIA）. After successful model establishment， rats in the JQC group received intragastric administration of JQC 1.47 g/kg daily； rats in the PAD4 inhibitor group received intraperitoneal injections of the PAD4 inhibitor 4 mg/kg weekly. Rats in the blank， model， and PAD4 inhibitor groups received 2 ml of pure water daily by gavage. All treatments lasted 4 weeks. Joint lesions of each group were assessed on day 7， 14， 21， 28， and 35 after model establishment， and arthritis index （AI） scores were recorded. At 24 h after the final administration， histopathology of knee joints， including HE staining， safranin O-fast green staining， and TRAP staining， was performed. Flow cytometry was used to detect the counts of M1 and M2 macrophages in peripheral blood. ELISA was used to determine serum levels of TRACP， NETs， TNF-α， IL-1β， and iNOS. Western Blotting and qRT-PCR were used to measure MPO， NE， RANKL， OPG， and p65 protein and mRNA expression in knee cartilage tissue. ResultsCompared with the blank control group， the model group showed increased AI scores （P＜0.05）， marked synovial inflammatory infiltration， angiogenesis， and bone-cartilage destruction， increased TRAP-positive osteoclasts， increased M1 macrophages and decreased M2 macrophages， elevated serum TRACP， NETs， TNF-α， IL-1β， and iNOS （P＜0.05）， elevated MPO， NE， RANKL， and p65 protein/mRNA expression and decreased OPG protein/mRNA expression in knee cartilage tissue （P＜0.05）. Compared with the model group， the JQC group exhibited improved synovial inflammation， angiogenesis， and bone-cartilage damage， reduced AI scores on day 21， 28， and 35， decreased osteoclast counts， decreased M1 macrophages and increased M2 macrophages， reduced serum TRACP， NETs， TNF-α， IL-1β， and iNOS （P＜0.05）， decreased MPO， NE， RANKL， and p65 protein/mRNA expression and increased OPG expression （P＜0.05）. Compared with the PAD4 inhibitor group， the JQC group showed significantly lower AI scores， reduced M1 macrophages， increased M2 macrophages （P＜0.05）， reduced serum TRACP， TNF-α， IL-1β， and iNOS， decreased MPO， RANKL， and p65 expression， and increased OPG levels （P＜0.05）. ConclusionThe therapeutic mechanism of JQC for RA may involve inhibition of NETs formation， downregulation of the RANKL/NF-κB signaling pathway， and regulation of macrophage M1/M2 polarization imbalance， thereby suppressing osteoclastogenesis and inflammatory bone destruction.

Objective To explore the relationship between developmental endothelial locus-1(Del-1)and inflammatory response and disease severity in patients with chronic obstructive pulmonary disease(COPD).Method 82 COPD patients admitted to Huai'an Fifth People's Hospital from January 2023 to July 2023 were selected as the COPD group.Among them,40 patients with acute exacerbation were included in the acute exacerbation group,and 42 patients in the stable phase were included in the stable group.Another 40 healthy volunteers who underwent physical examinations during the same period were selected as the control group.The levels of serum Del-1,C-reactive protein(CRP),interleukin-1β(IL-1β)and neutrophil to lymphocyte ratio(NLR)in all study subjects were detected.Pearson's method was used to analyze the correlation between serum Del-1 and inflammatory markers.The predictive value of serum Del-1 for acute exacerbation in COPD patients was analyzed using receiver operating characteristic(ROC)curves.Result The serum CRP,IL-1β and NLR levels in the COPD group were higher than those in the control group(t=12.047,13.107,9.404),the serum Del-1 level in the COPD group was 386.87±42.34 pg/ml,lower than that in the control group 512.63±60.21 pg/ml(t=13.343),and the differences were statistically significant(all P<0.05).The serum CRP,IL-1β and NLR levels in the acute exacerbation group were higher than those in the stable group(t=4.170,5.292,5.919),the serum Del-1 level in the acute exacerbation group was 347.64±40.69 pg/ml,lower than that in the stable group 424.23±48.31 pg/ml(t=7.746),and the differences were statistically significant(all P<0.05).Pearson analysis showed that the serum Del-1 level in COPD patients were negatively correlated with serum CRP,IL-1β and NLR levels(r=-0.534,-0.587,-0.612,all P<0.05).ROC analysis showed that serum Del-1 had a high predictive value for acute exacerbation in COPD patients,with an AUC(95%CI)of 0.886(0.812～0.960).When the optimal cutoffvalue was 380.65 pg/ml,the sensitivity and specificity were 82.50%and 85.00%,respectively.Conclusion Serum Del-1 is low expression in COPD patients and is ngeatively correlated with their inflammatory response and disease severity,it is expected to become a new biomarker for predicting the risk of acute exacerbation of COPD.

Objective:To explore the therapeutic efficacy and prognostic factors of combined rituximab and intensive chemotherapy for sporadic adult Burkitt lymphoma (BL) .Methods:This retrospective study examined the clinical and survival data of 30 patients newly diagnosed with BL between July 2011 and February 2023 at the Blood Diseases Hospital. Kaplan-Meier method was used for survival analysis, and the log-rank test was used for univariate analysis of prognostic factors.Results:The median age of the 30 patients was 43 years (24 - 66 years), and the male to female ratio was 3: 2. Extranodal invasion was present in 80% of the patients, with involvement of the bone marrow in 53.3% and central nervous system in 10.0%. The Ann Arbor stage was Ⅲ and Ⅳ in 86.7%. According to the number of Burkitt Lymphoma International Prognostic Index (BL-IPI) risk factors, patients were classified as low risk (0) in 20.0%, intermediate risk (1) in 43.3%, and high risk (≥2) in 36.7%. All patients were treated with an induction regimen of rituximab combined with intensive chemotherapy, with objective and complete response rates of 80.0% and 76.7%, respectively. The median follow-up was 49 months (6-153 months), and the 5-year progression-free survival (PFS) and overall survival (OS) rates were both (76.7±7.7) %. All patients with limited stage ( n=4) achieved continuous complete remission (CCR). Patients who had high risk, advanced stage sensitive to induction therapy ( n=10) sequentially received first-line autologous hematopoietic stem cell transplantation (auto-HSCT) as consolidation therapy; 9 patients achieved CCR, whereas 1 patient with central nervous system invasion developed early disease progression and died. The BL-IPI low, intermediate, and high risk groups had respective 5-year PFS rates of (83.3±15.2) %, 100.0%, and (45.5±15.0) % ( P=0.0069) and OS rates of (83.3±15.2) %, 100.0%, and (45.5±15.0) % ( P=0.0075). The main adverse effects of induction therapy were myelosuppression and secondary infections, which were effectively managed by appropriate symptomatic treatment. Univariate analysis demonstrated that worse PFS was associated with BL-IPI score ≥2 ( HR=4.90, 95% CI 1.02-23.45, P=0.0329) ; extranodal invasion at ≥2 sites ( HR=12.62, 95% CI 2.59-61.62, P=0.0021) ; and failure to achieve first complete response (CR1) after induction therapy ( HR=31.86, 95% CI 4.19-242.20, P<0.0001) . Conclusions:Intensive immunochemotherapy regimens were effective and well-tolerated by adult patients with highly aggressive BL. Treatment efficacy was ideal in patients with limited-stage disease, whereas prognosis was unsatisfactory in patients with high-risk BL-IPI. Sequential first-line auto-HSCT consolidation therapy may further improve outcomes in patients with high-risk advanced-stage disease who are sensitive to induction therapy. BL-IPI score ≥2, extranodal invasion at ≥2 sites, and failure to achieve CR1 after induction therapy were adverse prognostic factors in adult patients with BL.

OBJECTIVE To investigate the therapeutic mechanisms of electroacupuncture at"Tianshu"(ST25)and"Sanyinjiao"(SP6)acupoints combined with metformin in the treatment of type 2 diabetes mellitus(T2DM)using serum non-targeted metabolomics.METHODS Male SD rats were randomly divided into blank group,model group,metformin group,electroacupunc-ture group,and acupuncture-medicine combination(electroacupuncture combined with metformin)group.A type 2 diabetes model was established by high-fat diet combined with intraperitoneal injection of streptozotocin.The metformin group was treated with 250 mg·kg-1 metformin by gavage,the electroacupuncture group was treated with bilateral Tianshu and Sanyinjiao,the acupuncture-medicine combination group was treated with metformin by gavage combined with electroacupuncture,and the blank group and model group were treated with normal saline by gavage.All rats were treated 6 times a week for 7 weeks.After the intervention,the blood glucose level in the tail vein of the rats was measured using a blood glucose meter in the fasting state.The blood glucose levels of the rats were measured at 30,60,120,and 240 min after intraperitoneal injection of 50%glucose solution(4 mL·kg-1)to evaluate glu-cose tolerance.The serum insulin level of the rats was detected by ELISA and the insulin resistance index was calculated.The blood biochemical parameters were measured by an automatic blood biochemical analyzer.HE staining was used to evaluate the pathological conditions of the liver and pancreatic tissues of the rats.Ultra-performance liquid chromatography-mass spectrometry(UPLC-MS)technology was used for mass spectrometry detection to identify differential metabolites,and MetaboAnalyst 5.0 was used for pathway enrichment analysis.RESULTS Compared with the blank group,the fasting blood glucose,area under the glucose tolerance curve,and insulin resistance index of the model group rats were significantly increased(P<0.001),blood TP and GLB were significantly de-creased(P<0.01),AST,ALT,and ALP were significantly increased(P<0.05,P<0.01,P<0.001),and obvious inflammatory cell infiltration and pathological damage were observed in the liver and pancreas tissues;compared with the model group,the fasting blood glucose,area under the glucose tolerance curve,and insulin resistance index of the acupuncture-medicine combination group were sig-nificantly decreased(P<0.05,P<0.01,P<0.001),blood ALP was significantly decreased(P<0.01),TP and GLB were significant-ly increased(P<0.05),and the pathological damage of the liver and pancreas was significantly improved.Serum metabolomics showed that the metabolic profiles of the groups were well distinguished.Compared with the blank group,the differential metabolites in the model group were enriched in histidine metabolism,thiamine metabolism,taurine and hypotaurine metabolism,ascorbic acid and alde-hyde ester metabolism,valine,leucine and isoleucine biosynthesis pathways;compared with the model group,237 metabolites such as 3-aminoadipic acid,3-oxocyclobutanecarboxylic acid and phosphorylcholine in the acupuncture-medicine combination group were sig-nificantly reduced,and the pathways were enriched in histidine metabolism,linoleic acid metabolism,thiamine metabolism,taurine and hypotaurine metabolism,valine,leucine and isoleucine biosynthesis pathways.CONCLUSION Electroacupuncture combined with metformin can effectively improve the glucose and lipid metabolism of T2DM rats,and its potential mechanism may be related to the regulation of amino acid metabolism.

Objective:To preliminarily evaluate the efficacy and safety of a domestically developed bilateral interventional ultrasound renal denervation (RDN) system in patients with uncontrolled hypertension despite antihypertensive medication.Methods:A multicenter, single-arm trial was conducted. Patients with uncontrolled hypertension (≥2 antihypertensive drugs) were enrolled from April 2023 to April 2024 at the Second Affiliated Hospital of Chongqing Medical University, West China Hospital of Sichuan University, and the Second Affiliated Hospital of Harbin Medical University. RDN was performed using the UltraCure? bilateral interventional ultrasound system via femoral or brachial artery access. Multi-segmental "quadrant-based" ablation was performed in bilateral main renal arteries and branches/accessory arteries (diameter≥4 mm). Primary endpoints were changes in office systolic blood pressure (SBP) and 24-hour daytime SBP at 2-and 6-months post-procedure. The primary safety endpoints included the incidence of major adverse events, device-related adverse events, and puncture site complications.Results:Ten patients, mean aged 47.1 years, including 9 male, successfully completed RDN. At 2 and 6 months post-procedure, office SBP decreased by (19.7±15.2) mmHg ( P=0.002, 1 mmHg=0.133 kPa) and (13.8±13.9) mmHg ( P=0.013) from baseline, while the 24-hour daytime SBP decreased by (13.4±10.6) mmHg ( P=0.004) and (11.2±9.2) mmHg ( P=0.004). Apart from one case of a limited distal renal artery dissection, no other serious device/procedure-related adverse events were observed. At 6-month follow-up, the estimated glomerular filtration rate remained stable ((85.3±18.3) ml·min -1·1.73 m -2 vs. (82.3±19.2) ml·min -1·1.73 m -2, P=0.41). No renal artery stenosis was detected. Conclusions:The domestic interventional ultrasound RDN system could effectively reduce office and ambulatory blood pressure in patients with uncontrolled hypertension, demonstrating a favorable safety profile. Long-term efficacy requires confirmation through large-scale randomized controlled trials.

Objective:To report the 5-year survival outcomes and recurrence patterns of robotic total gastrectomy (RTG) for locally advanced proximal gastric cancer in order to provide more valuable long-term follow-up results for clinical practice.Methods:This was a prospective, single-arm, open-label clinical trial (FUGES-014; Clinical-Trials.gov, NCT03524287). Patients with locally advanced proximal gastric cancer who underwent RTG at Fujian Medical University Union Hospital from March 5, 2018, to February 10, 2020, were included in the analysis. To evaluate the long-term efficacy of RTG in the most objective manner possible, we performed a propensity score-matched (1∶2) comparative analysis with historical control patients who had undergone laparoscopic total gastrectomy (LTG) from the FUGES-002 study (ClinicalTrials.gov, NCT02333721) in which the 5-year disease-free survival (DFS), 5-year overall survival (OS), and recurrence patterns were compared between the two groups.Results:Prior to matching, there were 48 cases in the RTG group and 263 cases in the LTG group; patients in the LTG group had more advanced cT and pT stages ( P=0.044 and 0.006, respectively) compared to the RTG group. After matching, there were 48 cases in the RTG group and 96 cases in the LTG group; however, no statistically significant differences were observed in the baseline clinical characteristics between the two groups (all P>0.05). Both groups had a median follow-up of 72 months. The 5-year DFS rates were 75.0% (95%CI: 63.7%- 88.3%) in the RTG group and 61.4% (95%CI: 52.5%-72.0%) in the LTG group ( P=0.116). Similarly, the 5-year OS rates were 79.2% (95%CI: 68.5%-91.5%) and 64.6% (95%CI: 55.7%-74.9%) in the RTG and LTG groups, respectively ( P=0.100). Within 5 years after surgery, tumor recurrence occurred in 10 patients (20.8%) in the RTG group and 33 patients (34.4%) in the LTG group ( P=0.124), and peritoneal recurrence was the predominant pattern in both groups (8.3%[4/48] vs. 10.4%[10/96]; risk difference: -0.02, P=0.554). Gastric cancer-related death was the predominant cause of death in both groups (16.7% [8/48] vs. 31.2% [30/96]; risk difference: -0.15, P=0.064). Among patients stratified by different pathological stages, no statistically significant differences were found in DFS, OS, or recurrence rates between the RTG and LTG groups (all P>0.05). Conclusions:We find the long-term oncological outcomes of RTG for locally advanced proximal gastric cancer to be noninferior to those of LTG. RTG should therefore be considered as a valid option for standardized minimally invasive surgery for locally advanced proximal gastric cancer.

OBJECTIVE To investigate the therapeutic mechanisms of electroacupuncture at"Tianshu"(ST25)and"Sanyinjiao"(SP6)acupoints combined with metformin in the treatment of type 2 diabetes mellitus(T2DM)using serum non-targeted metabolomics.METHODS Male SD rats were randomly divided into blank group,model group,metformin group,electroacupunc-ture group,and acupuncture-medicine combination(electroacupuncture combined with metformin)group.A type 2 diabetes model was established by high-fat diet combined with intraperitoneal injection of streptozotocin.The metformin group was treated with 250 mg·kg-1 metformin by gavage,the electroacupuncture group was treated with bilateral Tianshu and Sanyinjiao,the acupuncture-medicine combination group was treated with metformin by gavage combined with electroacupuncture,and the blank group and model group were treated with normal saline by gavage.All rats were treated 6 times a week for 7 weeks.After the intervention,the blood glucose level in the tail vein of the rats was measured using a blood glucose meter in the fasting state.The blood glucose levels of the rats were measured at 30,60,120,and 240 min after intraperitoneal injection of 50%glucose solution(4 mL·kg-1)to evaluate glu-cose tolerance.The serum insulin level of the rats was detected by ELISA and the insulin resistance index was calculated.The blood biochemical parameters were measured by an automatic blood biochemical analyzer.HE staining was used to evaluate the pathological conditions of the liver and pancreatic tissues of the rats.Ultra-performance liquid chromatography-mass spectrometry(UPLC-MS)technology was used for mass spectrometry detection to identify differential metabolites,and MetaboAnalyst 5.0 was used for pathway enrichment analysis.RESULTS Compared with the blank group,the fasting blood glucose,area under the glucose tolerance curve,and insulin resistance index of the model group rats were significantly increased(P<0.001),blood TP and GLB were significantly de-creased(P<0.01),AST,ALT,and ALP were significantly increased(P<0.05,P<0.01,P<0.001),and obvious inflammatory cell infiltration and pathological damage were observed in the liver and pancreas tissues;compared with the model group,the fasting blood glucose,area under the glucose tolerance curve,and insulin resistance index of the acupuncture-medicine combination group were sig-nificantly decreased(P<0.05,P<0.01,P<0.001),blood ALP was significantly decreased(P<0.01),TP and GLB were significant-ly increased(P<0.05),and the pathological damage of the liver and pancreas was significantly improved.Serum metabolomics showed that the metabolic profiles of the groups were well distinguished.Compared with the blank group,the differential metabolites in the model group were enriched in histidine metabolism,thiamine metabolism,taurine and hypotaurine metabolism,ascorbic acid and alde-hyde ester metabolism,valine,leucine and isoleucine biosynthesis pathways;compared with the model group,237 metabolites such as 3-aminoadipic acid,3-oxocyclobutanecarboxylic acid and phosphorylcholine in the acupuncture-medicine combination group were sig-nificantly reduced,and the pathways were enriched in histidine metabolism,linoleic acid metabolism,thiamine metabolism,taurine and hypotaurine metabolism,valine,leucine and isoleucine biosynthesis pathways.CONCLUSION Electroacupuncture combined with metformin can effectively improve the glucose and lipid metabolism of T2DM rats,and its potential mechanism may be related to the regulation of amino acid metabolism.

Objective To explore the relationship between developmental endothelial locus-1(Del-1)and inflammatory response and disease severity in patients with chronic obstructive pulmonary disease(COPD).Method 82 COPD patients admitted to Huai'an Fifth People's Hospital from January 2023 to July 2023 were selected as the COPD group.Among them,40 patients with acute exacerbation were included in the acute exacerbation group,and 42 patients in the stable phase were included in the stable group.Another 40 healthy volunteers who underwent physical examinations during the same period were selected as the control group.The levels of serum Del-1,C-reactive protein(CRP),interleukin-1β(IL-1β)and neutrophil to lymphocyte ratio(NLR)in all study subjects were detected.Pearson's method was used to analyze the correlation between serum Del-1 and inflammatory markers.The predictive value of serum Del-1 for acute exacerbation in COPD patients was analyzed using receiver operating characteristic(ROC)curves.Result The serum CRP,IL-1β and NLR levels in the COPD group were higher than those in the control group(t=12.047,13.107,9.404),the serum Del-1 level in the COPD group was 386.87±42.34 pg/ml,lower than that in the control group 512.63±60.21 pg/ml(t=13.343),and the differences were statistically significant(all P<0.05).The serum CRP,IL-1β and NLR levels in the acute exacerbation group were higher than those in the stable group(t=4.170,5.292,5.919),the serum Del-1 level in the acute exacerbation group was 347.64±40.69 pg/ml,lower than that in the stable group 424.23±48.31 pg/ml(t=7.746),and the differences were statistically significant(all P<0.05).Pearson analysis showed that the serum Del-1 level in COPD patients were negatively correlated with serum CRP,IL-1β and NLR levels(r=-0.534,-0.587,-0.612,all P<0.05).ROC analysis showed that serum Del-1 had a high predictive value for acute exacerbation in COPD patients,with an AUC(95%CI)of 0.886(0.812～0.960).When the optimal cutoffvalue was 380.65 pg/ml,the sensitivity and specificity were 82.50%and 85.00%,respectively.Conclusion Serum Del-1 is low expression in COPD patients and is ngeatively correlated with their inflammatory response and disease severity,it is expected to become a new biomarker for predicting the risk of acute exacerbation of COPD.

Objective:To report the 5-year survival outcomes and recurrence patterns of robotic total gastrectomy (RTG) for locally advanced proximal gastric cancer in order to provide more valuable long-term follow-up results for clinical practice.Methods:This was a prospective, single-arm, open-label clinical trial (FUGES-014; Clinical-Trials.gov, NCT03524287). Patients with locally advanced proximal gastric cancer who underwent RTG at Fujian Medical University Union Hospital from March 5, 2018, to February 10, 2020, were included in the analysis. To evaluate the long-term efficacy of RTG in the most objective manner possible, we performed a propensity score-matched (1∶2) comparative analysis with historical control patients who had undergone laparoscopic total gastrectomy (LTG) from the FUGES-002 study (ClinicalTrials.gov, NCT02333721) in which the 5-year disease-free survival (DFS), 5-year overall survival (OS), and recurrence patterns were compared between the two groups.Results:Prior to matching, there were 48 cases in the RTG group and 263 cases in the LTG group; patients in the LTG group had more advanced cT and pT stages ( P=0.044 and 0.006, respectively) compared to the RTG group. After matching, there were 48 cases in the RTG group and 96 cases in the LTG group; however, no statistically significant differences were observed in the baseline clinical characteristics between the two groups (all P>0.05). Both groups had a median follow-up of 72 months. The 5-year DFS rates were 75.0% (95%CI: 63.7%- 88.3%) in the RTG group and 61.4% (95%CI: 52.5%-72.0%) in the LTG group ( P=0.116). Similarly, the 5-year OS rates were 79.2% (95%CI: 68.5%-91.5%) and 64.6% (95%CI: 55.7%-74.9%) in the RTG and LTG groups, respectively ( P=0.100). Within 5 years after surgery, tumor recurrence occurred in 10 patients (20.8%) in the RTG group and 33 patients (34.4%) in the LTG group ( P=0.124), and peritoneal recurrence was the predominant pattern in both groups (8.3%[4/48] vs. 10.4%[10/96]; risk difference: -0.02, P=0.554). Gastric cancer-related death was the predominant cause of death in both groups (16.7% [8/48] vs. 31.2% [30/96]; risk difference: -0.15, P=0.064). Among patients stratified by different pathological stages, no statistically significant differences were found in DFS, OS, or recurrence rates between the RTG and LTG groups (all P>0.05). Conclusions:We find the long-term oncological outcomes of RTG for locally advanced proximal gastric cancer to be noninferior to those of LTG. RTG should therefore be considered as a valid option for standardized minimally invasive surgery for locally advanced proximal gastric cancer.