To explore the effects of different exercise prescriptions on glycemic metabolism in East Asian patients with type 2 diabetes mellitus (T2DM) and to compare the differences in the impact of population characteristics and exercise components on glycemic metabolism.

Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

Objective:To explore the prognostic influencing factors of patients with pulmonary large cell neuroendocrine carcinoma (LCNEC), to develop a nomogram-based predictive model for the overall survival (OS) of LCNEC patients and to make validation.Methods:The clinical data of 2 947 patients with LCNEC in the Surveillance, Epidemiology, and End Results (SEER) database (the modeling group) and 147 patients with LCNEC in Beijing Chest Hospital Affiliated to Capital Medical University from 2010 to 2023 (the validation group). The data of patients in the both groups were compared. Cox proportional hazards model was used to screen out the factors influencing the OS of patients with LCNEC. A nomogram model was constructed to predict the OS based on the multivariate analysis result. Internal validation of the predictive model's performance was conducted through 500 repeated samplings based on the Bootstrap method. The predictive performance of the nomogram model was evaluated by using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. The consistency index (CI) was used to analyze the discrimination of the nomogram model in predicting the survival of LCNEC patients; calibration curves were used to analyze the consistency between the survival predicted by the nomogram model and the actual survival outcomes; and the decision curve analysis (DCA) was used to assess the net benefit of the model for actual clinical decision-making.Results:The differences in the proportions of patients with different age, gender, race, tumor staging, N stage, M stage, hepatic metastasis or not, pulmonary metastasis or not, chemotherapy and radiotherapy or not between the modeling group and the validation group were statistically significant (all P < 0.05). The median OS time of LCNEC patients in the modeling group was 14.0 months, with the 1-year OS rate of 53.3% and the 5-year OS rate of 21.2%; the median OS time of LCNEC patients in the validation group was 17.5 months, with the 1-year OS rate of 58.7%; there was no statistically significant difference in OS between the 2 groups ( P = 0.280). In the modeling group, the median OS time of female and male LCNEC patients was 18.0 and 12.0 months, respectively, and the difference in OS between the 2 groups was statistically significant ( P < 0.05); for patients with stage Ⅰ-Ⅱ, Ⅲ, and Ⅳ LCNEC, the median OS time was 48.0, 16.0, and 6.0 months, respectively, and the difference in OS among the 3 groups was statistically significant ( P < 0.05); the median OS time of patients receiving surgery and not receiving surgery was 28.0 and 8.0 months, respectively, and the difference in OS between the 2 groups was statistically significant ( P < 0.05). The differences in OS among female and male, patients in stages Ⅰ-Ⅱ, Ⅲ and Ⅳ, patients who underwent surgery or not were statistically significant (all P < 0.05). The results of multivariate Cox regression analysis in the modeling group showed that patients aged >60 years old (>60 years old vs. ≤60 years old: HR = 1.234, 95% CI: 1.114-1.367, P < 0.01), M 1 stage (M 1 stage vs. M 0 stage, HR = 2.646,95% CI: 2.385-2.935, P < 0.001), T 2-4 stage (T 2-4 stage vs. T 1 stage: HR = 1.199, 95% CI: 1.147-1.252, P < 0.001), N 1-3 stage (N 1-3 stage vs. N 0 stage: HR = 1.281, 95% CI: 1.225-1.340, P < 0.001) were independent risk factors of the OS in patients with LCNEC; female (female vs. male: HR = 0.877, 95% CI: 0.805-0.956, P = 0.003), surgery (yes vs. no: HR = 0.612, 95% CI: 0.554-0.676, P < 0.001), chemotherapy (yes vs. no: HR = 0.520, 95% CI: 0.470-0.575, P < 0.001) were independent protective factors of the OS in patients with LCNEC. A nomogram model for predicting 1, 3, and 5-year OS rates of LCNEC patients was constructed based on age, gender, T stage, N stage, M stage, surgery and chemotherapy. The result of ROC curve analysis indicated that the AUC of the nomogram model for predicting 1, 3, and 5-year OS rates in the modeling group was 0.822, 0.821 and 0.821, respectively, while the AUC of 1-year OS rate predicted by the validation group was 0.660. The CI of the modeling group and the validation group was 0.756 and 0.660, respectively. The calibration curve showed that 1, 3, and 5-year OS rates predicted by the modeling group were highly consistent with the actual OS rates. The DCA showed that the nomogram model for predicting OS in the modeling group and the validation group both had good clinical net benefits. Conclusions:The constructed nomogram model for predicting the prognosis of LCNEC patients is proved to be reliable and has good clinical values.

Objective To study the efficacy and safety of flexible ureteroscopy holmium laser lithotripsy(FURS)in the treatment of urinary tract stones of different sizes and positions.Methods A retrospective analysis was conducted on the clinical data of 121 patients with upper urinary tract stones from January 2021 to December 2023.According to the size of the stones,they were divided into the diameter ≤20 mm group(n=98)and the 20 mm＜diameter ≤40 mm group(n=23).According to the location of the stones,19 cases were divided into the renal pelvis stone group and 102 cases were non renal pelvis stones.The surgical related indicators and incidence of complications were compared between the groups.Result The operation time of the group with diameter ≤20 mm and the group with diameter 20 mm＜diameter ≤40 mm was(44.13±12.6)minutes and(57.52±20.98)minutes,respectively.The hospitalization periods were(4.55±1.54)days and(5.74±2.00)days,respectively.There were statistically significant differences between the two groups(P＜0.05).The stone clearance rates in the group with diameter ≤ 20 mum and the group with 20 mum＜diameter ≤ 40 mum were 84.69％and 78.26％,respectively.There was no statistically significant difference between the two groups(P＞0.05).The operation time of the subcalyx kidney stone group and the non-subcalyx kidney stone group was(44.05±11.08)minutes and(47.17±16.19)minutes respectively,the hospital stay was(4.74±1.52)days and(4.78±1.73)days respectively,and the ESWL selection rates after the operation were 5.26％and 10.78％respectively.The stone recurrence rates were 15.79％and 4.90％respectively,and there was no statistically significant difference between the two groups(P＞0.05).The stone clearance rates in the subcalyx kidney stone group and the non-subcalyx kidney stone group were 63.16％and 87.25％,respectively.There was a statistically significant difference between the two groups(P＜0.05).There was no statistically significant difference in the incidences of urosepsis,fever,low back pain,hematuria and total complications between the 20 mm＜diameter ≤40 mm group and the diameter ≤20 mm group(P＞0.05).There was no statistically significant difference in the incidences of urosepsis,fever,low back pain,hematuria and total complications between the non-inferior calyx stone group and the inferior calyx stone group(P＞0.05).Conclusion FURS treatment for upper urinary tract stones with a diameter of≤20 mm has shorter surgical and hospitalization times compared to patients with a diameter of≤40 mm.ESWL and lower stone recurrence rates are also preferred after surgery.FURS treatment for non lower renal calyx stones has a higher stone clearance rate compared to lower renal calyx stones.The safety of FURS treatment for upper urinary tract stones of different sizes and positions is equivalent.

To perform the phylogenetic characterization of an isolated porcine rotavirus(PoRV)and investigate its pathogenicity in suckling mice and piglets.A G4P[23]genotype PoRV strain JSJR2023 was successfully isolated from the diarrheic piglet feces through propagation in MA104 cells.The viral proliferation kinetics were analyzed using TCID50 assays,followed by complete genome sequencing through Sanger sequencing platforms.Comprehensive genotyping and phylogenetic reconstruction were conducted using MEGA7.0 with maximum likelihood algorithms.Pathogenicity was assessed in the following animal models:5-day-old C57BL/6 mice and 3-day-old piglets.Multidimensional evaluation included clinical monitoring(diarrhea scoring,growth parameters),virological detection,and histopathological analysis of intestinal tissues.The virus strain JSJR2023 could replicate efficiently in MA104 cells,achieving peak titers of 107.5 TCID50/mL.Whole genome genotype analysis showed that the strain belonged to G4-P[23]-I5-R1-C1-M1-A8-N1-T1-E1-H1.Phylogenetic analysis indicated that the VP3 and NSP4 genes of JSJR2023 strain were most closedrelated to human species rotaviruses,suggesting genetic reassortment between human and porcine RV strains.The animal experiments in suckling mice showed that the JSJR2023 strain infection caused diarrhea symptoms,intestinal edema and congestion,and shedding of intestinal villus epithelial cells.The pathogenicity experiments in piglets showed that compared with the control group,the challenged group of pig-lets had severe diarrhea symptoms,accompanied by reduced appetite and listlessness.Post-mortem examination revealed that the intes-tines were significantly thinner,congested,and filled with yellow watery contents.The challenged piglets showed typical pathological changes such as thinning of the intestinal wall and shortening and shedding of intestinal villi.In conclusion,this study successfully iso-lated a human-porcine recombinant G4P[23]PoRV strain and established the infection models in suckling mice and piglets,providing important tools for investigating the pathogenic mechanism of PoRV,evaluating vaccines and developing antiviral drug.

AIM:This study aims to investigate the mechanisms underlying skeletal muscle mitochondrial damage associated with decline in exercise function during high-altitude de-adaptation,using a mouse model.METHODS:Twen-ty-four healthy male C57BL/6J mice were randomly assigned to two groups:a high-altitude de-adaptation group and a plain control group.The model group was exposed to a low-pressure,low-oxygen chamber simulating an altitude of 7 000 meters for two weeks,followed by eight days of rearing in a plain environment.The control group was maintained in a plain envi-ronment for the same duration.Grip strength and pole-climbing tests were conducted on the 1st,3rd,and 5th days post-re-turn to assess muscle strength and motor coordination.Treadmill exercises were performed on the 4th and 8th days to eval-uate exercise endurance.After the treadmill exercise on the 8th day,serum,liver,and skeletal muscle tissues were col-lected.Levels of lactic acid(LA),glucose(GLU),creatine kinase(CK),lactate dehydrogenase(LDH),alanine trans-aminase(ALT),and aspartate aminotransferase(AST)in serum,as well as glycogen levels in the liver and muscle,were analyzed.Additionally,the expression of proteins related to mitochondrial biogenesis,fission,fusion,and oxidative phos-phorylation in muscle tissues was assessed using Western blot.RESULTS:(1)The model group exhibited significant re-ductions in grip strength,increased pole-climbing T-turn and total times,and decreased total time and distance in the ex-haustion running test.(2)Serum levels of LA,CK,LDH,ALT,and AST were elevated,while GLU levels decreased,and glycogen levels in both the liver and muscle were reduced in the model group following the treadmill exercise.(3)Ab-normal indicators in the model group did not return to normal by the end of the de-adaptation period.(4)Western blot analysis revealed decreased expression of mitochondrial oxidative phosphorylation proteins(ATP6V1A and Mt-CO2)and mitochondrial biogenesis proteins(PGC-1α and FGF21),increased levels of mitochondrial fusion proteins(OPA1 and MFN1),and no significant changes in fission protein expression(FIS1 and DRP1)in muscle tissue from the model group.CONCLUSION:Exercise capacity in mice during the high-altitude de-adaptation period significantly declined,particu-larly in terms of muscle strength,motor coordination,and endurance.This decline is closely associated with abnormal pro-tein expression related to skeletal muscle mitochondrial energy metabolism and production.

AIM:This study aims to investigate the mechanisms underlying skeletal muscle mitochondrial damage associated with decline in exercise function during high-altitude de-adaptation,using a mouse model.METHODS:Twen-ty-four healthy male C57BL/6J mice were randomly assigned to two groups:a high-altitude de-adaptation group and a plain control group.The model group was exposed to a low-pressure,low-oxygen chamber simulating an altitude of 7 000 meters for two weeks,followed by eight days of rearing in a plain environment.The control group was maintained in a plain envi-ronment for the same duration.Grip strength and pole-climbing tests were conducted on the 1st,3rd,and 5th days post-re-turn to assess muscle strength and motor coordination.Treadmill exercises were performed on the 4th and 8th days to eval-uate exercise endurance.After the treadmill exercise on the 8th day,serum,liver,and skeletal muscle tissues were col-lected.Levels of lactic acid(LA),glucose(GLU),creatine kinase(CK),lactate dehydrogenase(LDH),alanine trans-aminase(ALT),and aspartate aminotransferase(AST)in serum,as well as glycogen levels in the liver and muscle,were analyzed.Additionally,the expression of proteins related to mitochondrial biogenesis,fission,fusion,and oxidative phos-phorylation in muscle tissues was assessed using Western blot.RESULTS:(1)The model group exhibited significant re-ductions in grip strength,increased pole-climbing T-turn and total times,and decreased total time and distance in the ex-haustion running test.(2)Serum levels of LA,CK,LDH,ALT,and AST were elevated,while GLU levels decreased,and glycogen levels in both the liver and muscle were reduced in the model group following the treadmill exercise.(3)Ab-normal indicators in the model group did not return to normal by the end of the de-adaptation period.(4)Western blot analysis revealed decreased expression of mitochondrial oxidative phosphorylation proteins(ATP6V1A and Mt-CO2)and mitochondrial biogenesis proteins(PGC-1α and FGF21),increased levels of mitochondrial fusion proteins(OPA1 and MFN1),and no significant changes in fission protein expression(FIS1 and DRP1)in muscle tissue from the model group.CONCLUSION:Exercise capacity in mice during the high-altitude de-adaptation period significantly declined,particu-larly in terms of muscle strength,motor coordination,and endurance.This decline is closely associated with abnormal pro-tein expression related to skeletal muscle mitochondrial energy metabolism and production.

To perform the phylogenetic characterization of an isolated porcine rotavirus(PoRV)and investigate its pathogenicity in suckling mice and piglets.A G4P[23]genotype PoRV strain JSJR2023 was successfully isolated from the diarrheic piglet feces through propagation in MA104 cells.The viral proliferation kinetics were analyzed using TCID50 assays,followed by complete genome sequencing through Sanger sequencing platforms.Comprehensive genotyping and phylogenetic reconstruction were conducted using MEGA7.0 with maximum likelihood algorithms.Pathogenicity was assessed in the following animal models:5-day-old C57BL/6 mice and 3-day-old piglets.Multidimensional evaluation included clinical monitoring(diarrhea scoring,growth parameters),virological detection,and histopathological analysis of intestinal tissues.The virus strain JSJR2023 could replicate efficiently in MA104 cells,achieving peak titers of 107.5 TCID50/mL.Whole genome genotype analysis showed that the strain belonged to G4-P[23]-I5-R1-C1-M1-A8-N1-T1-E1-H1.Phylogenetic analysis indicated that the VP3 and NSP4 genes of JSJR2023 strain were most closedrelated to human species rotaviruses,suggesting genetic reassortment between human and porcine RV strains.The animal experiments in suckling mice showed that the JSJR2023 strain infection caused diarrhea symptoms,intestinal edema and congestion,and shedding of intestinal villus epithelial cells.The pathogenicity experiments in piglets showed that compared with the control group,the challenged group of pig-lets had severe diarrhea symptoms,accompanied by reduced appetite and listlessness.Post-mortem examination revealed that the intes-tines were significantly thinner,congested,and filled with yellow watery contents.The challenged piglets showed typical pathological changes such as thinning of the intestinal wall and shortening and shedding of intestinal villi.In conclusion,this study successfully iso-lated a human-porcine recombinant G4P[23]PoRV strain and established the infection models in suckling mice and piglets,providing important tools for investigating the pathogenic mechanism of PoRV,evaluating vaccines and developing antiviral drug.

Objective To study the efficacy and safety of flexible ureteroscopy holmium laser lithotripsy(FURS)in the treatment of urinary tract stones of different sizes and positions.Methods A retrospective analysis was conducted on the clinical data of 121 patients with upper urinary tract stones from January 2021 to December 2023.According to the size of the stones,they were divided into the diameter ≤20 mm group(n=98)and the 20 mm＜diameter ≤40 mm group(n=23).According to the location of the stones,19 cases were divided into the renal pelvis stone group and 102 cases were non renal pelvis stones.The surgical related indicators and incidence of complications were compared between the groups.Result The operation time of the group with diameter ≤20 mm and the group with diameter 20 mm＜diameter ≤40 mm was(44.13±12.6)minutes and(57.52±20.98)minutes,respectively.The hospitalization periods were(4.55±1.54)days and(5.74±2.00)days,respectively.There were statistically significant differences between the two groups(P＜0.05).The stone clearance rates in the group with diameter ≤ 20 mum and the group with 20 mum＜diameter ≤ 40 mum were 84.69％and 78.26％,respectively.There was no statistically significant difference between the two groups(P＞0.05).The operation time of the subcalyx kidney stone group and the non-subcalyx kidney stone group was(44.05±11.08)minutes and(47.17±16.19)minutes respectively,the hospital stay was(4.74±1.52)days and(4.78±1.73)days respectively,and the ESWL selection rates after the operation were 5.26％and 10.78％respectively.The stone recurrence rates were 15.79％and 4.90％respectively,and there was no statistically significant difference between the two groups(P＞0.05).The stone clearance rates in the subcalyx kidney stone group and the non-subcalyx kidney stone group were 63.16％and 87.25％,respectively.There was a statistically significant difference between the two groups(P＜0.05).There was no statistically significant difference in the incidences of urosepsis,fever,low back pain,hematuria and total complications between the 20 mm＜diameter ≤40 mm group and the diameter ≤20 mm group(P＞0.05).There was no statistically significant difference in the incidences of urosepsis,fever,low back pain,hematuria and total complications between the non-inferior calyx stone group and the inferior calyx stone group(P＞0.05).Conclusion FURS treatment for upper urinary tract stones with a diameter of≤20 mm has shorter surgical and hospitalization times compared to patients with a diameter of≤40 mm.ESWL and lower stone recurrence rates are also preferred after surgery.FURS treatment for non lower renal calyx stones has a higher stone clearance rate compared to lower renal calyx stones.The safety of FURS treatment for upper urinary tract stones of different sizes and positions is equivalent.

Objective:To explore the prognostic influencing factors of patients with pulmonary large cell neuroendocrine carcinoma (LCNEC), to develop a nomogram-based predictive model for the overall survival (OS) of LCNEC patients and to make validation.Methods:The clinical data of 2 947 patients with LCNEC in the Surveillance, Epidemiology, and End Results (SEER) database (the modeling group) and 147 patients with LCNEC in Beijing Chest Hospital Affiliated to Capital Medical University from 2010 to 2023 (the validation group). The data of patients in the both groups were compared. Cox proportional hazards model was used to screen out the factors influencing the OS of patients with LCNEC. A nomogram model was constructed to predict the OS based on the multivariate analysis result. Internal validation of the predictive model's performance was conducted through 500 repeated samplings based on the Bootstrap method. The predictive performance of the nomogram model was evaluated by using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. The consistency index (CI) was used to analyze the discrimination of the nomogram model in predicting the survival of LCNEC patients; calibration curves were used to analyze the consistency between the survival predicted by the nomogram model and the actual survival outcomes; and the decision curve analysis (DCA) was used to assess the net benefit of the model for actual clinical decision-making.Results:The differences in the proportions of patients with different age, gender, race, tumor staging, N stage, M stage, hepatic metastasis or not, pulmonary metastasis or not, chemotherapy and radiotherapy or not between the modeling group and the validation group were statistically significant (all P < 0.05). The median OS time of LCNEC patients in the modeling group was 14.0 months, with the 1-year OS rate of 53.3% and the 5-year OS rate of 21.2%; the median OS time of LCNEC patients in the validation group was 17.5 months, with the 1-year OS rate of 58.7%; there was no statistically significant difference in OS between the 2 groups ( P = 0.280). In the modeling group, the median OS time of female and male LCNEC patients was 18.0 and 12.0 months, respectively, and the difference in OS between the 2 groups was statistically significant ( P < 0.05); for patients with stage Ⅰ-Ⅱ, Ⅲ, and Ⅳ LCNEC, the median OS time was 48.0, 16.0, and 6.0 months, respectively, and the difference in OS among the 3 groups was statistically significant ( P < 0.05); the median OS time of patients receiving surgery and not receiving surgery was 28.0 and 8.0 months, respectively, and the difference in OS between the 2 groups was statistically significant ( P < 0.05). The differences in OS among female and male, patients in stages Ⅰ-Ⅱ, Ⅲ and Ⅳ, patients who underwent surgery or not were statistically significant (all P < 0.05). The results of multivariate Cox regression analysis in the modeling group showed that patients aged >60 years old (>60 years old vs. ≤60 years old: HR = 1.234, 95% CI: 1.114-1.367, P < 0.01), M 1 stage (M 1 stage vs. M 0 stage, HR = 2.646,95% CI: 2.385-2.935, P < 0.001), T 2-4 stage (T 2-4 stage vs. T 1 stage: HR = 1.199, 95% CI: 1.147-1.252, P < 0.001), N 1-3 stage (N 1-3 stage vs. N 0 stage: HR = 1.281, 95% CI: 1.225-1.340, P < 0.001) were independent risk factors of the OS in patients with LCNEC; female (female vs. male: HR = 0.877, 95% CI: 0.805-0.956, P = 0.003), surgery (yes vs. no: HR = 0.612, 95% CI: 0.554-0.676, P < 0.001), chemotherapy (yes vs. no: HR = 0.520, 95% CI: 0.470-0.575, P < 0.001) were independent protective factors of the OS in patients with LCNEC. A nomogram model for predicting 1, 3, and 5-year OS rates of LCNEC patients was constructed based on age, gender, T stage, N stage, M stage, surgery and chemotherapy. The result of ROC curve analysis indicated that the AUC of the nomogram model for predicting 1, 3, and 5-year OS rates in the modeling group was 0.822, 0.821 and 0.821, respectively, while the AUC of 1-year OS rate predicted by the validation group was 0.660. The CI of the modeling group and the validation group was 0.756 and 0.660, respectively. The calibration curve showed that 1, 3, and 5-year OS rates predicted by the modeling group were highly consistent with the actual OS rates. The DCA showed that the nomogram model for predicting OS in the modeling group and the validation group both had good clinical net benefits. Conclusions:The constructed nomogram model for predicting the prognosis of LCNEC patients is proved to be reliable and has good clinical values.