Necroptosis, a form of programmed cell death, initiates a series of biological responses and further culminates in necroinflammatory processes, consequently limiting the efficacy of cytokine antagonists in treating inflammatory diseases. To address this issue, DNAzyme R3-Dz specifically targeting receptor-interacting protein kinase 3 (RIP3) mRNA, a necrosome component, has been successfully developed and studied to elucidate the mechanism in cleaving its target mRNA. Then a polyamidoamine (PAMAM) derivative was constructed through the modification of nucleobase analog (termed AP) to achieve the R3-Dz delivery to macrophages. The AP/R3-Dz nanoparticles effectively downregulated the RIP3 expression, leading to subsequent decrease in the levels of reactive oxygen species (ROS) and damage-associated molecular patterns (DAMPs), ultimately inhibiting the necroinflammatory processes mediated by the NOD-like receptor family pyrin domain-containing 3 (NLRP3). Finally, AP/R3-Dz nanoparticles and their combination with the NLRP3 inhibitor MCC950 suppressed the necrotic phenotype and ameliorated the disease progression in diverse models, including gouty arthritis, autoimmune hepatitis and rheumatoid arthritis. In summary, the AP/R3-Dz nanoparticles in combination with MCC950 have been demonstrated to achieve the intervention in necroptosis and inflammation by dual disruption of the intricate feedback loop of necroinflammation and thus have promising potential in the treatment of inflammatory diseases.

Objective:To explore the effect of exercise on glycemic control and physical indicators among community-dwelling persons with type 2 diabetes mellitus (T2DM).Methods:A total of 42 T2DM patients undergoing regular follow-up at a community health center were divided into a control group and an exercise group. To minimize confounding factors, 1∶1 propensity score matching was performed, resulting in 21 patients in each group. Both groups received standardized diabetes management, including medication, dietary guidance and diabetes health education. The exercise group additionally performed exercises which integrated sports and medical care models. The experiment lasted 8 weeks. Before and after the intervention, glycosylated hemoglobin A1c (HbA1c) levels, body weight, body mass index (BMI), fat mass, visceral fat area (VFA), fat mass index (FMI) and appendicular skeletal muscle mass index (ASMI) were recorded and compared between the two groups. Moreover, the actual exercise compliance of the exercise group was observed, along with any adverse events such as hypoglycemia or exercise-related injuries, as well as changes in antidiabetic medication dosage.Results:After the intervention, significant improvement was observed in both groups in all of the measurements, but with the average HbA1c, BMI, fat mass, VFA and FMI values of the exercise group then significantly better than the control group′s averages. The average compliance rate in the exercise group was 60%. No cases of hypoglycemia or exercise-related injuries were reported during the intervention, and there were no changes in the use of anti-diabetes medications.Conclusions:Exercise effectively improves glycemic control and physical indicators among community-dwelling T2DM patients. However, exercise compliance needs improving.

Insufficient future liver remnant volume remains a critical limitation for single-stage resection in patients with hepatic malignancies. The techniques for promoting future liver remnant hypertrophy to realize two-stage hepatectomy include portal vein embolization， associating liver partition and portal vein ligation for staged hepatectomy， and portal vein ligation. In recent years， the application of auxiliary liver transplantation has further facilitated two-stage total hepatectomy. This article systematically reviews the clinical applications of these techniques and analyzes their advantages and limitations， so as to provide a reference for optimizing clinical decision-making.

Objective To conduct the reductive reservation for torsional ovary in different states(.un-necrotic ovary,suspected necrotic torsional ovary and torsional necrotic ovary)after the ovarian torsion in pre-maturity SD rat,and to investigate its effect on the ovarian reproductive function in maturity stage.Methods A total of 32 SD rats with 3 weeks old were selected and randomly divided into 4 groups,8 cases in each group.The animal model of ovarian torsion was made by using the Turner method,which was similar to the animal model of testicular torsion,and either group was selected to undergo the sham operation as the con-trol group(CG group).The non-necrotic torsional ovary detorsion group(NNTOD group),suspected necrotic torsional ovary detorsion group(SNTOD group)and necrotic torsional ovary detorsion group(NTOD group)were established respectively.When the animals were fed to sexual maturity at 8 weeks of age,the experimen-tal animals were sacrificed by vertebral dislocation method,and the ovary tissues on the torsional side were cut for HE staining and transmission electron microscopy to examine the changes of ovarian histomorphology and mitochondrial structure.Ovarian cell apoptosis was detected by Tunel assay.ELISA method was used to de-tect the follicle-stimulating hormone(FSH),luteinizing hormone(LH)and anti-mullerian duct hormone(AMH)levels in centrifugal blood.Results The ovarian structure in the CG group and NNTOD group was clear,the ovarian follicles at different levels were developed well;the electron microscopy showed normal mi-tochondria.The ovarian partial structure in the SNTOD group was disorganized,the number of follicles at all levels of growth was decreased;electron microscopic examination showed a little damage of mitochondria.In the NTOD group,the arrangement of ovarian structure was obviously disordered,the number of growing folli-cles at all levels was significantly reduced;the electron microscopy showed that most of the mitochondria were obviously swollen and severely damaged.Compared with the CG group,the apoptosis rate in the SNTOD group and NTOD group was significantly increased(P＜0.05).There was no statistically significant differ-ence between CG group and NNTOD group(P＞0.05).Compared with the NTOD group,the apoptosis rate in the SNTOD group was decreased(P＜0.05).Compared with the CG group,the levels of LH and FSH in the SNTOD and NTOD groups were increased,and the AMH level was decreased(P＜0.05).The LH and FSH levels in the SNTOD group were lower than those in the NTOD group,the AMH level was higher than that in the NTOD group(P＜0.05).Conclusion After reduction of the torsional suspected necrotic ovary in the prematurity rat,the ovarian reproductive function in the torsional side during sexual maturity period is slightly injured;while after reduction of torsional necrotic ovary restoration,its reproductive function is appar-ently damaged.

Objective To investigate the clinical efficacy of the combined therapy of promoting blood circulation and removing blood stasis and anisodamine hydrobromide in the treatment of sepsis-induced coagulopathy(SIC).Methods A total of 102 SIC patients treated in our hospital from Sep-tember 2021 to September 2024 were selected as study subjects.They were divided into control group(n=51)and experimental group(n=51)according to different treatment methods.The control group received conventional treatment,while the experimental group received an additional combined therapy of promoting blood circulation and removing blood stasis and anisodamine hydrobromide on the basis of the control group.Coagulation function and thrombotic risk were assessed in both groups before treatment and at 24,48,and 72 h after treatment.Clinical efficacy and treatment safety were com-pared,and lactate clearance rate was measured before treatment and at 2,6,and 24 h after treat-ment.Results After treatment,the levels of thrombin time(TT),prothrombin time(PT),acti-vated partial thromboplastin time(APTT),and D-dimer(D-D)decreased,while the platelet(PLT)count and fibrinogen(FIB)levels increased compared with treatment before,with all differ-ences being statistically significant(P＜0.05).At 24 hours post-treatment,the TT,PT,and D-D levels in the experimental group were lower than those in the control group(P＜0.05),whereas no significant differences were observed in the remaining indicators(P＞0.05).At 48 hours post-treat-ment,the TT,PT,APTT,and D-D levels in the experimental group were lower than those in the control group,while the PLT level was higher(P＜0.05).At 72 hours post-treatment,the TT,PT,and APTT levels in the experimental group were lower than those in the control group,whereas the PLT and FIB levels were higher(P＜0.05).The levels of the four new thrombotic indicators,namely thrombomodulin(TM),thrombin-antithrombin complex(TAT),plasmin-α2-antiplasmin complex(PIC),and tissue plasminogen activator-plasminogen activator inhibitor complex(t-PAIC),decreased with prolonged treatment duration in both groups,with differences in different time points being statistically significant(P＜0.05).At 24 hours post-treatment,the TM and TAT levels in the experimental group were lower than those in the control group,with both differences being statistical-ly significant(P＜0.05).At 48 hours post-treatment,the TM,PIC,and t-PAIC levels in the ex-perimental group were lower than those in the control group(P＜0.05).At 72 hours post-treat-ment,the levels of four indicators thrombosis in the experimental group were lower than those in the control group,but only the differences in TM and PIC levels were statistically significant(P＜0.05).The thromboelastography indicators,including R value,K value,and maximum amplitude(MA)decreased,while α angle increased with prolonged treatment duration in both groups(P＜0.05).At 24 and 48 hours post-treatment,the R value in the experimental group was lower than that in the control group,with both differences being statistically significant(P＜0.05).At 72 hours post-treatment,the R value,and MA in the experimental group were lower than those in the control group(P＜0.05).The Sequential Organ Failure Assessment(SOFA)score,SIC score,and Acute Physiology and Chronic Health Evaluation Ⅱ score decreased post-treatment in both groups compared with pretreatment levels,and were lower in the experimental group than in the con-trol group(P＜0.05).The lactate clearance rate increased with prolonged treatment duration in both groups(P＜0.05).At 2,6,and 24 hours post-treatment,the lactate clearance rate in the ex-perimental group was higher than that in the control group(P＜0.05).The 28-day survival rate was 100.00％in the experimental group,which was higher than 92.16％in the control group(P＜0.05).Conclusion The combined therapy of promoting blood circulation and removing blood sta-sis and anisodamine hydrobromide has good clinical efficacy in the treatment of SIC.It can improve patients' coagulation function,reduce thrombotic risk,and has high treatment safety.

Objective:To describe the epidemiological characteristics and changes of febrile seizure(FS)among children under 6 years old in Ningbo City,Zhejiang Province from 2015 to 2021.Methods:Based on the Ningbo Regional Health Information Platform,a dynamic cohort was established using vacci-nation registration information,and the cases of FS were identified by the diagnostic results of Chinese terms or International Classification of Diseases 10th revision(ICD-10)R56.0 code in the electronic medical records.The first visit of FS during the observation period was defined as a new case,and a re-currence case was defined as the case with a visit interval of more than 7 days.The 95％confidence in-terval(CI)of FS incidence density was calculated by the Poisson distribution.Results:From January 2015 to June 2020,there were 1.3 million children under 6 years old in Ningbo,with male accounting for 52.87％.The median follow-up time was 2.83(1.55-4.00)years.During the follow-up period,12 776 new onset cases had FS,with more males than females,with an overall incidence density of 4.34(95％CI:4.27-4.40)/1 000 person-years and a recurrence rate of 21.63％.There was a higher inci-dence density in children who were male,born in Ningbo and of non-mobility.The incidence density of FS was higher in urban areas than in rural and rural-urban fringe areas,and the incidence density was different among districts and counties.The peak density was found in children aged 18-23 months[8.42(95％CI:8.11-8.74)/1 000 person-years].From 2015 to 2019,the incidence density in-creased with calendar year(Ptrend＜0.001),and the highest was 5.62(95％CI:5.43-5.81)/1 000 person-years.The incidence density of FS decreased significantly during the period between 2020 and 2021.The incidence density was higher in winter.Conclusion:From 2015 to 2019,the overall inci-dence density of FS in children under 6 years old in Ningbo City presented an increasing trend.More at-tention should be paid to the health education,the improvement of the health maintenance model,the en-hancement of the cognition of FS,the identification and treatment of FS among high-risk population and regions so as to prevent its recurrence and reduce the disease burden during the corona virus disease 2019(COVID-19)epide-mic.

Objective To investigate the expressions of cyclin B2(CCNB2)and cyclin E1(Cyclin E1)in hepatocellular carcinoma(HCC)and their significance for the prognosis of HCC.Methods Sixty HCC patients were admitted and treated from October 2013 to October 2016.The expressions of CCNB2 and Cyclin E1 in 60 HCC tissues and adjacent normal tissues were detected by immunohistochemistry,and the relationship between the two and the clinicopathological characteristics of HCC patients was analyzed;Spearman method was performed to analyze the correlation of CCNB2 and Cyclin E1 expression;Kaplan-Meier was performed to analyze the relationship between CCNB2,Cyclin E1 expression and clinical prognosis;and univariate and multivariate Cox regression were performed to analyze the influencing factors of clinical prognosis of HCC patients.Results The positive expression rates of CCNB2 and Cyclin E1 in HCC(61.67％,56.67％)were significantly higher than those in adjacent normal tissues(20.00％,13.33％,P＜0.05);the positive expressions of CCNB2 and Cyclin E1 were positively correlated with serum AFP level,liver cirrhosis status,tumor thrombus and recurrence(P＜0.05).The expressions of CCNB2 and Cyclin E1 in HCC tissues were positively correlated(r=0.487,P=0.000).The positive expressions of CCNB2 and Cyclin E1 in HCC tissues predicted a lower survival time(x2=7.104,7.140,P=0.008,0.008).In addition,the positive expressions of CCNB2 and Cyclin E1 were independent factors affecting the prognosis of HCC patients(P＜0.05).Conclusion CCNB2 and Cyclin E1 are highly expressed in HCC and are associated with serum AFP level,cirrhosis status,tumor thrombus and recurrence,and can be used as independent prognostic markers.

Objective To investigate the expressions of cyclin B2(CCNB2)and cyclin E1(Cyclin E1)in hepatocellular carcinoma(HCC)and their significance for the prognosis of HCC.Methods Sixty HCC patients were admitted and treated from October 2013 to October 2016.The expressions of CCNB2 and Cyclin E1 in 60 HCC tissues and adjacent normal tissues were detected by immunohistochemistry,and the relationship between the two and the clinicopathological characteristics of HCC patients was analyzed;Spearman method was performed to analyze the correlation of CCNB2 and Cyclin E1 expression;Kaplan-Meier was performed to analyze the relationship between CCNB2,Cyclin E1 expression and clinical prognosis;and univariate and multivariate Cox regression were performed to analyze the influencing factors of clinical prognosis of HCC patients.Results The positive expression rates of CCNB2 and Cyclin E1 in HCC(61.67％,56.67％)were significantly higher than those in adjacent normal tissues(20.00％,13.33％,P＜0.05);the positive expressions of CCNB2 and Cyclin E1 were positively correlated with serum AFP level,liver cirrhosis status,tumor thrombus and recurrence(P＜0.05).The expressions of CCNB2 and Cyclin E1 in HCC tissues were positively correlated(r=0.487,P=0.000).The positive expressions of CCNB2 and Cyclin E1 in HCC tissues predicted a lower survival time(x2=7.104,7.140,P=0.008,0.008).In addition,the positive expressions of CCNB2 and Cyclin E1 were independent factors affecting the prognosis of HCC patients(P＜0.05).Conclusion CCNB2 and Cyclin E1 are highly expressed in HCC and are associated with serum AFP level,cirrhosis status,tumor thrombus and recurrence,and can be used as independent prognostic markers.

Objective:To describe the epidemiological characteristics and changes of febrile seizure(FS)among children under 6 years old in Ningbo City,Zhejiang Province from 2015 to 2021.Methods:Based on the Ningbo Regional Health Information Platform,a dynamic cohort was established using vacci-nation registration information,and the cases of FS were identified by the diagnostic results of Chinese terms or International Classification of Diseases 10th revision(ICD-10)R56.0 code in the electronic medical records.The first visit of FS during the observation period was defined as a new case,and a re-currence case was defined as the case with a visit interval of more than 7 days.The 95％confidence in-terval(CI)of FS incidence density was calculated by the Poisson distribution.Results:From January 2015 to June 2020,there were 1.3 million children under 6 years old in Ningbo,with male accounting for 52.87％.The median follow-up time was 2.83(1.55-4.00)years.During the follow-up period,12 776 new onset cases had FS,with more males than females,with an overall incidence density of 4.34(95％CI:4.27-4.40)/1 000 person-years and a recurrence rate of 21.63％.There was a higher inci-dence density in children who were male,born in Ningbo and of non-mobility.The incidence density of FS was higher in urban areas than in rural and rural-urban fringe areas,and the incidence density was different among districts and counties.The peak density was found in children aged 18-23 months[8.42(95％CI:8.11-8.74)/1 000 person-years].From 2015 to 2019,the incidence density in-creased with calendar year(Ptrend＜0.001),and the highest was 5.62(95％CI:5.43-5.81)/1 000 person-years.The incidence density of FS decreased significantly during the period between 2020 and 2021.The incidence density was higher in winter.Conclusion:From 2015 to 2019,the overall inci-dence density of FS in children under 6 years old in Ningbo City presented an increasing trend.More at-tention should be paid to the health education,the improvement of the health maintenance model,the en-hancement of the cognition of FS,the identification and treatment of FS among high-risk population and regions so as to prevent its recurrence and reduce the disease burden during the corona virus disease 2019(COVID-19)epide-mic.

Objective:To explore the effect of exercise on glycemic control and physical indicators among community-dwelling persons with type 2 diabetes mellitus (T2DM).Methods:A total of 42 T2DM patients undergoing regular follow-up at a community health center were divided into a control group and an exercise group. To minimize confounding factors, 1∶1 propensity score matching was performed, resulting in 21 patients in each group. Both groups received standardized diabetes management, including medication, dietary guidance and diabetes health education. The exercise group additionally performed exercises which integrated sports and medical care models. The experiment lasted 8 weeks. Before and after the intervention, glycosylated hemoglobin A1c (HbA1c) levels, body weight, body mass index (BMI), fat mass, visceral fat area (VFA), fat mass index (FMI) and appendicular skeletal muscle mass index (ASMI) were recorded and compared between the two groups. Moreover, the actual exercise compliance of the exercise group was observed, along with any adverse events such as hypoglycemia or exercise-related injuries, as well as changes in antidiabetic medication dosage.Results:After the intervention, significant improvement was observed in both groups in all of the measurements, but with the average HbA1c, BMI, fat mass, VFA and FMI values of the exercise group then significantly better than the control group′s averages. The average compliance rate in the exercise group was 60%. No cases of hypoglycemia or exercise-related injuries were reported during the intervention, and there were no changes in the use of anti-diabetes medications.Conclusions:Exercise effectively improves glycemic control and physical indicators among community-dwelling T2DM patients. However, exercise compliance needs improving.