AIM:To investigate the effects of Kuntai capsule combined with stem cell therapy on oxidative stress damage in rats with premature ovarian failure(POF),focusing on the Nrf2-ARE signaling pathway.METHODS:Bone marrow mesenchymal stem cells(BMSCs)from Sprague-Dawley rats were cultured from primary to third generation.Female Sprague-Dawley rats were selected,and mesenchymal stem cells were isolated.A POF rat model was established through intraperitoneal injection of cyclic phosphamide,and the model was randomly divided into five groups:POF group,Kuntai group,stem cell group,combination group,and combination+Brusatol group.Normal rats injected with physio-logical saline served as the control group,with 10 rats in each group.After the intervention,changes in body weight and ovarian index were analyzed.Serum levels of estrogen indicators[luteinizing hormone(LH),follicle-stimulating hormone(FSH),serum estradiol(E2),and anti-Müllerian hormone(AMH)]and oxidative stress markers[malondialdehyde(MDA),glutathione(GSH),and superoxide dismutase(SOD)]were measured.Ovarian tissue was isolated for histologi-cal examination using HE staining and for expression analysis of anti-apoptotic BCL-2 and pro-apoptotic BAX mRNA via RT-qPCR.Western blot analysis was conducted to assess the expression of Nrf2 and heme oxygenase-1(HO-1)proteins.RESULTS:Compared to the control group,the POF group exhibited fewer mature follicles and disorganized ovarian mor-phology,along with significantly reduced body weight gain,ovarian index,E2,AMH,SOD and GSH levels,BCL-2 mRNA,and Nrf2 and HO-1 protein expression.Conversely,LH,FSH,MDA levels,and BAX mRNA expression were significantly increased(P＜0.05).In comparison to the POF group,the Kuntai group,stem cell group,and combination group showed improved ovarian morphology,with the combination group demonstrating the most significant improvement.In these groups,body weight gain,ovarian index,E2,AMH,SOD,GSH levels,BCL-2 mRNA,and Nrf2 and HO-1 pro-tein expression were markedly increased,while LH,FSH,MDA levels,and BAX mRNA expression were notably de-creased,with significant statistical differences observed between the combination group and the Kuntai and stem cell groups(P＜0.05).In contrast,the combination+Brusatol group exhibited a reduction in mature follicles and disrupted follicular structure compared to the combination group,along with decreased body weight gain,ovarian index,E2,AMH,SOD and GSH levels,BCL-2 mRNA,and Nrf2 and HO-1 protein expression,while LH,FSH and MDA levels,and BAX mRNA expression were significantly increased(P＜0.05).CONCLUSION:The combination of Kuntai capsule and stem cell therapy effectively mitigates oxidative stress damage in POF rats,potentially through the activation of the Nrf2-ARE signaling pathway.

[Purpose]To analyze the incidence and mortality of pancreatic cancer in 2020 and the change trend from 2010 to 2020 in cancer registration areas of Gansu Province.[Methods]The data of pancreatic cancer from 2010 to 2020 were collected from cancer registries in Gansu Province.The crude incidence/mortality rate,age-standardized incidence/mortality rate by Chinese standard population(ASIRC/ASMRC)and world standard population(ASIRW/ASMRW),0～74 years old cumulative rate and proportion of pancreatic cancer were calculated.Joinpoint 4.7.0 software was used to calculate the average annual percentage change(AAPC)of ASIRC/ASMRC of pancreatic cancer in cancer registration areas of Gansu Province from 2010 to 2020.[Results]In 2020,a total of 838 new cases of pancreatic cancer were reported in the cancer registration areas of Gansu Province,with a crude incidence rate of 6.52/105,ASIRC and ASIRW of 4.03/105 and 4.49/105 respectively,accounting for 2.50％of all malignant tumor incidence.In 2020,702 cases of pan-creatic cancer deaths were reported in the cancer registration areas of Gansu Province,with a crude mortality rate of 5.46/105,ASMRC and ASMRW of 3.25/105 and 3.73/105,respectively,ac-counting for 3.98％of all malignant tumor deaths.From 2010 to 2020,a total of 2 413 cases of pancreatic cancer were reported in cancer registration areas in Gansu Province,accounting for 1.90％of all malignant tumors in the province.The crude incidence rate of pancreatic cancer was 5.28/105,the ASIRC was 4.18/105,the ASIRW was 4.63/105,and the cumulative rate of 0～74 years old was 0.49％.From 2010 to 2020,a total of 1 871 pancreatic cancer deaths were reported in cancer registration areas of Gansu Province,accounting for 2.38％of all malignant tumor deaths in the province.The crude mortality rate was 3.92/105,the ASMRC was 3.09/105,the ASMRW was 3.50/105,and the cumulative rate of 0～74 years old was 0.36％.In terms of sex and region,the incidence and mortality of pancreatic cancer from 2010 to 2020 in men were higher than those in women,and higher in rural areas than those in urban areas.From 2010 to 2020,the incidence and mortality were at a low level under the age of 44 years old,and increased significantly after 45 years old,reaching a peak in the age group of 80～84 years old.ASIRC showed no significant change from 2010 to 2020 with an AAPC of 0.41 1％(P＞0.05).From 2010 to 2020,the ASMRC showed an significantly increasing trend with an AAPC of 6.515％(P=0.014).[Conclusion]From 2010 to 2020,the ASRIC of pancreatic cancer in Gansu Province showed no significant change,while the ASMRC showed a significantly in-creasing trend.The incidence and mortality rates were higher in men than those in women and higher in rural areas than those in urban areas.Middle-aged and elderly men in rural areas are the key groups of prevention and treatment of pancreatic cancer,so targeted prevention and control measures should be carried out.

Objective To investigate the role and mechanism of inflammatory marker C5a in regulating the polarization of M2 macro-phages as well as its clinical application value in the prognosis evaluation of lung cancer.Methods The phorbol 12-myristate 13-ace-tate(PMA)-pulsed human monocytic leukemia cell line THP-1 was stimulated with C5a for 0,6,12,24,and 48 h or 0,1,2,3,6,and 12 h,and then the expression levels of M2 markers CD163 and CD206 mRNA were determined by real-time fluorescence quantita-tive PCR(qRT-PCR).The expression level of general control non-repressed protein 5(GCN5)with histone acetyltransferase(HAT)activity was detected by Western blot.Co-immunoprecipitation(co-IP)was used to determine the acetylation of GATA binding protein 3(GATA3),a key transcription factor for macrophages,and its binding ability to GCN5 and E1A binding protein p300(Ep300/p300).After the macrophages pre-treated with GCN5 inhibitor butyrolactone 3(MB-3)were stimulated with C5a,the expression levels of CD163 and CD206,acetylation of GATA3,and its binding ability to GCN5 were determined by Western blot and co-IP.The clinical significance of the expression of C5a receptor 1(C5aR1)and GCN5 in lung cancer tissues in the prognosis of lung cancer patients was analyzed using the KM plotter database.Results C5a could significantly increase the expression levels of CD163 and CD206 mRNA,expression of GCN5,acetylation of GATA3,and its binding ability to GCN5 in PMA-induced adherent macrophages,but did not affect the binding of GATA3 to p300.Inhibiting the activity of GCN5 not only significantly reduced the acetylation of GATA3 and its binding ability to GCN5,but also down-regulated the expressions of CD163 and CD206.The overall survival rate of lung cancer patients with high expression of C5aR1 or GCN5 was significantly reduced.Conclusion C5a promotes the polarization of M2 macrophages by indu-cing GCN5 to acetylate GATA3.The expressions of C5aR1 and GCN5 in lung cancer tissues may have certain clinical application value for the prognosis of the patients.

Objective The aim of this study is to analyze the expression level of cell-free DNA(cf-DNA),a biomarker of neutrophil extracellular traps(NETs),in children with Mycoplasma pneumoniae pneumonia(MPP),and to explore the predictive efficacy of cf-DNA(as a marker of NETs)for the severity of MPP in these children.Methods A total of 115 children with MPP were prospectively selected as the MPP group.Based on the disease severity,the MPP group was categorized into the mild group(n=75)and the severe group(n=40).During the same period,50 healthy children undergoing physical examinations were selected as the control group.The levels of serum cf-DNA in the MPP group and the control group,as well as the levels of C-reactive protein(CRP),D-dimer,lactate dehydrogenase(LDH),interleukin-6(IL-6),interferon-γ(IFN-γ),and tumor necrosis factor-α(TNF-α)in the MPP group were detected.The differences in the levels of serum cf-DNA and related inflammatory factors among the groups were compared,and the role of serum cf-DNA in evaluating the severity of MPP was analyzed.Results The level of serum cf-DNA in children of the MPP group was notably higher than that in the control group,with a more significant elevation observed in the severe group(P<0.05).The levels of CRP,D-dimer,LDH,IL-6,IFN-γ,and TNF-α were all higher in the severe group than in the mild group(P<0.05).Multivariate logistic regression analysis showed that the increased levels of serum cf-DNA,CRP,and IL-6 were closely related to the severity of MPP(P<0.05).The results of receiver operating characteristic(ROC)curve analysis showed that the area under the curve(AUC)of the combination of serum cf-DNA,CRP,and IL-6 for predicting severe MPP was 0.981,which was higher than that of each index alone(P<0.05).Conclusions Serum cf-DNA(as a marker of NETs)is closely related to the severity of MPP in children.The combined detection of cf-DNA,CRP,and IL-6 is more beneficial for assessing the severity of MPP in children.

Objective The aim of this study is to analyze the expression level of cell-free DNA(cf-DNA),a biomarker of neutrophil extracellular traps(NETs),in children with Mycoplasma pneumoniae pneumonia(MPP),and to explore the predictive efficacy of cf-DNA(as a marker of NETs)for the severity of MPP in these children.Methods A total of 115 children with MPP were prospectively selected as the MPP group.Based on the disease severity,the MPP group was categorized into the mild group(n=75)and the severe group(n=40).During the same period,50 healthy children undergoing physical examinations were selected as the control group.The levels of serum cf-DNA in the MPP group and the control group,as well as the levels of C-reactive protein(CRP),D-dimer,lactate dehydrogenase(LDH),interleukin-6(IL-6),interferon-γ(IFN-γ),and tumor necrosis factor-α(TNF-α)in the MPP group were detected.The differences in the levels of serum cf-DNA and related inflammatory factors among the groups were compared,and the role of serum cf-DNA in evaluating the severity of MPP was analyzed.Results The level of serum cf-DNA in children of the MPP group was notably higher than that in the control group,with a more significant elevation observed in the severe group(P<0.05).The levels of CRP,D-dimer,LDH,IL-6,IFN-γ,and TNF-α were all higher in the severe group than in the mild group(P<0.05).Multivariate logistic regression analysis showed that the increased levels of serum cf-DNA,CRP,and IL-6 were closely related to the severity of MPP(P<0.05).The results of receiver operating characteristic(ROC)curve analysis showed that the area under the curve(AUC)of the combination of serum cf-DNA,CRP,and IL-6 for predicting severe MPP was 0.981,which was higher than that of each index alone(P<0.05).Conclusions Serum cf-DNA(as a marker of NETs)is closely related to the severity of MPP in children.The combined detection of cf-DNA,CRP,and IL-6 is more beneficial for assessing the severity of MPP in children.

OBJECTIVE To explore the short-term efficacy,safety and related influencing factors of subcutaneous immunotherapy(SCIT)in children with allergic rhinitis(AR).METHODS Retrospective analyzed the clinical data of 147 children with AR who underwent SCIT at Shenzhen Hospital of Southern Medical University from August 2020 to May 2024.The clinical characteristics and laboratory parameters were collected,the visual analogue scale(VAS),total symptom score(TSS),total medication score(TMS)and combined symptom medication score(CSMS)were compared at the baseline and 3,6 and 12 months after treatment.The incidence of local adverse reactions(LRs)and systemic adverse reactions(SRs)during treatment was also documented.RESULTS A total of 147 children with AR aged 5-18 years were included in the study.A significant reduction was observed in VAS,TSS,TMS and CSMS at months 3,6 and 12 of follow up compared with baseline(all P<0.001),and the short-term onset time was months 3 after treatment.The level of VitD3 in the effective group was significantly higher than that in the ineffective group(P<0.001).Serum VitD3 level was negatively correlated with clinical symptom(R=-0.3,P=0.026).The total number of injections in 147 children was 3201.LRs occurred in 52 children(35.4％),the number of injections was 69(2.2％).SRs occurred in 21 children(14.3％),and the number of injections was 34(1.1％).No grade Ⅲ or Ⅳ SRs occurred.In the logistic regression analysis,body mass index(BMI)was a risk factor for LRs(OR:2.220,95％CI:1.009-4.887,P=0.048).CONCLUSION SCIT demonstrates significant early efficacy and a favorable safety profile safety in children with AR.Serum Vitamin D3 deficiency can affect the short-term efficacy of SCIT.Overweight and obese children are prone to develop local adverse reactions.

[Purpose]To analyze the incidence and mortality of pancreatic cancer in 2020 and the change trend from 2010 to 2020 in cancer registration areas of Gansu Province.[Methods]The data of pancreatic cancer from 2010 to 2020 were collected from cancer registries in Gansu Province.The crude incidence/mortality rate,age-standardized incidence/mortality rate by Chinese standard population(ASIRC/ASMRC)and world standard population(ASIRW/ASMRW),0～74 years old cumulative rate and proportion of pancreatic cancer were calculated.Joinpoint 4.7.0 software was used to calculate the average annual percentage change(AAPC)of ASIRC/ASMRC of pancreatic cancer in cancer registration areas of Gansu Province from 2010 to 2020.[Results]In 2020,a total of 838 new cases of pancreatic cancer were reported in the cancer registration areas of Gansu Province,with a crude incidence rate of 6.52/105,ASIRC and ASIRW of 4.03/105 and 4.49/105 respectively,accounting for 2.50％of all malignant tumor incidence.In 2020,702 cases of pan-creatic cancer deaths were reported in the cancer registration areas of Gansu Province,with a crude mortality rate of 5.46/105,ASMRC and ASMRW of 3.25/105 and 3.73/105,respectively,ac-counting for 3.98％of all malignant tumor deaths.From 2010 to 2020,a total of 2 413 cases of pancreatic cancer were reported in cancer registration areas in Gansu Province,accounting for 1.90％of all malignant tumors in the province.The crude incidence rate of pancreatic cancer was 5.28/105,the ASIRC was 4.18/105,the ASIRW was 4.63/105,and the cumulative rate of 0～74 years old was 0.49％.From 2010 to 2020,a total of 1 871 pancreatic cancer deaths were reported in cancer registration areas of Gansu Province,accounting for 2.38％of all malignant tumor deaths in the province.The crude mortality rate was 3.92/105,the ASMRC was 3.09/105,the ASMRW was 3.50/105,and the cumulative rate of 0～74 years old was 0.36％.In terms of sex and region,the incidence and mortality of pancreatic cancer from 2010 to 2020 in men were higher than those in women,and higher in rural areas than those in urban areas.From 2010 to 2020,the incidence and mortality were at a low level under the age of 44 years old,and increased significantly after 45 years old,reaching a peak in the age group of 80～84 years old.ASIRC showed no significant change from 2010 to 2020 with an AAPC of 0.41 1％(P＞0.05).From 2010 to 2020,the ASMRC showed an significantly increasing trend with an AAPC of 6.515％(P=0.014).[Conclusion]From 2010 to 2020,the ASRIC of pancreatic cancer in Gansu Province showed no significant change,while the ASMRC showed a significantly in-creasing trend.The incidence and mortality rates were higher in men than those in women and higher in rural areas than those in urban areas.Middle-aged and elderly men in rural areas are the key groups of prevention and treatment of pancreatic cancer,so targeted prevention and control measures should be carried out.

Objective: To analyze the serotypes and drug resistance of Salmonella isolated from food-borne disease surveillance samples in Longwan District, Wenzhou City, Zhejiang Province, so as to provide evidence for the prevention and treatment of Salmonella infection. Methods: Salmonella strains isolated from feces or anal swabs of patients with foodborne diarrhea in Longwan District People's Hospital from 2018 to 2024 were collected. After re-identification, slide agglutination test was used to identify serotypes. The drug susceptibility test of live Salmonella strains was performed using the broth microdilution method, and the resistance patterns were analyzed. Results: A total of 2 293 samples were collected, and 186 strains of Salmonella were isolated, with a detection rate of 8.11%. The detection rate was higher from May to October. A total of 28 Salmonella serotypes were identified, with S. typhimurium (72 isolates, 38.71%), S. enteritidis (31 isolates, 16.67%), and S. London (30 isolates, 16.13%) being dominant. Among the 121 Salmonella live strains, 20 strains were susceptible to 14 antibacterial drugs. A total of 101 strains were resistant to antibacterial drugs, and the drug resistance rate was 1.65%-67.77%, with the drug resistance rate of ampicillin being the highest, and the drug resistance rate of imipenem was the lowest. S. typhimurium had the highest resistance rate to tetracycline (78.26%). S. enteritidis had the highest resistance rate to ampicillin (100.00%). S. London had the highest resistance rate to tetracycline (66.67%). Fifty-five types of drug resistance patterns were detected, showing a number of drug resistance of 1-10, of which 76 strains were multi-drug resistant, accounting for 75.25%. The predominant multidrug resistance patterns were ampicillin/sulbactam-cefazolin-ampicillin-nalidixic acid (10.53%), tetracycline-ampicillin-nalidixic acid (9.21%), and ampicillin/sulbactam-ampicillin-nalidixic acid (7.89%). Conclusions Salmonella strains isolated from foodborne diseases in Longwan District were mainly detected in summer and autumn. S. typhimurium, S. enteritidis, and S. London were the predominant serotypes. The drug resistance of Salmonella to different antibacterial drugs was different, and the drug resistance spectrum showed diversity.

ObjectiveTo explore the effect and mechanism of Qigui Didang decoction， formulated based on the principle of Tonifying Deficiency and Unblocking Collaterals， on improving metabolic memory of db/db mice with diabetic nephropathy （DN） through silent information regulator 1 signal regulator 1 （Sirt1）/p53/nuclear factor kappa-B （NF-κB） p65 pathway. MethodsFifteen db/db mice were randomly divided into model group （10 mL·kg^-1·d^-1）， resveratrol group （20 mg·kg^-1·d^-1）， and Qigui Didang decoction group （3.34 g·kg^-1·d^-1） Another five db/m mice were selected as the normal group （10 mL·kg^-1·d^-1）. After the intervention， the kidney weight of each group was measured， and the kidney index （KI） was calculated. Fasting blood glucose （FBG）， creatinine （CRE）， β2-microglobulin （β2-MG）， blood urea nitrogen （BUN）， and cystatin C （CysC） were measured. Renal pathology was observed by hematoxylin-eosin （HE） staining and Masson staining. The mRNA and protein expression levels of Sirt1， NF-κB， tumor suppressor gene p53， interleukin-1β （IL-1β）， and cysteine aspartate protease-3 （Caspase-3） were detected using real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultsCompared with the normal group， the model group showed disordered renal structure， obvious renal damage， and markedly elevated levels of renal function indexes （CRE， β2-MG， BUN， and CysC） （P<0.01）. The KI and blood glucose were significantly increased （P<0.01）， while Sirt1 expression was markedly decreased （P<0.01）. Expression levels of NF-κB p65， p53， IL-1β， and Caspase-3 were increased significantly （P<0.05）. Compared with those in the model group， DN mice treated with Qigui Didang decoction exhibited significantly decreased FBG， improved renal function， and markedly decreased KI （P<0.01）， along with reduced CRE， β2-MG， BUN， and CysC levels （P<0.05）. Protein expression of Sirt1 was significantly upregulated （P<0.05）， while that of NF-κB p65， p53， IL-1β， and Caspase-3 was markedly decreased （P<0.05）. The mRNA expression levels of NF-κB p65， p53， IL-1β， and Caspase-3 were significantly decreased （P<0.05）. The staining results indicate improved renal fibrosis， significantly decreased fiber deposition （P<0.05）， and less inflammatory infiltration in the Qigui Didang decoction group. ConclusionThe findings suggest that Qigui Didang decoction can alleviate the metabolic memory effect of DN， thereby inhibiting renal cell apoptosis and inflammatory response in mice， and improving renal function. The mechanism of action is closely related to the Sirt1/p53/NF-κB p65 signaling pathway.

AIM:To investigate the effects of Kuntai capsule combined with stem cell therapy on oxidative stress damage in rats with premature ovarian failure(POF),focusing on the Nrf2-ARE signaling pathway.METHODS:Bone marrow mesenchymal stem cells(BMSCs)from Sprague-Dawley rats were cultured from primary to third generation.Female Sprague-Dawley rats were selected,and mesenchymal stem cells were isolated.A POF rat model was established through intraperitoneal injection of cyclic phosphamide,and the model was randomly divided into five groups:POF group,Kuntai group,stem cell group,combination group,and combination+Brusatol group.Normal rats injected with physio-logical saline served as the control group,with 10 rats in each group.After the intervention,changes in body weight and ovarian index were analyzed.Serum levels of estrogen indicators[luteinizing hormone(LH),follicle-stimulating hormone(FSH),serum estradiol(E2),and anti-Müllerian hormone(AMH)]and oxidative stress markers[malondialdehyde(MDA),glutathione(GSH),and superoxide dismutase(SOD)]were measured.Ovarian tissue was isolated for histologi-cal examination using HE staining and for expression analysis of anti-apoptotic BCL-2 and pro-apoptotic BAX mRNA via RT-qPCR.Western blot analysis was conducted to assess the expression of Nrf2 and heme oxygenase-1(HO-1)proteins.RESULTS:Compared to the control group,the POF group exhibited fewer mature follicles and disorganized ovarian mor-phology,along with significantly reduced body weight gain,ovarian index,E2,AMH,SOD and GSH levels,BCL-2 mRNA,and Nrf2 and HO-1 protein expression.Conversely,LH,FSH,MDA levels,and BAX mRNA expression were significantly increased(P＜0.05).In comparison to the POF group,the Kuntai group,stem cell group,and combination group showed improved ovarian morphology,with the combination group demonstrating the most significant improvement.In these groups,body weight gain,ovarian index,E2,AMH,SOD,GSH levels,BCL-2 mRNA,and Nrf2 and HO-1 pro-tein expression were markedly increased,while LH,FSH,MDA levels,and BAX mRNA expression were notably de-creased,with significant statistical differences observed between the combination group and the Kuntai and stem cell groups(P＜0.05).In contrast,the combination+Brusatol group exhibited a reduction in mature follicles and disrupted follicular structure compared to the combination group,along with decreased body weight gain,ovarian index,E2,AMH,SOD and GSH levels,BCL-2 mRNA,and Nrf2 and HO-1 protein expression,while LH,FSH and MDA levels,and BAX mRNA expression were significantly increased(P＜0.05).CONCLUSION:The combination of Kuntai capsule and stem cell therapy effectively mitigates oxidative stress damage in POF rats,potentially through the activation of the Nrf2-ARE signaling pathway.