OBJECTIVE To evaluate the efficacy and safety of cadonilimab plus chemotherapy in patients with advanced gastric adenocarcinoma or adenocarcinoma of gastroesophageal junction （AEG） with intermediate， low， or no human epidermal growth factor receptor 2 （HER2） expression. METHODS Patients with advanced gastric adenocarcinoma or AEG with intermediate， low， or no HER2 expression who were treated at Liaoning Cancer Hospital between October 1， 2024 and June 30， 2025 were retrospectively included. According to the treatment regimen received， the patients were divided into group A [cadonilimab plus oxaliplatin and capecitabine （XELOX）， n ＝54 ] ， group B （sintilimab plus XELOX， n ＝68）， and group C （tislelizumab plus XELOX， n ＝49）. Short-term efficacy after 4 cycles of treatment， survival outcomes， and adverse events were compared among the three groups. Cox regression and Logistic regression analyses were further performed to evaluate the effects of the treatment regimen and baseline data on survival outcomes and the risk of grade 3-4 treatment related adverse events （TRAEs）. RESULTS No statistically significant differences in objective response rate or disease control rate were observed among the three groups （ P ＞0.05）. The median progression-free survival was 7.56 （5.62， 8.11） months in group A， 7.23 （5.33， 8.23） months in group B， and 7.33 （5.42， 8.19） months in group C， with no statistically significant difference among the three groups （ P ＞0.05）. The median overall survival （mOS） was 11.67 （8.82， 13.88） months in group A， 9.78 （6.82， 12.73） months in group B， and 9.69 （6.78， 12.66） months in group C. The mOS was significantly longer in group A than in group B and group C （ P ＜0.05）， whereas no statistically significant difference was observed between group B and group C （ P ＞0.05）. The correlation analysis indicated that treatment regimen， Eastern Cooperative Oncology Group performance status （ECOG PS）， number of metastatic organs， and peritoneal metastasis may be associated with overall survival （OS）. No significant association was observed between treatment regimen and the risk of grade 3-4 TRAEs. The incidences of grade 1-2 or grade 3-4 TRAEs did not differ significantly among the three groups （ P ＞0.05）. CONCLUSIONS In patients with advanced gastric adenocarcinoma or AEG with intermediate， low， or no HER2 expression， cadonilimab plus XELOX may provide a more significant OS benefit with a safety profile comparable to that of sintilimab or tislelizumab plus XELOX. Further studies with larger sample sizes are required to validate these findings.

ObjectiveTo explore the correlation between the blood stasis score of coronary heart disease（CAD） and mild cognitive impairment（MCI）， as well as the changes in plasma metabolic profile of blood stasis in patients with CAD combined with MCI（CADMCI） through a cross-sectional study， and further explore the impact of different degrees of blood stasis on the plasma metabolite profile of CADMCI patients. MethodsAccording to the diagnostic criteria of CAD and CAD blood stasis， patients hospitalized in Xiyuan Hospital of China Academy of Chinese Medical Sciences from October 2022 to October 2023 were continuously included. According to the Montreal Cognitive Assessment（MoCA） scale score， the enrolled patients were divided into CADMCI blood stasis group and CAD blood stasis group. The association between blood stasis score and MCI was analyzed by multivariate Logistic regression model. The receiver operating characteristic（ROC） curve was drawn， and the area under the curve（AUC） was calculated to evaluate the sensitivity and specificity of the model. According to the blood stasis score， the first 30 patients in the CADMCI blood stasis group and CAD blood stasis group were divided into mild blood stasis and severe blood stasis. Ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was used to detect plasma metabolites in each group of patients. The differential metabolites were screened according to variable importance in the projection（VIP） value≥1， fold change（FC）<0.67 or >1.5， and P<0.05. ROC curve analysis was further used to evaluate the discriminatory efficiency of the screened differential metabolites for each group of samples. ResultsA total of 266 CAD patients were included in this study. Multivariate Logistic regression analysis showed that the CAD blood stasis score was significantly correlated with MCI［odds ratio（OR）=1.619， 95% confidence interval（CI） 1.223-2.142， P<0.001， ROC curve AUC was 0.615（95% CI 0.547-0.683， P=0.001）］， indicating that the CAD blood stasis score has a certain predictive value for MCI. Plasma non-targeted metabolomics analysis showed that the main differential metabolites between CAD blood stasis and CADMCI blood stasis were lipid metabolites， among which phosphatidylcholine［20∶4（5Z， 8Z， 11Z， 14Z）/P-18∶1（11Z）］ had the best discriminatory efficiency（ROC curve AUC=0.867， 95% CI 0.754-0.942）. Further analysis of the differential metabolites between mild and severe blood stasis showed that lipid metabolites were also the main differential metabolites between mild and severe blood stasis. Among them， 1α，25-dihydroxy-2β-（2-hydroxyethoxy） vitamin D₃ had the best efficacy in distinguishing mild and severe CAD blood stasis（AUC=0.813， 95% CI 0.649-0.951）， and phosphatidylcholine 34∶2 had the best efficacy in distinguishing mild and severe CADMCI blood stasis（AUC=0.819， 95% CI 0.640-0.941）. ConclusionThere is a significant correlation between CAD blood stasis score and MCI. Phosphatidylcholine metabolites play an important role in the pathogenesis of CADMCI blood stasis and severe blood stasis. The CAD blood stasis score combined with the detection of phosphatidylcholine metabolites can provide a reference for the development of early and efficient identification strategies for CADMCI.

AIM:To investigate whether total alkaloids of Cocculus orbiculatus(COTA)attenuate ulcerative colitis(UC)in mice via PINK1/parkin mitophagy pathway.METHODS:Sixty C57BL/6 mice were randomly divided into normal control group,model group,positive drug mesalazine group,and low-,medium-and high-dose(0.162,0.324 and 0.486 g/kg)COTA groups,with 10 mice in each group.Except for normal control group,the mice in all groups were given free access to 3%dextran sulfate sodium(DSS)solution for 7 consecutive days to establish a UC model in mice,and were then treated with COTA or mesalazine via oral gavage.The general condition of the mice was observed,and the colon length and disease activity index(DAI)score were determined.Colon histopathological damage was observed by HE staining.The serum levels of interleukin-1β(IL-1β),IL-6 and tumor necrosis factor-α(TNF-α)were detected by ELISA.The pro-tein levels of PINK1,parkin,microtubule-associated protein 1 light chain 3(LC3),P62 and beclin-1 in colon tissues were determined by Western blot.The protein expression of LC3 and parkin was detected by immunofluorescence.RE-SULTS:Compared with normal control group,the mice in model group showed varying degrees of soft stools or bloody stools,decreased body weight(P<0.05),increased DAI score,shortened colon length(P<0.05),and obvious pathologi-cal damage in the colon tissue.The serum levels of IL-1β,IL-6 and TNF-α were elevated(P<0.05).The protein levels of parkin,PINK1,LC3-II and beclin-1 were significantly decreased(P<0.05),while P62 protein expression was in-creased(P<0.05).Immunofluorescence showed a small number of autophagosomes in the colon tissue.In contrast,com-pared with model group,the mice in total alkaloids of Cocculus orbiculatus groups exhibited increased body weight(P<0.05),decreased DAI score,increased colon length(P<0.05),and reduced levels of IL-1β,IL-6 and TNF-α(P<0.05).The protein levels of parkin,PINK1,LC3 and beclin-1 were elevated(P<0.05),while P62 expression was re-duced(P<0.05),with numerous autophagosomes visible in the colon tissue via immunofluorescence.CONCLUSION:Total alkaloids of Cocculus orbiculatus can enhance the expression of mitophagy-related proteins PINK1,parkin,LC3 and beclin-1,activate mitophagy,and reduce the expression of inflammatory factors,thereby attenuating the inflammatory re-sponse in the colon mucosa of DSS-induced UC mice.

Objective:To understand the incidence rate of herpes zoster (HZ) and postherpetic neuralgia (PHN) in Beijing, and analyze the incidence trend of HZ and PHN from 2015 to 2022.Methods:Cases of HZ and PHN from 2015 to 2022 were retrieved from the Hospital Information Systems (HIS) of all primary and above hospitals/clinics in three districts representing the urban, inner suburban, and outer suburban areas of Beijing. After duplication screening, the first visit cases were screened, and the incidence characteristics were described. The incidence rate of HZ and PHN in each year by sex and age group and the age-standardized incidence rate were calculated. The annual percentage increase (APC) of incidence rate was calculated using the Joint regression model, and the change trend was analyzed.Results:The age-standardized incidence rate of HZ in Beijing from 2015 to 2022 ranged from 7.44‰ to 10.05‰, with an average annual incidence rate of 8.95 ‰, significantly increasing with age ( P<0.001). The Joinpoint regression model showed that the overall age-standardized incidence of HZ remained relatively stable, with no significant difference (APC=2.28%, t=1.56, P=0.170). However, the incidence rate among the 0-19-year-old group exhibited a trend of decrease (APC=-10.70%, t=-6.29, P<0.001). For PHN, the age-standardized incidence in Beijing ranged from 0.77‰ to 2.67‰, with an average annual incidence rate of 1.59‰ and a proportion of 9.48% to 26.86% among HZ cases. Both the incidence of PHN and its proportion among HZ cases increased with age ( P<0.001). The age-standardized incidence of PHN increased annually (APC=18.56%, t=9.02, P<0.001). Conclusion:The incidence rate of HZ and PHN in Beijing continues to be at a high level, and PHN shows an increasing trend over time.

[Purpose]To analyze the incidence and mortality of female breast cancer in Zhejiang cancer registration areas in 2021 and the trends from 2000 to 2021.[Methods]The data of cancer inci-dence,mortality and population data reported by cancer registration areas in Zhejiang Province from 2000 to 2021 were collected.The crude incidence/mortality rates,age-standardized rates ad-justed by Chinese standard population(ASIRC,ASMRC)and world standard population(ASIRW,ASMRW),cumulative rates(0～74 years old),truncated rates(35～64 years old),proportion of fe-male breast cancer and age-specific rate were calculated.The average annual percentage change(AAPC)of female breast cancer incidence and mortality rates in Zhejiang from 2000 to 2021 was calculated using Joinpoint software.[Results]In 2021,there were 7 262 new cases of female breast cancer in Zhejiang cancer registration areas,accounting for 12.70％of all new female can-cer cases.The crude incidence rate,ASIRC and ASIRW were 65.71/105,42.03/105 and 39.22/105,respectively.The cumulative incidence rate(0～74 years old)was 4.26％,and the truncated rate(35～64 years old)was 98.34/105.The ASIRC in urban and rural areas were 43.15/105 and 40.15/105,respectively.There were 992 deaths of female breast cancer,accounting for 6.97％of all female cancer deaths.The crude mortality rate,ASMRC and ASMRW were 8.98/105,4.62/105 and 4.47/105,respectively.The cumulative mortality rate(0～74 years old)was 0.48％,and the truncated rate(35～64 years old)was 8.89/105.The ASMRC in urban and rural areas were 4.79/105 and 4.34/105,respectively.The incidence rate of female breast cancer reached the peak at the age group of 60～64 years old,and the mortality rate reached the peak at the age group of 85 years old and above.From 2000 to 2021,the crude incidence rate,ASIRC and ASIRW of female breast cancer in Zhejiang cancer registration areas showed significant increasing trends(all P＜0.05).The crude mortality rate and ASMRW of female breast cancer also showed significant increasing trends(all P＜0.05).[Conclusion]The incidence rate of female breast cancer in Zhejiang Province was higher than the national average,while the mortality rate was lower than the national average in 2021.Both the incidence and mortality rates showed increasing trends from 2000 to 2021.Fur-thermore,distinct urban-rural disparities existed in both incidence and mortality characteristics.

Objective To explore the risk factors of nonalcoholic fatty liver disease(NAFLD)in obese children,and evaluate the diagnostic value of each index for NAFLD and establish a Nomogram prediction model.Methods A total of 207 obese children admitted at Department of Pediatrics the Second Hospital of Jiaxing from January 2022 to January 2025 were selected.These children were divided into two groups based on NAFLD diagnosis:non-NAFLD group(n=99)and NAFLD group(n=108).Differences in gender,age,body mass index(BMI),and related metabolic indicators were compared between two groups.Logistic regression was employed to analyze potential risk factors for NAFLD development,while receiver operating characteristic(ROC)curve and Nomograms were used to evaluate the predictive value of different factors for NAFLD.Results ROC curve analysis demonstrated diagnostic value for NAFLD in triglyceride-glucose index(TyG),triglyceride-to-cholesterol ratio,TyG-waist circumference,and TyG-BMI.Among these,the area under the curve(AUC)of TyG showed the highest value of 0.713,with an optimal cutoff of 8.189,sensitivity of 50.5％and specificity of 83.3％.Univariate Logistic regression analysis revealed multiple insulin resistance indicators associated with NAFLD development.Multivariate analysis identified homeostatic model assessment of insulin resistance(HOMA-IR)and TyG as independent risk factors,with TyG showing the best predictive value(OR=3.038 95％CI:1.089-8.475,P＜0.05).The constructed Nomogram prediction model demonstrated strong comprehensive discriminant capability(AUC=0.742).Conclusion The Nomogram model based on HOMA-IR,TyG and its derived indexes has certain clinical application value in the screening of NAFLD in children.

The aim of this study is to establish an gene editing method of Mesomycoplasma hyo-pneumoniae(Mhp)based on the homologous recombination principle.The restriction enzyme di-gestion and ligation method combined with gene synthesis were used to construct a shuttle plasmid to achieve replication in both Mhp and Escherichia coli(E.coli).The pGEM?-T vector was used as the skeleton.The oriC sequence of Mhp which can achieve the replication of the plasmid in Mhp was inserted into the vector.Sequences of the Spiroplasma promoter and puromycin resistance gene were then inserted into the above constructed plasmid to screen recombinant clones.The up-stream and downstream homologous arms of p97 were constructed to initiate homologous recombination.The recA gene of E.coli is inserted to improve the efficiency of homologous recom-bination.The obtained shuttle plasmid was then delivered into Mhp by electro-transformation or chemical transformation.A shuttle plasmid,pGEM?-Mhp-oriC-p 97,which can replicate in both Mhp and E.coli was constructed.With the transformation of this plasmid,the carried puromycin gene and recA gene can be expressed,the p97 gene can be edited.Finally,the genetically unstable p97 gene mutant was initially obtained.In this study,a tool for Mhp gene editing based on the principle of homologous recombination was established,which laid a foundation for the develop-ment of tools for studying the pathogenesis of Mhp.

Objective To analysis the relationship between the lactate-to-albumin ratio(LAR)and the 28-day prognosis in patients with sepsis.Methods Based on the Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ)database,patients with sepsis aged≥18 years were selected.Patients were divided into survival and death groups according to their 28-day prognosis.The LAR was divided into quartiles:Q1(LAR<0.45),Q2(0.45≤LAR<0.70),Q3(0.70≤LAR<1.18),and Q4(LAR≥1.18);and into two groups based on the median LAR:low LAR group(LAR≤0.70)and high LAR group(LAR>0.70).Demographic characteristics,comorbidities,laboratory indicators,clinical treatments,and disease severity scores of patients were extracted.LAR was included as a continuous variable and a four-category variable in multiple Logistic regression models,with trend tests performed.Subgroup analyses were conducted based on gender,age,comorbidities,and sequential organ failure assessment(SOFA)score.Receiver operator characteristic curve(ROC curves)were plotted to analyze the predictive efficacy of lactate,albumin(Alb),LAR and SOFA score for the prognosis of sepsis patients.Kaplan-Meier survival curves were plotted to compare the difference of 28-day cumulative survival rates of sepsis patients in the high and low LAR groups.Results A total of 9 169 patients with sepsis were included,with 6 799 in the survival group and 2 370 in the death group.Compared with the survival group,the death group had older age[years:70.80(58.64,82.25)vs.65.07(53.56,76.92)],higher levels of potassium,creatinine,blood urea nitrogen(BUN),white blood cell count(WBC),lactate,LAR,SOFA score,simplified acute physiology scoreⅡ(SAPSⅡ),and higher proportions of chronic obstructive pulmonary disease(COPD),heart failure,use of vasopressors within 48 hours,and continuous renal replacement therapy(CRRT)[potassium(mmol/L):5.0(4.5,5.7)vs.4.8(4.4,5.4),creatinine(μmol/L):132.60(88.40,212.16)vs.97.24(70.72,159.12),BUN(mmol/L):11.42(7.14,18.56)vs.7.85(5.25,13.57),WBC(×109/L):13.1(8.7,19.1)vs.11.4(7.6,16.4),lactate(mmol/L):2.9(1.8,5.1)vs.2.0(1.4,3.1),LAR:1.03(0.63,1.88)vs.0.62(0.42,0.98),SOFA score:9(6,12)vs.6(4,8),SAPSⅡscore:52(42,64)vs.38(30,47),COPD:8.19%(194/2 370)vs.6.57%(447/6 799),heart failure:29.96%(710/2 370)vs.26.31%(1 789/6 799),use of vasopressors within 48 hours:62.19%(1 474/2 370)vs.37.56%(2 554/6 799),CRRT:19.45%(461/2 370)vs.9.56%(650/6 799),all P<0.05],while lower levels of body weight,chloride,calcium,hemoglobin(Hb),platelet count(PLT),Alb and lower proportions of hypertension were observed in the death group[body weight(kg):75.8(63.6,92.3)vs.78.7(66.5,95.0),chloride(mmol/L):104(98,109)vs.104(100,108),calcium(mmol/L):1.07(1.00,1.15)vs.1.09(1.03,1.15),Hb(g/L):103(87,120)vs.105(90,121),PLT(×109/L):173(104,246)vs.174(118,243),Alb(g/L):29(24,34)vs.33(28,37),hypertension:35.36%(838/2 370)vs.38.34%(2 607/6 799),all P<0.05].In the Logistic regression model adjusted for all confounding factors,the odds ratio(OR)and 95%confidence interval(95%CI)of LAR were 1.74(1.64-1.85),P<0.001;when LAR was treated as a four-category variable,the OR values of Q2,Q3,and Q4 increased progressively compared with Q1,being 1.49(1.22-1.82),2.27(1.88-2.75),and 5.05(4.20-6.08),respectively,P<0.001.Subgroup analyses showed that LAR was an independent risk factor for the 28-day prognosis of sepsis in different subgroups based on gender,age,comorbidities,and SOFA score(all P<0.001),with no interaction effects with the subgroup variables(all P>0.05).ROC curve analysis showed that the AUC of LAR predicted the 28-day prognosis of patients with sepsis was 0.688(0.675-0.700),higher than that of lactate[0.655(0.642-0.668)]and Alb[0.636(0.623-0.649)],both P<0.001,and not significantly lower than that of SOFA score[0.699(0.687-0.712),P=0.108].Kaplan-Meier survival analysis showed that the 28-day cumulative survival rate was significantly higher in the low LAR group than in the high LAR group(Log-Rank test:χ2=533.24,P<0.001).Conclusion LAR is an independent risk factor for the 28-day prognosis of sepsis patients.Higher LAR is associated with adverse outcomes,and its predictive efficacy is superior to that of lactate and albumin.

Objective To observe the effects of a stepped early activity program combined with lower limb joint rehabilitation devices in mechanically ventilated patients in the intensive care unit(ICU).Methods Sixty mechanically ventilated patients admitted to the ICU of Tianjin First Central Hospital from October 2022 to June 2023 were selected as study subjects and randomly divided into an intervention group(n=30)and a control group(n=30)using a random number table.The control group received routine rehabilitation nursing combined with lower limb joint rehabilitation devices,while the intervention group was additionally treated with the stepped early activity program.The duration of mechanical ventilation,length of ICU stay,incidence of delirium,Medical Research Council(MRC)muscle strength scores,phase angle(PA),and skeletal muscle mass index(SMI)were compared between the two groups.Results The intervention group showed significantly shorter durations of mechanical ventilation and the length of ICU stay compared to the control group[mechanical ventilation time(days):9.20±4.51 vs.11.73±4.59,the length of ICU stay(days):10.73±5.37 vs.14.00±6.03,both P<0.05].Post-intervention MRC muscle strength scores,PA,and SMI significantly increased in both groups,with greater improvements observed in the intervention group[MRC muscle strength score:54.17±2.10 vs.50.17±3.51;PA(°):5.80±0.60 vs.5.49±0.54;SMI(kg/m2):6.87±0.46 vs.6.62±0.45,all P<0.05].No statistically significant difference was found in delirium incidence between the two groups[26.7%(8/30)vs.33.3%(10/30),P>0.05].Conclusion The combination of a stepped early activity program and lower limb joint rehabilitation devices effectively shortens mechanical ventilation time and the length of ICU stay,restores muscle strength,and promotes recovery in mechanically ventilated ICU patients,demonstrating significant clinical value.

Objective:To investigate the efficacy of vital pulp therapy versus pulp revascularization in the treatment of irreversible pulpitis and apical periodontitis in young permanent teeth. Methods:This study used a retrospective design. Fifty-six children with irreversible pulpitis and apical periodontitis in young permanent teeth, admitted to Shaoxing Stomatological Hospital from January 2022 to June 2024, were selected for the study. The children were divided into Group A ( n = 28) and Group B ( n = 28) based on treatment methods. Group A received vital pulp therapy, while Group B underwent pulp revascularization. The efficacy of both groups was compared 12 months after surgery. The root length and apical foramen size were compared between the two groups before surgery, as well as 3 and 12 months after surgery. The imaging findings were also compared between the two groups 3 and 12 months after surgery. Results:There was no significant difference in efficacy between the two groups ( P>0.05). The root lengths in Group A at 3 and 12 months after surgery were (13.17 ± 1.52) mm and (14.34 ± 1.68) mm, respectively, which were significantly greater than those in Group B [(11.86 ± 1.29) mm, (13.09 ± 1.45) mm; t = 3.48, 2.98, both P<0.05]. The apical foramen sizes in Group A at 3 and 12 months after surgery were (2.17 ± 0.32) mm and (1.61 ± 0.27) mm, respectively, and were significantly smaller than those in Group B [(2.53 ± 0.37) mm, (1.98 ± 0.31) mm; t = -7.03, -4.76, both P<0.05]. The proportion of children with an open apical foramen in Group A at 3 months after surgery was significantly lower than that in Group B [35.71% (10/28) vs. 64.29% (18/28); χ2 = 4.57, P<0.05). However, there was no statistically significant difference in the proportion of open apical foramina between the two groups at 12 months after surgery ( P>0.05). Conclusions:Vital pulp therapy shows good efficacy in the treatment of irreversible pulpitis and apical periodontitis in young permanent teeth. Compared with pulp revascularization, vital pulp therapy can remarkably reduce apical foramen size and increase root length, making it a valuable option for clinical practice.