OBJECTIVE To investigate the protective effect of 2-dodecyl-6-methoxy-2，5-diene-1，4-cyclohexanedione （DMDD）， an active component from Averrhoa carambola root， on myocardial injury in diabetic mice based on the nuclear receptor coactivator 4/ferritin heavy chain 1/autophagy-related protein 8 （NCOA4/FTH1/ATG8） axis. METHODS The successfully modeled diabetic mice were randomly divided into model group and DMDD low-， medium-， and high-dose （12.5， 25， 50 mg/kg） groups， while an additional non-modeled control group was established， with 6 mice in each group. Each group received the corresponding drug solution or an equal volume of normal saline intragastically once daily for 21 consecutive days. After the administration， the levels of fasting blood glucose （FBG）， serum lactate dehydrogenase （LDH）， and creatine kinase isoenzyme MB （CK-MB） were measured. Myocardial pathological changes， degree of fibrosis， and myocardial cell ultrastructure were observed. Myocardial cell death index and NCOA4 protein positive index were detected. The protein expression levels of NCOA4， FTH1， ATG8， solute carrier family 7 member 11 （SLC7A11）， and glutathione peroxidase 4 （GPX4） in cardiac tissue were measured. RESULTS Compared with model group， each DMDD group showed significant alleviation of cardiac pathological injury and varying degrees of improvement in the myocardial cell ultrastructure. The FBG and serum LDH and CK-MB levels， the myocardial cell death index and NCOA4 protein positive index，the protein expression levels of NCOA4， FTH1， and ATG8 in cardiac tissue were significantly decreased （ P ＜0.001）， while the protein expression levels of SLC7A11 and GPX4 were significantly increased （ P ＜0.001）. CONCLUSIONS DMDD can reduce blood glucose levels， alleviate myocardial histopathological injury， and inhibit cell death in diabetic mice. The mechanism is associated with inhibiting excessive activation of the NCOA4/FTH1/ATG8 axis and reducing ferritinophagy.

Objective To explore the prognostic factors for patients with descending duodenum gastrointestinal stromal tumors (GIST), analyze the impact of different surgical approaches on prognosis, and develop a predictive model for surgical approach selection. Methods This single-center retrospective cohort study included patients with primary descending duodenum GIST treated in Zhongshan Hospital, Fudan University from January 2010 to January 2015, with follow-up until August 2025. The primary outcomes were incidence of postoperative complications, disease-free survival (DFS) rate, and overall survival (OS) rate. Cox regression and logistic regression were used to identify factors influencing prognosis and surgical approach selection, respectively. A nomogram model for selecting the surgical approach was constructed. Results A total of 78 patients with descending duodenum GIST were included, with age of (56.14±11.76) years. The 1-, 5-, and 10-year OS rates were 100%, 98.7%, and 85.7%, respectively, and the corresponding DFS rates were 100%, 90.9%, and 82.3%. Intraoperative blood loss, postoperative gastroparesis, mucosal ulceration, maximum tumor diameter, and Ki-67-positive cell ratio were independent risk factors for DFS, while maximum tumor diameter and mitotic figure were independent risk factors for OS (P＜0.05). The 10-year DFS rate was higher in the local resection group than in the pancreaticoduodenectomy group (89.45% vs 74.24%; HR＝0.300, P＝0.013), but there was no statistical difference in OS between the two groups. The incidence of postoperative complications in the pancreaticoduodenectomy group was higher than that in the local resection group (P＜0.001). Maximum tumor diameter and distance from tumor to the duodenal papilla were independent factors influencing surgical approach selection. The nomogram model based on these two indices demonstrated good discrimination and accuracy upon internal validation. Conclusions The long-term prognosis of patients with descending duodenal GIST is favorable, and surgical treatment achieves satisfactory outcomes. The nomogram model developed in this study can effectively guide individualized surgical approach selection and provide a reference for clinical decision-making.

Based on the discussion of "eight weak areas" in The Inner Canon of Yellow Emperor （《黄帝内经》）， combined with the typical rash manifestations of atopic dermatitis， it is believed that atopic dermatitis is mostly deficiency-excess complex， and that pathogens intruding eight weak areas are the core of its pathogenesis. The external cause is exterior deficiencies， with heat， wind， dampness and other pathogenic qi attacking. The heart， lungs， kidneys out of balance， and excess pathogen are the internal cause， in which fire constraint and excessive heat are the basis of the disease， the wind invading leads to the progress of the changes， dampness obstructing channels and colla-terals make the condition persistent. Internal and external pathogens combination and retention result to the course of the disease lingering and difficult to cure. The internal treatment is to regulate zang-fu organs， and the formula could use self-prescribed modified Qingrun Tongluo Decoction （清润通络汤）， clearing heart and reducing fire in order to clear the heat and cool the blood， moistening lungs and generating metal to consolidate the exterior and dispel the wind， and nourishing kidneys and draining water to dispel the dampness and activate the collaterals. The external treatment applies maceration， fire acupuncture， wrapping to dredge the eight weak areas and regulate qi and blood in channel， so as to expel pathogens.

Objective:To investigate the expression of lysosome-associated membrane protein 3(LAMP3)and activating transcription factor 4(ATF4)in cervical cancer and their correlation with clinicopathological parameters.Methods:The expression of LAMP3 and ATF4 in normal cervical tissues,cervical intraepithelial lesions,and cervical cancer tissues was detected by SP immunohistochemistry.The relationships between the expression of these two proteins and patient clinicopathological parameters were analyzed,as well as the correlation between LAMP3 and ATF4 expression.Results:LAMP3 was negative or lowly expressed in both normal cervix tissues and high-grade squamous intraepithelial lesions,but highly expressed in cervical cancer tissues(38.3%),showing a statistically significant difference(χ2=14.113,P=0.001).ATF4 was highly expressed in 26.7%of the normal cervix tissues,10.0%of the high-grade squamous intraepithelial lesions,and 58.3%in the cervical cancer tissues,also showing a significant difference(χ2=11.078,P=0.004).In cervical cancer,LAMP3 expression was significantly associated with FIGO stage(χ2=10.139,P=0.006)and lymph node metastasis(χ2=8.475,P=0.004);ATF4 expression was significantly associated with tumor size(χ2=4.578,P=0.032),FIGO stage(χ2=8.971,P=0.009),and lymph node metastasis(χ2=7.881,P=0.005).There was a positive correlation between the expression of LAMP3 and ATF4 in cervical cancer tissues(r=0.388,P=0.002).Conclusion:LAMP3 and ATF4 are highly expressed in cervical cancer tissues and are positively correlated.Both of them play important roles in the development and progression of cervical cancer and could serve as potential therapeutic targets for cervical cancer treatment.

AIM:To investigate the mechanism by which exosomes(EXOs)derived from neural stem cells(NSCs)pretreated with astragaloside IV(ASIV)alleviate brain damage in rats after ischemic stroke.METHODS:Rat NSCs were isolated from fetal rats within 24 h of birth,cultured for 3 d,and subsequently treated with ASIV for additional 5 d.The EXOs from untreated NSCs and ASIV-pretreated NSCs(ASIV-EXOs)were isolated via ultracentrifugation of the cell supernatant.These EXOs were characterized using Western blot to detect specific markers such as CD63,tumor sus-ceptibility gene 101(TSG101)and calnexin.Nanoparticle analysis was employed to determine the size,and the morpholo-gy of the EXOs was observed under electron microscope.Six to eight-week-old SD male rats were randomly assigned to 6 groups:sham group,middle cerebral artery occlusion/reperfusion(MCAO/R)model group,edaravone(EDA)treatment(MCAO/R+EDA)group,EXOs treatement(MCAO/R+EXOs)group and ASIV-EXOs treatment(MCAO/R+ASIV-EXOs)group.Tail vein injections were administered within 2 h following the successful establishment of the MCAO/R model.The Zea Longa method was utilized to evaluate neurological deficits,while the TTC method was employed to assess brain infarc-tion.Pathological changes were examined through HE staining,and TUNEL and caspase-1 immunofluorescence double staining were conducted to detect cellular pyroptosis.Serum levels of interleukin-1β(IL-1β)and IL-18 were measured us-ing ELISA,and Western blot was performed to evaluate the expression of caspase-1,nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),gasdermin D(GSDMD),and IL-18 proteins in the ischemic area of the rat cerebral cortex across all groups.RE-SULTS:The MCAO/R group exhibited significantly higher neurological deficit scores compared to the sham group(P＜0.01)and lower scores in the administered groups relative to the MCAO/R group(P＜0.05).Cerebral infarction was mark-edly increased in the MCAO/R group compared to the sham group(P＜0.01),whereas the infarction area was reduced in the administered groups compared to the MCAO/R group(P＜0.05).Serum levels of IL-1β and IL-18 were significantly el-evated in the MCAO/R group versus the sham group(P＜0.01)and were lower in the administered groups compared to the MCAO/R group(P＜0.01).Moreover,IL-1β and IL-18 levels in the MCAO/R+ASIV-EXOs group were lower than those in the MCAO/R+EXOs group(P＜0.05).HE staining revealed pronounced sieve-like infarction foci in the ischemic area of the rat cerebral cortex in MCAO/R group,characterized by disorganized neuronal arrangements,reduced or absent Nys-trom's vesicles,shrunken or fragmented nuclei,and numerous red neurons.In contrast,drug-treated groups exhibited milder pathological changes with clearer neuronal structures and a significant reduction in red neuron counts.Immunofluo-rescence double staining indicated a significant increase in double-positive cells in the MCAO/R group compared to the sham group(P＜0.01),with a decrease in double-positive cells in the administered groups relative to the MCAO/R group(P＜0.05)and a further reduction in the MCAO/R+ASIV-EXOs group compared to the MCAO/R+EXOs group(P＜0.05).The expression levels of caspase-1,NLRP3,ASC,IL-18 and GSDMD proteins in the ischemic region of the rat cerebral cortex were significantly reduced in the administered groups compared to the MCAO/R group(P＜0.01),with further re-duction observed in the MCAO/R+ASIV-EXOs group compared to the MCAO/R+EXOs group(P＜0.05).CONCLU-SION:Exosomes derived from ASIV-pretreated NSCs attenuate brain damage in ischemic stroke rats,potentially through a mechanism involving the inhibition of pyroptosis mediated by the NLRP3/caspase-1 pathway.

Objective:To explore the effect of Tripterygium glycosides tablets combined with rituximab on the Wnt/β-catenin signaling pathway and nailfold microcirculation in adult patients with nephrotic syndrome (NS).Methods:Eighty adult patients with NS treated in the Affiliated Hospital of Jining Medical College from January 2022 to January 2023 were selected and they were randomly divided into two groups by treatment method, with 40 patients in each group. Both groups were treated with prednisone acetate, while the control group was treated with rituximab. The study group was treated with Tripterygium glycosides tablets based on the control group, and the treatment lasted for 6 months. After treatment for 6 months, the therapeutic effects, Wnt/β-catenin signaling pathway-related mRNA and proteins, nail fold microcirculation index and adverse effects were compared between the two groups.Results:After treatment for 6 months, the total effective rate in the study group was higher than that in the control group : 87.50%(35/40) vs. 67.50%(27/40), there was statistical difference ( χ2 = 4.59, P<0.05). After treatment for 3, 6 months, the levels of Wnt4, β-catenin mRNA and protein were lower than those before treatment, and in the study group were lower than those in the control group :after treatment for 3 months: 4.86 ± 0.55 vs. 6.11 ± 0.70, 5.02 ± 0.68 vs. 5.96 ± 0.74, 3.68 ± 0.61 vs. 4.13 ± 0.66, 3.42 ± 0.55 vs. 4.27 ± 0.59; after treatment for 6 months: 3.12 ± 0.44 vs. 4.59 ± 0.53, 3.05 ± 0.41 vs. 4.11 ± 0.46, 2.00 ± 0.53 vs. 2.86 ± 0.61, 1.24 ± 0.30 vs. 2.67 ± 0.32, there were statistical differences ( P<0.05). After treatment for 3, 6 months, the scores for the flow state and morphology of nailfold microcirculation in the study group were lower than those in the control group: after treatment for 3 months: (1.44 ± 0.26) scores vs. (1.58 ± 0.31) scores, (1.18 ± 0.24) scores vs. (1.49 ± 0.30) scores; after treatment for 6 months: (0.80 ± 0.10) scores vs. (1.38 ± 0.12) scores, (0.97 ± 0.11) scores vs. (1.25 ± 0.12) scores, there were statistical differences ( P<0.05). The incidence of adverse reactions between the two groups had no statistical difference ( P>0.05). Conclusions:The combination of Tripterygium glycosides tablets and rituximab has a definite effect on the treatment of adult NS, which is beneficial for improving nailfold microcirculation. The possible mechanism may be related to the downregulation of the Wnt/β-catenin signaling pathway.

Objective:To explore the effects of mechanical ventilation（MV）at birth transition on lung pathophysiology and pathobiology in a very preterm animal model.Methods:Based on the model of respiratory distress syndrome（RDS）in very preterm rabbits at gestational age 26（term 31）days well established by the research group using perinatal medication and lung-protective ventilation strategies（very low tidal volume 1-3 mL/kg），we conducted a secondary data analysis. The studied rabbits were re-grouped according to the MV length（≤3 h，3-6 h，6-9 h，9-12 h，and >12 h）. The changes in lung mechanics，histopathology，phospholipid biochemistry，and mRNA relative expression of inflammatory/growth factor in lung tissue were evaluated over the time course of MV. The trend of each variable was tested by ANOVA trend test（ F trend）and Jonckheere-Terpstra trend test（ J-T value）with corresponding P value. Results:With the prolonged MV length，there was improved mean dynamic compliance of respiratory system（ F trend=16.722， P trend<0.001），along with decreased mean peak inspiratory pressure（ F trend =42.226， P trend<0.001）. The content of total phospholipids，disaturated phosphatidylcholine（ J-T=1 222，1 197， P trend=0.018，0.034，respectively）and total protein（ J-T=1 247 ，P trend= 0.009）in bronchoalveolar lavage fluid gradually increased. The wet lung weight in the ≤3 h group was significantly higher than in the other groups（ F=6.819， P<0.001）. The lung injury score（total，or hemorrhage，or inflammation）had progressive exacerbation in the ≤3 h，3-6 h and 6-9 h groups. The lung tissue mRNA expression of major proinflammatory cytokines increased modestly over the time groups in contrast to decreased expression of growth factors，of which the change of keratinocyte growth factor reached statistical significance（ J-T=531， P trend =0.034）. Conclusion:In the 26-day very preterm rabbits，with prolonged MV time，the content of surfactant phospholipid in the alveolar increased gradually，the lung compliance and lung fluid clearance gradually improved. Nevertheless，ventilator-induced lung injury remained evolving. The study warrants further study on the pathogenesis and protective strategies of early postnatal acute lung injury and chronic lung disease.

Objective To investigate the effects of scribble planar cell polarity protein(SCRIB)on proliferation,apoptosis,and autophagy of glioblastoma(GBM)and elucidate its potential underlying mechanisms.Methods The expression level of SCRIB in GBM tissue was queried through the Biomarker Exploration of Solid Tumors(BEST)database.Lentivirus-mediated shRNA interference was employed to downregulate SCRIB expression in human glioblastoma cell lines U87 and U251,which were divided into negative control group(mock)and SCRIB shRNA interference groups(kd1 and kd2).SCRIB expression levels were detected using Western blotting(WB)and quantitative polymerase chain reaction(qPCR).EdU incorporation and cell apoptosis rates were detected by flow cytometry(FCM).CCK-8 assay was used to detect the proliferation vitality of U87 and U251 cells,and WB was used to detect the expression of proliferation-related proteins.Immunofluorescence(IF)staining was conducted to detect the expression of autophagy-related proteins LC3 and p62,followed by quantitative analysis across multiple fields.WB was also used to detect the expression levels of LC3,p62,and proteins in the JAK-STAT3 signaling pathway.Results Compared with that of normal tissues,SCRIB mRNA expression level was significantly upregulated in GBM tissues(P＜0.05).FCM results showed that EdU incorporation rates were significantly reduced(P＜0.001)while cell apoptosis rates were markedly increased(P＜0.001)in U87 and U251 cells with SCRIB knockdown.CCK-8 results indicated that compared with the mock group,the proliferation vitality of U87 and U251 cells in the SCRIB knockdown group was significantly downregulated(P＜0.001).IF staining showed that LC3 fluorescence aggregation was significantly enhanced(P＜0.001),while p62 fluorescence aggregation was significantly reduced(P＜0.001)in the SCRIB knockdown group.WB results showed that compared with the mock group,the protein expression levels of p27,LC3,p-JAK2 and p-STAT3 were upregulated,while C-Myc,Cyclin D1,MCM,PCNA and p62 were downregulated,with statistically significant differences(P＜0.05).Conclusion Downregulation of SCRIB may induce autophagy and apoptosis in glioblastoma cells by inhibiting the JAK-STAT3 signaling pathway,thereby suppressing cell proliferation.

Objective:To investigate the independent risk factors for the occurrence of early urinary incontinence after Holmium laser enucleation of the prostate(HoLEP), and to construct a clinical risk predictive model for postoperative urinary incontinence.Methods:A retrospective analysis was conducted on the clinical data of 384 patients who underwent HoLEP between February 2019 and July 2024 at the Second Affiliated Hospital of Zhengzhou University. The cohort had a mean age of (68.3 ± 6.5) years, with a body mass index (BMI) of 22.45 (20.11, 24.39) kg/m 2. The median duration of lower urinary tract symptoms was 60 (36, 60) months. Of the patients, 104 (27.1%) had a history of diabetes mellitus, 139 (36.2%) had hypertension, and 54 (14.1%) had a preoperative indwelling urinary catheter. Additionally, 136 patients (35.4%) had a preoperative prostate-specific antigen (PSA) level ≥ 4 ng/ml, and 197 patients (51.3%) had a preoperative residual urine volume ≥ 50 ml. The International Prostate Symptom Score (IPSS) was ≥ 19 in 227 cases (59.1%). Preoperative detrusor instability was observed in 169 cases (44.0%), with a median maximal urinary flow rate of 5.9 (4.5, 9.3) ml/s and a median urinary flow rate of 4.0 (3.4, 7.3) ml/s. Moreover, 148 cases (38.5%) had a preoperative prostate volume ≥ 65 ml, and the preoperative median maximum urethral length (MUL) was 13.99 (12.40, 16.24) mm. Postoperative follow-up allowed for division of the patients into two groups: those with recovery of urinary control function and those with early postoperative urinary incontinence. The general characteristics of both groups were compared. Independent risk factors for early postoperative urinary incontinence were identified through multifactorial logistic regression. Variables with statistically significant differences were included in a column chart model created using R software. Internal validation was performed through repeated sampling with the Bootstrap method to assess the model's discriminative ability. Calibration curves were plotted to examine the consistency between predicted and actual outcomes, and the Hosmer-Lemeshow test was used to evaluate the model's fit. Results:This study included 384 patients, with 313 in the urinary control function recovery group and 71 in the early incontinence group. There were statistically significant difference between the two groups in age [≥70 years old: 91 (29.1%) vs. 33 (46.5%)], prostate volume [≥65 ml: 110 (35.1%) vs. 38 (53.5%)], MUL [14.21 (12.63, 16.24) mm vs. 13.12 (12.21, 13.95) mm], and non-inhibitory contraction of the urethra muscle in both groups [125 (39.9%) vs. 44 cases (62.0%)] ( P < 0.05). No significant differences were observed between the two groups in terms of BMI, disease duration, history of diabetes mellitus, preoperative catheterization, IPSS, preoperative PSA, residual bladder urine volume, maximum urinary flow rate, average urinary flow rate, operative time, or duration of indwelling urinary catheterization ( P > 0.05). Multifactorial logistic regression analysis revealed that age ≥ 70 years ( OR = 0.414, 95% CI 0.230-0.746, P = 0.003), prostate volume ≥ 65 ml ( OR=0.451, 95% CI 0.251-0.812, P=0.008), MUL( OR=0.688, 95% CI 0.590-0.802, P<0.001), and detrusor instability, uninhibited detrusor contraction ( OR=0.526, 95% CI 0.279-0.994, P=0.048) were independent risk factors for early postoperative urinary incontinence following HoLEP. A prediction model was developed based on these findings, and internal validation showed a C-index of 0.753. The calibration curve was close to the ideal curve, indicating that the model has good predictive performance. Conclusions:Age ≥70 years, prostate volume ≥65 ml, MUL, and uninhibited contraction of the urethra muscle were independent influences on early urinary incontinence after HoLEP, and the nomogram constructed in this way had good predictive performance for the risk of developing early urinary incontinence after HoLEP.

Objective:To investigate the sero-conversion rate of HIV antibody and influencing factors in cross-border couples in Dehong Dai and Jingpo Autonomous Prefecture(Dehong).Methods:A cohort design was used to recruit HIV-negative people in cross-border couples in Dehong in 2017. Follow-up was conducted in 2023, and questionnaire survey and HIV test were carried out to calculate the sero-conversion rate of HIV antibody. Univariate and multivariate logistic regression models were used to analyze the influence factors for HIV infections.Results:A total of 36 278 HIV-negative persons in cross-border couples were included in the 2017 baseline survey, of whom 22 438 (61.9%) were tested in follow-up in 2023. The sero-conversion rate between 2017 and 2023 was 0.51% (115/22 438). Multivariate logistic regression analysis showed that length of marriage <6 years, Jingpo ethnic group, education level of primary school or below, drug use, illegal marriage and HIV infected spouse were the risk factors of HIV infection in male spouses, and length of marriage <6 years, Jingpo ethnic group, illegal marriage and HIV infected spouse were the risk factors in female spouses.Conclusions:The sero-conversion rate of HIV antibody in cross-border couples in Dehong was relatively high. HIV infection was mainly caused by secondary transmission in the couples, and men might also be infected through drug use. It is necessary to strengthen the registration and management of cross-border couples, especially the couples with discordant HIV infection status, and the intervention in drug users to reduce the risk for secondary transmission of HIV in the cross-border couples.