Ischemic stroke is the leading cause of death and disability among adults worldwide. T lymphocytes can be divided into αβT cells and γδT cells. Among them, αβT cells can be further divided into subgroups such as CD4? T cells, CD8? T cells, and natural killer (NK) cells. In CD4? T cells, T helper cells (Th) 1 and Th17 secrete pro-inflammatory cytokines, which can exacerbate ischemic brain injury; Th2 secretes anti-inflammatory factors, which can improve neurological function. Regulatory T cells (Tregs) exert neuroprotective effects through various mechanisms. CD8? T cells exacerbate ischemic brain injury by secreting cytokines and releasing granzyme, while NK cells can cause neuronal damage and blood-brain barrier damage by secreting interferon-γ. In addition, interleukin-17 secreted by γδT cells also plays a significant pro-inflammatory role in the pathological process of stroke. Therefore, a deeper understanding of the role of T lymphocytes can provide new ideas for the treatment of ischemic stroke.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective To investigate the correlation of postoperative cytokine levels with infarct size and reperfusion injury in acute myocardial infarction(AMI)patients having achieved success-ful recanalization after PCI.Methods Clinical data of 164 AMI patients who underwent successful PCI in our department between March 2022 and March 2024 were collected and retrospectively analyzed.The levels of IL-6 and TNF-α were measured at 1 d after PCI,and base on the cutoff level,the patients were categorized into a high IL-6 group(≥5.72 ng/L,93 cases)and a low IL-6 group(＜5.72 ng/L,71 cases),and also into a high TNF-α group(≥5.27 ng/L,108 cases)and a low TNF-α group(＜5.27 ng/L,56 cases).General information,infarct volume and reperfusion injury were compared between the groups.Multivariate logistic regression analysis was used to identify the influencing factors of IL-6 and TNF-α.Pearson correlation analysis was employed to assess the correlation of IL-6/TNF-α levels with infarct size,while Spearman correlation analysis was utilized to evaluate their correlation with reperfusion injury.ROC curves were plotted to de-termine the predictive value of the two cytokines for reperfusion injury.Results The high IL-6 group showed significantly higher ratio of diabetes,larger proportion of reperfusion injury,greater infarct size,increased cardiac troponin I(cTnI)level,and longer PCI time than the low IL-6 group(P＜0.01),and similar results were seen in the high TNF-α group when compared with the low TNF-α group(P＜0.01).Multivariate logistic regression analysis identified PCI time(OR=3.492,95％CI:2.253-5.411),cTnI(OR=5.126,95％CI:1.104-23.787),infarct size(OR=1.178,95％CI:1.026-1.352),and reperfusion injury(OR=3.283,95％CI:1.099-9.809)as independent risk factors for elevated IL-6,while PCI time(OR=3.101,95％CI:2.027-4.742),cTnI(OR=3.498,95％CI:1.730-7.072),infarct size(OR=1.234,95％CI:1.051-1.449),and reperfusion injury(OR=3.518,95％CI:1.017-12.170)as independent risk factors for increased TNF-α.Pear-son and Spearman analysis showed that the IL-6 and TNF-α levels were positively correlated with infarct volume and reperfusion injury(P＜0.01).ROC curve analysis indicated that the AUC value of IL-6 and TNF-α in predicting reperfusion injury was 0.693(95％CI:0.616-0.762)and 0.681(95％CI:0.604-0.752),with a sensitivity of 60.49％and 81.25％,and a specificity of 71.08％and 78.81％,respectively.Conclusion In AMI patients after PCI recanalization,elevated IL-6 and TNF-α levels are positively correlated with infarct size and reperfusion injury,and the levels can serve as biomarkers for assessing the occurrence of reperfusion injury.

Objective To investigate the correlation of postoperative cytokine levels with infarct size and reperfusion injury in acute myocardial infarction(AMI)patients having achieved success-ful recanalization after PCI.Methods Clinical data of 164 AMI patients who underwent successful PCI in our department between March 2022 and March 2024 were collected and retrospectively analyzed.The levels of IL-6 and TNF-α were measured at 1 d after PCI,and base on the cutoff level,the patients were categorized into a high IL-6 group(≥5.72 ng/L,93 cases)and a low IL-6 group(＜5.72 ng/L,71 cases),and also into a high TNF-α group(≥5.27 ng/L,108 cases)and a low TNF-α group(＜5.27 ng/L,56 cases).General information,infarct volume and reperfusion injury were compared between the groups.Multivariate logistic regression analysis was used to identify the influencing factors of IL-6 and TNF-α.Pearson correlation analysis was employed to assess the correlation of IL-6/TNF-α levels with infarct size,while Spearman correlation analysis was utilized to evaluate their correlation with reperfusion injury.ROC curves were plotted to de-termine the predictive value of the two cytokines for reperfusion injury.Results The high IL-6 group showed significantly higher ratio of diabetes,larger proportion of reperfusion injury,greater infarct size,increased cardiac troponin I(cTnI)level,and longer PCI time than the low IL-6 group(P＜0.01),and similar results were seen in the high TNF-α group when compared with the low TNF-α group(P＜0.01).Multivariate logistic regression analysis identified PCI time(OR=3.492,95％CI:2.253-5.411),cTnI(OR=5.126,95％CI:1.104-23.787),infarct size(OR=1.178,95％CI:1.026-1.352),and reperfusion injury(OR=3.283,95％CI:1.099-9.809)as independent risk factors for elevated IL-6,while PCI time(OR=3.101,95％CI:2.027-4.742),cTnI(OR=3.498,95％CI:1.730-7.072),infarct size(OR=1.234,95％CI:1.051-1.449),and reperfusion injury(OR=3.518,95％CI:1.017-12.170)as independent risk factors for increased TNF-α.Pear-son and Spearman analysis showed that the IL-6 and TNF-α levels were positively correlated with infarct volume and reperfusion injury(P＜0.01).ROC curve analysis indicated that the AUC value of IL-6 and TNF-α in predicting reperfusion injury was 0.693(95％CI:0.616-0.762)and 0.681(95％CI:0.604-0.752),with a sensitivity of 60.49％and 81.25％,and a specificity of 71.08％and 78.81％,respectively.Conclusion In AMI patients after PCI recanalization,elevated IL-6 and TNF-α levels are positively correlated with infarct size and reperfusion injury,and the levels can serve as biomarkers for assessing the occurrence of reperfusion injury.

Objective To investigate the impact of high mobility group box 1(HMGB1)on hydrogen peroxide(H2O2)-induced DNA damage and senescence in lens epithelial cells(LECs)under oxidative stress conditions.Methods Fluorescent quantitative real-time polymerase chain reaction(RT-PCR)technology was used to detect the mRNA expres-sion of HMGB1 in the anterior capsule tissue of patients with age-related cataract(ARC group)and epiretinal membrane(control group).Western blot analysis was employed to examine the changes in the protein expression of HMGB1 in the LEC line SRA01/04 after treatment with varying concentrations of H2O2(0,100,200,and 400 μmol·L-1).The optimal concentration was selected for subsequent establishment of a cellular oxidative damage model.The cultured SRA01/04 cells were divided into three groups:Control(untreated),HA(transfected with the control plasmid HA),and OE-HMGB1 groups(transfected with the HMGB1 plasmid).The mRNA and protein expression levels of HMGB1 were detected by RT-PCR and Western blot.The cultured SRA01/04 cells were divided into three groups:H2O2(treated with 400 μmol·L-1 H2O2),H2O2+HA(transfected with the control plasmid HA and simultaneously treated with 400 μmol·L-1 H2O2),and H2O2+OE-HMGB1 groups(transfected with the HMGB1 plasmid and simultaneously treated with 400 μmol·L-1 H2O2).Immunofluorescence was used to detect DNA oxidative damage in cells from each group.Western blot analysis was per-formed to assess the protein expression levels of phosphorylated histone H2A(γH2A),tumor protein p53(P53),cyclin-dependent kinase inhibitor 1A(P21),and cyclin-dependent kinase inhibitor 2A(P16)in cells from each group.Additional-ly,senescence-associated-β-galactosidase(SA-β-gal)staining was conducted to detect senescent changes in cells from each group.Results RT-PCR results indicated that the relative mRNA expression level of HMGB1 in the anterior capsule tissue of the ARC group was significantly decreased,compared with that in the control group(P＜0.001).Furthermore,in the H2O2-induced oxidative damage model,the relative protein expression level of HMGB1 decreased with the increase of the concentration of H2O2.Both RT-PCR and Western blot analyses revealed that the mRNA and protein expression levels of HMGB1 were both significantly elevated in the OE-HMGB1 group,compared with those in the HA group(both P＜0.001).The immunofluorescence staining results demonstrated that the protein expression of γH2A and the fluorescence intensity in the H2O2+OE-HMGB1 group were significantly decreases,compared with those in H2O2 and H2O2+HA groups(all P＜0.001).SA-β-gal staining results showed that the H2O2+OE-HMGB1 group had significantly less cells stained by SA-β-gal than H2O2 and H2O2+HA(both P＜0.001).Additionally,Western blot analysis revealed that,compared with those in H2O2 and H2O2+HA groups,the relative expression levels of senescence-associated proteins P53,P21,and P16 were significantly decreased in the H2O2+OE-HMGB1 group(all P＜0.01).Conclusion HMGB1 inhibits the accumula-tion of damaging DNA and senescence in LECs by enhancing DNA damage repair capabilities.

Renal carcinoma，a common malignant tumor of the urinary system，poses a significant disease burden . With innovations in artificial intelligence（AI）deep learning algorithms and the expanded clinical use of domestically developed surgical robots，renal carcinoma diagnosis and treatment have seen multi-dimensional breakthroughs. In molecular imaging and pathology diagnosis，AI drives multi-omics fusion diagnosis，while molecular imaging guides precise treatment. In surgical technology，5G-enabled telesurgery transcends geographical limits，and immersive virtual reality technology boosts surgical accuracy. Targeted therapy and immunotherapy revolutionizes advanced renal carcinoma treatment and opens up new therapeutic frontiers. Radiotherapy and energy therapy have become more precise. Despite these advances，bottlenecks persist in diagnosis and treatment. Future progress requires focusing on technological integration，clinical translation，and exploration of energy-based therapies to transition from "precise" to "intelligence" in renal carcinoma diagnosis and treatment.

Renal carcinoma，a common malignant tumor of the urinary system，poses a significant disease burden . With innovations in artificial intelligence（AI）deep learning algorithms and the expanded clinical use of domestically developed surgical robots，renal carcinoma diagnosis and treatment have seen multi-dimensional breakthroughs. In molecular imaging and pathology diagnosis，AI drives multi-omics fusion diagnosis，while molecular imaging guides precise treatment. In surgical technology，5G-enabled telesurgery transcends geographical limits，and immersive virtual reality technology boosts surgical accuracy. Targeted therapy and immunotherapy revolutionizes advanced renal carcinoma treatment and opens up new therapeutic frontiers. Radiotherapy and energy therapy have become more precise. Despite these advances，bottlenecks persist in diagnosis and treatment. Future progress requires focusing on technological integration，clinical translation，and exploration of energy-based therapies to transition from "precise" to "intelligence" in renal carcinoma diagnosis and treatment.

Objective To investigate the impact of high mobility group box 1(HMGB1)on hydrogen peroxide(H2O2)-induced DNA damage and senescence in lens epithelial cells(LECs)under oxidative stress conditions.Methods Fluorescent quantitative real-time polymerase chain reaction(RT-PCR)technology was used to detect the mRNA expres-sion of HMGB1 in the anterior capsule tissue of patients with age-related cataract(ARC group)and epiretinal membrane(control group).Western blot analysis was employed to examine the changes in the protein expression of HMGB1 in the LEC line SRA01/04 after treatment with varying concentrations of H2O2(0,100,200,and 400 μmol·L-1).The optimal concentration was selected for subsequent establishment of a cellular oxidative damage model.The cultured SRA01/04 cells were divided into three groups:Control(untreated),HA(transfected with the control plasmid HA),and OE-HMGB1 groups(transfected with the HMGB1 plasmid).The mRNA and protein expression levels of HMGB1 were detected by RT-PCR and Western blot.The cultured SRA01/04 cells were divided into three groups:H2O2(treated with 400 μmol·L-1 H2O2),H2O2+HA(transfected with the control plasmid HA and simultaneously treated with 400 μmol·L-1 H2O2),and H2O2+OE-HMGB1 groups(transfected with the HMGB1 plasmid and simultaneously treated with 400 μmol·L-1 H2O2).Immunofluorescence was used to detect DNA oxidative damage in cells from each group.Western blot analysis was per-formed to assess the protein expression levels of phosphorylated histone H2A(γH2A),tumor protein p53(P53),cyclin-dependent kinase inhibitor 1A(P21),and cyclin-dependent kinase inhibitor 2A(P16)in cells from each group.Additional-ly,senescence-associated-β-galactosidase(SA-β-gal)staining was conducted to detect senescent changes in cells from each group.Results RT-PCR results indicated that the relative mRNA expression level of HMGB1 in the anterior capsule tissue of the ARC group was significantly decreased,compared with that in the control group(P＜0.001).Furthermore,in the H2O2-induced oxidative damage model,the relative protein expression level of HMGB1 decreased with the increase of the concentration of H2O2.Both RT-PCR and Western blot analyses revealed that the mRNA and protein expression levels of HMGB1 were both significantly elevated in the OE-HMGB1 group,compared with those in the HA group(both P＜0.001).The immunofluorescence staining results demonstrated that the protein expression of γH2A and the fluorescence intensity in the H2O2+OE-HMGB1 group were significantly decreases,compared with those in H2O2 and H2O2+HA groups(all P＜0.001).SA-β-gal staining results showed that the H2O2+OE-HMGB1 group had significantly less cells stained by SA-β-gal than H2O2 and H2O2+HA(both P＜0.001).Additionally,Western blot analysis revealed that,compared with those in H2O2 and H2O2+HA groups,the relative expression levels of senescence-associated proteins P53,P21,and P16 were significantly decreased in the H2O2+OE-HMGB1 group(all P＜0.01).Conclusion HMGB1 inhibits the accumula-tion of damaging DNA and senescence in LECs by enhancing DNA damage repair capabilities.

Objective:To investigate the efficacy of mFOLFOX7 regimen systemic chemo-therapy combined with camrelizumab and apatinib for hepatocellular carcinoma (HCC) with Vp4 portal vain tumor thrombus (PVTT).Methods:The single-arm, open, exploratory clinical study was conducted. The clinicopathological data of 15 HCC patients with Vp4 PVTT who were admitted to the Sun Yat-sen Memorial Hospital of Sun Yat-sen University from April 2021 to October 2023 were collected. There were 14 males and 1 female, aged 48(range, 33-67)years. All patients underwent treatment with mFOLFOX7 regimen combined with camrelizumab and apatinib. Observa-tion indicators: (1) clinical efficacy; (2) survival of patients. Measurement data with skewed distribution were represented as M(rang), and count data were described as absolute numbers or percentages. Results:(1) Clinical efficacy. All 15 patients underwent treatment with mFOLFOX7 regimen combined with camrelizumab and apatinib. According to the response evaluation criteria in solid tumors version 1.1, the ratio of objective response, ratio of complete response, ratio of partial response, ratio of disease control, median progression free survival time and median total survival time of the 15 patients were 10/15, 1/15, 9/15, 15/15, not reached and not reached. The median progression free survival time and median total survival time were both >9 months. According to the modified response evaluation criteria in solid tumors, the ratio of objective response, ratio of complete response, ratio of partial response, ratio of disease control, median progression free survival time and median total survival time of the 15 patients were 12/15, 6/15, 6/15, 15/15, not reached and not reached. The median progression free survival time and median total survival time were both >9 months. Of the 15 patients, 7 cases were successfully treated with conversion therapy with the surgical conversion rate as 7/15, and all of them achieved R 0 resection. The other 6 cases were failed in conversion therapy, and there were 2 cases still undergoing conversion therapy. Of the 7 patients with successful conver-sion therapy, 5 cases achieved complete pathological remission, 1 case achieved major pathological remission with 90% of tumor tissue necrosis, and 1 case achieved complete remission through imaging examination, but new liver lesions appeared in multiple locations during further observation which were surgically removed. Results of histopathology examination on the patient confirmed multiple liver metastases. The proportion of treatment-associated adverse reactions in 15 patients was 13/15, with 7/15 having ≥grade 3 adverse reactions, including diarrhea (3/15), neutropenia (2/15), thrombo-cytopenia (2/15), and elevated aspartate aminotransferase (2/15). One patient may experience ≥1 adverse reaction. All patients were improved after symptomatic treatment. (2) Survival of patients. All 15 patients were followed up for 13.0(range, 2.0-31.0)months. During the follow-up period, 3 patients died. One case died of upper gastrointestinal bleeding after achieving partial remission, with a survival time of 7.5 months. One case died of multiple liver metastases of tumor, with tumors accounting for over 70% volume of liver and a survival time of 9.5 months. One case with multiple liver tumors and bilateral lung metastasis died due to disease progression after achieving partial remission, with a survival time of 13.5 months. The postoperative follow-up time for 7 patients undergoing surgical treatment was 14.0(range, 2.0-25.0)months. Of the 7 patients, 1 case experien-ced tumor recurrence 20.0 months after surgery, and 6 cases had no recurrence at last time of the follow-up (3 cases completed treatment and entered follow-up observation). The longest survival time was 31.0 months. Conclusion:The mFOLFOX7 regimen systemic chemotherapy combined with camrelizumab and apatinib for HCC with Vp4 PVTT is safe and feasible.

Objective:To compare the therapeutic effects of partial nephrectomy (PN) and cryoablation (CA) in patients with stage cT 1N 0M 0 renal cell carcinoma (RCC). Methods:A retrospective analysis was conducted on clinical data of patients with stage cT 1N 0M 0 RCC who underwent CA and PN treatment at The First Affiliated Hospital of Naval Medical University and Shanghai Ninth People's Hospital between March 2011 and December 2019. There were 50 cases in the CA group (36 from The First Affiliated Hospital of Naval Medical University and 14 from the Shanghai Ninth People's Hospital), and 1 323 cases in the PN group (all from The First Affiliated Hospital of Naval Medical University). PN included open surgery, laparoscopic surgery, or robotic surgery performed under general anesthesia through the abdominal or retroperitoneal approach. CA included laparoscopic surgery under general anesthesia and percutaneous treatment guided by CT or ultrasound under local anesthesia. Propensity score matching was performed based on baseline data of the patients to obtain balanced samples between the two groups using a 1∶2 nearest-neighbor matching method. After matching, comparisons were made between the two groups in terms of perioperative conditions, overall survival (OS), and recurrence-free survival (RFS). Results:After PSM, patient distributions were closely balanced in baseline data such as gender (male/female: 28/19 cases in CA group and 58/36 cases in PN group), age [66.0(53.0, 75.0) years vs. 59.5(50.0, 69.3) years], body mass index[ (24.1 ± 6.4) kg/m 2 vs. (24.1 ± 3.1) kg/m 2], Charlson comorbidity index [1(0, 2) vs. 1(0, 2)], history of malignant tumors [19.1% (9/47) vs. 17.0% (16/94)], preoperative estimated glomerular filtration rate (eGFR) [85.2(65.5, 97.1) ml/(min·1.73m 2) vs. 87.0(73.4, 100.4) ml/(min·1.73m 2)], and R. E.N.A.L. score [6(5, 7) vs. 7(6, 8)] between CA(n=47) and PN(n=94) group. There were significant differences in operative time [97.5(81.2, 117.5) min vs. 145.0(110.2, 185.0) min, P<0.001], estimated blood loss [85.0(50.0, 100.0) ml vs. 100.0(75.0, 200.0)ml, P=0.021], length of hospital stay [3.0(2.0, 4.0) days vs. 7.6(5.0, 9.0) days, P<0.001] between the CA and the PN group. No significant differences were observed in the incidence of postoperative complications [4.3% (2/47) vs. 5.3% (5/94), P=0.784], the eGFR within one week after surgery [83.7(65.6, 106.6) ml/(min·1.73m 2) vs. 83.2(66.7, 97.7) ml/(min·1.73m 2), P=0.645], the median follow-up time [ 93 (67, 126) months vs. 85 (68, 139) months, P=0.955], the RFS rate[81.8% vs. 96.8%, P=0.074], or the OS rate [85.7% vs. 97.8%, P=0.190] between the CA and the PN group. Conclusions:For patients with cT 1N 0M 0 stage RCC, CA and PN demonstrate comparable oncologic treatment efficacy, while CA offering the advantages of shorter surgical time, shorter hospital stay, and less blood loss.