ObjectiveTo explore the role of the histone deacetylase Sirtuin-1 （SIRT1）/p53 signaling pathway in promoting apoptosis of non-small cell lung cancer cells （NSCLC） induced by the co-stimulatory molecule B7 homolog 3 （B7-H3）. MethodsThe GEPIA 2 platform was used for survival analysis of NSCLC patients based on B7⁃H3 gene expression levels. The Gene Enrichment Analysis （GSEA） method was used to analyze the enrichment characteristics of B7⁃H3 molecules in the gene set of cell apoptosis. In the non-small cell lung cancer A549 cell line， B7⁃H3 was knocked down， and the protein expression levels of SIRT1 and p53 were detected by Western blot. B7⁃H3 was overexpressed in A549 cells and the apoptosis rate was analyzed by flow cytometry after Annexin V/PI double staining. Overexpression of B7⁃H3 and knockdown of SIRT1 were performed in A549 cell line. The expression levels of p53 and apoptosis-related proteins B-cell lymphoma/leukemia-2 （Bcl-2） and Bcl-2-associated X protein （Bax） were detected respectively by Western blot. Cell apoptosis rate was analyzed by flow cytometry after Annexin V/PI double staining. ResultsThe overall survival of the B7-H3 high-expression group was significantly lower than that of the low-expression group （P<0.01）. B7-H3 was significantly enriched in the cell apoptosis signaling pathway and the p53 signaling pathway （P<0.05）. Compared with the control group， the expression of SIRT1 was significantly downregulated， and p53 was significantly upregulated in the B7⁃H3 knockdown group （both P<0.001）. Overexpression of B7-H3 significantly up-regulated SIRT1 protein expression （P<0.05）， down-regulated p53 expression （P<0.01）， and markedly increased the Bcl-2/Bax ratio of apoptosis-related proteins （P<0.001）. The results of Annexin V/PI double staining showed that the apoptosis rate of A549 cells with overexpressed B7⁃H3 decreased （the apoptosis rate of the control group was 26.72%±4.13%， while that of the B7⁃H3 overexpression group was 13.87%±0.82%； P<0.01）. In B7-H3-overexpressing cell lines， SIRT1 knockdown significantly reversed apoptosis （P<0.05）， up-regulated p53 protein expression （P<0.001）， and markedly reduced the Bcl-2/Bax ratio （P<0.001）. ConclusionB7-H3 molecule inhibits the apoptosis of non-small cell lung cancer cells via the SIRT1/p53 signaling pathway.

Purpose: Adjuvant pembrolizumab improved disease-free survival (DFS) and overall survival (OS) versus placebo in participants with renal cell carcinoma (RCC) at increased risk of recurrence after nephrectomy in the global phase 3 KEYNOTE-564 study. This post hoc subgroup analysis evaluated the efficacy and safety of adjuvant pembrolizumab in East Asian (Japan, South Korea, and Taiwan) participants enrolled in KEYNOTE-564. Materials and Methods: Eligible participants were randomly assigned 1:1 to receive adjuvant pembrolizumab 200 mg or placebo intravenously every 3 weeks for ≤ 17 cycles. The primary endpoint was DFS by investigator assessment. OS was a key secondary endpoint. Safety was a secondary endpoint. Results: The East Asian subgroup included 126 participants (pembrolizumab, n=58; placebo, n=68). Median follow-up was 62.1 months (range, 49.6 to 73.0 months). Hazard ratio for DFS with pembrolizumab versus placebo was 0.70 (95% confidence interval 0.41 to 1.20). Median DFS was not reached with pembrolizumab versus 58.8 months with placebo; estimated 48-month rate was 61.3% versus 51.2%. Hazard ratio for OS was 0.47 (95% confidence interval, 0.15 to 1.49). Median OS was not reached with pembrolizumab and placebo; estimated 48-month rate was 94.8% versus 91.2%. Treatment-related adverse events occurred in 70.7% of participants (29.3% grade 3 or 4) receiving pembrolizumab and 36.8% of participants (0.0% grade 3 or 4) receiving placebo. No pembrolizumab-related deaths occurred. Conclusion In the KEYNOTE-564 East Asian subgroup, adjuvant pembrolizumab provided DFS and OS benefits versus placebo and had a safety profile consistent with the global results. These results further support pembrolizumab as adjuvant treatment for East Asian patients with RCC at increased risk of recurrence after nephrectomy.

The introduction of immunotherapy has significantly improved the pathological complete response (pCR) rate and tumor downstaging effect in patients receiving neoadjuvant therapy for gastric cancer, while simultaneously presenting new challenges and opportunities for surgical decision-making. The recommended number of cycles for neoadjuvant therapy is 2 to 4 cycles, and the recommended time interval for surgery is within 4 to 6 weeks after the last treatment. Laparoscopic and robotic-assisted minimally invasive surgeries have demonstrated relative advantages in postoperative recovery and safety. For cases achieving pCR or significant tumor regression after immunotherapy, active function-preserving surgeries or enrollment in clinical trial cohorts may be explored. Basic research indicates that preserving unaffected lymph nodes may maintain immune activity, challenging the traditional D2 lymphadenectomy scope, which requires further clinical evidence. Neoadjuvant immunotherapy has not significantly increased perioperative complications. This article aims to discuss the core issues in surgical decision-making for gastric cancer after neoadjuvant therapy, providing a detailed analysis from the perspectives of surgical timing, approach, scope, and complication management, with the hope of offering more references for surgical decision-making after neoadjuvant therapy.

Objective To explore the value of the combined detection of long intergenic non-coding RNA(RNA LINC)00665 and carbohydrate antigen 153(CA153)in the diagnosis and prognosis assessment of breast cancer.Methods 50 breast cancer patients admitted to Jiujiang First People's Hospital were selected to be included in breast cancer group from January to December 2023,50 breast fibroadenoma patients treated in the hospital during the same period of time were selected to be included in breast fibroadenoma group,and another 50 female healthy individuals undergoing physical examination in the hospital during the same period of time were selected to be control group.The clinical data of the enrolled patients were collected,and the levels of LINC00665 and CA153 were detected by reverse transcription quantitative polymerase chain reaction and electrochemiluminescence respectively.The differences in the expression levels of LINC00665 and CA153 among three groups were compared,and the correlation between the expression levels of serum LINC00665 and CA153 was analyzed by Spearman correlation analysis;The diagnostic value of LINC00665,CA153 and the combined detection of the two in the diagnosis of breast cancer was analyzed by receiver operating characteristic(ROC)curve,and the factors affecting the prognosis of breast cancer were analyzed by multifactorial regression.Results Compared with control group,serum LINC00665 and CA153 expression levels were higher in breast cancer group,and serum LINC00665 expression levels were higher in breast fibroadenoma group.Serum LINC00665 and CA153 expression was correlated with TNM stage,pathological type,and lymph node metastasis of breast cancer(P＜0.05).Spearman correlation analysis showed that there was a linear positive correlation between serum LINC00665 and CA153 expression in patients with breast cancer(r=0.651,P＜0.05).ROC curve analysis showed that the value of combined diagnosis of LINC00665 and CA153 was higher than that of individual diagnosis(P＜0.05).The results of multifactorial regression analysis showed that LINC00665,CA153,TNM stage,and lymph node metastasis were independent risk factors affecting the prognosis of breast cancer patients(P＜0.05).Conclusion The higher expression levels of serum LINC00665 and CA153 in breast cancer patients were correlated with TNM stage,pathologic type,and lymph node metastasis,which can be used in the diagnosis and prognosis evaluation of breast cancer.

Objective To explore the value of the combined detection of long intergenic non-coding RNA(RNA LINC)00665 and carbohydrate antigen 153(CA153)in the diagnosis and prognosis assessment of breast cancer.Methods 50 breast cancer patients admitted to Jiujiang First People's Hospital were selected to be included in breast cancer group from January to December 2023,50 breast fibroadenoma patients treated in the hospital during the same period of time were selected to be included in breast fibroadenoma group,and another 50 female healthy individuals undergoing physical examination in the hospital during the same period of time were selected to be control group.The clinical data of the enrolled patients were collected,and the levels of LINC00665 and CA153 were detected by reverse transcription quantitative polymerase chain reaction and electrochemiluminescence respectively.The differences in the expression levels of LINC00665 and CA153 among three groups were compared,and the correlation between the expression levels of serum LINC00665 and CA153 was analyzed by Spearman correlation analysis;The diagnostic value of LINC00665,CA153 and the combined detection of the two in the diagnosis of breast cancer was analyzed by receiver operating characteristic(ROC)curve,and the factors affecting the prognosis of breast cancer were analyzed by multifactorial regression.Results Compared with control group,serum LINC00665 and CA153 expression levels were higher in breast cancer group,and serum LINC00665 expression levels were higher in breast fibroadenoma group.Serum LINC00665 and CA153 expression was correlated with TNM stage,pathological type,and lymph node metastasis of breast cancer(P＜0.05).Spearman correlation analysis showed that there was a linear positive correlation between serum LINC00665 and CA153 expression in patients with breast cancer(r=0.651,P＜0.05).ROC curve analysis showed that the value of combined diagnosis of LINC00665 and CA153 was higher than that of individual diagnosis(P＜0.05).The results of multifactorial regression analysis showed that LINC00665,CA153,TNM stage,and lymph node metastasis were independent risk factors affecting the prognosis of breast cancer patients(P＜0.05).Conclusion The higher expression levels of serum LINC00665 and CA153 in breast cancer patients were correlated with TNM stage,pathologic type,and lymph node metastasis,which can be used in the diagnosis and prognosis evaluation of breast cancer.

Objective To investigate the risk factors for postoperative pulmonary embolism in patients with spontaneous cerebral hemorrhage,and construct and verify the nomogram model.Methods A retrospective cohort study was conducted on 558 patients admitted in the First Affiliated Hospital of Chongqing Medical University and the Three Gorges Hospital Affiliated to Chongqing University.And 393 of them who hospitalized from January 2015 to January 2021 were assigned into a modeling group,and the other 165 patients from February 2021 to January 2023 into a validation group.Univariate and multivariate stepwise logistic regression analyses were used to screen out the risk factors associated with pulmonary embolism after spontaneous cerebral hemorrhage surgery.Then a nomogram model was build based on these factors and verified.Results Based on age,blood loss,Glasgow coma scale(GCS)score,surgical treatments,levels of fibrin degradation products,D-dimer and hemoglobin,plasma osmolality,and deep vein thrombosis,a risk model of pulmonary embolism was built.Receiver operating characteristic(ROC)curve analysis showed the model had good discriminability for the presence of pulmonary embolism,and the area under the curve(AUC)value was 0.908.Hosmer-Lemeshow goodness-fit test indicated that the model had a good fit to the verification set(Chi-square=14.805,df=8,P=0.063),the correction curve was close to the ideal curve,and the prediction probability of the model was close to the actual occurrence probability,suggesting the model having good accuracy.Decision curve analysis revealed that the established nomogram model can get benefits under a large range of threshold probabilities.Conclusion We develop a prediction model for postoperative pulmonary embolism in patients with spontaneous cerebral hemorrhage after surgical treatment,which shows good prediction performance in both the training and validation groups,and can be used for accurate,prompt and quick identification for the occurrence of pulmonary embolism in clinical practice.

Objective:To investigate the role of complement C3a receptor in the diabetic nephropathy pathogenesis of db/db mice, and to provide a new target for prevention and treatment of diabetic nephropathy.Methods:Twelve 8-week-old male mice with type 2 diabetes mellitus (db/db mice) and 6 wild-type (db/m) mice were reared in the special pathogen free environment. The mice were grouped into db/m group, db/db group and C3a receptor antagonist group, with 6 mice in each group. db/db model mice were intraperitoneally injected with C3a receptor antagonist (SB290157, 10 mg/kg) once every two days for 8 weeks in C3a receptor antagonist group. Blood and urine samples were collected, and body weight of mice, fasting blood glucose, serum creatinine, blood urea nitrogen, urinary microalbumin/urinary creatinine and urinary N-acetyl-β- D-glucosaminidase (NAG) were detected. Renal tissues were collected, and HE, PAS and Masson stainings were used to observe the pathological changes. Immunohistochemistry, immunofluorescence and Western blotting were used to detect the protein expression levels of C3 and C3a receptor. Western blotting was used to analyze the protein expression levels of kidney injury molecule-1 (Kim-1), α-smooth muscle actin (α-SMA), zonula occluden-1 (ZO-1), vimentin and E-cadherin in renal tissues. Immunofluorescence was used to analyze the protein expression levels and distribution of α-SMA, ZO-1 and Kim-1, and immunohistochemistry was used to analyze the protein expression levels of interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α). TUNEL assay was used to detect apoptotic cells in renal tissues. Results:Compared with db/m group, body weight, fasting blood glucose, urinary microalbumin/urinary creatinine and urinary NAG in db/db group were significantly higher, while these indicators in C3a receptor antagonist group were slightly lower than those in db/db group (all P<0.01). There were no significant differences in serum creatinine and blood urea nitrogen among the three groups (all P>0.01). Compared with db/m group, db/db group had glomerular hypertrophy, necrosis and exfoliation of renal tubular epithelial cells, and dilation of renal tubules, and C3 and C3a receptor protein expression levels were higher (both P<0.01). Compared with db/db group, C3a receptor antagonist group had less glomerular lesions, mild necrosis of renal tubular epithelial cells and less tubular dilation. Compared with db/m group, the protein expression levels of Kim-1, IL-1 and TNF-α in kidney tissues of db/db group were significantly higher, while Kim-1, IL-1 and TNF-α in C3a receptor antagonist group were significantly lower than those in db/db group (all P<0.01). Compared with db/m group, the protein expression levels of α-SMA and vimentin of renal tubular epithelial cells in db/db group were significantly higher, while the protein expression levels of ZO-1 and E-cadherin were significantly lower (all P<0.01). Compared with db/db group, the protein expression levels of α-SMA and vimentin of renal tubular epithelial cells in C3a receptor antagonist group were significantly lower, and the protein expression levels of ZO-1 and E-cadherin were significantly higher (all P<0.01). Compared with db/m group, the number of apoptotic cells of kidney tissues in db/db group was increased, while the number of apoptotic cells in C3a receptor antagonist group was reduced compared with db/db group. Conclusions:The expression levels of C3 and C3a receptor of kidney tissues in db/db mice are significantly increased. Antagonistic C3a receptor can reduce the body weight, blood glucose, urinary microalbumin/urinary creatinine and urinary NAG, alleviate renal pathological injury, inhibit renal tissue inflammation, apoptosis and renal tubule epithelial-mesenchymal transition in db/db mice.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective To explore the feasibility of peritoneal dialysis catheter placement assisted by flexible ureteroscope.Methods A retrospective analysis was conducted on clinical data of 54 cases of end-stage renal disease receiving peritoneal dialysis catheter placement from May 2019 to March 2023.The placement method was chosen by the patient.In the conventional group,23 cases were guided by a metal guide wire for insertion of the peritoneal dialysis catheter,while in the flexible ureteroscope group,31 cases were guided by flexible ureteroscope instead of guide wire for insertion of the peritoneal dialysis catheter.The success rate of catheterization,surgical time,use of postoperative analgesic,complications related to peritoneal dialysis catheter,and postoperative creatinine decrease were compared between the two groups.Results The catheter placement was successfully performed in both groups.The total incidence of complications related to peritoneal dialysis catheter in the flexible ureteroscope group was lower than that in the conventional group[6.5%(2/31)vs.30.4%(7/23),χ2 =3.878,P =0.049].Between the conventional group and the flexible ureteroscope group,there were no statistically significant differences in the surgical time,postoperative analgesic usage,and the decrease of creatinine at 2 weeks after surgery(P>0.05).The median postoperative follow-up period was10 months(range,3-24 months)in the two groups,and there were no complications such as peritoneal leakage,intestinal perforation,or intraperitoneal bleeding.Conclusion The placement of peritoneal dialysis catheter guided by the flexible ureteroscope instead of metal guide wire is a safe,visible,and accurate method,which can reduce complications related to peritoneal dialysis catheter,and detect and manage comorbidities in the abdominal cavity.