Objective:To investigate the effect of immune checkpoint inhibitors on reducing residual lymph node metastasis in patients with gastric cancer.Methods:The cohort of this retrospective study comprised patients from Nanfang Hospital of Southern Medical University and the First Affiliated Hospital of Xiamen University who had undergone systemic treatment prior to gastrectomy with D2 lymphadenectomy and had achieved Grade 1 primary tumor regression (TRG1) from January 2014 to December 2023. After exclusion of patients who had undergone preoperative radiotherapy, data of 58 patients (Nanfang Hospital: 46; First Affiliated Hospital of Xiamen University: 12) were analyzed. These patients were allocated to preoperative chemotherapy (Chemotherapy group, N=36 cases) and preoperative immunotherapy plus chemotherapy groups (Immunotherapy group, N=22 cases). There were no significant differences between these groups in sex, age, body mass index, diabetes, tumor location, pathological type, Lauren classification, tumor differentiation, pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, mismatch repair protein status, number of preoperative treatment cycles, or duration of preoperative treatment (all P>0.05). The primary outcome measure was postoperative lymph node downstaging. Secondary outcomes included postoperative depth of invasion by tumor, number of lymph nodes examined, and factors affecting residual lymph node metastasis status. Results:Lymph node downstaging was achieved significantly more often in the Immunotherapy group than the Chemotherapy group (pN0: 90.9% [20/22] vs. 61.1% [22/36]; pN1: 4.5% [1/22] vs. 36.1% [13/36]; pN2: 4.5% [1/22) vs. 0; pN3: 0 vs. 2.8% [1/36], Z=-2.315, P=0.021). There were no significant difference between the two groups in number of lymph nodes examined (40.5±16.3 vs. 40.8±17.5, t=0.076, P=0.940) or postoperative depth of invasion by primary tumor (pT1a: 50.0% [11/22] vs. 30.6% [11/36]; pT1b: 13.6% [3/22] vs. 19.4% [7/36]; pT2: 13.6% [3/22] vs. 13.9% [5/36]; pT3: 13.6% [3/22] vs. 25.0% [9/36]; pT4a: 9.1% [2/22] vs. 11.1% [4/36], Z=-1.331, P=0.183). Univariate analysis revealed that both preoperative treatment regimens were associated with residual lymph node metastasis status in patients whose primary tumor regression was TRG1 (χ 2=6.070, P=0.014). Multivariate analysis incorporated the following factors: pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, number of preoperative treatment cycles, and preoperative treatment duration. We found that a combination of immunotherapy and chemotherapy administered preoperatively was an independent protective factor for reducing residual lymph node metastases in study patients whose primary tumor regression was TRG1 (OR=0.147, 95%CI: 0.026–0.828, P=0.030). Conclusion:Compared with preoperative chemotherapy alone, a combination of preoperative immunotherapy and chemotherapy achieved greater reduction of residual lymph node metastases in the study patients who achieved TRG1 tumor regression in their primary lesions.

Objective:To investigate the effect of immune checkpoint inhibitors on reducing residual lymph node metastasis in patients with gastric cancer.Methods:The cohort of this retrospective study comprised patients from Nanfang Hospital of Southern Medical University and the First Affiliated Hospital of Xiamen University who had undergone systemic treatment prior to gastrectomy with D2 lymphadenectomy and had achieved Grade 1 primary tumor regression (TRG1) from January 2014 to December 2023. After exclusion of patients who had undergone preoperative radiotherapy, data of 58 patients (Nanfang Hospital: 46; First Affiliated Hospital of Xiamen University: 12) were analyzed. These patients were allocated to preoperative chemotherapy (Chemotherapy group, N=36 cases) and preoperative immunotherapy plus chemotherapy groups (Immunotherapy group, N=22 cases). There were no significant differences between these groups in sex, age, body mass index, diabetes, tumor location, pathological type, Lauren classification, tumor differentiation, pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, mismatch repair protein status, number of preoperative treatment cycles, or duration of preoperative treatment (all P>0.05). The primary outcome measure was postoperative lymph node downstaging. Secondary outcomes included postoperative depth of invasion by tumor, number of lymph nodes examined, and factors affecting residual lymph node metastasis status. Results:Lymph node downstaging was achieved significantly more often in the Immunotherapy group than the Chemotherapy group (pN0: 90.9% [20/22] vs. 61.1% [22/36]; pN1: 4.5% [1/22] vs. 36.1% [13/36]; pN2: 4.5% [1/22) vs. 0; pN3: 0 vs. 2.8% [1/36], Z=-2.315, P=0.021). There were no significant difference between the two groups in number of lymph nodes examined (40.5±16.3 vs. 40.8±17.5, t=0.076, P=0.940) or postoperative depth of invasion by primary tumor (pT1a: 50.0% [11/22] vs. 30.6% [11/36]; pT1b: 13.6% [3/22] vs. 19.4% [7/36]; pT2: 13.6% [3/22] vs. 13.9% [5/36]; pT3: 13.6% [3/22] vs. 25.0% [9/36]; pT4a: 9.1% [2/22] vs. 11.1% [4/36], Z=-1.331, P=0.183). Univariate analysis revealed that both preoperative treatment regimens were associated with residual lymph node metastasis status in patients whose primary tumor regression was TRG1 (χ 2=6.070, P=0.014). Multivariate analysis incorporated the following factors: pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, number of preoperative treatment cycles, and preoperative treatment duration. We found that a combination of immunotherapy and chemotherapy administered preoperatively was an independent protective factor for reducing residual lymph node metastases in study patients whose primary tumor regression was TRG1 (OR=0.147, 95%CI: 0.026–0.828, P=0.030). Conclusion:Compared with preoperative chemotherapy alone, a combination of preoperative immunotherapy and chemotherapy achieved greater reduction of residual lymph node metastases in the study patients who achieved TRG1 tumor regression in their primary lesions.

Objective:To investigate the prognostic factors for liver transplantation for hepatocellular carcinoma beyond UCSF criteria but without macrovascular invasion.Methods:A retrospective analysis was performed for the clinical data of the hepatocellular carcinoma patients without macrovascular invasion beyond UCSF criteria who underwent liver transplantation at our center from Jan 2018 to Jun 2023. The receiver operating characteristic curve analysis was performed to assess the predictive power of potential prognosis factors.Results:With this criteria, the 1-, 3-year overall survival rates were 94.1% and 75.0%, respectively, and the 1-, 3-year tumor free survival rates were 82.4% and 38.1%, respectively. The maximum tumor size, number of tumors, AFP, PIVKA-Ⅱ before transplantation, and whether undergo pretransplant down-stage therapy were significant prognostic factors ( P<0.05). Combining the above prognostic factors to construct the receiver operating characteristic curve yielded an area under the curve of 0.967, with a sensitivity and specificity of 0.932, 0.952, respectively. Further, the differentiation, MVI and Ki-67 were significant prognostic factors ( P<0.05). Combining pathological factors to construct the receiver operating characteristic curve yielded an area under the curve of 0.927, with a sensitivity and specificity of 0.769, 1, respectively. Conclusion:The maximum tumor diameter, number of tumors, AFP, PIVKA-Ⅱ before transplantation, and pretransplant down-stage therapy and tumor differentiation, MVI and Ki-67 are all prognostic factors of liver transplantation for hepatocellular carcinoma without macrovascular invasion beyond UCSF criteria.

Objective:To investigate the current status of surgical intervention after conversion therapy for advanced gastric cancer.Methods:The retrospective cross-sectional investigation study was conducted. The investigation was conducted on clinicians who were qualified for the diagnosis and treatment of gastric cancer in 161 hospitals nationwide from December 11 to 22,2023. The questionnaire of "Survey on the Current Status of Surgical Intervention after Conversion Therapy for Advanced Gastric Cancer" was designed and distributed through WeChat based on the software platform of Wenjuanxing. Count data were expressed as absolute numbers and percentages.Results:(1) Results of the questionnaire. Of the 233 clinicians, the percentage of completed questionnaires, recovered questionnaires, and valid questionnaires were all of 100.00%(233/233). (2) Basic information of clinicians. Of the 233 clinicians, there were 213 males and 20 females. The numbers of clinicians aged ≤30 years, 31-40 years, 41-50 years, and >50 years were 1, 47, 109, and 76, respectively. The numbers of surgeons, internists, radiotherapists, and pathologists were 193, 36, 3, and 1, respectively. The numbers of chief physicians, deputy chief physicians, attending physicians, and resident physicians were 133, 75, 21, and 4, respectively. The numbers of clinicians with years of practice as >20 years, 11-20 years, 6-10 years, and ≤5 years were125, 88, 19, and 1, respectively. The numbers of clinicians from provincial-level tertiary general hospitals, provincial-level tertiary specialized oncology hospitals, municipal-level tertiary hospitals, and tertiary hospitals of B and below were 102, 58, 59, and 14, respectively. (3) Conversion therapy of advanced gastric cancer. Of the 233 clinicians, there were 54.94%(128/233) of clinicians whose units had admitted more than 100 gastric cases per year, 81.97%(191/233) of clinicians whose units had experience in surgical resection after conversion therapy of advanced gastric cancer, 66.52%(155/233) of clinicians whose units had proportion of successful surgical resection after conversion therapy of advanced gastric cancer exceeded 5%, and 51.50%(120/233) of clinicians whose units had the proportion of laparoscopic exploration+peritoneal lavage cytology to clarify the tumor stage at the initial diagnosis ≤10%. (4) Strategy selection after conversion therapy for advanced gastric cancer. Of the 233 clinicians, 63.52%(148/233) of them routinely mentioned to patients that they might be able to obtain chance of surgery after conversion therapy. There were 85.41%(199/233), 79.83%(186/233), and 68.67%(160/233) of clinicians considering possible risks as drug resistance, subsequent chemotherapy-immunotherapy or radiotherapy and other related adverse reactions and aggravation of distant toxicity, and distant organ metastasis for advanced gastric cancer patients to continue palliative care after conversion therapy. There were 85.41%(199/233), 50.21%(117/233), and 18.45%(43/233) of clinicians considering choices as multi-disciplinary treatment to evaluate the follow-up treatment strategy, laparoscopic exploration to clarify the possibility of surgery, and continuing the original program of palliative care for follow-up treatment of patients with advanced gastric cancer after conversion therapy. There were 97.85%(228/233) of clinicians considering re-evaluating the possibility of surgical resection when the tumor volume was significantly reduced after conversion therapy. (5) Selection of beneficiary population, treatment modality, and time point of evaluation of benefit for patients undergoing conversion surgery for advanced gastric cancer. A further questionnaire survey was conducted on the 228 clinicians who chose "to consider re-evaluating surgical resection when the volume of tumor reducted significantly after conversion therapy for advanced gastric cancer". There were 94.74%(216/228) of clinicians considering advanced gastric cancer patients with high expression of programmed death receptor ligand 1 as beneficiary population of conversion therapy. There were 82.46%(188/228) of clinicians considering advanced gastric cancer patients with liver oligometastases as beneficiary population of conversion therapy. There were 53.07%(121/228) of clinicians considering two-drug chemotherapy+immunotherapy regimen as preferred for HER2-negative patients, there were 67.54%(154/228) of clinicians considering chemotherapy + trastuzumab + immunotherapy regimen as preferred for HER2-positive patients. There were 83.33%(190/228) of clinicians considering resection treatment after 3-6 cycles of conversion therapy. There were 94.74%(216/228) of clinicians choosing enhanced computed tomography scan to evaluate the efficacy. In terms of tumor sign for laparoscopic surgery after conversion therapy, there were 92.54%(211/228) of clinicians choosing significant shrinkage of the primary focus and its surrounding lymph nodes from baseline. There were 63.16%(144/228) of clinicians choosing surgery after 3-4 weeks of drug withdrawal, and 57.02%(130/228) of clinicians considering to achieve R 0 resection. In terms of patients achieving pathologic complete remission (pCR) after surgery, there were 64.04%(146/228) of clinicians believing that postoperative treatment should be continued for 6-8 cycles of therapy followed by maintenance therapy up to 1 year. For patients with non-pCR, there were 59.65%(136/228) of clinicians believing that 6-8 cycles of postoperative maintenance therapy should be continued until 1 year. Conclusion:Most clinicians in China consider R 0 resection after conversion therapy for patients with advanced gastric cancer, followed by 6-8 cycles of treatment and maintenance therapy for another year.

Objective:To investigate the current status of surgical intervention after conversion therapy for advanced gastric cancer.Methods:The retrospective cross-sectional investigation study was conducted. The investigation was conducted on clinicians who were qualified for the diagnosis and treatment of gastric cancer in 161 hospitals nationwide from December 11 to 22,2023. The questionnaire of "Survey on the Current Status of Surgical Intervention after Conversion Therapy for Advanced Gastric Cancer" was designed and distributed through WeChat based on the software platform of Wenjuanxing. Count data were expressed as absolute numbers and percentages.Results:(1) Results of the questionnaire. Of the 233 clinicians, the percentage of completed questionnaires, recovered questionnaires, and valid questionnaires were all of 100.00%(233/233). (2) Basic information of clinicians. Of the 233 clinicians, there were 213 males and 20 females. The numbers of clinicians aged ≤30 years, 31-40 years, 41-50 years, and >50 years were 1, 47, 109, and 76, respectively. The numbers of surgeons, internists, radiotherapists, and pathologists were 193, 36, 3, and 1, respectively. The numbers of chief physicians, deputy chief physicians, attending physicians, and resident physicians were 133, 75, 21, and 4, respectively. The numbers of clinicians with years of practice as >20 years, 11-20 years, 6-10 years, and ≤5 years were125, 88, 19, and 1, respectively. The numbers of clinicians from provincial-level tertiary general hospitals, provincial-level tertiary specialized oncology hospitals, municipal-level tertiary hospitals, and tertiary hospitals of B and below were 102, 58, 59, and 14, respectively. (3) Conversion therapy of advanced gastric cancer. Of the 233 clinicians, there were 54.94%(128/233) of clinicians whose units had admitted more than 100 gastric cases per year, 81.97%(191/233) of clinicians whose units had experience in surgical resection after conversion therapy of advanced gastric cancer, 66.52%(155/233) of clinicians whose units had proportion of successful surgical resection after conversion therapy of advanced gastric cancer exceeded 5%, and 51.50%(120/233) of clinicians whose units had the proportion of laparoscopic exploration+peritoneal lavage cytology to clarify the tumor stage at the initial diagnosis ≤10%. (4) Strategy selection after conversion therapy for advanced gastric cancer. Of the 233 clinicians, 63.52%(148/233) of them routinely mentioned to patients that they might be able to obtain chance of surgery after conversion therapy. There were 85.41%(199/233), 79.83%(186/233), and 68.67%(160/233) of clinicians considering possible risks as drug resistance, subsequent chemotherapy-immunotherapy or radiotherapy and other related adverse reactions and aggravation of distant toxicity, and distant organ metastasis for advanced gastric cancer patients to continue palliative care after conversion therapy. There were 85.41%(199/233), 50.21%(117/233), and 18.45%(43/233) of clinicians considering choices as multi-disciplinary treatment to evaluate the follow-up treatment strategy, laparoscopic exploration to clarify the possibility of surgery, and continuing the original program of palliative care for follow-up treatment of patients with advanced gastric cancer after conversion therapy. There were 97.85%(228/233) of clinicians considering re-evaluating the possibility of surgical resection when the tumor volume was significantly reduced after conversion therapy. (5) Selection of beneficiary population, treatment modality, and time point of evaluation of benefit for patients undergoing conversion surgery for advanced gastric cancer. A further questionnaire survey was conducted on the 228 clinicians who chose "to consider re-evaluating surgical resection when the volume of tumor reducted significantly after conversion therapy for advanced gastric cancer". There were 94.74%(216/228) of clinicians considering advanced gastric cancer patients with high expression of programmed death receptor ligand 1 as beneficiary population of conversion therapy. There were 82.46%(188/228) of clinicians considering advanced gastric cancer patients with liver oligometastases as beneficiary population of conversion therapy. There were 53.07%(121/228) of clinicians considering two-drug chemotherapy+immunotherapy regimen as preferred for HER2-negative patients, there were 67.54%(154/228) of clinicians considering chemotherapy + trastuzumab + immunotherapy regimen as preferred for HER2-positive patients. There were 83.33%(190/228) of clinicians considering resection treatment after 3-6 cycles of conversion therapy. There were 94.74%(216/228) of clinicians choosing enhanced computed tomography scan to evaluate the efficacy. In terms of tumor sign for laparoscopic surgery after conversion therapy, there were 92.54%(211/228) of clinicians choosing significant shrinkage of the primary focus and its surrounding lymph nodes from baseline. There were 63.16%(144/228) of clinicians choosing surgery after 3-4 weeks of drug withdrawal, and 57.02%(130/228) of clinicians considering to achieve R 0 resection. In terms of patients achieving pathologic complete remission (pCR) after surgery, there were 64.04%(146/228) of clinicians believing that postoperative treatment should be continued for 6-8 cycles of therapy followed by maintenance therapy up to 1 year. For patients with non-pCR, there were 59.65%(136/228) of clinicians believing that 6-8 cycles of postoperative maintenance therapy should be continued until 1 year. Conclusion:Most clinicians in China consider R 0 resection after conversion therapy for patients with advanced gastric cancer, followed by 6-8 cycles of treatment and maintenance therapy for another year.

To assess relationships between xanthine oxidase (XOD) and nephropathogenic infectious bronchitis virus (NIBV) infection, 240 growing layers (35 days old) were randomly divided into two groups (infected and control) of 120 chickens each. Each chicken in the control and infected group was intranasally inoculated with 0.2 mL sterile physiological saline and virus, respectively, after which serum antioxidant parameters and renal XOD mRNA expression in growing layers were evaluated at 8, 15 and 22 days post-inoculation (dpi). The results showed that serum glutathione peroxidase and superoxide dismutase activities in the infected group were significantly lower than in the control group at 8 and 15 dpi (p < 0.01), while serum malondialdehyde concentrations were significantly higher (p < 0.01). The serum uric acid was significantly higher than that of the control group at 15 dpi (p < 0.01). In addition, the kidney mRNA transcript level and serum activity of XOD in the infected group was significantly higher than that of the control group at 8, 15 and 22 dpi (p < 0.05). The results indicated that NIBV infection could cause the increases of renal XOD gene transcription and serum XOD activity, leading to hyperuricemia and reduction of antioxidants in the body.
Antioxidants ; Chickens ; Glutathione Peroxidase ; Hyperuricemia ; Infectious bronchitis virus* ; Kidney ; Malondialdehyde ; RNA, Messenger* ; Superoxide Dismutase ; Uric Acid ; Xanthine Oxidase* ; Xanthine*

AIM: To investigate the effect of silymarin on homocysteine-induced cell viability and apoptosis in human umbilical vein endothelial cells (HUVECs). METHODS: Cell viability was analyzed by using MTT and LDH assay. Apoptotic cells were detected by using DNA fragmentation and flow cytometric analysis. The level of intracellular reactive oxygen species (ROS) and the potential of mitochondrial membrane were determined by flow cytometric assay. The activity of caspase-3, -6 and -9 were measured with microplate spectrofluorometer. Protein levels were examined by Western blotting. RESULTS: Treatment of cultured HUVECs with HCY for 48 h induced a significant decrease in cell viability, and the percentage of apoptosis increased to 76.8%. The level of intracellular ROS and activity of caspase-3, -6 and -9 enhanced, and the red/green ratios of mitochondrial membrane decreased. However, simultaneous treatment with silymarin exhibited cytoprotective effects, reduced formation of the DNA ladder, prevented the levels of Bax and Bcl-2 proteins and the accumulation of ROS as well as caspase-3, -6 and -9 activation, reconverted the potential of mitochondrial membrane, and the percentage of apoptosis/necrosis was significantly decreased to 12.7% in a dose-dependent manner. CONCLUSION: These results demonstrate that silymarin has the protective capacity to antagonize HCY-induced apoptosis in HUVECs. The antiapoptotic action of silymarin may be partially dependent on an anti-oxidative stress effects, inhibition of caspases activity, and maintenance of mitochondria function.