Objective:To explore the efficacy of different second-line treatment strategies in the real world after progression of first-line immunotherapy and its combination therapies in patients with driver gene-negative advanced non-small cell lung cancer (NSCLC) .Methods:A retrospective analysis was conducted on the clinical data of 93 driver gene-negative advanced NSCLC patients who received first-line immunotherapy and its combination therapies from January 1, 2018 to December 31, 2023 at the First Affiliated Hospital of Xinxiang Medical University and Xinxiang Central Hospital. Patients were categorized into immune checkpoint inhibitors (ICIs) -resistant ( n=43) and ICIs-responsive ( n=50) groups according to whether progression free survival (PFS) exceeded 6 months after first-line treatment. Patients were categorized into ICIs-treated ( n=55) and non-ICIs-treated ( n=38), anti-angiogenic-treated ( n=51) and non-anti-angiogenic-treated ( n=42) groups according to the different second-line treatment strategies after progression of first-line immunotherapy and its combination therapies. The median PFS2 (mPFS2) and median overall survival (mOS) 2 after second-line treatment of each group were compared. The Kaplan-Meier method was used for survival analysis. Results:The mPFS2 and mOS2 of 93 advanced NSCLC patients who progressed after first-line ICIs treatment were 4.9 months (95% CI: 4.1-5.7 months) and 14.7 months (95% CI: 11.2-18.2 months). The mPFS2 of patients in the first-line ICIs-responsive and ICIs-resistant groups were 6.0 and 3.8 months, respectively, with no statistically significant difference ( χ2=2.00, P=0.157), and the mOS2 were 25.3 and 11.3 months, respectively, with a statistically significant difference ( χ2=12.13, P<0.001). The mPFS2 of patients in the second-line ICIs-treated group and the non-ICIs-treated group were 5.2 and 4.6 months, respectively, with no statistically significant difference ( χ2=0.16, P=0.687). The mOS2 were 15.1 and 12.7 months, respectively, with no statistically significant difference ( χ2=0.01, P=0.930). The mPFS2 of patients in the second-line anti-angiogenic-treated and non-anti-angiogenic-treated groups were 4.5 and 6.0 months, respectively, with no statistically significant difference ( χ2=0.41, P=0.525), the mOS2 were 14.7 and 16.8 months, respectively, with no statistically significant difference ( χ2=0.01, P=0.943) . Conclusions:After progression of first-line ICIs therapy in patients with driver gene-negative advanced NSCLC, first-line ICIs-responsive patients have significantly longer OS after second-line treatment compared with ICIs-resistant patients. The efficacy of second-line therapy in patients after progression of first-line ICIs therapy does not show significant differences due to the type of treatment strategies.

Objective:This study aims to further enhance the quality of training for large-scale scientific instruments in higher education institutions and promote the long-term high-quality development of equipment platforms.Methods:We deeply analyzed the existing problems in the training of large-scale scientific instruments in higher education institutions, and combined the training goal of ″five understandings and five abilities″ for compound talents.Results:The training methods, processes, long-term quality guarantee measures and post-training assessment were refined. A ″four-dimensional integration″ closed-loop training system for large-scale scientific instruments in higher education institutions was constructed and formed.Conclusions:The implementation of the " four-dimensional integration" training system has showed a positive role in scientific research, talent cultivation, efficient utilization of equipment and facilities, and the long-term high-quality development of platforms in universities, providing references and inspiration for the implementation of large-scale instrument training for other university laboratories.

Neuronal intranuclear inclusion disease（NIID）is a rare hereditary neurodegenerative disorder that can affect multiple systems. However，it is uncommon for urinary dysfunction to be the initial symptom. This article reports five cases. The five patients began to experience voiding dysfunction such as frequent urination，weak urination，and incomplete urination at the mean ages of 55.4（47 - 65）years old. Four months to twelve years after urinary onset，neurological symptoms such as headache，memory decline，transient loss of consciousness，and unsteady gait began to appear. Four of the five cases had a family history. Brain MRI revealed the “ribbon sign” or “crest sign” in all cases. Skin biopsy revealed eosinophilic inclusions in the cell nuclei，and NOTCH2NLC gene testing identified abnormal GGC mutations. Three of the five patients underwent cystostomy due to secondary hydronephrosis，while the other two received no special treatment. After a follow-up of 18 to 35 months since diagnosis，the patients who underwent cystostomy had normal renal function. Neurological symptoms in all five patients worsened to varying degrees.

Neuronal intranuclear inclusion disease（NIID）is a rare hereditary neurodegenerative disorder that can affect multiple systems. However，it is uncommon for urinary dysfunction to be the initial symptom. This article reports five cases. The five patients began to experience voiding dysfunction such as frequent urination，weak urination，and incomplete urination at the mean ages of 55.4（47 - 65）years old. Four months to twelve years after urinary onset，neurological symptoms such as headache，memory decline，transient loss of consciousness，and unsteady gait began to appear. Four of the five cases had a family history. Brain MRI revealed the “ribbon sign” or “crest sign” in all cases. Skin biopsy revealed eosinophilic inclusions in the cell nuclei，and NOTCH2NLC gene testing identified abnormal GGC mutations. Three of the five patients underwent cystostomy due to secondary hydronephrosis，while the other two received no special treatment. After a follow-up of 18 to 35 months since diagnosis，the patients who underwent cystostomy had normal renal function. Neurological symptoms in all five patients worsened to varying degrees.

Objective:This study aims to further enhance the quality of training for large-scale scientific instruments in higher education institutions and promote the long-term high-quality development of equipment platforms.Methods:We deeply analyzed the existing problems in the training of large-scale scientific instruments in higher education institutions, and combined the training goal of ″five understandings and five abilities″ for compound talents.Results:The training methods, processes, long-term quality guarantee measures and post-training assessment were refined. A ″four-dimensional integration″ closed-loop training system for large-scale scientific instruments in higher education institutions was constructed and formed.Conclusions:The implementation of the " four-dimensional integration" training system has showed a positive role in scientific research, talent cultivation, efficient utilization of equipment and facilities, and the long-term high-quality development of platforms in universities, providing references and inspiration for the implementation of large-scale instrument training for other university laboratories.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective:To investigate the expulsion rate of GyneFix postpartum intrauterine device (PPIUD) placed immediately after cesarean section within one year and its influencing factors.Methods:A prospective cohort study was conducted. Women who volunteered to use a GyneFix PPIUD placed immediately after cesarean section (within 10 min after placenta delivery) for postpartum contraception were recruited from September 2017 to November 2020. The relevant information was collected through questionnaires before, during and 24 h after cesarean section. Outpatient follow-up was conducted at 42 d, 3 months, 6 months and 12 months after delivery to obtain information on expulsion of GyneFix PPIUD and unwanted pregnancy. Life table and Cox regression model were used to analyze the cumulative expulsion rate and related influencing factors.Results:A total of 470 subjects were recruited and 461 (98%) subjects were eligible for this study. The cumulative expulsion rate of GyneFix PPIUD within one year after cesarean section was 8.4% (95% CI: 7.0%-9.8%). Multivariate Cox regression analysis showed that women aged >35 years had significantly lower risk of PPIUD expulsion than those aged <25 years ( HR=0.16, 95% CI: 0.04-0.64). The risk of GyneFix PPIUD was not statistically significantly associated with cesarean section history and breastfeeding mode (all P>0.05). Nevertheless, this risk was statistically significant between hospitals. The Pearl index of contraceptive failure of the device was 2.37 (95% CI: 1.09-4.50) per 100 person-years. The rate of contraceptive failure was not associated with maternal age, breastfeeding mode, and history of cesarean delivery (all P>0.05). Conclusion:The one-year cumulative expulsion rate of GyneFix PPIUD placed immediately after cesarean section is 8.4%. Young mothers were at a higher risk of expulsion than their older counterparts. The device users should be counseled regarding the signs of expulsion. In case of expulsion, women should be offered reinsertion or other contraceptive methods. The training of service skills of GyneFix PPIUD should be strengthened in order to mitigate the risk of the device expulsion.

Objective:To investigate the expulsion rate of GyneFix postpartum intrauterine device (PPIUD) placed immediately after cesarean section within one year and its influencing factors.Methods:A prospective cohort study was conducted. Women who volunteered to use a GyneFix PPIUD placed immediately after cesarean section (within 10 min after placenta delivery) for postpartum contraception were recruited from September 2017 to November 2020. The relevant information was collected through questionnaires before, during and 24 h after cesarean section. Outpatient follow-up was conducted at 42 d, 3 months, 6 months and 12 months after delivery to obtain information on expulsion of GyneFix PPIUD and unwanted pregnancy. Life table and Cox regression model were used to analyze the cumulative expulsion rate and related influencing factors.Results:A total of 470 subjects were recruited and 461 (98%) subjects were eligible for this study. The cumulative expulsion rate of GyneFix PPIUD within one year after cesarean section was 8.4% (95% CI: 7.0%-9.8%). Multivariate Cox regression analysis showed that women aged >35 years had significantly lower risk of PPIUD expulsion than those aged <25 years ( HR=0.16, 95% CI: 0.04-0.64). The risk of GyneFix PPIUD was not statistically significantly associated with cesarean section history and breastfeeding mode (all P>0.05). Nevertheless, this risk was statistically significant between hospitals. The Pearl index of contraceptive failure of the device was 2.37 (95% CI: 1.09-4.50) per 100 person-years. The rate of contraceptive failure was not associated with maternal age, breastfeeding mode, and history of cesarean delivery (all P>0.05). Conclusion:The one-year cumulative expulsion rate of GyneFix PPIUD placed immediately after cesarean section is 8.4%. Young mothers were at a higher risk of expulsion than their older counterparts. The device users should be counseled regarding the signs of expulsion. In case of expulsion, women should be offered reinsertion or other contraceptive methods. The training of service skills of GyneFix PPIUD should be strengthened in order to mitigate the risk of the device expulsion.

Objective:To analyze the clinicopathological characteristics of differentiated early cardia cancer and to evaluate the short-term and long-term efficacy of endoscopic submucosal dissection (ESD).Methods:A total of 329 patients (331 lesions) who underwent ESD at Nanjing Drum Tower Hospital from October 2014 to December 2019 and were pathologically confirmed as differentiated early cardia cancer were included in the study and followed up. The endoscopic and pathological data of patients were reviewed to analyze the clinicopathological characteristics of differentiated early cardia cancer. The short-term (including en bloc resection rate, curative resection rate and incidence of short-term complications) and long-term efficacy (including incidence of metachronous cancer, recurrence and distant metastasis, and overall survival rate) of ESD was evaluated.Results:The ratio of male to female in 329 patients with differentiated early cardia cancer was 4∶1, and their age was 65.69±8.02 years. Tumor diameter of ≤2.0 cm accounted for 65.9% (218/331). Most lesions were located on the posterior wall (50.5%, 167/331), followed by the minor curve (36.3%, 120/331). The endoscopic morphology of 0-Ⅱc type accounted for 49.5% (164/331). There were 69.8% (231/331) lesions confined to the mucosal layer. The en bloc resection rate was 100.0% (329/329), and the curative resection rate was 83.3% (274/329). Short-term complications occurred in 28 patients (8.5%). With a median follow-up time of 39 months, 11 patients (3.3%) developed metachronous cancer, 2 (0.6%) developed distant metastasis, and no recurrence occurred. Seven patients died, and the overall survival rate during the follow-up period was 97.9% (322/329). The survival rate of patients with curative resection and additional surgery was 100.0% (3/3), while that without additional surgery was 99.3% (269/271). The survival rate of patients with non-curative resection and additional surgery was 96.0% (24/25), and that without additional surgery was 86.7% (26/30).Conclusion:Most differentiated early cardia cancers are well-differentiated adenocarcinomas, with less than 2 cm in diameter at the time of diagnosis with a low rate of ulcer and vascular invasion. ESD is safe and effective for the treatment of differentiated early cardia cancer with a high rate of curative resection, fewer intraoperative and postoperative complications, low incidences of metachronous cancer, distant metastasis and recurrence, and a high overall survival rate. However, additional surgical treatment is recommended for patients with non-curative resection.

Objective:To compare the safety and efficacy of laparoscopy and laparotomy for 5-10 cm intermediate-risk gastric stromal tumor, and to evaluate whether there was evident benefits of postoperative adjuvant treatment with imatinib.Methods:A retrospective study was conducted on 72 patients with moderate risk gastric stromal tumors (5-10 cm in diameter) who received operation in Nanjing Drum Tower Hospital from January 2010 to July 2020. There were 28 cases in the laparoscopy group and 44 cases in the laparotomy group. The clinical features, pathological data, perioperative results and hospitalization costs were compared between the two groups. The survival rates of postoperative adjuvant therapy with or without imatinib were analyzed and compared.Results:There was no significant difference in clinicopathological features between the two groups ( P>0.05). The incidences of postoperative complications in the laparoscopy group and the laparotomy group were 32.1% (9/28) and 52.3% (23/44) respectively, showing no significant difference ( P=0.094). Compared with the laparotomy group, both the hospital stay (12.5±3.2 days VS 15.0±3.5 days, P=0.004) and the median postoperative hospital stay (7.5 days VS 9.0 days, P=0.006) in the laparoscopy group were significantly shorter, and the first exhaust time was significantly shorter ( P=0.003). During the median follow-up period of 58 months (13-129 months), there was no tumor-related death. Two cases died of breast cancer and heart disease in the laparotomy group, and 1 case died irrelevant to gastric stromal tumor in the laparoscopy group. Of the 72 patients, 40 received postoperative imatinib adjuvant therapy, 22 cases (50.0%) in the laparotomy group and 18 cases (64.3%) in the laparoscopy group, with no significant difference in the proportion ( χ2=1.414, P=0.234). There was significant difference in the overall survival rate between the group treated with imatinib and the group without imatinib ( P=0.015). Conclusion:Laparoscopic resection is safe and effective for intermediate-risk gastric stromal tumor of 5-10 cm. Taking imatinib adjuvant treatment does not increase overall survival rate of patients with intermediate-risk gastric stromal tumors (5-10 cm), and there is no tumor-related death, recurrence or metastasis for those who did not accept imatinib adjuvant treatment after R0 resection.