Objective:To investigate the status of glucolipid metabolism and insulin resistance in patients with first-episode non-medicated schizophrenia, and to explore their relationship with psychiatric symptoms and cognitive function.Methods:One hundred and seventeen patients with first-episode non-medicated schizophrenia admitted to Wenzhou Seventh People′s Hospital from January 2018 to August 2020 were included in case group, and 61 healthy subjects with physical examination during the same period were used as control group. The glucose metabolism, including serum fasting blood glucose (FBG), 2 h postprandial blood glucose (2 h PBG), fasting insulin (FINS), fasting C peptide; lipid metabolism, including triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C); apolipoprotein A1 (Apo-A1) and homeostatic model assessment insulin resistance index (HOMA-IR) level were compared between 2 groups. The abnormal glucolipid metabolism and incidence rate of insulin resistance were counted in the two groups. According to the condition of abnormal glucolipid metabolism or insulin resistance in case group, the patients were divided into abnormal glucolipid metabolism group and non-abnormal group, and insulin resistance group and non-insulin resistance group. The psychiatric symptoms (positive and negative symptom scale, PANSS) and cognitive function (MATRICS consensus cognitive battery, MCCB) were compared between 2 groups. Pearson correlation analysis was used to explore the correlation between glucolipid metabolism and insulin resistance and psychiatric symptoms and cognitive function in case group.Results:The levels of glucolipid metabolism indexes of 2 h PBG, FINS, fasting C peptide, TG and HOMA-IR in case group were significantly higher than those in control group: (7.06 ± 1.88) mmol/L vs. (6.19 ± 1.53) mmol/L, (8.61 ± 2.46) mU/L vs. (6.25 ± 1.71) mU/L, (0.49 ± 0.16) nmol/L vs. (0.32 ± 0.09) nmol/L, (1.33 ± 0.47) mmol/L vs. (1.02 ± 0.24) mmol/L, 2.01 ± 0.71 vs. 1.51 ± 0.45 ( P<0.05); while the levels of HDL-C and Apo-A1 were significantly lower than those in control group: (1.19 ± 0.38) mmol/L vs. (1.57 ± 0.32) mmol/L, (1.21 ± 0.25) g/L vs. (1.43 ± 0.17) g/L ( P<0.05). The total incidence rate of abnormal glucolipid metabolism or insulin resistance in case group was significantly higher than that in control group: 62.39%(73/117) vs. 13.11%(8/61) ( P<0.05). The scores of dimensions of positive symptoms, negative symptoms and general psychopathology and total score of PANSS in combined group were significantly higher than those in non-abnormal group: (25.14 ± 5.09) scores vs. (22.95 ± 4.72) scores, (24.68 ± 5.25) scores vs. (22.05 ± 4.59) scores, (41.52 ± 5.85) scores vs. (38.12 ± 4.18) scores, (94.68 ± 11.64) scores vs. (85.43 ± 8.51) scores ( P<0.05). The above scores points in insulin resistance group were higher than points in non-insulin resistance group: (26.62 ± 4.18) scores vs. (23.62 ± 4.98) scores, (25.92 ± 5.07) scores vs. (23.02 ± 4.96) scores, (42.94 ± 5.26) scores vs. (39.43 ± 4.47) scores, (97.35 ± 10.07) scores vs. (89.37 ± 10.25) scores ( P<0.05). The scores of continuous performance test-identical pairs (CPT-IP), working memory (WM), brief visuospatial memory test-revised (BVMT-R) and Mayer-Salovey-Caruso emotional intelligence test (MSCEIT) of MCCB scale in abnormal glucolipid metabolism group were significantly lower than those in non-abnormal group: (23.82 ± 5.21) scores vs. (27.15 ± 4.69) scores, (21.72 ± 5.95) scores vs. (25.35 ± 5.14) scores, (19.56 ± 5.28) scores vs. (22.34 ± 5.43) scores, (22.62 ± 5.13) scores vs. (26.47 ± 4.96) scores ( P<0.05), and the scores in insulin resistance group were significantly lower: (22.26 ± 4.84) scores vs. (25.42 ± 5.12) scores, (20.35 ± 4.87) scores vs. (23.46 ± 5.08) scores, (18.05 ± 4.27) scores vs. (20.98 ± 5.71) scores, (21.15 ± 4.67) scores vs. (24.48 ± 5.02) scores ( P<0.05). Pearson correlation analysis showed that 2 h PBG in case group was positively correlated with PANSS positive symptoms ( P<0.05), and was negatively correlated with CPT-IP and MSCEIT in MCCB scale ( P<0.05). FINS and HOMA-IR were positively correlated with positive symptoms, negative symptoms and PANSS total score ( P<0.05), and were negatively correlated with CPT-IP, WM, BVMT-R and MSCEIT ( P<0.05). HDL-C was negatively correlated with positive symptoms ( P<0.05), and was positively correlated with CPT-IP, WM and MSCEIT ( P<0.05). Apo-A1 was negatively correlated with positive symptoms and negative symptoms ( P<0.05), and was positively correlated with CPT-IP and WM ( P<0.05). Conclusions:Abnormal glucolipid metabolism and insulin resistance have a higher detection rate in first-episode non-medicated schizophrenia, and have a certain relationship with the psychiatric symptoms and cognitive impairment of patients.

Pancreatic cancer is a common malignancy with the worst prognosis.Radical surgery has been the only curative treatment for pancreatic cancer.With the advancement of surgical techniques and the implementation of the concept of comprehensive treatment for cancer in recent years,neoadjuvant therapy for pancreatic cancer has received more attention.There are continuing controversies in the hotspots and difficulties,with opportunities and challenges coexisting.Four famous experts and their teams in pancreatic surgery discussed selection strategy of neoadjuvant therapy for pancreatic cancer based on clinical experiences.Professor Wang Chunyou proposed that surgery was prior for patients with a higher likelihood of achieving R0 resection for pancreatic cancer to avoid the possibility of tumor progression and loss the opportanity of radical resection during neoadjuvant therapy.For patients with less chance of radical resection for pancreatic cancer and unresectable pancreatic cancer,neoadjuvant therapy is worthy of a positive attempt.Professor Jin Gang and his team believed that neoadjuvant therapy played an important role in improving the survival time of patients with pancreatic head cancer,especially with borderline resectable pancreatic head cancer.After neoadjuvant therapy,pancreatic surgeons should pay attention to improvement of surgery safety and R0 resection rate.Professor Dai Menghua and his team suggested that patients with resectable pancreatic cancer and borderline resectable pancreatic cancer could benefit from neoadjuvant therapy,which required proof from clinical trials.Surgeons should choose the appropriate treatment strategy based on guidelines and individual conditions for patients with pancreatic cancer.Professor Shao Cheghao and his team suggested that surgical treatment after neoadjuvant therapy or translational therapy for locally advanced pancreatic head cancer is safe,effective and feasible,especially for pancreaticoduodenectomy with combined revascularization.For the treatment of patients with pancreatic head cancer after neoadjuvant chemotherapy,the choice of next treatment options,evaluation indicators,timing of surgery and surgical methods need to be further studied.

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.

Lung cancer remains the leading cause of cancer deaths worldwide and is the most common cancer in males. Immune-checkpoint inhibitors (ICIs) that target programmed cell death protein-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) have achieved impressive efficacy in the treatment of non-small-cell lung cancer (NSCLC) (Pardoll, 2012; Champiat et al., 2016; Gao et al., 2022). Although ICIs are usually well tolerated, they are often accompanied by immune-related adverse events (irAEs) (Doroshow et al., 2019). Non-specific activation of the immune system produces off-target immune and inflammatory responses that can affect virtually any organ or system (O'Kane et al., 2017; Puzanov et al., 2017). Compared with adverse events caused by chemotherapy, irAEs are often characterized by delayed onset and prolonged duration and can occur in any organ at any stage of treatment, including after cessation of treatment (Puzanov et al., 2017; von Itzstein et al., 2020). They range from rash, pneumonitis, hypothyroidism, enterocolitis, and autoimmune hepatitis to cardiovascular, hematological, renal, neurological, and ophthalmic irAEs (Nishino et al., 2016; Kumar et al., 2017; Song et al., 2020). Hence, we conducted a retrospective study to identify validated factors that could predict the magnitude of the risk of irAEs in patients receiving PD-1/PD-L1 inhibitors; our approach was to analyze the correlation between the clinical characteristics of patients at the start of treatment and relevant indicators such as hematological indices and the risk of developing irAEs. Then, we developed an economical, practical, rapid, and simple model to assess the risk of irAEs in patients receiving ICI treatment, as early as possible.
Male ; Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms/drug therapy* ; Immune Checkpoint Inhibitors/adverse effects* ; Programmed Cell Death 1 Receptor ; Retrospective Studies ; Apoptosis