Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Objective:To investigate pediatric colonoscopy procedures and the associated changes in the disease spectrum.Methods:The clinical data of 1 087 children who underwent pediatric colonoscopy at the Second Affiliated Hospital of Nanjing Medical University and Yili Prefecture Friendship Hospital Affiliated to Nanjing Medical University from January 2012 to December 2022 were retrospectively collected. Patients were divided into 0-3 ( n=165), 4-6 ( n=307), 7-10 ( n=275) and 11-14 ( n=340) years groups according to their age, and also divided into two time periods according to the examination time point, 2012-2017 ( n=302) and 2018-2022 ( n=785) groups. Indicators that were observed and analyzed included the primary reasons for colonoscopy, types and proportions of abnormalities, distribution of cases and symptoms by period and age group, and disease diagnosis and treatment before and after colonoscopy. Results:A total of 1 238 colonoscopies were completed in 1 087 children. Blood in the stool was the most common cause (337/1 087, 31.00%). The most abnormalities were found in intestinal polyps (190/1 087, 17.48%) and inflammatory bowel disease (IBD) (181/1 087, 16.65%), as well as in 95 cases (95/1 087, 8.74%) who were confirmed autism and requested colonoscopy placement for fecal microbiota transplantation (FMT). There were differences in case distribution and symptoms among different age groups: polyps were most common in the 0-3 years group (75/165, 45.45%), and IBD was most common in the 11-14 years group (97/340, 28.53%). Compared with 2012-2017, during 2018-2022, the proportion of colonoscopies for polyps in children decreased [from 49.67% (150/302) to 5.10% (40/785), P<0.001], while the proportion for IBD increased [from 12.25% (37/302) to 18.34% (144/785), P=0.016], and autism requiring colonoscopic duct placement for FMT increased [from 2.32% (7/302) to 11.21% (88/785), P<0.001]. Conclusion:Pediatric colonoscopy plays an important role in the diagnosis and treatment of pediatric diseases. With the increasing clinical application demands, diversified procedures such as pre-FMT colonoscopic duct placement are becoming important directions for the future development of pediatric colonoscopy.

Objective:To find the biomarkers that accurately predict the survival of patients with esophageal squamous cell carcinoma (ESCC).Methods:The immune related genes that were significantly related to the overall survival (OS) of patients with ESCC were screened from The Cancer Genome Atlas (TCGA) database to construct a prognostic risk score model. The prognoses of the high-risk and low-risk groups were compared by Kaplan-Meier method. The accuracy of the model was evaluated by the receiver operating characteristic (ROC) curve. Tumor tissue samples of 83 patients with pathological diagnosis of ESCC were collected from Anyang Cancer Hospital for external verification. Cox regression analysis was used to comprehensively evaluate the effects of prognostic risk score and various clinical characteristics on OS of patients with ESCC.Results:Seven immune-related genes that were significantly related to survival prognosis were selected from the TCGA database and included in the prognostic risk score model, which were S100A12, SLC40A1, FABP9, TNFSF10, IGHA2, IL1F10, and STC2. The 1- and 2-year survival rates of the low-risk group (40 cases) were 94.3% and 82.5%, respectively, while those of the high-risk group (40 cases) were 75.9% and 32.9%, respectively.The prognosis of the high-risk group was worse than that of the low-risk group ( P<0.001). The 83 external validation samples obtained consistent results by using the prognostic risk score model. The prognostic risk score was positively correlated with the content of CD4 + T lymphocytes in ESCC ( rs=0.259, P=0.020), but not correlated with the content of B lymphocytes, CD8 + T lymphocytes, neutrophils, macrophages or dendritic cells ( P>0.05). Conclusions:S100A12, SLC40A1, FABP9, TNFSF10, IGHA2, IL1F10, and STC2 were risk genes significantly associated with OS of patients with ESCC. The prognostic risk score was an independent prognostic factor for the OS of patients with ESCC, and it was correlated with the content of CD4 + T lymphocytes in ESCC tissue.

Objective:To find the biomarkers that accurately predict the survival of patients with esophageal squamous cell carcinoma (ESCC).Methods:The immune related genes that were significantly related to the overall survival (OS) of patients with ESCC were screened from The Cancer Genome Atlas (TCGA) database to construct a prognostic risk score model. The prognoses of the high-risk and low-risk groups were compared by Kaplan-Meier method. The accuracy of the model was evaluated by the receiver operating characteristic (ROC) curve. Tumor tissue samples of 83 patients with pathological diagnosis of ESCC were collected from Anyang Cancer Hospital for external verification. Cox regression analysis was used to comprehensively evaluate the effects of prognostic risk score and various clinical characteristics on OS of patients with ESCC.Results:Seven immune-related genes that were significantly related to survival prognosis were selected from the TCGA database and included in the prognostic risk score model, which were S100A12, SLC40A1, FABP9, TNFSF10, IGHA2, IL1F10, and STC2. The 1- and 2-year survival rates of the low-risk group (40 cases) were 94.3% and 82.5%, respectively, while those of the high-risk group (40 cases) were 75.9% and 32.9%, respectively.The prognosis of the high-risk group was worse than that of the low-risk group ( P<0.001). The 83 external validation samples obtained consistent results by using the prognostic risk score model. The prognostic risk score was positively correlated with the content of CD4 + T lymphocytes in ESCC ( rs=0.259, P=0.020), but not correlated with the content of B lymphocytes, CD8 + T lymphocytes, neutrophils, macrophages or dendritic cells ( P>0.05). Conclusions:S100A12, SLC40A1, FABP9, TNFSF10, IGHA2, IL1F10, and STC2 were risk genes significantly associated with OS of patients with ESCC. The prognostic risk score was an independent prognostic factor for the OS of patients with ESCC, and it was correlated with the content of CD4 + T lymphocytes in ESCC tissue.

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of gastrointestinal glomus tumors (GIGT). Methods: Totally 15 cases of GIGT were collected at the First Affiliated Hospital, Zhengzhou University, from January 2011 to June 2018. The clinicopathological features, immunophenotype, BRAF V600E mutation and prognosis were retrospectively analyzed. Results: The 15 patients′ age ranged from 37 to 59 years(median 49 years, mean 50 years). Eleven patients presented with intermittent abdominal pain and distention, three showed antral space-occupying lesions at physical examination, and one had abdominal pain accompanied by fecal blood. Fourteen tumors were located in the stomach, and one was in the ileum. Imaging showed the gastric glomus tumors were located in the submucosal layer with obvious enhancement in the arterial phase, and the ileum glomus tumor involved the whole layer of intestinal wall causing luminal obstruction. The maximum diameters of the tumors ranged from 1.5 to 3.0 cm (mean 2.3 cm). Grossly, the gastric glomus tumors were solid. Microscopically, the gastric glomus tumors were mostly located in the muscularispropria layer and were vascular. The tumor boundary was distinct but without capsule formation. The tumor cells were round or oval, and showed perivascular hemangiopericytoma-like or solid nest-like structures. The tumor cells were mildly pleomorphic, with rare mitosis and no necrosis. Two tumors had focal calcification, two showed mucosal invasion, two showed vascular invasion and five showed perineural invasion. The ileum glomus tumor was cellular, with prominent cellular atypia, and the mitotic count in hot spots was about 5-6/HPF. Immunohistochemistry showed that SMA and collage Ⅳ were strongly expressed in all the tumor cells; caldesmon and calponin were moderately expressed in some regions, and syn was weakly expressed in 12 cases. The Ki-67 proliferation index in the gastric glomus tumors ranged from 1% to 30% (mean 6%); and that in the ileum glomus tumor was about 70%. BRAF V600E mutations were not detected in any of 15 GIGTs. All patients did not receive radiotherapy or chemotherapy post operatively. Thirteen patients were followed up by telephone for 18-90 months (mean 42 months). Twelve patients with gastric glomus tumors survived without recurrence and metastasis, and the patient with ileum glomus tumor had liver metastasis 15 months after operation. Conclusions Glomus tumors is a rare mesenchymal tumor of the gastrointestinal tract. It should be differentiated from gastrointestinal stromal tumors, neuroendocrine tumor, leiomyoma, solitary fibrous tumor and paraganglioma. Most GIGTs are benign and have good prognosis. More experience is needed to understand the biologic behavior and prognostication of GIGTs.

In the course of pathophysiology,we gave full play to the advantages of network teaching platform to integrate teaching resources,broaden students' learning pathways,and enhance the interaction,which could benefit teachers as well as students.The traditional teaching mode and concept were changed by using Computer Aided Instruction (CAI) and relying on the network platform to carry out multi-level teaching methods such as flipped classroom and Task-Based Leaming (TBL).We gradually conducted formative assessment to promote learning.Thus,the interest and the enthusiasm of students in learning were elevated and the independent learning capability were cultivated.

OBJECTIVE: To investigate the current status of quality of working life( QWL) among medical staffs in Minhang District,Shanghai City,and to explore the relationship between QWL and occupational stress. METHODS: A stratified sampling method was used to select 522 medical staffs in Minhang District,Shanghai City. The QWL and occupational stress were assessed using the Quality of Working Life Scale and the Effort-Reward Imbalance Questionnaire,respectively.RESULTS: The total score of QWL of medical staffs was( 97. 7 ± 13. 8),and the detection rate of high occupational stress was34. 7%( 181/522). The total QWL score of medical workers in the high occupational stress group was lower than that in the low occupational stress group( P < 0. 01). The results of multivariable logistic regression analysis showed that occupational stress and average weekly working time were risk factors of reduction in QWL( P < 0. 01). CONCLUSION: Occupational stress is the influencing factor of QWL. The increased occupational stress may reduce the QWL of medical personnel.

Objective: To evaluate the safety and efficacy of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) 25/150/100 mg once daily combined with dasabuvir 250mg, twice daily in non-cirrhotic Chinese adult patients with newly diagnosed and treated chronic HCV genotype 1b infection. Methods: A randomized, double-blind, placebo-controlled, multicenter phase 3 clinical trial was conducted in mainland China, Korea, and Taiwan.Safety and efficacy of OBV/PTV/r plus DSV administered for 12 weeks were evaluated in a newly diagnosed and treated (interferon alpha /pegylated interferon alpha) and ribavirin non-cirrhotic adults with chronic HCVgenotype 1b infection. Patients randomly received OBV/PTV/r plus DSV for 12 weeks (Group A), or placebo for 12 weeks (Group B) followed by an open-label phase of OBV/PTV/r plus DSV for 12 weeks. Sustained response (SVR12) rate obtained at 12 weeks and (SVR24) 24 weeks after discontinuation of treatment, and the incidence of adverse events and laboratory abnormalities after double-blind and open-label phase treatment were assessed. Results: A total of 410 cases of Chinese patients were included and randomly assigned to group A and B (with 205 cases in each group) in a 1:1 ratio. The rates of SVR12 and SVR24 were 99% (95% CI: 94.8% - 99.8%) in the newly diagnosed patients in group A (205 patients) and the rates of SVR12 and SVR24 were 100% in treated patients (95% CI: 96.3% - 100%). Different baseline characteristics had no effect on SVR12 and SVR24 rates. Most of the adverse events occurred were mild, asymptomatic, and≥ 3 laboratory abnormalities during treatment were rare, including elevation of alanine aminotransferase (2 cases in double-blind stage A group), aspartate aminotransferase (Double-blind stage A (3 cases) and total bilirubin (1 case in open-label phase B group); however, those mild adverse events could be recovered after drug withdrawal or discontinuation. only1 person discontinued drugs due to adverse events (Group B, open-label phase). Conclusion The 12 weeks treatment course of OBV/PTV/r combined with DSV produced 99% ~ 100% rates of SVR12 and SVR24 in non-cirrhotic Asian adult patients with newly diagnosed and treated chronic HCV genotype 1b infection, and the tolerance and safety were good.

AIM:To observe the role of calcium-sensing receptor (CaSR) in the regulation of pulmonary artery tension.METHODS:The intracellular calcium concentration ([Ca2+]i) was detected by laser-scanning confocal micros-copy, and the pulmonary artery tension was determined by the pulmonary arterial ring technique .RESULTS: Increased levels of [Ca2+]o or Gd3+(an agonist of CaSR) induced the increase in [Ca2+]i and pulmonary artery constriction in a concentration-dependent manner.Additionally, the effects of Ca2+and Gd3+were inhibited by U73122 and D609 (specific inhibitor of PLC), and 2-APB and heparin (specific antagonist of IP3 receptor).However, U73343 (U73122 inactive ana-logue) did not take effect.CONCLUSION: CaSR may be involved in the regulation of pulmonary artery tension by in-creasing [Ca2+]i through G-protein-PLC-IP3 pathway.