Objective To study the effect of conditioned media for rat bone marrow mesenchymal stem cells (BMSCs-CM) on palmitic acid (PA)-induced insulin resistance (IR) in HepG2 cells and its underlying molecular mechanisms.Methods HepG2 cells were treated with or without BMSCs-CM and L-DMEM in the presence or absence of PA.Glucose utilization in HepG2 cells were detected with PAS,glucose and glycogen measurements.Western blotting was used to assess the expression of phospho-insulin receptor substrate (p-IRS),phosphatidylinositol 3-kinase (PI3 K) and p-AKT.Results (1) Incubation of HepG2 cells with 0.25 mmol/L PA for 24 hours significantly increased the glucose concentration and decreased the glycogen content (P ＜ 0.05) in the media.(2) Treatment with BMSCs-CM significantly ameliorated the glucose and glycogen alteration in cells pretreated with PA (P ＜ 0.05),however,no obvious effect of BMSCs-CM on the cell glucose and glycogen production.(3) BMSCs-CM treatment also increased protein expression of p-IRS,PI3K and p-AKT in PA incubated HapG2 cells (P＜ 0.05).The effect of BMSCs-CM on PI3K and p-AKT expression could be mimicked upon addition of 740Y-P,a PI3K agonist,but abolished by LY294002,a PI3K specific inhibitor.Conclusions BMSCs-CM could improve the insulin sensitivity in HepG2 cells pretreated with PA through upregulation of insulin signaling component expression.

Objective To observe the effect of human umbilical cord-derived mesenchymal stem cells (hMSCs) on type 2 diabetic rats, and to explore the possible mechanism. Methods Type 2 diabetic rats were induced by high-fat diet combined with a low dosage of streptozotocin ( STZ, 25 mg/ kg). After 3 × 106 hMSCs suspended in 1 ml PBS or 1ml 10-fold concentrated hMSC supernatant were intravenously infused into the rats via the tail vein, the blood glucose levels were measured every day. One week later, intraperitoneal glucose tolerance test and insulin tolerance test were performed to evaluate the effects of hMSCs on diabetic rats. Pancreatic tissues were collected for insulin/ glucagon immunofluorescence staining. Results After hMSCs infusion, blood glucose level and homeostasis model of assessment for insulin resistance index were significantly decreased in type 2 diabetic rats(both P<0. 01). The glucose tolerance and insulin tolerance were greatly alleviated by hMSCs(all P<0. 01). Intravenously infused 1ml 10-fold concentrated hMSC supernatant showed a similar result to hMSCs. Conclusion In type 2 diabetic rats, hMSCs are able to effectively lower the blood glucose level, improve insulin sensitivity, and increase the number of β cells, which seems to be mediated by their secreted molecules.

Objective To explore the utility of ADC histogram analysisin differentiation of clear cell renal cell carcinoma(ccRCC)and non-clear cell renal cell carcinoma(non-ccRCC)with r-Fov DWI. Methods Sixty-six renal tumors(46 patients with 47 ccRCCs and 18 patients with 19 non-ccRCCs)in 64 patients, who underwent preoperative routine renal MRI sequences and r-FOV DWI, were retrospectively evaluated. The whole-lesion ADC values derived from histogram anlysis(including ADC mean, ADC median, ADC_5th, ADC_25th, ADC_75th, ADC_95th, skew and kurtosis)were measured for each patient. All parameters between ccRCC and non-ccRCC were compared by using the Student's t test or Mann-Whitney U test. ROC analysis was used to assess the diagnostic performance of ADC histogram in distinguishing the two groups. Results The postive skewness of ADC histograms were mostly seen in the non-ccRCC group, while the negtative skewness were present in the majority of ccRCCs. The skewness was significantly higher in non-ccRCCs than those of ccRCCs(P<0.05). Mean ADC, median ADC, 5th percentile ADC, 25th percentile ADC, 75th percentile ADC and 95th percentile ADC(all P<0.05)were significantly lower in non-ccRCC . There was no significant difference of Kurtosis between two groups(P>0.05). 75th percentile ADC achieved the highest AUC(0.987)in differentiating ccRCC and non-ccRCC, whena cutoff value was 1.81× 10-3 mm2/s. The sensitivity and specificity were 100.0％and 94.7％. Conclusion ADC histograms of r-FOV DWI may be helpful to differentiate ccRCC from non-ccRCC, and the diagnostic accuracy of 75th percentile ADC is highest.

Objective: To explore the application of grid health education model in improving college students health literacy. Methods: The clustered stratified random sampling method was used among the pre-formative education freshmen in a Xi-an university, with 1 123 students randomly selected totally. The intervention group (578) received health literacy education based on grid health education model, while the control group (545) receuved the original health education model. The effect of gird model of health education on health literacy was compared between two groups of college students after one-semester intervention. Results: Insufficient health literacy was found among freshmen participants in Xi an(17.12%, 17.61%); health literacy on prevention and treatment of chronic diseases (15.92%, 16.70%) was significantly lower than the national average level of urban residents(22.73%). Health literacy of the two groups of college students was significantly improved(47.75%, 27.71%, χ 2=20.50, 5.47, P<0.05). The grid health education model had significant effects in improving health literacy among college students, except for health literacy on safety and emergency(P<0.05). Conclusion Health literacy of college students is insufficient compared to that of urban residents in China. Grid model of health education model is superior to conventional health education model, which is in line with the requirements of health education in colleges in the new era.

Objective:To investigate the consistency between the iodine-unstained area and the pathological size of endoscopic submucosal dissection (ESD) specimens of superficial esophageal cancer.Methods:A retrospective study was performed on data of 32 patients with superficial esophageal cancer who accepted ESD from May 2019 to April 2020 in the First Affiliated Hospital, Zhejiang University School of Medicine. The maximum transverse diameter and maximum longitudinal diameter of the iodine-unstained area were compared with the tumor pathological area. A size difference no more than 0.5 cm was considered as conformity, any difference between 0.5 and 1.0 cm was considered as non-conformity, and any difference no less than 1.0 cm was considered as serious non-conformity. At the same time, pink sign after spraying Lugo solution and the consistency of pink sign area with the iodine free area were observed.Results:A total of 32 patients with 33 lesions were enrolled in this study, including 23 males and 9 females and the age of the patients was 59.5±7.3 years. There were 19 (57.6%) lesions whose size of iodine-unstained area was consistent with the tumor pathological area. These 19 lesions were all positive for the pink sign, and the pink sign area overlapped with the iodine-unstained area. In addition, 4 (12.1%) iodine-unstained areas of the lesions did not match the size of the pathological area, and 10 (30.3%) iodine-unstained areas of the lesions were seriously inconsistent with the size of the pathological area. These 14 (42.4%) lesions were all positive for pink sign, and the pink sign area was significantly smaller than the iodine-unstained area. Among the 14 discordant lesions, 2 lesions underwent ESD according to the iodine-unstained area, which resulted in excessive resection and postoperative stenosis.Conclusion:Determining the extent of superficial esophageal cancer by iodine-unstained areas before ESD may lead to excessive resection of the lesions, which is related to the fact that the iodine-unstained areas of the lesions are sometimes significantly larger than the pink sign areas. Therefore, in order to achieve precise treatment, endoscopists can choose the iodine-unstained area with positive pink sign as the first choice for resection.

Objective　To investigate the efficacy and safety of early application of tirofiban after intravenous thrombolysis in patients with branch atheromatous disease.Methods　We retrospectively analyzed data collected from patients with BAD who were admitted to our hospital from March 2017 to July 2021.Subjects were classified into the alteplase-only control group and the alteplase+tirofiban treatment group.A propensity score matching analysis was performed to control substantial heterogeneity of subgroup.We compared the incidence of early neurological deterioration end,the rapeutic effect and bleeding risk between the two groups.Results　The incidence of early neurological deterioration was lower in the tirofiban treatment group than in the control group on day 1 (P<0.05).NHISS score were higher on day 1 and day 7 in the tirofiban treatment group as compared to the control group (P<0.05).MRS score on 90 days were higher in the tirofiban treatment group as compared to the control group (P<0.05).When compared to the control group,the proportion of patients with a favorable outcome (mRS,0~1 point) three months after stroke was greater in the tirofiban therapy group.The proportion of patients with dependence (mRS≥4 points) was lower in the tirofiban treatment group than in the control group.There was no case of intracranial hemorrhage in either group.Conclusion　Early adding low-dose tirofiban after intravenous thrombolysis could reduce early neurological deterioration and improve the long-term prognosis of patients with branch atheromatous disease.

Objective:To clarify the clinicopathological, especially molecular, features of early-onset gastric cancer with the aim of informing analysis of treatment strategies.Methods:In this retrospective case-control study, we examined data from a dedicated gastric cancer database in Zhongshan Hospital affiliated to Fudan University. The original cohort comprised 2506 patients with gastric cancer who had undergone gastrectomy in Zhongshan Hospital Fudan University from July 2020 to October 2021, including 198 with early-onset gastric cancer (aged ≤45 years) and 2,308 with non-early gastric cancer. We used a simple random sampling method to select 396 of the 2,308 patients aged >45 years (ratio of 1:2) as the control group and then compared molecular diagnostic data and clinicopathological features of the two groups.Results:The median age was 39 years in the early-onset gastric cancer group, while 66 years in the control group. The clinicopathological features of early-onset gastric cancer included female predominance (59.1% [117/198] vs. 27.8% [110/396], χ 2=54.816, P<0.001), less comorbidity (32.3% [64/198] vs. 57.1% [226/396], χ 2=32.355, P<0.001), poorer differentiation (93.9% [186/198] vs. 74.5% [295/396], χ 2=30.777, P<0.001) and higher proportion of diffuse type (40.4% [80/198] vs. 15.9% [63/396], χ 2=69.639, P<0.001), distant metastasis (7.1% [14/198] vs. 2.8% [11/396], χ 2=6.034, P=0.014). Regarding treatment, distal gastrectomy was more commonly performed than proximal gastrectomy (55.1% [109/198] vs. 47.0% [186/396], 1.5% [3/198] vs. 8.3% [33/396], χ 2=11.644, P=0.003). Family history of gastric cancer, TNM stage, tumor size, lymph node dissection, nerve invasion, nodes harboring metastases, range of lymph node dissection, digestive tract reconstruction procedure, implementation of laparoscopic surgery, combined resection, and preoperative treatment did not differ significantly between the two groups (all P>0.05). Molecular diagnosis showed there was a smaller percentage of mismatch repair deficiency in the early-onset gastric cancer than in the control group (1.0% [2/198] vs. 10.1% [40/396], χ 2=16.301, P<0.001), and a higher rate of positivity for Claudin 18.2 (77.8% [154/198] vs. 53.0% [210/396], χ 2=5.442, P<0.001). HER-2 and Epstein–Barr virus positivity rates did not differ significantly between the two groups. Conclusion:Early-onset gastric cancer is a distinct type of gastric cancer with a high degree of malignancy, and treatment targeting Claudin 18.2 may be effective.

Objective:To clarify the clinicopathological, especially molecular, features of early-onset gastric cancer with the aim of informing analysis of treatment strategies.Methods:In this retrospective case-control study, we examined data from a dedicated gastric cancer database in Zhongshan Hospital affiliated to Fudan University. The original cohort comprised 2506 patients with gastric cancer who had undergone gastrectomy in Zhongshan Hospital Fudan University from July 2020 to October 2021, including 198 with early-onset gastric cancer (aged ≤45 years) and 2,308 with non-early gastric cancer. We used a simple random sampling method to select 396 of the 2,308 patients aged >45 years (ratio of 1:2) as the control group and then compared molecular diagnostic data and clinicopathological features of the two groups.Results:The median age was 39 years in the early-onset gastric cancer group, while 66 years in the control group. The clinicopathological features of early-onset gastric cancer included female predominance (59.1% [117/198] vs. 27.8% [110/396], χ 2=54.816, P<0.001), less comorbidity (32.3% [64/198] vs. 57.1% [226/396], χ 2=32.355, P<0.001), poorer differentiation (93.9% [186/198] vs. 74.5% [295/396], χ 2=30.777, P<0.001) and higher proportion of diffuse type (40.4% [80/198] vs. 15.9% [63/396], χ 2=69.639, P<0.001), distant metastasis (7.1% [14/198] vs. 2.8% [11/396], χ 2=6.034, P=0.014). Regarding treatment, distal gastrectomy was more commonly performed than proximal gastrectomy (55.1% [109/198] vs. 47.0% [186/396], 1.5% [3/198] vs. 8.3% [33/396], χ 2=11.644, P=0.003). Family history of gastric cancer, TNM stage, tumor size, lymph node dissection, nerve invasion, nodes harboring metastases, range of lymph node dissection, digestive tract reconstruction procedure, implementation of laparoscopic surgery, combined resection, and preoperative treatment did not differ significantly between the two groups (all P>0.05). Molecular diagnosis showed there was a smaller percentage of mismatch repair deficiency in the early-onset gastric cancer than in the control group (1.0% [2/198] vs. 10.1% [40/396], χ 2=16.301, P<0.001), and a higher rate of positivity for Claudin 18.2 (77.8% [154/198] vs. 53.0% [210/396], χ 2=5.442, P<0.001). HER-2 and Epstein–Barr virus positivity rates did not differ significantly between the two groups. Conclusion:Early-onset gastric cancer is a distinct type of gastric cancer with a high degree of malignancy, and treatment targeting Claudin 18.2 may be effective.

BackgroundPatients demonstrating depressive disorder with psychotic symptoms often have increased risk of death and poor prognosis. A large amount of research has explored the factors influencing psychotic symptoms in adult patients with depressive disorder， but few has focused on adolescent patients. ObjectiveTo explore the influencing factors of psychotic symptoms in adolescent patients with depressive disorder， so as to provide references for early screening and intervention in clinic. MethodsA total of 96 adolescent patients who met the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） for depressive disorder and were seen in the psychiatry departments of Chaohu Hospital of Anhui Medical University and The Fourth People's Hospital of Hefei from September 2022 to January 2023 were included. Another 56 healthy individuals from the health examination center of Chaohu Hospital of Anhui Medical University were concurrently recruited as control group. Patients were assigned into psychotic group （n=32） and non-psychotic group （n=64） according to the presence or absence of psychotic symptoms. Hamilton Depression Scale-24 item （HAMD-24）， Positive and Negative Syndrome Scale （PANSS）， Positive and Negative Suicide Ideation （PANSI） and Childhood Trauma Questionnaire-Short Form （CTQ-SF） were used for evaluation. Plasma brain-derived neurotrophic factor （BDNF） concentration was obtained using Meso Scale Discovery electrochemiluminescence assay. Pearson and Spearman correlation analysis were adopted to determine the correlation of PANSS positive symptom subscale score with plasma BDNF concentration and clinical characteristics of adolescent depression patients with psychotic symptoms. Binary Logistic regression analysis was used to identify the factors influencing the presence of psychotic symptoms in adolescent patients with depressive disorder， and multiple linear regression analysis was utilized to screen the factors affecting the severity of psychotic symptoms. ResultsThe plasma BDNF concentration of adolescent patients with depressive disorder was lower than that of control group （t=-3.080， P<0.01）.The plasma BDNF concentration of psychotic group was lower than that of non-psychotic group （t=2.418， P<0.05）， while the body mass index （BMI） PANSI scores， CTQ-SF scores and HAMD-24 total scores were all higher than those of non-psychotic group （t=-2.024， -2.530， -2.187， -4.977， P<0.05 or 0.01）. Correlation analysis showed that PANSS positive symptom subscale scores were negatively correlated with anxiety/somatization factor score and weight factor score in HAMD-24 of psychotic group （r=-0.438， -0.498， P<0.05 or 0.01）. Binary Logistic regression showed that BMI， plasma BDNF concentration， HAMD-24 total scores and cognitive dysfunction factor score were the influencing factors of psychotic symptoms in adolescent patients with depressive disorder. Multiple linear regression analysis demonstrated that weight factor scores （β=-0.349， P<0.05） and anxiety/somatization factor score （β=-0.433， P<0.05） in HAMD-24 were the factors influencing the severity of psychotic symptoms. ConclusionHigh BMI， low plasma BDNF concentration， severe depressive symptoms and cognitive dysfunction may be the risk factors of psychotic symptoms in adolescent patients with depressive disorder， furthermore， BMI and anxiety symptoms are found to be associated with the severity of psychotic symptoms. ［Funded by Scientific Research Fund Project of Anhui Institute of Translational Medicine （number， 2022zhyx-B01）； Central Finance Supported Provincial Key Clinical Specialty Construction Project of Anhui Province in 2019］

The sustained cell proliferation resulting from dysregulation of the cell cycle and activation of cyclin-dependent kinases (CDKs) is a hallmark of cancer. The inhibition of CDKs is a highly promising and attractive strategy for the development of anticancer drugs. In particular, third-generation CDK inhibitors can selectively inhibit CDK4/6 and regulate the cell cycle by suppressing the G1 to S phase transition, exhibiting a perfect balance between anticancer efficacy and general toxicity. To date, three selective CDK4/6 inhibitors have received approval from the U.S. Food and Drug Administration (FDA), and 15 CDK4/6 inhibitors are in clinical trials for the treatment of cancers. In this perspective, we discuss the crucial roles of CDK4/6 in regulating the cell cycle and cancer cells, analyze the rationale for selectively inhibiting CDK4/6 for cancer treatment, review the latest advances in highly selective CDK4/6 inhibitors with different chemical scaffolds, explain the mechanisms associated with CDK4/6 inhibitor resistance and describe solutions to overcome this issue, and briefly introduce proteolysis targeting chimera (PROTAC), a new and revolutionary technique used to degrade CDK4/6.