Construction of albumin nanoparticles loading PROTAC and its inhibition effect on NAD+ in glioma cells / 药学实践杂志

Objective To prepare and optimize the formulation of Albumin nanoparticles loading PROTAC molecule and observe the inhibition effect of nanoparticles on the proliferation and NAD+ metabolism of glioma cells. Methods Albumin nanoparticles loading NPT-B2 were prepared and characterized with a thermal driving method, and the prescription was optimized. An HPLC method was established to determine the content of NPT-B2. The proliferation inhibition of NPT-B2 and B2-BSA-NPs on U251 cells were investigated by the CCK8 method, and the degradation effects of NPT-B2 and B2-BSA-NPs on NAMPT in glioma cells were investigated by western blotting. Results The HPLC method was stable, with good linearity, precision, and recovery rate. The nanoparticles had a particle size of about 55.48 nm, a potential of about −12.9 mV, an encapsulation rate of about 94.74%, and a drug loading amount of about 8.61%. The IC50 of NPT-B2 on glioma cells was 61.16 nmol/L, which had a degradation effect on NAMPT. The IC50 of B2-BSA-NPs on glioma was 41.21 nmol/L, which had a very significant degradation effect on NAMPT. Conclusion Albumin nanoparticles loading PROTAC molecules were constructed. The prescription was optimized to improve the drug encapsulation rate, and the low water solubility of PROTAC molecule was improved, which had a significant inhibitory effect on the proliferation and NAD+ energy metabolism of glioma cells.

Expression and clinical significance of B cell ectopic gene 2 in pancreatic cancer tissue / 中华胰腺病杂志

Objective:To investigate the expression of the B cell ectopic gene 2 (BTG2) in the pancreatic cancer tissue and analyze its relationship with the clinicopathological features and prognosis.Methods:46 pairs of pancreatic cancer tissues and corresponding adjacent tissues kept in paraffin in the pathology department, and 9 fresh pancreatic cancer tissues and corresponding adjacent tissues resected by surgery in Department of Pancreatic Surgery of Sinopharm Dongfeng General Hospital from June 2015 to December 2020 were collected. BTG2 gene expression in 46 pairs of pancreatic cancer tissues and corresponding adjacent tissues were detected by immunohistochemical staining, and high and low BTG2 expression groups were divided. BTG2 gene expression in 9 fresh pancreatic cancer tissues and corresponding adjacent tissues were detected by RT-PCR. The correlation between BTG2 protein expression level and clinicopathological features was analyzed. Furthermore, the survival curve and death risk curve were drawn using the Kaplan-Meier method, and the Cox regression hazards model was applied for the univariate and multivariate analysis of the factors affecting the prognosis of pancreatic cancer.Results:29 of 46 (63.04%) pancreatic cancer tissues had high BTG2 expression, and 38(82.61%) of corresponding adjacent tissues had high BTG2 expression; and BTG2 high expression rate of adjacent tissues was significantly higher than that of cancer tissues. Three out of 9 pancreatic cancer tissues were highly differentiated, and six cases had medium-and low differentiation. The BTG2 expression of highly differentiated pancreatic carcinoma was significantly higher than that of moderately and poorly differentiated carcinoma tissues [(0.66±0.07 vs 0.24±0.18); the expression level of adjacent tissues was significantly higher than that of cancer tissues (1.00±0.00 vs 0.38±0.30), and all differences were statistically significant (all P values <0.001). Low BTG2 expression in pancreatic cancer was associated with low tumor differentiation and vascular invasion (all P values <0.05), but was not correlated with tumor location, volume, lymph node metastasis, CA19-9 level and postoperative liver metastasis. The median survival of high BTG2 expression group was significantly longer than that of low BTG2 expression group (525 d vs 266 d, P<0.001). Among patients with survival time ≥300 d, the survival time was significantly higher in the high BTG2 expression group than in the BTG2 low expression group (616±135d vs 426±113 d), and the difference was statistically significant ( P<0.001). Among patients with survival time <300 d, there was no significant difference between BTG2 high and low expression group. The results of the univariate analysis showed that tumor differentiation degree, vascular invasion, BTG2 expression, CA19-9 levels, and postoperative liver metastasis were all associated with the prognosis of pancreatic cancer. The results of the multivariate analysis showed that BTG2 expression level ( HR=2.572, 95% CI1.140-5.802, P=0.023), vascular invasion ( HR=0.023, 95% CI0.072-0.572, P=0.003) and postoperative liver metastasis ( HR=0.240, 95% CI0.102-0.564, P<0.001) were independent risk factors affecting the prognosis of patients with pancreatic cancer. Conclusions:BTG2 expression in pancreatic cancer tissues was significantly lower than that in adjacent tissues, and its low expression was associated with strong aggressiveness, low differentiation degree and poor prognosis of pancreatic cancer. The effect of BTG2 on the prognosis in pancreatic cancer patients was mainly in the long term.

Monomorphic epithelial intestinal T-cell lymphoma: a clinicopathological characteristic analysis / 白血病·淋巴瘤

Objective:To investigate the histopathological morphology, immunophenotype, molecular pathological features, clinical prognosis and treatment of monomorphic epithelial intestinal T-cell lymphoma (MEITL).Methods:The clinicopathological data of 5 patients with MEITL in Sichuan Jinyu Medical Laboratory Center Co., Ltd from March 2019 to February 2021 were retrospectively analyzed, and literatures were reviewed. All cases were tested by using histopathology, immunohistochemistry, in situ hybridization of Epstein-Barr virus (EBV) and T-cell clonability assessment, and 1 case had second-generation sequencing (NGS) test. Clinical follow-up was performed in 2 patients.Results:All 5 MEITL cases were middle-aged and old men. The histopathology showed that intestinal wall was diffuse with tumor cells infiltrating, and the cells were obviously epitheliophilic. All the tumor cells CD3, CD8, CD56, GrB were positively expressed, and expressions of other T-cell markers were different, among which 1 case had CD30 positive and 1 case had CD20 positive. All 5 cases were negative for EBV by in situ hybridization. Monoclonal rearrangement of T-cell receptor gene was detected in all 5 cases. Mutations of BCOR, JAK3, STAT5B and ATM were detected in 1 case by using NGS. Among 2 cases followed-up, 1 patient relapsed 7 months after he had the initial onset and underwent the first operation, and then he had another operation. This patient finally died of extensive metastasis in the lung, liver and abdominal cavity as well as ascites 13 months later; another patient died 1 month after emergency surgery for perforation.Conclusions:MEITL is a rare primary T-cell lymphoma of the digestive tract. The oncogenic event in the pathogenesis of MEITL mainly involves mutations in the tumor suppressor gene SETD2 and mutations in one or more genes of the JAK/STAT pathway. Currently, there is no standard treatment for MEITL. Most treatment options include surgical resection and anthracycline-based chemotherapy.

Correlation between the ability of pull-up and the composition of upper limbs among male college students in Guangxi / 中国学校卫生

Objective@#To explore the correlation between pull-up ability and upper body composition of male college students in a college in Guangxi, and to provide scientific guidance for college students’ exercise.@*Methods@#A total of 685 male college students were randomly selected from a college in Guangxi.Pull up tests were implemented according to the national physical health test standards. Measurements of muscle mass, fat mass, fat percentage, etc. of the upper limbs were conducted by using the Ogilvy Body Composition Meter (TANITA MC-180). Data entry and analysis were performed by using SPSS 23.0.@*Results@#The pass rate of male college students in the region was 21.7%; There was a statistically significant difference in the fat mass and percentage of body fat between males with different pull-up ability (F=11.30，14.18，12.91，15.22，P<0.01).After controlling age, height, weight and BMI, partial correlation analysis showed that there was a negative correlation between the pull-up ability of male college students and the fat mass and limb fat rate of both upper limbs(r=-0.22, -0.33, -0.31, -0.38, P<0.01).@*Conclusion@#The ability of male students in Guangxi to pull up is needed to be improved. Pull-up exercises can reduce fat mass and fat percentage in the upper limbs and improve body composition.

Vitamin D receptor in subcutaneous adipose tissue and serum vitamin D LeveLs reLate to gestationaL diabetes meLLitus in overweight/obese pregnant women / 中华围产医学杂志

Objective To investigate the differences in the expression of vitamin D receptor (VDR) and serum vitamin D levels in subcutaneous adipose tissue between overweight/obese and normal-weight gravidas, and the relationship between these two indicators and gestational diabetes mellitus (GDM). Methods Women with full-term singleton pregnancies who underwent elective cesarean section in Changzhou Maternal and Child Health Care Hospital Affiliated to Nanjing Medical University from January 2015 to April 2017 were enrolled. Among them, there were 70 cases GDM women, including 35 normal-weight (NW-GDM group) and 35 overweight/obese women (OW-GDM group). During the same period, another 70 pregnant women with normal glucose tolerance who underwent scheduled cesarean delivery were selected as the control group, including 35 normal weight women (NW-control group) and 35 obese/overweight women (OW-control group). Fasting blood samples were collected before operation to determine the levels of different biomarkers, including vitamin D, lipid, fasting blood glucose, fasting insulin and adiponectin, and to calculate the homeostasis model assessment-insulin resistance (HOMA-IR). Two subcutaneous adipose tissue samples of the abdominal wall were taken during the operation to detect the expression and distribution of VDR protein with immunohistochemistry. Meanwhile, VDR mRNA transcription level was quantitatively analyzed using real-time fluorescence quantitative polymerase chain reaction. One-way analysis of variance, LSD, Kruskal-Wallis test, Mann-Whitney U test, Chi-square test and logistic regression analysis were used for statistical analysis. ResuLts (1) The body mass index (BMI) of the OW-control group and the OW-GDM group before pregnancy and delivery were all higher than that of the NW-control group and the NW-GDM group [BMI before pregnancy: (29.2±2.9), (29.4±3.8) vs (21.1±2.3) and (21.9±2.0) kg/m2, F=87.766; BMI before delivery: (35.2±3.4), (35.1±4.3) vs (27.9±2.8) and (28.8± 3.3) kg/m2, F=44.827; all P<0.001]. Newborn birth weight and the proportion of diabetic family history in the OW-GDM group were higher comparing to the NW- and OW- control group [(3 893±498) vs (3 501±402) and (3 625±332) g, F=4.751; 22.9%(8/35) vs 5.7%(2/35) and 5.7%(2/35), χ2=7.869; all P<0.05]. (2) In the OW-control group, the fasting insulin level and HOMA-IR were higher and the adiponectin and vitamin D concentration were lower than those in the NW-control group [13.3(12.3-14.5) vs 12.0(10.4-13.3) mmol/L, 2.7(2.4-3.0) vs 2.2(2.0-2.7), (61.8±20.4) vs (74.9±29.3) ng/ml, (21.6±7.2) vs (25.9±7.3) ng/ml; all P<0.05], and similar results were found between the OW-GDM group and the NW-GDM group [15.3(12.3-19.5) vs 12.0(10.1-15.8) mmol/L, 3.4(2.6-4.1) vs 2.6(2.1-3.2), (50.3±22.3) vs (62.1±23.2) ng/ml, (17.1±6.7) vs (20.6±7.9) ng/ml, all P<0.05]. Compared with the NW-control group, the NW-GDM group had higher fasting glucose and lower high density lipoprotein-cholesterol (HDL-C), adiponectin and vitamin D levels [4.6(4.3-5.1) vs 4.3(4.0-4.5) mmol/L, 1.7(1.6-1.9) vs 2.1(1.6~2.4) mmol/L, (62.1±23.2) vs (74.9±29.3) ng/ml, (20.6±7.9) vs (25.9±7.3) ng/ml; all P<0.05]. Compared with the OW-control group, fasting glucose, fasting insulin and HOMA-IR were higher and HDL-C, adiponectin and vitamin D levels were lower in the OW-GDM group [4.7(4.4-5.4) vs 4.5(4.2-4.7) mmol/L, 15.3(12.3-19.5) vs 13.3(12.3-14.5) mmol/L, 3.4(2.6-4.1) vs 2.7(2.4-3.0), 1.6(1.4-1.8) vs 1.9(1.7-2.2) mmol/L, (50.3±22.3) vs (61.8±20.4) ng/ml, (17.1±6.7) vs (21.6±7.2) ng/ml; all P<0.05]. (3)The overall vitamin D deficiency rate during the third trimester of the four groups was 78.6% (110/140), and the figure was 62.8% (22/35), 82.8% (29/35), 77.1% (27/35) and 91.4% (32/35) in the NW-control group, OW-control group, NW-GDM group and OW-GDM group (χ2=8.994, P=0.029), indicating a higher rate in the OW-GDM group than that in the NW-control group (χ2=8.102, P=0.004). (4) VDR was expressed in the nucleus of adipose tissue in all samples and statistic difference in protein expression was found among the four groups. VDR mRNA expression was higher in both GDM subgroups than that in the two control subgroups, and also higher in the two overweight/obese subgroups than in the corresponding normal-weight subgroups. (5)Serum vitamin D level was negatively correlated with fasting blood glucose and pre-pregnancy BMI, and positively correlated with adiponectin (P<0.05). The incidence of GDM was related to family history of diabetes, VDR mRNA, total cholesterol, HDL-C and HOMA-IR. ConcLusions GDM and overweight/obese patients had decreased serum vitamin D level and increased VDR in subcutaneous adipose tissue. These two factors are closely related to GDM.

Effects of hypoxia inducible factor-2α on promoting angiogenesis of residual hepatocellular carcinoma after high-intensity focused ultrasound ablation / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the dynamic features of angiogenesis in residual tumors after high intensity focused ultrasound (HIFU),and to determine the temporal effect and mechanism of hypoxia inducible factor-2 alpha (HIF-2a) in the angiogenic process of residual tumors.</p><p><b>METHODS</b>Xenograft tumors of HepG2 cells were generated by subcutaneously inoculating athymic BALB/c nu/nu mice with the hepatoma cells.About 30 days after inoculation,all mice (except in the control group) were treated by HIFU and assigned randomly to the following 7 groups according to various time intervals post-treatment:1st,3rd,5th day and 1st,2nd,3rd,4th week when the residual tumor tissues were obtained from the experimental groups.Protein levels of HIF-2a and vascular growth factor A (VEGF-A) were quantified by immunohistochemistry and western blotting,and mRNA levels were measured by (real-time quantitative) qPCR. Microvascular density (MVD) was calculated by counting the CD31-positive vascular endothelial cells identified by means of an immunohistochemical staining method.</p><p><b>RESULTS</b>Compared with results from the control group,the protein and mRNA levels of HIF-2a expression reached the highest level in the experimental mice at the 2nd week (P=0.000 and P < 0.01 respectively),and were decreased thereafter(3rd week and 4th week, P=0.000 and P < 0.05).VEGF-A expression in the residual tumor tissues group that received HIFU was significantly decreased,compared with the control group,at all time points uPto 1 week (all P=0.000 and P < 0.01),but the levels increased compared to controls in the 2nd through 4th week (all P=0.000, P < 0.05). Similar results were obtained for MVD.</p><p><b>CONCLUSION</b>HIFU treatment can inhibit angiogenesis in residual hepatoma tissues in the short-term (1 to 2 weeks post-treatment) in mice with hepatocellular carcinoma,but can promote angiogenesis overtime (2 to 4 weeks post-treatment); the angiogenic process may involve the HIF-2α/VEGFA pathway.</p>

Discussions of medical disputes on birth defects of newborns / 中华医院管理杂志

A variety of views and approaches were found in the appraisal and judgments of the people's courts in various provinces and cities,on medical disputes involving absence of a hand or foot of newborns,which result in different or event contradictory court decisions.This study made an analysis of the characteristics,nature,and classification of such cases as well as countermeasures of medical institutions,with recommendations on rational and appropriate handling of such cases,for the purposes of legitimate rights maintenance of both doctors and patients,and promotion of mutual understanding between the two parities,and establishment of a harmonious doctor-patient relationship.

Follow-up study on exercise tolerance and lung function of rehabilitation therapy in stationary COPD patients / 中国医学装备

Objective: To explore the effects of pulmonary rehabilitation on exercise tolerance ability. Methods:Fifteen (10 males,5 females)stable COPD patients, entered into 48 weeks of rehabilitation program. The lung function, 6 minutes walk distance(6MWD) were measured at pre, post and first post-maximal exercise training. Results: There was no significiant change in FEV1, FEV1/predict and FEV1/FVC at pre, post and first post-maximal exercise training in COPD patients. 6MWD significantly increased in COPD patients after 48 weeks exercise training program. There was no significant change in baseline and first post-maximal exercise training in COPD patients. Conclusion:There were no significant changes in parameters of lung function before and after training. The exercise tolerance in COPD patients was significantly improved by 48 weeks exercise training.

The effect of SiRNA -Oct4 expression on HCC cell line HepG2 / 中华普通外科杂志

Objective To investigate the expression of Oct4 in liver cancer, and the interrelation of the Oct4 and Wnt/β-catenin genes in hepatocellular carcinoma( HCC) cell line HepG2. Methods RTPCR technique was used to detect the expression of Oct4 and β-Catenin in HCC specimens; RNAi was used to knock-down the expression of Oct4 in HepG2, and the change of Wnt/β-catenin related genes were detected by Real time-PCR. Results In HCC specimens, the expression of Oct4 and β-Catenin in tumor and cirrhotic liver tissues were stronger than normal liver tissues. In SiRNA Oct4 HepG2 cells, the expression of Oct4 was downregulated, and β-catenin as well as Wnt10b were in a positive correlation with Oct4, TCF3 was in negative correlation with Oct4. Clone formation and move ability of the HepG2 were downregulated. Conclusions The expression of Oct4 was higher in tumor tissues than in normal liver tissues. Silencing Oct4 by SiRNA-0ct4 in HepG2 resulted in decreased ability of clone formation and cell movement.