OBJECTIVE:To compare the effects of repeated subcutaneous insulin administration vs. insulin pump continuous subcutaneous administration on related indexes of advanced age patients with gestational diabetes mellitus(GDM). METHODS:Inretrospective study,120 advanced age patients with GDM were randomly divided into group A(60 cases)and group B(60 cases). Group A was given Insulin aspart injection with initial dose of 0.5 U/(kg·d)subcutaneously before meal,adjusted according to fast-ing blood glucose(FPG)and postprandial 2 h blood glucose(2 hPG),and then given Isophane protamine biosynthetic human insu-lin injection with initial dose of 0.5 U/(kg·d)subcutaneously at bedtime,adjusted according to FPG and 2 hPG. Group B was giv-en Insulin aspart injection with initial dose of 0.5 U/(kg·d)added into insulin pump using 40% of total daily insulin as basic pump,increasing to 60% of total daily insulin if blood glucose control was poor,adjusted according to FPG and 2 hPG. Treatment course of 2 groups lasted for 4 weeks. The time of blood glucose reaching target,the amount of insulin were observed in 2 groups, and the levels of FPG,2 hPG,HbA1c,Hcy and Cys-C before and after treatment,the occurrence of patients and neonates compli-cations. RESULTS:The time of blood glucose reaching standard in group B was significantly shorter than group A;the amount of insulin,the incidence of hypoglycemia,premature birth,excessive amniotic fluid and gestational hypertension in group B were sig-nificantly lower than group A,with statistical significance(P<0.05). The incidence of neonatal respiratory distress syndrome in group B was significantly lower than group A,with statistical significance(P<0.05);but there was no statistical significance in the incidence of giant baby and malformation between 2 groups(P>0.05). After treatment,the levels of FPG,2 hPG,HbA1c,Hcy and Cys-C in 2 groups were significantly lower than before treatment,and the group B was significantly lower than the group A, with statistical significance(P<0.05). CONCLUSIONS:The insulin pump continuous subcutaneous administration is significantly better than repeated subcutaneous insulin administration in respects of controlling glucose level,reducing the amount of insulin,the levels of Cys-C and Hcy,maternal and neonatal complications.

Objective To investigate the effect of recombinant human growth hormone (rhGH) action on pregnancy rate of polycystic ovarian syndrome(PCOS).Methods The PCOS who were client in our hospital in February-August,2012 were investigated.The rhGH group (41 cases) were that all patients took rhGH at the same time ovulation.The control group (41 cases) were no medication group.The two groups had sex action after ovulation.Ovulation rate,pregnancy rate and endometrial score of the two groups were compared.Results Ovulation rate of rhGH group was 90.2％ (37/41),the control group was 68.2％ (28/41),the difference was statistically significant (x2 =3.459,P =0.036).Clinical pregnancy rate of RhGH group was 32.7％ (12/37),the control group was 25.0％ (7/28).The difference was statistics significance (x2 =4.319,P =0.032).Endometrial score of rhGH group was (14.96 ± 2.18),the control group was (12.77 ± 2.60) points,the difference between groups was statistically significant (t =-3.356,P =0.032).Conclusion Giving rhGH ovulation cycle specification can promote ovulation PCOS patients and improve the adverse factors affecting pregnancy,improving the pregnancy rate.

Objective To investigate the role of visfatin in the pathogenesis of gestational diabetes mellitus (GDM)and its correlation with insulin resistance.Methods The study recruited 58 pregnant women of 24 to 28 gestational weeks in People' s Hospital of Hebei Province from January to June 2013.Among them,30 were patients with GDM (GDM group),28 had normal oral glucose tolerance test and was referred as healthy pregnancy group (NGT group).Fourteen age-matched female who were first-degree relatives (FDR1)of type 2 diabetes mellitus patients,and 27 healthy nonpregnant women with normal oral glucose tolerance test were referred as high-risk group and normal controls (NC),respectively.The fasting plasma glucose (FPG),1 hour and 2 hours postprandial glucose levels were measured by glucose oxidase method.The fasting insulin (FIN)levels were measured by radioimmunoassay and the homeostatic model assessment-insulin resistance index (HOMA-IR)was calculated.The levels of total cholesterol (TC),triglycerdes (TG),high density lipoprotein cholesterol (HDL)and low density lipoprotein cholesterol (LDL)were determined.The visfatin levels were measured by ELISA.Results (1)The levels of FPG were significantly higher in GDM,FDRI and NC group [(5.5±0.7),(5.1±0.6),(5.2±0.4) mmol/L] than that in NGT group [(4.5 ± 0.3) mmol/L],respectively (P＜0.05).(2) The levels of INS [(14 ± 6) mU/L],HO MA-I R (4.0±2.0),1 hour [(10.9± 1.8) mmol/L] and 2 hours [(8.6± 1.8) mmol/L] postprandial glucose levels of GDM group were significantly higher than those in NGT group [(12±4) mU/L,2.0± 1.0,(7.4± 1.3) and (6.2 ±0.9) mmol/L],respectively (P＜0.05).(3)The levels of TC,TG,HDL and LDL levels in GDM group were (5.5±0.9),(2.8±0.8),(1.8±0.4)and(3.3±0.8) mmol/L,and were(5.9 ± 0.8),(2.5 ± 0.7),(1.9 ± 0.4) and (3.4 ± 0.6) mmol/L in NGT group.The levels of lipid in the two groups were significantly higher than those in FDR 1 or NC group,respectively (P＜0.05).(4) The levels of visfatin in GDM group and NGT group [(43 ± 10),(45 ± 12) μg/L] were significantly higher than that in FDR1 or NC group [(29±9),(36±7) μg/L],respectively (P＜0.05),but the visfatin levels in FDR 1 group were significantly lower than that in NC group (P＜0.05).The visfatin levels in GDM group were slightly lower than that in NGT group,but the difference was not statistically significant (P＞0.05).(5)The visfatin levels in NGT group were negatively correlated to the levels of FPG,HOMA-IR and TC(r=-0.38,-0.44,-0.47,respectively,P＜0.05).But the visfatin levels in GDM group were not correlated with the levels of FPG,HOMA-IR,TC (r=-0.16,-0.01,0.33,respectively,P＞ 0.05).While in NC group,the levels of visfatin were negatively correlated with FPG and 2 hours postprandial glucose (r=-0.48,-0.42,respectively,P＜0.05).Conclusion Visfatin may be an important adipokine that involved in the carbohydrate and lipid metabolism in GDM,and is related to the pathogensis of GDM and insulin resistance.

Abstract: Cancer immunotherapy, which is an attractive strategy harnessing the host's own immune system to remove tumor cells, has been widely used in clinical practice, yet with low response rate and immune-related adverse events. Unlike traditional chemotherapy, the targets of immunotherapy exhibit high spatial heterogeneity and are distributed in different cell types or secondary organelles, resulting in off-target and on-target toxicity, which greatly reduces the efficacy and safety of treatment. Due to the altered metabolic level, tumor tissues often display a lower pH than normal tissues. In addition, the endocytosis pathway is accompanied by continuous pumping of protons. Therefore, the variation of environmental pH values could serve as an ideal stimulus for precise drug delivery and release. In recent years, pH-responsive materials (e.g., polymers, biomacromolecules, lipid nanoparticles, biofilm, inorganic nanoparticles, and metal-organic frameworks) have been widely investigated in the field of cancer immunotherapy. This paper summarizes recent strategies of pH-responsive drug delivery systems based on different types of carriers, aiming to provide some reference for the design of next generation of tumor-targeting formulations in cancer immunotherapy.

Objective:To evaluate the effect of three teaching methods of case-based learning (CBL), problem-based learning (PBL) and blended learning (CBL+PBL) on the teaching of clinical clerkship of cardiovascular internal medicine among medical students.Methods:A total of 175 third-year medical students were divided into three groups (CBL, PBL and CBL+PBL). They entered the clinical clerkship in batches, and then received written examination and questionnaire survey after the teaching. The data were processed by SPSS 19.0 and were compared by one-way ANOVA or chi-square test (R × C) among groups.Results:The total average scores of students in CBL, PBL and CBL+PBL groups were 15.34±2.88, 14.67±2.98 and 17.13±2.82, respectively ( P<0.05), and the proportion of students with "excellent" scores were 27.4%(17/62), 14.5%(9/62) and 58.1%(36/162), respectively. Most students in CBL group did not agree that CBL helped to train literature access skills [70.7%(41/58)] or teamwork ability [82.8%(48/58)], compared with which 70.9%(39/55) in PBL group thought it helped to train literature access skills but only 7.3%(4/55) well accepted PBL. In addition, majority of students in CBL+PBL group believed it was helpful to gain learning interest [64.3%(36/56)] and train team cooperation ability [62.5%(35/56)], and [53.6%(30/56)] favored this teaching method. Conclusion:Compared with traditional CBL, PBL fails to attract students or improve teaching performance; while blended learning is benefited for the students and can improve teaching quality.

Objective:To investigate the clinical treatment options for cavernous transformation of portal vein (CTPV).Methods:Data of 65 CTPV patients receiving invasive treatment and followed up at the First Affiliated Hospital of Zhengzhou University between Apr 2011 and Apr 2021 were collected. Patients were divided into four groups based on different treatment option, 24 patients were treated with transjugular intrahepatic portosystemic stent-shunt (TIPS) and 11 patients with splenopneumopexy, while 22 patients underwent splenectomy and devascularization , 8 were treated by endoscopic variceal ligation . The difference of postoperative upper gastrointestinal bleeding and hepatic encephalopathy between the four groups were analyzed,Results:There were no difference between four groups in sex, age, preoperative serum aspartate aminotransferase, total bilirubin, albuminand Child-Turcotte-Pugh grade. The incidence of hepatic encephalopathy in the TIPS group was 33.3%±9.6%、46.5%±10.3% and 64.4%±13.1% in half year, 1 year, and 3 years , respectively. Postoperative hepatic encephalopathy rate was higher in TIPS group( χ2=31.191, P=0.000). Three patients in the TIPS group developed upper gastrointestinal hemorrhage within 6 months after the operation, and postoperative upper gastrointestinal bleeding rate was higher in splenopneumopexy group( χ2=7.542, P=0.006), Conclusion:The clinical treatment options for CTPV patients are complicated ,we should make individual treatment options depend on the etiology, clinical symptoms and site of blood flow obstruction.

Objective:To investigate the predictive value of controlled nutritional status (CONUT) score for overt hepatic encephalopathy (OHE) after transjugular intrahepatic portosys-temic stent-shunt (TIPSS) in Budd-Chiari syndrome patients.Method:The retrospective case-control study was conducted. The clinicopathological data of 48 Budd-Chiari syndrome patients who underwent TIPSS in the First Affiliated Hospital of Zhengzhou University from August 2014 to March 2021 were collected. There were 26 males and 22 females, aged (46±13)years. Observation indicators: (1) surgical situations and follow-up; (2) analysis of influencing factors of OHE after TIPSS; (3) predic-tion of OHE after TIPSS. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was performed using the t test. Measurement data with skewed distribution were represented by M( Q1, Q3), and comparison between groups was performed using the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was performed using the chi-square test or Fisher exact probability. Multivariate analysis was performed using the Logistic regression model with forward method. The receiver operating characteristic (ROC) curve was drawn and the area under the curve (AUC) was calculated to evaluate the efficacy. Comparison among AUC was performed using the Delong test. Results:(1) Surgical situations and follow-up. All 48 patients underwent TIPSS successfully, and the operation time of the 48 patients was (131±29)minutes. All patients were implanted with 8 mm covered stent. All 48 patients were followed up for 46(25,71)months, and there were 14 cases with OHE and 34 cases without OHE after TIPSS. Of the 14 cases with OHE, 12 cases were evaluated as West-Haven Ⅱ grade and 2 cases were evaluated as West-Haven Ⅲ grade. (2) Analysis of influencing factors of OHE after TIPSS. Results of multivariate analysis showed that history of hepatic encephalo-pathy and CONUT score were independent factors influencing the incidence of OHE of Budd-Chiari syndrome patients who underwent TIPSS ( odds ratio=8.36, 1.74, 95% confidence interval as 1.02?68.75, 1.12?2.69, P<0.05). (3) Prediction of OHE after TIPSS. Results of ROC curve showed that the AUC of the CONUT score, the Child-Pugh score of liver function and the integrated model of end-stage liver disease (iMELD) score in predicting the incidence of OHE after TIPSS was 0.77(95% confidence interval as 0.64?0.91, P<0.05), 0.71(95% confidence interval as 0.56?0.87, P<0.05) and 0.71(95% confidence interval as 0.53?0.88, P<0.05), respectively, and there was no significant difference between the AUC of the CONUT score and the Child-Pugh score of liver function or the iMELD score ( Z=0.84, 0.59, P>0.05). The optimal cutoff value of CONUT score in predicting the incidence of OHE after TIPSS was 7, with the sensitivity, specificity and Yodon index as 78.6%, 61.8% and 0.40, respectively. Conclusion:The CONUT score can be used to predict the incidence of OHE in Budd-Chiari syndrome patients who underwent TIPSS, and the discrimination of CONUT score is equivalent to the Child-Pugh score of liver function and the iMELD score.

Objective:To study the factors influencing short-term prognosis of patients with Budd-Chiari syndrome (B-CS) presenting with upper gastrointestinal bleeding and to assess the predictive value of platelet-albumin-bilirubin score (PALBI) on death within 30 d in these patients.Methods:A retrospective study was conducted on 74 patients with B-CS who presented with upper gastrointestinal bleeding and were treated at the First Affiliated Hospital of Zhengzhou University from January 2014 to February 2020. There were 51 males and 23 females, with age of (46.5±11.1) years old. These patients were divided into the survival group ( n=58) and the death group ( n=16) according to the disease outcomes up to 30 d of follow-up. Factors influencing short-term deaths of these patients were analyzed, and the predictive values of PALBI, ALBI, CTP and MELD scores on short-term prognosis of the patients were assessed. The receiver operating characteristic (ROC) curves were plotted, and the areas under the curve (AUC) were calculated and compared. Results:The differences between patients in the survival and death groups for white blood cell, platelet, PALBI score, PALBI classification, ALBI score, CTP score, MELD score, and presence or absence of hepatic encephalopathy were significantly different (all P<0.05). Multivariate logistic regression analysis showed that CTP score≥10 or CTP grade C ( OR=1.669, 95% CI: 1.048-2.661), and PALBI score >-2.09 or PALBI grade 3 ( OR=5.245, 95% CI: 2.128-12.924) were independent risk factors for predicting death within 30 days. The areas under the ROC curves for PALBI, ALBI, CTP and MELD score were 0.89, 0.72, 0.77 and 0.76, with the cut-off values of -1.92, -1.60, 8.50 and 13.60, respectively. The differences between the PALBI score and ALBI, CTP scores were significantly different ( P<0.05). Conclusion:The PALBI score showed a positive predictive value on short-term prognostic assessment of patients with B-CS presenting with upper gastrointestinal bleeding. It was comparable to the effect of the MELD score but was significantly better than the ALBI and CTP scores.

OBJEC TIVE To provide reference for clinical comprehensive evaluation of pediatric drugs in China. METHODS Taking pediatric anti-allergic drugs as an example ，the clinical comprehensive evaluation methods of pediatric drugs in medical institutions were explored from the aspects of theme selection ，evaluation content and dimension ，evaluation index ，evaluation method and evaluation result report. RESULTS & CONCLUSIONS During the clinical comprehensive evaluation of pediatric drugs，under the guidance of relevant national guidelines for clinical comprehensive evaluation ，the evaluation topics could be selected according to the three principles of importance ，relevance and evaluability ，and then an appropriate evaluation index system could be developed around the six dimensions of safety ， effectiveness， economy， suitability，accessibility and innovativeness；qualitative and quantitative data integration analysis of the drugs to be evaluated were performed. In the evaluation ， it is necessary to focus on children ’s clinical basic drug use practice and decision-making needs ，normatively，scientifically and reasonably define the core index set and standard data set required by different dimensions of evidence ，standardize the collection and use of real-world data ，and effectively combine other types of evidence to truly play its advantageous role in the clinical comprehensive evaluation of pediatric drugs in China.

Objective To investigate the effect of metformin on liver fibrosis in a mouse model of Budd-Chiari syndrome and its mechanism. Methods A total of 30 male C57 mice were randomly divided into sham-operation group (SHAM group) with 6 mice, sham operation+ metformin group (SHAM+M group) with 5 mice, Budd-Chiari model group (BCS group) with 10 mice, and Budd-Chiari model+metformin group (BCS+M group) with 9 mice. The mice in the model group were treated with partial ligation of the inferior vena cava, those in the SHAM group were not treated with ligation, and those in the metformin group were given 0.1% metformin in drinking water besides modeling. The mice were sacrificed after 6 weeks. HE staining and picrosirius red staining were used to observe liver histopathology and collagen deposition; immunohistochemistry was used to measure the expressions of α-smooth muscle actin (α-SMA) and fibrinogen; quantitative real-time PCR was used to measure the mRNA expression of hypoxia-inducible factor 1α (HIF-1α) and type Ⅰ collagen (collagen 1), and Western blot was used to measure the relative protein expression levels of HIF-1α, vascular endothelial growth factor (VEGF), fibrinogen, α-SMA, and collagen 1. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Pathological staining showed that compared with the SHAM group, the BCS group had significant liver fibrosis, disordered arrangement of hepatocytes near the central vein, sinusoidal expansion with red blood cell deposition and a small amount of inflammatory cell infiltration, and collagen deposition. The BCS group had significant increases in the mRNA expression levels of HIF-1α and collagen 1 and the protein expression levels of α-SMA, collagen 1, HIF-1α, VEGF, and fibrinogen (all P < 0.05); compared with the BCS group, the BCS+M group had significant alleviation of liver fibrosis, red blood cell deposition, and collagen deposition and significant reductions in the mRNA expression levels of HIF-1α and collagen 1 and the protein expression levels of α-SMA, collagen 1, HIF-1α, VEGF, and fibrinogen (all P < 0.05). Conclusion Metformin can improve congestive liver fibrosis caused by Budd-Chiari syndrome, possibly by reducing microthrombus in hepatic sinusoid and inhibiting the HIF-1α/VEGF pathway.