[Efficacy and safety of anti-PD-1 monoclonal antibody in advanced hepatocellular carcinoma after TACE combined with TKI therapy].

Objective: To evaluate the efficacy and safety of anti-programmed cell death 1 (PD-1) receptor monoclonal antibody (MoAb) in patients with advanced hepatocellular carcinoma (HCC) after treatment of transcatheter arterial chemoembolization (TACE) combined with tyrosine kinase inhibitor (TKI). Methods: From February 2019 to February 2020, 56 HCC patients who relapsed after TACE-TKI treatment in Department of Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University were enrolled. All patients received anti-PD-1 MoAb (sintilimab injection) and followed up every 6 weeks. According to mRECIST, the curative effect was evaluated as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD). Objective response rate (ORR) and disease control rate (DCR), progression-free survival (PFS) and treatment-related adverse events (TRAEs) were recorded. Univariate analysis by Chi-square test and binary logistic regression model was used to determine the influencing factors of DCR. The Kaplan-Meier method and Cox proportional hazard regression model were used to analyze the survival data. Results: A total of 48 patients were enrolled in this study including 42 males and 6 females, with a median age of 55 years (29-71 years). ECOG scores comprised of 0 in 24 cases, 1-2 in 24 cases. Thirty-six patients were in Child-Pugh grade A of liver function and 12 cases were grade B. The median follow-up time was 4.5 months. There were 2 patients achieved CR, 12 patients with PR and 16 with SD. ORR was 29.2%, DCR was 62.5%. The independent influencing factors of DCR was ECOG score and AFP level (P=0.031, P=0.012). Median PFS was 4.1 months (95%CI 2.7-5.4 months), and ECOG score was the independent influencing factor of PFS (P=0.042). Treatment-related adverse events were reported in 70.8% (34/48) patients. Incidence of grade Ⅲ-Ⅳ TRAEs was 22.9% (11/48). Conclusion: In patients with HCC who relapse from TACE and TKI treatment, anti-PD-1 monoclonal antibody is efficacious safe especially in those with ECOG 0 score.

[Analysis of genetic abnormalities and clinical outcome of fetus with ultrasonic nonstructural abnormality].

Objective: To analysis the incidence of abnormal genetics and the clinical outcome of fetuses with ultrasonic nonstructural abnormality. Methods: This study was conducted retrospectively. 631 pregnant women were enrolled in the Prenatal Diagnostic Center of Fujian Maternal and Child Health Hospital due to ultrasonic nonstructural abnormality from January 2016 to January 2019. According to different gestational weeks, amniotic fluid or umbilical cord blood samples were collected for chromosome karyotype analysis and SNP-array. According to the number of nostructural abnormalities, they were divided into 1 nostructural abnormality group, 2 nostructural abnormalities group, and ≥3 nostructural abnormalities group. Chi-square test was used for comparison between groups. Results: Of the 631 cases, 34 cases (5.4%, 34/631) had abnormal karyotypes, including 20 cases with abnormal chromosome number and 14 cases with abnormal chromosome structure. In results of SNP-array, there were 53 abnormal results (8.4%, 53/631), including 32 cases of pathogenic copy number variations (CNV) and 21 cases of variations of uncertain clinical significance (VOUS). The rates of pathogenic CNV were 4.57% (21/260), 4.76% (7/147) and 16.67% (4/24) in the group of 1, 2 and ≥3 nostructural abnormalities, respectively. The rate of the three groups showed a linear trend, and the difference was statistically significant (χ²=7.419,P<0.05). In the single nostructural abnormality group, the rate of pathogenic CNV of nasal bone dysplasia, fetal growth restriction (FGR) and thickened nuchal translucency (NT) were 8.11% (3/37), 7.04% (5/71) and 5.60% (7/125), respectively. Conclusions: Compared with the karyotype analysis, SNP-array can significantly improve the detection rate of genetic abnormalities in ultrasonic nonstructural abnormality. When multiple ultrasonic nonstructural abnormality were combined, the risk of genetic abnormalities showed an upward trend.

[Analysis on post-marketing effectiveness and immunogenicity of enterovirus-A71 vaccine].

Objective: To analyze the effectiveness and immunogenicity of enterovirus-A71(EV-A71) vaccine in immunization program. Methods: A cohort study was conducted in immunization clinics in Jing'an district in Shanghai from October to December 2017. Children who received EV-A71 vaccine based on a 2-dose schedule (on day 0 and day 30) were enrolled as vaccine group and those who received no EV-A71 vaccine were enrolled as control group. After 1-year follow-up, the effectiveness and neutralizing antibody level and the positive results of antibody immunogenicity in vaccine group were analyzed. Results: A total of 3 018 children aged 8-20 months were enrolled, in whom 1 211 were in vaccine group and 1 807 were in control group. The vaccine effectiveness was 100% against EV-A71-associated hand, foot, and mouth disease (HFMD) indicated by 1 year follow-up (95%CI: -66.99%-100.00%). The geometric mean titer of neutralizing antibody (GMT) was 41.76 (95%CI: 35.60-49.34) at day 60 and 28.44(95%CI: 23.59-34.54) at day 365 in 124 children in vaccine group. Conclusions: In children, EV-A71 vaccine elicited EV-A71-specific immune response. Less EV-A71-associated HFMD cases have been observed, further observation is needed.

[Analysis of selective endoscopy results during the epidemic of coronavirus disease 2019 (COVID-19)].

Objective: To explore the necessity and safety of selective endoscopy to detect gastrointestinal (GI) malignancy during the outbreak of coronavirus disease 2019 (COVID-19). Methods: A retrospective cohort study was carried out to analyze the clinical data of selective endoscopy performed at the Endoscopic Center, Zhongshan Hospital of Fudan University from February 20 to March 6, 2020. Clinical data included epidemiological questionnaire, chief complaints, endoscopic findings and biopsy pathology results, etc. All medical staff had blood test for IgM/IgG antibodies of COVID-19. Patients and their families were followed up by phone to determine whether they were infected with COVID-19. Meanwhile, the clinical data of selective endoscopy during the same period from February 20 to March 6, 2019 were collected as the control group to compare the overall results of endoscopy examinations during the epidemic and the detection rate of GI malignancy. Results: A total of 911 patients underwent endoscopy in the epidemic period group, and a total of 5746 cases in the control group, which was 6.3 times over the epidemic period group. In the epidemic period group, 544 cases received gastroscopy and 367 cases received colonoscopy, while 3433 cases received gastroscopy and 2313 cases received colonoscopy in the control group, which were both 6.3 times of epidemic period group. Gastroscopy revealed that 39 patients (7.2%) were diagnosed with upper GI malignancies in the epidemic period group and 77 patients (2.2%) in the control group with significant difference (χ(2)=40.243, P<0.001). The detection rate of gastric cancer in these two groups was 3.3% (n=18) and 1.7% (n=59) respectively with significant difference (χ(2)=6.254,P=0.012). The detection rate of esophageal cancer was 3.7% (n=20) and 0.5% (n=18) respectively with significant difference (χ(2)=49.303,P<0.001). Colonoscopy revealed that colorectal cancer was found in 32 cases (8.7%) of the epidemic period group and 88 cases (3.8%) of the control group with significant difference (χ(2)=17.888, P<0.001). During the epidemic period, no infection of medical staff was found through the blood test of IgM/IgG antibodies on COVID-19. No patient and family members were infected with COVID-19 by phone follow-up. Conclusion: Compared with the same period in 2019, the number of selective endoscopy decreases sharply during the epidemic period, while the detection rate of various GI malignant tumors increases significantly, which indicates that patients with high-risk symptoms of GI malignancies should still receive endoscopy as soon as possible. Provided strict adherence to the epidemic prevention standards formulated by the state and professional societies, it is necessary to carry out clinical diagnosis and treatment as soon as possible.

[Multi-center empirical study of virtual gastroscopy simulator in the examination of clinical practice skills of specialist physicians].

Objective: To study the role of virtual gastroscopy simulator in the examination of clinical practice skills of gastrointestinal specialists. Methods: A multi-center empirical study was carried out. In June 2018, ninety participants from three tertiary care teaching hospitals in China, including Zhongshan Hospital of Fudan University, Shanghai Tongji Hospital and Xiangya Hospital of Central South University, took part in the examination. Participants were selected as follows: 30 specialists without any experience of gastroscopy exams, 30 with basic knowledge (gastroscopy exams <500 cases) and 30 with good skill (gastroscopy exams ≥500 cases). These 90 students participated in this empirical study after theoretical study and simulator training. Among them, 50 (55.6%) were undergraduates, 25 (27.8%) masters, and 15 (16.7%) doctors; 42 (46.7%) were residents, 39 (43.3%) attending physicians, and 9 (10.0%) deputy chief physicians. The assessment was divided into two parts. The first part was to use the simulator (GI mentor II) for ballooning within 10 minutes, with a total score of 40 points. The second part was a complete gastroscopy exam on the simulator, including preparation before gastroscopy exam, gastroscopy exam, post - exam management and related knowledge quiz. The difficulty and discrimination of the assessment plan were evaluated by the extreme grouping method parameters (difficulty P definition: <0.3 was difficult, 0.3 to 0.7 was medium, ≥0.7 was easy; discrimination degree D definition: <0 was poor, 0 to 0.2 was medium, ≥0.2 was good), and by comparing the virtual gastroscopy assessment scores of different experience, academic, and professional title groups. The score analysis of the student group was expressed using the mastering rate (the average score divided by the total score). The data of the normal distribution was represented by (mean±SD) (range), and the data of the nonnormal distribution was represented by M (P25, P75). Kruskal-Wallis non-parametric test was used for comparison between groups. Results: The total score of 90 students was (82.9±10.9) (55.8 to 99.0), and the mastering rate was 82.9%. The overall difficulty of the first and the second parts were 0.78 and 0.76, respectively, and the difficulty level was easy. The overall discrimination of the first and the second parts were 0.70 and 0.67, respectively, and the discrimination was good. The stratified analysis was performed according to the professional title. The median score was 83.2 (75.5, 89.0) in the residents, 82.5 (71.7, 93.6) in the attending physicians, and 93.5 (88.5, 99.0) in the deputy chief physicians, and the difference was statistically significant (H=6.213, P=0.045). According to the stratification analysis of academic qualifications, the median score was 81.7 (73.0, 87.5) in participants with undergraduate degree, 91.0 (79.0, 95.0) in those with master degree and 88.0 (81.7, 93.5) in those with doctor degree, whose difference was statistically significant (H=9.233, P=0.010). The stratified analysis of the second part showed that the median scores of the "operational process" part of the low, medium and high basis group were 33.0 (30.5, 36.5), 34.0 (32.0, 36.0) and 37.0 (35.0, 37.5), respectively, whose difference was statistically significant (H=7.603, P=0.022). The median scores of the "operational process" section of the resident, attending physician, and deputy chief physician were 33.0 (30.5, 35.0) points, 36.0 (34.0, 37.5) points and 37.0 (37.0, 37.5) points, respectively, whose difference was statistically significant (H=18.563, P=0.001). Conclusions: The virtual gastroscopy simulator can reflect the true level of gastroscopy exam skills of the students. The examination questions are moderately difficult, and there is a good discrimination of the exam.

[Endoscopic minimally invasive treatment--from inside the lumen to outside the lumen, from the superficial layer to the deep layer].

Since the introduction of endoscopic submucosal dissection (ESD) in China in 2006, endoscopic minimally invasive treatment has experienced a booming development for more than 10 years, and its indications are gradually being expanded from inside the lumen to outside the lumen, from the superficial layer to the deep layer, from organic diseases to functional diseases. This article summaries the development of endoscopic minimally invasive resection in the past 10 years, from the perspective of mucosa, submucosa, muscularis, serosal and even extraluminal lesions, respectively, to introduce the role of endoscopic minimally invasive treatment. For mucosal lesions, ESD has become a first-line treatment for early gastric cancer; endoscopic treatment of colorectal lesions is still controversial in Europe and the United States, but is gradually being accepted. For submucosal tumors(SMT), the Expert Consensus for Endoscopic Diagnosis and Treatment of Submucosal Tumors in China (version 2018) was published in 2018, and the principles and related technical rules for gastrointestinal SMT have been highlighted. For serosal and even extraluminal lesions, natural orifice transluminal endoscopic surgery (NOTES) and tunnel endoscopic surgery, mainly including endoscopic myotomy (POEM) and endoscopic transmucosal tunneling tumor resection (STER), showed potential for development in preliminary studies, and showed good results in cholecystectomy, appendectomy, achalasia, gastroparesis and even extra-gastrointestinal tumor resection. This article describes the various endoscopic treatment techniques, and looks into their application prospects and future challenges.

[The renal protective effect and mechanism of liraglutide in diabetic mice induced by high-fat diet].

Objective: To investigate the protective effect of liraglutide on kidney of diabetic mice induced by high-fat diet and its possible mechanisms. Methods: C57BL/6J male mice were randomly divided into normal chow diet (NC) group and high-fat diet (HFD) group, which were fed with normal chow diet and HFD for 12 weeks respectively. After diet challenge, the mice were randomly divided into normal control group, normal chow diet with liraglutide treatment (NC+Lira) group, HFD group and high-fat diet with liraglutide treatment (HFD+Lira) group. The mice in NC+Lira and HFD+Lira groups were given intraperitoneal injection of liraglutide (400 µg·kg(-1)·d(-1)) for 8 weeks, while mice in NC and HFD groups were given intraperitoneal injection of same amount of normal saline. Urinary albumin and creatinine levels were measured by enzyme-linked immunosorbent assay (ELISA). Renal morphology was observed by HE staining. The expression levels of silent mating type information regulation 2 homolog 1 (SIRT1) and thioredoxin-interacting protein (TXNIP) were determined by Western blot. Results: Compared with HFD group, liraglutide significantly lowered the body weight [(30.98±1.29) g vs (39.43±2.58) g], fasting blood glucose (FBG) [(7.21±0.15) mmol/L vs (9.55±0.29) mmol/L] and urinary albumin/creatinine ratio (ACR) [(205.48±17.14) µg/mg vs (319.86±34.14) µg/mg] in HFD+Lira group (all P<0.05). HE staining showed that glomerular hypertrophy of HFD group alleviated after liraglutide treatment. The expression level of TXNIP in the kidney of HFD mice significantly decreased after liraglutide treatment (0.41±0.10 vs 3.50±0.70), while expression level of SIRT1 significantly increased (0.75±0.15 vs 0.32±0.04) (both P<0.05). Conclusion: Liraglutide could improve diabetic nephropathy by up-regulation of SIRT1 expression and down-regulation of TXNIP expression in diabetic mice induced by HFD.

[Insulin dose analysis during pregnancy in type 1 diabetic patients treated with insulin pump therapy].

Objective: To analyze the insulin dose of type 1 diabetic patients who treated with insulin pump therapy during pregnancy in order to explore the features of these patients' insulin requirement during gestation. Methods: A total of 12 well-controlled type 1 diabetic women patients who were treated with insulin pump therapy before and during gestation without any adverse pregnancy outcomes from June 2011 to December 2014 were selected from Guangdong Type 1 Diabetes Translational Medicine Study and included in the study. Demographic data, hemoglobin A1c (HbA1c) before pregnancy and before delivery, insulin dose, hypoglycemia episodes and pregnancy outcomes were collected to analyze the insulin dose of preconception, the 1(st,) the 2(nd) and the 3(rd) trimester to analyze the requirement of insulin before and throughout pregnancy. Results: Subjects were (26.9±2.6) years old, with a diabetes duration of (6.6±4.4) years. HbA1c were (5.8±0.5)% before conception. The preconception total daily insulin dose, basal rate, bolus and bolus proportion were (0.60±0.18)U/kg, (0.28±0.10)U/kg, (0.32±0.13)U/kg and (54.8±12.9)%, respectively. Both of the insulin dose indexes mentioned above changed significantly in different trimesters compared with that in preconception (P value was <0.001, 0.034, <0.001 and <0.001, respectively). The total daily insulin dose, bolus and bolus proportion kept increasing during pregnancy. In the 1(st,) the 2(nd) and the 3(rd) trimester, the total daily insulin dose rose by 0.2%, 45.4% and 72.7%, respectively, the bolus rose by 8.0%, 72.2% and 106.8%, respectively, and the bolus proportion rose by 8.0%, 16.8% and 19.0%, respectively. While the basal rate decreased by 9.0% in the 1(st) trimester and rose by 14.1% and 32.9% in the 2(nd) and 3(rd) trimester, respectively. Conclusions: In well-controlled pregnant women with type 1 diabetes mellitus, insulin requirement increased throughout pregnancy. Most of the increased insulin requirement was attributed to the bolus instead of the basal rate. When titrating the dose of insulin for the pregnant women complicated with type 1 diabetes mellitus, the physicians should consider their features of insulin requirement so as to optimize the glycemic control.

Cognitive fatigue effect on rehabilitation task performance in a haptic virtual environment system.

INTRODUCTION: This paper presents a study on an affordable rehabilitation approach to post-stroke patients. In this approach, a patient performs a task on a haptic virtual environment system and a physician examines the patient's task remotely based on the performing data. OBJECTIVES: The objective of this study is to test a hypothesis that an elevated cognitive fatigue state may significantly affect the patient's task performance so as to disturb judgment by physicians. METHODS: The study included the development of a test-bed for the experiment and an experimental study for the hypothesis. The study took the wrist coordination function of the upper limb as an example. RESULT: The study showed that the cognitive fatigue state has a significant influence on the patient's task performance; in other words, there is a noise (75% discrepancy from the true performance information) in the performance data. CONCLUSION: The study provides great potential for accurate assessment of the functional state from true patient task performance. The future work needs to focus on the removal of the noise. The limitation of this study is that the experiment was carried out on healthy subjects, although post-stroke patients are more susceptible to an elevated cognitive fatigue state from a common sense.

[Effect of continuous subcutaneous insulin infusion on the evaluation of ß cell function].

OBJECTIVE: To evaluate the impact of continuous subcutaneous insulin infusion (CSII) on ß-cell function assessment. METHODS: One hundred and twenty-five patients with type 2 diabetes (T2DM) admitted to Third Affiliated Hospital of Sun Yat-sen University treated with CSII were enrolled from May to December 2015. Blood samples were collected to measure their fasting blood glucose, haemoglobin A1c, blood lipids and plasma C peptide levels (fasting, 30 min and 120 min after a mixed meal) on the next day of their admission before CSII started. When patients achieved the target of fasting capillary glucose ≤ 7.0 mmol/L, C-peptide levels (0 min, 30 min and 120 min after a mixed meal) were measured. Then CSII were stopped at 10 pm with the same tests repeated on the next day. RESULTS: Compared with those measured before CSII [0 min: (0.35±0.20) nmol/L, 30 min: (0.57±0.31) nmol/L, 120 min: (0.84±0.54) nmol/L], C-peptide levels after stopping CSII at all time points [0 min: (0.41±0.16) nmol/L, 30 min: (0.71±0.33) nmol/L, 120 min: (1.37±0.75) nmol/L] increased (P=0.015, P=0.005, P<0.001) even glucose control was achieved, but significantly decreased immediately before CSII was stopped [0 min: (0.23±0.13)nmol/L, 30 min: (0.39±0.26) nmol/L, 120 min: (0.67± 0.50) nmol/L] (P<0.001, P<0.001, P=0.023). The C-peptide after stopping CSII increased to 141% (0 min), 127% (30 min) and 219% (120 min) respectively compared to those before stopping CSII. CONCLUSION: CSII therapy should be stopped for accurate evaluation of ß-cell function due to its"ß-cell rest"effect in T2DM.

[Immunomodulatory effect of oyster peptide on immunosuppressed mice].

OBJECTIVE: To evaluate the immunomodulating effect of oyster peptide on immunosuppressed mice. METHODS: ICR mice injected with cyclophosphamide (CTX) were adopted as the module group, with mice without treatment as the control group, and different dosages of oyster peptide (0.5 g/kg, 1.0 g/kg, and 2.0 g/kg) were given to the low, middle, and high groups for 15 days. The body weight, spleen, and thymus weight of the mice, structures under the microscope of the immune organs, numbers of white blood cells, ratios of T lymphocyte subsets, immune cytokines and numbers of nuclear cells, and DNA content in bone marrow were all assessed. RESULTS: Compared with the control group, the structures of thymus and spleen of the mice in the CTX group appeared obscure and shrunk when observed under microscope, the number of their white blood cells declined (P=0.04), the proportion of their CD3(+) T cells in peripheral blood declined (P=0.003), the proportion of their CD8(+) T cells in peripheral blood declined (P=0.002), the concentration of their IL-5 in peripheral blood significantly increased (P<0.01), the concentration of their nucleated cells and DNA density in bone marrow decreased (P=0.04, P<0.01). Oyster could improve the structures of thymus and spleen of the immunosuppressed mice. Compared with the CTX group, the number of white blood cells in 2.0 g/kg group increased (P=0.003), the proportion of CD3(+) T cells in peripheral blood in 1.0 g/kg group (P=0.04) and 2.0 g/kg group (P=0.02) increased, the proportion of CD8(+) T cells in peripheral blood in 2.0 g/kg group increased (P=0.002), the concentration of IL-5 in peripheral blood in all the oyster treated groups increased (P<0.01 in 0.5 g/kg, 1.0 g/kg, and 2.0 g/kg groups), the concentration of IL-17 in peripheral blood in 2.0 g/kg group decreased (P=0.03), the concentration of nucleated cells in bone marrow of all the oyster treated groups increased (0.5 g/kg vs. CTX, P=0.04; 1.0 g/kg vs. CTX, P=0.02; 2.0 g/kg vs. CTX P=0.01), the DNA content in bone marrow of all the oyster treated groups increased (P<0.01 in the 0.5 g/kg, 1.0 g/kg, and 2.0 g/kg groups). CONCLUSION: Oyster peptide could improve the structures of immune organs of the CTX-induced immunosuppressed mice, recover the imbalances of T lymphocyte subsets, improve the immune cytokines and increase numbers of nucleated cells and DNA content in bone marrow, thus improving the immunologic function.

[The influence of patatin-like phospholipase domain-containing protein 3 on palmitic acid-induced hepatocyte apoptosis].

OBJECTIVE: To explore the influence of patatin-like phospholipase domain-containing protein 3 (PNPLA3) on palmitic acid (PA)-induced hepatocyte apoptosis and its mechanism. METHODS: Human hepatocarcinoma cell line HepG2 cells were transfected with PNPLA3(WT)-pcDNA3.1 (PNPLA3(WT) group) and PNPLA3(I148M)-pcDNA3.1 (PNPLA3(I148M) group) plasmids respectively to overexpress wild type or mutant type PNPLA3, and cells transfected with empty vector pcDNA3.1 (NC group) were set as control group.After 24 h PA incubation, Oil red staining was used to determine lipid deposition, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) was used to measure apoptosis.Western blot was used to detect the protein level of endoplasmic reticulum (ER) stress and associated apoptosis.Enzyme-linked immunosorbent assay (ELISA) was used to test lysolecithin (LPC) levels in the cellular supernatant. RESULTS: After 24 h PA incubation, there was no significant difference in lipid deposition among three groups.Compared to NC group, the cell apoptosis rates of PNPLA3(WT) and PNPLA3(I148M) groups were increased by 2 times and 3 times respectively.The levels of ER stress PRKR-like endoplasmic reticulum kinase (PERK) pathway associated proteins, immunoglobulin-binding protein (BIP), p-PERK, p-eIF2α, and ER stress associated apoptosis pathway proteins, CCAAT/enhancer binding homologous protein (CHOP), p53 upregulated modulator of apoptosis (PUMA), Bax, caspase-3 were higher, and were more significant in PNPLA3(I148M) group.The LPC level in the supernatant of PNPLA3(WT) and PNPLA3(I148M) groups were about 5 times and 1.5 times of NC group respectively after PA incubation. CONCLUSION: PNPLA3 may be involved in palmitic acid-induced apoptosis mediated by hepatocyte ER stress through regulating LPC metabolism.

Clozapine prescription and quality of life in Chinese patients with schizophrenia treated in primary care.

OBJECTIVE: Clozapine is frequently used to treat schizophrenia in China. Maintenance treatment for clinically stable patients with schizophrenia is usually provided by Chinese primary care physicians, but no study has investigated the frequency of its use prescribed by primary care physicians. This study described the frequency, demographic and clinical characteristics of clozapine treatment and its impact on insight and quality of life (QOL) of patients with schizophrenia treated in primary care in China. METHOD: A total of 623 patients with schizophrenia treated in 22 primary care services in Guangzhou, China in 2013 formed the study sample. Patients' socio-demographic and clinical characteristics including psychopathology, medication side effects and QOL were recorded using a standardized protocol and data collection. RESULTS: The frequency of clozapine prescription was 35.6% with a mean daily dose of 127.7±88.2 mg. There were no significant differences between the patients with and without clozapine in either of the QOL domains after controlling the confounding factors. Multiple logistic regression analyses revealed that patients on clozapine had younger age of onset, more hospitalizations, more severe extrapyramidal side effects, but better insight and fewer prescriptions of first generation antipsychotics. CONCLUSIONS: Clozapine use was found to be common and associated with better insight in patients with schizophrenia treated in primary care in China. Further examination of the rationale and appropriateness of clozapine in primary care in China is warranted.

Association between TNFSF4 tagSNPs and myocardial infarction in a Chinese Han population.

Tumor necrosis factor superfamily member 4 (TNFSF4) plays an important role in atherosclerosis development. However, the biological significance of TNFSF4 variants on myocardial infarction (MI) pathogenesis remains poorly understood. We investigated the influence of 5 TNFSF4 tagging single nucleotide polymorphisms (rs3861950, rs17346501, rs7518045, rs1234313, and rs3850641) on individual susceptibility to MI in a Chinese population of 285 MI patients and 645 controls. Genotyping was performed using the polymerase chain reaction-ligase detection reaction method. In multivariate logistic regression analysis, only the TNFSF4 tagging single nucleotide polymorphism rs7518045 exhibited a significant effect on MI risk; A allele (odds ratio = 0.68, 95% confidence interval = 0.46-1.00, P = 0.048) and AA genotype (odds ratio = 0.64, 95% confidence interval = 0.42-0.97, P = 0.036) were associated with a decreased risk of MI compared with the G allele and the combined AG/GG genotype, respectively. Moreover, the haplotype rs3861950C-rs17346501C-rs7518045A-rs1234313G containing the rs7518045 A allele also exhibited a significant association with a decreased risk for MI (odds ratio = 0.42, 95% confidence interval = 0.21-0.84, P = 0.011). Our study showed that the A allele of the rs7518045 and haplotype rs3861950C-rs17346501C-rs7518045A-rs1234313G in the TNFSF4 gene were associated with decreased MI risk in a Chinese Han population. Further studies using larger sample sizes and in diverse ethnic populations are needed to confirm the general validity of our findings.

Proteomic analysis identifies differentially expressed proteins participating in forming Type III brush hair in Yangtze River Delta white goat.

The Yangtze River Delta white goat is a goat breed that can produce high quality brush hair (Type III hair) around the world. This study aimed to compare Type III hair and non-Type III hair goat skin tissues using differentially expressed proteins based on 2-dimensional gel electrophoresis technology. The differentially expressed protein spots were analyzed using the PDquest 8.0 software. Ten protein spots were detected as positive for mass spectrometric analysis based on a threshold of 2-fold change. Through matching based on Ultraflex III TOF/TOF and MASCOT database, four differentially expressed proteins were identified. Fibrinogen beta chain isoform 1 and ATP synthase beta subunit were upregulated in Type III hair, while succinyl-CoA:3-ketoacid-coenzyme A transferase 1-mitochondrial-like and actin-cytoplasmic 1 were upregulated in non-Type III hair. The 4 proteins play important roles in different aspects of hair follicle development. These findings could pave a good foundation for explaining the mechanism of forming Type III hair.

Overexpression of p300 correlates with poor prognosis in patients with cutaneous squamous cell carcinoma.

BACKGROUND: It has been suggested that the p300 transcriptional coactivator participates in the regulation of a wide range of cell biological processes, and mutations in p300 have been identified in various cancers. OBJECTIVES: To investigate p300 expression in cutaneous squamous cell carcinoma (cSCC) tissues and its effect on the outcome of patients with cSCC. METHODS: Immunohistochemistry (IHC) was performed on a tissue microarray to investigate p300 expression levels in cSCC tissues. Receiver operating characteristic (ROC) curve analysis, Kaplan-Meier plots and a Cox proportional hazards regression model were used to analyse the data. RESULTS: Based on the ROC curves, we defined the cut-off score for high p300 expression as > 55% of tumour cells positively stained. High expression of p300 was observed in 86 of 165 (52·1%) of the cSCC samples and six of 30 (20%) of the adjacent normal skin tissue samples (P < 0·001). High expression of p300 was positively correlated with lymph node metastasis (P = 0·006) and advanced clinical stage (P < 0·001). In univariate survival analysis, high expression of p300 was correlated with poor patient outcomes in terms of recurrence-free survival (P = 0·006) and overall survival (P < 0·001). Moreover, p300 expression was evaluated as an independent prognostic factor in a multivariate analysis (P = 0·004). CONCLUSIONS: Our results indicate that high p300 expression is associated with aggressive features of cSCC and suggest that p300 expression, as examined by IHC, will be a promising biomarker for predicting clinical outcomes in patients with cSCC.

Oxaliplatin and capecitabine concomitant with neoadjuvant radiotherapy and extended to the resting period in high risk locally advanced rectal cancer.

BACKGROUND: Conventional neoadjuvant chemoradiotherapy (CRT) is suboptimal for systemic control in locally advanced rectal cancer (LARC). To improve systemic control, we developed an alternative approach in which an intensified oxaliplatin and capecitabine (XELOX) chemotherapy regimen was administered concomitantly with radiation and extended to the resting period (consolidation chemotherapy) for high-risk LARC. The aim of the current study was to evaluate the short-term efficacy and toxicity of this strategy. METHODS: Patients with high-risk LARC were treated with CRT. Two cycles of XELOX were administered concomitantly with radiation. Thereafter, an additional cycle of the same regimen was administered during the resting period after completion of CRT. Tumor response, toxicities and surgical complications were recorded. RESULTS: This study includes 36 patients treated with the above strategy. All patients completed the planned concurrent CRT. Because of grade 3 toxicities, 2 patients were unable to complete the additional chemotherapy. Grade 3 toxicities were leucopenia (2.8 %), diarrhea (2.8 %) and radiodermatitis (2.8 %). All patients underwent optimal surgery with total mesorectal excision (TME) and a sphincter-saving procedure was performed in 27 patients (75 %). There was no perioperative mortality. Postoperative complications developed in 7 patients (19.4 %). Pathologic complete regression (pCR),"nearly pCR" (major regression), and moderate or minimal regression were achieved in 13 (36.1 %), 16 (44.4 %), and 7 patients (19.5 %), respectively. CONCLUSION: The preliminary results suggest that a XELOX regimen initially administered concomitantly with radiotherapy and then extended to the resting period in high-risk LARC patients is well tolerated. The strategy is highly effective in terms of pCR and nearly pCR rates, and thus warrants further investigation.

The beneficial effect of metformin on ß-cell function in non-obese Chinese subjects with newly diagnosed type 2 diabetes.

AIM: Studies with metformin suggest a favourable change in ß-cell function over sulphonylureas in the early course of obese type 2 diabetes mellitus (T2DM), but it remains unclear whether a similar effect is observed in non-obese individuals. Here we investigated the effects of metformin or glipizide gastrointestinal therapeutics system extended-release formulation (GITS) on ß-cell function in non-obese patients with newly diagnosed T2DM. METHODS: A total of 160 newly diagnosed patients with fasting glucose 7.0-13.0 mmol/L and body mass index <30 kg/m(2) from five centres in China were randomized to metformin or glipizide GITS for 24 weeks. Early insulin secretion [the ratio of area under the curve (AUC) of insulin to glucose during 0-30 min (InsAUC30 /GluAUC30 )] and insulin sensitivity [Matsuda index (ISIM )] were assessed during the standard meal tolerance test before and after therapy. Plasma glucagon-like peptide-1(GLP-1) and glucagon levels were also measured. RESULTS: Metformin improved InsAUC30 /GluAUC30 significantly (from 8.1 ± 0.6 pmol/mmol to 10.7 ± 0.7 pmol/mmol, p < 0.05), comparable to results with glipizide GITS. In the metformin-treated lean (body mass index < 25 kg/m(2) ) subgroup, the increase in ISIM was not significant, but the improvement in InsAUC30 /GluAUC30 was of great magnitude. Increased GLP-1 responses during meal tolerance test and decreased fasting glucagon level were observed after metformin treatment. Correlation analysis showed that the improvement of InsAUC30 /GluAUC30 was associated with the changes in HbA1c (r = -0.374, p = 0.000), ISIM (r = 0.356, p = 0.001), and ΔGLP-10-30 (r = 0.225, p = 0.02). CONCLUSIONS: Metformin improved ß-cell function in non-obese subjects with newly diagnosed T2DM, which was partly independent of the change in insulin sensitivity in these subjects. This study provides evidence-based data to support metformin use in non-obese patients with T2DM as the first-line agent, which can improve both insulin sensitivity and ß-cell function.

Peroral endoscopic remyotomy for failed Heller myotomy: a prospective single-center study.

BACKGROUND AND STUDY AIMS: Recurrence/persistence of symptoms occurs in approximately 20 % of patients after Heller myotomy for achalasia. Controversy exists regarding the therapy for patients in whom Heller myotomy has failed. The aim of the current study was to evaluate the efficacy and feasibility of peroral endoscopic myotomy (POEM), a new endoscopic myotomy technique, for patients with failed Heller myotomy. PATIENTS AND METHODS: A total of 12 patients with recurrence/persistence of symptoms after Heller myotomy, as diagnosed by established methods and an Eckardt score of ≥ 4, were prospectively included. The primary outcome was symptom relief during follow-up, defined as an Eckardt score of ≤ 3. Secondary outcomes were procedure-related adverse events, lower esophageal sphincter (LES) pressure on manometry, reflux symptoms, and medication use before and after POEM. RESULTS: All 12 patients underwent successful POEM after a mean of 11.9 years (range 2 - 38 years) from the time of the primary Heller myotomy. No serious complications related to POEM were encountered. During a mean follow-up period of 10.4 months (range 5 - 14 months), treatment success was achieved in 11/12 patients (91.7 %; mean score pre- vs. post-treatment 9.2 vs. 1.3; P < 0.001). Mean LES pressure was 29.4 mmHg pre-treatment and 13.5 mmHg post-treatment (P < 0.001). One patient developed mild reflux symptoms and required intermittent medication with proton pump inhibitors. CONCLUSIONS: POEM seems to be a promising new treatment for failed Heller myotomy resulting in short-term symptom relief in > 90 % of cases. Previous Heller myotomy may make subsequent endoscopic remyotomy more challenging, but does not prevent successful POEM.