[Drug-induced bile duct injury: progress and challenges].

Drug-induced bile duct injury is a specific kind of drug-induced liver injury that has two main pathological types, namely ductopenia, or vanishing bile duct syndrome, and secondary sclerosing cholangitis. However, in recent years, the reports of new drugs that cause bile duct injury have been constantly increasing, and these drugs have different clinicopathological features and a novel pathogenesis. Therefore, this paper summarizes and analyzes the progress and challenges in the etiology, pathogenesis, diagnosis and treatment, and other aspects of drug-induced bile duct injury.

[Factors influencing bilirubin elevation and its correlation with UGT1A1 gene polymorphism in the early postoperative period of transjugular intrahepatic portosystemic shunt].

Objective: To investigate the factors influencing total bilirubin elevation and its correlation with UGT1A1 gene polymorphism in the early postoperative period of transjugular intrahepatic portosystemic shunt (TIPS). Methods: 104 cases with portal hypertension and esophageal variceal hemorrhage (EVB) treated with elective TIPS treatment were selected as the study subjects and were divided into a bilirubin-elevated group and a normal bilirubin group according to the total bilirubin elevation level during the early postoperative period. Univariate analysis and logistic regression were used to analyze the factors influencing total bilirubin elevation in the early postoperative period. PCR amplification and first-generation sequencing technology were used to detect the polymorphic loci of the UGT1A1 gene promoter TATA box, enhancer c.-3279 T > G, c.211G > A, and c.686C > A. Logistic regression was used to analyze the correlation of four locus alleles and genotypes with elevated total bilirubin in the early postoperative period. Results: Among the 104 cases, 47 patients were in the bilirubin elevated group, including 35 males (74.5%) and 12 females (25.5%), aged (50.72 ± 12.56) years. There were 57 cases in the normal bilirubin group, including 42 males (73.7%) and 15 females (26.3%), aged (51.63 ± 11.10) years. There was no statistically significant difference in age (t = -0.391, P = 0.697) and gender (χ(2) = 0.008, P = 0.928) between the two groups of patients. Univariate analysis revealed that preoperative alanine transaminase (ALT) level (χ(2) = 5.954, P = 0.015), total bilirubin level (χ(2) = 16.638, P < 0.001), MELD score (χ(2) = 10.054, P = 0.018), Child-Pugh score (χ(2) = 6.844, P = 0.022), and postoperative portal vein branch development (χ(2) = 6.738, P = 0.034) were statistically significantly different between the two groups. Logistic regression analysis showed that preoperative ALT level, total bilirubin level, and portal vein branch development after TIPS were correlated with the elevated total bilirubin in the early postoperative period. The polymorphism of the c.211G > A locus of the UGT1A1 gene correlation had elevated total bilirubin in the early postoperative period of TIPS. The risk of elevated total bilirubin was increased in the population carrying allele A (P = 0.001, OR = 4.049) in the early postoperative period. Allelic polymorphisms in the TATA box promoter region and enhancer c.-3279 T > G and c.686C > A had no statistically significant difference between the bilirubin-elevated group and the normal bilirubin group. Conclusion: The preoperative ALT level, total bilirubin level, and portal vein branch development are correlated with the elevated total bilirubin in early postoperative patients. The polymorphisms of the UGT1A1 gene and enhancer c.211G > A are correlated with the occurrence of elevated total bilirubin in the early postoperative period of TIPS. Allele A carrier may have a higher risk of elevated total bilirubin in the early postoperative period.

[Effect of a novel radio-frequency atmospheric-pressure glow discharge plasma jet treatment on crosslinking of dentin collagen].

OBJECTIVE: To investigate the effect of a noval radio-frequency atmospheric-pressure glow discharge (RF-APGD) plasma jet on crosslinking of dentin collagen. METHODS: (1) Twenty intact third molars were collected. The middle dentin discs were prepared for each tooth by low-speed water-cooled Isomet saw, and then immersed in 10% (mass fraction) H3PO4 solution for 16 h to obtain fully demine-ralized dentin collagen. The twenty dentin discs were then randomly divided into five groups. The control group was untreated while the four experimental groups were treated by plasma jet with gas temperature of 4 ℃ for different times (20 s, 30 s, 40 s, and 50 s). The structure and crosslinking degree of dentin collagen were characterized by attenuated total reflection-Fourier transform infrared spectroscopy. The surface morphology of demineralized dentin was observed by scanning electron microscope, and the microstructure was observed by transmission electron microscope. (2) Fourty non-caries third molars were collected to prepare 5 g fine dentin powder, then completely demineralized with 10% H3PO4 solution. The control group was untreated, while the four experimental groups were treated by plasma jet for 20 s, 30 s, 40 s and 50 s. The crosslinking degree of each group was determined by ninhydrin colorimetric method. (3) Forty intact third molars were collected to obtain dentin strips. Only two central symmetrical dentin strips (nasty 80) were taken from each tooth and immersed in 10% H3PO4 solution for 16 h to obtain fully demineralized dentin collagen. Eighty dentine collagen fiber strips were randomly divided into five groups. The control group was untreated and the axial surfaces of dentin collagen fiber strips in the expe-rimental groups were treated with the plasma jet for 20 s, 30 s, 40 s and 50 s. The ultimate tensile strength of dentin was measured by universal mechanical machine. RESULTS: (1) The surface morphology of demineralized dentin observed by scanning electron microscope showed that the network structure of collagen fibers on the surface of demineralized dentin treated with the plasma jet for 20 s, 30 s and 40 s could maintain the uncollapsed three-dimensional structure, and part of the microstructure was destroyed after plasma jet treated for 50 s. After being treated by plasma jet for 20 s, 30 s and 40 s, the three-dimensional structure was uncollapsed, and the typical periodic transverse pattern of natural type Ⅰ collagen fiber could be seen. The results of infrared spectra showed that the secondary conformation of dentin collagen fibers was the same as that of the control group after being treated with the plasma jet, and the intensity of amide band was significantly increased after being treated for 30 s and 40 s. (2) The results of ninhydrin crosslinking test showed that the crosslinking ratio of dentin collagen treated by plasma jet for 30 s and 40 s was the highest, and the difference was statistically significant (P < 0.05). (3) The results of dentin ultimate tensile strength showed that the control group was (1.67±0.24) MPa, and the plasma jet treated 20 s, 30 s, 40 s and 50 s groups were (4.21±0.15) MPa, (7.06±0.30) MPa, (7.32±0.27) MPa, and (6.87±0.17) MPa, which were significantly different from that of the control group (P < 0.05). CONCLUSION: The novel RF-APGD plasma jet treatment can promote the crosslinking degree of demineralized dentin collagen and improve their ultimate tensile strength.

[The value of ischemia modified albumin level for predicting in-hospital mortality in patients with acute aortic dissection].

Objective: To investigate the value of ischemia modified albumin (IMA) level for predicting in-hospital mortality in patients with acute aortic dissection (AAD). Methods: A total of 195 patients with AAD from the Department of Cardio-Vascular Surgery of Affiliated Hospital of North Sichuan Medical College from January 2017 to November 2019 were consecutively collected, with 126 males and 69 females. Based on whether they died during hospitalization or not, these patients were divided into 2 groups: survival group and mortality group. The baseline data and IMA levels at admission of the two groups were recorded. Univariate logistic regression analysis was used to identify the independent risk factors, and multivariate logistic regression analysis was further performed on variables with statistical significance in univariate analysis. The area under the receiver operating characteristic (ROC) curve was calculated to determine the value of IMA for predicting in-hospital mortality in patients with AAD. Results: Forty-two AAD patients died and 153 survived, and the mortality rate was 21.5%. Logistic regression analysis showed that age (OR=2.143,95%CI:1.247-4.826,P=0.011), Stanford type A (OR=6.751,95%CI:3.189-14.291,P<0.001), drug therapy (OR=5.133,95%CI:2.463-10.700,P<0.001), IMA level (OR=4.452,95%CI:2.231-8.953,P=0.004) were independent risk factors for in-hospital mortality in patients with AAD, however surgery was a protective factor (OR=0.195,95%CI:0.093-0.406,P<0.001). The area under the ROC curve for IMA level in predicting in-hospital mortality with AAD was 0.838 (95%CI: 0.774-0.901, P<0.001), with a cut-off value of 86.55 U/ml, and the sensitivity and specificity were 83.3% and 75.2%, respectively. Conclusions: IMA may serve as a simple risk assessment indicator for patients with AAD. IMA level at admission is an independent predictor of in-hospital mortality. For patients with higher IMA level, early surgical intervention should be performed.

[Status of HVPG clinical application in China in 2021].

Objective: The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China. Methods: This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems. Results: According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%). Conclusion: Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

[Diagnosis and treatment status of perioperative anemia in patients with gastrointestinal neoplasms: a multi-center study in Hubei Province].

Objective: To investigate the incidence and treatment of perioperative anemia in patients with gastrointestinal neoplasms in Hubei Province. Methods: The clinicopathological data of 7 474 patients with gastrointestinal neoplasms in 62 hospitals in 15 cities (state) of Hubei Province in 2019 were collected in the form of network database. There were 4 749 males and 2 725 females. The median age of the patients was 62 years (range: 17 to 96 years). The hemoglobin value of the first time in hospital and the first day after operation was used as the criterion of preoperative anemia and postoperative anemia. Anemia was defined as male hemoglobin <120 g/L and female hemoglobin <110.0 g/L, mild anemia as 90 to normal, moderate anemia as 60 to <90 g/L, severe anemia as <60 g/L. The t test and χ2 test were used for inter-group comparison. Results: The overall incidence of preoperative anemia was 38.60%(2 885/7 474), and the incidences of mild anemia, moderate anemia and severe anemia were 25.09%(1 875/7 474), 11.37%(850/7 474) and 2.14%(160/7 474), respectively. The overall incidence of postoperative anemia was 61.40%(4 589/7 474). The incidence of mild anemia, moderate anemia and severe anemia were 48.73%(3 642/7 474), 12.20%(912/7 474) and 0.47%(35/7 474), respectively. The proportion of preoperative anemia patients receiving treatment was 26.86% (775/2 885), and the proportion of postoperative anemia patients receiving treatment was 14.93% (685/4 589). The proportions of preoperative anemia patients in grade ⅢA, grade ⅢB, and grade ⅡA hospitals receiving treatment were 26.12% (649/2 485), 32.32% (85/263), and 29.93% (41/137), and the proportions of postoperative anemia patients receiving treatment were 14.61% (592/4 052), 22.05% (73/331), and 9.71% (20/206). The proportion of intraoperative blood transfusion (16.74% (483/2 885) vs. 3.05% (140/4 589), χ²=434.555, P<0.01) and the incidence of postoperative complications (17.78% (513/2 885) vs. 14.08% (646/4 589), χ²=18.553, P<0.01) in the preoperative anemia group were higher than those in the non-anemia group, and the postoperative hospital stay in the preoperative anemia group was longer than that in the non-anemia group ((14.1±7.3) days vs. (13.3±6.2) days, t=5.202, P<0.01). Conclusions: The incidence of perioperative anemia in patients with gastrointestinal neoplasms is high. Preoperative anemia can increase the demand for intraoperative blood transfusion and affect the short-term prognosis of patients. At present, the concept of standardized treatment of perioperative anemia among gastrointestinal surgeons in Hubei Province needs to be improved.

[Research on the relationship between V444A mutation of ABCB11 gene and primary intrahepatic stone].

Objective: To investigate the relationship between V444A mutation of the ABCB11 gene and primary intrahepatic stone (PIS). Methods: A total of 164 patients (including 91 males and 73 females, with an average age of (46.0±13.0) years) with PIS and 164 healthy (including 99 males and 65 females, with an average age of (43.8±16.7) years) volunteers were enrolled in this case-control study between October 2017 and June 2019. TaqMan-MGB was used for detecting the V444A polymorphism site of the ABCB11 gene. All the genotypes and allele frequencies were calculated. Pearson chi-squared test was performed to detect the differences in allele and genotype distribution between the two groups. Logistic regression analysis was used to identify genotypes associated with PIS. Results: There was no significant difference in age and gender between the two groups(both P>0.05). The distributions of V444A allele and genotype accorded with Hardy-Weinberg equilibrium law (P=0.161), which indicated that the selected control group represented statistically acceptable sample. Two alleles of T and C, and three genotypes of TT, TC and CC were detected in the locus of V444A. The T and C allele frequencies in the PIS group and the control group were 28.4% vs 35.4%, and 71.6% vs 64.6%, respectively. The frequencies of the T and C alleles were not different between the two groups (P=0.054). The frequencies of TT, TC and CC genotypes in the two groups were 5.5%, 45.7%, 48.8%, and 14.6%, 41.5%, 43.9%, respectively, with significant difference between the two groups (P=0.023). Logistic regression analysis revealed the V444A polymorphism (TC heterozygous mutation) was associated with PIS. Conclusion: ABCB11 gene polymorphism at the site of V444A may be related to the susceptibility of PIS.

[mTOR signaling pathway-mediated autophagy involved in inhibition of osteoblast differentiation induced by cadmium in human bone marrow mesenchymal stem cells].

Objective: To investigate the role of autophagy mediated by mTOR signaling pathway in the inhibition of osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) induced by cadmium. Methods: HBMSCs were divided into 0, 2.5 or 5.0 µmol/L groups according to the exposure dose of cadmium chloride (CdCl2), and each group was treated for 1 day, 4 days and (or) 7 days. The ALP activity and mRNA and protein expression levels of osteogenesis markers (ALP, RUNX2 and OSTERIX), autophagy-related proteins (LC3 and Beclin-1) and mTOR signaling pathway related proteins (mTOR, p-mTOR and p-p70S6K) expression, alkaline phosphatase staining and alizarin red staining were detected. MHY 1485 was selected as the signaling pathway activator. The control group, CdCl2 group (5.0 µmol/L), MHY 1485 group and CdCl2+MHY 1485 combined treatment group were set. After 7 days of treatment, the expression levels of autophagy related proteins and mTOR signaling pathway related proteins of hBMSCs in each group were detected. Results: There was no significant difference in ALP activity between 0, 2.5 and 5.0 µmol/L groups on day 1 and 4 (P>0.05); On day 7, compared with the 0 µmol/L group, the ALP activity, expression of osteogenic markers (ALP, RUNX2, OSTERIX) and mTOR signaling pathway related proteins (mTOR, p-mTOR, p-p70S6K) expression decreased in the 2.5 and 5.0 µmol/L group (P<0.05). Compared with the 0 µmol/L group, the staining of the 2.5 and 5.0 µmol/L groups became lighter, and the formation of ALP and mineralized nodules was reduced. Compared with the CdCl2 group, the autophagy related protein expression in the CdCl2+MHY 1485 combined treatment group decreased, and the mTOR signaling pathway related protein expression increased. The difference was statistically significant (P<0.05). Conclusion: The inhibition of osteogenic differentiation of hBMSCs by cadmium may be related to autophagy mediated by mTOR signaling pathway.

[The relationship between migration time and the prevalence of myopia of children and adolescents aged 6-18 years old in Shenzhen].

Objective: To analyze the relationship between migration time and the prevalence of myopia of children and adolescents aged between 6 and 18 years old in Shenzhen. Methods: From April to May 2019, 26 618 children and adolescents from 14 schools in six streets of Baoan District, including Fuyong, Shajing, Xin'an, Xixiang, Songgang and Shiyan, were included in the study by using random cluster sampling method. The demographic characteristics, migration status, self-reported myopia, screen time in the last seven days, outdoor activities in the last one month and other information were collected through the questionnaire. The differences of myopia among children and adolescents with different characteristics were compared by χ2 test, and the relationship between migration time and the prevalence of myopia was analyzed by multivariate unconditional logistic regression model. Results: The age of 26 618 study participants was (12.37±3.49) years old, and the overall prevalence of myopia was 49.4%. Multivariate logistic regression analysis showed that after controlling for relevant confounding factors, compared with migrant children and adolescents of migrant workers who migrated for 1-2 years, those of migrant workers who had migrated for more than 6 years had a higher risk of myopia [OR (95%CI): 1.48 (1.14-1.92)]. After being grouped by phase of school, in the lower grade group of primary school, the children and adolescents of migrant workers who had migrated for more than 6 years had a higher risk of myopia compared with those of migrant workers who migrated for 1-2 years [OR (95%CI): 1.96 (1.20-2.74)]. In the high school group, compared with the children and adolescents of migrant workers who migrated for 1-2 years, those of migrant workers who had migrated for 3-5 years and ≥6 years had a higher risk of myopia [OR (95%CI): 6.03 (1.29-28.15) and 6.52 (1.51-28.11), respectively]. Conclusion: The migration time is related to the prevalence of myopia of the children and adolescents of migrant workers.

[Interaction of health literacy and second-hand smoke exposure on psychopathological symptoms of middle school students].

Objective: To explore the interaction of health literacy and second-hand smoke exposure on psychopathological symptoms of middle school students. Methods: From November 2015 to January 2016, 22 628 middle school students from Shenyang of Liaoning Province, Bengbu of Anhui Province, Xinxiang of Henan Province, Ulanqab of Inner Mongolia Autonomous Region, Chongqing Municipality, and Yangjiang of Guangdong Province were enrolled by using the multi-stage cluster convenience sampling method. A questionnaire was used to collect the data including demographic information, health literacy, second-hand smoke exposure, and psychopathological symptoms. A multivariate logistic regression model was used to analyze the interaction of health literacy and second-hand smoke exposure on psychopathological symptoms of middle school students. Results: The age of students was (15.36±1.79) years old, of which 10 990 were boys, accounting for 48.6% of total students. The detection rate of psychopathological symptoms was 29.1% (6 581/22 628). The detection rate of psychopathological symptoms in those who were exposed to second-hand smoke was 38.1% (2 401/6 304), which was higher than that in the non-second-hand smoke exposure group [25.6% (4 180/16 324)] (P<0.001). The OR (95%CI) of the interaction between medium and low levels of overall health literacy, low level of interpersonal dimension of health literacy and second-hand smoke exposure was 1.19 (1.15-1.24), 2.00 (1.92-2.10) and 1.59 (1.52-1.66), respectively. Conclusion: There was a positive interaction between middle and low levels of overall health literacy, low level of interpersonal dimension of health literacy and second-hand smoke exposure on psychopathological symptoms of middle school students.

[Effect of a novel cold atmospheric plasma jet treatment with different temperatures on resin-dentin bonding].

OBJECTIVE: To investigate the effect of different treatment temperatures of a novel cold atmospheric plasma jet treatment on the resin-dentin bonding. METHODS: (1) Fifty-two freshly extracted, non-carious and intact third molars were collected. The occlusal one-third of the crown was removed by means of a water-cooled low-speed Isomet saw. One dentin disc [(900 ±100) µm] was prepared for each tooth. The fifty-two dentin discs were randomly divided into control group and experimental groups, of which four were in control group, and forty-eight were divided into four experimental groups according to the different treatment temperatures (4 °C, 10 °C, 20 °C and 30 °C) of the novel radio-frequency atmospheric-pressure glow discharge (RF-APGD) plasma jet, twelve in each group. Each experimental group was divided into three subgroups according to different treatment time (10 s, 20 s and 30 s), with four in each subgroup. The occlusal one-third of the crown was removed by means of a water-cooled low-speed Isomet saw. The morphology of demineralized dentin surfaces was analyzed using field emission scanning electron microscopy. (2) Twenty unerupted, non-carious and intact third molars were randomly divided into five groups, four in each group: control group, untreated; 4 °C, 10 °C, 20 °C and 30 °C experimental groups, each group was treated with the RF-APGD plasma jet for 20 s. The micro-tensile resin dentin bond strength was tested after 20 s RF-APGD plasma jet treatment with different temperatures, using a universal mechanical machine. RESULTS: (1) The field emission scanning electron microscopy results indicated that when compared with the control group, a 10 s RF-APGD plasma jet treatment with 30 °C and 20 °C collapsed the collagen scaffold. Collagen fibrils maintained an uncollapsed three-dimensional structure after the 4 °C RF-APGD plasma jet treatment for even 30 s treatment. (2) The microtensile resin dentin bond strength results of the 4 °C RF-APGD plasma jet treatment group (57.8±0.7) MPa were significantly higher than that of the control group [(47.4±0.5) MPa] and 10 s, 20 s and 30 s RF-APGD plasma treatment group [(51.9±0.7) MPa,(29.7±1.0) MPa and (22.2±1.5) MPa] with statistically significant difference (P<0.05). Compared with the control group, the micro-tensile bond strength increased about 21.9% and 9.5% after 4 °C and 10 °C RF-APGD plasma jet treatment, respectively. CONCLUSION: Compared with other treatment temperatures, this novel RF-APGD plasma jet treatment with the temperature of 4 °C can preserve the three-dimensional morphology of demineralized dentin better, and can improve the resin-dentin bonding.

[Association of health literacy and smoking behaviors among middle school students in six cities of China].

Objective: To explore the association between the health literacy (HL) and smoking behaviors in middle school students. Methods: From November 2015 to January 2016, middle school students in Shenyang City of Liaoning Province, Bengbu City of Anhui Province, Xinxiang City of Henan Province, Ulanqab City of Inner Mongolia Autonomous Region, Chongqing City and Yangjiang City of Guangdong Province were enrolled by using a multistage stratified cluster sampling method. A total of 23 137 questionnaires were issued and 22 628 questionnaires were valid. A questionnaire survey was conducted to collect demographic information, HL and smoking behaviors. The low, middle, and high-level group were classified according to the tertile of HL score. A multiple logistic regression model was conducted to explore the association between the HL and smoking behaviors. Results: The age of subjects was (15.4±1.8) years old, and HL score was (104.1±18.7) points. The proportion of former smoking, recent smoking and passive smoking was 9.2% (2 071), 2.8% (635) and 27.9% (6 304), respectively. The proportion of former smokers who tried to quit smoking was 50.1% (1 037/2 071). Compared to the high-level HL, the low-level HL increased the risk of former smoking [OR (95%CI): 1.85 (1.61-2.13)], recent smoking [OR (95%CI): 1.68 (1.33-2.14)] and passive smoking [OR (95%CI): 1.34 (1.23-1.46)], and decreased the likelihood of smoking cessation [OR (95%CI): 0.70 (0.53-0.92)], after adjusting for the gender, school type, registered residence, household structure, accommodation type, educational level of patients, and self-reported family economic status. Conclusion: The HL of middle school students was related to their smoking behaviors.

[Correlation of health literacy and mobile phone use dependence with psychopathological symptoms in middle school students].

Objective: To explore the correlation of health literacy and mobile phone use dependence with psychopathological symptoms in middle school students. Methods: 22 628 middle school students in Shenyang, Bengbu, Xinxiang, Ulanqab, Chongqing and Yangjiang were enrolled by multistage cluster sampling method from November 2015 to January 2016. Chinese Adolescent Interactive Health Literacy Questionnaire (CAIHLQ), Self-rating Questionnaire for Adolescent Problematic Mobile Phone Use (SQAPMPU) and Multidimensional Sub-health Questionnaire of Adolescents (MSQA) were applied to acquire basic characteristics, health literacy, mobile phone use dependence and psychopathological symptoms of subjects. Subjects were classified into three groups, low level (P(75)), according to the percentile of the questionnaire score. Multivariate logistic regression model was used to analyze the correlation of health literacy, mobile phone with psychopathological symptoms. Results: The students were (15.4±1.8) years old with 10 990 boys (48.6%). The score of health literacy of students were (104.1±18.7) points. The rate of mobile phone use dependence was 25.4% (5 752/22 628) and the rate of psychopathological symptoms was 29.1% (6 581/22 628). Compared with high health literacy level, medium and low health literacy levels were related to psychopathological symptoms, with OR (95%CI) about 2.30 (2.10-2.52) and 5.40 (4.89-5.97), respectively. Compared with mobile phone use independence, mobile phone use dependence was related to psychopathological symptoms, with OR (95%CI) about 3.60(3.37-3.85). The highest rate of psychopathological symptoms occurred in students with mobile phone use dependence and low health literacy level [68.0% (1 345/1 977)], with OR (95%CI) about 19.59 (17.07-22.48). Conclusion: Health literacy and mobile phone use dependence are related factors of psychopathological symptoms in middle school students.

[A phase II, single-arm, open-label, multicenter clinical study to evaluate the efficacy and safety of sofosbuvir combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection].

Objective: To evaluate the efficacy and safety of sofosbuvir (Nanjing Zhengda Tianqing Pharmaceutical Co., Ltd.) combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection. Methods: Treatment-naïve or treatment experienced genotype 2 chronic hepatitis C patients from sixteen research centers of China were screened. All subjects received once-daily dose of sofosbuvir (400 mg) combined with ribavirin (body weight < 75 kg, 1 000 mg/day, 400 mg in the morning and 600 mg in the evening; body weight > 75 kg, 1 200 mg/d, 600 mg in the morning and 600 mg in the evening) for 12 weeks. Patients were followed-up for a period of 12 weeks after discontinuation of treatment. Continuous variables were expressed as mean ± standard deviation. The proportion of subjects with virologic response at different follow-up time points and 95% confidence intervals were estimated by maximum likelihood ratio and Clopper-Pearson interval. Results: 132 cases with genotype 2 chronic hepatitis C virus infection from sixteen research centers of China were included, 12 cases of whom were associated with cirrhosis, and the remaining 120 cases were not associated with cirrhosis. One hundred and thirty-one cases completed the study, and one patient lost to follow-up at week 4 after the end of treatment. The sustained virological response rate was 96.2% (95% confidence interval: 92.37% - 99.16%) after 12 weeks of drug withdrawal. Virological relapse occurred in four cases. Of the 132 subjects enrolled in the study, 119 (90.2%) reported 617 adverse events during treatment, of which 359 (76.5%) were TEAE related to sofosbuvir and/or ribavirin. There were nine TEAEs of grade 3 and above, and six cases (4.5%) of them had six severe adverse events. Only one serious adverse event was associated with sofosbuvir and ribavirin (unstable angina pectoris). There were no adverse events leading to drug discontinuation or death. Conclusion: Sofosbuvir combined with ribavirin has a high SVR rate in the treatment of genotype 2 chronic hepatitis C virus infection, and most of the adverse events occurred were mild with acceptable safety profile.

Gene therapy research in Asia.

Gene therapy has shown great potential for the treatment of diseases that previously were either untreatable or treatable but not curable with conventional schemes. Recent progress in clinical gene therapy trials has emerged in various severe diseases, including primary immunodeficiencies, leukodystrophies, Leber's congenital amaurosis, haemophilia, as well as retinal dystrophy. The clinical transformation and industrialization of gene therapy in Asia have been remarkable and continue making steady progress. A total of six gene therapy-based products have been approved worldwide, including two drugs from Asia. This review aims to highlight recent progress in gene therapy clinical trials and discuss the prospects for the future in China and wider Asia.

Modified recombinant adenoviruses increase porcine circovirus 2 capsid protein expression and induce enhanced immune responses in mice.

Porcine circovirus type 2 (PCV2) is the primary viral pathogen of porcine circovirus associated disease (PCVAD) and vaccination is an important method to prevent and control the disease. The expression of PCV2 capsid protein (Cap) in adenovirus vector system has been investigated, but the poor immune responses limit its application. In this study, transcriptional enhancer element largest intron of the human cytomegalovirus (Intron A) and woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) were applied to increase the immunogenicity of PCV2 Cap adenovirus-based vaccine. Western blot and indirect immunofluorescence assay (IFA) analysis showed that modified adenoviruses with Intron A and WPRE alone or both could significantly increase the expression of Cap compared to the unmodified adenoviruses. Furthermore, the humoral and cellular immune responses of the constructed recombinant adenoviruses were evaluated in mice. Indirect ELISA, virus neutralizing test and western blot showed that modified adenoviruses elicited higher humoral immune responses than unmodified adenovirus, and Intron A-WPRE-modified virus immunized group had better immune response than the others. Besides, the results of lymphocyte proliferation response and cytokines release assay showed that enhanced cellular immune responses were induced by modified adenoviruses. These results demonstrated that Intron A and WPRE significantly improved the expression of the Cap protein in adenovirus vector system and enhanced the immune responses in mice, making the adenovirus vector system more applicable against PCV2.

Circulating B7-H4 in serum predicts prognosis in patients with hepatocellular carcinoma.

B7-H4 is member of the B7 family that negatively regulates the immune response, which are important for fine-tuning of the tumor microenvironment. Dysregulation of B7-H4 expression has been associated with tumor progression. However, expression level of B7-H4 in hepatocellular carcinoma (HCC) tissues is still a controversial topic. In addition, whether serum B7-H4 expression of HCC patients has any clinical value is unknown. We compared serum levels of B7-H4 in patients with HCC and healthy controls by using the ELISA method. Association between serum B7-H4 expression level and clinical parameters of HCC was further investigated. Log-rank test and Kaplan-Meier method were employed to evaluate the overall survival rate of HCC patients. Univariate and multivariate analysis of prognostic factors were performed with the Cox regression model. Our results showed that HCC patients had significantly higher serum B7-H4 level as compared with healthy controls (P < 0.001). In addition, serum B7-H4 expression was correlated with HCC clinical parameters including serum AFP expression and TNM stage. HCC patients in the higher serum B7-H4 expression group had a poorer 5-year overall survival rate (P = 0.028). Moreover, serum B7-H4 expression was shown to be an independent prognostic factor for HCC (P = 0.034). The findings from this study suggest that serum B7-H4 is an independent prognostic indicator for HCC and may be a promising biomarker for early diagnosis as well as disease prognosis of HCC.

Identification, molecular characterization, and tissue expression of parathyroid hormone-related protein gene (PTHrP) from water buffalo (Bubalus bubalis).

Parathyroid hormone-related protein (PTHrP) is involved in the deposition of milk calcium in mammal lactation, but its role in buffalo is unclear. In this study, the full-length coding sequence of the water buffalo PTHrP gene was first isolated using reverse transcription-polymerase chain reaction. The protein was then subjected to molecular characterization using bioinformatic methods, and the tissue expression pattern was further assayed by semi-quantitative reverse-transcription polymerase chain reaction. The water buffalo PTHrP gene contains an open reading frame of 534 base pairs encoding a polypeptide of 177 amino acid residues, a theoretical molecular weight of 20.32 kDa, and an isoelectric point of 10.00. In addition, water buffalo PTHrP was predicted to contain a signal peptide, a typical hydrophobic region with no hydrophobic transmembrane regions, and to exert its function in the cell nucleus. A conserved domain of parathyroid superfamily from amino acids 34-114 was observed in the polypeptide. Sequence comparison and the phylogenetic analysis showed that the sequence of the water buffalo PTHrP protein shared high homology with that of other mammals, particularly cattle and goat. Among the 16 tissues examined, the PTHrP gene was only expressed in adipose tissue, placenta, uterine wall, hypophysis, and mammary gland tissue, but gene expression levels were higher in the uterus wall and adipose tissue. The results of this study suggest that the PTHrP gene plays an important role in the deposition of milk calcium of water buffalo.

Sequence characterization, polymorphism, and tissue expression profile of an effector immediate-early gene: activity-regulated cytoskeletal associated protein gene (Arc/Arg3.1) in swamp and river buffalo.

The activity-regulated cytoskeletal associated protein (Arc/Arg3.1) has been implicated in experience-dependent synaptic plasticity and memory formation. However, information regarding its coding gene in buffalo remains scarce. In this study, the full-length of Arc/Arg3.1 was isolated and characterized (accession No. JX491649) and genetic variations of six river buffalo and eight swamp buffalo were investigated. A tissue expression profile was obtained using semi-quantitative reverse transcription-polymerase chain reaction. The coding region sequence of Arc/Arg3.1 contained 1191 nucleotides encoding a putative protein of 396 amino acids with a theoretical isoelectric point (pI) and molecular weight (Mw) of 5.4 and 45.2 kDa, respectively. Four polymorphisms (c.63T>C, c.228T>C, c.558G>A, and c.625G>C) were found in buffalo; however, only substitution c.625G>C was non-synonymous, leading to an amino acid change from Val to Leu at the 209th position of the Arc/Arg3.1 protein sequence. Bioinformatics analysis revealed that this substitution had no significant effect on Arc/Arg3.1 function (subPSEC = -1.4039, Pdeleterious = 0.1685), which indicated that Arc/Arg3.1 was highly conserved and functionally important in buffalo. Phylogenetic analysis revealed that the gene is closely related to that of Bos taurus and Bos grunniens. The gene was moderately expressed in the hypophysis and the placenta; it was weakly expressed in the kidney, milk, mammary gland, cerebrum, lung, heart, rumen, fat, and uterus; and it was almost silent in the muscle, liver, and skin. These findings will provide further insights into the structure and function of the immediate-early gene in buffalo.