Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Objective: To investigate the distribution of blood pressure and analyze the associated factors of blood pressure of the elderly with type 2 diabetes in Jiangsu Province. Methods: The elderly over 60 years old participants with type 2 diabetes in the communities of Huai'an City and Changshu City, Jiangsu Province were selected in this study. They were divided into two groups: taking antihypertensive drugs and not taking antihypertensive drugs. The demographic characteristics, such as age and sex, and relevant factors were collected by questionnaire. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by physical examination. The percentile of SBP and DBP in each age group of men and women were described. The kernel density estimation curve was used to show the blood pressure distribution. The trend of blood pressure with age was fitted by locally weighted regression. The logistic regression model was used to analyze relevant factors of blood pressure. Results: A total of 12 949 participants were included in this study, including 7 775 patients in the antihypertensive drug group and 5 174 patients in the group without antihypertensive drugs. The SBP of participants was concentrated at 140-160 mmHg, and their DBP was concentrated at 75-85 mmHg. There were significant differences in the distribution of blood pressure among the subgroups of body mass index (BMI) and rural areas whether taking antihypertensive drugs and not. For participants aged under 80 years old, the SBP showed an increasing trend with age and the DBP showed a decreasing trend with age. Age, BMI ≥24 kg/m², fasting blood glucose ≥7.0 mmol/L, living in rural areas and no smoking were influencing factors of the elevated SBP; BMI ≥24 kg/m², male, living in rural areas, no smoking, drinking alcohol and not receiving drug hypoglycemic treatment were influencing factors of the elevated DBP. Conclusion: The SBP of older diabetic adults in Jiangsu Province is at a high level, and the distribution of blood pressure is significantly different between men and women in taking antihypertensive drugs group. The SBP presents a rising trend and the DBP is decreasing at the age of 60-80 years. The blood pressure level of this population are mainly affected by age, BMI, urban and rural areas, smoking.
Adult ; Aged ; Humans ; Male ; Female ; Middle Aged ; Aged, 80 and over ; Blood Pressure/physiology* ; Diabetes Mellitus, Type 2/epidemiology* ; Antihypertensive Agents/therapeutic use* ; Smoking ; Body Mass Index ; Hypertension/epidemiology*

OBJECTIVES: To study the clinical phenotype and genetic features of 16p11.2 microdeletion-related epilepsy in children. METHODS: The medical data of 200 children with epilepsy who underwent a genetic analysis of epilepsy by the whole exon sequencing technology were collected retrospectively, of whom 9 children with epilepsy had 16p11.2 microdeletion. The clinical phenotype and genetic features of the 9 children with 16p11.2 microdeletion were analyzed. RESULTS: The detection rate of 16p11.2 microdeletion was 4.5% (9/200). The 9 children with 16p11.2 microdeletion were 3-10 months old. They experienced focal motor seizures with consciousness disturbance, and some of the seizures developed into generalized tonic-clonic seizures. The interictal electroencephalogram showed focal or multifocal epileptiform discharge, and all 9 children responded well to antiepileptic drugs. The 9 children had a 16p11.2 deletion fragment size of 398-906 kb, and the number of deleted genes was 23-33 which were all pathogenic mutations. The mutation was of maternal origin in 2 children, of paternal origin in 1 child, and de novo in the other children. CONCLUSIONS 16p11.2 microdeletion can be detected in some children with epilepsy. Most of the 16p11.2 microdeletion is de novo mutation and large gene fragment deletion. The onset of 16p11.2 microdeletion-related epilepsy in children is mostly within 1 year of life, and the epilepsy is drug-responsive.
Anticonvulsants ; Epilepsy/genetics* ; Humans ; Phenotype ; Retrospective Studies ; Seizures/genetics*

Objective: To investigate the relationship between socioeconomic status (SES) and all-cause mortality in patients with type 2 diabetes. Methods: A total of 17 553 patients with type 2 diabetes were recruited under the National Basic Public Health Service Project in Changshu county, Qingjiangpu district, and Huai'an district in Huai'an city of Jiangsu province as participants. Latent class analysis was applied to classify the individuals based on five socioeconomic indicators. Then, Cox proportional hazards regression models were used to estimate the associations of different levels of SES with all-cause mortality, and stratified analysis was performed according to age and area. Results: Among 100 529.08 person-years of the fo1low-up, the median follow-up time was 5.7 years, and 1 829 deaths occurred during the follow-up period. According to the relevant results of the latent class model, the model of the "three classes" was the best. The related population was then divided into low SES (8 256 people, 47.0%), medium SES (4 427 people, 25.2%), and high SES groups (4 870 people, 27.8%). Compared to patients with high SES, the multivariate-adjusted hazard ratio (95%CI) of all-cause mortality associated with low SES for males and females were 1.84 (1.53-2.21) and 1.41 (1.51-1.72), respectively. Stratified analysis showed that the hazard ration (95%CI) of all-cause mortality associated with low SES for males and females were 1.99 (1.12-2.95) and 2.01 (1.20-3.23), respectively, in people younger than 60 years old, and were 1.90 (1.57-2.31) and 1.40 (1.13-1.73) in people over 60 years old. The HR values (95%CI) for all-cause mortality associated with low SES for the male and females were 1.54 (1.17-2.04) and 1.27 (1.02-1.59) in the urban population with 2.11 (1.55-2.85) and 2.64 (1.17-3.35) in rural population, respectively. Conclusions: Lower SES increased the risk of all-cause mortality in type 2 diabetic patients, which is more significant in younger and rural populations.
United States ; Female ; Humans ; Male ; Middle Aged ; Latent Class Analysis ; Diabetes Mellitus, Type 2 ; Prospective Studies ; Social Class ; Income

It is a major public health task to promote the construction of modern disease prevention and control system in the prevention and control of the novel coronavirus pneumonia epidemic. In this study, we identified the current situation and challenges in the construction of disease prevention and control system in Shanghai, including the infrastructures, disciplines, human resources, information system, operational mechanism, and legalization. It is proposed that we should promote the construction of modern disease prevention and control system in Shanghai, which is aimed to improve the capacity in the disease prevention and control services, response to the major epidemics and public health emergencies, and scientific research in public health, in accordance with municipal functional orientation large-scale metropolitan public health security requirements in Shanghai. Moreover, we should promote policy-making, including upgrading infrastructures, facilitating discipline construction and scientific research innovation, optimizing development environment for human resources, accelerating comprehensive information construction, improving systems and mechanisms, and strengthening legal governance.

Objective: To evaluate the associations of sarcopenia, handgrip strength and calf circumference with cognitive impairment among Chinese older adults. Methods: Totally 2,525 older adults were recruited from the Healthy Aging and Biomarkers Cohort Study. Cognitive impairment was assessed by the Chinese Mini-Mental State Examination. Handgrip strength was calculated from the means of the right and left hand values. Calf circumference was measured at the site of maximum circumference of the non-dominant leg. The formula developed by Ishii was used to define sarcopenia. Multiple logistic regression was performed to evaluate the associations of sarcopenia, handgrip strength, and calf circumference with cognitive impairment. Results: The prevalence of cognitive impairment was 34.36%. The adjusted odds ratio ( Conclusion Sarcopenia, identified by low handgrip strength and low calf circumference, was positively associated with cognitive impairment.
Aged ; Aged, 80 and over ; China/epidemiology* ; Cognitive Dysfunction/etiology* ; Female ; Hand Strength ; Humans ; Leg/anatomy & histology* ; Logistic Models ; Male ; Sarcopenia/pathology*

Objectives: To evaluate the impact of COVID-19 pandemic on the mental health of Malaysian university and pre-university students, especially after the shift to online academic activities, following almost one year of experiencing the pandemic Methods: A cross-sectional online survey was conducted among Malaysian pre-university and university students, nationwide, using perceived stress scale-10 questionnaire and another validated 11-construct questionnaire. Key findings: : The online questionnaires were filled out by 383 Malaysian pre-university and university students. About 40% of the respondents reported moderate to severe level of loneliness and social isolation. There was a significant correlation between suicidal thoughts and the social isolation. The prevalence of moderate to severe suicidal thoughts (14% of the respondents) was more than the reported prevalence before COVID-19 pandemic. The residential state, gender and ethnicity of the respondents did not show an association with depressive and suicidal thoughts of the respondents. Conclusion Loneliness and feeling social isolation were the most prevalent problems, as reported by the students. Suicidal Thoughts are more prevalent, compared to pre-COVID-19 reports. The educators and institution managers must seek for appropriate methods to address the critical condition.

Objective The aim is to investigate the association between body mass index (BMI) and risk of all-cause mortality among patients with type 2 diabetes. Methods A total of 17 638 patients with type 2 diabetes registered in the management of National Basic Public Health Services in two areas of southern and northern Jiangsu were recruited. Cox proportional risk regression model was used to calculate the hazard ratio(HR) value and 95% confidence interval (95% CI) of different BMI groups in the follow-up period. Results The subjects were followed up for a total of 77 451 person-years with an average duration of 4.39 years, and 1 274 patients died during the follow-up period. The number of death in low weight group (BMI<18.5 kg/m2), normal weight group (18.5 kg/m2≤BMI<24 kg/m2), overweight (24 kg/m2≤BMI<28 kg/m2) and obese group (BMI≥28 kg/m2) were 39, 575, 484 and 176 respectively.The corresponding mortalities were 15.6%, 9.5%, 6.2% and 5.1%, respectively. Compared to normal weight group, the adjusted HR of all-cause mortality in low weight, overweight and obese group were 1.66 (95% CI: 1.20-2.30), 0.68 (95% CI: 0.61-0.77), 0.58 (95% CI: 0.48-0.68), respectively. Conclusions Low-weight patients have the highest risk of all-cause mortality compared with normal counterparts, while both overweight and obese people have a lower risk of death. Overweight and obesity may reduce the risk of all-cause mortality in type 2 diabetic patients.

OBJECTIVETo investigate the neuro-protective effects of Acanthopanax senticosus Harms (EAS) on mesencephalic mitochondria and the mechanism of action, using a mouse model of Parkinson's disease (PD).

METHODSThe chemical fingerprint analysis of the extract of Acanthopanax senticosus Harms (EAS) was performed using the ultra performance liquid chromatograph and time of flight mass spectrometry. Thirty mice were randomly divided into the control group, the MPTP model group, and the EAS treated group with MPTP (MPTP+EAS group, 10 in each group). The MPTP model group and the MPTP+EAS group received MPTP-HCl (30 mg/kg i.p) once a day for 5 days. The control group received an equal volume of saline (20 mL/kg i.p) once a day for 5 days. Induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride daily (MPTP-HCl, 30 mg/kg) for 5 days, the PD mice were treated with EAS at 45.5 mg/kg daily for 20 days. The behavioral testing of mice was carried out using the pole-climbing test. The integrity and functions of neurons were examined in mesencephalic mitochondria in a PD mouse model, including nicotinamide adenine dinucleotide dehydrogenase ubiquinone flavoprotein 2 (NDUFV2), mitochondrially encoded nicotinamide adenine dinucleotide dehydrogenase 1 (MT-ND1), succinate dehydrogenase complex subunit A (SDHA), and succinate dehydrogenase cytochrome b560 subunit (SDHC).

RESULTSAfter treatment with EAS, the behavioral changes induced by MPTP were attenuated significantly (P<0.05). EAS protected the mesencephalic mitochondria from swelling and attenuated the decreases in their membrane potential (both P<0.05), which was supported by an ultra-structural level analysis. The changes in reactive oxygen species (ROS), malonic dialdehyde (MDA), oxidative phosphorylation (OXPHOS) system 4 subunits levels and PD-related proteins expressions (parkin, Pink1, DJ-1, α-synuclein, and Lrrk2) reverted to near normal levels (all P<0.05), based on the results of immune-histological and Western blotting observations.

CONCLUSIONSThe neuro-protective effects of EAS are linked to protecting mice against MPTP-induced mitochondrial dysfunction and structural damage. Therefore, EAS is a promising candidate for the prevention or treatment of mitochondrial neurodegenerative disorders, such as PD.

OBJECTIVETo investigate the antitumor effect of lycorine on renal cell carcinoma ACHN cells and explore the possible mechanism.

METHODSWe used flow cytometry to examine the effect of lycorine on ACHN cell cycle and apoptosis. The cell proliferation, migration and invasion were assessed with MTS assay, wound healing assay, and Transwell assay, respectively. Colony forming assay was performed, and the mRNA and protein levels of Bax, Bcl-2, survivin, caspase-3, cyclin D1 and CDK4 were measured with qRT-PCR and Western blotting.

RESULTSLycorine obviously inhibited the proliferation of ACHN cells with an IC(50) of 24.34 µmol/L. Lycorine also induced apoptosis of ACHN cells, caused cell cycle arrest at G(0)/G(1) phase, and suppressed the colony forming ability of the cells in a dose-dependent manner. The migration and invasion of ACHN cells were significantly inhibited by 5 µmol/L lycorine. Lycorine up-regulated the mRNA levels of CDK4, Bax, caspase-3 while down-regulated the levels of survivin, Bcl-2 and Cyclin D1; the protein levels of CDK4 and Bax were increased and cyclin D1, Bcl-2 and surviving expressions were decreased, but caspase-3 expression showed no significant changes following the treatment.

CONCLUSIONLycorine has obvious antitumor effect against ACHN cells, suggesting its value as a new therapeutic agent for renal cell carcinoma.

Amaryllidaceae Alkaloids ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; Carcinoma, Renal Cell ; pathology ; Caspase 3 ; metabolism ; Cell Cycle Checkpoints ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; Cyclin D1 ; metabolism ; Cyclin-Dependent Kinase 4 ; metabolism ; Humans ; Inhibitor of Apoptosis Proteins ; metabolism ; Phenanthridines ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; bcl-2-Associated X Protein ; metabolism