Exploring the multicomponent synergy mechanism of Zuogui Wan on postmenopausal osteoporosis by a systems pharmacology strategy.

OBJECTIVE: To explore the multi-component synergistic mechanism of Zuogui Wan (, ZGW) in treating postmenopausal osteoporosis (PMOP). METHODS: The main components and target genes of ZGW were screened via the Traditional Chinese Medicine Systems Pharmacology (TCMSP). In addition, the target gene sets of PMOP were derived from the GeneCards and Online Mendelian Inheritance in Man databases. The search tool for recurring instances of neighbouring genes (STRING) 11.0 software was used to analyze the interaction among intersecting genes. Cytoscape 3.6.1 software and the Matthews correlation coefficient (MCC) algorithm were used to screen the core genes. Fifty Sprague-Dawley female rats were randomly divided into the sham-operated (Sham) group and the four ovariectomized (OVX) subgroups. Rats subjected to Sham or OVX were administered with the vehicle (OVX, 1 mL water/100 g weight), 17ß-estradiol (E2, 50 µg·kg-1·d-1), and lyophilized powder of ZGW at a low dose of 2.3 (ZGW-L) and high dose of 4.6 (ZGW-H) g·kg-1·d-1 for three months. The bone density and bone strength were assessed using dual-energy X-ray and three-point bending tests, respectively. Furthermore, enzyme-linked immun-osorbent assay, Hematoxylin-eosin staining, and western blot analysis were used to determine the potential pharmacological mechanisms of action of ZGW in PMOP. RESULTS: A total of 117 active compounds of ZGW were screened from the TCMSP. Furthermore, 108 intersecting genes of drugs and diseases were identified. Using STRING software and the MCC algorithm, ten core genes, including C-X-C chemokine living 8 (CXCL8), C-C chemokine receptor type 2 (CCR2), alpha-2a active receptor (ADRA2A), melatonin receptor type 1B (MTNR1B), and amyloid-beta A4 protein (APP), were identified. The anti-osteoporosis regulation network of ZGW was constructed using the Cytoscape software. The animal experiments demonstrated that ZGW groups significantly reduced the serum levels of ß-C-terminal telopeptide of type I collagen (ß-CTX) and increased serum levels of bone-specific alkaline phosphatase (BALP) (P < 0.05, P < 0.01). The OVX group exhibited a significant decrease in bone mineral density and bone strength compared with the Sham group (P < 0.01). Moreover, treatment with ZGW resulted in increased trabecular thickness, improved arrangement of trabecular structure, and reduced empty bone lacunae. Furthermore, treatment with ZGW significantly increased the protein expression of CXCL8, ADRA2A, and CCR2 (P < 0.05, P < 0.01), and significantly decreased the protein expression of Runx2 (P < 0.01). Furthermore, the ZGW and E2 groups demonstrated significantly increased BMD (P < 0.05, P < 0.01), improved bone strength (P < 0.05, P < 0.01), reduced expression of CXCL8, ADRA2A, and CCR2, and increased runt-related transcription factor 2 levels in bone tissue (P < 0.05, P < 0.01) compared with the OVX group. However, there were no significant differences in MTNR1B and APP expression among the groups. CONCLUSION: ZGW shows synergistic mechanisms in PMOP through multiple components, targets, and pathways.

Copper homeostasis dysregulation promoting cell damage and the association with liver diseases / 中华医学杂志(英文版)

Copper plays an important role in many metabolic activities in the human body. Copper level in the human body is in a state of dynamic equilibrium. Recent research on copper metabolism has revealed that copper dyshomeostasis can cause cell damage and induce or aggravate some diseases by affecting oxidative stress, proteasome, cuprotosis, and angiogenesis. The liver plays a central role in copper metabolism in the human body. Research conducted in recent years has unraveled the relationship between copper homeostasis and liver diseases. In this paper, we review the available evidence of the mechanism by which copper dyshomeostasis promotes cell damage and the development of liver diseases, and identify the future research priorities.

Effects of raw and wine-processed Schisandra chinensis on neuro-endocrine-immune network in insomnia mice and its mechanism / 中国药房

OBJECTIVE To investigate the effect of raw and wine-processed Schisandra chinensis on neuro-immune-endocrine network in insomnia mice and its mechanism. METHODS Fifty mice were randomly divided into blank group， model group， diazepam group， raw S. chinensis group and wine-processed S. chinensis group， with 10 mice in each group. Except for blank group， the mice in the other groups were intraperitoneally injected with thyroxine solution to establish mice model of insomnia； at the end of each day’s modeling， the corresponding doses of diazepam，raw and wine-processed S. chinensis were given by gavage. The blank group and model group were given constant volume of normal saline. The general state of the mice was observed and recorded， and the total activity distance and upright times of the mice were detected； the EEG and EMG signals of mice were recorded， and the time ratio of sleep wake time （wake）， non-rapid eye movement （NREM） and rapid eye movement （REM） was analyzed； the contents of neurotransmitters [γ-aminobutyric acid （GABA）， 5-hydroxytryptamine （5-HT）， dopamine （DA）， norepinephrine （NE）， cortisol （CORT）] in brain suprachiasmatic nucleus （SCN） were detected； and the expressions of tumor necrosis factor α （TNF-α） and interleukin 1β （IL-1β） were detected； the mRNA expressions of clock gene Bmal1， circadian clock gene Clock and cycle gene Per2 were all detected. RESULTS Compared with the blank group， the mental state of the model group mice was relatively depressed， the amount of food and water increased， the body mass decreased， the hair was rough and shiny， and the circadian rhythm was irregular； the total activity distance and upright times decreased significantly； the time ratio of wake increased significantly， while the time ratios of REM and NREM decreased significantly； the content of 5- HT in brain SCN decreased significantly， while the content of NE， DA and CORT increased significantly； the fluorescence intensity of IL-1β and TNF-α was significantly increased； the relative expression level of Bmal1 and Clock mRNA was significantly increased， while the relative expression level of Per2 mRNA was significantly decreased （P＜0.05 or P＜0.01）. Compared with the model group， the general state of mice in diazepam group， raw S. chinensis group and wine-processed S. chinensis group was improved obviously， and most of the above index levels were significantly reversed （P＜0.05 or P＜0.01）. CONCLUSIONS Raw and wine-processed S. chinensis have a certain therapeutic effect on insomnia mice， the mechanism of which may be related to the regulation of neuro-endocrine-immune system related biological indicators in insomnia mice.

Effectiveness of increasing alcohol excise taxes in the management of alcohol-associated liver disease in China / 临床肝胆病杂志

Increasing alcohol excise taxes has been confirmed by the World Health Organization as the most cost-effective public policy for reducing alcohol consumption at the population level. In recent years, studies in foreign countries have believed that increasing alcohol excise taxes can improve the burden of alcohol-associated liver disease (ALD), but it is still unclear whether this policy is applicable to ALD management in China. Therefore, with reference to related research evidence in China and globally, this article analyzes the key factors influencing the effectiveness of the policy of increasing alcohol excise taxes from the perspective of ALD management in China, including tax shifting, price elasticity of demand, and unrecorded alcohol, and introduces other public policies that help curb ALD. We think that increasing alcohol excise taxes is currently a useful but not effective policy for improving the burden of ALD in China.

The fate of flavonoids after oral administration: a comprehensive overview of its bioavailability.

Despite advancements in synthetic chemistry, nature remains the primary source of drug discovery, and this never-ending task of finding novel and active drug molecules will continue. Flavonoids have been shown to possess highly significant therapeutic activities such as anti-inflammatory, anti-oxidant, anti-viral, anti-diabetic, anti-cancer, anti-aging, neuroprotective, and cardioprotective, etc., However, it has been found that orally administered flavonoids have a critical absorption disorder and, therefore, have low bioavailability and show fluctuating pharmacokinetic and pharmacodynamic responses. A detailed investigation is required to assess and analyze the variation in the bioavailability of flavonoids due to interactions with the intestinal barrier. This review will emphasize on the bioavailability and the pharmacological applications of flavonoids, key factors affecting their bioavailability, and strategies for enhancing bioavailability, which may lead to deeper understanding of the extent of flavonoids as a treatment and/or prevention for different diseases in clinics.

Research progress on pathogenicity and mechanism of important virulence factors of Moraxella catarrhalis / 中华检验医学杂志

Moraxella catarrhalis ( Mca) is a kind of gram-negative diplococcus which can exist in the respiratory tract of the human. It could be a non-symptom diplococcus on the health people. Otitis media occurs when the Mca reaches the middle ear along the eustachian tube. Sometimes the patients could suffer from the acute exacerbation of chronic obstructive pulmonary disease or pneumonia due to lung lesions caused by Mca. Little is known about the pathogenesis of the Mca, which leads to an incomplete understanding of its pathogenicity. This review aims to clarify the relationships between the Mca and the related diseases and the mechanism of the significant virulence factors. We hope to raise awareness of Mca and also provide some ideas for clinical diagnosis of relevant diseases it caused.

Population differences of metabolic associated fatty liver disease and nonalcoholic fatty liver disease based on a community elderly population / 临床肝胆病杂志

Objective To investigate the population differences of the newly named "metabolic associated fatty liver disease" (MAFLD) and the former name "nonalcoholic fatty liver disease" (NAFLD). Methods From November 2020 to January 2021, a cross-sectional survey was conducted among 624 elderly individuals aged above 65 years in a community in Beijing, China, and related data were collected, including demographic data, past history, laboratory markers, liver ultrasound, and liver elasticity. According to the presence or absence of fatty liver based on ultrasonic diagnosis, the individuals were divided into fatty liver group with 389 individuals and non-fatty liver group with 235 individuals. The independent samples t -test was used for comparison of normally distributed continuous data between the two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between the two groups; the chi-square test was used for comparison of categorical data between the two groups. Results Among the 389 patients with fatty liver, 387(99.5%) were diagnosed with MAFLD and 368(94.6%) were diagnosed with NAFLD, and there were 19 patients with a history of heavy alcohol consumption and 2 with positive surface antigen. A total of 366 patients met the diagnostic criteria for both MAFLD and NAFLD, accounting for 94.6% of the MAFLD patients and 99.5% of the NAFLD patients. Compared with the non-fatty liver group, the MAFLD group had significant increases in body mass index (BMI) ( t =-11.228, P < 0.05), waist circumference ( Z =-8.532, P < 0.05), hip circumference ( Z =-6.449, P < 0.05), waist-hip ratio ( Z =-5.708, P < 0.05), alanine aminotransferase ( Z =-5.027, P < 0.05), aspartate aminotransferase ( Z =-2.880, P < 0.05), platelet count ( t =-3.623, P < 0.05), triglyceride ( Z =-8.489, P < 0.05), fasting blood glucose ( Z =-3.516, P < 0.05), HbA1c ( Z =-2.884, P < 0.05), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) ( Z =-0.394, P < 0.05), high-sensitivity C-reactive protein ( Z =-4.912, P < 0.05), controlled attenuation parameter (CAP) ( t =13.744, P < 0.05), and liver stiffness measurement (LSM) ( Z =-7.69, P < 0.05), as well as a significant reduction in high-density lipoprotein cholesterol (HDL-C) ( t =6.348, P < 0.001). Meanwhile, MAFLD patients had more metabolic associated diseases, such as overweight, obesity, central obesity, dyslipidemia, and hypertension ( χ 2 =9.978, 65.472, 36.571, 9.797, and 5.128, all P < 0.05). In the MAFLD group, 30.7% of the patients had non-obese fatty liver disease (BMI < 25 kg/m 2 ), and 11.1% had lean fatty liver disease (BMI < 23 kg/m 2 ); compared with the obese MAFLD patients, the non-obese MAFLD patients had significantly lower age ( Z =-3.042, P < 0.05), BMI ( Z =-15.705, P < 0.05), waist circumference ( Z =-9.589, P < 0.05), hip circumference ( Z =-10.275, P < 0.05), HOMA-IR ( Z =-2.081, P < 0.05), CAP ( t =-3.468, P < 0.05), LSM ( Z =-3.630, P < 0.05), and NAFLD fibrosis score ( t =-4.433, P < 0.05). According to LSM value, advanced liver fibrosis accounted for 3.6% of the MAFLD population, and 10% of the MAFLD population could not be excluded for advanced liver fibrosis. Conclusion The diagnosis of MAFLD can basically cover the NAFLD population in the elderly people, and it is supposed that MAFLD can almost directly replace the concept of NAFLD in similar populations. However, further studies are needed to investigate its application in other populations.

Exploration of ethnomedicinal plants and their practices in human and livestock healthcare in Haripur District, Khyber Pakhtunkhwa, Pakistan.

BACKGROUND: The utilization of plants and plant resources for various ethnobotanical purposes is a common practice in local towns and villages of developing countries, especially in regard to human and veterinary healthcare. For this reason, it is important to unveil and document ethnomedicinal plants and their traditional/folk usage for human and livestock healthcare from unexplored areas. Here we advance our findings on ethnomedicinal plants from Haripur District, Pakistan, not only for conservation purposes, but also for further pharmacological screenings and applied research. METHODOLOGY: Information of ethnomedicinal plants was obtained using a carefully planned questionnaire and interviews from 80 local people and traditional healers (Hakims) in Haripur District, Pakistan, from 2015 to 2017. Informed consent was obtained from each participant before conducting the interview process. Quantitative ethnobotanical indices, such as relative frequency of citation (RFC), use value (UV) and Jaccard index (JI), were calculated for each recorded species. Correlation analysis between the RFC and UV was tested by Pearson's correlation, SPSS (ver. 16). RESULTS: A total of 80 plant species (33 herbs, 24 trees, 21 shrubs and 2 climbers) belonging to 50 families were being used in the study area to treat livestock and human diseases. Lamiaceae was the most dominant family with 7 species (8.7%), followed by Fabaceae with 6 species (7.5%), and Moraceae with 5 species (6.2%). Local people used different methods of preparation for different plant parts; among them, decoction/tea (22 species) was the popular method, followed by powder/grained (20 species) and paste/poultice (14 species). It was observed that most of the species (~ 12 to 16 species) were utilized to treat human and livestock digestive system-related problems, respectively. The Jaccard index found that plant usage in two studies (District Abbottabad and Sulaiman Range) was more comparable. Local people mainly relied on folk medicines due to their rich accessibility, low cost and higher efficacy against diseases. Unfortunately, this important traditional knowledge is vanishing fast, and many medicinal plants are under severe threat. The most threats associated to species observed in the study area include Dehri, Garmthun, Baghpur, Najafpur and Pharala. CONCLUSION: The study has indicated that local people have higher confidence in the usage of ethnomedicinal plants and are still using them for the treatment of various ailments. Comparative analysis with other studies may strongly reflected the novel use of these plants, which may be due to the deep-rooted and unique socio-cultural setup of the study area. However, awareness campaigns, conservation efforts and pharmacological and applied research are required for further exploration and may be a step in the right direction to unveil prospective pharmaceuticals.

Radiofrequency thermocoagulation of the sulcus bottom in type II focal cortical dysplasia-related epilepsy with tapered implantation of electrodes: a case report.

We report a 15-year-old male patient with recurrent epileptic seizures for 12 years. Oral multiple drugs do not work well to his condition. MRI FLAIR scans revealed focal cortical dysplasia type II in the right parietal lobe. The diagnosis of the patient was drug-refractory epilepsy, FCD-related secondary epilepsy. According to the shape of the FCD lesion, electrodes were implanted in a tapered pattern along the bottom of the sulcus to completely destroy the focus. Magnetic resonance imaging at 6 months after surgery revealed that the FCD at the sulcus bottom was completely destroyed. After 26 months of follow-up, the patient had undergone no epileptic seizures, reaching Engel class I. For FCD that are located deep in the brain and adjacent to functional areas, craniotomy has a high risk. And stereoelectroencephalography-guided radiofrequency thermocoagulation may be a preferred treatment.

The cut off value of liver stiffness measurement needs to be lowered to predict liver fibrosis after sustained virologic response in chronic hepatitis C patients / 临床肝胆病杂志

Objective To further verify the ability of noninvasive diagnostic method for liver fibrosis in predicting liver fibrosis in chronic hepatitis C patients followed up after sustained virologic response (SVR) based on liver biopsy. Methods A prospective cohort study was performed for the chronic hepatitis C patients who attended Beijing YouAn Hospital, Capital Medical University, from October 2015 to December 2017, and all patients were followed up regularly after SVR and underwent liver biopsy. The diagnostic efficiency of the noninvasive diagnostic method for liver fibrosis was verified based on pathological results. The receiver operating characteristic (ROC) curve was used to evaluate the ability of LSM, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) in the diagnosis of liver fibrosis, and STATA and R language were used to compare the area under the ROC curve (AUC). Results A total of 96 patients were successfully enrolled. The LSM after SVR was significantly lower than that at baseline, and LSM had a significantly larger AUC than APRI (0.89 vs 0.67, P < 0.05) and FIB (0.89 vs 0.69, P < 0.05) in the diagnosis of liver cirrhosis after SVR. LSM at a cut-off value of 7.95 kPa, and based on the best specificity, the diagnosis of liver cirrhosis could be considered when LSM was greater than 9.15 kPa, with a positive likelihood ratio of 5.91%; progressive liver fibrosis could be excluded based on LSM < 6.85 kPa, with a negative predictive value of 0.98. Follow-up time and antiviral regimen had no influence on the diagnostic ability of LSM. Conclusion The cut off value of LSM needs to be lowered to predict liver fibrosis after SVR in chronic hepatitis C patients.

Association of inosine triphosphate pyrophosphatase gene polymorphisms with ribavirin combined with direct-acting antiviral agent in treatment of hepatitis C patients with hemolytic anemia / 临床肝胆病杂志

Objective To investigate the influencing factors for ribavirin (RBV)-induced hemolytic anemia in the treatment of chronic hepatitis C, and to provide a reference for the early prediction of ribavirin-related hemolytic anemia in clinical practice. Methods A total of 49 patients with chronic hepatitis C who attended or were hospitalized in Hebei Petrochina Central Hospital from January 2018 to July 2019 and received antiviral therapy with direct-acting antiviral agent (DAA) and RBV were enrolled, with a major allele of C allele and a minor allele of A allele at the rs1127354 locus of the inosine triphosphate pyrophosphatase (ITPA) gene, and the patients with AA and AC genotypes were compared with those with CC genotype. During treatment, RBV was reduced to 600 mg when hemoglobin (Hb) level was < 100 g/L and was withdrawn when Hb level was < 85 g/L. Routine blood test, liver function, liver stiffness measurement, HCV RNA, HCV genotype, and ITPA genotype were measured before antiviral therapy, and the routine blood test was performed at weeks 2, 4, 8, and 12 of treatment. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. Results A total of 49 patients were enrolled in this study, among whom 22 had chronic hepatitis C and 27 had liver cirrhosis, with a sustained virologic response (SVR) rate of 95.9%. The dose of RBV was reduced in 3 patients (2 in the AA/AC group and 1 in the CC group) due to anemia, and RBV was withdrawn in 3 patients (1 in the AA/AC group and 2 in the CC group); all these 6 patients had liver cirrhosis and finally achieved SVR. During the anti-HCV therapy with DAA+RBV, there was relatively mild RBV-related hemolysis, and the maximum reduction in Hb from baseline was compared between the patients with AA/AC genotype at ITPA rs1127354 and those with CC genotype, which showed no significant difference between the two groups ( Z =-0.18, P =0.87). Conclusion During the treatment with RBV+DAA, RBV is withdrawn or reduced for liver cirrhosis patients due to anemia, and no obvious statistical relation is observed between ITPA genotype and the maximum reduction in Hb from baseline. Therefore, detection of ITPA genotype before the application of RBV does not improve safety during treatment, and it is not recommended to perform conventional detection of ITPA gene polymorphisms.

Association of inosine triphosphate pyrophosphatase gene polymorphisms with ribavirin combined with direct-acting antiviral agent in treatment of hepatitis C patients with hemolytic anemia / 临床肝胆病杂志

Objective To investigate the influencing factors for ribavirin (RBV)-induced hemolytic anemia in the treatment of chronic hepatitis C, and to provide a reference for the early prediction of ribavirin-related hemolytic anemia in clinical practice. Methods A total of 49 patients with chronic hepatitis C who attended or were hospitalized in Hebei Petrochina Central Hospital from January 2018 to July 2019 and received antiviral therapy with direct-acting antiviral agent (DAA) and RBV were enrolled, with a major allele of C allele and a minor allele of A allele at the rs1127354 locus of the inosine triphosphate pyrophosphatase (ITPA) gene, and the patients with AA and AC genotypes were compared with those with CC genotype. During treatment, RBV was reduced to 600 mg when hemoglobin (Hb) level was < 100 g/L and was withdrawn when Hb level was < 85 g/L. Routine blood test, liver function, liver stiffness measurement, HCV RNA, HCV genotype, and ITPA genotype were measured before antiviral therapy, and the routine blood test was performed at weeks 2, 4, 8, and 12 of treatment. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. Results A total of 49 patients were enrolled in this study, among whom 22 had chronic hepatitis C and 27 had liver cirrhosis, with a sustained virologic response (SVR) rate of 95.9%. The dose of RBV was reduced in 3 patients (2 in the AA/AC group and 1 in the CC group) due to anemia, and RBV was withdrawn in 3 patients (1 in the AA/AC group and 2 in the CC group); all these 6 patients had liver cirrhosis and finally achieved SVR. During the anti-HCV therapy with DAA+RBV, there was relatively mild RBV-related hemolysis, and the maximum reduction in Hb from baseline was compared between the patients with AA/AC genotype at ITPA rs1127354 and those with CC genotype, which showed no significant difference between the two groups ( Z =-0.18, P =0.87). Conclusion During the treatment with RBV+DAA, RBV is withdrawn or reduced for liver cirrhosis patients due to anemia, and no obvious statistical relation is observed between ITPA genotype and the maximum reduction in Hb from baseline. Therefore, detection of ITPA genotype before the application of RBV does not improve safety during treatment, and it is not recommended to perform conventional detection of ITPA gene polymorphisms.

On precision management of standardized residency training for rehabilitation medicine residents based on mobile phone platform / 中华医学教育探索杂志

In order to improve the management efficiency of standardized residency training for rehabilitation medicine and ensure the quality of training for trainees, we have conducted a precise management exploration of standardized residency training for rehabilitation medicine residents based on mobile phone platforms. An highly efficient and precise rehabilitation medicine residents training system has been constructed by applying some widely used APPs and network functions in China, such as WeChat, Sojump, Teachermate, Ding Talk, etc. With the mobile phone WeChat as the medium, the management framework of the residency training base has been built. The student information input, assessment, evaluation and feedback system have been completed through the questionnaire star as the medium. The Internet extension of teaching and training activities has been realized by the teachermate. Through the Ding Talk, the individualized precise graduation examination arrangements for the trainees have been achieved, and the customized skill training arrangements and records have also been achieved. Through the use of these modern teaching techniques and training methods, the precise and efficient management of the rehabilitation medicine standardized residency training has been basically realized.

Value of Model for End-Stage Liver Disease and Child-Turcotte-Pugh score in predicting the prognosis of patients with hepatic sinus obstruction syndrome associated with Gynura segetum (Lour.) Merr / 临床肝胆病杂志

ObjectiveTo investigate the value of Model for End-Stage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP) score in predicting the prognosis of patients with hepatic sinusoidal obstruction syndrome (HSOS) associated with Gynura segetum (Lour.) Merr. MethodsA total of 49 patients with HSOS associated with Gynura segetum (Lour.) Merr. who were admitted to Beijing YouAn Hospital, Beijing Ditan Hospital, The Fifth Medical Center of Chinese PLA General Hospital, Tianjin Third Central Hospital, and The First Affiliated Hospital of Xinxiang Medical University from January 2012 to July 2018 were enrolled and followed up for three years, with death as the outcome event. MELD and CTP scores were calculated according to the laboratory examination and clinical data on admission, and according to CTP score, the patients were divided into CTP class A (CTP score 5-6) group(n=8), CTP class B (CTP score 7-9) group(n=23), and CTP class C (CTP score ≥10) group(n=18). The patients were divided into death group(n=12) and survival group(n=37) according to the clinical outcome during follow-up. The Mann-Whitney U test was used for comparison of continuous data between groups, and the Kruskal-Wallis H test was used for ranked data. The area under the receiver operator characteristic (ROC) curve (AUC) was used to investigate the ability of CTP and MELD scores in predicting death. The Kaplan-Meier survival curves were used to determine the long-term prognosis of patients with different CTP and MELD scores, and the log-rank test was used for comparison. The ROC curve was used to evaluate the performance of these two scoring systems in predicting death. ResultsA total of 12 patients died during the 3-year follow-up period. The patients with HSOS had a median MELD score of 13.443 (8.792-18.379), and the death group had a significantly higher MELD score than the survival group ［19.84 (15.49-25.41) vs 11.58 (8.60-15.79), Z=-3.511, P＜0.001］. The patients with HSOS had a CTP score of 6-12, and of all 49 patients, 8 (16.3%) had CTP class A HSOS, 23 (46.9%) had CTP class B HSOS, and 18 (36.7%) had CTP class C HSOS. The mortality rate of the patients increased significantly with the increase in CTP score (χ2=16.078, P＜0.05). The mortality rates of the patients with CTP class A, B, and C HSOS were 0.0%, 13.0%, and 50.0%, respectively (χ2=10343, P＜0.05). The Kaplan-Meier analysis showed that the patients with a MELD score of ＜14.294 4 had a significantly better 3-year prognosis than those with a MELD score of ≥14.294 4 (χ2=14.893, P＜0.001). The higher the CTP score, the poorer the 3-year prognosis of patients (χ2=11.083, P＜0.05). CTP class had an AUC of 0.780 (95% confidence interval ［CI］: 0.639-0.922) in predicting the prognosis of HSOS patients, while MELD score had an AUC of 0.840 (95%CI: 0.722-0.958), and there was no significant difference between the two scores (Z=2.63, P＞0.05). ConclusionBoth MELD and CTP scores can predict the risk of death in patients with HSOS, with similar performance in predicting the prognosis of patients, and further studies are needed to validate their clinical value.

Clinical study on liver function, virology, serological changes and the safety of drug withdrawal in pregnant women who are chronic HBV carriers during pregnancy and postpartum / 中华肝脏病杂志

Objective@#To observe the changes of liver function, virology and serology and the safety of drug withdrawal in pregnant women who are chronic hepatitis B virus (HBV) carriers.@*Methods@#A prospective clinical cohort was established to enroll pregnant women who are chronic HBV carriers and they were divided into the nucleoside/nucleotide analogs (NAs) intervention group and the non-NAs intervention group according to patients' wishes. Liver function, HBV DNA and HBV serological markers were detected at gestation, postpartum 6 weeks, 12 weeks, 24 weeks, 36 weeks and 48 weeks.@*Results@#351 patients were enrolled, 320 in the NAs intervention group and 31 in the non-NAs intervention group. The proportion of postpartum hepatitis flares in both groups was higher than that in pregnancy (39.4% vs 12.5%, P < 0.001; 38.7% vs 3.2%, P = 0.001). Six weeks postpartum was the peak period of hepatitis flares, and 96.0% (121/126) of the hepatitis flares occurred within 24 weeks postpartum. At 6 weeks postpartum, there were 6 cases of alanine aminotransferase (ALT) ≥ 10 times upper limit of normal (ULN) in the NAs intervention group. The rate of the hepatitis flare after drug withdrawal was 16.7% (34/203).@*Conclusion@#Regardless of the presence or absence of NAs intervention, pregnant women who are chronic HBV carriers have a certain proportion of hepatitis flares during pregnancy and postpartum, and the hepatitis flare even have a tendency to be severe. Therefore, drug withdrawal after delivery is not always safe, which requires close observation and classification. At 6 weeks postpartum, the incidence of hepatitis flares was high, and those who meet the treatment indications can get better therapeutic effects if given appropriate treatment. The vast majority (96%) of postpartum hepatitis flares occur within 24 weeks, so it is recommended to follow up to at least 24 weeks postpartum after discontinuation.

Targeted elimination of mutant mitochondrial DNA in MELAS-iPSCs by mitoTALENs

Mitochondrial diseases are maternally inherited heterogeneous disorders that are primarily caused by mitochondrial DNA (mtDNA) mutations. Depending on the ratio of mutant to wild-type mtDNA, known as heteroplasmy, mitochondrial defects can result in a wide spectrum of clinical manifestations. Mitochondria-targeted endonucleases provide an alternative avenue for treating mitochondrial disorders via targeted destruction of the mutant mtDNA and induction of heteroplasmic shifting. Here, we generated mitochondrial disease patient-specific induced pluripotent stem cells (MiPSCs) that harbored a high proportion of m.3243A>G mtDNA mutations and caused mitochondrial encephalomyopathy and stroke-like episodes (MELAS). We engineered mitochondrial-targeted transcription activator-like effector nucleases (mitoTALENs) and successfully eliminated the m.3243A>G mutation in MiPSCs. Off-target mutagenesis was not detected in the targeted MiPSC clones. Utilizing a dual fluorescence iPSC reporter cell line expressing a 3243G mutant mtDNA sequence in the nuclear genome, mitoTALENs displayed a significantly limited ability to target the nuclear genome compared with nuclear-localized TALENs. Moreover, genetically rescued MiPSCs displayed normal mitochondrial respiration and energy production. Moreover, neuronal progenitor cells differentiated from the rescued MiPSCs also demonstrated normal metabolic profiles. Furthermore, we successfully achieved reduction in the human m.3243A>G mtDNA mutation in porcine oocytes via injection of mitoTALEN mRNA. Our study shows the great potential for using mitoTALENs for specific targeting of mutant mtDNA both in iPSCs and mammalian oocytes, which not only provides a new avenue for studying mitochondrial biology and disease but also suggests a potential therapeutic approach for the treatment of mitochondrial disease, as well as the prevention of germline transmission of mutant mtDNA.

Human-robot global Simulink modeling and analysis for an end-effector upper limb rehabilitation robot / 生物医学工程学杂志

Robot rehabilitation has been a primary therapy method for the urgent rehabilitation demands of paralyzed patients after a stroke. The parameters in rehabilitation training such as the range of the training, which should be adjustable according to each participant's functional ability, are the key factors influencing the effectiveness of rehabilitation therapy. Therapists design rehabilitation projects based on the semiquantitative functional assessment scales and their experience. But these therapies based on therapists' experience cannot be implemented in robot rehabilitation therapy. This paper modeled the global human-robot by Simulink in order to analyze the relationship between the parameters in robot rehabilitation therapy and the patients' movement functional abilities. We compared the shoulder and elbow angles calculated by simulation with the angles recorded by motion capture system while the healthy subjects completed the simulated action. Results showed there was a remarkable correlation between the simulation data and the experiment data, which verified the validity of the human-robot global Simulink model. Besides, the relationship between the circle radius in the drawing tasks in robot rehabilitation training and the active movement degrees of shoulder as well as elbow was also matched by a linear, which also had a remarkable fitting coefficient. The matched linear can be a quantitative reference for the robot rehabilitation training parameters.

Surveillance of antimicrobial resistance in Peking Union Medical College Hospital in 2017 / 中国感染与化疗杂志

Objective To investigate the antimicrobial resistance of clinical bacterial isolates in Peking Union Medical College Hospital (PUMCH) in 2017. Methods A total of 9 515 non-duplicate clinical isolates were collected from January 1 to December 31, 2017. Disc diffusion test (Kirby-Bauer method) and E-test method were employed to determine antimicrobial susceptibility. Results Gram-negative bacilli and gram-positive cocci accounted for 68.2％ and 31.8％, respectively among the 9 515 clinical isolates. Methicillin-resistant strains in S. aureus (MRSA) and coagulase-negative Staphylococcus (MRCNS) accounted for 25.6％ and 73.3％, respectively. Extended-spectrum β-lactamases (ESBLs) -producing strains accounted for 47.6％ (877/1 842), 27.6％ (335/1 213) and 33.0％ (59/179) in E. coli, Klebsiella spp (K. pneumoniae and K. oxytoca) and P. mirabilis, respectively. Enterbacteriaceae strains were still highly susceptible to carbapenems, with an overall resistance rate of ≤ 3.8％. The resistance rates of K. pneumoniae to imipenem and meropenem were 8.5％ and 8.2％, respectively. About 72.7％ and 70.4％ of A. baumannii isolateswere resistant to imipenem and meropenem. The resistance rate of P. aeruginosa to imipenem and meropenem was 14.8％ and 10.0％, respectively. The prevalence of extensively drug-resistant strains in A. baumannii, P. aeruginosa and K. pneumoniae was 31.7％ (239/753), 1.0％ (10/1 035), and 3.0％ (33/1 117), respectively. Conclusions The common bacterialisolates show various level of resistance to antimicrobial agents. Laboratory staff should improve communication with clinicians to prevent the spread of resistant strains.

Antitumor efficacy of bispecific antibody mAb04-MICA to human leukemia cell K562 in vitro and in vivo / 中国药科大学学报

This study aimed to investigate the efficacy of a bispecific antibody mAb04-MICA on human leukemia cell K562 both in vitro and vivo. mAb04-MICA was previously found to posses excellent anti-angiogenic activity, and have the ability to recruit immune surveillance in tumor microenvironment. In this study, the affinity of mAb04-MICA to VEGFR2 and NKG2D was identified by ELISA. CCK8 was used to detect the effect of mAb04-MICA on K562 proliferation. The cross reactivity of mAb04-MICA to murine VEGFR2 was determined by flow cytometry assay. To evaluate the antitumor activity of mAb04-MICA,tumor volume,tumor weight and the survival of K562 tumor-bearing nude mice were analyzed. The anti-angiogenic activity was determined by immunohisto-chemistry. The results indicated that mAb04-MICA could target to VEGFR2 and NKG2D,and inhibit K562 pro-liferation specifically. Besides,mAb04-MICA showed high binding capacity to murine VEGFR2. The bispecific antibody exhibited superior antitumor efficacy to the maternal monoclonal antibody and prolonged the survival of tumor-bearing mice. The expression of Ki-67,p-VEGFR2,VEGF and CD34 in mAb04-MICA treated group was significantly reduced. The results indicated that mAb04-MICA could attenuate the phosphorylation of VEGFR2 and impair angiogenesis of the tumor microenviroment. Therefore,mAb04-MICA could be further developed as a potential tumor targeted immunotherapeutic agent for leukemia.

Prenatal diagnosis and PAH gene mutations in 55 pedigrees with phenylketonuria / 中华围产医学杂志

Objective To investigate phenylalanine hydroxylase ( PA H ) gene mutations and to perform prenatal diagnosis in 55 pedigrees with classical phenylketonuria (PKU). Methods Subjects of this study were 55 probands diagnosed with PKU in the Gansu Provincial Maternal and Child Health Care Hospital from 2013 to 2017 and their pedigrees. Sanger sequencing/Multiplex ligation-dependent probe amplification (MLPA) was used to investigate PA H gene mutations in these probands and their parents. Sanger sequencing/MLPA, linkage analysis of three common short tandem repeats (STR) including PAH-26, PAH-STR and PAH-32 in the PA H gene and paternity testing were used in combination for prenatal diagnosis of 60 fetuses in the 55 pedigrees. Results Among the 110 alleles in the 55 probands, 108 mutant alleles (98.2%) were found by Sanger sequencing. The 108 mutant alleles located in 38 regions resulting in 22 missense mutations, nine splice site mutations, five nonsense mutations and two microdeletion. The most common mutations were c.728G>A (22.2%, 24/108), c.442-1G>A (5.6%, 6/108), c.611A>G (5.6%, 6/108), c.764T>C (5.6%, 6/108), c.1068C>A (5.6%, 6/108) and c.331C>T (4.6%, 5/108). Loss of heterozygosity in 4-5 and 4-7 exons were detected by MLPA in two probands, in which only one mutation was unidentified. Prenatal diagnosis for the 60 fetuses were successfully performed. Among them, 17 fetuses (28.3%) were affected, 29 fetuses (48.3%) were heterozygous carriers and fetuses 14(23.4%) were unaffected ones. Conclusions Combination of Sanger sequencing/MLPA, linkage analysis and paternity testing could provide accurate prenatal diagnosis in pedigrees with PKU.