A novel bioassay to assess bioactivity of PEG-rhGH using Nb2-11 cells / 药学学报

In this study, we established a novel bioassay to determine the activity of polyethylene glycolated recombinant human growth hormone (PEG-rhGH) using Nb2-11 cells. We performed experimental condition optimization and methodological verification, and then detected the relative potency of PEG-rhGH products using this method. We demonstrated that the bioactivity of PEG-rhGH in promoting Nb2-11 cell proliferation displays a dose-response relationship, which conformed to the four-parameter model. Using PEG-rhGH reference as a control, we analyzed the relative potency of six batches of PEG-rhGH products, as well as linearity, regression and parallelism of the obtained curves. The relative potency of six batches of PEG-rhGH products was 95% to 105%. These results implied that the new bioassay established may be employed in quality control of PEG-rhGH products.

Collaborative study to evaluate a reporter gene assay for recombinant human follicle-stimulating hormone bioactivity / 药学学报

The goal of this work was to explore the prospect of standardized application of an in-vitro bioactivity assay for recombinant human follicle-stimulating hormone based on a reporter gene. The relative accuracy, intermediate precision, linearity and applicable range of the method were validated according to the General Rules of Chinese Pharmacopoeia 2020 edition Volume IV (9401). Three laboratories used this method to determine the in-vitro biological activities of six batches of drug product and three batches of drug substance manufactured by two different companies. The consistency of the potency determined by three laboratories, the intra-laboratory precision and inter-laboratory precision were analyzed. The method was optimized during the collaborative validation. The results of method validation meet the requirements of the General Rules of Chinese Pharmacopoeia 2020 edition Volume IV (9401). Aiming to resolve the problems found in the collaborative validation, the medium for cell seeding, the pre-diluted buffer solution of standard and sample, and the means of removing and discarding supernatant after stimulation were optimized. After optimization, there was no significant difference in the bioactivity among the different laboratories (P > 0.05), indicating statistical equivalency. Intra-laboratory and inter-laboratory precision were good and the geometric coefficient of variation (GCV%) were both less than 15%. In conclusion, the reporter gene assay has good intra-laboratory repeatability and inter-laboratory reproducibility and is suitable for analyzing recombinant human follicle-stimulating hormone drug product and drug substance by different manufacturers. It is expected to be used as a standardized method for the determination of the in-vitro bioactivity of such products.

An Epidemiologic Survey and Violent Behavior Analysis of Antisocial Personality Disorder in Young Men in Chengdu / 法医学杂志

OBJECTIVES@#To investigate the epidemiological characteristics of antisocial personality disorder (ASPD) in young men in Chengdu and explore the characteristics and risks of violence.@*METHODS@#Stratified random sampling was used to conduct a self-assessment questionnaire survey in 4 108 males aged from 18 to 34 in Chengdu, including general demographic characteristics, structured clinical interview for the diagnostic and statistical manual of mental disorders-Ⅳ axis Ⅱ disorders (SCID-Ⅱ) personality disorder screen questionnaire, violence questionnaire, psychosis screening questionnaire (PSQ), Alcohol Use Disorders Identification Test (AUDIT) and drug use. χ2 test, univariate and multivariate logistic regression were used for analysis and odds ratio (OR) was calculated.@*RESULTS@#The positive rate of ASPD was 5.91%, which was associated with young age, unmarried, unemployment state, low educational level, violent behavior, psychotic symptoms, alcohol and drug use (P<0.05). Young men with ASPD also had a risk (P<0.05) of violence (OR was 8.51), multiple violence (OR was 16.57), injury (OR was 6.68), intentional violence (OR was 11.41), etc., the risk decreased after controlling for psychotic symptoms and substance abuse, but was still statistically significant.@*CONCLUSIONS@#The risk of violence, severe violence and intentional violence in young men in Chengdu is high, and psychotic symptoms and substance abuse increase the risk of ASPD violence and relate characteristics.

Serum Betatrophin level in patients with polycystic ovary syndrome and its relationship with metabolic parameters / 中华内分泌外科杂志

Objective:To investigate the relationship between serum Betatrophin levels and metabolic parameters in patients with polycystic ovary syndrome (PCOS) .Methods:98 patients with PCOS (PCOS group) treated in Zhengzhou People’s Hospital from Dec. 2017 to Sep. 2019 were selected. They were divided into non-obese group ( n=45) and obese group ( n=53) according to BMI value; They were divided into non-IR group ( n= 21) and IR group ( n=77) according to HOMA-IR value; They were divided into non-hyperandrogen group ( n=24) and hyperandrogen group ( n=74) according to TT level; Another 90 healthy women were taken as the control group. The baseline data, lipid metabolism indexes, hormone indexes, glucose metabolism indexes and Betatrophin levels of the two groups were recorded. Pearson test and logisitc regression model were used to analyze the influencing factors related to the increase of serum Betatrophin level in patients with PCOS. Results:Compared with the control group, PCOS group had higher level of BMI, body fat, WHR, VLDL, LDL, TG, TC, FAI, TT, LH, DHEA-S, 17-OHP, FSH, FBG, FINS, and HOMA-IR, while the HDL level was significantly lower. The difference was significant ( P<0.01). Serum Betatrophin level in obese group was significantly higher than that in the control group (163.99±126.97 vs 110.99±102.97), and the difference was statistically significant ( t=3.21, P<0.001) ; serum Betatrophin level in IR group was higher than that in the control group (160.26±136.80 vs 133.17±112.06), and the serum Betatrophin level in IR group was higher than that in the control group (173.51±147.85 vs 144.26±124.56), but the difference was not statistically significant ( P>0.05). Serum Betatrophin levels in PCOS group were positively correlated with BMI, WHR, TG, FAI, FBG, FINS ( P<0.05), and negatively correlated with HDL ( P<0.05). Logistic analysis showed that BMI, WHR and TG were independent factors affecting the increase of serum Betatrophin level. Conclusion:Serum Betatrophin levels of PCOS patients are significantly increased, and BMI, WHR, TG, HDL, FAI, FBG, FINS may play an important role in the occurrence and development of PCOS and obesity, insulin resistance, blood lipids and androgen metabolism disorders.

The associations of muscle size and density with handgrip strength and timed up and go test / 中华老年医学杂志

Objective:The aim of this study was to explore the associations of muscle size and density with handgrip strength(HGS)and the Timed Up and Go(TUG)test.Methods:Totally 301 participants living in the Xinjiekou community near Beijing Jishuitan Hospital were recruited for CT imaging of the hip and a 1-cm slice of the mid-thigh.The cross-sectional area and density of the gluteus maximus and the mid-thigh muscles were estimated by the Osirix viewer based on CT images.HGS and TUG were also performed in these subjects.Logistic regression analysis was used to evaluate the correlations of muscle density and size with TUG and grip strength.Results:In women, after adjustment for age and BMI, the density of the gluteus maximus was negatively correlated with TUG( P trend=0.0366), while the size of the gluteus maximus and the mid-thigh muscles was not correlated with TUG.In men, the density or size of these muscles was not correlated with TUG.After adjustment for age and BMI, the density of the gluteus maximus was positively correlated with grip strength( P trend=0.0334)and the size of the mid-thigh muscles was also positively correlated with grip strength( P trend=0.0155)in men, but they were not correlated with grip strength in women. Conclusions:There were sex differences in the relationship between muscle size or density and grip strength or timed up and go.The density of the gluteus maximus is associated with muscle strength and physical performance while the size of the mid-thigh muscles is correlated with muscle strength.

The correlation between carotid blood flow and the parameters derived by pulse oximetry plethysmographic waveform during cardiopulmonary resuscitation in a porcine model / 中华急诊医学杂志

Objective:To explore the correlation between carotid blood flow and the parameters derived by pulse oximetry Plethysmographic waveform in cardiopulmonary resuscitation, so as to provide a new index for carotid blood flow monitoring in cardiopulmonary resuscitation.Methods:Seven male domestic pigs were utilized for cardiac arrest model through ventricular fibrillation induced by electrical stimulation. Eight minutes after cardiac arrest, artificial chest compression was given for 4 min, and epinephrine 20 μg/kg was injected intravenously at 2 min after chest compression. The compression frequency, compression depth, right carotid blood flow, pulse oximetry plethysmographic waveform, aortic pressure, right atrium pressure and end tidal carbon dioxide partial pressure were continuously monitored and recorded. From 30 s to 4 min after chest compression, the values of the mean right carotid blood flow, the area under curve (AUC) of pulse oximetry plethysmographic waveform, the mean perfusion index, the mean coronary perfusion pressure and the average end-tidal carbon dioxide partial pressure during 6 s before time point were calculated every 30 s. The correlations between right carotid blood flow and the AUC of pulse oximetry plethysmographic waveform and perfusion index were analyzed respectively.Results:Ventricular fibrillation was induced successfully in seven animals. There were no significant differences in the mean chest compression frequency and depth per min during 4 min of chest compression. Right carotid blood flow at 30 s after chest compression was (92.7±32.7) mL/min, and decreased to (48.5±23.5) mL/min at 1 min after chest compression ( P<0.05). There was no significant difference in blood flow before and after epinephrine injection ( P>0.05). The AUC of the blood oxygen plethysmographic waveform and perfusion index showed synchronous change trends with right carotid blood flow. Both coronary perfusion pressure and end-tidal carbon dioxide partial pressure showed different change trends with right carotid blood flow. There was a positive correlation between the right carotid blood flow and the AUC of blood oxygen plethysmographic waveform ( r=0.66, P<0.01), and also a positive correlation between right carotid blood flow and perfusion index ( r=0.57, P<0.01). Conclusions:Carotid blood flow is positively correlated with the AUC of blood oxygen plethysmographic waveform and perfusion index in a porcine model of cardiopulmonary resuscitation. Real-time monitoring of the two parameters derived by pulse oximetry plethysmographic waveform can reflect the changes of carotid blood flow to a certain extent.

Dahuang Zhechong pills inhibit liver cancer growth in a mouse model by reversing Treg/Th1 balance / 中国天然药物

The infiltration of immune cells into the hepatocellular carcinoma microenvironment is the main reason why hepatocellular carcinoma patients are prone to carcinoma recurrence and the disease are incurable. Notably, the infiltration of Treg cells is the main trigger. Dahuang Zhechong pill (DHZCP) is a traditional Chinese herbal compound successful in the treatment of hepatitis and hepatocellular carcinoma. DHZCP can heal and nourish while slowing the onset of the disease, thereby strengthening the body's immune function. It can localize tumors and ultimately achieve the goal of eliminating tumors. In this study, an orthotopic liver cancer model of mice was used to explore the mechanism of DHZCP enhancing anti-tumor immunity, which showed more Th1 cells in the peripheral blood and spleen after DHZCP treatment, while more IFN-γ was secreted to activate CD8+ T cells and Treg cell production was inhibited, thereby suppressing the growth of HCC. Finally, we also analyzed the potential components of DHZCP from the perspective of modern targets using network pharmacology methods and experimental results.

Local vibration therapy promotes the recovery of nerve function in rats with sciatic nerve injury / 中西医结合学报

OBJECTIVE@#It has been reported that local vibration therapy can benefit recovery after peripheral nerve injury, but the optimized parameters and effective mechanism were unclear. In the present study, we investigated the effect of local vibration therapy of different amplitudes on the recovery of nerve function in rats with sciatic nerve injury (SNI).@*METHODS@#Adult male Sprague-Dawley rats were subjected to SNI and then randomly divided into 5 groups: sham group, SNI group, SNI + A-1 mm group, SNI + A-2 mm group, and SNI + A-4 mm group (A refers to the amplitude; n = 10 per group). Starting on the 7th day after model initiation, local vibration therapy was given for 21 consecutive days with a frequency of 10 Hz and an amplitude of 1, 2 or 4 mm for 5 min. The sciatic function index (SFI) was assessed before surgery and on the 7th, 14th, 21st and 28th days after surgery. Tissues were harvested on the 28th day after surgery for morphological, immunofluorescence and Western blot analysis.@*RESULTS@#Compared with the SNI group, on the 28th day after surgery, the SFIs of the treatment groups were increased; the difference in the SNI + A-2 mm group was the most obvious (95% confidence interval [CI]: [5.86, 27.09], P < 0.001), and the cross-sectional areas of myocytes in all of the treatment groups were improved. The G-ratios in the SNI + A-1 mm group and SNI + A-2 mm group were reduced significantly (95% CI: [-0.12, -0.02], P = 0.007; 95% CI: [-0.15, -0.06], P < 0.001). In addition, the expressions of S100 and nerve growth factor proteins in the treatment groups were increased; the phosphorylation expressions of ERK1/2 protein in the SNI + A-2 mm group and SNI + A-4 mm group were upregulated (95% CI: [0.03, 0.96], P = 0.038; 95% CI: [0.01, 0.94], P = 0.047, respectively), and the phosphorylation expression of Akt in the SNI + A-1 mm group was upregulated (95% CI: [0.11, 2.07], P = 0.031).@*CONCLUSION@#Local vibration therapy, especially with medium amplitude, was able to promote the recovery of nerve function in rats with SNI; this result was linked to the proliferation of Schwann cells and the activation of the ERK1/2 and Akt signaling pathways.

Research progress in mechanism of Chinese herbal compounds and monomers in delaying lumbar intervertebral disc degeneration / 中国中药杂志

Traditional Chinese medicine has unique advantages in the treatment of degenerative bone and joint diseases, and its widely used in clinical practice. In recent years, many scholars have conducted a large number of basic studies on the delay of intervertebral disc degeneration by herbal compound and monomeric components from different perspectives. In order to further elucidate its mechanism of action, this paper summarizes the in vivo and in vitro experimental studies conducted at the level of both herbal compound and single components, respectively, in order to provide references for the basic research on the treatment of lumbar intervertebral disc degeneration by Chinese medicine. A summary shows that commonly used herbal compound prescriptions include both classical prescriptions such as Duhuo Jisheng Decoction, as well as clinical experience prescriptions such as Yiqi Huoxue Recipe. Angelicae Sinensis Radix, Chuanxiong Rhizoma, Rehmanniae Radix Praeparata, Achyranthis Bidentatae Radix, and Eucommiae Cortex were used most frequently. Tonic for deficiency and blood stasis activators were used most frequently. The most utilized monomeric components include icariin, ginsenoside Re, salvianolic acid B and aucubin. The main molecular mechanisms by which herbal compound and monomeric components delay of lumbar intervertebral disc degeneration include improving the intervertebral disc microenvironment, promoting the synthesis of aggregated proteoglycans and type Ⅱ collagen in the intervertebral disc, reducing the degradation of the extracellular matrix, and inhibiting apoptosis in the nucleus pulposus cells, etc. The main signaling pathways involved include Wnt/β-catenin signaling pathway, MAPK-related signaling pathway, mTOR signaling pathway, Fas/FasL signaling pathway, PI3 K/Akt signaling pathway, NF-κB signaling pathway, JAK/STAT signaling pathway, and hedgehog signaling pathway, etc.

Effects of mindfulness training on clinical efficacy in patients with nitrous oxide addiction / 中华行为医学与脑科学杂志

Objective:To study the effect of mindfulness-based training intervention on clinical efficacy in patients with nitrous oxide(laughing gas) addiction.Methods:From June 2019 to June 2020, sixty-six patients with nitrous oxide addiction in Beijing Gaoxin Hospital were selected and randomly divided into experimental group( n=33) and control group( n=33). The control group received Taijiquan training and physical training, while the experimental group added mindfulness-based training intervention on the basis of Taijiquan training and physical training.Symptom checklist 90 (SCL-90) scores and visual analog scales (VAS) craving scores were compared between the two groups at admission and 8 weeks after treatment.SPSS 22.0 software was used for statistical analysis.Independent sample t test and paired sample t test were used to compare the differences between groups and within groups. Results:(1)Before treatment, there were no significant differences in subscale scores of SCL-90 between the two groups except for depression factor((2.45±0.86), (2.03±0.46), t=2.474, P<0.05). After treatment, the subscale scores of somatization((1.38±0.35), (1.68±0.34), t=-3.656, P<0.05), phobic anxiety((1.49±0.37), (1.81±0.30), t=-3.993, P<0.05), paranoid ideation((1.50±0.47), (1.88±0.31), t=-3.898, P<0.05) and psychotism((1.34±0.54), (1.55±0.27), t=-3.094, P<0.05) of SCL-90 in the experimental group were significantly lower than those in the control group.(2)Before treatment, there was no significant difference in VAS craving score between the two groups( t=0.857, P=0.395). After treatment, the score of VAS in the experimental group was significantly lower than that in the control group( t=27.427, P<0.05). Conclusion:Mindfulness training intervention can effectively improve the clinical symptoms of patients with nitrous oxide addiction, which is worthy of clinical application.

The predictive value of mean arterial pressure and end expiratory carbon dioxide on severe cardiovascular collapse in early stage after emergency endotracheal intubation / 中华急诊医学杂志

Objective:To analyze the changes of mean arterial pressure (MAP) and end expiratory carbon dioxide (ETCO 2) in patients after emergency endotracheal intubation (ETI). To explore the values of MAP and ETCO 2 monitoring in early prediction of severe cardiovascular collapse (CVC) after emergency ETI. Methods:The clinical data of adult patients who underwent ETI from March 2015 to May 2020 were collected consecutively in the emergency departments of Peking Union Medical College Hospital. The values of MAP and ETCO 2 were observed and recorded at 5, 10, 30, 60 and 120 min after intubation. According to whether severe CVC occurred after ETI, the patients were divided into the severe CVC group and non-severe CVC group. The values of MAP and ETCO 2 were compared at the same time points between the two groups and the adjacent time points within the groups. The correlation between MAP and ETCO 2 after ETI was also analyzed. ROC curve was used to analyze the ability of MAP and ETCO 2 at 5 min and 10 min after ETI to predict severe CVC. Results:Totally 116 patients were enrolled in this study, among them 75 (64.7%) cases had severe CVC after ETI. The majority were male and elderly patients in the severe CVC group. The values of MAP and ETCO 2 in 5, 10, 30, 60 and 120 min after ETI in severe CVC group were significantly lower than those in the non-severe CVC group. The values of MAP and ETCO 2 in the two groups showed simultaneous decrease from 5 min to 30 min after ETI, reached the lowest value at 30 min after ETI, and appeared the synchronous recover from then to 120 min after ETI. After ETI, the changes of MAP was correlated with that of ETCO 2 ( rs = 0.653, P<0.01). At 5 min after ETI, MAP could predict severe CVC (AUC=0.86, P<0.01), MAP≤72 mmHg was the best cutoff value (sensitivity 78.7%, specificity 87.8%); ETCO 2 could also predict severe CVC (AUC=0.85, P<0.01), and ETCO 2≤35 mmHg was the best cutoff value (sensitivity 77.3%, specificity 85.4%). At 10 min after ETI, MAP could predict severe CVC (AUC = 0.90, P<0.01), MAP≤67 mmHg was the best cutoff value (sensitivity 89.3%, specificity 85.4%), ETCO 2 could also predict severe CVC (AUC=0.87, P<0.01), and ETCO 2≤33 mmHg was the best cutoff value (sensitivity 81.3%, specificity 78.0%). There was no significant difference in the ability of prediction between any two indexes of the MAP and ETCO 2 at 5 min and 10 min after ETI ( P>0.05). Conclusions:Patients with severe CVC after ETI have early signs of decreased MAP and ETCO 2, but the delayed recognition and insufficient intervention may be related to the occurrence and development of severe CVC. MAP and ETCO 2 at the early stage after ETI have high accuracy in predicting severe CVC. MAP≤72 mmHg, ETCO 2≤35 mmHg at 5 min after intubation, MAP≤67 mmHg and ETCO 2≤33 mmHg at 10 minutes after intubation all suggest the possibility of severe CVC.

Cut-off values of lesion and vessel quantitative flow ratio in de novo coronary lesion post-drug-coated balloon therapy predicting vessel restenosis at mid-term follow-up / 中华医学杂志(英文版)

BACKGROUND@#Drug-coated balloons (DCBs) have emerged as potential alternatives to drug-eluting stents in specific lesion subsets for de novo coronary lesions. Quantitative flow ratio (QFR) is a method based on the three-dimensional quantitative coronary angiography and contrast flow velocity during coronary angiography (CAG), obviating the need for an invasive fractional flow reserve procedural. This study aimed to assess the serial angiographic changes of de novo lesions post-DCB therapy and further explore the cut-off values of lesion and vessel QFR, which predict vessel restenosis (diameter stenosis [DS] ≥50%) at mid-term follow-up.@*METHODS@#The data of patients who underwent DCB therapy between January 2014 and December 2019 from the multicenter hospital were retrospectively collected for QFR analysis. From their QFR performances, which were analyzed by CAG images at follow-up, we divided them into two groups: group A, showing target vessel DS ≥50%, and group B, showing target vessel DS <50%. The median follow-up time was 287 days in group A and 227 days in group B. We compared the clinical characteristics, parameters during DCB therapy, and QFR performances, which were analyzed by CAG images between the two groups, in need to explore the cut-off value of lesion/vessel QFR which can predict vessel restenosis. Student's t test was used for the comparison of normally distributed continuous data, Mann-Whitney U test for the comparison of non-normally distributed continuous data, and receiver operating characteristic (ROC) curves for the evaluation of QFR performance which can predict vessel restenosis (DS ≥50%) at mid-term follow-up using the area under the curve (AUC).@*RESULTS@#A total of 112 patients with 112 target vessels were enrolled in this study. Group A had 41 patients, while group B had 71. Vessel QFR and lesion QFR were lower in group A than in group B post-DCB therapy, and the cut-off values of lesion QFR and vessel QFR in the ROC analysis to predict target vessel DS ≥50% post-DCB therapy were 0.905 (AUC, 0.741 [95% confidence interval, CI: 0.645, 0.837]; sensitivity, 0.817; specificity, 0.561; P < 0.001) and 0.890 (AUC, 0.796 [95% CI: 0.709, 0.882]; sensitivity, 0.746; specificity, 0.780; P < 0.001).@*CONCLUSIONS@#The cut-off values of lesion QFR and vessel QFR can assist in predicting the angiographic changes post-DCB therapy. When lesion/vessel QFR values are <0.905/0.890 post-DCB therapy, a higher risk of vessel restenosis is potentially predicted at follow-up.

Value of cone-beam breast CT in differentiating benign from malignant dense breast masses / 中华放射学杂志

Objective:To investigate the value of logistic regression model based on the features of cone-beam breast CT (CBBCT) for the identification of benign and malignant masses in dense breast.Methods:The data of 106 patients (130 masses) with dense breast who underwent contrast-enhanced CBBCT examination and obtained pathological results from May 2011 to August 2020 were retrospectively analyzed as the training set. From August 2020, the data of 49 patients (54 masses) who met the same criteria were prospectively and consecutively collected and used as the validation set. Taking pathological results as the gold standard, the training set was divided into benign and malignant groups. The t-test, χ 2 test and Fisher′s exact test were used to compare the differences in CBBCT image characteristics between the two groups in the training set. A binary logistic regression model was established by multivariate analysis. ROC curves were used to assess the diagnostic efficacy of the model as a whole in the training and validation sets and the diagnostic efficacy of each feature in the model, and the cut-off value of the intensity (ΔCT) value was determined. The H-L method was used to test the goodness of fit of the model. Decision curve analysis (DCA) was drawn to validate the clinical power of the model. Results:Univariate analysis showed that the breast parenchymal background enhancement (BPE), shape, margin, lobulation, spiculation, density, calcifications, ΔCT value, enhancement pattern, non-mass enhancement, ipsilateral increased vascularity (IIV), and peripheral vascular signs had statistical difference between benign group and malignant group ( P<0.05). BPE, margin, ΔCT value and IIV were included in the multivariate analysis, the equation was logit( P′)=-8.510+0.830×BPE+0.822×margin+1.919× ΔCT+1.896 × IIV. The are a under curve of the model in the training set was 0.879 ( P<0.001) and in the validation set was 0.851 ( P=0.001). The are a under curve of BPE, margin, ΔCT value, and IIV in the diagnosis of malignant mass were 0.645, 0.711, 0.712, 0.775 (all P<0.05); the best cut-off value of ΔCT was 50.38 HU. The fit of this model was good ( P = 0.776). The DCA curve showed that when the risk threshold was 0.05-0.97, the net benefit rate was>0, and this model had some clinical value. Conclusion:The logistic regression model based on the features of CBBCT is helpful to distinguish benign and malignant masses in dense breasts.

Research progress on characteristics of gastrointestinal flora in patients with Crohn's disease and the efficacy of fecal microbiota transplantation / 中华临床营养杂志

Crohn's disease (CD) is a chronic nonspecific inflammatory bowel disease that can involve the whole digestive tract. At present, the pathogenesis is believed to be mainly related to environment, genetics and intestinal microecology changes. Compared with healthy people, CD patients demonstrate different degrees of flora imbalance in the digestive tract, and the flora composition varies across different regions. In recent years, reconstruction of gastrointestinal microecological balance has become the focus of research. Fecal microbiota transplantation as a new treatment strategy has been gradually applied in clinical practice. Here we reviewed the changes of flora across different regions of digestive tract in patients with CD and the relevant pathogenic mechanism, as well as the progress of fecal microbiota transplantation in the treatment of CD.

Effects of naltrexone hydrochloride combined with trazodone on preventing relapse in heroin addicts after detoxification / 中国基层医药

Objective:To investigate the effects of naltrexone hydrochloride combined with trazodone on preventing relapse in heroin addicts after detoxification.Methods:A total of 274 opioid heroin addicts who received treatment in Beijing Gaoxin Hospital between June 2016 and January 2019 were included in this study. After detoxification with methadone, all patients were randomly assigned to receive either naltrexone hydrochloride combined with trazodone (group 1, n = 60) or naltrexone hydrochloride alone (group 2, n = 60) for preventing relapse in heroin addicts. The effects on relapse prevention were determined in each group. Results:There were no significant differences in age distribution, sex composition, marital status, and drug use between groups 1 and 2 (all P > 0.05). After 6 months of treatment, the non-relapse rate was 86.7% (52/60) and 6.7% (4/60) in groups 1 and 2 respectively, in the case of unchanged personal life status. There was significant difference in non-relapse rate between groups 1 and 2 ( χ2 = 77.1, P < 0.001). Conclusion:Naltrexone hydrochloride combined with trazodone exhibits superior efficacy in preventing relapse in opioid heroin addicts after detoxification to naltrexone hydrochloride alone.

Clinical Efficacy of Modified Chaihu Shugansan Combined with Xuanfu Daizhetang on Depression of Patients of Patients with Gastroesophageal Reflux Disease / 中国实验方剂学杂志

Objective:To observe the clinical efficacy modified Chaihu Shugansan combined with Xuanfu Daizhetang on anxiety and depression of patients with gastroesophageal reflux disease （GERD） and Qi stagnation and phlegm obstruction syndromes in clinic and the effect on neuropeptide factor and pro-inflammatory factor. Method:Patients 200 cases were divided into control group and observation group. Patients in control group got omeprazole enteric-coated tablets， 20 mg/time， 1 time/day， flupentixol and melitracen tablets， 1 tablet/time， 2 times/day， and Dalitong granules， 1 bag/time， 3 times/day. In addition to omeprazole enteric-coated tablets in control group， patients in observation group were also added with syndrome differentiation-based treatment of modified Chaihu Shugansan combined with Xuanfu Daizhetang， 1 dose/day. The treatment lasted for 8 weeks. Before and after treatment， scores of acid regurgitation， heartburn， poststernal pain， syndrome of Qi stagnation and phlegm obstruction， gastroesophageal reflux disease questionnaire （GerdQ）， Hamilton anxiety Scale-14 （HAMA-14） and Hamilton depression scale-17 （HAMD-17） were scored； And upper gastrointestinal endoscopy， levels of peripheral vasoactive intestinal peptide （VIP）， 5-hydroxytryptamine （5-HT）， tumor necrosis factor-<italic>α </italic>（TNF-<italic>α</italic>）， interleukin-1 （IL-1）， IL-6 were detected. All the patients （GerdQ<8） got follow-up for 16 weeks， and the recurrence and safety were recorded. Result:After treatment， scores of GerdQ， endoscope， main symptoms and syndrome of Qi stagnation and phlegm obstruction on observation group were lower than those in control group （<italic>P</italic><0.01）， and scores of HAMA-14 and HAMD-17 decreased in both groups （<italic>P</italic><0.01）， but with no statistically significant difference in both groups. The comprehensive efficacy of main symptoms in observation group was better than that in control group （<italic>Z</italic>=2.076， <italic>P</italic><0.05）. The curative effect of traditional Chinese medicine （TCM） syndrome in observation group was superior to that in control group （<italic>Z</italic>=2.151， <italic>P</italic><0.01）. The effect of endoscope was better than that in control group （<italic>Z</italic>=2.103， <italic>P</italic><0.05）. And levels of VIP， 5-HT， TNF-<italic>α</italic>， IL-1 and IL-6 in observation group were lower than those in control group. During the 16-week follow-up， the recurrence rate in observation group was 19.23% （15/78）， which was lower than 35.38% （23/65） in control group （<inline-formula><alternatives><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:msup><mml:mrow><mml:mi>χ</mml:mi></mml:mrow><mml:mrow><mml:mn mathvariant="normal">2</mml:mn></mml:mrow></mml:msup></mml:math><graphic specific-use="big" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/EF9122E2-D647-4d34-AB25-83CBA259DE55-M002.jpg"><?fx-imagestate width="3.30199981" height="3.64066648"?></graphic><graphic specific-use="small" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/EF9122E2-D647-4d34-AB25-83CBA259DE55-M002c.jpg"><?fx-imagestate width="3.30199981" height="3.64066648"?></graphic></alternatives></inline-formula>=4.741， <italic>P</italic><0.05）. The average recurrence time of the observation group was lower than that of the control group（<italic>P</italic><0.01）. Conclusion:Modified Chaihu Shugansan combined with Xuanfu Daizhetang can significantly improve the main symptoms and TCM syndromes， relieve depression， anxiety and other adverse emotions， promote the healing of gastroesophageal mucosa， reduce the recurrence rate and delay the recurrence time among patients with GERD and Qi stagnation and phlegm obstruction syndromes. The mechanism of action may be related to the expression of neuropeptide factor and the inhibition of pro-inflammatory factor.

Prenatal diagnosis of Joubert syndrome caused by de novo mutations of CPLANE1 gene / 中华围产医学杂志

We report a case of fetal cerebellar vermis dysplasia diagnosed prenatally by ultrasonography. Ultrasonography of the 27-year-old woman at 20 +6 gestational weeks revealed partial separation of the cerebellar vermis (Dandy-Walker variants), unclosable upper and lower lips, and polydactyly, based on which a preliminary diagnosis of multiple fetal malformations was made. Karyotype and chromosomal microarray (CMA) analysis of the amniotic fluid showed no abnormality. After genetic counseling, amniocentesis was performed again for a whole-exome sequencing test. The results suggested that there are compound heterozygous variations of c.3435G>A(P.W1145X) and c.2941C>G(p. p981A) in the exon 19 and exon 17 of the CPLANE1 gene, which were both de novo mutations and inherited from the father and mother, respectively. The fetus was diagnosed as Joubert syndrome. Given the facial and limb deformities and a significant risk of neurological abnormalities of the fetus, the patient and her family decided to terminate the pregnancy.

Research progress of metabonomics and nutritional intervention in Crohn's disease / 中华临床营养杂志

Crohn's disease (CD) is a chronic nonspecific intestinal inflammatory disease with unclear etiology and pathogenesis. At present, it is believed that CD can cause different degrees of metabolic abnormalities, and that the related metabolites also play an important role in the development and progression of the disease. In recent years, metabonomics is becoming more and more well-developed and has provided guidance for clinicians on rational nutritional support. Here is a review on the metabolic changes of multiple systems in CD patients, the application of metabonomics in CD diagnosis and treatment, and the research progress of clinical nutrition intervention.

Quantitative Evaluation of Gastrocnemius Medialis Stiffness During Passive Stretching Using Shear Wave Elastography in Patients with Parkinson’s Disease: A Prospective Preliminary Study

Objective@#To prospectively investigate the feasibility of shear wave elastography (SWE) as a new quantitative and objective method for evaluating the stiffness of the gastrocnemius medialis (GM) muscle during passive stretching in patients with Parkinson’s disease (PD). @*Materials and Methods@#SWE of the GM muscle was performed in 28 patients with PD [13 female and 15 male; mean age ± standard deviation (SD): 63.0 ± 8.5 years] and 12 healthy controls (5 female and 7 male; mean age ± SD: 59.3 ± 6.4 years) during passive ankle rotation. A Young’s modulus-ankle angle curve was constructed. The GM slack angle and baseline Young’s modulus (E 0) were compared between the markedly symptomatic and mildly symptomatic sides of patients with PD, and healthy controls. Additionally, the correlation between the GM slack angle and the severity of rigidity, and the observer reproducibility of SWE in determining the GM slack angle were evaluated. @*Results@#The GM slack angle was smaller on both the markedly and mildly symptomatic sides in patients with PD than in healthy controls (mean ± SD of -29.13° ± 3.79° and -25.65° ± 3.39°, respectively, vs. -21.22° ± 3.52°; p < 0.001 and p = 0.006, respectively). Additionally, in patients with PD, the GM slack angle on the markedly symptomatic side was smaller than that on the mildly symptomatic side (p = 0.003). The E 0 value was lower on both the markedly and mildly symptomatic sides in patients with PD than in healthy controls (mean ± SD of 10.11 ± 2.85 kPa and 10.08 ± 1.88 kPa, respectively, vs. 12.23 ± 1.02 kPa; p = 0.012 and p < 0.001, respectively). However, no significant difference was found between the markedly and mildly symptomatic sides in patients with PD (p = 0.634). A negative linear relationship was observed between the GM slack angle and lower limb rigidity score on the markedly symptomatic side in patients with PD (r = -0.719; p < 0.001). The intraclass correlation coefficients for observer reproducibility of SWE ranged from 0.880 to 0.951. @*Conclusion@#The slack angle determined by SWE may be a useful quantitative and reproducible method for evaluating muscle stiffness in patients with PD.

Intensive statin versus low-dose statin + ezetimibe treatment for fibrous cap thickness of coronary vulnerable plaques / 中华医学杂志(英文版)

BACKGROUND@#Acute coronary syndromes mainly result from abrupt thrombotic occlusion caused by atherosclerotic vulnerable plaques (VPs) that suddenly rupture or erosion. Fibrous cap thickness (FCT) is a major determinant of the propensity of a VP to rupture and is recognized as a key factor. The intensive use of statins is known to have the ability to increase FCT; however, there is a risk of additional adverse effects. However, lower dose statin with ezetimibe is known to be tolerable by patients. The present study aimed to investigate the effect of intensive statin vs. low-dose stain + ezetimibe therapy on FCT, as evaluated using optical coherence tomography.@*METHOD@#Patients who had VPs (minimum FCT 90°) and deferred from intervention in our single center from January 2014 to December 2018 were included in the trial. They were divided into the following two groups: intensive statin group (rosuvastatin 15-20 mg or atorvastatin 30-40 mg) and combination therapy group (rosuvastatin 5-10 mg or atorvastatin 10-20 mg + ezetimibe 10 mg). At the 12-month follow-up, we compared the change in the FCT (ΔFCT%) between the two groups and analyzed the association of ΔFCT% with risk factors. Fisher exact test was used for all categorical variables. Student's t test or Mann-Whitney U-test was used for analyzing the continuous data. The relationship between ΔFCT% and risk factors was analyzed using linear regression analysis.@*RESULT@#Total 53 patients were finally enrolled, including 26 patients who were in the intensive statin group and 27 who were in the combination therapy group. At the 12-month follow-up, the serum levels of total cholesterol (TC), total triglyceride, low-density lipoprotein (LDL-C), hypersensitive C-reactive protein (hs-CRP), and lipoprotein-associated phospholipase A2 (Lp-PLA2) levels were reduced in both the groups. The ΔTC%, ΔLDL-C%, and ΔLp-PLA2% were decreased further in the combination therapy group. FCT was increased in both the groups (combination treatment group vs. intensive statin group: 128.89 ± 7.64 vs. 110.19 ± 7.00 μm, t = -9.282, P < 0.001) at the 12-month follow-up. The increase in ΔFCT% was more in the combination therapy group (123.46% ± 14.05% vs. 91.14% ± 11.68%, t = -9.085, P < 0.001). Based on the multivariate linear regression analysis, only the serum Lp-PLA2 at the 12-month follow-up (B = -0.203, t = -2.701, P = 0.010), ΔTC% (B = -0.573, t = -2.048, P = 0.046), and Δhs-CRP% (B = -0.302, t = -2.963, P = 0.005) showed an independent association with ΔFCT%.@*CONCLUSIONS@#Low-dose statin combined with ezetimibe therapy maybe provide a profound and significant increase in FCT as compared to intensive statin monotherapy. The reductions in Lp-PLA2, ΔTC%, and Δhs-CRP% are independently associated with an increase in FCT.