Cloning of transcription factor PcFBA-1 in Pogostemon cabin and its interaction with FPPS promoter / 中国中药杂志

Farnesyl diphosphate synthase(FPPS) is a key enzyme at the branch point of the sesquiterpene biosynthetic pathway, but there are no reports on the transcriptional regulation of FPPS promoter in Pogostemon cabin. In the early stage of this study, we obtained the binding protein PcFBA-1 of FPPS gene promoter in P. cabin. In order to explore the possible mechanism of PcFBA-1 involved in the regulation of patchouli alcohol biosynthesis, this study performed PCR-based cloning and sequencing analysis of PcFBA-1, analyzed the expression patterns of PcFBA-1 in different tissues by fluorescence quantitative PCR and its subcellular localization using the protoplast transformation system, detected the binding of PcFBA-1 protein to the FPPS promoter in vitro with the yeast one-hybrid system, and verified its transcriptional regulatory function by dual-luciferase reporter gene assay. The findings demonstrated that the cloned PcFBA-1 had an open reading frame(ORF) of 1 131 bp, encoding a protein of 376 amino acids, containing two conserved domains named F-box-like superfamily and FBA-1 superfamily, and belonging to the F-box family. Moreover, neither signal peptide nor transmembrane domain was contained, implying that it was an unstable hydrophilic protein. In addition, as revealed by fluorescence quantitative PCR results, PcFBA-1 had the highest expression in leaves, and there was no significant difference in expression in roots or stems. PcFBA-1 protein was proved mainly located in the cytoplasm. Furthermore, yeast one-hybrid screening and dual-luciferase reporter gene assay showed that PcFBA-1 was able to bind to FPPS promoter both in vitro and in vivo to enhance the activity of FPPS promoter. In summary, this study identifies a new transcription factor PcFBA-1 in P. cabin, which directly binds to the FPPS gene promoter to enhance the promoter activity. This had laid a foundation for the biosynthesis of patchouli alcohol and other active ingre-dients and provided a basis for metabolic engineering and genetic improvement of P. cabin.

Data mining and analysis of the rules of prescriptions in the treatment of epigastric pain in A Hundred Years of Traditional Chinese Medicine Clinicians in China / 国际中医中药杂志

Objective:To analyze the prescriptions for the treatment for epigastric pain in A Hundred Years of Traditional Chinese Medicine Clinicians in China. Methods:The clinical medical records of well-known TCM doctors for the treatment of epigastric pain were included in the A Hundred Years of Traditional Chinese Medicine Clinicians in China. The database of clinical prescriptions and medicines was built, and the ancient and the Ancient and Modern Medical Records Cloud Platform (V 2.1) was applied and the evaluation of drug efficacy, sex, taste, and menstruation were conducted. Descriptive analysis, association rules, hierarchical clustering, and complex network analysis were applied in the rule of medication, drug pairs and core prescriptions. Results:Data was cleaned according to the inclusion and exclusion criteria, and 270 prescriptions were collected, involving 265 kinds of drugs, and the cumulative frequency of drug use was 3 249. The analysis showed that the drugs commonly used by famous traditional Chinese medicine doctors for the treatment of epigastric pain were mainly warm drugs, tast-balance drugs, and mildly cold drugs. The main flavors of medicines were pungent medicines, bitter medicines, sweet medicines, and effects were mainly drugs that regulate qi, clear heat, and invigorate the spleen. The frequency of drug meridians mainly belonged to spleen meridian, stomach meridian, lung meridian, liver meridian, heart meridian. The effects of the drug were mainly to dry dampness, reduce side effects, regulate qi, clear heat, invigorate spleen, and soften liver and analgesics. Association rule analysis found that the commonly used drug pairs were Pinellia- Tangerine Peel, Atractylodes Macrocephala- Poria, Poria- Tangerine Peel, Atractylodes- Tangerine Peel, Amomum tangerine Peel, Ochre- generation- Inula, Rhizoma Coptis- Evodia, and so on. Cluster analysis showed that Liujunzi Decoction, Zuojin Pill, and Shaoyao Gancao Decoction were mainly used. The drug complex network diagram showed that the core prescription of the drug is Xiangsha Liujunzi Decoction. Conclusion:The well-known TCM doctor focuses on strengthening the spleen and regulating qi, reconciling qi and blood, The treatment identified that the mutual warming and clearing, tonifying and deoppilation, and neutral are the main principles.

Neurological deficit and neurobehavioral evaluation of non-human primate ischemic stroke model / 国际脑血管病杂志

Because the clinical studies of neuroprotective drugs ended in failure, the Stroke Treatment Academy Industry Roundtable recommended the use of non-human primates for preclinical research on stroke. Non-human primates are the bridge between basic experiment and clinical research, and the experimental results are of great reference value. However, non-human primate stroke models have a variety of neurological deficits and behavioral evaluation methods, and the scoring methods also have their own emphases. It is easy to have differences in the evaluation, or there are deficiencies in the scale itself, resulting in inaccurate scoring, which directly affects the experimental results and the implementation of subsequent research. This article summarizes the neurological deficits and behavioral evaluation methods of non-human primate stroke model.

Feasibility of a Clinical-Radiomics Model to Predict the Outcomes of Acute Ischemic Stroke

Objective@#To develop a model incorporating radiomic features and clinical factors to accurately predict acute ischemic stroke (AIS) outcomes. @*Materials and Methods@#Data from 522 AIS patients (382 male [73.2%]; mean age ± standard deviation, 58.9 ± 11.5 years) were randomly divided into the training (n = 311) and validation cohorts (n = 211). According to the modified Rankin Scale (mRS) at 6 months after hospital discharge, prognosis was dichotomized into good (mRS ≤ 2) and poor (mRS > 2); 1310 radiomics features were extracted from diffusion-weighted imaging and apparent diffusion coefficient maps. The minimum redundancy maximum relevance algorithm and the least absolute shrinkage and selection operator logistic regression method were implemented to select the features and establish a radiomics model. Univariable and multivariable logistic regression analyses were performed to identify the clinical factors and construct a clinical model. Ultimately, a multivariable logistic regression analysis incorporating independent clinical factors and radiomics score was implemented to establish the final combined prediction model using a backward step-down selection procedure, and a clinical-radiomics nomogram was developed. The models were evaluated using calibration, receiver operating characteristic (ROC), and decision curve analyses. @*Results@#Age, sex, stroke history, diabetes, baseline mRS, baseline National Institutes of Health Stroke Scale score, and radiomics score were independent predictors of AIS outcomes. The area under the ROC curve of the clinical-radiomics model was 0.868 (95% confidence interval, 0.825–0.910) in the training cohort and 0.890 (0.844–0.936) in the validation cohort, which was significantly larger than that of the clinical or radiomics models. The clinical radiomics nomogram was well calibrated (p > 0.05). The decision curve analysis indicated its clinical usefulness. @*Conclusion@#The clinical-radiomics model outperformed individual clinical or radiomics models and achieved satisfactory performance in predicting AIS outcomes.

Relationship between body mass index and sexual development in Chinese children / 中华儿科杂志

Objective: To investigate the relationship between body mass index (BMI) and sexual development in Chinese children. Methods: A nationwide multicenter and population-based large cross-sectional study was conducted in 13 provinces, autonomous regions and municipalities of China from January 2017 to December 2018. Data on sex, age, height, weight were collected, BMI was calculated and sexual characteristics were analyzed. The subjects were divided into four groups based on age, including ages 3-<6 years, 6-<10 years, 10-<15 years and 15-<18 years. Multiple Logistic regression models were used for evaluating the associations of BMI with sexual development in children. Dichotomous Logistic regression was used to compare the differences in the distribution of early and non-early puberty among normal weight, overweight and obese groups. Curves were drawn to analyze the relationship between the percentage of early puberty and BMI distribution in girls and boys at different Tanner stages. Results: A total of 208 179 healthy children (96 471 girls and 111 708 boys) were enrolled in this study. The OR values of B2, B3 and B4+ in overweight girls were 1.72 (95%CI: 1.56-1.89), 3.19 (95%CI: 2.86-3.57), 7.14 (95%CI: 6.33-8.05) and in obese girls were 2.05 (95%CI: 1.88-2.24), 4.98 (95%CI: 4.49-5.53), 11.21 (95%CI: 9.98-12.59), respectively; while the OR values of G2, G3, G4+ in overweight boys were 1.27 (95%CI: 1.17-1.38), 1.52 (95%CI: 1.36-1.70), 1.88 (95%CI: 1.66-2.14) and in obese boys were 1.27 (95%CI: 1.17-1.37), 1.59 (95%CI: 1.43-1.78), and 1.93 (95%CI: 1.70-2.18) (compared with normal weight Tanner 1 group,all P<0.01). Analysis in different age groups found that OR values of obese girls at B2 stage and boys at G2 stage were 2.02 (95%CI: 1.06-3.86) and 2.32 (95%CI:1.05-5.12) in preschool children aged 3-<6 years, respectively (both P<0.05). And in the age group of 6-10 years, overweight girls had a 5.45-fold risk and obese girls had a 12.54-fold risk of B3 stage compared to girls with normal BMI. Compared with normal weight children, the risk of early puberty was 2.67 times higher in overweight girls, 3.63 times higher in obese girls, and 1.22 times higher in overweight boys, 1.35 times higher in obese boys (all P<0.01). Among the children at each Tanner stages, the percentage of early puberty increased with the increase of BMI, from 5.7% (80/1 397), 16.1% (48/299), 13.8% (27/195) to 25.7% (198/769), 65.1% (209/321), 65.4% (157/240) in girls aged 8-<9, 10-<11 and 11-<12 years, and 6.6% (34/513), 18.7% (51/273), 21.6% (57/264) to 13.3% (96/722), 46.4% (140/302), 47.5% (105/221) in boys aged 9-<10, 12-<13 and 13-<14 years, respectively. Conclusions: BMI is positively correlated with sexual development in both Chinese boys and girls, and the correlation is stronger in girls. Obesity is a risk factor for precocious puberty in preschool children aged 3-<6 years, and 6-<10 years of age is a high risk period for early development in obese girls.

Interaction between cyclosporine A and voriconazole in patients with allogeneic hematopoietic stem cell transplantation / 药学实践杂志

Objective To analyze the drug-drug interaction (DDI) between intravenous voriconazole (VRZ) and intravenous cyclosporine (CsA) in patients after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and provide an individualized and accurate clinical drug delivery. Methods In a self-contrast study, Allo-HSCT patients from January 2019 to December 2019 were enrolled according to the inclusion and exclusion criteria. These patients were treated with CsA and VRZ successively and the blood concentration of CsA and VRZ before and after 5-7 days of VRZ administration were determined with LC-MS/MS. The correlation between the concentration of VRZ and concentration/dose (C/D) ratio of CsA was analyzed with SPSS20.0. Results A total of 15 patients with ALLo-HSCT were enrolled. Wilcoxon sign rank sum test was used to compare the change of median C/D of CsA before and after VRZ administration, which had shown significant difference (P<0.001). Spearman correlation analysis was conducted on the increase of C/D ratio between VRZ and CsA, which had no significant correlation between them (ρ=−0.273, P=0.32). Conclusions There was obvious drug-drug interaction (DDI) between CsA and VRZ. VRZ increased CsA blood concentration significantly, but there was no significant correlation between VRZ blood concentration and the degree of concentration increase, which might be related to individual difference.

Mechanism of action and clinical significance of hypoxia-inducible factors in hepatocellular carcinoma / 临床肝胆病杂志

Due to the rapid proliferation and growth of tumor cells, hypoxic microenvironment exists in many solid tumors, and hypoxia inducible factors (HIF) are critical for sensing oxygen tension within tumors and subsequently mediating the activation of hypoxia responses. Hepatocellular carcinoma (HCC) is one of the most hypoxic tumors. This article summarizes the mechanism of action of HIF in promoting the development and progression of HCC by promoting glycolysis, angiogenesis, invasion and metastasis, immune escape, and cancer stem cell formation. At present, the development of targeted drugs for HIF inhibitors has broad prospects in the treatment of HCC, and the detection of HIF also has a potential value in prognostic evaluation HCC.

Expert Consensus on Rheumatic Immune Diseases Responding Specifically to Traditional Chinese Medicine / 中国实验方剂学杂志

In the clinical practice of rheumatic immune diseases in traditional Chinese medicine （TCM），it`s still unclear about the dominant diseases and breakthrough points. It`s urgent missions to formulate TCM diagnosis and treatment guidelines widely recognized and integrated by traditional Chinese medicine and Western medicine. In order to clarify the dominant diseases and breakthrough points in rheumatism，China association of Chinese medicine initiated a research group covering experts in the field of rheumatism of traditional Chinese medicine and Western medicine. Based on questionnaire survey and on-site discussion，experts had reached the following consensus. Evidence-based medicine research using modern medical methods and scientific methods should be carried out to provide objective clinical evidences. "Four mutuality" were put forward as the basis for the work of integrated traditional Chinese and Western medicine，that is the mutual communication using the exchangeable context，the mutual explanation using common theories，the mutual certification using common standards，and the mutual integration using common means. Key works should focus on solving refractory rheumatism in the future. In terms of dominant diseases and breakthrough points，this paper introduces 21 breakthrough points in 6 dominant diseases，including rheumatoid arthritis，ankylosing spondylitis，Sjogren's syndrome，hyperuricemia and gout，systemic lupus erythematosus and fibromyalgia syndrome. Advice on this discussion can provide valuable references for developing the treatment scheme of rheumatism with TCM and integrated Chinese and Western medicine and clinical practice and scientific research.

Effect of oral acitretin on the height and bone development of children: a retrospective analysis of 106 cases / 中华皮肤科杂志

Objective:To evaluate the effect of oral acitretin on the height and bone development of children.Methods:Clinical and imaging data were collected from 106 children receiving oral acitretin for at least 1 month in Department of Dermatology, Beijing Children′s Hospital from March 2007 to January 2021, and retrospectively analyzed. The main outcome measures were height and near-adult height. Multivariate logistic regression analysis was carried out to investigate relevant factors for short stature in children, and non-inferiority test was used to analyze the proximity of the actual height to target height of children who had reached near-adult height. The secondary outcome measures were bone age and epiphyseal closure. Wilcoxon signed-rank test was used to analyze differences in the value of bone age minus chronological age between the baseline and last follow-up, and the premature closure of epiphysis was also evaluated.Results:Among the 106 children, 62 were males and 44 were females; 84 were diagnosed with pustular psoriasis, 10 with psoriasis vulgaris, 11 with pityriasis rubra pilaris, and 1 with lupus miliaris disseminatus faciei. These children received oral acitretin at doses of <1 mg·kg -1·d -1 for 1 - 90 months. Among the 96 children aged under 18 years, 91 (94.8%) were of normal stature, and 5 (5.2%) were short in stature; among the 83 children receiving acitretin monotherapy, 81 (97.6%) were of normal stature, and 2 (2.4%) of short stature. Binary logistic regression analysis showed that the risk of short stature caused by acitretin combined with glucocorticoid therapy was 76.57 times higher than that of acitretin monotherapy ( OR = 77.57, 95% CI: 2.20 - 2 738.82, P = 0.017) , while the type of disease, gender, age at onset, age at initial treatment with acitretin, course of treatment, and average daily dose of acitretin did not significantly affect the stature of children ( P = 0.988, 0.214, 0.087, 0.078, 0.066, 0.350, respectively) . At the last follow-up visit, 13 children who had reached near-adult height were of normal stature, and the non-inferiority test showed that their near-adult height was not inferior to the target height (Satterthwaite = 0.23, P = 0.030) . Bone age was evaluated in 45 children at baseline and last follow-up visit, there was no significant difference in the value of bone age minus chronological age between the baseline and last follow-up ( Z = -0.85, P = 0.250) , and no patients experienced premature closure of epiphysis before and after the treatment. Conclusion:This study preliminarily revealed that oral acitretin at doses of <1 mg·kg -1·d -1 for less than 90 months might not significantly affect the height and bone development of children.

Expert consensus on diagnosis and treatment of severe fever with thrombocytopenia syndrome / 中华临床感染病杂志

Since 2010, the incidence of severe fever with thrombocytopenia syndrome (SFTS) has been increased. Owing the progress in diagnosis and treatment, the overall mortality of SFTS in China has decreased, while the mortality in critical SFTS patients is still high. In order to provide guidance and working procedures for clinicians to diagnose and treat critical SFTS, the National Medical Center for Major Public Health Events invited experts to discuss and formulate this consensus based on their experience and up-to-date knowledge on SFTS.

Rauwolfia vomitoria extract suppresses benign prostatic hyperplasia by reducing expression of androgen receptor and 5α-reductase in a rat model / 中西医结合学报

OBJECTIVE@#Herbal medicine is an important therapeutic option for benign prostatic hyperplasia (BPH), a common disease in older men that can seriously affect their quality of life. Currently, it is crucial to develop agents with strong efficacy and few side effects. Herein we investigated the effects of the extract of Rauwolfia vomitoria, a shrub grown in West Africa, on BPH.@*METHODS@#Rats with testosterone-induced BPH were treated with R. vomitoria. Prostates were histologically analyzed by Hematoxylin and eosin staining. Proliferation index and the expression levels of androgen receptor and its associated proteins were quantified through immunohistochemistry and immunoblotting. Androgen receptor target genes were examined by quantitative real-time polymerase chain reaction. The sperm count and body weight of rats were also measured.@*RESULTS@#The oral administration of R. vomitoria extract significantly reduced the prostate weight and prostate weight index in BPH rats, supported by the decreased thickness of the prostate epithelial layer and increased lumen size. Similar effects were observed in the BPH rats treated with the reference drug, finasteride. R. vomitoria extract significantly reduced the testosterone-induced proliferation markers, including proliferating cell nuclear antigen and cyclin D1, in the prostate glands of BPH rats; it also reduced levels of androgen receptor, its associated protein steroid 5α-reductase 1 and its downstream target genes (FK506-binding protein 5 and matrix metalloproteinase 2). Notably, compared with the finasteride group, R. vomitoria extract did not significantly reduce sperm count.@*CONCLUSION@#R. vomitoria suppresses testosterone-induced BPH development. Due to its milder side effects, R. vomitoria could be a promising therapeutic agent for BPH.

Advances of the Regulation of microRNAs in Follicular Development / 中国医学科学院学报

In recent years,microRNAs(miRNAs)have been detected at different stages of follicular development and in different cells of follicles.Extracellular vesicle(EV)-derived miRNAs have also been detected in the follicular fluid of mature follicles.miRNAs participate in the regulation of normal follicular development,and the regulation disorder may lead to the occurrence of some ovarian diseases.In order to further systematically elucidate the regulatory mechanism of miRNAs on follicular development and find suitable EV-derived miRNAs that can predict oocyte development,we reviewed the functions of miRNAs in follicular development from the perspectives of granulosa cell development,oocyte development,and hormone synthesis.

Clinical effects of pretarsal orbicularis-tarsus fixation technique in double eyelidplasty / 中华医学美学美容杂志

Objective:To evaluate the aesthetic outcome of the pretarsal orbicularis-tarsus fixation technique in incisional double eyelid blepharoplasty.Methods:Postoperative results were evaluated from 798 patients who underwent the orbicularis-tarsus fixation blepharoplasty from January 2015 to December 2018. Based on an incisional maneuver, soft tissue was carefully removed to expose the superior edge of tarsus, then the pretarsal orbicularis oculi muscle was anchored on the tarsus. For skin closure, both skin margins, a small bite of subcutaneous tissue and the pretarsal fascia were interruptedly sutured to enhance cicatricial adhesion.Results:All patients successfully underwent double eyelidplasty using this modified technique. The follow-up period ranged from two to forty-six months, with a mean period of twenty months. Ninety-six percent of the patients were satisfied with postoperative outcomes. Twenty-two cases of palpebral fold asymmetry and ten cases of unsatisfactory fold formation near the inner canthus were encountered. However, all the defects had been well improved by minor revisions. No supratarsal crease drooping or disappearing, suture spitting out, scar hypertrophy or crease depression were observed postoperatively.Conclusions:The orbicularis-tarsus fixation method is a reliable technique for double eyelid plasty. It enables high feasibility and long-lasting result, with lower risk of postoperative complications.

Hemiarthroplasty versus reverse shoulder arthroplasty for complex proximal humeral fractures in the aged: a meta-analysis / 中华创伤骨科杂志

Objective:To compare the advantages and disadvantages of hemiarthroplasty (HA) and reverse shoulder arthroplasty (RSA) in the treatment of complex proximal humeral fractures in the elderly patients.Methods:Pubmed, the Cochrane Library, EMBASE, and Chinese databases like CNKI, Wanfang Data and Weipu were searched for studies comparing HA and RSA in the treatment of complex proximal humeral fractures in the elderly (>60 years) from 2000 to 2020. After the studies were included and excluded by a set of inclusion and exclusion criteria and evaluated for their quality, their radiological and functional data were extracted and analyzed using software Stata 14.0.Results:Included in this meta-analysis were 11 studies with a total of 771 patients. RSA was superior to HA in outcomes like forward flexion ( SMD=-1.043, 95% CI: -1.551 to -0.534, P=0.000), abduction ( SMD=-0.811, 95% CI: -1.470 to -0.153, P=0.016), Constant score ( SMD=-0.699, 95% CI: -1.118 to -0.280, P=0.001), American Shoulder Elbow Surgeons’ Form (ASES) ( SMD=-0.931, 95% CI: -1.256 to -0.606, P<0.001), and Simple Shoulder Test (SST) ( SMD=-0.598, 95% CI: -1.181 to -0.016, P=0.044). HA led to a higher complication rate ( RR=2.14, 95% CI: 1.11 to 4.14, P=0.024), a higher joint stiffness rate ( RR=6.467,95% CI: 1.923 to 21.755, P=0.003) and a higher revision rate ( RR=5.796, 95% CI: 1.927 to 17.434, P=0.002). There were no statistically significant differences between RSA and HA in tuber healing rate ( RR=0.850, 95% CI: 0.669 to 1.080, P=0.182), internal rotation ( SMD=0.536, 95% CI: -0.394 to 1.466, P=0.259), external rotation ( SMD=-0.366, 95% CI: -0.916 to 0.184, P=0.192), implant infection ( RR=1.550, 95% CI: 0.330 to 7.286, P=0.579) or Disabilities of the Arm, Shoulder and Hand (DASH) score ( SMD=0.286, 95% CI: -0.278 to 0.850, P=0.032). Although there was no significant difference between RSA and HA in visual analogue scale (VAS) score ( SMD=0.440, 95% CI: -0.113 to 0.993, P=0.119), RSA scored better ( SMD=-1.101, 95% CI: -2.090 to -0.112, P=0.029). Conclusion:For elderly patients (>60 years) with complex proximal humeral fracture, RSA may be a more effective surgical intervention which can lead to better early and mid-term clinical outcomes than HA.

Diagnostic value of different imagines for choledocholithiasis abdominal pain / 中国医师杂志

Objective:To evaluate direct bilirubin /total bilirubin(D/T), B-mode ultrasound(BUS), multislice spiral computed tomography (MSCT), magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS) in the diagnosis of choledocholithiasis abdominal pain (CAP).Methods:We retrospectively analyzed the materials of patients who were diagnosed with choledocholithiasis abdominal pain by above imagines in the emergency department of Beijing Friendship Hospital during March 2016 to December 2018. The stones were taken out by endoscopic retrograde cholangiopancreatography or surgical operation as the golden standard.Results:Among 256 patients, 195 cases, 138 cases, 107 cases and 26 cases were diagnosed by EUS, MRCP, CT and BUS, respectively. The sensitivity were 0.86, 0.62, 0.45, 0.13, respectively. The specificity were 0.86, 0.81, 0.75, 0.87. The positive predictive value were 0.97, 0.96, 0.91, 0.83.The negative predictive value were 0.55, 0.19, 0.21, 0.16. The accuracy rate were 0.88, 0.64, 0.48, 0.30, respectively. The sensitivity of D/T and D/T combined with EUS in the diagnosis of CAP were 0.57 and 0.67, and the accuracy were 0.16 and 0.56, respectively.Conclusions:EUS has a high diagnostic value for CAP. MRCP is superior to CT in the value of diagnosis of CAP. BUS in imaging diagnosis of CAP value is relatively low, but D/T combined with BUS can improve the sensitivity and accuracy of diagnosis for CAP.

Study on the relationship of interleukin-37 and osteoprotegerin with coronary artery disease and its risk degree / 中国医师进修杂志

Objective:To investigate the relationship of interleukin (IL)-37, osteoprotegerin with coronary artery disease and its stenosisdegree.Methods:The prospective research method was used. From April 2018 to June 2019, two hundred and eleven suspected or diagnosed coronary artery disease patients who had chest pain or discomfort in Dalian Friendship Hospital were selected. The patients underwent selective percutaneous coronary angiography and completed coronary stenosis score (Gensini score). According to the degree of coronary stenosis, 211 patients were divided into the control group(coronary stenosis<50%, 45 cases), single-vessel stenosis group (single-vessel stenosis ≥ 50%, 52 cases), double-vesselstenosis group (double-vesselstenosis ≥ 50%, 58 cases), and triple-vessel stenosis group (triple-vessel stenosis ≥ 50%, 56 cases). The levels of fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein a, uric acid, creatinine were measured by the automatic biochemical analyzer. The serum levels of IL-37 and osteoprotegerin were detected by enzyme-linked immunosorbent assay.Results:There were no statistical differences in FBG, uric acid, creatinine, TC, TG, LDL-C, HDL-C, ApoA1 and ApoB among 4 groups ( P>0.05). In the control group, single-vessel stenosis group, double-vessel stenosis group and triple-vessel stenosis group, lipoprotein a was (0.266 ± 0.060), (0.283 ± 0.070), (0.289 ± 0.066) and (0.307 ± 0.084) mg/L respectively; coronary stenosis score was (8.27 ± 7.08), (437.45 ± 98.47), (493.72 ± 125.19) and (522.61 ± 149.34) scores respectively; IL-37 was (342.27 ± 122.36), (437.45 ± 98.47), (493.72 ± 125.19) and (522.61 ± 149.34) ng/L respectively; osteoprotegerin was (378.29 ± 111.95), (458.39 ± 115.37), (502.50 ± 116.88) and (533.39 ± 139.83) ng/L respectively; and there were statistical differences among 4 groups ( P<0.05 or <0.01). IL-37, osteoprotegerin and lipoproteina were positively correlated with coronary stenosis score ( r = 0.43, 0.42 and 0.23, P<0.05), the osteoprotegerin was positively correlated with IL-37( r = 0.73, P<0.05). The multivariate linear regression analysis result showed that the IL-37 and osteoprotegerin were independent protective factors of coronary stenosis degree( β = 0.07 and 0.07, t = 2.72 and 2.57, P<0.01 or <0.05),and lipoproteina was independent risk factor of coronary stenosis degree ( β = 0.97, t = 2.89, P<0.01). Conclusions:IL-37 and osteoprotegerin are positively correlated with the degree of coronary stenosis. They are anti-inflammatory and protective factors of coronary heart disease.

Production of Functional Hepatobiliary Organoids from Human Pluripotent Stem Cells

The research on human hepatobiliary development and disorders has been constrained by minimal access to human fetal tissue, and low accuracy of animal models. To overcome this problem, we have established a system for the differentiation of human pluripotent stem cells (hPSCs) into functional hepatobiliary organoids (HBOs). We have previously reported that our 45-d approach closely mimics key stages of hepatobiliary development, starting with the differentiation of hiPSC into endoderm and a small part of mesoderm, and subsequently into hepatoblast-like cells, followed by the parallel generation of hepatocyte-like cells and cholangiocyte-like cells, formation of immature HBO expressing early hepatic and biliary markers, and mature HBO displaying hepatobiliary functionality. In this study, we present an updated version of our previous protocol, which only needs 35 days to achieve maturation in vitro. Furthermore, a hepatobiliary culture medium is developed to functionally maintain the HBOs for more than 1.5 months. The capacity of this approach for producing large amounts of functional HBOs and enabling long-term culture in vitro holds promise for applications on developmental research, disease modeling, as well as screening of therapeutic agents.

Caspase recruitment domain-containing protein 9 gene deficiency associated invasive candidiasis: a case report and literature review / 中华神经科杂志

Objective:To summarize the clinical characteristics, diagnosis and treatment of caspase recruitment domain-containing protein 9 (CARD9) gene deficiency associated invasive candidiasis, and report a novel mutation in CARD9 gene.Methods:The clinical characteristics, laboratory tests, treatment and the outcome of follow-up in a boy with invasive candidiasis were described. The boy′s main clinical manifestations were central nervous system infection and retroperitoneal mass. Whole-exome sequencing was performed and Sanger sequencing was verified to identify the CARD9 gene mutations in the patient and his parents. A literature search for “CARD9”and “invasive candidiasis”was conducted in PubMed, Wanfang and CNKI databases from their establishment to May 2020.Results:A 10-year-old boy suffered onset symptom of chronic diarrhea, which lasted for two months. The symptom was followed by progressive neurological symptoms such as headache, vomiting, seizures and disorder of consciousness. His unusual medical history was absent. Candida albicans were cultured several times in cerebrospinal fluid and blood, and yeast-like fungi were found in the stool high power field of vision. Cerebral magnetic resonance imaging indicated obstructive hydrocephalus and abdominal CT scan showed retroperitoneal mass and thickening of the intestinal wall. The whole-exome sequencing analyses of blood samples from the boy and his parents were performed. The results showed that there was a homozygous mutation of c.952-12_956delinsAG in the CARD9 gene, which was an unreported pathogenic mutation. This was confirmed by Sanger sequencing. There was no significant relief from intravenous combined antifungal medications. After lateral ventricular drainage surgery and injection of amphotericin B into the lateral ventricle, improvement of clinical symptoms and cerebral spinal fluid abnormalities was observed after nine weeks, and the retroperitoneal mass shrank. At follow-up after four-month oral combined antifungal medications, the child had no complaint except fatigue. However, cerebral spinal fluid analysis showed increased protein level and decreased glucose. Persistent hydrocephalus and periventricular white matter abnormal signals were revealed on the brain magnetic resonance imaging and the smaller retroperitoneal mass than before on the abdominal CT scan. In addition to this case, totally 21 cases with CARD9 gene deficiency associated invasive candidiasis have been reported worldwide, most of which featured central nervous system infections.Conclusions:CARD9 gene deficiency is an autosomal recessive primary immunodeficiency that confers human susceptibility to fungal disease. The associated invasive candidiasis often affects the central nervous system and makes the patient severely ill. Adequate systemic antifungal therapies should be given, and patients with hydrocephalus need surgical treatment. A novel mutation is reported that expands the variant diversity of CARD9 gene. For patients with unexplained invasive candidiasis, including those without a history of previous recurrent infection, genetic testing is recommended for primary immunodeficiency including CARD9 gene deficiency.

The application and research progress of nuclear medicine in digestive diseases / 中国医师杂志

Nuclear medicine can not only display the anatomical structure of organs or lesions, but also provide the information of blood flow, function, metabolism and receptor density of organs and lesions in digestive system . It is not only complementary to computer tomography (CT) and magnetic resonance imaging (MRI) in organic diseases of digestive system, but aslo has unique clinical value in functional diseases of digestive system.

Early identification of the severity of acute pancreatitis by platelet and coagulation markers / 中国医师杂志

Objective:To investigate whether platelet and coagulation-related indicators can be used as early indicators of severity of acute pancreatitis.Methods:A total of 142 patients with acute pancreatitis admitted to Beijing Friendship Hospital from 2017 to 2018 were included in this study. According to the Ranson score, they were divided into mild group and severe group. Severe pancreatitis was used as the outcome index. Univariate logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed on single indicators with statistically significant differences between mild and severe patients to determine the discriminative value of disease severity.Results:According to the Ranson score, 142 patients were divided into severe and mild groups, 43 patients with severe disease, and 99 patients with mild disease. There was a statistically significant difference in platelet, fibrinogen (FIB), and D-Dimer between the two groups on the first day of admission ( P<0.05). The area under ROC curve and 95% CI of platelets (PLT) , FIB and D-Dimer were 0.61 (0.52, 0.71), 0.70 (0.59, 0.80) and 0.72 (0.62, 0.82), respectively. Multivariate logistic regression models of PLT, FIB and D-Dimer were fitted, and ROC curve was analyzed. The area of ROC curve of PLT combined with D-Dimer was 0.74 (0.65, 0.83), and the area of ROC curve of FIB combined with D-Dimer was 0.75 (0.66, 0.85). Conclusions:Platelet, FIB and D-Dimer can be used as independent risk factors to judge the severity of pancreatitis. The early predicative value of FIB combined with D-Dimer on the severity of the disease is higher than that of the PLT combined with D-Dimer.