Acupuncture and moxibustion has certain advantages in the treatment of post-stroke spastic paralysis，but the treatment methods and diagnosis and treatment ideas are complicated. This paper sortes out the representative contemporary acupuncture and moxibustion schools in the treatment of post-stroke spastic paralysis, analyzes their academic origins，summarizes and compares the theory，acupoint selection and technique characteristics of different schools in the diagnosis and treatment of this disease，so as to provide some references for guiding optimal treatment schemes selection in clinic.
Humans ; Moxibustion ; Muscle Spasticity/therapy* ; Acupuncture Therapy ; Schools ; Acupuncture Points ; Stroke/therapy*

Betulinic acid (BA) exerts protective effects on organs in septic animals. However, whether BA can improve cardiac function in sepsis and the underlying mechanism remain unclear. Here, male Sprague-Dawley rats were pretreated with BA (25 mg/ kg/ d, i. g.) for 5 days and then intraperitoneally injected with lipopolysaccharide (LPS, 10 mg/ kg). The rats were anesthetized to determine transthoracic echocardiography using a high-resolution imaging system for small animals after they were treated with LPS for 6 h. Histopathologic alterations were examined by HE staining. Myocardial injury markers (cTnI and CK-MB) and inflammatory factors (TNF-α, IL-1β and IL-6) in the serum were measured by the enzyme-linked immunosorbent assay. Autophagy-related proteins (p62 and LC3 Ⅱ) and AKT-modulated autophagy pathways in the myocardium were determined by Western blotting. Pretreatment with BA markedly improved left ventricular ejection fraction (EF) and fraction shortening (FS) (P<0. 05), improved myocardial histomorphology, and significantly inhibited cTnI, CK-MB, TNF-α, IL-1β and IL-6 (P<0. 05) in the septic rat serum. BA markedly decreased p62 (P<0. 01), increased LC3 Ⅱ (P< 0. 001), and significantly down-regulated p-AKT (Thr308), p-AMPKα (Ser485/ 491), p-mTOR (Ser2448) and p-S6K (Thr389) (P<0. 05), while markedly up-regulated p-AMPKα (Thr172) and pULK1 (Ser317) (P<0. 01) in septic rat hearts. The findings indicate that BA can attenuate sepsis-induced myocardial dysfunctions associated with down-regulating autophagy inhibiting pathways mediated by AKT/ mTOR and AKT/ AMPK pathways.

Non-syndromic oral cleft (NSOC), a common birth defect, remains to be a critical public health problem in China. In the context of adjustment of childbearing policy for two times in China and the increase of pregnancy at older childbearing age, NSOC risk prediction will provide evidence for high-risk population identification and prenatal counseling. Genome-wide association study and second generation sequencing have identified multiple loci associated with NSOC, facilitating the development of genetic risk prediction of NSOC. Despite the marked progress, risk prediction models of NSOC still faces multiple challenges. This paper summarizes the recent progress in research of NSOC risk prediction models based on the results of extensive literature retrieval to provide some insights for the model development regarding research design, variable selection, model-build strategy and evaluation methods.
Humans ; Cleft Palate/genetics* ; Cleft Lip/genetics* ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Risk Factors ; Polymorphism, Single Nucleotide

ObjectiveTo observe the effect of Chonglian oral liquid on inflammatory and immune markers as well as the clinical outcomes of patients with mild-to-moderate corona virus disease 2019（COVID-19） and comprehensively evaluate its efficacy and safety. MethodA clinical randomized controlled trial （RCT） was conducted， involving 120 confirmed cases of mild-to-moderate COVID-19. The patients were randomly divided into two groups， with 55 cases in the observation group and 56 cases in the control group. According to the updated diagnosis and treatment protocol， the control group received standard western medical treatment， while the observation group received Chonglian oral liquid in addition to standard western medical treatment. Both groups were treated continuously for 10 days. The traditional Chinese medicine （TCM） syndrome scores， syndrome efficacy， fever abatement time， nucleic acid negative conversion time， inflammatory and immune markers， improvement in imaging findings， clinical outcomes， and occurrence of adverse events were compared between the two groups. ResultBoth groups showed a significant decrease in TCM syndrome scores after treatment （P<0.01）. Compared with the control group after treatment， the observation group exhibited a more significant improvement in cough， dry throat， sore throat， fatigue， and muscle pain （P<0.05）. The total effective rate in the observation group was 100% （55/55）， significantly higher than 98.21% （55/56） in the control group （Z=3.707， P<0.01）. The observation group also showed a significantly shorter duration of fever abatement and nucleic acid negative conversion compared with the control group after treatment （P<0.05）. Both groups had a significant increase in lymphocyte count （LYM）， lymphocyte percentage （LYM%）， mature T lymphocytes （CD3⁺）， and helper/inducer T lymphocytes （CD4⁺） after treatment （P<0.01）. Compared with the control group after treatment， the observation group showed greater improvement in these markers （P<0.05）. In terms of inflammatory markers， both groups had a significant decrease compared with those before treatment （P<0.01）. The observation group exhibited lower levels of high-sensitivity C-reactive protein （hs-CRP）， interleukin-6 （IL-6）， and procalcitonin （PCT） than the control group after treatment （P<0.05）. There was no statistically significant difference in imaging efficacy evaluation and clinical outcomes between the two groups. No adverse events were reported in either group during the treatment period. ConclusionChonglian oral liquid combined with standard western medical treatment significantly improves clinical symptoms， shortens fever abatement and nucleic acid negative conversion time， regulates immune function， and inhibits inflammatory responses in patients with mild-to-moderate COVID-19， leading to improved clinical efficacy.

OBJECTIVE: To explore the association between de novo mutations (DNM) and non-syndromic cleft lip with or without palate (NSCL/P) using case-parent trio design. METHODS: Whole-exome sequencing was conducted for twenty-two NSCL/P trios and Genome Analysis ToolKit (GATK) was used to identify DNM by comparing the alleles of the cases and their parents. Information of predictable functions was annotated to the locus with SnpEff. Enrichment analysis for DNM was conducted to test the difference between the actual number and the expected number of DNM, and to explore whether there were genes with more DNM than expected. NSCL/P-related genes indicated by previous studies with solid evidence were selected by literature reviewing. Protein-protein interactions analysis was conducted among the genes with protein-altering DNM and NSCL/P-related genes. R package "denovolyzeR" was used for the enrichment analysis (Bonferroni correction: P=0.05/n, n is the number of genes in the whole genome range). Protein-protein interactions among genes with DNM and genes with solid evidence on the risk factors of NSCL/P were predicted depending on the information provided by STRING database. RESULTS: A total of 339 908 SNPs were qualified for the subsequent analysis after quality control. The number of high confident DNM identified by GATK was 345. Among those DNM, forty-four DNM were missense mutations, one DNM was nonsense mutation, two DNM were splicing site mutations, twenty DNM were synonymous mutations and others were located in intron or intergenic regions. The results of enrichment analysis showed that the number of protein-altering DNM on the exome regions was larger than expected (P < 0.05), and five genes (KRTCAP2, HMCN2, ANKRD36C, ADGRL2 and DIPK2A) had more DNM than expected (P < 0.05/(2×19 618)). Protein-protein interaction analysis was conducted among forty-six genes with protein-altering DNM and thirteen genes associated with NSCL/P selected by literature reviewing. Six pairs of interactions occurred between the genes with DNM and known NSCL/P-related genes. The score measuring the confidence level of the predicted interaction between RGPD4 and SUMO1 was 0.868, which was higher than the scores for other pairs of genes. CONCLUSION Our study provided novel insights into the development of NSCL/P and demonstrated that functional analyses of genes carrying DNM were warranted to understand the genetic architecture of complex diseases.
Asians ; Case-Control Studies ; Cleft Lip/genetics* ; Cleft Palate/genetics* ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Genotype ; Humans ; Mutation ; Parents ; Polymorphism, Single Nucleotide ; Whole Exome Sequencing

Next-generation sequencing has revolutionized family-based association tests for rare variants. As the lower power of genome wide association study for detecting casual rare variants, methods aggregating effects of multiple variants have been proposed, such as burden tests and variance component tests. This paper summarizes the methods of rare variants association test that can be applied for family data, introduces their principles, characteristics and applicable conditions and discusses the shortcomings and the improvement of the present methods.
Computer Simulation ; Family Relations ; Genetic Association Studies ; Genetic Variation ; Genome-Wide Association Study/methods* ; Humans

OBJECTIVE: To estimate the univariate heritability of resting heart rate and common chronic disease such as hypertension, diabetes, and dyslipidemia based on extended pedigrees in Fujian Tulou area and to explore bivariate heritability to test for the genetic correlation between resting heart rate and other relative phenotypes. METHODS: The study was conducted in Tulou area of Nanjing County, Fujian Province from August 2015 to December 2017. The participants were residents with Zhang surname and their relatives from Taxia Village, Qujiang Village, and Nanou Village or residents with Chen surname and their relatives from Caoban Village, Tumei Village, and Beiling Village. The baseline survey recruited 1 563 family members from 452 extended pedigrees. The pedigree reconstruction was based on the family information registration and the genealogy booklet. Univariate and bivariate heritability was estimated using variance component models for continuous variables, and susceptibility-threshold model for binary variables. RESULTS: The pedigree reconstruction identified 1 seven-generation pedigree, 2 five-generation pedigrees, 23 four-generation pedigrees, 186 three-generation pedigrees, and 240 two-generation pedigrees. The mean age of the participants was 57.2 years and the males accounted for 39.4%. The prevalence of hypertension, diabetes, dyslipidemia in this population was 49.2%, 10.0%, and 45.2%, respectively. The univariate heritability estimation of resting heart rate, hypertension, and dyslipidemia was 0.263 (95%CI: 0.120－0.407), 0.404 (95%CI: 0.135－0.673), and 0.799 (95%CI: 0.590－1), respectively. The heritability of systolic blood pressure, diastolic blood pressure, fasting glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol was 0.379, 0.306, 0.393, 0.452, 0.568, 0.852, and 0.387, respectively. In bivariate analysis, there were phenotypic correlations between resting heart rate with hypertension, diabetes, diastolic blood pressure, fasting glucose, and triglyceride. After taking resting heart rate into account, there were strong genetic correlations between resting heart rate with fasting glucose (genetic correlation 0.485, 95%CI: 0.120－1, P<0.05) and diabetes (genetic correlation 0.795, 95%CI: 0.181－0.788, P<0.05). CONCLUSION Resting heart rate was a heritable trait and correlated with several common chronic diseases and related traits. There was strong genetic correlation between resting heart rate with fasting glucose and diabetes, suggesting that they may share common genetic risk factors.
Blood Pressure ; Chronic Disease ; Female ; Heart Rate ; Humans ; Hypertension ; Male ; Middle Aged ; Pedigree

Objective To analyze the components of attentional bias on anger and disgust emotional faces in college students with social anxiety disorder.Methods DSM-V was used for clinical diagnosis after the initial screening with Interaction Anxiousness Scale.The subjects meet the inclusion criteria were divided into social anxiety disorder group (SAD group) and healthy control group (HC group).Koster's improved dot-probe paradigm was used in a 2 (group:SAD group,HC group) ×2 (emotion categories:anger,disgust)mixed-design experiment,and the different characteristics of attentional bias between the two groups on different emotional faces were compared.Results In SAD group,under the condition of angry faces,the response times to the probe targets with the same or different positions from the negative faces were (369.7±53.0)ms and (447.2±54.3) ms,while the response times were (429.6±70.2) ms and (444.2±55.8) ms under the condition of disgust faces,and the SAD group showed attentional bias towards both anger and disgust faces (t =24.15 and 2.45,P＜0.05).Under the condition of anger faces,the response time of HC group to the consistent and inconsistent position of probe target were (466.9±40.0) ms and (483.8±43.8) ms,and the HC group had an attentional bias towards anger faces(t=6.58,P＜0.05).The response time under disgust faces was (493.8±43.6)ms and (498.0±46.7)ms in HC group,and did not show an attentional bias towards disgust(t=1.65,P=0.108).The scores of attentional orientation to anger faces in SAD group were significantly higher than those in the HC group(F=19.26,P＜0.001),but there was no significant difference between the two groups towards disgust faces (F=0.02,P=0.897).Compared with disgust faces,the attentional orientation to anger faces was faster in both HC and SAD groups (F=101.66 and 8.00,P＜0.05).Compared with the HC group,the SAD group had an impaired attentional disengagement from anger faces(F=8.66,P=0.004).Conclusion The students with social anxiety disorder have attentional bias towards both anger and disgust facial expressions,which manifested as facilitated attentional orientation and impaired attentional disengagement to anger faces.

Objective: To explore the correlation of ultrasound-guided fine-needle aspiration(US-FNA) combined with BRAF V600E mutation detection and ultrasound features and central cervical lymph nodes metastasis of classic papillary thyroid cancer(PTC) for providing a reliable molecular basis for clinical preoperative evaluation of patients. Methods: Ninty-three cases of patients collected from October 2017 to November 2018 in Gansu Province Hospital were enrolled, who underwent general ultrasonic examination TI-RADS ≥4a, the US-FNA highly suspicious of PTC, thyroid surgery including total thyroidectomy and central cervical lymph node dissection, with the postoperative pathologic results of classical PTC and whether the central cervical lymph node metastasis happened in the patients. Part of the specimen applied HE staining for cytological diagnosis, the other part of specimen was used real-time for detection of BRAF V600E gene mutation by fluorescent quantitative polymerase chain reaction (PCR) method. Results: Univariate analysis showed that the occurrence of cervical lymph node metastasis for classic PTC were significantly correlated with gender(χ²=10.303, P=0.002), BRAF V600E mutation(χ²=31.204, P=0.000) and extrathyroidal invasion(χ²=12.848, P=0.000). Multi-logistic regression analysis showed that BRAF V600E mutation(OR=13.324, 95%CI=4.058-43.744, P=0.000) and extrathyroidal invasion(OR=5.738, 95%CI=1.766-18.643, P=0.004) were the risk predictors of cervical lymph node metastasis of classic PTC. Gender(OR=0.385, 95%CI=0.112-1.324, P=0.130) was not the risk predictor. Conclusions US-FNA combined with BRAF V600E mutation and extrathyroidal invasion are the risk factors in predicting central cervical lymph node metastasis in classic PTC. Patients with these two risk factors should be elected to undergo prophylactic central cervical lymph node dissection.

Objective: To describe the status of non-steroidal anti-inflammatory drugs (NSAIDs) use in areas with a high incidence of upper gastrointestinal cancer in China. Methods: This study was based on the National Key Research and Development Program of "National Precision Medicine Cohort of Esophageal Cancer" and "Study on Identification and Prevention of High-risk Populations of Gastrointestinal Malignancies (Esophageal cancer, Gastric cancer and Colorectal cancer)" . From January 2017 to August 2018, 212 villages or communities with a high incidence of esophageal cancer or gastric cancer were selected from 12 regions in 6 provinces. A total of 35 910 residents aged between 40 and 69 years old who met the inclusion criteria and signed the informed consent were investigated and enrolled in this study. The use of NSAIDs, demographic characteristics, health-related habits, height, weight, and blood pressure were collected by the questionnaire and physical examination. The status of main NSAIDs (aspirin, acetaminophen and ibuprofen) use with the difference varying in genders, age groups and regions were analyzed by using χ² test and Cochran-Armitage trend analysis method. Results: Of 35 910 subjects, the mean age was (54.6±7.1) years old and males accounted for 43.42% (15 591). The overall prevalence of NSAIDs intake was 4.56% (1 638), but it significantly varied in different provinces (P<0.001). The overall prevalence of NSAIDs intake was 4.87% (1 750) in females, which was significantly higher than that in males 4.24% (1 524) (P<0.001). The prevalence of NSAIDs intake increased with age (P for trend <0.001). As the frequency of NSAIDs intake increased, the incidence of gastrointestinal symptoms, gastrointestinal ulcers and black stools increased (P for trend <0.05 for all). Conclusion The use of NSAIDs is prevalent in some areas with a high incidence of upper gastrointestinal cancer in China. The increased use of NSAIDs may lead to more adverse effects related to the gastrointestinal tract.