Based on WANG Xugao's “thirty methods of treating the liver”， it is believed that the occurrence and development of childhood tic disorders follow the dynamic progression from liver qi disease to liver fire disease and then liver wind disease. The basic pathogenesis of three stages are characterized by binding constraint of liver qi， liver fire hyperactivity， and internal stirring of liver wind. Moreover， liver-blood deficiency and stagnation， and malnutrition of liver yin as the main point in terms of the imbalance of liver qi， blood， yin， and yang should be considered， as well as the imbalance relationship of the five zang organs such as the involvement of other organs and the gradually reach of the other organs. Guided by the principles of “thirty methods of treating the liver”， the treatment of tic disorders in liver qi stage should focus on soothing the liver and rectifying qi， soothing the liver and unblocking the collaterals， using Xiaochaihu Decoction （小柴胡汤） and Sini Powder （四逆散）. The treatment of tic disorders in liver fire stage involves clearing， draining and resolving liver heat， using Longdan Xiegan Decoction （龙胆泻肝汤）， Xieqing Pill （泻青丸）， Danggui Longhui Pill （当归龙荟丸）， and Huagan Decoction （化肝煎）. The treatment of tic disorders in liver wind stage involves extinguishing wind and subduing yang， using Lingjiao Gouteng Decoction （羚角钩藤汤） and Liuwei Dihuang Pill （六味地黄丸）. Throughout the treatment process， attention should be paid to harmonizing the liver's qi， blood， yin， and yang， as well as addressing the pathology of other organs.

ObjectivePhosphatidylinositol 3 kinases (PI3Ks) play an important role in cell directional movement by regulating F-actin. However, the structure and function of PI3Ks are complex. The role of PI3Ks in cell electrotaxis is not fully understood. Therefore, in this study, the model organism Dictyostelium discoideum cells were used as experimental materials to explore the role of PI3K1 and PI3K2 in electrotaxis. MethodsFirstly, PI3K1 coding gene pikA knockout mutant and PI3K2 coding gene pikB knockout mutant were constructed by CRISPR/Cas9 system. Secondly, two mutants were placed in a DC electric field with a strength of 12 V/cm and the electrotaxis were analyzed. ResultsData analysis showed that the direction index of wild-type cells in DC electric field was (0.86±0.03), while the direction index of pikA^- and pikB^- mutants in DC electric field was (0.95±0.02) and (0.94±0.03), respectively. In addition, the average trajectory speed of wild-type cells in the electric field was (3.34±0.08) μm/min, while the average trajectory speed of pikA^- and pikB^- mutants were (4.85±0.20) μm/min and (5.48±0.15) μm/min, respectively. The t test showed that there were significant differences in the directedness index and speed between the mutant and wild type. Western blot results showed that both phosphorylated Akt and phosphorylated ERK were significantly increased in pikA^- and pikB^- mutants. ConclusionPI3K1 and PI3K2 may inhibit the electrotaxis of Dictyostelium discoideum cells by increasing the activity of Akt and ERK.

This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 μm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 μL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 μmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.
Humans ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Asteraceae/chemistry* ; Lung Neoplasms/drug therapy*

OBJECTIVE: To explore the underlying mechanism of inhibition by Jinkui Shenqi Pills (JKSQP) on glucocorticoid-enhanced axial length elongation in experimental lens-induced myopia (LIM) guinea pigs. METHODS: Sixty 2-week old male guinea pigs were randomly divided into 4 groups with 15 guinea pigs in each group, according to the random numbers generated by SPSS software: control, LIM, saline and JKSQP groups. The control group includes animals with no treatment, while the guinea pigs in the other 3 groups received lens-induced myopization on the right eyes throughout the experiment (for 8 weeks). The saline and JKSQP groups were given daily intraperitoneal injections of 10 mg/kg hydrocortisone for 2 consecutive weeks at the same time, and then orally administered either saline or JKSQP [13.5 g/(kg•d) for 6 consecutive weeks. Body weight, anal temperature and animal appearance were observed and recorded to evaluate the GC-associated symptoms. The ocular parameters, including refraction and axial length, were measured by streak retinoscopy and A-scan ultrasonography, respectively. The levels of plasma hormones associated with the hypothalamic-pituitary-adrenal axis (HPAA), including free triiodothyronine, free thyroxine, estradiol and testosterone, were measured by radioimmunoassay, and cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate were measured by enzyme-linked immunosorbent assay. In addition, the mRNA and protein expressions of retinal amphiregulin (AREG) was measured by quantitative real-time polymerase chain reaction and Western blotting, respectively. RESULTS: JKSQP effectively increased body weight and anal temperature, improved animal appearance and suppressed axial length elongation in glucocorticoid-enhanced myopic guinea pigs with normalization of 4 HPAA-associated plasma hormones (all P<0.05). The plasma level of cAMP was significantly increased, whereas the plasma level of cGMP and the mRNA and protein expressions of retinal AREG were decreased after treatment with JKSQP (all P<0.05). CONCLUSION JKSQP exhibited a significant inhibitory effect on axial length elongation with decreased expression of AREG in the retina, and normalized 4 HPAA-associated plasma hormones and the expression of cAMP and cGMP in GC-enhanced myopic guinea pigs.
Guinea Pigs ; Male ; Animals ; Glucocorticoids ; Hypothalamo-Hypophyseal System ; Pituitary-Adrenal System ; Myopia/metabolism* ; Body Weight ; RNA, Messenger ; Disease Models, Animal

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Abstract: Objective　To analyze the association between drug resistance and the risk of latent tuberculosis infection and disease among household contacts of patients with pulmonary tuberculosis, and to explore whether the compensatory mutation of drug-resistant Mycobacterium tuberculosis will enhance its pathogenicity or transmission ability. Methods　The English and Chinese databases, including PubMed, web of science, EMBASE, Cochrane library database, CNKI and Wanfang database, were searched by computer from the time of establishment of the database to January 2022. Cohort studies on the risk of infection and disease among household contacts of patients with drug-resistant and sensitive pulmonary tuberculosis were searched and screened according to the inclusion and exclusion criteria. The data were extracted and evaluated by NOS scale, using stata16.0 software meta-analysis to calculate the combined effect of tuberculosis infection and disease risk of family contacts, and carry out heterogeneity test, subgroup analysis and sensitivity analysis. Results　A total of 7 cohort studies involving 9653 TB index cases and 29, 734 house contacts were included. The results of meta-analysis showed that compared with drug-sensitive pulmonary tuberculosis patients, the risk of tuberculosis infection in house contacts of drug-resistant pulmonary tuberculosis patients was increased (OR=1.56, 95%CI=1.25-1.96, P<0.001), but there was no difference in the risk of incidence (RR=1.06, 95%CI=0.80-1.41, P=0.67>0.05). Subgroup analysis showed that the risk of latent tuberculosis infection in house contacts was affected by the study area, and the size of family contacts had an impact on the risk of TB . Sensitivity analysis showed that the results of meta-analysis were robust. Conclusion　Compared with drug sensitive TB patients, household contacts with drug-resistant TB patients had a higher risk of tuberculosis, but there was no difference in the risk of TB among the two groups.

Humans ; Pharyngeal Neoplasms ; Esophageal Neoplasms/surgery*

BACKGROUND: Early detection of gastric cancer (GC) has been the topic of major efforts in China. This study aimed to explore the risk factors associated with GC and to provide evidence for the selection of a high-risk population of GC. METHODS: Based on the cancer screening cohort of the National Cancer Screening Program in Urban China, GC patients diagnosed by endoscopy and pathological examinations constituted the case group, and controls were 1:3 matched by sex and age (±5 years) individually. The variables were selected by univariable analysis of factors such as body mass index (BMI), dietary habits, lifestyle, stomach disease history, and family history of GC; and multivariable logistic regression was used to analyze the influencing factors of GC and to calculate the odds ratio (OR) of related factors and its 95% confidence interval (CI). RESULTS: A total of 215 GC cases and 645 matched healthy controls were included in the final analysis, with a median age of 61 years for the case and control groups. Overall analysis showed that high educational level (above primary school) (OR = 0.362, 95% CI = 0.219-0.599, P < 0.001), overweight/obesity (BMI ≥24 kg/m2; OR = 0.489, 95% CI = 0.329-0.726, P < 0.001), cigarette smoking (OR = 3.069, 95% CI = 1.700-5.540, P < 0.001), alcohol consumption (OR = 1.661, 95% CI = 1.028-2.683, P = 0.038), history of stomach disease (OR = 6.917, 95% CI = 4.594-10.416, P < 0.001), and family history of GC in first-degree relatives (OR = 4.291, 95% CI = 1.661-11.084, P = 0.003) were significantly correlated with the occurrence of GC. Subgroup analyses by age and gender indicated that GC risk was still increased in the presence of a history of stomach disease. A history of chronic gastritis, gastric ulcer, or gastric polyposis was positively associated with GC, with adjusted ORs of 4.155 (95% CI = 2.711-6.368), 1.839 (95% CI = 1.028-3.288), and 2.752 (95% CI = 1.197-6.326). CONCLUSIONS Subjects who smoke, drink, with history of stomach disease and family history of GC in first-degree relatives are the high-risk populations for GC. Therefore, attention should be paid to these subjects for GC screening.
Case-Control Studies ; Humans ; Middle Aged ; Overweight ; Risk Factors ; Stomach Neoplasms/etiology*

OBJECTIVE: To elucidate the underlying mechanism of Panax notoginseng saponin (PNS) on gastric epithelial cell injury and barrier dysfunction induced by dual antiplatelet (DA). METHODS: Human gastric mucosal epithelial cell (GES-1) was cultured and divided into 4 groups: a control, a DA, a PNS+DA and a LY294002+PNS+DA group. GES-1 apoptosis was detected by flow cytometry, cell permeability were detected using Transwell, level of prostaglandins E2 (PGE2), 6-keto-prostaglandin F1α (6-keto-PGF1α) and vascular endothelial growth factor (VEGF) in supernatant were measured by enzyme linked immunosorbent assay (ELISA), expression of phosphatidylinositide 3-kinase (PI3K), phosphorylated-PI3K (p-PI3K), Akt, phosphorylated-Akt (p-Akt), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), glycogen synthase kinase-3β (GSK-3β) and Ras homolog gene family member A (RhoA) were measured by Western-blot. RESULTS: DA induced apoptosis and hyper-permeability in GES-1, reduced supernatant level of PGE2, 6-keto-PGF1α and VEGF (P<0.05). Addition of PNS reduced the apoptosis of GES-1 caused by DA, restored the concentration of PGE2, 6-keto-PGF1α and VEGF (P<0.05). In addition, PNS attenuated the alteration of COX-1 and COX-2 expression induced by DA, up-regulated p-PI3K/p-Akt, down-regulated RhoA and GSK-3β. LY294002 mitigated the effects of PNS on cell apoptosis, cell permeability, VEGF concentration, and expression of RhoA and GSK-3β significantly. CONCLUSIONS PNS attenuates the suppression on COX/PG pathway from DA, alleviates DA-induced GES-1 apoptosis and barrier dysfunction through PI3K/Akt/ VEGF-GSK-3β-RhoA network pathway.
Cyclooxygenase 1 ; Epithelial Cells/metabolism* ; Glycogen Synthase Kinase 3 beta ; Humans ; Panax notoginseng ; Phosphatidylinositol 3-Kinases/metabolism* ; Platelet Aggregation Inhibitors ; Proto-Oncogene Proteins c-akt/metabolism* ; Saponins/pharmacology* ; Vascular Endothelial Growth Factor A ; rhoA GTP-Binding Protein

BACKGROUND: A novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in Wuhan, China, has been rapidly spreading around the world. This study investigates the epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19) patients in Zhejiang Province who did or did not have a history of Wuhan exposure. METHODS: We collected data from medical records of confirmed COVID-19 patients in Zhejiang Province from Jan. 17 to Feb. 7, 2020 and analyzed epidemiological, clinical, and treatment data of those with and without recorded recent exposure in Wuhan. RESULTS: Patients in the control group were older than those in the exposure group ((48.19±16.13) years vs. (43.47±13.12) years, P<0.001), and more were over 65 years old (15.95% control vs. 5.60% exposure, P<0.001). The rate of clustered onset was also significantly higher in the control group than in the exposure group (31.39% vs. 18.66%, P<0.001). The symptom of a sore throat in patients in the exposure group was significantly higher than that in the control group (17.30% vs. 10.89%, P=0.01); however, headache in the exposure group was significantly lower than that in the control group (6.87% vs. 12.15%, P=0.015). More patients in the exposure group had a significantly lower level of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) than those in the control group. There was no significant difference in any degree of COVID-19 including mild, severe, and critical between the two groups. CONCLUSIONS From the perspective of epidemiological and clinical characteristics, there was no significant difference between COVID-19 patients with and without Wuhan exposure history.
Adolescent ; Adult ; Aged ; Aspartate Aminotransferases ; blood ; Betacoronavirus ; Case-Control Studies ; Child ; Child, Preschool ; China ; epidemiology ; Coronavirus Infections ; epidemiology ; physiopathology ; therapy ; Female ; Humans ; Infant ; Infant, Newborn ; L-Lactate Dehydrogenase ; blood ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; epidemiology ; physiopathology ; therapy ; Retrospective Studies ; Young Adult