Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

Objective To determine the effective dose of dexmedetomidine administered intranasally combined with oral midazolam sedation before pediatric magnetic resonance image(MRI).Methods This is a prospective modified sequential study.Children scheduled for MRI at the Children's Hospital of Zhejiang University School of Medicine from February to March 2023,aged 1 month to 6 years old,with a weight of 6.0-23.5 kg,were enrolled in this study.All children received 0.5 mg/kg oral midazolam,followed by intranasal dexmedetomidine.The initial dose of dexmedetomidine was 0.5 μg/kg,and the intranasal dose of dexmedetomidine was determined using the modified Dixon's up-and-down method with increments or decrements of 0.1 μg/kg.Probit analysis was used for calculating the half effective dose(ED50),95%effective dose(ED95)and the corresponding 95%confidence interval(CI)of intranasal dexmedetomidine combined with oral midazolam for pediatric sedation during MRI.The sedation onset time,wake-up time,vital signs and adverse reactions were recorded.Results Among all the children,the sedation onset time of successful sedation children was(31.21±7.47)min,and the wake-up time was(81.21±26.04)min.The ED50 for effective sedation with intranasal dexmedetomidine combined with oral medication at a dose of 0.5 mg/kg was calculated to be 0.392 μg/kg,with a 95%CI of 0.302-0.461 μg/kg;the ED95 was 0.549 μg/kg,with a 95%CI of 0.473-0.996 μg/kg.There was a statistically significant difference(P<0.05)in heart rate and diastolic blood pressure after sedation compared to the baseline before medication.Two cases of restlessness during the awakening period were observed,but no other adverse reactions occurred.Conclusions The sedation regimen of intranasal dexmedetomidine combined with oral midazolam is non-invasive,easy to implement,safe,and effective.It can be widely used in pediatric MRI.

ObjectiveProteoglycan TPG-1 isolated from Trametes robiniophila（Huaier） has proved to have anti-hepatoma activity， and this paper aims to explore the molecular mechanism. MethodHuman hepatoma SK-HEP-1 cells were treated with TPG-1 （0， 0.05， 0.1， 0.25， 0.5， 1 g·L^-1）. Then cell survival was detected by methyl thiazolyl tetrazolium （MTT） and apoptosis by flow cytometry. In addition， expression of genes in SK-HEP-1 cells treated with or without TPG-1 was examined by DNA microarray to preliminarily explore the anti-hepatoma molecular mechanism of TPG-1. ResultTPG-1 inhibited the proliferation of SK-HEP-1 cells as compared with the blank group （P<0.01）. After treatment with 1 g·L^-1 TPG-1 for 48 h， the apoptosis rate of SK-HEP-1 cells increased （P<0.01）， and TPG-1 promoted the cleavage of cysteinyl aspartate specific proteinase （Caspase）-3 and Caspase-7， the key mediators of apoptosis （P<0.01）. Additionally， TPG-1 （1 g·L^-1） suppressed the migration of SK-HEP-1 cells （P<0.05）. A total of 971 differentially expressed genes （DEGs） were identified in SK-HEP-1 cells after treatment with TPG-1， with 486 up-regulated and 485 down-regulated. These DEGs were mainly involved in the Gene Ontology （GO） terms of interleukin-6 （IL-6） biosynthesis， antigen processing and presentation， superoxide dismutase activity， positive regulation of mitogen-activated protein kinase kinase kinase （MAPKKK） cascade， nature killer （NK） cell chemotaxis， and chemokine biosynthesis， and the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathways of nucleotide-binding oligomerization domain （NOD）-like receptor signaling pathway， apoptosis， Toll-like receptor signaling pathway， retinoic acid-inducible gene-Ⅰ （RIG-Ⅰ）-like receptor signaling pathway， T-cell receptor signaling pathway， and chemokine signaling pathway. Western blot results showed that TPG-1 （1 g·L^-1） activated mitogen-activated protein kinase （MAPK） signaling pathway in SK-HEP-1 cells （P<0.01）. ConclusionProteoglycan TPG-1 inhibited the proliferation and migration， and induced apoptosis of human hepatoma SK-HEP-1 cells. Up-regulation of MAPK signaling pathway may be responsible for the growth inhibition of human hepatoma SK-HEP-1 cells by TPG-1.

As a traditional Chinese medicine, Chinese dragon's blood has multiple effects, such as activating blood to remove blood stasis, softening and dispelling stagnation, astringent and hemostasis, clearing swelling and relieving pain, regulating menstruation and rectifying the blood, so it is called "an effective medicine of promoting blood circulation". It has been widely used clinically to treat a variety of diseases. With the further research on Chinese dragon's blood, its anti-tumor medicinal value is gradually emerging. Modern pharmacological studies have shown that Chinese dragon's blood exerts anti-tumor effects mainly by inhibiting cell proliferation, inducing apoptosis, inducing DNA damage and cell cycle arrest, inducing senescence and autophagy of tumor cells, inhibiting metastasis and angiogenesis, as well as reversing multidrug resistance. This article focuses on the research progress on anti-tumor effects of Chinese dragon's blood extract and its chemical components, with a view to provide new references for the in-depth research and reasonable utilization of Chinese dragon's blood.
China ; Dracaena ; Female ; Plant Extracts ; Resins, Plant

In December 2019, an outbreak of viral pneumonia began in Wuhan, Hubei Province, which caused the spread of infectious pneumonia to a certain extent in China and neighboring countries and regions, and triggered the epidemic crisis. The coronavirus disease 2019(COVID-19) is an acute respiratory infectious disease listed as a B infectious disease, which is managed according to standards for A infectious disease. Traditional Chinese medicine and integrated traditional Chinese and Western medicine have played an active role in the prevention and control of this epidemic. China's ethnomedicine has recognized infectious diseases since ancient times, and formed a medical system including theory, therapies, formula and herbal medicines for such diseases. Since the outbreak of the COVID-19 epidemic, Tibet Autonomous Region, Qinghai Province, Inner Mongolia Autonomous Region, Xinjiang Uygur Autonomous Region and Chuxiong Autonomous Prefecture of Yunnan, Qiandongnan Autonomous Prefecture of Guizhou have issued the prevention and control programs for COVID-19 using Tibetan, Mongolian, Uygur, Yi and Miao medicines. These programs reflect the wisdom of ethnomedicine in preventing and treating diseases, which have successfully extracted prescriptions and preventive measures for the outbreak of the epidemic from their own medical theories and traditional experiences. In this paper, we summarized and explained the prescriptions and medicinal materials of ethnomedicine in these programs, and the origin of Tibetan medicine prescriptions and Mongolian medicine prescriptions in ancient books were studied. These become the common characteristics of medical prevention and treatment programs for ethnomedicine to formulate therapeutic programs under the guidance of traditional medicine theories, recommend prescriptions and prevention and treatment methods with characteristics of ethnomedicine, and focus on the conve-nience and standardization. However, strengthening the support of science and technology and the popularization to the public, and improving the participation of ethnomedicine in national public health services and the capacity-building to deal with sudden and critical diseases are key contents in the development of ethnomedicine in the future.
Betacoronavirus ; China ; Coronavirus Infections ; drug therapy ; Humans ; Medicine, Traditional ; Pandemics ; Pneumonia, Viral ; drug therapy ; Tibet

This study aims to investigate the effect of Huaier aqueous extract on the growth and metastasis of human non-small cell lung cancer NCI-H1299 cells and its underlying mechanisms. MTT assay was used to detect the effect of Huaier aqueous extract on the proliferation of NCI-H1299 cells. Flow cytometry was used to examine the effect of Huaier aqueous extract on the apoptosis, cell cycle, and ROS level of NCI-H1299 cells. Wound healing assay was used to evaluate the effect of Huaier aqueous extract on the migration ability of NCI-H1299 cells. Western blot was used to detect the levels of proteins involving apoptosis, epithelial-mesenchymal transition(EMT), and MAPK signaling pathway in NCI-H1299 cells exposed to Huaier aqueous extract. The results showed that Huaier aqueous extract inhibited the proliferation of NCI-H1299 cells, and induced cell-cycle arrest at the phase S. Huaier aqueous extract promoted the apoptosis of NCI-H1299 cells by down-regulating the expression of anti-apoptotic protein Bcl-2. Moreover, Huaier aqueous extract increased ROS level and induced ferroptosis in NCI-H1299 cells. EMT played a critical role in cancer metastasis. Huaier aqueous extract reduced the migration ability of NCI-H1299 cells by inhibiting EMT of NCI-H1299 cells. In addition, this study revealed that Huaier aqueous extract inhibited MAPK signaling pathway in human non-small cell lung cancer NCI-H1299 cells, which may be one of Huaier's mechanisms in inhibiting growth and metastasis of NCI-H1299 cells. This study provides a new theoretical basis for the clinical treatment of lung cancer with Huaier, and important reference significance for further studies on the anti-tumor mechanisms of Huaier.
Apoptosis ; Carcinoma, Non-Small-Cell Lung ; Cell Line, Tumor ; Cell Proliferation ; Complex Mixtures ; Humans ; Lung Neoplasms ; Trametes

AIM:To investigate the effect of urantide on the liver function and histomorphology in the rats with atherosclerosis (AS).METHODS:The AS Wistar rat model was induced by intraperitoneal injection of vitamin D3 (VD3) and feeding with high-fat diet.The rats were randomly divided into normal control group, AS model group, positive medicine group and urantide group.The liver function indexes of the rats were measured by biochemical test, and the pathological changes of the aorta and liver of the rats were observed by hematoxylin-eosin (HE) staining.The mRNA expression of urotensinⅡ (UII) and GPR14 at mRNA and protein levels in rat livers was determined by RT-qPCR and Western blot.RESULTS:The levels of alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , γ-glutamyltransferase (γ-GT) , lactate dehydrogenase (LDH) , total bilirubin (TBIL) , indirect bilirubin (IBIL) and alkaline phosphatase (ALP) in AS model group were significantly increased compared with normal control group (P<0.05).The above indexes in urantide group were remarkably decreased compared with AS model group (P<0.05).No change of the levels of direct bilirubin (DBIL) , total protein (TP) , globulin (GLB) and albumin (ALB) in each group was observed.Urantide postponed hepatocyte fatty degeneration and repaired hepatocyte injury in the AS rats.Compared with normal control group, the mRNA and protein levels of UII and GPR14 in the liver were significantly increased in AS model group (P<0.05).With the prolongation of dosing time, the mRNA and protein levels of UII and GPR14 in the liver were significantly decreased in urantide group compared with AS model group (P<0.05).CONCLUSION:Urantide significantly attenuates the liver damage caused by liver fatty degeneration in AS rats.

Objective To provide new ideas for establishment of prevention and control strategy for non-communicable chronic disease (NCD) that are suitable for Chinese people. Methods Sampling survey of patients with chronic disease from 14 provinces combined with literature study and researches on national statistical data were conducted to investigate the application situation and problems of traditional Chinese medicine in the prevention and control of NCD. Results Status of utilization and satisfaction of traditional Chinese medicine in the prevention and control of NCD has developed well. The main problems in the promotion and application of TCM lie in insufficient investment, lagging behind of construction of prevention and control system, insufficient professionals and ineffective heritance of practical technique. Conclusion In order to tackle these problems, relevant laws and regulations should be implemented;information management system with TCM features should be improved;construction of diversified technological innovation system should be reinforced, practical and strong technology should be promoted;construction of TCM prevention and control system for chronic diseases should be perfected.

Objective To explore the role of tendon synovial sheaths in tendon regeneration in vivo. Methods Thirty-six Roman chicken were randomly divided into Group A and B, with 18 chicken in each group. In Group A, the synovial sheaths of the deep flexor tendons in the left middle toes were separated from the up, right and down side without cutting off the tendons themselves. The allograft decellularized tendons were coated with synovial sheaths which were detached partly and fixed on the left side of the normal deep flexor tendons in the middle toes of the left foot. In Group B, the allograft decellularized tendons were directly implanted on the left side of the deep flexor tendons without coating of synovial sheaths. The normal deep flexor tendons from the right foot were used as the control group. The maximum loads and elastic modulus of the tendons at 4th, 8th and 12th week were obtained by mechanical testing, and HE staining was conducted to observe histological changes of the tendons. Results The maximum load at 8th and 12th week and elastic modulus at 4th, 8th and 12th week in Groups A were greater than those in Group B, with significant differences (P<0.05). Group A showed more densely deposited matrices and longitudinally aligned collagen fibers than Group B, and inflammatory cells and fibrous tissues could hardly be found in Group A. In Group B, the collagen fibers were decreased gradually, with disordered alignment. Furthermore, more inflammatory cells infiltration and hyperplasia of fibrous tissues were found in Group B. Conclusions The synovial sheaths can contribute to tendon regeneration, indicating that a proper environment in vivo plays an important role in the engineered tendons. This study has a positive effect on finding proper tendon replacements for patients with tendon deficiency.

OBJECTIVE: To study ApoB gene genetic polymorphism of Han nationality and Mongolian nationality in midwest area of Inner Mongolia. METHODS: Some unrelated individuals of Han nationality and Mongolian nationality in midwest area of Inner Mongolia were selected. Polymerase chain reaction-restriction fragment length polymorphism technology was used to check the presence of Xba I (X+) and EcoR I (E-) sites of rare alleles. The genotype frequency, allelic frequency and population genetics parameters were calculated. RESULTS: The frequencies of Xba I (X+) and EcoR I (E-) rare alleles were 2% and 4.6% in Han population. There was no Xba I (X+) or EcoR I (E-) rare alleles found in Mongolian nationality. CONCLUSION The allelic frequencies of ApoB gene Xba I and EcoR I sites are very different in different races. These sites may be used in identification of ethnicity.
Alleles ; Apolipoprotein B-100/genetics* ; Asian People/genetics* ; China ; Ethnicity ; Gene Frequency ; Genotype ; Humans ; Mongolia ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length