GPR126, also known as ADGRG6, is one of the most deeply studied aGPCRs. Initially, GPR126 was thought to be a receptor associated with muscle development and was primarily expressed in the muscular and skeletal systems. With the deepening of research, it was found that GPR126 is expressed in multiple mammalian tissues and organs, and is involved in many biological processes such as embryonic development, nervous system development, and extracellular matrix interactions. Compared with other aGPCRs proteins, GPR126 has a longer N-terminal domain, which can bind to ligands one-to-one and one-to-many. Its N-terminus contains five domains, a CUB (complement C1r/C1s, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a SEA (Sperm protein, Enterokinase, and Agrin) domain, a hormone binding (HormR) domain, and a conserved GAIN domain. The GAIN domain has a self-shearing function, which is essential for the maturation, stability, transport and function of aGPCRs. Different SEA domains constitute different GPR126 isomers, which can regulate the activation and closure of downstream signaling pathways through conformational changes. GPR126 has a typical aGPCRs seven-transmembrane helical structure, which can be coupled to Gs and Gi, causing cAMP to up- or down-regulation, mediating transmembrane signaling and participating in the regulation of cell proliferation, differentiation and migration. GPR126 is activated in a tethered-stalk peptide agonism or orthosteric agonism, which is mainly manifested by self-proteolysis or conformational changes in the GAIN domain, which mediates the rapid activation or closure of downstream pathways by tethered agonists. In addition to the tethered short stem peptide activation mode, GPR126 also has another allosteric agonism or tunable agonism mode, which is specifically expressed as the GAIN domain does not have self-shearing function in the physiological state, NTF and CTF always maintain the binding state, and the NTF binds to the ligand to cause conformational changes of the receptor, which somehow transmits signals to the GAIN domain in a spatial structure. The GAIN domain can cause the 7TM domain to produce an activated or inhibited signal for signal transduction, For example, type IV collagen interacts with the CUB and PTX domains of GPR126 to activate GPR126 downstream signal transduction. GPR126 has homology of 51.6%-86.9% among different species, with 10 conserved regions between different species, which can be traced back to the oldest metazoans as well as unicellular animals.In terms of diseases, GPR126 dysfunction involves the pathological process of bone, myelin, embryo and other related diseases, and is also closely related to the occurrence and development of malignant tumors such as breast cancer and colon cancer. However, the biological function of GPR126 in various diseases and its potential as a therapeutic target still needs further research. This paper focuses on the structure, interspecies differences and conservatism, signal transduction and biological functions of GPR126, which provides ideas and references for future research on GPR126.

The aim of this study was to investigate the impact of overexpressing 70-kD heat shock pro-teins(Hsp70)on glycolysis in C2C12 cells during myogenesis and adipogenesis.Using C2C12 cells as the research material,adenovirus was used to overexpress the Hsp70 gene,and changes in the expression of glycolytic genes were detected using fluorescence quantitative PCR and Western blotting techniques.The study indicated that during C2C12 cell myogenic differentiation,the expression trend of the Hsp70 gene was consistent with that of Gsk3β,Pkm,Prkag3,Pfkm,and Hk-2 genes,suggesting a relationship between Hsp70 and the glycolytic pathway during myogenic differentiation.Overexpression of Hsp70 in the later stages of myogenic differentiation significantly upregulated the expression of Gsk3β,Pkm,Prk-ag3,and Pfkm genes(P＜0.05),with no significant impact on Hk-2 gene expression(P＞0.05).Dur-ing C2C12 cell adipogenic induction,the expression trend of the Hsp70 gene was similar to that of Gsk3β,Pkm,Prkag3,Pfkm,and Hk-2 genes,indicating a relationship between Hsp70 and the glycolytic path-way during adipogenic induction.Following Hsp70 overexpression,in the later stages of adipogenic in-duction,the number of lipid droplets was significantly higher compared to the control group,with a sig-nificant upregulation of Gsk3β,Pkm,Prkag3,and Pfkm gene expression(P＜0.05),while Hk-2 gene expression was not significantly affected(P＞0.05).In conclusion,Hsp70 in C2C12 cells in myogenic and adipogenic states promoted the breakdown of glycogen into 6-phospho-glucose,thereby enhancing the glycolytic pathway,providing insights into the functional role of the Hsp70 gene in glycolysis in C2C12 cells.

PURPOSE: High explosives are used to produce blast waves to study their biological effects. The lungs are considered as the critical target organ in blast-effect studies. The degree of lung hemorrhaging is related to both the explosive power and the increased lung weight. We studied the characteristics of the biological effects from an air explosion of a thermobaric bomb in a high-altitude environment and the lethality and lung injury severity of goats in different orientations and distances. METHODS: Goats were placed at 2.5, 3, 4, and 5 m from the explosion center and exposed them to an air blast at an altitude of 4700-meter. A group of them standing oriented to the right side and the other group seated facing the explosion center vertically. The lung injuries were quantified according to the percentage of surface area contused, and using the pathologic severity scale of lung blast injury (PSSLBI) to score the 4 injury categories (slight, moderate, serious and severe) as 1, 2, 3, and 4, respectively. The lung coefficient (lung weight [g]/body weight [kg]) was the indicator of pulmonary edema and was related to lung injury severity. Blast overpressure data were collected using blast test devices placed at matching locations to represent loadings to goats. All statistical analyses were performed using SPSS, version 26.0, statistical software (SPSS, Inc., Chicago, IL, USA). RESULTS: In total, 127 goats were involved in this study. Right-side-standing goats had a significantly higher mortality rate than those seated vertical-facing (p < 0.05). At the 2.5 m distance, the goat mortality was nearly 100%, whereas at 5 m, all the goats survived. Lung injuries of the right-side-standing goats were 1 - 2 grades more serious than those of seated goats at the same distances, the scores of PSSLBI were significantly higher than the seated vertical-facing goats (p < 0.05). The lung coefficient of the right-side-standing goats were significantly higher than those of seated vertical-facing (p < 0.05). Mortality, PSSLBI, and the lung coefficient results indicated that the right-side-standing goats experienced severer injuries than the seated vertical-facing goats, and the injuries were lessened as the distance increased. The blast overpressure was consistent with these results. CONCLUSION The main killing factors of the thermobaric bomb in the high-altitude environment were blast overpressure, blast wind propulsions and burn. The orientation and distances of the goats significantly affected the blast injury severity. These results may provide a research basis for diagnosing, treating and protecting against injuries from thermobaric explosions.
Animals ; Lung Injury/etiology* ; Blast Injuries ; Goats ; Explosions ; Lung/pathology*

BACKGROUND: Familial hypercholesterolemia (FH) is a common autosomal dominant hereditary disease. Its early diagnosis and intervention significantly improve the patient's quality of life. However, there are few types of research on the FH pathogenic genes in China. METHODS: In this study, we recruited a family diagnosed with FH and used whole exome sequencing (WES) to analyze the proband variants. Intracellular cholesterol level, reactive oxygen species (ROS) level, and the expression of pyroptosis-related genes were detected after overexpression of wild-type or variant LDLR in L02 cells. RESULTS: A heterozygous missense variant predicted to be deleterious to LDLR (c.1879G > A, p.Ala627Thr) was identified in the proband. Mechanistically, intracellular cholesterol level, ROS level, and the expression of pyroptosis-related genes, nucleotide-binding oligomerization domain-like receptor family protein 3 (NLRP3) inflammasome and components (caspase 1, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and NLRP3), gasdermin D (GSDMD), interleukin (IL) -18, IL-1β was elevated in the variant LDLR group, which was attenuated by inhibition of ROS. CONCLUSIONS FH is associated with a variant (c.1879G>A, p.Ala627Thr) in the LDLR gene. Regarding the mechanism, the ROS/NLRP3-mediated pyroptosis in hepatic cells may contribute to the pathogenesis of the LDLR variant.

Through literature research and standard retrieval, Corydalis-derived medicinal materials, the origins, and related standards were summarized. Finally, 27 medicinal materials were screened out, involving 71 species(varieties). Among them, only 11 are recorded in Chinese Pharmacopoeia(2020), National Standard for Chinese Patent Drugs·Tibetan Medicine, Tibetan Medicine Standards, and other local standards, including Corydalis Bungeanae Herba and Corydalis Herba. The names and original plants of the medicinal materials are different in different standards, and the phenomena of "same medicinal material with different names" and "same name for different medicinal materials" are prominent. Most standards only include the traits, microscopic identification, and physico-chemical property identification, with unsound quality criteria. Thus, efforts should be made to strengthen the sorting of Corydalis medicinal plants, herbal textual research, and investigation of the resources and utilization. Moreover, via modern techniques, the chemical components and medicinal material basis of different original plants should be explored and sound quality standards should be established to improve the safety and quality of Corydalis-derived medicinal materials. Summarizing Corydalis medicinal plants, Corydalis-derived medicinal materials, and related standards, this study is expected to provide a reference for the standard formulation, quality evaluation, expansion of drug sources, and rational development and utilization of Corydalis resources.
Corydalis ; Drugs, Chinese Herbal/chemistry* ; Medicine, Chinese Traditional ; Medicine, Tibetan Traditional ; Plants, Medicinal/chemistry* ; Reference Standards

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a worldwide life-threatening pandemic. Lianhua Qingwen is believed to possess the ability to treat or significantly improve the symptoms of COVID-19. These claims make it important to systematically evaluate the effects of using Lianhua Qingwen with Western medicine to treat COVID-19. OBJECTIVE: To evaluate the safety and efficacy of combination therapy, employing Lianhua Qingwen with Western medicine, to treat COVID-19, using a meta-analysis approach. SEARCH STRATEGY: China National Knowledge Infrastructure, Wanfang Database, VIP Database, PubMed, Embase, and Cochrane Library databases were searched for studies evaluating the effect of Lianhua Qingwen-Western medicine combination therapy in the treatment of COVID-19. INCLUSION CRITERIA: (1) Research object: hospitalized patients meeting the diagnostic criteria of COVID-19 were included. (2) Intervention measures: patients in the treatment group received Lianhua Qingwen treatment combined with Western medicine, while the control group received either Western medicine or Chinese medicine treatment. (3) Research type: randomized controlled trials and retrospective study were included. DATA EXTRACTION AND ANALYSIS: Two researchers extracted the first author, the proportion of males and females, age, body temperature, course of treatment, rate of disappearance of main symptoms, duration of fever, adverse reactions, and total effectiveness from the literature. Odds ratio (OR) and 95% confidence interval (CI) were used as the effect value for count data, and mean difference (MD) and 95% CI were used as the effect value for measurement data. RESULTS: Six articles met the inclusion criteria, including a total of 856 COVID-19 patients. The meta-analysis showed that Lianhua Qingwen combination therapy achieved higher rates of fever reduction (OR = 3.43, 95% CI [1.78, 6.59], P = 0.0002), cough reduction (OR = 3.39, 95% CI [1.85, 6.23], P < 0.0001), recovery from shortness of breath (OR = 10.62, 95% CI [3.71, 30.40], P < 0.0001) and recovery from fatigue (OR = 2.82, 95% CI [1.44, 5.53], P = 0.003), higher total effectiveness rate (OR = 2.51, 95% CI [1.73, 3.64], P < 0.00001), and shorter time to recovery from fever (MD = -1.00, 95% CI [-1.04, 0.96], P < 0.00001), and did not increase the adverse reaction rate (OR = 0.65, 95% CI [0.42, 1.01], P = 0.06), compared to the single medication control. CONCLUSION The Lianhua Qingwen and Western medicine combination therapy is highly effective for COVID-19 patients and has good clinical safety. As only a small number of studies and patients were included in this review, more high-quality, multicenter, large-sample-size, randomized, double-blind, controlled trials are still needed for verification.
COVID-19 ; Drugs, Chinese Herbal ; Female ; Humans ; Male ; Multicenter Studies as Topic ; Pandemics ; Randomized Controlled Trials as Topic ; Retrospective Studies ; SARS-CoV-2

Objective: To compare the differences between CAS risk model and CHA₂DS₂-VASc risk score in predicting all cause death, thromboembolic events, major bleeding events and composite endpoint in patients with nonvalvular atrial fibrillation. Methods: This is a retrospective cohort study. From the China Atrial Fibrillation Registry cohort study, the patients with atrial fibrillation who were>18 years old were randomly divided into CAS risk score group and CHA₂DS₂-VASc risk score group respectively. According to the anticoagulant status at baseline and follow-up, patients in the 2 groups who complied with the scoring specifications for anticoagulation were selected for inclusion in this study. Baseline information such as age and gender in the two groups were collected and compared. Follow-up was performed periodically to collect information on anticoagulant therapy and endpoints. The endpoints were all-cause death, thromboembolism events and major bleeding, the composite endpoint events were all-cause death and thromboembolism events. The incidence of endpoints in CAS group and CHA₂DS₂-VASc group was analyzed, and multivariate Cox proportional risk model was used to analyze whether the incidence of the endpoints was statistically different between the two groups. Results: A total of 5 206 patients with AF were enrolled, average aged (63.6±12.2) years, and 2092 (40.2%) women. There were 2 447 cases (47.0%) in CAS risk score group and 2 759 cases (53.0%) in CHA₂DS₂-VASc risk score group. In the clinical baseline data of the two groups, the proportion of left ventricular ejection fraction<55%, non-paroxysmal atrial fibrillation, oral warfarin and HAS BLED score in the CAS group were lower than those in the CHA₂DS₂-VASc group, while the proportion of previous diabetes history and history of antiplatelet drugs in the CAS group was higher than that in the CHA₂DS₂-VASc group, and there was no statistical difference in other baseline data. Patients were followed up for (82.8±40.8) months. In CAS risk score group, 225(9.2%) had all-cause death, 186 (7.6%) had thromboembolic events, 81(3.3%) had major bleeding, and 368 (15.0%) had composite endpoint. In CHA₂DS₂-VASc risk score group, 261(9.5%) had all-cause death 209(7.6%) had thromboembolic events, 112(4.1%) had major bleeding, and 424 (15.4%) had composite endpoint. There were no significant differences in the occurrence of all-cause death, thromboembolic events, major bleeding and composite endpoint between anticoagulation in CAS risk score group and anticoagulation in CHA₂DS₂-VASc risk score group (log-rank P =0.643, 0.904, 0.126, 0.599, respectively). Compared with CAS risk score, multivariable Cox proportional hazards regression models showed no significant differences for all-cause death, thromboembolic events, major bleeding and composite endpoint between the two groups with HR(95%CI) 0.95(0.80-1.14), 1.00(0.82-1.22), 0.83(0.62-1.10), 0.96(0.84-1.11), respectively. All P>0.05. Conclusions: There were no significant differences between CAS risk model and CHA₂DS₂-VASc risk score in predicting all-cause death, thromboembolic events, and major bleeding events in Chinese patients with non-valvular atrial fibrillation.
Adolescent ; Anticoagulants ; Atrial Fibrillation/drug therapy* ; Cohort Studies ; Female ; Hemorrhage/complications* ; Humans ; Male ; Retrospective Studies ; Risk Assessment ; Stroke/epidemiology* ; Stroke Volume ; Thromboembolism/etiology* ; Ventricular Function, Left

Today, there is greater awareness on the association between oral diseases and respiration diseases after the outbreak of COVID-19. However, confusion regarding the oral health management and medical risk prevention for patients with chronic airway diseases has been remained among dental clinicians. Therefore, the dental experts of the Fifth General Dentistry Special Committee, Chinese Stomatological Association, combined with the experts of respiratory and critical care medicine, undertook the formation of consensus on the oral health management of patients with chronic airway diseases in order to help dental clinicians to evaluate medical risks and make better treatment decision in clinical practice. In the present consensus report, the relationship of oral diseases and chronic airway diseases, the oral health management and the treatment recommendations of patients with chronic airway diseases are provided.
COVID-19 ; Consensus ; Humans ; Oral Health ; Oral Medicine

With the aging process of population in the society, the prevalence of cardiovascular diseases (CVD) in China is increasing continuously and the number of dental patients with CVD is increasing gradually too. Due to the lack of guidelines for dental patients with CVD in our country, how to implement standardized preoperative evaluation and perioperative risk prevention remains a problem to be solved for dentists at present. The present expert consensus was reached by combining the clinical experiences of the expert group of the Fifth General Dentistry Special Committee, Chinese Stomatological Association and respiratory and cardiology experts in diagnosis and treatment for CVD patients, and by systematically summarizing the relevant international guidelines and literature regarding the relationship between CVD and oral diseases and the diagnosis and treatment of dental patients with heart failure, hypertension and antithrombotic therapy. The consensus aims to provide, for the dental clinicians, the criteria on diagnosis and treatment of CVD in dental patients in China so as to reduce the risk and complications, and finally to improve the treatment levels of dental patients with CVD in China.
Cardiovascular Diseases/prevention & control* ; China/epidemiology* ; Consensus ; Dental Care ; Humans ; Oral Medicine

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*