Objective To observe the expression and localization of group Ⅰ metabotropic glutamate receptors (mGluR1/ 5) in rat superior cervical ganglion (SCG) and the effect of chronic intermittent hypoxia (CIH) on mGluR1/ 5 protein level. Methods Twelve male SD rats were randomly divided into control group(Ctrl)and CIH group(CIH), 6 rats in each group. After 6 weeks of modeling, the effect of CIH on mGluR1/ 5 protein level was detected by Western blotting, the expression and distribution of mGluR1/ 5 in SCG were detected by immunohistochemistry and double-immunofluorescent staining. Results mGluR1/ 5 was expressed in rat SCG. mGluR1 was distributed in neurons and small intensely fluorescent (SIF) cells, but not in satellite glial cells (SGCs), nerve fibers and blood vessels, whereas mGluR5 was mainly distributed in nerve fibers and a little in neurons, but not in SGCs, SIF cells and blood vessels. CIH increased the protein levels of mGluR1/ 5 (P<0. 01) in rat SCG. Conclusion Both mGluR1 and mGluR5 are expressed in the rat SCG, but their distribution are different, and the increased protein levels of both may be involved in CIH-induced hypertension.

Objective:To analyze the international status and level of clinical trial quality in China, and explore the advantages and value of scientific regulation of clinical research quality in China.Methods:The data is sourced from the relevant reports publicly released by the National Medical Products Administration (NMPA), the inspection reports and announcements published by the Center for Food and Drug Inspection of the NMPA, the inspection data displayed on the official website of the U.S. Food and Drug Administration (FDA), as well as clinical diagnosis and treatment guidelines issued by the National Comprehensive Cancer Network (NCCN) of United States and the Chinese Society of Clinical Oncology (CSCO) (data as of July 21, 2023). This data provides an analysis of the regulatory status of the implementation of clinical drug trials in China, inspection data, and the approval and market entry of new oncology drugs and feedback from their practical application.Results:The clinical trial quality inspection systems of China and the United States are generally aligned, with similar inspection subjects, focus areas, and public disclosure pathways. However, each has its characteristics in terms of inspection targets and types. The quality of clinical trial data in China has been continuously improving. Between 2009-2015 and 2016-July 2023, China underwent 25 and 20 FDA Bioresearch Monitoring (BIMO) inspections, respectively. The inspection results showing "No Action Indicated" (NAI) improved from 48.0% to 85.0%, while "Voluntary Action Indicated" (VAI) decreased from 44.0% to 15.0%. Official Action Indicated (OAI) measures were required in 2009 and 2012. Compared to the 2009-2015 period, there has been a clear upward trend in the quality of clinical trial data since 2016. From 2016 to July 2023, the number of new oncology drugs developed by Chinese pharmaceutical companies and included in professional guidelines has steadily increased. Specifically, 37 drugs (58.7%) were included in the 2022 edition of the CSCO guidelines, and 15 drugs (23.8%) were included in the 2023 edition of the NCCN guidelines, with 10 of these drugs featured in both guidelines.Conclusions:The implementation quality of clinical trials in China has gained a certain level of international recognition and competitiveness. This progress is attributed to national macro-level guidance, a unique institutional model, and clinical practices aligned with international standards. In the future, it will be necessary to further strengthen the scientific regulatory system and enhance clinical research capabilities to continue advancing the high-quality development of clinical trials.

Objective:To analyze the international status and level of clinical trial quality in China, and explore the advantages and value of scientific regulation of clinical research quality in China.Methods:The data is sourced from the relevant reports publicly released by the National Medical Products Administration (NMPA), the inspection reports and announcements published by the Center for Food and Drug Inspection of the NMPA, the inspection data displayed on the official website of the U.S. Food and Drug Administration (FDA), as well as clinical diagnosis and treatment guidelines issued by the National Comprehensive Cancer Network (NCCN) of United States and the Chinese Society of Clinical Oncology (CSCO) (data as of July 21, 2023). This data provides an analysis of the regulatory status of the implementation of clinical drug trials in China, inspection data, and the approval and market entry of new oncology drugs and feedback from their practical application.Results:The clinical trial quality inspection systems of China and the United States are generally aligned, with similar inspection subjects, focus areas, and public disclosure pathways. However, each has its characteristics in terms of inspection targets and types. The quality of clinical trial data in China has been continuously improving. Between 2009-2015 and 2016-July 2023, China underwent 25 and 20 FDA Bioresearch Monitoring (BIMO) inspections, respectively. The inspection results showing "No Action Indicated" (NAI) improved from 48.0% to 85.0%, while "Voluntary Action Indicated" (VAI) decreased from 44.0% to 15.0%. Official Action Indicated (OAI) measures were required in 2009 and 2012. Compared to the 2009-2015 period, there has been a clear upward trend in the quality of clinical trial data since 2016. From 2016 to July 2023, the number of new oncology drugs developed by Chinese pharmaceutical companies and included in professional guidelines has steadily increased. Specifically, 37 drugs (58.7%) were included in the 2022 edition of the CSCO guidelines, and 15 drugs (23.8%) were included in the 2023 edition of the NCCN guidelines, with 10 of these drugs featured in both guidelines.Conclusions:The implementation quality of clinical trials in China has gained a certain level of international recognition and competitiveness. This progress is attributed to national macro-level guidance, a unique institutional model, and clinical practices aligned with international standards. In the future, it will be necessary to further strengthen the scientific regulatory system and enhance clinical research capabilities to continue advancing the high-quality development of clinical trials.

The biological clock(also known as the circadian rhythm)is the fundamental reliance for all organisms on Earth to adapt and survive in the Earth's rotation environment.Circadian rhythm is the most basic regulatory mechanism of life activities,and plays a key role in maintaining normal physiological and biochemical homeostasis,disease occurrence and treatment.Recent studies have shown that the biologi-cal clock plays an important role in the development of oral tissues and in the occurrence and treatment of oral diseases.Since there is cur-rently no guiding literature on the research methods of biological clock in stomatology,researchers mainly conduct research based on pub-lished references,which has led to controversy about the research methods of biological clock in stomatology,and there are many confusions about how to rationally apply the research methods of circadia rhythms.In view of this,this expert consensus summarizes the characteristics of the biological clock and analyzes the shortcomings of the current biological clock research in stomatology,and organizes relevant experts to summarize and recommend 10 principles as a reference for the rational implementation of the biological clock in stomatology research.

Purpose To explore the value of contrast-enhanced ultrasound(CEUS)in the differential diagnosis of gallbladder polypoid lesions(GPLs)(diameter≥10 mm).Materials and Methods A prospective enrollment of 229 patients with GPLs who underwent cholecystectomy in 17 hospitals from December 1 2021 to June 30 2024 was conducted to analyze the relationship between general data,conventional ultrasound,CEUS characteristics and the nature of GPLs.Multivariate Logistic regression was employed to identify independent risk factors for neoplastic polyps,the differential diagnostic value of different indicators was compared.Results Among 229 patients with GPLs,there were 108 cases of cholesterol polyps,102 cases of adenoma and 19 cases of gallbladder cancer.Age(Z=-4.476,P<0.001),polyp number(χ2=15.561,P<0.001),diameter(Z=-8.149,P<0.001),echogenicity(χ2=9.241,P=0.010),vascularity(χ2=23.107,P<0.001),enhancement intensity(χ2=47.610,P<0.001),enhancement pattern(χ2=6.468,P=0.011),vascular type(χ2=84.470,P<0.001),integrity of gallbladder wall(χ2=7.662,P=0.006)and stalk width(Z=-9.831,P<0.001)between cholesterol polyps and neoplastic polyps were statistically significant.Age,location,diameter,echogenicity,enhancement pattern,vascular type and stalk width between adenoma and gallbladder cancer were statistically significant(Z=-4.333,-3.902,-5.042,all P<0.05).Multivariate Logistic regression analysis showed that hyper-enhancement,branched vascular type and stalk width were independent risk factors for neoplastic polyps(OR=4.563,5.770,3.075,all P<0.001).The combination of independent risk factors was better than single factor and diameter in the differential diagnosis of cholesterol polyps and neoplastic polyps(all P<0.01).Conclusion CEUS can effectively identify the nature of GPLs and provide a valuable imaging reference for the selection of treatment methods.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To investigate the diagnostic value of 62-slice spiral CT and its post-processing techniques for tibial plateau fracture(TPF)and its influence on treatment regimens selection.Methods A total of 173 TPF patients diagnosed and treated in our hospital from January 2021 to December 2022 were included,and the diagnostic accuracy,classification diagostic accuracy and fracture collapse degree accuracy of X-ray and CT scans were compared,with surgical and pathological diagnosis as the gold standard.Results CT and its post-processing technique can more clearly show the direction of fracture line,the displacement direction of fracture fragments and the collapse degree of articular surface than X-ray.The fracture morphology of 171 patients seen during the operation was consistent with CT and its post-processing images.The diagnostic accuracy of X-ray for TPF was 93.64%,which was lower than that of CT and its post-processing techniques(98.84% ),and the difference was statistically significant(χ2=6.474,P=0.011).The overall accuracy of X-ray in evaluating the degree of fracture collapse was significantly lower than that of CT 3D reconstruction(65.32% vs.90.75%;χ2=32.644,P<0.001).The total accuracy of CT and its post-processing techniques for TPF Schatzker classification(97.69% )was higher than that of X-ray(88.44% ),and the difference was statistically significant(χ2=11.462,P=0.001).Different CT reconstruction models had statistically significant difference on the total accuracy of TPF Schatzker classification diagnosis(χ2=40.647,P<0.001),and the diagnosis accuracy of volume reconstruction was the highest(96.53% ).Conclusion The application of CT and its post-processing techniques can effectively evaluate TPF,articular surface collapse and fracture classification,and provide imaging reference for clinical decision-making.

Objective:To establish a mesenchymal stem cell(MSC)-based in vitro cell model for the evaluation of mouse bone marrow acute graft-versus-host disease(aGVHD).Methods:Female C57BL/6N mice aged 6-8 weeks were used as bone marrow and lymphocyte donors,and female BALB/c mice aged 6-8 weeks were used as aGVHD recipients.The recipient mouse received a lethal dose(8.0 Gy,72.76 cGy/min)of total body γ irradiation,and injected with donor mouse derived bone marrow cells(1× 107/mouse)in 6-8 hours post irradiation to establish a bone marrow transplantation(BMT)mouse model(n=20).In addition,the recipient mice received a lethal dose(8.0 Gy,72.76 cGy/min)of total body γ irradiation,and injected with donor mouse derived bone marrow cells(1 × 107/mouse)and spleen lymphocytes(2 × 106/mouse)in 6-8 hours post irradiation to establish a mouse aGVHD model(n=20).On the day 7 after modeling,the recipient mice were anesthetized and the blood was harvested post eyeball enucleation.The serum was collected by centrifugation.Mouse MSCs were isolated and cultured with the addition of 2％,5％,and 10％recipient serum from BMT group or aGVHD group respectively.The colony-forming unit-fibroblast(CFU-F)experiment was performed to evaluate the potential effects of serums on the self-renewal ability of MSC.The expression of CD29 and CD105 of MSC was evaluated by immunofluorescence staining.In addition,the expression of self-renewal-related genes including Oct-4,Sox-2,and Nanog in MSC was detected by real-time fluorescence quantitative PCR(RT-qPCR).Results:We successfully established an in vitro cell model that could mimic the bone marrow microenvironment damage of the mouse with aGVHD.CFU-F assay showed that,on day 7 after the culture,compared with the BMT group,MSC colony formation ability of aGVHD serum concentrations groups of 2％and 5％was significantly reduced(P＜0.05);after the culture,at day 14,compared with the BMT group,MSC colony formation ability in different aGVHD serum concentration was significantly reduced(P＜0.05).The immunofluorescence staining showed that,compared with the BMT group,the proportion of MSC surface molecules CD29+and CD 105+cells was significantly dereased in the aGVHD serum concentration group(P＜0.05),the most significant difference was at a serum concentration of 10％(P＜0.001,P＜0.01).The results of RT-qPCR detection showed that the expression of the MSC self-renewal-related genes Oct-4,Sox-2,and Nanog was decreased,the most significant difference was observed at an aGVHD serum concentration of 10％(P＜0.01,P＜0.001,P＜0.001).Conclusion:By co-culturing different concentrations of mouse aGVHD serum and mouse MSC,we found that the addition of mouse aGVHD serum at different concentrations impaired the MSC self-renewal ability,which providing a new tool for the field of aGVHD bone marrow microenvironment damage.

Objective To explore the associations of parental smoking and alcohol consumption during the periconceptional period and their interactions with risk of congenital heart disease(CHD)in offspring.Methods The parents of children with simple CHD aged 0 to 1 year(n=683)were recruited as the case group,while the parents of healthy children aged 0 to 1 year(n=740)served as the control group.A case-control study was conducted,and a questionnaire was used to collect information on perinatal exposures.After controlling for relevant confounding factors using multivariate logistic regression analysis and propensity score matching,the associations of parental smoking and alcohol consumption during the periconceptional period and their interactions with CHD were examined,as well as the cumulative effects of smoking and drinking on CHD risk.Results Maternal active smoking(OR=2.91,95%CI:1.60-5.30),passive smoking(OR=1.94,95%CI:1.56-2.42),and alcohol consumption(OR=2.59,95%CI:1.89-3.54),as well as paternal smoking(OR=1.52;95%CI:1.22-1.90)and drinking(OR=1.48,95%CI:1.19-1.84),were associated with an increased risk of CHD in offspring.There was no interaction between parental smoking and drinking behaviors during the periconceptional period concerning the risk of CHD in offspring(P>0.05).The more parents'smoking and drinking behaviors during the perinatal pregnancy,the higher the risk of CHD in their offspring(OR=1.50,95%CI:1.36-1.65).Conclusions Parental smoking and alcohol consumption during the periconceptional period are associated with the occurrence of CHD in offspring,and there is a cumulative effect on CHD risk,suggesting that reducing tobacco and alcohol exposure during the periconceptional period may lower the incidence of CHD.

Objective To explore characteristics of co-infection of Chlamydia pneumoniae(Cpn)and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),and identify their effect on SARS-CoV-2-induced inflammatory response.Methods Patients with coronavirus disease 2019(COVID-19)who received treatment in a hospital in Chenzhou City from December 20,2022 to February 20,2023 were selected.According to the severity of COVID-19,severe and critical cases were classified as the severe symptom group,while mild and moderate cases were classified as the mild symptom group.Meanwhile,according to the age of patients(≥18 years old as adults,＜18 years old as juveniles),they were divided into the adult severe symptom group,adult mild symptom group,juvenile severe symptom group,and juvenile mild symptom group.Propensity score was adopted to match age,gender,and under-lying diseases of patients in severe symptom and mild symptom group in a 1∶1 ratio.Bronchoalveolar lavage fluid(BALF),throat swabs,and serum specimens of patients were collected.Cpn IgG/IgM antibody was detected by enzyme-linked immunosorbent assay(ELISA),levels of 12 common cytokines(including interleukin-8[IL-8])in BALF were detected by flow cytometry,differences among groups were compared.Results A total of 102 patients were included,with 61 severe and critical(severe symptom)patients,as well as 41 mild and moderate(mild symp-tom)patients.There were 71 patients aged ≥18 years and 31 juvenile patients aged＜18 years.There were 39 pa-tients in the adult severe symptom group and 32 in the adult mild symptom group,and 30 pairs were successfully matched through propensity score analysis.There were 22 patients in the juvenile severe symptom group and 9 in the juvenile mild symptom group,and 8 pairs were successfully matched through propensity score analysis.Among COVID-19 patients,the positive rates of Cpn IgG and IgM were 36.27％(n=37)and 8.82％(n=9),respective-ly,with 1 case positive for both Cpn IgG and IgM.The level of interferon(IFN)-α in serum specimens from adult patients with severe symptom combined with positive Cpn IgG was higher than that of IgG negative patients(P=0.037).There was no statistically significant difference in the levels of other cytokines in BALF and serum speci-mens between the two groups of patients(all P＞0.05).The levels of IL-8 and IL-17 in serum specimens of patients with positive Cpn IgG in the adult mild symptom group were both higher than those in Cpn IgG negative patients(both P＜0.05).The levels of IL-8 in both BALF and serum specimens from Cpn IgM positivity patients in the ju-venile mild symptom group were higher than those from patients with negative Cpn IgM(both P＜0.05).Logistic regression analysis results showed that Cpn IgG and IgM positivity were not risk factors for the development of se-vere COVID-19.Conclusion Combined Cpn infection is not a risk factor for the development of severe symptom in COVID-19 patients,and Cpn infection has limited impact on the secretion of inflammatory factors caused by SARS-CoV-2.