Humans ; Parathyroid Neoplasms/genetics* ; Molecular Biology ; Parathyroid Glands

OBJECTIVE To investigate the effects of the peroxisome proliferator-activated receptors δ （PPARδ） agonist GW501516 on the injury of pulmonary artery endothelial cells （PAECs） induced by hypoxia and its mechanism. METHODS The cytotoxic effects of GW501516 were observed by detecting the relative survival rate of PAECs； the protein expression of PPARδ was determined by Western blot assay. The cellular model of PAECs injury was established under hypoxic conditions； using antioxidant N-acetylcysteine （NAC） as positive control， the effects of GW501516 on cell injury and reactive oxygen species （ROS） production were investigated by detecting cell apoptotic rate， cell viability， lactate dehydrogenase （LDH） activity and ROS levels. Using nuclear factor erythroid 2-related factor 2（Nrf2） activator dimethyl fumarate （DMF） as positive control， PAECs were incubated with GW501516 and/or Nrf2 inhibitor ML385 under hypoxic conditions； the mechanism of GW501516 on PAECs injury induced by hypoxia was investigated by detecting cell injury （cell apoptosis， cell viability， LDH activity）， the levels of superoxide dismutase （SOD）， glutathione peroxidase （GPx）， catalase （CAT）， malondialdehyde （MDA） and ROS， the expressions of Nrf2， heme oxygenase-1 （HO-1） and cleaved-caspase-3 （C-caspase-3） protein. RESULTS The results demonstrated that hypoxia inhibited the protein expression of PPARδ （P＜0.05）， while GW501516 promoted the protein expression of PPARδ in hypoxia- exposed PAECs without obvious cytotoxic effects. GW501516 inhibited the apoptosis of PAECs， improved cell viability， and reduced LDH activity and ROS levels. GW501516 could up-regulate the protein expression of HO-1 in PAECs and the levels of SOD， GPx and CAT， while down-regulated the levels of MDA and ROS by activating the Nrf2 pathway （P＜0.05）； but Nrf2 inhibitor ML385 could reverse the above effects of GW501516 （P＜0.05）. GW501516 exerted similar effects to Nrf2 activator DMF in down-regulating the expression of C-caspase-3 and inhibiting the injury of PAECs under conditions of hypoxia （P＜0.05）. Moreover， Nrf2 inhibitor ML385 reversed the 163.com inhibition effects of GW501516 on PAECs injury （P＜0.05）. CONCLUSIONS GW501516 can relieve the hypoxia-induced injury of PAECs via the inhibition of oxidative stress， the mechanism of which may be associated with activating Nrf2.

Objective:To analyze the lympho-vascular space invasion (LVSI) in different molecular subtypes of the cancer genome atlas (TCGA) molecular subtypes of endometrial cancer (EC) and to evaluate the prognostic value of LVSI in EC patients with different molecular subtypes.Methods:A total of 258 patients diagnosed EC undergoing surgery in Peking University People′s Hospital from January 2016 to June 2022 were analyzed retrospectively. Among 258 patients, 14 cases were classified as POLE-ultramutated subtype, 43 as high-microsatellite instability (MSI-H) subtype, 155 as copy-number low (CNL) subtype, and 46 as copy-number high (CNH) subtype. Fifty-four patients were positive for LVSI, while 203 tested negative.Results:(1) The incidence of LVSI was found to be highest in the CNH subtype (32.6%,15/46), followed by the MSI-H subtype (27.9%, 12/43), the CNL subtype (16.9%, 26/154), and the POLE-ultramutated subtype (1/14), with statistically significant differences ( χ2=7.79, P=0.044). (2) Staging and deep myometrial invasion were higher in the LVSI positive group than those in the LVSI negative group (all P<0.05), except for the POLE-ultramutated subtype. The grade, lymph node metastasis, and the expression of nuclear antigen associated with cell proliferation (Ki-67) were significantly higher in LVSI positive patients than those in LVSI negative EC patients with both MSI-H and CNL subtypes (all P<0.05). In CNL subtypes patients, LVSI was also associated with age, histology subtype,and progesterone receptor (PR; all P<0.05). (3) Of the 257 EC patients, 25 cases recurred during the follow-up period, with a recurrence rate of 9.7% (25/257); among them, the recurrence rate of LVSI positive patients was 22.2% (12/54), which was significantly higher than those with LVSI negative (6.4%, 13/203; χ2=12.15, P<0.001). During the follow-up period, none of the 14 patients with POLE-ultramutated had recurrence; among CNL patients, the recurrence rate was 19.2% (5/26) in LVSI positive patients, which was significantly higher than that in LVSI negative ones (5.5%, 7/128; χ2=3.94, P=0.047); where as no difference were found in both MSI-H [recurrence rates in LVSI positive and negative patients were 2/12 and 9.7% (3/31), respectively] and CNH subtype [recurrence rates between LVSI positive and negative patients were 5/15 and 9.7% (3/31), respectively] EC patients (both P>0.05). After log-rank test, the 3-year recurrence free survival (RFS) rate were significantly lower in LVSI positive patients from CNL subtype and CNH subtype than those in LVSI negative patients (CNL: 80.8% vs 94.5%; CNH: 66.7% vs 90.3%; both P<0.05). (4) Lymph node metastasis ( HR=6.93, 95% CI: 1.15-41.65; P=0.034) had a significant effect on the 3-year RFS rate of EC patients with MSI-H subtype. Multivariate analysis revealed that PR expression ( HR=0.04, 95% CI: 0.01-0.14; P<0.001) was significantly associated with the 3-year RFS rate of CNL subtype patients. Conclusions:LVSI has the highest positivity rate in CNH subtype, followed by MSI-H subtype, CNL subtype, and the lowest positivity rate in POLE-ultramutated subtype. LVSI is significantly associated with poor prognosis in CNL subtype patients and may affect the prognosis of CNH subtype patients. However, LVSI is not an independent risk factor for recurrence across all four TCGA molecular subtypes.

AIM:To examine how the variation of the β1-adrenergic receptor gene affects the occurrence of ventricular arrhythmias and the prognosis over a 6-month period in individuals suffering from acute ST-segment elevation myocardial infarction(STEMI).METHODS:A study was conducted retrospectively,where patients diagnosed STEMI and treated at Yunfu City People's Hospital between January 2021 and February 2023 were included based on predefined criteria.The patients were then divided into three groups according to their genotypes of the β1-adrenergic receptor Arg389Gly gene polymorphism:CC group(Arg389Arg),CG group(Arg389Gly),and GG group(Gly389Gly).Discrep-ancies in initial clinical data upon admission[such as Killip classification,heart rate,systolic and diastolic blood pres-sure,left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVDD),and serum tumor necro-sis factor alpha(TNF-α),N-terminal pro-B-type natriuretic peptide(NT-proBNP),creatine kinase MB(CK-MB)and high-sensitivity C-reactive protein(hs-CRP)],and outcomes gathered during a 6-month follow-up via telephone after dis-charge(heart rate,NT-proBNP,CK-MB,LVEF,LVDD,and occurrences of major adverse cardiac events)were com-pared across the three groups.RESULTS:The study enrolled a total of 178 STEMI patients with ventricular arrhythmias,comprising 87 cases in CC group(48.9％),73 cases in CG group(41.0％),and 18 cases in GG group(10.1％).There were no notable variances in demographic characteristics such as age,sex,weight,BMI,smoking history,alcohol con-sumption history,comorbidities,blood pressure,heart rate,Killip classification(III amd IV),TNF-α,NT-proBNP,CK-MB,hs-CRP,LVEF and LVDD across the three groups(P>0.05).Following a 6-month monitoring period,the cardiac function parameters in CG and GG groups exhibited significant improvement compared to those in CC group(P<0.05),with noteworthy lower levels of NT-proBNP and CK-MB in GG group in contrast to CG group(P<0.05).Notably,there were significant discrepancies in the incidence of major adverse cardiac events during the follow-up period among the study groups,with 17 cases in CC group(19.5％),5 cases in CG group(6.9％),and 1 case in GG group(5.6％)(χ2=6.887,P<0.05).CONCLUSION:There is no correlation between the severity of STEMI accompanied by ventricular arrhyth-mias and the β1-adrenergic receptor Arg389Gly gene polymorphism.However,this gene variant is connected with en-hancements in cardiac function and short-term prognosis post-treatment.

China has classified the Corona Virus Disease 2019(COVID-19) as a statutory category B infectious disease and managed it according to Category B since January 8, 2023.In view that Omicron variant is currently the main epidemic strain in China, in order to guide the treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection in children with the times, refer to the Diagnosis and Treatment Protocol for Novel Coronavirus Infection (Trial 10 th Edition), Expert Consensus on Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fourth Edition) and the Diagnosis and Treatment Strategy for Pediatric Related Viral Infections.The Expert Consensus on the Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fifth Edition) has been formulated and updated accordingly on related etiology, epidemiology, pathogenic mechanism, clinical manifestations, auxiliary examination, diagnosis and treatment, and added key points for the treatment of COVID-19 related encephalopathy, fulminating myocarditis and other serious complications for clinical reference.

OBJECTIVE To analyze existing problems of pharmacoeconomic evaluation research in China and to improve the standardization and scientificity of research， so as to provide more high-quality evidence for government decision-making. METHODS Retrieved from CNKI， Wanfang database， VIP， PubMed， Web of Science from 2018 to 2022， the literature related to pharmacoeconomic evaluation in China was collected； Excel 2016 software was used to extract the key information of the included literature which met inclusion criteria. The Quality of Health Economic Studies （QHES） scale was used to evaluate the quality of the included literature. RESULTS A total of 113 pieces of literature were included in this study， involving 85 pieces of Chinese literature and 28 pieces of English literature. The overall score of QHES included literature was 65.7， of which the average score of Chinese literature was 62.0 and English literature was 76.9. The median quality scores for the literature in 2018， 2019， 2020， 2021 and 2022 were 62.0， 70.5， 59.3， 71.0， and 73.0， respectively. Of these， 65 pieces of literature reported the research perspective； 36 reported the discount rate indistinctly； 25 provided unclear definitions of thresholds； and 53 used two sensitivity analysis methods. Among different items of the QHES scale， item 2 （research perspective）， item 8 （time range and discount rate）， item 14 （potential bias） and item 16 （sources of funding） had low percentage of scores. CONCLUSIONS From 2018 to 2022， pharmacoeconomic evaluation literature published by Chinese academics has generally shown a fluctuating upward trend in terms of quality， but there is still some room for improvement. The main problems in current pharmacoeconomics research in China include unclear understanding of the research perspective， single measurement of cost and health outcomes， unreasonable design of time horizon， indistinct description of the threshold or discount rate， and lack of sensitivity analysis.

Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ dysfunction.Studies on the therapeutic effect and mechanism of immunomod-ulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various im-mune cells remain limited.This study aimed to investigate the protective effects and underlying mechanism of artesunate(ART)on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing(scRNA-seq)and experimental validations.The scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during sepsis.ART could restore neutrophils'chemotaxis and immune function in the septic spleen.It inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during sepsis.ART also promoted the differentiation and activity of splenic B cells in mice with sepsis.These results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the host.Overall,this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis,thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.

Objective:To confirm the reuse of mismatched regenerated motor axons of brachial plexus and explore the effect of target organs on their regeneration in a rat model.Methods:This study was carried out between January 2021 and December 2021 at the research laboratory of the Department of Microsurgery, Orthopaedic Trauma and Hand Surgery, the First Affiliated Hospital of Sun Yat-sen University. Animals were randomly assigned into 2 groups, as a regeneration group (RGen) with 5 subgroups and a reuse group (RUs) with 3 subgroups. There were 6 rats per subgroup with 42 rats in total. It was observed that in the groups of RGen1-4, after the transection and suture of the musculocutaneous nerve, the motor axons of the proximal end could accurately grow into the distal corresponding endoneural tube. It was also observed that in the mismatched regenerated group, motor axons were the axons that grew into the endoneurial tube of the lateral forearm cutaneous nerve (LFCN), and other non-target organ contacts were made to the regenerated nerves after mismatch. It was specifically further divided into RGen1, the group without an organ for nerve to make contact with; RGen2, the group with skin as the target organ with nerves contact by neurorrhaphy; RGen3, the group with skin as the target organ with originally reserved natural nerve contact; RGen4, the group with muscle as the target organ with nerves contact by neurorrhaphy and RGen5, a control group. After 8 weeks, the positive area (PA), mean density (MD) and integral optical density (IOD) were measured, with AChE and ChAT fluorescence staining of the medial branch of LFCN, to evaluate the regenerated nerves after mismatch. Of the RUs group, firstly, the innervating branches of the flexor carpi radialis (FCR) were dissected and exposed, then further assigned according to initially innervated FCR (RUs1), contacted with regenerated nerves after mismatch (RUs2) and denervated (RUs3), respectively. After 8 weeks, compound muscle action potential (CMAP) and wet weight ratio of FCR were taken. Masson staining of FCR was also performed to evaluate muscle reinnervation by the regenerated nerves after mismatch. Data analysis with One-Way ANOVA and Bonferroni 0.05 indicated a statistically significant difference.Results:In the RGen groups, after AChE staining, the PA, MD and IOD of RGen3 and RGen4 were higher than that of RGen1 and RGen5, and PA of RGen4 were higher than that of RGen2, with a statistically significant difference ( P<0.05). After ChAT staining, the values of PA and IOD of RGen3 and RGen4 were higher than that of RGen1 and RGen5, and PA of RGen4 were higher than that of RGen2, with a statistically significant difference ( P<0.05). In the RUs, electrophysiological assessment showed that no CMAP was observed in RUs3, there was no significant difference in Latency of RUs1 and RUs2. The difference was statistically significant ( P<0.05). Wet weight rate of muscle of RUs1 (98.91%±3.86%) was higher than that of RUs3 (86.67%±4.68%) with a statistically significant difference ( P<0.01), but no significant difference when compared with RU2 (92.74%±3.88%). Masson staining showed that the CVF value of RUs2 (8.61%±1.16%) was significantly higher than that of RUs1 (3.17%±0.76%), and statistic significantly lower than that of RUs3 (16.44%±2.26%)( P<0.01). Conclusion:Target organ contact can promote the regenerated nerves after mismatched regeneration, and the muscle target organs exhibit greater facilitation than the cutaneous target organs. Besides, regenerated nerves after mismatch can establish effective innervation with muscle target organs, comfirming their effective reuse.

The biological samples of oral genetic diseases and rare diseases are extremely precious. Collecting and preserving these biological samples are helpful to elucidate the mechanisms and improve the level of diagnose and treatment of oral genetic diseases and rare diseases. The standardized construction of biobanks for oral genetic diseases and rare diseases is important for achieving these goals. At present, there is very little information on the construction of these biobanks, and the standards or suggestions for the classification and coding of biological samples from oral and maxillofacial sources, and this is not conducive to the standardization and information construction of biobanks for special oral diseases. This consensus summarizes the background, necessity, principles, and key points of constructing the biobank for oral genetic diseases and rare diseases. On the base of the group standard "Classification and Coding for Human Biomaterial" (GB/T 39768-2021) issued by the National Technical Committee for Standardization of Biological Samples, we suggest 76 new coding numbers for different of biological samples from oral and maxillofacial sources. We hope the consensus may promote the standardization, and smartization on the biobank construction as well as the overall research level of oral genetic diseases and rare diseases in China.

Enamel formation is a complex physiological process that depends on the coordinated regulation of multiple mechanisms. This process is quite sensitive to various local and systemic interference factors. Therefore, during the long period from the embryonic stage to adolescence or even adulthood, various interference factors may lead to enamel developmental defects. Among them, early life is the most sensitive stage to environmental factors exposure, while it is also the critical period of enamel development of deciduous and permanent teeth. Environmental factors exposure during this period often leads to varying degrees of enamel development defects. In this review, we generalize the research progress of environmental factors affecting enamel developmental defects, summarize the potential mechanisms of environmental factors leading to enamel developmental defects, and conclude the clinical management strategies based on tertiary prevention. This work hopes to provide a theoretical basis for preventing abnormal teeth development from the critical time window of early life, propose eugenics health consultation and promote children ′s oral health management.