Objective: To investigate the impact of RHAG 808A variant, commonly identified in the Chinese population, on RhAG protein, RhD and RhCE antigens expression through in vivo and in vitro expression analysis. Methods: A missense mutation of RHAG gene (c. 808G>A, p. Val270Ile) with high frequency was found in KMxD database. Bioinformatics analysis was performed using Polyphen-2 and Provean software. High resolution melting (HRM) method was utilized to screen for the variant carriers in the blood donors. The expression of RhAG protein, RhD and RhCE antigens on the surface of red cells of variant carriers were detected via flow cytometry. Wild-type and mutant vectors of RHAG were constructed and transfected into HEK 293T cells for in vitro expression analysis. Then, the expression of RhAG protein, RhD and RhCE antigens were analyzed by flow cytometry. Results: Polyphen-2 and Provean software suggested that the amino acid change (p. Val270Ile) of RhAG protein may be harmful or neutral respectively. Among the 999 blood donors from Guangzhou Blood Center, 4 homozygous carriers and 99 heterozygous carriers of RHAG 808A mutant allele were identified. The frequency of this allele was 5.4% (107/1 998). No significant differences in RhAG protein, RhD and RhCE antigens expression level was identified between the homozygous carriers, heterozygous carriers of RHAG 808A variant allele and the wild-type individuals. In vitro analysis for antigen expression study obtained the similar results. Conclusion: The RHAG 808A variant allele commonly identified in the Chinese population has no effect on the expression of RhAG protein, RhD and RhCE antigens, so the variant should be a population polymorphism site.

Objective To provide valuable insights for improving China’s special drug approval system by conducting an in-depth analysis of the practices of the U.S. Food and Drug Administration （FDA） in granting Emergency Use Authorizations （EUAs） for drugs. Methods A retrospective analysis was conducted on the FDA’s EUA decision-making process for COVID-19 therapeutics between January 2020 and June 2023. Results During the COVID-19 pandemic, the FDA adopted a series of regulatory science approaches to facilitate rapid approval of COVID-19 therapeutic drugs. The FDA granted EUA for a total of 15 COVID-19 therapeutic drugs and 4 COVID-19 vaccines, including expanded indications for marketed drugs, EUA for investigational drugs, revocation of EUA, and marketing after EUA. The main mechods for the rapid approval of EUA drugs by the FDA included the use of existing clinical trial data, omission of animal efficacy testing, merging of phase 1 and phase 2 clinical trials, and the use of clinical outcomes as surrogate endpoints, among other regulatory science methods. Conclusion The practices of the FDA in Emergency Use Authorization (EUA) of drugs, particularly its incorporation of regulatory scientific methods into the EUA process and the establishment of proactive monitoring mechanisms for drugs granted EUA, are worthy of emulation by China. It is suggested that China consider the experience of the FDA in the EUA system for drugs to further optimize and improve its special approval system for drugs.

Objective: To investigate the prevalence and influencing factors of dyslipidemia among residents in Chengdu City, so as to provide insights into improving the prevention and control of dyslipidemia. Methods: Based on the baseline survey of the Natural Population Cohort Study in Southwest China, residents aged 30 to 79 years was selected from 34 towns (communities) in 5 counties (districts) of Chengdu City using the multi-stage stratified cluster random sampling method in 2018. Demographic information and lifestyle behaviors were collected through questionnaires. Blood pressure, fasting blood glucose, serum uric acid, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were collected through physical examination and laboratory tests. A multivariable logistic regression model was used to identify the factors affecting dyslipidamia. Results: A total of 21 113 participants were surveyed, including 9 331 males (44.20%) and 11 782 females (55.80%), and had a mean age of (50.80±12.32) years. The prevalence rate of dyslipidemia was 35.64%, and the prevalence rates of high TG, low-HDL-C, high TC and high LDL-C were 17.25%, 11.88%, 10.11% and 7.35%, respectively. Multivariable logistic regression analysis identified gender (male, OR=1.584, 95%CI: 1.463-1.716), age (50 to 79 years old, OR：1.221-1.444, 95%CI: 1.079-1.632), residence (urban, OR=1.123, 95%CI: 1.052-1.198), marital status (not married, OR=1.246, 95%CI: 1.128-1.376), educational level (high school and above, OR=0.914, 95%CI: 0.849-0.983), current smoking (OR=1.220, 95%CI: 1.121-1.327), drinking (1 to 2 d/week, OR=1.525, 95%CI: 1.368-1.700; 3 to 5 d/week, OR=1.857, 95%CI: 1.575-2.191; almost every day, OR=1.512, 95%CI: 1.269-1.801), sedentary time in leisure time (>2 h/d, OR=1.123, 95%CI: 1.046-1.206), central obesity (OR=2.212, 95%CI: 1.986-2.265), hypertension (OR=1.489, 95%CI: 1.388-1.598), diabetes (OR=1.998, 95%CI: 1.833-2.157) and hyperuricemia (OR=2.012, 95%CI: 1.848-2.192) as factors affecting dyslipidemia. Conclusion The prevalence of dyslipidemia among residents in Chengdu City was mainly associated with smoking, drinking, sedentary time, central obesity, hypertension, diabetes and hyperuricemia.

【Objective】 To study the effect of RHAG variants identified in Chinese population on mRNA splicing by minigene splicing assay(MSA) in vitro. 【Methods】 The pSplicePOLR2G minigene expression plasmids were constructed for 10 RHAG mutations with relatively high distribution frequency in Chinese population near splicing sites or synonymous mutations by analyzing the RHAG gene data in the KMxD database. Then, the wild-type and mutant plasmids were transfected into HEK 293T cells, and RNA was extracted 48 hours after transfection. After reverse transcription, specific primers were used for PCR amplification, and then agarose gel electrophoresis and capillary electrophoresis were performed to determine whether the mutations will affect the normal splicing of exons. 【Results】 MSA in vitro showed that 2 mutations (c.158-5delT, c. 807+ 3A>C) near the splicing site reduced the amount of normal transcripts slightly. The remaining 8 synonymous mutations(c.312G>A, c. 341+ 3G>A, c. 609C>T, c. 681G>A, c. 861G>A, c. 957T>A, c. 984T>C and c. 1139-7G>A) had no impact on the splicing of RHAG mRNA. 【Conclusion】 This study showed that RHAG gene was conservative in terms of splicing, and the mutations near splicing sites and synonymous mutations were less likely to cause abnormal splicing of RHAG gene.

The association among plasma trimethylamine-N-oxide (TMAO), FMO3 polymorphisms, and chronic heart failure (CHF) remains to be elucidated. TMAO is a microbiota-dependent metabolite from dietary choline and carnitine. A prospective study was performed including 955 consecutively diagnosed CHF patients with reduced ejection fraction, with the longest follow-up of 7 years. The concentrations of plasma TMAO and its precursors, namely, choline and carnitine, were determined by liquid chromatography-mass spectrometry, and the FMO3 E158K polymorphisms (rs2266782) were genotyped. The top tertile of plasma TMAO was associated with a significant increment in hazard ratio (HR) for the composite outcome of cardiovascular death or heart transplantation (HR = 1.47, 95% CI = 1.13-1.91, P = 0.004) compared with the lowest tertile. After adjustments of the potential confounders, higher TMAO could still be used to predict the risk of the primary endpoint (adjusted HR = 1.33, 95% CI = 1.01-1.74, P = 0.039). This result was also obtained after further adjustment for carnitine (adjusted HR = 1.33, 95% CI = 1.01-1.74, P = 0.039). The FMO3 rs2266782 polymorphism was associated with the plasma TMAO concentrations in our cohort, and lower TMAO levels were found in the AA-genotype. Thus, higher plasma TMAO levels indicated increased risk of the composite outcome of cardiovascular death or heart transplantation independent of potential confounders, and the FMO3 AA-genotype in rs2266782 was related to lower plasma TMAO levels.
Carnitine ; Choline/metabolism* ; Chronic Disease ; Heart Failure/genetics* ; Humans ; Methylamines ; Oxygenases ; Prospective Studies

PURPOSE: The maximum width between the mesial and distal labial transitional line angles, described as “esthetic width” herein, could significantly influence the visual perception of the teeth and smile. This study aimed to conduct biometric research on esthetic width and to explore whether regular distribution exists in the esthetic width of human teeth. MATERIALS AND METHODS: A total of 4,264 maxillary and mandibular anterior teeth were measured using the Geomagic studio software program. The proportions of maxillary to mandibular homonymous teeth and proportions between the adjacent teeth were calculated. Bilateral symmetry and the correlation between the esthetic and mesiodistal widths were both accounted for during the measurement procedures. RESULTS: The mean esthetic widths were 6.773 ± 0.518 mm and 4.329 ± 0.331 mm for maxillary and mandibular central incisors, respectively, 5.451 ± 0.487 mm and 5.008 ± 0.351 mm for maxillary and mandibular lateral incisors, respectively, and 3.340 ± 0.353 mm and 5.958 ± 0.415 mm for maxillary and mandibular canines, respectively. Except for the mandibular canines, no significant difference in esthetic width was found among homonymous teeth from the same jaw. A high linear correlation was found between the esthetic and mesiodistal widths of the same tooth, except for the maxillary canines. Esthetic width proportions among different tooth categories showed some regular patterns, which were similar to those of the mesiodistal width. CONCLUSION Esthetic width is regularly distributed among the teeth in the Chinese population. This could provide an important reference for anterior dental restorations and dimension recovery in esthetic reconstruction of anterior teeth.

Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation. Currently, the therapeutic role of ferroptosis on cancer is gaining increasing interest. Baicalin an active component in

OBJECTIVE：To study the imp rovement effects of β-boswellic acid on hippocampal neurons cells injury of rats induced by oxygen-glucose deprivation. METHODS ：The hippocampal neurons cell of rats were divided into normal control group ， model group and β-boswellic acid low-concentration ，medium-concentration and high-concentration groups （1，10，100 μmol/L）. Except for normal control group ，other groups were cultured with relevant medium and given oxygen glucose deprivation to induce oxygen-glucose deprivation induced injury model. MTT assay was adopted to detect cell viability. Chemical colorimetry was used to detect LDH activity in cell culture supernatant. Hoechst-PI staining was used to detect the morphology change of cells. Flow cytometry was used to detect early apoptosis rate of cells. The expression of apoptosis-related protein （Bcl-2，Bax and cleaved caspase-3） were detected by Western blot. RESULTS ：Compared with model group ，the survival rate of cells and protein expression of Bcl- 2 were increased significantly in β-boswellic acid medium-concentration and high-concentration groups （P＜ 0.01），while LDH activity ，early apoptosis rate ，protein expression of cleaved caspase- 3 and Bax were all decreased significantly （P＜0.05 or P＜0.01）. The densely stained nuclei and fragmentation decreased significantly. CONCLUSIONS ：β-boswellic acid can relieve oxygen-glucose deprivation induced injury of hippocampal neurons cells ，the mechanism of which may be associated with down-regulating the protein expression of cleaved caspase- 3 and Bax and up-regulating the protein expression of Bcl- 2.

Esophageal squamous-cell carcinoma (ESCC) is one of the most lethal malignancies in the world and occurs at particularly higher frequency in China. While several genome-wide association studies (GWAS) of germline variants and whole-genome or whole-exome sequencing studies of somatic mutations in ESCC have been published, there is no comprehensive database publically available for this cancer. Here, we developed the Chinese Cancer Genomic Database-Esophageal Squamous Cell Carcinoma (CCGD-ESCC) database, which contains the associations of 69,593 single nucleotide polymorphisms (SNPs) with ESCC risk in 2022 cases and 2039 controls, survival time of 1006 ESCC patients (survival GWAS) and gene expression (expression quantitative trait loci, eQTL) in 94 ESCC patients. Moreover, this database also provides the associations between 8833 somatic mutations and survival time in 675 ESCC patients. Our user-friendly database is a resource useful for biologists and oncologists not only in identifying the associations of genetic variants or somatic mutations with the development and progression of ESCC but also in studying the underlying mechanisms for tumorigenesis of the cancer. CCGD-ESCC is freely accessible at http://db.cbi.pku.edu.cn/ccgd/ESCCdb.
Aged ; Asian Continental Ancestry Group ; genetics ; China ; epidemiology ; Databases, Genetic ; Esophageal Squamous Cell Carcinoma ; genetics ; Female ; Genetic Predisposition to Disease ; Genetic Variation ; Genome-Wide Association Study ; Humans ; Internet ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; genetics ; User-Computer Interface

Objective To investigate the effect and mechanism of emodin (EM) in renal interstitial fibrosis of unilateral ureteral obstruction (UUO) mice.Methods Male C57BL/6J mice were randomly divided into 4 groups,including sham operation group (n=8),UUO operation group (n=8),UUO operation+losartan (LST) group (n=8) and UUO operation+EM group (n=8).The mice in each group were ingested the suspensions by gavage for 14 days after surgery.Mice in UUO+LST and UUO+ EM groups were given 10 mg· kg-1· d-1 LST and 20 mg· kg-1 · d-1 EM,respectively.LST and EM were mixed with 0.5％ sodium carboxymethyl cellulose.Mice in sham group and UUO group were given 0.5％ sodium carboxymethyl cellulose.The mice were sacrificed at the 14th day.Interstitial fibrosis was observed by HE,Masson and PAS stain.Real-time PCR was used to detect LC3,Beclin-1 and mTOR mRNA.Protein expressions of TGF-β1,α-SMA,E-cadherin,LC3,Beclin-1,PI3K,p-Akt and mTOR were detected by Western blotting.The autophagy was observed with transmission electron microscopy in the renal tissue.Results Compared with sham mice,UUO mice at the 14th day displayed obvious renal fibrosis.Meanwhile,UUO mice had increased expressions of TGF-β1 and α-SMA (all P ＜ 0.01),and decreased expressions of E-cadherin (P ＜ 0.01).Their renal expressions of PI3K,p-Akt and mTOR were also raised (all P ＜ 0.01).Compared with those in UUO group,in UUO+LST group and UUO+EM group,expressions of autophagy protein LC3 and Beclin-1 were increased (all P ＜ 0.01),and the number of autophagic was increased.Additionally,expressions of TGF-β1 and α-SMA were reduced in UUO+LST group and UUO+EM group (all P ＜ 0.01),while the expression of E-cadherin was increased by emodin treatment (P＜ 0.05).And expressions of PI3K,p-Akt and mTOR were decreased in UUO + LST group and UUO + EM group (all P ＜ 0.05),meanwhile renal tissue fibrosis significantly reduced.Conclusions Emodin can promote autophagy,ameliorate renal interstitial fibrosis and protect renal function through PI3K/Akt/mTOR signaling pathway.