Objective:To observe the genetic variation of SH2B3 in patients with myeloid neoplasms.Methods:The results of targeted DNA sequencing associated with myeloid neoplasms in the Department of Hematology,Xuanwu Hospital,Capital Medical University from November 2017 to November 2022 were retrospectively analyzed,and the patients with SH2B3 gene mutations were identified.The demographic and clinical data of these patients were collected,and characteristics of SH2B3 gene mutation,co-mutated genes and their correlations with diseases were analyzed.Results:The sequencing results were obtained from 1 005 patients,in which 19 patients were detected with SH2B3 gene mutation,including 18 missense mutations(94.74％),1 nonsense mutation(5.26％),and 10 patients with co-mutated genes(52.63％).Variant allele frequency(VAF)ranged from 0.03 to 0.66.The highest frequency mutation was p.Ile568Thr(5/19,26.32％),with an average VAF of 0.49,involving 1 case of MDS/MPN-RS(with SF3B1 mutation),1 case of MDS-U(with SF3B1 mutation),1 case of aplastic anemia with PNH clone(with PIGA and KMT2A mutations),2 cases of MDS-MLD(1 case with SETBP1 mutation).The other mutations included p.Ala567Thr in 2 cases(10.53％),p.Arg566Trp,p.Glu533Lys,p.Met437Arg,p.Arg425Cys,p.Glu314Lys,p.Arg308*,p.Gln294Glu,p.Arg282Gln,p.Arg175Gln,p.Gly86Cys,p.His55Asn and p.Gln54Pro in 1 case each.Conclusion:A wide distribution of genetic mutation sites and low recurrence of SH2B3 is observed in myeloid neoplasms,among of them,p.Ile568Thr mutation is detected with a higher incidence and often coexists with characteristic mutations of other diseases.

Liver size is regulated by circadian clock and exhibits a diurnal rhythm. Pregnane X receptor (PXR) and peroxisome proliferator-activated receptor α (PPARα), members of nuclear receptor superfamily, are important regulators of liver size. We previously demonstrated that mPXR agonist pregnenolone 16α-carbonitrile (PCN) and mPPARα agonist pirinixic acid (WY-14643) promoted liver enlargement and liver regeneration after partial hepatectomy. However, whether PXR or PPARα activation-induced liver enlargement exhibits diurnal rhythm with normal liver diurnal oscillations remains unclear. The aim of this study was to investigate the diurnal rhythm of PXR or PPARα activation-induced liver enlargement. Male C57BL/6 mice were intraperitoneally injected with corn oil, PCN or WY-14643 for three days, and liver samples were weighed and collected at various time points for analysis. The animal experiment protocol was reviewed and approved by Institutional Animal Care and Use Committee of Sun Yat-sen University (approval No. SYSU-IACUC-2023-001613, SYSU-IACUC-2023-001783). The results showed that PXR or PPARα activation at various time points significantly induced liver enlargement, and liver size maintained normal diurnal oscillations during PXR or PPARα activation-induced hepatomegaly, without significant effects on the expression of core clock genes. This study reveals PXR or PPARα activation-induced liver enlargement exhibits diurnal rhythm with normal liver diurnal oscillations, and provides novel data for nuclear receptor-induced liver enlargement and liver diurnal rhythm.

Objective: To describe the distribution characteristics of hypertension among adult twins in the Chinese National Twin Registry (CNTR) and to provide clues for exploring the role of genetic and environmental factors on hypertension. Methods: A total of 69 220 (34 610 pairs) of twins aged 18 and above with hypertension information were selected from CNTR registered from 2010 to 2018. Random effect models were used to describe the population and regional distribution of hypertension in twins. To estimate the heritability, the concordance rates of hypertension were calculated and compared between monozygotic twins (MZ) and dizygotic twins (DZ). Results: The age of all participants was (34.1±12.4) years. The overall self-reported prevalence of hypertension was 3.8%(2 610/69 220). Twin pairs who were older, living in urban areas, married, overweight or obese, current smokers or ex-smokers, and current drinkers or abstainers had a higher self-reported prevalence of hypertension (P<0.05). Analysis within the same-sex twin pairs found that the concordance rate of hypertension was 43.2% in MZ and 27.0% in DZ, and the difference was statistically significant (P<0.001). The heritability of hypertension was 22.1% (95%CI: 16.3%- 28.0%). Stratified by gender, age, and region, the concordance rate of hypertension in MZ was still higher than that in DZ. The heritability of hypertension was higher in female participants. Conclusions: There were differences in the distribution of hypertension among twins with different demographic and regional characteristics. It is indicated that genetic factors play a crucial role in hypertension in different genders, ages, and regions, while the magnitude of genetic effects may vary.
Adult ; Female ; Humans ; Male ; Alcohol Drinking ; Diseases in Twins/genetics* ; Hypertension/genetics* ; Twins, Dizygotic/genetics* ; Twins, Monozygotic/genetics*

Objective: To describe the distribution characteristics of hyperlipidemia in adult twins in the Chinese National Twin Registry (CNTR) and explore the effect of genetic and environmental factors on hyperlipidemia. Methods: Twins recruited from the CNTR in 11 project areas across China were included in the study. A total of 69 130 (34 565 pairs) of adult twins with complete information on hyperlipidemia were selected for analysis. The random effect model was used to characterize the population and regional distribution of hyperlipidemia among twins. The concordance rates of hyperlipidemia were calculated in monozygotic twins (MZ) and dizygotic twins (DZ), respectively, to estimate the heritability. Results: The age of all participants was (34.2±12.4) years. This study's prevalence of hyperlipidemia was 1.3% (895/69 130). Twin pairs who were men, older, living in urban areas, married,had junior college degree or above, overweight, obese, insufficient physical activity, current smokers, ex-smokers, current drinkers, and ex-drinkers had a higher prevalence of hyperlipidemia (P<0.05). In within-pair analysis, the concordance rate of hyperlipidemia was 29.1% (118/405) in MZ and 18.1% (57/315) in DZ, and the difference was statistically significant (P<0.05). Stratified by gender, age, and region, the concordance rate of hyperlipidemia in MZ was still higher than that in DZ. Further, in within-same-sex twin pair analyses, the heritability of hyperlipidemia was 13.04% (95%CI: 2.61%-23.47%) in the northern group and 18.59% (95%CI: 4.43%-32.74%) in the female group, respectively. Conclusions: Adult twins were included in this study and were found to have a lower prevalence of hyperlipidemia than in the general population study, with population and regional differences. Genetic factors influence hyperlipidemia, but the genetic effect may vary with gender and area.
Adult ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; China/epidemiology* ; Diseases in Twins/genetics* ; Hyperlipidemias/genetics* ; Metabolic Diseases ; Twins, Dizygotic ; Twins, Monozygotic/genetics*

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Objective: To describe the distribution characteristics of type 2 diabetes in twins in Chinese National Twin Registry (CNTR), provide clues and evidence for revealing the influence of genetic and environmental factors for type 2 diabetes. Methods: Of all twins registered in the CNTR during 2010-2018, a total 18 855 twin pairs aged ≥30 years with complete registration information were included in the analysis. The random effect model was used to describe the population and area distribution characteristics and concordance of type 2 diabetes in twin pairs. Results: The mean age of the subjects was (42.8±10.2) years, the study subjects included 10 339 monozygotic (MZ) twin pairs and 8 516 dizygotic (DZ) twin pairs. The self-reported prevalence rate of type 2 diabetes was 2.2% in total population and there was no sighificant difference between MZ and DZ. Intra-twin pairs analysis showed that the concordance rate of type 2 diabetes was 38.2% in MZ twin pairs, and 16.0% in DZ twin pairs, the difference was statistically significant (P<0.001). The concordance rate of type 2 diabetes in MZ twin parts was higher than that in DZ twin pairs in both men and women, in different age groups and in different areas (P<0.05). Further stratified analysis showed that in northern China, only MZ twin pairs less than 60 years old were found to have a higher concordance rate of type 2 diabetes compared with DZ twin pairs (P<0.05). In southern China, the co-prevalence rate in male MZ twin pairs aged ≥60 years was still higher than that in DZ twin pairs (P<0.05). Conclusion: The twin pairs in this study had a lower self-reported prevalence of type 2 diabetes than the general population. The study results suggested that genetic factors play a role in type 2 diabetes prevalence in both men and women, in different age groups and in different areas, however, the effect might vary.
Adult ; China/epidemiology* ; Diabetes Mellitus, Type 2/genetics* ; Diseases in Twins/genetics* ; Female ; Humans ; Male ; Middle Aged ; Registries ; Twins, Dizygotic ; Twins, Monozygotic/genetics*

Objective: To describe the distribution characteristics of coronary heart disease in adult twins recruited from Chinese Twin Registry (CNTR), and provide clues and evidence for the effect of genetic and environmental influences on coronary heart disease. Methods: By using the data of CNTR during 2010-2018, a total of 34 583 twin pairs aged ≥18 years who completed questionnaire survey and had related information were included in the current study to analyze the population and area distribution characteristics of coronary heart disease. Random effect models were used to compare the differences between groups. The concordane rate of coronary heart disease were calculated respectively in monozygotic (MZ) twin pairs and dizygotic (DZ) twin pairs to estimate the heritability. Results: The twin pairs included in this analysis were aged (34.2±12.4) years. The overall prevalence rate of coronary heart disease in twin pairs was 0.7%. Twin pairs who were women, older, obese and lived in northern China had higher prevalence of coronary heart disease (P<0.05). Intra-pair analysis in the same-sex twin pairs found that the concordane rate of coronary heart disease was higher in MZ twin pairs (25.3%) than in DZ twins (7.4%), and the difference was statistically significant (P<0.001). The overall heritability of coronary heart disease was 19.3% (95%CI: 11.8%-26.8%). Stratified by gender, age and area, the concordane rate was still higher in MZ twin pairs than in DZ pairs. Participants who were women, aged 18-30 years or ≥60 years and lived in northern China had a higher heritability of coronary heart disease. Conclusion: The distribution of coronary heart disease in twin pairs differed in populations and areas. The prevalence of coronary heart disease was affected by genetic factors, but the effect varied with age, gender and area.
Adolescent ; Adult ; China/epidemiology* ; Coronary Disease/genetics* ; Diseases in Twins/genetics* ; Female ; Humans ; Male ; Twins, Dizygotic ; Twins, Monozygotic/genetics*

Objective: To explore the gene-lifestyle interaction on coronary heart disease (CHD) in adult twins of China. Methods: Participants were selected from twin pairs registered in the Chinese National Twin Registry (CNTR). Univariate interaction model was used to estimate the interaction, via exploring the moderation effect of lifestyle on the genetic variance of CHD. Results: A total of 20 477 same-sex twin pairs aged ≥25 years were recruited, including 395 CHD cases, and 66 twin pairs both had CHD. After adjustment for age and sex, no moderation effects of lifestyles, including current smoking, current drinking, physical activity, intake of vegetable and fruit, on the genetic variance of CHD were found (P>0.05), suggesting no significant interactions. Conclusion: There was no evidence suggesting statistically significant gene-lifestyle interaction on CHD in adult twins of China.
Adult ; China/epidemiology* ; Coronary Disease/genetics* ; Diseases in Twins/genetics* ; Humans ; Life Style ; Twins/genetics* ; Twins, Dizygotic ; Twins, Monozygotic

ObjectiveTo investigate the therapeutic effect of Xuebijing injection （XBJ） on sodium taurocholate （Na-Tc）-induced severe acute pancreatitis （SAP） in rats. MethodForty rats were randomly assigned into 5 groups： sham operation group， SAP model group， and low-， medium-， and high-dose （4， 8， 12 mL·kg·d^-1， respectively） XBJ groups. SAP model was established by retrograde injection of Na-Tc （1 mL·kg^-1） into the biliary and pancreatic ducts. XBJ was injected intraperitoneally 3 days before and 0.5 h after modeling. The ascitic fluid volume and the pancreas weight-to-body weight ratio were measured. The pathological changes of pancreatic tissue were observed via hematoxylin-eosin （HE） staining. The protein levels of formyl peptide receptor 1 （FPR1） and nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） in pancreatic tissue were detected by immunohistochemistry. Western blot was employed to determine the expression levels of NADH-ubiquinone oxidoreductase chains 1-6 （MT-ND1， MT-ND2， MT-ND3， MT-ND4， MT-ND5， and MT-ND6） in rat plasma. ResultCompared with sham operation group， the SAP model group showcased increased ascitic fluid volume and pancreas weight-to-body weight ratio （P<0.05）， serious lesions in pancreatic tissue， increased total pathological score （P<0.05）， and up-regulated protein levels of FPR1 and NLRP3 in pancreatic tissue （P<0.05）. The model group had lower MT-ND2 level （P<0.05） and higher MT-ND1， MT-ND3， and MT-ND6 levels in plasma （P<0.05） than the sham operation group， while MT-ND4 and MT-ND5 had no significant differences between the two groups. Compared with SAP model group， the XBJ treatment decreased ascitic fluid volume and pancreas weight-to-body weight ratio （P<0.01）， ameliorated pancreatic lesions， and down-regulated the protein levels of FPR1 and NLRP3 in pancreatic tissue （P<0.01）. The treatments， especially high-dose XBJ （P<0.01）， down-regulated the expression of MT-ND1 （P<0.01）， MT-ND3 （P<0.01）， MT-ND6 （P<0.01）， and MT-ND4 and did not change that of MT-ND5. ConclusionXBJ may antagonize partial mitochondrial N-formyl peptides and excessive inflammatory response mediated by FPR1/NLRP3 to treat SAP in rats.