Objective To investigate the mechanism by which Senegenin(SEN)alleviates microglial inflammatory response through the nuclear factor erythroid 2-related factor 2(Nrf2)/NOD-like receptor protein 3(NLRP3)pathway.Methods BV2 mouse microglia cells were randomly divided into control group,model group,SEN group and MCC950 group.Cells in control group were not treated,and cells in model group were added with 1 μg/ml lipopolysaccharide(LPS);Cells in SEN group were added with 1 μg/ml LPS+4 μmol/L SEN,and cells in MCC950 group were added with 1 μg/ml LPS+10 μmol/L MCC950 for 24 hours.CCK-8 method was used to detect the effect of different concentrations of SEN on the viability of BV2 cells.Griess method was used to determine the release amount of nitric oxide(NO)in the supernatant.Real-time fluorescent quantitative PCR was used to determine the mRNA expression levels of NLRP3,lymphocyte apoptosis-associated spect-like protein containing a CARD(ASC),caspase-1,interleukin(IL)-1β and IL-18 mRNA.Immunofluorescence staining was used to detect the expression levels of ASC,IL-1β,Nrf2 and heme oxygenase-1(HO-1).Western blotting was used to detect the expression levels of NLRP3,caspase-1,ASC,IL-1β,IL-18,Nrf2,HO-1,nuclear factor kappa B(NF-κB)and inducible nitric oxide synthase(iNOS).Results The results of CCK-8 method showed that there was no significant difference in the viability of BV2 cells treated with 2～20 μmol/L SEN compared with control group(P>0.05).Compared with control group,the viability of BV2 cells in model group decreased significantly(P<0.05).Compared with model group,the viability of BV2 cells in 4 μmol/L SEN group was significantly restored(P<0.05).Compared with control group,the results of Griess method showed that the release amount of NO in cells of model group increased significantly(P<0.05);the results of real-time PCR showed that the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 mRNA in cells of model group increased significantly(P<0.05);the results of Western blotting showed that the protein expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 proteins in cells of model group increased significantly(P<0.05),and the immunofluorescence staining results showed that the expression levels of iNOS and NF-κB protein in cells of model group increased,and the expression levels of Nrf2 and HO-1 decreased,with statistically significant differences(P<0.05).Compared with model group,the release amount of NO in cells of SEN group and MCC950 group decreased,and the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 mRNA and proteins decreased,with statistically significant differences(P<0.05);in the SEN group,the expression levels of iNOS and NF-κB decreased,and immunofluorescence staining showed that Nrf2 was translocated into the nucleus,and the expression levels of Nrf2 and HO-1 proteins increased significantly,with statistically significant differences(P<0.05).Conclusions SEN could alleviate the inflammatory response of mouse microglia cells induced by LPS and inhibit the activation and expression of NLRP3 inflammasome,with an effect comparable to that of the inflammasome inhibitor MCC950.The mechanism may be related to the regulation of the expression of upstream factors Nrf2 and HO-1.

Recently, male reproductive health has attracted extensive attention, with the adverse effects of circadian disruption on male fertility gradually gaining recognition. However, the mechanism by which circadian disruption leads to damage to male reproductive system remains unclear. In this review, we first summarized the dual regulatory roles of circadian clock genes on the male reproductive system: (1) circadian regulation of testosterone synthesis via the hypothalamic-pituitary-testicular (HPT) and hypothalamic-pituitary-adrenal (HPA) axes; (2) non-circadian regulation of spermatogenesis. Next, we further listed the possible mechanisms by which circadian disruption impairs male fertility, including interference with the oscillatory function of the reproductive system, i.e., synchronization of the HPT axis, crosstalk between the HPT axis and the HPA axis, as well as direct damage to germ cells by disturbing the non-oscillatory function of the reproductive system. Future research using spatiotemporal omics, epigenomic assays, and neural circuit mapping in studying the male reproductive system may provide new clues to systematically unravel the mechanisms by which circadian disruption affects male reproductive system through circadian clock genes.
Male ; Humans ; Animals ; Circadian Clocks/physiology* ; Hypothalamo-Hypophyseal System/physiology* ; Circadian Rhythm/genetics* ; Spermatogenesis/physiology* ; Pituitary-Adrenal System/physiology* ; Testis/physiology* ; Testosterone/biosynthesis* ; CLOCK Proteins ; Infertility, Male/physiopathology*

A high-performance liquid chromatography method using pre-column derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate was developed to determine the content of 15 amino acids in the medicinal snakes Bungarus Parvus, Agkistrodon, and Zaocys. The results showed that the total amino acid(TAA) content ranged from 277.13 to 515.05 mg·g~(-1), with the top four amino acids in all three species being glutamic acid(Glu), glycine(Gly), aspartic acid(Asp), and lysine(Lys). The essential amino acid(EAA) content ranged from 74.56 to 203.94 mg·g~(-1), with Agkistrodon exhibiting the highest content. The non-essential amino acid(NEAA), semi-essential amino acid(semi-EAA), and medicinal amino acid(MAA) content ranged from 189.06 to 318.23, 12.89 to 33.53, and 179.83 to 342.33 mg·g~(-1), respectively, with Zaocys having the highest content in these categories. Amino acid nutritional value was evaluated using the amino acid ratio(RAA), amino acid ratio coefficient(RCAA), and amino acid ratio coefficient score(SRCAA), and the results indicated that all three medicinal snakes possessed good nutritional value. The amino acid composition was similar across the species, though significant differences in content were observed. Based on these differences, an orthogonal partial least squares-discriminant analysis(OPLS-DA) model was established, which could clearly distinguish between the three medicinal snake species. The key differences in amino acid content included Gly, tyrosine(Tyr), Glu, and serine(Ser), which may be related to the observed clinical application differences among the species. Further research into the mechanisms of these differential amino acids is expected to provide more insights into the clinical application disparities of these three medicinal snake species.
Amino Acids/chemistry* ; Animals ; Nutritive Value ; Chromatography, High Pressure Liquid ; Snakes/classification* ; Bungarus

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To observe the therapeutic efficacy and mechanism of Gushi Zaizao Pills for steroid-induced osteonecrosis of the femoral head(SONFH).Methods Male SD rats were randomly divided into normal group,model group,Xianling Gubao Capsules group and Gushi Zaizao Pills group.Except for the normal group,the rats in all other groups were replicated the SONFH model.After successful modeling,the continuous drug administration was carried out for six weeks.The thymus and spleen of the rats were taken to calculate the immune organ indices,the contents of interleukin 1β(IL-1β)and tumor necrosis factor α(TNF-α)in rat synovial fluid were detected by enzyme-linked immunosorbent assay(ELISA),the percentage of empty lacunae and area ratio of trabecular bone was detected by hematoxylin-eosin(HE)staining,and the femoral head parameters[reduction of bone volume fraction(BV/TV),trabecular number(Tb.N),trabecular thickness(Tb.Th)and trabecular separation(Tb.Sp)]were analyzed by Micro-CT,and bone strength of femoral head was detected by small animal bone strength tester.Results Compared with the normal group,the spleen and thymus indicators were significantly decreased in the model group,the levels of IL-1β and TNF-α in rat synovial fluid were significantly increased,the percentage of empty lacunae was increased,the area ratio of trabecular bone was decreased,the BV/TV,Tb.N and Tb.Th were decreased,the Tb.Sp was increased,the bone strength of femoral head was significantly decreased,the differences being all statistically significant(P＜0.05 or P＜0.01).Compared with the model group,the spleen and thymus indicators were significantly increased in Xianling Gubao Capsules group and Gushi Zaizao Pills group,the levels of IL-1β and TNF-α in rat synovial fluid were decreased,the percentage of empty lacunae was significantly decreased,the area ratio of trabecular bone was significantly increased,the BV/TV,Tb.N and Tb.Th were increased,the Tb.Sp was decreased,and the bone strength of femoral head was significantly increased,the differences being all statistically significant(P＜0.05 or P＜0.01).Conclusion Gushi Zaizao Pills can effectively prevent the further development of SONFH by regulating cellular immunity and reducing the secretion of inflammatory factors,thereby reducing the pathological damage of the femoral head and enhancing the bone strength.

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*

Objective To investigate the effect of caloric restriction(CR)on myocardial ischemia/reperfusion injury(MI/RI)in mice and its mechanism.Methods C57 mice were randomly divided into normal diet group(AL group,free feeding)and CR group(diet decreased by 10% every 2 weeks)for 8 weeks and monitored for weight changes.Each group was divided into sham operation group and MI/RI group,total 4 groups,AL + Sham group,AL + I/R group,CR + Sham group and CR + I/R group).The left anterior descending coronary artery was ligated for 30 minutes and then reperfused for 24 hours in mice of MI/RI group and mice in Sham group were only threaded but not ligated.The mice were determined for myocardial ischemia and infarct size by Evans blue/TTC staining,observed for the pathology of myocardium by HE staining,determined for the activities of lactate dehydrogenase(LDH),superoxide dismutase(SOD)and the contents of creatine kinase-MB(CK-MB)and malondialdehvde(MDA)in myocardium by the corresponding kits,determined for serum levels of IL-1β and IL-18 by ELISA and detected for the expression of pyroptosis-associated proteins in myocardium by Western blot.Results After 8weeks,the weights of mice in CR group[(24.54 ± 0.41)g]were significantly lower than those in AL group[(31.46 ±0.25)g](t = 14.34,P<0.05).Compared with those in AL + I/R group,the area of myocardial ischemia in CR + I/R group showed no significant difference(t = 0.783 0,P>0.05),while the area of myocardial infarction decreased significantly(t = 7.250,P<0.01);The myocardial arrangement was relatively neat,and the degree of pathological changes was obviously reduced;LDH activity,CK-MB and MDA contents decreased significantly(t = 4.331,2.875 and 5.343 respectively,each P<0.05),while SOD activity increased significantly(t = 4.211,P<0.05);Serum levels of IL-1β and IL-18 decreased significantly(t = 3.375 and 4.266 respectively,each P<0.05);The expression levels of nod-like receptor protein 3(NLRP3),gasdermin D(GSDMD),apoptosis-associated speckle-like protein(ASC)and caspase-1 significantly decreased(t = 3.412,3.420,3.480 and 2.585 respectively,each P<0.05).Conclusion CR alleviated MI/RI in mice,and its mechanism was related to the inhibition of cardiac pyroptosis.

Objective: To describe the current status and trends in the treatment of patent ductus arteriosus (PDA) among very preterm infants (VPI) admitted to the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) from 2019 to 2021, and to compare the differences in PDA treatment among these units. Methods: This was a cross-sectional study based on the CHNN VPI cohort, all of 22 525 VPI (gestational age<32 weeks) admitted to 79 tertiary NICU within 3 days of age from 2019 to 2021 were included. The overall PDA treatment rates were calculated, as well as the rates of infants with different gestational ages (≤26, 27-28, 29-31 weeks), and pharmacological and surgical treatments were described. PDA was defined as those diagnosed by echocardiography during hospitalization. The PDA treatment rate was defined as the number of VPI who had received medication treatment and (or) surgical ligation of PDA divided by the number of all VPI. Logistic regression was used to investigate the changes in PDA treatment rates over the 3 years and the differences between gestational age groups. A multivariate Logistic regression model was constructed to compute the standardized ratio (SR) of PDA treatment across different units, to compare the rates after adjusting for population characteristics. Results: A total of 22 525 VPI were included in the study, with a gestational age of 30.0 (28.6, 31.0) weeks and birth weight of 1 310 (1 100, 1 540) g; 56.0% (12 615) of them were male. PDA was diagnosed by echocardiography in 49.7% (11 186/22 525) of all VPI, and the overall PDA treatment rate was 16.8% (3 795/22 525). Of 3 762 VPI who received medication treatment, the main first-line medication used was ibuprofen (93.4% (3 515/3 762)) and the postnatal day of first medication treatment was 6 (4, 10) days of age; 59.3% (2 231/3 762) of the VPI had been weaned from invasive respiratory support during the first medication treatment, and 82.2% (3 092/3 762) of the infants received only one course of medication treatment. A total of 143 VPI underwent surgery, which was conducted on 32 (22, 46) days of age. Over the 3 years from 2019 to 2021, there was no significant change in the PDA treatment rate in these VPI (P=0.650). The PDA treatment rate decreased with increasing gestational age (P<0.001). The PDA treatment rates for VPI with gestational age ≤26, 27-28, and 29-31 weeks were 39.6% (688/1 737), 25.9% (1 319/5 098), and 11.4% (1 788/15 690), respectively. There were 61 units having a total number of VPI≥100 cases, and their rates of PDA treatment were 0 (0/116)-47.4% (376/793). After adjusting for population characteristics, the range of standardized ratios for PDA treatment in the 61 units was 0 (95%CI 0-0.3) to 3.4 (95%CI 3.1-3.8). Conclusions: From 2019 to 2021, compared to the peers in developed countries, VPI in CHNN NICU had a different PDA treatment rate; specifically, the VPI with small birth gestational age had a lower treatment rate, while the VPI with large birth gestational age had a higher rate. There are significant differences in PDA treatment rates among different units.
Infant ; Infant, Newborn ; Male ; Humans ; Female ; Ductus Arteriosus, Patent/drug therapy* ; Infant, Premature ; Cross-Sectional Studies ; Ibuprofen/therapeutic use* ; Infant, Very Low Birth Weight ; Persistent Fetal Circulation Syndrome ; Infant, Premature, Diseases/therapy*

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.