Objective To study the effect of IL-12 on Th1/Th2 cytokine expression level and the role of IL-12 in the shi ft ing of Th1/Th2 immune response against blood-stage Plasmodium b e ighei infection in mice. Methods [WT5”BZ ]BALB/c mice were infected with 5?105 parasitized RBC and received doses of 0.03 or 0.15 ?g/d of IL-12 on the day of infection and daily for 6 days post -in fection. The levels of IFN-? and IL-4 in sera or supernatants of splenic lymp hocyte cultured in vitro were detected by the EL ISA method. Results Compared with spleen cells fro m untreated mice, spleen cells from 0.03 ?g dose of IL-12-treated mice produ ced significantly higher level of Th1-associated cytokine IFN -?, but lower level of Th2-associated cytokine IL-4 in response to PHA or sA g stimulation on day 7 post-infection, whereas spleen cells from 0.15 ?g dose I L-1 2-treated mice produced significantly lower levels of IFN-? and IL-4. The le vel of IFN-? was apparent in the sera of mice treated with 0.03 or 0.15 ?g/d I L-12 on day 3 post-infection and peaked on the day 5 post-infection, but level of I FN-? even was significantly lower in mice treated with 0.15 ?g/d IL-12 comp ara ble to that in control mice on day 7 post-infection. The level of IFN-? was n ot detected in the sera of control mice through 7 days post-infection. [WT5” H Z] Conclusion Appropriate dose of IL-12 regulates the deve lop ment of resistance to P.berghei via a CD 4+ T h1 response, which involves the cytokines IFN-?. [HT5”SS] However, higher doses of IL-12 dramatically inhibite immune pro t ective ability, which may be detrimental to resistance against P .berghei infection. [

OBJECTIVETo evaluate efficacy of dexmedetomidine in preventing shivering after general anesthesia in women undergoing laparoscopic surgery.

METHODSEighty patients scheduled for laparoscopic gynecological surgery were randomized into dexmedetomidine group (n=40) and control group (n=40) to receive 1.0 µg/kg dexmedetomidine or an equal volume of saline slowly injected (for over 10 min) at 30 min before the anticipated completion of surgery. The postoperative incidences of shivering and the side effects were recorded.

RESULTSThe patients in the control group showed a significantly higher postoperative incidence of shivering (37.5%) than those in dexmedetomidine group (P<0.05). Heart rate and mean arterial pressure showed significant variations postoperatively in dexmedetomidine group (P<0.05), which had a significantly greater sedation score (P<0.05), a higher incidence of dry mouth (P=0.000), but a significantly lower incidence of nausea and vomiting than the control group (P<0.05).

CONCLUSIONDexmedetomidine can lower the incidence of shivering after general anesthesia for laparoscopic gynecological surgery.

Adult ; Anesthesia, General ; adverse effects ; Dexmedetomidine ; therapeutic use ; Female ; Gynecologic Surgical Procedures ; adverse effects ; methods ; Humans ; Laparoscopy ; adverse effects ; methods ; Prospective Studies ; Shivering ; Single-Blind Method

Objective:To investigate the effect of Astragaloside Ⅳ on high glucose-induced cardiomyocyte pyroptosis.Methods:H9c2 cells were cultured in vitro and divided into control group(5.5 mmol/L glucose), high glucose group(33.3 mmol/L glucose), Astragaloside Ⅳ group(33.3 mmol/L glucose+ 100μmol/L Astragaloside Ⅳ), and NLRP3 inhibitor group(33.3 mmol/L glucose+ 1μmol/L MCC950). Cell counting kit 8(CCK-8)was used to detect the activity of H9c2 cells.Lactate dehydrogenase(LDH)kit was used to detect the content of LDH in cell supernatant.Superoxide anion fluorescent probe(DHE)was used to detect the level of intracellular reactive oxygen species(ROS). Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)and Western blot were used to detect the mRNA and protein expression levels of pyroptosis-related genes.Immunofluorescence was used to detect the fluorescence intensity of NLRP3.Enzyme-linked immunosorbent assay(ELISA)was used to detect the level of inflammatory factors in cell supernatant.Results:When the concentration of Astragaloside Ⅳ was 100 μmol/L, it could significantly inhibit the decrease of cardiomyocyte viability induced by high glucose( P<0.01)and reduce LDH release( P<0.01). Compared with the control group, the level of ROS was increased( P<0.01), the mRNA and protein expressions of pyroptosis-related molecules were up-regulated( P<0.01 for all), the fluorescence intensity of NLRP3 was increased( P<0.01), and the levels of inflammatory factors in the cell supernatant were increased in the high glucose group( P<0.01). Compared with the high glucose group, the ROS level was decreased( P<0.01), the mRNA and protein expressions of pyroptosis-related molecules were down-regulated( P<0.05 or P<0.01), the fluorescence intensity of NLRP3 was decreased( P<0.01), and the levels of inflammatory factors in cell supernatant were decreased( P<0.05 or P<0.01)in Astragaloside Ⅳ group and inhibitor group. Conclusions:Astragaloside Ⅳ plays a protective role in high glucose-induced cardiomyocyte injury by inhibiting NLRP3/Caspase-1 signaling pathway and inhibiting pyroptosis.Moreover, it can improve the anti-inflammatory and antioxidant properties in cell models.

Objective:To delve into the intricate relationship between common genetic variations across the entire genome and the risk of non-syndromic cleft lip with or without cleft palate(NSCL/P).Methods:Utilizing summary statistics data from genome-wide association studies(GW AS),a thorough investigation to evaluate the impact of common variations on the genome were undertook.This involved assessing single nucleotide polymorphism(SNP)heritability across the entire genome,as well as within specific genomic regions.To ensure the robustness of our analysis,stringent quality control measures were applied to the GWAS summary statistics data.Criteria for inclusion encompassed the absence of missing values,a minor allele frequency≥1％,P-values falling within the range of 0 to 1,and clear SNP strand orientation.SNP meeting these stringent criteria were then meticulously included in our analy-sis.The SNP heritability of NSCL/P was calculated using linkage disequilibrium score regression.Addi-tionally,hierarchical linkage disequilibrium score regression to partition SNP heritability within coding re-gions,promoters,introns,enhancers,and super enhancers were employed,and the enrichment levels within different genomic regions using LDSC(v1.0.1)software were further elucidated.Results:Our study drew upon GWAS summary statistics data obtained from 806 NSCL/P trios,comprising a total of 2 418 individuals from the Chinese population.Following rigorous quality control procedures,490 593 out of 492 993 SNP were deemed suitable for inclusion in SNP heritability calculations.The observed SNP heritability of NSCL/P was 0.55(95％CI:0.28-0.82).Adjusting for the elevated disease pre-valence within our sample,the SNP heritability scaled down to 0.37(95％CI:0.19-0.55)based on the prevalence observed in the general Chinese population.Notably,our enrichment analysis unveiled significant enrichment of SNP heritability within enhancer regions(15.70,P=0.04)and super enhan-cer regions(3.18,P=0.03).Conclusion:Our study sheds light on the intricate interplay between common genetic variations and the risk of NSCL/P in the Chinese population.By elucidating the SNP heritability landscape across different genomic regions,we contribute valuable insights into the genetic basis of NSCL/P.The significant enrichment of SNP heritability within enhancer and super enhancer re-gions underscores the potential role of these regulatory elements in shaping the genetic susceptibility to NSCL/P.This paves the way for further research aimed at uncovering novel genetic pathogenic factors un-derlying NSCL/P pathogenesis.

One of the most common birth defects is cleft palate only (CPO) of which non-syndromic cleft palate only (NSCPO) accounts for 50%. NSCPO is a complex disease where multiple genes and environmental factors contribute to its risk. Unlike non-syndromic cleft lip with or without cleft palate (NSCL/P), previous genome-wide association studies only identified a few common genetic variations achieving genome-wide significance. This review summarizes the recent findings on genetic epidemiology of NSCPO. According to the current evidence, the candidate genes are divided into three categories: candidate genes with strong evidence, candidate genes with suggestive evidence, and candidate genes with inadequate evidence. The findings of epigenetic studies, the next generation sequencing studies, interaction analysis on NSCPO are also reviewed.