Objective To investigate the effect of Lianpu Yin on duodenal microinflammation in rats with functional dyspepsia(FD)by regulating NLRP3 activation.Methods Wistar rats were randomly divided into blank group and model group.FD rats were reconstructed by iodoacetamide method(2%sucrose solution containing 0.1%iodoacetamide),and the model was verified.FD model rats were randomly divided into model group,Lianpu Yin group and Moxapride group by random number expression method.After a period of two weeks of administration,measurements were taken to determine the body mass,three-hour food consumption,as well as the rates of gastric emptying and intestinal propulsion.The pathological structure of duodenal tissue was observed by HE staining.The serum levels of IL-1β and IL-18 were quantified using the enzyme-linked immunosorbent assay(ELISA)method.The expression levels of NLRP3 and Caspase-1 in each group were detected by Western blot.Expression levels of NLRP3 and Caspase-1 proteins were detected by immunofluorescence.Results Compared with the blank group,body weight,food intake at 3 h,gastric emptyand intestinal propulsion rate in model group were significantly decreased(P<0.01),and inflammatory infiltration of duodenum tissue appeared in the model group.Meanwhile,the expressions of NLRP3 and Caspase-1 proteins,as well as the levels of IL-1β and IL-18 in the duodenal tissue of the model group,showed significant increasing(P<0.05).Compared with the model group,rats in the Lianpu Yin and Moxapride groups displayed significant increasing in body weight,gastric emptying rate,and intestinal propulsion rate(P<0.01).Additionally,inflammatory infiltration of duodenum tissue reduced in these groups.Furthermore,NLRP3 and Caspase-1 protein expressions,as well as IL-1β and IL-18 levels,significantly decreased in the Lianpu Yin and Moxapride groups compared to the model group(P<0.05).Conclusion Lianpu Yin can treat FD rats by inhibiting duodenal microinflammation and then restoring gastrointestinal motility,which may be related to the abnormal activation of NLRP3 inflammasome.

AIM To study the chemical constituents from ethyl acetate fraction of Balanophora harlandii Hook.f.and their tyrosinase inhibitory activity.METHODS Separation and purification were performed using silica gel,MCI,ODS,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The monophenolase inhibitory activity was determined by the tyrosinase-catalyzed oxidation of L-tyrosine.RESULTS Twenty-four compounds were isolated and identified as sesamin(1),methyl caffeate(2),quercetin(3),5,7-dihydroxychromanone(4),methyl 3,4-dihydroxybenzoate(5),esculetin(6),kaempferol(7),naringenin(8),pyrogallic acid(9),pinosylvin(10),methyl propionate(11),caffeic acid(12),saccharinol(13),ferulic acid(14),trans-p-hydroxycinnamic acid(15),cinnamic acid(16),vanillic acid(17),vanillin(18),4-hydroxyacetophenone(19),4-hydroxybenzaldehyde(20),apigenin(21),(-)-isolariciresinol(22),(-)-secoisolariciresinol(23)and meso-2,3-di(3′,4′-methylenedioxybenzyl)butane-1,4-diol(24).The IC50 values of compounds 3,5,7,8,19,and 20 ranged from(0.246 5±0.028 3)to(1.278 2±0.021 3)mmol/L.CONCLUSION Compounds 1-9、11、15、17-21、24 are isolated from this plant for the first time,and 1,6,9,17-19,24 are first isolated from genus Balanophora.Compounds 3、5、7、8、19 and 20 have tyrosinase inhibitory activity.

Objective To explore the mechanism of Bushen Zhupai Decoction in treating ovarian fibrosis in polycystic ovary syndrome(PCOS)model rats based on IL-17/TRAF6/NF-κB signaling pathway.Methods Totally 60 SPF grade female SD rats were randomly divided into blank group,model group,Yousiyue group and TCM low-,medium-and high-dosage groups,with 10 rats in each group.The PCOS model was replicated by gavage of 1 mg/kg letrozole for 21 days.The Yousiyue group was given a 10 mg/kg solution of drospirenone ethinylestradiol tablets by gavage,TCM low-,medium-and high-dosage groups were given 8.82,17.64 and 35.28 g/kg of Bushen Zhupai Decoction by gavage,once a day for 28 consecutive days.HE and Masson staining were used to observe the morphology of ovarian tissue and ovarian fibrosis,the contents of serum IL-17,IL-18 and IL-1β were detected by ELISA,the mRNA expression of IL-17,TRAF6,NF-κB p65 and TGF-β1 in ovarian tissue were determined by RT-qPCR,the protein expression of TRAF6,NF-κB p65,TGF-β1,α-SMA,E-cadherin and the positive expression of IL-17RA,TRAF6,NF-κB p65,TGF-β1 and α-SMA in ovarian tissue were detected by Western blot and immunohistochemical staining respectively.Results Compared with the blank group,the body mass,ovarian mass and ovarian index significantly increased of rats in model group,with follicular cystic dilation,thinning of granulosa cell layer,and significant increase in fibrosis positive range(P<0.01),the serum contents of IL-17,IL-18 and IL-1β significantly increased(P<0.01),the expressions of IL-17,TRAF6,NF-κB p65,TGF-β1 mRNA and IL-17RA,TRAF6,NF-κB p65,TGF-β1 and α-SMA proteins significantly increased(P<0.01,P<0.05),the expression of E-cadherin protein significantly decreased(P<0.01).Compared with the model group,the ovarian index of rats in Yousiyue group and TCM medium-and high-dosage groups significantly decreased(P<0.01,P<0.05),the rats in TCM high-dosage group showed dominant follicles,increased thickness of granulosa cell layer,and significantly reduced fibrosis positive range(P<0.01),the serum contents of IL-17,IL-18 and IL-1β significantly decreased in Yousiyue group and TCM low-,medium-and high-dosage groups(P<0.01),the mRNA expressions of IL-17,TRAF6,NF-κB p65,TGF-β1,and the protein expressions of IL-17RA,TRAF6,NF-κB p65,TGF-β1 and α-SMA in ovarian tissue significantly decreaed in TCM high-dosage group(P<0.01,P<0.05),the expression of E-cadherin protein significantly increased(P<0.01).Conclusion Bushen Zhupai Decoction can decrease the body mass,improve the ovarian index,decrease the expressions of inflammatory factors and improve the status of ovarian fibrosis in PCOS rats.The mechanism may be related to the regulation of IL-17/TRAF6/NF-κB signaling pathway.

AIM To study the chemical constituents from salt-processed Litchi Semen and their antioxidant activities.METHODS The 85％ethanol extract from salt-processed Litchi Semen was isolated and purified by silica gel,Sephadex LH-20,MCI,ODS and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.DPPH and ABTS+free radical scavenging method were used to evaluate their antioxidant activities.RESULTS Fifteen compounds were isolated and identified as dehydrocostuslactone(1),ananosmoside A(2),funingensin A(3),(2S)-pinocembrin-7-O-(6-O-α-L-rhamnopyranosyl-β-D-glucopyranoside)(4),liquiritienin(5),quercetin(6),rutin(7),isorhamnetin-3-O-β-rutinoside(8),procyanidin A2(9),procyanidin A1(10),ethyl protocatechuate(11),5-hydroxymethylfurfural(12),di(2-ethyl-hexyl)phthalate(13),nicotinamide(14),(10E,15Z)-9,12,13-trihydroxyoctadeca-10,15-dienoic acid(15).Compounds 6-7,9-10 exhibited scavenging activities against DPPH radicals with IC50 values of(12.929±1.232),(14.104±0.946),(10.417±1.736),(6.944±0.030)μmol/L,respectively.Compounds 6-10 exhibited scavenging activities against ABTS+radicals with IC50 values of(21.952±0.577),(25.683±0.625),(22.970±1.336),(20.210±1.435),(18.725±0.324)μmol/L,respectively.CONCLUSION Compounds 1,5,14-15 are isolated from Litchi genus for the first time.Compounds 6-7,9-10 have strong in vitro antioxidant activities.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

Objective:To prepare ((2-(2-chlorophenyl)-3-(4-((2- 18F-fluoroethyl)oxy)phenyl)-5, 6, 7, 8-tetrahydrooxepino[3, 2-c]pyrazol-8-yl)amino)methanoic acid methyl ester ( 18F-JR-1001) and evaluate its binding affinity to the cannabinoid type 1 receptor (CB1R). Methods:18F-JR-1001 was synthesized using an integrated automated synthesis module, and its radiochemical yield (RCY) and molar activity were determined. Cell-specific uptake, lipid-water partition coefficient (log P), competitive binding assays, and in vitro stability tests were performed. Rimonabant-fed rat models (blocking group) with pre-occupied CB1R were established. Radioautography and microPET/CT imaging were conducted on both the blocking group and normal Sprague-Dawley (SD) rats to evaluate the brain uptake of 18F-JR-1001 and its blood-brain barrier (BBB) penetration capability. Results:The RCY of the synthetic 18F-JR-1001 after decay correction was (32.5±9.2)% ( n=10), with the molar activity of (194.6±67.3)GBq/μmol. Cell experiments demonstrated that 18F-JR-1001 exhibited specificity for CB1R, with log P of 3.40±0.11 ( n=3) and half-maximal inhibitory concentration of 0.975nmol/L. Within 3h at 37℃, the radiochemical purity of 18F-JR-1001 in physiological saline and blood remained above 92%, with no significant radioactive by-product peaks observed. Radioautography showed that the whole brain uptake of 18F-JR-1001 in the blocking group was 65.6% of that in normal SD rats. MicroPET/CT imaging showed that the mean whole brain uptake of 18F-JR-1001 in the blocking group was 0.4706, which was lower than that in normal SD rats (1.0561). Additionally, continuous scanning for 60min demonstrated that 18F-JR-1001 exhibited good BBB penetration capability. Conclusion:The synthesized 18F-JR-1001 meets the requirements of production and application, and is proved the potential as a CB1R-targeted tracer in the in vitro experiments, microPET/CT imaging and radioautography.

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

Objective To observe the value of nomogram of ultrasound combined with laboratory indexes for predicting axillary lymph node metastasis(ALNM)of stage cT1N0 breast invasive ductal carcinoma(IDC).Methods A total of 77 cases with pathologically diagnosed stage cT1N0 single breast IDC were retrospectively collected,including 23 cases with and 54 cases without ALNM.Univariate and multivariate binary logistic regression analysis were used to analyze clinical data,laboratory indicators and ultrasonic manifestations,then the independent predictors of ALNM of stage cT1N0 breast IDC were screened to establish laboratory indexes model,ultrasound model and combined model,respectively,and nomogram of the combined model was drawn.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive efficacy of each model.The consistency of results of combined model and actual results was analyzed using calibration curve.Decision curve analysis(DCA)was used to explore the clinical value of each model.Results Serum carbohydrate antigen 153(CA153)(OR=1.132),platelet-to-lymphocyte ratio(PLR)(OR=1.020)and echo attenuation behind the lesion on ultrasound(OR=8.789)were all independent predictors of ALNM in stage cT1N0 breast IDC(all P＜0.05),and the area under the curve(AUC)of laboratory indexes model,ultrasound model and combined model for predicting ALNM of stage cT1N0 breast IDC was 0.757,0.616 and 0.836,respectively.The consistency of the predicted results of combined model and actual results was good.When the threshold was higher than 0.15,the net benefit of combined model was higher than that of the other 2 models.Conclusion Nomogram of ultrasound combined with laboratory indexes could effectively predict ALNM of stage cT1N0 breast IDC.

Objective:To analyze the iodine nutrition status of children and adolescents and influencing factors in Zhejiang Province, providing scientific basis for optimizing iodine deficiency disorders (IDD) prevention and control strategies.Methods:In June 2022, a multistage stratified sampling method was used to divide 16 counties (cities, districts, abbreviated as counties) in Zhejiang Province into three categories based on their geographical locations (average distance from the coastline): coastal areas (including Dinghai District, Jiaojiang District, Sanmen County, Cixi City and Lucheng District), sub-coastal areas (including Wuxing District, Haining City, Linping District, Fuyang District and Fenghua District), and inland areas(including Suichang County, Changshan County, Shengzhou City, Jindong District, Dongyang City and Yongjia County). One county was selected from each category, and one township (street) was selected from each county. Two administrative villages (neighborhood committees) were selected from each township (street). Ten households including all children and adolescents aged 6-17 in each household were selected from each administrative village (neighborhood committee). Demographic information and personal dietary characteristics were collected via questionnaires, while household salt and a random urine sample were tested for iodine level. Trend analysis was conducted using a χ 2trend test, and a multivariate logistic stepwise regression model was used to analyze the influencing factors of urinary iodine levels. Results:A total of 755 children and adolescents aged 6-17 were selected, including 387 males (51.26%) and 368 females (48.74%), with an age of (11.24 ± 3.32) years. There were 269 children and adolescents in coastal areas (35.63%) and 409 children and adolescents in urban areas (54.17%). A total of 755 household salt samples were collected, with a median salt iodine concentration of 21.80 mg/kg. These included 263 non-iodized salt samples, 38 unqualified iodized salt samples, and 454 qualified iodized salt samples. The coverage rate of iodized salt was 65.17% (492/755), and the consumption rate of qualified iodized salt was 60.13% (454/755). The distribution of salt iodine quality among children and adolescents in different geographical locations showed statistically significant differences (χ 2 = 111.95, P < 0.001), with the proportion of non-iodized salt gradually decreasing from coastal areas to inland areas (χ 2trend = 90.17, P < 0.001). A total of 755 urine samples were collected, with a median urinary iodine concentration of 186.60 μg/L. The proportions of urinary iodine < 100, 100-199, 200-299, and ≥300 μg/L were 16.95% (128/755), 37.62% (284/755), 24.37% (184/755), and 21.06% (159/755), respectively. The χ 2trend test revealed a nonlinear positive correlation between salt iodine level and urinary iodine level (χ 2regression = 21.98, P < 0.001; χ 2partial = 6.96, P < 0.001). The frequency distribution of urinary iodine in children and adolescents from different geographical locations and between urban and rural areas showed statistically significant differences (χ 2 = 29.63, 16.56, P < 0.001). Among them, the proportion of children and adolescents with urinary iodine < 100 μg/L gradually decreasing from coastal areas to inland areas (χ 2trend = 6.15, P = 0.013). The results of multivariate logistic regression analysis revealed that sub-coastal regions, inland regions, and urban-rural regions ( OR = 1.57, 1.53, 1.64, 95% CI: 1.11-2.24, 1.03-2.27, 1.17-2.32, P < 0.05) were significantly associated with urinary iodine levels in children and adolescents aged 6-17. Conclusions:In 2022, the iodine nutrition of children and adolescents in Zhejiang Province is generally suitable, but there is a risk of iodine deficiency among coastal children and adolescents. Geographic location and urban/rural areas are influencing factors on iodine nutrition status of children and adolescents in Zhejiang Province.