OBJECTIVES: This study aims to investigate the optimal dose ratio and mechanisms of the primary active components in Yinchenhao decoction (geniposide, chlorogenic acid, and rhubarb polysaccharides) for ameliorating metabolic-associated steatotic liver disease (MASLD). METHODS: C57BL/6 mice were randomly divided into the normal control group, model control group, uniform design groups 1-6, and Yinchenhao Decoction group; except for the normal control group, mice in all other groups were fed a Western diet to establish a MASLD model, and after 8 weeks of modeling, mice in the uniform design groups 1-6 and Yinchenhao Decoction group were given the corresponding drugs by gavage. At 12 weeks, all mice were sacrificed: their body weight and liver weight were measured, hematoxylin-eosin staining was used to observe the histopathological changes of liver tissue, the plasma levels of alanine transaminase (ALT) and aspartate transaminase (AST) were detected, and the levels of total cholesterol (TC) and triglycerides (TG) in plasma and liver were measured. Based on these results, the optimal uniform design group was identified; subsequently, with plasma AST, plasma TG, and liver TC levels as screening indicators, the optimal dose ratio was obtained via a regression equation, which was further verified from two dimensions, namely functional indicators and tissue morphology. Meanwhile, glucose tolerance test and insulin tolerance test were conducted to evaluate glucose metabolic homeostasis and insulin sensitivity in mice, periodic acid-Schiff staining was used to observe glycogen accumulation, quantitative reverse transcription-polymerase chain reaction was employed to detect the mRNA expression of genes related to glycolipid metabolism and bile acid metabolism, Western blotting was performed to measure the protein expression of molecules involved in bile acid metabolism, and commercial kits were used to determine the plasma levels of total bilirubin (TBIL), direct bilirubin (DBIL), and total bile acid (TBA). RESULTS: Combinations of geniposide, chlorogenic acid, and rhubarb polysaccharide all reduced the liver-to-body weight ratio, alleviated liver injury, and decreased lipid accumulation, among which the uniform design group 6 (200 mg/kg geniposide+160 mg/kg chlorogenic acid+340 mg/kg rhubarb polysaccharide) exhibited the optimal efficacy. Meanwhile, regression analysis indicated that the dosage ratio of uniform design group 6 was the optimal one for MASLD intervention. Validation experiments showed that, compared with single-drug intervention, the optimal dosage ratio resulted in significantly lower body weight, as well as lower plasma levels of ALT, AST and TC in mice (all P<0.05), along with a more pronounced reduction in the area of hepatic lipid accumulation. Mechanistic investigation experiments demonstrated that intervention with the optimal dosage ratio significantly improved glucose tolerance and insulin sensitivity in mice (all P<0.05), reduced hepatic glycogen deposition, and downregulated the mRNA expression of glycolipid metabolism-related genes such as Gsk3, G6pc, Pck1, Fbp1, Fasn, Srebp-1c, Scd1, Slc27a2, and Slc27a5 (all P<0.05); it also decreased plasma levels of TBIL, DBIL, and TBA (all P<0.05), reversed the abnormal protein expression of bile salt export pump (BSEP), farnesoid X receptor (FXR), and cholesterol-7α-hydroxylase (CYP7A1) in the liver (all P<0.05), and reversed the abnormal mRNA expression of bile acid metabolism-related genes including Nr1h4, Cyp7a1, Cyp27a1, Slc10a1, and Slco1a1 (all P<0.05). CONCLUSIONS The combination of geniposide (200 mg/kg), chlorogenic acid (160 mg/kg), and rhubarb polysaccharide (340 mg/kg) exerts the optimal ameliorative effect on MASLD in mice. This superior efficacy is presumably achieved by synergistically regulating the key nodes of glycolipid metabolism and bile acid metabolism, ultimately optimizing the therapeutic outcome.

Human NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavoenzyme expressed at high levels in multiple solid tumors, making it an attractive target for anticancer drugs. Bioactivatable drugs targeting NQO1, such as β-lapachone (β-lap), are currently in clinical trials for the treatment of cancer. β-Lap selectively kills NQO1-positive (NQO1⁺) cancer cells by inducing reactive oxygen species (ROS) via catalytic activation of NQO1. In this study, we demonstrated that cryptotanshinone (CTS), a naturally occurring compound, induces NQO1-dependent necrosis without affecting NQO1 activity. CTS selectively kills NQO1⁺ cancer cells by inducing NQO1-dependent necrosis. Interestingly, CTS directly binds to NQO1 but does not activate its catalytic activity. In addition, CTS enables activation of JNK1/2 and PARP, accumulation of iron and Ca²⁺, and depletion of ATP and NAD⁺. Furthermore, CTS selectively suppressed tumor growth in the NQO1⁺ xenograft models, which was reversed by NQO1 inhibitor and NQO1 shRNA. In conclusion, CTS induces NQO1-dependent necrosis via the JNK1/2/iron/PARP/NAD⁺/Ca²⁺ signaling pathway. This study demonstrates the non-enzymatic function of NQO1 in inducing cell death and provides new avenues for the design and development of NQO1-targeted anticancer drugs.

Objective To investigate the value of contrast-enhanced ultrasound(CEUS)liver imaging reporting and data system version 2017(LI-RADS v2017)in the differential diagnosis between hepatocellular carcinoma(HCC)and other hepatic malignancies(OM)less than or equal to 3 cm.Methods The clinical and imaging data of 163 liver lesions less than or equal to 3 cm in 126 patients with pathologically-confirmed liver malignancy were retrospectively analyzed.The patient underwent CEUS from Jan.2018 to Jun.2022 in our hospital,including 133 with HCC and 30 with OM.Nodules were classified based on the CEUS features according to the CEUS LI-RADS v2017.The evaluation of CEUS characteristics and CEUS LI-RADS v2017 in differential diagnosis of HCC and OM were calculated based on pathological findings.Results There were significant differences in the characteristics of arterial phase enhancement,timing of washout onset and washout degree between the HCC group and the OM group(all P＜0.001).The HCC group was mainly LR-3(20 lesions,15.04%),LR-4(25 lesions,18.80%)and LR-5(82 lesions,61.65%),and the OM group was mainly LR-M(28 lesions,93.33%).The specificity and positive predictive value of late washout for HCC were 93.33%(28/30)and 98.06%(101/103),respectively;and the sensitivity of early washout for OM was 93.33%(28/30).With LR-5 as the criterion to diagnose HCC,the sensitivity was 61.65%(82/133),the specificity was 93.33%(28/30),and the positive predictive value was 97.62%(82/84);with LR-4/5 as the criterion to diagnose HCC,the sensitivity was 80.45%(107/133),the specificity was 93.33%(28/30),and the positive predictive value was 98.17%(107/109),with the sensitivity of LR-4/5 being significantly higher than those of LR-5(P=0.001).With LR-M as the criterion to diagnose OM,the sensitivity was 93.33%(28/30)and the specificity was 95.49%(127/133).Conclusion The CEUS LI-RADS v2017 can effectively distinguish HCC from OM less than or equal to 3 cm.LR-5 has a low sensitivity for HCC,while LR-4/5 can improve the sensitivity for HCC.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective:To assess the nutritional status and risk of children with cyclic vomiting syndrome（CVS）and to provide a clinical evidence for nutritional support.Methods:A total of 160 children diagnosed with CVS and 160 healthy controls were prospectively enrolled in the study，who were admitted to Beijing Tsinghua Changgung Hospital from April 2021 to February 2024.Nutritional status was assessed by anthropometric indices（height，weight，and body mass index），and it was expressed in standard deviation score（Z score）.Nutritional risk screening tool STRONGkids was applied to nutritional risk screening，and the laboratory assessment（albumin，pre-albumin，hemoglobin，urea nitrogen and creatinine）were measured.Results:Among the 160 cases，there were 73 males and 87 females，including 18 cases of mild seizures and 142 cases of moderate and severe seizures，with the average onset age of（47.54±2.96）months and an average diagnosis age of（74.89±3.68）months.The average duration from the first attack to diagnosis was（27.35±2.36）months，and the average course of the disease was（41.35±2.63）months.The malnutrition rate of children in CVS was 36.9%（59/160），of which 18.1%（29/160）was severely malnourished.There was a statistically significant difference in the weight-for-age Z-score（WAZ），height-for-age Z-score（HAZ），and body mass index-for-age Z-score（BAZ）between the CVS group and the control group（ P<0.001）.We found a statistically significant difference in laboratory indicators（albumin，pre-albumin，hemoglobin，urea nitrogen and creatinine）between the two groups（all P<0.001）and hemoglobin was positively correlated with WAZ，HAZ and BAZ（ r=0.346,0.250,0.277，all P<0.01）.Using the STRONGkids nutritional risk screening tool，there were 43 cases with moderate nutritional risk and 117 cases with high nutritional risk，and children with high nutritional risk were likely to have lower WAZ，HAZ and BAZ than the children with moderate nutritional risk，and there was a significant difference in WAZ，HAZ，BAZ，hemoglobin，and creatinine between the two groups（ P<0.05）.And there was a correlation between the degree of CVS attack and nutritional risk grouping（ r=0.543， P<0.001）. Conclusion:Children with CVS have a high incidence of malnutrition，and the serum albumin，prealbumin，hemoglobin，urea nitrogen and creatinine levels are of great value for nutritional assessment.The STRONGkids score method helps to evaluate nutritional risk in children with CVS.

Objective:To investigate the characteristics of gut microbiota distribution in children with cyclic vomiting syndrome（CVS）complicated by constipation.Methods:The children with CVS, aged from 1 to 16 years, who were admitted to Beijing Tsinghua Changgung Hospital from June 2022 to January 2024, were divided into constipation group and normal group(non-constipation group) according to whether they were complicated with constipation or not.The clinical data and stool samples of children were collect. The abundance, diversity and composition of intestinal flora in fecal samples of two groups were detected by metagenomics sequencing.Results:A total of 20 children with CVS were collected, including 10 patients in constipation group and 10 patients in normal group.There were no significant differences in general demographic data between the two groups, including age at admission, age at first onset, body mass index, gender distribution, disease severity, endoscopic findings, and abdominal pain patterns.Microbiome analysis yielded 470 operational taxonomic units (OTUs), with 414 OTUs identified in normal group and 56 OTUs in constipation group. The abundance and diversity of intestinal flora in constipation group were significantly lower than those in normal group. Principal coordinate analysis and principal component analysis indicated significant structural differences in gut microbiota composition between the two groups. LEfSe analysis revealed distinct taxonomic patterns between the two groups, with the normal group demonstrating predominant representation of Firmicutes at the phylum level, while the constipation group showed higher relative abundance of Bacteroidetes and Actinobacteria. KEGG pathway analysis revealed that the carbon metabolism pathways was significantly enriched in the constipation group.Conclusion:There are significant differences in intestinal flora between CVS children with and without comorbid constipation.Bacteroides and Actinomycetes play an important role in constipation of children with CVS. The diversity and metabolic function of intestinal flora may be one of the pathological mechanisms of CVS complicated with constipation.

Objective:To analyze hemodynamic characteristics during the initial phase of the head-up tilt test (HUTT) in children with postural orthostatic tachycardia syndrome (POTS) and the value for predicting vasovagal syncope(VVS).Methods:This was a case-control study involving 123 POTS patients who underwent HUTT in the Pediatric Cardiovascular Department at the Children's Hospital,Capital Institute of Pediatrics,from January 2021 to August 2023.According to HUTT results,participants were divided into POTS combined with VVS group( n=82) and POTS group( n=41).The general conditions,clinical symptoms,24-hour urine sodium levels,and hemodynamics changes during the initial phase of HUTT between the two groups were compared. Results:The prevalence of POTS combined with VVS was 66.13% (82/123).There were no significant differences in age,sex,body mass index,24-hour urinary sodium,heart rate,heart rate variability,and maximum heart rate variability during the initial phase of HUTT between the two groups( P>0.05).Compared to the POTS group,the 10-minute systolic blood pressure(SBP10),10-minute diastolic blood pressure (DBP10),and 10-minute mean blood pressure(MBP10) in the POTS combined with VVS group were significantly lower [SBP10: 104(98.8,114.3) vs. 111(105,121.5)mmHg, Z=-3.071, P<0.05; DBP10: 63.44±8.36 vs. 68.29±6.43 mmHg, t=-3.265, P <0.05; MBP10: 78.31±9.74 vs. 83.28±7.30 mmHg, t =-2.879, P<0.05].Receiver operating characteristic curve analysis showed that DBP10,the difference between baseline DBP and DBP at 10-minute (△DBP10),and the in creasing rate of DBP10(△DBPR10) were predictive factors for POTS combined with VVS,with cut-off values of 67.5 mmHg (AUC=0.687,sensitivity 67.5%,specificity 72.0%),7.5 mmHg (AUC=0.633,sensitivity 43.9%,specificity 79.3%),and -2.84% (AUC=0.631,sensitivity 92.7%,specificity 31.7%),respectively.The combined predictive value was more significant (AUC=0.709, P<0.05),with sensitivity and specificity of 70.7% and 67.1%,respectively.In terms of age,DBP10 exhibited a higher predictive value in patients aged 13-18 years,with a DBP10 cut-off of 64.5 mmHg,AUC of 0.762,sensitivity of 92.7%,and specificity of 31.7%. Conclusion:The rate of HUTT-proven VVS in POTS was 66.13%.△DBP10,DBP10 and △DBPR10 have predictive value for POTS combined with VVS.Additionally,DBP10 shows a higher predictive value in patients aged 13-18 years.

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.