The biotransformation processes in the human body play a crucial role in maintaining the inter-nal environment's stability by converting exogenous compounds and endogenous metabolites into substances with increased polarity or water solubility.This alteration in toxicity or pharmacological effects facilitates their excretion from the body.Sulfation,an important type of phase Ⅱ biotransformation reaction,is primarily me-diated by members of the cytosolic sulfotransferases(also known as sulfotransferases,SULTs)superfamily.Recent studies have uncovered the significant roles of SULTs in drug metabolism,tumorigenesis,inflammato-ry responses,hormone regulation,and energy metabolism.This article provides a comprehensive review of the regulatory roles and molecular mechanisms of the SULTs superfamily members in carbohydrate and lipid me-tabolism,aiming to offer new insights into the mechanism research and drug development for disorders related to carbohydrate and lipid metabolism dysregulation.

Objective To analyze the main epidemiological characteristics of fungal infection in this hospital in the past 7 years,and to provide reference for clinical treatment and prevention and control strategies of fun-gal infection.Methods The fungal data and clinical data of related patients isolated from clinical samples in Peking Union Medical College Hospital from early January 2018 to the end of May 2024 were selected,and the main epidemiological characteristics of fungal infection in this hospital were identified and described through multi-angle statistical analysis.Results A total of 4 479 patients with filamentous fungal infection were en-rolled.The proportion of male patients[57.5％(2 576/4 479)]was higher than that of female patients[42.5％(1 903/4 143)],mainly distributed in internal medicine,Intensive Care Unit(ICU)and emergency de-partment,among which internal medicine accounted for the highest proportion[50.0％(2 241/4 479)].About 90.0％of the specimens were from the lower respiratory tract,in addition to specimens from skin and soft tis-sue,tissue,ear and blood culture.In terms of seasonal distribution,there are more patients in winter.The fun-gi were mainly composed of Aspergillus,Mucor,Cerdosporium,Fusarium and Penicillium,among which As-pergillus was the most abundant,accounting for 74.6％of the total.Aspergillus fumigatus was the most a-bundant Aspergillus,accounting for 42.5％of the total Aspergillus(1 418/3 340).Among the related infec-tions caused by mold,Aspergillus was the most common in the lower respiratory tract,accounting for 76.8％.Among them,Aspergillus fumigatus accounted for the highest proportion(33.6％).98.6％of the molds infected the ear were Aspergillus,of which Aspergillus niger and Aspergillus terreus were the most common.Skin infections are mainly caused by Sporothrix schenckii,Trichophyton rubrum,Microsporum ca-nis.The results of in vitro drug sensitivity test showed that the four common Aspergillus isolated in this hos-pital were sensitive to voriconazole,and amphotericin B had better antifungal activity against Mucorales in vitro.Conclusion Based on the main epidemiological characteristics of fungal infections in this hospital,it is recommended that special attention be paid to the admission of patients in the respiratory department during the peak infection period in autumn and winter.In the treatment of fungal infections in different regions and on different body parts,attention should be paid to the differences in the distribution of bacterial species.

Objective:To retrieve, screen, evaluate and integrate the relevant evidence of nursing management for patent foramen ovale detected by contrast transesophageal echocardiography (cTEE) to provide a basis for clinical practice.Methods:A systematic search was conducted in relevant Chinese and English databases, guideline websites, and professional association websites such as China National Knowledge Infrastructure, Wanfang database, PubMed, and MedLink, etc. Relevant literatures on the detection of patent foramen ovale by cTEE were included, including guidelines, expert conconsensus, clinical decisions, evidence summaries, and systematic reviews. The search period was from the establishment of the database to July 31, 2024. Two evidence-based nursing researchers evaluated the quality of the literature and extracted relevant evidence in combination with clinical situations.Results:A total of 15 literatures were included. Among them, there were 3 guidelines, 6 expert consensuses, 3 clinical decisions, 2 quasi-experiments, and 1 systematic review. Thirty pieces of evidence were summarized from five aspects: assessment, education and publicity, preparation before examination, detection during examination, care after examination.Conclusions:The best evidence for the nursing management of patent foramen ovale detected by cTEE is of high quality and strong authority, which can provide evidence-based basis for standardizing clinical practice and accurately and efficiently detecting patent foramen ovale.

Objective To explore the association of the TSLP gene polymorphisms at rs3806932,rs11466741 and rs2289278 loci with childhood asthma and serum TSLP levels,and to analyze the effects of gene-environment interactions on asthma risk in children.Methods A total of 145 children with asthma and 108 healthy controls were included.Genotyping was performed using KASP and MassARRAY SNP technologies,and serum TSLP levels were measured by ELISA.Differences in allele and genotype frequencies between the two groups were analyzed,along with the impact of genetic models on asthma risk.Differences in serum TSLP levels across groups were compared.Linkage disequilibrium and haplotype analysis were performed using Haploview 4.2,and GMDR 0.9 software was used to assess gene-environment interactions.Results No significant differences were found in the allele and genotype frequencies of the three TSLP gene loci between the two groups(P＞0.05).Under the co-dominant model,children with the AG genotype at the rs3806932 locus had 1.750 times the risk of developing asthma compared to those with the AA genotype(95％CI:1.018-3.010,P=0.043).Under co-dominant and overdominant models,children with the CT genotype at the rs11466741 locus had 1.705 times the asthma risk compared to those with the CC genotype(95％CI:1.006-2.891,P=0.048),and 1.698 times the risk compared to those with the CC-TT genotype(95％CI:1.019-2.827,P=0.041).Serum TSLP levels were significantly higher in asthma patients with the CT genotype than those with the CC genotype at the rs11466741 locus(P=0.032).Serum TSLP levels were higher in the asthma group with allergic rhinitis(AR)compared to the group without AR(P＜0.01).No significant differences were observed in the distribution of haplotypes frequencies(AC,GT,GC)between the two groups(P＞0.05).GMDR analysis showed that the highest asthma risk was observed in children with heterozygous genotypes(CT,AG)at both rs11466741 and rs2289278,or those with the CT genotype at rs11466741,a history of passive smoking,and a cesarean section delivery(P＜0.05).Conclusion Polymorphisms in the TSLP gene at rs3806932 and rs11466741 are associated with an increased risk of childhood asthma.Variants at the rs11466741 locus affect serum TSLP levels in children with asthma.Asthma combined with AR leads to elevation of serum TSLP levels.The interaction between rs11466741 and rs2289278,along with environmental factors(passive smoking and cesarean section),contributes to the increase of asthma risk in children.

Objective:To investigate the interaction of risk factors for diabetic retinopathy (DR) occurrence.Methods:A cross-sectional study was performed.A total of 6 783 diabetic patients with complete survey data from 2005 to 2018 in the National Health and Nutrition Survey database were enrolled, among which 4 426 patients were included according to inclusion criteria and were divided into non-DR diabetes group of 3 491 cases and DR group of 935 cases.The related risk factors were collected, including age, gender, race, residential status, education, annual household income, body mass index (BMI), fasting glucose, glycosylated hemoglobin, duration of diabetes, family history of diabetes, comorbidities, smoke, alcohol use, sleep, physical activity.Patient Health Questionnaire (PHQ-9) was used to assess the psychological status.After the categorization of all variables, risk factors of DR were analyzed by logistic regression, and the interaction between factors was further analyzed.Results:Multivariate analysis showed that female[odds ratio ( OR)=1.33, 95% confidence interval ( CI): 1.02-1.72], duration of diabetes ≥10 years ( OR=1.03, 95% CI: 1.02-1.04), insulin therapy ( OR=2.38, 95% CI: 1.87-3.05), urinary albumin creatinine ratio (UACR) ≥30 mg/g ( OR=1.55, 95% CI: 1.22-1.96) and depression ( OR=1.44, 95% CI: 1.13-1.83) were risk factors for DR, and BMI≤28 kg/m 2 ( OR=0.70, 95% CI: 0.55-0.89) was a protective factor for DR.Furthermore, interaction analysis revealed additive interaction between UACR ≥30 mg/g and insulin therapy [relative excess risk due to interaction ( RERI)=2.46, 95% CI: 0.84-4.09, attributable proportion due to interaction ( AP)=0.44, 95% CI: 0.26-0.63, synergy index ( S)=2.16, 95% CI: 1.37-3.41).The UACR ≥30 mg/g and longer diabetic duration ≥10 years had both multiplicative ( OR=1.67, 95% CI: 1.00-2.76) and additive interactions ( RERI=2.02, 95% CI: 0.79-3.25, AP=0.47, 95% CI: 0.27-0.66, S=2.53, 95% CI: 1.37-4.68). Conclusions:Patients with diabetes treated with insulin, with a duration of diabetes ≥10 years and accompanied by UACR ≥30 mg/g are at higher risk of developing DR than those with a single risk factor.

Objective:To develop a pre-processing workflow of real world data (RWD) derived from multicenter clinical laboratories so that the level of data standardization can be improved, and subsequently to produce more robust real world evidence (RWE).Methods:Purpose sampling was used to invite senior experts with experience in clinical research utilizing RWD, covering the fields of clinical laboratory, epidemiology, biostatistics, and clinical medicine. In-depth, semi-structured individual interviews were conducted and thematic analysis was used to analyze the collected data.Results:The in-depth interviews were completed in 16 experts. The experts unanimously agreed that pre-processing RWD derived from multicenter clinical laboratories is necessary prior to its application in research. Based on experts' insights, a comprehensive pre-processing workflow for RWD was constructed, comprising six key steps: ①developing a variable list based on research questions and distributing it to each clinical laboratory; ②conducting an initial quality assessment of RWD based on existing quality control results in clinical laboratories; ③cleaning the data; ④determining whether RWD (including categorical and continuous variables) is heterogeneity among different clinical laboratories; ⑤exploring potential sources of heterogeneity;⑥pre-processing RWD based on identified causes contributing to heterogeneity.Conclusion:The pre-processing workflow of RWD was established, to provide a methodological reference for controlling systematic errors in RWD derived from multicenter clinical laboratories, thereby enhancing the validity of RWE.

Objective To investigate the clinical and metabolic factors associated with the development and regression of metabolic dysfunction-associated fatty liver disease(MAFLD)in the physical examination population.Methods A retrospective observational study was conducted on 6 809 individuals who underwent physical examination in a physical examination institution in Beijing from December 2013 to December 2019,with a mean follow-up time of 52.1±13.5 months.According to the new diagnostic criteria for MAFLD,these individuals were divided into MAFLD group and non-MAFLD group,and the two groups were compared in terms of demographic indicators,body measurement indicators,and laboratory indicators at the first(baseline)and last physical examinations.The two-independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test was used for comparison of categorical data.A Logistic regression analysis was used to investigate the impact of various observation indicators on the development and regression of MAFLD.Results In this study,there were 4 533 individuals(66.6%)in the non-MAFLD group at baseline,among whom 15.6%developed MAFLD at the last physical examination.Compared with the non-MAFLD population,the MAFLD population had significantly higher age(Z=-6.739),number of male patients(χ2=178.534),body weight(Z=-22.302),body mass index(BMI)(Z=-22.818),waist circumference(Z=-23.117),hip circumference(Z=-18.446),systolic blood pressure(SBP)(Z=-13.301),diastolic blood pressure(DBP)(Z=-13.491),fasting blood glucose(FBG)(Z=-11.787),triglyceride(TG)(Z=-16.623),low-density lipoprotein cholesterol(LDL-C)(Z=-10.256),alanine aminotransferase(ALT)(Z=-14.250),aspartate aminotransferase(AST)(Z=-7.481),and proportion of patients with metabolic syndrome(MetS)at baseline(χ2=185.283),and there were more patients with increases in body weight,waist circumference,hip circumference,TG,TC,ALT,and AST at the final physical examination(all P<0.05);these patients had a lower level of HDL-C at baseline(Z=15.416),and there were more patients with a reduction at the last physical examination(P<0.05).There were 2 276 individuals(33.4%)in the MAFLD group at baseline,among whom 23.8%showed regression of MAFLD at the last physical examination.Compared with the population without regression of MAFLD,the population with regression of MAFLD had a significantly younger age(Z=2.185),a significantly higher number of female patients(χ2=0.340),significantly lower levels of body weight(Z=-8.909),BMI(Z=-10.205),waist circumference(Z=-11.183),hip circumference(Z=-7.178),SBP(Z=-3.627),DBP(Z=-3.443),TG(Z=-5.945),ALT(Z=-9.664),and AST(Z=-5.904),and a significantly lower proportion of patients with MetS(χ2=42.082),and there were more patients with reductions in body weight,waist circumference,hip circumference,blood pressure,TG,TC,ALT,and AST at the final physical examination(all P<0.05);these patients had a higher level of HDL-C at baseline(Z=6.778),and there were more patients with an increase at the last physical examination(P<0.05).The multivariate Logistic regression analysis showed that sex and changes in body weight and HDL-C during physical examination were independently associated with the development and regression of MAFLD(all P<0.05).Conclusion There is a relatively high prevalence rate of MAFLD among the physical examination population in Beijing,with a higher proportion of male patients.There are significant metabolic disorders and liver function abnormalities,and changes in body weight and HDL-C are the most important predictive indicators for the development and regression of MAFLD.

OBJECTIVES: To investigate the efficacy of Ag₂Se nanoparticles for eliminating intracellular Porphyromonas gingivalis (P. gingivalis) in esophageal cancer and examine the effect of P. gingivalis clearance on progression of esophageal cancer. METHODS: Ag₂Se nanoparticles were synthesized via a chemical synthesis method. The effects of Ag₂Se nanoparticles on P. gingivalis viability and colony-forming ability were assessed using fluorescence staining and colony formation assays. In a mouse model bearing subcutaneous murine esophageal cancer cell allograft with P. gingivalis infection, the effect of treatment with Ag₂Se nanoparticles on the abundance of P. gingivalis in the tumor tissues was quantified using RNAscope in situ hybridization and quantitative polymerase chain reaction (qPCR), and the changes in tumor volume were monitored. The biosafety of Ag₂Se nanoparticles was assessed by examining liver and kidney functions and pathological changes in the major organs of the mice. RESULTS: Transmission electron microscopy revealed that the synthesized Ag₂Se nanoparticles were uniformly dispersed spherical particles with a diameter around 50 nm. In vitro experiments demonstrated that exposure to Ag₂Se nanoparticles significantly reduced the viability and clonal proliferation capacity of P. gingivalis in a dose-dependent manner. In the tumor-bearing mice, treatment with Ag₂Se nanoparticles significantly reduced the abundance of P. gingivalis in tumor tissues and suppressed tumor cell proliferation. No significant damages to the liver and kidney functions or the major organs were observed in Ag₂Se nanoparticle-treated mice, demonstrating good biocompatibility of Ag₂Se nanoparticles. CONCLUSIONS Ag₂Se nanoparticles exhibit significant bactericidal and inhibitory effects against P. gingivalis, and can effectively eliminate intracellular P. gingivalis to suppress the growth of esophageal cancer allograft in mice, suggesting the potential of Ag₂Se nanoparticles in the treatment of esophageal cancer.
Animals ; Porphyromonas gingivalis/drug effects* ; Mice ; Esophageal Neoplasms/pathology* ; Nanoparticles ; Metal Nanoparticles ; Bacteroidaceae Infections ; Cell Line, Tumor

OBJECTIVE: To investigate the effect and mechanism of Hyssopus cuspidatus Boriss. extract (HCE) in ovalbumin (OVA)-induced allergic asthma. METHODS: Components identification of HCE was conducted using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry. Mice were sensitized with OVA to establish asthmatic model, and dexamethasone was used as positive control. Respiratory reactivity, white cells counting in bronchoalveolar lavage fluid and peripheral blood, cytokine level measurement in serum and lung tissue, and histologic examination were performed to evaluate the therapeutic effect of HCE on asthma. Network pharmacology approach was used for mechanism prediction. Western blotting and untargeted lipidomics method were applied for mechanism validation. RESULTS: Fifty-two compounds were identified in HCE, predominantly terpenoids and flavonoids. HCE markedly reduced airway resistance, the eosinophil infiltration in lung tissues, and the levels of immunoglobulin E, interleukin-4, interleukin-5, and interleukin-13. Network pharmacology analysis suggested phosphatidylinositol 3-kinases (PI3K), c-Jun N-terminal kinase (JNK), and p38 Mitogen-activated protein kinase (p38 MAPK) may be key proteins of HCE in the treatment of allergic asthma. Western blot results indicated that the levels of phosphorylated PI3K, JNK, and P38 were downregulated in HCE-treated group. Moreover, HCE significantly upregulated the levels of ceramide and sphingomyelin and downregulated the level of phosphatidylcholine. CONCLUSION HCE inhibited allergic asthma via PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation.

Purpose: This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy. Materials and Methods: Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety. Results: Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways. Conclusion This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.