AIM To investigate the effects of Gan Jiang-Huang Qin-Huang Lian-Ren Shen Decoction(GJHQHLRSD)on the pyroptosis,pathway of colonic epithelial cells in mouse models of ulcerative colitis(UC).METHODS Among the 63 C57BL/6J mice,13 were randomly selected and assigned to the model group,and the others were divided into the control group,the positive Sulfasalazine Enteric-Coated Tablets group(0.6 g/kg),and low,medium,and high dose GJHQHLRSD groups(3.9,7.8,15.6 g/kg),with 10 mice in each group.The UC mouse model was established using DSS,and the corresponding drugs were administered by gavage.The mice had their general condition observed;their disease activity index(DAI)score assessed;their colon length measured;their histopathological damage of the colon analyzed using HE staining;their colonic IL-1β,IL-8,and TNF-α levels measured by ELISA method;their colonic NLRP3,GSDMD,pro-IL-1β,pro-caspase-1,and IL-1βprotein expression detected by Western blot method;and their cell pyroptosis detected by TUNEL and GSDMD fluorescence double staining.RESULTS Compared with the control group,the model group exhibited significant decrease in body weight and a shortened colon length(P＜0.01);increases in DAI score,levels of IL-1β,IL-8,TNF-α,as well as the protein expressions of NLRP3,GSDMD,and active-caspase-1(P＜0.05,P＜0.01);significant increase of colonic GSDMD and TUNEL positivity;indicating increased tissue damage and inflammatory response.Compared with the model group,the groups intervened with GJHQHLRSD showed a significant increase in body weight and colonic elongation(P＜0.05,P＜0.01);decreases in DAI score,levels of IL-1β,IL-8,TNF-α,as well as the protein expressions of NLRP3,GSDMD,and active-caspase-1(P＜0.05,P＜0.01);a gradient decrease in positivity of GSDMD and TUNEL;indicating a significantly reduced colonic pathological damage.CONCLUSION GJHQHLRSD can improve the DSS-induced inflammatory reaction of colonic mucosa in UC mice,and its mechanism mainly involves the NLRP3/caspase-1,thereby the regulation of the cell pyroptosis process.

Objective:This study aims to analyze the trends,hotspots,and interrelations in research on retroperito-neal tumors through bibliometric methods,providing the latest scientific information support for clinicians and research-ers.Methods:Data were sourced from the SCI-expanded database of the Web of Science Core Collection,covering the period from 2004 to 2023.Statistical analysis and visualization of the number of publications,total citations,average citations per article,countries,institutions,journals,and keywords were conducted using Microsoft Excel 2019,VOS-viewer,and CiteSpace.Results:A total of 6,842 relevant articles were retrieved,with a total of 113 753 citations and an average of 16.63 citations per article.The number of publications had been increasing annually,peaking in 2022.The United States,China,and Japan are the major research countries,with the United States contributing the most.Memo-rial Sloan Kettering Cancer Center and the University of Texas MD Anderson Cancer Center are the leading research in-stitutions.The journal with the most publications was the Cureus Journal of Medical Science.Gronchi Alessandro was the most prolific author.The ain keywords were"Management","Surgery",and"Tumor",and the most cited papers focus on surgery and multicenter studies.Conclusion:Research on retroperitoneal tumors is increasing annually,with hot-spots focusing on treatment methods and prognosis analysis.The United States is the main contributor to this field,with significant international collaboration.Future research should further explore the pathogenesis of retroperitoneal tumors and more effective treatment strategies.

Kv1.3,a voltage-gated potassium channel,is highly expressed in T lymphocytes,the nervous system,and vascular smooth muscle cells.It plays a critical role in membrane excitability and electrical signal transduction,serving as an important target for studying T-cell function and providing a promising direction for developing therapeutics against autoimmune and inflammatory diseases.Therefore,the de-velopment of specific inhibitors of Kv1.3 channel has emerged as a novel therapeutic strategy for these disorders.In this study,we isolated and purified a novel Kv1.3-inhibitory peptide toxin,LmKTx13,from the venom of the scorpion Lychas mucronatus using reversed-phase high-performance liquid chroma-tography(RP-HPLC).LmKTx13 consists of 38 amino acid residues,including six cysteines that form three disulfide bonds.Whole-cell patch-clamp recordings revealed that LmKTx13 potently inhibited Kv1.3 with an IC50 of 7.92±3.0 nmol/L.Selectivity analysis showed that 2 μmol/L LmKTx13 also in-hibited Kv1.2 and Kv1.7,but exhibited no significant effects on other potassium channel subtypes or voltage-gated sodium channels.Further investigation into the mechanism demonstrated that LmKTx13 acts as a pore-blocking inhibitor of Kv1.3.By analyzing the effects of LmKTx13 on Kv1.3 channel gating ki-netics and performing sequence alignment of the pore regions of Kv1.3 and Kv1.5,we constructed site-directed mutants and identified the pore region of Kv1.3 as the critical binding site for LmKTx13.Key residues involved in the interaction included T425,G427,and H451.In summary,we discovered a no-vel pore-blocking Kv1.3 inhibitor,LmKTx13,from L.mucronatus venom,which exhibits high affinity and selectivity for Kv1.3.These findings highlight its potential as a potential lead molecule for developing Kv1.3-targeted therapeutics.

Objective To explore the clinical and genetic characteristics of children with holocarboxylase synthetase(HLCS)deficiency.Methods A retrospective analysis was conducted on the clinical data of 3 children with HLCS deficiency who were admitted to Children's Hospital Affiliated to Zhengzhou University from December 2014 to January 2024.Relevant literature indexed in CNKI,Wanfang Data,PubMed and other databases was reviewed to summarize the clinical characteristics and HLCS gene mutations of children with HLCS deficiency.Results All 3 children were male,with onset age of 4-6 months.The main clinical manifestations included shortness of breath,vomiting,diarrhea,and poor mental state,and partial cases were complicated by growth retardation and neurological symptoms.Laboratory tests showed metabolic acidosis in all cases,blood amino acid and acylcarnitine profiles as well as urinary organic acid analysis suggested multiple carboxylase deficiency.Genetic testing revealed compound heterozygous mutation in the HLCS gene of all 3 children,among which the c.1892delT(p.L631X)mutation was previously unreported.According to the guidelines of the American College of Medical Genetics and Genomics(ACMG),the c.1892delT(p.L631X)mutation was rated as pathogenic mutation(PVS1+PM2_supporting+PM3).Biotin supplementation was effective in all cases.Literature review included 27 English literatures and 29 Chinese literatures,reporting a total of 133 children with HLCS deficiency caused by HLCS gene mutation.Common clinical manifestations included metabolic acidosis,skin lesions,vomiting,feeding difficulties,dyspnea,diarrhea,and neurological symptoms,etc.Conclusions Blood amino acid and acylcarnitine profiles,urine organic acid analysis,and gene testing are helpful for the diagnosis of HLCS deficiency.Timely biotin supplementation leads to a good prognosis.The mutation of HLCS gene is considered as the genetic etiology of HLCS deficiency in 3 children,among which the c.1892delT(p.L631X)mutation is a newly discovered mutation.

Objective To investigate the status of population dynamics and distribution changes of Aedes aegypti in Guangdong Province.Methods Continuous monitoring was conducted from May 2018 to July 2024 in Wushi Town and Qishui Town,Leizhou City,Zhanjiang City,Guangdong Province.Additionally,a survey of the distribution of Ae.aegypti along the Leizhou Peninsula coast was carried out.Results The density of Ae.aegypti in Zhanjiang showed a gradual decline from 2018 to 2024.The last detection of adult Ae.aegypti in Wushi Town was in September 2021,and the last larva was found in October 2023.No Ae.aegypti was detected in Qishui Town during surveys from 2021 to 2024.A survey of 18 coastal villages in the Leizhou Peninsula revealed no detections of Ae.aegypti.Conclusions This study provides a basis for understanding the distribution and population density fluctuations of Ae.aegypti,assessing its invasion risk,and scientifically conducting relevant prevention and control efforts.

Kv1.3,a voltage-gated potassium channel,is highly expressed in T lymphocytes,the nervous system,and vascular smooth muscle cells.It plays a critical role in membrane excitability and electrical signal transduction,serving as an important target for studying T-cell function and providing a promising direction for developing therapeutics against autoimmune and inflammatory diseases.Therefore,the de-velopment of specific inhibitors of Kv1.3 channel has emerged as a novel therapeutic strategy for these disorders.In this study,we isolated and purified a novel Kv1.3-inhibitory peptide toxin,LmKTx13,from the venom of the scorpion Lychas mucronatus using reversed-phase high-performance liquid chroma-tography(RP-HPLC).LmKTx13 consists of 38 amino acid residues,including six cysteines that form three disulfide bonds.Whole-cell patch-clamp recordings revealed that LmKTx13 potently inhibited Kv1.3 with an IC50 of 7.92±3.0 nmol/L.Selectivity analysis showed that 2 μmol/L LmKTx13 also in-hibited Kv1.2 and Kv1.7,but exhibited no significant effects on other potassium channel subtypes or voltage-gated sodium channels.Further investigation into the mechanism demonstrated that LmKTx13 acts as a pore-blocking inhibitor of Kv1.3.By analyzing the effects of LmKTx13 on Kv1.3 channel gating ki-netics and performing sequence alignment of the pore regions of Kv1.3 and Kv1.5,we constructed site-directed mutants and identified the pore region of Kv1.3 as the critical binding site for LmKTx13.Key residues involved in the interaction included T425,G427,and H451.In summary,we discovered a no-vel pore-blocking Kv1.3 inhibitor,LmKTx13,from L.mucronatus venom,which exhibits high affinity and selectivity for Kv1.3.These findings highlight its potential as a potential lead molecule for developing Kv1.3-targeted therapeutics.

Objective To explore the predictive factors of recurrence of chronic suppurative otitis media(CSOM)after otoendoscopic surgery,and construct a risk quantified nomogram model.Methods The clinical data of 485 patients with CSOM who underwent otoendoscopic surgery in our hospital from February 2021 to February 2023 were retrospectively analyzed.The patients were divided into the recurrence group and the non-recurrence group according to the recurrence situation during the follow-up period.The clinical data of patients between the two groups were compared,and the predictive factors of postoperative recurrence were analyzed by Cox regression method.A risk quantified nomogram model was constructed based on these predictive factors.The predictive efficiency of the model was verified by receiver operating characteristic(ROC)curve,and the calibration degree of the model was verified by Hosmer-Lemeshow goodness of fit analysis,and the clinical net benefit of the model was evaluated by decision curve analysis(DCA)method.Results Follow-up ranged from 6 to 39 months,with a median of 21(11,32)months,the postoperative recurrence rate was 14.64%(71/485).Combined with recurrent upper respiratory tract infections(HR=3.019,95%CI:1.609 to 5.664),combined with chronic rhinosinusitis(HR=2.428,95%CI:1.529 to 3.856),combined with adenoid hypertrophy(HR=2.214,95%CI:1.381 to 3.551),middle ear risk index(MERI)score(HR=2.863,95%CI:1.445 to 5.675),the seven-item eustachian tube dysfunction questionnaire(ETDQ-7)score(HR=2.679,95%CI:1.505 to 4.765)and inadequate drainage of the surgical cavity(HR=2.373,95%CI:1.503 to 3.746)were the risk factors for postoperative recurrence(P<0.05).A risk quantified nomogram model of recurrence after otoendoscopic surgery in CSOM patients was constructed based on the predictive factors of Cox regression analysis,among them the risk value ranges of patients who combined with recurrent upper respiratory tract infections,combined with chronic rhinosinusitis,combined with adenoid hypertrophy,MERI score,ETDQ-7 score,and inadequate drainage of the surgical cavity were 0 to 65 points,0 to 56 points,0 to 52 points,0 to 76 points,0 to 64 points,and 0 to 76 points,respectively.The area under the curve of ROC,sensitivity and specificity of the model for predicting postoperative recurrence were 0.928(95%CI:0.875 to 0.948),85.92%and 88.89%,respectively.There was no significant difference between the predicted probability of postoperative recurrence and the actual probability(P>0.05).The threshold probability of postoperative recurrence predicted by the model in the range of 4%to 92%could obtain clinical net benefit.Conclusion The predictive factors of recurrence after otoendoscopic surgery in CSOM patients include combined with recurrent upper respiratory tract infections,combined with chronic rhinosinusitis,combined with adenoid hypertrophy,MERI score,ETDQ-7 score and inadequate drainage of the surgical cavity,the risk quantified nomogram model based on these factors is highly effective in predicting postoperative recurrence.

AIM To study the chemical constituents from dichloromethane fraction of Dalbergia odorifera T.Chen heartwood.METHODS Separation and purification were performed using silica gel,Sephadex LH-20,thin-layer chromatography,and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Twenty-four compounds were isolated and identified as 7,2′-dihydroxy-4′-methoxy-isoflavanol(1),vanillin(2),2,2′-oxybis-(1,4-di-tert-butylbenzene)(3),7-hydroxy-6-methoxyflavone(4),sativan(5),5-hydroxy-4′,7-dimethoxyisoflavone(6),2-hydroxy-4,4′-dimethoxychalcone(7),7,2′,3′,4′-tetramethoxydihydroisoflavone(8),2,4,2′-trihydroxy-4′-methoxybenzil(9),ethyl-3-hydroxy-3-phenyl-2-propenoate(10),6,7-dimethoxy-2,3-dihydr-ochromen-4-one(11),sophorophenolone(12),apocynin(13),ethyl-2,4-dihydroxybenzoate(14),ethylparaben(15),methyl-2,4-dihydroxybenzoate(16),5,7-dihydroxy-6-methoxyflavanone(17),7-hydroxyflavanone(18),mimosifoliol(19),7-hydroxy-4′-methoxyisoflavane(20),virolane(21),5-hydroxy-7-methoxychromone(22),3-hydroxyl-5-methoxy-stilbene(23),2′,4′-dihydroxydihydrochalcone(24).CONCLUSION Compound 8 is new natural product,2-6,15,17-18 are isolated from this plant for the first time,7,9-14,16,20-24 are first isolated from genus Dalbergia.

Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.

AIM To investigate the effects of Gan Jiang-Huang Qin-Huang Lian-Ren Shen Decoction(GJHQHLRSD)on the pyroptosis,pathway of colonic epithelial cells in mouse models of ulcerative colitis(UC).METHODS Among the 63 C57BL/6J mice,13 were randomly selected and assigned to the model group,and the others were divided into the control group,the positive Sulfasalazine Enteric-Coated Tablets group(0.6 g/kg),and low,medium,and high dose GJHQHLRSD groups(3.9,7.8,15.6 g/kg),with 10 mice in each group.The UC mouse model was established using DSS,and the corresponding drugs were administered by gavage.The mice had their general condition observed;their disease activity index(DAI)score assessed;their colon length measured;their histopathological damage of the colon analyzed using HE staining;their colonic IL-1β,IL-8,and TNF-α levels measured by ELISA method;their colonic NLRP3,GSDMD,pro-IL-1β,pro-caspase-1,and IL-1βprotein expression detected by Western blot method;and their cell pyroptosis detected by TUNEL and GSDMD fluorescence double staining.RESULTS Compared with the control group,the model group exhibited significant decrease in body weight and a shortened colon length(P＜0.01);increases in DAI score,levels of IL-1β,IL-8,TNF-α,as well as the protein expressions of NLRP3,GSDMD,and active-caspase-1(P＜0.05,P＜0.01);significant increase of colonic GSDMD and TUNEL positivity;indicating increased tissue damage and inflammatory response.Compared with the model group,the groups intervened with GJHQHLRSD showed a significant increase in body weight and colonic elongation(P＜0.05,P＜0.01);decreases in DAI score,levels of IL-1β,IL-8,TNF-α,as well as the protein expressions of NLRP3,GSDMD,and active-caspase-1(P＜0.05,P＜0.01);a gradient decrease in positivity of GSDMD and TUNEL;indicating a significantly reduced colonic pathological damage.CONCLUSION GJHQHLRSD can improve the DSS-induced inflammatory reaction of colonic mucosa in UC mice,and its mechanism mainly involves the NLRP3/caspase-1,thereby the regulation of the cell pyroptosis process.