To investigate the clinical features and peripheral blood immune cell subsets ofelderly (≥60 years old) onset rheumatoid arthritis (EORA) patients.

Objective To explore the clinical characteristics of patients with diffuse large B-cell lymphoma (DLBCL) accompanied with KMT2D gene mutation and the impact of its co-mutated genes on prognosis. Methods Clinical data of 155 newly diagnosed DLBCL patients were obtained. The second-generation sequencing method was used to detect 475 hotspot genes, including KMT2D mutation. Patients were divided into the KMT2D mutation group and KMT2D wild-type group based on the presence or absence of KMT2D gene mutation. Clinical characteristics, differences in co-mutated genes, and survival differences between the two groups were compared. Results The frequency of KMT2D mutation was 31%, which is predominantly observed in elderly patients (P=0.07) and less in the double-expressor phenotype (P=0.07). Compared with the KMT2D wild-type group, KMT2D gene mutation was associated with higher co-mutation rates of CDKN2A (OR=2.82, P=0.01) and BCL2 (OR=3.84, P=0.016), while being mutually exclusive with MYC gene mutation (OR=0.11, P=0.013). In univariate survival analysis, no statistically significant difference in overall survival (OS) was found between the KMT2D mutation group and the wild-type group (P=0.54). Further analysis of the prognostic significance of KMT2D with other gene mutations indicated that patients with KMT2D^mutBTG2^mut had poorer OS than those with KMT2D^wt BTG2^mut (P=0.07) and KMT2D^wt BTG2^wt (P=0.05). On the contrary, patients with KMT2D^mut CD79B^mut had better OS than those with KMT2D^mut CD79B^wt (P=0.09), with no prognostic impact observed for other co-mutated genes. Multivariate Cox regression analysis revealed that Ann Arbor stages Ⅲ and Ⅳ (HR=2.751, 95%CI: 1.169-6.472, P=0.02), elevated LDH levels (HR=2.461, 95%CI: 1.396-4.337, P=0.002), Ki-67 index>80% (HR=1.875, 95%CI: 1.066-3.299, P=0.029), and KMT2D^mutBTG2^mut(HR=4.566, 95%CI: 1.348-15.471, P=0.015) were independent risk factors for OS in patients with DLBCL (P<0.05). Conclusion DLBCL patients with KMT2D mutation often have multiple gene mutations, among which patients with a co-mutated BTG2 gene have poor prognosis.

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

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.

Objective:To investigate the overall drug resistance, drug resistance trend and distribution of drug resistance mutation sites in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients with antiviral therapy failure in Yunnan Province.Methods:The demographic data and genotype drug resistance of HIV/AIDS population with antiviral therapy failure in Yunnan Province from January 2021 to December 2023 were collected and analyzed by cross-sectional investigation. Statistical analyses were performed using chi-square test.Results:Among 15 159 HIV/AIDS patients, 12 215 cases tested positive by amplification. The circulating recombinant form (CRF) 08_BC was the predominant genetic subtype, accounting for 54.97%(6 714/12 215), followed by CRF01_AE (16.14%(1 972/12 215)) and CRF07_BC (14.48% (1 769/12 215)). When the viral load was ≥200 to <1 000 copies/mL, the incidence of drug resistance was 21.48%(99/461). When it was ≥1 000 to <10 000 copies/mL, the incidence was 51.29%(2 867/5 590). When it was ≥10 000 to <100 000 copies/mL, the incidence was 69.39% (3 979/5 734). When it was ≥100 000 copies/mL, the incidence was 81.86%(352/430). A total of 7 297 drug resistant cases were detected, with a drug resistance rate of 59.74% (7 297/12 215), thus the estimated drug resistance incidence rate among the antiviral treated population in Yunnan Province was 2.00% (7 297/364 238). From 2021 to 2023, the annual drug resistance rates among patients were 60.71%(2 554/4 207), 60.28%(1 671/2 772), and 58.67% (3 072/5 236), respectively, with no statistically significant difference ( χ2=4.47, P=0.107). Among the population with antiviral therapy failure, the drug resistance rates of non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor (NRTI), and protease inhibitor (PI) were 93.70%(6 837/7 297), 44.10%(3 218/7 297) and 5.15%(376/7 297), respectively. The mutation sites with the highest frequencies among the three classes of drugs including NRTI, NNRTI and PI were M184V/I (46.13%(2 123/4 602)), K103N/S (37.14%(2 648/7 129)), L33F (15.50%(82/529)) and M46I/L (15.50%(82/529)), respectively. Analysis of the degree of drug resistance showed that among NNRTI drugs, nevirapine (49.01%(5 987/12 215)) and efavirenz (48.00%(5 863/12 215)) had the highest drug resistance rates, followed by emtricitabine (23.59%(2 882/12 215)) and lamivudine (23.58%(2 881/12 215)) among NRTI drugs. Conclusions:Among HIV/AIDS patients with antiviral therapy failure in Yunnan Province from 2021 to 2023, CRF08_BC is the main genetic subtype. The drug resistance rate of patients increases with the increase of HIV-1 viral load. There is no significant change in the drug resistance rate from 2021 to 2023. NNRTI has the highest drug resistance rate, followed by NRTI, and PI has the lowest. The main mutation sites are M184V/I for NRTI, K103N/S for NNRTI, and M46I/L and L33F for PI. The drug resistance rates of nevirapine, efavirenz, emtricitabine and lamivudine are relatively high.

A solid-phase extraction-ultra-performance liquid chromatography-tandem mass spectrometry(SPE-UPLC-MS/MS)method was established for simultaneous determination of 10 kinds of neonicotinoid pesticide residues in aquaculture water.Based on the chemical properties of neonicotinoid pesticides and the matrix characteristics of aquaculture water,suitable temporary storage methods for water samples and appropriate solid-phase extraction columns were selected,and the extraction conditions(including elution solvents and sample loading volumes)were optimized.The method employed acetonitrile and 5 mmol/L ammonium acetate solution(containing 0.1%formic acid)as the mobile phase and an Oasis HLB solid-phase extraction column combined with PSA as a dispersive sorbent for sample purification.The method exhibited good linearity in detection of neonicotinoid in concentration range of 0.2-50 ng/mL(R2>0.99797),with a detection limit of 0.5 ng/L and a quantification limit of 1 ng/L,which were significantly lower than the maximum acceptable method detection limits(9-500 ng/L)for neonicotinoid insecticides in water published by the European Commission.In pond water,rice-fish water,and seawater,the average recoveries of the 10 target analytes were 74.6%-114.1%,with relative standard deviations ranging from 0.3%to 9.6%.Using this method,actual sample tests were conducted on the Pearl River water,Zhaoqing pond water,and Qingyuan rice-fish aquaculture water.The total concentration of five neonicotinoid pesticides in the Pearl River water ranged from 154.8 to 246.6 ng/L,the total concentration of four neonicotinoid pesticides in the Zhaoqing pond water was 95.0-176.1 ng/L,and the total concentration of three neonicotinoid pesticides in the Qingyuan rice-fish aquaculture water was 2.3-11.7 ng/L.This method was simple in operation,highly sensitive,and had strong resistance to interference.It was suitable for detection of trace neonicotinoid pesticides in aquaculture water and could provide technical support for construction of a green aquaculture environment and resolution of international trade disputes.

The inclusion complex of taxifolin(TAX)with hydroxypropyl-β-cyclodextrin(HP-β-CD)was prepared by saturated aqueous solution method,and the preparation conditions such as molar ratio,volume ratio of solution,inclusion temperature and inclusion time were selected by single-factor experiment.The orthogonal design of three-level four-factor L9(34)was used to screen the preparation process of the inclusion complex,and the inclusion complex was prepared with optimal preparation process.The prepared inclusion complex was characterized by scanning electron microscopy(SEM),nuclear magnetic resonance(1H NMR,2D NMR),Fourier transform infrared spectroscopy(FT-IR),ultraviolet-visible(UV-Vis)absorption spectroscopy and X-ray powder diffraction(XRD).The inclusion ratio,biostability,solubility and in vitro release of the inclusion complex were investigated.The results of orthogonal experiments showed that the optimum conditions for preparation of the inclusion complex were as follows:the molar ratio of TAX to HP-β-CD was 1:1,the volume ratio of methanol to ultra-pure water was 1:8,the inclusion time was 8 h,and the inclusion temperature was 30℃.Under the optimal conditions,the inclusion ratio between TAX and HP-β-CD was calculated to be 1:1 by Job's curve method.According to the change of UV-vis absorption spectra,the host-guest complexation constant of 4.9488×104 L/mol was obtained by Benesi-Hildebrand curve method.The solubility of TAX increased from 1.2665 mg/mL to 19.3469 mg/mL after inclusion,demonstrating that HP-β-CD could serve as an effective host molecule for TAX,which could significantly enhance the bio-stability and solubility of the formed inclusion complex.

Objective:To investigate the relationship between the morphology of bone marrow plasma cells, the identification of M protein, and the detection of minimal residual disease(MRD)by flow cytometry in elderly patients with multiple myeloma(MM).Additionally, the impact on progression-free survival(PFS)is analyzed.Methods:A total of 60 elderly MM patients with bone marrow morphology reports and corresponding flow MRD detection, collected from February 1, 2017, to January 31, 2022, at Beijing Chaoyang Hospital Affiliated to Capital Medical University, were included in this study.We collected data on plasma cells from morphological examination and flow cytometry-based MRD detection. By combining these findings with M-protein identification results from 35 cases, we analyzed the correlations among these three parameters. Patients were stratified into two groups based on median values of: flow cytometry MRD(0.246% of nucleated cells), morphological plasma cell percentage(3.5%), and M-protein quantification(2.5 g/dl).This stratification enabled evaluation of their prognostic value for PFS.Results:A total of 60 elderly MM patients were enrolled, including 41 males with age of 65.0(63.0, 68.5)years and 19 females with age of 67.0(64.0, 72.0)years The morphology of bone marrow in 60 elderly patients with MM revealed 10 cases of primitive plasma cells(16.67%), 48 cases of immature plasma cells(80.00%), and 2 cases with no plasma cells(3.33%).A positive correlation was observed between the proportion of bone marrow plasma cells and the corresponding flow MRD in terms of both the proportion of nuclear cells and the proportion of plasma cells.Specifically, the proportion of the morphological protoplasma group showed a strong correlation with flow MRD(proportion of plasma cells)( r=0.82, P<0.01), while the proportion of the morphological immature plasma group exhibited moderate correlations with flow MRD(proportion of nuclear cells)( r=0.74, P<0.05)and flow MRD(proportion of plasma cells)( r=0.70, P<0.01).No significant correlation was found between the type and quantity of M protein and flow MRD( P>0.05).The PFS time for the flow MRD ≥0.246%(nucleated cells)group was shorter than that of the<0.246% group( P<0.05).There was no significant difference in PFS between the groups with plasma cell ratios ≥3.5% and<3.5%( P=0.15).Additionally, no significant difference in PFS was observed between patients with M protein quantitation ≥2.5 g/dl and those with M protein quantitation<2.5 g/dl( P=0.94). Conclusions:The proportion of bone marrow plasma cells correlates with flow MRD in elderly patients with MM, and a high MRD load indicates a poor prognosis.However, no significant correlation was found between M protein levels and flow MRD or PFS.Clinical attention should focus on the dynamic monitoring of plasma cell morphology and flow MRD.Nevertheless, the morphological detection of plasma cells remains crucial for auxiliary diagnosis due to its intuitiveness, cost-effectiveness, and broad applicability.