Objective To elucidate the changes in the gut microbiota and molecular mechanism of huaier in enhancing the efficacy of oxaliplatin (OXA) chemotherapy in gastric cancer (GC). Methods The effects of huaier on the gut microbiota structure and intestinal barrier function in MKN45-bearing mice were analyzed by using 16S rRNA sequencing, RT-qPCR, and IHC. UPLC-MS and network pharmacology, as well as in vivo experimental approaches, were employed to investigate the key bioactive constituents of huaier systematically and elucidate the underlying mechanisms by which huaier exerts therapeutic effects against GC. The expression of the PI3K/AKT/SREBP pathway was detected in cancer cells and tissues via Western blot analysis. The safety profile of huaier combined with OXA was verified through serum biochemistry and HE-stained tissue section analyses. Results Huaier inhibited the PI3K/AKT/SREBP pathway by increasing the abundance of Akkermansia muciniphila, reduced lipid droplet deposition, and ultimately enhanced the sensitivity to OXA in the treatment of GC. Conclusion This study demonstrates the value of huaier in gastric cancer treatment by enhancing chemosensitivity and provides novel insights into its systemic therapeutic effects through molecular mechanisms and gut microbiota modulation.

Objective:To investigate the short-term efficacy and safety of rituximab (RTX) in children with calcineurin inhibitor (CNI) resistant steroid resistant nephrotic syndrome (SRNS).Methods:A retrospective case analysis was conducted. Thirteen children with CNI resistant SRNS who were regularly treated with RTX (375 mg/m 2 per dose (maximum dose 500 mg), 1 dose per week, a total of 4 doses) in Department of Nephrology, Children′s Hospital of Fudan University from January 2016 to December 2023 were enrolled. The general data, disease related information, urinary protein/creatinine, serum albumin, blood creatinine before RTX treatment, immunosuppressants, adverse events, and monthly urinary protein/creatinine, serum albumin, and blood creatinine indexes within 6 months after RTX treatment were collected. The changes of urinary protein/creatinine, serum albumin and estimated glomerular filtration rate (eGFR) before and after RTX at 3 and 6 months were analyzed by using paired sample t test and Wilcoxon signed-rank test. Results:Among the 13 patients, 8 were male and 5 were female. The age of disease onset was 4.0 (2.9, 6.8) years and the age of RTX treatment was 9.8 (5.9, 13.6) years. There were 8 cases of focal segmental glomerulosclerosis, 3 cases of minimal change disease and 2 cases of mesangial proliferative glomerulonephritis. No clinically significant gene variation was detected in 12 cases and the other one did not receive gene test. Before RTX treatment, 11 cases were in chronic kidney disease stage G1, and 1 case each was in stage G2 and stage G3. Ten children completed 4 doses of RTX treatment, 1 patient completed 3 doses, and 2 patients completed 2 doses. Urinary protein/creatinine in 13 children at 3 and 6 months after RTX treatment was significantly lower than baseline (0.60 (0.13, 2.04), 0.49 (0.28, 1.10) vs. 1.44 (0.76, 4.11) mg/mg, Z=-2.34, -2.34, both P<0.05), and serum albumin was significantly higher than baseline ((35±8), (34±7) vs. (30±6) g/L, t=2.30, 2.60, both P<0.05). The eGFR at 6 months after RTX treatment was not significantly different from the baseline ((110±32) vs. (113±35) ml/(min·1.73 m 2), t=-0.76, P>0.05)). No serious adverse reactions occurred in this study. Conclusion:RTX could reduce urinary protein and increase serum albumin in short-term treatment in children with CNI resistant SRNS without significant side effects.

Objective:To analyze the epidemiological characteristics of wasting, spinal curvature abnormalities and multimorbidity among children and adolescents aged 6-18 in Inner Mongolia and explore the related factors of these two health problems.Methods:In September 2022, a stratified random cluster sampling method was employed to select 188 635 children and adolescents aged 6-18 in Inner Mongolia for physical examinations and questionnaire surveys. Data on height, weight, as well as dietary behavior, physical activity, classroom environment, academic tasks, writing posture, and screen behavior were collected. The epidemiological characteristics of wasting, spinal curvature abnormalities and multimorbidity were analyzed. Additionally, a multivariate logistic regression model was used to analyze the factors associated with wasting, spinal curvature abnormalities and multimorbidity.Results:A total of 188 635 children and adolescents aged 6-18 years participated in this study, including 95 393 boys (50.6%) with an average age of (11.53±3.32) years. The detection rate of wasting was 3.79%, with a higher detection rate in boys (4.18%) than in girls (3.38%) ( P<0.001). The detection rate of spinal curvature abnormalities was 3.64%, with a higher detection rate in girls (4.04%) than in boys (3.25%) ( P<0.001). The detection rate of multimorbidity between wasting and spinal curvature abnormalities was 0.17%, and there was no statistically significant difference between genders ( P>0.05). The detection rates of wasting, spinal curvature abnormalities, and multimorbidity all increased with age ( P t<0.001). The multivariate logistic regression analysis showed that, after adjusting for gender, age, urban/rural status, and school grade, compared to children and adolescents who exercised ≥1 hour of moderate-to-vigorous physical activity (MVPA) for at least 5 days per week and had daily screen time <2 hours, those who exercised <5 days per week ( OR=1.28, 95% CI: 1.19-1.37) and had daily screen time ≥2 hours ( OR=1.11, 95% CI: 1.03-1.19) had a higher risk of wasting. Compared to children and adolescents who had ≥5 physical education (PE) classes per week, adjusted desk and chair height,<1 hour of after-school study/writing time, and whose parents or teachers rarely or never reminded them about posture, those with <5 PE classes per week ( OR=1.11, 95% CI: 1.02-1.21), unadjusted desk and chair height ( OR=1.08, 95% CI: 1.01-1.15),≥1 hour of after-school study/writing time ( OR=1.15, 95% CI: 1.07-1.24), frequent reminders from parents ( OR=1.16, 95% CI: 1.09-1.23), and frequent reminders from teachers ( OR=1.10, 95% CI: 1.04-1.16) had a higher risk of spinal curvature abnormalities. Compared to children and adolescents who did not consume sugary drinks daily, exercised ≥1 hour of MVPA for at least 5 days per week, and whose teachers rarely or never reminded them about posture, those who consumed sugary drinks daily ( OR=1.61, 95% CI: 1.00-2.46), exercised <5 days per week ( OR=1.33, 95% CI: 1.01-1.79), and had teachers who frequently reminded them about posture ( OR=1.35, 95% CI: 1.05-1.75) had a higher risk of multimorbidity between wasting and spinal curvature abnormalities. Conclusion:The detection rates of wasting, spinal curvature abnormalities and multimorbidity among children and adolescents aged 6-18 in Inner Mongolia are generally low, with an increasing trend observed with age. Both lifestyle and school environmental factors are associated with wasting, spinal curvature abnormalities and multimorbidity.

Objective:To investigate the efficacy and safety of trastuzumab deruxtecan (T-DXd) in the treatment of metastatic breast cancer.Methods:A retrospective case series study was conducted. The clinical data of 38 breast cancer patients with metastasis in other parts who received T-DXd treatment in Xi'an International Medical Center Hospital from August 2021 to August 2024 were analyzed. The clinical efficacy and incidence of adverse reactions in patients were recorded, comparison of clinical efficacy in stratified patients based on clinical characteristics was performed, and the progression-free survival (PFS) was analyzed using Kaplan-Meier method.Results:All 38 patients were female, with a median age [ M ( Q1, Q3)] of 55 (42, 60) years; according to the guidelines of the American Society of Clinical Oncology/College of American Pathologists, 13 cases (34.2%) were positive for human epidermal growth factor receptor 2 (HER2) and 25 cases (65.8%) were low in HER2 expression; the Eastern Cooperative Oncology Group (ECOG) physical status scores of 23 cases (60.5%) were 0-2 points and 15 cases (39.5%) were 3-4 points; the median number of T-DXd treatment lines was 4 (2,16) lines. According to the Response Evaluation Criteria in Solid Tumors 1.1, the objective response rate (ORR) of T-DXd treatment was 34.2% (13/38), and the disease control rate (DCR) was 78.9% (30/38); the ORR of patients aged ≤ 50 years old was higher than that of patients aged >50 years old [56.3% (9/16) vs. 18.2% (4/22)], patients with HER2 positive was lower than that of patients with low HER2 expression [100.0 (13/13) vs. 68.0% (17/25)], patients with previous tyrosine kinase inhibitor (TKI) treatment was higher than that of patients without TKI treatment [100.0% (12/12) vs. 69.2% (18/26)], and the DCR of patients with T-DXd treatment for ≥ 4 cycles was higher than that of patients with T-DXd treatment for 1-3 cycles [100.0% (25/25) vs. 38.5% (5/13)], and the differences were statistically significant (all P < 0.05). Among the 38 patients, 19 (50.0%) stopped medication due to disease progression, 11 (28.9%) stopped medication due to economic reasons, 1 (0.8%) stopped medication due to grade 3 nausea and vomiting, and 1 (0.8%) stopped medication due to grade 2 interstitial lung disease (ILD), while the remaining 6 (15.8%) were undergoing T-DXd treatment. The median follow-up time was 9.5 (3.9, 17.8) months, and 16 cases (42.1%) progressed and died; the median PFS time was 5.9 months (95% CI: 3.1-8.7 months). Adverse reactions were mostly grade 1-2; common hematological adverse reactions included leukopenia [18 cases (47.3%)], neutropenia [16 cases (42.1%)], thrombocytopenia [11 cases (28.9%)], and anemia [15 cases (39.5%)]. Non-hematological adverse reactions included nausea [28 cases (73.7%)], vomiting [15 cases (39.5%)], decreased appetite [20 cases (52.6%)], fatigue [22 cases (57.9%)], alopecia [22 cases (57.5%)], elevated aspartate aminotransferase [20 cases (52.6%)], and elevated alanine aminotransferase [15 cases (39.5%)] were more common. Two cases developed interstitial lung disease (ILD), classified as grade 1 and grade 2, respectively. After discontinuation of medication and treatment with methylprednisolone, they returned to normal. Conclusions:T-DXd ≥ 2 line therapy has good efficacy and safety in the treatment of HER2 positive or low expression metastatic breast cancer. Bone marrow suppression and gastrointestinal adverse reactions are the most common, and the occurrence of ILD should be noted in the treatment.

OBJECTIVE To determine the species,quantity,and dispersion patterns of airborne pollen in two districts and five counties of Handan City,Hebei Province.METHODS The gravity sedimentation method was employed from October 1,2023,to September 30,2024,for daily and consecutive pollen exposure slides in two districts(Congtai District and Yongnian District)and five counties(Qiu County,Daming County,Cheng'an County,Cixian County,and She County)of Handan City,Hebei Province.The types of pollen were counted and identified under an optical microscope,and the pollen data were statistically analyzed.RESULTS The annual pollen quantity in the two districts and five counties of Handan City ranged from 24 031 grains/1 000 mm2 to 85 131 grains/1 000 mm2.The dissemination of major allergenic pollen presented two peaks.The first peak occurred in spring(March to April),mainly composed of Platanus(25.15％),Broussonetia(13.61％),Pinus(8.48％);the second peak occurred in(August to September),mainly consisting of Humulus/Cannabis(13.71％)and Artemisia(8.44％).Pollen in spring was significantly higher than that in summer and autumn.CONCLUSION The major allergenic airborne pollen in the two districts and five counties of Handan City exhibited two peaks in spring and summer-autumn,with Platanus pollen,Broussonetia pollen,Pinus pollen,Humulus/Cannabis pollen,and Artemisia pollne being the dominant pollen types.Among them,Platanus pollen was the absolute dominant pollen in this region.

OBJECTIVES: To investigate the inhibitory effect of multimerin-2 (MMRN2) overexpression on growth and metastasis of cutaneous melanoma cells. METHODS: Clinical data of patients with cutaneous melanoma were obtained from the GEO database to compare MMRN2 expressions between normal and tumor tissues. A protein-protein interaction network was constructed using the STRING database, and the intersecting genes from GEPIA2.0 were subjected to GO and KEGG enrichment analysis. The prognostic relevance of MMRN2 expression level was assessed using Cox regression and "timeROC". The correlations of MMRN2 expression level with immune infiltration and angiogenesis-related genes were analyzed using GSCA database and the ssGSEA algorithm. Colony-forming assay, Transwell assay, and wound healing assay were used to examine the changes in proliferation and migration of cultured cutaneous melanoma cells following MMRN2 knockdown. In a mouse model bearing cutaneous melanoma xenograft, the effect of MMRN2 knockdown on vital organ pathologies, survival of the mice and GM-CSF, CXCL9, and TGF‑β1 protein expressions were analyzed. RESULTS: MMRN2 was significantly upregulated in metastatic cutaneous melanoma (P<0.001). Protein interaction network analysis identified 15 intersecting genes, which were enriched in endothelium development and cell-cell junctions. In patients with cutaneous melanoma, a high MMRN2 expression was correlated with a poor prognosis, an advanced T stage, a greater Breslow depth, and ulceration (P<0.05). MMRN2 expression level was strongly correlated with 24 immune cell types (P<0.001), fibroblasts, endothelial cells, and expressions of the pro-angiogenic genes (KCNJ8, SLCO2A1, NRP1, and COL3A1; P<0.001). In cultured B16F10 cells, MMRN2 knockdown significantly suppressed cell proliferation, migration and invasion and caused remo-deling of the immunosuppressive microenvironment. CONCLUSIONS MMRN2 overexpression drives progression of cutaneous melanoma by enhancing tumor metastasis, angiogenesis and immune evasion, highlighting its potential as a therapeutic target for melanomas.
Humans ; Melanoma/metabolism* ; Animals ; Cell Movement ; Prognosis ; Skin Neoplasms/metabolism* ; Mice ; Cell Proliferation ; Neoplasm Invasiveness ; Cell Line, Tumor ; Protein Interaction Maps

OBJECTIVES: To explore the mechanisms of Qingre Lidan Jiedu Recipe (QLJR) for improving cognitive dysfunction in rats with high copper load. METHODS: Seventy-five male SD rats were randomized into normal control group, model group, QLJR group, penicillamine (PCA) group, and QLJR+ PCA group. Except for those in the control group, all the rats were fed a high-copper diet for 12 weeks. The effects of the treatments on cognitive function of the rats were assessed using the Barnes maze and passive avoidance tests. Hippocampal expressions of NIX, FUNDC1 and LC3 of the rats were detected using Western blotting and immunofluorescence staining, and changes in mitochondrial morphology were observed with transmission electron microscopy. RESULTS: Behavioral tests showed prolonged target hole latency, shortened latency to enter the dark chamber, and increased error counts of the rats in the model group, which were significantly improved in QLJR+PCA group; the error counts were significantly lower in QLJR+PCA group than in either QLJR or PCA group. Among all the groups, the hippocampal expressions of NIX and FUNDC1 were the lowest and LC3 I/II expression the highest in the model group; NIX and FUNDC1 expressions were significantly higher and LC3 I expression was lower in QLJR+PCA group than in QLJR group and PCA group. Immunofluorescence staining revealed weakened NIX and FUNDC1 expressions and enhanced LC3 expression in the hippocampus of the rats in the model group as compared with those in the normal control and QLJR+PCA groups, but their expressions did not differ significantly between QLJR and PCA groups. The rats in the model group showed obvious structural disarray of the mitochondria, which were improved in all the treatment groups. CONCLUSIONS QLJR improves cognitive dysfunction in rats with high copper load possibly by regulating mitophagy.
Animals ; Male ; Rats, Sprague-Dawley ; Rats ; Drugs, Chinese Herbal/therapeutic use* ; Copper/toxicity* ; Mitophagy/drug effects* ; Hippocampus/drug effects* ; Cognition Disorders/drug therapy* ; Cognitive Dysfunction/chemically induced*

Objective This study aims to investigate the effects of transcatheter arterial chemoembolization(TACE)using EqualSpheres,CalliSpheres,and Lipiodol loaded with idarubicin on VX2 liver cancer in rabbits.Methods Twelve New Zealand white rabbits were randomly assigned to three groups:EqualSpheres group,CalliSpheres group,and Lipiodol group(n=4 per group).The VX2 liver cancer animal model was successfully established through ultrasound-guided percutaneous puncture.EqualSpheres,CalliSpheres,and Lipiodol were employed as embolization agents loaded with idarubicin for the embolization procedure.Peripheral blood samples were collected at intervals of 5 minutes,0.5,1,4,12 and 24 hours following embolization and were centrifuged to obtain serum.At 24 hours post-TACE treatment,the rabbits in both the experimental and control groups were euthanized,and both liver cancer tissues and normal liver tissues were collected.UPLC-MS/MS was used to measure the drug concentration of idarubicin in peripheral blood and tissue samples,and Graphpad software was used to construct drug concentration-time curves in peripheral blood.The pharmacokinetic curves were constructed to evaluate the dynamic in vivo distribution characteristics.Results The average drug concentration in the EqualSpheres group(920.06 ng/mL)was significantly higher than that in both the CalliSpheres group(79.47 ng/mL)and the Lipiodol group(118.71 ng/mL).However,the average drug concentration in normal liver tissue of all the three groups was lower,and the difference was not statistically significant.The peripheral blood drug concentration of the three groups decreased at 5 minutes post-TACE and increased over the next 24 hours.The average blood concentration curve of EqualSpheres group increased more steadily compared to the CalliSpheres group and the Lipiodol group.The Cmax of the Lipiodol group was reached at 0.5 hours,measuring 11.54 ng/mL.Both the CalliSpheres group and the EqualSpheres group achieved their Cmax at 5 minutes,with values of 7.82 and 8.36 ng/mL,respectively.Conclusion EqualSpheres loaded with idarubicin achieve a high drug concentration at the tumor site while maintaining a low concentration in peripheral blood over 24 hours.This study demonstrates the stable drug release capability of idarubicin-loaded EqualSpheres.

Abstract: To explore the relationship between the replication-associated bromodomain protein 4 ( BRD4)and human papillomavirus (HPV) 16(HPV16) viral load in cervical squamous cell carcinoma and CIN Ⅰ tissues , confirm the effects of BRD4 degradation agent MZ1 on viral load . Methods : Thirty HPV16-positive cervi- cal cancer specimens and 30 non-cervical cancer specimens were collected , and the viral load of the samples was detected by real-time fluorescence quantitative PCR , and the expression of BRD4 was analyzed by immunohisto- chemistry and Western blot. Results : The viral load was higher in the samples of cervical cancer group than in the samples of non-cancer group , the difference is statistically significant ( P < 0. 01) . Immunohistochemistry results showed that the expression of BRD4 were significantly higher in cervical cancer specimens than in noncancerous specimens , the difference is statistically significant (P < 0. 05) . BRD4 expression was significantly and positively correlated with high viral loads , the difference is statistically significant (P < 0. 001) . the BRD4 degradation agent MZ1 significantly reduced the viral load , the difference is statistically significant (P < 0. 01) . Conclusion BRD4 may be involved in the replication of HPV16 virus , and BRD4 degradation agent MZ1 can inhibit the replication of HPV16 virus .

Objective To explore the mechanisms of Qingre Lidan Jiedu Recipe(QLJR)for improving cognitive dysfunction in rats with high copper load.Methods Seventy-five male SD rats were randomized into normal control group,model group,QLJR group,penicillamine(PCA)group,and QLJR+PCA group.Except for those in the control group,all the rats were fed a high-copper diet for 12 weeks.The effects of the treatments on cognitive function of the rats were assessed using the Barnes maze and passive avoidance tests.Hippocampal expressions of NIX,FUNDC1 and LC3 of the rats were detected using Western blotting and immunofluorescence staining,and changes in mitochondrial morphology were observed with transmission electron microscopy.Results Behavioral tests showed prolonged target hole latency,shortened latency to enter the dark chamber,and increased error counts of the rats in the model group,which were significantly improved in QLJR+PCA group;the error counts were significantly lower in QLJR+PCA group than in either QLJR or PCA group.Among all the groups,the hippocampal expressions of NIX and FUNDC1 were the lowest and LC3 I/II expression the highest in the model group;NIX and FUNDC1 expressions were significantly higher and LC3 I expression was lower in QLJR+PCA group than in QLJR group and PCA group.Immunofluorescence staining revealed weakened NIX and FUNDC1 expressions and enhanced LC3 expression in the hippocampus of the rats in the model group as compared with those in the normal control and QLJR+PCA groups,but their expressions did not differ significantly between QLJR and PCA groups.The rats in the model group showed obvious structural disarray of the mitochondria,which were improved in all the treatment groups.Conclusion QLJR improves cognitive dysfunction in rats with high copper load possibly by regulating mitophagy.