To investigate the efficacy and safety of glucocorticoids combined with cyclophosphamide (CTX) and rituximab (RTX) in elderly patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis with renal involvement.

Chronic liver diseases with common causes including viral infections， alcohol abuse， and autoimmune diseases. Alkaloids， as a class of plant-derived compounds， have shown significant potential in regulating chronic liver diseases. Recent studies have shown that alkaloids are able to exert a therapeutic effect on chronic liver diseases through multiple pathways. These compounds have a regulatory effect on key pathological processes such as liver fibrosis， inflammatory response， oxidative stress， and cell apoptosis， and they also regulate the metabolic homeostasis of hepatocytes by modulating multiple signaling pathways， thereby playing a role in regulating chronic liver diseases. This article reviews the role and mechanism of alkaloids in the treatment of chronic liver diseases， in order to provide new ideas and directions for the treatment of chronic liver diseases.

Hypertension is a systemic chronic vascular disease. From the perspective of Traditional Chinese Syndromes, hypertension belongs to the category of liver fire, vertigo, liver yang, headache and so on. Chinese medicine treatment of hypertension has gradually become a hot research topic, and using Chinese herbal medicine to reduce blood pressure has also achieved good results. In recent years, researches on anti-hypotension of Bidens pilosa L. has gradually increased. The related research of Bidens pilosa L., including the ancient literature, modern research, functional components and mechanism were mainly summarized, the application of Bidens pilosa L. in lowering blood pressure were anticipated, with a view to provide reference for the further development and utilization of Bidens pilosa L. in treatment of hypertension.

A 32-year-old female patient experienced a foreign body sensation in her esophagus on the evening of September 22, 2024, after consuming undercooked grass carp at a restaurant in Wuhan. Esophagoscopy conducted at the hospital revealed no abnormalities. Three days later, she had a stabbing pain in the pharynx. On October 8, upon self-examination, she noticed a red brown worm exhibiting stretching and contracting movements attached near the uvula in her pharynx and then went to the hospital. During the removal of the worm, the doctor observed the ulcers on the mucous membrane. Serological antibody tests for seven common human parasitic worms, including Schistosoma japonicum, Paragonimus westermani, Clonorchis sinensis, cysticercus of Taenia solium, sparganum, hydatid cyst, and Trichinella spiralis, were all negative. The isolated worm was reddish brown, measuring 4 mm in length and 2 mm in width. Staining with hydrochloric carmine dye revealed a morphology consistent with Clinostomum complanatum (Rud., 1819), characterized by an oral sucker at the anterior end, a pharynx connecting to intestinal branches, and two intestinal branches extending to the posterior end of the body with small sub-branches. The ventral sucker, larger than the oral sucker, was located at the front 1/4 of the body. A pair of testes were arranged longitudinally in the mid-posterior part, with an ovary located between the two testes and a uterus located above the upper testis. A comprehensive search of 188 databases comprising more than 460 million full-text articles through the library of Huazhong University of Science and Technology confirmed the first reported case of Clinostomum complanatum infection in humans in China.

BACKGROUND: Durvalumab after chemoradiotherapy (CRT) failed to bring survival benefits to patients with epidermal growth factor receptor ( EGFR ) mutations in PACIFIC study (evaluating durvalumab in patients with stage III, unresectable NSCLC who did not have disease progression after concurrent chemoradiotherapy). We aimed to explore whether locally advanced inoperable patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs) and the optimal treatment regimen. METHODS: We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from inception to December 31, 2022 and performed a meta-analysis based on a Bayesian framework, with progression-free survival (PFS) and overall survival (OS) as the primary endpoints. RESULTS: A total of 1156 patients were identified in 16 studies that included 6 treatment measures, including CRT, CRT followed by durvalumab (CRT-Durva), TKI monotherapy, radiotherapy combined with TKI (RT-TKI), CRT combined with TKI (CRT-TKI), and TKI combined with durvalumab (TKI-Durva). The PFS of patients treated with TKI-containing regimens was significantly longer than that of patients treated with TKI-free regimens (hazard ratio [HR] = 0.37, 95% confidence interval [CI], 0.20-0.66). The PFS of TKI monotherapy was significantly longer than that of CRT (HR = 0.66, 95% CI, 0.50-0.87) but shorter than RT-TKI (HR = 1.78, 95% CI, 1.17-2.67). Furthermore, the PFS of RT-TKI or CRT-TKI were both significantly longer than that of CRT or CRT-Durva. RT-TKI ranked first in the Bayesian ranking, with the longest OS (60.8 months, 95% CI = 37.2-84.3 months) and the longest PFS (21.5 months, 95% CI, 15.4-27.5 months) in integrated analysis. CONCLUSIONS: For unresectable stage III EGFR mutant NSCLC, RT and TKI are both essential. Based on the current evidence, RT-TKI brings a superior survival advantage, while CRT-TKI needs further estimation. Large randomized clinical trials are urgently needed to explore the appropriate application sequences of TKI, radiotherapy, and chemotherapy. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022298490.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; ErbB Receptors/genetics* ; Lung Neoplasms/drug therapy* ; Mutation/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Chemoradiotherapy ; Antibodies, Monoclonal/therapeutic use*

Objective: To investigate the mechanism of action of curcumol on mitochondrial autophagy in hepatic stellate cells and its molecular mechanism against liver fibrosis. Methods : Hepatic stellate cells were divided into blank group, model group(lipopolysaccharide 5 mg/L), and low, medium and high curcumol group(12.5, 25 and 50 mg/L); Thiazolyland(MTT) was used to detect the effects of curcumol on the viability of hepatic stellate cells; flow cytometry was used to detect the effects of curcumol on apoptosis of hepatic stellate cells; 5,5′,6,6′-Tetrachloro-1,1′,3,3′-tetraethylimidacarbocyanine iodide(JC-1) was used to detect the mitochondrial membrane potential; effects of curcumol on mitochondrial morphology and autophagosome were detected by transmission electron microscopy; effect of curcumol on mitochondrial localisation were detected by fluorescent probe; Immunoblotting assay was performed to detect the effects of curcumin on PTEN-induced putative kinase 1(PINK1), Parkinson's disease protein(Parkin), microtubule-associated protein light chain 3(LC3), autophagy-associated protein(Beclin1), mitochondrial inner membrane translocase 23(Timm23), mitochondrial outer membrane translocase 20(Tomm20), Bcl-2 associated X protein(Bax), B lymphocytoma-2(Bcl2), cleaved-cysteine protease 3(Caspase3), α-smooth muscle actin(ɑ-SMA), collagen type Ⅰ(Collagen Ⅰ), and collagen type Ⅲ(Collagen Ⅲ) protein expression. Results : Compared with the blank control group, cell proliferation rate, Caspase3, Bcl2, LC3Ⅱ, Beclin1, PINK1, Parkin, ɑ-SMA, CollagenⅠ, CollagenⅢ proteins significantly increased in the model group(P<0.01), co-localisation of mitochondria and lysosomes increased, and the number of mitochondrial autophagosome significantly increased(P<0.01), while Timm23 and Tomm20 proteins, mitochondrial membrane potential decreased significantly(P<0.01), apoptosis rate decreased, and Bax protein expression decreased. Compared with the model group, after curcumol intervention, cell proliferation rate, Bcl2, Timm23, Tomm20, α-SMA, CollagenⅠ and CollagenⅢ protein expression significantly decreased in the curcumol low-, medium-and high-concentration groups(P<0.01), and the mitochondrial membrane potential significantly decreased(P<0.01), whereas apoptosis rate, Caspase3, Bax, LC3Ⅱ, Beclin1, PINK1 and Parkin proteins significantly increased(P<0.05), the co-localisation of mitochondria and lysosomes increased, and the number of mitochondrial autophagosome significantly increased(P<0.01). Conclusion Curcumol exerts ameliorative effects on hepatic fibrosis by modulating mitochondrial hyperautophagy mediated by the PINK1/Parkin signaling pathway, and promoting hepatic stellate cell apoptosis.

Objective To investigate the molecular mechanism of hepatic fibrosis(HF)regulation by liver sinusoidal endothelial cells(LSECs)via endothelial mesenchymal transition(EnMT),and to predict the natural active components using bioinformatics,machine learning,and cellular experiments.Methods HF and EnMT gene matrices were obtained and the intersecting genes were extracted and enriched using Limma difference analysis and weighted gene co-expression network analysis(WGCNA).The diagnostic genes were screened using a combination of random forest method,support vector machine-recursive feature elimination and network topology analysis,and immune infiltration analysis and prediction of natural active ingredients were performed.The expression of diagnostic genes and the pharmacological effects of the predicted ingredients were finally verified by cellular experiments.Results Differential analysis yielded 3034 EnMT-associated and 4133 HF-associated differential genes.WGCNA analysis yielded 4589 EnMT-associated Hub genes and 763 HF-associated Hub genes.Thirty-eight intersecting genes were extracted,which were mainly enriched in the pathways of basement membrane and extracellular matrix receptor interaction.Four diagnostic genes,CFP,COL4A2,ITGA1,and GRPEL1,were screened by multidimensional analysis.Immune infiltration analysis showed that the diagnostic genes were closely associated with mast cell resting state,memory B cells,and memory CD4+T cells.Reverse transcription-polymerase chain reaction analysis showed significantly increased mRNA expression levels of the four diagnostic genes in the Jagged1-induced model group(P＜0.05).The predicted components,sterol,kaempferol,and quercetin,all had good binding activities with the diagnostic genes.Enzyme-linked immunosorbent assay result confirmed that all three active components significantly reduced the expression of collagen type Ⅳ α2 chain protein in Jagged1-induced LSECs,with quercetin having the most significant effect(P＜0.01).Conclusions This study elucidated the molecular mechanism of hepatic sinusoidal endothelial cells involved in the pathological process of HF through mesenchymal transition.We also propose a diagnostic marker system including CFP,COL4A2,ITGA1,and GRPEL1 as core genes.The result also suggest that natural active ingredients,such as quercetin,may exert anti-HF pharmacological effects by targeting these diagnostic genes.

Objective To investigate the effect of postoperative reduction quality in femoral neck fracture internal fixation on mechanical properties of the femoral head from the perspective of trabecular bone biomechanics.Methods From patients who underwent hip replacement surgery for femoral neck fractures,a total of 26 femoral head slice specimens were obtained.The central axis of the primary compressive trabeculae was defined as the 0° group,with the intersection point of the primary compressive trabeculae and the femoral calcar serving as the center.By rotating the specimens to simulate different reduction angles,the cut femoral head slice specimens were randomly divided into five groups:-10°,-5°,0°,5°,and 10°,representing femoral heads with varying reduction qualities.The specimens were subjected to single compression load tests and fatigue load tests.The load was set from 70 N to 1 400 N,at a frequency of 1 Hz,with 10 000 cycles.Axial stiffness,displacement,and the number of collapse cycles were measured,to compare the biomechanical properties of femoral head specimens under different reduction qualities.Results There were differences in the axial stiffness,displacement,and number of collapse cycles among the femoral head specimens in different groups.Under 800 N load,the axial stiffness of 0° group was significantly greater than that of±10° groups(P＜0.05).The axial stiffness of 0° group was also greater than that of the±5° groups,but the differences were not statistically significant(P＞0.05).The axial stiffness of±5° groups was greater than that of±10° groups(P＜0.05).0° group had a lower displacement than±5° groups and±10° groups.However,the differences in displacement between 0° group and±5° groups were not statistically significant(P＞0.05),while the differences between the 0° group and±10° groups were statistically significant(P＜0.05).The differences in displacement between±5° groups and±10° groups were also statistically significant(P＜0.05).0° group had a significantly higher number of collapse cycles than±10° groups(P＜0.05).The number of collapse cycles in 0° group was also higher than that in±5° groups,but the differences were not statistically significant(P＞0.05).The number of collapse cycles in±5° groups was significantly higher than that±10° groups(P＜0.05).Conclusions The quality of reduction after internal fixation of femoral neck fractures significantly affects the biomechanical properties of the femoral head.This study provides a scientific basis for optimizing treatment and postoperative management,aiming to improve clinical outcomes and patients' quality of life.

Objective To address the current issues of strong subjectivity in drug classification,vague classification standards,and complex influencing factors,this study aims to explore a scientific method for drug classification to reduce inventory costs and improve inventory effectiveness.Methods A total of 700 drugs were randomly selected from the historical data of a tertiary hospital in Beijing from 2021 to 2022 as the research subjects.The classification was conducted using the Principal Component Analysis(PCA)algorithm and the K-means clustering algorithm(K-means).Results The optimal number of classifications was determined to be 4,with a silhouette coefficient of 0.347 0.The 700 drugs were divided into four categories,with 363 in the first category,186 in the second,94 in the third,and 57 in the fourth.The drug classification method studied in this paper was simulated and applied to the drug inventory management of a certain tertiary hospital in the second quarter of 2023.The simulation results indicated that the classification method studied in this paper could reduce inventory costs and improve inventory effectiveness.Conclusion The drug classification method based on PCA algorithm and K-means clustering algorithm can provide a reliable basis for the management of drug inventory classification.

Objective To investigate the molecular mechanism of hepatic fibrosis(HF)regulation by liver sinusoidal endothelial cells(LSECs)via endothelial mesenchymal transition(EnMT),and to predict the natural active components using bioinformatics,machine learning,and cellular experiments.Methods HF and EnMT gene matrices were obtained and the intersecting genes were extracted and enriched using Limma difference analysis and weighted gene co-expression network analysis(WGCNA).The diagnostic genes were screened using a combination of random forest method,support vector machine-recursive feature elimination and network topology analysis,and immune infiltration analysis and prediction of natural active ingredients were performed.The expression of diagnostic genes and the pharmacological effects of the predicted ingredients were finally verified by cellular experiments.Results Differential analysis yielded 3034 EnMT-associated and 4133 HF-associated differential genes.WGCNA analysis yielded 4589 EnMT-associated Hub genes and 763 HF-associated Hub genes.Thirty-eight intersecting genes were extracted,which were mainly enriched in the pathways of basement membrane and extracellular matrix receptor interaction.Four diagnostic genes,CFP,COL4A2,ITGA1,and GRPEL1,were screened by multidimensional analysis.Immune infiltration analysis showed that the diagnostic genes were closely associated with mast cell resting state,memory B cells,and memory CD4+T cells.Reverse transcription-polymerase chain reaction analysis showed significantly increased mRNA expression levels of the four diagnostic genes in the Jagged1-induced model group(P＜0.05).The predicted components,sterol,kaempferol,and quercetin,all had good binding activities with the diagnostic genes.Enzyme-linked immunosorbent assay result confirmed that all three active components significantly reduced the expression of collagen type Ⅳ α2 chain protein in Jagged1-induced LSECs,with quercetin having the most significant effect(P＜0.01).Conclusions This study elucidated the molecular mechanism of hepatic sinusoidal endothelial cells involved in the pathological process of HF through mesenchymal transition.We also propose a diagnostic marker system including CFP,COL4A2,ITGA1,and GRPEL1 as core genes.The result also suggest that natural active ingredients,such as quercetin,may exert anti-HF pharmacological effects by targeting these diagnostic genes.