To investigate the effects of Biyan Jiedu Capsules on the proliferation and apoptosis of nasopharyngeal carcinoma cells and their molecular mechanism, nasopharyngeal carcinoma cells CNE1 and CNE2 were used. They were divided into control group(30% blank serum medium), low-(10% drug-containing serum + 20% blank serum medium), medium-(20% drug-containing serum + 10% blank serum medium), and high-(30% drug-containing serum medium) concentration group of Biyan Jiedu Capsules according to in vitro experiment. After 24 h of intervention, the effects of Biyan Jiedu Capsules on the proliferation of CNE1 and CNE2 were detected by CCK-8 assay, clonal formation experiment, and EdU staining. The effect of Biyan Jiedu Capsules on apoptosis of CNE1 and CNE2 was detected by flow cytometry. Western blot was used to detect the effect of Biyan Jiedu Capsules on the expression of X-linked apoptosis inhibitor protein(XIAP), survivin, proliferating cell nuclear antigen(PCNA), and PI3K/Akt pathway-related proteins in CNE1 and CNE2. The results showed that compared with the control group, the survival rate of CNE1 and CNE2 in the medium and high concentration groups of Biyan Jiedu Capsules could be decreased in a concentration-dependent way(P<0.05, P<0.01). At the same time, EdU staining and clonal formation experiments showed that the proliferation of CNE1 and CNE2 was significantly inhibited in the medium and high concentration groups of Biyan Jiedu Capsules(P<0.05, P<0.01). Flow cytometry showed that the apoptosis rate of CNE1 and CNE2 was significantly increased in all concentration groups of Biyan Jiedu Capsules(P<0.01), and the apoptosis rate was concentration-dependent. Western blot showed that the expressions of XIAP, survivin, PCNA, p-PI3K, and p-Akt in all concentration groups of Biyan Jiedu Capsules were significantly down-regulated(P<0.05, P<0.01). In conclusion, Biyan Jiedu Capsules can inhibit the proliferation and induce apoptosis of nasopharyngeal carcinoma cells possibly by down-regulating the PI3K/Akt signaling pathway.
Humans ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms/physiopathology* ; Proto-Oncogene Proteins c-akt/genetics* ; Cell Line, Tumor ; Drugs, Chinese Herbal/pharmacology* ; Phosphatidylinositol 3-Kinases/genetics* ; Signal Transduction/drug effects* ; Capsules ; Carcinoma/drug therapy*

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

OBJECTIVE: To screen anti-tumor drugs that improve antigen processing and presentation in acute myeloid leukemia (AML) cells. METHODS: A TCR-like or TCR mimic antibody that can specifically recognize HLA-A*0201:WT1_126-134 ( RMFPNAPYL) complex (hereafter referred to as HLA-A2:WT1) was synthesized to evaluate the function of antigen processing and presentation machinery (APM) in AML cells. AML cell line THP1 was incubated with increasing concentrations of IFN-γ, hypomethylating agents (HMA), immunomodulatory drugs (IMiD), proteasome inhibitors (PI) and γ-secretase inhibitors (GSI), followed by measuring of HLA-ABC, HLA-A2 and HLA-A2:WT1 levels by flow cytometry at consecutive time points. RESULTS: The TCR-like antibody we generated only binds to HLA-A*0201⁺WT1⁺ cells, indicating the specificity of the antibody. HLA-A2:WT1 level of THP-1 cells detected with the TCR-like antibody was increased significantly after co-incubation with IFN-γ, showing that the HLA-A2:WT1 TCR like antibody could evaluate the function of APM. Among the anti-tumor agents screened in this study, GSI (LY-411575) and HMA (decitabine and azacitidine) could significantly increase the HLA-A2:WT1 level. The IMiD lenalidomide and pomalidomide could aslo upregulate the expression of HLA-A2:WT1 complex under certain concentrations of the drugs and incubation time. As proteasome inhibitors, carfilzomib could significantly decreased the expression of HLA-A2:WT1, while bortezomib had no significant effect on HLA-A2:WT1 expression. CONCLUSION HLA-A2:WT1 TCR-like antibody can effectively reflect the APM function. Some of the anti-tumor drugs can affect the APM function and immunogenicity of tumor cells.
Humans ; Leukemia, Myeloid, Acute/immunology* ; Antineoplastic Agents/pharmacology* ; Antigen Presentation/drug effects* ; HLA-A2 Antigen/immunology* ; Receptors, Antigen, T-Cell/immunology* ; Cell Line, Tumor ; Interferon-gamma

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Autophagy is a cellular self-degradation process that maintains homeostasis and has been shown to promote tumor progression in advanced stages.Pancreatic cancer cells and the surrounding stromal cells exhibit high levels of autophagy.Therefore,targeting au-tophagy has emerged as a promising therapeutic strategy for pancreatic cancer.This review focuses on research targeting autophagy in pancreatic cancer treatment,elaborating on the roles and underlying mechanisms of autophagy in pancreatic cancer cell proliferation,metas-tasis,modulation of the tumor immune microenvironment,and drug resistance.Additional-ly,we summarize preclinical and clinical studies investigating autophagy-targeted therapies both as monotherapy and in combination with other treatments,aiming to provide new theo-retical rationale and therapeutic strategies for pancreatic cancer management.

ObjectiveTo investigate whether there are differences in the efficacy of Gegen Qinliantang with different contents of Puerariae Lobatae Radix on the acute enteritis （AE） model mice and provide a scientific basis for the interpretation of Gegen Qinliantang in the treatment of "Xie Re Li". MethodsA total of 112 male BALB/c mice were randomly divided into a blank group，model group，single Puerariae Lobatae Radix group，non-Puerariae Lobatae Radix group，regular dose Gegen Qinliantang group （regular dose group），half-dose Puerariae Lobatae Radix group，and doubled-dose Puerariae Lobatae Radix group， with 16 mice in each group. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of the colon tissue. Western blot was employed to detect the expression of ZO-1 （a protein in the tight junction） and Occludin in the colon tissue， as well as the changes of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）. ResultsCompared with the blank group，the DAI scores of the mice in the model group were significantly higher （P<0.05），and the histopathological sections of their colon tissues showed mucosal damage，glandular atrophy，disordered arrangement，and a large number of inflammatory cells infiltration，and the expression of ZO-1 and Occludin proteins in their colon tissues was significantly down-regulated （P<0.05，P<0.01）. The expression of inflammatory factors TNF-α and IL-1β was significantly up-regulated （P<0.05，P<0.01）. Compared with the model group，the DAI scores of mice in all dosing groups decreased significantly （P<0.05），with the most significant effect in the regular dose group. After 7 d of drug administration，the regular dose group had the best impact on the repair of colonic mucosa in the AE mouse model. The regular dose group significantly down-regulated the expression of TNF-α （P<0.05） and significantly up-regulated the expression of ZO-1 protein （P<0.05）. The doubled-dose Puerariae Lobatae Radix group significantly down-regulated the expression of IL-1β protein （P<0.01），and there was no significant difference between all dosing groups and the model group in terms of the expression of Occludin protein. After 14 d of drug administration，the best effect on the repair of colonic mucosa in the AE mouse model was observed in the doubled dose Puerariae Lobatae Radix group. All groups except the non-Puerariae Lobatae Radix group significantly down-regulated the expression of TNF-α （P<0.01）. Meanwhile，the regular dose group and doubled-dose Puerariae Lobatae Radix group significantly elevated the expression level of Occludin protein （P<0.01）. The doubled-dose Puerariae Lobatae Radix group also significantly inhibited the expression of IL-1β protein （P<0.05） and up-regulated ZO-1 protein expression （P<0.05）. ConclusionGegen Qinliantang can reduce the pathological damage of colon tissue， protect the barrier function and structure of intestinal epithelial cells， and reduce the expression of inflammatory factors， so as to achieve the therapeutic effect of AE model mice. When comparing the therapeutic efficacy of Gegen Qinliantang containing different Gegen contents， Gegen Qinliantang with the proportion of the original formula of Zhongjing was the most effective in AE model mice.

ObjectiveTo investigate whether there are differences in the efficacy of Gegen Qinliantang with different contents of Puerariae Lobatae Radix on the acute enteritis （AE） model mice and provide a scientific basis for the interpretation of Gegen Qinliantang in the treatment of "Xie Re Li". MethodsA total of 112 male BALB/c mice were randomly divided into a blank group，model group，single Puerariae Lobatae Radix group，non-Puerariae Lobatae Radix group，regular dose Gegen Qinliantang group （regular dose group），half-dose Puerariae Lobatae Radix group，and doubled-dose Puerariae Lobatae Radix group， with 16 mice in each group. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of the colon tissue. Western blot was employed to detect the expression of ZO-1 （a protein in the tight junction） and Occludin in the colon tissue， as well as the changes of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）. ResultsCompared with the blank group，the DAI scores of the mice in the model group were significantly higher （P<0.05），and the histopathological sections of their colon tissues showed mucosal damage，glandular atrophy，disordered arrangement，and a large number of inflammatory cells infiltration，and the expression of ZO-1 and Occludin proteins in their colon tissues was significantly down-regulated （P<0.05，P<0.01）. The expression of inflammatory factors TNF-α and IL-1β was significantly up-regulated （P<0.05，P<0.01）. Compared with the model group，the DAI scores of mice in all dosing groups decreased significantly （P<0.05），with the most significant effect in the regular dose group. After 7 d of drug administration，the regular dose group had the best impact on the repair of colonic mucosa in the AE mouse model. The regular dose group significantly down-regulated the expression of TNF-α （P<0.05） and significantly up-regulated the expression of ZO-1 protein （P<0.05）. The doubled-dose Puerariae Lobatae Radix group significantly down-regulated the expression of IL-1β protein （P<0.01），and there was no significant difference between all dosing groups and the model group in terms of the expression of Occludin protein. After 14 d of drug administration，the best effect on the repair of colonic mucosa in the AE mouse model was observed in the doubled dose Puerariae Lobatae Radix group. All groups except the non-Puerariae Lobatae Radix group significantly down-regulated the expression of TNF-α （P<0.01）. Meanwhile，the regular dose group and doubled-dose Puerariae Lobatae Radix group significantly elevated the expression level of Occludin protein （P<0.01）. The doubled-dose Puerariae Lobatae Radix group also significantly inhibited the expression of IL-1β protein （P<0.05） and up-regulated ZO-1 protein expression （P<0.05）. ConclusionGegen Qinliantang can reduce the pathological damage of colon tissue， protect the barrier function and structure of intestinal epithelial cells， and reduce the expression of inflammatory factors， so as to achieve the therapeutic effect of AE model mice. When comparing the therapeutic efficacy of Gegen Qinliantang containing different Gegen contents， Gegen Qinliantang with the proportion of the original formula of Zhongjing was the most effective in AE model mice.

Objective To investigate the effect of health failure mode and effect analysis(HFMEA)in optimizing the management process of postoperative diabetes insipidus in children undergoing neurosurgery.Methods Based on HFMEA,a management flowchart for postoperative diabetes insipidus in children undergoing neurosurgery was created.Brainstorming was adopted to identify failure modes in the workflow,analyze risk factors,and develop improvement measures,thereby refining the management flowchart.The amelioration and prognosis of diabetes insipidus in these children before(October 2022 to November 2023)and after(January 2024 to February 2025)implementation of the management flowchart were compared.Results The HFMEA-based management process for postoperative diabetes insipidus in children undergoing neurosurgery alleviated the symptoms of diabetes insipidus regarding the number of diabetes insipidus in the pediatric intensive care unit(P=0.006),the average daily urine output in the pediatric intensive care unit(P=0.001),the proportion of electrolyte abnormalities at discharge/transfer(P=0.037),the duration of mechanical ventilation(P=0.007),and the length of stay in the intensive care unit(P=0.001).Conclusion The HFMEA-based management process for postoperative diabetes insipidus in children undergoing neurosurgery is beneficial to the optimization of the management process,the alleviation of postoperative diabetes insipidus,and the improvement of prognosis in these children.
Humans ; Diabetes Insipidus/etiology* ; Neurosurgical Procedures/adverse effects* ; Child ; Postoperative Complications/therapy* ; Healthcare Failure Mode and Effect Analysis ; Intensive Care Units, Pediatric ; Risk Factors

Nitrofurantoin(NFT)is a nitrofuran antibiotic commonly used as a veterinary drug to treat bacterial infections in animals.However,due to the low solubility and bioaccumulation properties,NFT is prone to leave excessive residues in animal-derived foods and water systems,posing serious threats to human health and ecosystems.Therefore,there is an urgent need to develop an efficient and rapid detection method for NFT.In this work,nitrogen-doped carbon nanomaterials with unique bowl-like structures(N-CNBs)were synthesized via a hydrothermal-carbonization method.The morphology,surface structure,and specific surface area of N-CNBs were characterized using transmission electron microscopy(TEM),scanning electron microscopy(SEM),and X-ray photoelectron spectroscopy(XPS).The N-CNB modified glassy carbon electrode(N-CNB/GCE)was prepared,and the electrochemical test revealed that the N-CNB/GCE exhibited higher conductivity and larger electrochemical active surface area compared to bare GCE and nitrogen-doped hollow carbon nanosphere-modified electrode(N-HCNS/GCE).Additionally,the N-CNB/GCE demonstrated superior electrocatalytic activity toward NFT.An NFT electrochemical sensor was constructed based on N-CNB/GCE.The detection conditions of the sensor were optimized,and differential pulse voltammetry(DPV)was employed for NFT detection under optimal experimental conditions.The established NFT electrochemical sensor had a wide linear range of 0.4-500 μmol/L,a low detection limit(S/N=3)of 0.015 μmol/L and high selectivity,with excellent stability and reproducibility.The practical feasibility of this sensor was confirmed by analysis of NFT in milk and tap water samples,with spiked recoveries ranging from 94.2%to 108.9%.

Triple-negative breast cancer (TNBC) represents a distinctive subtype, characterized by the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). Due to its high inter-tumor and intra-tumor heterogeneity, TNBC poses significant chanllenges for personalized diagnosis and treatment. The advant of clustered regular interspaced short palindromic repeats (CRISPR) technology has profoundly enhanced our understanding of the structure and function of the TNBC genome, providing a powerful tool for investigating the occurrence and development of diseases. This review focuses on the application of CRISPR/Cas technology in the personalized diagnosis and treatment of TNBC. We begin by discussing the unique attributes of TNBC and the limitations of current diagnostic and treatment approaches: conventional diagnostic methods provide limited insights into TNBC, while traditional chemotherapy drugs are often associated with low efficacy and severe side effects. The CRISPR/Cas system, which activates Cas enzymes through complementary guide RNAs (gRNAs) to selectively degrade specific nucleic acids, has emerged as a robust tool for TNBC research. This technology enables precise gene editing, allowing for a deeper understanding of TNBC heterogeneity by marking and tracking diverse cell clones. Additionally, CRISPR facilitates high-throughput screening to promptly identify genes involved in TNBC growth, metastasis, and drug resistance, thus revealing new therapeutic targets and strategies. In TNBC diagnostics, CRISPR/Cas was applied to develop molecular diagnostic systems based on Cas9, Cas12, and Cas13, each employing distinct detection principles. These systems can sensitively and specifically detect a variety of TNBC biomarkers, including cell-specific DNA/RNA and circulating tumor DNA (ctDNA). In the realm of precision therapy, CRISPR/Cas has been utilized to identify key genes implicated in TNBC progression and treatment resistance. CRISPR-based screening has uncovered potential therapeutic targets, while its gene-editing capabilities have facilitated the development of combination therapies with traditional chemotherapy drugs, enhancing their efficacy. Despite its promise, the clinical translation of CRISPR/Cas technology remains in its early stages. Several clinical trials are underway to assess its safety and efficacy in the treatment of various genetic diseases and cancers. Challenges such as off-target effects, editing efficiency, and delivery methods remain to be addressed. The integration of CRISPR/Cas with other technologies, such as 3D cell culture systems, human induced pluripotent stem cells (hiPSCs), and artificial intelligence (AI), is expected to further advance precision medicine for TNBC. These technological convergences can offer deeper insights into disease mechanisms and facilitate the development of personalized treatment strategies. In conclusion, the CRISPR/Cas system holds immense potential in the precise diagnosis and treatment of TNBC. As the technology progresses and becomes more costs-effective, its clinical relevance will grow, and the translation of CRISPR/Cas system data into clinical applications will pave the way for optimal diagnosis and treatment strategies for TNBC patients. However, technical hurdles and ethical considerations require ongoing research and regulation to ensure safety and efficacy.