BACKGROUND:β-Caryophyllene has a variety of pharmacological activities such as antioxidant,anti-inflammatory and anti-apoptotic,which may have a better therapeutic effect on osteoarthritis.OBJECTIVE:To investigate the effect and mechanism of β-caryophyllene on mouse osteoarthritis.METHODS:Forty C57BL/6J mice were randomly divided into sham group,model group,low-dose β-caryophyllene group and high-dose β-caryophyllene group,with 10 mice in each group.Hulth method was used to construct an osteoarthritis model in the latter three groups.Four weeks after modeling,70 and 140 mg/kg/d β-caryophyllene was intragastrically given in the low-and high-dose β-caryophyllene groups,respectively,and normal saline was given by gavage in the sham group and the model group,once a day,for 4 weeks.After administration,knee joint morphological changes were observed by hematoxylin-eosin staining,serum levels of inflammatory factors(tumor necrosis factor-α,interleukin-1β,interleukin-6,and interleukin-10)were detected by ELISA,and oxidative stress indexes(glutathione peroxidase,superoxide dismutase,and malondialdehyde)were detected by chemiluminescence.The expression levels of key proteins in the Sonic hedgehog(Shh)/glioma associated oncogene homolog 1(Gli1)signaling pathway were detected by immunohistochemistry and western blot.RESULTS AND CONCLUSION:(1)Compared with the sham group,a large number of inflammatory cells infiltrated in the knee joint of mice in the model group,cartilage tissue was seriously damaged,serum levels of tumor necrosis factor-α,interleukin-1β,interleukin-6,interleukin-10 and malondialdehyde were significantly increased(P＜0.01),the activities of glutathione peroxidase and superoxide dismutase were significantly decreased(P＜0.01),and the relative expression levels of Shh and Gli1 in the knee joint were significantly increased(P＜0.01).(2)Compared with the model group,in the low-and high-dose β-caryophyllene groups,inflammatory cell infiltration in the mouse knee joint was decreased,cartilage tissue injury was alleviated,serum levels of tumor necrosis factor-α,interleukin-1 β,interleukin-6 and malondialdehyde were significantly decreased(P＜0.05),the activities of glutathione peroxidase and superoxide dismutase were significantly increased(P＜0.01),and the expression levels of Shh and Gli1 in the knee joint were significantly decreased(P＜0.01).The above-mentioned improvements were more significant in the high-dose β-caryophyllene group than the low-dose β-caryophyllene group.To conclude,β-caryophyllene can improve osteoarthritis,and its mechanism may be related to reducing inflammation and oxidative stress damage by regulating the Shh/Gli1 signaling pathway.

OBJECTIVE To explore the influencing factors for successful detoxification in patients undergoing methadone maintenance therapy. METHODS A retrospective selection of 161 methadone maintenance therapy patients from the South Branch of Zhongshan Second People’s Hospital （including methadone maintenance treatment sites in Shiqi District， Xiqu District， Development Zone of Zhongshan City） from January 1， 2012， to January 1， 2025， was conducted as the study object. Data collected included patients’ sociodemographic information， drug abuse history， laboratory test results， medication records， etc. Patients were divided into the unsuccessful detoxification group and the successful detoxification group based on whether methadone detoxification was achieved. Univariate， univariate Cox regression， and multivariate Cox proportional hazards regression were used for influencing factor analysis， and the Kaplan-Meier method was employed for survival analysis. RESULTS Among the 161 methadone maintenance therapy patients， 96 were in the successful detoxification group and 65 in the unsuccessful detoxification group， yielding a successful detoxification rate of 59.63%. Multivariate Cox proportional hazards regression analysis revealed that age， registered residence status， age at first drug use， and duration of drug abuse were key influencing factors for successful detoxification in methadone maintenance therapy patients （P＜0.05）. Specifically， the successful detoxification rate for patients with Zhongshan local registered residence was 8.364 times higher than that for patients with non-local registered residence； for every 1-year increase in patient age， the successful detoxification rate decreased by 22.7%； for every 1-year increase in age at first drug use， the successful detoxification rate rose by 33.4%； and for every 1-year increase in duration of drug abuse， the successful detoxification rate increased by 33.5%. Survival analysis showed that the successful detoxification rate in the methadone low-dose group （≤30.8 mg） was significantly higher than that in the methadone high-dose group （＞30.8 mg） （P＝0.015）， and the successful detoxification rate in the population with Zhongshan local registered residence was significantly higher than that in those with non-local registered residence （P＜0.001）. CONCLUSIONS Age， registered residence status， age at first drug use， and duration of drug abuse are key influencing factors for successful detoxification in patients undergoing methadone maintenance therapy， and the last methadone dose may be associated with successful detoxification.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

This article systematically analyzed the historical evolution of the origin， scientific name， producing area， quality evaluation， harvesting and processing， and other aspects of Quisqualis Fructus by consulting the ancient materia medica， medical books， prescription books， local literature and combining with the modern literature and standards， summarized and explored the development rules of its medicinal properties and efficacy along with their underlying causes， in order to provide support for the development and utilization of famous classical formulas containing this herb. According to the textual research， Shijunzi was first recorded as Liuqiuzi in Nanfang Caomuzhuang of the Jin dynasty， and the name of Shijunzi was first used in Kaibao Bencao of the Song dynasty， which has been consistently used throughout subsequent dynasties， and there were also aliases such as Junziren， Sijunzi， and Dujilizi. The mainstream source of Quisqualis Fructus used in the past dynasties has been the dried mature fruits of Quisqualis indica， a plant belonging to the family Combretaceae. In modern times， its variety Q. indica var. villosa has also been recorded as the medicinal material of Quisqualis Fructus. In 2007， the Flora of China（English edition） designated Q. indica var. villosa as a synonym of Q. indica. Today， the accepted name of Shijunzi is updated to Combretum indicum. According to ancient herbal records， the producing areas of Quisqualis Fructus were Guangdong， Hong Kong， Macao， Guangxi， Hainan， Sichuan and Fujian， and then gradually expanded to Yunnan， Taiwan， Jiangxi and Guizhou. Since the Song dynasty， two major production regions have gradually emerged in Sichuan， Chongqing and Fujian. Currently， it is primarily cultivated in Chongqing， Guangxi and other areas， with Chongqing yielding the highest output. Since modern times， superior quality has been defined by large size， a purple-black surface， plump grains， and a yellowish-white kernel. According to ancient herbal records， the harvesting period of Quisqualis Fructus was the July and August of the lunar calendar， mostly used raw after shelling or with the shell intact， it underwent processing methods such as cleaning， slicing， mixing， steaming， roasting， stewing， and frying. Currently， the harvesting period is autumn， followed by sun-drying or low-heat drying， with processing methods including cleaning， stir-frying， and stewing. In ancient and modern literature， the records of the properties， functions and indications of Quisqualis Fructus are basically the same， that is， sweet in taste， warm in nature， predominantly non-toxic， belonging to the spleen and stomach meridians. It possesses effects of insecticide， decontamination and invigorating spleen for ascariasis， enterobiasis， abdominal pain due to worm accumulation and infantile malnutrition.The contraindications for use primarily include avoiding consumption by individuals without parasitic infestations， limiting use for those with spleen-stomach deficiency-cold， refraining from drinking hot tea during medication， and avoiding excessive intake. Based on the textual research， it is suggested that the dried mature fruits of Q. indica should be used as the medicinal material for the development of famous classical formulas containing Quisqualis Fructus. Processing methods may be chosen according to prescription requirements， and the raw products is recommended for medicinal use if not specified.

[摘 要] 目的：评估汉曲优（HLX02，Zercepac®）与帕妥珠单抗联合化疗在人表皮生长因子受体2（HER-2）阳性、非特殊型浸润性乳腺癌患者中的新辅助治疗效果，并与传统曲妥珠单抗原研药赫赛汀联合帕妥珠单抗方案的疗效和安全性进行对比。方法：本研究为一项多中心回顾性队列研究。纳入2020年5月至2024年9月于莆田学院附属医院及漳州正兴医院接受汉曲优或赫赛汀（均联合帕妥珠单抗及化疗）新辅助治疗的132例HER-2阳性乳腺癌患者。主要终点为病理完全缓解（pCR）率（依据Miller-Payne系统G5级定义）。次要终点包括客观缓解率（ORR，基于RECIST 1.1标准）、不良事件（采用CTCAE 5.0和PRO-CTCAE标准评估）发生率、生活质量（EORTC QLQ-C30量表）及治疗费用。采用SPSS 27.0软件进行统计分析，为控制混杂偏倚，应用倾向性评分匹配（PSM）以1∶1比例匹配组间基线特征。结果：经筛选后共117例患者纳入分析（汉曲优组65例，赫赛汀组52例）。经PSM匹配后，两组各42例患者，基线特征均衡。汉曲优组与赫赛汀组的pCR率无显著差异（66.67% vs 69.05%，P = 0.815）。两组的ORR（83.33% vs 85.71%，P = 0.763）、各级别不良事件发生率及生活质量评分均无统计学差异（均P > 0.05）。然而，汉曲优组患者自付费用显著低于赫赛汀组[（40 358.82 ± 15 042.69）元 vs （51 170.20 ± 15 664.63）元，P = 0.002]。结论：本真实世界研究表明，在新辅助治疗中，汉曲优联合帕妥珠单抗相较于赫赛汀联合帕妥珠单抗，在HER-2阳性IBC-NST患者中表现出相当的疗效和相似的安全性，且能显著减轻患者的经济负担，为国产生物类似药的临床应用提供了循证依据。

Diabetic kidney disease（DKD） is a chronic kidney structural and functional disorder caused by diabetes. With the global prevalence of diabetes continuing to rise， DKD has gradually become a major cause of chronic kidney disease and end-stage renal disease（ESRD）， posing a serious threat to patients' quality of life and long-term health outcomes. Studies have shown that apoptosis plays a pivotal role in the development and progression of DKD， with its mechanisms involving abnormal activation of multiple signaling pathways such as Toll-like receptor 4（TLR4）/nuclear transcription factor-κB（NF-κB）/B-cell lymphoma-2（Bcl-2）/cysteinyl aspartate-specific proteinase（Caspase）-3， protein kinase R-like endoplasmic reticulum kinase（PERK）/eukaryotic initiation factor 2α（eIF2α）/activating transcript factor 4（ATF4）/CCAAT enhancer-binding protein homologous protein（CHOP）， phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β）， Janus kinase 2（JAK2）/signal transducer and activator of transcription 3（STAT3）， adenosine monophosphate-activated protein kinase（AMPK）/mammalian target of rapamycin（mTOR） and silent information regulator 1（SIRT1）/tumor suppressor protein 53（p53）， thereby accelerating renal pathological damage in DKD. Extensive evidence-based medical studies have confirmed that traditional Chinese medicine（TCM）， leveraging its unique therapeutic advantages of multi-target， multi-component and multi-pathway approaches， has demonstrated remarkable efficacy and favorable safety profiles in treating DKD. Recent studies have demonstrated that active components of TCM can specifically target and modulate key effectors in apoptotic signaling pathways. Meanwhile， traditional compound formulations exert synergistic effects through multiple approaches such as replenishing deficiency and activating blood circulation， detoxifying and dredging collaterals， tonifying kidney essence， and removing stasis and purging turbidity， thereby comprehensively regulating critical pathological processes including endoplasmic reticulum stress and mitochondrial apoptosis pathways. This combined therapeutic approach of molecular targeting and holistic regulation provides novel strategies for delaying the progression of DKD. Based on this， this paper provides an in-depth analysis of key apoptotic signaling pathways and their regulatory mechanisms， while systematically summarizing recent research advances regarding the therapeutic effects of TCM active components， compound formulations， and proprietary Chinese medicines on DKD through modulation of these pathways， with particular emphasis on their underlying molecular mechanisms. These findings not only elucidate the modern scientific connotation and theoretical basis of TCM in treating DKD but also establish a solid theoretical and practical foundation for promoting the wider clinical application and further research of TCM in the field of DKD treatment.

A 51-year-old male presented with nasal obstruction, followed by progressive hearing loss and blurred vision. Imaging identified space-occupying lesions in the paranasal sinuses, orbits, and paraspinal regions, while laboratory tests confirmed positive anti-proteinase 3 anti-neutrophil cytoplasmic antibody(PR3- ANCA) immunoglobulin G (IgG)and markedly elevated serum IgG4. Despite treatment with corticosteroids, immunosuppressants, and radiotherapy, the patient exhibited steroid dependency with relentless disease progression. Following multidisciplinary consultation, a diagnosis of inflammatory myofibroblastic tumor (IMT) coexisting with ANCA- associated vasculitis (AAV) was favored, though IgG4-related disease remained a critical differential. Ultimately, profound immunosuppression precipitated a severe herpesvirus infection, leading to disseminated intravascular coagulation and multiple organ dysfunction syndrome. This case underscores the rarity and diagnostic complexity of concurrent IMT and AAV, highlights the therapeutic dilemma of balancing primary disease control against fatal opportunistic infections, and emphasizes the critical role of multidisciplinary collaboration in the diagnosis and treatment of complex diseases.

ObjectiveTo explore the role of the histone deacetylase Sirtuin-1 （SIRT1）/p53 signaling pathway in promoting apoptosis of non-small cell lung cancer cells （NSCLC） induced by the co-stimulatory molecule B7 homolog 3 （B7-H3）. MethodsThe GEPIA 2 platform was used for survival analysis of NSCLC patients based on B7⁃H3 gene expression levels. The Gene Enrichment Analysis （GSEA） method was used to analyze the enrichment characteristics of B7⁃H3 molecules in the gene set of cell apoptosis. In the non-small cell lung cancer A549 cell line， B7⁃H3 was knocked down， and the protein expression levels of SIRT1 and p53 were detected by Western blot. B7⁃H3 was overexpressed in A549 cells and the apoptosis rate was analyzed by flow cytometry after Annexin V/PI double staining. Overexpression of B7⁃H3 and knockdown of SIRT1 were performed in A549 cell line. The expression levels of p53 and apoptosis-related proteins B-cell lymphoma/leukemia-2 （Bcl-2） and Bcl-2-associated X protein （Bax） were detected respectively by Western blot. Cell apoptosis rate was analyzed by flow cytometry after Annexin V/PI double staining. ResultsThe overall survival of the B7-H3 high-expression group was significantly lower than that of the low-expression group （P<0.01）. B7-H3 was significantly enriched in the cell apoptosis signaling pathway and the p53 signaling pathway （P<0.05）. Compared with the control group， the expression of SIRT1 was significantly downregulated， and p53 was significantly upregulated in the B7⁃H3 knockdown group （both P<0.001）. Overexpression of B7-H3 significantly up-regulated SIRT1 protein expression （P<0.05）， down-regulated p53 expression （P<0.01）， and markedly increased the Bcl-2/Bax ratio of apoptosis-related proteins （P<0.001）. The results of Annexin V/PI double staining showed that the apoptosis rate of A549 cells with overexpressed B7⁃H3 decreased （the apoptosis rate of the control group was 26.72%±4.13%， while that of the B7⁃H3 overexpression group was 13.87%±0.82%； P<0.01）. In B7-H3-overexpressing cell lines， SIRT1 knockdown significantly reversed apoptosis （P<0.05）， up-regulated p53 protein expression （P<0.001）， and markedly reduced the Bcl-2/Bax ratio （P<0.001）. ConclusionB7-H3 molecule inhibits the apoptosis of non-small cell lung cancer cells via the SIRT1/p53 signaling pathway.

Background In 2021, chronic obstructive pulmonary disease (COPD) emerged as the forth leading cause of death in the world. However, the impact of air pollutants on COPD is still inconsistent across current studies. Objective To analyze the relationship between ambient sulfur dioxide (SO₂) exposure and hospital admissions for COPD in Lanzhou, and to examine the modified effects of SO₂ across different genders, age groups, and seasons. Methods A total of 20718 hospital admission records for COPD were collected from Lanzhou between 2016 and 2020, alongside synchronized data on SO₂ concentration and meteorological variables. A generalized additive model integrated with a distributed lag nonlinear model was used to assess the relationship and the lag effects between SO₂ exposure and COPD admissions. Potential confounders, including meteorological factors, day-of-the-week effect, and holidays, were controlled for, with a maximum lag period set at 7 d. Two-pollutant models and sensitivity analyses were conducted to ensure robustness. Results are expressed as relative risks (RR) with 95% confidence intervals (95%CI). Results During the study period, the average daily number of COPD admissions was 11.34±7.03. The average mass concentration of SO₂ was (23.72±12.35) μg·m⁻³. SO₂ exposure was positively correlated with COPD admissions; specifically, each 10 μg·m⁻³ increase in SO₂ concentration was associated with an RR of 1.440 (95%CI: 1.317, 1.573). Stratified analyses found that at a cumulative lag of 7 d, the RRs were higher among females, individuals aged ≥65 years, and during the cold season. Conversely, no significant increase in COPD admission risk related to SO₂ was observed during the warm season. For every 10 μg·m⁻³ increase in SO₂ concentration, the RR was 1.483 (95%CI: 1.311, 1.678) for females, 1.441 (95%CI: 1.311, 1.583) for those aged > 65 years， and 1.595 (95%CI: 1.313, 1.937) during the cold season. Conclusion Short-term exposure to ambient SO₂ exposure in Lanzhou is associated with an increased risk of COPD admission. The association is more pronounced among females, the elderly (aged> 65 years) and during the cold season.

Organophosphate flame retardants (OPFRs) have been widely used as the main alternatives to bromine-based flame retardants, resulting in their widespread detection in environmental media and even in human blood. The potential health risks arising therefrom, particularly the direct impacts on the blood system, have become a focus in the field of environmental health. This article systematically reviewed the latest research progress on the hematotoxicity of OPFRs, covering three core aspects: the toxic effects aspect, which systematically elaborated on the bidirectional interference of OPFRs with coagulation function, their toxic effects on the hematopoietic system, and their disruptive effects on blood biochemical metabolism; the mechanistic analysis aspect, which dissected the multi-pathway, multi-target toxic mechanism network of OPFRs, including common pathways based on oxidative stress and inflammatory responses, the direct and indirect regulation of coagulation function mediated by nuclear receptors and endocrine disruption, and the disturbance of blood cell production at the source through disruption of the hematopoietic microenvironment; and the risk assessment aspect, which, in response to the limitations of traditional methods, focused on the application prospects and core advantages of novel approaches based on structure-activity relationships in filling data gaps and achieving precise risk prediction. This review aims to systematically summarize the research progress on the mechanisms of OPFR-induced hematotoxicity, providing systematic theoretical support for subsequent in-depth mechanistic studies, targeted epidemiological investigations, and the optimization of risk assessment models.