[摘 要] 目的：探讨复发/转移性鼻咽癌（NPC）接受含PD-1单抗免疫治疗的临床特征和预后影响因素。方法：回顾性分析2019年3月至2024年7月期间南部战区总医院确诊的95例NPC患者的临床资料和外周血生化及免疫学指标。预后分析采用Kaplan-Meier曲线，组间比较使用Log-rank检验，采用Cox比例风险模型进行单因素和多因素分析。结果：95例患者中男性81例，女性14例，中位年龄49.72岁（16~74岁），Ⅳ期91例（95.79%），所有患者均采用免疫治疗，联合或不联合化疗方案治疗，中位无进展生存期（mPFS）为10.5个月，客观缓解率（ORR）70.53%，疾病控制率（DCR）89.47%，接受含铂治疗方案患者PFS相对更长，且差异有统计学意义。紫杉醇 + 顺铂 + 氟尿嘧啶（TPF）对比吉西他滨 + 顺铂（GP）和紫杉醇 + 顺铂（TP）显示出更长的PFS，但差异无统计学意义。不同PD-1单抗治疗组间的PFS未显示出有统计学意义的差异。单因素及多因素Cox回归分析结果显示，肿瘤复发状态、初始血浆EBV感染状态、治疗周期数、基线外周血SII是复发/转移性NPC患者接受PD-1抑制剂治疗疗效预测的独立相关因素（均P < 0.05），并且非复发患者、初始血浆EBV DNA阳性、接受 ≥ 4治疗周期、基线外周血SII < 772.81的患者接受PD-1抑制剂治疗预后相对更好。结论：在接受PD-1抑制剂治疗的复发/转移性NPC患者中，非复发患者、初始血浆EBV DNA阳性、≥ 4治疗周期且外周血SII < 772.81者PFS相对更长，可早期识别免疫治疗效果不佳患者并精准干预。

Stroke is the leading cause of death and disability among adults in China， and its common complications include digestive system abnormalities， cognitive impairment， depression， stroke-associated pneumonia， and hemiplegia. The combination of traditional Chinese and Western medicine has great potential in treating post-stroke complications. Xinglou Chengqitang （XLCQT） is a representative prescription of alleviating the disease in the upper part by treating the lower part. It has definite therapeutic effect and high safety. Clinically， XLCQT is often used to treat stroke and its complications. However， the quantity and quality of clinical trials of XLCQT in treating post-stroke complications need to be improved. Additionally， since the basic research is weak， the material basis and multi-target mechanism for the efficacy of this prescription are unknown. This article reviews XLCQT in terms of the pharmacodynamic basis， medicinal properties， safety evaluation， and progress in clinical research and mechanisms in treating post-stroke complications. This article summarizes 22 key active ingredients of XLCQT in treating acute stroke complicated with syndrome of phlegm heat and fu-organ excess. Among these key active ingredients， resveratrol， kaempferol， luteolin， chrysoeriol， apigenin， （+）-catechin， and adenosine have good pharmacokinetic properties and high bioavailability. The mechanisms of XLCQT in treating post-stroke complications are complex， including inflammatory response， brain-gut axis， hypothalamic-pituitary-adrenal （HPA） axis， intestinal flora， neurotrophic factors， autophagy， oxidative stress， and free radical damage. This review helps to deeply understand the pharmacodynamic basis and mechanisms of XLCQT in treating post-stroke complications and provides a theoretical basis for the clinical application of XLCQT against post-stroke complications and the development of drugs.

To standardize the clinical application of oral Chinese patent medicines （CPMs）， and address the safety issues arising from their dosage form characteristics， irrational clinical use， and the lack of targeted pharmacovigilance systems， the China Association of Chinese Medicine organized the formulation and release of Pharmacovigilance Guidelines for Clinical Application of Oral Chinese Patent Medicines， aiming to inform the safe clinical use of oral CPMs and related pharmacovigilance work. According to the principles of GB/T1.1—2020 and the Drug Administration Law of the People's Republic of China （2019 revision）， the Institute of Basic Research in Clinical Medicine， China Academy of Chinese Medical Sciences， led a drafting group comprising 18 institutions. After multiple rounds of expert interviews， literature retrieval， evidence screening， and extensive solicitation of opinions， the Guidelines were registered internationally. Systematic standardization focused on safety monitoring， risk identification， assessment， control， and other aspects. The Guidelines clarified the characteristics of oral CPMs in terms of safety monitoring， known risks， and potential risks， compared to non-oral CPMs. Then， risk control measures were proposed， including medication in special populations and irrational medication. As a special guideline for pharmacovigilance in the clinical application of oral CPMs， the Guidelines systematically construct a technical system in line with the characteristics of traditional Chinese medicine （TCM）， which is essential for improving the clinical safety management of oral CPMs and provides an important reference for medical institutions， pharmaceutical manufacturers， and regulatory authorities.

To standardize the clinical application of oral Chinese patent medicines （CPMs）， and address the safety issues arising from their dosage form characteristics， irrational clinical use， and the lack of targeted pharmacovigilance systems， the China Association of Chinese Medicine organized the formulation and release of Pharmacovigilance Guidelines for Clinical Application of Oral Chinese Patent Medicines， aiming to inform the safe clinical use of oral CPMs and related pharmacovigilance work. According to the principles of GB/T1.1—2020 and the Drug Administration Law of the People's Republic of China （2019 revision）， the Institute of Basic Research in Clinical Medicine， China Academy of Chinese Medical Sciences， led a drafting group comprising 18 institutions. After multiple rounds of expert interviews， literature retrieval， evidence screening， and extensive solicitation of opinions， the Guidelines were registered internationally. Systematic standardization focused on safety monitoring， risk identification， assessment， control， and other aspects. The Guidelines clarified the characteristics of oral CPMs in terms of safety monitoring， known risks， and potential risks， compared to non-oral CPMs. Then， risk control measures were proposed， including medication in special populations and irrational medication. As a special guideline for pharmacovigilance in the clinical application of oral CPMs， the Guidelines systematically construct a technical system in line with the characteristics of traditional Chinese medicine （TCM）， which is essential for improving the clinical safety management of oral CPMs and provides an important reference for medical institutions， pharmaceutical manufacturers， and regulatory authorities.

Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.

As one of the chronic diseases with high incidence in contemporary society, cervical spondylosis has increasing patient groups who gradually present a low age, and it seriously affects social and public health. Although modern medicine has made great progress in the pathological research and clinical treatment of cervical spondylosis, patients still face gastrointestinal side effects of nonsteroidal anti-inflammatory drugs(NSAIDs), neck pain, limited mobility, upper limb numbness, and other symptoms after conservative or surgical treatment. In the theory of traditional Chinese medicine(TCM), cervical spondylosis belongs to the categories of "Bi syndrome" "stiff neck" "stiff Bi", etc. With the change of the times, the change of lifestyle, and the application of western medicine treatment, the etiology and pathogenesis of TCM in cervical spondylosis also show new characteristics. In terms of etiology and pathogenesis, it involves the invasion of wind, cold, and dampness, long-term strain, liver and kidney deficiency, Qi and blood stasis, which are associated with factors such as cervical degeneration, muscle tension and spasm, intervertebral disc herniation, and nerve root compression in modern medicine. In terms of the evolution of pathogenesis, in the early stage, wind, cold, and dampness, were more common in Xuanfu, resulting in unfavorable muscles and bones, poor flow of Qi and blood, and cervical spondylosis and radiculopathy. Medium-term phlegm stasis and internal knots, sluggish muscles and veins, and long-term weathering and fire are more likely to occur in the vertebral artery and sympathetic radiculopathy. In the later stage, the positive Qi is depleted; the true Yin is damaged, and the viscera Qi and blood are deficient, which is most common in cervical myelopathy. The strategy of treating cervical spondylosis with TCM classic formulas applies Gegen Decoction, Wutou Decoction, Qianghuo Shengshi Decoction, Mahuang Jiazhu Decoction to patients with wind, cold, and dampness. Patients with phlegm dampness and blood stasis are treated with Huoxue Xiaoling Dan, Jinlingzi Powder, Siwu Decoction, Banxia Baizhu Tianma Decoction, Shuanghe Decoction, etc. For those patients with liver, spleen, and kidney deficiency, Huangqi Guizhi Wuwu Decoction, Tianma Gouteng Decoction, Guishao Dihuang Pills, Shenling Baizhu Powder, and Lizhong Decoction are used to invigorate the spleen, nourish Qi and blood, and tonify liver and kidney. In clinical practice, the authors advocate a safe and effective treatment plan of classic formulas based on deficiency and excess, the integration of formulas and syndromes, and the combination of modern research results, so as to relieve symptoms, reduce recurrence, and reduce medical burden.
Humans ; Spondylosis/drug therapy* ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/therapeutic use* ; Cervical Vertebrae/pathology*

Chronic obstructive pulmonary disease （COPD） is a common clinical chronic airway disease with high morbidity， high mortality， a heavy disease burden， and complex mechanisms that have not been fully elucidated. Clinical problems promote the continuous progress of basic research. The establishment and evaluation of animal models is an important way to delve into the pathogenesis and treatment strategies of COPD. On the basis of the etiology， pathogenesis， diagnostic criteria， and syndrome differentiation of COPD in traditional Chinese medicine （TCM） and Western medicine， this paper summarizes the establishment methods and characteristics of existing animal models of COPD and analyzes the fitting degree of the models with the disease characteristics in Western medicine and syndrome characteristics in TCM. The results showed that the animal models of COPD in Western medicine were mainly induced by single factors and compound factors， and the model with the highest fitting degree was established by cigarette smoke combined with lipopolysaccharide and hormone. The model showed a fitting degree of 84% with the disease characteristics in Western medicine and 70% with the syndrome characteristics in TCM， being consistent with the clinical characteristics of COPD induced by multiple factors. Most of the animal models of COPD in TCM were established on the basis of disease models and combined with TCM etiology and pathogenesis characteristics， and prepared by syndrome differentiation. Among them， the model of accumulation of cold and water retention in lung had the highest fitting degree of 92% with the TCM diagnostic criteria. The models of phlegm-heat obstructing lung and phlegm-stasis obstructing lung had the fitting degree of 94% with clinical manifestations in Western medicine and the highest fitting degree with the diagnostic criteria in Western medicine. Different animal models of COPD have their own advantages and disadvantages， and most of them simply replicate the manifestations of COPD at a certain stage， failing to reflect the multiple causes and the dynamic changes of TCM etiology and pathogenesis. Moreover， the syndromes of these models fail to match the clinical syndromes in TCM. Therefore， establishing the animal models reflecting clinical characteristics of COPD in TCM and Western medicine and improving the model evaluation criteria are important contents to promote the overall development of integrated traditional Chinese and western medicine for COPD.

BACKGROUND: The proportion of patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations is relatively high in China. However, these patients currently lack significant benefits from available neoadjuvant treatment options. This study aims to explore the potential application value of neoadjuvant targeted therapy by evaluating its efficacy and safety in patients with EGFR-mutant resectable lung adenocarcinoma. METHODS: A multicenter retrospective study was used to analyze the treatment effect of patients with stage IIA-IIIB EGFR-mutant lung adenocarcinoma who underwent surgical resection after receiving neoadjuvant targeted therapy from July 2019 to October 2024. RESULTS: A total of 24 patients with EGFR-mutant lung adenocarcinoma from three centers were included in this study. All patients successfully underwent surgery and achieved R0 resection of 100.0%. The objective response rate (ORR) was 83.3% (20/24) . The major pathologic response (MPR) rate was 37.5% (9/24), with 2 patients (8.3%) achieving pathological complete response (pCR). During neoadjuvant therapy, 13 out of 24 patients (54.2%) experienced adverse events of grade 1-2, with no occurrences of ≥ grade 3. The most common treatment-related adverse events were rash (n=4, 16.7%), mouth sores (n=2, 8.3%), and diarrhea (n=2, 8.3%). The median follow-up time was 33.0 months, no deaths occurred in all patients, and the overall survival (OS) rate was 100.0%. The 1-year disease-free survival (DFS) rate was 91.1%, and the 2-year DFS rate remained at 86.2%. CONCLUSIONS The application of neoadjuvant targeted therapy in patients with EGFR-mutant resectable lung adenocarcinoma is safe and feasible, and is expected to become a highly promising neoadjuvant treatment option for the patients with EGFR-mutant lung adenocarcinoma.
Humans ; ErbB Receptors/metabolism* ; Male ; Female ; Middle Aged ; Adenocarcinoma of Lung/surgery* ; Neoadjuvant Therapy ; Lung Neoplasms/surgery* ; Aged ; Retrospective Studies ; Mutation ; Adult

Non-small cell lung cancer (NSCLC), as the predominant histological subtype of lung cancer, accounts for approximately 85% of all lung cancer cases. In recent years, immune checkpoint inhibitors (ICIs), represented by programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors, have achieved breakthrough advancements in patients with driver gene-negative NSCLC. They have been established as a key component of first-line treatment regimens and have significantly improved clinical outcomes. However, limited clinical evidence has emerged showing the phenomenon of histological transformation from NSCLC to small cell lung cancer (SCLC) in patients experiencing disease progression after ICIs monotherapy or combination therapy. Systematic research data on the clinical characteristics, molecular biological basis, and subsequent treatment strategies for such transformation events are currently lacking. This article reports a case of SCLC transformation occurring in a patient with KRAS-mutated lung adenocarcinoma after 16 months of ICIs combination therapy and provides a systematic review of 22 similar published cases. The study demonstrates that small cell transformation is a critical mechanism of immunotherapy resistance, and transformed patients exhibit poor prognosis. The research emphasizes the importance of dynamic monitoring of neuron-specific enolase (NSE) and standardized repeat biopsies during treatment, providing a basis for clinical practice. This aids in enhancing the recognition and management capabilities for this rare histological transformation, ultimately improving patient outcomes.
Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/immunology* ; Carcinoma, Non-Small-Cell Lung/immunology* ; Small Cell Lung Carcinoma/genetics* ; Male ; Middle Aged ; Female

The interaction between m⁶A-methylated RNA and chromatin modification remains largely unknown. We found that targeted inhibition of bromodomain-containing protein 4 (BRD4) by siRNA or its inhibitor (JQ1) significantly decreases mRNA m⁶A levels and suppresses the malignancy of breast cancer (BC) cells via increased expression of demethylase AlkB homolog 5 (ALKBH5). Mechanistically, inhibition of BRD4 increases the mRNA stability of ALKBH5 via enhanced binding between its 3' untranslated regions (3'UTRs) with RNA-binding protein RALY. Further, BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21 (TRIM21) and ALKBH5, resulting in the ubiquitination and degradation of ALKBH5 protein. JQ1-increased ALKBH5 then demethylates mRNA of extra spindle pole bodies like 1 (ESPL1) and reduces binding between ESPL1 mRNA and m⁶A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3), leading to decay of ESPL1 mRNA. Animal and clinical studies confirm a critical role of BRD4/ALKBH5/ESPL1 pathway in BC progression. Further, our study sheds light on the crosstalks between histone modification and RNA methylation.