[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。

In recent years, the incidence of dry eye disease(DED)is increasing, positioning it as one of the most prevalent diseases affecting the ocular surface. Inflammatory response is the pathological basis of DED, involving various inflammatory mediators and inflammatory signaling pathways. Consequently, anti-inflammatory treatment emerges as a fundamental strategy for preventing and managing DED. This review summarizes the classic inflammatory factors involved in the development and progression of DED, including interleukins, tumor necrosis factor, matrix metalloproteinases, chemokines, and cell adhesion molecules. It also discusses the relevant inflammatory signaling pathways: the MAPKs pathway, NF-κB pathway, Wnt pathway and TLR pathway. Additionally, this review addresses the mechanisms of action and alterations in relevant biomarkers associated with current first-line recommended anti-inflammatory therapies, including corticosteroids, immunosuppressants, nonsteroidal anti-inflammatory drugs, and traditional Chinese medicine approaches to inflammation management. This comprehensive overview aims to enhance understanding of the inflammatory mechanisms underlying DED while exploring future therapeutic prospects.

In recent years, the incidence of dry eye disease(DED)is increasing, positioning it as one of the most prevalent diseases affecting the ocular surface. Inflammatory response is the pathological basis of DED, involving various inflammatory mediators and inflammatory signaling pathways. Consequently, anti-inflammatory treatment emerges as a fundamental strategy for preventing and managing DED. This review summarizes the classic inflammatory factors involved in the development and progression of DED, including interleukins, tumor necrosis factor, matrix metalloproteinases, chemokines, and cell adhesion molecules. It also discusses the relevant inflammatory signaling pathways: the MAPKs pathway, NF-κB pathway, Wnt pathway and TLR pathway. Additionally, this review addresses the mechanisms of action and alterations in relevant biomarkers associated with current first-line recommended anti-inflammatory therapies, including corticosteroids, immunosuppressants, nonsteroidal anti-inflammatory drugs, and traditional Chinese medicine approaches to inflammation management. This comprehensive overview aims to enhance understanding of the inflammatory mechanisms underlying DED while exploring future therapeutic prospects.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

In 2022， Hainan provincial government launched the project for the prevention and control of viral hepatitis with the goals of a hepatitis B screening rate of 90%， a diagnostic rate of 90%， and a treatment rate of 80% among people aged 18 years and above by the year 2025， and the main intervention measures include population-based prevention， case screening， antiviral therapy， and health management. As of December 31， 2024， a total of 6.875 million individuals in the general population had been screened for hepatitis B， with a screening rate of 95.6%. A total of 184 710 individuals with positive HBsAg were identified， among whom 156 772 were diagnosed through serological reexamination， resulting in a diagnostic rate of 84.9%. A total of 50 742 patients with chronic hepatitis B were identified， among whom 42 921 had hepatitis B-specific health records established for health management， with a file establishment rate of 84.6%. A total of 31 553 individuals received antiviral therapy， with a treatment rate of 62.2%. A total of 2.503 million individuals at a high risk of hepatitis C were screened， among whom 4 870 tested positive for HCV antibody and 3 858 underwent HCV RNA testing， resulting in a diagnostic rate of 79.2%， and 1 824 individuals with positive HCV RNA were identified， among whom 1 194 received antiviral therapy， with a treatment rate of 65.5%. In addition， 159 301 individuals with negative HBsAg and anti-HBs and an age of 20 — 40 years were inoculated with hepatitis B vaccine free of charge. Through the implementation of the project for the prevention and control of viral hepatitis， a large number of hepatitis patients have been identified， treated， and managed in the province within a short period of time， which significantly accelerates the efforts to eliminate the crisis of viral hepatitis.

OBJECTIVE To investigate the effects of osthole （OST） on skin wound healing and angiogenesis in rats by regulating the sonic hedgehog （SHH） signaling pathway. METHODS Full-layer skin defect wound model rats were established and then randomly separated into Model group， OST low-dose， medium-dose and high-dose groups （OST-L group， OST-M group， OST-H group， 20， 30， 40 mg/kg OST）， high-dose OST+SHH inhibitor cyclopamide group （OST-H+cyclopamide group， 40 mg/kg OST+10 mg/kg cyclopamide）， with 12 rats in each group. Another 12 rats were selected as the control group. The wound healing of rats on 1， 7 and 14 days of administration was observed， and the wound healing rate of rats in each group was measured. The pathological changes and collagen deposition in rat wound tissue were observed； the levels of angiopoietin-1 （Ang-1） and basic fibroblast growth factor （bFGF） in wound tissue of rats were detected； the relative expressions of vascular endothelial growth factor A （VEGFA） and vascular endothelial growth factor receptor-2 （VEGFR-2） mRNA were also detected in wound tissue of rats； the protein expressions of VEGFA， VEGFR-2， SHH and glioma-associated oncogene homolog-1 （GLI1） were determined in wound tissue of rats. RESULTS Compared with Model group， the healing rate of skin wound， relative expression of collagen protein， the levels of Ang-1 and bFGF， the mRNA and protein expressions of VEGFA and VEGFR-2， and the protein expressions of SHH and GLI1 were all significantly increased in OST-M and OST-H groups （P＜0.05）. The wound tissue underwent significant re- epithelialization， with reduced inflammatory cell infiltration and granulation tissue edema， and an increase in the number of new blood vessels. SHH inhibitor cycloparamide weakened the promoting effects of OST on skin wound healing and angiogenesis in rats. CONCLUSIONS OST may promote skin wound healing and angiogenesis in rats by activating the SHH signaling pathway.

In managing metabolic dysfunction-associated steatotic liver disease, which affects over 30% of the general population, effective noninvasive biomarkers for assessing disease severity, monitoring disease progression, predicting the development of liver-related complications, and assessing treatment response are crucial. The advantage of simple fibrosis scores lies in their widespread accessibility through routinely performed blood tests and extensive validation in different clinical settings. They have shown reasonable accuracy in diagnosing advanced fibrosis and good performance in excluding the majority of patients with a low risk of liver-related complications. Among patients with elevated serum fibrosis scores, a more specific fibrosis and imaging biomarker has proved useful to accurately identify patients at risk of liver-related complications. Among specific fibrosis blood biomarkers, enhanced liver fibrosis is the most widely utilized and has been approved in the United States as a prognostic biomarker. For imaging biomarkers, the availability of vibration-controlled transient elastography has been largely improved over the past years, enabling the use of liver stiffness measurement (LSM) for accurate assessment of significant and advanced fibrosis, and cirrhosis. Combining LSM with other routinely available blood tests enhances the ability to diagnose at-risk metabolic dysfunction-associated steatohepatitis and predict liver-related complications, some reaching an accuracy comparable to that of liver biopsy. Magnetic resonance imaging-based modalities provide the most accurate quantification of liver fibrosis, though the current utilization is limited to research settings. Expanding their future use in clinical practice depends on factors such as cost and facility availability.

ObjectiveTo investigate the status of tooth loss in people aged 50 and above, so as to understand their oral health status and provide scientific evidences for promoting oral health of middle-aged and elderly people. MethodsA total of 400 patients who visited the department of stomatology at Sijing Hospital in Songjiang District of Shanghai were performed oral health examinations and their information was collected according to the national epidemiological survey standards for oral health. ResultsThere were statistically significant differences in tooth loss among people aged 50 and above with different ages, educational levels, occupations, types of medical insurance and chronic diseases (P<0.05), but gender and monthly income had no statistically significant correlations with tooth loss (P>0.05). Among lifestyle factors, smoking, alcohol consumption and tea drinking had no statistically significant impacts on the number of remaining teeth (P>0.05), but toothbrushing frequency, flossing frequency, toothpick use frequency, toothbrush replacement frequency, and tooth loosening were statistically associated with the number of remaining teeth (P<0.05). Multiple linear regression analyses indicated that a total of 7 related factors including age, educational level, occupation, medical payment type, chronic disease, tooth loosening and toothpick use frequency were significantly associated with the number level of remaining teeth in individuals aged 50 and above. ConclusionAge, chronic disease, and tooth loosening were influencing factors affecting the number of teeth left in people aged 50 and above. It is recommended to strengthen oral health education and improve healthcare awareness to reduce the risk of tooth loss in people aged 50 and above.

ObjectiveTo explore the effect of Buzhong Yiqitang on exercise-induced fatigue and its potential mechanism. MethodsSixty male SPF-grade C57BL/6J mice were randomized into blank， model， low-， medium-， high-dose （4.1， 8.2， 16.4 g·kg^-1， respectively） Buzhong Yiqitang， and vitamin C （0.04 g·kg^-1） groups. The blank and model groups were administrated with normal saline. Each group was administrated with corresponding agents by gavage at a dose of 0.2 mL once a day. Except the blank group， other groups underwent a 6-weeks exhaustive swimming test under negative gravity. At the end of the experiment， blood was collected， and the thymus， spleen， liver， and kidney weights were measured. Serum levels of lactic acid （LD）， blood urea nitrogen （BUN）， creatine kinase （CK）， and malondialdehyde （MDA） were assessed by kits to evaluate fatigue. Hematoxylin-eosin staining was performed to observe pathological changes in the skeletal muscle. Electron microscopy was used to examine the skeletal muscle cell ultrastructure， with a focus on mitochondrial morphological changes. The adenosine triphosphate （ATP） content and activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， and Ⅴ in skeletal muscle were determined by kits. The expression levels of key genes and proteins in the PTEN-induced putative kinase 1 （PINK1）-mediated mitochondrial homeostasis pathways in the skeletal muscle were evaluated via Real-time PCR and Western blot， respectively. ResultsCompared with the blank group， the model group showed reductions in weight gain rate （P<0.01） and thymus index （P<0.01）， rises in serum levels of LD， BUN， MDA， and CK （P<0.01）， disarrangement of skeletal muscle， broken muscle fibers， inflammatory cell infiltration in muscle fiber gaps， abnormal morphological changes （increased vacuolated mitochondria and disappearance of cristae） of mitochondria in skeletal muscle cells， and decreased mitochondria. In addition， the skeletal muscle in the model group showed reduced content of ATP， weakened activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， and Ⅴ （P<0.05）， up-regulated mRNA levels of PINK1， E3 ubiquitin-protein ligase （Parkin）， hairy/enhancer-of-split related with YRPW motif 1 （HEY1）， dynamin-related protein 1 （Drp1）， sequestosome 1 （p62）， and hypoxia-inducible factor 1 alpha （HIF-1α） （P<0.05）， and down-regulated protein level of microtubule-associated protein 1-light chain 3B （LC3B） （P<0.01）. Compared with the model group， Buzhong Yiqitang prolonged the swimming exhaustion time （P<0.01）， increased the weight gain rate （P<0.01） and thymus index （P<0.01）， lowered the serum levels of LD， BUN， MDA， and CK （P<0.05， P<0.01）. The skeletal muscle in the Buzhong Yiqitang groups showed neat arrangement， reduced inflammatory cells， intact mitochondria with dense cristae， and increased mitochondria. In addition， the skeletal muscle in the Buzhong Yiqitang groups showcased increased ATP content， enhanced activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， and Ⅴ （P<0.05， P<0.01）， up-regulated protein levels of PINK1， Parkin， HEY1， LC3B， and Drp1 and mRNA level of HIF-1α （P<0.05， P<0.01）， and down-regulated expression level of p62 （P<0.05， P<0.01）. ConclusionBuzhong Yiqitang can prevent and treat exercise-induced fatigue by regulating the mitochondrial homeostasis of skeletal muscle via the HIF-1α/PINK1/Parkin and HIF-1α/HEY1/PINK1 signaling pathways.

ObjectiveTo explore the effect of Buzhong Yiqitang on exercise-induced fatigue and its potential mechanism. MethodsSixty male SPF-grade C57BL/6J mice were randomized into blank， model， low-， medium-， high-dose （4.1， 8.2， 16.4 g·kg^-1， respectively） Buzhong Yiqitang， and vitamin C （0.04 g·kg^-1） groups. The blank and model groups were administrated with normal saline. Each group was administrated with corresponding agents by gavage at a dose of 0.2 mL once a day. Except the blank group， other groups underwent a 6-weeks exhaustive swimming test under negative gravity. At the end of the experiment， blood was collected， and the thymus， spleen， liver， and kidney weights were measured. Serum levels of lactic acid （LD）， blood urea nitrogen （BUN）， creatine kinase （CK）， and malondialdehyde （MDA） were assessed by kits to evaluate fatigue. Hematoxylin-eosin staining was performed to observe pathological changes in the skeletal muscle. Electron microscopy was used to examine the skeletal muscle cell ultrastructure， with a focus on mitochondrial morphological changes. The adenosine triphosphate （ATP） content and activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， and Ⅴ in skeletal muscle were determined by kits. The expression levels of key genes and proteins in the PTEN-induced putative kinase 1 （PINK1）-mediated mitochondrial homeostasis pathways in the skeletal muscle were evaluated via Real-time PCR and Western blot， respectively. ResultsCompared with the blank group， the model group showed reductions in weight gain rate （P<0.01） and thymus index （P<0.01）， rises in serum levels of LD， BUN， MDA， and CK （P<0.01）， disarrangement of skeletal muscle， broken muscle fibers， inflammatory cell infiltration in muscle fiber gaps， abnormal morphological changes （increased vacuolated mitochondria and disappearance of cristae） of mitochondria in skeletal muscle cells， and decreased mitochondria. In addition， the skeletal muscle in the model group showed reduced content of ATP， weakened activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， and Ⅴ （P<0.05）， up-regulated mRNA levels of PINK1， E3 ubiquitin-protein ligase （Parkin）， hairy/enhancer-of-split related with YRPW motif 1 （HEY1）， dynamin-related protein 1 （Drp1）， sequestosome 1 （p62）， and hypoxia-inducible factor 1 alpha （HIF-1α） （P<0.05）， and down-regulated protein level of microtubule-associated protein 1-light chain 3B （LC3B） （P<0.01）. Compared with the model group， Buzhong Yiqitang prolonged the swimming exhaustion time （P<0.01）， increased the weight gain rate （P<0.01） and thymus index （P<0.01）， lowered the serum levels of LD， BUN， MDA， and CK （P<0.05， P<0.01）. The skeletal muscle in the Buzhong Yiqitang groups showed neat arrangement， reduced inflammatory cells， intact mitochondria with dense cristae， and increased mitochondria. In addition， the skeletal muscle in the Buzhong Yiqitang groups showcased increased ATP content， enhanced activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， and Ⅴ （P<0.05， P<0.01）， up-regulated protein levels of PINK1， Parkin， HEY1， LC3B， and Drp1 and mRNA level of HIF-1α （P<0.05， P<0.01）， and down-regulated expression level of p62 （P<0.05， P<0.01）. ConclusionBuzhong Yiqitang can prevent and treat exercise-induced fatigue by regulating the mitochondrial homeostasis of skeletal muscle via the HIF-1α/PINK1/Parkin and HIF-1α/HEY1/PINK1 signaling pathways.