The classic formula Mulisan is the 45th of the 93 formulas in the Catalogue of Ancient Classic Formulas （second batch） of Han medicine published by the National Administration of Traditional Chinese Medicine. It consists of Ostreae Concha， Astragali Radix， Ephedrae Radix et Rhizoma， and wheat， with the effect of replenishing qi and stopping sweating. It is a common formula in the clinical treatment with traditional Chinese medicine. This study analyzes the historical evolution， composition， dosage， original plants and their processing methods， decocting method， efficacy， indications， and modern clinical application of Mulisan by tracing， comparative analysis， and bibliometric methods. The results showed that Mulisan firstly appeared in the Pulse Classic written by WANG Shuhe in the Western Jin Dynasty. The formulation idea can be traced back to the Important Prescriptions Worth a Thousand Gold for Emergency in the Tang Dynasty. The herb composition， dosage， efficacy， and indications of Mulisan were first recorded in the Treatise on Diseases， Patterns， and formulas Related to Unification of the Three Etiologies in the Southern Song dynasty. In terms of original plants and their processing methods， Ostreae Concha is the shell of Ostrea rivularis， which should be calcined before use. Astragali Radix and Ephedrae Radix et Rhizoma are the dried roots of Astragalus membranaceus var. mongholicus and Ephedra sinica， respectively， the raw material of which should be used. Wheat is the dried mature fruit of T. aestivum， which can be used without processing， while the stir-fried fruit， being thin and deflated， demonstrates better effect. The composition of Mulisan is Ostreae Concha 8.26 g， Astragali Radix 8.26 g， Ephedrae Radix et Rhizoma 8.26 g， and wheat 7.92 g. The medicinal materials should be ground into coarse powder and decocted with 450 mL water to reach a volume of 240 mL， and the decoction should be taken warm. In modern clinical practice， Mulisan has a wide range of indications， including spontaneous sweating and night sweating caused by Yang deficiency or Qi deficiency. The clinical disease spectrum treated by Mulisan involves endocrine system diseases， neurological diseases， respiratory system diseases， and cancer. This formula plays a significant role in the treatment of internal medicine diseases in traditional Chinese medicine. This study aims to provide a scientific basis for the subsequent research， development， and clinical application of Mulisan.

The classic formula Mulisan is the 45th of the 93 formulas in the Catalogue of Ancient Classic Formulas （second batch） of Han medicine published by the National Administration of Traditional Chinese Medicine. It consists of Ostreae Concha， Astragali Radix， Ephedrae Radix et Rhizoma， and wheat， with the effect of replenishing qi and stopping sweating. It is a common formula in the clinical treatment with traditional Chinese medicine. This study analyzes the historical evolution， composition， dosage， original plants and their processing methods， decocting method， efficacy， indications， and modern clinical application of Mulisan by tracing， comparative analysis， and bibliometric methods. The results showed that Mulisan firstly appeared in the Pulse Classic written by WANG Shuhe in the Western Jin Dynasty. The formulation idea can be traced back to the Important Prescriptions Worth a Thousand Gold for Emergency in the Tang Dynasty. The herb composition， dosage， efficacy， and indications of Mulisan were first recorded in the Treatise on Diseases， Patterns， and formulas Related to Unification of the Three Etiologies in the Southern Song dynasty. In terms of original plants and their processing methods， Ostreae Concha is the shell of Ostrea rivularis， which should be calcined before use. Astragali Radix and Ephedrae Radix et Rhizoma are the dried roots of Astragalus membranaceus var. mongholicus and Ephedra sinica， respectively， the raw material of which should be used. Wheat is the dried mature fruit of T. aestivum， which can be used without processing， while the stir-fried fruit， being thin and deflated， demonstrates better effect. The composition of Mulisan is Ostreae Concha 8.26 g， Astragali Radix 8.26 g， Ephedrae Radix et Rhizoma 8.26 g， and wheat 7.92 g. The medicinal materials should be ground into coarse powder and decocted with 450 mL water to reach a volume of 240 mL， and the decoction should be taken warm. In modern clinical practice， Mulisan has a wide range of indications， including spontaneous sweating and night sweating caused by Yang deficiency or Qi deficiency. The clinical disease spectrum treated by Mulisan involves endocrine system diseases， neurological diseases， respiratory system diseases， and cancer. This formula plays a significant role in the treatment of internal medicine diseases in traditional Chinese medicine. This study aims to provide a scientific basis for the subsequent research， development， and clinical application of Mulisan.

Objective: To analyze the timeliness of antir-etroviral therapy (ART) and its influencing factors among newly reported HIV/AIDS cases in Wenzhou City, Zhejiang Province from 2016 to 2023, so as to provide a reference for improving the ART effect of HIV/AIDS cases. Methods: Newly reported HIV/AIDS cases in Wenzhou City from 2016 to 2023 were selected as the research subjects. Demographic information, the situation of the first CD4+ T lymphocyte (CD4 cell) test, baseline CD4 cell count, and ART situation were collected through the Chinese Disease Prevention and Control Information System. The timely rate of ART was analyzed, and the influencing factors for timely ART among HIV/AIDS cases were analyzed using a multivariable logistic regression model. Results: A total of 4 500 newly reported HIV/AIDS cases in Wenzhou City from 2016 to 2023 were included, among which 3 679 were males, accounting for 81.76%, and 821 were females, accounting for 18.24%. The median age was 46.24 (interquartile range, 26.23) years. Among these cases, 3 606 received timely ART, with a timely rate of 80.13%. The timely rate of ART increased from 57.54% in 2016 to 91.97% in 2023 (P<0.05). Multivariable logistic regression analysis showed that unmarried/divorced/widowed (OR=0.769, 95%CI: 0.641-0.922), detainees (OR=0.492, 95%CI: 0.269-0.900), untimely first CD4 cell test (OR=0.278, 95%CI: 0.234-0.330), baseline CD4 cell count ≥200 cells/µL (OR=0.709, 95%CI: 0.595-0.843) or undetected (OR=0.131, 95%CI: 0.080-0.213) were associated with a lower timeliness for ART among HIV/AIDS cases. Conclusion From 2016 to 2023, the timely rate of ART among newly reported HIV/AIDS cases in Wenzhou City showed an upward trend, which was mainly affected by marital status, case source, timeliness of the first CD4 cell test, and baseline CD4 cell count.

BACKGROUND: Without timely and effective rehabilitation, hearing loss may profoundly affect human life quality. China has a large population of hearing-impaired individuals, which imposes a heavy health burden on society. Moreover, this population is projected to increase rapidly owing to China's aging society. METHODS: We used data from a population-representative epidemiological investigation of hearing loss and ear diseases in four Chinese provinces. We estimated the national prevalence using multiple linear regression of the age-group proportions and prevalence in 31 provinces with clustering analysis. We used years lived with disability (YLDs) to analyze the disease burden and forecasted the prevalence of hearing loss by 2060 in China. RESULTS: An estimated 115 million people had moderate-to-complete hearing loss in 2015 across the 31 provinces of China (8.4% of 1.37 billion people). Of these, 85.7% were older than age 50 years (99 million people) and 2.4% were younger than 20 years old (2.8 million people). Of all YLDs attributable to hearing loss, 68.9% were attributable to moderate-to-complete cases. By 2060, a projected 242 million people in China will have moderate-to-complete hearing loss, a 110.0% increase from 2015. CONCLUSIONS The hearing loss prevalence in China is high. Population aging and socioeconomic factors substantially affect the prevalence and severity of hearing loss and the disease burden. The prevalence and severity of hearing loss are unevenly distributed across different provinces. Future public health policies should take these trends and regional variations into account.
Humans ; China/epidemiology* ; Hearing Loss/epidemiology* ; Prevalence ; Middle Aged ; Male ; Female ; Adult ; Aged ; Adolescent ; Young Adult ; Child ; Child, Preschool ; Infant ; Aged, 80 and over ; Cost of Illness

Colorectal polyps are important early markers of colorectal cancer, and their early detection is crucial for cancer prevention. Although existing polyp segmentation models have achieved certain results, they still face challenges such as diverse polyp morphology, blurred boundaries, and insufficient feature extraction. To address these issues, this study proposes a parallel coordinate fusion network (PCFNet), aiming to improve the accuracy and robustness of polyp segmentation. PCFNet integrates parallel convolutional modules and a coordinate attention mechanism, enabling the preservation of global feature information while precisely capturing detailed features, thereby effectively segmenting polyps with complex boundaries. Experimental results on Kvasir-SEG and CVC-ClinicDB demonstrate the outstanding performance of PCFNet across multiple metrics. Specifically, on the Kvasir-SEG dataset, PCFNet achieved an F1-score of 0.897 4 and a mean intersection over union (mIoU) of 0.835 8; on the CVC-ClinicDB dataset, it attained an F1-score of 0.939 8 and an mIoU of 0.892 3. Compared with other methods, PCFNet shows significant improvements across all performance metrics, particularly in multi-scale feature fusion and spatial information capture, demonstrating its innovativeness. The proposed method provides a more reliable AI-assisted diagnostic tool for early colorectal cancer screening.
Humans ; Colonic Polyps/diagnostic imaging* ; Colorectal Neoplasms/diagnostic imaging* ; Neural Networks, Computer ; Image Processing, Computer-Assisted/methods* ; Algorithms ; Early Detection of Cancer

In epidemiological statistics, the incidence rate and mortality rate of malignant lung tumors rank among the top. Non-small cell lung cancer (NSCLC) constitutes an important part of lung cancer and has become a key focus of clinical research and treatment. Among the genomic characteristics of NSCLC, the Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation is one of the main tumor drivers, accounting for approximately 25% of all NSCLC cases. The existence of this mutation is closely related to the treatment response and prognosis of patients. Therefore, the treatment strategy for KRAS-mutated NSCLC is an important topic in the field of tumor research. In the current era, immunomodulatory therapy has rapidly gained popularity and developed rapidly in oncology due to its unique mechanism of action and remarkable clinical efficacy. The treatment strategies targeting the KRAS-mutated of NSCLC have gradually become a research hotspot. The advent of immune checkpoint inhibitors (ICIs) has opened up a new therapeutic avenue for patients with such cancers, and clinical studies have shown significant effects in improving survival rates. Nevertheless, there are still many challenges in the application of immunotherapy, such as the complexity of the tumor microenvironment, individual differences among patients, and drug resistance mechanisms. This article reviews the progress of immunotherapy for KRAS-mutated NSCLC, focusing on the specific application of immunotherapy, the exploration of combination therapies, and the results of related clinical trials. At the same time, it discusses the possible future development directions of KRAS-mutated NSCLC treatment, providing a reference for clinical treatment practice.
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Humans ; Carcinoma, Non-Small-Cell Lung/immunology* ; Lung Neoplasms/immunology* ; Proto-Oncogene Proteins p21(ras)/immunology* ; Immunotherapy/methods* ; Mutation ; Animals

In recent years, the widespread application of chest computed tomography (CT) screening has led to a significant increase in the detection rate of pulmonary nodules. As a critical diagnostic tool for early-stage lung cancer, video-assisted thoracic surgery (VATS) has emerged as the preferred therapeutic approach for pulmonary nodules. Clinical evidence demonstrates that precise preoperative localization significantly enhances surgical success rates (reducing conversion to thoracotomy), minimizes complications, and shortens operation time. This comprehensive review systematically evaluates six cutting-edge localization techniques: percutaneous puncture-assisted localization, electromagnetic navigation bronchoscopy (ENB) localization, 3D-printed auxiliary localization, basin-analysis-based localization, robotic navigation system localization, and mixed reality (MR)-guided localization. By critically analyzing their operational principles, efficacy, safety profiles, and clinical applicability, this paper aims to provide evidence-based recommendations for optimizing clinical decision-making in pulmonary nodule management.
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Humans ; Lung Neoplasms/diagnosis* ; Solitary Pulmonary Nodule/diagnostic imaging* ; Thoracic Surgery, Video-Assisted/methods* ; Multiple Pulmonary Nodules/diagnostic imaging* ; Tomography, X-Ray Computed

Bispecific killer cell engagers (BiKEs) are a powerful tool to incite the killing power of natural killer (NK) cells. Here, we posited that the BiKE technology could be utilized to deplete activated immune cells expressing programmed death-1 (PD-1⁺ cells), and hence treat autoimmune diseases since these cells drive the disorders. We designed and generated PD-1 BiKE that targets an activating NK cell receptor, CD16, and PD-1. PD-1 BiKE showed specific binding to PD-1⁺ cells and engaged CD16 simultaneously. PD-1 BiKE enhanced NK cell-mediated apoptosis and depletion of PD-1⁺ Raji cells, but not PD-1^- Raji cells. Further, PD-1 BiKE induced apoptosis of primary PD-1⁺ T lymphocytes that are highly relevant to autoimmune disease progression. The BiKE depleted 42% of primary T cells that were stimulated in vitro. Importantly, those ablated primary T cells were activated cells. Meanwhile, naive T cells were spared by the BiKE treatment, supporting the crucial selectivity of PD-1 BiKE-directed cell depletion. Lastly, PD-1 BiKE is more effective than a conventional depleting antibody in the depletion of PD-1⁺ cells. The current work supports PD-1 BiKE is a selective, potent, and safe tool to deplete PD-1⁺ cells.

Ferroptosis of chondrocytes is a significant contributor to osteoarthritis (OA), for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis. Here, we screen for anti-ferroptotic drugs in Food and Drug Administration (FDA)-approved drug library via a high-throughput manner in chondrocytes. We identified a group of FDA-approved anti-ferroptotic drugs, among which vitamin K showed the most powerful protective effect. Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix (ECM) degradation in chondrocytes. Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus (DMM) mouse model. Mechanistically, transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6 (Gas6). Furthermore, exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase (AXL)/phosphatidylinositol 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) axis. Together, we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis, indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.

Background Regional differences in economic development, natural environment, health care level, and social structure may lead to differences in the provincial distribution of the health status of the elderly population. Objective To explore the provincial distribution characteristics, regional differences, and influencing factors of the self-assessed health of the elderly population, with the aim of providing a policy basis for improving the health of the elderly population and promoting healthy aging according to local conditions. Methods Using 31 provinces (municipalities and autonomous regions) in China as the basicstudy unit and based on the method of Wagstaff, the self-rated health data of the elderly population (aged 60 years and above) in each province from the 2010 and 2020 national censuses and the 2015 1% National Population Sample Survey were converted into ill-health scores as a measure of self-assessed health, and higher scores represented worse health status perception. Global Moran's I was used to evaluate spatial autocorrelation, range [−1, 1], with a value of 1 as a perfect clustered pattern. Local Moran's I was used to evaluate the tendency of local autocorrelation, and high-high aggregation/low-low aggregation indicated that both target province and its neighboring provinces showed higher/lower ill-health scores. Spatial econometric models were selected by Lagrange multiplier test and Hausman test to explore influencing factors of the self-assessed health of the elderly population. Results In 2010, 2015, and 2020, the national ill-health scores of the elderly population were 1.831, 1.873, and 1.547, respectively, and the corresponding Global Moran's I statistics were 0.347, 0.482, and 0.511, respectively (P<0.01), indicating that the ill-health scores of the elderly population showed a significant spatial positive autocorrelation, and the degree of spatial aggregation was increasing gradually. From 2010 to 2020, the high-high aggregation of ill-health scores among the elderly population was concentrated in the inland northwest, while the low-low aggregation was concentrated in the southeast coast, gradually showing a "southeast-central-northwest" stepped incremental pattern of differentiation. The Lagrange multiplier test and Hausman test suggested that the fixed-effects spatial lagged model was a better choice, and the regression model showed a spatial autocorrelation in the ill-health scores of the elderly population, with an autocorrelation coefficient of 0.3969 (P<0.001); the ill-health scores of the elderly population were negatively correlated with the natural logarithms of gross regional product per capita, and the number of beds in health care facilities per 1000 population, with regression coefficients of −0.8297 and −0.0454 (P<0.05) respectively, and positively correlated with the annual average concentration of PM_2.5, illiteracy rate, and the number of health technicians per 1000 population, with regression coefficients of 0.0033, 0.0297, and 0.0765 (P<0.05), respectively. Conclusion From 2010 to 2020, the overall self-assessed health level of China's elderly population showed an upward trend and a spatial positive autocorrelation, with better self-assessed health in the southeast coast and poorer ratings in the northwestern inland. Additionally, there was a gradual decline in self-assessed health of the elderly population from the southeast to the central regions and further to the northwest in terms of spatial distribution. Economic development level, environmental pollution, health resource allocation, and education level are important factors influencing the self-assessed health of the elderly population.