AIM: To explore the efficacy of 0.05% cyclosporine A combined with olopatadine eye drops in treating allergic conjunctivitis-related dry eye disease.METHODS: A total of 63 patients(63 eyes)with allergic conjunctivitis-related dry eye disease in the People's Hospital of Guangxi Zhuang Autonomous Region from August 2022 to April 2023 were enrolled and randomly divided into control group(n=33)and observation group(n=30). The patients of the control group were administrated with 0.1% olopatadine eye drops and 0.3% sodium hyaluronate eye drops, while the observation group was administrated with 0.1% olopatadine eye drops and 0.05% cyclosporine A eye drops. The ocular surface disease index(OSDI), total ocular symptom score(TOSS), conjunctival congestion score, conjunctival papillae and follicle score, Schirmer I test(SⅠt), tear meniscus height(TMH), meibomian gland secretion ability and property score, meibomian gland loss area score, corneal fluorescein staining(CFS), tear film break-up time(BUT), noninvasive first tear film break-up time(NIBUTf), noninvasive average tear film break-up time(NIBUTav)before and after treatment and the drug safety during the treatment period of both groups of patients were evaluated.RESULTS: After treatment, OSDI, TOSS, conjunctival congestion score, conjunctival papillae and follicle score, SⅠt, TMH, meibomian gland secretion ability score and property score, CFS, BUT, NIBUTf, and NIBUTav of the observation group showed improvements compared with those before treatment(all P<0.017). Among these, OSDI, TOSS, conjunctival congestion score, conjunctival papillae and follicle score, BUT, NIBUTf, and NIBUTav demonstrated significant improvement compared with the control group(all P<0.05). There was no statistically significant difference in meibomian gland loss area score between the two groups before and after treatment(P>0.05). During the treatment period, there were no local or systemic adverse reactions.CONCLUSION: The combined use of 0.05% cyclosporine A and olopatadine eye drops can significantly improve ocular discomfort symptoms of patients with dry eye disease associated with allergic conjunctivitis, such as red eyes, itchy eyes and foreign body sensation, promote tear film stability and have high safety.

Lung cancer exhibits the highest incidence and mortality rates among cancers globally, with a five-year overall survival rate alarmingly below 20%. Targeting autophagy, though a controversial therapeutic strategy, is extensively employed in clinical practice. Current research is actively pursuing various therapeutic strategies using small molecules to exploit the dual function of autophagy. Nevertheless, the pivotal question of enhancing or inhibiting autophagy in cancer therapy merits further attention. This review aims to provide a comprehensive overview of the mechanisms of autophagy in lung cancer. It also explores recent advances in targeting cytotoxic autophagy and inhibiting protective autophagy with small molecules to induce cell death in lung cancer cells. Notably, most autophagy-targeting drugs, primarily natural small molecules, have demonstrated that activating cytotoxic autophagy effectively induces cell death in lung cancer, as opposed to inhibiting protective autophagy. These insights contribute to identifying druggable targets and drug candidates for potential autophagy-related lung cancer therapies, offering promising approaches to combat this disease.

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

ObjectiveTo investigate the mechanism by which Feixin decoction treats hypoxic pulmonary hypertension （HPH） by regulating the peroxisome proliferator-activated receptor gamma （PPARγ）/nuclear factor-kappa B （NF-κB）/NOD-like receptor pyrin domain containing 3 （NLRP3） signaling pathway. MethodsForty-eight male SD rats were randomly allocated into normal， hypoxia， and low-， medium- and high-dose （5.85， 11.7， 23.4 g·kg^-1， respectively） Feixin decoction groups， with 8 rats in each group. Except the normal group， the remaining five groups were placed in a hypoxia chamber with an oxygen concentration of （10.0±0.5）% for 8 h per day， 28 days， and administrated with corresponding drugs during the modeling process. After 4 weeks of treatment， echocardiographic parameters ［pulmonary artery acceleration time （PAT）， pulmonary artery ejection time （PET）， right ventricular anterior wall thickness （RVAWd）， and tricuspid annular plane systolic excursion （TAPSE）］ were measured for each group. The right ventricular systolic pressure （RVSP） was measured by the right heart catheterization method， and the right ventricular hypertrophy index （RVHI） was calculated by weighing the heart. The pathological changes in pulmonary arterioles were observed by hematoxylin-eosin staining. The co-localization of α-smooth muscle actin （α-SMA） with NLRP3， N-terminal gasdermin D （N-GSDMD）， and cysteinyl aspartate-specific proteinase-1 （Caspase-1） in pulmonary arteries was detected by immunofluorescence. The protein levels of PPARγ， NF-κB， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， N-GSDMD， interleukin-1β （IL-1β）， interleukin-18（IL-18）， and cleaved Caspase-1 in the lung tissue was determined by Western blot. The ultrastructural changes in pulmonary artery smooth muscle cells （PASMCs） were observed by transmission electron microscopy. ResultsCompared with the normal group， the hypoxia group showed increased RVSP and RVHI （P<0.01）， decreased right heart function （P<0.01）， increased pulmonary vascular remodeling （P<0.01）， increased co-localization of α-SMA with NLRP3， N-GSDMD， and Caspase-1 in pulmonary arterioles （P<0.01）， up-regulated protein levels of NF-κB， NLRP3， ASC， N-GSDMD， IL-1β， IL-18， and cleaved Caspase-1 in the lung tissue （P<0.05， P<0.01）， a down-regulated protein level of PPARγ （P<0.05， P<0.01）， and pyroptosis in PASMCs. Compared with the hypoxia group， Feixin decoction reduced RVSP and RVHI， improved the right heart function and ameliorated pulmonary vascular remodeling （P<0.05， P<0.01）， decreased the co-localization of α-SMA with NLRP3， N-GSDMD， and Caspase-1 （P<0.05， P<0.01）， down-regulated the protein levels of NF-κB， NLRP3， ASC， N-GSDMD， IL-1β， IL-18， and cleaved Caspase-1 in the lung tissue （P<0.05， P<0.01）， up-regulated the protein level of PPARγ （P<0.05， P<0.01）， and alleviated pyroptosis in PASMCs. ConclusionFeixin decoction can ameliorate pulmonary vascular remodeling and right heart dysfunction in chronically induced HPH rats by regulating pyroptosis in PASMCs through the PPARγ/NF-κB/NLRP3 pathway.

This study explored the drying kinetics of Salviae Miltiorrhizae Radix et Rhizoma(SM), established the suitable models simulating the drying kinetics, and then analyzed the dynamic changes of active components during the drying processes with different methods, aiming to provide a basis for the establishment of suitable drying methods and the quality control of SM. The drying kinetics were studied based on the drying curve, drying rate, moisture effective diffusion coefficient, and drying activation energy, and the appropriate drying kinetics model of SM was established. The drying performance of different methods, such as hot air drying, infrared drying, and microwave drying of SM was evaluated, and the changes in the content of 10 salvianolic acids and 6 tanshinones during drying were analyzed by UPLC-TQ-MS. The Technique for Order Preference by Similarity to an Ideal Solution(TOPSIS) was employed to evaluate the quality of SM dried with different methods. The results showed that the drying rate and moisture effective diffusion coefficient of SM increased with the rise in drying temperature, and the maximum drying rates of different methods were in the order of microwave drying > infrared drying > hot air drying, slice > whole root. The drying rate decreased with the rise in temperature and the extension of drying time. The activation energy of hot air drying was higher than that of infrared drying in SM. The most suitable model for simulating the drying process of SM was the Page model. The TOPSIS results suggested infrared drying at 50 ℃ was the optimal drying method for SM. During the drying process, the content of salvianolic acids increased in different degrees with the loss of moisture, among which salvianolic acid B showed the largest increase of 44 times compared with that in the fresh medicinal material. Tanshinones also existed in the fresh herb of SM, and the content of tanshinone Ⅱ_A increased by 3 times after drying. The results provided a basis for the establishment of suitable drying methods and the quality control of SM.
Salvia miltiorrhiza/chemistry* ; Desiccation/methods* ; Drugs, Chinese Herbal/chemistry* ; Rhizome/chemistry* ; Kinetics ; Quality Control ; Abietanes

In this study, potential quality markers(Q-markers) of Schisandrae Chinensis Fructus for treating bronchial asthma were predicted based on analytic hierarchy process(AHP), entropy weight method(EWM), fingerprint, and network pharmacology. AHPEWM was employed to quantitatively identify the Q-markers of Schisandrae Chinensis Fructus. AHP was used to weight the primary indicators(effectiveness, measurability, and specificity), while EWM was employed to analyze the secondary indicators of each primer indicator. Further, through fingerprint combined with network pharmacology, a ″component-target-pathway″ network was constructed to screen the components of Schisandrae Chinensis Fructus for treating bronchial asthma. It was finally determined that schisandrol A,schisandrin A, and schisandrin B were potential Q-markers of Schisandrae Chinensis Fructus in the treatment of bronchial asthma. This study is the first to comprehensively use AHP-EWM, fingerprint, and network pharmacology to screen the key Q-markers of Schisandrae Chinensis Fructus in the treatment of bronchial asthma. This study provides a scientific basis for improving the quality standard of Schisandrae Chinensis Fructus and lays a foundation for studying its material basis in treating bronchial asthma.
Schisandra/chemistry* ; Asthma/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Network Pharmacology ; Humans ; Entropy ; Lignans/analysis* ; Fruit/chemistry* ; Quality Control ; Cyclooctanes ; Polycyclic Compounds/analysis*

Asthma is a chronic inflammatory disease involving multiple inflammatory cells and cytokines. Its pathogenesis is complex, involving various cells and cytokines. Traditional Chinese medicine(TCM) theory suggests that the pathogenesis of asthma is closely related to the dysfunction of internal organs such as the lungs, spleen, and kidneys. In contrast, modern immunological studies have revealed the central role of T helper 1(Th1)/T helper 2(Th2) and T helper 17(Th17)/regulatory T(Treg) cellular immune imbalance in the pathogenesis of asthma. Th1/Th2 imbalance is manifested as hyperfunction of Th2 cells, which promotes the synthesis of immunoglobulin E(IgE) and the activation of eosinophil granulocytes, leading to airway hyperresponsiveness and inflammation.Meanwhile, Th17/Treg imbalance exacerbates the inflammatory response in the airways, further contributing to asthma pathology.Currently, therapeutic strategies for asthma are actively exploring potential targets for regulating the balance of Th1/Th2 and Th17/Treg immune responses. These targets include cytokines, transcription factors, key proteins, and non-coding RNAs. Precisely regulating the expression and function of these targets can effectively modulate the activation and differentiation of immune cells. In recent years,traditional Chinese medicine active ingredients have shown unique potential and prospects in the field of asthma treatment. Based on this, the present study systematically summarizes the efficacy and specific mechanisms of TCM active ingredients in treating asthma by regulating Th1/Th2 and Th17/Treg immune balance through literature review and analysis. These active ingredients, including flavonoids, terpenoids, polysaccharides, alkaloids, and phenolic acids, exert their effects through various mechanisms, such as inhibiting the activation of inflammatory cells, reducing the release of cytokines, and promoting the normal differentiation of immune cells. This study aims to provide a solid foundation for the widespread application and in-depth development of TCM in asthma treatment and to offer new ideas for clinical research and drug development of asthma.
Asthma/genetics* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Th2 Cells/drug effects* ; Th17 Cells/drug effects* ; T-Lymphocytes, Regulatory/drug effects* ; Th1 Cells/drug effects* ; Animals ; Cytokines/immunology* ; Medicine, Chinese Traditional

By employing the analytic hierarchy process(AHP), the CRITIC method(a weight determination method based on indicator correlations), and the AHP-CRITIC hybrid weighting method, the weight coefficients of evaluation indicators were determined, followed by a comprehensive score comparison. The grey correlation analysis was then performed to analyze the results calculated using the hybrid weighting method. Subsequently, a backpropagation-artificial neural network(BP-ANN) model was constructed to predict the extraction process parameters and optimize the extraction process for Shenxiong Huanglian Jiedu Granules(SHJG). In the extraction process, an L_9(3~4) orthogonal experiment was designed to optimize three factors at three levels, including extraction frequency, water addition amount, and extraction time. The evaluation indicators included geniposide, berberine, ginsenoside Rg_1 + Re, ginsenoside Rb_1, ferulic acid, and extract yield. Finally, the optimal extraction results obtained by the orthogonal experiment, grey correlation analysis, and BP-ANN method were compared, and validation experiments were conducted. The results showed that the optimal extraction process involved two rounds of aqueous extraction, each lasting one hour; the first extraction used ten times the amount of added water, while the second extraction used eight times the amount. In the validation experiments, the average content of each indicator component was higher than the average content obtained in the orthogonal experiment, with a higher comprehensive score. The optimized extraction process parameters were reliable and stable, making them suitable for subsequent preparation process research.
Drugs, Chinese Herbal/analysis* ; Neural Networks, Computer

OBJECTIVE: To investigate the clinical features, treatment and prognosis of extranodal NK/T-cell lymphoma, nasal type (ENKTL) with skin lesions as initial symptom. METHODS: The clinical data of 11 ENKTL patients with skin lesions as initial symptom were retrospectively analyzed from August 2016 to January 2023 in Wuhan First Hospital and Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. RESULTS: Among the 11 patients, there were 6 males and 5 females, with a median age of 50(32-80) years. All patients had different forms of skin lesions as initial clinical symptom, including rash, ulcerative mass, painful skin nodules, infiltrating macula, etc. Most of the skin lesions were involved in the limbs and trunk but also appeared in the lower limbs alone. Five patients had hemophagocytic lymphohistiocytosis (HLH) at initial diagnosis, and 8 patients had B symptoms. All patients were diagnosed with advanced clinical staging (Lugano staging IV), and classified as high risk (PINK-E score ≥3). Immunohistochemical examination revealed that the positive rates of CD56 and EBER were both 100%, and the median Ki-67 index was 75%(50%-80%). Plasma EBV-DNA tests were all positive (≥5×10² copies/ml). Most of the induction chemotherapy regimens were combination chemotherapy (MESA, p-Gemox, SMILE) containing pegaspargase or L-asparaginase, or combined with PD-1 monoclonal immunotherapy, or HLH regimens (HLH-04 regimen, L-DEP). The median follow-up time and overall survival (OS) time were both 4.5(0.5-27) months. During the follow-up period, all 8 patients who did not receive autologous hematopoietic stem cell transplantation (ASCT) died, most of whom died of rapid disease progression. Three patients received ASCT, one died of central nervous system recurrence after transplantation, and two survived. The OS of three patients who underwent ASCT was 21, 27, and 19 months, and PFS was 11, 20, and 13 months, respectively. The plasma EBV-DNA copy number was monitored irregularly after transplantation, and the load of EBV was consistent with the changes of the disease. CONCLUSIONS Early clinical symptoms of ENKTL patients with skin lesions as initial symptom are more atypical, and early diagnosis is particularly difficult. The disease progresses rapidly and the prognosis is poor. There is still no uniform standard for the best treatment strategy. The survival of patients can be significantly prolonged by applying ASCT as soon as possible after complete remission obtained by high-dose induction chemotherapy.
Humans ; Male ; Female ; Lymphoma, Extranodal NK-T-Cell/diagnosis* ; Middle Aged ; Adult ; Retrospective Studies ; Aged ; Prognosis ; Aged, 80 and over