1.Time series study on influence of sulfur dioxide exposure on hospitalization of chronic obstructive pulmonary disease in Lanzhou from 2016 to 2020
Sheng LIN ; Boxi FENG ; Yongyue LI ; Yiwei HUANG ; Kai ZHENG ; Mingxuan LIU ; Yingying YANG ; Xingmin WEI ; Jianjun WU
Journal of Environmental and Occupational Medicine 2026;43(4):451-457
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
2.Research progress on effects, toxic mechanisms, and risk assessment of organophosphate flame retardants on blood system
Ziyuan LI ; Lin LU ; Xiaoting JIN ; Yuxin ZHENG
Journal of Environmental and Occupational Medicine 2026;43(4):509-515
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.
3.Compact Fundus Imaging System Using Shack-Hartmann Wavefront Sensing for High-speed Auto-focus
Zhe-Kai LIN ; Long CHEN ; Geng-Yong ZHENG ; Jin-Tian HUANG ; Jia-Xin DONG ; Shang-Pan YANG ; Wen-Zheng DING ; Ding-An HAN ; Xue-Hua WANG ; Ya-Guang ZENG
Progress in Biochemistry and Biophysics 2026;53(4):1076-1086
ObjectiveThe widespread adoption of portable fundus cameras for primary care and community screening is hindered by limitations in current autofocus(AF) technologies. Image-based methods relying on sharpness evaluation require iterative searches, resulting in slow convergence, while projection-based techniques are susceptible to optical artifacts and calibration errors. To address these challenges, this study introduces a novel AF system based on direct wavefront sensing, designed to deliver simultaneous high speed, high precision, and operational robustness within the compact form factor essential for portable ophthalmic devices. MethodsOur approach fundamentally reimagines the AF process by directly measuring the ocular wavefront aberration. We developed a custom portable fundus camera integrating a miniaturized Shack-Hartmann wavefront sensor (SHWS) into the optical path. An 850 nm laser diode projects a point source onto the retina via oblique illumination to minimize corneal reflections. Light scattered from this spot carries the eye’s refractive error through the imaging optics and is directed to the SHWS, positioned at a plane optically conjugate to the primary color CMOS imaging sensor. A microlens array within the SHWS samples the incident wavefront, generating a pattern of focal spots on a CCD. Real-time centroid analysis of these spots provides a map of local wavefront slopes. These measurements are processed through a singular value decomposition (SVD) algorithm to fit a Zernike polynomial basis set, enabling real-time reconstruction of the wavefront phase. The defocus component (S) is extracted from the second-order Zernike coefficients, providing a direct, quantitative measure of the refractive error in diopters. This value serves as a precise error signal in a closed-loop control system, which commands a voice-coil actuated focusing lens to its null position in a single, deterministic step, eliminating the need for iterative search algorithms. ResultsComprehensive evaluation demonstrated the system’s high performance. Testing on a calibrated model eye (OEMI-7) established a highly linear relationship between the computed defocus S and the focusing lens position across a ±20 Diopter (D) compensation range, achievable within a 5 mm mechanical travel. The system achieved a focusing precision of 0.08 D, corresponding to an 18-fold improvement over a conventional projection spot-size method tested under identical conditions. The total focus acquisition time, encompassing wavefront measurement, computation, and lens actuation, averaged under 0.5 s. Clinical validation with 25 human volunteers (50 eyes, refractive range -15 D to +10 D) confirmed practical efficacy. The wavefront-sensing AF succeeded in 92% of attempts with a mean time of 0.5 s, substantially outperforming a projection-based benchmark which achieved only a 32% success rate with an average time of 4.25 s. The system provided instantaneous directional guidance and maintained stability during minor ocular movements. Objective assessment of image quality, via amplitude contrast of retinal vasculature, showed consistent and significant enhancement following AF correction across the entire tested diopter range. ConclusionThis work successfully implements and validates a direct wavefront-sensing autofocus paradigm for portable fundus cameras. By directly quantifying and compensating for the optical defocus aberration, this method bypasses the fundamental limitations of image-processing and projection-based techniques, enabling rapid, precise, and deterministic diopter compensation. The developed system delivers an exceptional combination of a wide operational range (±20 D), high accuracy (0.08 D), fast convergence (0.5 s), and a compact physical footprint. This technology provides a practical and high-performance focusing solution capable of enhancing the reliability, throughput, and diagnostic utility of portable retinal imaging in large-scale screening applications. Future efforts will be directed towards system cost optimization and performance adaptation for diverse ocular conditions.
4.Analysis of influencing factors for successful detoxification in patients undergoing methadone maintenance therapy
Guodong MO ; Yue LIN ; Yinghui CHEN ; Lichuang ZHUANG ; Leisheng ZHENG ; Baoguo WANG
China Pharmacy 2026;37(2):210-214
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.
5.Expert consensus on neoadjuvant PD-1 inhibitors for locally advanced oral squamous cell carcinoma (2026)
LI Jinsong ; LIAO Guiqing ; LI Longjiang ; ZHANG Chenping ; SHANG Chenping ; ZHANG Jie ; ZHONG Laiping ; LIU Bing ; CHEN Gang ; WEI Jianhua ; JI Tong ; LI Chunjie ; LIN Lisong ; REN Guoxin ; LI Yi ; SHANG Wei ; HAN Bing ; JIANG Canhua ; ZHANG Sheng ; SONG Ming ; LIU Xuekui ; WANG Anxun ; LIU Shuguang ; CHEN Zhanhong ; WANG Youyuan ; LIN Zhaoyu ; LI Haigang ; DUAN Xiaohui ; YE Ling ; ZHENG Jun ; WANG Jun ; LV Xiaozhi ; ZHU Lijun ; CAO Haotian
Journal of Prevention and Treatment for Stomatological Diseases 2026;34(2):105-118
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.
6.Herbal Textual Research on Quisqualis Fructus in Famous Classical Formulas
Xiuping WEN ; Shiying CHEN ; Ying TAN ; Guanwen ZHENG ; Huilong XU ; Wen XU ; Chengzi YANG ; Zehao HUANG ; Yu LIN ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):225-237
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.
7.Optimization of Extraction Process and Material Basis Analysis of Modified Banxia Xiexintang
Yuling LIU ; Ruying TANG ; Dongxue ZHENG ; Qiling ZHANG ; Xinmin LIU ; Donghan BAI ; Longfei LIN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):129-139
ObjectiveTo optimize and validate the optimal sequential alcohol-water extraction process of modified Banxia Xiexintang(MBXT) based on pharmacodynamic evaluation, combined with the G1-entropy weight method and Box-Behnken response surface methodology, and to systematically and comprehensively analyze the material basis of this formula, providing a scientific basis for its quality control and industrial production. MethodsRats were randomly divided into the normal group, model group, metformin group, and MBXT water extraction, water extraction and ethanol precipitation, sequential ethanol-water extraction groups. Except for the normal group, a polycystic ovary syndrome with insulin resistance(PCOS-IR) model was established in all rats via a high-fat diet combined with letrozole induction. Enzyme-linked immunosorbent assay(ELISA) biochemical assay kits and hematoxylin-eosin(HE) staining were used to compare sex hormone levels in serum and ovarian histopathology, thereby screening extraction process routes. Based on this, a comprehensive score was constructed using the G1-entropy weight method based on the transfer rates of index components(berberine hydrochloride and baicalin) and the dry extract rate. Box-Behnken response surface methodology was then utilized to optimize the extraction process parameters. Finally, the chemical constituents of the sample from the optimal process were qualitatively analyzed by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap mass spectrometry(UPLC-Q-Orbitrap-MS). ResultsPharmacodynamic findings revealed that compared with the normal group, serum testosterone(T) and luteinizing hormone(LH) levels were significantly elevated in the model group, while estradiol(E2) and follicle-stimulating hormone(FSH) levels were significantly decreased(P<0.01), with polycystic changes observed in ovarian tissues. Compared with the model group, all treatment groups significantly reversed the changes in sex hormone levels, with the sequential ethanol-water extraction group showing the optimal effect in improving the aforementioned indicators and pathological morphology, followed by subsequent process optimization. The optimized process involved adding 12 times the amount of 70% ethanol for extracting twice, each lasting 120 min, and adding 12 times the amount of water for extracting thrice, each lasting 90 min. Validation test results showed that under optimal process conditions, the average transfer rates of berberine hydrochloride and baicalin were 76.05% and 93.38%, respectively. MS analysis identified a total of 377 compounds, including 112 flavonoids, 41 terpenoids, 28 organic acids, 22 coumarins, and 8 alkaloids, while elucidating the cleavage patterns of key components. ConclusionThe optimized sequential ethanol-water extraction process is stable and feasible, effectively preserving the material basis of MBXT for treating PCOS-IR. It further clarifies the main chemical composition of this formula, providing a scientific basis for the development and quality control of its preparations.
8.Exploring Mechanism of Modified Banxia Xiexintang in Ameliorating Metabolic Disorders and Reproductive Function in PCOS-IR Rats Based on Metabolomics and Transcriptomics
Donghan BAI ; Ruying TANG ; Longfei LIN ; Yuling LIU ; Dongxue ZHENG ; Qiling ZHANG ; Xinmin LIU ; Hui LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):140-149
ObjectiveTo evaluate the therapeutic effects of modified Banxia Xiexintang(MBXT) on polycystic ovary syndrome with insulin resistance(PCOS-IR) rats and reveal its potential mechanisms based on the integrated analysis of transcriptomics and metabolomics. MethodsFemale SD rats were selected, and a PCOS-IR model was established by intragastric administration of letrozole combined with a high-fat diet for 21 days. The modeled rats were randomly divided into the model group, MBXT low-, medium-, and high-dose groups(6.62, 13.23, 26.46 g·kg-1), and metformin group(0.158 g·kg-1), with a normal group set up separately. After 14 days of administration, the estrous cycle was observed, ovarian morphology was examined by hematoxylin-eosin(HE) staining, and the levels of testosterone(T), estradiol(E2), follicle-stimulating hormone(FSH), and luteinizing hormone(LH) in serum were detected by enzyme-linked immunosorbent assay(ELISA). Serum metabolites and ovarian tissue gene expression were detected using ultra-performance liquid chromatography-quadrupole-electrostatic orbitrap mass spectrometry(UPLC-Q-Orbitrap-MS) and RNA-Seq technology, respectively, followed by multi-omics integrated analysis. ResultsPharmacodynamic findings revealed that all MBXT dose groups could reversed abnormal estrous cycles in PCOS-IR rats, improve polycystic ovarian lesions, and normalize dysregulated serum hormone levels(T, LH, E2, FS, P<0.05, P<0.01). Metabolomic analysis revealed that compared with the model group, MBXT reversed 278 differential metabolites such as estrone and S-formylglutathione, mainly involving pathways such as steroid hormone biosynthesis, glutathione metabolism, and lipid peroxidation regulation. Transcriptomic analysis identified 434 differentially expressed genes, and enrichment analysis revealed that MBXT significantly regulated lipid peroxidation defense systems, including glutathione metabolism, peroxisome function, and fatty acid metabolism, thereby intervening in ferroptosis processes. It also engaged in inflammation-related pathways such as the chemokine signaling pathway. Integrated analysis revealed that both metabolomics and transcriptomics co-enriched metabolic pathways associated with ferroptosis and fatty acid metabolism. And key Hub genes[such as Ras-related C3 botulinum toxin substrate 2 gene(Rac2) and Fas ligand gene(Faslg)] showed significant correlations with differential metabolites. ConclusionMBXT can effectively ameliorate reproductive dysfunction and metabolic disorders in PCOS-IR rats. Its mechanism may be related to remodeling the immune-metabolism network, particularly by regulating MHC-mediated immune responses, inhibiting local ovarian ferroptosis, and enhancing steroid hormone synthesis pathways.
9.Investigation on Mechanism of Modified Banxia Xiexintang in Improving Ovarian Dysfunction of PCOS-IR Rats by Inhibiting Ferroptosis via AMPK/FASN/GPX4 Signaling Pathway
Donghan BAI ; Ruying TANG ; Longfei LIN ; Yuling LIU ; Dongxue ZHENG ; Qiling ZHANG ; Xinmin LIU ; Hui LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):150-160
ObjectiveTo investigate the mechanism of modified Banxia Xiexintang(MBXT) in improving ovarian dysfunction in polycystic ovary syndrome with insulin resistance(PCOS-IR) rats by inhibiting ferroptosis through the adenosine monophosphate(AMP)-activated protein kinase(AMPK)/fatty acid synthase(FASN)/glutathione peroxidase 4(GPX4) signaling pathway. MethodsSeventy-six female SD rats were randomly divided into a normal group(n=13) and a modeling group(n=63). The modeling group established a PCOS-IR model by intragastric administration of letrozole combined with a high-fat diet for 21 days. After successful modeling, these rats were randomly divided into the model group, MBXT low-, medium-, and high-dose groups(6.62, 13.23, 26.46 g·kg-1), metformin group(0.158 g·kg-1), and high-dose of MBXT combined with ferroptosis inducer Erastin group(15 mg·kg-1), with 10 rats in each group. After 14 days of intervention, ovarian pathological morphology was observed by hematoxylin-eosin(HE) staining, the mitochondrial ultrastructure of granulosa cells was observed by transmission electron microscopy(TEM), ovarian reactive oxygen species(ROS) levels were detected by dihydroethidium(DHE) probe, biochemical methods were used to detect Fe2+, malondialdehyde(MDA), glutathione(GSH) and other indicators in ovarian tissues, serum sex hormone and insulin levels were measured by enzyme-linked immunosorbent assay(ELISA), and the protein expressions of AMPK, FASN, acyl-CoA synthetase long-chain family member 4(ACSL4), GPX4, and solute carrier family 7 member 11(SLC7A11) in ovarian tissues were detected by Western blot. ResultsCompared with the normal group, the model group showed polycystic changes in the ovaries, with atrophy of mitochondria in granulosa cells and increased membrane density. Serum levels of testosterone(T), luteinizing hormone(LH), and insulin were significantly increased(P<0.01). The levels of ROS, MDA, 4-hydroxynonenal(4-HNE), and Fe2+ in ovarian tissues were significantly elevated(P<0.01), while adenosine triphosphate(ATP), GSH, and reduced nicotinamide adenine dinucleotide phosphate (NADPH) levels were significantly decreased(P<0.01). The phosphorylation levels of AMPK and acetyl-CoA carboxylase (ACC), as well as the protein expressions of SLC7A11, GPX4, and ferroptosis suppressor protein 1(FSP1) were significantly downregulated(P<0.01), whereas the expressions of FASN, ACSL4, and nuclear receptor coactivator 4(NCOA4) were significantly upregulated(P<0.01). Compared with the model group, MBXT intervention at various doses improved the above pathological changes and biochemical indicators in a dose-dependent manner, with the high-dose group showing the most significant effect(P<0.01). Compared with the MBXT high-dose group, the high-dose of MBXT combined with ferroptosis inducer Erastin group restored ovarian ferroptosis characteristics in rats, with increased ROS and lipid peroxidation products, and altered expressions of key proteins(P<0.05, P<0.01). ConclusionMBXT can effectively improve ovarian function and metabolic disorders in PCOS-IR rats. Its mechanism may be related to activating the AMPK/ACC signaling pathway, downregulating FASN and ACSL4 to reduce lipid peroxidation substrates, and restoring glucose-6-phosphate dehydrogenase/phosphoglycerate dehydrogenase(G6PD/PHGDH) metabolic flux to enhance the GPX4/FSP1 antioxidant defense system, thereby inhibiting ferroptosis in ovarian granulosa cells.
10.Exploring Mechanism of Xiaoqinglongtang Against High Altitude Pulmonary Edema Based on Integrative Pharmacology Model
Rongrong WANG ; Chuchu WANG ; Qi XU ; Qin JIAN ; Junzhi LIN ; Ruli LI ; Chuan ZHENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):137-148
ObjectiveTo explore the potential mechanism of Xiaoqinglongtang(XQL) in the prevention and treatment of high altitude pulmonary edema(HAPE) by network pharmacology, molecular docking, and molecular dynamics simulation, and to verify it by in vivo animal model. MethodsIn this study, the active ingredients, drug targets, and HAPE-related targets of XQL were collected from BATMAN-TCM, GeneCards, and Online Mendelian Inheritance in Man(OMIM) databases. The protein-protein interaction(PPI) network was constructed by using intersection targets, and the core targets were screened and visualized by Cytoscape software. Functional annotation and pathway analysis of the intersection targets were performed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) functional enrichment. AutoDock and GROMACS were used to evaluate the binding ability of active ingredients to key targets. In the experimental verification part, a mouse model of HAPE induced by hypobaric hypoxia(simulated 6 000 m altitude for 48 h) was established. The control effect was evaluated by hematoxylin-eosin(HE) staining, lung tissue water content, lung tissue wet/dry weight ratio, real-time quantitative polymerase chain reaction(Real-time PCR) detection of gene expression levels, and immunohistochemistry and Western blot detection of key protein expression. ResultsA total of 355 active ingredients of XQL, 2 142 targets, 716 HAPE-related targets, and 236 intersection targets were obtained by network pharmacology analysis. Key core targets such as interleukin (IL)-6, tumor necrosis factor (TNF), protein kinase B1 (Akt1), and hypoxia-inducible factor-1α (HIF-1α) were screened. The results of GO analysis of common targets involved 738 biological processes(BP), 72 cellular components(CC), and 135 molecular functions(MF). KEGG analysis effectively enriched two important signaling pathways: Phosphoinositol 3-kinase (PI3K)/Akt and HIF-1α. The results of molecular docking and molecular dynamics simulation showed that the screened active ingredients had good binding ability with key targets. In the HAPE model induced by hypobaric hypoxia(6 000 m, 48 h), the lung tissue water content, lung tissue wet/dry weight ratio, and pathological injury score of the model group were significantly increased(P<0.01), accompanied by exudation of a large number of red blood cells in the alveoli and alveolar interstitium, a significant increase in inflammatory cells, a significant widening of the alveolar septum, and mutual fusion between the alveoli. The XQL administration group significantly improved the above pathological changes(P<0.01). The results of inflammatory factor expression showed that compared with the control group, the model group showed significantly up-regulated expression of TNF-α, IL-6, and IL-1β in the lung tissue(P<0.01). Compared with the model group, the XQL administration group had significantly decreased expression of inflammatory factors(P<0.05, P<0.01). The mRNA expression of key pathway related genes PI3K, Akt1, mammalian target of rapamycin(mTOR), and HIF-1α was significantly increased in the model group(P<0.01), and decreased in a concentration-dependent manner after XQL administration(P<0.05, P<0.01). The expression levels of key proteins PI3K, phosphorylation(p)-PI3K, Akt1, p-Akt1, mTOR, p-mTOR, and HIF-1α in lung tissue were analyzed by immunohistochemistry and Western blot. Compared with the blank group, the model group showed increased expression of key proteins(P<0.05, P<0.01). Compared with the model group, the XQL administration group exhibited decreased expression of key proteins(P<0.05, P<0.01). ConclusionXQL can reduce lung inflammation and improve HAPE. The mechanism may be related to the regulation of PI3K/Akt/mTOR and HIF-1α pathways. This study provides a new idea and a theoretical basis for the treatment of HAPE with XQL.


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