1.Mechanisms of Shenqi Wenfei Prescription in Intervening in Chronic Obstructive Pulmonary Disease in Rats Based on ROS/TXNIP/NLRP3 Signaling Pathway
Di WU ; Mengyao SHI ; Lu ZHANG ; Tong LIU ; Jiabing TONG ; Cheng YANG ; Zegeng LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):78-87
ObjectiveTo investigate the effects and underlying mechanisms of Shenqi Wenfei prescription (SQWF) on chronic obstructive pulmonary disease (COPD). MethodsA rat model of COPD with lung Qi deficiency was established using lipopolysaccharide (LPS) combined with cigarette smoke. Forty-eight SD rats were randomly divided into a blank group, a model group, low-, medium-, and high-dose SQWF groups (2.835, 5.67, 11.34 g·kg-1), and a Yupingfeng group (1.35 g·kg-1). Drug administration began on day 29 after modeling and continued for 2 weeks. The general condition of the rats was observed, and the lung function in each group was assessed. Hematoxylin-eosin (HE) staining was used to observe pathological changes in lung tissue. The proportion of inflammatory cells in bronchoalveolar lavage fluid (BALF) was measured. Apoptosis in lung tissue was examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. The release level of lactate dehydrogenase (LDH) in BALF was detected by a microplate assay. Reactive oxygen species (ROS) levels in lung tissue were detected using fluorescent probes. The levels of malondialdehyde (MDA), total superoxide dismutase (SOD), and reduced glutathione (GSH) in BALF were measured by biochemical methods. Ultrastructural changes in lung cells were observed via transmission electron microscopy. Double immunofluorescence staining was performed to detect the expression of thioredoxin-interacting protein (TXNIP) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in lung tissue. Western blot analysis was used to detect the protein expression of TXNIP, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), cysteinyl aspartate-specific protease-1 (Caspase-1), Caspase-1 p20, gasdermin D (GSDMD), GSDMD N-terminal active fragment (GSDMD-N), interleukin-1β (IL-1β), and IL-18 in lung tissue. Serum IL-1β and IL-18 levels were measured by ELISA. ResultsCompared with the blank group, the model group showed lassitude, fatigue, tachypnea, and audible phlegm sounds, and lung function significantly declined (P0.01). Pulmonary emphysema and inflammatory cell infiltration were obvious. The level of inflammatory cells in BALF increased significantly (P0.05). The number of TUNEL-positive cells increased (P0.01). Levels of LDH, ROS, and MDA in BALF increased significantly (P0.01), while GSH and SOD activities decreased significantly (P0.01). Lung tissue cells showed irregular morphology, swollen mitochondria, disrupted cell membranes, and abundant vesicles, i.e., pyroptotic bodies. Protein levels of TXNIP, NLRP3, ASC, Caspase-1, Caspase-1 p20, GSDMD, GSDMD-N, IL-1β, and IL-18 in lung tissue were significantly elevated (P0.01), and serum IL-1β and IL-18 levels also increased significantly (P0.01). Compared with the model group, each medication group showed alleviation of qi deficiency symptoms and improved lung function (P0.01). Pulmonary emphysema and inflammatory cell infiltration were reduced. Inflammatory cell levels decreased (P0.05). The number of TUNEL-positive cells decreased significantly (P0.01). Levels of LDH, ROS, and MDA decreased significantly (P0.05), while GSH and SOD activities significantly increased (P0.01). Morphological and structural damage in lung tissue was improved to varying degrees. Protein levels of TXNIP, NLRP3, ASC, Caspase-1, Caspase-1 p20, GSDMD, GSDMD-N, IL-1β, and IL-18 in lung tissue significantly decreased (P0.01), and serum IL-1β and IL-18 levels also decreased significantly (P0.05). ConclusionSQWF can improve lung function and alleviate inflammatory responses in COPD rats. Its mechanism may be related to regulating the ROS/TXNIP/NLRP3 pathway and inhibiting pyroptosis.
2.Mechanisms of Shenqi Wenfei Prescription in Intervening in Chronic Obstructive Pulmonary Disease in Rats Based on ROS/TXNIP/NLRP3 Signaling Pathway
Di WU ; Mengyao SHI ; Lu ZHANG ; Tong LIU ; Jiabing TONG ; Cheng YANG ; Zegeng LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):78-87
ObjectiveTo investigate the effects and underlying mechanisms of Shenqi Wenfei prescription (SQWF) on chronic obstructive pulmonary disease (COPD). MethodsA rat model of COPD with lung Qi deficiency was established using lipopolysaccharide (LPS) combined with cigarette smoke. Forty-eight SD rats were randomly divided into a blank group, a model group, low-, medium-, and high-dose SQWF groups (2.835, 5.67, 11.34 g·kg-1), and a Yupingfeng group (1.35 g·kg-1). Drug administration began on day 29 after modeling and continued for 2 weeks. The general condition of the rats was observed, and the lung function in each group was assessed. Hematoxylin-eosin (HE) staining was used to observe pathological changes in lung tissue. The proportion of inflammatory cells in bronchoalveolar lavage fluid (BALF) was measured. Apoptosis in lung tissue was examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. The release level of lactate dehydrogenase (LDH) in BALF was detected by a microplate assay. Reactive oxygen species (ROS) levels in lung tissue were detected using fluorescent probes. The levels of malondialdehyde (MDA), total superoxide dismutase (SOD), and reduced glutathione (GSH) in BALF were measured by biochemical methods. Ultrastructural changes in lung cells were observed via transmission electron microscopy. Double immunofluorescence staining was performed to detect the expression of thioredoxin-interacting protein (TXNIP) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in lung tissue. Western blot analysis was used to detect the protein expression of TXNIP, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), cysteinyl aspartate-specific protease-1 (Caspase-1), Caspase-1 p20, gasdermin D (GSDMD), GSDMD N-terminal active fragment (GSDMD-N), interleukin-1β (IL-1β), and IL-18 in lung tissue. Serum IL-1β and IL-18 levels were measured by ELISA. ResultsCompared with the blank group, the model group showed lassitude, fatigue, tachypnea, and audible phlegm sounds, and lung function significantly declined (P0.01). Pulmonary emphysema and inflammatory cell infiltration were obvious. The level of inflammatory cells in BALF increased significantly (P0.05). The number of TUNEL-positive cells increased (P0.01). Levels of LDH, ROS, and MDA in BALF increased significantly (P0.01), while GSH and SOD activities decreased significantly (P0.01). Lung tissue cells showed irregular morphology, swollen mitochondria, disrupted cell membranes, and abundant vesicles, i.e., pyroptotic bodies. Protein levels of TXNIP, NLRP3, ASC, Caspase-1, Caspase-1 p20, GSDMD, GSDMD-N, IL-1β, and IL-18 in lung tissue were significantly elevated (P0.01), and serum IL-1β and IL-18 levels also increased significantly (P0.01). Compared with the model group, each medication group showed alleviation of qi deficiency symptoms and improved lung function (P0.01). Pulmonary emphysema and inflammatory cell infiltration were reduced. Inflammatory cell levels decreased (P0.05). The number of TUNEL-positive cells decreased significantly (P0.01). Levels of LDH, ROS, and MDA decreased significantly (P0.05), while GSH and SOD activities significantly increased (P0.01). Morphological and structural damage in lung tissue was improved to varying degrees. Protein levels of TXNIP, NLRP3, ASC, Caspase-1, Caspase-1 p20, GSDMD, GSDMD-N, IL-1β, and IL-18 in lung tissue significantly decreased (P0.01), and serum IL-1β and IL-18 levels also decreased significantly (P0.05). ConclusionSQWF can improve lung function and alleviate inflammatory responses in COPD rats. Its mechanism may be related to regulating the ROS/TXNIP/NLRP3 pathway and inhibiting pyroptosis.
3.Qualitative and Quantitative Analysis of Chemical Constituents in Gualou Niubangtang by UPLC-Q-TOF-MS/MS and HPLC
Yiyi ZHANG ; Jing YANG ; Yuqing CHENG ; Huimin GAO ; Jin QIN ; Li YAO ; Xiyang DU ; Raorao LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):179-187
ObjectiveThis paper aims to clarify the material basis of Gualou Niubangtang and establish a quantitative analysis method for its main constituents, providing a reference for the overall quality control of this preparation. MethodsThe constituents in the formula were systematically characterized based on ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Identification was performed by matching with the UNIFI 9.6 software and utilizing database platforms such as PubChem, ChemicalBook, and ChemSpider, combined with relevant literature reports. A quantitative analysis method for the seven main constituents in Gualou Niubangtang was established by using high performance liquid chromatography (HPLC). ResultsUPLC-Q-TOF-MS/MS analysis identified 155 constituents, including 69 flavonoids, 36 terpenoids, 23 phenylpropanoids, 8 phenylethanoid glycosides, and 19 other types of constituents. In the established quantitative analysis method, the seven main constituents showed good linearity within their respective linear ranges. The precision, repeatability, stability, and spike recovery all met the required standards. The results showed that the content ranges of geniposide, liquiritin, hesperidin, arctiin, baicalin, oroxylin A-7-O-β-D-glucuronide, and wogonoside in 15 batches of Gualou Niubangtang were 13.67-21.25, 1.20-7.64, 5.45-7.45, 22.97-33.51, 29.95-39.07, 2.58-4.80, and 6.56-9.31 mg·g-1, respectively. ConclusionThis study successfully characterizes and attributes multi-category constituents in Gualou Niubangtang, clarifying that its material basis is primarily composed of flavonoids, terpenoids, phenylethanoid glycosides, and phenylpropanoids. Furthermore, it enables the quantification of seven constituents within the formula. This work lays a foundation for research on the quality control, action mechanism, and clinical application of this formula.
4.Association of mixed exposure to lithium, vanadium, uranium, and bismuth in early pregnancy with gestational weight gain
Jiao LI ; Qi LI ; Shuang CHENG ; Jiayi SONG ; Xiaohui GUO ; Xiang WANG ; Di CHENG ; Kefeng FAN ; Ju WANG
Journal of Environmental and Occupational Medicine 2026;43(4):475-484
Background Gestational weight gain is closely related to maternal and infant health outcomes. Pregnant women are simultaneously exposed to four metals—lithium (Li), vanadium (V), uranium (U), and bismuth (Bi)—through inhalation of fine particulate matter and consumption of contaminated food and water. Existing studies suggest that exposure to these metals may be associated with gestational weight gain. However, no study has yet explored the complex relationships between exposure to mixtures of these four metals and weight gain at different stages of pregnancy. Objective To investigate the associations between mixed exposure to Li, V, U, and Bi in early pregnancy and the average weekly gestational weight gain during both early pregnancy and mid-to-late pregnancy. Methods This prospective study recruited eligible women in early pregnancy from an obstetrics clinic of a tertiary hospital in Jinan, China, between September 2021 and July 2023. Pre-pregnancy weight, current weight (at 11+0 to 13+6 weeks of gestation), and spot urine samples (≥5.0 mL) were collected at enrollment. Urinary concentrations of Li, V, Bi, and U were determined using inductively coupled plasma mass spectrometry. Participants were followed up in late pregnancy (≥28 weeks of gestation) to collect information on physical activity via questionnaire; weight measurements at the last antenatal visit (35+0 to 37+6 weeks of gestation) were obtained from the hospital information system. After adjusting for covariates, multiple linear regression and generalized additive models were used to assess the associations of individual metals with weekly weight gain in early pregnancy and in mid-to-late pregnancy. Bayesian kernel machine regression (BKMR) and quantile-based g-computation (Qgcomp) were applied to evaluate the joint effects of the metal mixture exposure on weekly weight gain at the two gestational stages. Results A total of 313 pregnant women were included. The geometric means of urinary Li, V, U, and Bi concentrations were 37.07, 0.20, 0.06, and 0.04 μg·L−1, respectively; after creatinine adjustment, the corresponding values were 46.82, 0.25, 0.07, and 0.05 μg·g−1 (Cr). The mean weekly gestational weight gain was (0.19±0.25) kg in early pregnancy and (0.53 ± 0.18) kg in mid-to-late pregnancy. Both multiple linear regression and generalized additive models showed that urinary V concentration was positively associated with average weekly gestational weight gain in early pregnancy, while no significant associations were found for other metals or for gestational weight gain in mid-to-late pregnancy. In the BKMR model with early-pregnancy weight gain as the outcome, V had the strongest association [posterior inclusion probability (PIP)=0.773]. When other metals were fixed at their medians, V showed a positive non-linear association with the outcome. A significant single-metal effect of V and its interaction with Li were observed. Compared with the 50th percentile of the metal mixture, the average weekly weight gain in early pregnancy increased by 0.016 (95%CI: 0.003, 0.029) and 0.018 (95%CI: 0.001, 0.036) at the 60th and 65th percentiles, respectively; conversely, at the 25th percentile, it decreased by 0.026 (95%CI: 0.002, 0.050). Overall, the joint effect of the metal mixture on early- pregnancy weight gain showed an upward trend. In the BKMR model for mid-to-late pregnancy gestational weight gain, all PIPs were<0.5, and no significant single-metal effects, interactions, or joint effects were identified. Qgcomp results confirmed a positive association between the metal mixture and early-pregnancy weight gain (b=0.031, 95%CI: 0.010, 0.051; P<0.01), with V contributing the highest positive weight (0.71). No significant association was found for weight gain in mid-to-late pregnancy (b=0.007, P=0.339). Conclusion Higher levels of co-exposure to the Li, V, Bi, and U metal mixture during early pregnancy may be associated with increased average weekly weight gain in early pregnancy. Among these metals, V exhibits a predominant role and appears to interact with Li. No association is observed between early-pregnancy metal mixture exposure and average weekly gestational weight gain in mid-to-late pregnancy. These findings suggest that monitoring and managing metal exposure during early pregnancy may be crucial for the rational regulation of gestational weight gain.
5.Short-term and Long-term Clinical Outcomes of Combined Caudate Lobectomy for Intrahepatic Cholangiocarcinoma Involving the Hepatic Hilus: A Propensity Score Analysis
Di ZENG ; Yaoqun WANG ; Ningyuan WEN ; Bei LI ; Nansheng CHENG ; Jiong LU
Gut and Liver 2025;19(3):438-453
Background/Aims:
Extended hepatectomy combined with caudate lobe resection has been approved for the radical resection of hilar cholangiocarcinoma. There was a lack of credible research on the clinical value of caudate lobectomy (CL) for intrahepatic cholangiocarcinoma involving the hepatic hilus when combined with hepatectomy. We aimed to compare the short-term and long-term outcomes of the combined procedure with those of only CL for curative resection of intrahepatic cholangiocarcinoma involving the hepatic hilus.
Methods:
This single-center retrospective cohort study of patients with hilar cholangiocarcinoma was conducted from January 2007 to December 2021. Patients who underwent radical resection were enrolled in this study. The short-term and long-term clinical outcomes of the groups were compared before and after propensity score matching (PSM).
Results:
A total of 282 patients were included. There were no statistically significant differences in perioperative clinical outcomes between the CL group and the non-CL group before and after PSM. Compared to patients in the non-CL group, patients in the CL group had significantly longer overall survival before and after PSM (p=0.007 before PSM, p=0.033 after PSM). Moreover, compared to the non-CL group, the CL group had longer disease-free survival before and after PSM (p<0.001 before PSM, p=0.019 after PSM).
Conclusions
The postoperative complications of the CL group were comparable to those of the non-CL group. CL improved the long-term survival of patients with intrahepatic cholangiocarcinoma involving the hepatic hilus when combined with hepatectomy. Therefore, hepatectomy combined with caudate lobe resection should be performed for patients with hilar cholangiocarcinoma.
6.Percutaneous coronary intervention vs . medical therapy in patients on dialysis with coronary artery disease in China.
Enmin XIE ; Yaxin WU ; Zixiang YE ; Yong HE ; Hesong ZENG ; Jianfang LUO ; Mulei CHEN ; Wenyue PANG ; Yanmin XU ; Chuanyu GAO ; Xiaogang GUO ; Lin CAI ; Qingwei JI ; Yining YANG ; Di WU ; Yiqiang YUAN ; Jing WAN ; Yuliang MA ; Jun ZHANG ; Zhimin DU ; Qing YANG ; Jinsong CHENG ; Chunhua DING ; Xiang MA ; Chunlin YIN ; Zeyuan FAN ; Qiang TANG ; Yue LI ; Lihua SUN ; Chengzhi LU ; Jufang CHI ; Zhuhua YAO ; Yanxiang GAO ; Changan YU ; Jingyi REN ; Jingang ZHENG
Chinese Medical Journal 2025;138(3):301-310
BACKGROUND:
The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China.
METHODS:
This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences.
RESULTS:
Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n = 278] vs . 43.7% [ n = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses.
CONCLUSION
This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans
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Percutaneous Coronary Intervention/methods*
;
Male
;
Female
;
Coronary Artery Disease/drug therapy*
;
Retrospective Studies
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Renal Dialysis/methods*
;
Middle Aged
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Aged
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China
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Proportional Hazards Models
;
Treatment Outcome
7.Research progress on chemical constituents, pharmacological effects of Anemarrhenae Rhizoma and predictive analysis of its quality markers.
Wen-Jun WANG ; Ze-Min YANG ; An LIU ; Li-Dong SHAO ; Jin-Tang CHENG
China Journal of Chinese Materia Medica 2025;50(4):934-945
Anemarrhenae Rhizoma is bitter, sweet, and cold in nature, and has the effects of clearing heat, dispelling fire, nourishing Yin, and moisturizing dryness. It is associated with the lung, stomach, and kidney meridians, and is mainly distributed in the northwestern and northern regions of China. Modern research has shown that Anemarrhenae Rhizoma contains various chemical active constituents, including steroidal saponins, flavonoids, polysaccharides, lignans, volatile oils, and alkaloids. These constituents exhibit pharmacological effects such as anti-tumor, hypoglycemic, anti-inflammatory, and neuroprotective activities. However, there have been few comprehensive summaries of Anemarrhenae Rhizoma in recent years, which has limited its in-depth research and development. The complexity of traditional Chinese medicine constituents, along with their quality and efficacy, is easily influenced by processing, preparation, and the growing environment and resource distribution. This paper summarizes the resources, chemical constituents, and pharmacological effects of Anemarrhenae Rhizoma, and predicts its quality markers(Q-markers) from several aspects, including the specificity of chemical composition, properties related to preparation and active ingredients, measurability of chemical components, compounding environment, construction of the ″active ingredient-target″ network pathway, and differences in active ingredient content from different origins and parts. These predicted Q-markers may provide a basis for improving the quality evaluation system of Anemarrhenae Rhizoma.
Anemarrhena/chemistry*
;
Drugs, Chinese Herbal/pharmacology*
;
Rhizome/chemistry*
;
Humans
;
Animals
;
Quality Control
8.Effect of medicinal parts and harvest seasons on nature-flavor correlation of plant-based Chinese materia medica.
Qi-Ao MA ; Guang YANG ; Hong-Chao WANG ; Ying LI ; Meng CHENG ; Tie-Lin WANG ; Kai SUN ; Xiu-Lian CHI
China Journal of Chinese Materia Medica 2025;50(15):4228-4237
This study selected 6 529 plant-based Chinese materia medica(PCMM) from Chinese Materia Medica as research subjects and applied a random permutation test to explore the overall correlation characteristics between nature and flavor, as well as the correlation characteristics after distinguishing different medicinal parts and harvest seasons. The results showed that the overall correlation characteristics between nature and flavor in PCMM were significantly associated in the following pairs: cold and bitter, cool and bitter, cool and astringent, cool and light, neutral and sweet, neutral and astringent, neutral and light, neutral and sour, hot and pungent, and warm and pungent. When analyzing the data by distinguishing medicinal parts and/or harvest seasons, new correlation patterns emerged, characterized by the disappearance of some significant correlations and the emergence of new ones. When analyzing by medicinal parts alone, significant correlations were found in the following cases: cold and light in leaves, cold and salty in barks, cool and sweet in fruits and seeds, neutral and pungent in whole herbs, neutral and salty in stems, and warm and salty in flowers. However, no significant correlations were found between cool and bitter in stems and other types of herbs, cool and astringent in fruits, seeds, flowers, and other types of herbs, cool and light in leaves, fruits, seeds, barks, flowers and other types of herbs, neutral and sweet in barks, neutral and astringent in whole herbs and stems, neutral and light in leaves, fruits, seeds, and flowers, neutral and sour in whole herbs, stems, barks, flowers, and other types of herbs, and hot and pungent in whole herbs, stems, flowers, and other types of herbs. When analyzing by harvest season alone, significant correlations were found in the following cases: cold and salty, and cool and sour in herbs harvested in winter, and neutral and salty in herbs harvested year-round. However, no significant correlation was found between cool and light in herbs harvested in winter. When considering both medicinal parts and harvest seasons, compared to the independent influence of medicinal parts, 14 new significant correlations emerged(e.g., the correlation between cool and bitter in stems harvested in spring), while 53 previously significant correlations disappeared(e.g., the correlation between cool and bitter in barks harvested in summer). Compared to the independent influence of harvest seasons, 11 new significant correlations appeared(e.g., the correlation between cold and light in barks harvested in autumn), while 50 previously significant correlations disappeared(e.g., the correlation between hot and pungent in leaves harvested in winter). This study is the first to reveal the influence of medicinal parts and harvest seasons on the correlation between nature and flavor in PCMM, which highlights that these two factors can interact and jointly affect nature-flavor correlations. Further research is needed to explore the underlying mechanisms. This study provides a deeper understanding of the inherent scientific connotations of herbal properties and offers a theoretical foundation for the cultivation and harvesting of PCMM.
Seasons
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Plants, Medicinal/growth & development*
;
Drugs, Chinese Herbal/chemistry*
;
Taste
9.Transzonal Projections and Follicular Development Abnormalities in Polycystic Ovary Syndrome
Di CHENG ; Yu-Hua CHEN ; Xia-Ping JIANG ; Lan-Yu LI ; Yi TAN ; Ming LI ; Zhong-Cheng MO
Progress in Biochemistry and Biophysics 2025;52(10):2499-2511
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder affecting a substantial proportion of women of reproductive age. It is frequently associated with ovulatory dysfunction, infertility, and an increased risk of chronic metabolic diseases. A hallmark pathological feature of PCOS is the arrest of follicular development, closely linked to impaired intercellular communication between the oocyte and surrounding granulosa cells. Transzonal projections (TZPs) are specialized cytoplasmic extensions derived from granulosa cells that penetrate the zona pellucida to establish direct contact with the oocyte. These structures serve as essential conduits for the transfer of metabolites, signaling molecules (e.g., cAMP, cGMP), and regulatory factors (e.g., microRNAs, growth differentiation factors), thereby maintaining meiotic arrest, facilitating metabolic cooperation, and supporting gene expression regulation in the oocyte. The proper formation and maintenance of TZPs depend on the cytoskeletal integrity of granulosa cells and the regulated expression of key connexins, particularly CX37 and CX43. Recent studies have revealed that in PCOS, TZPs exhibit significant structural and functional abnormalities. Contributing factors—such as hyperandrogenism, insulin resistance, oxidative stress, chronic inflammation, and dysregulation of critical signaling pathways (including PI3K/Akt, Wnt/β‑catenin, and MAPK/ERK)—collectively impair TZP integrity and reduce their formation. This disruption in granulosa-oocyte communication compromises oocyte quality and contributes to follicular arrest and anovulation. This review provides a comprehensive overview of TZP biology, including their formation mechanisms, molecular composition, and stage-specific dynamics during folliculogenesis. We highlight the pathological alterations in TZPs observed in PCOS and elucidate how endocrine and metabolic disturbances—particularly androgen excess and hyperinsulinemia—downregulate CX43 expression and impair gap junction function, thereby exacerbating ovarian microenvironmental dysfunction. Furthermore, we explore emerging therapeutic strategies aimed at preserving or restoring TZP integrity. Anti-androgen therapies (e.g., spironolactone, flutamide), insulin sensitizers (e.g., metformin), and GLP-1 receptor agonists (e.g., liraglutide) have shown potential in modulating connexin expression and enhancing granulosa-oocyte communication. In addition, agents such as melatonin, AMPK activators, and GDF9/BMP15 analogs may promote TZP formation and improve oocyte competence. Advanced technologies, including ovarian organoid models and CRISPR-based gene editing, offer promising platforms for studying TZP regulation and developing targeted interventions. In summary, TZPs are indispensable for maintaining follicular homeostasis, and their disruption plays a pivotal role in the pathogenesis of PCOS-related folliculogenesis failure. Targeting TZP integrity represents a promising therapeutic avenue in PCOS management and warrants further mechanistic and translational investigation.
10.Herbal Textual Research on Picrorhizae Rhizoma in Famous Classical Formulas
Feng ZHOU ; Yihan WANG ; Yanmeng LIU ; Xiaoqin ZHAO ; Kaizhi WU ; Cheng FENG ; Wenyue LI ; Wei ZHANG ; Wentao FANG ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):228-239
This article systematically analyzes the historical evolution of the name, origin, quality evaluation, harvesting, processing and other aspects of Picrorhizae Rhizoma by referring to the medical books, prescription books, and other documents of the past dynasties, combined with relevant modern research materials, in order to provide a basis for the development and utilization of famous classical formulas containing this medicinal herb. The research results indicate that Picrorhizae Rhizoma was first recorded in New Revised Materia Medica from the Tang dynasty. Throughout history, Huhuanglian has been used as its official name, and there are also aliases such as Gehu Luze, Jiahuanglian and Hulian. The main source of past dynasties is the the rhizomes of Picrorhiza kurrooa and P. scrophulariiflora. In ancient times, Picrorhizae Rhizoma was mainly imported by foreign traders via Guangzhou and other regions, and also produced in China, mainly in Xizang. In ancient times, it was harvested and dried in early August of the lunar calendar, while in modern times, it is mostly harvested from July to September, with the best quality being those with thick and crispy rhizomes without impurities, and bitter taste. Throughout history, Picrorhizae Rhizoma was collected, washed, sliced, and dried before being used as a raw material for medicine, it has a bitter and cold taste, mainly used to treat bone steaming, hot flashes, infantile chancre fever, and dysentery. There is no significant difference in taste and efficacy between ancient and modern times. Based on the research results, it is recommended that the rhizomes of P. scrophulariiflora in the 2020 edition of Chinese Pharmacopoeia, or the rhizomes of P. kurrooa, can be used in famous classical formulas containing this medicinal herb, which can be processed according to the processing requirements marked by the original formula. For those without clear processing requirements, the dried raw products are used as medicine.

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