1.Signaling Pathways Related to Polycystic Ovary Syndrome and Regulation by Traditional Chinese Medicine: A Review
Manman YAO ; Liya MA ; Dawei ZHANG ; Xuelin ZHANG ; Xuan ZHOU ; Yu TANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):301-312
Polycystic ovary syndrome (PCOS) is one of the most prevalent gynecological diseases, and its incidence is increasing year by year, seriously affecting the physical and mental health of female patients. The pathogenesis of this disease is complex and has not been fully clarified. At present, PCOS is mainly treated by Western medicine, which, however, has poor efficacy and induces various adverse reactions. Therefore, developing safe and effective therapies has become a difficult problem that needs to be solved. Studies have confirmed that traditional Chinese medicine (TCM) can regulate phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB), transforming growth factor-β (TGF-β)/Smads, secreted glycoprotein/β-catenin (Wnt/β-catenin), adenosine monophosphate-activated protein kinase (AMPK), and advanced glycation endproduct/receptor for advanced glycation endproducts (AGE/RAGE) signaling pathways to ameliorate insulin resistance, inhibit inflammation and oxidative stress, regulate endocrine hormone disorders, and intervene in apoptosis and autophagy, thus alleviating the symptoms, slowing down the disease progression, and improving the ovarian function. The treatment of PCOS with TCM has demonstrated definite effects and high safety. Therefore, exploring this disease from cellular and molecular perspectives can provide a theoretical basis for its clinical treatment and new drug development. However, there is a lack of systematic reviews on the modulation of relevant signaling pathways by TCM in the treatment of PCOS. This article reviews the research progress in the treatment of PCOS with the active ingredients and compound prescriptions of TCM by regulating relevant signaling pathways in recent years, with the aim of providing evidence to support the promotion of TCM for treating PCOS in the future.
2.Establishment and validation of a risk prediction model for 90-day mortality in patients with acute-on-chronic liver failure based on sarcopenia
Huina CHEN ; Ming KONG ; Siqi ZHANG ; Manman XU ; Yu CHEN ; Zhongping DUAN
Journal of Clinical Hepatology 2025;41(6):1135-1142
ObjectiveTo establish and validate a new prediction model for the risk of death in patients with acute-on-chronic liver failure (ACLF) based on sarcopenia and other clinical indicators, and to improve the accuracy of prognostic assessment for ACLF patients. MethodsA total of 380 patients with ACLF who were admitted to Beijing YouAn Hospital, Capital Medical University, from January 2019 to January 2022 were enrolled, and they were divided into training group with 228 patients and testing group with 152 patients in a ratio of 6∶4 using the stratified random sampling method. For the training group, CT images were used to measure the cross-sectional area of the skeletal muscle at the third lumbar vertebra (L3), and L3 skeletal muscle index (L3-SMI) was calculated. Sarcopenia was diagnosed based on the previously established L3-SMI reference values for healthy adults in northern China. Univariate and multivariable Cox regression analyses were used to establish a sarcopenia-ACLF model which integrated sarcopenia and clinical risk factors, and a nomogram was developed for presentation. The area under the ROC curve (AUC) was used to assess the predictive performance of the model, the calibration curve was used to assess the degree of calibration, and a decision curve analysis was used to investigate the clinical application value of the model. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to plot survival curves, and the Log-rank test was used for comparison between groups. The DeLong test was used for comparison of AUC between different models. ResultsThe multivariate Cox regression analysis showed that sarcopenia (hazard ratio [HR]=1.962, 95% confidence interval [CI]: 1.185 — 3.250, P=0.009), total bilirubin (HR=1.003, 95%CI: 1.002 — 1.005, P<0.001), international normalized ratio (HR=1.997, 95%CI: 1.674 — 2.382, P<0.001), and lactic acid (HR=1.382, 95%CI: 1.170 — 1.632, P<0.001) were included in the sarcopenia-ACLF model. In the training cohort, the sarcopenia-ACLF model had a larger AUC than MELD-Na score in predicting 90-day mortality in patients with ACLF (0.80 vs 0.73, Z=1.97, P=0.049). In the test cohort, the sarcopenia-ACLF model had a significantly larger AUC than MELD score (0.79 vs 0.69, Z=2.70, P=0.007) and MELD-Na score (0.79 vs 0.68, Z=2.92, P=0.004). The calibration curve showed that the model had good calibration ability, with a relatively good consistency between the predicted risk of mortality and the observed results. The DCA results showed that within a reasonable range of threshold probabilities, the sarcopenia-ACLF model showed a greater net benefit than MELD and MELD-Na scores in both the training cohort and the test cohort. ConclusionThe sarcopenia-ACLF model developed in this study provides a more accurate tool for predicting the risk of 90-day mortality in ACLF patients, which provides support for clinical decision-making and helps to optimize treatment strategies.
3.RBM14 enhances transcriptional activity of p23 regulating CXCL1 expression to induce lung cancer metastasis.
Wen ZHANG ; Yulin PENG ; Meirong ZHOU ; Lei QIAN ; Yilin CHE ; Junlin CHEN ; Wenhao ZHANG ; Chengjian HE ; Minghang QI ; Xiaohong SHU ; Manman TIAN ; Xiangge TIAN ; Yan TIAN ; Sa DENG ; Yan WANG ; Xiaokui HUO ; Zhenlong YU ; Xiaochi MA
Acta Pharmaceutica Sinica B 2025;15(6):3059-3072
Metastasis serves as an indicator of malignancy and is a biological characteristic of carcinomas. Epithelial-mesenchymal transition (EMT) plays a key role in the promotion of tumor invasion and metastasis and in the enhancement of tumor cell aggressiveness. Prostaglandin E synthase 3 (p23) is a cochaperone for heat shock protein 90 (HSP90). Our previous study showed that p23 is an HSP90-independent transcription factor in cancer-associated inflammation. The effect and mechanism of action of p23 on lung cancer metastasis are tested in this study. By utilizing cell models in vitro and mouse tail vein metastasis models in vivo, the results provide solid evidence that p23 is critical for promoting lung cancer metastases by regulating downstream CXCL1 expression. Rather than acting independently, p23 forms a complex with RNA-binding motif protein 14 (RBM14) to facilitate EMT progression in lung cancer. Therefore, our study provides evidence for the potential role of the RBM14-p23-CXCL1-EMT axis in the metastasis of lung cancer.
4.Postoperative Stage-based Functional Protection Strategies for Lung Cancer Based on Theory of "Lungs Governing Qi"
Luchang CAO ; Guanghui ZHU ; Ruike GAO ; Manman XU ; Xiaoyu ZHU ; Wei HOU ; Ying ZHANG ; Jie LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):86-93
Lung cancer (LC) is a significant global public health issue, with both its incidence and mortality rates ranking among the highest worldwide. The age-standardized incidence and mortality rates are increasing annually, posing a serious threat to the life and health of LC patients. Radical surgical resection is the primary treatment for malignant lung tumors. However, postoperative multidimensional functional impairments, including respiratory, mucosal, and psychological functions, are common. These impairments not only reduce patients' quality of life and affect their treatment tolerance and duration, but also negatively correlate with prognosis, facilitating disease recurrence and metastasis. At present, postoperative functional dysfunction after LC surgery remains a key clinical challenge that urgently needs to be addressed. There is a lack of standardized and regulated postoperative rehabilitation treatment management and traditional Chinese medicine (TCM) differentiation and treatment strategies for LC. Focusing on the core underlying pathogenesis of "Qi sinking" after LC surgery, and guided by the classical TCM theory of "lungs governing Qi", this study, based on the core concept of the "five perspectives on treatment" theory, innovatively proposes the respiratory dysfunction as the core pathogenesis of "Qi sinking in the chest" during the rapid rehabilitation phase, mucosal dysfunction as the core pathogenesis of "Yin deficiency and Qi sinking" during the postoperative adjuvant treatment phase, and the psychological dysfunction as the core pathogenesis of "Qi sinking with emotional constraint" during the consolidation phase. Accordingly, stage-specific dynamic functional protection strategies are constructed. In the rapid rehabilitation phase, the strategy emphasizes tonifying Qi and uplifting sinking Qi, with differentiation and treatment based on the principle of ''descending before ascending''. In the adjuvant treatment phase, the approach focuses on nourishing Yin and uplifting Qi, with prescription combinations that integrate unblocking and tonification. In the consolidation phase, the strategy aims to resolve constraint and uplift Qi, with clinical treatment emphasizing a combination of dynamic and static methods. At each stage of functional rehabilitation, clinical differentiation and treatment should support healthy Qi and eliminate pathogenic factors simultaneously. This study is the first to propose the concept of postoperative functional protection in TCM, offering a new approach for TCM differentiation and treatment in the full-cycle, stage-based, and dynamic protection of postoperative function in LC patients. It is expected to contribute to the construction and development of an integrated TCM-Western medicine comprehensive program for cancer prevention and treatment in China.
5.A Hierarchical Strategy for Differentiation and Treatment of Recurrent Aphthous Oral Ulcers Related to Targeted Therapy for Lung Cancer Based on Yin Deficiency and Qi Collapse
Luchang CAO ; Guanghui ZHU ; Ruike GAO ; Manman XU ; Xiaoyu ZHU ; Ming LIN ; Ying ZHANG ; Jie LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):116-125
Tumor treatment-related adverse reactions are a major focus of clinical concern, among which recurrent aphthous oral ulcers (RAU) associated with targeted therapy for lung cancer (LC) are among the most painful and distressing for patients. Currently, modern medical interventions show limited efficacy, and there is an urgent need for more effective treatment strategies. This study differentiates RAU associated with targeted therapy for LC from chemotherapy-related and ordinary oral ulcers, elucidates the pathophysiological basis of such ulcers, and traces the theoretical origin of "Yin deficiency and Qi collapse". Based on the new system of "five perspectives on diagnosis and treatment" for tumor prevention and treatment, with a focus on the core and symptom perspectives and rooted in the traditional concept of "lung dominating Qi", we innovatively propose the concept of "medicine-induced ulcer" and are the first to introduce the theory of "Yin deficiency and Qi collapse" into the syndrome differentiation and treatment of RAU associated with targeted therapy for LC (i.e., medicine-induced ulcer). We propose that "Yin deficiency and Qi collapse" is the core pathogenesis of medicine-induced ulcers, in which the collapse of formless Qi is the key to their onset, while the deficiency and stasis of tangible Yin and blood constitute the root of recurrence. A hierarchical strategy for syndrome differentiation and treatment is established: first treating the collapse of formless Qi, then replenishing tangible deficiencies, and concurrently preventing recurrence. We emphasize that treatment should address both root and manifestation, with appropriate prioritization. In the acute phase, while relieving symptoms and promoting ulcer healing by nourishing Qi, uplifting collapse, and generating body fluids, attention should also be paid to nourishing spleen Yin, facilitating the circulation of nutritive Qi, and alleviating stasis to target the root pathogenesis and reduce recurrence. A verified case is presented to support this approach. This study enriches the theoretical framework and clinical methods of traditional Chinese medicine (TCM) in the treatment of RAU associated with targeted therapy for LC, promotes symptom management of treatment-related adverse reactions through integrated TCM and Western medicine, and provides theoretical support for the construction and development of a comprehensive differentiation and treatment system for lung cancer prevention, treatment, and rehabilitation.
6.Dynamic changes of prognostic scores and related clinical indicators in hepatitis B virus-related acute-on-chronic liver failure patients without underlying liver cirrhosis and their relationship with clinical outcomes
Wenling WANG ; Manman XU ; Yu WU ; Jiateng ZHANG ; Huaibin ZOU ; Yu CHEN
Journal of Clinical Hepatology 2025;41(9):1771-1778
ObjectiveTo investigate the dynamic trajectories of prognostic scores and key clinical indicators in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients without liver cirrhosis, to clarify their association with outcomes, and to provide new evidence for individualized prognostic assessment. MethodsA prospective study was conducted for the data of 154 non-cirrhotic HBV-ACLF patients who attended Beijing YouAn Hospital of Capital Medical University from January 2016 to December 2023, including prognostic scores and key biochemical indicators on Days 3, 7, 14, 21, and 28 of the disease course. According to the outcome of patients at 1 year, they were divided into death/liver transplantation group with 43 patients, liver cirrhosis group with 23 patients, and non-liver cirrhosis group with 88 patients, and the trajectory heterogeneity of different outcome subgroups was analyzed. A one-way analysis of variance was used for comparison of normally distributed continuous data among the three groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data among the three groups; the Wilcoxon test was used between two groups. the chi-square test was used for comparison of categorical data between groups. The mean and its 95% confidence interval (CI) were calculated for each indicator at difference time points; the linear interpolation method was used to connect the means at adjacent time points and construct the group-specific longitudinal trend curve; the 95%CI was visualized using the semi-transparent ribbon area, with the transparency parameter (α=0.2) optimized to enhance the visual discrimination of overlapping intervals across multiple groups. A linear mixed-effects model was used to compare the longitudinal changing trend of each indicator between the patients with different outcomes; likelihood ratio was used to evaluate the significance of the interaction effect between time and group, and in case of the significant interaction effect, the slope based on the estimated marginal mean was used for comparison between two groups. ResultsThere were significant differences between the three groups in the incidence rates of ascites and grade Ⅲ — Ⅳ hepatic encephalopathy, MELD score, MELD-Na score, CLIF-C ACLF score, COSSH-ACLF Ⅱ score, total bilirubin (TBil), international normalized ratio (INR), alpha-fetoprotein, blood sodium, alanine aminotransferase, and procalcitonin at the baseline(all P0.05). The analysis of dynamic trajectories showed that the death/liver transplantation group had high levels of prognostic scores and the biochemical parameters of TBil and INR (TBil400 μmol/L, INR2.5), as well as a low level of platelet count (PLT) (100×10⁹/L). The non-liver cirrhosis group had rapid improvements in indicators, with TBil200 μmol/L, INR1.5, and PLT100×10⁹/L by day 28, while the liver cirrhosis group showed a trend of recovery, with TBil200 μmol/L, INR2.0, and PLT 100×10⁹/L on day 28, with significant global heterogeneity in the temporal trends of the above indicators across the three groups (all P0.01). ConclusionDynamic monitoring of prognostic scores and key clinical indicators can effectively stratify the 1-year outcomes of non-cirrhotic patients with HBV-ACLF. Patients with poor prognosis were typically characterized by INR 2.5 and TBil 400 μmol/L. Among those who survived beyond 1 year, individuals who subsequently progressed to cirrhosis were frequently identified by the presence of INR 1.5, TBil 200 μmol/L, and PLT 100×10⁹/L at day 28.
7.Reliability and Validity Evaluation of TCM Identification Scale of Five Human Qualities in Elderly People
Manman LU ; Rui YU ; Baozhao JU ; Feng GU ; Huan ZHANG ; Zengjin JIAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):153-160
ObjectiveBased on the Huangdi Neijing,a traditional Chinese medicine(TCM)identification scale of five human qualities was constructed and applied in elderly people to evaluate its reliability and validity. MethodsBased on the original text of the Huangdi Neijing and a review of relevant ancient and modern literature, an identification scale of five human qualities was developed through Delphi expert interviews. Offline surveys were conducted to evaluate the feasibility,reliability,and validity of its application in elderly people,and the scale was evaluated and revised. ResultsThe scale of five human qualities is divided into five subscales:wood,fire,earth,metal,and water. Each subscale is divided into four dimensions:morphological structure,psychological characteristics,tolerance,and physiological characteristics,with a total of 75 items. The survey results in elderly people show that:(1) The recovery rate and completion rate are 100%,and the average filling time is 23.3 min. 85.5% of the samples are completed within the preset time. (2) Reliability analysis results:The homogeneity reliability of each subscale,Chronbach's α,ranges from 0.702 to 0.793. The scores of each subscale in the split-half reliability range from 0.758 to 0.841, indicating that the internal consistency of the scale is good. (3) Validity analysis results. Content validity:During the development stage of the scale,the item pool,dimensions,and structure of the scale are designed reasonably, and the content is complete. The evaluation of content validity shows that the item-level content validity index (I-CVI) ranges from 0.83 to 1.00, and the scale-level content validity index for universal agreement (S-CVI/UA) is 0.92,indicating good content validity of the scale. Construct validity extracts 22 common factors based on an eigenvalue of 1,with a contribution rate of 62.333% to the overall system. The number of common factors in the five subscales is 4,5,4,5,and 4,respectively,with contribution rates of 52.64%,53.376%,51.445%,51.359%,and 50.714%,respectively,indicating the required structure for physical fitness measurement in elderly people. ConclusionThe scale constructed in this study has high reliability and validity,and it is suitable for evaluating the physical condition of elderly people in TCM.
8.Real-world characteristics and treatment patterns in Chinese patients with newly diagnosed endometrial cancer.
Aijun YIN ; Dong WANG ; Yanlin LUO ; Ruifang AN ; Shuzhong YAO ; Yufei SHEN ; Li SUN ; Cuirong LEI ; Yan TIAN ; Li WANG ; Dan ZHONG ; Manman XU ; Yuanyuan JIANG ; Min ZHANG ; Binqi ZHANG ; Huirong MAO ; Fengshi DONG ; Yu ZHANG ; Beihua KONG
Chinese Medical Journal 2025;138(13):1624-1626
9.Role of stimulator of interferon genes in postoperative cognitive dysfunction in aged mice: relationship with pyroptosis in hippocampal cells
Baojie JIAO ; Manman QI ; Yan LI ; Mengya GAO ; Tiange ZHANG ; Wenbo SUN
Chinese Journal of Anesthesiology 2025;45(2):178-183
Objective:To evaluate the role of stimulator of interferon genes (STING) in postoperative cognitive dysfunction (POCD) and the relationship with pyroptosis in hippocampal cells in aged mice.Methods:Forty-eight SPF healthy male C57BL/6 mice, aged 18 months, weighing 23-28 g, were assigned to 4 groups ( n=12 each) using a random number table method: control group (C group), POCD group (P group), STING inhibitor C-176 group (PC group), and C-176 solvent group (PV group). The mice underwent Morris water maze training for 4 days prior to model establishment. Mice in P, PC and PV groups underwent tibial fracture and intramedullary pin fixation under sevoflurane anesthesia to establish the POCD model, while mice in C group received no treatment. The STING inhibitor C-176 (750 nmol/200 μl) and an equal volume of C-176 solvent were intraperitoneally injected at 30 min before establishment of the model in PC and PV groups, respectively. The open field test was performed on the 5th day after model preparation, the novel object recognition test was conducted on the 6th day, and the Morris water maze test was performed on the 7th day. Mice were sacrificed under anesthesia to collect the hippocampus for determination of the expression of STING, phosphorylated STING (p-STING), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), cleaved caspase-1, and gasdermin-D (GSDMD)-NT by Western blot. Results:There were no statistically significant differences in the parameters of the training phase of the Morris water maze test and the open field test among the four groups ( P>0.05). Compared with C group, the recognition index in the novel object recognition test was significantly decreased, the number of crossing the original platform was reduced and the duration spent in the target quadrant was shortened in the Morris water maze test, and the expression of STING, NLRP3, cleaved caspase-1, and GSDMD-NT in hippocampal neurons was up-regulated in P, PC and PV groups, and the expression of p-STING was significantly up-regulated in P and PV groups ( P<0.05). Compared with P group, the recognition index in the novel object recognition test was significantly increased, the number of crossing the original platform was reduced and the duration spent in the target quadrant was prolonged in the Morris water maze test, and the expression of p-STING, NLRP3, cleaved caspase-1, and GSDMD-NT in hippocampal neurons was down-regulated in PC group ( P<0.05). Compared with PC group, the recognition index in the novel object recognition test was significantly decreased, the number of crossing the original platform was reduced and the duration spent in the target quadrant was shortened in the Morris water maze test, and the expression of p-STING, NLRP3, cleaved caspase-1 and GSDMD-NT was up-regulated in PV group ( P<0.05). Conclusions:STING is involved in the development of POCD in aged mice, and the mechanism may be related to promotion of pyroptosis in hippocampal cells.
10.Preliminary exploration of the mode and timing of delivery for complex fetal congenital heart disease
Junshu XIE ; Manman HAN ; Xiuju YIN ; Tiantian HAN ; Qiuyan PEI ; Lin ZHANG ; Huili ZHANG ; Shoujun LI ; Xiaohong ZHANG
Chinese Journal of Obstetrics and Gynecology 2025;60(10):763-771
Objective:To investigate the mode and timing of delivery in pregnant women with complex fetal congenital heart disease (CHD) detected by prenatal ultrasound.Methods:The clinical data of 123 fetuses with complex CHD detected by prenatal ultrasound in Peking University People′s Hospital from January 2016 to December 2023 were retrospectively analyzed. Pregnant women with indications for prenatal diagnosis underwent G-banding karyotype analysis, single nucleotide polymorphism array (SNP arrry) or whole exome sequencing after informed consent. Integrated managements were provided for pregnant women with complex CHD during pregnancy and perinatal period, and to determine the mode and timing of delivery. Infants with complex CHD received timely treatment or referral after birth.Results:The gestational age at ultrasound diagnosis of the 123 fetuses with complex CHD was (23.7±3.4) weeks. There were 11 cases (8.9%) of total anomalous pulmonary venous connection (TAPVC), 14 cases (11.4%) of anomalous pulmonary valve (PVA), 7 cases (5.7%) of right ventricle double outlet (RVDO), 13 cases (10.6%) of anomalous aortic arch, 69 cases (56.1%) of transposition of the great arteries (TGA), 9 cases (7.3%) of other types. All cases were treated with fetal preservation after prenatal consultation. Among the 72 cases undergoing prenatal diagnosis, 9 cases (12.5%) had chromosomal variations. Fifty-five cases (44.7%, 55/123) underwent trial of labor, of which 46 cases (37.4%, 46/123) had successful vaginal delivery, including 6 cases of forceps delivery, and other 9 cases of failed trial of labor transferred to cesarean section. A total of 77 cases of pregnant women underwent cesarean section. Except for the 21 cases of pregnant women who asked for cesarean section, the cesarean section rate of pregnant women with complex CHD was 45.5% (56/123), which was not significantly different from the average cesarean section rate of the same period in our hospital (40.2%; χ2=7.34, P=0.270). The gestational age at delivery of the 123 fetuses with complex CHD was (37.9±1.4) weeks, the birth weight of the neonates was (3 099±480) g, and the umbilical artery blood pH value was 7.31±0.05. The oxygen saturation of 86 cases before and after alprostadil infusion were (72.8±6.0)% and (80.5±5.0)%, respectively, and the difference was statistically significant ( t=4.38, P<0.001). One hundred and fourteen children underwent surgical treatment, 112 of them (98.2%) had good postoperative reexamination. Only 2 cases (1.8%) died after surgery, and 14.0% (16/114) had the possibility of secondary surgery. Conclusions:Fetal complex CHD is not an indication for cesarean section, and the delivery mode could be selected according to the obstetric situation. If the mother and child are in stable condition, the delivery is planned after 39 weeks of gestation. For children with low oxygen saturation after birth, alprostadil could be pumped to maintain the open ductus arteriosus, and timely referral to the pediatric cardiac surgery for subsequent surgical treatment, which could achieve a good prognosis.

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