1.Improvement mechanism of Pangshi antai zhixue decoction on spontaneous abortion with heat syndrome by regulating NLRP3 inflammasome
Liya MA ; Xingfei WU ; Liujun WU ; Yanduo SHEN ; Bingheng XIE ; Jiale ZHANG ; Jinhao HAO ; Meng YU ; Yumiko NAKAYAMA ; Minghao ZHANG ; Dawei ZHANG
China Pharmacy 2025;36(1):37-43
OBJECTIVE To investigate the mechanism of Pangshi antai zhixue decoction in the improvement of spontaneous abortion with heat syndrome by regulating the NOD-like receptor protein 3 (NLRP3) inflammasome. METHODS The binding activities of 13 main components in Pangshi antai zhixue decoction with NLRP3, apoptosis-associated speck-like protein , containing a CARD (ASC), and caspase-1 precursor (pro- No.20-21ZY1053) caspase-1) were predicted by molecular docking. Sixty 1-day-old pregnant rats were randomly divided into normal group, model group, dexamethasone group (0.002 g/kg), and Pangshi antai zhixue decoction low-, medium-, and high-dose groups (11.025, 22.05, 44.10 g/kg), with 10 rats in each group. Each group was given distilled water/corresponding medicinal solution intragastrically, once a day, for 12 consecutive days. Except for normal group, other groups were given traditional Chinese medicine for warming yang and mifepristone to establish a model of spontaneous abortion with heat syndrome. 24 h after the last medication, serum levels of triiodothyronine (T3), thyroxine (T4), interleukin-2 (IL-2), IL-4, IL-6, IL-10, and interferon-γ (IFN-γ) were all detected; the abortion rate and uterine coefficient were calculated; the pathological morphology of the pregnant uterus was observed; protein expressions of NLRP3, ASC and caspase-1 were detected. RESULTS The molecular docking results showed that the binding energies of 13 main components of Pangshi antai zhixue decoction with NLRP3, ASC, and pro-caspase-1 were all less than -5 kJ/moL. The animal experiment results showed that compared with normal group, the uterine coefficient and serum levels of IL-4, IL-6 and IL-10 were decreased significantly in model group (P<0.05); the abortion rate and serum levels of T3, T4, IL-2 and IFN-γ as well as protein expressions of NLRP3, ASC and caspase-1 were increased significantly (P<0.05); there were abortion lesions in the pregnant endometrium. Compared with the model group, most of the quantitative indicators mentioned above were significantly reversed in Pangshi antai zhixue decoction groups (P<0.05), and the endometrial miscarriage lesions in pregnancy were improved to varying degrees. CONCLUSIONS Pangshi antai zhixue decoction influences the immune balance between mother and fetus by regulating the formation of NLRP3 inflammasome, down-regulating pro-inflammatory cytokines such as IFN-γ and IL-2, and up-regulating anti-inflammatory cytokines such as IL-4, IL-6 and IL-10, thereby improving spontaneous abortion with heat syndrome.
2.Traditional Chinese Medicine Regulates Metabolic Reprogramming Mechanism to Intervene in Inflammation-cancer Transformation of Gastric Mucosa
Xinyi LIANG ; Jiale MA ; Huizhen LI ; Shuangmei ZHAO ; Mengtong LENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):252-260
Gastric cancer (GC) has an insidious onset and is mostly diagnosed in the middle and late stages after clinical detection. It is one of the malignant tumors with high incidence and mortality rates in the world. At present, the treatment plans are optimized mainly in terms of surgery, radiotherapy, and intervention, while the endpoints of clinical trials, such as patients' overall survival, progression-free survival, and disease-free survival, are still unsatisfactory. Therefore, effectively delaying the dynamic inflammation-cancer transformation has become an urgent bottleneck in the prevention and treatment of GC. In 1920s, Professor Otto Warburg discovered the phenomenon that tumor cells can accelerate glycolysis. Since then, the abnormal metabolic network inside tumor cells has gradually entered into researchers' view, and the hot academic research topic of metabolic reprogramming has been proposed. Tumor cells can meet their own energy consumption and adapt to external changes by adjusting their metabolic pathways to achieve rapid proliferation. In recent years, traditional Chinese medicine (TCM) is resolutely pursuing innovation in inheritance and the continuous refinement of research has led to the precision-oriented transition of TCM theories. Therefore, linking TCM with the treatment of tumors and precancerous diseases has certain research connotations. The searching and review of the publications in this field revealed that the number of publications in tumor-related metabolism increased dramatically, while there were only a few studies using TCM as a therapeutic solution. The research group has long been committed to the study of precancerous lesions of gastric cancer (PLGC) in Chinese and Western medicine. This article explained the dynamic process of inflammation-cancer transformation from the perspective of spleen deficiency-Qi stagnation-collateral stasis. The molecules of hypoxia-inducible factor (HIF)-1α, cancer-Myc (c-Myc), apolipoprotein E (APOE) and pyruvate kinase M2 (PKM2) were selected to reflect the biological connotation of inflammation-cancer transformation. The current achievements of TCM in regulating the metabolic reprogramming to intervene in inflammation-cancer transformation were summarized, with a view to providing more information for TCM to intervene in the inflammation-cancer transformation of gastric mucosa.
3.Traditional Chinese Medicine Regulates Metabolic Reprogramming Mechanism to Intervene in Inflammation-cancer Transformation of Gastric Mucosa
Xinyi LIANG ; Jiale MA ; Huizhen LI ; Shuangmei ZHAO ; Mengtong LENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):252-260
Gastric cancer (GC) has an insidious onset and is mostly diagnosed in the middle and late stages after clinical detection. It is one of the malignant tumors with high incidence and mortality rates in the world. At present, the treatment plans are optimized mainly in terms of surgery, radiotherapy, and intervention, while the endpoints of clinical trials, such as patients' overall survival, progression-free survival, and disease-free survival, are still unsatisfactory. Therefore, effectively delaying the dynamic inflammation-cancer transformation has become an urgent bottleneck in the prevention and treatment of GC. In 1920s, Professor Otto Warburg discovered the phenomenon that tumor cells can accelerate glycolysis. Since then, the abnormal metabolic network inside tumor cells has gradually entered into researchers' view, and the hot academic research topic of metabolic reprogramming has been proposed. Tumor cells can meet their own energy consumption and adapt to external changes by adjusting their metabolic pathways to achieve rapid proliferation. In recent years, traditional Chinese medicine (TCM) is resolutely pursuing innovation in inheritance and the continuous refinement of research has led to the precision-oriented transition of TCM theories. Therefore, linking TCM with the treatment of tumors and precancerous diseases has certain research connotations. The searching and review of the publications in this field revealed that the number of publications in tumor-related metabolism increased dramatically, while there were only a few studies using TCM as a therapeutic solution. The research group has long been committed to the study of precancerous lesions of gastric cancer (PLGC) in Chinese and Western medicine. This article explained the dynamic process of inflammation-cancer transformation from the perspective of spleen deficiency-Qi stagnation-collateral stasis. The molecules of hypoxia-inducible factor (HIF)-1α, cancer-Myc (c-Myc), apolipoprotein E (APOE) and pyruvate kinase M2 (PKM2) were selected to reflect the biological connotation of inflammation-cancer transformation. The current achievements of TCM in regulating the metabolic reprogramming to intervene in inflammation-cancer transformation were summarized, with a view to providing more information for TCM to intervene in the inflammation-cancer transformation of gastric mucosa.
4.Celastrol-loaded ginsenoside Rg3 liposomes boost immunotherapy by remodeling obesity-related immunosuppressive tumor microenvironment in melanoma.
Hongyan ZHANG ; Jingyi HUANG ; Yujie LI ; Wanyu JIN ; Jiale WEI ; Ninghui MA ; Limei SHEN ; Mancang GU ; Chaofeng MU ; Donghang XU ; Yang XIONG
Acta Pharmaceutica Sinica B 2025;15(5):2687-2702
Obesity usually exacerbates the immunosuppressive tumor microenvironment (ITME), hindering CD8+ T cell infiltration and function, which further represents a significant barrier to the efficacy of immunotherapy. Herein, a multifunctional liposomal system (CR-Lip) for encapsulating celastrol (CEL) was utilized to remodel obesity-related ITME and improve cancer immunotherapy, wherein Ginsenoside Rg3 (Rg3) was detected interspersed in the phospholipid bilayer and its glycosyl exposed on the surface of the liposome. CR-Lip had a relatively uniform size (116.5 nm), facilitating favorable tumor tissue accumulation through the interaction between Rg3 and glucose transporter 1 overexpressed in obese tumor cells. Upon reaching the tumor region, CR-Lip was found to induce the immunogenic cell death (ICD) of HFD tumor cells. Notably, the level of PHD3 in HFD tumor cells was effectively boosted by CR-Lip to effectively block metabolic reprogramming and increase the availability of major free fatty acids fuel sources. In vivo, experiments studies revealed that the easy-obtained nano platform stimulated enhanced the production of various cytokines in tumor tissues, DC maturation, CD8+ T-cell infiltration, and synergistic anticancer therapeutic potency with aPD-1 (tumor inhibition rate = 82.1%) towards obesity-related melanoma. Consequently, this study presented an efficacious approach to tumor immunotherapy in obese mice by encompassing tumor eradication, inducing ICD, and reprogramming metabolism. Furthermore, it offered a unique insight into a valuable attempt at the immunotherapy of obesity-associated related tumors.
5.Construction and Testing of Health LifeStyle Evidence (HLSE)
Chen TIAN ; Yong WANG ; Yilong YAN ; Yafei LIU ; Yao LU ; Mingyao SUN ; Jianing LIU ; Yan MA ; Jinling NING ; Ziying YE ; Qianji CHENG ; Ying LI ; Jiajie HUANG ; Shuihua YANG ; Yiyun WANG ; Bo TONG ; Jiale LU ; Long GE
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1413-1421
Healthy lifestyles and good living habits are effective strategies and important approaches to prevent chronic non-communicable diseases. With the development of evidence-based medicine, the evidence translation system has made some achievements in clinical practice. There is, however, no comprehensive, professional and efficient system for translating lifestyle evidence globally. Therefore, the Health Lifestyle Evidence (HLSE) Group of Lanzhou University constructed the HLSE Evidence Translation System (
6.Mechanism of Tongxie yaofang reducing colon hypermotility in IBS-D rats by regulating gut microbiota-ENS-MM crosstalk
Long PENG ; Jiale MA ; Yixuan YIN ; Xi BU ; Shuangmei ZHAO
China Pharmacy 2024;35(13):1605-1611
OBJECTIVE To study the effects of Tongxie yaofang reducing colon hypermotility in irritable bowel syndrome with diarrhea (IBS-D) rats by regulating gut microbiota-enteric nervous system (ENS)-muscularis macrophages (MM) crosstalk. METHODS Forty newborn male SD rats were randomly divided into control group, model group, TCM group [Tongxie yaofang 2.68 g/(kg·d), calculated by raw material], and positive control group [Live combined bifidobacterium and lactobacillus tablets 0.27 g/(kg·d)], with 10 rats in each group. Except for the control group, the IBS-D model of liver stagnation and spleen deficiency syndrome was induced in the other 3 groups with the method of mother-child separation+chronic restraint+Folium Sennae- induced diarrhea. After modeling, the administration groups were given relevant drug liquid intragastrically, once a day, for consecutive 2 weeks. At the end of modeling and after administration, the fecal properties (the incidence and the rate of loose stools), colonic motility (colon emptying time), and visceral sensitivity [abdominal withdrawal reflex (AWR) scores under different pressures] of rats were observed in each group. The concentration of lipopolysaccharide (LPS) in serum was detected after medication, and the expressions and distribution of bone morphogenetic protein 2 (BMP2), colony stimulating factor 1 (CSF1) and Toll-like receptor 4 (TLR4) in colon tissue were detected; the diversity, species composition and differences of gut microbiota were also determined. RESULTS At the end of modeling, compared with the control group, all rats of the other three groups suffered from loose stools (100%), the rate of loose stools and AWR scores at different pressures increased significantly, and colon emptying time was shortened significantly (P<0.01 or P<0.05). The incidences of loose stools were 20% in TCM group and 80% in the positive control group; the rate of loose stools and AWR scores at different pressures, serum concentration of LPS and protein expressions of CSF1 and TLR4 in muscle layer of colon tissue in TCM group significantly decreased, compared with the model group; colon emptying time, the average optical density of BMP2 protein in muscle layer of colon tissue, and the indexes of Chao 1, Shannon and Faith’s PD and Simpson E-mail:772699670@qq.com index of rats in TCM group were all prolonged or increased significantly, compared with the model group (P<0.01 or P< E-mail:aiwangzi312@163.com 0.05). The relative abundance ratio of Firmicutes/Bacteroidetes, from low to high, was in the order of TCM group, control group, positive control group and model group; the species composition of gut microbiota in TCM group was closer to control group, with dominant bacterial genera including Prevotella and Blautia. CONCLUSIONS Tongxie yaofang can regulate the expressions of BMP2 and CSF1, the key proteins of gut microbiota-ENS-MM crosstalk, by changing the gut microbiota, thus alleviating the abnormal hyperfunction of colon motility in IBS-D rats.
7.Construction and Testing of Health LifeStyle Evidence (HLSE)
Chen TIAN ; Yong WANG ; Yilong YAN ; Yafei LIU ; Yao LU ; Mingyao SUN ; Jianing LIU ; Yan MA ; Jinling NING ; Ziying YE ; Qianji CHENG ; Ying LI ; Jiajie HUANG ; Shuihua YANG ; Yiyun WANG ; Bo TONG ; Jiale LU ; Long GE
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1413-1421
Healthy lifestyles and good living habits are effective strategies and important approaches to prevent chronic non-communicable diseases. With the development of evidence-based medicine, the evidence translation system has made some achievements in clinical practice. There is, however, no comprehensive, professional and efficient system for translating lifestyle evidence globally. Therefore, the Health Lifestyle Evidence (HLSE) Group of Lanzhou University constructed the HLSE Evidence Translation System (
8.Correlation analysis between Pirani score and talo-navicular angle,calcaneo-cuboid angle and tibio-calcaneall angle of infant clubfoot under ultrasound
Wenjing WANG ; Bing XIA ; Yingmei DONG ; Panpan HE ; Zhiwei CHENG ; Fengqun MA ; Chaohua WANG ; Fuyun LIU ; Weiming HU ; Feipeng WANG ; Yufeng ZHAO ; Hezhou LI ; Jiale FU
Chinese Journal of Surgery 2024;62(3):210-215
Objective:To explore the evaluation effect of ultrasonography and Pirani score on tarsal deformity, treatment effect and pseudo-correction of congenital clubfoot in infants and young children, and the correlation between the two methods.Methods:This is a retrospective case series study. The clinical data of 26 children (40 feet) with congenital clubfoot who were evaluated by ultrasonography in the Third Affiliated Hospital of Zhengzhou University from January 2020 to January 2023 were retrospectively collected. There were 16 males and 10 females. The age at the first ultrasound examination was ( M(IQR)) 9.0 (18.0) days (range: 1 to 46 days). All patients were treated with Ponseti method by the same physician. The Pirani scores before and after treatment and at the last examination, and the talonavicular angle, calcaneocuboid angle and tibiocalcaneal angle measured by ultrasound were collected, and the treatment and follow-up were recorded. Paired sample t test, repeated measures analysis of variance or Kruskal-Wallis test were used for data comparison, and Spearman correlation analysis was used for correlation analysis. The receiver operating characteristic curve was used to calculate the efficacy of ultrasound in evaluating different Pirani scores. Results:The number of plaster fixation in 26 children was 4.0 (1.0) times (range: 2 to 8 times). The medial talonavicular angle and posterior tibiocalcaneal angle were significantly improved after treatment and at the last follow-up compared with those before treatment, and the differences were statistically significant (all P<0.01). There was no difference in lateral calcaneocuboid angle before and after treatment and at the last follow-up ( F=1.971, P>0.05). Pseudo-correction occurred in 2 cases (2 feet) during the treatment, with an incidence of 5%. Correlation analysis showed that there was a moderate positive correlation between talonavicular angle and Pirani midfoot score ( r=0.480, P<0.01). There was no correlation between calcaneocuboid angle and Pirani midfoot score ( r=0.114, P=0.105). There was a moderate negative correlation between tibial heel angle and Pirani hindfoot score ( r=-0.566, P<0.01). The cut-off point of Pirani midfoot score of 1.5 was 38.78°, the sensitivity was 0.90, the specificity was 0.56, and the area under the curve was 0.75. The cut-off value of angle was 27.51 °, the sensitivity was 0.16, the specificity was 0.92, and the area under the curve was 0.44.The cut-off points of Pirani midfoot score of 3.0 were 45.08°and 9.96°, the sensitivity was 0.94 and 0.91, the specificity was 0.37 and 0.42, and the area under the curve was 0.59 and 0.62, respectively. The cut-off values of Pirani hindfoot score of 2.0 and 3.0 were 167.46° and 160.15°, respectively. The sensitivity was 0.75 and 0.67, the specificity was 0.81 and 0.83, and the area under the curve was 0.78 and 0.71, respectively. Conclusion:Ultrasound can complement with Pirani score, visually and dynamically observe the morphology and position changes of talonavicular joint, calcaneocuboid joint and tibiotalocalcaneal joint, monitor the recovery and pseudo-correction of tarsal bones, and better evaluate the therapeutic effect.
9.Correlation analysis between Pirani score and talo-navicular angle,calcaneo-cuboid angle and tibio-calcaneall angle of infant clubfoot under ultrasound
Wenjing WANG ; Bing XIA ; Yingmei DONG ; Panpan HE ; Zhiwei CHENG ; Fengqun MA ; Chaohua WANG ; Fuyun LIU ; Weiming HU ; Feipeng WANG ; Yufeng ZHAO ; Hezhou LI ; Jiale FU
Chinese Journal of Surgery 2024;62(3):210-215
Objective:To explore the evaluation effect of ultrasonography and Pirani score on tarsal deformity, treatment effect and pseudo-correction of congenital clubfoot in infants and young children, and the correlation between the two methods.Methods:This is a retrospective case series study. The clinical data of 26 children (40 feet) with congenital clubfoot who were evaluated by ultrasonography in the Third Affiliated Hospital of Zhengzhou University from January 2020 to January 2023 were retrospectively collected. There were 16 males and 10 females. The age at the first ultrasound examination was ( M(IQR)) 9.0 (18.0) days (range: 1 to 46 days). All patients were treated with Ponseti method by the same physician. The Pirani scores before and after treatment and at the last examination, and the talonavicular angle, calcaneocuboid angle and tibiocalcaneal angle measured by ultrasound were collected, and the treatment and follow-up were recorded. Paired sample t test, repeated measures analysis of variance or Kruskal-Wallis test were used for data comparison, and Spearman correlation analysis was used for correlation analysis. The receiver operating characteristic curve was used to calculate the efficacy of ultrasound in evaluating different Pirani scores. Results:The number of plaster fixation in 26 children was 4.0 (1.0) times (range: 2 to 8 times). The medial talonavicular angle and posterior tibiocalcaneal angle were significantly improved after treatment and at the last follow-up compared with those before treatment, and the differences were statistically significant (all P<0.01). There was no difference in lateral calcaneocuboid angle before and after treatment and at the last follow-up ( F=1.971, P>0.05). Pseudo-correction occurred in 2 cases (2 feet) during the treatment, with an incidence of 5%. Correlation analysis showed that there was a moderate positive correlation between talonavicular angle and Pirani midfoot score ( r=0.480, P<0.01). There was no correlation between calcaneocuboid angle and Pirani midfoot score ( r=0.114, P=0.105). There was a moderate negative correlation between tibial heel angle and Pirani hindfoot score ( r=-0.566, P<0.01). The cut-off point of Pirani midfoot score of 1.5 was 38.78°, the sensitivity was 0.90, the specificity was 0.56, and the area under the curve was 0.75. The cut-off value of angle was 27.51 °, the sensitivity was 0.16, the specificity was 0.92, and the area under the curve was 0.44.The cut-off points of Pirani midfoot score of 3.0 were 45.08°and 9.96°, the sensitivity was 0.94 and 0.91, the specificity was 0.37 and 0.42, and the area under the curve was 0.59 and 0.62, respectively. The cut-off values of Pirani hindfoot score of 2.0 and 3.0 were 167.46° and 160.15°, respectively. The sensitivity was 0.75 and 0.67, the specificity was 0.81 and 0.83, and the area under the curve was 0.78 and 0.71, respectively. Conclusion:Ultrasound can complement with Pirani score, visually and dynamically observe the morphology and position changes of talonavicular joint, calcaneocuboid joint and tibiotalocalcaneal joint, monitor the recovery and pseudo-correction of tarsal bones, and better evaluate the therapeutic effect.
10.Risk factors of neonates with necrotizing enterocolitis require surgical therapy
Weitao ZHONG ; Tulian LIN ; Jiale CHEN ; Qiuming HE ; Yan TIAN ; Zuyi MA ; Pengjian ZOU ; Juan HE ; Wei ZHONG
Chinese Journal of Neonatology 2023;38(1):29-33
Objective:To study the risk factors of surgical therapy in neonates with necrotizing enterocolitis (NEC).Methods:From January 2016 to July 2020, neonates with a confirmed diagnosis of NEC (Bell's Stage Ⅱ and above) admitted to our hospital were retrospectively enrolled. They were assigned into surgical group and conservative group according to whether surgeries were performed. The conditions during perinatal period, clinical characteristics and laboratory examinations at the onset of NEC were compared between the two groups. Multivariate Logistic regression analysis was used to determine the risk factors of surgical therapy.Results:A total of 177 neonates with NEC were identified, including 62 cases (35.0%) in the surgical group and 115 cases (65.0%) in the conservative group. Multivariate Logistic regression analysis showed that male gender ( OR=3.178,95% CI 1.457~6.929, P=0.004), comorbidity with shock ( OR=3.434, 95% CI 1.112~10.607, P=0.032), mechanical ventilation>7 d before NEC onset ( OR=3.663, 95% CI 1.098~12.223, P=0.035) and lymphocytes <2.0×10 9/L ( OR=4.121, 95% CI 1.801~9.430, P=0.001) at the onset of NEC were independent risk factors for surgical therapy. Conclusions:Male gender, comorbidity with shock, mechanical ventilation >7 d before NEC and lymphocytopenia at the onset are independent risk factors for surgical therapy in neonates with NEC (Stage Ⅱ and above).

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