1.Comparison of the predictive performance of SARIMA, Prophet, and BSTS models in forecasting the incidence of hand, foot, and mouth disease
LU Wenhai ; KONG Xiaojie ; SONG Lixia ; LU Chunru ; YU Bikun ; XIE Yan
Journal of Preventive Medicine 2026;38(1):79-84
Objective:
To compare the predictive performance of the seasonal autoregressive integrated moving average (SARIMA) model, the Prophet model, and the Bayesian structural time series (BSTS) model in forecasting the incidence of hand, foot, and mouth disease (HFMD) , so as to provide a basis for optimizing the early warning system of this disease.
Methods:
Weekly incidence data of HFMD in Longgang District, Shenzhen City from 2014 to 2024 were collected. The HFMD incidence data from 2014-2019 and 2023 were used as the training set to construct SARIMA, Prophet, and BSTS models, while the data from 2024 were used as the test set to compare and evaluate the predictive performance of the three models. The technique for order preference by similarity to ideal solution (TOPSIS) method was employed to calculate the C-value. This approach integrates multiple evaluation metrics, such as the mean absolute error (MAE), mean squared error (MSE), root mean squared error (RMSE), and symmetric mean absolute percentage error (SMAPE), to comprehensively assess model performance.
Results:
A total of 150 111 cases of HFMD were reported in Longgang District from 2014 to 2024, with an average annual incidence of 400.72/105. The weekly incidence fluctuated between 0 and 63.78/105, exhibiting a bimodal seasonal pattern characterized by a primary peak from May to July and a secondary peak from September to October. In the training set, all three models demonstrated a good fit to the bimodal epidemic trend of HFMD, with the BSTS model achieving the best fit. The BSTS model yielded performance metrics as follows: MAE=0.124, MSE=0.050, RMSE=0.223, SMAPE=0.021, and a C-value of 1.000. In the test set, all three models, including SARIMA, Prophet, and BSTS, performed well for short-term predictions (≤16 weeks), with the Prophet model showing relatively superior predictive performance. However, the prediction accuracy of all models declined as the forecast horizon extended. During the primary peak period (May-July), the Prophet model exhibited better predictive performance, whereas the BSTS model performed relatively better during the secondary peak period (September-October).
Conclusions
For the short-term forecasting of weekly HFMD incidence, the Prophet model outperformed both the SARIMA and BSTS models. During the primary peak period, the Prophet model demonstrated superior predictive performance, whereas the BSTS model exhibited better accuracy in forecasting the secondary peak period.
2.Clinical Observation on 60 Cases of Knee Osteoarthritis Treated with Heat-Sensitive Moxibustion
Lu TIAN ; Hongwu XIE ; Meihua LIU ; Jing ZHANG ; Shaozhong XU ; Changjun LI ; Zhixiong KOU
Journal of Traditional Chinese Medicine 2025;66(5):492-500
ObjectiveTo explore the central neuroregulation mechanism of heat-sensitive moxibustion for knee osteoarthritis on pain relief. MethodsThirty patients who did not have experience of Deqi (得气) during heat-sensitive moxibustion treatment were assigned to the "non-Deqi group", while another 30 patients who had experience of Deqi were assigned to the "Deqi group". Both groups received moxibustion at the left Heding (EX-LE2) acupoint. In the Deqi group, after the patients experienced sensation of Deqi at the acupoint, moxibustion was applied at approximately 3 cm from the skin for 10 minutes; in the non-Deqi group, moxibustion was also applied at approximately 3 cm from the skin for 10 minutes. Both groups received treatment once daily for 10 consecutive days. Knee joint pain was assessed before and after treatment using the visual analog scale (VAS). Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed on all participants before the first treatment session and after the final session on the 10th day. The fractional amplitude of low-frequency fluctuations (fALFF) maps before and after treatment were processed using the SPM12 module by MATLAB. ResultsAfter treatment, VAS scores in both groups were significantly lower than before treatment (P<0.05 or P<0.01), with the Deqi group showing significantly lower VAS scores than the non-Deqi group (P<0.01). Compared to before treatment, the Deqi group exhibited significant activation in the prefrontal cortex (t = 6.28), white matter (t = 6.36), and left temporal lobe (t = 9.33), while significant inhibition was observed in the occipital lobe (t = -9.86) and right cerebrum (t = -4.54, P<0.01); in the non-Deqi group, significant changes after treatment were observed in the left occipital lobe (t = -6.42), left medial frontal gyrus (t = -4.35), left middle frontal gyrus (t = -4.74), right superior frontal gyrus (t = -4.82), right superior temporal gyrus (t = -6.61), and right cerebellar posterior lobe (t = -8.64), all of which were in inhibited states (P<0.01). Compared to the non-Deqi group, the Deqi group exhibited significant activation after treatment in the external nucleus (t = 5.77), white matter (t = 3.58), right cerebrum (t = 5.84), left cerebellum (t = 5.35), and left cerebrum (t = 4.32), while significant inhibition was observed in the prefrontal cortex (t = -4.16), occipital lobe (t = -4.87), and precentral gyrus (t = -4.46, P<0.01). ConclusionsHeat-sensitive moxibustion provides better analgesic effects for knee osteoarthritis under state of Deqi. Its central neuroregulation mechanism may be related to the involvement of the frontal lobe, temporal lobe, occipital lobe, external nucleus, white matter, right cerebrum, left cerebellum, left cerebrum, and precentral gyrus in modulating pain signals.
3.Effects and mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure
Meiling MAO ; Jianqi LU ; Zhide ZHU ; Yan PANG ; Liyu XIE ; Jiayong CHEN ; Xinyu WU ; Xiang XIAO ; Junshen LU ; Weiqi SHI
China Pharmacy 2025;36(2):160-165
OBJECTIVE To investigate the effects and potential mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure (CHF). METHODS The CHF model was established by ligating the left anterior descending branch of the coronary artery. Modeled rats were divided into model group, Qiangxin decoction low-dose and high-dose groups (12.25, 24.50 g/kg, calculated by crude drug), and chemical medicine group (Sacubitril valsartan sodium tablets, 10.42 mg/kg), with 10 rats in each group; control group was set up without treatment. Each group of rats was orally administered with the corresponding medication or normal saline twice a day for 28 consecutive days. After the last medication, the contents of N-terminal pro-brain natriuretic peptide (NT-proBNP) and adenosine triphosphate (ATP) in serum and phosphatidic acid (PA) and cardiolipin (CL) in myocardial tissue were all detected; the pathological damage and collagen fibrosis of rat myocardial tissue were observed; the apoptosis of myocardial cells was determined; the ultrastructure of myocardial tissue was observed; the protein expressions of mitofusin 1 (Mfn1), Mfn2, optic atrophy protein 1 (OPA1) and dynamin-related protein 1 (Drp1) were all detected in myocardial tissue. RESULTS Compared with control group,the serum content of NT-proBNP, apoptotic rate of myocardial cells, and relative expressions of S-OPA1 and Drp1 proteins were all increased significantly; serum content of ATP,contents of PA and CL, and relative expressions of Mfn1, Mfn2 and L-OPA1 proteins were all significantly reduced (P<0.05). There were abnormal membrane tissue structure in various layers of myocardial tissue, degeneration and necrosis of myocardial cells, and severe fibrosis; the mitochondria were swollen, with reduced or absent cristae, and uneven matrix density. After intervention with Qiangxin decoction, the levels of the aforementioned quantitative indicators in serum and myocardial tissue of rats (excluding CL content in the Qiangxin decoction low- dose group) were significantly reversed (P<0.05); the pathological damage of myocardial tissue had significantly improved, fibrosis had significantly reduced, mitochondrial morphology tended to be normal, cristae had increased, and matrix density was uniform. CONCLUSIONS Qiangxin decoction can regulate myocardial mitochondrial function and structural integrity of CHF rats, thereby improving myocardial energy metabolism and antagonizing myocardial fibrosis, the mechanism of which may be associated with activating PA/Mfn/CL signaling pathway.
4.Effects and mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure
Meiling MAO ; Jianqi LU ; Zhide ZHU ; Yan PANG ; Liyu XIE ; Jiayong CHEN ; Xinyu WU ; Xiang XIAO ; Junshen LU ; Weiqi SHI
China Pharmacy 2025;36(2):160-165
OBJECTIVE To investigate the effects and potential mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure (CHF). METHODS The CHF model was established by ligating the left anterior descending branch of the coronary artery. Modeled rats were divided into model group, Qiangxin decoction low-dose and high-dose groups (12.25, 24.50 g/kg, calculated by crude drug), and chemical medicine group (Sacubitril valsartan sodium tablets, 10.42 mg/kg), with 10 rats in each group; control group was set up without treatment. Each group of rats was orally administered with the corresponding medication or normal saline twice a day for 28 consecutive days. After the last medication, the contents of N-terminal pro-brain natriuretic peptide (NT-proBNP) and adenosine triphosphate (ATP) in serum and phosphatidic acid (PA) and cardiolipin (CL) in myocardial tissue were all detected; the pathological damage and collagen fibrosis of rat myocardial tissue were observed; the apoptosis of myocardial cells was determined; the ultrastructure of myocardial tissue was observed; the protein expressions of mitofusin 1 (Mfn1), Mfn2, optic atrophy protein 1 (OPA1) and dynamin-related protein 1 (Drp1) were all detected in myocardial tissue. RESULTS Compared with control group,the serum content of NT-proBNP, apoptotic rate of myocardial cells, and relative expressions of S-OPA1 and Drp1 proteins were all increased significantly; serum content of ATP,contents of PA and CL, and relative expressions of Mfn1, Mfn2 and L-OPA1 proteins were all significantly reduced (P<0.05). There were abnormal membrane tissue structure in various layers of myocardial tissue, degeneration and necrosis of myocardial cells, and severe fibrosis; the mitochondria were swollen, with reduced or absent cristae, and uneven matrix density. After intervention with Qiangxin decoction, the levels of the aforementioned quantitative indicators in serum and myocardial tissue of rats (excluding CL content in the Qiangxin decoction low- dose group) were significantly reversed (P<0.05); the pathological damage of myocardial tissue had significantly improved, fibrosis had significantly reduced, mitochondrial morphology tended to be normal, cristae had increased, and matrix density was uniform. CONCLUSIONS Qiangxin decoction can regulate myocardial mitochondrial function and structural integrity of CHF rats, thereby improving myocardial energy metabolism and antagonizing myocardial fibrosis, the mechanism of which may be associated with activating PA/Mfn/CL signaling pathway.
5.Causal association of obesity and chronic pain mediated by educational attainment and smoking: a mediation Mendelian randomization study
Yunshu LYU ; Qingxing LU ; Yane LIU ; Mengtong XIE ; Lintong JIANG ; Junnan LI ; Ning WANG ; Xianglong DAI ; Yuqi YANG ; Peiming JIANG ; Qiong YU
The Korean Journal of Pain 2025;38(2):177-186
Background:
Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship.
Methods:
This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders.
Results:
The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively.
Conclusions
The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.
6.Shaoyaotang Containing Serum Mediates Fas/FasL Pathway to Inhibit Lipopolysaccharide Induced Inflammation and Apoptosis of Caco-2 Cells
Yuting YANG ; Dongsheng WU ; Hui CAO ; Yu ZHANG ; Nianjia XIE ; Bo ZOU ; Daguang CHEN ; Erle LIU ; Yi LU ; Zhaowen LYU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):62-69
ObjectiveTo investigate the effects of different concentrations of Shaoyaotang-containing serum on lipopolysaccharide (LPS)-induced inflammation of human colorectal adenocarcinoma (Caco-2) cells by inhibiting apoptosis via activating the tumor necrosis factor (TNF) receptor superfamily member 6 (Fas)/Fas ligand (FasL) pathway. MethodsCaco-2 cells were allocated into blank, model (LPS, 10 mg·L-1), Shaoyaotang-containing serum (5%, 10%, 15%, 20%), and Fas inhibitor (KR-33493, 20 mmol·L-1) groups. Except the blank group, the other groups were stimulated with 10 mg·L-1 LPS for 24 h for the modeling of inflammation. After successful modeling, the blank, Fas inhibitor, and model groups were treated with blank serum, and the Shaoyaotang-containing serum groups were treated with the serum samples at corresponding concentrations for 24 h. The Fas inhibitor group was subjected to KR-33493 pretreatment for 1 h. Cell proliferation and viability were examined by the cell-counting kit-8 (CCK-8) method. The levels of interleukin (IL)-6, IL-1β, and TNF-α were measured by enzyme-linked immunosorbent assay. Apoptosis was detected by flow cytometry. The protein and mRNA levels of Fas, FasL, cysteinyl aspartate-specific proteinase (Caspase)-3, Caspase-9, B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax) were determined by Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), respectively. ResultsCompared with the blank group, the model group presented a decrease in cell survival rate (P<0.01). Compared with that in the model group, the cell survival rate showed no significant change in the 5% Shaoyaotang-containing serum group but increased in the 10%, 15%, and 20% Shaoyaotang-containing serum groups (P<0.01). Since there was no statistical difference between the 5% Shaoyaotang-containing serum group and the model group, 10%, 15%, and 20% Shaoyaotang-containing sera were selected for the follow-up study. Compared with the blank group, the model group showed risen levels of IL-6, IL-1β, and TNF-α (P<0.01), an increased apoptosis rate (P<0.01), up-regulated protein and mRNA levels of Fas, FasL, Caspase-3, Caspase-9, and Bax (P<0.01), and down-regulated protein and mRNA levels of Bcl-2 (P<0.01). Compared with the model group, the Fas inhibitor group and the 10%, 15%, and 20% Shaoyaotang-containing serum groups showed declined levels of IL-6, IL-1β, and TNF-α (P<0.01), decreased apoptosis rates (P<0.01), down-regulated protein and mRNA levels of Fas, FasL, Caspase-3, Caspase-9, and Bax (P<0.05, P<0.01), and up-regulated protein and mRNA levels of Bcl-2 (P<0.05, P<0.01). In addition, the 15% and 20% Shaoyaotang-containing serum groups had lower levels of IL-6, IL-1β, and TNF-α (P<0.05, P<0.01), lower apoptosis rates (P<0.05, P<0.01), lower protein and mRNA levels of Fas, FasL, Caspase-3, Caspase-9, and Bax (P<0.05, P<0.01), and higher protein and mRNA levels of Bcl-2 (P<0.05, P<0.01) than the 10% Shaoyaotang-containing serum group. ConclusionThe Shaoyaotang-containing serum can reduce the content of inflammatory factors in Caco-2 cells, down-regulate the protein and mRNA levels of Fas, FasL, Caspase-3, Caspase-9, and Bax, and up-regulate the protein and mRNA levels of Bcl-2 under the intervention of LPS by regulating the Fas/FasL pathway and inhibiting the apoptosis of intestinal epithelial cells in ulcerative colitis.
7.Shaoyaotang Alleviates Damage of Tight Junction Proteins in Caco-2 Cell Model of Inflammation by Regulating RhoA/ROCK Pathway
Nianjia XIE ; Dongsheng WU ; Hui CAO ; Yu ZHANG ; Yuting YANG ; Bo ZOU ; Da ZHAO ; Yi LU ; Mingsheng WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):70-77
ObjectiveTo investigate the protective effect and mechanism of Shaoyaotang (SYD) on the lipopolysaccharide (LPS)-induced damage of tight junction proteins in the human colorectal adenocarcinoma (Caco-2) cell model of inflammation via the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil forming protein kinase (ROCK) pathway. MethodsCaco-2 cells were grouped as follows: Blank, model (LPS, 10 mg·L-1), SYD-containing serum (10%, 15%, and 20%), and inhibitor (Fasudil, 25 μmol·L-1). After 24 hours of intervention, the cell viability in each group was examined by the cell-counting kit 8 (CCK-8) method. Enzyme-linked immunosorbent assay was employed to determine the levels of endothelin-1 (ET-1), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of RhoA, ROCK2, claudin-5, and zonula occludens-1 (ZO-1) in cells of each group. ResultsCompared with the blank group, the model group showcased a marked reduction in the cell viability (P<0.01), elevations in the levels of ET-1, TNF-α, IL-1β, and IL-6 (P<0.01), declines in both mRNA and protein levels of ZO-1 and claudin-5 (P<0.01), and rises in mRNA and protein levels of RhoA and ROCK2 (P<0.01). Compared with the model group, the Shaoyaotang-containing serum (10%, 15%, and 20%) groups had enhanced cell viability (P<0.01), lowered levels of ET-1, TNF-α, IL-1β, and IL-6 (P<0.01), up-regulated mRNA and protein levels of ZO-1 and claudin-5 (P<0.05, P<0.01), and down-regulated mRNA and protein levels of RhoA and ROCK2 (P<0.01). Moreover, the inhibitor group and the 15% and 20% Shaoyaotang-containing serum groups had lower levels of ET-1, TNF-α, IL-1β, and IL-6 (P<0.05, P<0.01), higher mRNA and protein levels of ZO-1 and claudin-5 (P<0.05, P<0.01), and lower mRNA and protein levels of RhoA and ROCK2 (P<0.05, P<0.01) than the 10% Shaoyaotang-containing serum group. ConclusionThe Shaoyaotang-containing serum can lower the levels of LPS-induced increases in levels of inflammatory cytokines and endothelin to ameliorate the damage of tight junction proteins of the Caco-2 cell model of inflammation by regulating the expression of proteins in the RhoA/ROCK pathway.
8.Shaoyaotang Containing Serum Mediates Fas/FasL Pathway to Inhibit Lipopolysaccharide Induced Inflammation and Apoptosis of Caco-2 Cells
Yuting YANG ; Dongsheng WU ; Hui CAO ; Yu ZHANG ; Nianjia XIE ; Bo ZOU ; Daguang CHEN ; Erle LIU ; Yi LU ; Zhaowen LYU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):62-69
ObjectiveTo investigate the effects of different concentrations of Shaoyaotang-containing serum on lipopolysaccharide (LPS)-induced inflammation of human colorectal adenocarcinoma (Caco-2) cells by inhibiting apoptosis via activating the tumor necrosis factor (TNF) receptor superfamily member 6 (Fas)/Fas ligand (FasL) pathway. MethodsCaco-2 cells were allocated into blank, model (LPS, 10 mg·L-1), Shaoyaotang-containing serum (5%, 10%, 15%, 20%), and Fas inhibitor (KR-33493, 20 mmol·L-1) groups. Except the blank group, the other groups were stimulated with 10 mg·L-1 LPS for 24 h for the modeling of inflammation. After successful modeling, the blank, Fas inhibitor, and model groups were treated with blank serum, and the Shaoyaotang-containing serum groups were treated with the serum samples at corresponding concentrations for 24 h. The Fas inhibitor group was subjected to KR-33493 pretreatment for 1 h. Cell proliferation and viability were examined by the cell-counting kit-8 (CCK-8) method. The levels of interleukin (IL)-6, IL-1β, and TNF-α were measured by enzyme-linked immunosorbent assay. Apoptosis was detected by flow cytometry. The protein and mRNA levels of Fas, FasL, cysteinyl aspartate-specific proteinase (Caspase)-3, Caspase-9, B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax) were determined by Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), respectively. ResultsCompared with the blank group, the model group presented a decrease in cell survival rate (P<0.01). Compared with that in the model group, the cell survival rate showed no significant change in the 5% Shaoyaotang-containing serum group but increased in the 10%, 15%, and 20% Shaoyaotang-containing serum groups (P<0.01). Since there was no statistical difference between the 5% Shaoyaotang-containing serum group and the model group, 10%, 15%, and 20% Shaoyaotang-containing sera were selected for the follow-up study. Compared with the blank group, the model group showed risen levels of IL-6, IL-1β, and TNF-α (P<0.01), an increased apoptosis rate (P<0.01), up-regulated protein and mRNA levels of Fas, FasL, Caspase-3, Caspase-9, and Bax (P<0.01), and down-regulated protein and mRNA levels of Bcl-2 (P<0.01). Compared with the model group, the Fas inhibitor group and the 10%, 15%, and 20% Shaoyaotang-containing serum groups showed declined levels of IL-6, IL-1β, and TNF-α (P<0.01), decreased apoptosis rates (P<0.01), down-regulated protein and mRNA levels of Fas, FasL, Caspase-3, Caspase-9, and Bax (P<0.05, P<0.01), and up-regulated protein and mRNA levels of Bcl-2 (P<0.05, P<0.01). In addition, the 15% and 20% Shaoyaotang-containing serum groups had lower levels of IL-6, IL-1β, and TNF-α (P<0.05, P<0.01), lower apoptosis rates (P<0.05, P<0.01), lower protein and mRNA levels of Fas, FasL, Caspase-3, Caspase-9, and Bax (P<0.05, P<0.01), and higher protein and mRNA levels of Bcl-2 (P<0.05, P<0.01) than the 10% Shaoyaotang-containing serum group. ConclusionThe Shaoyaotang-containing serum can reduce the content of inflammatory factors in Caco-2 cells, down-regulate the protein and mRNA levels of Fas, FasL, Caspase-3, Caspase-9, and Bax, and up-regulate the protein and mRNA levels of Bcl-2 under the intervention of LPS by regulating the Fas/FasL pathway and inhibiting the apoptosis of intestinal epithelial cells in ulcerative colitis.
9.Shaoyaotang Alleviates Damage of Tight Junction Proteins in Caco-2 Cell Model of Inflammation by Regulating RhoA/ROCK Pathway
Nianjia XIE ; Dongsheng WU ; Hui CAO ; Yu ZHANG ; Yuting YANG ; Bo ZOU ; Da ZHAO ; Yi LU ; Mingsheng WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):70-77
ObjectiveTo investigate the protective effect and mechanism of Shaoyaotang (SYD) on the lipopolysaccharide (LPS)-induced damage of tight junction proteins in the human colorectal adenocarcinoma (Caco-2) cell model of inflammation via the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil forming protein kinase (ROCK) pathway. MethodsCaco-2 cells were grouped as follows: Blank, model (LPS, 10 mg·L-1), SYD-containing serum (10%, 15%, and 20%), and inhibitor (Fasudil, 25 μmol·L-1). After 24 hours of intervention, the cell viability in each group was examined by the cell-counting kit 8 (CCK-8) method. Enzyme-linked immunosorbent assay was employed to determine the levels of endothelin-1 (ET-1), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of RhoA, ROCK2, claudin-5, and zonula occludens-1 (ZO-1) in cells of each group. ResultsCompared with the blank group, the model group showcased a marked reduction in the cell viability (P<0.01), elevations in the levels of ET-1, TNF-α, IL-1β, and IL-6 (P<0.01), declines in both mRNA and protein levels of ZO-1 and claudin-5 (P<0.01), and rises in mRNA and protein levels of RhoA and ROCK2 (P<0.01). Compared with the model group, the Shaoyaotang-containing serum (10%, 15%, and 20%) groups had enhanced cell viability (P<0.01), lowered levels of ET-1, TNF-α, IL-1β, and IL-6 (P<0.01), up-regulated mRNA and protein levels of ZO-1 and claudin-5 (P<0.05, P<0.01), and down-regulated mRNA and protein levels of RhoA and ROCK2 (P<0.01). Moreover, the inhibitor group and the 15% and 20% Shaoyaotang-containing serum groups had lower levels of ET-1, TNF-α, IL-1β, and IL-6 (P<0.05, P<0.01), higher mRNA and protein levels of ZO-1 and claudin-5 (P<0.05, P<0.01), and lower mRNA and protein levels of RhoA and ROCK2 (P<0.05, P<0.01) than the 10% Shaoyaotang-containing serum group. ConclusionThe Shaoyaotang-containing serum can lower the levels of LPS-induced increases in levels of inflammatory cytokines and endothelin to ameliorate the damage of tight junction proteins of the Caco-2 cell model of inflammation by regulating the expression of proteins in the RhoA/ROCK pathway.
10.Comprehensive Clinical Evaluation of Xiaojie'an Capsules in Treatment of Uterine Fibroids with Qi Stagnation and Blood Stasis Syndrome
Yutong MA ; Zhenkai LU ; Yanming XIE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):235-243
ObjectiveTo systematically organize the relevant research on the treatment of uterine fibroids with Xiaojie'an capsules through clinical evidence evaluation and comprehensive value analysis in the "6+1" dimension,highlighting the efficacy and characteristics of Xiaojie'an capsules. MethodsBased on evidence-based medicine,epidemiology,pharmacoeconomics,health technology assessment (HTA), and other methodologies,this study adopted qualitative and quantitative evaluation methods. Through a questionnaire survey,official website data information,published literature, and secondary evaluation of real world data,a total of "6+1" dimensions were used to build an evaluation system for the safety,effectiveness,economy,innovation,suitability,accessibility of Chinese patent medicines, and characteristics of traditional Chinese medicines. Results① Safety:From January 2009 to March 2023,the National Adverse Drug Reaction Monitoring Center reported 159 cases (248 cases) of general adverse reactions and four cases of serious adverse reactions to Xiaojie'an capsules,all of which were classified as general adverse reactions after expert judgment. Through literature search,a total of 6 865 patients were treated with Xiaojie'an capsules,of which 26 articles reported adverse reactions to Xiaojie'an capsules,resulting in a total of 244 adverse reactions. The clinical manifestations of adverse reactions to Xiaojie'an capsules include nausea,vomiting,stomach discomfort,diarrhea,rash,itching,dizziness,headache,insomnia,etc. The prognosis was good, and the drug surveillance system was sound. Based on the evaluation of known risks and sufficient evidence,in terms of known risk assessment, according to the monitoring results of the spontaneous reporting system (SRS), there were four cases of serious adverse reactions to Xiaojie'an capsules. After expert discussion, the four cases of serious adverse reactions were finally judged as general adverse reactions, and the known risks were considered to be small in combination with the known risk evaluation criteria. According to the types of studies carried out on Xiaojie'an capsules (randomized controlled trial and its systematic review, SRS data analysis, real world human experience studies, and non-clinical safety studies) and the evaluation criteria of sufficient evidence, it was considered that Xiaojie'an capsules had sufficient evidence. The safety evidence of this variety was sufficient, and the result was confirmed. ② Effectiveness: Meta-analysis results showed that the combination of Xiaojie'an capsules and Mifepristone tablets had better clinical efficacy compared to Mifepristone tablets alone and had a better effect in reducing the maximum uterine fibroid volume. Due to limitations and imprecision caused by downgrading factors,the quality of evidence was evaluated as Grade C. Based on comprehensive effectiveness evidence and value evaluation,the effectiveness evidence of this variety was relatively sufficient, and the results were clear ③ Economy:The economic evaluation results showed that treating one more patient with uterine fibroid required an additional cost of 5 438.57 yuan by using the combination of Xiaojie'an capsules and Mifepristone tablets,which was lower than the patient's willingness to pay (36 883 yuan according to 2022 National Bureau of Statistics data). This suggested that compared with using Mifepristone tablets alone,the combination of Xiaojie'an capsules and Mifepristone tablets had a certain economy. The sensitivity analysis results were relatively robust,indicating that this variety had good economy ④ Innovation:Currently,most traditional Chinese medicine treatments for uterine fibroids advocate the method of attacking evil,which can easily harm the body. However,Xiaojie'an capsules not only soften and disperse nodules but also balance supporting the body and supplementing deficiency. The comprehensive evaluation showed sufficient evidence of the innovation of this variety,and the results were confirmed. ⑤ Suitability: The service information of Chinese patent medicines derived from the drug was complete,and the questionnaire survey results showed that the drug was suitable for clinicians,nurses,pharmacists, and patients in multiple dimensions such as individual compliance,system, and management. The comprehensive evaluation of the suitability of the product had sufficient evidence and clear results. ⑥ Accessibility:The daily cost of Xiaojie'an capsules was 16.97 yuan,and the treatment cost was 407.16 yuan. It was affordable for urban residents and rural residents and was available for sale in 23 provinces, cities,municipalities,and autonomous regions across the country. The medicinal resources were abundant and sustainably supplied,and there was sufficient evidence of accessibility with clear results. ⑦ Characteristics of traditional Chinese medicine:Xiaojie'an capsules were derived from the classic Dai medicine formula of Dr. CHEN Benshan,a renowned Dai doctor,and they have been clinically used for over 20 years. Dai medicine originated from Xishuangbanna,Yunnan province,with the core theory of "four pagodas and five elements". The comprehensive evaluation showed that this variety exhibited significant characteristics of traditional Chinese medicine. ⑧ Comprehensive evaluation of clinical value:Based on the "6+1" dimensions mentioned above,combined with the multi-criteria decision analysis (MCDA) model and calculations using CSC v2.0 software,the results showed that there was sufficient evidence for the clinical value of Xiaojie'an capsules,and the results were clear. ConclusionThe comprehensive evaluation of Xiaojie'an capsules has sufficient evidence of safety and innovation,and the results are confirmed. The evidence of effectiveness,suitability,and accessibility is relatively sufficient,with clear results. The economy is good,and the characteristics of traditional Chinese medicine are prominent. The comprehensive evaluation of clinical value believes that there is sufficient evidence of the clinical value of Xiaojie'an capsules,and the results are clear. In the future,it is recommended to focus on clinical value, conduct high-quality and effective research that is in line with the characteristics of traditional Chinese medicine, and improve acute toxicity testing to provide a scientific and objective basis for clinical efficacy and safety research.


Result Analysis
Print
Save
E-mail