1.Disease burden of chronic kidney disease attributable to high BMI in China and trend prediction in 1992-2021
Hong LIU ; Guimao YANG ; Yan SUI ; Xia ZHANG ; Xuebing CHENG ; Yaxing WU ; Xu GUO ; Yanfeng REN
Journal of Public Health and Preventive Medicine 2025;36(1):27-31
Objective To analyze the disease burden of chronic kidney diseases (CKD) attributed to high body mass index (BMI) in China from 1992 to 2021 and predict the disease burden for the next decade, and to provide evidence for the prevention and treatment of CKD. Methods Using the Global Burden of Disease (GBD) database and the Joinpoint model, the average annual percentage rate change (AAPC) of the mortality rate and disability-adjusted life year (DALY) rate was calculated to describe and analyze the CKD disease burden attributed to high BMI in China from 1992 to 2021. The ARIMA model was employed to predict and analyze the change trend of the CKD disease burden. Results From 1992 to 2021, the mortality rate and DALY rate attributed to high BMI-induced chronic kidney disease showed an upward trend. Compared to 1992, the attributed number of deaths increased by 324.38%, and DALYs increased by 268.56%; the mortality rate increased by 64.00%, and the DALY rate grew by 51.62%. From 1992 to 2021, the mortality rate and DALY rate for males were lower than those for females, but the growth rate for males exceeded that of females. From 1992 to 2021, the mortality rate and DALY rate of chronic kidney disease attributed to high BMI in China increased with age. The average annual change rate of chronic kidney disease attributed to high BMI in China from 1992 to 2021 (mortality rate: 1.40 per 100,000 (95% CI: 1.04–1.76), DALY rate: 1.43 per 100 000 (95% CI: 1.17–1.70)) was higher than thHuaiyin Normal University, Huai'anher social demographic index (SDI) regions. The ARIMA model predicted that the age-standardized mortality rate increased from 2.91 per 100 000 in 2022 to 3.05 per 100 000 in 2026, and the age-standardized DALY rate increased from 69.65 per 100 000 in 2022 to 73.58 per 100 000 in 2026. Conclusion Chronic kidney disease attributed to high BMI in China is on the rise, and it will continue to grow in the future. The focus of CKD prevention and control should be on males and the elderly, while active measures should be taken to reduce the occurrence and progression of chronic kidney disease.
2.Efficacy Mechanism of Xianlian Jiedu Prescription Against Colorectal Cancer Recurrence vias Regulating Angiogenesis
Yanru XU ; Lihuiping TAO ; Jingyang QIAN ; Weixing SHEN ; Jiani TAN ; Chengtao YU ; Minmin FAN ; Changliang XU ; Yueyang LAI ; Liu LI ; Dongdong SUN ; Haibo CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):79-87
ObjectiveTo explore effect of Xianlian Jiedu prescription on the recurrence of colorectal cancer (CRC) and investigate the related mechanisms. MethodsA postoperative recurrence model was established in 25 Balb/c mice by injecting CT26 cells subcutaneously into the armpit, followed by surgical removal of 99% of the subcutaneous tumor. The mice were randomly divided into model group, low-dose Xianlian Jiedu prescription (XLJDP-L) group (6.45 g·kg-1·d-1), medium-dose Xianlian Jiedu prescription (XLJDP-M) group (12.9 g·kg-1·d-1), high-dose Xianlian Jiedu prescription (XLJDP-H) group (25.8 g·kg-1·d-1), and 5-fluorouracil (5-FU) group (1×10-3 g·kg-1·d-1). The mice were euthanized after 14 days of continuous intervention, and recurrent tumor tissue was harvested. Hematoxylin and eosin (HE) staining was used to observe pathological and morphological changes in the recurrent tumor tissue. Immunohistochemistry (IHC) was employed to assess the expression of proliferating cell nuclear antigen (Ki67), vascular endothelial growth factor (VEGF), and platelet-endothelial cell adhesion molecule (CD31) in recurrent tumor tissue. The Western blot was used to detect the protein expression levels of angiopoietin-2 (ANG-2), VEGF, phosphorylated-protein kinase B (p-Akt), protein kinase B (Akt), phosphorylated-phosphatidylinositol 3-kinase (p-PI3K), and phosphatidylinositol 3-kinase (PI3K) in recurrent tumor tissue. ResultsBefore treatment, there were no statistical differences in tumor volume, tumor weight, and body mass among the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group compared to the model group, indicating model stability. After treatment, compared with those in the model group, the tumor volume and tumor weight in the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group were significantly reduced (P<0.01), showing dose dependency. Meanwhile, there were no significant differences in body weight among the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group compared to the model group. HE staining showed that compared with that in the model group, tumor tissue in the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group had loosely arranged cells, increased intercellular spaces, small and shriveled nuclei, light staining, fewer mitotic figures and atypical nuclei, and increased necrotic areas. IHC showed that compared with those of the model group, the positive rates of Ki67, VEGF, and CD31 in the recurrent tumor tissue of the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group were significantly reduced (P<0.01) in a dose-dependent manner. Western blot results showed that compared with those of the model group, the protein expression levels of ANG-2 and VEGF in the recurrent tumor tissue of the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group were significantly downregulated (P<0.05, P<0.01), and the p-Akt/Akt and p-PI3K/PI3K ratios were significantly decreased in a dose-dependent manner (P<0.05, P<0.01). ConclusionXianlian Jiedu prescription significantly inhibits the recurrence of CRC in mice after subcutaneous tumor surgery. The mechanism may involve regulating the PI3K/Akt pathway and downregulating key angiogenic proteins such as ANG-2, VEGF, and CD31.
3.Influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis
Danqing XU ; Huan MU ; Yingyuan ZHANG ; Lixian CHANG ; Yuanzhen WANG ; Weikun LI ; Zhijian DONG ; Lihua ZHANG ; Yijing CHENG ; Li LIU
Journal of Clinical Hepatology 2025;41(2):269-276
ObjectiveTo investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis, and to establish a predictive model. MethodsA total of 217 patients who were diagnosed with decompensated hepatitis C cirrhosis and were admitted to The Third People’s Hospital of Kunming l from January, 2019 to December, 2022 were enrolled, among whom 63 patients who were readmitted within at least 1 year and had no portal hypertension-related complications were enrolled as recompensation group, and 154 patients without recompensation were enrolled as control group. Related clinical data were collected, and univariate and multivariate analyses were performed for the factors that may affect the occurrence of recompensation. The independent-samples t test was used for comparison of normally distributed measurement data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed measurement data between two groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A binary Logistic regression analysis was used to investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis, and the receiver operating characteristic (ROC) curve was used to assess the predictive performance of the model. ResultsAmong the 217 patients with decompensated hepatitis C cirrhosis, 63 (29.03%) had recompensation. There were significant differences between the recompensation group and the control group in HIV history (χ2=4.566, P=0.034), history of partial splenic embolism (χ2=6.687, P=0.014), Child-Pugh classification (χ2=11.978, P=0.003), grade of ascites (χ2=14.229, P<0.001), albumin (t=4.063, P<0.001), prealbumin (Z=-3.077, P=0.002), high-density lipoprotein (t=2.854, P=0.011), high-sensitivity C-reactive protein (Z=-2.447, P=0.014), prothrombin time (Z=-2.441, P=0.015), carcinoembryonic antigen (Z=-2.113, P=0.035), alpha-fetoprotein (AFP) (Z=-2.063, P=0.039), CA125 (Z=-2.270, P=0.023), TT3 (Z=-3.304, P<0.001), TT4 (Z=-2.221, P=0.026), CD45+ (Z=-2.278, P=0.023), interleukin-5 (Z=-2.845, P=0.004), tumor necrosis factor-α (Z=-2.176, P=0.030), and portal vein width (Z=-5.283, P=0.005). The multivariate analysis showed that history of partial splenic embolism (odds ratio [OR]=3.064, P=0.049), HIV history (OR=0.195, P=0.027), a small amount of ascites (OR=3.390, P=0.017), AFP (OR=1.003, P=0.004), and portal vein width (OR=0.600, P<0.001) were independent influencing factors for the occurrence of recompensation in patients with decompensated hepatitis C cirrhosis. The ROC curve analysis showed that HIV history, grade of ascites, history of partial splenic embolism, AFP, portal vein width, and the combined predictive model of these indices had an area under the ROC curve of 0.556, 0.641, 0.560, 0.589, 0.745, and 0.817, respectively. ConclusionFor patients with decompensated hepatitis C cirrhosis, those with a history of partial splenic embolism, a small amount of ascites, and an increase in AFP level are more likely to experience recompensation, while those with a history of HIV and an increase in portal vein width are less likely to experience recompensation.
4.Multidimensional Analysis of Mechanisms of Nuciferine Against Cerebral Ischemia Based on Transcriptomic Data
Yingying QIN ; Peng LI ; Sha CHEN ; Yan LIU ; Jintang CHENG ; Qingxia XU ; Guohua WANG ; Jing ZHOU ; An LIU ; Chang CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):184-191
ObjectiveStudies have shown that nuciferine has anti-cerebral ischemia effect, but the specific mechanism of action has not been elaborated. Based on the transcriptome results, the pharmacological mechanism of nuciferine against cerebral ischemia was analyzed from multiple dimensions including tissue, cell, pathological process, biological process and signaling pathway. MethodsThirty SD rats were randomly divided into the sham group, model group and nuciferine group(40 mg·kg-1) according to weight. Except for the sham group, the model of middle cerebral artery occlusion(MCAO) was established by thread embolization method after 30 min of administration in the other two groups. Twenty-four hours after surgery, transcriptome sequencing was used to detect the gene expression profiles in the cortex penumbra of rat cerebral tissue, and gene ontology(GO) and kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were performed for differentially expressed genes. The mechanismof nuciferine against cerebral ischemia was analyzed from 5 dimensions of tissue, cell, pathological process, biological process and signaling pathway by the transcriptome-based multi-scale network pharmacology platform(TMNP). ResultsTranscriptome sequencing and gene quantitative analysis showed that 667 genes were significantly reversed by nuciferine. Further enrichment analysis of KEGG and GO suggested that the pathways of nuciferine involved regulating stress response, ion transport, cell proliferation and differentiation, and synaptic function. TMNP research found that at the tissue level, nuciferine could significantly improve the cerebral tissue injury caused by ischemia. At the cellular and pathological levels, nuciferine could play an anti-cerebral ischemia role by improving the state of various nerve cells, mobilizing immune cells, regulating inflammation. And at the level of biological processes and signaling pathways, nuciferine mainly acted on the processes such as vascular remodeling, inflammation-related signaling pathways, and synaptic signaling. ConclusionCombined with the results of transcriptome sequencing, gene quantitative analysis and TMNP, the mechanism of nuciferine against cerebral ischemia may be related to processes such as intervening in stress response and inflammation, affecting vascular remodeling and regulating synaptic function. These results can provide a basis and reference for further study of the pharmacological mechanism of nuciferine against cerebral ischemia.
5.Clinical Characteristics and Influencing Factors of Rheumatoid Arthritis in Patients with Cold Dampness Obstruction Syndrome
Yanyu CHEN ; Yanqi LI ; Longxiao LIU ; Liubo ZHANG ; Tianyi LAN ; Nan ZHANG ; Cheng XIAO ; Yuan XU ; Qingwen TAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):140-146
ObjectiveTo study the clinical characteristics and influencing factors of rheumatoid arthritis (RA) in the patients with cold dampness obstruction syndrome. MethodsThe RA patients treated in the Department of Traditional Chinese Medicine and Rheumatology of the China-Japan Friendship Hospital from August 2022 to June 2024 were selected. The demographic information, clinical data, laboratory test results, and traditional Chinese medicine (TCM) symptom information were collected for syndrome differentiation, on the basis of which the characteristics and influencing factors of cold dampness obstruction syndrome were analyzed. ResultsA total of 258 RA patients were selected in this study, including 88 (34.1%) patients with cold dampness obstruction syndrome, 53 (20.5%) patients with dampness and heat obstruction syndrome, 31 (12.0%) patients with wind dampness obstruction syndrome, 29 (11.2%) patients with liver-kidney deficiency syndrome, 19 (7.4%) patients with Qi-blood deficiency syndrome, 14 (5.4%) patients with phlegm-stasis obstruction syndrome, 15 (5.8%) patients with stasis obstructing collateral syndrome and 9 (3.5%) patients with Qi-Yin deficiency syndrome. The patients were assigned into two groups of cold dampness obstruction syndrome and other syndromes. The group of cold dampness obstruction syndrome had lower joint fever, 28-tender joint count (TJC28), and 28-joint disease activity score (DAS28)-C-reactive protein (CRP) and higher central sensitization, cold feeling of joints, fear of wind and cold, cold limbs, and abdominal distention than the group of other syndromes (P<0.05). The binary logistic regression analysis showed that central sensitization (OR 5.749, 95%CI 2.116-15.616, P<0.001) and DAS28-CRP (OR 0.600, 95% CI 0.418-0.862, P=0.006) were the independent factors influencing cold dampness obstruction syndrome in RA. ConclusionCold dampness obstruction syndrome is a common syndrome in RA patients. It is associated with central sensitization, cold feeling of joints, abdominal distension and may be a clinical syndrome associated with central sensitization.
6.Impact factors for early extubation and drainage volume after sublobectomy: A propensity score matching study
Caiyi ZHANG ; Xingchi LIU ; Shiguang XU ; Wei XU ; Ming CHENG ; Boxiao HU ; Bo LIU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(01):87-93
Objective To compare the incidence of complications after removal of chest drainage tube in the early and late stages after sublobectomy for non-small cell lung cancer (NSCLC), and to analyze the factors affecting postoperative pleural drainage volume (PDV), so as to explore the countermeasures and achieve rapid postoperative rehabilitation. Methods The patients with NSCLC who underwent minimally invasive sublobectomy in our hospital from January to October 2021 were enrolled. According to the median time of extubation, the patients were divided into an early extubation group (time with tube≤3 days) and a late extubation group (time with tube>3 days). The patients were matched via propensity score matching with a ratio of 1:1 and a caliper value of 0.02. The incidence of complications and perioperative parameters after removal of the thoracic drainage tube were analyzed and compared between the two groups, and univariate and multiple linear regression analyses were performed. Results A total of 157 patients were enrolled, including 79 males and 78 females, with an average age of (58.22±11.06) years. There were 76 patients in the early extubation group, 81 patients in the late extubation group, and 56 patients were in each group after propensity score matching. Compared with late extubation group, there was no significant difference in the incidence of infection after extubation (10.7% vs. 16.1%, P=0.405) or pleural effusion after extubation (5.4% vs. 3.6%, P=0.647) in early extubation group, and there was no second operation in both groups. Univariate analysis showed that smoking history (P=0.001), postoperative serum albumin reduction value (P=0.017), surgical approach (P=0.014), lesion location (P=0.027), differentiation degree (P=0.041), TNM stage (P=0.043), number of dissected lymph nodes (P=0.016), and intraoperative blood loss (P=0.016) were infuencing factors for increased postoperative PDV. Multiple linear regression analysis showed that smoking history (P=0.002), postoperative serum albumin reduction value (P=0.041), and the number of dissected lymph nodes (P=0.023) were independent risk factors for increased postoperative PDV. Conclusion There is no significant difference in the incidence of complications after extubation between early and late extubations. Preoperative smoking history, excessive postoperative serum albumin decreases, and excessive number of dissected lymph nodes during the surgery are independent risk factors for increased postoperative PDV.
7.Study on Cardiac Aging Phenotypes of SHJHhr Mice
Rongle LIU ; Hao CHENG ; Fusheng SHANG ; Shufu CHANG ; Ping XU
Laboratory Animal and Comparative Medicine 2025;45(1):13-20
ObjectiveTo investigate the spontaneous premature cardiac aging in SHJHhr mice. MethodsA comparative study was conducted between SHJHhr mice (SHJHhr group) and wild-type ICR mice (WT group) at different ages (10 and 24 weeks). Cardiac function was analyzed using a small animal in vivo ultrasound imaging system. After euthanasia, organs were collected and weighed to assess the extent of cardiac atrophy. Cardiac pathological damage was observed using hematoxylin-eosin (HE) staining. Cardiac fibrosis was analyzed using Masson staining. Myocardial cell area was analyzed after wheat germ agglutinin (WGA) staining. The activities of oxidative damage indicators in myocardial tissue, including superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT), as well as the content of 8-hydroxy-2'-deoxyguanosine (8-OHdG), were measured using enzyme-linked immunosorbent assay. Real-time fluorescence quantitative PCR was used to measure the mRNA expression levels of factors associated with inflammation, fibrosis, and oxidative stress. Colorimetric assay was used to measure malondialdehyde (MDA) levels. ResultsCompared to WT group mice of the same age, 10-week-old mice in the SHJHhr group showed no significant differences in stroke volume (SV), ejection fraction (EF), fractional shortening (FS), or heart and lung weights. However, at 24 weeks of age, mice in the SHJHhr group had significantly lower SV, EF, and FS values compared to mice of the same age in the WT group (P<0.05), with no significant change in lung weight but a significant reduction in heart weight (P<0.05). Histological analysis of heart tissue from 24-week-old mice revealed no significant difference in cardiac fibrosis levels between SHJHhr and WT groups, but WGA staining showed a significant reduction in myocardial cell area in mice in the SHJHhr group (P<0.05). PCR analysis revealed a significant downregulation of mRNA levels of oxidative stress factors Sod2, Gpx1, and Cat genes (P<0.05). Biochemical assays indicated significantly reduced activities of oxidative damage-related enzymes SOD, GPX, and CAT in myocardial tissue (P<0.05), while the levels of oxidative damage markers 8-OHdG and MDA significantly increased (P<0.05). ConclusionMice in the SHJHhr group exhibit premature cardiac aging, which may be associated with oxidative stress damage in myocardial tissue.
8.Establishment of a method for acquisition, perfusion, preservation and transportation of the genetically modified donor pig kidneys
Feiyan ZHU ; Yaobo ZHAO ; Hongfang ZHAO ; Taiyun WEI ; Wenjie CHENG ; Kai LIU ; Yuexiao BAO ; Yaling LOU ; Hongjiang WEI ; Kaixiang XU
Organ Transplantation 2025;16(2):272-279
Objective To establish a method for acquisition, perfusion, preservation and transportation of the genetically modified pig kidneys. Methods An eight genetically modified pig was utilized as experimental subject. Prior to kidneys procurement, the health status of the pig was assessed through hematology examination, and the vascular structure of the kidneys was examined using imaging techniques. Following kidneys acquisition, the pig kidneys were perfused and subsequently packaged into the cryogenic storage container labeled "For Organ Transportation Only" for interprovincial transport after communicating the transportation process with transportation department. To evaluate pathological damage to the pig kidneys, a serious of methods were employed such as hematoxylin-eosin (HE) staining, real-time fluorescent quantitative polymerase chain reaction (RT-qPCR), terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) fluorescence staining and enzyme-linked immune absorbent assay (ELISA). Results The preoperative examination of the eight genetically modified pig showed that the serum creatinine was 73.2 μmol/L, blood urea nitrogen was 2.8 mmol/L and hemoglobin was 116 g/L, all within the normal range, indicating normal renal function. CT angiography revealed no lesions in the pig kidneys, and no dilation, stenosis or premature branching of the blood vessels. The total time of obtaining the left and right kidneys from the eight genetically modified pig was (125 ± 10) min, with a blood loss of (20 ± 2) mL. The warm ischemia times were 3 min and 7 min, respectively. The perfusion and trimming times of the left and right kidneys were 36 min and 41 min, respectively. After perfusion, both kidneys were white and moist. The cold preservation and transportation time was 8 h. HE staining showed that some glomeruli were shrunk, and the lumens of the surrounding renal tubules were slightly depressed and swollen with partial inner membrane shedding and microvacuoles formed when the kidneys were preserved for 8 h. The level of cysteinyl aspartate-specific proteinase-3 messenger RNA in the kidneys tissue gradually increased with the extension of cold preservation time after 2 h (P<0.05). TUNEL fluorescence staining showed that only a small number of cells underwent apoptosis after 8 h of cold preservation, which was not significantly different from that at 0 h (P>0.05). ELISA results showed that the contents of lactate dehydrogenase (LDH) and creatinine in the preservation solution remained relatively stable, but the content of kidney injury molecule 1 (KIM-1) gradually increased with the extension of preservation time, suggesting that the pig kidneys had mild injury. Conclusions By establishing methods for acquisition, perfusion, preservation and transportation of the kidneys from genetically modified donor pig, it is possible to effectively and reliably use genetically modified pig kidneys for xenotransplantation.
9.Prospective study of association between dietary macronutrients and lung function in school aged children
LI Lu, CHEN Mengxue, LI Ruirui, LIU Xueting, WANG Xiaoyu, XU Yujie, XIONG Jingyuan, CHENG Guo
Chinese Journal of School Health 2025;46(2):200-204
Objective:
To explore the longitudinal associations between dietary macronutrients and lung function in schoolaged children, so as to provide the nutritional research evidence for promoting children s lung health.
Methods:
In November 2021, two primary schools located in Chengdu, Sichuan Province were selected from the Southwest China Childhood Nutrition and Growth (SCCNG) cohort by a stratified cluster random sampling method, enrolling a total of 1 112 school aged children aged 8 to 13 years. At baseline, the dietary and sociodemographic characteristics of the children were assessed. One year later, the forced vital capacity (FVC) of the children was measured and converted into Z scores (FVC- Z ), while the vital capacity index (VCI) was also calculated. Generalized linear regression analysis was employed to examine the associations between dietary macronutrients and lung function, considering interactions with gender and age, followed by stratified analysis.
Results:
After adjusting for confounding factors, the analysis results of the generalized linear regression model showed that the carbohydrate energy ratio was negatively correlated with FVC- Z ( β =-0.02) and VCI ( β =-0.16), while the fat energy ratio showed a positive correlation with FVC- Z ( β =0.03) and VCI ( β =0.23) ( P <0.05). The protein energy ratio was positively correlated with FVC- Z ( β =0.09) and VCI ( β =0.60) specifically in girls ( P <0.05). Additionally, there was an interaction effect of age on the associations between macronutrients and lung function ( P <0.01); in children aged 8-9 and 10-11, the carbohydrate energy supply ratio was negatively correlated with FVC- Z ( β =-0.04, -0.03) and VCI ( β =-0.29, -0.21), and fat energy supply ratio was positively correlated with FVC- Z ( β =0.07, 0.05) and VCI ( β =0.46, 0.32) ( P <0.05).
Conclusions
There are age and sex differences in the association of dietary macronutrients with lung function, with a low carbohydrate, high fat diet promoting lung function in children. Additionally, protein intake appears to have a positive influence on the lung function of girls. The early school age period may represent a critical window for dietary interventions aimed at promoting lung health.
10.Efficacy and Mechanism of Shuanghua Drink in Treating Primary Dysmenorrhea Based on COX-2/NF-κB Signaling Pathway
Yuncheng MA ; Yuanyuan SHI ; Zhen LIU ; Yuxi WANG ; Yuan TIAN ; Qian LI ; Xiaozhu WANG ; Cheng HE ; Wenhui XU ; Weiling WANG ; Jian GAO ; Ting WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):72-80
ObjectiveTo evaluate the efficacy of Shuanghua drink in treating primary dysmenorrhea in the rat model and explore its mechanism of action. MethodsAn oxytocin-induced writhing mouse model was established to evaluate the analgesic effect of Shuanghua drink. Forty-eight non-pregnant female institute of cancer research (ICR) mice were randomly divided into six groups, including a blank group, a model group, an ibuprofen group (85.00 mg·kg-1), a low-dose group of Shuanghua drink (7.14 mL·kg-1), a medium-dose group of Shuanghua drink (14.28 mL·kg-1), and a high-dose group of Shuanghua drink (28.57 mL·kg-1). Each group consisted of eight mice. All treatment groups received daily intragastric administration at corresponding doses for 10 consecutive days. One hour after the final administration, 2 U of oxytocin was intraperitoneally injected per mouse. The writhing latency and number of writhing within 20 minutes were recorded. A primary dysmenorrhea rat model was established by using estradiol benzoate and oxytocin to evaluate the inhibitory effect of Shuanghua drink on the contraction of uterine smooth muscle. Forty-eight non-pregnant female Sprague-Dawley (SD) rats were divided into six groups, including a blank group, a model group, an ibuprofen group (51.00 mg·kg-1), a low-dose group of Shuanghua drink (4.28 mL·kg-1), a medium-dose group of Shuanghua drink (8.57 mL·kg-1), and a high-dose group of Shuanghua drink (17.10 mL·kg-1). Each group consisted of eight rats. Rats received subcutaneous injections of estradiol benzoate for 10 consecutive days to enhance uterine sensitivity. On the eleventh day, oxytocin (2 U/rat) was intraperitoneally administered to induce abnormal uterine contractions for establishing the primary dysmenorrhea model. All treatment groups received daily intragastric administration from the second day of modeling for 10 days. The effects of Shuanghua drink were evaluated by using parameters including uterine motility and the variation rate of uterine motility. The mechanism of action was investigated in rats with primary dysmenorrhea. The content of prostaglandin F2α (PGF2α), prostaglandin E2 (PGE2), thromboxane B2 (TXB2), prostacyclin metabolite (6-keto-PGF1α), and β-endorphin (β-EP) in uterine tissue of rats was detected by using enzyme-linked immunosorbent assay (ELISA). The changes in the content of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) were analyzed via colorimetric assay. Western blot was performed to determine the content of phosphorylated inhibitor of kappa B kinase beta (p-IKKβ)/IKKβ, phosphorylated inhibitor of kappa B alpha (p-IκBα), IκBα, phosphorylated p65 (p-p65), p65, and cyclooxygenase-2 (COX-2) proteins in uterine tissue of rats. ResultsIn the oxytocin-induced writhing mouse model, the model group exhibited significantly shortened writhing latency and increased writhing frequency compared to the control group (P<0.01). Both the ibuprofen group and the high-dose group of Shuanghua drink displayed prolonged writhing latency (P<0.05), while the ibuprofen group and the low-dose, medium-dose, and high-dose groups of Shuanghua drink exhibited reduced writhing frequency (P<0.01). In the primary dysmenorrhea rat model, the uterine motility and its variation rate in the model group were significantly higher than those in the blank group (P<0.01). These parameters were markedly suppressed by ibuprofen and Shuanghua drink at all tested doses (P<0.01). For the mechanism of action, the model group showed significantly increased PGF2α/PGE2, TXB2/6-keto-PGF1α, NO, and iNOS in uterine tissue (P<0.05, P<0.01) and significantly decreased β-EP (P<0.01). These parameters were significantly attenuated in the ibuprofen group and the low-dose, medium-dose, and high-dose groups of Shuanghua drink. The PGF2α/PGE2 (P<0.01), TXB2/6-keto-PGF1α (P<0.01), NO (medium-dose group P<0.05), and iNOS (P<0.01) were reduced, and the β-EP (medium-dose group P<0.05) was up-regulated. Compared to the model group, the ibuprofen group and medium-dose group of Shuanghua drink showed significantly increased content of β-EP in the serum of rats (P<0.05). Compared to the blank group, the model group showed significantly elevated expressions of COX-2, p-IKKβ/IKKβ, p-IκBα/IκBα, and p-p65/p65 proteins (P<0.01) and significantly reduced anti-inflammatory protein IκBα (P<0.05). Compared to the model group, the ibuprofen group and the low-dose, medium-dose, and high-dose groups of Shuanghua drink showed significantly reduced expressions of COX-2 (P<0.01), p-IKKβ/IKKβ (P<0.01), p-IκBα/IκBα (P<0.05, P<0.01), and p-p65/p65(P<0.01) and up-regulated expression of IκBα protein (P<0.05, P<0.01). ConclusionShuanghua drink effectively alleviates primary dysmenorrhea through analgesia and suppression of abnormal contractions of uterine smooth muscle. Its mechanism may be mediated by reduced levels of PGF2α/PGE2, TXB2/6-keto-PGF1α, iNOS, and NO, elevated β-EP level, and inhibited COX-2/NF-κB signaling pathway.


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