Aim To explore the mechanism of Jiawei Shaofu Zhuyu decoction in antagonizing endometriosis fibrosis by regulating mitophagy.Methods After the animal model was constructed,the syndrome was evalu-ated by general condition,organ water content and ther-mal imaging.The curative effect was evaluated by the weight of ectopic focus and the degree of adhesion.The pathological changes were compared using HE stai-ning,transmission electron microscopy,Masson and Sir-ius red staining.The expression of PINK1 and Parkin was detected by immunohistochemistry.The expression of mRNA and protein was determined by qPCR and Western blot,and the level of serum ROS was detected by ELISA.Results The autonomic activity of model mice was weakened,the water content of organs rose,and the temperature of limbs and lower abdomen was reduced by thermal imaging.HE staining showed obvi-ous hyperplasia of ectopic epithelium and glands.Transmission electron microscopy showed mitochondrial and endoplasmic reticulum structure damage,and nor-mal autophagy structure disappeared.Masson and Siri-us red staining showed increased collagen deposition;immunohistochemistry showed decreased expression of PINK1 and Parkin in ectopic foci.qPCR and Western blot showed that the expression of PINK1,Parkin,Bec-lin1,LC3 mRNA and protein in ectopic foci of model mice decreased,the expression of p62 mRNA and pro-tein increased,and serum ROS increased.The syn-drome performance of model mice was improved after the intervention of Jiawei Shaofu Zhuyu decoction;the inflammatory infiltration of ectopic foci was relieved,the morphology of mitochondria and endoplasmic retic-ulum was restored,and normal autophagy structure ap-peared.The degree of collagen deposition and fibrosis was reduced;the mRNA and protein expression of PINK1,Parkin,Beclin1 and LC3 increased.The ex-pression of p62 mRNA and protein decreased,and the level of ROS decreased.Conclusions Jiawei Shaofu Zhuyu decoction can improve the fibrosis of ectopic le-sions in mice with endometriosis of cold-dampness sta-sis syndrome,which may be related to the regulation of mitophagy.

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

Aim To explore the mechanism of Jiawei Shaofu Zhuyu decoction in antagonizing endometriosis fibrosis by regulating mitophagy.Methods After the animal model was constructed,the syndrome was evalu-ated by general condition,organ water content and ther-mal imaging.The curative effect was evaluated by the weight of ectopic focus and the degree of adhesion.The pathological changes were compared using HE stai-ning,transmission electron microscopy,Masson and Sir-ius red staining.The expression of PINK1 and Parkin was detected by immunohistochemistry.The expression of mRNA and protein was determined by qPCR and Western blot,and the level of serum ROS was detected by ELISA.Results The autonomic activity of model mice was weakened,the water content of organs rose,and the temperature of limbs and lower abdomen was reduced by thermal imaging.HE staining showed obvi-ous hyperplasia of ectopic epithelium and glands.Transmission electron microscopy showed mitochondrial and endoplasmic reticulum structure damage,and nor-mal autophagy structure disappeared.Masson and Siri-us red staining showed increased collagen deposition;immunohistochemistry showed decreased expression of PINK1 and Parkin in ectopic foci.qPCR and Western blot showed that the expression of PINK1,Parkin,Bec-lin1,LC3 mRNA and protein in ectopic foci of model mice decreased,the expression of p62 mRNA and pro-tein increased,and serum ROS increased.The syn-drome performance of model mice was improved after the intervention of Jiawei Shaofu Zhuyu decoction;the inflammatory infiltration of ectopic foci was relieved,the morphology of mitochondria and endoplasmic retic-ulum was restored,and normal autophagy structure ap-peared.The degree of collagen deposition and fibrosis was reduced;the mRNA and protein expression of PINK1,Parkin,Beclin1 and LC3 increased.The ex-pression of p62 mRNA and protein decreased,and the level of ROS decreased.Conclusions Jiawei Shaofu Zhuyu decoction can improve the fibrosis of ectopic le-sions in mice with endometriosis of cold-dampness sta-sis syndrome,which may be related to the regulation of mitophagy.

Interventions for endometriosis(EMs)include surgical excision of lesions and hormonal therapy,which usually have limited efficacy and adverse drug reactions.Traditional Chinese medicine(TCM)has the multi-component and multi-target characteristics,which can help patients achieve good clinical benefits by intervening in different parts of the disease.In this paper,we briefly discuss the modern pharmacology of Sanlang and Curcuma longa,and deeply summarize the possible mechanisms of action of TCM monomer and classical compound extracts and their active ingredients through signal pathways in inflammation,immune system,angiogenesis,hormone regulation,etc.,so as to provide theoretical bases for the clinical use of TCM monomers,drug-to-drug groups and compounds in the treatment of EMs.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

OBJECTIVE: To observe the therapeutic effects and underlying mechanism of baicalin against colon cancer. METHODS: The effects of baicalin on the proliferation and growth of colon cancer cells MC38 and CT26. WT were observed and predicted potential molecular targets of baicalin for colon cancer therapy were studied by network pharmacology. Furthermore, molecular docking and drug affinity responsive target stability (DARTS) analysis were performed to confirm the interaction between potential targets and baicalin. Finally, the mechanisms predicted by in silico analyses were experimentally verified in-vitro and in-vivo. RESULTS: Baicalin significantly inhibited proliferation, invasion, migration, and induced apoptosis in MC38 and CT26 cells (all P<0.01). Additionally, baicalin caused cell cycle arrest at the S phase, while the G₀/G₁ phase was detected in the tiny portion of the cells. Subsequent network pharmacology analysis identified 6 therapeutic targets associated with baicalin, which potentially affect various pathways including 39 biological processes and 99 signaling pathways. In addition, molecular docking and DARTS predicted the potential binding of baicalin with cyclin dependent kinase inhibitor 2A (CDKN2A), protein kinase B (AKT), caspase 3, and mitogen-activated protein kinase (MAPK). In vitro, the expressions of CDKN2A, MAPK, and p-AKT were suppressed by baicalin in MC38 and CT26 cells. In vivo, baicalin significantly reduced the tumor size and weight (all P<0.01) in the colon cancer mouse model via inactivating p-AKT, CDKN2A, cyclin dependent kinase 4, cyclin dependent kinase 2, interleukin-1, tumor necrosis factor α, and activating caspase 3 and mouse double minute 2 homolog signaling (all P<0.05). CONCLUSION Baicalin suppressed the CDKN2A protein level to prevent colon cancer and could be used as a therapeutic target for colon cancer.
Flavonoids/pharmacology* ; Colonic Neoplasms/prevention & control* ; Animals ; Cell Line, Tumor ; Molecular Docking Simulation ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Cyclin-Dependent Kinase Inhibitor p16/metabolism* ; Mice ; Mice, Inbred BALB C ; Cell Movement/drug effects* ; Humans ; Gene Expression Regulation, Neoplastic/drug effects* ; Cell Cycle Checkpoints/drug effects*

The present study aimed to investigate the protective role of Shaofu Zhuyu Decoction(SFZY) against endometriosis fibrosis in mice, and decipher the underlying mechanism through the phosphatase and tensin homolog deleted on chromosome ten(PTEN)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) pathway. Eighty-five BALB/c female mice were randomly assigned into a blank group, a model group, high-, medium, and low-dose SFZY(SFZY-H, SFZY-M, and SFZY-L, respectively) groups, and a gestrinone suspension(YT) group. The model of endometriosis was induced by intraperitoneal injection of uterine fragments. The mice in different groups were administrated with corresponding groups by gavage 14 days after modeling, and the blank group and model group with equal volume of distilled water by gavage. The treatment lasted for 14 days. The body weight, paw withdrawal latency caused by heat stimuli, and total weight of dissected ectopic focus were compared between different groups. The pathological changes of the ectopic tissue were observed via hematoxylin-eosin(HE) and Masson staining. Real-time PCR was employed to measure the mRNA levels of α-smooth muscle actin(α-SMA) and collagen type Ⅰ(collagen-Ⅰ) in the ectopic tissue. The protein levels of PTEN, Akt, mTOR, p-Akt, and p-mTOR in the ectopic tissue were determined by Western blot. Compared with the blank group, the modeling first decreased and then increased the body weight of mice, increased the total weight of ectopic focus, and shortened the paw withdrawal latency. Compared with the model group, SFZY and YT increased the body weight, prolonged the paw withdrawal latency, and decreased the weight of ectopic focus. Furthermore, the drug administration, especially SFZY-H and YT(P<0.01), recovered the pathological and reduced the area of collagen deposition. Compared with the blank group, the modeling up-regulated the mRNA levels of α-SMA and collagen-Ⅰ in the ectopic focus, and such up-regulation was attenuated after drug intervention, especially in the SFZY-H and YT groups(P<0.05,P<0.01). Compared with the blank group, the modeling down-regulated the protein level of PTEN and up-regulated the protein levels of Akt, mTOR, p-Akt, and p-mTOR(P<0.01, P<0.001). Drug administration, especially SFZY-H and YT, restored such changes(P<0.01). SFZY may significantly attenuate the focal fibrosis in the mouse model of endometriosis by regulating the PTEN/Akt/mTOR signaling pathway.
Female ; Animals ; Mice ; Humans ; Proto-Oncogene Proteins c-akt/genetics* ; Choristoma ; Endometriosis/genetics* ; TOR Serine-Threonine Kinases/genetics* ; RNA, Messenger ; Signal Transduction ; Body Weight ; Mammals ; PTEN Phosphohydrolase/genetics*

Background/Aims: Antidepressants are effective in patients with functional dyspepsia (FD). However, stigma associated with FD and antidepressants may affect treatment adherence. This study aims to explore possible communication strategies to alleviate stigma and improve adherence in patients with FD. Methods: In this randomized, single-center, and single-blind trial, 160 patients with FD initiating antidepressant treatment were recruited. Different communication strategies were performed when prescribing antidepressants. Participants in Group 1 were told that brain is the “headquarters” of gut, and that antidepressants could act as neuromodulators to relieve symptoms of FD through regulating the functions of gut and brain. Participants in Group 2 were told that antidepressants were empirically effective for FD. Stigma scores, medication-related stigma, treatment compliance, and efficacy were analyzed. Results: After 8-week antidepressant treatment, the proportion of patients with FD with decreased stigma scores in Group 1 was significantly higher than in Group 2 (internalized stigma: 64.10% vs 12.00%; perceived stigma: 55.13% vs 13.33%; P < 0.01). Medication-related stigma was lower in Group 1 than in Group 2 (P < 0.05 for 3 of 4 questions). Concurrently, patients in Group 1 had better treatment compliance (0.71 ± 0.25 vs 0.60 ± 0.25, P < 0.01) and efficacy. In Group 1, participants with decreased post-treatment stigma scores showed better treatment compliance and efficacy than those with non-decreased scores. Decrease in stigma scores positively correlated with treatment compliance. Conclusion Improving knowledge of patients with FD of the disease and antidepressants via proper communication may be an effective way to alleviate stigma and promote adherence.

Previously, we discovered that cells contain a 5-hydroxytryptamine (5-HT) degradation system (5DS), which includes 5-HT_2A receptor (5-HT_2AR), 5-HT synthase, and monoamine oxidase A (MAO-A). Among these, 5-HT_2AR has the ability to regulate the expression of 5-HT synthase and MAO-A, and activation of 5DS causes upregulation of these proteins at the same time, resulting in the production of reactive oxygen species (ROS) in the mitochondria. In this study, we investigated the relationship between interstitial pneumonia (IP) and 5DS activation, as well as the therapeutic effect of inhibiting 5DS on IP. Animal models of bleomycin (BLM)-induced IP in mice and radiation (Rad)-induced IP in rats were established, and the models were treated with the 5-HT_2AR antagonist sarpogrelate hydrochloride (SH), 5-HT synthesis inhibitor carbidopa (CDP), and their combination (SH∶CDP = 2∶1). The animal experiments were carried out in accordance with the regulations of the Animal Ethics Committee of China Pharmaceutical University. In the two IP models, immunohistochemistry staining and Western blot analysis showed that the expression of 5-HT synthase was significantly upregulated in all cells of lung tissue, while the expression of 5-HT_2AR and MAO-A was most significantly upregulated in the macrophages. Treatment with SH or CDP significantly reduced pulmonary interstitial thickening, alveolar atrophy with collapse, massive macrophage infiltration and interstitial fibrosis in the two IP models, as measured by HE and Masson staining, and a combination of both almost eliminated the lung tissue lesions. Moreover, treatment with the combination of SH and CDP almost completely eliminated increased ROS and malondialdehyde levels, decreased superoxide dismutase activity, increased tumor necrosis factor-α and interleukin-1β levels, and upregulated nuclear factor-κB phosphorylation and α‍-smooth muscle actin, matrix metalloproteinase-2, and collagen expression. SH and CDP worked together to create a synergistic effect. The findings suggested that the activation of 5DS, as evidenced by increased 5-HT synthesis in all cells of lung tissue and increased 5-HT synthesis and degradation in macrophages, is probably related to the occurrence of IP and that inhibition of 5DS can effectively treat IP.

Objective: To understand the prevalence of chronic kidney disease (CKD) and related factors in adults in Anhui province based on the data of Chinese Chronic Diseases and Nutrition Surveillance program (2018) in Anhui. Methods: Multi-stage stratified cluster random sampling was used to select participants aged ≥18 years. Moreover, questionnaire survey, body measurements and laboratory tests were conducted. The complex weighting method was used to estimate the prevalence of CKD in residents with different characteristics, and complex sampling data logistic regression model was used for multivariate analysis to identify related risk factors. Results: A total of 7 181 participants were included. The overall prevalence of CKD was 11.06% in adults in Anhui, and the prevalence was 12.49% in women and 9.59% in men (P<0.05). The moderate, high and very high risk for CKD progression were 8.66%, 2.02% and 0.38%, respectively. Multivariate analysis showed that age (OR=1.03, 95%CI: 1.00-1.05), BMI (OR=1.05, 95%CI: 1.01-1.09), being woman (OR=1.38,95%CI: 1.22-1.55), hypertension (OR=2.50, 95%CI: 1.76-3.56), diabetes (OR=2.28, 95%CI: 1.51-3.43), dyslipidemia (OR=1.26, 95%CI: 1.11-1.43) and hyperuricemia (OR=2.16, 95%CI: 1.68-2.78) were risk factors for CKD. Conclusion: The prevalence of CKD in adults in Anhui was relatively high and age, gender, BMI, hypertension, diabetes, dyslipidemia and hyperuricemia were found to be associated with the prevalence of CKD. To prevent CKD and its complications, attention should be paid to the management of related risk factors, including overweight and obesity, hypertension, diabetes, dyslipidemia and hyperuricemia.
Adult ; Male ; Female ; Humans ; Adolescent ; Cross-Sectional Studies ; Prevalence ; Hyperuricemia/epidemiology* ; Renal Insufficiency, Chronic/epidemiology* ; Hypertension/epidemiology*