TMT-based quantitative proteomics analysis of neuroprotective effects of Forsythoside A on the MPTP-induced Parkinson's disease mouse model.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder characteristized by the presence of dyskinesia and the progressive loss of dopaminergic neurons. Although certain drugs can mitigate the symptoms of PD, they are unable to delay the disease progression, and their prolonged use may result in complications. Therefore, there exists an urgent necessity to identify potential agents that can effectively delay PD progression with fewer side effects. Recent research has unveiled that several traditional Chinese medicines (TCM) exhibit neuroprotective properties in various models pertinent to PD. Forsythoside A (FSA), the primary bioactive compound derived from TCM Lianqiao, has undergone extensive research in animal models of Alzheimer's disease and cerebral ischemia. However, the investigation into the impact of FSA on PD is limited in existing research. In this study, we aimed to evaluate the neuroprotective effects of FSA on MPTP-induced PD mouse model. FSA demonstrated significant improvements in the behavioral and neuropathological changes triggered by MPTP in mice. Furthermore, it exerted a suppressive effect on the activations of astrocyte and microglia. Meanwhile, Tandem mass tag (TMT)-based quantitative proteomics of striatal tissue and bioinformatics analysis were performed to elucidate the underlying mechanisms of FSA on PD mouse model. Proteomics demonstrated a total of 68 differentially expressed proteins (DEPs) were identified between HFSA and MPTP groups including 26 upregulated and 42 downregulated. Systematic bioinformatics analysis of the 68 DEPs illustrated that they were predominantly related to estrogen signaling pathway and calcium signaling pathway. The related DEPs (PLCß4, Grm2, HPAC and Cox4i1) expression levels were verified by Western blot. FSA effectively restored the altered expression of the four DEPs induced by MPTP. Summarily, FSA exerted remarkable neuroprotective effects in MPTP-induced mice. Further, our research may provide proteomics insights that contribute to the further exploration of FSA as a potential treatment for PD.

Exploring the mechanisms underlying the therapeutic effect of the Radix Bupleuri-Rhizoma Cyperi herb pair on hepatocellular carcinoma using multilevel data integration and molecular docking.

Traditional Chinese medicine (TCM) is a promising and effective treatment for cancer with minimal side effects through a multi-active ingredient multitarget network. Radix Bupleuri and Rhizoma Cyperi are listed as herbs dispersing stagnated liver Qi in China. They have been used clinically to treat liver diseases for many years and recent pharmacological studies have shown that they inhibit the proliferation of hepatocellular carcinoma (HCC). However, the pharmacological mechanisms, potential targets, and clinical value of the Radix Bupleuri-Rhizoma Cyperi herb pair (CXP) for suppressing HCC growth have not been fully elucidated. We identified 44 CXP targets involved in the treatment of HCC using the GEO dataset and HERB database. An analysis of the Traditional Chinese Medicine System Pharmacology Database (TCMSP) showed that CXP exerts synergistic effects through 4 active ingredients, including quercetin, stigmasterol, isorhamnetin, and kaempferol. GO and KEGG analyses revealed that CXP mainly regulates HCC progression through metabolic pathways, the p53 signaling pathway, and the cell cycle. Additionally, we applied The Cancer Genome Atlas (TCGA)-liver hepatocellular carcinoma (LIHC) database to perform the expression patterns, clinical features, and prognosis of 6 genes (CCNB1, CDK1, CDK4, MYC, CDKN2A, and CHEK1) in cell cycle pathways to reveal that CXP suppresses HCC clinical therapeutic value. Moreover, based on molecular docking, we further verified that CXP exerts its anti-HCC activity through the interaction of multiple active components with cell cycle-related genes. We systematically revealed the potential pharmacological mechanisms and targets of CXP in HCC using multilevel data integration and molecular docking strategies.

Obstetric and perinatal outcomes in female survivors of childhood or adolescent cancer: Protocol of a meta-analysis of population-based cohort studies.

INTRODUCTION: Approximately 80% of children, adolescents and young adults (CAYA) cancer patients are expected to fully recover and survive for five years or more. The reproductive health is a particular area of their concern. Evidence demonstrates that previous therapeutic treatments for cancer and comorbidities may have harmful effects on female fertility and delivery outcomes, which will significantly affect patient quality of life. However, these reports are heterogeneous. Therefore, the purpose of this study is to provide the up-to-date evidence on the risk of adverse obstetric and perinatal outcomes in female survivors of childhood or adolescent cancer. METHODS AND ANALYSIS: This meta-analysis will be carried out and reported with adherence to the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines and the Cochrane Handbook. We will search online databases including PubMed, Cochrane Library, and Embase from inception to August, 2022 to identify all relevant cohort studies examining the relationship between cancer and subsequent obstetric and perinatal outcomes. Data extraction from eligible studies will be conducted and crosschecked separately by two investigators using pre-tested standardized data extraction forms. Discrepancies will be resolved via a third investigator. Methodological quality assessment for each study will be conducted using the Newcastle-Ottawa scale (NOS) tool. We will apply the DerSimonian-Laird random-effects model to calculate the pooled estimates. Further sources of heterogeneity will be explored by performing subgroup analysis based on multiple study characteristics. Potential publication bias will be assessed by inspection of a funnel plot, Begg's and Egger's regression tests of funnel plot asymmetry. ETHICS AND DISSEMINATION: Ethical approval will not be required as all data used for this pooled analysis will be obtained from published cohort studies. The results of this study will be disseminated in a peer-reviewed journal and conference presentation. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/K6QBG.

Elucidating the pharmacological mechanism by which Si-Wu-Tang induces cellular senescence in breast cancer via multilevel data integration.

Traditional Chinese medicine (TCM) is a promising strategy for effectively treating cancer by inducing cellular senescence with minimal side effects. Si-Wu-Tang (SWT) is a TCM composed of four herbs that is commonly used in China for the treatment of gynecological diseases; SWT can prevent breast cancer (BC), but the molecular mechanism by which SWT induces cellular senescence and its clinical application value remain unknown. We identified 335 differentially expressed genes (DEGs) in SWT-treated MCF-7 cells through Gene Expression Omnibus (GEO) dataset analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed the enrichment of biological processes and key signaling pathways including cellular senescence, the cell cycle, the MAPK signaling pathway, and the p53 signaling pathway. Additionally, SWT induced BC cell senescence by upregulating the expression of 33 aging/senescence-induced genes (ASIGs). According to LASSO regression analysis, NDRG1, ERRFI1, SOCS1, IRS2, IGFBP4, and BIRC3 levels were associated with BC prognosis and were used to develop risk scores. ERRFI1, SOCS1, IRS2, IGFBP4, and BIRC3 were identified as protective factors (P < 0.05, HR < 1), while NDRG1 was identified as a risk factor (P < 0.05, HR > 1). Notably, patients with low risk scores had increased senescence-associated secretory phenotypes (SASPs) and immune cell infiltration. Overall, we systematically integrated biological databases and biocomputational methods to reveal the mechanisms by which SWT induces senescence in breast cancer and its clinical value.

[Effect of electroacupuncture at Baliao points on intrauterine residue and uterine volume restoration after uterine curettage of incomplete abortion].

OBJECTIVE: To observe the clinical therapeutic effect of the combination of electroacupuncture (EA) at Baliao points (bilateral Shangliao [BL 31], Ciliao [BL 32], Zhongliao [BL 33] and Xialiao [BL 34]) and oral administration of mifepristone tablets and its influence on uterine volume restoration after uterine curettage of incomplete abortion as compared with simple oral administration of mifeprstone tablets. METHODS: A total of 58 patients after uterine curettage of incomplete abortion were randomized into an EA group and a western medication group, 29 cases in each one. In the western medication group, mifepristone tablets were administered orally, 2 tablets each time, once daily. In the EA group, on the base of the treatment as the western medication group, EA was applied to Baliao points, with disperse-dense wave, once daily, 50 min each time. The treatment for 3 days was as one course and 2 courses of treatment were required, at the interval of 1 day in the two courses. Before and after treatment, the area of intrauterine residue and blood flow signal positive rate of color Doppler flow imaging (CDFI) were recorded in patients of the two groups respectively. The days of vaginal bleeding and the rate of second operation were recorded after treatment in patients of the two groups. Using the three-dimensional ultrasound B reconstruction, the uterine endometrial volume after menstruation resumption was measured in patients of the two groups, and the clinical therapeutic effect was evaluated. RESULTS: After treatment, the intrauterine residue area and CDFI blood flow signal positive rate were all reduced as compared with the values before treatment in patients of the two groups (P<0.05). After treatment, the intrauterine residue area and CDFI blood flow signal positive rate in the EA group were less than those in the western medication group (P<0.05). After treatment, the days of vaginal bleeding in patients of the EA group were less than that in the western medication group and the rate of second operation was lower than the western medication group (P<0.05). The uterine endomentrial volume after menstruation resumption in the EA group was larger than that in the western medication group after treatment (P<0.05). The total effective rate was 55.2% (16/29) in the EA group, higher than 37.9% (11/29) in the western medication group (P<0.05). CONCLUSION: The combined treatment of electroacupuncture at Baliao points and oral administration of mifepristone tablets effectively promotes uterine contraction, softens and discharges intrauterine residue and contributes to uterine volume restoration in the patients after uterine curettage of incomplete abortion. The therapeutic effect of this combined therapy is better than simple oral administration of mifepristone tablets.

[Effect of electroacupuncture on postpartum uterine contraction pain and uterine involution: a randomized controlled trial].

OBJECTIVE: To observe the effect of electroacupuncture on postpartum uterine contraction pain and uterine involution. METHODS: A total of 80 patients with postpartum uterine contraction pain were randomly divided into an observation group and a control group, 40 cases in each group. The observation group was treated with electroacupuncture at Dahe (KI 12), Zhongzhu (KI 15), Hegu (LI 4), Xuehai (SP 10), etc. for 30 min, once a day, 3 days were as one course, and 2 courses with 1-day interval were required. The control group was treated with oral Xinshenghua tablet, 4 tablets each time, 3 times a day for 7 days. Before treatment, 24, 48, 72 h into treatment and after treatment, the visual analogue scale (VAS) score was observed; the maximum anteroposterior diameter of uterine hemorrhage, the area of hemorrhage, the space between uterus fundus and umbilical cord, and the summation of three diameters of uterus before and after treatment were compared, and the time of postpartum uterine contraction pain disappeared was recorded in the two groups. RESULTS: Compared before treatment, the VAS scores of 24, 48, 72 h into treatment and after treatment were decreased in both groups (P<0.05), and those in the observation group were lower than the control group (P<0.05). Compared before treatment, the maximum anteroposterior diameter of uterine hemorrhage, the area of hemorrhage and the summation of three diameters of uterus after treatment were decreased (P<0.05), the space between uterus fundus and umbilical cord was increased in both groups (P<0.05), and those in the observation group were superior to the control group (P<0.05). The number of days required to treat the uterine contraction pain in the observation group was shorter than the control group (P<0.05). CONCLUSION: Electroacupuncture can effectively relieve postpartum uterine contraction pain, accelerate the discharge of residual uterine hemorrhage in the uterine cavity, and promote uterine involution.

[Effect of warming acupuncture on uterine blood perfusion in patients with failed high-quality freeze-thawed embryo transfer].

OBJECTIVE: To observe the effect of warming acupuncture on uterine blood perfusion in the patients with failed high-quality freeze-thawed embryo transfer (FET) and explore its effect mechanism on the improvement of clinical pregnancy rate after re-tranfer. METHODS: A total of 72 patients of failed high-quality FET were randomized into an observation group and a control group, 36 cases in each one. In the observation group, after the menstrual period ended, warming acupuncture started at the acupoints located on the abdomen, e.g. Qihai (CV 6), Guanyuan (CV 4), Zhongji (CV 3) and Qugu (CV 2) and those on the lumbar sacral region, e.g. Shenshu (BL 23), Mingmen (GV 4) and Yaoyangguan (GV 3), 50 min in each treatment, once daily, at the interval of 1 day after 4-day treatment. The treatment was discontinued till the patients were at the ovulatory stage. In the control group, nuangong yunzi capsules were taken orally and continuously after the end of menstrual period, 3 capsules each time, three times a day and stopped at the ovulatory stage. The treatment of one menstrual cycle was taken as one course and the treatment for 3 menstrual cycles was required. Before and after treatment, the uterine artery pulsation index (PI), endometrial thickness, endometrial type, uterine blood perfusion, the recovery time of sufficient uterine blood flow, the endomentrial receptivity (ER) during the implantation window period and the clinical pregnancy rate were observed in the two groups. RESULTS: After treatment, the endometrial thickness was increased and PI decreased obviously in the two groups (P<0.05) and PI in the observation group was lower than that in the control group (P<0.05). After treatment, the proportion of type a and type A of endometrium was increased markedly in the two groups (P<0.05) and the proportion in the observation group was higher than the control group (P<0.05). After treatment, the case proportion of sufficient uterine blood flow was increased obviously in the two groups (P<0.05) and the value in the observation group was higher than the control group [83.3% (30/36) vs 69.4% (25/36), P<0.05]. After treatment, the proportion of ER during the implantation window period was increased remarkably in the two groups (P<0.05) and the value in the observation group was higher than the control group [72.2% (26/36) vs 50.0% (18/36), P<0.05]. The recovery time of sufficient uterine blood flow in the observation group was shorter than the control group (P<0.05) and the clinical pregnancy rate was higher than the control group [47.2% (17/36) vs 33.3% (12/36), P<0.05]. CONCLUSION: Warming acupuncture enhances uterine blood perfusion and improves uterine endometrial receptivity so that the clinical pregnancy rate is increased after re-transfer in the patients with failed high-quality freeze-thawed embryo transfer.

[Effect of wheat-grain moxibustion at Yinbai (SP 1) on the menstrual period prolongation after IVF-ET down-regulation treatment].

OBJECTIVE: To compare the clinical effect between wheat-grain moxibustion at Yinbai (SP 1) and oral administration of dydrogesterone tablet for menstrual period prolongation after down-regulation treatment of in vitro fertilization embryo transfer (IVF-ET). METHODS: A total of 54 patients with prolonged menstrual period after down-regulation treatment of IVF-ET were randomly divided into an observation group and a control group, 27 cases in each one. In the observation group, when the menstrual period delayed more than 7 days, the wheat-grain moxibustion at Yinbai (SP 1) was performed, once a day, with an interval of 1 day between two 3-day treatments; when the menstrual blood was cleaned, the ovulation was continued and the eggs were taken. In the control group, when the menstrual period delayed more than 7 days, the oral administration of dydrogesterone tablet was provided, 10 mg each time, twice a day; when the menstrual blood was cleaned, the ovulation was continued and the eggs were taken. The number of days for menstrual blood to be cleaned, the area change of uterine cavity hemorrhage, the morphology of endometrium, the blood supply of endometrium, the number of oocytes obtained, the grade of frozen embryo and the clinical effect were observed between the two groups after treatment. RESULTS: Compared with the control group, the number of days for menstrual blood to be cleaned was shorter in the observation group after treatment (P<0.05); the area of uterine cavity hemorrhage in the observation group was smaller than that in the control group (P<0.05); the morphology of endometrium and the supply of blood flow in the observation group were superior to those in the control group (P<0.05). However, there was no significant difference in the number of oocytes obtained and available frozen embryo between the two groups (P>0.05). The cured rate in the observation group was 100.0% (27/27), higher than 33.3% (9/27) in the control group (P<0.05). CONCLUSION: The wheat-grain moxibustion at Yinbai (SP 1) could more effectively treat prolonged menstrual period after IVF-ET down-regulation treatment, which is beneficial to the preparation of the endometrium, and has no effect on the oocyte collection and embryo culture.

[Effect of electroacupuncture at Shaoze (SI 1) on breast milk volume and composition in postpartum hypogalactia].

OBJECTIVE: To observe the effect of electroacupuncture at Shaoze (SI 1) on breast milk volume and nutrient composition in postpartum hypogalactia. METHODS: A total of 62 women with postpartum hypogalactia were randomized into an observation group (31 cases, 3 cases dropped off) and a control group (31 cases, 3 cases dropped off). Electroacupuncture was exerted at Shaoze (SI 1) in the observation group and at Shangyang (LI 1) in the control group, 10 Hz in frequency, 30 min each time, once a day. The treatment for 5 times as one course and 3 courses of treatment were required totally. Separately, before treatment and at the end of 1 course and 3 courses of treatment, the breast milk volume was measured and the composition was analyzed. The breast milk volume, nutrient composition (lactose, fat and protein), breast milk energy and density were observed in the two groups. After treatment, the clinical effect was compared between the two groups. RESULTS: In the observation group, after 1 course of treatment, the breast milk volume and the values of lactose and protein in the breast milk were increased as compared with those before treatment, the breast milk energy and density were increased as compared with those before treatment (all P<0.05). After 3 courses of treatment, the breast milk volume and the values of nutrient composition (lactose, fat and protein) were improved as compared with those before treatment, and the breast milk energy and density were increased obviously as compared with those before treatment in the observation group (all P<0.05). In the control group, after 1 course and 3 courses of treatment, only breast milk volume was increased obviously as compared with that before treatment (both P<0.05). After 1 course of treatment, the nutrient composition (lactose and protein), breast milk energy and density in the observation group were higher than those in the control group (all P<0.05). After 3 courses of treatment, the levels of breast milk volume, nutrient composition (lactose, fat and protein), breast milk energy and density in the observation group were all higher than those in the control group (all P<0.05). The effective rate was 92.9% (26/28) in the observation group, which was higher than 17.9% (5/28) in the control group (P<0.05). CONCLUSION: Electroacupuncture at Shaozhe (SI 1) increases breast milk volume in patients with postpartum hypogalactia and promotes the production of the nutrient composition in breast milk, as well as the breast milk energy and density.

[Clinical observation on the therapeutic effect of warm acupuncture on endometrial cavity fluid from in vitro fertilization-embryo transfer].

OBJECTIVE: To observe the clinical effect of warm acupuncture on endometrial cavity fluid (ECF) from in vitro fertilization-embryo transfer (IVF-ET), and to explore the mechanism of warm acupuncture on ECF. METHODS: Twenty-nine patients who were prepared for IVF-ET from 2016 to 2019 and whose transplantation was cancelled due to ECF found by vaginal B-ultrasound examination were divided into an observation group (14 cases) and a control group (15 cases) according to random number table method. The warm acupuncture was applied at Zhongwan (CV 12), Qihai (CV 6), Guanyuan (CV 4), Zhongji (CV 3), Guilai (ST 29), Zigong (EX-CA 1), Zusanli (ST 36), Sanyinjiao (SP 6) after the end of menstruation in the observation group, the treatment lasted for 60 min, once a day, 5 times as a course, with 2 days interval between the courses and 3 consecutive courses of treatment were given, until the embryo transfer was performed in the IVF assisted pregnancy cycle. After the end of menstruation, fresh leonurus japonicus capsule was given in the control group, 3 times a day, 0.8 g each time, 7 days as a course, and 3 courses of continuous treatment were received, until the embryo transfer was performed in the IVF assisted pregnancy cycle. The changes of ECF before and after treatment, the time required to prepare for embryo transfer during IVF assisted pregnancy cycle, and the clinical outcome of embryo transfer were observed in the two groups. RESULTS: The decrease of ECF in the observation group was more significant than that in the control group (P<0.05). The time required for the embryo transfer in the IVF assisted pregnancy cycle in the observation group was shorter than that in the control group (P<0.05). The clinical pregnancy rate in the observation group was 42.9% (6/14), which was significantly higher than 26.7% (4/15) in the control group (P<0.05). CONCLUSION: Warm acupuncture may improve the clinical pregnancy rate by raising the local temperature of the lower abdomen, accelerating the blood circulation around the uterus and appendages, promoting the absorption of ECF, improving the uterine environment and endometrial receptivity.

[Clinical observation on hailong juanxiao recipe combined with kechuanping mounting on yongquan acupoint in treating children' bronchial asthma in the stage of attack].

OBJECTIVE: To observe the effect of children' bronchial asthma in the stage of attack treated by Hailong Juanxiao Recipe combined with Kechuanping sticking on Yongquan acupoint (HKSYA). METHODS: One hundred and fifty children aging between 4-14 years old with bronchial asthma were randomly divided into HKSYA group (treated group, 75 cases) and Western medicine control group (control group, 75 cases). The clinical efficacy, eosinophilis (EOS) in peripheral blood and serum IgE of the patients were determined after 2 weeks of treatment. RESULTS: The clinical efficacy in the treated group was 89.3%, compared with the control group (64.0%), the difference was significant (P < 0.05). EOS and IgE in both groups after treatment were obviously lower with significant difference when compared with before treatment (P < 0.01 or P < 0.05). CONCLUSION: HKSYA could improve the clinical symptoms and the observation item, and enhance the clinical efficacy.