Bushen Huoxue Recipe inhibits endometrial epithelial-mesenchymal transition through the transforming growth factor-ß/nuclear factor kappa-B pathway to improve polycystic ovary syndrome-mediated infertility.

OBJECTIVE: To investigate the target and mechanism of action of Bushen Huoxue Recipe (BSHX) for the treatment of infertility in polycystic ovary syndrome (PCOS), to provide a basis for the development and clinical application of herbal compounds. METHODS: Prediction and validation of active ingredients and targets of BSHX for the treatment of PCOS by using network pharmacology-molecular docking technology. In an animal experiment, the rats were randomly divided into four groups (control group, model group, BSHX group, metformin group, n = 16 in each group), and letrozole combined with high-fat emulsion gavage was used to establish a PCOS rat model. Body weight, vaginal smears, and number of embryos were recorded for each group of rats. Hematoxylin-eosin (HE) staining was used to observe the morphological changes of ovarian and endometrial tissues, and an enzyme-linked immunosorbent assay (ELISA) was used to detect the serum inflammatory factor levels. Expression levels of transforming growth factor-ß (TGF-ß), transforming growth factor beta activated kinase 1 (TAK1), nuclear factor kappa-B (NF-κB), Vimentin, and E-cadherin proteins were measured by western blot (WB). RESULTS: Ninety active pharmaceutical ingredients were obtained from BSHX, involving 201 protein targets, of which 160 were potential therapeutic targets. The active ingredients of BSHX exhibited lower binding energy with tumor necrosis factor-α (TNF-α), TGF-ß, TAK1, and NF-κB protein receptors (< -5.0 kcal/mol). BSHX significantly reduced serum TNF-α levels in PCOS rats (p < .01), effectively regulated the estrous cycle, restored the pathological changes in the ovary and endometrium, improved the pregnancy rate, and increased the number of embryos. The results of WB suggested that BSHX can down-regulate protein expression levels of TGF-ß and NF-κB in endometrial tissue (p < .05), promote the expression level of E-cadherin protein (p < .001), intervene in the endometrial epithelial-mesenchymal transition (EMT) process. CONCLUSIONS: TGF-ß, TAK1, NF-κB, and TNF-α are important targets of BSHX for treating infertility in PCOS. BSHX improves the inflammatory state of PCOS, intervenes in the endometrial EMT process through the TGF-ß/NF-κB pathway, and restores endometrial pathological changes, further improving the pregnancy outcome in PCOS.

Integrated serum pharmacochemistry and network pharmacology to explore the mechanism of Yi-Shan-Hong formula in alleviating chronic liver injury.

BACKGROUND: Chronic liver injury (CLI) is a complex condition that requires effective therapeutic interventions. The Yi-Shan-Hong (YSH) formula is an empirically derived remedy that has shown effectiveness and safety in the management of chronic liver damage. However, the bioactive components and multifaceted mechanisms of YSH remain inadequately understood. PURPOSE: To examine the bioactive compounds and functional processes that contribute to the therapeutic benefits of YSH against CLI. METHODS: Serum pharmacochemistry and network pharmacology were employed to identify active compounds and possible targets of YSH in CLI. In addition, YSH was also given in three doses to d-(+)-galactosamine hydrochloride (D-GalN) -induced CLI rats to test its therapeutic efficacy. RESULTS: The analysis of serum samples successfully detected 25 compounds from YSH. Searches on the databases resulted in 277 genes as being correlated with chemicals in YSH, and 397 genes associated with CLI. In vivo experiments revealed that YSH displayed a notable therapeutic impact on liver injury caused by d-GalN. This was evidenced by enhanced liver function and histopathological improvements, reduced oxidative stress response, proinflammatory factors, and fibrosis levels. Importantly, no discernible adverse effects were observed. Furthermore, the administration of YSH treatment reversed the activation of AKT phosphorylation caused by d-GalN, aligning with the findings of the network pharmacology study. CONCLUSION: These findings provide preclinical evidence of YSH's therapeutic value in CLI and highlight its hepatoprotective action via the PI3K/AKT signaling pathway.

Virtual reality-based surgical planning simulator for tumorous resection in FreeForm Modeling: an illustrative case of clinical teaching.

The importance of virtual reality (VR) has been emphasized by many medical studies, yet it has been relatively under-applied to surgical operation. This study characterized how VR has been applied in clinical education and evaluated its tutorial utility by designing a surgical model of tumorous resection as a simulator for preoperative planning and medical tutorial. A 36-year-old male patient with a femoral tumor who was admitted to the Affiliated Jiangmen Traditional Chinese Medicine Hospital was randomly selected and scanned by computed tomography (CT). The data in digital imaging and communications in medicine (*.DICOM) format were imported into Mimics to reconstruct a femoral model, and were generated to the format of *.stl executing in the computer-aided design (CAD) software SenSable FreeForm Modeling (SFM). A bony tumor was simulated by adding clay to the femur, the procedure of tumorous resection was virtually performed with a toolkit called Phantom, and its bony defect was filled with virtual cement. A 3D workspace was created to enable the individual multimodality manipulation, and a virtual operation of tumorous excision was successfully carried out with indefinitely repeated running. The precise delineation of surgical margins was shown to be achieved with expert proficiency and inexperienced hands among 43 of 50 participants. This simulative educator presented an imitation of high definition, those trained by VR models achieved a higher success rate of 86% than the rate of 74% achieved by those trained by conventional methods. This tumorous resection was repeatably handled by SFM, including the establishment of surgical strategy, whereby participants felt that respondent force feedback was beneficial to surgical teaching programs, enabling engagement of learning experiences by immersive events which mimic real-world circumstances to reinforce didactic and clinical concepts.

Electroacupuncture promotes synaptic plasticity in rats with chronic inflammatory pain-related depression by upregulating BDNF/TrkB/CREB signaling pathway.

BACKGROUND: Chronic inflammatory pain (CIP) frequently coincides with depression among patients. The onset and development of pain and depression are associated with altered neural synaptic plasticity. Electroacupuncture (EA) can effectively relieve CIP and depression. However, the underlying mechanisms have not been fully illustrated. OBJECTIVE: To explore whether EA can relieve CIP and depression by regulating hippocampal synaptic plasticity, and the present study offers foundational evidence for the efficacy of EA in treating CIP-related depression (CIPD). METHODS: Rats were divided into four groups: 0.9% normal saline group, complete Freund's adjuvant (CFA) group, CFA + duloxetine group, and CFA + EA group. Pain hypersensitivity was detected by mechanical withdrawal threshold and thermal paw withdrawal latency, and the depression level was gauged using the open field test, the sucrose preference test, and the forced swimming test. The morphology of the hippocampal neurons was observed using Nissl staining. The protein expression levels of synuclein (Syn), postsynaptic density protein-95 (PSD-95), brain-derived neurotrophic factors (BDNFs), tyrosine-protein kinase B (TrKB), p-TrkB, cAMP response element binding protein (CREB), and p-CREB were measured by western blotting and immunofluorescence staining. BDNF and TrkB mRNA expression were detected using quantitative real-time polymerase chain reaction (PCR) (qRT-PCR). The content of 5-hydroxytryptamine (5-HT) and γ-aminobutyric acid (GABA) was detected using enzyme-linked immunosorbent assay, and the glutamic acid (Glu) content was determined using the ultraviolet colorimetry method. The hippocampal neuron ultrastructure was observed using transmission electron microscopy. RESULTS: EA could alleviate CIP and related depressive behaviors as well as protect the hippocampal neuronal structure from damage and regulate 5-HT/GABA/Glu levels in the hippocampus. Additionally, EA could significantly increase the expression of synapse-associated proteins such as PSD-95 and Syn by activating the BDNF/TrKB/CREB signaling pathway. CONCLUSION: EA improves pain and depressive behaviors in CIPD rats, and the mechanism may be related to synaptic plasticity mediated by the BDNF/TrKB/CREB signaling pathway.

Effect of Bushen Huoxue recipe on serum metabolomics in polycystic ovary syndrome rats.

OBJECTIVE: To investigate the effect of Bushen Huoxue Recipe (BSHXR) on serum metabolomics in polycystic ovary syndrome rat (PCOSR). METHODS: In our study, twenty-four 6-week-old Sprague-Dawley (SD) female rats were randomly divided into three groups: treatment group, model group and blank group. The blank group and other groups were gavaged in different ways each morning, and the rats were treated with normal saline or BSHXR containing liquid each afternoon. Liquid chromatography-mass spectrometry (LC-MS) was employed to study serum metabolites in the treatment group after the study as well as in the model and blank groups. RESULTS: There was a tendency to normalize the histomorphology of ovarian pathology and the abnormal sex hormone level of PCOSR was significantly improved after BSHXR treatment. The level of serum metabolites was greatly changed in PCOSR treated with the BSHXR. We identified 32 metabolic targets of BSHXR in PCOSR using LC-MS, and further revealed BSHXR targeted five major metabolic pathway: retrograde endocannabinoid signaling, taurine and hypotaurine metabolism, glycerophospholipid metabolism, primary bile acid biosynthesis, arginine and proline metabolism. Conclusion: Our study found that BSHXR plays a role in the treatment of PCOS by regulating key metabolic pathways in the PCOSR.

Electroacupuncture ameliorates pain in cervical spondylotic radiculopathy rat by inhibiting the CaMKII/CREB/BDNF signaling pathway and regulating spinal synaptic plasticity.

BACKGROUND: Central sensitization is one of the important mechanisms underlying neuropathic and radicular pain due to cervical spondylotic radiculopathy (CSR). Recent studies have shown that the calmodulin-dependent protein kinase II (CaMKII)/cAMP-response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway mediates central sensitization through its involvement in spinal cord synaptic plasticity. Our group has previously found that electroacupuncture (EA) has a good analgesic effect on CSR. However, the central analgesic mechanism of EA for CSR is not yet clear. METHODS: The rats were randomly divided into Blank group, Sham-operated group, CSR group, and EA group. We prepared the CSR rat model using the fish wire extrusion method. The behavioral and mechanical pain thresholds of the rats in each group were measured 5 days after successful modeling and 7 days after the intervention. The first intervention was started 5 days after successful modeling, and the EA group was treated by acupuncture at the bilateral LI4 and LR3 points on the same side as one group, connected to a G6805-I electroacupuncture apparatus with continuous waves at 1.5 Hz. The remaining groups were not subjected to EA intervention. The treatment was administered once a day for 7 consecutive days and then executed. We used WB, immunofluorescence, and qRT-PCR to detect the expression of CaMKII/CREB/BDNF signaling pathway-related factors in the synaptic of rat spinal cord in each group. RESULTS: EA improved pain threshold and motor function in CSR rats, inhibited the expression of BDNF, P-TrkB, CAMKII, and P-CREB in spinal cord synapses, reduced the expression of pain factor c-fos and postsynaptic membrane protein molecule neuroligin2, exerted a modulating effect on spinal cord synaptic plasticity in CSR rats, and suppressed the overactive synaptic efficacy. CONCLUSION: EA mediates central sensitization and exerts analgesic effects on CSR by modulating spinal synaptic plasticity, which may be related to the inhibition of CaMKII/CREB/BDNF signaling pathway.

Electroacupuncture attenuates chronic inflammatory pain and depression comorbidity by inhibiting hippocampal neuronal apoptosis via the PI3K/Akt signaling pathway.

In chronic inflammatory pain (CIP) and depression, neuroapoptosis has been identified as a contributing factor. Electroacupuncture (EA) shows promise as an alternative therapy for this comorbidity. However, the underlying mechanism remains unclear. This study aimed to investigate the effects of EA on hippocampal neuronal apoptosis in rats with CIP and depression. Rats received plantar injections of complete Freund's adjuvant (CFA) on days 0 and 14. They were then divided into groups: sham operation, model, EA, and duloxetine. EA was administered at Hegu (LI4) and Taichong (LR3) from days 15 to 28, while the duloxetine group received duloxetine and distilled water daily (0.1 mg/ml). Pain behavior was assessed using the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) tests. Depression-like behavior was evaluated through the sucrose preference test (SPT), open-field test (OFT), and forced swim test (FST). Hematoxylin and eosin (HE) staining was employed to assess pathological changes in the hippocampus. Nerve cell apoptosis was determined using TUNEL fluorescence staining. Western blot analysis was conducted to measure the protein expression of Bcl-2, Bax, p-PI3K/PI3K, and p-Akt/Akt. EA demonstrated significant pain intensity reduction and alleviation of pain-related depressive symptoms. Our findings from the HE staining confirmed that CIP induced by CFA led to morphological changes in the hippocampus, while EA effectively reversed these pathological alterations. Moreover, EA intervention remarkably reduced neuronal apoptosis and exhibited an upregulation of Bcl-2 protein expression accompanied by a decrease in Bax expression. Additionally, EA activated the PI3K/Akt signaling pathway. Overall, our study suggests that EA holds the potential to improve pain and depressive behaviors in rats with CIP and depression comorbidity, potentially mediated through the activation of the PI3K/Akt pathway, leading to a reduction in hippocampal neuronal apoptosis.

Electroacupuncture Attenuates Neuropathic Pain in a Rat Model of Cervical Spondylotic Radiculopathy: Involvement of Spinal Cord Synaptic Plasticity.

Purpose: Cervical spondylotic radiculopathy (CSR) is a common neurologic condition that causes chronic neck pain and motor functions, with neuropathic pain (NP) being the primary symptom. Although it has been established that electroacupuncture (EA) can yield an analgesic effect in clinics and synaptic plasticity plays a critical role in the development and maintenance of NP, the underlying mechanisms have not been fully elucidated. In this study, we explored the potential mechanisms underlying EA's effect on synaptic plasticity in CSR rat models. Materials and Methods: The CSR rat model was established by spinal cord compression (SCC). Electroacupuncture stimulation was applied to LI4 (Hegu) and LR3 (Taichong) acupoints for 20 min once a day for 7 days. Pressure pain threshold (PPT) and mechanical pain threshold (MPT) were utilized to detect the pain response of rats. A gait score was used to evaluate the motor function of rats. Enzyme-linked immunosorbent assay (ELISA), Western blot (WB), immunohistochemistry (IHC), immunofluorescence (IF), and transmission electron microscopy (TEM) were performed to investigate the effects of EA. Results: Our results showed that EA alleviated SCC-induced spontaneous pain and gait disturbance. ELISA showed that EA could decrease the concentration of pain mediators in the cervical nerve root. WB, IHC, and IF results showed that EA could downregulate the expression of synaptic proteins in spinal cord tissues and promote synaptic plasticity. TEM revealed that the EA could reverse the synaptic ultrastructural changes induced by CSR. Conclusion: Our findings reveal that EA can inhibit SCC-induced NP by modulating the synaptic plasticity in the spinal cord and provide the foothold for the clinical treatment of CSR with EA.

Guizhi Fuling Wan inhibits autophagy of granulosa cells in polycystic ovary syndrome mice via H19/miR-29b-3p.

OBJECTIVE: To investigate the potential molecular mechanism of traditional Chinese medicine Guizhi Fuling Wan (GZFLW) inhibiting granulosa cells (GCs) autophagy in polycystic ovary syndrome (PCOS). METHODS: Control GCs and model GCs were cultured and treated with blank serum or GZFLW-containing serum. The levels of H19 and miR-29b-3p in GCs were detected using qRT-PCR, target genes of miR-29b-3p were identified using luciferase assay. The protein expressions of Phosphatase and tensin homolog (PTEN), Matrix Metalloproteinase (MMP)-2, and Bax were measured using western blot. The level of autophagy was detected via MDC staining, the degree of autophagosomes and autophagic polymers was observed using dual fluorescence-tagged mRFP-eGFP-LC3. RESULTS: GZFLW intervention reduced the expression of autophagy-related proteins PTEN, MMP-2 and Bax, by upregulating the expression of miR-29b-3p and downregulated the expression of H19 (p < .05 or p < .01). The number of autophagosomes and autophagy polymers was significantly decreased by GZFLW treatment. However, the inhibition of miR-29b-3p and overexpression of H19 induced a significant increase in the number of autophagosomes and autophagic polymers, which attenuated the inhibitory effect of GZFLW on autophagy (p < .05 or p < .01). In addition, inhibition of miR-29b-3p or overexpression of H19 can attenuate the effect of GZFLW on the expression of PTEN, MMP-2 and Bax proteins (p < .05 or p < .01). CONCLUSION: Our study found that GZFLW inhibits autophagy in PCOS GCs via H19/miR-29b-3p pathway.

Analysis on Value of Continuous Nursing Based on WeChat in Improving Healthy Quality of Life and Self-Management Behavior of Patients with Diabetic Nephropathy.

Objective: To explore the value of continuous nursing (CN) based on WeChat in improving healthy quality of life and self-management behavior of patients with diabetic nephropathy (DN). Methods: A total of 100 patients with DN who were treated in our hospital from November 2019 to January 2020 were selected. Thereinto, 54 patients who received CN based on WeChat were considered as the research group, and 46 patients who received the routine nursing intervention were considered as the control group. Peripheral blood samples were collected before nursing intervention (T0), 1 month after intervention (T1), and 2 months after intervention (T2) to test blood glucose, blood lipid, and renal function. Exercise of self-care agency (ESCA) scale and general self-efficacy scale (GSES) was conducted to evaluate patients' self-management ability, and a short-form 36-item health survey (SF-36) was conducted to evaluate their quality of life. Finally, the treatment compliance and satisfaction of patients were investigated. Results: There was no marked difference in blood glucose, blood lipid, and renal function between groups at T0 (P > 0.05), but the research group was better than the control group at T1 and T2 (P < 0.05). After the nursing intervention, the scores of ESCA, GSES, and SF-36 in the research group were higher (P < 0.05). In addition, the treatment compliance rate and satisfaction of the research group were also higher. Conclusion: CN based on WeChat can effectively improve the self-management behavior and quality of life of DN patients, which is extremely suitable for such chronic diseases with extremely long treatment cycles and can provide a more effective guarantee for their recovery.

[Effect of staged acupuncture on serum irisin level and neurological rehabilitation in patients with ischemic stroke].

OBJECTIVE: To observe the effect of staged acupuncture on serum irisin level, neurological deficit, balance ability and spasticity in patients with ischemic stroke. METHODS: Sixty patients with ischemic stroke were randomly divided into a staged acupuncture group and a routine acupuncture group, 30 cases in each group; another 30 healthy subjects were selected as a normal group. The patients with ischemic stroke were treated with aspirin (100 mg each time, once a day, changing to 50 mg for prophylactic dose after 4 weeks). The patients in the staged acupuncture group were treated with staged acupuncture (acupoints were selected according to the soft paralysis period, spasticity period and recovery period, sequelae period) and rehabilitation treatment, while the patients in the routine acupuncture group were treated with acupuncture of soft paralysis-period as the staged acupuncture group and rehabilitation treatment. All the treatment was given once a day, 5 times a week, 2 weeks as a course of treatment, and 4 consecutive courses of treatment were provided. Before treatment and at 2 weeks, 4 weeks, 6 weeks and 8 weeks into treatment, the serum irisin level was measured, and the scores of National Institutes of Health stroke scale (NIHSS), Fugl-Meyer assessment scale-balance (FM-B) and comprehensive spasticity scale (CSS) were compared, and the correlation between the serum irisin level and NIHSS and FM-B scores in the two groups was analyzed. RESULTS: Before treatment, the serum irisin levels in the two groups were lower than those in the normal group (P<0.01). Compared before treatment, the serum irisin levels and FM-B scores were increased (P<0.01), and the NIHSS scores were decreased at 2, 4, 6 and 8 weeks into treatment in the two groups (P<0.01). At 4, 6 and 8 weeks into treatment, in the staged acupuncture group, the serum irisin levels and FM-B scores were higher than those in the routine acupuncture group (P<0.01, P<0.05), and the NIHSS scores were lower than those in the routine acupuncture group (P<0.01). After treatment, the CSS scores in the two groups were increased first and then decreased. Compared before treatment, the CSS scores were increased at 2, 4, 6 and 8 weeks into treatment in the two groups (P<0.01). At 4, 6 and 8 weeks into treatment, the CSS scores in the staged acupuncture group were lower than those in the routine acupuncture group (P<0.01). The serum irisin level was negatively correlated with NIHSS score (r =-0.772, P =0.000), and positively correlated with FM-B score (r =0.675, P =0.000). CONCLUSION: The severity of neurological deficit and balance ability are related to serum irisin level in patients with ischemic stroke. The staged acupuncture could increase the serum irisin level, improve the neurological function, balance ability and spasticity in patients with ischemic stroke.

Baicalein Attenuates Severe Polymicrobial Sepsis via Alleviating Immune Dysfunction of T Lymphocytes and Inflammation.

OBJECTIVE: To investigate the effect of baicalein on polymicrobial sepsis-induced immune dysfunction and organ injury. METHODS: A sepsis model was induced in Sprague-Dawley rats via caecal ligation and puncture (CLP). Specific pathogen free rats were randomly divided into a sham group, CLP group and CLP + baicalein (Bai) group (n=16 each). Rats in the CLP + Bai group were intravenously injected with baicalein (20 mg/kg) at 1 and 10 h after CLP. Survival rate, bacterial load, and organ damage were assessed. Then each group was evaluated at 6, 12, and 24 h to investigate the effect of baicalein on immune cells and inflammatory cytokines in septic rats. RESULTS: Baicalein treatment significantly improved the survival of septic rats, decreased the bacterial burden, and moderated tissue damage (spleen, liver, and lung), as observed by haematoxylin and eosin staining. Septic rats treated with baicalein had strikingly increased proportions of CD3+CD4+ T cells and ratios of CD4+/CD8+ T cells in the peripheral blood and spleen (all P<0.05). Moreover, baicalein treatment decreased the apoptotic rate of whole white blood cells and spleen cells at 24 h after surgery (P<0.05). Baicalein significantly reduced the levels of tumor necrosis factor α and interleukin-6 (IL-6) and increased IL-10, and the expression levels of galectin 9 were also raised in the spleen (P<0.01). CONCLUSION: Baicalein may be an effective immunomodulator that attenuates overwhelming inflammatory responses in severe abdominal sepsis.

Direct moxibustion exerts an analgesic effect on cervical spondylotic radiculopathy by increasing autophagy via the Act A/Smads signaling pathway.

BACKGROUND: Direct moxibustion (DM) is reported to be useful for cervical spondylotic radiculopathy (CSR), but the analgesic mechanism remains unknown. Autophagy plays a protective role in neuronal apoptosis, Act A/Smads signaling pathway has been confirmed to be associated with the activation of autophagy. The study aimed to explore the effect of DM on autophagy in rats with CSR and the involvement of Act A/Smads signaling pathway. METHODS: Rats were randomly divided into Sham, CSR, CSR + DM, CSR + DM + 3-MA (PI3K inhibitor), and CSR + DM + SB (Act A inhibitor) group. Three days after establishment of CSR model with a fish line inserted under the axilla of the nerve roots, DM at Dazhui (GV14) was performed six times once for seven consecutive days. Western blot and immunofluorescence staining were used to observe the expression of the neuronal autophagy molecule LC3II/I, Atg7, and Act A/Smads signaling molecule Act A, p-Smad2, and p-Smad3. Bcl-2/Bax mRNA expression was measured by real time PCR. RESULTS: DM improved the pain threshold and motor function of CSR rats and promoted the expression of Act A, p-Smad2, p-Smad3, LC3II/I, and Atg7 in the entrapped-nerve root spinal dorsal horn. DM reduced the expression of Bax mRNA and decreased the number of apoptotic neurons. 3-MA and Act A inhibitor SB suppressed the expression of above-mentioned proteins and reduced the protective effect of DM on apoptotic neurons. CONCLUSION: DM exerts analgesic effects by regulating the autophagy to reduce cell apoptosis and repair nerve injury, and this feature may be related to the Act A/Smads signaling pathway.

Utilizing network pharmacology to explore potential mechanisms of YiSui NongJian formula in treating myelodysplastic syndrome.

The study aims to explore potential mechanisms of YiSui NongJian formula (YSNJF) in treating myelodysplastic syndromes (MDS) by network pharmacology-based strategy. Active compounds and corresponding potential therapeutic targets of YSNJF were harvested by utilizing the database of TCMSP (Traditional Chinese Medicine Systems Pharmacology) and BATMAN-TCM (Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine). MDS targets were adopted from GeneCard, KEGG (Kyoto Encyclopedia of Genes and Genomes), TTD (Therapeutic Target Database), DrugBank, and DisGeNet. Then a network of YSNJF- compounds-target-MDS network was harvested. The protein-protein interaction (PPI) network was then generated by the Sting database and subjected to Cytoscape software to harvest major and core targets network by topological analysis. Genes from the core targets network were further subjected to Gene Ontology (GO) and KEGG enrichment analysis to figure out potential targeting pathways. Finally, a compounds-targets-pathways network was generated by Cytoscape. A total of 210 active compounds and 768 corresponding potential therapeutic targets were harvested from ingredients of YSNJF. MDS was shown to have 772 potential treating targets with 98 intersected targets corresponding to 98 active compounds in YSNJF. Topological analysis revealed that 15 targets formed the core PPI network. Further, GO and KEGG enrichment analysis revealed that those core targets were mainly enriched on cell cycle- and immune-related pathways. The present study revealed that therapeutic effects of YSNJF on MDS might be achieved through regulating cell cycle- and immune-related pathways.

Resuming Sensitivity of Tamoxifen-Resistant Breast Cancer Cells to Tamoxifen by Tetrandrine.

BACKGROUND: Tamoxifen is one of the medicines for adjuvant endocrine therapy of hormone-dependent breast cancer. However, development of resistance to tamoxifen occurs inevitably during treatment. This study aimed to determine whether sensitivity of tamoxifen-resistant breast cancer cells (TAM-R) could be reinstated by tetrandrine (Tet). METHODS: All experiments were conducted in TAM-R cells derived from the MCF-7 breast cancer cell line by long-term tamoxifen exposure. Cell growth, apoptosis, and autophagy were end-points that evaluated the effect of Tet (0.9 µg/ml, 1.8 µg/ml, and 3.75 µg/ml) alone or in combination with TAM (1 µM). Cell apoptosis was determined by an ELISA assay and autophagy was determined by fluorescent staining using the Enzo autophagy detection kit. Immunoblotting was used to evaluate markers for apoptosis, autophagy, and related signal pathway molecules. RESULTS: Growth of TAM-R cells was significantly inhibited by Tet. Combination of Tet with tamoxifen induced a greater inhibition on cell growth than tamoxifen alone, which was predominantly due to enhancement of pro-apoptotic effect of TAM by Tet. Autophagy was significantly inhibited in TAM-R cells treated with Tet plus TAM as shown by increased autophagosomes and the levels of LC3-II and p62. At 0.9 µg/ml, Tet increased the levels of both apoptosis and autophagy markers. Among them increase in p53 levels was more dramatic. CONCLUSIONS: Tet as a monotherapy inhibits TAM-R cells. Tet potentiates the pro-apoptotic effect of TAM via inhibition of autophagy.

Efficacy of coenzyme Q10 supplementation on glucose metabolism, lipid profiles, and biomarkers of inflammation in women with polycystic ovary syndrome: A protocol for a systematic review and meta-analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the common gynecological endocrine system diseases. It is characterized by excessive androgen, rare or anovulation, and polycystic ovary morphology. Coenzyme Q10 (CoQ10) is a fat-soluble natural vitamin, which has a continuous oxidation-reduction cycle and is an effective antioxidant that can protect ovaries from oxidative damage. This study aims to systematically summarize and analyze the scientific literatures on glucose metabolism index, lipid profiles, inflammatory factor, and sex hormone level of PCOS patients treated with CoQ10 to provide a reference basis for clinical treatment. METHODS: We will retrieve the following electronic databases from the built-in until March 2021: Cochrane Library, PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Clinical Trials. gov, Chinese Scientific Journal Database (VIP), and Wang-fang database. Two reviewers will independently scan the articles searched, de-duplication, filtering, quality assessment. Differences will be resolved by discussion between the 2 reviewers or by a third reviewers. All analyses were systematic to evaluate interventions based on the Cochrane handbook. Meta-analysis and/or subgroup analysis will be performed on the basis of the included studies. DISCUSSION: This review will be to investigate the efficacy of CoQ10 supplementation on glucose metabolism, lipid profiles, and biomarkers of inflammation in women with PCOS and provide a high-quality synthesis to assess whether CoQ10 is an effective and safe intervention for PCOS. The results of the analysis will be published in a scientific journal after peer-review. SYSTEMATIC REVIEW REGISTRATION: INPLASY 2020100013.

Efficacy of different forms of Guizhi Fuling Wan on reproduction and metabolism in women with polycystic ovary syndrome: A protocol for a meta-analysis of randomized controlled trials.

BACKGROUND: Polycystic ovary syndrome (PCOS), is a common endocrine disorder in women characterized by increased androgen levels, ovulatory dysfunction, and polycystic ovaries. Western medicine is widely used for the treatment of PCOS, but patient satisfaction is low, largely due to its associated gastrointestinal symptoms of nausea and diarrhea. Guizhi Fuling Wan (GFW) is a traditional Chinese medicine used to remove blood stasis and dissipate phlegm for treating gynecological diseases that was invented by Zhang Zhongjing in the Eastern Han dynasty. In recent years, GFW has been widely used to treat patients with PCOS. This study aims to assess the efficacy and safety of GFW in the treatment of PCOS through a systematic review and meta-analysis. METHODS: All randomized controlled trials connected with GFW targeting PCOS will be searched in the following electronic bibliographic databases from their earliest recorded publications to December 2020 without any language restrictions: MEDLINE, Embase, PubMed, Web of Science, China National Knowledge Infrastructure, Chinese Biological Medicine Database, Wan-fang data, Chinese Technical Periodicals, and other databases. The primary outcomes include Sex hormone levels, ovulation rate, pregnancy rate, and total effective rate. The secondary outcomes were Total cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein, fasting glucose, fasting insulin, insulin sensitivity index, body mass index, hypertrichosis score, acne score, adverse reactions, etc. Two reviewers will independently conduct cations retrieval, de-duplication, filtering, quality assessment, and data analysis by Endnote X9.1 and Review Manager software (RevMan V.5.3). Meta-analysis and/or subgroup analysis will be performed on the included data. DISCUSSION: This study will investigate the application of GFW in the treatment or prevention of PCOS, and provide a high-quality synthesis to judge whether GFW is an effective and safe intervention for PCOS. PROSPERO REGISTRATION NUMBER: CRD42020192405.

Cytological and genetic characterisation of dominant GMS line Shaan-GMS in Brassica napus L.

Genic male sterility (GMS) is an effective pollination control system applied in the hybrid breeding of Brassica napus L. Shaan-GMS is a spontaneous mutant of dominant GMS in B. napus. In this research, anther abortion in the homozygous two-type line 9A15AB derived from Shaan-GMS was characterised with the combined use of light microscopy and transmission electron microscopy. Results indicated that the most striking differences between the fertile and sterile plants occurred in the tapetum in the early microsporocyte stage. In sterile plants, the tapetal cells were irregularly arranged, multi-layered and occupied the growing space of microsporocytes. When entering into meiosis, the tapetum cells degraded and the cytoplasm fused. Some oval monolayer or bilayer membrane organelles existed in the tapetal cells in sterile anthers. Mitochondria in the tapetal cells were abnormal, and middle layer cells degraded early. Pollen mother cells of Shaan-GMS degenerated at the start of meiosis and ceased at the anaphase I stage, with no dyads or tetrads formed. The combined effects of the abnormal development of the tapetum, the middle layer cells and meiosis lead to male sterility in Shaan-GMS. Inheritance of male sterility of Shaan-GMS is controlled by a monogenically multiallelic locus with three different alleles (Ms, ms and Mf), with a relationship expressed as Mf > Ms and Ms > ms. The findings help lay the foundation for illustrating the mechanism of male sterility and the utilisation of Shaan-GMS in rapeseed.

Composition characterization and biotransformation of dissolved, particulate and algae organic phosphorus in eutrophic lakes.

Characteristics and transformation of organic phosphorus in water are vital to biogeochemical cycling of phosphorus and support of blooms of phytoplankton and cyanobacteria. Using solution 31P nuclear magnetic resonance (NMR), combined with field surveys and lab analyses, composition and structural characteristics of dissolved phosphorus (DP), particulate phosphorus (PP) and organic P in algae were studied in two eutrophic lakes in China, Tai Lake and Chao Lake. Factors influencing migration and transformation of these constituents in lake ecosystems were also investigated. A method was developed to extract, flocculate and concentrate DP and PP from lake water samples. Results showed that orthophosphate (Ortho-P) constituted 32.4%-81.3% of DP and 43.7%-54.9% of PP, respectively; while monoester phosphorus (Mono-P) was 13.2%-54.0% of DP and 32.9%-43.7% of PP, respectively. Phosphorus in algae was mostly organic P, especially Mono-P, which was ≥50% of TP. Environmental factors and water quality parameters such as temperature (T), electrical conductivity (EC), pH, secchi depth (SD), dissolved oxygen (DO), chemical oxygen demand (CODcr), chlorophyll-a (Chl-a), affected the absolute and relative concentrations of various P components in the two lakes. Increased temperature promoted bioavailable P (Ortho-P and Mono-P) release to the lake waters. The results can provide an important theoretical basis for the mutual conversion process of organic P components between various media in the lake water environment.

The value of serum metabolomics analysis in predicting the response to cardiac resynchronization therapy.

OBJECTIVE: To construct a prediction model based on metabolic profiling for predicting the response to cardiac resynchronization therapy (CRT). METHODS: Peripheral venous (PV) and coronary sinus (CS) blood samples were collected from 25 patients with heart failure (HF) at the time of CRT implantation, and PV blood samples were obtained from ten healthy controls. The serum samples were analyzed by liquid chromatography-mass spectrometry (LC-MS). As per the clinical and echocardiographic assessment at the 6-month follow-up, the HF patients were categorized as CRT responders and non-responders. RESULTS: HF patients had altered serum metabolomic profiles that were significantly different from those of the healthy controls. Differential metabolites were also observed between CRT responders and non-responders. A prediction model for CRT response (CRT-Re) was constructed using the concentration levels of the differential metabolites, L-arginine and taurine. The optimal cutoff value of the CRT-Re model was found to be 0.343 by ROC analysis (sensitivity, 88.2%; specificity, 87.5%; Area under curve (AUC) = 0.897, P = 0.002). The concentration levels of the differential metabolites, L-arginine and lysyl-gamma-glutamate, in PV serum were significantly correlated with that in CS serum (r = 0.945 and 0.680, respectively, all P < 0.001). CONCLUSIONS: Our results suggest that serum-based metabolic profiling may be a potential complementary screening tool for predicting the outcome of CRT.