Integrative approach using network pharmacology, bioinformatics, and experimental methods to explore the mechanism of cantharidin in treating colorectal cancer.

Cantharidin, a terpenoid produced by blister beetles, has been used in traditional Chinese medicine to treat various ailments and cancers. However, its biological activity, impact, and anticancer mechanisms remain unclear. The Cantharidin chemical gene connections were identified using various databases. The GSE21815 dataset was used to collect the gene expression information. Differential gene analysis and gene ontology analyses were performed. Gene set enrichment analysis was used to assess the activation of disease pathways. Weighted gene co-expression network analysis and differential analysis were used to identify illness-associated genes, examine differential genes, and discover therapeutic targets via protein-protein interactions. MCODE analysis of major subgroup networks was used to identify critical genes influenced by Cantharidin, examine variations in the expression of key clustered genes in colorectal cancer vs. control samples, and describe the subject operators. Single-cell GSE188711 dataset was preprocessed to investigate Cantharidin's therapeutic targets and signaling pathways in colorectal cancer. Single-cell RNA sequencing was utilized to identify 22 cell clusters and marker genes for two different cell types in each cluster. The effects of different Cantharidin concentrations on colorectal cancer cells were studied in vitro. One hundred and ninety-seven Cantharidin-associated target genes and 480 critical genes implicated in the development of the illness were identified. Cantharidin significantly inhibited the proliferation and migration of HCT116 cells and promoted apoptosis at certain concentrations. Patients on current therapy develop inherent and acquired resistance. Our study suggests that Cantharidin may play an anti-CRC role by modulating immune function.

Co-inoculation of Soybean Seedling with Trichoderma asperellum and Irpex laceratus Promotes the Absorption of Nitrogen and Phosphorus.

Soybean are one of the main oil crops in the world. The study demonstrated that co-inoculation with Trichoderma asperellum (Sordariomycetes, Hypocreomycetidae) and Irpex laceratus (Basidiomycota, Polyporales) isolated from Kosteletzkya virginica can promote the growth of soybean seedlings. The two fungi were found to produce various enzymes, including cellulase, amylase, laccase, protease, and urease. Upon inoculation, T. asperellum mainly colonized within the phloem of the roots in soybean seedlings, while I. laceratus mainly in the xylem and phloem of the roots. Physiological parameters, such as plant height, root length, and fresh weight, were significantly increased in soybean seedlings co-inoculated with T. asperellum and I. laceratus. Moreover, the expression of key genes related to N and P absorption and metabolism was also increased, leading to improved N and P utilization efficiency in soybean seedlings. These results indicate that the two fungi may have complementary roles in promoting plant growth, co-inoculation with T. asperellum and I. laceratus can enhance the growth and nutrient uptake of soybean. These findings suggest that T. asperellum and I. laceratus have the potential to be used as bio-fertilizers to improve soybean growth and yield.

Compound Kushen injection combined with transarterial chemoembolization for hepatocellular carcinoma: An evidence map and overview of systematic reviews.

ETHNOPHARMACOLOGICAL RELEVANCE: For the treatment of hepatocellular carcinoma (HCC), compound Kushen injection (CKi) is commonly used in combination with transarterial chemoembolization (TACE). AIMS OF THE STUDY: Our objective was to evaluate the reporting quality, methodological quality, risk of bias, and certainty of evidence for CKi combined with TACE for the treatment of patients with HCC by conducting systematic reviews (SRs). The purpose of this study was to improve the clinical application of CKis, strengthen clinical decision-making regarding CKis, and inform future research. MATERIALS AND METHODS: We used eight databases to systematically search SRs of CKi combined with TACE for HCC through February 21, 2023. The quality of reporting of SRs was evaluated using the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, methodological quality using A MeaSurement Tool to Assess systematic Reviews 2, risk of bias using the Risk of Bias in Systematic Review, and certainty of evidence using the Grading of Recommendations Assessment. Finally, the assessment results were visualized by the evidence mapping method. This overview has been registered on PROSPERO with the registration title "Compound Kushen injection for hepatocellular carcinoma: An overview of systematic reviews" and registration number CRD42022369120. RESULTS: A total of 12 SRs meeting the inclusion criteria were included. In terms of reporting quality, 42% of SRs reported relatively complete reports and 58% had certain deficiencies. The methodological quality of all SRs was " critically low". The risk of bias was evaluated as low in 33% of SRs and high in 67% of SRs. The results of the evidence synthesis showed that, in the "moderate" level of evidence, CKi combined with TACE resulted in a 12.7%-21.5% benefit for one-year survival rate, 11.7%-17.2% benefit for objective response rate (ORR), 20.5%-27.1% benefit for quality of life, 22.2% benefit for nausea and vomiting, and 24.7%-27.4% benefit for leukopenia in HCC patients. CONCLUSION: In conclusion, CKi combined with TACE improved survival, ORR and quality of life in patients with HCC, and reduced adverse events. The results should be interpreted with caution due to the low methodological quality of the included SRs. The clinical efficacy of CKis must be confirmed in a large number of randomized controlled trials.

Eleutheroside E from pre-treatment of Acanthopanax senticosus (Rupr.etMaxim.) Harms ameliorates high-altitude-induced heart injury by regulating NLRP3 inflammasome-mediated pyroptosis via NLRP3/caspase-1 pathway.

Eleutheroside E, a major natural bioactive compound in Acanthopanax senticosus (Rupr.etMaxim.) Harms, possesses anti-oxidative, anti-fatigue, anti-inflammatory, anti-bacterial and immunoregulatory effects. High-altitude hypobaric hypoxia affects blood flow and oxygen utilisation, resulting in severe heart injury that cannot be reversed, thereby eventually causing or exacerbating high-altitude heart disease and heart failure. The purpose of this study was to determine the cardioprotective effects of eleutheroside E against high-altitude-induced heart injury (HAHI), and to study the mechanisms by which this happens. A hypobaric hypoxia chamber was used in the study to simulate hypobaric hypoxia at the high altitude of 6000 m. 42 male rats were randomly assigned to 6 equal groups and pre-treated with saline, eleutheroside E 100 mg/kg, eleutheroside E 50 mg/kg, or nigericin 4 mg/kg. Eleutheroside E exhibited significant dose-dependent effects on a rat model of HAHI by suppressing inflammation and pyroptosis. Eleutheroside E downregulated the expressions of brain natriuretic peptide (BNP), creatine kinase isoenzymes (CK-MB) and lactic dehydrogenase (LDH). Moreover, The ECG also showed eleutheroside E improved the changes in QT interval, corrected QT interval, QRS interval and heart rate. Eleutheroside E remarkably suppressed the expressions of NLRP3/caspase-1-related proteins and pro-inflammatory factors in heart tissue of the model rats. Nigericin, known as an agonist of NLRP3 inflammasome-mediated pyroptosis, reversed the effects of eleutheroside E. Eleutheroside E prevented HAHI and inhibited inflammation and pyroptosis via the NLRP3/caspase-1 signalling pathway. Taken together, eleutheroside E is a prospective, effective, safe and inexpensive agent that can be used to treat HAHI.

Pretreatment with Notoginsenoside R1 attenuates high-altitude hypoxia-induced cardiac injury via activation of the ERK1/2-P90RSK-Bad signaling pathway in rats.

High-altitude cardiac injury (HACI) is one of the common tissue injuries caused by high-altitude hypoxia that may be life threatening. Notoginsenoside R1 (NG-R1), a major saponin of Panax notoginseng, exerts anti-oxidative, anti-inflammatory, and anti-apoptosis effects, protecting the myocardium from hypoxic injury. This study aimed to investigate the protective effect and molecular mechanism of NG-R1 against HACI. We simulated a 6000 m environment for 48 h in a hypobaric chamber to create a HACI rat model. Rats were pretreated with NG-R1 (50, 100 mg/kg) or dexamethasone (4 mg/kg) for 3 days and then placed in the chamber for 48 h. The effect of NG-R1 was evaluated by changes in Electrocardiogram parameters, histopathology, cardiac biomarkers, oxidative stress and inflammatory indicators, key protein expression, and immunofluorescence. U0126 was used to verify whether the anti-apoptotic effect of NG-R1 was related to the activation of ERK pathway. Pretreatment with NG-R1 can improve abnormal cardiac electrical conduction and alleviate high-altitude-induced tachycardia. Similar to dexamethasone, NG-R1 can improve pathological damage, reduce the levels of cardiac injury biomarkers, oxidative stress, and inflammatory indicators, and down-regulate the expression of hypoxia-related proteins HIF-1α and VEGF. In addition, NG-R1 reduced cardiomyocyte apoptosis by down-regulating the expression of apoptotic proteins Bax, cleaved caspase 3, cleaved caspase 9, and cleaved PARP1 and up-regulating the expression of anti-apoptotic protein Bcl-2 through activating the ERK1/2-P90RSK-Bad pathway. In conclusion, NG-R1 prevented HACI and suppressed apoptosis via activation of the ERK1/2-P90RSK-Bad pathway, indicating that NG-R1 has therapeutic potential to treat HACI.

iMSEA: A Novel Metabolite Set Enrichment Analysis Strategy to Decipher Drug Interactions.

Drug combinations are commonly used to treat various diseases to achieve synergistic therapeutic effects or to alleviate drug resistance. Nevertheless, some drug combinations might lead to adverse effects, and thus, it is crucial to explore the mechanisms of drug interactions before clinical treatment. Generally, drug interactions have been studied using nonclinical pharmacokinetics, toxicology, and pharmacology. Here, we propose a complementary strategy based on metabolomics, which we call interaction metabolite set enrichment analysis, or iMSEA, to decipher drug interactions. First, a digraph-based heterogeneous network model was constructed to model the biological metabolic network based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Second, treatment-specific influences on all detected metabolites were calculated and propagated across the whole network model. Third, pathway activity was defined and enriched to quantify the influence of each treatment on the predefined functional metabolite sets, i.e., metabolic pathways. Finally, drug interactions were identified by comparing the pathway activity enriched by the drug combination treatments and the single drug treatments. A data set consisting of hepatocellular carcinoma (HCC) cells that were treated with oxaliplatin (OXA) and/or vitamin C (VC) was used to illustrate the effectiveness of the iMSEA strategy for evaluation of drug interactions. Performance evaluation using synthetic noise data was also performed to evaluate sensitivities and parameter settings for the iMSEA strategy. The iMSEA strategy highlighted synergistic effects of combined OXA and VC treatments including the alterations in the glycerophospholipid metabolism pathway and glycine, serine, and threonine metabolism pathway. This work provides an alternative method to reveal the mechanisms of drug combinations from the viewpoint of metabolomics.

GC-MS and UHPLC-QTOFMS-assisted identification of the differential metabolites and metabolic pathways in key tissues of Pogostemon cablin.

Pogostemon cablin is an important aromatic medicinal herb widely used in the pharmaceutical and perfume industries. However, our understanding of the phytochemical compounds and metabolites within P. cablin remains limited. To our knowledge, no integrated studies have hitherto been conducted on the metabolites of the aerial parts of P. cablin. In this study, twenty-three volatile compounds from the aerial parts of P. cablin were identified by GC-MS, predominantly sesquiterpenes. Quantitative analysis showed the highest level of patchouli alcohol in leaves (24.89 mg/g), which was 9.12 and 6.69-fold higher than in stems and flowers. UHPLC-QTOFMS was used to analyze the non-volatile compounds of leaf, stem and flower tissues. The differences in metabolites between flower and leaf tissues were the largest. Based on 112, 77 and 83 differential metabolites between flower-leaf, flower-stem and leaf-stem, three tissue-specific biomarkers of metabolites were identified, and the differential metabolites were enriched in several KEGG pathways. Furthermore, labeling differential metabolites in the primary and secondary metabolic pathways showed that flowers accumulated more lipids and amino acids, including proline, lysine and tryptophan; the leaves accumulated higher levels of terpenoids, vitamins and flavonoids, and stems contained higher levels of carbohydrate compounds. Based on the role of acetyl coenzyme A, the distribution and possible exchange mechanism of metabolites in leaves, stems and flowers of P. cablin were mapped for the first time, laying the groundwork for future research on the metabolites in P. cablin and their regulatory role.

The Effect of Traditional Chinese Medicine on Postviral Olfactory Dysfunction: A Systematic Review and Meta-Analysis.

Objective: The aim of this study is to evaluate the efficacy and safety of traditional Chinese medicine (TCM) for postviral olfactory dysfunction (PVOD). Methods: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, China Network Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), Chinese Biomedical and Medical (CBM) Database, and Wanfang Database were electronically searched from their inception to July 25, 2022. Two authors independently performed study selection, data extraction, and quality assessment to ensure systematic quality evaluation. Randomized controlled trials (RCTs) comparing TCM with olfactory training and/or drug therapy (OTDT) were included. The outcomes were the effective rate, QOD-P, TDI score, UPSIT score, and adverse effects. Cochrane RoB was the guideline used to evaluate the methodological quality of the included trials. RevMan 5.3 software was used for statistical analysis. Results: A total of 6 RCTs involving 467 patients with PVOD were selected. Compared with OTDT, TCM plus OTDT decreased QOD-P (MD = -1.73, 95% CI (-2.40, -1.06), P < 0.0001) but did not increase the effective rate (T&T) (RR = 1.28, 95% CI (0.86, 1.90), P=0.22, I 2 = 61%). Compared with no treatment, TCM seemed to increase the treatment success rate (UPSIT) (RR = 3.17, 95% CI (1.78, 5.65), P < 0.0001, I 2 = 0%), but there was no statistically significant difference in improving the UPSIT score (MD = 3.44, 95% CI (-1.36, 8.24), P=0.16). Compared with drug therapy, TCM plus drug therapy appeared to increase the effective rate (ΔVAS) (RR = 2.36, 95% CI (1.41, 3.94), I 2 = 0%), but there was no statistically significant difference in improving the TDI score (MD = 2.10, 95% CI (-1.99, 6.19), P=0.31). No significant differences in adverse reactions were reported between TCM and OTDT. Conclusion: TCM may be an effective treatment for PVOD. With a lack of high-quality RCTs, further large-scale and high-quality RCTs are still warranted.

Effective materials and mechanisms study of Tibetan herbal medicine Lagotis integra W. W. Smith treating DSS-induced ulcerative colitis based on network pharmacology, molecular docking and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Lagotis integra W. W. Smith (L. integra W. W. Smith) is an important origin plant of the famous Tibetan medicine HERBA LAGOTIS. It was documented to treat "Chi Ba" disease clinically, the symptoms of which are similar to ulcerative colitis (UC). AIMS OF THIS STUDY: To screen out the active components and study the mechanisms of L. integra W. W. Smith treating UC. MATERIALS AND METHODS: The components of L. integra W. W. Smith were comprehensively analyzed using UHPLC-Q-TOF/MS method. The mechanisms were investigated using network pharmacology method including target prediction, protein-protein interaction network analysis and gene enrichment analysis. Then, the mechanisms were verified using Dextran Sulfate Sodium (DSS)-induced UC model. Finally, the core active components were further screened out through molecular docking. RESULTS: The results showed that 32 major components were identified including 8 flavonoids, 9 phenylpropanoid glycosides, 13 iridoid glycosides and 1 phenolic acid. 76 potential core therapeutic targets and top 5 key targets, which were AKT serine/threonine kinase 1 (AKT1), vascular endothelial growth factor (VEGFA), tumor necrosis factor-α (TNF-α), epidermal growth factor receptor (EGFR) and caspase-3 (CASP3), were screened out according to network pharmacology analysis. Animal experiments confirmed that those compounds could downregulate the expression levels of the 5 key target proteins in colonic tissue of mice to exert excellent anti-UC effect. Molecular docking results showed that the main active components were echinacoside, hemiphroside B, plantamajoside, plantainoside D, 10-O-trans-isoferuloyl catalpol and scutellarioside II. CONCLUSIONS: For the first time, our study provides insights into the effective materials and molecular mechanisms of L. integra W. W. Smith treating UC, which contributes to the understanding of its pharmacodynamics.

Pretreatment with rosavin attenuates PM2.5-induced lung injury in rats through antiferroptosis via PI3K/Akt/Nrf2 signaling pathway.

Inflammation and oxidative stress caused by fine particulate matter (PM2.5) increase the incidence and mortality rates of respiratory disorders. Rosavin is the main chemical component of Rhodiola plants, which exerts anti-oxidative and antiinflammatory effects. In this research, the potential therapeutic effect of rosavin was investigated by the PM2.5-induced lung injury rat model. Rats were instilled with PM2.5 (7.5 mg/kg) suspension intratracheally, while rosavin (50 mg/kg, 100 mg/kg) was delivered by intraperitoneal injection before the PM2.5 injection. It was observed that rosavin could prevent lung injury caused by PM2.5. PM2.5 showed obvious ferroptosis-related ultrastructural alterations, which were significantly corrected by rosavin. The pretreatment with rosavin downregulated the levels of tissue iron, malondialdehyde, and 4-hydroxynonenal, and increased the levels of glutathione. The expression of nuclear factor E2-related factor 2 (Nrf2) was upregulated by rosavin, together with other ferroptosis-related proteins. RSL3, a specific ferroptosis agonist, reversed the beneficial impact of rosavin. The network pharmacology approach predicted the activation of rosavin on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. LY294002, a potent PI3K inhibitor, decreased the upregulation of Nrf2 induced by rosavin. In conclusion, rosavin prevented lung injury induced by PM2.5 stimulation and suppressed ferroptosis via upregulating PI3K/Akt/Nrf2 signaling pathway.

[Activity of Codonopsis canescens against rheumatoid arthritis based on TLRs/MAPKs/NF-κB signaling pathways and its mechanism].

This paper aims to explore the activity of Codonopsis canescens extract against rheumatoid arthritis(RA) based on the Toll-like receptors(TLRs)/mitogen-activated protein kinases(MAPKs)/nuclear factor kappa B(NF-κB) signaling pathways and its mechanism. The ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) was used to identify the components of C. canescens extract. Forty-eight male SD rats were randomly divided into six groups, namely the normal group, the model group, the methotrexate(MTX) tablet group, and the low, medium, and high-dose C. canescens extract(ZDS-L, ZDS-M, and ZDS-H) groups, with 8 rats in each group. The model of collagen-induced arthritis in rats was induced by injection of bovine type Ⅱ collagen emulsion. MTX(2.5 mg·kg~(-1)), ZDS-L, ZDS-M, and ZDS-H(0.3 g·kg~(-1), 0.6 g·kg~(-1), and 1.2 g·kg~(-1)) were administrated by gavage. Rats in the normal group and the model group received distilled water. MTX was given once every three days for 28 days, and the rest medicines were given once daily for 28 days. Body weight, degree of foot swelling, arthritis index, immune organ index, synovial histopathological changes, and serum levels of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), and interleukin-6(IL-6) were observed. Protein expressions of TLR2, TLR4, NF-κB p65, p38 MAPK, and p-p38 MAPK in rats were determined by Western blot. Thirty-four main components were identified by UPLC-Q-TOF-MS, including 15 flavonoids, 7 phenylpropanoids, 4 terpenoids, 4 organic acids, 2 esters, and 2 polyalkynes. As compared with the normal group, the body weight of the model group was significantly decreased(P<0.01), and foot swelling(P<0.05, P<0.01), arthritis index(P<0.01), and the immune organ index(P<0.01) were significantly increased. The synovial histopathological injury was obviously observed in the model group. The serum levels of inflammatory factors TNF-α, IL-1ß, and IL-6 were significantly increased(P<0.01), and the protein expression levels of TLR2, TLR4, NF-κB p65, p-p38 MAPK/p38 MAPK in the synovial tissue were significantly increased(P<0.01) in the model group. As compared with the model group, the body weights of the ZDS dose groups were increased(P<0.01), and the degree of foot swelling(P<0.01) and the arthritis index were decreased(P<0.05, P<0.01). The immune organ index was decreased(P<0.01) in the ZDS dose groups, and the synovial tissue hyperplasia and inflammatory cell infiltration were alleviated. The serum levels of TNF-α, IL-1ß, and IL-6 were significantly decreased(P<0.05, P<0.01), and the protein expression levels of TLR2, TLR4, NF-κB p65, p-p38 MAPK/p38 MAPK were decreased(P<0.05, P<0.01) in the ZDS dose groups. C. canescens extract containing apigenin, tricin, chlorogenic acid, aesculin, ferulic acid, caffeic acid, and oleanolic acid has a good anti-RA effect, and the mechanism may be related to the inhibition of TLRs/MAPKs/NF-κB signaling pathways.

Antimicrobial and anti-biofilm activity of Polygonum chinense L.aqueous extract against Staphylococcus aureus.

Polygonum chinense Linn. (Polygonum chinense L.) is one of the main raw materials of Chinese patent medicines such as Guangdong herbal tea. The increasing antibiotic resistance of S. aureus and the biofilm poses a serious health threat to humans, and there is an urgent need to provide new antimicrobial agents. As a traditional Chinese medicine, the antibacterial effect of Polygonum chinense L. has been reported, but the antibacterial mechanism of Polygonum chinense L.aqueous extract and its effect on biofilm have not been studied in great detail, which hinders its application as an effective antibacterial agent. In this study, the mechanism of action of Polygonum chinense L.aqueous extract on Staphylococcus aureus (S. aureus) and its biofilm was mainly evaluated by morphological observation, flow cytometry and laser confocal experiments. Our findings demonstrate that Polygonum chinense L.aqueous extract has a significant bacteriostatic effect on S. aureus. The result of growth curve exhibits that Polygonum chinense L.aqueous extract presents a significant inhibitory effect against S. aureus. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) reveals that Polygonum chinense L.aqueous extract exerts a potent destruction of the cell wall of S. aureus and a significant inhibitory effect on the formation of S. aureus biofilm. In addition, flow cytometry showed the ability of Polygonum chinense L.aqueous extract to promote apoptosis by disrupting cell membranes of S. aureus. Notably, confocal laser scanning microscopy (CLSM) images illustrated the ability of Polygonum chinense L.aqueous to inhibit the formation of S. aureus biofilms in a dose-dependent manner. These results suggested that Polygonum chinense L.aqueous is a promising alternative antibacterial and anti-biofilm agent for combating infections caused by planktonic and biofilm cells of S. aureus.

Efficacy and safety of acupuncture for chemotherapy-induced leukopenia: A systematic review and meta-analysis.

BACKGROUND: Leukopenia is one of most common types of myelosuppression secondary to chemotherapy. The main methods used to treat leukopenia after chemotherapy have various limitations. Several studies have reported the role of acupuncture in the prevention and treatment of leukopenia, but the quality of the study is uneven. Here, we used a systematic review and meta-analysis to evaluate the efficacy and safety of acupuncture in the treatment of leukopenia after chemotherapy. METHODS: We searched the databases of the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Library, Medline (via PubMed), EMBASE (via embase.com), the China National Knowledge Infrastructure Database (CNKI), the Chinese Biomedical Literature Database (CBM), the Chinese Scientific Journal Database (VIP database) and the Wanfang database to collect randomized clinical trials (RCTs) on acupuncture in the treatment of leukopenia after chemotherapy. Cochrane systematic reviewer manual 5.2 was used for bias risk assessment. RevMan5.3 statistical software was applied for statistical analysis. RESULTS: Fifteen RCTs were included in this study, with a total of 1130 patients. Meta-analysis results showed that acupuncture can increase white blood cell (WBC) count after chemotherapy [MD = 1.18, 95% CI (0.80, 1.57), P < .00001], reduce the incidence of myelosuppression [RR = 0.38, 95% CI (0.23, 0.63), P = .0002], and improve the clinical treatment effectiveness [RR = 1.20, 95% CI (1.00, 1.43), P = .05]. The differences were statistically significant. CONCLUSION: It is recommended to use acupuncture in the treatment of leukocytopenia after chemotherapy, but this result needs further research for verification.

The modulatory effect of 100 Hz electroacupuncture on striatal synaptic plasticity in unilateral lesioned 6-OHDA rats.

Recent studied have reported that impaired striatal synaptic plasticity played a crucial role in Parkinson's disease (PD). Previous studies have suggested that electroacupuncture (EA) alleviated the motor deficits in PD patients and animal models. However, the mechanisms underlying this protection need to be further elucidated. In this study, we found that EA-induced improvement of motor deficits in the 6-hydroxydopamine (6-OHDA) rat model doesn't act through dopaminergic system. EA rescued the decreased striatal long-term potentiation (LTP) in 6-OHDA rats. In addition, the declined expression of N-methyl-D-aspartic acid receptor subunit 2B (NR2B) in the striatum was remarkably up-regulated by EA. The EA-induced improvement of LTP can be eliminated by NR2B-selective inhibitor. It is indicated that EA-induced recovery of striatal LTP was correlated with the up-regulation of NR2B subunit. EA was also found to rescue the decreased dendritic arborization and the spine density in the striatum of 6-OHDA rats. Meanwhile, EA suppressed striatal glutamate content and vesicular glutamate transporter 1 which is expressed in cortico-striatal glutamatergic projections. The decrease of striatal glutamate content induced by decortication, EA treatment or a combination of both reversed the loss of striatal spine density in 6-OHDA rats. It is indicated that EA-induced reduction of cortico-striatal glutamate transmission contributes to the recovery of striatal spine density. In conclusion, the therapeutic effect of EA on the motor deficits of 6-OHDA rats was mediated by rescuing cortico-striatal glutamate transmission and striatal synaptic plasticity.

Effect of Pulmonary Rehabilitation on Postoperative Clinical Status in Patients with Lung Cancer and Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

Pulmonary rehabilitation (PR) has a curative effect in patients undergoing pneumonectomy for lung cancer. Nevertheless, the contribution of PR to the clinical status of patients with chronic obstructive pulmonary disease (COPD) undergoing lung resection has not been adequately elucidated. The aim of this systematic review of randomized and nonrandomized controlled trials was to appraise the impact of PR compared to conventional treatment based on postoperative clinical status in patients with lung cancer and COPD. Literature in English from PubMed, Cochrane Library, Science Citation Index, and Embase databases and in Chinese from the Chinese National Knowledge Infrastructure and the WANFANG Database was retrieved from inception to November 2021, employing the keywords "Pulmonary Neoplasms," "Chronic Obstructive Pulmonary Diseases," "Physical Therapy Modalities," and "pulmonary rehabilitation." Only studies that reported PR results were included. This review was registered in the International Prospective Register of Systematic Reviews (number: CRD42021224343). A total of nine controlled trials with 651 patients were included. Postoperative pulmonary complications (PPCs) were the primary outcome measure. PR decreased the risk of complications after surgery compared to regular treatment (odds ratio (OR) 0.21, 95% confidence interval (CI) 0.12-0.37, P < 0.01). PR reduced the risk of pneumonia after surgery compared to regular treatment (OR 0.36, 95% CI 0.15-0.86, P=0.02). There was a significant difference in the postoperative length of stay (mean difference -2.13 days, 95% CI -2.65 to -1.61 days, P < 0.05). PR was an effective intervention that decreased PPCs in patients suffering from lung cancer and COPD. However, due to the limitations of the available data, the results should be interpreted with caution.

Epimedium for Osteoporosis Based on Western and Eastern Medicine: An Updated Systematic Review and Meta-Analysis.

Background: The efficacy of conventional pharmacotherapy on osteoporosis was limited and accompanied with serious side effects. Epimedium might have the potential to be developed as agents to treat osteoporosis. The present systematic review and meta-analysis integrating Western medicine and Eastern medicine ("WE" medicine) was to evaluate the efficacy of Epimedium on osteoporosis. Methods: Eleven electronic databases were searched to identify the randomized controlled trials (RCTs) comparing Epimedium as an adjunctive or alternative versus conventional pharmacotherapy during osteoporosis. Bone mineral density (BMD), effective rate, and Visual Analog Scale (VAS) were measured as primary outcomes. The secondary outcomes were pain relief time, bone metabolic markers, and adverse events. Research quality evaluation was conducted according to the modified Jadad scale. Review Manager 5.4 was utilized to perform analyses, and the data were pooled using a random-effect or fixed-effect model to calculate the weighted mean difference (WMD), standardized mean difference (SMD), risk ratio (RR), and 95% confidence intervals (CI). Results: Twelve RCTs recruiting 1,017 patients were eligible. Overall, it was possible to verify that, in the Epimedium plus conventional pharmacotherapy group, BMD was significantly improved (p = 0.03), effective rate was significantly improved (p = 0.0001), and VAS was significantly decreased (p = 0.01) over those in control group. When compared to conventional pharmacotherapy, Epimedium used alone improved BMD (p = 0.009) and effective rate (p < 0.0001). VAS was lower (p < 0.00001), and the level of alkaline phosphatase (ALP) was significantly decreased (p = 0.01) in patients taking Epimedium alone compared with those given conventional pharmacotherapy. Results of subgroup analyses yielded that the recommended duration of Epimedium as an adjuvant was >3 months (p = 0.03), the recommended duration of Epimedium as an alternative was ≤3 months (p = 0.002), and Epimedium decoction brought more benefits (SMD = 2.33 [1.92, 2.75]) compared with other dosage forms. No significant publication bias was identified based on statistical tests (t = 0.81, p = 0.440). Conclusions: Epimedium may improve BMD and effective rate and relieve pain as an adjuvant or alternative; Epimedium as an alternative might regulate bone metabolism, especially ALP, with satisfying clinical efficacy during osteoporosis. More rigorous RCTs are warranted to confirm these results.

Effectiveness of intervention for aromatase inhibitor-associated musculoskeletal symptoms: A protocol for systematic review and meta-analysis.

BACKGROUND: Aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) are among the most common prominent side effects in patients using aromatase inhibitors (AIs) for breast cancer. Muscle and joint pain, morning stiffness, arthritis, and bone loss are common clinical symptoms in individuals. Traditional Chinese medicine (TCM) has been demonstrated to be useful in the treatment of AIMSS in previous investigations, although the sample sizes were limited, and systematic reviews were inadequate. The effectiveness and safety of TCM in the treatment of AIMSS will be investigated in this study. METHODS: Randomized controlled trials from January 2010 to October 2021 were limited to English or Chinese. We searched PubMed, EMBASE, Cochrane Library, Web of Science, Medline, China Biomedical Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang database, and the VIP database. Two researchers reviewed the literature and retrieved the data independently. Review Manager V5.3.was used to conduct the statistical analysis. RESULTS: This systematic review and meta-analysis presents the most recent data on the use of TCM to treat AIMSS and offers a scientifically sound foundation for therapeutic practice. Upon completion, the findings will be submitted to a peer-reviewed journal. ETHICS AND DISSEMINATION: As the systematic review protocol did not involve human subjects, ethical approval was not required. PROSPERO REGISTRATION NUMBER: CRD42020192553.

Infectious diseases prevention and control using an integrated health big data system in China.

BACKGROUND: The Yinzhou Center for Disease Prevention and Control (CDC) in China implemented an integrated health big data platform (IHBDP) that pooled health data from healthcare providers to combat the spread of infectious diseases, such as dengue fever and pulmonary tuberculosis (TB), and to identify gaps in vaccination uptake among migrant children. METHODS: IHBDP is composed of medical data from clinics, electronic health records, residents' annual medical checkup and immunization records, as well as administrative data, such as student registries. We programmed IHBDP to automatically scan for and detect dengue and TB carriers, as well as identify migrant children with incomplete immunization according to a comprehensive set of screening criteria developed by public health and medical experts. We compared the effectiveness of the big data screening with existing traditional screening methods. RESULTS: IHBDP successfully identified six cases of dengue out of a pool of 3972 suspected cases, whereas the traditional method only identified four cases (which were also detected by IHBDP). For TB, IHBDP identified 288 suspected cases from a total of 43,521 university students, in which three cases were eventually confirmed to be TB carriers through subsequent follow up CT or T-SPOT.TB tests. As for immunization screenings, IHBDP identified 240 migrant children with incomplete immunization, but the traditional door-to-door screening method only identified 20 ones. CONCLUSIONS: Our study has demonstrated the effectiveness of using IHBDP to detect both acute and chronic infectious disease patients and identify children with incomplete immunization as compared to traditional screening methods.

Molecular Mechanism of Gleditsiae Spina for the Treatment of High-Grade Serous Ovarian Cancer Based on Network Pharmacology and Pharmacological Experiments.

Background: Gleditsiae Spina, widely used in traditional Chinese medicine, has a good curative effect on malignant tumors such as ovarian cancer, but the mechanism is not clear. So, we aimed to analyze the pharmacological mechanism of Gleditsiae Spina in the treatment of high-grade serous ovarian cancer (HGSC) based on network pharmacology and biological experiments. Methods: The main active ingredients of Gleditsiae Spina were identified by high performance liquid chromatography (HPLC) and mass spectrometry (MS), and the active ingredients were performed by ADME screening. The component targets of Gleditsiae Spina were screened using the PharmMapper platform, and differentially expressed genes in normal and HGSC tissues were identified through the GEO database. Thereafter, the network of "active ingredient-targets" was constructed by cytoscape 3.7.2 software. The protein-protein interaction network was established by the BioGenet database to mine the potential protein function. Biological processes and pathways were analyzed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. The binding ability of the core components of the Gleditsiae Spina and the core target of HGSC was verified by molecular docking and molecular dynamics simulation, and the therapeutic effect of Gleditsiae Spina was proved in vitro through cytotoxicity experiments. The effect of Gleditsiae Spina on the core pathway is obtained by western blotting. Results: Gleditsiae Spina had cytotoxicity on HGSC based on network pharmacology and biological experiments. Luteolin, genistein, D-(+)-tryptophan, ursolic acid, and berberine are the identified core active ingredients of Gleditsiae Spina for regulating HGSC, with HPSE, PI3KCA, AKT1, and CTNNB1as the ideal targets. The prediction results were verified by molecular docking, molecular dynamic simulation, cell viability, and western blot analysis. Conclusion: Gleditsiae Spina mainly downregulates the expression of heparanase and ß-catenin to affect the composition of tumor cytoplasmic matrix and can regulate the PI3K-AKT pathway, integrating multiple targets and multiple pathways to play a therapeutic role. It also provides a theoretical basis for the prevention of ovarian cancer and its treatment using traditional Chinese medicine in the future.

Yunnan Baiyao Adjuvant Treatment for Patients with Hemoptysis: A Systematic Review and Meta-Analysis.

BACKGROUND: Yunnan Baiyao (YNBY) is a traditional Chinese medicine used to treat bleeding. We evaluated the efficacy of YNBY plus conventional pharmaceutical treatment (CPT) versus CPT alone in patients with hemoptysis. METHODS: A total of eight electronic databases were searched. The outcomes in the included studies were effective rate, hemoptysis volume, duration of hemoptysis and hospitalization, number of cases requiring endotracheal intubation, and adverse events (AEs). The studies were used to calculate risk ratios (RRs) or mean differences (MDs) with corresponding 95% confidence intervals. Risk of bias for included trials was assessed using the Cochrane risk of bias tool. RESULTS: Thirteen RCTs were analyzed consisting of a total of 1379 patients. Treatment with YNBY + CPT had a greater effective rate than CPT alone (RR: 1.18; 95% CI: 1.13 to 1.23; P < 0.001; I 2 = 0%), a lower hemoptysis volume (MD: -107.37; 95% CI: -121.69 to -93.06; P < 0.001; I 2 = 0%), a shorter duration of hemoptysis (MD: -2.70; 95% CI: -2.96 to 2.43; P < 0.001; I 2 = 0%) and hospitalization (MD: -2.38; 95% CI: -2.93 to -1.83; P < 0.001; I 2 = 9%), and a reduction in the incidence of AEs (RR: 0.34; 95% CI: 0.23 to 0.51; P < 0.001; I 2 = 0%). YNBY + CPT treatment provided no significant difference in reducing the number of cases requiring endotracheal intubation compared to CPT alone (RR: 0.49; 95% CI: 0.15 to 1.60; P=0.24; I 2 = 0%). CONCLUSION: YNBY plus CPT showed better efficacy than CPT for patients with hemoptysis. Our study provides medical evidence for the efficacy and safety of YNBY for hemoptysis.