The Relationship between Dietary Habits and Gastroesophageal Reflux Disease: A Two-Sample Mendelian Randomization Study.

PURPOSE: This study aimed to explore the potential causal relationship between dietary habits and Gastroesophageal Reflux Disease (GERD). METHODS: Using the inverse-variance weighted method, a two-sample Mendelian randomization (MR) analysis was performed to investigate the causal relationship between 22 dietary habits and GERD. The stability and reliability of the results were assessed using leave-one-out analysis, heterogeneity tests, and tests for horizontal pleiotropy based on the effect measure odds ratio (OR) and 95% confidence interval (CI). RESULTS: The results of the MR analysis indicated a positive association between alcohol drinking (OR=1.472; 95% CI, 1.331 to 1.629; p<1.0×10-3) and salt added to food (OR=1.270; 95% CI, 1.117 to 1.443; p<1.0×10-3) with the risk of GERD. Conversely, bread intake (OR=0.613; 95% CI, 0.477 to 0.790; p<1.0×10-3), cereal intake (OR=0.613; 95% CI, 0.391 to 0.677; p<1.0×10-3), cheese intake (OR=0.709; 95% CI, 0.593 to 0.846; p<1.0×10-3), dried fruit intake (OR=0.535; 95% CI, 0.404 to 0.709; p<1.0×10-3), fresh fruit intake (OR=0.415; 95% CI, 0.278 to 0.619; p<1.0×10-3), and oily fish intake (OR=0.746; 95% CI, 0.633 to 0.879; p<1.0×10-3) were negatively associated with the risk of GERD. Sensitivity analysis showed no evidence of reverse causation, pleiotropy, or heterogeneity. CONCLUSION: Alcohol and salt added to food raised GERD risk, while bread intake, cereal intake, cheese intake, intake of certain dried fruits and certain fresh fruits, and oily fish lowered it. Our study affirms the potential causal link between these diets and GERD, offering insights into targeted prevention strategies.

An anti-infection and biodegradable TFRD-loaded porous scaffold promotes bone regeneration in segmental bone defects: experimental studies.

BACKGROUND: Addressing segmental bone defects remains a complex task in orthopedics, and recent advancements have led to the development of novel drugs to enhance the bone regeneration. However, long-term oral administration can lead to malnutrition and poor patient compliance. Scaffolds loaded with medication are extensively employed to facilitate the restoration of bone defects. METHODS: Inspired by the local application of total flavonoids of Rhizoma Drynariae (TFRD) in the treatment of fracture, a novel 3D-printed HA/CMCS/PDA/TFRD scaffold with anti-infection, biodegradable and induced angiogenesis was designed, and to explore its preclinical value in segmental bone defect of tibia. RESULTS: The scaffold exhibited good degradation and drug release performance. In vitro, the scaffold extract promoted osteogenesis by enhancing bone-related gene/protein expression and mineral deposition in BMSCs. It also stimulated endothelial cell migration and promoted angiogenesis through the upregulation of specific genes and proteins associated with cell migration and tube formation. This may be attributed to the activation of the PI3k/AKT/HIF-1α pathway, facilitating the processes of osteogenesis and angiogenesis. Furthermore, the HA/CMCS/PDA/TFRD scaffold was demonstrated to alleviate infection, enhance angiogenesis, promote bone regeneration, and increase the maximum failure force of new formed bone in a rat model of segmental bone defects. CONCLUSION: Porous scaffolds loaded with TFRD can reduce infection, be biodegradable, and induce angiogenesis, presenting a novel approach for addressing tibial segmental bone defects.

Total flavonoids of Rhizoma drynariae promote angiogenesis and osteogenesis in bone defects.

Bone defects are difficult to heal, which conveys a heavy burden to patients' lives and their economy. The total flavonoids of Rhizoma drynariae (TFRD) can promote the osteogenesis of distraction osteogenesis. However, the dose effect is not clear, the treatment period is short, and the quality of bone formation is poor. In our study, we observed the long-term effects and dose effects of TFRD on bone defects, verified the main ingredients of TFRD in combination with network pharmacology for the first time, explored its potential mechanism, and verified these findings. We found that TFRD management for 12 weeks regulated osteogenesis and angiogenesis in rats with 4-mm tibial bone defects through the PI3K/AKT/HIF-1α/VEGF signaling pathway, especially at high doses (135 mg kg-1  d-1 ). The vascularization effect of TFRD in promoting human umbilical vein endothelial cells was inhibited by PI3K inhibitors. These results provide a reference for the clinical application of TFRD.

Total flavonoids of Rhizoma Drynariae enhances CD31hiEmcnhi vessel formation and subsequent bone regeneration in rat models of distraction osteogenesis by activating PDGF­BB/VEGF/RUNX2/OSX signaling axis.

Total flavonoids of Rhizoma Drynariae (TFRD), extracted from the kidney­tonifying Traditional Chinese medicine Rhizoma Drynariae, can be effective in treating osteoporosis, bone fractures and defects. However, the pharmacological effects of TFRD on the specific vessel subtype CD31hiEmcnhi during distraction osteogenesis (DO) remains unclear. The present study aimed to investigate the effects of TFRD on CD31hiEmcnhi vessels in a rat model of DO. In the present study, tibial DO models were established using 60 rats with a distraction rate of 0.2 mm per day for 20 days. Co­immunofluorescence staining of CD31 and endomucin (Emcn) was conducted to determine CD31hiEmcnhi vessels. Radiographic, angiographic and histological analyses were performed to assess bone and vessel formation. Tube formation, alkaline phosphatase (ALP) and Von Kossa staining assays were performed to test angiogenesis of endothelial precursor cells (EPCs) and osteogenesis of bone marrow­derived mesenchymal stem cells (BMSCs). Additionally, expression levels of platelet­derived growth factor (PDGF)­BB, VEGF, runt­related transcription factor 2 (RUNX2) and Osterix (OSX) were determined by western blotting and reverse transcription­quantitative PCR. The in vivo assays demonstrated that TFRD markedly promoted CD31hiEmcnhi vessel formation during DO, whereas PDGF­BB neutralizing antibody suppressed vessel formation. Furthermore, the ALP, Von Kossa staining and tube formation assays indicated that TFRD notably elevated the angiogenic capacity of EPCs and osteogenic capacity of BMSCs under stress conditions, which was significantly suppressed by blocking PDGF­BB. The protein and mRNA levels of PDGF­BB, VEGF, RUNX2 and OSX were upregulated by TFRD, but downregulated by blocking PDGF­BB. Thus, TFRD could facilitate CD31hiEmcnhi vessel formation and subsequently enhance angiogenic­osteogenic coupling to regenerate bone defects during DO via the PDGF­BB/VEGF/RUNX2/OSX signaling axis, which indicated that CD31hiEmcnhi vessels could be a potential novel therapeutic target for DO, and TFRD may represent a promising drug for promoting bone regeneration in DO by increasing CD31hiEmcnhi vessels.

Network pharmacology and molecular docking approach to elucidate the mechanisms of Liuwei Dihuang pill in diabetic osteoporosis.

BACKGROUND: Diabetic osteoporosis (DOP) is one of the chronic complications of diabetes mellitus, but without a standardized treatment plan till now. Liuwei Dihuang pill (LDP) has gradually exerted a remarkable effect on DOP in recent years; its specific mechanism is not clear yet. METHODS: We adopted network pharmacology approaches, including multi-database search, pharmacokinetic screening, network construction analysis, gene ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis and molecular docking to elaborate the active components, signaling pathways and potential mechanisms of LDP in the treatment of DOP. RESULTS: Twenty-seven active ingredients and 55 related disease targets have been found through integrated network pharmacology. Functional enrichment analysis shows that five key active ingredients, including beta-sitosterol, stigmasterol, diosgenin, tetrahydroalstonine, and kadsurenone, may give full scope to insulin secretion estrogen-level raising and angiogenesis in biological process through the pivotal targets. In addition, the underlying effect of PI3K/AKT/FOXO and VEGF pathways is also suggested in the treatment. CONCLUSION: Based on systematic network pharmacology methods, we predicted the basic pharmacological effects and potential mechanisms of LDP in the treatment of DOP, revealing that LDP may treat DOP through multiple targets and multiple signaling pathways, which provide evidence for the further study of pharmacological mechanism and broader clinical thinking.

Exploring the treatment of COVID-19 with Yinqiao powder based on network pharmacology.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In China, Yinqiao powder is widely used to prevent and treat COVID-19 patients with Weifen syndrome. In this study, the screening and verification of active ingredients, target selection and DisGeNET scoring, drug-ingredient-gene network construction, protein-protein interaction network construction, molecular docking and surface plasmon resonance (SPR) analysis, gene ontology (GO) functional analysis, gene tissue analysis, and kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were used to explore the active ingredients, targets, and potential mechanisms of Yinqiao powder in the treatment of COVID-19. We also predicted the therapeutic effect of Yinqiao powder using TCM anti-COVID-19 (TCMATCOV). Yinqiao powder has a certain therapeutic effect on COVID-19, with an intervention score of 20.16. Hesperetin, eriodictyol, luteolin, quercetin, and naringenin were the potentially effective active ingredients against COVID-19. The hub-proteins were interleukin-6 (IL-6), mitogen-activated protein kinase 3 (MAPK3), tumor necrosis factor (TNF), and tumor protein P53 (TP53). The potential mechanisms of Yinqiao powder in the treatment of COVID-19 are the TNF signaling pathway, T-cell receptor signaling pathway, Toll-like receptor signaling pathway, and MAPK signaling pathway. This study provides a new perspective for discovering potential drugs and mechanisms of COVID-19.

Total Flavonoids of Rhizoma Drynariae Enhances Angiogenic-Osteogenic Coupling During Distraction Osteogenesis by Promoting Type H Vessel Formation Through PDGF-BB/PDGFR-ß Instead of HIF-1α/ VEGF Axis.

Background: Total flavonoids of Rhizoma Drynariae (TFRD), extracted from the kidney-tonifying traditional Chinese medicine Rhizoma Rrynariae, has been proved to be effective in treating osteoporosis, bone fractures and defects. However, pharmacological effects of TFRD on type H vessels, angiogenic-osteogenic coupling in distraction osteogenesis (DO) and the mechanism remain unclear. This study aims at investigating whether type H vessels exist in the DO model, effects of TFRD on angiogenic-osteogenic coupling and further elucidating the underlying mechanism. Methods: Rats models of DO and bone fracture (FR) were established, and then were separately divided into TFRD and control subgroups. Imageological and histological analyses were performed to assess bone and vessel formation. Immunofluorescent staining of CD31 and endomucin (Emcn) was conducted to determine type H vessel formation. Matrigel tube formation, ALP and Alizarin Red S staining assays were performed to test the effects of TFRD on angiogenesis or osteogenesis of endothelial precursor cells (EPCs) or bone marrow-derived mesenchymal stem cells (BMSCs). Additionally, expression levels of HIF-1α, VEGF, PDGF-BB, RUNX2 and OSX were determined by ELISA, qPCR or western blot, respectively. Results: The in vivo results indicated more formed type H vessels in DO groups than in FR groups and TFRD obviously increased the abundance of type H vessels. Moreover, groups with higher abundance of type H vessels showed better angiogenesis and osteogenesis outcomes. Further in vitro experiments showed that TFRD significantly promoted while blocking PDGF-BB remarkably suppressed the angiogenic activity of EPCs under stress conditions. The levels of p-AKT and p-ERK1/2, downstream mediators of the PDGF-BB pathway, were up-regulated by TFRD but blocked by function blocking anti-PDGF-BB antibody. In contrast, the activated AKT and ERK1/2 and corresponding tube formation were not affected by the HIF-1α inhibitor. Besides, blocking PDGF-BB inhibited the osteogenic differentiation of the stretched BMSCs, but TFRD enhanced the osteogenic activity of BMSCs and ameliorated the inhibition, with more calcium nodes, higher ALP activity and mRNA and protein levels of RUNX2 and OSX. Conclusion: Type H vessels exist in the DO model and TFRD enhances angiogenic-osteogenic coupling during DO by promoting type H vessel formation via PDGF-BB/PDGFR-ß instead of HIF-1α/VEGF axis.

Intelligent rehabilitation assistant system to promote the early functional recovery of the elderly patients with femoral neck fracture after hemiarthroplasty (HA): A protocol for a randomized controlled trial.

BACKGROUND: Femoral neck fracture is a common type of hip fracture, which has a high morbidity and mortality. Surgical treatment is the first choice. However, the functional rehabilitation after operation has not been paid enough attention. In addition, the quality of exercise is difficult to quantify, and the rehabilitation is lack of standards. Therefore, the intelligent rehabilitation assistant system which could record exercise details, might be used to evaluate the quality and adherence to the prescribed exercise to this fragile group of patients has great relevance, so as to provide new ideas for postoperative rehabilitation of hip fracture. METHODS: This is an opening, prospective, double-dummy RCT. Fifty femoral neck fractures patients, older than 65 years and are about to hospitalize for HA, will be invited to study. The sample will be divided into monitoring group and control group randomly at a 1:1 ratio. The prescribed exercises need to be done continuously for 2 weeks. The monitoring group needs additional use intelligent rehabilitation assistant system. Each subject will receive a total of 4 follow-up visits at the designated time (2 weeks, 4 weeks, 12 weeks, and 24 weeks). The following factors will be talked as dependent variables:Each subject will receive a total of 4 follow-up visits at the designated time, and the findings will be analyzed statistically considering a 5% significance level (P < .05). DISCUSSION: Exercise under monitor may improve patients compliance and exercise quality, and accelerate the rehabilitation process. This protocol reported in accordance with the CONSORT 2010 checklist and SPIRIT 2013 Checklist. TRIAL REGISTRATION: The trial is registered at Chinese Clinical Trials Registry (ChiCTR2000033213, May 24, 2020).

Research hotspots and trends of bone defects based on Web of Science: a bibliometric analysis.

BACKGROUND: Bone defects can be seen everywhere in the clinic, but it is still a challenge for clinicians. Bibliometrics tool CiteSpace is based on the principle of "co-citation analysis theory" to reveal new technologies, hotspots, and trends in the medical field. In this study, CiteSpace was used to perform co-citation analysis on authors, countries (regions) and institutions, journals and cited journals, authors and cited literature, as well as keywords to reveal leaders, cooperative institutions, and research hotspots of bone defects and predict development trends. METHOD: Data related to bone defect from 1994 to 2019 were retrieved from the Web of Science core collection; then, we use Excel to construct an exponential function to predict the number of annual publications; conduct a descriptive analysis on the top 10 journals with the largest number of publications; and perform co-citation analysis on authors, countries (regions) and institutions, journals and cited journals, authors and cited reference, and keywords using CiteSpace V5.5 and use the Burst Detection Algorithm to perform analysis on the countries (regions) and institutions and keywords, as well as cluster the keywords using log-likelihood ratio. RESULTS: A total of 5193 studies were retrieved, and the number of annual publications of bone defects showed an exponential function Y = 1×10- 70e0.0829x (R2 = 0.9778). The high-yield author was Choi Seong-Ho at Yonsei University in South Korea. The high-yielding countries were the USA and Germany, and the high-yielding institutions were the Sao Paulo University and China and the Chinese Academy of Sciences which were the emerging research countries and institutions. The research results were mainly published in the fields of dentistry, bone, and metabolism. Among them, the Journal of Dental Research and Journal of Bone and Mineral Research were high-quality journals that report bone defect research, but the most cited journal was the Clinical Orthopaedics and Related Research. Hot keywords were regeneration, repair, in vitro, bone regeneration, reconstruction, and graft. The keywords that were strongly cited in 2010-2019 were transportation, osteogenic differentiation, proliferation, and biomaterials. After 2018, proliferation, osteogenic differentiation, stromal cells, transmission, and mechanical properties have become new vocabulary. The drug delivery, vascularization, osteogenic differentiation and biomaterial properties of bone defects were expected to be further studied. CONCLUSION: The application of CiteSpace can reveal the leaders, cooperating institutions and research hotspots of bone defects and provide references for new technologies and further research directions.

Epidemiological characteristics of dengue in mainland China from 1990 to 2019: A descriptive analysis.

In the past 30 years, dengue has undergone dramatic changes in China every year. This study explores the epidemiological trend of dengue in China during this period to identify high-risk seasons, regions, ages, susceptible populations, and provide information for dengue prevention and control activities.Dengue data from 1990 to 2019 were derived from the Public Health Science Data Center, Web of Science, China National Knowledge Infrastructure, PubMed, and Centers for Disease Control and Prevention of the corresponding province. GraphPad Prism 7 was conducted to generate disease evolution maps, occupational heat maps, and monthly heat maps of dengue cases and deaths in mainland China and Guangdong Province. Excel 2016 was used to create a cyclone map of age and gender distribution. Powerpoint 2016 was performed to create geographic maps.From 1990 to 2019, the annual number of dengue cases showed an increasing trend and reaching a peak in 2014, with 46,864 dengue cases (incidence rate: 3.4582/100,000), mainly contributed by Guangdong Province (45,189 cases, accounting for 96.43%). Dengue pandemics occurred every 4 to 6 years. The prevalence of dengue fever was Autumn, which was generally prevalent from June to December and reached its peak from September to November. The provinces reporting dengue cases each year have expanded from the southeastern coastal region to the southwest, central, northeast, and northwest regions, and the provinces with a high incidence were Guangdong, Guangxi, Yunnan, Fujian, and Zhejiang. People aged 25 to 44 years were more susceptible to dengue virus infection. And most of them were male patients. Dengue mainly occurs in the following groups: students, business service staffs, workers, farmers, retired staffs, housewives, and the unemployed. Four provinces reported deaths from dengue, namely Guangdong Province, Zhejiang Province, Henan Province, and Hunan Province.The dengue fever epidemic occurred every 4 to 6 years, mostly in autumn. The endemic areas were Guangdong, Guangxi, Yunnan, Fujian, and Zhejiang provinces. People aged 25 to 44 years, men, students, business service staffs, workers, farmers, retired staffs, housewives, and the unemployed were more susceptible to dengue fever. These findings help to develop targeted public health prevention and control measures.

Effect of Electroacupuncture and Counseling on Sub-Threshold Depression: A Study Protocol for a Multicenter Randomized Controlled Trial.

BACKGROUND: Sub-threshold depression is common and could impair function, as well as increase the risk of developing major depression. Despite evidence of efficacy for electroacupuncture (EA) and counseling in the treatment of sub-threshold depression, the sample size is insufficient and the level of evidence remains low. This study aims to evaluate the effectiveness of sub-threshold depression treatments by comparing the treatment effects among EA, counseling, and combination therapy, as well as to further study their mechanism. METHODS: This study is a multicenter, randomized, single blind clinical trial that will be conducted in settings at four clinical centers in China. The randomized controlled trial (RCT) will examine the effectiveness of EA intervention, compared with counseling and combination therapy. A total of 138 sub-threshold depression patients (18 to 55 years of age with Beck Depression Inventory (BDI-II) score ≥ 14 points and Hamilton Depression Scale (HAMD-17) score: 7 points ≤ HAMD total score <17 points) will be recruited. The participants will be randomly assigned to receive the above treatments. The interventions will be delivered over a 6-week period (EA: 3 times a week for 6 weeks; 30 min a session. Counseling: once a week for 6 weeks; 50-60 min a session). The primary outcome measure will be the HAMD-17; BDI-II. The secondary outcome measures will be: Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), and Pittsburgh Sleep Quality Index (PSQI). The assessments will occur at baseline, 2, 4, and 6 weeks and a follow-up period. Recruitment will commence in March 2020 and is anticipated to occur over a 2-year period. DISCUSSION: This study intends to conduct a multicenter randomized controlled trial to compare the effectiveness among EA, counseling and the combined therapy in the treatment of patients with sub-threshold depression, and to further study the mechanisms of effect. CHINESE CLINICAL TRIAL REGISTRY REGISTRATION: www.chictr.org.cn/, identifier ChiCTR1900028530.

Acupoint catgut embedding for insomnia: Protocol for a systematic review and data mining.

BACKGROUND: Insomnia is a common sleep disorder characterized by chronically disturbed sleep or loss of sleep, and even cognitive dysfunction. Acupoint catgut embedding is widely used to treat sleep disorders. However, there is no systematic review and data mining of the effectiveness and potential acupoints prescription of acupoint catgut embedding for insomnia. METHODS: Randomized controlled trials (RCTs) from the Web of Science, PubMed, Cochrane Library, Springer, Wanfang database, China National Knowledge Infrastructure, VIP Chinese Science and Technology Journals Database, and 2 clinical trial registration center will be included. The search time will be established from each database to December 30, 2019. The outcome measures will be Pittsburgh sleep quality index (PSQI), clinical effective rate, International Unified Sleep Efficiency Value (IUSEV) and adverse events. Data from RCTs that meets the inclusion criteria will be analyzed through RevMan V.5.3 software. Risk of bias and publication bias will be analyzed to identify the quality of the included studies. Besides, Traditional Chinese Medicine inheritance support system (TCMISS) will be used to analyze the potential acupoints prescriptions. RESULTS: This study will clarify PSQI, IUSEV, clinical effective rate, adverse events, and potential acupoint prescriptions of acupoint catgut embedding for patients with insomnia. CONCLUSION: Our study will provide evidence of acupoint catgut embedding for insomnia, which may be beneficial to practitioners in the field of non-pharmacological interventions.PROSPERO registration number: CRD42019144636.

Comparison between the induced membrane technique and distraction osteogenesis in treating segmental bone defects: An experimental study in a rat model.

Previous studies have suggested that treatment plans for segmental bone defects (SBDs) are affected by the bone defect sizes. If the selected treatment was not the most appropriate, it would not contribute to bone healing, but increase complications. The induced membrane technique (IM) and distraction osteogenesis (DO) have been proved to be effective in treating SBDs. However, the differences between the two in therapeutic effects on SBDs with different sizes are still unclear. Thus, we aimed to observe the effects of IM and DO on different sizes of SBDs and to further determine what method is more appropriate for what defect size. Rat models of 4-, 6-and 8-mm mid-diaphyseal defects using IM and DO techniques were established. X-rays, micro-CT, histological and immunohistochemical examinations were performed to assess bone repair. Faster bone formation rate, shorter treatment duration, higher expressions of OPN and OCN and higher parameters of bone properties including bone mineral density (BMD), bone volume/total tissue volume (BV/TV), mineral apposition rate (MAR) and mineral surface/bone surface (MS/BS) were found in 4-mm SBDs treated with DO than in those with IM treatment. However, the results were reversed and IM outperformed DO in bone repair capacity for 8-mm SBDs, while no significant difference emerges in the case of 6-mm SBDs. This study suggests that the therapeutic effects of IM and DO may be subjected to sizes of bone defects and the best treatment size of defects is different between the two. For small-sized SBDs, DO may be more suitable and efficient than IM, but IM has advantages over DO for over-sized SBDs, while DO and IM show similar bone repair capability in moderate-sized SBDs, which would offer a new insight into how to choose DO and IM for SBDs in clinical practice and provide references for further clinical research.

Identified the Synergistic Mechanism of Drynariae Rhizoma for Treating Fracture Based on Network Pharmacology.

BACKGROUND: Drynariae Rhizoma (DR) has been widely used in the prevention and treatment of various fractures. However, the specific mechanisms of DR's active ingredients have not been elucidated. The purpose of this study was to explore the synergistic mechanisms of DR for treating fracture. METHODS: A network pharmacology approach integrating ingredient screening, target exploration, active ingredients-gene target network construction, protein-protein interaction network construction, molecular docking, gene-protein classification, gene ontology (GO) functional analysis, KEGG pathway enrichment analysis, and signaling pathway integration was used. RESULTS: This approach identified 17 active ingredients of DR, interacting with 144 common gene targets and 143 protein targets of DR and fracture. NCOA1, GSK3B, TTPA, and MAPK1 were identified as important gene targets. Five most important protein targets were also identified, including MAPK1, SRC, HRAS, RXRA, and NCOA1. Molecular docking found that DR has a good binding potential with common protein targets. GO functional analysis indicated that common genes involve multiple processes, parts and functions in biological process, cellular component, and molecular function, including positive regulation of transcription from RNA polymerase II promoter, signal transduction, cytosol, extracellular exosome, cytoplasm, and protein binding. The KEGG pathway enrichment analysis indicated that common gene targets play a role in repairing fractures in multiple signaling pathways, including MAPK, PI3K/AKT, Ras, and VEGF signaling pathways. MAPK and PI3K/AKT signaling pathways were involved in osteoblast formation, Ras signaling pathway was involved in enhancing mesenchymal stromal cell migration, and VEGF signaling pathway was involved in angiogenesis. CONCLUSION: The study revealed the correlation between DR and fracture and the potential synergistic mechanism of different targets of DR in the treatment of fractures, which provides a reference for the development of new drugs.

Acupuncture for Primary Osteoporosis: Evidence, Potential Treatment Prescriptions, and Mechanisms.

Many clinical trials and meta-analyses related to acupuncture for osteoporosis (OP) have been published. However, identifying the evidence from these studies still remains a challenge for acupuncturists. We conducted a systematic search of the Chinese Biomedical Medicine (CBM), VIP Database, Wanfang Data, China National Knowledge Infrastructure (CNKI), PubMed, Springer, Cochrane Library, and Embase to identify relevant trials, systematic reviews, and/or meta-analyses up to October 31, 2018. Data were extracted to assess the methodological quality using Veritas plots and to explore potential acupuncture prescriptions using the Traditional Chinese Medicine inheritance support system (TCMISS). In addition, potential mechanisms of core acupoints identified by data mining were summarized based on published studies. A total of 218 clinical trials and ten meta-analyses were included, involving 212 acupuncture prescriptions, 102 acupoints, 13 meridians, three extra meridians, and one Ashi point. The mean Veritas score of publication year, type of study, Assessment of Multiple Systematic Reviews 2, Preferred Reporting Items for Systematic Reviews and Meta-Analyses, heterogeneity, and publication bias were 5.5, 7.2, 6, 5.6, 5.8, and 7.5, respectively. The study of Pan et al. received the highest Veritas score of 8.67 points. The most frequently used meridian was BL. Acupoint combinations BL23 and BL20, BL23 and GV4, and BL23 and ST36 were used frequently. The core acupoints association networks were acupoints BL23, BL20, ST36, GV4, SP6, CV4, and KI3. The potential mechanisms of core acupoints involved upregulated expression of members in OPG/RANKL, Wnt/ß-catenin, and MAPK pathways, such as LRP5, ß-catenin, Runx2, and OPG. In conclusion, our Veritas plots enable acupuncturists to evaluate key attributes of meta-analysis quality related to acupuncture for primary OP and to improve the quality of evidence-based medicine relating to acupuncture. Data mining analysis revealed an association network of meridians, acupoint combinations, core acupoints, and the underlying mechanisms of acupuncture for primary OP.

Acupuncture for fecal incontinence: Protocol for a systematic review and data mining.

BACKGROUND: Fecal incontinence is a socially and emotionally destructive condition that has a negative impact on personal image, self-confidence, and quality of life. Acupuncture is commonly used to treat chronic conditions, including fecal incontinence. However, no relevant systematic review or meta-analysis has been designed to evaluate the effects of acupuncture on fecal incontinence. METHODS: We will identify relevant randomized controlled trials (RCTs) from the Cochrane Library, Medline, Embase, PubMed, Springer, Web of Science, China National Knowledge Infrastructure, VIP Chinese Science and Technology Journals Database, Wanfang database, and clinical trial registration center from their inception to February 28, 2019. The primary outcome measures will be clinical effective rate, functional outcomes, and quality of life. Data that meets the inclusion criteria will be extracted and analyzed using RevMan V.5.3 software. Two reviewers will evaluate the studies using the Cochrane Collaboration risk of bias tool. Publication bias will be assessed by funnel plots, Egger test, and Begg test using the Stata software. Acupoints characteristics will be analyzed by Traditional Chinese Medicine inheritance support system. RESULTS: This study will analyze the clinical effective rate, functional outcomes, quality of life, daily average number of fecal incontinence, and effective prescriptions of acupuncture for patients with fecal incontinence. CONCLUSION: Our findings will provide evidence for the effectiveness and potential treatment prescriptions of acupuncture for patients with fecal incontinence. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019119680.

Alpha lipoic acid combined with epalrestat: a therapeutic option for patients with diabetic peripheral neuropathy.

BACKGROUND: Alpha lipoic acid (ALA), a type of antioxidant, is used in combination with epalrestat in the treatment of diabetic peripheral neuropathy (DPN). However, whether combined treatment is superior to epalrestat monotherapy is controversial. METHODS: We conducted a systematic search of PubMed, Cochrane Library and Chinese databases to identify all randomized controlled trials (RCTs) up to October 31, 2017. Data were extracted to evaluate methodological quality and analyzed using Review Manager 5.3.0 software. RESULTS: Twelve studies were included. Compared to epalrestat monotherapy, ALA 600 mg/d once a day (qd) combined with epalrestat 50 mg three times a day (tid) augmented the total effectiveness rate (14 days - risk ratio [RR]: 1.40, 95% CI: 1.16-1.69, P=0.0005; 28 days - RR: 1.48, 95% CI: 1.27-1.72, P<0.00001); at the same, it could improve the median motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV), peroneal MNCV, and SNCV after 14, 21, and 28 days of treatment and could reduce the Toronto Clinical Scoring System (TCSS) (weighted mean difference [WMD]: -1.60, 95% CI: (-2.91, -0.29), P=0.02) and Total Symptom Score (TSS) (WMD: -0.93, 95% CI: -1.27, -0.60, P<0.00001) after 21 days of treatment. The treatment strategy of ALA 300 mg/d qd combined with epalrestat 50 mg tid had the same effects in regard to the total effectiveness rate (RR: 1.37, 95% CI: 1.18-1.59, P<0.0001), median MNCV (WMD: 6.12, 95% CI: 5.04, 7.20, P=0.00001), median SNCV (WMD: 6.70, 95% CI: 5.75, 7.65, P=0.00001), peroneal MNCV (WMD: 6.68, 95% CI: 5.82, 7.55, P=0.00001), and peroneal SNCV (WMD: 4.27, 95% CI: 3.34, 5.20, P=0.00001) after 28 days of treatment. CONCLUSION: ALA combined with epalrestat is an effective option for DPN patients. Future large-sample RCTs should be conducted to further confirm this finding.

Imaging features and differential diagnosis of multiple diaphyseal sclerosis: A case report and review of literature.

RATIONALE: Multiple diaphyseal sclerosis (MDS), known as Ribbing disease, is a rare congenital bone disease resulting from autosomal recessive inheritance. The case study involved a 22-year-old female patient who had been diagnosed with chronic sclerosing osteomyelitis due to lack of knowledge about MDS. Previous studies reported rarely on this condition. PATIENT CONCERNS: A 22-year-old female with MDS was analyzed. DIAGNOSES: MDS is characterized radiographically by a fusiform widening of the diaphyseal portion of the long bones, which is caused by a thickening of the cortex with obstruction of the medullary cavity. The pathologies are observed utilizing diagnostic imagery and are often difficult to identify. INTERVENTION: The patient was following a suggested regimen of oral celecoxib capsules at 200 mg/day for 6 days. OUTCOMES: The patient's diagnosis was revised to the rare condition of Ribbing disease by reviewing the clinical history and distinctive radiography images and because the symptoms were alleviated by celecoxib capsule. We also present a review of the literature on the diagnosis and differential diagnosis of MDS based on clinical and imaging features. LESSONS: MDS is rare and may often be initially misdiagnosed as another type of sclerosing bone dysplasia, thus, it is important to be aware of the existence of MDS. Once MDS is suspected, differential diagnosis should be performed to exclude other sclerosing bone dysplasias, taking into account clinical history, distinctive radiographic appearance, distribution, and laboratory and histopathologic findings. Laboratory evaluation and pathologic findings are nonspecific but assist in excluding other diagnoses. More evidence is needed to illustrate the effectiveness of medical or surgical treatments for patients with MDS.

Effect of acupuncture on in vitro fertilization: An updated systematic review and data mining protocol.

BACKGROUND: Although many patients try to seek acupuncture to improve in vitro fertilization (IVF) outcomes, evidence regarding its efficacy and acupoints characters are lacking. The aim of this protocol is to evaluate the effectiveness and safety, as well as the acupoints characteristics of acupuncture in the treatment of female undergoing IVF, by conducting a systematic review and data mining. METHODS: The following 6 databases will be searched from their inception to April 30, 2018: PubMed, Chinese National Knowledge Infrastructure, Wanfang, VIP database, Embase, and Cochrane Library. The randomized controlled trials (RCTs) or case-control studies of acupuncture that assess clinical effects and side effects in female undergoing IVF are included. The primary outcome measures will be number of oocytes retrieved, fertilization rate, oocyte cleavage rate, high-quality embryos rate, ovarian hyperstimulation syndrome (OHHS) incidence rate, clinical pregnancy rate (CPR), biochemical pregnancy rate (BPR), implantation rate, and cycle cancellation rate. Two reviewers will independently undertake data extraction and quality assessments. Data will be synthesized by RevMan V.5.3 software. Acupoints characteristics will be excavated using Traditional Chinese Medicine inheritance support system (TCMISS). Reporting bias will be assessed by Funnel plots, Begg test, and Egger test. RESULTS: This review will assess the clinical efficacy and safety, as well as the acupoints characteristics of acupuncture on IVF. CONCLUSION: These findings will summarize the current evidence of acupuncture on IVF outcomes and may provide guidance for clinicians and infertile women to select acupuncture for IVF.

Effect of Zhizhu Kuanzhong capsule on functional dyspepsia: Protocol for a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Functional dyspepsia (FD) is a gastrointestinal disorder affecting people in the globe. Spleen-deficiency syndrome is one of its basic syndromes. Zhizhu Kuanzhong capsule was the most frequent Chinese herbal formula used in the spleen-deficiency researches. We aim to assess the effectiveness and safety of Zhizhu Kuanzhong capsule on FD. METHODS: A systematic literature search for randomized controlled trials (RCTs) from their inception until December 31, 2017 will be conducted using 7 databases: PubMed, Cochrane Library, Embase, VIP Database, Chinese National Knowledge Infrastructure, Wanfang Data, and Chinese BioMedical Database. Inclusion the trials of Zhizhu Kuanzhong capsule which evaluate motilin level, clinical syndrome, and side effect in people with FD. The primary outcome measures will be motilin level, clinical syndrome integral, and clinical total effective rate. Data extraction and risk of bias assessments will be performed by 2 reviewers independently. Methodological and reporting quality of included studies will be assessed by the consolidated standards of reporting trials for Chinese herbal medicine formulas. All statistical analyses will be conducted using RevMan V.5.3 software. Funnel plots, Begg's test, and Egger's test will be developed to evaluate reporting bias. RESULTS: This review will assess the effect of Zhizhu Kuanzhong capsule on clinical total effective rate, symptom remission rate, plasma motilin level, and safety of FD in patients. CONCLUSION: The conclusion of our study will provide updated evidence to judge whether Zhizhu Kuanzhong capsule is an effective intervention for patients with FD.