Establishment of bone-targeted nano-platform and the study of its combination with 2-deoxy-d-glucose enhanced photodynamic therapy to inhibit bone metastasis.

At present, simple anti-tumor drugs are ineffective at targeting bone tissue and are not purposed to treat patients with bone metastasis. In this study, zoledronic acid (ZOL) demonstrated excellent bone-targeting properties as a bone-targeting ligand. The metal-organic framework (MOF) known as ZIF-90 was modified with ZOL to construct a bone-targeting-based drug delivery system. Chlorin e6 (Ce6) was loaded in the bone-targeted drug delivery system and combined with 2-deoxy-D-glucose (2-DG), which successfully treated bone tumors when enhanced photodynamic therapy was applied. The Ce6@ZIF-PEG-ZOL (Ce6@ZPZ) nanoparticles were observed to have uniform morphology, a particle size of approximately 210 nm, and a potential of approximately -30.4 mV. The results of the bone-targeting experiments showed that Ce6@ZPZ exhibited a superior bone-targeted effect when compared to Ce6@ZIF-90-PEG. The Ce6@ZPZ solution was subjected to 660 nm irradiation and the resulting production of reactive oxygen species increased over time, which could be further increased when Ce6@ZPZ was used in combination with 2-DG. Their combination had a stronger inhibitory capacity against tumor cells than either 2-DG or Ce6@ZPZ alone, increasing the rate of tumor cell apoptosis. The apoptosis rate caused by HGC-27 was 61.56% when 2-DG was combined with Ce6@ZPZ. In vivo results also showed that Ce6@ZPZ combined with 2-DG maximally inhibited tumor growth and prolonged mice survival compared to the other experimental groups. Therefore, the combination of PDT and glycolytic inhibitors serves as a potential option for the treatment of cancer.

Effects of soft robotic exosuit on ambulation ability in stroke patients: a systematic review.

BACKGROUND: Robot-assisted gait training is incorporated into guidelines for stroke rehabilitation. It is a promising tool combined with conventional therapy for low ambulatory patients. The heavy weight and bulky appearance of a robotic exoskeleton limits its practicality. On the other hand, soft robotic exosuit (SRE) based on its light weight and inconspicuous property, is better tolerated by patients in daily life. The aim of this study is to review the efficacy of the SRE with regard to walking ability and biomechanical properties in stroke patients. METHODS: Electronic searches were carried out in PubMed, Embase, Cochrane Library, Web of Science, and the Physiotherapy Evidence Database. Clinical trials that investigated the effectiveness of SREs on ambulation ability in patients with post-stroke hemiparesis were eligible. Qualitative data synthesis was subsequently performed. RESULTS: Nine studies were identified as relevant, involving a total of 83 patients. For the assessment of SRE efficacy, outcome measures were walking ability and biomechanical properties. In terms of both immediate effect and training effect, SREs improved the walking speed, walking distance, peak ankle dorsiflexion angle during swing phase, peak paretic propulsion, stride length and compensated gait in stroke patients. CONCLUSIONS: SRE improved the ambulation ability of stroke patients in terms of walking ability and biomechanical properties. The small number of studies limits the generalizability of interpretation. More controlled studies with better quality are required to reach a more solid conclusion on this issue.

Feasibility of Aerobic Exercise Training to Mitigate Cardiotoxicity of Breast Cancer Therapy: A Systematic Review and Meta-Analysis.

BACKGROUND: Current anticancer treatments for breast cancer (BC) may cause cardiotoxicity. This study aimed to investigate the effectiveness of aerobic exercise in mitigating cardiotoxicity caused by BC therapy. MATERIALS AND METHODS: PubMed, Embase, Cochrane Library, Web of Science, and the Physiotherapy Evidence Database were searched until February 7, 2023. Clinical trials investigating the effectiveness of exercise training, including aerobic exercise, in BC patients receiving treatments that could cause cardiotoxicity were eligible. Outcome measures included cardiorespiratory fitness (CRF) (peak oxygen consumption, VO2peak), left ventricular ejection fraction, and peak oxygen pulse. Intergroup differences were determined by standard mean differences (SMD) and 95% confidence intervals (CIs). Trial sequential analysis (TSA) was utilized to ensure whether the current evidence was conclusive. RESULTS: Sixteen trials involving 876 participants were included. Aerobic exercise significantly improved CRF measured by VO2peak in mL/kg/min (SMD 1.79, 95% CI 0.99-2.59) when compared to usual care. This result was confirmed through TSA. Subgroup analyses revealed that aerobic exercise given during BC therapy significantly improved VO2peak (SMD 1.84, 95% CI 0.74-2.94). Exercise prescriptions at a frequency of up to 3 times per week, an intensity of moderate to vigorous, and a >30-minute session length also improved VO2peak. CONCLUSION: Aerobic exercise is effective in improving CRF when compared to usual care. Exercise performed up to 3 times per week, at a moderate-to-vigorous intensity, and having a session length >30 minutes is considered effective. Future high-quality research is needed to determine the effectiveness of exercise intervention in preventing cardiotoxicity caused by BC therapy.

Progress in traditional Chinese medicine against chronic gastritis: From chronic non-atrophic gastritis to gastric precancerous lesions.

Chronic gastritis (CG) is a persistent inflammation of the gastric mucosa that can cause uncomfortable symptoms in patients. Traditional Chinese medicine (TCM) has been widely used to treat CG due to its precise efficacy, minimal side effects, and holistic approach. Clinical studies have confirmed the effectiveness of TCM in treating CG, although the mechanisms underlying this treatment have not yet been fully elucidated. In this review, we summarized the clinical research and mechanisms of TCM used to treat CG. Studies have shown that TCM mechanisms for CG treatment include H. pylori eradication, anti-inflammatory effects, immune modulation, regulation of gastric mucosal cell proliferation, apoptosis, and autophagy levels.

The Application of Soft Robotic Gloves in Stroke Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Wearable robotic devices have been strongly put into use in both the clinical and research fields of stroke rehabilitation over the past decades. This study aimed to explore the effectiveness of soft robotic gloves (SRGs) towards improving the motor recovery and functional abilities in patients with post-stroke hemiparesis. Five major bibliographic databases, PubMed, Embase, Cochrane Library, Web of Science, and the Physiotherapy Evidence Database, were all reviewed for enrollment regarding comparative trials prior to 7 March 2023. We included adults with stroke and compared their rehabilitation using SRGs to conventional rehabilitation (CR) on hand function in terms of the Fugl-Meyer Upper Extremity Motor Assessment (FMA-UE), Fugl-Meyer Distal Upper Extremity Motor Assessment (FMA-distal UE), box and blocks test score, grip strength test, and the Jebsen-Taylor hand function test (JTT). A total of 8 studies, comprising 309 participants, were included in the analysis. Compared to CR, rehabilitation involving SRGs achieved better FMA-UE (MD 6.52, 95% CI: 3.65~9.39), FMA-distal UE (MD 3.27, 95% CI: 1.50~5.04), and JJT (MD 13.34, CI: 5.16~21.53) results. Subgroup analysis showed that stroke latency of more than 6 months and training for more than 30 min offered a better effect as well. In conclusion, for patients with stroke, rehabilitation using SRGs is recommended to promote the functional abilities of the upper extremities.

Anti-tumour effect of Huangqin Decoction on colorectal cancer mice through microbial butyrate mediated PI3K/Akt pathway suppression.

Introduction. Huangqin Decoction (HQD), a Chinese herbal formula, is widely used for various diseases, including colorectal cancer (CRC).Hypothesis/Gap Statement. We proposed that microbial butyrate mediated PI3K/Akt pathway suppression might involve the anti-cancer effect of HQD.Aim. This study aimed to evaluate the potential mechanism of HQD against CRC.Methodology. An azoxymethane plus dextran sulphate sodium induced CRC mouse model was used, and the intestinal flora and faecal short-chain fatty acid changes were detected, respectively, after HQD administration with 16S rRNA sequencing and gas chromatography coupled with mass spectrometry. Disease activity index, colon length and levels of inflammatory cytokines were measured to evaluate the effect of HQD on intestinal inflammation. Tumour size, number and histopathology were assessed to reflect the impact of HQD on tumour burden. Apoptosis and PI3K/Akt pathway activity were measured by TUNEL staining and Western-blotting. In vitro, the effects of sodium butyrate (NaB) on the viability of CRC cell lines were detected by the Cell-counting Kit-8. The apoptotic cells were determined by TUNEL staining. Cell migration and invasion were assessed by wound healing assay and Transwell assay, respectively. Western-blotting and immunofluorescent staining were used to test the activity of PI3K/Akt pathway.Results. Animal study showed that HQD could improve the gut dysbiosis, increase the abundance of Clostridium and the level of faecal butyric acid. Then, we found that HQD could attenuate colitis, reduce tumour burden, promote cell apoptosis and suppress PI3K/Akt pathway activity in CRC mice. In vitro experiment revealed that NaB treatment could inhibit cell growth, migration and invasion in CRC cell lines. Additionally, NaB enhanced cellular apoptosis, and reduced phosphorylated PI3K and Akt expressions. Interestingly, addition of 740Y-P, an agonist of PI3K, reversed the NaB effects on CRC cells.Conclusion. Overall, in this study, we revealed that HQD could induce apoptosis through microbial butyrate mediated PI3K/Akt inhibition and perform anti-CRC activity.

Effect and Optimal Timing of Extracorporeal Shock-Wave Intervention to Patients With Spasticity After Stroke: A Systematic Review and Meta-analysis.

OBJECTIVE: This study investigated the efficacy of extracorporeal shock wave therapy as well as the optimal intervention timing for extracorporeal shock wave therapy for patients with spasticity after stroke. DESIGN: A search of randomized controlled trials was conducted in different electronic databases. We performed a meta-analysis to measure the effect of extracorporeal shock wave therapy versus sham interventions on spasticity and limb functionality. The meta-regression analysis was performed to determine the adequate intervention timing of extracorporeal shock wave therapy. The follow-up period of the outcomes was divided into the short (<2 wks), mid (>2 wks and ≤4 wks), and long (>4 wks and ≤3 mos) terms. RESULTS: Thirteen studies with 677 participants were evaluated. Spasticity significantly improved throughout the follow-up duration. Limb functionality significantly improved in the short-term follow-up period. The meta-regression analysis showed that patients with stroke duration less than 45 mos may be benefited from extracorporeal shock wave therapy in improving limb function in all follow-up periods. CONCLUSIONS: Extracorporeal shock wave therapy is an effective method for reducing spasticity in patients with stroke, and the effect could be maintained for up to 3 mos. Its effects on limb functionality could persist for at least 2 wks. Patients who had stroke for less than 45 mos may have significant benefit from extracorporeal shock wave therapy in all follow-up periods.

Different pedagogies for acquisition of knowledge and skill: a systematic review and network meta-analysis.

BACKGROUND: This network meta-analysis aimed to assess the efficacy of different educational methods for healthcare professionals. METHODS: A systematic literature search was conducted to identify relevant randomised controlled trials. The standardised mean difference (SMD) with 95% CI was estimated using network meta-analysis for knowledge acquisition and skill performance, and ranked the effects of different educational methods using the surface under the cumulative ranking area (SCURA) technique. RESULTS: Fifty-five randomised controlled trials including of 4292 participants were identified. Compared with no intervention, the results demonstrated all education methods achieved significant improvements in knowledge acquisition (SMD 1.73-2.66). Only education methods involving high fidelity virtual patient simulation reported significantly better skill performance (SMD 1.25-1.81). High fidelity virtual patient simulation plus self-directed learning was the most effective educational method both in terms of knowledge acquisition (SMD 2.66, 95% CI 1.4 to 4.12, SCURA 0.78) and skill performance (SMD 1.81, 95% CI 0.42 to 3.2, SCURA 0.89). CONCLUSIONS: Our study demonstrates all educational methods have positive effects on knowledge acquisition, but education methods involving high fidelity virtual patient simulation are better at improving skill performance than other methods.

Methods of Weaning From Mechanical Ventilation in Adult: A Network Meta-Analysis.

Background/Objective: The aim of study is to assess the efficacy of each ventilator weaning method for ventilated patients in intensive care units (ICUs). Methods: A systematic search was conducted using PubMed, Embase, and China National Knowledge Infrastructure to identify randomized control studies on ventilated patients regarding extubation associated outcomes (weaning success or failure, proportion requiring re-intubation, or mortality) from inception until April 01, 2020. Commonly used ventilation modes involved pressure support ventilation, synchronized intermittent mandatory ventilation, automatic tube compensation, continuous positive airway pressure, adaptive support ventilation, neurally adjusted ventilatory assist, proportional assisted ventilation, and SmartCare. Pooled estimates regarding extubation associated outcomes were calculated using network meta-analysis. Results: Thirty-nine randomized controlled trials including 5,953 patients met inclusion criteria. SmartCare and proportional assist ventilation were found to be effective methods in increasing weaning success (odds ratio, 2.72, 95% confidence interval (CI), 1.33-5.58, P-score: 0.84; odds ratio, 2.56, 95% CI, 1.60-4.11, P-score: 0.83; respectively). Besides, proportional assist ventilation had superior in reducing proportion requiring re-intubation rate (odds ratio, 0.48, 95% CI, 0.25-0.92, P-score: 0.89) and mortality (odds ratio, 0.48, 95% CI, 0.26-0.92, P-score: 0.91) than others. Conclusion: In general consideration, our study provided evidence that weaning with proportional assist ventilation has a high probability of being the most effective ventilation mode for patients with mechanical ventilation regarding a higher rate of weaning success, a lower proportion requiring reintubation, and a lower mortality rate than other ventilation modes.

Chronic stress accelerates the process of gastric precancerous lesions in rats.

Background: Gastrointestinal cancers account for 20% of all deaths worldwide. Gastric cancer (GC) patients are susceptible to psychological change, especially depression which is commonly induced by chronic stress. Gastric precancerous lesions (GPL) is an important prodromal stage in the occurrence of gastric cancer. Chronic stress influences the prognosis of GC and may influence the process of GPL as well. Methods: Sixty SD rats were randomly divided into a control group, GPL group, and GPL+CUMS group. In the GPL group, 200µg/mL N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) free drinking method combined with intermittent fasting was applied to establish the GPL animal model. Based on this, we combined the GPL rats with chronic unpredicted mild stress (CUMS) to establish a comprehensive model. We then evaluated their behavior by open field tests and sucrose preference tests. We tested the IL-6, IL-10, TNF-α, Ghrelin, Leptin and Somatostatin (SS) levels in serum and observed the expression of Ghrelin and Gastrokine 2(GKN2) in the gastric mucosa of rats with tumors by immunofluorescence. Results: Our results showed that GPL and GPL+CUMS rats all displayed a significantly decreased total distance and mean velocity traveled in the open field test. The percentages of sucrose preference were significantly decreased in the GPL+CUMS group compared to the control group. In addition, IL-6 and TNF-α were significantly increased in both the GPL and GPL+CUMS groups. Furthermore, the GPL+CUMS group showed significantly increased TNF-α levels in serum compared to the GPL rats. Our results showed that the expression of NF-κB, p53, and BCL-2 were significantly increased while BAX was reduced in the GPL and GPL+CUMS groups. Moreover, Ghrelin and Leptin levels in serum were significantly decreased in the GPL and GPL+CUMS groups. SS levels in serum were significantly increased in the GPL+CUMS group. Additionally, we found that the GPL+CUMS rats with tumors not only had strong expression of GKN2 on the luminal side and the lamina propria of the gastric mucosa and tumor, but also had expression of Ghrelin on the luminal side of the gastric mucosa. The areas that showed strong expression of GKN2 and Ghrelin, are all located around the blood vessels in the tumor. Conclusions: GPL rats under chronic stress would aggravate the conditions of GPL, shorten the process of GPL, and increase the risk of tumorigenesis. In addition, the close monitoring of the mental health of cancer survivors and precancerous lesion patients is suggested to be of great significance in the prevention and treatment of cancer.

Acupuncture, from the ancient to the current.

Acupuncture is characterized by the insertion of a fine metal needle through the skin of the human body at an acupuncture point (acupoint) in Traditional Chinese Medicine (TCM). It is an ancient form of therapy, and has a long history of prosperity and decline. Due to the persistent efforts of TCM practitioners, a number of well-designed clinical trials regarding acupuncture have been published in the past decade. Besides, numerous basic researches aiming to reveal the mechanisms of acupuncture have also been conducted. Several scientific explanations have been obtained to interpret the arcane TCM theory. This review provides brief information of acupuncture, including its history, status, evidence, and mechanisms.

Corrigendum: The Efficacy and Safety of Qiming Granule for Dry Eye Disease: A Systematic Review and Meta-Analysis.

[This corrects the article DOI: 10.3389/fphar.2020.00580.].

Exploration in the Mechanism of Kaempferol for the Treatment of Gastric Cancer Based on Network Pharmacology.

BACKGROUND: Kaempferol is a natural polyphenol in lots of Chinese herbs, which has shown promising treatment for gastric cancer (GC). However, the molecular mechanisms of its action have not been systematically revealed yet. In this work, a network pharmacology approach was used to elucidate the potential mechanisms of kaempferol in the treatment of GC. METHODS: The kaempferol was input into the PharmMapper and SwissTargetPrediction database to get its targets, and the targets of GC were obtained by retrieving the Online Mendelian Inheritance in Man (OMIM) database, MalaCards database, Therapeutic Target Database (TTD), and Coolgen database. The molecular docking was performed to assess the interactions between kaempferol and these targets. Next, the overlap targets of kaempferol and GC were identified for GO and KEGG enrichment analyses. Afterward, a protein-protein interaction (PPI) network was constructed to get the hub targets, and the expression and overall survival analysis of the hub target were investigated. Finally, the overall survival (OS) analysis of hub targets was performed using the Kaplan-Meier Plotter online tool. RESULTS: A total of 990 genes related to GC and 10 overlapping genes were determined through matching the 24 potential targets of kaempferol with disease-associated genes. The result of molecular docking indicated that kaempferol can bind with these hub targets with good binding scores. These targets were further mapped to 140 GO biological process terms and 11 remarkable pathways. In the PPI network analysis, 3 key targets were identified, including ESR1, EGFR, and SRC. The mRNA and protein expression levels of EGFR and SRC were obviously higher in GC tissues. High expression of these targets was related to poor OS in GC patients. CONCLUSIONS: This study provided a novel approach to reveal the therapeutic mechanisms of kaempferol on GC, which will ease the future clinical application of kaempferol in the treatment of GC.

Systematic Elucidation of the Mechanism of Quercetin against Gastric Cancer via Network Pharmacology Approach.

This study was aimed at elucidating the potential mechanisms of quercetin in the treatment of gastric cancer (GC). A network pharmacology approach was used to analyze the targets and pathways of quercetin in treating GC. The predicted targets of quercetin against GC were obtained through database mining, and the correlation of these targets with GC was analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Next, the protein-protein interaction (PPI) network was constructed, and overall survival (OS) analysis of hub targets was performed using the Kaplan-Meier Plotter online tool. Finally, the mechanism was further analyzed via molecular docking of quercetin with the hub targets. Thirty-six quercetin-related genes were identified, 15 of which overlapped with GC-related targets. These targets were further mapped to 319 GO biological process terms and 10 remarkable pathways. In the PPI network analysis, six hub targets were identified, including AKT1, EGFR, SRC, IGF1R, PTK2, and KDR. The high expression of these targets was related to poor OS in GC patients. Molecular docking analysis confirmed that quercetin can bind to these hub targets. In conclusion, this study provided a novel approach to reveal the therapeutic mechanisms of quercetin on GC, which will ease the future clinical application of quercetin in the treatment of GC.

Proportional assist ventilation versus pressure support ventilation for weaning from mechanical ventilation in adults: a meta-analysis and trial sequential analysis.

BACKGROUND: Pressure support ventilation (PSV) is the prevalent weaning method. Proportional assist ventilation (PAV) is an assisted ventilation mode, which is recently being applied to wean the patients from mechanical ventilation. Whether PAV or PSV is superior for weaning remains unclear. METHODS: Eligible randomized controlled trials published before April 2020 were retrieved from databases. We calculated the risk ratio (RR) and mean difference (MD) with 95% confidence intervals (CIs). RESULTS: Seven articles, involving 634 patients, met the selection criteria. Compared to PSV, PAV was associated with a significantly higher rate of weaning success (fixed-effect RR 1.16; 95% CI 1.07-1.26; I2 = 0.0%; trial sequential analysis-adjusted CI 1.03-1.30), and the trial sequential monitoring boundary for benefit was crossed. Compared to PSV, PAV was associated with a lower proportion of patients requiring reintubation (RR 0.49; 95% CI 0.28-0.87; I2 = 0%), a shorter ICU length of stay (MD - 1.58 (days), 95% CI - 2.68 to - 0.47; I2 = 0%), and a shorter mechanical ventilation duration (MD - 40.26 (hours); 95% CI - 66.67 to - 13.84; I2 = 0%). There was no significant difference between PAV and PSV with regard to mortality (RR 0.66; 95% CI 0.42-1.06; I2 = 0%) or weaning duration (MD - 0.01 (hours); 95% CI - 1.30-1.28; I2 = 0%). CONCLUSION: The results of the meta-analysis suggest that PAV is superior to PSV in terms of weaning success, and the statistical power is confirmed using trial sequential analysis.

Efficacy and safety of Huaier granules combined with chemotherapy for gastric cancer: A protocol for systematic review and meta-analysis.

BACKGROUND: Huaier granules, the aqueous product of Huaier (Trametes robiniophila Murr.) extract, are a broad-spectrum anti-tumor drug and have been widely used for the treatment of gastric cancer (GC). The aim of this study is to systematically investigate the efficacy and safety of Huaier granules combined with chemotherapy in the treatment of GC. METHODS: Three English databases and four Chinese databases will be searched from its inception to July 2020. Two methodological trained researchers will select the qualified studies for data extraction independently. Cochrane Risk of Bias tool will be used to assess the risk of bias of included studies. The RevMan 5.2 and stata 14.0 software will be applied for statistical analyses. Statistical heterogeneity will be computed by Cochrane X and I tests. Sensitivity analysis will be conducted to evaluate the stability of the results. The publication bias will be evaluated by funnel plots and Egger's test. The quality of evidence will be assessed by the GRADE system. RESULTS: The results of our research will be published in a peer-reviewed journal. CONCLUSION: The conclusion of our systematic review will provide evidence to judge whether Huaier granules combined with chemotherapy is an effective intervention for patient with GC. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/9BVJD.

Effects of herb-partitioned moxibustion for diarrhoea-predominant irritable bowel syndrome: A protocol for systematic review and meta-analysis.

BACKGROUND: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common functional intestinal disease characterized by abdominal pain and diarrhea. Herb-partitioned moxibustion (HPM), a characteristic external therapy, is effective in treating IBS-D. However, no systematic review has been carried out to assess the efficacy and safety of HPM for IBS-D. The aim of this study will systematically evaluate the efficacy and safety of HPM for the treatment of patients with IBS-D. METHODS: We will perform the comprehensive literature search in both English and Chinese electronic database including PubMed, Embase, Cochrane Library, Web of Science database, Medline, Chinese BioMedical Literature Database, China National Knowledge Infrastructure, Wanfang database, Chongqing VIP information, and SinoMed from their inception to July 2020. All randomized controlled trials of HPM for the treatment of IBS-D will be included. RevManV5. 3 will be applied to analyze the data. RESULTS: This study will provide high-quality synthesis of current evidence of effectiveness and safety on HPM for patients with IBS-D. CONCLUSION: The conclusion of our systematic review will provide evidence to judge whether HPM is an effective intervention for IBS-D. TRIAL REGISTRATION NUMBER: 10.17605/OSF.IO/3JXCZ.

Efficacy and safety of Kanglaite injection for gastric cancer: A protocol for systematic review and meta-analysis.

BACKGROUND: Kanglaite injection is a broad-spectrum anti-tumor drug, which is extracted from the seeds of the Chinese medicinal herb Coix lacryma-jobi, and has been widely used for the treatment of gastric cancer (GC). This study aimed to systematically investigate the efficacy and safety of Kanglaite injection for the treatment of GC. METHODS: We will perform the comprehensive literature search in English and Chinese electronic database from its inception to June 2020. Two trained researchers will independently select the qualified studies for data extraction and assess the quality and risk of bias. Cochrane Risk of Bias tool will be used to assess the risk of bias of included studies. The outcomes included overall response rate, complete response rate, 3-year progression-free survival rate, 3-year overall survival rate, and different types of treatment-related adverse events. Funnel plot analysis and Egger test will be used to assess the publication bias. Finally, the quality of evidence will be assessed by the grading of recommendations assessment, development, and evaluate system . We will calculate the risk ratio as well as their 95% confidence intervals of these outcomes and pool the results using RevMan 5.4 software and STATA 16.0 software. RESULTS: The results of our research will be published in a peer-reviewed journal. CONCLUSION: The conclusion of our systematic review will provide evidence to judge whether Kanglaite injection is an effective intervention for patient with GC. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/HF679.

Effects of rebamipide for chronic atrophic gastritis: A protocol for systematic review and meta-analysis.

BACKGROUND: Chronic atrophic gastritis (CAG) is defined as an important precancerous disease with high risk of gastric cancer. Rebamipide is a mucosal protective agent widely used in the treatment of chronic gastritis. The aim of this systematic review is to assess the efficacy and safety of rebamipide for the treatment of patients with CAG. METHODS AND ANALYSIS: We will perform a comprehensive retrieval in the following electronic databases: PubMed, Embase, MEDLINE, Cochrane Library Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI) database, Wanfang Data Knowledge Service Platform, Chinese Scientific Journals Database (VIP), Chinese Biomedical Literature Service System (SinoMed) and other sources. Two trained researchers will select the qualified studies for data extraction and assess the quality and risk of bias, independently. Then the meta-analyses will be conducted by using the RevMan 5.2 and stata 14.0. The heterogeneity of data will be investigated by Cochrane X and I tests. Sensitivity analysis will be conducted to evaluate the stability of the results. Funnel plot analysis and Egger test will be used to assess the publication bias. Finally, the quality of evidence will be assessed by the GRADE system. RESULTS: The results of our research will be published in a peer-reviewed journal. CONCLUSION: The conclusion of our systematic review will provide evidence to judge whether rebamipide is an effective intervention for patient with CAG. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/BKC3E.