A systematic review of ozone therapy for treating chronically refractory wounds and ulcers.

This study aims at evaluating the efficacy and safety of ozone therapy for chronic wounds. The Cochrane Library, PubMed, Ovid Embase, Web of Science, and Chinese Biomedical Literature Database were searched. Randomised controlled trials (RCTs) about participants with chronic wounds were included. Risk of bias assessment was performed by the Cochrane risk-of-bias tool. A randomised-effects model was applied to pool results according to the types of wounds or ulcers. Among 12 included studies, ozone was implemented by topical application (ozone gas bath, ozonated oil, ozone water flushing) and systematic applications including autologous blood immunomodulation and rectal insufflation. The results indicated compared with standard control therapy for diabetic foot ulcers, ozone therapy regardless of monotherapy or combined control treatment markedly accelerated the improvement of the wound area(standardised mean difference(SMD) = 66.54%, 95% confidence interval (CI) = [46.18,86.90], P < .00001) and reduced the amputation rate (risk ration (RR) = 0.36, 95% CI = [0.24,0.54], P < .00001). But there is no improvement in the proportion of participants with completely healed wounds and length of hospital stay. No adverse events associated with ozone treatment have been reported. And the efficacy of ozone therapy for other wound types is still uncertain because of no sufficient studies. More high-quality randomised controlled trials are needed to confirm the efficacy and safety of ozone therapy for chronic wounds or ulcers.

Effect of cold atmospheric plasma therapy on wound healing in patients with diabetic foot ulcers: protocol for a systematic review and meta-analysis.

INTRODUCTION: Diabetic foot ulcer (DFU), one of the most common and serious consequences of diabetes, affects many individuals and often leads to amputation, death and other disastrous outcomes. Diabetic foot ulcers have a relatively poor response to therapy, which increases the likelihood of recurrence. Cold atmospheric plasma (CAP) therapy is an emerging treatment method for DFU that can reduce bacterial loads and speed up the healing of chronic wounds. Although some studies have reported that CAP could improve the wound healing speed compared with conventional traditional therapy, the samples in these studies are small and not sufficiently representative. The purpose of the current systematic review and meta-analysis is to evaluate the effectiveness and safety of CAP in DFU treatment and provide a scientific basis for its clinical application. METHODS AND ANALYSIS: The following databases will be searched: Wanfang, China Biology and Medicine CD, Embase, PubMed and The Cochrane Library. We will retrieve publications, conference documents, current trials and internal reports written in English or Chinese related to the effect of CAP therapy on wound healing in patients with diabetic foot ulcers up to 30 June 2022. The selected articles will be read independently by two reviewers, and valid information such as first author, publication date and outcome indicators will be extracted. Researchers will also assess the quality of the literature using the Cochrane risk-of-bias tool 2. RevMan 5.3.5, EndNote X7 and STATA V.13.0 will be used for data analysis. ETHICS AND DISSEMINATION: No ethical review is necessary for this systematic review because it is based on previously published data and does not include patient intervention. A peer-reviewed publication will publish the findings of this investigation.

Alterations in the gut virome are associated with type 2 diabetes and diabetic nephropathy.

Although changes in gut microbiome have been associated with the development of T2D and its complications, the role of the gut virome remains largely unknown. Here, we characterized the gut virome alterations in T2D and its complications diabetic nephropathy (DN) by metagenomic sequencing of fecal viral-like particles. Compared with controls, T2D subjects, especially those with DN, had significantly lower viral richness and diversity. 81 viral species were identified to be significantly altered in T2D subjects, including a decrease in some phages (e.g. Flavobacterium phage and Cellulophaga phaga). DN subjects were depleted of 12 viral species, including Bacteroides phage, Anoxybacillus virus and Brevibacillus phage, and enriched in 2 phages (Shigella phage and Xylella phage). Multiple viral functions, particularly those of phage lysing host bacteria, were markedly reduced in T2D and DN. Strong viral-bacterial interactions in healthy controls were disrupted in both T2D and DN. Moreover, the combined use of gut viral and bacterial markers achieved a powerful diagnostic performance for T2D and DN, with AUC of 99.03% and 98.19%, respectively. Our results suggest that T2D and its complication DN are characterized by a significant decrease in gut viral diversity, changes in specific virus species, loss of multiple viral functions, and disruption of viral-bacterial correlations. The combined gut viral and bacterial markers have diagnostic potential for T2D and DN.

Effects of electroacupuncture on bladder dysfunction and the expression of PACAP38 in a diabetic rat model.

Objective: To explore the effects and the possible mechanism of electroacupuncture (EA) on diabetic bladder dysfunction (DBD) in streptozotocin-high fat diet (STZ-HFD) induced type 2 diabetes mellitus (T2DM) rats. Methods: The experiment was divided into Control, diabetic bladder dysfunction, electroacupuncture, and Sham electroacupuncture group. After 8 weeks of electroacupuncture intervention, the body mass, 24 h urine volume, intraperitoneal glucose tolerance test (IPGTT), and urodynamics were detected. After the wet weight of the bladder was detected, the hematoxylin-eosin (HE), Masson's trichrome, and TUNEL were used to analyze histological changes. The PACAP38 expressions in the bladder were detected by Real-time PCR and Western blot. Results: Compared to the Control group, the bladder wet weight, 24 h urine volume, blood glucose, maximum bladder capacity, bladder compliance, bladder wall thickness, the smooth muscle/collagen ratio, and apoptosis rate of the diabetic bladder dysfunction group were significantly increased. Moreover, the body mass and leak point pressure were significantly reduced. Compared with the Sham electroacupuncture group, the bladder wet weight, maximum bladder capacity, bladder compliance, bladder wall thickness, and apoptosis rate of the electroacupuncture group were significantly reduced. In contrast, the leak point pressure was increased. The PACAP38 mRNA and PACAP38 protein expression of the diabetic bladder dysfunction group were significantly lower than the Control group, while electroacupuncture treatment could upregulate PACAP38 mRNA levels and PACAP38 protein expression of diabetic bladder dysfunction model rats. Conclusion: electroacupuncture could ameliorate bladder dysfunction in the diabetic bladder dysfunction model rats by reversing bladder remodeling, which might be mainly mediated by regulating the PACAP38 level.

Protective Effect of Keluoxin against Diabetic Nephropathy in Type 2 Diabetic Mellitus Models.

Diabetic nephropathy (DN) is a chronic kidney disease that develops in patients with diabetes mellitus (DM). Renal dysfunction and persistent proteinuria are the main clinical features of DN. Podocyte injury is an important cause of persistent proteinuria and diabetic kidney disease (DKD) progression. Traditional Chinese patent medicines can improve renal function by enhancing autophagy and promoting apoptosis. Keluoxin is a Chinese patent medicine that has the effect of invigorating qi and nourishing yin, activating blood, and eliminating blood stasis. Therefore, we hypothesized that Keluoxin may have a protective effect against diabetic nephropathy in rats with type 2 DM. Rats induced with diabetes through streptozocin (STZ) injection and a high-fat and high-sugar diet were treated with Keluoxin (0.63 g/kg/day) for 8 weeks, and renal function, biochemical indicators, and histopathological changes in renal tissues were observed. Immunofluorescence staining and western blot analysis were used to detect the expression of autophagy-related proteins. The results showed that Keluoxin reduced blood glucose and lipid levels, improved renal function, and alleviated renal histopathological changes in rats with DN. The therapeutic effect was similar to that of Irbesartan (15.6 mg/kg/day). It is inferred that the mechanism works through reducing the obstruction of downstream pathways of autophagy by improving the lysosomal degradation function and alleviating podocyte injury. This study demonstrates that Keluoxin could regulate autophagy in podocytes, alleviate kidney injury in rats with DN, and have a protective effect on renal function; its mechanism can thus be a potential therapy for DN.

Probiotics, Pre-biotics and Synbiotics in the Treatment of Pre-diabetes: A Systematic Review of Randomized Controlled Trials.

Objectives: This study aimed to review the data from randomized controlled trials (RCTs) and identify evidence for microbiota's role and use of probiotics, pre-biotics, or synbiotics in pre-diabetes. Methods: RCTs of pro-, pre-, synbiotics for the treatment of pre-diabetes population will be summarized. We searched for EMBASE, MEDLINE, Web of Science, Cochrane Central, Clinical Trials (ClinicalTrials.gov) from inception to February 2021. Results: The gut microbiota influences host metabolic disorders via the modulation of metabolites, including short-chain fatty acids (SCFAs), the endotoxin lipopolysaccharides (LPS), bile acids (BA) and trimethylamine N-oxide (TMAO), as well as mediating the interaction between the gastrointestinal system and other organs. Due to the limited sources of studies, inconsistent outcomes between included studies. Probiotics can decrease glycated hemoglobin (HbA1c) and have the potential to improve post-load glucose levels. The supplementation of probiotics can suppress the rise of blood cholesterol, but the improvement cannot be verified. Pre-biotics are failed to show an evident improvement in glycemic control, but their use caused the changes in the composition of gut microbiota. A combination of probiotics and pre-biotics in the synbiotics supplementation is more effective than probiotics alone in glycemic control. Conclusion: In the current studies using probiotics, pre-biotics or synbiotics for the treatment of pre-diabetes, the benefits of modulating the abundance of gut microbiota were partially demonstrated. However, there is insufficient evidence to show significant benefits on glucose metabolism, lipid metabolism and body composition.

Eliminating the Detrimental Effect of Secondary Doping on PEDOT : PSS Hole Transporting Material Performance.

Secondary doping has a long history of use in conductivity enhancement in poly(3,4-ethylenedioxythiophene) : poly(styrene sulfonate) (PEDOT : PSS). However, very little research has addressed its detrimental effect on application performance of PEDOT : PSS in organic solar cells. Herein, it was shown that the uneven drying of secondary dopant-water mixture results in a nonuniform/continuous film structure, causing severe damage to the device efficiencies (dropping about 8 and 23 % for poly[(2,6-(4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)-benzo[1,2-b:4,5-b']dithiophene))-alt-(5,5-(1',3'-di-2-thienyl-5',7'-bis(2-ethylhexyl)benzo[1',2'-c:4',5'-c']dithiophene-4,8-dione))] (PBDB-T) : 3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-indanone))-5,5,11,11-tetrakis(4-hexylphenyl)-dithieno[2,3-d:2',3'-d']-s-indaceno[1,2-b:5,6-b']dithiophene (ITIC) and poly[(2,6-(4,8-bis(5-(2-ethylhexyl)-4-fluorothiophen-2-yl)benzo[1,2-b:4,5-b']dithio-phene))-co-(1,3-di(5-thiophene-2-yl)-5,7-bis(2-ethylhexyl)-benzo[1,2-c:4,5-c']dithiophene-4,8-dione))](PM6) : (3,9-bis(1-oxo-2-methylene-3-(1,1-dicyanomethylene)-5,6-difluoroindanone)-5,5,11,11-tetrakis(4-n-hexylphenyl)-dithieno[2,3d:2',3'd']-s-indaceno[1,2b:5,6b']dithiophene (IT-4F) cells, respectively) and thermal stabilities. Moreover, a simple yet robust dialysis treatment was proposed to solve the issue of noncontinuity and retain the secondary doping's advantages of quinoid structure simultaneously, thus demonstrating a significant enhancement in device performance. This study will be of great importance to the future exploration of the next generation of post-treatment strategy.

Serum vitamin D levels and type 2 diabetic erectile dysfunction: A protocol for systematic review and meta-analysis.

INTRODUCTION: Diabetic erectile dysfunction (DED) has gradually become a worldwide problem. Due to the mechanism of DED is not clear, it is impossible to treat it pertinently. Recently, some studies have shown that vitamin D is associated with DED, type 2 diabetes mellitus (T2DM) and erectile dysfunction (ED), but there is no systematic review and meta-analysis on the relationship between vitamin D and DED. METHODS AND ANALYSIS: The databases of English databases (PubMed, MEDLINE, EMBASE, Web of Science, Cochrane Library) and Chinese databases (China National Knowledge Infrastructure, China Biology Medicine Database, Wanfang Database, VIP Database) will be retrieved. The search strategy that will be run in the PubMed and tailored to the other database when necessary is presented in . RevMan 5.3 and Stata 11.0 will be used for Systematic Review and Meta-analysis. This protocol reported under the Preferred Reporting ltems for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement, and we will report the systematic review by following the PRISMA statement.(Table is included in full-text article.) RESULTS:: Through a systematic review, and meta-analysis when necessary, we can obtain the relationship between vitamin D and DED. We will share our findings in the third quarter of 2021. CONCLUSION: The association between serum vitamin D levels and type 2 diabetic erectile dysfunction will be assessed. Besides, the results of this review may provide some help for clinicians to make decisions. ETHICS AND DISSEMINATION: Ethical approval is not required as the review is a secondary study based on published literature. The results will be published in a public issue journal to provide evidence-based medical evidence for urologists and andrologists to make better clinical decisions. PROTOCOL REGISTRATION NUMBER: INPLASY202040164.

The effect of Qigong Wuqinxi for osteopenia and primary osteoporosis: A protocol for systematic review and meta analysis.

INTRODUCTION: Osteoporosis (OP) and related fragility fractures are a significant public health problem which leads to pain, disability, loss function of independence, considerable complications and increased mortality. Exercise training is the only alternative strategy to improve multiple skeletal and fall risk factors simultaneously. Wuqinxi is 1 of the Chinese mind-body exercises using to improve physical and mental health and fight against diseases for thousands of years. Our study aims to systematically review the existing literature to further explore the efficacy and safety of Wuqinxi in the prevention and treatment of osteopenia and OP. METHODS AND ANALYSIS: The following electronic databases (PubMed, Science Citation Index, Embase (Ovid) database, the Cochrane Library, the China National Knowledge Infrastructure, the China Biology Medicine disc, the China Science and Technology Journal Database, the Wan fang Database, ClinicalTrials.gov and the Chinese Clinical Trial Registry Platform) will be searched from the beginning to 1 June 2020. Only randomized controlled trials will be enrolled, in which the intervention group must include a form of Wuqinxi, while the control group can involve other conventional treatment or no intervention. The potential outcome measures will include bone mineral density values, bone turnover markers, fragility fractures, quality of life, pain scores, and adverse events. The Cochrane risk of bias assessment tool will be used to assess the risk of bias in each study. RESULTS: The current study is a protocol for systematic review and meta-analysis without results, and data analysis will be carried out after the protocol. We will share our findings in the third quarter of 2021. CONCLUSION: This review aims to evaluate up-to-date evidence of Wuqinxi for bone health in English or Chinese language studies, and explore whether Wuqinxi can be used as an adjuvant treatment for osteoporosis and osteopenia. ETHICS AND DISSEMINATION: Ethical approval is not required as the review is a secondary study based on published literature. The results of the study will be published in peer-reviewed publications and disseminated electronically or in print. PROTOCOL REGISTRATION NUMBER: INPLASY202040135.

The effectiveness of acupoint catgut embedding in hyperlipidemia with obesity: Protocol for a systematic review and meta-analysis.

BACKGROUND: Hyperlipidemia is a common disease characterized as blood lipid metabolism disorders, which is always companied with obesity. Hyperlipidemia is the leading cause of the cardiovascular disease (CVD) closely associated with mortality, and the risk can further elevate in the obese population. Additionally, it induces stroke and acute pancreatitis. Studies demonstrated that acupoint catgut embedding is an effective therapy for hyperlipidemia with obesity. Whereas, there is no systematic review and meta-analysis to support the point. Thus, we intend to conduct a systematic review and meta-analysis to testify its effectiveness in hyperlipidemia with obesity. METHODS: We will include articles by searching the following database: PubMed, Embase, Web of Science, Cochrane Controlled Trials Register (CENTRAL), China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database (CBM), Chinese Science Journal Database (VIP), and Wanfang database. Whats more, the manual search can be executed as the complement of database searching. Endnote X8 and RevMan V.5.3 will be used to complete the process of study selection, data analysis, as well as date management. RESULT: The primary outcomes contain the reduction of TC, TG, LDL-C, HDL-C, and BMI, body weight (WB), waist circumference(WC), body fat percent (F%) from baseline to the end of studies. The second outcome is the number of adverse events during the total trial. CONCLUSION: We will summarize sufficient evidence to confirm the therapeutic effect and safety of acupoint catgut embedding in hyperlipidemia with obesity. INPLASY REGISTRATION NUMBER: INPLASY202040036.

The effect of varicocele repair for sperm DNA fragmentation: A protocol for systematic review and meta-analysis.

INTRODUCTION: Sperm DNA integrity has been considered as one of the important determinants of normal fertilization and embryonic development in natural and assisted pregnancy. It is difficult for men with high levels of sperm DNA fragmentation (SDF) in semen to conceive their partners naturally and assist in conception. The studies have found that the level of SDF in the semen of patients with varicocele (VC) was on the high side. In recent years, the effect of VC surgery on DNA fragmentation index has attracted the attention of researchers. In this study, we will evaluate the effectiveness of VC repair as a way to alleviate SDF and improve male fertility. METHODS AND ANALYSIS: Electronic databases including English databases (PubMed, MEDLINE, EMBASE, Web of Science, Cochrane Library) and Chinese databases (China National Knowledge Infrastructure, China Biology Medicine Database, Wanfang Database, VIP Database) will be searched from their inception to December 2020 to recognize related studies. All the randomized controlled trials of microsurgical varicocelectomy for the management of VC patients will be included. The potential outcome will include improvement in SDF, oxidative stress markers (reactive oxygen species, nitric oxide, and lipid peroxidation products), sperm chromatin compaction, other advanced sperm function characteristics, follow-up of fertility results. We will conduct this study strictly according to the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: The study is a protocol for systematic review and meta-analysis without results, and data analysis will be carried out after the protocol. We will share our findings on April 5th of 2021. CONCLUSION: This systematic review will provide more evidence to assess whether varicocelectomy is an effective intervention for patients with SDF. The results will be published in a public issue journal and offer the urologists help to make clinical decisions. ETHICS AND DISSEMINATION: Formal ethical approval is not required in this protocol. We will collect and analyze data based on published research. Since this research does not involve patients, personal privacy will not be affected. The results of this review will be distributed to peer-reviewed journals or submitted to relevant conferences. PROTOCOL REGISTRATION NUMBER: INPLASY202070119.

Cardiovascular risk factors in children and adolescents with subclinical hypothyroidism: A protocol for meta-analysis and systematic review.

INTRODUCTION: Subclinical hypothyroidism (SH) is serum thyrotropin (TSH) slightly increased, while serum free thyroxine (FT4) levels are normal, and patients may have no abnormal symptoms, or only slight hypothyroidism, there are many studies proving that SH does increase cardiovascular risk in adults. However, there are few studies in children and adolescents. In order to explore whether children with subclinical hypothyroidism have a higher cardiovascular risk, we designed this meta-analysis. METHODS: The protocol of this systematic review and meta-analysis was registered on the NPLASY (No. 202040182). The following electronic databases will be searched from the inception through the present to find studies that live up to our standard: PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP. And we will include case-control studies, cohort studies, and cross-sectional studies. For including study, we will use the Newcastle-Ottawa Scale to evaluate their quality. Then 2 researchers will independently extract the required information. I statistics and subgroups will be used to analyze heterogeneity. We conduct a sensitivity analysis by excluding literature successively. When the system review contains >10 articles, Egger test will be conducted to evaluate publication bias. RESULTS: From this study, we will assess the cardiovascular risk of children and adolescents with SH from multiple perspectives. CONCLUSION: The conclusion of this paper will provide evidence for cardiovascular risk of SH children and provide basis for prevention and treatment of SH. ETHICS AND DISSEMINATION: This meta-analysis does not collect personal primary data, so there is no need for formal moral recognition. The results of the system review will be presented to national and international conferences for publication.

The efficacy of vitamin D supplementation on painful diabetic neuropathy: Protocol for a systematic review and meta-analysis.

BACKGROUND: Painful diabetic neuropathy (PDN) is one of the main and severe complications of diabetic patients, which not only accelerates the occurrence of ulcers of diabetic foot and amputation of lower extremities but also severely affects the quality of life. It is common that vitamin D deficiency in diabetic patients and especially in these patients diagnosed with diabetic peripheral neuropathy. Previous studies have proved that there is an apparent vitamin D deficiency in PDN patients, and vitamin D supplementation can effectively improve patients' pain symptoms and neurologic function. However, the evidence of these studies is unconvincing. Therefore, our research objective is to explore the effectiveness and security of vitamin D supplements on PDN. METHODS: We will include randomized controlled trials on vitamin D supplementation in the treatment of PDN. And we will retrieve 8 electronic databases concerning this theme. The English databases mainly retrieve PubMed, Web of Science, Embase, and the Cochrane Library, while CNKI, VIP, CBM, and Wanfang database will be used to retrieve the Chinese Literature. There is no definite time limit for retrieval literatures, and the languages will be limited to Chinese and English. Besides, some clinical registration tests and gray literatures are also researched by us. The primary outcomes of our study are the amelioration of pain symptoms and assessment of peripheral nerve function. And some changes of biochemical indicators including fasting blood glucose, 2 hours postprandial blood glucose, glycosylated hemoglobin, calcium, and serum vitamin D level from preintervention and postintervention, adverse events will be regarded as secondary outcomes. The Review Manager RevMan5.3 will be used for meta-analysis of studies are included. RESULTS: In this systematic review and meta-analysis, higher quality data evidence on vitamin D supplementation for PDN will be provided. CONCLUSION: Our study will eventually provide a proof of the efficacy and safety of vitamin D supplementation in patients with PDN, and to add a new option for the prevention and treatment of PDN patients. INPLASY REGISTRATION NUMBER: INPLASY202050065.

Effects of ozone for treating chronically refractory wounds and ulcers: A protocol for systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: The prevalence of chronically refractory wounds and ulcers is growing rapidly. However, the treatment options are not completely effective. Ozone has been demonstrated as being useful in promoting wound healing as well as adverse events in individual studies. Consequently, it is necessary to conduct a meta-analysis of high-quality trials to find out whether ozone therapy is effective and safe in these chronic wounds. METHODS: We will search the Cochrane Library, PubMed, the Web of Science, Embase, CBM, and the Chinese Clinical Registry website without restriction on language, date, or study setting. Randomized controlled trials of ozone therapy for chronical wounds or ulcers will be retrieved in diverse databases from inception to May 2020. The primary outcome of the meta-analysis is the proportion of participants with completely healed wounds; time to achieve complete ulcer healing; change in wound size. The secondary outcomes include the incidence of adverse events, amputation, quality of life, length of hospital stay, and cost. Two reviewers will adopt the Cochrane Collaboration's risk of bias tool to assess the randomized controlled trials and all relevant data will be analyzed by utilizing the Review Manager software V5.3.0. RESULTS: This study will offer a high-quality synthesis of the effectiveness and safety of ozone for treating chronically refractory wounds and ulcers. CONCLUSION: This systematic review and meta-analysis will find out the available evidence to assess whether ozone therapy is beneficial to wound healing and side effects, producing evidence reference for clinical practice on the treatment of wound care.

Blood DNA methylation and type 2 diabetes mellitus: A protocol for systematic review and meta-analysis.

BACKGROUND: Epidemiology of type 2 diabetes (T2D) is affected by genetic and environmental factors. Deoxyribonucleic acid (DNA) methylation as a kind of epigenetic mechanism has been reported to affect the pathogenesis of T2D. Both global DNA methylation and candidate genes were observed differentially methylated and identified changes. Peripheral blood biomarkers could have significant clinical utility due to the noninvasive operation and showed efficacy in measuring T2D-related DNA methylation. Moreover, due to the reversible feature of DNA methylation, it can be an effective therapy for T2D. METHODS: This study will be conducted according to the preferred reporting items for systematic review and meta-analysis protocols 2015 statement. The protocol of this systematic review and meta-analysis was registered on international platform of registered systematic review and meta-analysis protocols (No. 202040136). The following electronic bibliographic databases will be searched from inception: EMBASE, MEDLINE, Web of Science, Cochrane Central, China National Knowledge Infrastructure, Wanfang and China Science and Technology Journal Database, and Clinical Trials (ClinicalTrials.gov). A search strategy will be developed using a combination of medical subheadings words and keywords related to T2D, human peripheral blood, and DNA methylation. Two reviewers will screen the literature, and a third reviewer will adjudicate in case of disagreements. All the data will be extracted by 2 independent reviewers. The Cochrane Risk of Bias Assessment Tool will be used to assess the bias of randomized controlled studies, and the Newcastle-Ottawa scale for nonrandomized controlled studies. All the assessment will be investigated by 2 independent reviewers. The overall quality of extracted data will be assessed by using the grading of recommendations, assessment, development, and evaluation assessment tool. Disagreements and conflicts will be resolved by discussing it with a third reviewer. The narrative synthesis and meta-analysis of all evidence will be performed as the main findings analyzed.

Retinal blood oxygen saturation and vascular endothelial growth factor-A in early diabetic retinopathy: A protocol for systematic review and meta-analysis.

BACKGROUND: Diabetic retinopathy (DR) remains the most common microvascular complication of diabetes; both its high prevalence and associated high risk of vision loss lead it to the major global health burden. Despite significant research efforts, there still remains much of the underlying pathology not fully understand. In the past studies, inner retinal blood flow disturbances are widely assessed as a potential biomarker of DR. However, the results have been variable and even contradictory. Improved methods to figure out the metabolic disturbances associated with DR are essential. Some research showed that both vascular endothelial growth factor-A and blood oxygen saturation are higher in DR patients and correlated with disease severity. Therefore, we decided to conduct a systematic review and meta-analysis to find out the connection of them and provide robust evidence on the mechanism underlying this connection to help us better understand the pathophysiology behind the hypoxic retina and find better ways to treat DR. METHODS: This study will be conducted according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. We will do electronic searches from PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang database, CNKI, and VIP database. Two reviewers will screen all the references independently and any disagreement will be solved by the third involvement. All data will be extracted by 2 independent reviewers according to a standardized data extraction sheet. Based on the type of studies, 2 reviewers will independently use different scales to assess the risk of bias. Any disagreements and conflicts will be resolved by discussing it with a third reviewer. We will conduct a random-effects meta-analysis. Individual and pooled odds ratios/relative risks and associated 95% confidence intervals will be calculated as well as between-study heterogeneity. The potential for publication bias will also be evaluated. If possible, we will explore reasons for potential between-study heterogeneity. RESULTS: This study is a protocol for systematic review and meta-analysis without results. Associated data analysis will be carried out after the protocol. CONCLUSION: The protocol aims to guide a meta-analysis whose purpose is investigating the association between retinal blood oxygen saturation and vascular endothelial growth factors in patients with early DR and trying to find out the mechanism that the changing of retinal oxygen saturation in patients with DR. INPLASY REGISTRATION NUMBER: INPLASY202040161.

Acupuncture for the treatment of radiation-induced xerostomia among patients with cancer: A protocol for a systematic review and meta-analysis.

BACKGROUND: With the number of cancer patients growing, radiotherapy and chemotherapy have been a necessary treatment. Unfortunately, there are many side effects after radiation and chemotherapy, one of which is xerostomia that always harasses patients. Although there are many ways of treatment of xerostomia, they have many disadvantages. With the rare side effects and the excellent effect, acupuncture has been widely applied to dry mouth after radiotherapy, but it has not been recognized as the standard treatment. Because acupuncture prescription is mostly different and the sample size of studies is small, we need more high-quality meta-analysis to provide relatively reliable evidence for the treatment of radiation-induced xerostomia. The objective of this study is to assess the curative effect of acupuncture treatment of cancer patients after radiotherapy and provide more reliable evidence for acupuncture treatment of xerostomia after radiotherapy for cancer patients. METHODS: We will search the following databases: CENTRAL (The Cochrane Central Register of Controlled Trials), MEDLINE, EMBASE, PubMed, CNKI (China National Knowledge Infrastructure), VIP (China Science and Technology Journal Database), Wan Fang Data Knowledge Service Platform. At any rate, 2 review authors will assess all randomized controlled trials (RCTs), seemingly conformance to the inclusion criteria, to confirm qualification, determine the risk of bias and extract data using a running data extraction form. The revolution of disagreements is a discussion. We will use the approach recommended by Cochrane reviews to assess the bias in studies. Risk ratios (RR) and 95% confidence intervals (CIs) will be used to assess the treatment effects of an intervention for dichotomous results. We will use mean differences (MD) and standard deviation (SD) to aggregate the data of every trial for continuous results. The heterogeneity test of Cochran and quantification of the I statistic will be used to assess the variation of treatment effects. Only if there are studies of semblable comparisons reporting the same results, we will conduct a meta-analysis. RESULTS: From the study, we will evaluate the efficacy of acupuncture for xerostomia patients who has cancer and been treated by radiation. CONCLUSION: The conclusion of this study will be the evidence, which can ensure the efficacy of acupuncture for cancer patients with radiation-evoked xerostomia among and provide guidance for the treatment of xerostomia. INPLASY REGISTRATION NUMBER: INPLASY202040211.