Mapping of systematic reviews on traditional medicine across health conditions: a protocol for a systematic map.

INTRODUCTION: Traditional medicine (TM) is an important part of healthcare either as the main healthcare system or as a complement to conventional medicine. The effectiveness of TM has been assessed in clinical trials that have been synthesised into thousands of systematic reviews (SRs). This study is commissioned by the World Health Organization (WHO) and is aimed at providing a systematic map of SRs of TM interventions across health conditions, as well as identifying gaps in the research literature in order to prioritise future primary research. METHODS AND ANALYSIS: This is the protocol for a systematic map of SRs reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). We will search 17 electronic databases to identify SRs of TM. The literature search covers the last 5 years, from January 2018 to December 2022. At least two independent reviewers will perform the database search, screening of eligible SRs, data extraction and quality assessments using the A MeaSurement Tool to Assess Systematic Reviews (AMSTAR 2). The characteristics and extent of SRs will be analysed according to disease classification, and type of TM intervention, and visualised by means of (interactive) graphical maps. ETHICS AND DISSEMINATION: Ethical approval is not required as this is a systematic map of published studies. The findings of the study will be disseminated through online-available maps, presentations and scientific publications. PROSPERO REGISTRATION NUMBER: CRD42023416355.

Proposing a novel molecular subtyping scheme for predicting distant recurrence-free survival in breast cancer post-neoadjuvant chemotherapy with close correlation to metabolism and senescence.

Background: High relapse rates remain a clinical challenge in the management of breast cancer (BC), with distant recurrence being a major driver of patient deterioration. To optimize the surveillance regimen for distant recurrence after neoadjuvant chemotherapy (NAC), we conducted a comprehensive analysis using bioinformatics and machine learning approaches. Materials and methods: Microarray data were retrieved from the GEO database, and differential expression analysis was performed with the R package 'Limma'. We used the Metascape tool for enrichment analyses, and 'WGCNA' was utilized to establish co-expression networks, selecting the soft threshold power with the 'pickSoftThreshold' algorithm. We integrated ten machine learning algorithms and 101 algorithm combinations to identify key genes associated with distant recurrence in BC. Unsupervised clustering was performed with the R package 'ConsensusCluster Plus'. To further screen the key gene signature of residual cancer burden (RCB), multiple knockdown studies were analyzed with the Genetic Perturbation Similarity Analysis (GPSA) database. Single-cell RNA sequencing (scRNA-seq) analysis was conducted through the Tumour Immune Single-cell Hub (TISCH) database, and the XSum algorithm was used to screen candidate small molecule drugs based on the Connectivity Map (CMAP) database. Molecular docking processes were conducted using Schrodinger software. GMT files containing gene sets associated with metabolism and senescence were obtained from GSEA MutSigDB database. The GSVA score for each gene set across diverse samples was computed using the ssGSEA function implemented in the GSVA package. Results: Our analysis, which combined Limma, WGCNA, and machine learning approaches, identified 16 RCB-relevant gene signatures influencing distant recurrence-free survival (DRFS) in BC patients following NAC. We then screened GATA3 as the key gene signature of high RCB index using GPSA analysis. A novel molecular subtyping scheme was developed to divide patients into two clusters (C1 and C2) with different distant recurrence risks. This molecular subtyping scheme was found to be closely associated with tumor metabolism and cellular senescence. Patients in cluster C2 had a poorer DRFS than those in cluster C1 (HR: 4.04; 95% CI: 2.60-6.29; log-rank test p < 0.0001). High GATA3 expression, high levels of resting mast cell infiltration, and a high proportion of estrogen receptor (ER)-positive patients contributed to better DRFS in cluster C1. We established a nomogram based on the N stage, RCB class, and molecular subtyping. The ROC curve for 5-year DRFS showed excellent predictive value (AUC=0.91, 95% CI: 0.95-0.86), with a C-index of 0.85 (95% CI: 0.81-0.90). Entinostat was identified as a potential small molecule compound to reverse high RCB after NAC. We also provided a comprehensive review of the EDCs exposures that potentially impact the effectiveness of NAC among BC patients. Conclusion: This study established a molecular classification scheme associated with tumor metabolism and cancer cell senescence to predict RCB and DRFS in BC patients after NAC. Furthermore, GATA3 was identified and validated as a key gene associated with BC recurrence.

Acupuncture for the treatment of trigeminal neuralgia: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Few systematic reviews have examined the effects of acupuncture on trigeminal neuralgia. This review aims to provide up-to-date evidence on the efficacy of acupuncture for managing pain in patients with trigeminal neuralgia. METHODS: Eleven databases were searched from inception until November 2022 for relevant articles Two researchers independently conducted study selection, data extraction, and evaluation. The present review solely targeted randomized controlled trials (RCTs). The Cochrane risk of bias assessment tool 2.0 was employed to assess the risk of bias. Data were compiled using RevMan 5.4.1 software, and the quality of the evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Thirty studies involving 2295 patients were included in this review. Compared with carbamazepine, acupuncture led to improvements in pain scores (15 RCTs, mean difference (MD) - 1.40, 95% confidence interval (CI)-1.82 to -0.98 [95% prediction interval, -3.137,0.343], p < 0.00001, low certainty of evidence (CoE)), response rates (29 RCTs, risk ratio (RR) 1.20, 95% CI 1.15 to 1.25 [95% prediction interval, 1.067, 1.346], p < 0.00001, low CoE), frequency of pain attacks (2 RCTs, MD -2.53, 95% CI -4.11 to -0.96, P = 0.002, low CoE), and adverse effects (13 RCTs, risk difference (RD) -0.15, 95% CI -0.19 to -0.11 [95% prediction interval, -0.193, -0.108], P < 0.00001, very low CoE). CONCLUSION: Although the quality of evidence is low, compared with carbamazepine, acupuncture may improve trigeminal neuralgia-related pain. Further rigorously designed studies are warranted to confirm the effects of acupuncture on patients with trigeminal neuralgia.

Using Acupuncture for Adjunct Treatment for Cancer-Related Fatigue in Breast Cancer Patients Is Practicable. Reply to Hu et al. Is Acupuncture an Ideal Adjunctive Treatment for Cancer-Related Fatigue? Comment on "Choi et al. Acupuncture for Managing Cancer-Related Fatigue in Breast Cancer Patients: A Systematic Review and Meta-Analysis. Cancers 2022, 14, 4419".

We are grateful for the relevant comments by Hu et al. [...].

Acupuncture for Treating Attention Deficit Hyperactivity Disorder in Children: A Systematic Review and Meta-Analysis.

Background and Objectives: Attention-deficit hyperactivity disorder (ADHD) is a common childhood disorder characterized by inattention, hyperactivity, and impulsivity. However, it is uncertain whether the use of acupuncture (AT) in children with ADHD is supported by the current evidence. This review aims to provide updated evidence of the effectiveness of acupuncture in children with ADHD. Methods: Nine databases were searched from their inception to 28 July 2022. Two authors independently screened potentially eligible studies. The quality assessment of the selected studies was performed using Version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). The characteristics of the included studies were presented in a tabular form, and a meta-analysis was performed on the treatment effects of AT on ADHD symptoms. Results: Fourteen studies involving 1185 patients evaluating the efficacy of AT for ADHD treatment were included in this review. Compared to conventional medicine alone, the meta-analysis indicated that AT as an add-on to conventional medicine has a positive effect on improving conduct problems, learning problems, hyperactivity-impulsivity, and hyperactivity symptoms in ADHD patients. Similarly, AT alone was found to improve learning problems, hyperactivity-impulsivity, and hyperactivity symptoms in ADHD patients and exhibited better total treatment efficacy than conventional medicine alone. No major adverse events were reported. The risk of bias of the included studies was generally concerning. Conclusions: Evidence on the effectiveness of AT for ADHD patients is currently too limited to provide recommendations for its usage. More studies with the proper methodology are needed for the validation of AT interventions in treating children with ADHD.

A nationwide survey on the management of the COVID-19 pandemic and respiratory disease in South Korea.

Background: This study aimed to explore individual prevalence of respiratory symptoms and to describe the Korean population's treatment approaches, preventive health behaviors, and mental health conditions during the pandemic. Methods: We analyzed responses from an online nationwide survey, conducted between February 2021 to May 2021, about people's experiences during the pandemic. Statistical analysis was also performed to see if there were any significant differences in treatment and prevention strategies between different groups of respondents (between those had respiratory symptoms, compared with those who did not, and between those tested positive for COVID-19, compared with those who did not). Results: A total of 2,177 survey respondents completed the survey and, of these, only 142 had experienced symptoms. The most frequently reported respiratory infections related symptoms were runny or blocked nose (47.6%), cough (45.5%), fever (44.1%), sore throat (42.0%), and fatigue (30.1%). More than half of the respondents (53.1%) used complementary and alternative medicine (CAM) approaches as means of preventive measures. In terms of preventive behaviors, the more emphasized behaviors were mask-wearing (58.9%) and hand-washing after coming home (42.7%). The majority of the respondents (64.9%) did not show signs of mental health issues. Conclusion: In South Korea, conventional medicine was mainly used for COVID-19 treatment whereas CAM was commonly used as preventive measures. COVID-19 was also found to have less impact on the general population's mental health. The findings of this study may shed light on how the pandemic impacted the general population.

Acupuncture for treating attention deficit hyperactivity disorder in children: A protocol for systematic review and meta-analysis.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) patients often use complementary and alternative medicine to treat symptoms, and acupuncture is one option. This systematic review aims to assess whether acupuncture is an effective treatment for attention deficit hyperactivity disorder (ADHD). METHODS: We will search nine databases from their inception: PubMed, AMED, CINAHL, EMBASE, the Cochrane Central Register of Controlled Trials, RISS, KoreaMed, KISS, and the China National Knowledge Infrastructure database. Two investigators will independently review the selected studies, extract the data, and analyze them. The Cochrane Risk of Bias Assessment Tool will be used to assess the risk of bias. DISCUSSION: Because this is a systematic review, no ethical approval is needed. The systematic review will be published in a peer-reviewed journal and disseminated both electronically and in print. The review will be updated to support health policy and practice. TRIAL REGISTRATION NUMBER: Reviewregistry1345.

Acupuncture for Managing Cancer-Related Fatigue in Breast Cancer Patients: A Systematic Review and Meta-Analysis.

Breast cancer (BC) is the most common cancer in women and is a serious threat to women's health. Cancer-related fatigue (CRF) is a distressing symptom in BC patients during and after chemotherapy or radiation therapy that severely affects quality of life (QoL). AT is widely used for fatigue management. However, the effect of AT on CRF is still uncertain. This study aimed to evaluate the efficacy and safety of AT in the management of CRF in patients with BC. Eleven databases were searched through June 2022. Two researchers independently performed the database search, study selection, data extraction, and risk of bias assessment. Study selection was performed based on predefined Participants, Intervention, Comparators, Outcomes, Study design (PICOS) criteria, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed when reporting the results. A meta-analysis was performed according to the Cochrane systematic review method using RevMan 5.3. A total of 12 studies including a total of 1084 participants were included. The results showed that AT had a beneficial effect compared with sham AT (n = 256, SMD = -0.26, 95% CI [-0.51, -0.01], p = 0.04, I2 = 0%) and a long-term effect on fatigue score (n = 209, MD = -0.32, 95% CI [-0.59, -0.04], p = 0.02, I2 = 0%). Meta-analysis showed that AT had a beneficial effect compared with usual care (UC) on fatigue scores (n = 238, SMD = -0.39, 95% CI [-0.66 to -0.12], p = 0.005, I2 = 0%). Of the 12 articles, 3 articles were judged as having a low risk of bias in all domains and hence were of high quality. No serious adverse effects were identified. AT is an effective and safe treatment for CRF, and AT is more effective than sham AT or UC or wait-list control (WLC). Nevertheless, the methodological quality of most of these studies was low, and the included studies/sample sizes were small, so the ability to derive decisive implications was limited. Further research is needed to confirm these findings.

Chimeric Oncolytic Adenovirus Armed Chemokine Rantes for Treatment of Breast Cancer.

The immunosuppressive state in the tumor microenvironment (TME) of breast cancer makes it difficult to treat with immunotherapy. Oncolytic viruses not only lyse tumor cells but also reshape the TME. Therefore, they can play a multi-mechanism synergistic effect with immunotherapy. In this study, an oncolytic adenovirus Ad5F11bSP-Rantes was constructed and used as a vector to express the chemokine Rantes. The objective of this study was to test the dual mechanisms of the oncolytic effect mediated by virus replication and the enhanced anticancer immune response mediated by Rantes chemotaxis of immune cells. It was found that Ad5F11bSP-Rantes has strong infectivity and effective killing activity against breast cancer cells. In the established triple negative breast cancer (TNBC) xenograft model in NCG mice whose immune system was humanized with human peripheral blood mononuclear cells (PBMCs), Ad5F11bSP-Rantes achieved 88.33% tumor inhibition rate. Rantes expression was high in mouse blood, a large number of CD3+ lymphocytes infiltrated in tumor tissues and E-cadherin was up-regulated in cancer cells, suggesting that Ad5F11bSP-Rantes altered the TME and induced a reversal of cancer cell epithelial-mesenchymal transition (EMT). In conclusion, oncolytic adenovirus can exert the oncolytic effect and the chemotactic effect of immune cells and realize the synergy of multiple anticancer effects. This strategy creates a candidate treatment for the optimization of breast cancer, especially TNBC, combination therapy.

Acupoint herbal patching for bronchitis: A systematic review and meta-analysis.

BACKGROUND: Acupoint herbal patching (AHP) has long been used to treat patients with bronchitis in East Asia. This review assessed the efficacy and safety of AHP as a treatment for bronchitis. METHODS: We performed a literature search using the 9 databases and included randomized controlled trials (RCTs) or quasi-RCTs that used AHP for bronchitis. The methodological quality of each RCT was assessed using the Cochrane Handbook version 5.3, the risk of bias tool, and Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Seven RCTs were included based on the inclusion criteria. All RCTs were published in China and had a high risk of bias. Three RCTs compared AHP with conventional drug therapy for the treatment of bronchitis. The meta-analysis also showed a significant improvement in treatment effectiveness (relative risk [RR] 1.28, 95% confidence interval [CI] 1.15, 1.42; P < .00001; I2 = 0%). Two RCTs investigated AHP combined with conventional drug therapy versus conventional drug therapy. The meta-analysis showed that AHP was significantly more effective than conventional therapy in terms of treatment effective rate (RR 1.16, 95% CI 1.03, 1.29; P = .01; I2 = 0%). Three RCTs reported adverse events, and none reported severe adverse events. CONCLUSIONS: AHP appears to be more effective than conventional drug therapy alone or a placebo. Furthermore, the AHP appears to be a safe treatment option. However, due to the small number of included trials and their poor methodological quality, future studies should include larger sample sizes and well-designed RCTs. TRIAL REGISTRATION NUMBER: PROSPERO: CRD 42018110380.

Herbal Medicine Intervention for the Treatment of COVID-19: A Living Systematic Review and Cumulative Meta-Analysis.

Background: Integrative herbal medicine has been reported to have beneficial effects in the treatment of coronavirus disease 2019 (COVID-19). Aim: To compile up-to-date evidence of the benefits and risks of herbal medicine for the treatment of COVID-19 symptoms. Methods: Eleven databases, including PubMed, Cochrane Register of Controlled Trials (CENTRAL), Embase, Allied and Complementary Medicine Database (AMED), Chinese National Knowledge Infrastructure Database (CNKI), Wanfang Database, and Chinese Science and Technique Journals Database (VIP), Research Information Service System (RISS), Korean Medical database (KMBase), Korean Association of Medical Journal database (KoreaMed), and OASIS database, were searched from 15 June, 2020, until 28 March 2022. Randomized controlled trials (RCTs), published in any language, reporting the efficacy and safety outcomes of herbal medicine in patients of all ages with a PCR-confirmed diagnosis of COVID-19 were included in this analysis. Data extraction and quality assessments were performed independently. Results: Random-effects meta-analyses showed evidence of favorable effects of treatment with herbal medicine when added to standard treatment, versus standard treatment alone, on the total effective rate (p = 0.0001), time to remission from fever (p < 0.00001), rate of remission from coughing (p < 0.0001), fatigue (p = 0.02), sputum production (p = 0.004), improvement of manifestations observed on chest computed tomography scans (p < 0.00001), incidence of progression to severe COVID-19 (p = 0.003), all-cause mortality (p = 0.003), time to a negative COVID-19 coronavirus test (p < 0.0001), and duration of hospital stay (p = 0.0003). There was no evidence of a difference between herbal medicine added to standard treatment, versus standard treatment alone, on the rate of remission from symptoms such as a fever, sore throat, nasal congestion and discharge, diarrhea, dry throat, chills, and the rate of conversion to a negative COVID-19 coronavirus test. Meta-analysis showed no evidence of a significant difference in adverse events between the two groups. There was an unclear risk of bias across the RCTs included in this analysis, indicating that most studies had methodological limitations. Conclusion: Current evidence suggests that herbal medicine added to standard treatment has potential benefits in the treatment of COVID-19 symptoms but the certainty of evidence was low.

Comment on "Efficacy of ginseng and its ingredients as adjuvants to chemotherapy in non-small cell lung cancer" by H. Zhu, H. Liu, J. H. Zhu, S. Y. Wang, S. S. Zhou, M. Kong, Q. Mao, F. Long, Z. J. Fang and S.-L. Li, Food Funct., 2021, 12, 2225.

This comment raises concerns about the article "Efficacy of ginseng and its ingredients as adjuvants to chemotherapy in non-small cell lung cancer".

Delayed generation of functional virus-specific circulating T follicular helper cells correlates with severe COVID-19

Effective humoral immune responses require well-orchestrated cellular interactions between B and T follicular helper (Tfh) cells. Whether this interaction is impaired and associated with COVID-19 disease severity is unknown. Here, longitudinal acute and convalescent blood samples from 49 COVID-19 patients across mild to severe disease were analysed. We found that during acute infection activated and SARS-CoV-2-specific circulating Tfh (cTfh) cell frequencies expanded with increasing disease severity. The frequency of activated and SARS-CoV-2-specific cTfh cells correlated with plasmablast frequencies and SARS-CoV-2 antibody titers, avidity and neutralization. Furthermore, cTfh cells but not other memory CD4 T cells, isolated from severe patients induced more pronounced differentiation of autologous plasmablast and antibody production in vitro compared to cTfh cells isolated from mild patients. However, the development of virus-specific cTfh cells was delayed in patients that displayed or later developed severe disease compared to those that maintained a mild or moderate disease. This correlated with a delayed induction of high-avidity and neutralizing virus-specific antibodies. Our study therefore suggests that impaired generation of functional virus-specific cTfh cells delays the production of high-quality antibodies to combat the infection at an early stage and thereby enabling progression to more severe COVID-19 disease.

Using ginseng for menopausal women's health care: A systematic review of randomized placebo-controlled trials.

PURPOSE: This systematic review aimed to update the evidence of ginseng on menopausal women's health care. METHODS: We searched six databases (PubMed, AMED, EMBASE, the Cochrane Library, RISS, and KoreaMed) from their inception to April 2022 and included all placebo-controlled RCTs comparing any type of ginseng in menopausal women. The methodological quality of all studies was assessed using the Cochrane Risk of Bias Tool 2.0. RESULTS: We included 15 RCTs with our inclusion criteria. The majority of studies considered bias a concern. Ginseng reduced menopausal symptoms in three studies (n = 515; standardized mean difference (SMD): -0.40, 95% confidence interval (CI): -0.73 to -0.07, P = 0.02) and lowed hot flashes (n = 515; SMD: -0.34, 95% CI: -0.66 to -0.01, P = 0.04). The meta-analysis of three other studies failed to show that ginseng was beneficial for sexual function (n = 491; SMD: 0.31, 95% CI: -0.30 to 0.92, P = 0.32). Three RCTs showed positive effects of ginseng on the quality of life score (n = 515, SMD: -0.31, 95% CI: -0.61 to -0.01, P = 0.05). In two studies, ginseng failed to produce significant effects on the vaginal maturation index and vaginal pH. Another three RCTs failed to demonstrate a beneficial effect of Korean red ginseng (KRG) on endometrial thickness. CONCLUSION: This study demonstrated that ginseng can significantly reduce hot flashes, menopausal symptoms, and quality of life in menopausal women. In contrast, neither KRG nor ginseng appeared to have any direct effect on sexual dysfunction, hormones or biomarkers, or endometrial thickness. More rigorous RCTs are needed to overcome the current limitations.

Herbal medicine for COVID-19: An overview of systematic reviews and meta-analysis.

BACKGROUND: As coronavirus disease 2019 (COVID-19) continues to spread throughout countries, researchers and scientific groups have published a large number of scientific papers examining effective treatments and prevention strategies for COVID-19, including herbal medicine. It has become difficult to navigate the increasing volume of scientific material on the pandemic, and critical appraisal of these outcomes is needed. This overview of systematic reviews (SRs) aims to synthesize evidence from SRs and summarize the effects of herbal medicine interventions in the treatment of COVID-19. METHODS: Four databases were searched from inception up to October 20, 2021. SRs analyzing primary studies of the efficacy of herbal medications for treating COVID-19 were included. Two reviewers selected the studies and retrieved the data independently. The AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews) was used to assess the methodological quality of the included SRs. RESULTS: A total of 21 SRs on herbal medicine treatments for COVID-19 were included. All SRs were published between May 2020 and September 2021. Thirteen of the SRs included only randomized controlled trials (RCTs), whereas the remaining eight included evidence from nonrandomized trials in addition to RCTs, with a significant overlap identified across the RCTs. Twelve SRs concluded that existing evidence was insufficient to form a definite judgment, nine found that herbal therapy was useful, and none indicated that herbal medicine had no benefit. The AMSTAR 2 tool revealed that the methodological quality of the included SRs was generally low. CONCLUSION: In this overview of SRs, we reviewed herbal medicine-related evidence from 21 SRs that were published after the outbreak of COVID-19. This study shows that while there is considerable evidence demonstrating the advantages of herbal medicine interventions, the quality of the evidence is inadequate to provide solid and accurate judgments about the effectiveness of herbal medicine therapies for COVID-19. Despite the crisis caused by the pandemic, clinical studies and SRs should comply with established methodological standards.

Acupuncture and Moxibustion for Cancer-Related Fatigue: An Overview of Systematic Reviews and Meta-Analysis.

Although acupuncture (AT) is used in the treatment of CRF, the evidence from different systematic reviews (SRs) of AT has not yet been comprehensively evaluated. Moxibustion, which is a treatment method that is well established within Traditional East Asian Medicine, applies the heat of burning herbs towards or onto special points on the skin. Commonly, the herb Artemisia vulgaris, is used. It has been used for palliative cancer care, as well as for CRF. The aim of this overview was to evaluate the efficacy of AT and moxibustion in the management of CRF. Eleven databases were searched through for studies that were published from their dates of inception to February 2022. The study selection, the data extraction, and the assessment were performed independently by two researchers. The methodological and report quality were assessed by using the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) tool. The evidence quality was evaluated by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Fifteen SRs on AT (n = 10) and moxibustion (n = 5) treatments for CRF were included, and they include 169 randomized controlled trials and 14,392 participants. All of the SRs that were evaluated by the AMASTAR-2 had more than one deficiency, and so all of the SRs were rated as either low or critically low. For the GRADE, 18 outcomes were rated as very-low-quality evidence, 13 as low-quality evidence, 3 as moderate-quality evidence, and 0 as high-quality evidence. Most of the SRs reached the potential benefits of AT for CRF. No serious adverse effects were identified. In conclusion, the evidence suggests that, despite the advantages of AT in terms of the improvement in and the safety of the treatment of CRF, the methodological quality of most of these studies is low, which limits our ability to draw definitive meanings. Further research of high quality is needed in order to confirm these findings.

Use of Traditional, Complementary and Integrative Medicine During the COVID-19 Pandemic: A Systematic Review and Meta-Analysis.

Background: Traditional, Complementary and Integrative Medicine (TCIM) has been reported to use for symptom management of coronavirus disease 2019 (COVID-19). The objective of this review was to identify the overall usage prevalence of TCIM interventions for COVID-19. Methods: Surveys on the general population and observational studies on the COVID-19 patient chart review were located in the search of PubMed, EMBASE and Cochrane Central Register of Controlled Trials databases in September 2021. Observational studies, such as cross-sectional studies, surveys, cohort studies and hospital-based patient case reviews, published in any language, reporting the usage of TCIM in the patients with COVID-19 or the general population during the COVID-19 pandemic were included in this review. Data screening and extraction were performed independently by two reviewers. The reporting quality of the included studies was assessed with the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement. To conduct a meta-analysis of the usage prevalence of various TCIM interventions, the effect size of the proportion for each intervention was calculated with the inverse variance method. The main outcome was usage prevalence of TCIM interventions among patients with COVID-19 or the general population during the COVID-19 pandemic. Results: A total of 62 studies were included in this review. The overall TCIM usage prevalence was estimated to be 0.64 (95% CI 0.54-0.73). The overall prevalence did not differ between the population-based survey (0.65, 95% CI 0.48-0.81) and the hospital-based patient case review (0.63, 95% CI 0.52-0.73). Statistical heterogeneity and comparatively low quality in reporting were observed, which should be cautiously considered when interpreting the results. Conclusion: Various TCIM interventions were reported to be used with comparatively high frequency. Future international collaborative research might overcome the main limitation of this study, i.e., the heterogeneity of the included data. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=278452, identifier: CRD42021278452.

Triple-serotype chimeric oncolytic adenovirus exerts multiple synergistic mechanisms against solid tumors.

BACKGROUND: Oncolytic virotherapy has become an important branch of cancer immunotherapy. This study investigated the efficacy of an oncolytic adenovirus (OAV), OncoViron, with synergistic mechanisms in the treatment of multiple solid tumors. METHODS: An OAV, OncoViron, was constructed and investigated by cytological experiments and implanted tumor models of multiple solid tumor cell lines to certify its anticancer efficacy, the synergistic effects of viral oncolysis and transgene anticancer activity of OncoViron, as well as oncolytic virotherapy combined with immunotherapy, were also verified. RESULTS: The selective replication of OncoViron mediated high expression of anticancer factors, specifically targeted a variety of solid tumors and significantly inhibited cancer cell proliferation. On a variety of implanted solid tumor models in immunodeficient mice, immunocompetent mice, and humanized mice, OncoViron showed great anticancer effects on its own and in combination with programmed death 1 (PD-1) antibody and chimeric antigen receptor (CAR) T cells. Pathological examination, single-cell sequencing, and spatial transcriptome analysis of animal implanted tumor specimens confirmed that OncoViron significantly altered the gene expression profile of infected cancer cells, not only recruiting a large number of lymphocytes, natural killer cells, and mononuclear macrophages into tumor microenvironment (TME) and activated immune cells, especially T cells but also inducing M1 polarization of macrophages and promoting the release of more immune cytokines, thereby remodeling the TME for coordinating PD-1 antibody or CAR T therapy. CONCLUSIONS: The chimeric OncoViron is a novel broad-spectrum anticancer product with multiple mechanisms of synergistic and potentiated immunotherapy, creating a good opportunity for combined immunotherapy against solid tumors.