Objective To analyze the changing trend and influencing factors of the disease burden of older adults with metabolic dysfunction-associated steatotic liver disease(MASLD)globally and in China from 1990 to 2021,and to predict its future trend.Methods Data on the prevalence and disability-adjusted life years(DALYs)of MASLD among individuals aged 60 years and older from the Global Burden of Disease(GBD)2021 database were extracted for a global context,China,and five socio-demographic index(SDI)regions.Joinpoint regression analysis was employed to calculate the average annual percent change(AAPC)in the age-standardized prevalence(ASPR)and DALY rates(ASDR)from 1990 to 2021,and the subgroup analyses were conducted by age and gender.A three-factor decomposition model was used to quantify the relative impacts of aging,population growth,and epidemiological change on the changes in disease burden,while a Bayesian age-period-cohort model was applied to predict the trend in disease burden of older adults with MASLD from 2022 to 2035.Results The number of MASLD patients in the global and Chinese elderly populations was 366,398,400 cases and 98,916,800 cases in 2021,respectively,representing an increase of 176.40%and 230.71%compared to 1990.The number of DALYs was 1,834,700 person-years and 234,100 person-years,showing increases of 139.52%and 127.06%,respectively.During the period from 1990 to 2021,ASPR[AAPC=0.67%,95%CI(0.62%,0.72%)]and ASDR[AAPC=0.20%,95%CI(0.06%,0.34%)]of MASLD in the global elderly population exhibited a significant upward trend.ASPR[AAPC=0.65%,95%CI(0.55%,0.75%)]of MASLD in the elderly population in China showed a significantly upward trend,while ASDR[AAPC=-0.49%,95%CI(-0.92%,-0.06%)]showed a significantly downward trend.Subgroup analyses by gender indicated that in both 1990 and 2021,the number of prevalence and DALYs in the elderly female populations were higher than those in the corresponding male populations globally and in China.Additionally,while the ASDR of MASLD among the elderly in high-middle and low SDI regions regions showed significant downward trends from 1990 to 2021,the number of patients and DALYs across the five SDI regions increased in 2021 compared to 1990.The 60～64 age group accounted for the highest proportion of case numbers and DALYs among the global elderly population with MASLD in 2021,whereas the 65～69 age group ranked the first in China.Decomposition analysis revealed that population growth was the primary influencing factor for the increase in disease burden of MASLD across all areas,contributing the most(122.09%)to the increase in DALYs in China.The prediction model indicated that by 2035,the number of cases and DALYs in the global elderly population would increase by 65.80%and 43.11%,respectively,compared to 2021,while in China,the increases would be 104.95%and 24.78%,respectively.Conclusion The disease burden of MASLD in the elderly populations globally and in China remains substantial and is expected to continue increasing in the future.It is recommended to promote healthy lifestyle practices while actively adopting a multidisciplinary management approach for elderly MASLD patients and enhancing the research and development of effective drugs to alleviate the burden associated with this disease.

Objective To analyze the disease burden of hypertension in the elderly population from 1990 to 2021 and to predict future trends in China and globally,thereby providing insights for public health de-cision-making regarding older adults with hypertension in China.Methods Data on hypertension-related deaths and disability adjusted life years(DALYs)for individuals aged ≥60 years was extracted from the Global Burden of Disease(GBD)2021 database for the world,China,and five sociodemographic index(SDI)re-gions.Age-standardized mortality and DALYs rates for hypertension in the elderly population were calculated,and Joinpoint regression was used to assess trend changes of disease burden,with results reported as average annual percentage change(AAPC).Additionally,subgroup analyses were conducted based on age and sex.The relative impact of aging,population growth,and epidemiological changes on disease burden was analyzed using a three-factor decomposition method.Future projections for the disease burden from 2022 to 2040 were per-formed using a Bayesian model.Results From 1990 to 2021,both age-standardized mortality and DALYs rates for hypertension in the elderly population demonstrated a significant downward trend globally and in China(both AAPC values were negative,all P＜0.001).However,in 2021,the number of deaths attributed to hy-pertension among the elderly increased by 68.37％globally and by 157.85％in China compared to 1990,while DALYs rose by 61.74％globally and 125.98％in China.Notably,except for the high SDI region,the other four SDI regions witnessed significant increases in deaths and DALYs due to hypertension in 2021 compared to 1990.Furthermore,the burden of hypertension was generally higher among elderly males than females in China.In 2021,the highest number of DALYs due to hypertension was observed in the 70-74 years group,while deaths were predominantly concentrated in the 80-84 years group.Decomposition analysis indicated that popu-lation growth was the primary factor contributing to the increases in deaths and DALYs due to hypertension among the elderly globally and in China.Predictive analysis suggested that the disease burden of hypertension among the elderly in China,encompassing overall,male,and female populations,is expected to continue rising from 2022 to 2040.Conclusions Although age-standardized mortality and DALYs rates for hypertension among the elderly in China have shown a downward trend over the past three decades,the absolute burden re-mains substantial.There is an urgent need for the formulation and implementation of more effective public health policies and clinical interventions to address this critical public health challenge.

BACKGROUND:The relationship between hepatocellular carcinoma (HCC) and gut microbiota has gained attention for its impact on HCC immunotherapy. METHODS:Key gut microbial metabolites, including bile acids, toll-like receptor 4, short-chain fatty acids, and bacterial toxins, contribute to HCC progression and influence immune responses through the gut-liver axis. As immune checkpoint inhibitors (ICIs) become common in HCC treatment, modulating the gut microbiota offers new strategies to enhance ICIs efficacy. However, individual differences in microbial composition introduce challenges, with some HCC patients showing resistance to ICIs. RESULTS:This review summarizes the latest findings on the role of gut microbiota in HCC and explores emerging therapeutic approaches, including fecal microbiota transplantation, probiotics, antibiotics, and natural compounds. CONCLUSIONS:The focus is on translating these insights into personalized medicine to optimize ICIs responses and improve HCC treatment outcomes.

BACKGROUND:While immune-related adverse events (irAEs) have been linked to improved outcomes in melanoma and non-small cell lung cancer (NSCLC), their prognostic role in hepatocellular carcinoma (HCC), a malignancy arising in a unique immune microenvironment shaped by chronic inflammation and cirrhosis, remains unexplored. This meta-analysis investigated the relationship between irAEs and the effectiveness of immune checkpoint inhibitors (ICIs) in HCC. METHODS:Following PRISMA guidelines, we systematically reviewed studies from PubMed, Embase and the Cochrane Library (through December 2024) that evaluated the association between irAEs and ICIs' effectiveness in HCC. The primary outcomes were progression-free survival (PFS) and overall survival (OS), and the secondary outcomes were objective response rate (ORR) and disease control rate (DCR). Subgroup analyses assessed irAEs' types, severity and corticosteroid impact. RESULTS:Among 24 retrospective studies (4798 patients), irAEs occurrence correlated with superior ORR (OR, 2.18; 95% CI, 1.64-2.89), DCR (OR, 3.09; 95% CI, 1.81-5.27), PFS (HR, 0.62; 95% CI, 0.51-0.75) and OS (HR, 0.76; 95% CI, 0.61-0.95). Dermatologic and endocrine irAEs were associated with improved survival (PFS: HR, 0.45 and 0.50; OS: HR, 0.51 and 0.59, respectively), while pulmonary, gastrointestinal and hepatobiliary irAEs did not show such relations. Low-grade irAEs (Grades 1 and 2) were linked to better survival (PFS: HR, 0.47; OS: HR, 0.48), unlike high-grade events. Corticosteroid use for irAEs management did not impair survival (PFS: HR, 0.97; OS: HR, 0.91). CONCLUSION:irAEs, particularly dermatologic, endocrine and low-grade events, were associated with improved ICIs' effectiveness in HCC. Early irAEs detection and corticosteroid management preserve survival benefits. However, more large-scale prospective studies are needed to verify our findings.

Background and Aims: Liver cancer is a digestive system malignancy that poses a significant public health challenge globally. This study aimed to analyze and compare the epidemiological trends of liver cancer attributed to hepatitis B (LCHB) and alcohol use (LCAL) over the past 32 years. Methods: Data on mortality and disability-adjusted life years for LCHB and LCAL in China, globally, and across five sociodemographic index regions were obtained from the Global Burden of Disease 2021 database and comprehensively analyzed. Results: In 2021, the global and Chinese death counts and disability-adjusted life years attributed to LCHB and LCAL showed substantial increases compared to 1990. China had the highest number of deaths from LCHB and LCAL among 204 countries and regions. Gender and age disparities were notable, with males and those aged 40-75 years bearing a higher burden than females and other age groups. Global age-period-cohort analysis revealed an escalating risk of death from LCHB with age, alongside a lower risk in younger cohorts and more recent periods. The mortality risk for LCAL also increased with age but exhibited distinct cohort and period effects compared to LCHB. Decomposition analysis indicated that shifts in the global burden of LCHB and LCAL were influenced by population growth, with population aging playing a crucial role in China. Conclusions: A significant burden of LCHB and LCAL persists, highlighting the need for tailored prevention, screening, and control strategies to mitigate their incidence, as well as the identification of advanced therapeutics to reduce mortality.

Background Non-alcoholic fatty liver disease (NAFLD) is a major global health problem due to its great disease and economic burdens. Tea is a popular beverage consumed by billions of peopleglobally owing to its health benefits. However, the evidence regarding the association between tea intake and NAFLD risk is inconsistent. Objective To examine the genetically predicted causal association between tea intake and NAFLD risk using the two-sample Mendelian randomization (MR) method. Methods Single‐nucleotide polymorphisms (SNPs) strongly associated with tea intake were obtained from a large dataset (N = 447,485) in the United Kingdom Biobank, and summary‐level genetic data for NAFLD (2,275 cases and 375,002 controls) were collected from the FinnGen consortium. The two-sample MR method was used to investigate the causal association between tea intake and NAFLD risk. The random‐effects inverse‐variance weighted (IVW) was used as the primary approach for estimating the causal effect, and MR Egger, weighted median, simple mode, and weighted mode were used to verify the robustness of the primary results. Results Twenty-four valid SNPs were selected as the instrumental variables for tea intake. The IVW results indicated that tea intake was not causally associated with NAFLD risk (Odds ratio: 1.48; 95% confidence interval: 0.64, 3.43; p = 0.364); moreover, the results from other methods were consistent with this finding. A leave-one-out analysis further demonstrated the robustness of our results. No evidence of heterogeneity, outliers, or horizontal pleiotropy was found. Conclusion Our results do not support tea intake being causally associated with a decreased risk of NAFLD.

Recently, several meta-analyses (MAs) have focused on the health effects of resveratrol. However, the methodological and reporting quality of these MAs has not yet been fully evaluated so far. Therefore, the present study evaluated the quality of these MAs through a methodological systematic review. Systematic searches were conducted in PubMed, Embase, Web of Science, and Cochrane Library from inception until May 20, 2022, and PubMed was used to update the search until September 6, 2023. The methodological and reporting quality of the selected MAs was evaluated using AMSTAR-2 and PRISMA 2009. Fifty-one MAs published during 2013-2023 were included. In each review, the number of primary studies ranged from 3 to 37, and the number of participants ranged from 50 to 2114. Among the first-listed primary outcomes, only 23 (45.10%) were "positive." As for the methodological quality, most MAs (44, 86.27%) on resveratrol were rated critically low. Inadequate reporting of the included MAs mainly involved items 2 ("Structured summary"), 5 ("Protocol and registration"), 8 ("Search"), 9 ("Study selection"), 10 ("Data collection process"), 12 ("Risk of bias in individual studies"), and 24 ("Summary of evidence") based on the PRISMA 2009. Additionally, journal's impact factor, number of authors, and funding support were positively associated with the overall methodological quality but were not statistically significant (p > 0.05). Future MAs on resveratrol require better design, implementation, and reporting by following the Cochrane Handbook, AMSTAR-2, and PRISMA.

Background To evaluate the impact of radiosensitivity on outcomes of spinal metastases treated with stereotactic body radiotherapy (SBRT) and identify the correlated prognostic factors.Methods The authors retrospectively reviewed the records of all patients who underwent SBRT with no prior radiation for spinal metastases between October 2015 and October 2020 at Sun Yat-sen University Cancer Center. On the basis of radiosensitivity, patients were divided into two groups-radiosensitive and radioresistant. The endpoints included local control (LC), overall survival (OS), pain relief, and time to pain relief.Results A total of 259 (82.5%) patients with 451 lesions were assessable with a median follow-up time of 10.53 months. The 1-, 2-, and 3-year OS rates were 59%, 52%, and 44%, respectively. The median survival was 33.17 months. Higher Karnofsky Performance Scale score and shorter time to diagnosis of spinal metastases from primary cancer at consult predicted for better OS (p = 0.02 and p < 0.001, respectively). The presence of other metastases (p = 0.04) and pain at enrollment assessed by the Brief Pain Inventory predicted for worse OS (p = 0.01). The 6-, 12-, and 24-month LC rates were 88%, 86%, and 82%, respectively. Younger age was identified for better LC and pain relief (p < 0.001 and p = 0.04, respectively). There was no variable independently associated with time to pain relief. As for toxicity, no Grade = 3 toxicity was observed.Conclusions Regardless of radiosensitivity, SBRT is feasible and appears to be an effective treatment paradigm for patients with spinal metastases, with limited accepted toxicities.

Objective: Vascularized composite allografts (VCAs) refer to the transplantation of multiple types of tissues during plastic and reconstructive surgery. Several publications have emerged in the field of VCA. However, there are no bibliometric studies on this topic. The aim was to multidimensionally analyze the knowledge base and hotspots in this subject. Methods: We retrieved all publications related to VCA from the Web of Science Core Collection (WoSCC), published from 2002 to 2021. Next, scientometric analysis of different items was performed using various bibliometrics software to explore knowledge base, research hotspots, and advancement trends in this field. Results: We included a total of 3,190 English articles from 2002 to 2021. The number of publications increased steadily annually. The United States produced the highest number of publications, followed by China. Most publications were from Harvard University, followed by Johns Hopkins University. The most authoritative academic journal was Plastic and Reconstructive Surgery. Transplantation occupied the first rank of co-cited journal list. Maria Z Siemionow may have the highest influence in the VCA field with the highest number of citations (n = 88) and co-cited references (n = 1252). Clinical studies on different allografts, immunosuppression, and tissue engineering were both the knowledge base and recent topics in VCA research. Conclusions: The first bibliometric study comprehensively summarized the trends and development of VCA research with steady growth over the past two decades. Currently, the most active topics are the clinical application of multiple allografts, immunosuppression strategies/therapies, and translation of tissue engineering to clinical practice.

BackgroundRandomized controlled trials (RCTs) are the gold standard for evaluating the efficacy and safety of medical interventions. Phytotherapy, which plays a critical role in the prevention and treatment of many clinical conditions, is also evaluated by RCTs. In recent years, the transparency, methodology, and generalizability of RCTs, as well as disparities in gender and geographical location among researchers, have attracted much attention from the scientific community. However, these aspects of RCTs in phytotherapy interventions have not been fully evaluated. Therefore, a methodological project (i.e., SMART-PT, tranSparency and Methodological chAracteristics of Randomized controlled Trials of PhytoTherapy interventions) was designed to overcome these knowledge gaps and provide key references for relevant future RCTs.MethodsThe SMART-PT project consists of five studies that will be conducted using RCTs derived from two high-impact phytotherapy journals, Phytomedicine and Phytotherapy Research. RCTs published in Phytomedicine and Phytotherapy Research were searched using the PubMed database from inception to February 13, 2023. Study selection was performed by two independent researchers, and data extraction and quality assessment will also be conducted independently by two researchers. First, we will investigate the reporting completeness, data-sharing level, and presence of spin among the included RCTs (Study 1). Second, we will evaluate the risk of bias in the included RCTs and the statistical fragility of primarily binary outcomes, and the likelihood ratio will be used to reinterpret statistically nonsignificant primary outcomes (Study 2). Third, we will evaluate the reporting completeness of phytotherapy interventions in the included RCTs as well as the trustworthiness of the RCTs (Study 3). Fourth, we will investigate the reporting of sociodemographic features and representation of participants in the included RCTs (Study 4). Finally, we will investigate the reporting completeness of the abstracts, the representation of gender, and geographical region of the listed authors among the included RCTs (Study 5). R 4.2.3, Stata 17/SE, and Excel 2019 will be used to analyze the data and create graphics.Results and DiscussionOne-hundred and fifty-two double-arm, parallel-group, superiority RCTs were included in the SMART-PT project. The results of the five meta-research studies will be submitted for publication in peer-reviewed journals.

The features and significance of somatic mutation profiles in hepatocellular carcinoma (HCC) have not been completely elucidated to date. In this study, 39 tumor specimens from HCC patients were collected for gene variation analysis by next-generation sequencing (NGS), and a correlation analysis between mutated genes and clinical characteristics was also conducted. The results were compared with genome data from cBioPortal database. Our study found that T > G/A > C transversions (Tv) and C > T/G > A transitions (Ti) were dominant. The sequence variations of TP53, MUC16, MUC12, MUC4 and others, and the copy number variations (CNVs) of FGF3, TERT, and SOX2 were found to be more frequent in our cohort than in cBioPortal datasets, and they were highly enriched in pathways in cancer and participated in complex biological regulatory processes. The TP53 mutation was the key mutation (76.9%, 30/39), and the most common amino acid alteration and mutation types were p.R249S (23.5%) and missense mutation (82.3%) in the TP53 variation. Furthermore, TP53 had more co-mutations with MUC17, NBPF10, and AHNAK2. However, there were no significant differences in clinical characteristics between HCC patients with mutant TP53 and wild-type TP53, and the overall survival rate between treatment via precision medication guided by NGS and that via empirical medication (logrank p = 0.181). Therefore, the role of NGS in the guidance of personalized targeted therapy, solely based on NGS, may be limited. Multi-center, large sample, prospective studies are needed to further verify these results.

Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and many patients are diagnosed with advanced disease. The treatment of advanced liver cancer has made significant strides in recent years, owing to the practice of immunotherapy drugs. Numerous studies have been published on immunotherapy for HCC; however, no relevant bibliometric study has been published. This study aims to gain a better understanding of the current situation and to identify potential new research directions by conducting a bibliometric analysis on immunotherapy for HCC. Methods We searched the Web of Science Core Collection (WoSCC) for articles related to immunotherapy for HCC. Three software (VOSviewer, CiteSpace, and python) were primarily used to assess the contribution and co-occurrence relationships of various countries/regions, institutes, journals, and, authors as well as to identify research hotspots and promising future trends in this research field. Results A total of 1,641 English articles published between 2011 and 2020 were collected, with the number of articles increasing nearly every year. The majority of publications originated from China (n = 893, 54.42%), followed by the United States and Japan. The Sun Yat-sen University contributed the most publications (n = 97, 5.91%). Nakatsura Tetsuya (n = 26) and Llovet JM (n = 366) were ranked first in the top ten authors and co-cited authors. Cancer Immunology Immunotherapy was the most productive academic journal on immunotherapy for HCC [n = 46, 2.80%; impact factor (IF) 2020 = 6.9679]. Aggregation and identification of critical nodes in the co-cited network demonstrated a shift in the field of HCC immunotherapy. Initially, the hotspots were predominantly “glypican-3”, “cytokine-induced killer cells”, and “ny-eso-1”, while the emphasis has shifted in recent years to “landscape”, “camrelizumab”, “combination therapy”, and “immune score”. Conclusion Increased attention has been paid to HCC with the advancement of immunotherapy. At the moment, the most active frontiers are focused on better understanding the immunological landscape of liver cancer, screening the population that can benefit from immunotherapy, and the clinical application of immune checkpoint inhibitors, particularly in combination with other therapeutic options (such as local therapy and targeted therapy).

Background:Acupuncture has been widely used to relieve migraine-related symptoms.However,the findings of previous systematic reviews(SRs)and meta-analyses(MAs)are still not completely consis-tent.Their quality is also unknown,so a comprehensive study is needed.Objective:To evaluate the reporting and methodological quality of these MAs concerning acupuncture for migraine,and summarize evidence about the efficacy and safety of acupuncture for migraine.Search strategy:PubMed,Embase,Cochrane Library,China National Knowledge Infrastructure,Chinese Biomedical Databases,Wanfang Data,and VIP databases were searched from inception to September 2020,with a comprehensive search strategy.Inclusion criteria:The pairwise MAs of randomized controlled trials(RCTs)concerning migraine treated by acupuncture or acupuncture-based therapies,with a control group that received sham acupuncture,medication,no treatment,or acupuncture at different acupoints were included.Data extraction and analysis:Two independent investigators screened studies,extracted relevant data,and assessed reporting and methodological quality using Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)2009 and A Measurement Tool to Assess Systematic Reviews 2(AMSTAR 2),then all results were cross-checked.Spearman correlation test was used to evaluate the cor-relation between reporting and methodological quality scores.Results:A total of 20 MAs were included in this study.The included MAs indicated that acupuncture was efficacious and safe in preventing and treating migraine when compared with control intervention.There was a high correlation between reporting and methodological quality scores(rs=0.87,P＜0.001).The quality of the included SRs needs to be improved mainly with regard to protocol and prospective regis-tration,using a comprehensive search strategy,summarizing the strength of evidence body for key out-comes,a full list of excluded studies with reasons for exclusion,reporting of RCTs'funding sources,and assessing the potential impact of risk of bias in RCTs on MA results.Conclusion:Acupuncture is an effective and safe intervention for preventing and treating migraine,and could be considered as a good option for patients with migraine.However,the reporting and method-ological quality of MAs included in this overview is suboptimal.In the future,AMSTAR 2 and PRISMA tools should be followed when making and reporting an SR with MA.

BACKGROUND:Gut microbiota and microbe-derived metabolites are involved in the development of HCC. Bile acids (BAs) are the most important gut microbiota-modulated endogenous signaling molecules.METHODS:We tested serum bile acid levels and gut microbiome compositions in patients with HCC, chemical-induced HCC mouse models (DEN-HCC mice) and mouse orthotopic implanted liver tumor models with vancomycin treatment (vancomycin-treated mice). Then, we screened an important kind of HCC-related BAs, and verified its effect on the growth of HCC in vivo and in vitro.RESULTS:We found that the remarkably decreasing percentages of serum secondary BAs in the total bile acids of patients and DEN-HCC mice, especially, conjugated deoxycholic acids (DCA). The relative abundance of the bile salt hydrolase (BSH)-rich bacteria (Bifidobacteriales, Lactobacillales, Bacteroidales, and Clostridiales) was decreased in the feces of patients and DEN-HCC mice. Then, in vancomycin-treated mice, vancomycin treatment induced a reduction in the BSH-rich bacteria and promoted the growth of liver tumors. Similarly, the percentage of conjugated DCA after vancomycin treatment was significantly declined. We used a kind of conjugated DCA, Glyco-deoxycholic acid (GDCA), and found that GDCA remarkably inhibited the growth of HCC in vivo and in vitro.CONCLUSIONS:We conclude that the remarkably decreasing percentages of serum conjugated DCA may be closely associated with HCC, which may be induced by the reducing gut BSH-rich bacteria. The mechanisms may be correlated with conjugated DCA directly inhibiting the growth and migration of HCC cells.

Background: Several quantitative systematic reviews of Kanglaite (KLT), an herb preparation used to treat cancer and malignant pleural effusion, have been published in recent years. However, the clinical evidence reported in these studies has not been pursued further and the methodological quality of these meta-analyses remains unknown. Therefore, an overview was designed to map the evidence landscape based on the published meta-analyses on KLT in cancer treatment. Methods: Two bibliographic databases (PubMed and Embase) were searched from inception to 25 November 2021. Two independent reviewers were involved in study selection, data abstraction, and methodological quality assessment using AMSTAR 2. The principal features of publications and the clinical outcomes of efficacy and safety were synthesized narratively, and results of methodological quality were reported as frequencies and percentages with the corresponding 95% confidence intervals. The evidence map was used to visualize the overall quality. Excel 2016 and Stata 17/SE were used for data analysis. Results: Thirteen meta-analyses published in English were included for in-depth analysis. Among them, the year of publication ranged from 2008 to 2021, and the number of included patients ranged from 488 to 2,964. Regarding the cancer type, seven articles focused on non-small cell lung cancer, two on malignant pleural effusion, and four reviews on digestive system malignancies, such as hepatocellular carcinoma and pancreatic cancer. Almost all included meta-analyses reported that KLT as adjunctive therapy could improve various efficacy outcomes (such as disease response rates, quality of life, immune indicators) and reduce the rate of occurrence of adverse reactions, such as nausea and vomiting, leukopenia, and anemia. In terms of their methodological quality, three meta-analyses were of low quality, whereas 10 studies were critically low in quality. The methodological flaws main involved items 2 ( "predesigned protocol and registration informatio''), 3 ( "rationale of study design for inclusion "), 4 ( "comprehensive search strategy''), 5 ( "literature selection in duplicate''), 7 ( "list of excluded studies with reasons''), 8 ( "adequate information on included studies''), 10 ( "funding support for included primary studies''), and 12 ( "evaluation of the potential impact of risk of bias'') based on the AMSTAR 2 tool. Conclusion: Current evidence reveals that KLT is effective and safe as an adjunctive treatment for non-small cell lung cancer, malignant pleural effusion, and digestive system malignancies (such as hepatocellular carcinoma). However, the results assessed in this overview should be further verified using well-designed and clearly reported clinical trials and meta-analyses of KLT.

Background: Many meta-analyses (MAs) on Chinese medicine (CM) as an adjunctive treatment for gastric cancer have been published in recent years. However, the pooled evidence reported in MAs and their methodological quality remain unknown. Therefore, we designed a study to comprehensively evaluate and summarize the current evidence of CMs for gastric cancer in published MAs. Methods: A systematic search on MAs published in English from inception to 1st September 2021 was conducted in PubMed and Embase. The AMSTAR-2 tool was used to evaluate the methodological quality of the included MAs, and the results of the quality assessment were visualized using the evidence mapping method. Stata 17/SE was used for statistical analysis (Registration number: INPLASY202190005). Results: A total of 20 MAs (16 pairwise and 4 network MAs) were included from 118 records. These MAs were published in 14 journals from 2013 to 2021, with the number of patients and trials ranging from 688 to 6,857, and from 10 to 85, respectively. A large number of CMs (e.g., AiDi, FuFangKuShen, and HuaChanSu) in combination with chemotherapy for gastric cancer were identified among the included MAs. According to the pooled results reported in MAs, when compared to chemotherapy alone, CMs in combination with chemotherapy not only improve various outcomes on efficacy (e.g., objective response rate, quality of life) but also reduce various adverse reactions (e.g., leucopenia, nausea and vomiting). Only 2 MAs were low in terms of the overall methodological quality, while the other 18 MAs were all critically low. The methodology was required to be advanced significantly, mainly involving: study protocol and registration, explanation for the inclusion of study design, list of excluded studies with justifications, adequate details of included studies, reporting on funding sources of primary studies, and evaluation of the potential impact of risk of bias. In addition, MAs that received funds support (β = 2.68; 95%CI: 0.40 to 4.96; p = 0.024) or were published in journals with higher impact factor (β = 2.81; 95%CI: 0.69 to 4.92; p = 0.012) had a higher score on the overall methodological quality in the univariate analysis, but the results were not statistically significant according to the multivariate analysis. Conclusion: Combining CMs with chemotherapy can potentially improve clinical outcomes and reduce the relevant adverse effects in patients with gastric cancer. However, the methodological quality of relevant MAs requires significant improvement, and the current evidence needs to be validated through multinational trials that are well-designed and have a large sample size.

To evaluate the efficacy and safety of stereotactic body radiotherapy (SBRT) in treating spinal metastases. Two reviewers performed independent literature searches of the PubMed database, searching literatures of the efficacy and safety of SBRT in metastatic spinal diseases. A total of 67 studies were included in the review. Regarding SBRT for de novo spinal metastases, the 1- and 2-year local control (LC) rates were 51–100% and 56–96%, respectively. The local failure rate was 10.5–47.5%, with most studies reporting a local failure rate of < 30%. The 1- and 2-year overall survival (OS) rates were 25.7–80% and 25–60.7%, respectively. The pain relief rate was 41.6–100%. In the postoperative scenario, the LC rate was 70–100%, and the local failure rate was 11.7–33%. Regarding the reirradiated setting, the 1-year LC rate was 71–83%, the local failure rate was 6.0–25.5%, and the 1-year OS rate was 28–68%. The pain relief rate was approximately 35.7–77%. Between studies on single- and multi-fraction SBRT, the 1- and 2-year LC rates with single-fraction SBRT were 71–95% and 70–96%, respectively; the 1- and 2-year OS rates with single-fraction SBRT were 43.5–46% and 43.5–49%, respectively. For the management of spinal metastases, it appears that regardless of the clinical scenario in which SBRT is applied, a high rate of LC is achieved, particularly with single-fraction SBRT, regardless of histology. Additionally, spinal SBRT can establish durable pain palliation with acceptable toxicities.

BACKGROUND:Although a number of systematic reviews and meta-analyses of saffron (Crocus sativus L.) have been published, no study has comprehensively summarized the clinical evidence from meta-analyses, or assessed the reporting or methodological quality of these reviews.PURPOSE:The present meta-research study was designed to fill the gaps in knowledge to inform future studies and allow enhanced clinical decision-making on saffron.METHODS:The PubMed, Cochrane Library, Embase, and CNKI databases were systematically searched from inception to April 3 rd, 2021, for meta-analyses of clinical trials that assessed the efficacy and safety of saffron. PRISMA 2009 and AMSTAR-2 were employed to assess the reporting and methodological quality of meta-analyses identified in the search, respectively. The present study was registered on PROSPERO with registration number CRD42020220274.RESULTS:Nineteen eligible systematic reviews with meta-analyses published in English were identified from 235 records. These meta-analyses were published in 12 peer-reviewed journals from 2013 to 2021. The heterogeneous results indicated that saffron significantly reduced fasting blood glucose, waist circumference, diastolic blood pressure, concentrations of total cholesterol and low-density lipoprotein cholesterol, and improved symptoms of depression, cognitive function and sexual dysfunction compared with controls (mainly placebos). Common side effects of saffron consumption included nausea, dry mouth, poor appetite, and headache, but no serious adverse reactions were reported. Primary analysis and sensitivity analysis confirmed that the reporting and methodological quality of reviews included in the study were highly correlated (p < 0.001). The quality of meta-analyses of saffron requires improvement by including a structured abstract, a prospective protocol and registration, explanation of the study designs within each study that is reviewed, the searches, risk of bias assessment, literature selection, and reporting of funding sources.CONCLUSION:The available evidence indicates that saffron is a safe plant for administration as a medicine and can improve diverse clinical outcomes, but the scientific quality of the published systematic reviews needs to be improved. Moreover, the clinical effects of saffron need to be confirmed through high-quality randomized trials in multiple countries with large sample sizes.

Abstract Purpose To evaluate the impact of histologies on outcomes of spinal metastases treated with stereotactic body radiotherapy (SBRT) and identify the correlated prognostic factors. Methods The authors retrospectively reviewed the records of all patients who underwent SBRT with no prior radiation for spinal metastases between October 2015 and October 2020 at Sun Yat-sen University Cancer Center. Propensity score matching (PSM) was applied to balance the distribution of related baseline characteristics. The endpoints included overall survival (OS), local control (LC), pain relief, and time to pain relief. Results A total of 202 consecutive patients with 345 spinal metastases were treated with a median follow-up time of 16.02 months (range, 0.73–57.90 months). The 1- and 2-year OS rates were 57% and 50%, respectively. The median survival was 35.63 months. A higher Karnofsky Performance Scale (KPS) score at consult predicted for better OS (P = 0.020). The presence of pain at enrollment assessed by the Brief Pain Inventory (BPI) predicted for worse OS (P = 0.038). The 1-year LC rate was 92.0%. The pain relief rate was 76.30% (103/135 patients). Younger age was identified to be prognostic for better pain relief (P = 0.037). In the univariate and multivariate analysis, no variable was independently associated with time to pain relief. As for toxicity, no Grade ≥ 3 toxicity was observed. Conclusions SBRT is feasible and appears to be an effective treatment paradigm for patients with spinal metastases, with limited accepted toxicities.