IntroductionAn increasing number of patients with metastatic colorectal cancer (mCRC) have achieved no evidence of diseases (NED) status after surgery or other treatments. However, the latest guidelines for colorectal cancer do not recommend an appropriate treatment for patients with mCRC who achieve NED status. Capecitabine metronomic chemotherapy has the advantages of significant efficacy and minimal adverse reactions, it is a potential effective method for maintenance treatment for mCRC, but no RCTs have been reported. Therefore, we designed a randomized controlled trial to evaluate the efficacy and safety of capecitabine metronomic chemotherapy for mCRC patients who achieve NED.Methods/designThis study is a prospective, randomized controlled study that evaluates the efficacy and safety of capecitabine metronomic chemotherapy for patients with mCRC who achieve NED status. 240 eligible participants will be randomly assigned to either a capecitabine metronomic chemotherapy group or a "watch and wait" group at a 1:1 allocation ratio. Eligible patients diagnosed with stage IV mCRC, both the primary tumor and the metastases, are those who have achieved R0 resection (or complete destruction by ablation) and reached NED. Participants who are enrolled in the capecitabine group will receive capecitabine (500 mg/m2 body surface area twice daily) for 2 years. Meanwhile, those who are assigned to the control group will receive regular imaging examination and follow-up only. All participants will follow up for 1 year after receiving 2 years of intervention. The primary outcomes will be disease-free survival (DFS) from randomization, stratified by preoperative chemotherapy, metastatic organs, number of metastases, lenght of previous systemic treatment, response to previous chemotherapy. Secondary outcomes will include overall survival (OS), 1-year,2-year,3-year survival rate and adverse reactions.DiscussionAs a potentially effective treatment, low-dose capecitabine metronomic chemotherapy has been explored in clinical practice. The results of this trial will provide evidence on the efficacy and safety of capecitabine metronomic chemotherapy for patients with mCRC who have reached NED status.Trial registrationChinese Clinical Trial Registry (ChiCTR2100047149, protocol version number F2.0).

ABSTRACT:Antithrombotic therapy can prevent recurrent deep vein thrombosis (DVT) and pulmonary embolism (PE). It is, however, associated with an increased risk for major bleeding. This meta-analysis systematically reviewed the evidence regarding the duration of antithrombotic therapy to assess benefits and harms. We systematically searched for randomized controlled trials (RCTs) that compared shorter (3-6 months) with longer (>6 months) courses of anticoagulation for the primary treatment of venous thromboembolism (VTE) or that compared discontinued with indefinite antithrombotic therapy for the secondary prevention of VTE. Pairs of reviewers screened the eligible trials and collected data. This study included 22 RCTs (11 617 participants). Pooled estimates showed that, for the primary treatment of unprovoked VTE, VTE provoked by chronic risk factors or transient risk factors, treating patients with a longer course (>6 months) of anticoagulation, as opposed to a shorter course (3-6 months), probably reduced recurrent PE (risk ratio [RR], 0.66; 95% confidence interval [CI], 0.42-1.02) and DVT (RR, 0.85; 95% CI, 0.63-1.14), but it was associated with increased mortality (RR, 1.43; 95% CI, 0.85-2.41) (moderate certainty) and a higher risk for major bleeding (RR, 2.02; 95% CI, 1.02-3.98; high certainty). For the secondary prevention of unprovoked VTE and VTE provoked by chronic risk factors, when compared with discontinuing treatment, indefinite anticoagulation therapy was associated with decreased mortality (RR, 0.54; 95% CI, 0.36-0.81), a reduction in recurrent PE (RR, 0.25; 95% CI, 0.16-0.41) and DVT (RR, 0.15; 95% CI, 0.10-0.21), and an increase in the risk for bleeding (RR, 1.98; 95% CI, 1.18-3.30), all supported by high certainty. Indefinite antiplatelet therapy may be associated with decreased mortality (RR, 0.95; 95% CI: 0.53-1.68; low certainty), probably a reduction in recurrent PE (RR, 0.65; 95% CI, 0.41-1.03) and DVT (RR, 0.44; 95% CI, 0.17-1.13) (moderate certainty), and may increase the risk for bleeding (RR, 1.28; 95% CI, 0.48-3.41; low certainty). In summary, for the primary treatment of all types of VTE, shorter (3-6 months) duration of anticoagulation is more beneficial. For the secondary prevention of unprovoked VTE or VTE provoked by chronic risk factors, indefinite antithrombotic treatment is more beneficial.

BACKGROUND:Qu-yu-jie-du (QYJD) decoction is an established traditional Chinese medicine (TCM) formulation. For over ten years, there has been empirical evidence in support of its benefits for colorectal cancer patients, yet RCT validation for it as a postoperative maintenance therapy is lacking. Despite achieving no evidence of disease (NED) status after curative-intent resection in metastatic colorectal cancer (mCRC), up to 60 % of patients relapse within five years, with no guideline-recommended maintenance therapy. PURPOSE:To determine whether QYJD decoction improves disease-free survival (DFS) and modulates inflammation/lactate metabolism in postoperative mCRC-NED patients. METHODS/DESIGN:In this single-center randomized trial, 140 stage IV mCRC patients achieving post-resection NED status were randomized at a ratio of 1:1 to either a QYJD group (200 mL/day for 2 years) or a control group (routine follow-up). Two patients per group withdrew consent prior to the intervention, resulting in an intention-to-treat (ITT) population of 136 patients (68 per group) for the final analysis. All received standard adjuvant chemotherapy. The primary outcome was DFS; secondary outcomes were OS, 1-/2-/3-year survival rates, adverse events, and inflammation/lactate metabolism markers. RESULTS:Compared to the control group, QYJD decoction significantly improved DFS throughout the observation period (HR = 0.515, p = 0.004). The 1-year DFS rate was 91.2 % (62/68) in the QYJD group versus 73.5 % (50/68) in the control group (p < 0.01); the 2-year DFS rate was 56.9 % (40/68) in the QYJD group versus 35.1 % (25/68) in the control group (p = 0.002); and the 3-year DFS rate was 47.4 % (32/68) in the QYJD group versus 32.4 % (22/68) in the control group (p = 0.03). Significant differences were observed across all time points (1-year, 2-year, and 3-year) for DFS. Regarding overall survival (OS), the 2-year OS rate was 95.4 % (65/68) in the QYJD group versus 85.1 % (58/68) in the control group (p = 0.01), and the 3-year OS rate was 68.7 % (47/68) in the QYJD group versus 57.7 % (39/68) in the control group (HR = 0.407, p = 0.019). QYJD also significantly reduced inflammatory markers and lactate dehydrogenase (LDH) (p < 0.05). The most common adverse events were grade 1 hematologic toxicity, anorexia, diarrhea, and nausea, which were generally mild and manageable. CONCLUSION:QYJD decoction significantly improves DFS and shows OS benefits in postoperative mCRC-NED patients. It also reduces systemic inflammation/LDH, and in terms of safety, only causes mild adverse events. TRIAL REGISTRATION:Chinese Clinical Trial Registry (ChiCTR2100053521, registered on November 24, 2021).

Background:Sarcoma is a heterogeneous malignancy arising from interstitial tissue. Anthracycline-based therapy is the first-line treatment recommended by guidelines for patients with locally advanced or metastatic unresectable sarcoma. Recently, targeted therapies, in particular tyrosine kinase inhibitors (TKIs), have made significant progress in the treatment of sarcoma, and their efficacy has been investigated in randomized controlled trials. The aim of this meta-analysis is to evaluate the efficacy of TKIs in patients with advanced or metastatic sarcoma who have previously received chemotherapy. Methods:We completed a meta-analysis after conducting literature searches in PubMed, Embase, and Cochrane. The single-drug, placebo-controlled, randomized controlled clinical trials of TKIs in patients with advanced or progressive sarcoma who have previously received chemotherapy are available for inclusion in the study. The observation results were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). The subgroup analysis was performed according to histological subtypes of sarcoma. Results:This study included 6 studies, including 1033 patients. The ORR (OR: 7.99, 95% CI: 3.62-19.61, P < .00001), DCR (OR: 2.54, 95% CI: 1.27-5.08, P = .009), PFS (HR: 0.46, 95% CI: 0.34-0.62, P < .00001), and OS (HR: 0.80, 95% CI: 0.67-0.96, P = .02) of patients treated with TKIs were better than those in the placebo group. Conclusions:In patients with advanced sarcoma, TKIs have been shown to have advantages in terms of ORR, DCR and PFS and OS. Multi-targeted TKIs may be considered as one of the second-line treatment options for sarcoma patients who have received prior chemotherapy.

Background: Currently, the optimal treatment for neoadjuvant therapy for locally advanced esophageal cancer is not clear, and there is no evidence that neoadjuvant chemoradiotherapy (nCRT) is superior to neoadjuvant chemotherapy (nCT). Due to the publication of new clinical trials and defects in previous meta-analyses, we conducted an updated meta-analysis to evaluate the efficacy and safety of nCRT and nCT. Methods: The following databases were searched for studies: PubMed, EMBASE, and Cochrane library (updated to April 22, 2023). All randomized trials comparing nCRT with nCT in locally advanced esophageal cancer met the inclusion criteria. Data were analyzed using Review Manager 5.4.1 (Cochrane collaboration software). Primary outcomes assessed from the trials included overall survival (OS), progression-free survival (PFS), pathological complete response (pCR), R0 resection rate, postoperative complications, postoperative mortality, and grade 3 or higher adverse events (3 + AEs). Results: This systematic review and meta-analysis included 7 randomized controlled studies involving 1372 patients (686 receiving nCRT and 686 receiving nCT). Compared with nCT, nCRT significantly improved OS (HR = 0.80; 95% CI: 0.68–0.94), PFS (HR = 0.78; 95% CI: 0.66–0.93), pCR (OR = 13.00; 95% CI: 7.82–21.61) and R0 resection (OR = 1.84; 95% CI: 1.32–2.57), but was associated with higher postoperative mortality (OR = 2.31; 95% CI: 1.26–4.25) and grade 3 + AEs (OR = 2.21; 95% CI: 1.36–3.58). There was no significant difference in postoperative complications between nCRT and nCT (OR = 1.15; 95% CI: 0.82–1.61). Subgroup analysis showed significant survival benefit in squamous cell carcinoma (HR = 0.80; 95% CI: 0.68–0.98), but not in adenocarcinoma (HR = 0.80; 95% CI: 0.63–1.08). Conclusions: Our meta-analysis found superior efficacy associated with nCRT compared with nCT in both tumor regression and prolonged survival, but increased the risk of postoperative mortality and grade 3 + AEs. Esophageal squamous cell carcinoma was more likely to benefit from nCRT than esophageal adenocarcinoma in the term of OS.

Abstract Purpose Transarterial chemoembolization (TACE) with tyrosine kinase inhibitors (TKIs) has been increasingly used to treat unresectable hepatocellular carcinoma (uHCC). However, the superiority of combination therapy to TACE monotherapy remains controversial. Therefore, here we performed a meta-analysis to evaluate the efficacy and safety of TACE plus TKIs in patients with uHCC. Methods We searched four databases for eligible studies. The primary outcome was time to progression (TTP), while the secondary outcomes were overall survival (OS), tumor response rates, and adverse events (AEs). Pooled hazard ratios (HRs) with 95% confidence intervals (95% CIs) were collected for TTP and OS, and the data were analyzed using random-effects meta-analysis models in STATA software. OR and 95% CIs were used to estimate dichotomous variables (complete remission[CR], partial remission[PR], stable disease[SD], progressive disease[PD], objective response rate[ORR], disease control rate[DCR], and AEs) using RStudio’s random-effects model. Quality assessments were performed using the Newcastle–Ottawa scale (NOS) for observational studies and the Cochrane risk of bias tool for randomized controlled trials (RCTs). Results The meta-analysis included 30 studies (9 RCTs, 21 observational studies) with 8246 patients. We judged the risk of bias as low in 44.4% (4/9) of the RCTs and high in 55.6% (5/9) of the RCTs. All observational studies were considered of high quality, with a NOS score of at least 6. Compared with TACE alone or TACE plus placebo, TACE combined with TKIs was superior in prolonging TTP (combined HR 0.72, 95% CI 0.65–0.80), OS (combined HR 0.57, 95% CI 0.49–0.67), and objective response rate (OR 2.13, 95% CI 1.23–3.67) in patients with uHCC. However, TACE plus TKIs caused a higher incidence of AEs, especially hand-foot skin reactions (OR 87.17%, 95%CI 42.88–177.23), diarrhea (OR 18.13%, 95%CI 9.32–35.27), and hypertension (OR 12.24%, 95%CI 5.89–25.42). Conclusions Our meta-analysis found that TACE plus TKIs may be beneficial for patients with uHCC in terms of TTP, OS, and tumor response rates. However, combination therapy is also associated with a significantly increased risk of adverse reactions. Therefore, we must evaluate the clinical benefits and risks of combination therapy. Further well-designed RCTs are needed to confirm our findings. Trial registration PROSPERO registration number: CRD42022298003.

ObjectiveZolbetuximab is a “first-in-class” chimeric lgG1 monoclonal antibody targeting Claudin18.2 (CLDN 18.2). In recent years, several important trials have been published showing that zolbetuximab is associated with improved prognosis in patients with advanced gastric or gastro-esophageal junction (G/GEJ) adenocarcinoma. This promises great change to the current treatment landscape. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of zolbetuximab for first-line treatment of advanced CLDN 18. 2-positive G/GEJ adenocarcinoma.MethodsThe following databases were searched for relevant studies: PubMed, EMBASE, and Cochrane library (updated 10 June 2023). All randomized trials comparing zolbetuximab plus chemotherapy versus first-line chemotherapy alone for first-line treatment of advanced CLDN 18. 2-positive G/GEJ adenocarcinoma were eligible for inclusion. Data were analyzed using Review Manager 5.4.1 (Cochrane collaboration software). Primary outcomes and measures included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs).ResultsThis systematic review and meta-analysis included three randomized controlled studies involving 1,402 patients (699 receiving zolbetuximab plus chemotherapy and 703 receiving chemotherapy alone). Compared with chemotherapy alone, zolbetuximab plus chemotherapy significantly improved OS (HR = 0.73; 95% CI: 0.68–0.84) and PFS (HR = 0.64; 95% CI: 0.50–0.82), but did not result in a higher ORR (RR = 0.92; 95% CI: 0.82–1.03). Further analysis of CLDN 18.2 expression showed a more significant benefit for OS (HR = 0.69; 95% CI: 0.55–0.87; p = 0.002) and PFS (HR = 0.61; 95% CI: 0.44–0.84; p = 0.003) from zolbetuximab in patients with high expression, while there was significant benefit in patients with lower expression. In terms of AEs, zolbetuximab plus chemotherapy was associated with higher risk of grade 3 and higher AEs, but increased risk of nausea and vomiting were more common.ConclusionThis systematic review and meta-analysis revealed that the effect of zolbetuximab plus chemotherapy was superior to that of chemotherapy alone for first-line treatment of advanced CLDN 18.2-positive G/GEJ adenocarcinoma. Thus, zolbetuximab plus chemotherapy represents a new first-line treatment for these patients. Zolbetuximab plus chemotherapy was associated with higher risk of grade 3 and higher AEs, but was generally manageable.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero, identifier (CRD42023437126).

Rationale: Colon carcinoma is the most common type of cancer, and a leading cause of cancer-related death. Clinically, the most common sites of metastases from colon carcinoma are the liver, lungs, peritoneum, and lymph nodes, while the incidence of metastases to the prostate is low. There are few relevant studies on colon carcinoma, most of them being case reports. Patient concerns: A 76-year-old man treated with radical resection of right colon carcinoma due to primary poorly differentiated adenocarcinoma of the cecum. Postoperative pathological examination suggested that he had cancer at the junction of the ascending colon and the cecum. He had received adjuvant chemotherapy after surgery. One year later, he received transurethral plasma resection of the prostate due to urinary system discomfort. Postoperative pathological immunohistochemistry suggested prostate metastasis of colorectal carcinoma, and he received individualized treatment, but this produced no clear survival benefit. Diagnoses: Ascending colon cecal junction carcinoma with prostate metastasis. Interventions: Radical resection, chemotherapy, anti-androgen therapy, surgery to relieve primary lesion obstruction symptoms, and local radiotherapy of the prostate. Outcomes: At present, clinical cases of colon carcinoma with prostate metastasis are rare. By sharing a rare case of ascending colon cecal junction carcinoma with prostate metastasis and reviewing the relevant literature, this paper explores and optimizes the clinical treatment of colon carcinoma with prostate metastasis.

Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers and is on the rise annually. It is characterized by low differentiation, high malignancy, and rapid growth. Consequently, treatment options are limited, and the patient's prognosis is poor. The emergence of immunotherapy has partially improved the survival and prognosis of SCLC patients. However, a unique response known as "pseudoprogression" during immunotherapy has raised concerns. The occurrence of tumor enlargement despite a positive response to immune checkpoint inhibitor therapy undoubtedly affects the assessment of clinical drug efficacy and the selection of subsequent treatment strategies. In this article, we analyze a clinical case of pseudoprogression in a patient with SCLC who received immune therapy (Durvalumab). Currently, there is insufficient evidence-based medicine to guide the diagnosis, differentiation and subsequent treatment strategies for pseudoprogression in SCLC following immunotherapy. Through this case report and literature review, we aim to provide diagnostic and therapeutic insights for the clinical use of immunotherapy in advanced SCLC. Additionally, we hope that fellow readers of this article can engage in further collaborative discussions through more clinical research.

Rationale:Colorectal cancer is the second leading cause of cancer-related deaths in the world. About 50% of patients will have metastases during the course of the disease. The common sites of metastasis are the liver, lung, peritoneum, lymph, etc. Metastatic carcinoma to the testes is uncommon. We found a case of ascending colon cancer metastasized to the testis in the clinic. Patient concerns:We reported a 50-year-old male patient who was found to have testicular metastases >4 years after intestinal cancer surgery, and multiple metastases in the peritoneum and pelvis were found 1 week later. Diagnoses:After enhanced computed tomography and pathological biopsy, the patient was diagnosed with testicular metastasis of colon cancer. Interventions:Capecitabine combined with bevacizumab is currently undergoing palliative treatment. Outcomes:The patients died of tumor progression on June 28, 2021. Lessons:The testicular metastasis of colorectal cancer is a sign of peritoneum and multiple metastases. When the testicular metastasis occurs in colorectal cancer patients, it usually indicates that the patient has a poor prognosis.

Objective. Systematically evaluate the efficacy of physical ablation combined with TKI in the treatment of advanced non-small cell lung cancer (NSCLC). Methods. We performed a comprehensive search of databases including OVID, PubMed, EMBASE, the Cochrane Library, and three Chinese databases (China National Knowledge Infrastructure, Wanfang Database, and Chongqing Weipu Database). The aim was to identify randomized controlled trials (RCT) investigating physical ablation as the treatment for advanced NSCLC. We also evaluated the methodological quality of the included studies and summarized the data extracted for meta-analysis with Review Manager 5.3. Results. A total of 9 studies, including 752 patients, were evaluable. The meta-analysis results show that the complete response rate (CRR) (RR: 2.23, 95% CI: 1. 46 to 3.40, P 0.01), partial response rate (PRR) (RR: −2.25, 95% CI: 1.41 to 3.59, P 0.01), and disease control rate (DCR) (RR: −2.80, 95% CI: 1.64 to 4.80, P < 0.01) of patients with advanced NSCLC who received physical ablation combined with TKI therapy were higher than those who did not receive physical ablation therapy. The control groups from seven of the studies had a total of 606 patients with targeted therapies and chemotherapy. The complete response rate was (CRR) (RR: 2.48, 2.4895% CI: 1.55 to 2.47, P 0.01), partial response rate (PRR) (RR: −1.66, 95% CI: 1.20 to 2.31, P < 0.01), and disease control rate (DCR) (RR: −2.68, 95% CI: 1.41 to 5.06, P < 0.01) for patients with advanced NSCLC who had received physical ablation combined with targeted therapies and chemotherapy, compared to patients who had not received physical ablation therapy. This difference was statistically significant. Above all, these results showed that the clinical efficacy of physical ablation combined EGFR-TKIs therapy (regardless of whether it was combined with chemotherapy) was better than that of EGFR-TKIs therapy alone. Conclusion. Physical ablation combined with TKI treatment in patients with advanced NSCLC can improve efficacy.

Venous thromboembolism (VTE) is a relatively frequent complication in hospitalized patients, especially in those with risk factors. The benefit of using direct oral anticoagulants (DOACs) for prevention is controversial. This systematic review was performed as part of the American Society of Hematology (ASH) guidelines on VTE, developed in partnership with McMaster University. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Epistemonikos were used as data sources from date of inception to November 2019. We included randomized trials in patients hospitalized for an acute medical disease, evaluating any DOACs vs other pharmacological prophylaxis, and included 3 trials with low risk of bias. We analyzed the effects of DOACs vs low-molecular-weight heparins (LMWHs) at 2 different time points: at the end of the short-term treatment phase (both drugs given for the same period of time) and at the end of the extended prophylaxis period (extended DOACs vs a shorter course of LMWHs). We observed that the use of DOACs did not reduce the risk of pulmonary embolism or symptomatic deep venous thrombosis (DVT) in comparison with LMWHs. However, the risk of major bleeding was slightly increased. Additionally, we observed that the benefit of DOACs previously reported was largely based on the reduction of asymptomatic DVT and was not apparent when only symptomatic events were considered. The use of DOACs in hospitalized medical patients slightly increases the risk of major bleeding with no appreciable benefit over LMWHs.

Abstract Background: Heart failure with reduced ejection fraction (HFrEF) has contributed to an increasing number of deaths and readmissions over the past few decades. Despite the appearance of standard treatments, including diuretics, β-receptor blockers and angiotensin-converting enzyme inhibitor (ACEI), there are still a large number of patients who have progressive deterioration of heart function and, inevitably, end-stage heart failure. In recent years, new medications for treating chronic heart failure have been clinically applied, but there is controversy surrounding drug selection and whether patients with HFrEF benefit from these medications. Therefore, we aimed to compare and rank different new pharmacological treatments in patients with HFrEF. Methods: We performed a network meta-analysis to identify both direct and indirect evidence from relevant studies. We searched MEDLINE, EMBASE, and PsycINFO through the OVID database and CENTRAL through the Cochrane Library for clinical randomized controlled trials investigating new pharmacological treatments in patients with HFrEF published up to September 30, 2018. We included trials of ivabradine, levosimendan, omega-3, tolvaptan, recombinant human B-type natriuretic peptide (rhBNP), isosorbide dinitrate and hydralazine (ISDN/HYD) and angiotensin-neprilysin inhibition (LCZ696). We extracted the relevant information from these trials with a predefined data extraction sheet and assessed the risk of bias with the Cochrane risk of bias tool. Based on these items, more than half of the entries were judged as having an overall low to moderate risk of bias; the remaining studies had a high or unclear risk of bias. The outcomes investigated were left ventricle ejection fraction (LVEF %), heart rate (HR) and serum level of B-type natriuretic peptide (BNP). We performed a random-effects network meta-analysis within a Bayesian framework. Results: We deemed 32 trials to be eligible that included 3810 patients and 32 treatments. Overall, 32 (94.1%) trials had a low to moderate risk of bias, while 2 (5.9%) trials had a high risk of bias. The quality of the included studies was rated as low in regard to allocation concealment and blinding and high in regard to other domains according to the Cochrane tools. As for increasing LVEF%, levosimendan was better than placebo (–3.77 (–4.96, –2.43)) and was the best intervention for improving ventricle contraction. As for controlling HR, n3-PUFA was better than placebo (4.01 (–0.44, 8.48)) and was the best choice for regulating HR. As for decreasing BNP, omega-3 was better than placebo (941.99 (–47.48, 1952.89) and was the best therapy for improving ventricle wall tension. Conclusions: Our study confirmed the effectiveness of the included new pharmacological treatments for optimizing the structural performance and improving the cardiac function in the management of patients with HFrEF and recommended several interventions for clinical practice.

Thrombolytic therapy might reduce venous thromboembolism-related mortality and morbidity, but it could also increase the risk of major bleeding. We systematically reviewed the literature to evaluate the effectiveness and safety of thrombolytics in patients with pulmonary embolism (PE) and/or deep venous thrombosis (DVT). We searched Medline, Embase, and Cochrane databases for relevant randomized controlled trials up to February 2019. Multiple investigators independently screened and collected data. We included 45 studies (4740 participants). Pooled estimates of PE studies indicate probable reduction in mortality with thrombolysis (risk ratio [RR], 0.61; 95% confidence interval [CI], 0.40-0.94) (moderate certainty) and possible reduction in nonfatal PE recurrence (RR, 0.56; 95% CI, 0.35-0.89) (low certainty). Pooled estimates of DVT studies indicate the possible absence of effects on mortality (RR, 0.77; 95% CI, 0.26-2.28) (low certainty) and recurrent DVT (RR, 0.99; 95% CI, 0.56-1.76) (low certainty), but possible reduction in postthrombotic syndrome (PTS) with thrombolytics (RR, 0.70; 95% CI, 0.59-0.83) (low certainty). Pooled estimates of the complete body of evidence indicate increases in major bleeding (RR, 1.89; 95% CI, 1.46-2.46) (high certainty) and a probable increase in intracranial bleeding (RR, 3.17; 95% CI 1.19-8.41) (moderate certainty) with thrombolytics. Our findings indicate that thrombolytics probably reduce mortality in patients with submassive- or intermediate-risk PE and may reduce PTS in patients with proximal DVT at the expense of a significant increase in major bleeding. Because the balance between benefits and harms is profoundly influenced by the baseline risks of critical outcomes, stakeholders involved in decision making would need to weigh these effects to define which clinical scenarios merit the use of thrombolytics.

Objectives: This study evaluates the efficacy of Chinese herbal medicines after percutaneous coronary intervention (PCI). Background: PCI is the primary treatment for coronary atherosclerotic heart disease (CHD). However, many patients experience restenosis within 6 months after PCI. Chinese herbal medicines are widely used in patients after PCI. Clinical studies have found that Chinese herbal medicines may prevent restenosis. Methods: Eight databases were searched for randomized controlled trials (RCTs) investigating the use of Chinese herbal medicines after PCI. The search period was from the date of database inception to June 2017. We used the Cochrane risk of bias tool to estimate the methodological quality of the studies. The primary outcome was the restenosis rate, and secondary outcomes were the angina recurrence rate and major adverse cardiac events (MACEs). Data were analyzed with RevMan 5.3, and the quality of evidence was assessed with the GRAD approach. Results: Eleven RCTs with a total of 1,383 patients were included. The major outcome was the restenosis rate, and the results showed a significant effect of Chinese herbal medicines on reduction in the rate of restenosis (risk ratio [RR] = 0.46, 95% CI: 0.35-0.60, p < 0.00001, I2 = 0%). Chinese herbal medicine treatment also decreased the angina recurrence rate (RR = 0.41, 95% CI: 0.29-0.57, p < 0.00001, I2 = 0%). The results revealed a lower rate of MACEs in the Chinese medicine group than in the control group (RR = 0.49, 95% CI: 0.34-0.71, p = 0.0001, I2 = 0%). We evaluated the quality of evidence with the GRADE system; the quality of evidence for the restenosis rate and angina was low, and the quality of evidence for MACEs was estimated to be moderate. Conclusion: According to existing research evidence, the use of Chinese herbal medicines may reduce the incidence of MACEs. Chinese herbal medicines may reduce restenosis and angina recurrence rates after PCI, but the evidence is limited.

Background. Whether traditional Chinese medicine preparation combined therapy can improve the efficacy of chemotherapy is controversial. This meta-analysis evaluates the efficacy of traditional Chinese medicine preparation combined with chemotherapy. Method. Three databases were searched from inception through August 2018. Eligible randomized controlled trials (RCTs) involving the combined treatment of chemotherapy and traditional Chinese medicine preparation compared to chemotherapy alone for treating cancer were retrieved. The methodological quality of the included RCTs was assessed with Cochrane Collaboration’s risk of bias assessment tool. Meta-analysis was adopted to make comprehensive comparisons between the experimental and control groups. Results. Four RCTs were included in this review, comprising 256 subjects. The majority of the RCTs were judged as being of poor methodological quality. Meta-analysis showed that the combination of traditional Chinese medicine preparation and chemotherapy appeared to be more effective than chemotherapy alone, for the treatment of cancer, as assessed by the disease control rate (RR: 1.41, 95% CI: 1.11 to 1.79) and the objective response rate (RR: 2.71, 95% CI: 1.28 to 5.77). There were no statistically significant differences between the groups in terms of bone marrow suppression (RR: 0.88, 95% CI: 0.57 to 1.37) or gastrointestinal reaction (RR: 1.12, 95% CI 0.75 to 1.69). Conclusions. Traditional Chinese medicine preparation combined with chemotherapy may improve objective response rates and disease control rates more than chemotherapy alone. The evidence that combined traditional Chinese medicine preparation can reduce the side effects of chemotherapy is insufficient. More rigorous randomized controlled trials are needed to confirm these conclusions.

BACKGROUND Exercise may effectively reduce side effects caused by chemotherapy. However, no meta-analyses of exercise during or postchemotherapy for cancer patients have been definitely performed to guide clinical practice. AIMS To evaluate and summarize available scientific evidence to provide recommendations of an exercise intervention for cancer patients undergo chemotherapy. METHODS A systematic review and meta-analysis were performed with databases searching of MEDLINE, Cochrane Library, and Embase from their inception to October 15, 2017. Literature was selected to identify randomized controlled trials of exercise during or postchemotherapy for cancer patients. Risk-of-bias assessment was performed by two reviewers independently. Data were analyzed using the Cochrane Collaboration's RevMan 5.3 (Review Man, Copenhagen, Denmark). RESULTS A total of 10 trials with 838 participants were included in our study. Exercise could have a beneficial effect in cancer patients undergo chemotherapy in the outcome of physical fitness (MD: 0.16, 95% CI: 0.08-0.25, p < .01 and MD: 2.46, 95% CI: 1.44-3.47, p < .01) and depression (MD: -1.36, 95% CI: -2.68 to -0.04, p = .04), but not in FACT-G, FACT-B, anxiety, weight, and BMI (all p > .05). Exercise sequence (during or postchemotherapy) did not influence the effect of exercise for cancer patients undergo chemotherapy. In total, six studies were assessed as an overall low risk of bias. Subgroup analyses and sensitivity analyses reached results similar to those of the meta-analyses, which reflected our results were reliable and robust. LINKING EVIDENCE TO ACTION Exercise seems to have a beneficial effect on physical fitness and depression, but not on quality of life, anxiety, weight, and BMI. More specific and detailed description of the implementation of exercise programs should be proposed in the future.

Danshensu, the major water-soluble component of Radix Salviae Miltiorrhizae (Danshen), is the basic chemical structure of various salvianolic acids. This study was to evaluate the anti-tumor activity of danshensu in a series of in vitro and in vivo models. The effect of danshensu on B16F10 melanoma cell and HUVEC proliferation were assessed by MTS assay, and cell invasion and migration were investigated by transwell chamber assay. The effect of danshensu on angiogenesis was evaluated by HUVEC migration assay, tube formation assay and chick chorioallantoic membrane assay. The expression of MMP-2, -9 and VEGF in B16F10 melanoma cell were detected by western blotting after danshensu treatment. The role of danshensu in tumor metastasis in vivo was evaluated by spontaneous and experimental B16F10 melanoma metastasis model. Although danshensu had no inhibitory effect on B16F10 melanoma cell and HUVEC proliferation, it significantly inhibited B16F10 melanoma cell invasion (at 0.05, 0.5, 5 μM) and migration (at 0.5, 5 μM). It also dramatically suppressed VEGF-induced endothelial migration (at 0.5, 5 μM), tube formation in vitro (at 4, 20 μM) and new vessel formation in CAM in vivo (100 μg/egg). Danshensu (at 5, 50 μM) significantly down-regulates protein expression of MMP-2, -9 and VEGF in B16F10 melanoma cell. In animal model, danshensu (20, 40 mg/kg) also possessed inhibitory effect on lung metastasis in spontaneous (46-day treatment) and experimental (23-day treatment) B16F10 melanoma metastasis model. All these results suggest that danshensu has anti-tumor activity by affecting on tumor angiogenesis and tumor invasion.

PURPOSE:It was to assess antiangiogenic effect of β-elemene in vitro and in vivo, and it was involved in inhibiting melanoma growth and metastasis, as well as to elucidate its intrinsic mechanism.METHODS:Inhibitive effect of β-elemene on B16F10 cells was performed by cell proliferation assay. Angiogenesis assays in vitro including rat aortic ring and chick embryo chorioallantoic membrane were used, as well as melanoma growth and metastasis assay in C57BL/6 mice. Vascular endothelial growth factor (VEGF) expression in vitro and in vivo was measured respectively by western blot analysis and enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry analysis of CD34 and VEGF expression in primary melanoma was also presented.RESULTS:β-Elemene inhibited B16BF10 cell proliferation starting from 200 μM, but VEGF from 20 μM. Both 20 and 50 μM β-elemene in vitro inhibited VEGF-induced sprouting vessel of rat aortic ring and microvessel formation of chick embryo chorioallantoic membrane. In vivo, tumor size of primary melanoma in mice intraperitoneally treated with β-elemene was significantly smaller than that of the control; CD34 expression of primary melanoma was also suppressed; and the metastatic melanoma colonies and content of melanin in lung were detected obviously decreased in mice of β-elemene-treated groups. Furthermore, results of VEGF expressing in primary melanoma, serum and lung of mice also disclosed that VEGF was inhibited in vivo.CONCLUSIONS:β-Elemene inhibited melanoma growth and metastasis through suppressing VEGF-mediated angiogenesis. It is a natural potential antiangiogenic agent.

Ethnopharmacological relevance: Curcuma zedoaria (Berg.) Rosc., a traditional Chinese herb, was used widely but absolutely prohibited for the pregnant in clinic. Based on that there is abundant angiogenesis in endometrium and placenta during gestation period, we hypothesized that some components from it could inhibit angiogenesis and then damaged the supply of oxygen and nutrition to the embryo, which finally led to gestation failure.Aim of the study: This study was set to demonstrate whether essential oil, major components of Curcuma zedoaria had anti-angiogenic effect.Materials and methods: Essential oil of Curcuma zedoaria (EO-CZ) was abstracted by steam distillation extraction. Cell proliferation assay and two angiogenic models, rat aortic ring assay and chick embryo chorioallantoic membrane assay were presented. Furthermore, melanoma growth and experimental lung metastasis assay in mice were performed to evaluate its anti-angiogenesis effect in vivo. Immunohistochemical analysis and enzyme-linked immunosorbent assay (ELISA) were used to respectively detect the expression of CD34 and matrix metalloproteinases (MMPs).Results: EO-CZ exhibited anti-proliferative effect on B16BL6 and SMMC-7721 cells, the IC50, respectively was 41.8 mu g/ml and 30.71 mu g/ml, and on HUVEC (Human Umbilical Vein Endothelial Cells) cells with IC50 of far more than 120 mu g/ml. Both 20 mu g/ml and 40 mu g/ml EO-CZ indicated significant suppression on sprouting vessels of aortic ring and formation of microvessels in chick embryo chorioallantoic membrane in vitro. Moreover, solid melanoma grown in left oxter of mice was obviously inhibited after oral intake of 100 and 200 mg/kg of EO-CZ a day for 28 days, and CD34 expression indicating angiogenesis in melanoma reduced significantly compared with control; melanoma metastatic nodules in lung were detected to be inhibited, as well as MMP-2 and MMP-9 expression in serum.Conclusions: Essential oil, a fat-soluble fraction of Curcuma zedoaria, presented anti-angiogenic activity in vitro and in vivo, resulting in suppressing melanoma growth and lung metastasis. And this was associated with down-regulating MMPs. (C) 2010 Elsevier Ireland Ltd. All rights reserved.