Diphenolic boldine, an aporphine alkaloid: inhibitory effect evaluation on α-glucosidase by molecular dynamics integrating enzyme kinetics.

Screening α-glucosidase inhibitors with novel structures is an important field in the development of anti-diabetic drugs due to their application in postprandial hyperglycemia control. Boldine is one of the potent natural antioxidants with a wide range of pharmacological activities. Virtual screening and biochemical inhibition kinetics combined with molecular dynamics simulations were conducted to verify the inactivation function of boldine on α-glucosidase. A series of inhibition kinetics and spectrometry detections were conducted to analyze the α-glucosidase inhibition. Computational simulations of molecular dynamics/docking analyses were conducted to detect boldine docking sites' details and evaluate the key binding residues. Boldine displayed a typical reversible and mixed-type inhibition manner. Measurements of circular dichroism and fluorescence spectrum showed boldine changed the secondary structure and loosened the tertiary conformation of target α-glucosidase. The computational molecular dynamics showed that boldine could block the active pocket site through close interaction with binding key residues, and two phenolic hydroxyl groups of boldine play a core function in α-glucosidase inhibition via ligand binding. This investigation reveals the boldine function on interaction with the α-glucosidase active site, which provides a new inhibitor candidate.Communicated by Ramaswamy H. Sarma.

A meta-analysis of application of PD-1/PD-L1 inhibitor-based immunotherapy in unresectable locally advanced triple-negative breast cancer.

Aims: The purpose of this study was to explore the efficacy of immunotherapy for patients with triple-negative breast cancer (TNBC). Materials & methods: Randomized clinical trials comparing immunotherapy with chemotherapy for advanced TNBC patients were included. Results: A total of six articles (3183 patients) were eligible for this meta-analysis. PD-1/PD-L1 inhibitor-based immunotherapy combined with chemotherapy can significantly increase the progression-free survival (hazard ratio [HR] = 0.82; 95% CI = 0.76-1.14; p < 0.001) of unresectable locally advanced or metastatic TNBC patients without effect on overall survival, compared with chemotherapy. Conclusion: PD-1/PD-L1 inhibitors-based immunotherapy can safely improve progression-free survival in patients with unresectable locally advanced or metastatic TNBC, but has no effect on overall survival.

Breast cancer is a malignant tumor. It is most common in females. Triple-negative breast cancer is one type of malignant tumor that is not sensitive to treatment and is prone to recurrence. It can easily lead to death. Treatment mainly relies on chemotherapy. Immunotherapy is a new treatment method ad includes PD-1/L1 inhibitors. This research was conducted to assess its effects. Immunotherapy has good effects and can alleviate symptoms. It can improve prognosis and extend life. It has some side effects, mainly in the lungs and thyroid, but these side effects are controllable.

The effect and safety of CDK4/6 inhibitors combined endocrine therapy on HR+, HER2-breast cancer: a meta-analysis of randomized controlled trials.

INTRODUCTION: The purpose of this meta-analysis is to evaluate the efficacy and safety of cyclin-dependent kinase4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) on hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC). MATERIAL AND METHODS: A search was conducted in the PubMed, Embase, Web of Science, and Cochrane Library databases before July 2022. RESULTS: A total of 19 studies comprising 19,004 patients were eligible for this meta-analysis. This meta-analysis found that for unresectable locally advanced or metastatic HR+, HER2- BC, CDK4/6i combined with ET can significantly improve the progression-free survival (PFS) (hazard ratio = 0.59, p < 0.001), overall survival (OS) (hazard ratio = 0.77, p < 0.001), objective response rate (ORR) [risk ratio (RR) = 1.32, p = 0.001)], disease control rate (DCR) (RR = 1.10, p < 0.001), and clinical benefit response (CBR) (RR = 1.15, p = 0.001). For early HR+, HER2- BC, CDK4/6i combined with ET improved ORR (RR = 1.14, p = 0.05) and invasive disease free survival (iDFS) (hazard ratio = 0.87, p = 0.045) but had no effect on pathologic complete response (pCR) (RR = 1.75, p = 0.33), distant recurrence free survival (DRFS) (hazard ratio = 0.83, p = 0.311), and OS (hazard ratio = 1.08, p = 0.705). CONCLUSION: CDK4/6i combined with ET can improve the prognosis of patients with unresectable locally advanced or metastatic HR+, HER2- BC, but it has no obvious effect on patients with early HR+, HER2- BC. It is generally safe and manageable.

The relationship between tobacco and breast cancer incidence: A systematic review and meta-analysis of observational studies.

Background: The effect of tobacco on breast cancer (BC) is controversial. The purpose of this study was to investigate the relationship between tobacco and BC. Methods: A search was conducted in PubMed, EBSCO, Web of Science and Cochrane Library databases before February 2022. The adjusted odd ratio (OR) and corresponding 95% confidence interval (CI) were used to examine the relationship between active or passive smoking and BC risk. Results: A total of 77 articles composed of 2,326,987 participants were included for this meta-analysis. Active (OR=1.15, 95% CI=1.11-1.20, p<0.001) and passive (OR=1.17, 95% CI=1.09-1.24, p<0.001) smoking increased the risk of BC in the female population, especially premenopausal BC (active smoking: OR=1.24, p<0.001; passive smoking: OR=1.29, p<0.001), but had no effect on postmenopausal BC (active smoking: OR=1.03, p=0.314; passive smoking: OR=1.13, p=0.218). Active smoking increased the risk of estrogen receptor-positive (ER+) BC risk (OR=1.13, p<0.001), but had no effect on estrogen receptor-negative (ER-) BC (OR=1.08, p=0.155). The risk of BC was positively associated with the duration and intensity of smoking, negatively associated with the duration of smoking cessation. Active smoking increased the risk of BC in the multiparous population (OR=1.13, p<0.001), but had no effect on the nulliparous population (OR=1.05, p=0.432), and smoking before the first birth (OR=1.22, 95% CI=1.17-1.27) had a greater impact on the risk of BC than smoking after the first birth (OR=1.08, 95% CI=1.04-1.12). Conclusion: Smoking (active and passive) increased the risk of BC in women. The effect of smoking on BC was influenced by smoking-related factors (duration, intensity, years of quitting), population-related factors (fertility status), and BC subtypes. Systematic Review Registration: identifier CRD42022322699.

The association between caffeine exposure during pregnancy and risk of gestational hypertension/preeclampsia: A meta-analysis and systematical review.

BACKGROUND: The potential effect of caffeine exposure during pregnancy on gestational hypertension (GH)/preeclampsia has attracted attention but remains unclear. METHODS: A systematic literature search of PubMed, Embase, and Cochrane Library databases was performed until March 2022. Observational studies assessing the association between caffeine exposure during pregnancy and the risk of GH/preeclampsia were included. The study protocol was registered in PROSPERO: CRD42022322387. RESULTS: Ten studies involving 114 984 pregnant women (2548 diagnosed with GH and 2473 diagnosed with preeclampsia) were included. Comparing caffeine exposure with noncaffeine exposure, no significant association was found between caffeine exposure during pregnancy and the risk of GH (odds ratio [OR] = 0.99, 95% confidence interval [CI]: 0.90-1.08, p = 0.800) and preeclampsia (OR = 1.13, 95% CI: 0.97-1.31, p = 0.114). Subgroup analyses comparing low to moderate doses with no/lowest doses showed that caffeine exposure during pregnancy was not significant associated with GH (OR = 1.00, p = 0.987) or preeclampsia (OR = 1.03, p = 0.648). Besides, subgroup analyses comparing high doses with no/lowest doses showed that caffeine exposure during pregnancy was not significant associated with GH (OR = 1.06, p = 0.623) or preeclampsia (OR = 1.18, p = 0.192). CONCLUSION: This study found that caffeine exposure during pregnancy was not significantly associated with the risk of GH/preeclampsia.

Relationship Between SGLT-2i and Ocular Diseases in Patients With Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials.

Background: This meta-analysis was conducted to explore the association between sodium-glucose cotransporter 2 inhibitors (SGLT-2is) and ocular diseases in type 2 diabetes mellitus (T2DM) patients. Methods: PubMed, Cochrane Central Registry of Controlled Trials, Web of Science and Springer were searched for articles on randomized controlled trials (RCTs) involving T2DM patients treated with SGLT-2i versus placebo or other hypoglycemic agents published prior to August 2021. The primary outcome of this meta-analysis was incidence of ocular diseases, which was assessed using risk ratios (RR) and 95% confidence intervals (CI). We reviewed 47 papers and compared the effect of SGLT-2i with the effect of the control groups (placebo and other hypoglycemic drugs) on the incidence of ocular diseases. Results: Compared with controls, overall SGLT-2i use in T2DM patients was not associated with incidences of cataract, glaucoma, retinal disease and vitreous disease. Ertugliflozin (RR=0.47, P=0.01) reduced the risk for retinal disease, while empagliflozin (RR=0.44, P=0.05) reduced the risk for diabetic retinopathy (DR) compared with controls. SGLT-2i (RR=0.50, P=0.02), perhaps empagliflozin (RR=0.47, P=0.06), reduced the risk of retinal disease compared with active hypoglycemic agents. Canagliflozin (RR=4.50, P=0.03) increased the risk for vitreous disease compared with placebo. Conclusions: There was no significant correlation between overall SGLT-2i and ocular diseases (cataract, glaucoma, retinal disease, vitreous disease, corneal disease, conjunctival disease, uveal disease, eye haemorrhage and vision problems) in T2DM patients. Ertugliflozin and empagliflozin may protect against ocular diseases, but canagliflozin may promote ocular diseases.

Comparison of hybrid coronary revascularization versus coronary artery bypass grafting in patients with multivessel coronary artery disease: a meta-analysis.

BACKGROUND: Percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are widely used in the treatment of coronary heart disease, but the best revascularization method for multivessel coronary artery disease (MVD) patients is still controversial. Hybrid coronary revascularization (HCR), together with CABG and PCI, have been proved to be feasible methods, but the long-term effect of HCR is not as clear as CABG. METHOD: By October 2020, we retrieved articles from PubMed, Web of science, EMBASE and Cochrane library databases. The main results are based on major adverse cardiovascular and cerebral events (MACCE). RESULT: A total of 18 articles (3 randomized controlled trials (RCTs) and 15 observational studies) were included in this meta-analysis. The outcomes of MACCE in the HCR group at perioperative, short-term (30 days to 1 year), medium-term (1 year to 5 years) and long-term (5 years and above) follow-up period were similar to those in the CABG group. The mortality rates of patients in perioperative, short-term and medium-term follow-up were similar to those in the CABG group, but lower than that in the CABG group at long-term follow-up (OR = 0.35, 95% CI 0.18-0.69, p = 0.002). The revascularization rate was higher in the HCR group during the perioperative period (OR = 3.50, 95% CI 2.07-5.94, p < 0.001), short-term (OR = 3.28, 95% CI 1.62-6.64, p < 0.001) and mid-term follow-up (OR = 2.84, 95% CI 1.64-4.92, p < 0.001). CONCLUSION: Our results reveal that HCR is a safe and therapeutically effective alternative in treatments for MVD patients. It has not only less short-term adverse effect, but also better long-term effect, especially in death.

PD-1/L1 With or Without CTLA-4 Inhibitors Versus Chemotherapy in Advanced Non-Small Cell Lung Cancer.

BACKGROUND: With the use of immune-checkpoint inhibitors (ICIs) in advanced or metastatic non-small cell lung cancer (NSCLC), whether ICIs or chemotherapy is more effective still remains controversial. This study was conducted to evaluate the efficacy of programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), cytotoxic T-lymphocyte protein 4 (CTLA-4) alone or in their combination vs chemotherapy in patients with advanced or metastatic NSCLC. METHODS: This meta-analysis was conducted from PubMed, Web of Science, Medline, Embase, and the Cochrane Library up to March 2021 to identify relevant randomized controlled trials. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoint was adverse events (AEs). This meta-analysis's Prospero registration number is CRD42022323570. RESULTS: The search process has identified 13 studies containing 7918 patients with advanced or metastatic NSCLC. The benefit of PD-1/L1 or CTLA-4 inhibitors alone or in combination compared with chemotherapy for advanced or metastatic NSCLC was elucidated in both OS [HR = .75, 95% CI (.70-.80), P < .001] and PFS [HR = .83, 95% CI (.73-.95), P < .001]. Besides, ICIs were associated with fewer AEs compared to chemotherapy. CONCLUSION: PD-1/L1 or CTLA-4 inhibitors alone or in combination, with fewer AEs, was associated with significant improvements in terms of OS and PFS than chemotherapy in advanced or metastatic NSCLC.

The relationship between night shift work and breast cancer incidence: A systematic review and meta-analysis of observational studies.

The purpose of this study was to investigate the relationship between night shift work and breast cancer (BC) incidence. A search was performed in PubMed, EBSCO, Web of Science, and Cochrane Library databases before June 2021. The exposure factor of this study is night shift work, the primary outcome is the risk of BC. A total of 33 observational studies composed of 4,331,782 participants were included. Night shift work increases the risk of BC in the female population (hazard ratio [HR] = 1.20, 95% confidence interval [Cl] = 1.10-1.31, p < 0.001), especially receptor-positive BC, including estrogen receptor (ER)+ BC (HR = 1.35, p < 0.001), progesterone receptor (PR)+ BC (HR = 1.30, p = 0.003), and human epidermal growth factor receptor 2 (HER2)+ BC (HR = 1.42, p < 0.001), but has no effect on HER2- BC (HR = 1.10, p = 0.515) and ER-/PR- BC (HR = 0.98, p = 0.827). The risk of BC was positively correlated with night shift working duration, frequency, and cumulative times. For women who start night work before menopause, night work will increase the incidence of BC (HR = 1.17, p = 0.020), but for women who start night work after menopause, night work does not affect BC (HR = 1.04, p = 0.293). Night work can increase the incidence of BC in the female population. The effect of long working hours, frequency, and the cumulative number of night shifts on BC is influenced by menopausal status.

Prognostic Impact of Surgical Margin in Hepatectomy on Patients With Hepatocellular Carcinoma: A Meta-Analysis of Observational Studies.

OBJECTIVE: This study aims to comprehensively evaluate the prognostic impact of the surgical margin in hepatectomy on patients diagnosed with hepatocellular carcinoma (HCC). METHODS: A comprehensive and systematic search for eligible articles published in English before July 2021 was conducted across PubMed, Cochrane Library, Web of Science, and Embase electronic databases. The overall survival (OS) and disease-free survival (DFS) were the primary endpoints. RESULTS: In total, 37 observational studies with 12,295 cases were included in this meta-analysis. The results revealed that a wide surgical margin (≥1 cm) was associated with better OS (hazard ration (HR), 0.70; 95% confidence interval (CI), 0.63-0.77) and DFS (HR, 0.66; 95% CI, 0.61-0.71) compared to a narrow surgical margin (<1 cm). Subgroup analyses were conducted based on median follow-up time, gender, country, hepatitis B surface antigen (HBsAg) status, tumor number, and liver cirrhosis. The prognostic benefit of a wide surgical margin was consistent in most subgroups, however, analysis of studies from Western countries showed that margin width was not associated with prognosis. CONCLUSION: In summary, a surgical margin wider than 1 cm prolongs the long-term prognosis of HCC patients compared to a surgical margin narrower than 1 cm.

Efficacy and safety of SGLT-2i in overweight/obese, non-diabetic individuals: a meta-analysis of randomized controlled trials.

INTRODUCTION: Sodium-glucose cotransporter 2 inhibitor (SGLT-2i) has been shown to decrease blood glucose levels in type 2 diabetes mellitus (T2DM) patients and potentially yield additional benefits in weight loss. This meta-analysis aimed to investigate the efficacy and safety of giving SGLT-2i to overweight/obese, non-diabetic individuals. MATERIAL AND METHODS: The search was underpinned by PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and Springer to identify English-language papers on randomized controlled trials (RCTs) on the use of SGLT-2i in overweight/obese, nondiabetic individuals published in and before March 2021, to study its effectiveness and safety. Results were evaluated by weighted mean difference (WMD), standardized mean difference (SMD), risk ratio (RR), and 95% confidence interval (CI). RESULTS: We reviewed 13 papers and compared the SGLT-2i group with the control group (other drugs and placebo) and found that SGLT-2i reduced weight (WMD = -1.33, p = 0.002) and waist circumference (WMD = -1.94, p = 0.03) in overweight/obese, non-diabetic individuals. The use of SGLT-2i is more effective than other interventions in terms of weight loss ≥ 5% (RR = 2.04, p < 0.001), but not in terms of weight loss ≥ 10% (RR = 1.83, p = 0.22). In addition, there were no significant changes in other metabolic parameters, like fasting plasma glucose (FPG), lipids, blood pressure, etc. SGLT-2i increased the risk of infections in urinary tract (RR = 1.91, p = 0.009) and reproductive system (RR = 4.09, p < 0.001). CONCLUSIONS: SGLT-2i is a promising candidate to reduce weight and waist circumference to a limited extent in overweight/obese, nondiabetic individuals. Generally, it is safe and effective. However, it potentially increased the risk of urogenital infections, which cannot be ignored.

A meta-analysis of the effect and safety of platinum-based neoadjuvant chemotherapy in treatment of resectable triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is the most aggressive and fatal subtype of breast cancer. The effectiveness of platinum-based neoadjuvant chemotherapy in treatment of cancer has many divergent opinions. A search was conducted in the PubMed, EBSCO, Web of Science and Cochrane Library databases for relevant studies published before August 2020. The primary endpoint was pathological complete response (pCR) while the secondary endpoints were objective response rate (ORR), overall survival (OS) and progression-free survival (PFS). Nine randomized controlled trials comprised of 1873 patients were included in this meta-analysis. Platinum-based neoadjuvant chemotherapy showed significant improvements in pCR (RR = 1.51, 95% CI, 1.25-1.82, P < 0.001), ORR (RR = 1.20, 95% CI, 1.07-1.34, P = 0.001), OS (HR=0.56; 95% CI, 0.15-0.96, P < 0.001) and PFS (HR = 0.48, 95% CI, 0.22-0.73, P < 0.001) compared to nonplatinum neoadjuvant chemotherapy. Moreover, addition of platinum compounds did not significantly increase the side effects of any grade. However, there was an increase in blood toxicity of grade 3 patients which meant that it was mainly confined to the bone marrow/blood system. Platinum-based neoadjuvant chemotherapy can safely improve short-term and long-term outcomes in resectable TNBC patients.

A study of Pb2+ induced unfolding and aggregation of arginine kinase from Euphausia superba: kinetics and computational simulation integrating study.

Arginine kinase is a crucial phosphagen kinase in invertebrates, which is associated to the environmental stress response, plays a key role in cellular energy metabolism. In this study, we investigated the Pb2+-induced inhibition and aggregation of Euphausia superba arginine kinase (ESAK) and found that significantly inactivated ESAK in a dose-dependent manner (IC50 = 0.058 ± 0.002 mM). Spectrofluorimetry results showed that Pb2+ induced tertiary structural changes via the internal polarity increased and the non-polarity decreased in ESAK and directly induced ESAK aggregation. The ESAK aggregation process induced by Pb2+ occurred with multi-phase kinetics. The addition of osmolytes did not show protective effect on Pb2+-induced inactivation of ESAK. The computational molecular dynamics (MD) simulation showed that three Pb2+ interrupt the entrance of the active site of ESAK and it could be the reason on the loss of activity of ESAK. Several important residues of ESAK were detected that were importantly contributed the conformation and catalytic function of ESAK. Our study showed that Pb2+-induced misfolding of ESAK and the complete loss of activity irreversibly, which cannot be recovered by osmolytes.Communicated by Ramaswamy H. Sarma.

Prognostic Influence of Spontaneous Tumor Rupture in Patients With Hepatocellular Carcinoma After Hepatectomy: A Meta-Analysis of Observational Studies.

Objective: This study aims to comprehensively analyze the influence of spontaneous tumor rupture on the prognosis of hepatocellular carcinoma patients following hepatic resection. Methods: We systematically searched four online electronic databases, including PubMed, Embase, Web of Science, and Cochrane Library, for eligible studies published from inception to March 2021. The main endpoints were overall survival (OS) and disease-free survival (DFS). Results: This meta-analysis included 21 observational articles with 57,241 cases. The results revealed that spontaneous tumor rupture was associated with worse OS (hazard ratio (HR), 1.65; 95% confidence interval (CI), 1.33-2.05) and DFS (HR, 1.42; 95% CI, 1.12-1.80) in resectable hepatocellular carcinoma patients. This phenomenon was observed in most subgroups, which were classified by recorded survival time, age, country, alpha-fetoprotein (AFP) concentration, liver cirrhosis, and microvascular invasion. However, in subgroups of macrovascular invasion positive, spontaneous tumor rupture was not a risk factor for OS (HR, 1.55; 95% CI, 0.99-2.42) and DFS (HR, 1.23; 95% CI, 0.91-1.65) in hepatocellular carcinoma patients after hepatectomy. For macrovascular invasion negative, compared with non-ruptured hepatocellular carcinoma patients, ruptured hepatocellular carcinoma patients exhibited worse prognosis for OS (HR, 1.55; 95% CI, 0.99-2.42) and DFS (HR, 1.23; 95% CI, 0.91-1.65) following hepatectomy. Conclusions: Spontaneous tumor rupture was a prognostic risk factor for hepatocellular carcinoma patients after hepatic resection. However, in macrovascular invasion patients, spontaneous tumor rupture was not a prognostic risk factor.

The combinative effects of orem self-care theory and PDCA nursing on cognitive function, neurological function and daily living ability in acute stroke.

OBJECTIVE: The combined effects of Orem Self-care Theory and PDCA nursing on cognitive function, neurological function and daily living ability of patients with acute stroke were analyzed in this research. METHODS: 126 patients, who admitted to our hospital with acute stroke from January 2019 to March 2020, were enrolled in this study as research subjects. The subjects were divided into control-group (n=61) and observation-group (n=65) in accordance with their admission time. The control-group received routine nursing care; and the observation-group, was applied with the combined nursing interventions of Orem's self-care mode and PDCA nursing management in addition to conventional treatment. Subsequently, the changes in daily living ability (ADL score), neurological function (GCS score, NIHSS score) and cognitive function (MoCA and MMSE scores) of the two groups before and after receiving nursing care were compared accordingly. RESULTS: After the implementation of nursing measures, the ADL scores of the two groups improved dramatically than before (P<0.05), and observation-group had obviously higher post-intervention scores than that of the control-group (P<0.05); The GCS scores of the two groups were remarkably higher than those before nursing (P<0.05), and the observation-group had critically higher post-intervention scores than those of the control-group (P<0.05); The NIHSS scores of the two groups decreased substantially than before (P<0.05), and the observation-group had dramatically lower scores than the control-group (P<0.05); The MMSE score in two groups increased remarkably than before nursing (P<0.05), and the post-intervention score of observation-group was significantly higher than that of control-group (P<0.05). CONCLUSION: On the basis of Orem Self-care theory, the application of PDCA nursing in daily nursing work to acute stroke patients can actively improve their cognitive function, neurological function and daily life ability. This has a positive role in promoting medical staff to improve the quality of care and provide patients with more comprehensive and thoughtful nursing services.

The relationship between dairy products intake and breast cancer incidence: a meta-analysis of observational studies.

BACKGROUND: The effect of dairy products intake on breast cancer (BC) is highly controversial. This study aims to investigate the relationship between dairy intake and BC incidence. METHODS: A search was carried out in PubMed, EBSCO, Web of Science, and Cochrane Library databases before January 2021. The primary objective was the risk of BC and intake of dairy products were exposure variables. RESULTS: The meta-analysis comprised 36 articles with 1,019,232 participants. Total dairy products have a protective effect on female population (hazard ratio (HR) =0.95, 95% confidence interval (CI) =0.91-0.99, p = 0.019), especially for estrogen receptor-positive (ER+) (HR = 0.79, p = 0.002) and progesterone receptor-positive (PR+) BC (HR = 0.75, p = 0.027). For ER+/PR+ BC, there is a trend of protection, but it has not reached statistical significance (HR = 0.92, p = 0.075). Fermented dairy products can reduce BC risk in postmenopausal population (HR = 0.96, 95%CI = 0.93-0.99, p = 0.021), but have no protective effect on premenopausal population (HR = 0.98, 95%CI = 0.94-1.03, p = 0.52). Non-fermented dairy products have no significant effect on BC occurrence (p > 0.05). High-fat dairy products are harmful to women, without statistical difference (HR = 1.06, 95%CI = 1.00-1.13, p = 0.066). On the contrary, low-fat dairy products can protect the premenopausal population (HR = 0.94, 95%CI = 0.89-1.00, p = 0.048). CONCLUSION: The intake of dairy products can overall reduce BC risk in the female population, but different dairy products have varying effects on different BC subtypes and menopausal status.

The Role of Hepatic Arterial Infusion Chemotherapy in the Treatment of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: The main aim of this study was to investigate comprehensively the clinical effect of hepatic arterial infusion chemotherapy (HAIC) on patients suffering from hepatocellular carcinoma (HCC). METHODS: The following electronic databases were searched for eligible articles published from inception to July 2020: PubMed, Web of Science, Embase, and Cochrane Library. The main final indicators were overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). RESULTS: A total of 26 studies entailing 4,506 cases were included for a meta-analysis. The results showed that HAIC could improve advanced HCC patients' OS (HR, 0.49; 95% CI: 0.37-0.61) and PFS (HR, 0.52; 95% CI: 0.36-0.68). Remarkably, compared with Japan (HR, 0.58) and Korea (HR, 0.54), for the unresectable HCC patients, the HAIC group achieved higher efficacy on OS than the control group in China (HR, 0.24). The resectable HCC patients, who received HAIC adjuvant chemotherapy, exhibited favorable prognosis for OS (HR, 0.58; 95% CI: 0.27-0.88) and DFS (HR, 0.49; 95% CI: 0.31-0.68). CONCLUSION: HAIC improved long-term survival for both resectable and unresectable HCC patients in comparison with other therapies. However, the clinical effect of HAIC needs to be ascertained by large-scale well-designed studies.

SGLT-2i and Risk of Malignancy in Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials.

Background: Currently, the association between sodium-glucose cotransporter 2 inhibitor (SGLT-2i) and malignancy risk has yet to be fully elucidated. This meta-analysis aimed to determine the relationship between SGLT-2i and malignancy risk in type 2 diabetes (T2D) patients. Methods: We searched PubMed, ScienceDirect, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science to identify randomized controlled trials (RCTs) published up to August 2020 related to T2D patients treated with SGLT-2i vs. placebo or other hypoglycemic agents. The meta-analysis's primary outcome was malignancies' incidence, and the results were evaluated using risk ratio (RR) and 95% confidence interval (CI). Results: We reviewed 76 articles (77 RCTs), comprising 45,162 and 43,811 patients in SGLT-2i and control groups, respectively. Compared with the control group, SGLT-2i had no significant association with augmented overall malignancy risk in T2D patients (RR = 1.05, 95% CI = 0.97-1.14, P = 0.20), but ertugliflozin may upsurge the risk (RR = 1.80, 95% CI = 1.02-3.17, P = 0.04). Compared with active hypoglycemic agents, dapagliflozin may increase (RR = 2.71, 95% CI = 1.46-6.43, P = 0.02) and empagliflozin may decrease (RR = 0.67, 95% CI = 0.45-0.98, P = 0.04) the malignancy risk. Compared with placebo, empagliflozin may exhibit risk increase (RR = 1.25, 95% CI = 1.05-1.49, P = 0.01), primarily in digestive system (RR = 1.48, 95% CI = 0.99-2.21, P = 0.05). Conclusions: Our results proposed that in diverse comparisons, ertugliflozin and dapagliflozin seemed to increase the malignancy risk in T2D patients. Empagliflozin may cause malignancy risk reduction compared with active hypoglycemic agents but increase overall risk primarily in the digestive system compared with placebo. In short, the relationship between SGLT-2i and malignancy in T2D patients remains unclear.

MicroRNA 26a targets Ezh2 to regulate apoptosis in mouse ovarian granulosa cells.

In the mammalian ovary, <1% of the follicles ovulate, with most undergoing degenerative atresia during ovarian follicular development. Follicular atresia is caused by the apoptosis of granulosa cells (GCs), although the precise underpinning mechanism remains unidentified. MiR-26a regulates various cellular events, including cell division, apoptotic signaling, and cell differentiation, migration, and autophagy. Here, we demonstrated that miR-26a regulated apoptosis in GCs in the mouse ovary through Ezh2, a key regulator of GC viability. We also found that transcription of miR-26a changed in response to an LH antagonist and a GnRH agonist. In addition, miR-26a transcription was downregulated following LH-induced transition of GCs to granulosa-lutein cells (GLCs). Dual-luciferase reporter assays confirmed Ezh2 as a miR-26a target. Exogenous expression in GCs of miR-26a mimics resulted in decreased Ezh2 expression, while miR-26a inhibition in GCs induced the opposite phenotype. Ezh2 silencing additionally reduced the anti-apoptotic effect of miR-26a inhibition in GCs. These data highlight the critical role of miR-26a in targeting Ezh2 and regulating apoptosis in mouse ovarian GCs.Abbreviations: GC: Granulosa cell; GLCs: Granulosa-lutein cells; LH: Luteinizing hormone; miRNA: MicroRNA; NC: Negative control; Cyt-c: Cytochrome c; GnRH: Gonadotropin releasing hormone; i.p.: intraperitoneal injection; cKO: conditional knock-out; WB: Western blotting; hCG: Human chorionic gonadotropin; NPC: nasopharyngeal carcinoma.

Neoadjuvant chemotherapy increases the 5-year overall survival of patients with resectable cervical cancer: A systematic review and meta-analysis.

Cervical cancer is a global health challenge in women. Neoadjuvant chemotherapy (NACT) is a recent prospect for alternative cervical cancer treatments. This study investigated the efficacy of NACT against resectable cervical cancer based on the medium and long-term survival of patients with the disease. We searched through PubMed, Web of Science, EBSCO and Cochrane Library for relevant reports published by June 2020. The primary outcomes were 3-year and 5-year progression-free survival (PFS) and overall survival (OS) of patients with resectable cervical cancer. Overall, 22 publications encompassing 5627 patients fulfilled the inclusion criteria. We found NACT not to affect both 3-year PFS and OS as well as 5-year PFS of patients with resectable cervical cancer. However, NACT significantly improves the 5-year OS of patients with resectable cervical cancer (HR = 0.83, 95% CI: 0.73-0.94, p = 0.013). Subgroup analysis (RCTs, non-RCTs, NACT + surgery + AT vs. surgery + AT, NACT + surgery + AT vs. CCRT/RT/CRT) further revealed NACT had no significant effect on 5-year PFS of patients with resectable cervical cancer, converse to the 5-year OS subgroup analysis, which validated the beneficial effect of NACT in patients with resectable cervical cancer. In addition, the effect of NACT was most significant in the non-RCTs subgroup (p = 0.012). NACT may improve the long-term prognosis of patients with resectable cervical cancer. However, further large-scale multicenter studies are needed to validate this finding.