Oolong tea of different years protects high-fat diet-fed mice against obesity by regulating lipid metabolism and modulating the gut microbiota.

Long-term stored oolong tea has recently attracted considerable attention concerning its salutary effect. In this study, the anti-obesity effect of different years' oolong tea on high-fat diet-fed mice was compared. Wuyi rock tea of 2001, 2011, and 2020 were chosen to be the representative samples of oolong tea. The results showed that eight-week administration of 2001 Wuyi rock tea (WRT01), 2011 Wuyi rock tea (WRT11), and 2020 Wuyi rock tea (WRT20) extracts (400 mg per kg per d) significantly decreased the body weight and attenuated the obesity in high-fat diet-fed mice. 2001 and 2011 Wuyi rock teas reduced obesity mainly through regulating lipid metabolism and activating the AMPK/SREBP-1 pathway, downregulating the expression of SREBP-1, FAS, and ACC and upregulating CPT-1a expression; while the 2011 and 2020 Wuyi rock teas by moderating the gut microbiota dysbiosis, reshaping the gut microbiota, and promoting the growth of beneficial bacteria, especially Akkermansia. 2011 Wuyi rock tea was proven to be more effective in reducing body weight gain and liver oxidative stress than the others. Collectively, all three Wuyi rock teas of different years alleviated high-fat diet-induced obesity by regulating lipid metabolism and modulating gut microbiota, whereas the emphasis of their internal mechanism is different with different storage ages.

Six types of tea extracts attenuated high-fat diet-induced metabolic syndrome via modulating gut microbiota in rats.

An important puzzle for tea consumers is which type of tea is effective in treating metabolic syndrome (MS). In this study, the effects of six types of tea extracts (TEs) on high-fat diet (HFD)-induced MS, as well as chemical components of six TEs, were investigated and compared. Each TE consisted of representative tea originated from different places in China to avoid one-sidedness of sampling. All six TEs were found to attenuate MS and ameliorate intestinal barrier function in HFD-fed rats. Further, white tea performed better in body weight control, while dark tea had more advantages in protecting intestinal barrier. Moreover, all six TEs alleviated the gut microbiota dysbiosis, which was manifested by decreased Firmicutes/Bacteroidetes ratio and enriched beneficial bacteria, such as Akkermansia, Bacteroides, and Bifidobacterium. Together, all six TEs attenuate HFD-induced MS although their efficiency varies, and this therapeutic effect is related to the modulation of gut microbiota.

Different nutrient compositions in diet and taking hypoglycemic drugs can modulate gut microbial flora.

The diet structure of diabetic patients is different from that of normal people. Diabetic patients also need to take hypoglycemic drugs to regulate blood sugar. Both dieting and drugs affect the gut microbiota of diabetic patients. In this letter, we discuss that different dietary patterns and the use of hypoglycemic agents may have an impact on changes in gut microbiota in diabetic patients.

Progress in the Relationship between Vitamin D Deficiency and the Incidence of Type 1 Diabetes Mellitus in Children.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease, due to a large number of islet ß cells damaged, resulting in an absolute lack of insulin, ultimately relying on insulin therapy. Vitamin D is a fat-soluble sterol derivative that not only participates in calcium and phosphorus metabolism but also acts as an immunomodulatory role by binding to nuclear vitamin D receptors to regulate the expression of transcription factors. Increasing evidence has shown that vitamin D has immunoregulation and anti-inflammatory effects, and it may play a role in T cell regulatory responses due to downregulation in the expression of cathepsin G and inhibition of CD4+ T cell activation and protection of ß cells from immune attack and is beneficial in decreasing oxidative stress in T1DM patients. Epidemiologic evidence demonstrates involvement of vitamin D deficiency in T1DM pathogenesis, with the immune system improperly targeting and destroying its own islet ß cells. In addition, polymorphisms in genes critical for vitamin D metabolism may increase the risk of islet autoimmunity and T1DM. In this paper, the relationship between vitamin D deficiency and the molecular mechanism of T1DM was discussed.

A Multicenter Randomized Trial Assessing ZENFlow Carrier-Free Drug-Coated Balloon for the Treatment of Femoropopliteal Artery Lesions.

Backgrounds and Objectives: Drug-coated balloons (DCBs) have shown promising benefits in improving the outcomes for patients with peripheral artery disease. Several randomized clinical trials have reported that paclitaxel-coated balloon significantly reduce the rates of restenosis and the need for reintervention in comparison with regular balloon angioplasty. Due to the differences in excipients, paclitaxel dose, and coating techniques, variable clinical outcomes have been observed with different DCBs. In this study, we aimed to evaluate the safety and efficacy of a novel ZENFlow carrier-free DCB in the treatment of femoropopliteal artery occlusive disease. Methods: In this randomized controlled trial conducted at 15 sites, 192 patients with Rutherford class 3-5 were randomly assigned into two groups: drug-coated balloon group and percutaneous transluminal angioplasty group. The primary endpoint was a late lumen loss at 6 months based on blinded angiographic core laboratory evaluations, and the secondary endpoints included primary patency rate, binary restenosis, clinically driven target lesion revascularization, ankle-brachial index, Rutherford class change, and major adverse events. Results: In this multicenter trial, 93 patients received DCB angioplasty, whereas 99 patients underwent regular balloon angioplasty. The late lumen loss at 6-month follow-up was 0.50 ± 0.82 and 1.69 ± 0.87 mm in the drug-coated balloon and percutaneous transluminal angioplasty groups, respectively (p < 0.001). During the 12-month follow-up period, the drug-coated balloon group showed a significantly higher primary patency rate (54 vs. 31.3%, p = 0.009) and markedly lower rates of target vessel restenosis (22.1 vs. 64.3%, p < 0.001) and clinically driven target lesion revascularization rate (5.4 vs. 19.2%, p = 0.006) than the percutaneous transluminal angioplasty group. Compared with the percutaneous transluminal angioplasty group, the drug-coated balloon group had significant improvements in the ankle-brachial index and Rutherford class. The all-cause mortality rate was comparable, and no device-related deaths occurred in either groups. Conclusions: Balloon angioplasty using a ZENFlow carrier-free drug-coated balloon is a safe and effective treatment method for femoropopliteal artery lesions. This novel drug-coated balloon catheter achieved satisfactory early and 1-year outcomes in this trial. Clinical Trial Registration: https://clinicaltrials.gov, identifier: NCT03844724.

A systematic review and meta-analysis on the association between C-reactive protein levels and adverse limb events after revascularization in patients with peripheral arterial disease.

OBJECTIVE: Patients with peripheral arterial disease (PAD) are predisposed to postprocedure adverse limb events (ALE). Previous single-center studies investigating the relationship between baseline C-reactive protein (CRP) levels and postprocedure ALE have reported inconsistent results. Therefore, we performed a systematic review and meta-analysis of reported data to determine the association between CRP levels and the occurrence of postprocedure ALE in patients with PAD. METHODS: Studies investigating the association between the CRP levels and postprocedure ALE (ie, target vessel revascularization, amputation, restenosis, disease progression, composite endpoint of any of these ALE) were identified in the Medline, EMBASE, and Cochrane databases. Meta-analyses of the reported hazard ratios (HRs) were conducted using an inverse variance-weighted random effects model. Subgroup analyses were performed to determine the differences in outcomes between open surgery and endovascular treatment. Pooled estimates are reported as HRs to compare higher and lower CRP levels and odds ratio or relative risk per unit increase in logeCRP (natural logarithm C-reactive protein). RESULTS: A total of eight studies involving 1460 participants were included in our meta-analysis. Patients with higher baseline CRP levels had a greater risk of ALE (HR, 1.09; 95% confidence interval, 1.00-1.18; P = .04) compared with those with lower baseline CRP levels. The pooled estimate of odds ratio and relative risk for ALE was 2.25 (95% confidence interval, 1.49-3.41; P < .01) per unit increase in logeCRP. Subgroup analyses found no significant differences in the pooled estimates in studies of open surgery vs endovascular treatment. CONCLUSIONS: Our results have demonstrated that high baseline CRP levels are predictive of ALE in patients with PAD after lower limb revascularization.

[Treatment of Concomitant Intra-abdominal Malignancy and Abdominal Aortic Aneurysm].

Objective To explore the outcomes in patients who receive the endovascular abdominal aortic aneurysm repair(EVAR)and have concomitant intra-abdominal malignancy.Methods Between January 2014 and December 2019,all the patients who underwent surgery for malignancy and/or EVAR were retrospectively reviewed.Results Twenty-eight abdominal aortic aneurysm(AAA)patients with concomitant intra-abdominal malignancy were included.The patients were treated by two-stage operation and the priority was given for EVAR in 21 patients.There was no perioperative death or major complications.In the follow-up,one patient developed graft thrombosis and one had type Ⅱ endoleak.There was no AAA-associated death.Conclusions It is preferred that EVAR should come first followed by operation for malignancy.Details of treatment strategy still need further investigation.

Cancer Cells Upregulate NRF2 Signaling to Adapt to Autophagy Inhibition.

While autophagy is thought to be an essential process in some cancer cells, it is unknown if or how such cancer cells can circumvent autophagy inhibition. To address this, we developed a CRISPR/Cas9 assay with dynamic live-cell imaging to measure acute effects of knockout (KO) of autophagy genes compared to known essential and non-essential genes. In some cancer cells, autophagy is as essential for cancer cell growth as mRNA transcription or translation or DNA replication. However, even these highly autophagy-dependent cancer cells evolve to circumvent loss of autophagy by upregulating NRF2, which is necessary and sufficient for autophagy-dependent cells to circumvent ATG7 KO and maintain protein homeostasis. Importantly, however, this adaptation increases susceptibly to proteasome inhibitors. These studies identify a common mechanism of acquired resistance to autophagy inhibition and show that selection to avoid tumor cell dependency on autophagy creates new, potentially actionable cancer cell susceptibilities.

[Femoral-popliteal Arteriosclerosis Obliterans:Review of Evidence-based Studies on Drug-eluting Endovascular Treatment].

Atherosclerosis-related diseases have increasingly become health concerns with the increased living conditions and aging.Globally,about 200 million people have suffered from arteriosclerosis obliterans(ASO),which can even be life-threatening in some cases.The past seven decades have witnessed the rapid advances in the treatment of ASO,which has developed from surgery to endovascular interventions including plain balloon angioplasty,bare metal stent placement,drug-coated balloon,and drug-eluting stent.However,the roles of these new techniques for femoral-popliteal lesions,especially their real-world clinical outcomes and indications,remain unclear.This article reviews the latest evidences on the use of drug-eluting devices in treating femoral-popliteal arteriosclerosis obliterans.

A meta-analysis of laparoscopic surgery versus conventional open surgery in the treatment of colorectal cancer.

BACKGROUND: This meta-analysis aimed to explore the overall effect and safety of anterior laparoscopic surgery versus conventional open surgery for patients with colorectal cancer based on eligible randomized controlled trials (RCTs), especially the difference in the postoperative incidence of deep venous thrombosis (DVT). METHODS: PubMed, Cochrane, and Embase were searched based on keywords to identify eligible studies before February 2018. Only RCTs were eligible. We analyzed the main outcomes using the relative risk (RR) or mean difference (MD) along with 95% confidence interval (95% CI). RESULTS: In this meta-analysis, we analyzed a total of 24 studies with 4592 patients in the laparoscopic surgery group and 3865 patients in the open surgery group. The results indicated that compared with the open surgery, laparoscopic surgery significantly decreased estimated blood loss (SMD: -1.14, 95%CI: -1.70 to -0.57), hospital stay (SMD: -1.12, 95%CI: -1.76 to -0.47), postoperative mortality (RR: 0.60, 95%CI: 0.41-0.86) and postoperative complication (RR: 0.83, 95%CI: 0.72-0.95). However, the operative time (WMD: 40.46, 95%CI: 35.94-44.9) was statistically higher in the laparoscopic surgery group than the open surgery group, and there was no significant difference in the incidence of DVT between the 2 groups (RR: 0.96, 95%CI: 0.46-2.02). CONCLUSION: Laparoscopic surgery is superior to open surgery for patients with colorectal cancer. But the 2 surgeries showed no significant difference in the incidence of DVT.

The Efficacy and Safety of AngioJet Rheolytic Thrombectomy in the Treatment of Subacute Deep Venous Thrombosis in Lower Extremity.

BACKGROUND: The aim of this study is to examine the efficacy and safety of AngioJet rheolytic thrombectomy for the treatment of subacute deep venous thrombosis (DVT) in lower limbs. METHODS: A retrospective study was performed on 90 patients with subacute DVT (15-90 days) in lower limbs in our center from November 2015 to December 2016. In total, 27 patients with subacute DVT in lower limbs treated with AngioJet rheolytic thrombectomy were included in the study, including 17 men and 10 women. The onset time of thrombosis was between 15 and 75 days. Five patients were diagnosed bilaterally; 5 patients were diagnosed in the right lower limb; and 17 patients were affected by thrombosis in left lower limb. All the 27 cases received AngioJet rheolytic thrombectomy. RESULTS: After AngioJet thrombectomy, 17 cases were improved to grade II (50-99%), and 10 cases were grade I (<50%). Nineteen cases were treated with subsequent catheter-directed thrombolysis (CDT), and the average time of thrombolysis was 3.2 days, with an average urokinase administration dose of 7.32 million units. Among the 27 cases, 21 of them received iliac venous balloon dilation, with 10 of them being implanted with the iliac vein stent; 12 stents were implanted in total. Finally, the angiography suggested that 25 cases (92.6%) obtained a recanalization rate higher than grade II, and no serious complications occurred during the perioperative period. All patients were followed up regularly for 3 to 15 months, and 2 patients died from malignant tumor during the follow-up period. Twenty-three cases were followed up for more than 6 months; 17 cases finished 12-month follow-up. The primary patency rate at 6 and 12 months was 96.3% and 88.9%, respectively. The Villalta score of postoperative postthrombosis syndrome symptom at 6 and 12 months was 3.3 ± 2.8 and 3.5 ± 2.8, respectively. CONCLUSIONS: It is safe and feasible to use the AngioJet rheolytic thrombectomy in the treatment of subacute DVT in lower limbs. In patients without high risk of bleeding, combination of AngioJet thrombectomy and CDT is an effective treatment to reduce the thrombus volume.

LncRNA ANRIL promotes angiogenesis and thrombosis by modulating microRNA-99a and microRNA-449a in the autophagy pathway.

The objective of the present study was to investigate the mechanism whereby long-chain non-coding RNA (LncRNA) antisense non-coding RNA (ANRIL) in the INK4 locus promotes angiogenesis and thrombosis by the miR-99a and miR-449a interventional autophagy pathway. The expression of LncRNA ANRIL, autophagy-related gene beclin1, and miR-99a and miR-449a in human umbilical vein endothelial cells (HUVECs) was determined by qRT-PCR. Thrombomodulin expression was examined by Western blotting assays. The levels of autophagy-related factors were determined by ELISA. CCK-8 assays were used to assess cell viabilities. Apoptosis was detected by flow cytometry via annexin V-FITC/propidium iodide double labeling and TUNEL assays. The interaction between ANRIL, miR-99a and miR-449a was studied using luciferase reporter assays. The role of ANRIL in autophagy was assessed in rats. Our data revealed that ANRIL and beclin-1 were highly expressed, while miR-99a and miR-449a were down-regulated in HUVECs serum of the autophagy model. Luciferase reporter assays, in vitro rescue assays, and Matrigel assays demonstrated that ANRIL increased beclin-1 expression via miR-99a and miR-449a sponges to upregulate thrombomodulin and promote angiogenesis. In addition, in vivo experiments confirmed that knockdown of ANRIL reduced thrombosis in rats. In conclusion, ANRIL promotes angiogenesis and thrombosis by upregulating the expression of miR-99a and miR-449a during autophagy.

Endovascular Repair of Complex Aortoiliac Aneurysm with the Sandwich Technique in Sixteen Patients.

BACKGROUND: This study aimed to evaluate the safety and efficiency of the sandwich technique in endovascular repair of complex aortoiliac aneurysm. METHODS: Sixteen patients (mean age 69.6 years, ranging from 58 to 78 years) with complex aortoiliac aneurysm were studied retrospectively from October 2013 to September 2017 in two vascular centers of teaching hospitals. Computed tomography angiography (CTA) was performed to make individual therapy. They were all performed endovascular repair with sandwich technique, including one with the sandwich, chimney, and fenestrated techniques during the same procedure. All patients were followed up at 1 month, 3 months, 6 months, 12 months, and yearly thereafter with X-ray, ultrasound, and/or CTA. RESULTS: The initial technical success was 81.25%, and the assisted technical success was 100%. At final angiography, little flow of a type I and a type III endoleak was found in two patients with observation. Two type II endoleaks were also detected. During the perioperative period, two patients suffered myocardial infarction. One pulmonary infection and one urinary infection happened. No death or cerebrovascular events occurred. During the follow-up (mean 18 months, ranging from 2 to 45 months), three stent occlusions were detected. One case got reintervened for his external iliac artery stent thrombosis in the first month postoperatively. The other two were under observation. A readmission happened to one man for his right brachial artery pseudoaneurysm in the third month postoperatively. One patient died of nonaneurysmal related reason in the eighth month. No aneurysmal related death, rupture, or new endoleak was found. No paralysis, claudication, or bowel ischemia was complained of. The primary patency of the preserved branches were 94.7%, 92.0%, 92.0%, 92.0%, 92.0% separately in first, sixth, 12th, 24th, and 36th month. CONCLUSIONS: For patients who are not candidates for open surgery or conventional endovascular repair with complex aortoiliac aneurysm, the sandwich technique is a feasible alternative to management.

Deubiquitylase USP9X maintains centriolar satellite integrity by stabilizing pericentriolar material 1 protein.

Centriolar satellites are small cytoplasmic granules that play important roles in regulating the formation of centrosomes and primary cilia. Ubiquitylation of satellite proteins, including the core satellite scaffold protein pericentriolar material 1 (PCM1), regulates centriolar satellite integrity. Currently, deubiquitylases that control centriolar satellite integrity have not been identified. In this study, we find that the deubiquitylase USP9X binds PCM1, and antagonizes PCM1 ubiquitylation to protect it from proteasomal degradation. Knockdown of USP9X in human cell lines reduces PCM1 protein levels, disrupts centriolar satellite particles and causes localization of satellite proteins, such as CEP290, to centrosomes. Interestingly, knockdown of mindbomb 1 (MIB1), a ubiquitin ligase that promotes PCM1 ubiquitylation and degradation, in USP9X-depleted cells largely restores PCM1 protein levels and corrects defects caused by the loss of USP9X. Overall, our study reveals that USP9X is a constituent of centriolar satellites and functions to maintain centriolar satellite integrity by stabilizing PCM1.

Orthotopic renal autotransplantation for young-onset and medical treatment-requiring complex renovascular hypertension.

OBJECTIVE: In this article, we aim to prove the safety and effectiveness of orthotopic renal autotransplantation using ex vivo repair for the treatment of complex renovascular hypertension (RVH). METHODS: We retrospectively reviewed five consecutive patients (three women, two men) with young-onset RVH from January 2009 to August 2014. Orthotopic renal autotransplantation using ex vivo repair was performed and perioperative data were collected for statistical analysis. RESULTS: The median age at diagnosis was 20 years (range, 11 to 27 years). Technique success was achieved in all the patients with no in-hospital or late deaths. During a median follow-up of 3.4 years (range, 1.5 to 6 years), the postoperative blood pressure was decreased compared with preoperative level (204 ± 8/133 ± 8 mm Hg vs 129 ± 3/78 ± 5 mm Hg; p < 0.0001). The postoperative anti-hypertensive medications number was reduced (3.4 ± 0.4 vs 0.2 ± 0.2; p < 0.0001). Early and late renal functions were both well preserved as measured by no changes in serum creatinine level ( p > 0.05). The primary patent rate was 100% (5/5) at one-year follow-up. CONCLUSION: In our small series, orthotopic renal autotransplantation using ex vivo repair was safe and effective for the resolution of complex young-onset RVH.

[Interval-spaced Sessions of Partial Splenic Artery Embolization in Juvenile Patients with Hypersplenism].

Objective To determine whether interval-spaced sessions of partial splenic artery embolization(PSE) is a safe and effective alternative treatment for hypersplenism in juvenile patients. Methods Eight patients(3 males and 5 females) were included in this retrospective study.All patients were diagnosed as hypersplenism and underwent PSE in 2-3 sessions separated by 1-2 month intervals.Immediate,short,and long term follow-up were done.The effectiveness of the treatment was evaluated.Results No major postoperative complication was noted.No patient developed septic shock,splenic abscess,or spleen rupture.Postoperative pain and fever were common and manageable;only two patients developed loculated pleural effusions,which were well alleviated after conservative treatment.All patients showed significant increase in thrombocytes and white blood cells count after the first session of embolization.The cell counts became remarkable after the last session and remained at normal levels during the follow-up period.Conclusions PSE using 2-3 interval-spaced sessions can effectively decrease spleen size and reverse hypersplenism in juvenile patients.Also,it may reduce the postoperative complications commonly seen in traditional PSE.

Effect of Adequate Anticoagulantion Therapy on the Outcome of Spontaneous Isolated Dissection of Superior Mesenteric Artery.

Objective To investigate the optimal treatment strategy of spontaneous isolated dissection of superior mesenteric artery (SIDSMA) and the effect of anticoagulation therapy on the prognosis of SIDSMA. Methods The clinical data of 29 patients presented with acute or subacute mesenteric ischemia (a history of less than 14 days) due to SIDSMA admitted to the Department of Vascular Surgery of Peking Union Medical College Hospital from January 1st 2003 to December 31th 2016 were retrospectively analyzed. Results In this study,28 cases were male and the remaining one was female,with an average age of (49.1±7.6) years. The emergency endovascular treatment were performed on 4 cases with severe mesenteric intestinal ischemia,and the symptoms were relieved postoperatively. The remaining 25 cases were treated with conservative treatment. Among 13 cases who were received adequate anticoagulantion therapy,symptoms were relieved or disappeared in 9 cases (69.2%),whereas conservative treatment was ineffective in 4 cases (30.8%),for whom surgical intervention were performed. Among 12 cases who received conservative treatment without sufficient anticoagulation,the abdominal pain was relieved in only 2 cases (16.7%) and the remaining 10 cases (83.3%) were converted to surgical intervention. The success rate of conservative treatment for patients with adequate anticoagulant therapy was significantly higher than that of patients who had not received adequate anticoagulant therapy (P=0.015). Conclusions Adequate anticoagulation therapy has good therapeutic effect in most SIDSMA cases with acute or subacute mesenteric ischemia. For patients with severe mesenteric ischemia or those fail to respond to initial conservative treatment,endovascular treatment may be a more reasonable option.

Human Papillomavirus 16 E7 Stabilizes APOBEC3A Protein by Inhibiting Cullin 2-Dependent Protein Degradation.

APOBEC3 (A3) mutation signatures have been observed in a variety of human cancer genomes, including those of cervical and head and neck cancers caused by human papillomavirus (HPV) infection. However, the driving forces that promote off-target A3 activity remain mostly unclear. Here, we report a mechanism for the dramatic increase of A3A protein levels in HPV-positive keratinocytes. We show that expression of the viral protein E7 from high-risk HPVs, but not E7 from low-risk HPVs, significantly prolongs the cellular half-life of A3A protein in human keratinocytes and HPV-positive cancer cell lines. We have mapped several residues within the cullin 2 (CUL2) binding motif of HPV16 E7 as being important for mediating A3A protein stabilization. Furthermore, we provide direct evidence that both A3A and HPV16 E7 interact with CUL2, suggesting that the E7-CUL2 complex formed during HPV infection may regulate A3A protein levels in the cell. Using an in vitro cytidine deaminase assay, we show that E7-stabilized A3A remains catalytically active. Taken together, our findings suggest that the HPV oncoprotein E7 dysregulates endogenous A3A protein levels and thus provides novel mechanistic insight into cellular triggers of A3 mutations in HPV-positive cancers.IMPORTANCE Human papillomavirus (HPV) is causally associated with over 5% of all human malignancies. Several recent studies have shown that a subset of cancers, including HPV-positive head and neck and cervical cancers, have distinct mutational signatures potentially caused by members of the APOBEC3 cytidine deaminase family. However, the mechanism that induces APOBEC3 activity in cancer cells is poorly understood. Here, we report that the HPV oncoprotein E7 stabilizes the APOBEC3A (A3A) protein in human keratinocytes by inhibiting ubiquitin-dependent protein degradation in a cullin-dependent manner. Interestingly, the HPV E7-stabilized A3A protein maintains its deaminase activity. These findings provide a new insight into cancer mutagenesis enhanced by virus-induced A3A protein stabilization.