Ceftazidime-avibactam: Combination therapy versus monotherapy in the challenge of pneumonia caused by carbapenem-resistant Klebsiella pneumoniae.

This research focused on evaluating the clinical results of patients suffering from pneumonia caused by carbapenem-resistant Klebsiella pneumoniae (CRKP), who received treatment with either ceftazidime-avibactam (CZA) alone or in combination with other antibiotics. From January 2020 to December 2023, we retrospectively analyzed CRKP-related pneumonia patients treated in two Chinese tertiary hospitals. Mortality was measured at 14 and 30 days as the primary outcome. Secondary outcomes included the 14-day microbiological cure rate and the 14-day clinical cure rate. Factors contributing to clinical failure were evaluated via both univariate analysis and multivariate logistic regression. To account for confounding factors, propensity score matching (PSM) was utilized. Among the 195 patients with CRKP infections, 103 (52.8 %) received CZA combination therapy, and 92 (47.2 %) patients received CZA monotherapy. The combination therapy group exhibited superior clinical and microbiological cure rates compared to the monotherapy group, with a 14-day clinical cure rate of 60.1 % vs. 45.7 % (P = 0.042) and a 14-day microbiological cure rate of 72.8 % vs. 58.6 % (P = 0.038), respectively. Combination therapy reduced mortality rates at 14 days (7.8 % vs. 17.4 %, P = 0.041), but not at 30 days (14.6 % vs. 25.0 %, P = 0.066). Even after using PSM, the group treated with the CZA combination continued to had a lower mortality rate at 14 days (5.9 % vs. 17.6 %, P = 0.039). The 14-day clinical cure rate for the combination therapy group was 63.2 %, and the 14-day microbial cure rate was 77.9 %. Both of these statistics were notably greater than those observed in the monotherapy group. Furthermore, the multivariate logistic regression model indicated a significant link between combination therapy and a decrease in clinical failure. Carbapenems were noted to be the most effective class of concomitant agents. Our findings indicate that patients with pneumonia due to CRKP benefit from combination treatment of CZA rather than monotherapy; administering carbapenem in combination with CZA in the early stages could provide considerable survival benefits.

The Regulatory Effect of Vitamin D on Pancreatic Beta Cell Secretion in Patients with Type 2 Diabetes.

Increasing evidence suggests that vitamin D is one of the causes of accelerated development of Insulin Resistance (IR) and islet cell secret dysfunction. Numerous studies have shown that vitamin D can reduce inflammation, activate the transcription of the insulin receptors and related genes, and increase insulin-mediated glucose transport, thereby reducing IR. This article reviews the molecular mechanisms related to vitamin D deficiency and pancreatic ß-cell dysfunction in patients with Type 2 Diabetes (T2D).

Recombinant Human Hepatocyte Growth Factor Plasmids for Treating Patients with Chronic Limb Threatening Ischaemia: A Systematic Review and Meta-analysis.

OBJECTIVE: Recombinant human hepatocyte growth factor (HGF) plasmids are novel alternatives to salvage limbs in patients with chronic limb threatening ischaemia (CLTI). A systematic review and meta-analysis of data was conducted to assess the therapeutic efficacy of HGF plasmids in patients with CLTI. DATA SOURCES: Randomised controlled studies evaluating HGF plasmid efficacy in patients with CLTI were identified using MEDLINE, Embase, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov databases. REVIEW METHODS: Meta-analyses of the reported relative risk (RR) or mean difference (MD) were conducted. Subgroup analyses were performed to determine the efficacy of HGF plasmids in cohorts excluding Buerger's disease. Certainty of evidence for each outcome was assessed. RESULTS: Seven studies (n = 655 participants) were included. Based on low certainty evidence, patients treated with HGF had a significantly higher complete ulcer healing rate (RR 1.99, 95% confidence interval [CI] 1.30 - 3.04; p = .002) than patients treated with placebo. HGF treatment was associated with reduced visual analogue scale (VAS) scores of pain severity (MD -1.56, 95% CI -2.12 - -1.00; p < .001) vs. placebo in patients with CLTI assessed at three month follow up (low certainty evidence); no significant differences were observed in major amputation (RR 0.91, 95% CI 0.48 - 1.73; p = .77) (low certainty evidence) or all cause mortality rate (RR 0.93, 95% CI 0.38 - 2.27; p = .87) (low certainty evidence) between patients treated with HGF and placebo. Low certainty evidence suggested no significant differences in change in ankle brachial index at six months (MD 0.00, 95% CI -0.09 - 0.09; p = 1.0) between patients treated with HGF and placebo. The complete ulcer healing rate and improved three month VAS scores of pain severity benefits persisted in subgroup analyses (low certainty evidence). CONCLUSION: Low certainty evidence suggested that HGF treatment is associated with an increased complete ulcer healing rate and reduced ischaemic pain in patients with CLTI.

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.

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.

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.

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.

[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.

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.

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.

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.

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.

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.