A circuitous route for in vitro multi-enzyme cascade production of cytidine triphosphate to overcome the thermodynamic bottleneck.

Cytidine triphosphate (CTP), as a substance involved in the metabolism of phospholipids, proteins and nucleic acids, has precise drug effects and is a direct precursor for the synthesis of drugs such as citicoline. In this study, we established an in vitro six-enzyme cascade system to generate CTP. To avoid thermodynamic bottlenecks, we employed a circuitous and two-stage reaction strategy. Using cytidine as the key substrate, the final product CTP is obtained via the deamination and uridine phosphorylation pathways, relying on the irreversible reaction of cytidine triphosphate synthase to catalyze the amination of uridine triphosphate. Several extremophilic microbial-derived deaminases were screened and characterized, and a suitable cytidine deaminase was selected to match the first-stage reaction conditions. In addition, directed evolution modification of the rate-limiting enzyme CTP synthetase in the pathway yielded a variant that successfully relieved the product feedback inhibition, along with a 1.7-fold increase in activity over the wild type. After optimizing the reaction conditions, we finally carried out the catalytic reaction at an initial cytidine concentration of 20 mM, and the yield of CTP exceeded 82% within 10.0 h.

Engineering of the Lrp/AsnC-type transcriptional regulator DecR as a genetically encoded biosensor for multilevel optimization of L-cysteine biosynthesis pathway in Escherichia coli.

L-cysteine is an important sulfur-containing amino acid being difficult to produce by microbial fermentation. Due to the lack of high-throughput screening methods, existing genetically engineered bacteria have been developed by simply optimizing the expression of L-cysteine-related genes one by one. To overcome this limitation, in this study, a biosensor-based approach for multilevel biosynthetic pathway optimization of L-cysteine from the DecR regulator variant of Escherichia coli was applied. Through protein engineering, we obtained the DecRN29Y/C81E/M90Q/M99E variant-based biosensor with improved specificity and an 8.71-fold increase in dynamic range. Using the developed biosensor, we performed high-throughput screening of the constructed promoter and RBS combination library, and successfully obtained the optimized strain, which resulted in a 6.29-fold increase in L-cysteine production. Molecular dynamics (MD) simulations and electrophoretic mobility shift analysis (EMSA) showed that the N29Y/C81E/M90Q/M99E variant had enhanced induction activity. This enhancement may be due to the increased binding of the variant to DNA in the presence of L-cysteine, which enhances transcriptional activation. Overall, our biosensor-based strategy provides a promising approach for optimizing biosynthetic pathways at multiple levels. The successful implementation of this strategy demonstrates its potential for screening improved recombinant strains.

Design of Double Conductive Layer and Grid-Assistant Face-to-Face Structure for Wide Linear Range, High Sensitivity Flexible Pressure Sensors.

Recently, flexible pressure sensors have drawn great attention because of their potential application in human-machine interfaces, healthcare monitoring, electronic skin, etc. Although many sensors with good performance have been reported, researchers mostly focused on surface morphology regulation, and the effect of the resistance characteristics on the performance of the sensor was still rarely systematically investigated. In this paper, a strategy for modulating electron transport is proposed to adjust the linear range and sensitivity of the sensor. In the modulating process, we constructed a double conductive layer (DCL) and grid-assistant face-to-face structure and obtained the sensor with a wide linear range of 0-700 kPa and a high sensitivity of 57.5 kPa-1, which is one of the best results for piezoresistive sensors. In contrast, the sensor with a single conductive layer (SCL) and simple face-to-face structure exhibited a moderate linear range (7 kPa) and sensitivity (2.8 kPa-1). Benefiting from the great performance, the modulated sensor allows for clear pulse wave detection and good recognition of gait signals, which indicates the great application potential in human daily life.

Gaining insight into the effect of laccase expression on humic substance formation during lignocellulosic biomass composting.

The aim is to enhance lignin humification by promoting laccase activities which can promote lignin depolymerization and reaggregation during composting. 1-Hydroxybenzotriazole (HBT) is employed to conduct laccase mediator system (LMS), application of oxidized graphene (GO) in combination to strengthen LMS. Compared with control, the addition of GO, HBT, and GH (GO coupled with HBT) significantly improved laccase expression and activities (P < 0.05), with lignin humification efficiency also increased by 68.6 %, 36.7 %, and 107.8 %. GH treatment induces microbial expression of laccase by increasing the abundance and synergy of core microbes. The unsupervised learning model, vector autoregressive model and Mantel test function were combined to elucidate the mechanism of action of exogenous materials. The results showed that GO stabilized the composting environment on the one hand, and acted as a support vector to stabilize the LMS and promote the function of laccase on the other. In GH treatment, degradation of macromolecules and humification of small molecules were promoted simultaneously by activating the dual function of laccase. Additionally, it also reveals the GH enhances the humification of lignocellulosic compost by converting phenolic pollutants into aggregates. These findings provide a new way to enhance the dual function of laccase and promote lignin humification during composting. It could effectively achieve the resource utilization of organic solid waste and reduce composting pollution.

Ultrawide linear range, high sensitivity, and large-area pressure sensor arrays enabled by pneumatic spraying broccoli-like microstructures.

Large-area pressure sensor arrays with a wide linear response range and high sensitivity are beneficial to map the inhomogeneous interface pressure, which is significant in practical applications. Here, we demonstrate a pneumatic spraying method to prepare large-area microstructure films (PSMF) for high performance pressure sensor arrays. The sprayed surface morphology is designable by controlling the spraying parameters. It is worth noting that the constructed "broccoli" like morphology with a swollen top and shrunken bottom inspired a new mechanism to enlarge the linear response range by decreasing the series resistance with pressure increasing. At the same time, the pneumatic sprayed "broccoli" has a rough surface due to droplet stacking, which reduces the initial current effectively. Hence, the sensor achieves a 10 000 kPa ultrawide linear response range with a high sensitivity (98.71 kPa-1), and low detection (5 Pa). The prepared sensor has a small static response error (4.4%) and 5000 cycle full-range dynamic response durability. Finally, the constructed sensor arrays can distinguish the pressure distribution in different ranges clearly, which indicates a great potential in health care, motion detection, and the tire industry.

Molecular mechanisms of circular RNA in breast cancer: a narrative review.

Background and Objective: Breast cancer is presently the most prevalent cancer and the leading cause of cancer-related deaths in women worldwide. Circular RNA (circRNA) is a class of closed circRNAs lacking a 5'-end cap structure and a 3'-end polyA tail, which is highly stable and widely involved in a variety of pathophysiological processes such as cell proliferation, differentiation, and apoptosis. In recent years, accumulating studies have shown that circRNAs play an important role in the development and prognosis of breast cancer, but there are fewer literature reviews on their intrinsic molecular mechanisms which is the aim of this study. Methods: This review synthesizes the findings of literature retrieved from searches of PubMed and Google Scholar databases, hand searches, and authoritative texts. Citations mainly originate from the past 3 years. The articles need to describe the role of circRNA in breast cancer; no language restrictions were imposed. Key Content and Findings: This review summarizes the latest relevant literature and systematically reviews the four main mechanisms of circRNA in breast cancer from the perspective of circRNA function. At the same time, we describe the formation mechanism, characterization, and biological functions of circRNAs. Conclusions: We reviewed the status of actual knowledge about circRNA biogenesis and functions and summarized novel findings regarding the molecular mechanism of circRNA in breast cancer. Meanwhile, this review explores the possibility of circRNAs for becoming new biodiagnostic indicators and therapeutic targets in breast cancer.

Comparison of survival benefit and safety between surgery following conversion therapy versus surgery alone in patients with surgically resectable hepatocellular carcinoma at CNLC IIb/IIIa stage: a propensity score matching study.

OBJECTIVE: The objective of this study is to evaluate and compare the survival benefit and safety of surgery following conversion therapy versus surgery alone in patients diagnosed with surgically resectable hepatocellular carcinoma (HCC) at China Liver Cancer Staging (CNLC) IIb/IIIa stage. METHODS: A total of 95 patients diagnosed with surgically resectable CNLC IIb/IIIa HCC were retrospectively enrolled in our study from November 2018 to December 2022. Among them, 30 patients underwent conversion therapy followed by hepatectomy, while the remaining 65 received surgery alone. The primary endpoint was recurrence-free survival (RFS). Propensity score matching (PSM) was employed to minimize bias in the retrospective analysis. RESULTS: Compared to the surgery alone group, the conversion therapy group demonstrated a significantly prolonged median RFS (17.1 vs. 7.0 months; P=0.014), a reduced incidence of microvascular invasion (MVI, 23.3% vs. 81.5%; P<0.001), and a comparable rate of achieving Textbook Outcome in Liver Surgery (TOLS, 83.3% vs. 76.9%; P=0.476). Multivariate analysis indicated that conversion therapy was independently associated with improved RFS after hepatectomy (HR=0.511, P=0.027). The same conclusions were obtained after PSM. CONCLUSIONS: The findings of our study offer preliminary evidence that preoperative conversion therapy significantly prolongs RFS in patients with surgically resectable HCC at CNLC IIb/IIIa stage. Furthermore, combining conversion therapy and hepatectomy represents a relatively safe treatment strategy.

Weight reduction and the risk of gallbladder and biliary disease: A systematic review and meta-analysis of randomized clinical trials.

In this meta-analysis, we aim to evaluate the risk of gallbladder and biliary disease of weight management strategies and investigate the association between weight reduction and risk of gallbladder or biliary disease. Randomized controlled trials (RCTs) with a duration of at least 12 weeks that compare antiobesity medications (AOMs) with placebo or bariatric surgery with less intensive weight management strategy were concluded. Weight management strategy was associated with a significant increased risk of gallbladder or biliary disease (OR 1.361, 95% CI 1.147 to 1.614, P < 0.001, I2 = 3.5%), cholelithiasis, cholecystitis, and cholecystectomy compared with placebo or controls. The increased risk of gallbladder or biliary disease was observed both in pharmacotherapies subgroup and bariatric surgery subgroup. With regards of specific pharmacotherapies, an increased risk of gallbladder or biliary disease was observed in trials with glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatments. In addition, trials with indication of obesity and overweight treatment and trials with higher doses showed significant higher risk of gallbladder or biliary disease compared with placebo or controls. In conclusion, weight management strategy was associated with an increased risk of gallbladder or biliary disease when compared with placebo or control groups.

Engineering the thermal stability of a polyphosphate kinase by ancestral sequence reconstruction to expand the temperature boundary for an industrially applicable ATP regeneration system.

ATP-dependent energy-consuming enzymatic reactions are widely used in cell-free biocatalysis. However, the direct addition of large amounts of expensive ATP can greatly increase cost, and enzymatic production is often difficult to achieve as a result. Although a polyphosphate kinase (PPK)-polyphosphate-based ATP regeneration system has the potential to solve this challenge, the generally poor thermal stability of PPKs limits the widespread use of this method. In this paper, we evaluated the thermal stability of a PPK from Sulfurovum lithotrophicum (SlPPK2). After directed evolution and computation-supported design, we found that SlPPK2 is very recalcitrant and cannot acquire beneficial mutations. Inspired by the usually outstanding stability of ancestral enzymes, we reconstructed the ancestral sequence of the PPK family and used it as a guide to construct three heat-stable variants of SlPPK2, of which the L35F/T144S variant has a half-life of more than 14 h at 60°C. Molecular dynamics simulations were performed on all enzymes to analyze the reasons for the increased thermal stability. The results showed that mutations at these two positions act synergistically from the interior and surface of the protein, leading to a more compact structure. Finally, the robustness of the L35F/T144S variant was verified in the synthesis of nucleotides at high temperature. In practice, the use of this high-temperature ATP regeneration system can effectively avoid byproduct accumulation. Our work extends the temperature boundary of ATP regeneration and has great potential for industrial applications.IMPORTANCEATP regeneration is an important basic applied study in the field of cell-free biocatalysis. Polyphosphate kinase (PPK) is an enzyme tool widely used for energy regeneration during enzymatic reactions. However, the thermal stability of the PPKs reported to date that can efficiently regenerate ATP is usually poor, which greatly limits their application. In this study, the thermal stability of a difficult-to-engineer PPK from Sulfurovum lithotrophicum was improved, guided by an ancestral sequence reconstruction strategy. The optimal variant has a 4.5-fold longer half-life at 60°C than the wild-type enzyme, thus enabling the extension of the temperature boundary for ATP regeneration. The ability of this variant to regenerate ATP was well demonstrated during high-temperature enzymatic production of nucleotides.

Dapagliflozin treatment and cardiovascular outcome in RBP4/TTRVal30Met (transthyretin cardiac amyloidosis) mice.

AIMS: Whether sodium-glucose co-transporter 2 inhibitors are effective for heart failure caused by ATTR-CA (transthyretin cardiac amyloidosis) remains uncertain. The aim of this study is to investigate the cardiovascular prognosis in ATTR-CA mice model with dapagliflozin treatment. METHODS AND RESULTS: Humanized RBP4/TTRVal50Met and RBP4/TTR mice models were constructed with clustered regularly interspaced short palindromic repeats and associated Cas9 endonuclease (CRISPR-Cas9) techniques and multiple generations breeding. A total of 6 RBP4/TTR mice received placebo treatment, when 12 RBP4/TTRVal50Met received dapagliflozin (1 mg/kg/day, 6 mice) and placebo (6 mice) treatment. Fasting glucose, intraperitoneal glucose tolerance test, and plasma brain natriuretic peptide (BNP) concentration were measured at Day 0, Week 2, and Week 4. BNP, transforming growth factor-beta (TGF-ß), collagen type I alpha 1 (COL1A1) protein levels, and Cola1, TGFß1, TNFα, IL-1ß, BNP relative quantities in cardiac, along with cardiac pathology examination including right ventricular collagen percentage, ventricular septum thickness, left ventricular wall thickness, and left ventricular internal diameter were measured at Week 4 after treatment procedure. All 18 mice completed the experiment. The baseline characteristics were balanced among three treatment groups. In placebo-treated mice, the cardiac BNP relative quantity was significantly higher in RBP4/TTRVal50Met mice than RBP4/TTR mice (RBP4[KI/KI], TTR [KI/KI]: 0.72 ± 0.46, RBP4[KI/KI], TTRVal50Met [KI/KI]: 1.44 ± 0.60, P = 0.043), indicating more significant heart failure progression in ATTR-CA mice than normal mice. In ATTR-CA mice, the cardiovascular prognosis measurements including heart failure (plasma BNP concentration and relative quantities of BNP), cardiac inflammation (relative quantities of Cola1, TGFß1, TNFα, and IL-1ß), and pathological changes (right ventricular collagen percentage, ventricular septum thickness, left ventricular wall thickness, and left ventricular internal diameter) were statistically comparable between those under dapagliflozin and placebo treatment. CONCLUSIONS: Dapagliflozin did not improve cardiovascular prognosis including the progression of heart failure, cardiac inflammation, and pathological changes in ATTR-CA mice compared with placebo. The results of this study were not in support of dapagliflozin's therapeutic effects for ATTR-CA. More pre-clinical and clinical researches to validate these findings and demonstrate the underlying mechanisms are still required.

Upper tract urothelial carcinoma accompanied by hyperthermia: A case report.

Upper tract urothelial carcinoma (UTUC) is a relatively rare malignant neoplasm of the urinary system. Due to its highly aggressiveness, the tumor has already undergone invasive growth when most UTUC patients are diagnosed. In addition, the most common cause of fever in cancer patients is infection, and cancer patients with neoplastic fever are relatively rare. We reported a 58-year-old man with invasive high-grade UTUC accompanied by hyperthermia.

Tailoring linear and nonlinear plasmons of metal/MoS2/metal nanostructures.

We investigated the linear and nonlinear response of the localized surface plasmons (LSPs) and surface plasmon polaritons (SPPs) in metal and MoS2 nanostructures. The results show that the response of LSPs and SPPs has an important influence on the energy exchange. SPPs with unique non-radiative characteristics can be used as energy recovery tanks to reuse the radiated energy of LSPs and promote the production of hot carriers. The energy exchange through plasmon modes can promote the transfer of hot electrons in the Au grating, the MoS2 layer, and the metal film. The fundamental field induces the increase of the second harmonic wave by introducing the second-order nonlinear source. In addition, the evolution of the lifetime of linear and nonlinear plasmonic modes is also investigated to study the underlying mechanism of the micro process in the plasmonic-photonic interaction. The plasmonic energy exchanging configuration overcomes the challenge by utilizing hot carriers. It is instructive in terms of improving the linear and nonlinear performance of plasmonic opto-electronic devices.

Indirect comparison of efficacy and safety of chiglitazar and thiazolidinedione in patients with type 2 diabetes: A meta-analysis.

BACKGROUND: Chiglitazar is an emerging pan-agonist of all peroxisome proliferator activated receptors (PPAR)-α, δ and γ, and has therapeutic potential for type 2 diabetes (T2D). However, to date, no clinical studies or meta-analyses have compared the efficacy and safety of chiglitazar and traditional PPAR-γ agonist thiazolidinediones (TZDs). A meta-analysis concerning this topic is therefore required. AIM: To compare the efficacy and safety of chiglitazar and TZD in patients with T2D. METHODS: PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials, Reference Citation Analysis and Clinicaltrial.gov websites were searched from August 1994 to March 2022. Randomized controlled trials (RCTs) of chiglitazar or TZD vs placebo in patients with T2D were included. Indirect comparisons and sensitivity analyses were implemented to evaluate multiple efficacy and safety endpoints of interest. RESULTS: We included 93 RCTs that compared TZD with placebo and one that compared chiglitazar with placebo. For efficacy endpoints, the augmented dose of chig-litazar resulted in greater reductions in hemoglobin (Hb)A1c [weighted mean difference (WMD) = -0.15%, 95% confidence interval (CI): -0.27 to -0.04%], triglycerides (WMD = -0.17 mmol/L, 95%CI: -0.24 to -0.11 mmol/L) and alanine aminotransferase (WMD = -5.25 U/L, 95%CI: -8.50 to -1.99 U/L), and a greater increase in homeostasis model assessment-ß (HOMA-ß) (WMD = 17.75, 95%CI: 10.73-24.77) when compared with TZD treatment. For safety endpoints, the risks of hypoglycemia, edema, bone fractures, upper respiratory tract infection, urinary tract infection, and weight gain were all comparable between the augmented dose of chiglitazar and TZD. In patients with baseline HbA1c ≥ 8.5%, body mass index ≥ 30 kg/m2 or diabetes duration < 10 years, the HbA1c reduction and HOMA-ß increase were more conspicuous for the augmented dose of chiglitazar compared with TZD. CONCLUSION: Augmented dose of chiglitazar, a pan-activator of PPARs, may serve as an antidiabetic agent with preferable glycemic and lipid control, better ß-cell function preserving capacity, and does not increase the risk of safety concerns when compared with TZD.

Pushing Optical Virus Detection to a Single Particle through a High-Q Quasi-bound State in the Continuum in an All-dielectric Metasurface.

Bound states in the continuum (BICs) have emerged as a powerful platform for boosting light-matter interactions because they provide an alternative way of realizing optical resonances with ultrahigh quality factors, accompanied by extreme field confinement. In this work, we realized an optical biosensor by harnessing a quasi-BIC (qBIC) supported by an all-dielectric metasurface with broken symmetry, whose unit cell is composed of a silicon cuboid with two asymmetric air holes. Thanks to the excellent field confinement within the air gap of a metasurface enabled by such a high-Q qBIC, the figure of merit (FOM) of the biosensor is up to 2136.35 RIU-1. Futhermore, we demonstrated that such a high-Q metasurface can push the detection limit to a few virus particles. Our results may find exciting applications in extreme biochemical sensing like COVID-19 with ultralow concentrations.

Safety and Efficacy of Partial Omentectomy in Laparoscopic Distal Gastrectomy for pT3-T4a Stage Gastric Cancer.

Purpose: Partial omentectomy (PO) has been gradually applied in laparoscopic gastrectomy for gastric cancer (GC); however, its efficacy remains unclear. The purpose of this study was to assess the safety and efficacy of PO in laparoscopic distal gastrectomy for pT3-T4a stage GC. Patients and Methods: From June 2019 to May 2021, 108 patients with pT3 or pT4a stage GC who underwent laparoscopic distal gastrectomy were retrospectively included and divided into the PO (n=58) and total omentectomy (TO, n=50) groups. The surgical outcomes, recurrence patterns and postoperative 2-year overall survival (OS) rates were compared between the PO and TO groups. Results: The PO group showed a shorter operation time than the TO group (183.9±21.6 vs 197.6±22.7 min, p=0.002). Less intraoperative blood loss (155.3±113.0 vs 178.8±154.4 mL, p=0.336) and intraoperative complications (5.1% vs 12.0%, p=0.298) were also observed in the PO group than in the TO group, but the difference was not significant. The numbers of retrieved lymph nodes (LNs) and metastatic LNs, postoperative hospital stays and postoperative complications in the two groups were comparable (p>0.05). Moreover, the postoperative overall recurrence rates (25.9% vs 26.0%, p=0.987) and the 2-year OS rates (63.8% vs 65.4%, p=0.437) in the PO and TO groups were also comparable. TO was not an independent prognostic factor for GC patients (HR=0.806, p=0.443). Conclusion: In laparoscopic distal gastrectomy, PO could provide better surgical outcomes and comparable oncological outcomes compared to TO for patients with pT3-T4a stage GC, suggesting that PO may be an acceptable surgical procedure for these patients.

Synthesis of block copolymer with cis-1,4-polybutadiene and isotactic-rich polystyrene using α-diimine nickel catalysts.

A series of styrene-butadiene di-block copolymers with high cis-1,4 unit content (greater than 92%) polybutadiene (PB) and isotactic-rich polystyrene (PS) (mmmm > 65%) was synthesized using α-diimine nickel catalysts (Ni-diimine). Four different Ni-diimine catalysts were synthesized via a complexing reaction between nickel (II) naphthenate and laboratory-made α-diimine ligands L1, L2, L3 and L4, which have different steric volume structures. The results indicate that the Ni-diimine catalyst prepared using the L4 ligand with a higher steric volume can effectively initiate the block polymerization of butadiene and styrene, and the resulting polymer has distinguished cis-1,4 structure unit PB and high isotactic-selective PS block. Differential scanning calorimetry and electrochemical performance tests show that these block copolymers with cis-1,4-regulated and isotactic-selective polymerization have advantages in terms of high-temperature and low-temperature resistance as well as corrosion resistance. Therefore, these copolymers are expected to be widely used in some harsh industrial environments.

Decorated bacteria-cellulose ultrasonic metasurface.

Cellulose, as a component of green plants, becomes attractive for fabricating biocompatible flexible functional devices but is plagued by hydrophilic properties, which make it easily break down in water by poor mechanical stability. Here we report a class of SiO2-nanoparticle-decorated bacteria-cellulose meta-skin with superior stability in water, excellent machining property, ultrathin thickness, and active bacteria-repairing capacity. We further develop functional ultrasonic metasurfaces based on meta-skin paper-cutting that can generate intricate patterns of ~10 µm precision. Benefited from the perfect ultrasound insulation of surface Cassie-Baxter states, we utilize meta-skin paper-cutting to design and fabricate ultrathin (~20 µm) and super-light (<20 mg) chip-scale devices, such as nonlocal holographic meta-lens and the 3D imaging meta-lens, realizing complicated acoustic holograms and high-resolution 3D ultrasound imaging in far fields. The decorated bacteria-cellulose ultrasonic metasurface opens the way for exploiting flexible and biologically degradable metamaterial devices with functionality customization and key applications in advanced biomedical engineering technologies.

Anti-inflammatory therapies were associated with reduced risk of myocardial infarction in patients with established cardiovascular disease or high cardiovascular risks: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: We aimed to evaluate the association between anti-inflammatory therapies and the incidence of cardiovascular events in patients with established cardiovascular disease (CVD) or high cardiovascular risks. METHODS: Literature retrieval was conducted in PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrial.gov website from the inception to December 2022. Randomized controlled trials comparing anti-inflammatory therapies with placebo in patients with established CVD or high cardiovascular risks were included. The results of the meta-analysis were computed as the risk ratio (RR) with 95% confidence interval (CI). RESULTS: Compared with placebo, anti-inflammatory therapies were associated with decreased incidence of myocardial infarction (MI) (RR = 0.93, 95% CI, 0.88 to 0.98), which was mainly driven by therapies targeting central IL-6 signaling pathway (RR = 0.83, 95% CI, 0.74 to 0.93). IL-1 inhibitors treatment was associated with reduced risks of heart failure (RR = 0.38, 95% CI, 0.18 to 0.80) while lower incidence of stroke was observed in patients with colchicine treatment (RR = 0.47, 95% CI, 0.28 to 0.77). MI events were less frequent in patients over 65 years of age (RR = 0.90, 95% CI, 0.83 to 0.98) or with follow-up duration over 1 year (RR = 0.90, 95% CI, 0.85 to 0.96) when comparing anti-inflammatory therapies with placebo. CONCLUSIONS: Anti-inflammatory therapies, especially those targeting the central IL-6 signaling pathway, may serve as promising treating strategies to ameliorate the risk of MI. IL-1 inhibitor and colchicine were associated with decreased risks of heart failure and stroke, respectively. MI risk reduction by anti-inflammatory therapies seemed to be more prominent in older patients with long follow-up duration.

Safety and efficacy of left colic artery preservation in laparoscopic anterior resection for lower rectal cancer.

Background: To evaluate the safety and efficacy of left colic artery (LCA) preservation in laparoscopic anterior resection with D3 lymphadenectomy for lower rectal cancer. Methods: A total of 117 patients with lower rectal cancer who received laparoscopic anterior resection were retrospectively analyzed. Results: No differences were detected in terms of the numbers of harvested lymph nodes and metastatic lymph nodes, the intraoperative and postoperative complications or the postoperative recurrence and survival rates between the two groups (p > 0.05), but the LCA preservation group showed a lower anastomotic leakage rate than the LCA nonpreservation group (2/49 vs 12/68). Conclusion: LCA preservation may help reduce the incidence of anastomotic leakage without impairing surgical and oncological outcomes.

A large ectopic hepatocellular carcinoma with adrenal infiltration: a rare case report.

Ectopic hepatocellular carcinoma (EHCC) originates from the ectopic liver, which refers to a liver organ or tissue unrelated to surrounding tissues. EHCC is a rare disease that lacks specific clinical signs, and preoperative diagnosis is often difficult. In a 61-year-old male patient with positive hepatitis B virus antibody, abdominal contrast-enhanced computed tomography scan showed a large heterogenously enhancing mass both on arterial and portal venous phase imaging arising from the right adrenal gland. Similar enhancement features were seen on magnetic resonance imaging. Serum potassium, aldosterone, cortisol, and plasma metanephrines were normal. The tumor markers of serum alpha-fetoprotein and alpha-fetoprotein-L3% were increased to 23.69 ng/mL and 82.1%, respectively. Exploratory laparotomy was performed and operative findings showed that the retroperitoneal tumor was disconnected from the right kidney and the liver, but invaded the right adrenal gland. Immunohistochemical examination showed that Arginase-1 was positive expression, and the retroperitoneal tumor was finally diagnosed as EHCC. We report a rare EHCC with adrenal infiltration that is difficult to diagnose preoperatively and mimics a retroperitoneal tumor or adrenal tumor, and we present a review of the literature on EHCC case reports.