Optimal approach for ultrasound-guided transversus abdominis plane (TAP) blocks for abdominal surgeries: a protocol for systematic review and meta-analysis.

INTRODUCTION: Transversus abdominis plane (TAP) blocks are commonly used for postoperative analgesia after various abdominal surgeries. There are several different approaches for performing TAP blocks, mainly including posterior, lateral and subcostal approaches. An increasing number of randomised controlled trials (RCTs) have compared the analgesic effects of different TAP block approaches, but the results have not been consistent. This protocol aims to determine the optimal approach of ultrasound-guided TAP blocks for postoperative analgesia after abdominal surgery. METHODS AND ANALYSIS: Four databases, including Web of Science, PubMed, EMBASE and the Cochrane Library will be systematically searched to identify RCTs that compared the analgesic effects of different ultrasound-guided TAP block approaches. The search interval will range from the inception of the databases to 30 July 2024. The postoperative opioid consumption over 24 hours will be defined as the primary outcome. The secondary outcomes will include the analgesia duration, postoperative pain scores at rest and during movement at different timepoints and the incidence of adverse effects. All the statistical analyses will be conducted using RevMan V.5.4. The quality of evidence will be evaluated by the Grading of Recommendations Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: Ethical approval will not be needed. The results will be submitted to one peer-reviewed journal when completed. PROSPERO REGISTRATION NUMBER: CRD42024510141.

Hereditary hemochromatosis caused by a C282Y/H63D mutation in the HFE gene: A case report.

Hereditary hemochromatosis (HH) is a disease characterized by disordered iron metabolism. It often involves mutations of the HFE gene, which encodes the homeostatic iron regulator protein (HFE), as well as mutations affecting hepcidin antimicrobial peptide, hemojuvelin, or transferrin receptor 2. Historically, HH has been observed primarily in European and European diaspora populations, while classical HH is rare in Asian populations, including in China. In this article, we report a rare case of HH in a Chinese man that could be attributed to a heterozygous C282Y/H63D HFE mutation. Based on clinical examination, liver biopsy, and genetic testing results, the patient was diagnosed with HH. Clinical signs and symptoms and serum iron-related test results were recorded for a period of two years after the patient began treatment. Over this observation period, the patient was subjected to 25 phlebotomies (accounting for a total blood loss of 10.2 L). His serum ferritin levels decreased from 1550 µg/L to 454 µg/L, his serum iron concentration decreased from 40 µmol/L to 24.6 µmol/L, and his transferrin saturation decreased from 97.5% to 55.1%. Early diagnosis is essential for patients with HH to obtain good outcomes. Regular phlebotomy after diagnosis can improve HH symptoms and delay HH disease progression.

Excretory/secretory products from Trichinella spiralis adult worms ameliorate myocardial infarction by inducing M2 macrophage polarization in a mouse model.

BACKGROUND: Ischemia-induced inflammatory response is the main pathological mechanism of myocardial infarction (MI)-caused heart tissue injury. It has been known that helminths and worm-derived proteins are capable of modulating host immune response to suppress excessive inflammation as a survival strategy. Excretory/secretory products from Trichinella spiralis adult worms (Ts-AES) have been shown to ameliorate inflammation-related diseases. In this study, Ts-AES were used to treat mice with MI to determine its therapeutic effect on reducing MI-induced heart inflammation and the immunological mechanism involved in the treatment. METHODS: The MI model was established by the ligation of the left anterior descending coronary artery, followed by the treatment of Ts-AES by intraperitoneal injection. The therapeutic effect of Ts-AES on MI was evaluated by measuring the heart/body weight ratio, cardiac systolic and diastolic functions, histopathological change in affected heart tissue and observing the 28-day survival rate. The effect of Ts-AES on mouse macrophage polarization was determined by stimulating mouse bone marrow macrophages in vitro with Ts-AES, and the macrophage phenotype was determined by flow cytometry. The protective effect of Ts-AES-regulated macrophage polarization on hypoxic cardiomyocytes was determined by in vitro co-culturing Ts-AES-induced mouse bone marrow macrophages with hypoxic cardiomyocytes and cardiomyocyte apoptosis determined by flow cytometry. RESULTS: We observed that treatment with Ts-AES significantly improved cardiac function and ventricular remodeling, reduced pathological damage and mortality in mice with MI, associated with decreased pro-inflammatory cytokine levels, increased regulatory cytokine expression and promoted macrophage polarization from M1 to M2 type in MI mice. Ts-AES-induced M2 macrophage polarization also reduced apoptosis of hypoxic cardiomyocytes in vitro. CONCLUSIONS: Our results demonstrate that Ts-AES ameliorates MI in mice by promoting the polarization of macrophages toward the M2 type. Ts-AES is a potential pharmaceutical agent for the treatment of MI and other inflammation-related diseases.

Factors that predict compliance in a virtual cardiac rehabilitation program.

BACKGROUND: Despite the well-established benefits of cardiac rehabilitation (CR) for patients with cardiovascular disease (CVD), participation in CR remain low. Virtual CR programs present a unique opportunity to promote utilization. To date, few virtual CR cohorts have been analyzed for compliance. This study aims to determine factors that predict compliance within a large virtual CR program in the United States. METHODS: We analyzed 1409 patients enrolled in the Kaiser Permanente Mid-Atlantic States Virtual CR program that consists of 12 CR sessions via telephone. Demographic characteristics, as well as body weight, blood pressure, HbA1c level, and smoking status were collected at admission. Patients were further classified by CVD diagnosis codes. Compliance was defined as at least 75% (9/12 sessions) attendance. Data was analyzed using simple and multiple regression models with significance defined as P < 0.05. RESULTS: Age was the single strongest predictor for virtual CR compliance (adjusted R2 = 0.58; P < 0.001), and non-compliant patients were younger. HbA1C level, CVD diagnosis codes, and smoking status each moderately predicted compliance (adjusted R2 = 0.48, 0.42, and 0.31, respectively; P < 0.001). Smoking and HbA1C level combined in a multiple regression model significantly improved prediction of compliance (adjusted R2 = 0.79, P < 0.01). Sex, baseline weight or hypertension were not significant predictors of CR compliance. CONCLUSIONS: Age, diabetes, CVD diagnoses, smoking status at admission are independent predictors of compliance in a large virtual CR program. Targeted intervention could be designed accordingly to improve CR compliance.

Pathogen hijacks programmed cell death signaling by arginine ADPR-deacylization of caspases.

Caspases are evolutionarily conserved cysteine proteases that are essential for regulating cell death and are involved in multiple development and disease processes, including immunity. Here, we show that the bacterial type III secretion system (T3SS) effector CopC (Chromobacterium outer protein C) from the environmental pathogen Chromobacterium violaceum attacks caspase-3/-7/-8/-9 by ADPR-deacylization to dysregulate programmed cell death, including apoptosis, necroptosis, and pyroptosis. This modification involves ADP-ribosylation- and deamination-mediated cyclization on Arg207 of caspase-3 by a mechanism that requires the eukaryote-specific protein calmodulin (CaM), leading to inhibition of caspase activity. The manipulation of cell death signaling by CopC is essential for the virulence of C. violaceum in a mouse infection model. CopC represents a family of enzymes existing in taxonomically diverse bacteria associated with a wide spectrum of eukaryotes ranging from humans to plants. The unique activity of CopC establishes a mechanism by which bacteria counteract host defenses through a previously unrecognized post-translational modification.

Endothelial ARHGEF26 is an angiogenic factor promoting VEGF signalling.

AIMS: Genetic studies have implicated the ARHGEF26 locus in the risk of coronary artery disease (CAD). However, the causal pathways by which DNA variants at the ARHGEF26 locus confer risk for CAD are incompletely understood. We sought to elucidate the mechanism responsible for the enhanced risk of CAD associated with the ARHGEF26 locus. METHODS AND RESULTS: In a conditional analysis of the ARHGEF26 locus, we show that the sentinel CAD-risk signal is significantly associated with various non-lipid vascular phenotypes. In human endothelial cell (EC), ARHGEF26 promotes the angiogenic capacity, and interacts with known angiogenic factors and pathways. Quantitative mass spectrometry showed that one CAD-risk coding variant, rs12493885 (p.Val29Leu), resulted in a gain-of-function ARHGEF26 that enhances proangiogenic signalling and displays enhanced interactions with several proteins partially related to the angiogenic pathway. ARHGEF26 is required for endothelial angiogenesis by promoting macropinocytosis of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) on cell membrane and is crucial to Vascular Endothelial Growth Factor (VEGF)-dependent murine vessel sprouting ex vivo. In vivo, global or tissue-specific deletion of ARHGEF26 in EC, but not in vascular smooth muscle cells, significantly reduced atherosclerosis in mice, with enhanced plaque stability. CONCLUSIONS: Our results demonstrate that ARHGEF26 is involved in angiogenesis signaling, and that DNA variants within ARHGEF26 that are associated with CAD risk could affect angiogenic processes by potentiating VEGF-dependent angiogenesis.

Development of Models to Predict Postoperative Complications for Hepatitis B Virus-Related Hepatocellular Carcinoma.

BACKGROUND: Surgical treatment remains the best option for patients with hepatocellular carcinoma (HCC) caused by chronic hepatitis B virus (HBV) infection. However, there is no optimal tool based on readily accessible clinical parameters to predict postoperative complications. Herein, our study aimed to develop models that permitted risk of severe complications to be assessed before and after liver resection based on conventional variables. METHODS: A total of 1,047 patients treated by hepatectomy for HCC with HBV infection at three different centers were recruited retrospectively between July 1, 2014, and July 1, 2018. All surgical complications were recorded and scored by the Comprehensive Complication Index (CCI). A CCI ≥26.2 was used as a threshold to define patients with severe complications. We built two models for the CCI, one using preoperative and one using preoperative and postoperative data. Besides, CCI and other potentially relevant factors were evaluated for their ability to predict early recurrence and metastasis. All the findings were internally validated in the Hangzhou cohort and then externally validated in the Lanzhou and Urumqi cohorts. RESULTS: Multivariable analysis identified National Nosocomial Infections Surveillance (NNIS) index, tumor number, gamma-glutamyltransferase (GGT), total cholesterol (TC), potassium, and thrombin time as the key preoperative parameters related to perioperative complications. The nomogram based on the preoperative model [preoperative CCI After Surgery for Liver tumor (CCIASL-pre)] showed good discriminatory performance internally and externally. A more accurate model [postoperative CCI After Surgery for Liver tumor (CCIASL-post)] was established, combined with the other four postoperative predictors including leukocyte count, basophil count, erythrocyte count, and total bilirubin level. No significant association was observed between CCI and long-term complications. CONCLUSION: Based on the widely available clinical data, statistical models were established to predict the complications after hepatectomy in patients with HBV infection. All the findings were extensively validated and shown to be applicable nationwide. Such models could be used as guidelines for surveillance follow-up and the design of post-resection adjuvant therapy.

MiR-770 promotes oral squamous cell carcinoma migration and invasion by regulating the Sirt7/Smad4 pathway.

Oral squamous cell carcinoma (OSCC) is a common malignant cancer with unfavorable prognosis, and the epithelial-to-mesenchymal transition (EMT) is a critical contributor to OSCC metastasis. Recently, we have shown that sirtuin 7 (Sirt7) is associated with EMT and OSCC metastasis by acetylating small mother against decapentaplegic 4 (Smad4). Nonetheless, the mechanism of Sirt7 downregulation in OSCC cells remains unknown. This study analyzed the potential microRNAs that were predicted to regulate Sirt7 expression by online databases. We identified miR-770 as an upstream regulator of Sirt7 that targets its 3'-untranslated region. The expression of miR-770 was observed to be negatively correlated with the mRNA expression of Sirt7 in metastatic OSCC tumors, and higher miR-770 expression was correlated with poorer OSCC patient survival. Our in vitro data indicated that miR-770 promoted OSCC cell migration and invasion, and this process was dependent on Sirt7/Smad4 signaling. Furthermore, in vivo metastasis experiments indicated that miR-770 overexpression led to more prominent OSCC metastasis and downregulated Sirt7 expression. Collectively, our results revealed a new role of Sirt7 downregulation in metastatic OSCC and suggested that miR-770 is a potential target in counteracting OSCC metastasis.

Assessment of Quality of Life of Free Anterolateral Thigh Flap for Reconstruction of Tissue Defects of Total or Near-Total Glossectomy.

BACKGROUND: The aim of this study was to evaluate quality of life of free anterolateral thigh flap (ALTFF) for reconstruction of tissue defects of total or near-total glossectomy. METHODS: Quality of life was assessed by means of the University of Washington Quality of Life (UW-QOL) and the 14-item Oral Health Impact Profile (OHIP-14), after 12 months postoperatively. RESULTS: 65 of 79 questionnaires were returned (82.27%). In the UW-QOL, the best-scoring domain was "shoulder," whereas the lowest scores were for "chewing" and "pain." In the OHIP-14, the lowest-scoring domain was "handicap," followed by "Social disability" and "Psychological disability." CONCLUSION: Free anterolateral thigh perforator flaps for reconstruction of total or near-total glossectomy defects after cancer resection would have significantly influenced the patients' oral functions and quality of life.

Dopamine neurons in the ventral periaqueductal gray modulate isoflurane anesthesia in rats.

AIMS: General anesthesia has been applied in surgery for more than 170 years, and there is little doubt that GABAA receptors have an important role as anesthetic molecular targets, but its neural mechanisms remain unclear. Increasing researchers have shown that dopaminergic pathways in the brain are crucial for sleep and wake. General anesthesia-induced unconsciousness and natural sleep share some neural correlates. However, the role of GABAA receptors in ventral periaqueductal gray (vPAG) dopamine (DA) neurons in the isoflurane-induced unconsciousness has yet to be identified. METHODS: In the present study, we used calcium fiber photometry recording to explore that the activity of ventral periaqueductal gray (vPAG) neurons. Then, rats were unilaterally microinjected with 6-hydroxydopamine into the vPAG area to determine the role of vPAG-DA neurons in isoflurane-induced-anesthesia. Furthermore, thirty SD rats were divided into three groups: a GABAA R agonist-muscimol group, a GABAA R antagonist-gabazine group, and a control group. Finally, whole-cell patch clamp was used to examine the effects of isoflurane and GABAA receptor agonist/antagonist on vPAG-DA neurons. RESULTS: The vPAG neurons were markedly inhibited during isoflurane anesthesia induction and that these neurons were activated during emergence from isoflurane anesthesia. Lesion to the vPAG-DA neurons shortened the induction time and prolonged the emergence time while increasing δ power in isoflurane anesthesia. Intracerebral injection of the GABAA receptor agonist (muscimol) into the vPAG accelerated the induction of anesthesia and delayed recovery from isoflurane anesthesia, with a decrease of δ power and an augment of ß power. Injection of GABAA receptor antagonist gabazine generated the opposite effects. Isoflurane enhanced GABAergic transmission, and GABAA receptor agonist partly increased isoflurane-induced inhibition of vPAG-DA neurons, while GABAA receptor antagonist evidently attenuated GABAergic transmission. CONCLUSION: Our results suggest that vPAG-DA neurons are involved in isoflurane anesthesia through activation of the GABAA receptor.

HOXC13-AS accelerates cell proliferation and migration in oral squamous cell carcinoma via miR-378g/HOXC13 axis.

Oral squamous cell carcinoma (OSCC) is an aggressive cancer type in head and neck. A number of long non-coding RNAs (lncRNAs) are discovered to serve regulatory roles in OSCC. HOXC13 antisense RNA (HOXC13-AS) has been proved to behave as a tumor-facilitator in nasopharyngeal carcinoma, but its regulatory role in OSCC has never been investigated. In this study, GEPIA indicated that HOXC13-AS and its neighbor gene HOXC13 were upregulated in HNSC samples, and we consistently unveiled their upregulation in OSCC tissues and cell lines. Silencing HOXC13-AS abrogated OSCC cell proliferation, migration, and epithelial-to-mesenchymal transition (EMT). Moreover, HOXC13 overexpression rescued the influences of HOXC13-AS silence on OSCC cellular processes and in vivo tumor growth. Mechanistically, HOXC13-AS upregulated HOXC13 expression in OSCC through sequestering miR-378g, which was proved to exert suppressive functions in the malignant behaviors of OSCC cells. Further, HOXC13 was revealed to be positively correlated with HOXC13-AS and negatively with miR-378g in expression in OSCC samples. In sum, our findings suggested that HOXC13-AS functioned as a ceRNA to accelerate the malignant behaviors of OSCC cells via miR-378g/HOXC13 axis, shedding a new light on the lncRNA-targeted treatment for OSCC.

Nitroalkenes confer acute cardioprotection via adenine nucleotide translocase 1.

Electrophilic nitrated lipids (nitroalkenes) are emerging as an important class of protective cardiovascular signaling molecules. Although species such as nitro-linoleate (LNO(2)) and nitro-oleate can confer acute protection against cardiac ischemic injury, their mechanism of action is unclear. Mild uncoupling of mitochondria is known to be cardioprotective, and adenine nucleotide translocase 1 (ANT1) is a key mediator of mitochondrial uncoupling. ANT1 also contains redox-sensitive cysteines that may be targets for modification by nitroalkenes. Therefore, in this study we tested the hypothesis that nitroalkenes directly modify ANT1 and that nitroalkene-mediated cardioprotection requires ANT1. Using biotin-tagged LNO(2) infused into intact perfused hearts, we obtained mass spectrometric (MALDI-TOF-TOF) evidence for direct modification (nitroalkylation) of ANT1 on cysteine 57. Furthermore, in a cell model of ischemia-reperfusion injury, siRNA knockdown of ANT1 inhibited the cardioprotective effect of LNO(2). Although the molecular mechanism linking ANT1-Cys(57) nitroalkylation and uncoupling is not yet known, these data suggest that ANT1-mediated uncoupling may be a mechanism for nitroalkene-induced cardioprotection.

Advanced oxidation protein products induce vascular calcification by promoting osteoblastic trans-differentiation of smooth muscle cells via oxidative stress and ERK pathway.

Vascular calcification is an actively regulated process similar to bone formation. Advanced oxidation protein products (AOPPs) have been demonstrated to be novel markers of oxidant-mediated protein damage. The present study investigated the role of AOPPs in inducing osteoblastic trans-differentiation and calcification of smooth muscle cells in vitro. We found that AOPPs directly increased the calcium deposition and expression of core binding factor-alpha1 (CBF-alpha1) and osteopontin (OPN) and significantly decreased SM-alpha-actin expression in human aortic smooth muscle cells (HASMCs). AOPPs increased intracellular oxidative stress, which was inhibited by vitamin E. Vitamin E also inhibited AOPP-induced calcium content and osteoblast differentiation of HASMCs. Furthermore, the inhibitor of ERK significantly suppressed the effects of AOPPs on calcification and osteoblast marker expression. These findings suggest that AOPPs induce vascular calcification by promoting osteoblast differentiation of smooth muscle cells via oxidative stress and ERK pathway.