Varied immune responses of HBV-specific B cells in patients undergoing pegylated interferon-alpha treatment for chronic hepatitis B.

BACKGROUND & AIMS: The changes of HBV-specific B-cells in chronic hepatitis B (CHB) patients underwent pegylated interferon-alfa (PEG-IFNα) treatment and achieved functional cure remain unclear. We aimed to evaluate the alterations in HBV-specific B-cells during treatment and therefore explored the mechanism of functional recovery of HBsAg-specific B-cells. METHODS: We included 39 nucleos(t)ide analogues-treated CHB patients who received sequential combination therapy with PEG-IFNα and 8 treatment-naive CHB patients. HBV-specific B-cells were characterized ex vivo using fluorescent labeled HBsAg and HBcAg. The frequency, phenotype, and subsets of HBV-specific B-cells and follicular helper T cells (Tfh-cells) were detected using flow cytometry. The functionality of HBV-specific B-cells was quantified through ELISpot assays. RESULTS: During treatment, the fraction of activated memory B-cells (MBCs) among HBsAg-specific B-cells and the expression of IgG, CXCR3, and CD38 increased. Antibody-secretion capacity of HBsAg-specific B-cell was restored after treatment only in patients with a functional cure and it showed a positive correlation with serum hepatitis B surface antibody levels. The phenotype and function of HBsAg-specific B-cells differed between patients with and without functional cure. Patients with functional cure exhibited IgG+ classical MBCs and plasmablasts in HBsAg-specific B-cells. HBcAg-specific B-cells displayed both attenuated antibody secretion with reduced IgG expression and an IgM+ atypical type of MBCs after treatment, irrespective of with and without functional cure. The number of CD40L+ Tfh-cells increased after PEG-IFNα treatment and positively correlated with HBsAg-specific B-cell activation. CONCLUSIONS: After PEG-IFNα treatment, HBsAg- and HBcAg-specific B-cells exhibit various changes in antibody secretion. Their functional differences are reflected in the alterations in phenotypes and subtypes. The presence of CD40L+ Tfh-cells is associated with the active recovery of HBsAg-specific B-cells. IMPACT AND IMPLICATIONS: HBV-related complications and hepatocellular carcinoma remain the leading causes of mortality from chronic liver disease worldwide, and a cure is rarely achieved with antiviral therapies. Elucidating the immunological mechanisms underlying the functional cure of CHB patients offers a promising therapeutic strategy for viral clearance, such as therapeutic vaccine. We analyzed the alterations in HBV-specific B-cells in patients treated with PEG-IFNα and identified novel pathways for immunotherapeutic boosting of B cell immunity.

Single-cell sequencing identifies inflammation-promoting fibroblast-neutrophil interaction in peri-implantitis.

AIM: To reveal the cellular composition and molecular environment of the periodontal and peri-implant inflammatory infiltrates through a single-cell sequencing technique, which may explain the pathological difference between these two diseases. A special focus was placed on the phenotypes and potential roles of neutrophils and fibroblasts in peri-implant/periodontal tissue immunity. MATERIALS AND METHODS: High-throughput single-cell transcriptomic profiling of peri-implant tissues from patients with peri-implantitis as well as periodontal tissues from patients with periodontitis and healthy donors was performed. Immunofluorescence analysis was carried out to further validate the identified cell subtypes and their involvement in peri-implantitis and periodontitis. RESULTS: Based on our single-cell resolution analysis, a quantified proportional increase of neutrophil (Neu) subtypes was shown in peri-implantitis. Among these, a predominance of Neutro_CXCR2 was revealed. We also found the involvement of inflammation-promoting fibroblasts as well as a predominance of CXCL8+ fibroblast-CXCR2+ neutrophil interaction in peri-implantitis. CONCLUSIONS: Our study indicated that the predominance of CXCL8+ fibroblast-CXCR2+ neutrophil interaction might underline the enhanced host response in peri-implantitis compared with periodontitis. This information offers a molecular basis by which fibroblast and neutrophil subtypes might be diagnostically and therapeutically targeted in peri-implantitis.

Mesenchymal stem cell-derived exosomes as a new drug carrier for the treatment of spinal cord injury: A review.

Spinal cord injury (SCI) is a devastating traumatic disease seriously impairing the quality of life in patients. Expectations to allow the hopeless central nervous system to repair itself after injury are unfeasible. Developing new approaches to regenerate the central nervous system is still the priority. Exosomes derived from mesenchymal stem cells (MSC-Exo) have been proven to robustly quench the inflammatory response or oxidative stress and curb neuronal apoptosis and autophagy following SCI, which are the key processes to rescue damaged spinal cord neurons and restore their functions. Nonetheless, MSC-Exo in SCI received scant attention. In this review, we reviewed our previous work and other studies to summarize the roles of MSC-Exo in SCI and its underlying mechanisms. Furthermore, we also focus on the application of exosomes as drug carrier in SCI. In particular, it combs the advantages of exosomes as a drug carrier for SCI, imaging advantages, drug types, loading methods, etc., which provides the latest progress for exosomes in the treatment of SCI, especially drug carrier.

Development a novel nomogram model for predicting significant hepatic histological changes in chronic hepatitis B virus carriers.

A proportion of chronic hepatitis B virus (HBV) carriers with normal alanine transaminase (ALT) present with significant liver histological changes (SLHC). To construct a noninvasive nomogram model to identify SLHC in chronic HBV carriers with different upper limits of normal (ULNs) for ALT. The training cohort consisted of 732 chronic HBV carriers who were stratified into four sets according to different ULNs for ALT: chronic HBV carriers I, II, III, and IV. The external validation cohort comprised 277 chronic HBV carriers. Logistic regression and least absolute shrinkage and selection operator analyses were applied to develop a nomogram model to predict SLHC. A nomogram model-HBGP (based on hepatitis B surface antigen, gamma-glutamyl transpeptidase, and platelet count) demonstrated good performance in diagnosing SLHC with area under the curve (AUCs) of 0.866 (95% confidence interval [CI]: 0.839-0.892) and 0.885 (95% CI: 0.845-0.925) in the training and validation cohorts, respectively. Furthermore, HBGP displayed high diagnostic values for SLHC with AUCs of 0.866 (95% CI: 0.839-0.892), 0.868 (95% CI: 0.838-0.898), 0.865 (95% CI: 0.828-0.901), and 0.853 (95% CI: 0.798-0.908) in chronic HBV carriers I, II, III, and IV, respectively. Additionally, HBGP showed greater ability in predicting SLHC compared with the existing predictors. HBGP has shown high predictive performance for SLHC, and thus may lead to an informed decision on the initiation of antiviral treatment.

Improving the performance of reference-frame-independent quantum key distribution with advantage distillation technology.

The reference-frame-independent quantum key distribution (RFI-QKD) has the advantage of tolerating reference frames that slowly vary. It can generate secure keys between two remote users with slowly drifted and unknown reference frames. However, the drift of reference frames may inevitably compromise the performance of QKD systems. In the paper, we employ the advantage distillation technology (ADT) to the RFI-QKD and the RFI measurement-device-independent QKD (RFI MDI-QKD), and we then analyze the effect of ADT on the performance of decoy-state RFI-QKD and RFI MDI-QKD in both asymptotic and nonasymptotic cases. The simulation results show that ADT can significantly improve the maximum transmission distance and the maximum tolerable background error rate. Furthermore, the performance of RFI-QKD and RFI MDI-QKD in terms of the secret key rate and maximum transmission distance are still greatly improved when statistical fluctuations are taken into account. Our work combines the merits of the ADT and RFI-QKD protocols, which further enhances the robustness and practicability of QKD systems.

Metal-Free Covalent Organic Frameworks for Electrocatalytic Oxygen Reduction Reaction.

Exploring efficient and low-cost electrocatalysts for the oxygen reduction reaction (ORR) is important for renewable energy conversion. Covalent organic frameworks (COFs) have recently risen as ideal candidates for catalyzing ORR, but this field is still in its infancy. Herein, a new framework material (named as COF-JLU82) containing bifluorenylidene and benzoselenadiazole units with periodic alternating arrangement is designed and synthesized. The metal-free COF-JLU82 exhibits good electrocatalytic activity with a half-wave potential of 0.68 V, Tafel slope of 72.79 mV dec-1 and the conversion frequency (TOF) of 0.0044 s-1 , which is better than the previously reported COF-JLU23. This study enriches the types of COF-based ORR electrocatalysts and promotes the development of more highly efficient metal-free ORR electrocatalysts.

A liposomal carbohydrate vaccine, adjuvanted with an NKT cell agonist, induces rapid and enhanced immune responses and antibody class switching.

BACKGROUND: Congenital disorders of glycosylation (CDGs) are genetic diseases caused by gene defects in glycan biosynthesis pathways, and there is an increasing number of patients diagnosed with CDGs. Because CDGs show many different clinical symptoms, their accurate clinical diagnosis is challenging. Recently, we have shown that liposome nanoparticles bearing the ALG1-CDG and PMM2-CDG biomarkers (a tetrasaccharide: Neu5Ac-α2,6-Gal-ß1,4-GlcNAc-ß1,4-GlcNAc) stimulate a moderate immune response, while the generated antibodies show relatively weak affinity maturation. Thus, mature antibodies with class switching to IgG are desired to develop high-affinity antibodies that may be applied in medical applications. RESULTS: In the present study, a liposome-based vaccine platform carrying a chemoenzymatic synthesized phytanyl-linked tetrasaccharide biomarker was optimized. The liposome nanoparticles were constructed by dioleoylphosphatidylcholine (DOPC) to improve the stability and immunogenicity of the vaccine, and adjuvanted with the NKT cell agonist PBS57 to generate high level of IgG antibodies. The results indicated that the reformulated liposomal vaccine stimulated a stronger immune response, and PBS57 successfully induce an antibody class switch to IgG. Further analyses of IgG antibodies elicited by liposome vaccines suggested their specific binding to tetrasaccharide biomarkers, which were mainly IgG2b isotypes. CONCLUSIONS: Immunization with a liposome vaccine carrying a carbohydrate antigen and PBS57 stimulates high titers of CDG biomarker-specific IgG antibodies, thereby showing great potential as a platform to develop rapid diagnostic methods for ALG1-CDG and PMM2-CDG.

Development and validation of a novel model to predict liver-related mortality in patients with idiosyncratic drug-induced liver injury.

BACKGROUND: Early identification of patients with high mortality risk is critical for optimizing the clinical management of drug-induced liver injury (DILI). We aimed to develop and validate a new prognostic model to predict death within 6 months in DILI patients. METHODS: This multicenter study retrospectively reviewed the medical records of DILI patients admitted to three hospitals. A DILI mortality predictive score was developed using multivariate logistic regression and was validated with area under the receiver operating characteristic curve (AUC). A high-mortality-risk subgroup was identified according to the score. RESULTS: Three independent DILI cohorts, including one derivation cohort (n = 741) and two validation cohorts (n = 650, n = 617) were recruited. The DILI mortality predictive (DMP) score was calculated using parameters at disease onset as follows: 1.913 × international normalized ratio + 0.060 × total bilirubin (mg/dL) + 0.439 × aspartate aminotransferase/alanine aminotransferase - 1.579 × albumin (g/dL) - 0.006 × platelet count (109/L) + 9.662. The predictive performance for 6-month mortality of DMP score was desirable, with an AUC of 0.941 (95% CI: 0.922-0.957), 0.931 (0.908-0.949) and 0.960 (0.942-0.974) in the derivation, validation cohorts 1 and 2, respectively. DILI patients with a DMP score ≥ 8.5 were stratified into high-risk group, whose mortality rates were 23-, 36-, and 45-fold higher than those of other patients in the three cohorts. CONCLUSIONS: The novel model based on common laboratory findings can accurately predict mortality within 6 months in DILI patients, which should serve as an effective guidance for management of DILI in clinical practice.

Porous organic polymers for light-driven organic transformations.

As a new generation of porous materials, porous organic polymers (POPs), have recently emerged as a powerful platform of heterogeneous photocatalysis. POPs are constructed using extensive organic synthesis methodologies, with various functional organic units being connected via high-energy covalent bonds. This review systematically presents the recent advances in POPs for visible-light driven organic transformations. Herein, we firstly summarize the common construction strategies for POP-based photocatalysts based on two major approaches: pre-design and post-modification; secondly, we categorize and summarize the synthesis methods and organic reaction types for constructing various types of POPs. We then classify and introduce the specific reactions of current light-driven POP-mediated organic transformations. Finally, we outline the current state of development and the problems faced in light-driven organic transformations by POPs, and we present some perspectives to motivate the reader to explore solutions to these problems and confront the present challenges in the development process.

Astragalus (Astragalus mongholicus) Improves Ventricular Remodeling via ESR1 Downregulation RhoA/ROCK Pathway.

Astragalus (Astragalus mongholicus) alleviates myocardial remodeling caused by hypertension. However, the detailed molecular mechanism is unclear. This study aims to investigate the effect of Astragalus on ventricular remodeling in ovariectomized spontaneous hypertensive rats (OVX-SHR).Female SHR/NCrl rats were subjected to bilateral ovariectomy to establish the OVX-SHR model and treated with Astragalus extract by gavage. The hemodynamics and cardiac function parameters were measured. HE and Masson staining were used to detect the pathological structure of myocardial remodeling and observe the hyperplasia of myocardial collagen fibers. The immunohistochemistry tested the level of α-SMA. The expression levels of inflammatory cytokines, IκB, p65, Cleaved-Caspase3, RhoA, and ROCK1/2 were detected using Western blot. The method of qRT-PCR measured the expression of matrix metalloproteinase (MMP-2 and MMP-9).Hemodynamic and cardiac function parameters were significantly improved after a high dose of Astragalus extract and Valsartan treatment. The myocardial integrity of the model group was significantly reduced, arranged loosely, and disordered, while the expression of α-SMA was increased. However, Astragalus extract and Valsartan treatments significantly reduced the pathological damage and α-SMA. The levels of TNF-α, IL-1ß, IL-6, TGF-ß, MMP-2, and MMP-9 in the model group were increased but decreased after Astragalus extract treatment. Adding an ESR1 inhibitor attenuated the improvement effect of Astragalus extract on myocardial remodeling and restored the expression of RhoA and ROCK1/2.Astragalus extract attenuates the cardiac damage in OVX-SHR by downregulating the RhoA/ROCK pathway through ESR1.

Hepatitis B Surface Antigen Levels Can Be Used to Rule Out Cirrhosis in Hepatitis B e Antigen-Positive Chronic Hepatitis B: Results From the SONIC-B Study.

BACKGROUND: Serum hepatitis B surface antigen (HBsAg) levels correlate with the duration of chronic hepatitis B virus (HBV) infection and may predict the extent of hepatic fibrosis. METHODS: We analyzed data from the SONIC-B database, which contains data from 8 global randomized trials and 2 large hepatology centers. Relationship between HBsAg levels and presence of significant fibrosis (Ishak 3-4) or cirrhosis (Ishak 5-6) were explored, and clinically relevant cutoffs were identified to rule out cirrhosis. RESULTS: The dataset included 2779 patients: 1866 hepatitis B e antigen (HBeAg)-positive; 322 with cirrhosis. Among HBeAg-positive patients, lower HBsAg levels were associated with higher rates of significant fibrosis (odds ratio [OR], 0.419; P < .001) and cirrhosis (OR, 0.435; P < .001). No relationship was observed among HBeAg-negative patients. Among HBeAg-positive patients, genotype-specific HBsAg cutoffs had excellent negative predictive values (>97%) and low misclassification rates (≤7.1%) and may therefore have utility in ruling out cirrhosis. Diagnostic performance of the HBsAg cutoffs was comparable among patients in whom cirrhosis could not be ruled out with fibrosis 4 (FIB-4). CONCLUSIONS: Hepatitis B virus genotype-specific HBsAg cutoffs may have utility in ruling out presence of cirrhosis in HBeAg-positive patients with genotypes B, C, and D and can be an adjunct to FIB-4 to reduce the need for further testing.

Histological assessment based on liver biopsy: the value and challenges in NASH drug development.

Nonalcoholic steatohepatitis (NASH) is increasingly recognized as a serious disease that can lead to cirrhosis, hepatocellular carcinoma (HCC), and death. However, there is no effective drug to thwart the progression of the disease. Development of new drugs for NASH is an urgent clinical need. Liver biopsy plays a key role in the development of new NASH drugs. Histological findings based on liver biopsy are currently used as the main inclusion criteria and the primary therapeutic endpoint in NASH clinical trials. However, there are inherent challenges in the use of liver biopsy in clinical trials, such as evaluation reliability, sampling error, and invasive nature of the procedure. In this article, we review the advantages and value of liver histopathology based on liver biopsy in clinical trials of new NASH drugs. We also discuss the challenges and limitations of liver biopsy and identify future drug development directions.

Long-term clinical outcomes of short implant (6mm) in relation to Implant Disease Risk Assessment (IDRA).

AIM: To evaluate the long-term survival of short implants and to investigate the association of the Implant Disease Risk Assessment (IDRA) with the occurrence of biological complications. MATERIAL AND METHODS: This study was designed as a cohort study with a median follow-up of 10.0 years. Patients who had received 6-mm implants were reviewed and assigned into low-, moderate-, and high-risk groups (Group L, M, and H) based on the IDRA tool. The implant survival, biological complications, soft tissue condition, hardware complications, and marginal bone loss (MBL) were evaluated. Kaplan-Meier curves and Cox regression were performed for survival analysis. RESULTS: A hundred and ten patients were included. The overall cumulative survival rate was 90.9% (L:100.0%, M: 93.3%, and H: 80.6%). A higher risk profile was significantly associated with a decreased implant survival (hazard ratio: 4.11, 95% CI: 1.17-14.36, p < .05). Higher risk profile (hazard ratio: 2.63, 95% CI: 1.32-5.25, p < .05) was a potential risk factor for biological complications. At follow-up, significant differences in bleeding index, modified plaque index, and peri-implant probing depth were found among groups (p < .01). No significant difference was found in MBL. CONCLUSION: Acceptable long-term clinical outcomes could be achieved after 10 years for short implants. Despite a statistically nonsignificant difference in MBL, patients with a high-risk profile of IDRA seem to be at greater risk of implant loss and biological complications.

Healthcare needs, experiences and treatment burden in primary care patients with multimorbidity: An evaluation of process of care from patients' perspectives.

BACKGROUND: Patients with multimorbidity often experience treatment burden as a result of fragmented, specialist-driven healthcare. The 'family doctor team' is an emerging service model in China to address the increasing need for high-quality routine primary care. OBJECTIVE: This study aimed to explore the extent to which treatment burden was associated with healthcare needs and patients' experiences. METHODS: Multisite surveys were conducted in primary care facilities in Guangdong province, southern China. Interviewer-administered questionnaires were used to collect data from patients (N = 2160) who had ≥2 clinically diagnosed long-term conditions (multimorbidity) and had ≥1 clinical encounter in the past 12 months since enrolment registration with the family doctor team. Patients' experiences and treatment burden were measured using a previously validated Chinese version of the Primary Care Assessment Tool (PCAT) and the Treatment Burden Questionnaire, respectively. RESULTS: The mean age of the patients was 61.4 years, and slightly over half were females. Patients who had a family doctor team as the primary source of care reported significantly higher PCAT scores (mean difference 7.2 points, p < .001) and lower treatment burden scores (mean difference -6.4 points, p < .001) when compared to those who often bypassed primary care. Greater healthcare needs were significantly correlated with increased treatment burden (ß-coefficient 1.965, p < .001), whilst better patients' experiences were associated with lower treatment burden (ß-coefficient -0.252, p < .001) after adjusting for confounders. CONCLUSION: The inverse association between patients' experiences and treatment burden supports the importance of primary care in managing patients with multimorbidity. PATIENT CONTRIBUTION: Primary care service users were involved in the instrument development and data collection.

Concomitant extrahepatic autoimmune diseases do not compromise the long-term outcomes of primary biliary cholangitis.

BACKGROUND: Primary biliary cholangitis (PBC) patients often have concomitant extrahepatic autoimmune (EHA) diseases including Sjögren's syndrome (SS), systemic sclerosis (SSc), rheumatoid arthritis (RA), and autoimmune thyroid disease. The present study aimed to describe the prevalence of EHA diseases in PBC and explore the impact of EHA diseases on the long-term outcomes of PBC in Chinese patients. METHODS: Medical records of PBC patients diagnosed in our institute were retrospectively reviewed. Patients were followed up by a standardized telephone interview. The endpoints were defined as liver-related death and/or liver transplantation. RESULTS: Totally 247 of the 985 (25.1%) PBC patients enrolled in the study had at least one concomitant EHA disease. Sjögren's syndrome (n = 140, 14.2%) was the most frequent one, followed by rheumatoid arthritis (RA) (n = 56, 5.7%) and Hashimoto's thyroiditis (n = 45, 4.6%). Patients with EHA diseases were more common in females (P < 0.001) and in those with a family history of autoimmune disease (P = 0.017). Overall, no differences were found between PBC patients with and without EHA diseases in terms of biochemical response rates to ursodeoxycholic acid, the incidence of hepatic events, or transplant-free survival. RA and EHA ≥ 2 were protective factors for hepatic events in univariate Cox analysis, but the results became insignificant in multivariate analysis. CONCLUSIONS: Concomitant EHA diseases were common in PBC patients but did not compromise the long-term outcomes of PBC.

Closed reduction and posterior percutaneous internal fixation for simple displaced talar neck fracture: a retrospective comparative study.

PURPOSE: Open reduction and internal fixation (ORIF) is the most commonly used surgical technique for talar neck fracture, but there are high risks for complications and poor functional outcomes. In this study, we reported the closed reduction and percutaneous internal fixation (CRPIF) technique of the bilateral approach of the Achilles tendon for simple displaced talar neck fracture, in comparison with ORIF. METHODS: Data of 15 patients in the CRPIF group and 22 in the ORIF group were included. The American Orthopaedic Foot and Ankle Society (AOFAS) score, Visual Analog Scale (VAS) score, 12-item Short-Form Survey (SF-12) score, range of motion (ROM), complications, and radiographic results were recorded and compared. RESULTS: The mean follow-up in the CRPIF group was 33.9 months. Complications included two cases of avascular necrosis (AVN) and two cases of osteoarthritis. All patients achieved bony union and recovered their pre-operative mobility. The mean follow-up in the ORIF group was 39 months. Complications included two cases of bony nonunion, nine AVN, and seven cases of osteoarthritis. Moreover, the mobility of the ORIF group was significantly lower than the CRPIF group post-operatively. The AOFAS score, VAS score, and SF-12 physical component score (PCS) for the CRPIF group were better improved than those for the ORIF group (ALL, P < 0.05). CONCLUSIONS: The CRPIF technique of the bilateral approach of the Achilles tendon was an effective method for the treatment of simple displaced talar neck fractures. Compared with the ORIF, the limited blood supply of the talus was protected, provide better functional outcomes and biomechanical fixation, and lower incidence of resurgery and complication in the CRPIF.

Security Analysis of Sending or Not-Sending Twin-Field Quantum Key Distribution with Weak Randomness.

Sending-or-not sending twin-field quantum key distribution (SNS TF-QKD) has the advantage of tolerating large amounts of misalignment errors, and its key rate can exceed the linear bound of repeaterless quantum key distribution. However, the weak randomness in a practical QKD system may lower the secret key rate and limit its achievable communication distance, thus compromising its performance. In this paper, we analyze the effects of the weak randomness on the SNS TF-QKD. The numerical simulation shows that SNS TF-QKD can still have an excellent performance under the weak random condition: the secret key rate can exceed the PLOB boundary and achieve long transmission distances. Furthermore, our simulation results also show that SNS TF-QKD is more robust to the weak randomness loopholes than the BB84 protocol and the measurement-device-independent QKD (MDI-QKD). Our results emphasize that keeping the randomness of the states is significant to the protection of state preparation devices.

Photocatalytic Hydrogen Production on a sp2 -Carbon-Linked Covalent Organic Framework.

Two-dimensional covalent organic frameworks (2D-COFs) have emerged as attractive platforms for solar-to-chemical energy conversion. In this study, we have implemented a gradient heating strategy to synthesize a sp2 -carbon-linked triazine-based COF, COF-JLU100, exhibiting high crystallinity, large surface area, good durability and carrier mobility for solar-driven photocatalytic hydrogen evolution. The Pt-doped COF-JLU100 demonstrated a high hydrogen evolution rate of over 100 000 µmol g-1 h-1 for water splitting under visible-light illumination (λ>420 nm). Experimental and theoretical studies corroborate that the cyano-vinylene segments in COF-JLU100 extend the π-delocalization and enable fast charge transfer and separation rates as well as good dispersion in water. Moreover, COF-JLU100 can be prepared by low-cost and easily available monomers and has excellent stability, which is desirable for practical solar-driven hydrogen production.

Surgical Challenges in Multi-Vessel Minimally Invasive Coronary Artery Bypass Grafting.

OBJECTIVES: Minimally invasive coronary artery bypass grafting (MICS CABG) has emerged as an alternative treatment for patients with multi-vessel coronary artery disease, but there are certain surgical challenges inherent in the adoption of this approach. The present study was conducted to provide insight regarding the outcomes associated with our first 118 cases, to discuss the surgical difficulties encountered in these patients, and to outline the potential countermeasures. METHODS: Between January 2017 and January 2020, 118 patients underwent multi-vessel MICS CABG. These patients were stratified into two groups based upon whether they did or did not experience surgical challenges, and early clinical outcomes were compared between these groups to assess the incidence of technical difficulties and associated factors. RESULTS: Surgical challenges arose in 38 of the 118 cases in this study, including 13 cases of exposure-related difficulties, 11 cases of proximal anastomosis-related difficulties, 15 cases of distal anastomosis-related difficulties, 4 cases of LITA-related difficulties, and 3 cases of lung-related difficulties. Relative to the other 80 patients, those patients for whom intraoperative technical challenges arose experience significant increases in operative duration (4.94 ± 0.89 vs. 5.59 ± 1.11 h, P=0.001), intraoperative blood loss (667 ± 313 vs. 892 ± 532 mL, P=0.005), length of the ICU admission (17.59 ± 3.51 vs. 22.59 ± 17.31 h, P=0.015), and the duration of postoperative hospitalization (5.96 ± 1.23 vs. 6.71 ± 1.92 days, P=0.012). There were no significant differences between these groups with respect to the mean graft number, major complications such as stroke or organ dysfunction, or one-year graft patency. CONCLUSIONS: There is a substantial learning curve associated with performing off-pump MICS CABG to treat multi-vessel disease. Surgical challenges encountered during this procedure may increase the operative duration, intraoperative blood loss, ICU admission, and the duration of postoperative hospitalization. However, these issues do not appear to compromise the efficacy of complete revascularization, and early clinical outcomes associated with this procedure remain acceptable.

Dexmedetomidine Resists Intestinal Ischemia-Reperfusion Injury by Inhibiting TLR4/MyD88/NF-κB Signaling.

BACKGROUND: Intestinal ischemia/reperfusion (I/R) is a common clinical problem that occurs during various clinical pathological processes. Dexmedetomidine (DEX), a widely used anesthetic adjuvant agent, can induce protection against intestinal I/R in vivo; however, the underlying mechanism is not fully understood. In the present study, we aimed to investigate the protective effects of DEX and examine whether its mechanism was associated with the TLR4/MyD88/NF-κB signaling pathway. METHODS: Sprague-Dawley rats were pretreated with DEX and then subjected to I/R-induced intestinal injury. In vivo, intestinal histopathological examination and scoring were performed, the levels of serum intestinal fatty acid-binding protein (I-FABP), intestinal tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and expression levels of TLR4, MyD88, and NF-κB in the intestine were determined. In in vitro experiments, the human colon carcinoma cell line (Caco-2) was incubated with DEX before deprivation/reoxygenation (OGD/R) treatment. The cell viability of Caco-2 cells, the levels of lactate dehydrogenase (LDH), TNF-α, and IL-1ß in the supernatant, as well as protein expression of TLR4, MyD88, and NF-κB in Caco-2 cells, were measured. Statistical analysis was performed using SPSS version 21.0. RESULTS: DEX preconditioning significantly reduced the intestinal pathological Chiu's score, serum I-FABP, intestinal TNF-α, IL-1ß levels, and the protein expression of TLR4, MyD88, and NF-κB in the rats with intestinal I/R injury. Similarly, in vitro, DEX pretreatment protected against OGD/R-induced Caco-2 cell damage and inhibited TLR4/MyD88/NF-κB signaling, as evidenced by increased cell viability, decreased LDH activity, reduced TNF-α and IL-1ß levels, as well as downregulated TLR4, MyD88, and NF-κB protein levels. CONCLUSIONS: Our findings suggested that DEX could reduce intestinal I/R injury in rats and OGD/R damage in Caco-2 cells, and this protection might be attributed to antiinflammatory effects and inhibition of the TLR4/MyD88/NF-κB signaling pathway.