The use of transcutaneous electrical acupoint stimulation to reduce opioid consumption in patients undergoing off-pump CABG: a randomized controlled trial.

BACKGROUND: High doses of long-acting opioids were used to facilitate off-pump coronary artery bypass grafting procedure, which may result in opioid-related adverse events after surgery. Transcutaneous electrical acupoint stimulation (TEAS) had been reported to be effective in reducing intraoperative opioids consumption during surgery. The aim of this study is to assess whether TEAS with difference acupoints can reduce the doses of opioid analgesics. METHODS: This was a multicenter, randomized, controlled, double-blind trial. Patients underwent off-pump coronary artery bypass grafting under general anesthesia were enrolled. Eligible patients were randomly and equally grouped into sham acupuncture group (n = 105), regional acupoints combination group (n = 105), or distal-proximal acupoints combination group (n = 105) using a centralized computer-generated randomization system. Transcutaneous electrical acupoint stimulation was applied for 30 min before anesthesia induction. The primary outcome was the doses of sufentanil during anesthesia. Secondary outcomes included the highest postoperative vasoactive-inotropic scores within 24 h, intraoperative propofol consumption, length of mechanical ventilation, duration of cardiac care unit and postoperative hospital stay, incidence of postoperative complications, and mortality within 30 days after surgery. RESULTS: Of the 315 randomized patients, 313 completed the trial. In the modified intention-to-treat analysis, the doses of sufentanil were 303.9 (10.8) µg in the distal-proximal acupoints group, significantly lower than the sham group, and the mean difference was - 34.9 (- 64.9 to - 4.9) µg, p = 0.023. The consumption of sufentanil was lower in distal-proximal group than regional group (303.9 vs. 339.5), and mean difference was - 35.5 (- 65.6 to - 5.5) µg, p = 0.020. The distal-proximal group showed 10% reduction in opioids consumption comparing to both regional and sham groups. Secondary outcomes were comparable among three groups. CONCLUSION: Transcutaneous electrical acupoint stimulation with distal-proximal acupoints combination, compared to regional acupoints combination and sham acupuncture, significantly reduced sufentanil consumption in patients who underwent off-pump coronary artery bypass grafting surgery.

Bletilla striata polysaccharide-coated andrographolide nanomicelles for targeted drug delivery to enhance anti-colon cancer efficacy.

Background: Vitamin E, which is also known as tocopherol, is a compound with a polyphenol structure. Its esterified derivative, Vitamin E succinate (VES), exhibits unique anticancer and healthcare functions as well as immunomodulatory effects. Natural polysaccharides are proved to be a promising material for nano-drug delivery systems, which show excellent biodegradability and biocompatibility. In this study, we employed a novel bletilla striata polysaccharide-vitamin E succinate polymer (BSP-VES) micelles to enhance the tumor targeting and anti-colon cancer effect of andrographolide (AG). Methods: BSP-VES polymer was synthesized through esterification and its structure was confirmed using 1H NMR. AG@BSP-VES was prepared via the dialysis method and the drug loading, entrapment efficiency, stability, and safety were assessed. Furthermore, the tumor targeting ability of AG@BSP-VES was evaluated through targeted cell uptake and in vivo imaging. The antitumor activity of AG@BSP-VES was measured in vitro using MTT assay, Live&Dead cell staining, and cell scratch test. Results: In this study, we successfully loaded AG into BSP-VES micelles (AG@BSP-VES), which exhibited good stability, biosafety and sustained release effect. In addition, AG@BSP-VES also showed excellent internalization capability into CT26 cells compared with NCM460 cells in vitro. Meanwhile, the specific delivery of AG@BSP-VES micelles into subcutaneous and in-situ colon tumors was observed compared with normal colon tissues in vivo during the whole experiment process (1-24 h). What's more, AG@BSP-VES micelles exhibited significant antitumor activities than BSP-VES micelles and free AG. Conclusion: The study provides a meaningful new idea and method for application in drug delivery system and targeted treatment of colon cancer based on natural polysaccharides.

A case report of pulmonary atresia with intact ventricular septum: an extraordinary finding of subsystemic right ventricle.

Background: Massive tricuspid regurgitation (TR) is the most common feature of pulmonary atresia with intact ventricular septum (PA/IVS), and mild or absent TR is observed in severe right ventricular (RV) dysplasia or RV-to-coronary fistulous connections, resulting in non-biventricular (BV) outcomes postnatally. Case summary: We report a case of fetal severe pulmonary stenosis with IVS diagnosed at 26 weeks of gestation. The severity of RV hypoplasia did not worsen or reach indications for intrauterine intervention, while the jet velocity of TR decreased significantly during pregnancy. The fetus was definitely diagnosed with PA/IVS with mild RV dysplasia after birth. Unusually, the fetus did not experience severe TR and myocardial sinusoids, the TR jet velocity was maintained at 2.0 m/s, and the coronary artery was almost normal. The incapable RV cannot pump blood into pulmonary circulation after RV decompression from valvular perforation and balloon dilation. It may be an extraordinary finding of subsystemic RV. Conclusion: PA/IVS is a heterogeneous disease with various degrees of RV dysplasia. Mild or no baseline TR is a reliable indicator with non-BV outcomes for fetal PA/IVS, even with acceptable dysplasia RV structures.

Inhaled Nitric Oxide ReDuce postoperatIve pulmoNAry complicaTions in patiEnts with recent COVID-19 infection (INORDINATE): protocol for a randomised controlled trial.

BACKGROUND: A history of SARS-CoV-2 infection has been reported to be associated with an increased risk of postoperative pulmonary complications (PPCs). Even mild PPCs can elevate the rates of early postoperative mortality, intensive care unit (ICU) admission and prolong the length of ICU and/or hospital stays. Consequently, it is crucial to develop perioperative management strategies that can mitigate these increased risks in surgical patients who have recently been infected with SARS-CoV-2. Accumulating evidence suggests that nitric oxide (NO) inhalation might be effective in treating COVID-19. NO functions in COVID-19 by promoting vasodilation, anticoagulation, anti-inflammatory and antiviral effects. Therefore, our study hypothesises that the perioperative use of NO can effectively reduce PPCs in patients with recent SARS-CoV-2 infection. METHOD AND ANALYSIS: A prospective, double-blind, single-centre, randomised controlled trial is proposed. The trial aims to include participants who are planning to undergo surgery with general anaesthesia and have been recently infected with SARS-CoV-2 (within 7 weeks). Stratified allocation of eligible patients will be performed at a 1:1 ratio based on the predicted risk of PPCs using the Assess Respiratory Risk in Surgical Patients in Catalonia risk index and the time interval between infection and surgery.The primary outcome of the study will be the presence of PPCs within the first 7 days following surgery, including respiratory infection, respiratory failure, pleural effusion, atelectasis, pneumothorax, bronchospasm and aspiration pneumonitis. The primary outcome will be reported as counts (percentage) and will be compared using a two-proportion χ2 test. The common effect across all primary components will be estimated using a multiple generalised linear model. ETHICS AND DISSEMINATION: The trial is approved by the Institutional Review Board of Xijing Hospital (KY20232058-F1). The findings, including positive, negative and inconclusive results, will be published in scientific journals with peer-review processes. TRIAL REGISTRATION NUMBER: NCT05721144.

Explanatory deep learning to predict elevated pulmonary artery pressure in children with ventricular septal defects using standard chest x-rays: a novel approach.

Objective: Early risk assessment of pulmonary arterial hypertension (PAH) in patients with congenital heart disease (CHD) is crucial to ensure timely treatment. We hypothesize that applying artificial intelligence (AI) to chest x-rays (CXRs) could identify the future risk of PAH in patients with ventricular septal defect (VSD). Methods: A total of 831 VSD patients (161 PAH-VSD, 670 nonPAH-VSD) was retrospectively included. A residual neural networks (ResNet) was trained for classify VSD patients with different outcomes based on chest radiographs. The endpoint of this study was the occurrence of PAH in VSD children before or after surgery. Results: In the validation set, the AI algorithm achieved an area under the curve (AUC) of 0.82. In an independent test set, the AI algorithm significantly outperformed human observers in terms of AUC (0.81 vs. 0.65). Class Activation Mapping (CAM) images demonstrated the model's attention focused on the pulmonary artery segment. Conclusion: The preliminary findings of this study suggest that the application of artificial intelligence to chest x-rays in VSD patients can effectively identify the risk of PAH.

Hepatocyte growth factor is protective in early stage but bone-destructive in late stage of experimental periodontitis.

BACKGROUND AND OBJECTIVE: Clinical studies found high levels of hepatocyte growth factor (HGF) expression in patients with periodontitis. Studies suggest that HGF plays an important role in periodontitis, is involved in inflammation, and modulates alveolar bone integrity in periodontitis. This study aims to investigate the effects and mechanisms of HGF in the progression of experimental periodontitis. METHODS: We used silk thread ligation to induce periodontitis in HGF-overexpressing transgenic (HGF-Tg) and wild-type C57BL/6J mice. The effects of HGF overexpression on alveolar bone destruction were assessed by microcomputed tomography imaging at baseline and on days 7, 14, 21, and 28. We analyzed the cytokines (IL-6 and TNF-α) and lymphocytes in periodontitis tissues by enzyme-linked immunosorbent assay and flow cytometry. The effects of HGF on alveolar bone destruction were further tested by quantifying the systemic bone metabolism markers CTXI and PINP and by RNA sequencing for the signaling pathways involved in bone destruction. Western blotting and immunohistochemistry were performed to further elucidate the involved signaling pathways. RESULTS: We found that experimental periodontitis increased HGF production in periodontitis tissues; however, the effects of HGF overexpression were inconsistent with disease progression. In the early stage of periodontitis, periodontal inflammation and alveolar bone destruction were significantly lower in HGF-Tg mice than in wild-type mice. In the late stage, HGF-Tg mice showed higher inflammatory responses and progressively aggravated bone destruction with continued stimulation of inflammation. We identified the IL-17/RANKL/TRAF6 pathway as a signaling pathway involved in the HGF effects on the progression of periodontitis. CONCLUSION: HGF plays divergent effects in the progression of experimental periodontitis and accelerates osteoclastic activity and bone destruction in the late stage of inflammation.

Genetic identification of familial hypercholesterolemia within whole genome sequences in 6820 newborns.

Familial hypercholesterolemia (FH) is defined as a monogenic disease, characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels. FH remains underdiagnosed and undertreated in Chinese. We whole-genome sequenced 6820 newborns from Qingdao of China to investigate the FH-related gene (LDLR, APOB, PCSK9) mutation types, carrier ratio and genotype-phenotype correlation. In this study, the prevalence of FH in Qingdao of China was 0.47% (95% CI: 0.32%-0.66%). The plasma lipid levels of FH-related gene mutation carriers begin to increase as early as infant. T-CHO and LDL-C of FH infants was higher by 48.1% (p < 0.001) and 42.9% (p < 0.001) relative to non-FH infants. A total of 22 FH infants and their parent participate in further studies. The results indicated that FH infant parent noncarriers have the normal plasma lipid level, while T-CHO and LDL-C increased in FH infants and FH infant parent carriers, but no difference between the groups. This highlights the importance of genetic factors. In conclusion, the spectrum of FH-causing mutations in the newborns of Qingdao, China was described for the first time. These data can serve as a considerable dataset for next-generation sequencing analysis of the Chinese population with FH and potentially helping reform regional policies for early detection and prevention of FH.

Role and mechanism of miR-871-3p/Megf8 in regulating formaldehyde-induced cardiomyocyte inflammation and congenital heart disease.

OBJECTIVE AND DESIGN: We aimed to investigate the molecular mechanism underlying formaldehyde (FA)-induced congenital heart disease (CHD) using in vitro and in vivo models. MATERIALS AND SUBJECTS: Neonatal rat heart tissues and H9C2 cells were used for in vitro studies, while FA-exposed new-born rats were used for in vivo studies. TREATMENT: H9C2 cells were exposed to FA concentrations of 0, 50, 100 and 150 µM/mL for 24 h. METHODS: Whole transcriptome gene sequencing identified differentially expressed miRNAs in neonatal rat heart tissues, while Real-time quantitative PCR (RT-qPCR) assessed miR-871-3p and Megf8 expression. RNA pull-down and dual-luciferase reporter assays determined miR-871-3p and Megf8 relationships. Inflammatory cytokine expression was assessed by western blotting. A FA-induced CHD model was used to validate miR-871-3p regulatory effects in vivo. RESULTS: We identified 89 differentially expressed miRNAs, with 28 up-regulated and 61 down-regulated (fold change ≥ 2.0, P < 0.05). Inflammation (interleukin) and signalling pathways were found to control FA-induced cardiac dysplasia. miR-871-3p was upregulated in FA-exposed heart tissues, modulated inflammation, and directly targeted Megf8. In vivo experiments showed miR-871-3p knockdown inhibited FA-induced inflammation and CHD. CONCLUSION: We demonstrated miR-871-3p's role in FA-induced CHD by targeting Megf8, providing potential targets for CHD intervention and improved diagnosis and treatment strategies.

Rescue angioplasty and/or stenting after mechanical thrombectomy: who can benefit?

BACKGROUND: Angioplasty and/or stenting is a rescue therapy for mechanical thrombectomy (MT) in acute intracranial large vessel occlusion. This study was undertaken to determine whether rescue angioplasty and/or stenting improves the outcome after MT and to investigate whether outcomes differ by subgroup of rescue indication. METHODS: We performed propensity score matching (PSM) with data from a prospective multicenter registry of patients with acute large vessel occlusion receiving endovascular treatment. Patients were divided into the MT alone group and the MT with rescue therapy group. The primary outcome was functional independence (modified Rankin Scale score of 0-2) at 90 days. PSM was also performed in the failed MT (modified Thrombolysis In Cerebral Infarction (mTICI) 0-2a) and the residual severe stenosis (mTICI 2b-3) subgroups, respectively. RESULTS: 326 patients of mean±SD age 62.7±12.0 years (90 women, 27.6%) were matched from 1274 patients. In the matched cohort, functional independence at 90 days was higher in the rescue therapy group than in the MT alone group (44.2% vs 29.5%; OR 1.90, 95% CI 1.18 to 3.06, P=0.008). In the failed MT subgroup with 66 matched pairs, more patients had functional independence in the rescue therapy group than in the MT alone group (39.0% vs 17.0%; OR 3.12, 95% CI 1.29 to 7.59, P=0.01). In the residual stenosis subgroup with 63 matched pairs, functional independence rates were similar in the rescue therapy and the MT alone groups (51.6% vs 55.7%; OR 0.85, 95% CI 0.42 to 1.72, P=0.65). CONCLUSION: Rescue angioplasty and/or stenting could improve the clinical outcome in patients with acute large vessel occlusion with failed MT, while no benefit was seen in those with residual severe stenosis but substantial reperfusion.

The transcription factor TBP promotes hepatocellular carcinoma progression by activating AKT3.

The present work was performed to clarify the role of TATA-binding protein (TBP) in hepatocellular carcinoma (HCC). TBP expression in adjacent liver tissues and HCC tissue sample was detected by immunohistochemistry and qRT-PCR. With CCK-8, BrdU, flow cytometry, and transwell assays, the malignancy of cancer cell lines were evaluated. The binding sites of TBP and AKT serine/threonine kinase 3 (Akt3) promoter region were predicted by PROMO database, and the binding relationship between TBP and AKT3 promoter was verified with dual luciferase reporter gene assay and ChIP-qPCR assay. The effect of TBP on AKT3 expression was examined by immunoblotting. The signaling pathways associated with AKT3 were predicted by gene set enrichment analysis (GSEA) with LinkedOmics database. It was revealed that, TBP expression in HCC tissues and cell lines was up-regulated, which was associated with the short survival time of patients. Up-regulation of TBP promoted the viability and aggressiveness of HCC cells, while knockdown of TBP had opposite effects. TBP could bind with AKT3 promoter region, and TBP overexpression promoted the expression of AKT3, while its knockdown worked oppositely. Additionally, TBP/AKT3 axis modulated mTOR expression in HCC cells. In conclusion, TBP promotes the transcription of AKT3, thus accelerating the malignant progression of HCC.

[Role and mechanisms of CHI3L1 in coronary artery lesions in a mouse model of Kawasaki disease-like vasculitis]. / CHI3L1åœ¨å·å´Žç— æ ·è¡€ç®¡ç‚Žå°é¼ æ¨¡åž‹å† çŠ¶åŠ¨è„‰æŸä¼¤ä¸­çš„ä½œç”¨åŠæœºåˆ¶ç ”ç©¶.

OBJECTIVES: To explore the role and potential mechanisms of chitinase-3-like protein 1 (CHI3L1) in coronary artery lesions in a mouse model of Kawasaki disease (KD)-like vasculitis. METHODS: Four-week-old male SPF-grade C57BL/6 mice were randomly divided into a control group and a model group, with 10 mice in each group. The model group mice were intraperitoneally injected with 0.5 mL of lactobacillus casei cell wall extract (LCWE) to establish a mouse model of KD-like vasculitis, while the control group mice were injected with an equal volume of normal saline. The general conditions of the mice were observed on the 3rd, 7th, and 14th day after injection. Changes in coronary artery tissue pathology were observed using hematoxylin-eosin staining. The level of CHI3L1 in mouse serum was measured by enzyme-linked immunosorbent assay. Immunofluorescence staining was used to detect the expression and localization of CHI3L1, von Willebrand factor (vWF), and α-smooth muscle actin (α-SMA) in coronary artery tissue. Western blot analysis was used to detect the expression of CHI3L1, vWF, vascular endothelial cadherin (VE cadherin), Caspase-3, B cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), nuclear factor κB (NF-κB), and phosphorylated NF-κB (p-NF-κB) in coronary artery tissue. RESULTS: The serum level of CHI3L1 in the model group was significantly higher than that in the control group (P<0.05). Compared to the control group, the expression of CHI3L1 in the coronary artery tissue was higher, while the expression of vWF was lower in the model group. The relative expression levels of CHI3L1, Bax, Caspase-3, NF-κB, and p-NF-κB were significantly higher in the model group than in the control group (P<0.05). The relative expression levels of vWF, VE cadherin, and Bcl-2 were lower in the model group than in the control group (P<0.05). CONCLUSIONS: In the LCWE-induced mouse model of KD-like vasculitis, the expression levels of CHI3L1 in serum and coronary arteries increase, and it may play a role in coronary artery lesions through endothelial cell apoptosis mediated by inflammatory reactions.

Tranexamic acid in patients with post-traumatic elbow stiffness: protocol for a randomised, double-blind, placebo-controlled trial investigating the effectiveness of tranexamic acid at reducing the recurrence of heterotopic ossification after open elbow arthrolysis.

INTRODUCTION: Exaggerated inflammatory response is one of the main mechanisms underlying heterotopic ossification (HO). It has been suggested that the antifibrinolytic drug tranexamic acid (TXA) can exert a significant anti-inflammatory effect during orthopaedic surgery. However, no prospective studies have yet investigated the effects of TXA on HO recurrence in patients following open elbow arthrolysis (OEA). METHODS AND ANALYSIS: Here, we present a protocol for a single-centre, randomised, double-blind, placebo-controlled trial to investigate the effectiveness of TXA on HO recurrence after OEA in a single hospital. A minimum sample size of 138 eligible and consenting participants randomised into treatment and control groups in a 1:1 manner will be included. Patients will receive 2 g of intravenous TXA (experimental group) or placebo (normal saline, control group) administered before skin incision. The primary outcome is HO recurrence rate within 12 months after surgery. The secondary outcomes are the serum immune-inflammatory cytokines including erythrocyte sedimentation rate, C reactive protein, interleukin (IL)-6, IL-1ß, IL-13 at the first and third day postoperatively, and elbow range of motion and functional score at 1.5, 6, 9 and 12 months after surgery. After completion of the trial, the results will be reported in accordance with the extensions of the Consolidated Standards of Reporting Trials Statement for trials. The results of this study should determine whether TXA can reduce the rates of HO occurrence after OEA. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Medical Ethics Committee of the Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (reference number 2022-123-(1)). The results of this study will be disseminated through presentations at academic conferences and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2300068106.

Association Between Loop Diuretics and Mortality in Patients With Cardiac Surgery-Associated Acute Kidney Injury: A Retrospective Propensity Score-Weighted Analysis.

BACKGROUND: Although loop diuretics (LDs) have been widely used in clinical practice, their effect on mortality when administered to patients experiencing cardiac surgery-associated acute kidney injury (CS-AKI) remains unknown. The study aimed to investigate the effectiveness of LD use in patients with CS-AKI. METHODS: Patients who underwent cardiac surgery with AKI were identified from the Medical Information Mart for Intensive Care III. Postoperative LD use in intensive care units (ICUs) was exposure. There were 2 primary outcome measures, the in-hospital mortality and ICU mortality; both were treated as time-to-event data and were analyzed via multivariable Cox proportional hazard models. Inverse probability weighting (IPW) was used to minimize bias. RESULTS: The study enrolled a total of 5478 patients, with a median age of 67 years, among which 2205 (40.3%) were women. The crude in-hospital and ICU mortality rates were significantly lower in the LD use group (525 of 4150 [12.7%] vs 434 of 1328 [32.7%], P < .001; 402 of 4150 [9.69%] vs 333 of 1328 [25.1%], P < .001). Adjusted hazard ratios suggested significant reductions in both in-hospital (hazard ratio [HR], 0.428; 95% confidence interval [CI], 0.374-0.489) and ICU mortality (HR, 0.278; 95% CI, 0.238-0.327). The IPW data showed a similar reduction, in-hospital mortality (HR, 0.434; 95% CI, 0.376-0.502) and ICU mortality (HR, 0.296; 95% CI, 0.251-0.349). Such association may act differently for patients with different fluid balance (P value for interaction < .001). CONCLUSIONS: LD use is associated with lower hospital and ICU mortality in CS-AKI patients in general. Patients under different conditions showed diverse responses toward such treatment indicating that personalized management is needed.

Ropivacaine Promotes Axon Regeneration by Regulating Nav1.8-mediated Macrophage Signaling after Sciatic Nerve Injury in Rats.

BACKGROUND: Continuous nerve block with ropivacaine is commonly performed after repair surgery for traumatic peripheral nerve injuries. After peripheral nerve injury, tetrodotoxin-resistant voltage-gated sodium channel Nav1.8 is upregulated and contributes to macrophage inflammation. This study investigated whether ropivacaine promotes peripheral nerve regeneration through Nav1.8-mediated macrophage signaling. METHODS: A sciatic nerve transection-repair (SNT) model was established in adult Sprague-Dawley rats of both sexes. The rats received 0.2% ropivacaine or 10 µM Nav1.8-selective inhibitor A-803467 around the injured site or near the sacrum for 3 days. Nerve regeneration was evaluated using behavioral, electrophysiologic, and morphological examinations. Moreover, myelin debris removal, macrophage phenotype, Nav1.8 expression, and neuropeptide expression were assessed using immunostaining, enzyme-linked immunosorbent assay, and Western blotting. RESULTS: Compared to the SNT-plus-vehicle group, the sensory, motor, and sensory-motor coordination functions of the two ropivacaine groups were significantly improved. Electrophysiologic (mean ± SD: recovery index of amplitude, vehicle 0.43 ± 0.17 vs. ropivacaine 0.83 ± 0.25, n = 11, P < 0.001) and histological analysis collectively indicated that ropivacaine significantly promoted axonal regrowth (percentage of neurofilament 200 [NF-200]-positive area: vehicle 19.88 ± 2.81 vs. ropivacaine 31.07 ± 2.62, n = 6, P < 0.001). The authors also found that, compared to the SNT-plus-vehicle group, the SNT-plus-ropivacaine group showed faster clearance of myelin debris, accompanied by significantly increased macrophage infiltration and transition from the M1 to M2 phenotype. Moreover, ropivacaine significantly attenuated Nav1.8 upregulation at 9 days after sciatic nerve transection (vehicle 4.12 ± 0.30-fold vs. ropivacaine 2.75 ± 0.36-fold, n = 5, P < 0.001), which coincided with the increased expression of chemokine ligand 2 and substance P. Similar changes were observed when using the selective Nav1.8 channel inhibitor A-803467. CONCLUSIONS: Continuous nerve block with ropivacaine promotes the structural and functional recovery of injured sciatic nerves, possibly by regulating Nav1.8-mediated macrophage signaling.

FUNDC2, a mitochondrial outer membrane protein, mediates triple-negative breast cancer progression via the AKT/GSK3ß/GLI1 pathway.

Triple-negative breast cancer (TNBC) lacks effective therapeutic targets and has a poor prognosis, easy recurrence and metastasis. It is urgent and important to explore TNBC treatment targets. Through mass spectrometry combined with qRT-PCR validation in luminal A cells and TNBC cells, high-content screening and clinical sample analysis, FUNDC2 was discovered as a novel target. The function of the outer mitochondrial membrane protein FUNDC2 in breast cancer is still unclear. In this study, we find that FUNDC2 expression in TNBC tissues is significantly higher than that in luminal subtype breast cancer tissues. FUNDC2 silencing in TNBC cells significantly reduces cell proliferation, migration and invasion. As demonstrated in vivo using subcutaneous tumor xenografts in mice, FUNDC2 suppression significantly inhibits tumor growth. The underlying mechanism might be mediated by inactivating its downstream signal AKT/GSK3ß and GLI1, a key factor of the Hedgehog signaling pathway. Therefore, FUNDC2 may promote TNBC progression and provide a therapeutic target for treating TNBC.

Impact of SARS-CoV-2 infection on postoperative complications of patients undergoing surgery after general outbreak in China: a protocol for multicentre prospective cohort study.

INTRODUCTION: There is currently limited evidence addressing perioperative prognosis of surgical patients during COVID-19 pandemic; especially targeting on the Chinese population since the wave in 2022. Considering a distinct feature from the rest of the world demonstrated and the fast mutation and spread of the virus, evidence most relevant to China is urgently in need. The objective of this study is to seek for supporting evidence via evidence-based risk evaluations for postoperative complications to accumulate experience for coming infection waves. METHODS AND ANALYSIS: This protocol proposes a multicentral, prospective, observational cohort study aiming to explore the link between SARS-CoV-2 infection and postoperative complications among surgical patients under general or regional anaesthesia between 16 January 2023 and 31 December 2023. A retrospective cohort covering the same period in 2019 is extracted for historic reference. Data are extracted from the health information system and anaesthesia information management system. The COVID-19 information is collected via an online survey. Missing values in weight or height will be imputed by each other with age and gender via multiple imputation. Other missing values will not be handled specially. Standard descriptive statistics will be reported followed by statistical modelling. Binomial regression with logit link is used for binary outcome. The time-to-event outcome is analysed using Cox regression with discharge from hospital further treated as a competing state. Hierarchical models will be assessed to account for temporal or central random effects. Temporal trends will be displayed with future expectations. ETHICS AND DISSEMINATION: Ethical approval is obtained from the ethical committee in Xijing Hospital (No. KY20232002-C-1); approvals are expected for each participating institute. Verbal consent will be informed and obtained prior to online survey collection. Personal information remains confidential, and publications will be deidentified. TRIAL REGISTRATION NUMBER: NCT05677815.

Enhancement of recombinant human interleukin-22 production by fusing with human serum albumin and supplementing N-acetylcysteine in Pichia Pastoris.

Interleukin-22 (IL-22) plays an important role in the treatment of organ failure, which can induce anti-apoptotic and proliferative signaling pathways; Nevertheless, the practical utilization of IL-22 is hindered by the restricted efficacy of its production. Pichia pastoris presents a viable platform for both industrial and pharmaceutical applications. In this study, we successfully generated a fusion protein consisting of truncated human serum albumin and human IL-22 (HSA-hIL-22) using P. pastoris, and examined the impact of antioxidants on HSA-hIL-22 production. We have achieved the production of HSA-hIL-22 in the culture medium at a yield of approximately 2.25 mg/ml. Moreover, 0-40 mM ascorbic acid supplementation did not significantly affect HSA-hIL-22 production or the growth rate of the recombinant strain. However, 80 mM ascorbic acid treatment had a detrimental effect on the expression of HSA-hIL-22. In addition, 5-10 mM N-acetyl-l-cysteine (NAC) resulted in an increase of HSA-hIL-22 production, accompanied by a reduction in the growth rate of the recombinant strain. Conversely, 20-80 mM NAC supplementation inhibited the growth of the recombinant strains and reduced intact HSA-hIL-22 production. However, neither NAC nor ascorbic acid exhibited any effect on superoxide dismutase (SOD) and malondialdehyde (MDA) levels, except that NAC increased GSH content. Furthermore, our findings indicate that recombinant HSA-hIL-22, which demonstrated the ability to stimulate the proliferation of HepG2 cells, possesses bioactivity. In addition, NAC did not affect HSA-hIL-22 bioactivity. In conclusion, our study demonstrates that NAC supplementation can enhance the secretion of functional HSA-hIL-22 proteins produced in P. pastoris without compromising their activity.

Fabrication and Biological Activities of All-in-One Composite Nanoemulsion Based on Blumea balsamifera Oil-Tea Tree Oil.

Nanoemulsion is a new multi-component drug delivery system; the selection of different oil phases can give it special physiological activity, and play the role of "medicine and pharmaceutical excipients all-in-one". In this paper, we used glycyrrhizic acid as the natural surfactant, and Blumea balsamifera oil (BB) and tea tree oil (TTO) as the mixed oil phase, to obtain a new green functional composite nanoemulsion. Using the average particle size and polydispersion index (PDI) as the evaluation criteria, the effects of the oil ratio, oil content, glycyrrhizic acid concentration, and ultrasonic time on the nanoemulsion were systematically investigated. The stability and physicochemical properties and biological activities of BB-TTO NEs prepared via the optimum formulation were characterized. The optimal prescription was BB: TTO = 1:1, 5% oil phase, 0.7% glycyrrhizic acid, and 5 min ultrasonication time. The mean particle size, PDI, and zeta potential were 160.01 nm, 0.125, and -50.94 mV, respectively. The nanoemulsion showed non-significant changes in stability after centrifugation, dilution, and 120 days storage. These nanoemulsions were found to exhibit potential antibacterial and anti-inflammatory activities. The minimal inhibitory concentration (MIC) of BB-TTO NEs against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa is 2975 µg/mL, 2975 µg/mL, and 5950 µg/mL, respectively. A lower level of inflammatory cell infiltration and proportion of fibrosis were found in the synovial tissue of AIA rats treated with BB-TTO NEs. These findings demonstrate that the BB-TTO NEs produced in this study have significant potential for usage in antibacterial and anti-inflammatory areas.

Early Posttraumatic Antifibrinolysis Reduces Perioperative Hidden Blood Loss in Elderly Patients with an Intertrochanteric Fracture: A Randomized Controlled Trial.

BACKGROUND: This study aimed to determine the efficacy and safety of posttraumatic antifibrinolysis with multidose tranexamic acid (TXA) in reducing perioperative hidden blood loss (HBL) in elderly intertrochanteric fracture patients. METHOD: Ninety-six elderly intertrochanteric fracture patients admitted to our department from June 2021 to September 2022 were randomized into two groups. The control group (Group A) received 100 mL of normal saline, while the experimental group (Group B) received 1.5 g of TXA intravenously q12 h from postadmission Day 1 (PAD1) to the day before surgery, and both groups received 1.5 g of TXA q12 h from postoperative Day 1 (POD1) to POD3. Haemoglobin (Hb), haematocrit (Hct), coagulation parameters, fibrinogen degradation product (FDP), and D-dimer (D-D) were recorded from PAD1 to POD3. HBL was calculated using the gross formula and recorded as the primary outcome. RESULT: In all-over analyses, the patients in Group B had lower perioperative HBL (on PAD3, POD1, and POD3), preoperative HBL (HBLpre), decline of haemoglobin (ΔHb-on PAD3), allogeneic blood transfusion (ABT) rate, FDP (on PAD3), and D-D (on PAD3) compared with Group A. No significant differences were exhibited in postoperative HBL (HBLpost) between the 2 groups. In subgroup analyses, for patients who received intervention within 24 h, the result is consistent with the whole. For patients who received intervention over 72 h of injury, there were no significant differences in perioperative HBL, ΔHb, ABT rate, FDP, and D-D between the 2 groups. There were no significant differences in APTT, PT, the rate of venous thromboembolism, wound complications, or 90-day mortality between the 2 groups. CONCLUSION: For elderly intertrochanteric fracture patients, early posttraumatic antifibrinolysis with multidose TXA is effective in reducing perioperative HBL, which mainly manifests as the reduction of preoperative HBL, especially for patients injured within 24 h. Application of TXA beyond 72 h of injury was ineffective.

The crosstalk between M1 macrophage polarization and energy metabolism disorder contributes to polystyrene nanoplastics-triggered testicular inflammation.

Ubiquitous microplastics have become a threat to animal and human health, due to their potential toxicity, persistent nature and consequent bioaccumulation. Supporting evidence elucidates that polystyrene nanoplastics (PS-NPs) can destroy blood-testis barrier integrity, thus causing testicular hypoplasia and impairment of spermatogenesis. Nevertheless, how PS-NPs modulate macrophage polarization-energy metabolism crosstalk has not been fully investigated in testicular tissue. Here, we observed that polystyrene PS-NPs exposure contributes to severe vacuolization in the seminiferous tubules, accompanied by apoptosis of testicular tissue and infiltration of M1 macrophages. Meanwhile, we found that PS-NPs could trigger the M1 polarization phenotype, which activated ROS-macrophage migration inhibitory factor (MIF)/NF-κB signaling that in turn induced apoptosis of GC2 cells in the GC2-macrophage cell coculture model. Simultaneously, we confirmed that PS-NPs exposure increased 3-phospho-D-glycerate, phosphoenolpyruvate and lactate concentrations, accompanied by decreased pyruvate and adenosine triphosphate (ATP) production, likely due to downregulated pyruvate kinase M2 (PKM2) dimer expression. In conclusion, the mechanism of PS-NPs-induced testicular inflammation can be mediated by promoting the infiltration of M1 macrophages, thereby resulting in an ROS burst and subsequent induction of energy metabolism disorders. The current study will provide new insights into PS-NPs-induced male reproductive toxicity and highlight the context-specific roles of testicular macrophages.