The protective effects of ruscogenin against lipopolysaccharide-induced myocardial injury in septic mice.

ABSTRACT: Sepsis-induced myocardial dysfunction (SIMD) commonly occurs in individuals with sepsis and is a severe complication with high morbidity and mortality rates. The current study aimed to investigate the effects and potential mechanisms of the natural steroidal sapogenin ruscogenin (RUS) against lipopolysaccharide (LPS)-induced myocardial injury in septic mice. We found that RUS effectively alleviated myocardial pathological damage, normalized cardiac function, and increased survival in septic mice. RNA sequencing (RNA-seq) demonstrated that RUS administration significantly inhibited the activation of the NOD-like receptor signaling pathway in the myocardial tissues of septic mice. Subsequent experiments further confirmed that RUS suppressed myocardial inflammation and pyroptosis during sepsis. Additionally, cultured HL-1 cardiomyocytes were challenged with LPS, and we observed that RUS could protect these cells against LPS-induced cytotoxicity by suppressing inflammation and pyroptosis. Notably, both the in vivo and in vitro findings indicated that RUS inhibited NLRP3 upregulation in cardiomyocytes stimulated with LPS. As expected, knockdown of NLRP3 blocked the LPS-induced activation of inflammation and pyroptosis in HL-1 cells. Furthermore, the cardioprotective effects of RUS on HL-1 cells under LPS stimulation were abolished by the novel NLRP3 agonist BMS-986299. Taken together, our results suggest that RUS can alleviate myocardial injury during sepsis, at least in part by suppressing NLRP3-mediated inflammation and pyroptosis, highlighting the potential of this molecule as a promising candidate for SIMD therapy.

Caffeic acid attenuates tissue damage and inflammatory response in Klebsiella pneumonia by modulating AhR-Src-STAT3-IL-10 signaling pathway.

CA is a plant derivative with antibacterial and antiviral pharmacological effects, however, the therapeutic effect of CA on Klebsiella pneumonia and its mechanism study is still unclear. A rat KP model was established in vitro, a pneumonia cell model was established in vivo, the histopathological changes in the lungs were observed by HE staining after CA treatment, the expression of relevant inflammatory factors was detected by ELISA, the changes in the expression of proteins related to the AhR-Src-STAT3-IL-10 signaling pathway were detected by Western blot and immunofluorescence in the lungs, and the interactions between the proteins were verified by COIP relationship. The results showed that CA was able to attenuate the injury and inflammatory response of lung tissues, and molecular docking showed that there were binding sites between CA and AhR, and COIP demonstrated that AhR interacted with both STAT3 and Ser. In addition, CA was able to up-regulate the expression levels of pathway-related proteins of AhR, IL-10, p-Src, and p-STAT3, and AhR knockdown was able to reduce LPS-induced inflammatory responses and up-regulate pathway-related proteins, whereas CA treatment of AhR-knockdown-treated A549 cells did not show any statistically significant difference compared with the AhR knockdown group, demonstrating that CA exerts its pharmacological effects. These findings elucidated the mechanism of CA in the treatment of KP and demonstrated that CA is a potential therapeutic agent for KP.

Endoscopic retrograde cholangiopancreatography for diagnosing and treating pediatric biliary and pancreatic diseases.

BACKGROUND: This study evaluated the safety and effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) in pediatric patients with biliary and pancreatic diseases. A retrospective analysis was conducted on 57 ERCP procedures performed in 41 children, primarily for treating pancreatic diseases. The overall success rate was 91.2%, with no major complications observed. Post-ERCP pancreatitis (PEP) occurred in 8.8% of cases. Follow-up examinations over one year showed no recurrence of biliary or pancreatic diseases. Notably, endoscopic treatment led to a significant increase in body mass index (BMI). These findings demonstrate the valuable role of ERCP in managing such conditions. AIM: To evaluate the safety and efficacy of ERCP for the management of biliary and pancreatic diseases in pediatric patients. METHODS: We conducted a retrospective analysis of data from children aged 1-18 years who underwent ERCP for biliary and pancreatic diseases at Beijing Children's Hospital between January 2021 and December 2022. The collected data included procedure time, endoscopic treatment, success rate, and postoperative complications. RESULTS: Forty-one children underwent 57 ERCP procedures, including 14 with biliary duct disease and 27 with pancreatic disease. The mean age of the patients was 7.48 ± 3.48 years. Biliary duct-related treatments were performed 18 times, and pancreatic disease treatments were performed 39 times. ERCP was primarily used to treat pediatric pancreatic diseases [68.4% (39/57) of the procedures]. The overall success rate was 91.2% (52/57 patients). PEP was noted in five patients (8.8%, 5/57), and no instances of bleeding, perforation, or cholangitis were observed. The patients were followed up for over one year, and no recurrence of biliary or pancreatic diseases was detected. Importantly, BMI significantly increased after endoscopic treatment compared to that before treatment (P = 0.001). CONCLUSION: The high success rate and lack of major complications support the valuable role of ERCP in the management of pediatric biliary and pancreatic diseases in the pediatric population.

Liquid nitrogen frozen cells for chemotherapy drug delivery and vaccination of melanoma.

PURPOSE: Cancer vaccine (CV) has thrived as a promising tool for cancer prevention and treatment. However, how to maintain the integrity and diversity of individualized vaccine antigens and activate the adaptive immune system is still challenging. METHODS: Herein, a preventive and therapeutic vaccine platform for in situ effective multi-model synergistic therapy is developed. In our study, we process B16F10 cells by liquid nitrogen frozen (LNF) to obtain LNF cells, the characterization of LNF cells were conducted. Moreover,  the anti-tumor effect and immune activation ability were studied, and the role as a CV were investigated. RESULTS: The LNF cells preserve intact cellular structure and tumor-associated self-antigen gp100. Moreover, LNF cells have the ability of loading and releasing doxorubicin (DOX). Except for the anti-tumor effect of chemotherapy brought by DOX, the LNF cells can promote the maturation of dendritic cells (DCs) and induce immune response by activating CD4+ and CD8+ T cells, particularly with the existence of adjuvant, R848. Specifically, the CD8+ T cells of mice in LNF-DOX/R848 group are 6 times of that in PBS group in tumor microenvironment, and twice in spleen. Therefore, LNF cells can also be utilized as a CV. Vaccination with LNF/R848 cells effectively suppress the tumor growth in mice by fivefold as compared to the control group. CONCLUSION: In this work, we obtain the LNF cells with a simple procedure. The LNF cells not only provides a tumor cells-based multi-modal system for cancer therapy but inspires new insights into future development of individualized CVs strategies. This study processes live B16F10 cells by liquid nitrogen frozen to obtain LNF cells, which preserve cell integrity and homologous targeting ability. The LNF cells can load and deliver drug and can serve as tumor vaccine. Results demonstrated the LNF cells have effective prophylactic ability, and ideal anti-tumor ability with the loaded drug and adjuvant.

Prognostic significance of age on superficial spreading melanoma after resection: lessons from SEER database involving 12 536 patients.

BACKGROUND: This study sought to analyse the impact of elderly age on long-term prognosis of superficial spreading melanoma (SSM) after surgery. METHODS: A population-based cohort of patients undergoing resection for SSM from 2004 to 2015 was collected, using data from National Cancer Institute' Surveillance, Epidemiology, and End Results (SEER)* Stat software. Patients were divided into the non-elderly group (≤70 years) and elderly group (>70 years). Baseline characteristics and long-term survivals were compared between the two groups. A 1:1 propensity score matching (PSM) was used to reduce the risk of bias. The impact of the elderly age on overall survival (OS) and cause-specific mortality (CSM) was estimated by Cox-regression and competing-risk regression models. RESULTS: Among 12 536 patients with SSM after resection included into the cohort, 8664 patients were ≤70 years, and 3872 were >70 years. Patients in the elderly group had higher incidences of multiple tumours, worse tumour stage and infiltration degree, lymphatic metastasis, and larger size of primary lesions. Using PSM, 3581 pairs of patients were created. On matched analysis, the elderly group was associated with worse OS and CSM. On multivariable Cox-regression and competing-risk regression analyses, elderly age was identified as an independent risk factor of OS and CSM after adjusting for other prognostic variables. CONCLUSIONS: The elderly age of patients was independently associated with worse OS and CSM after resection of SSM when baseline and tumour characteristics were balanced. Adjuvant therapy and individualized strategy on follow-up should be made for elderly patients after resection of SSM.

Sintilimab-Induced Diabetic Ketoacidosis in a Patient with Radiation and Multichemorefractory Penile Cancer: A Case Report and Literature Review.

Penile squamous cell carcinoma (PSCC) is a rare disease. The treatment options for advanced penile cancer are often limited, and the prognosis remains poor. We reported a 52-year-old male recurrent and metastatic PSCC patient with high PD-L1 expression (90%) and TMB (14.4 muts/Mb). He had undergone penectomy, bilateral inguinal lymph node dissection, and excision of the abdominal wall mass. Despite cisplatin-based concurrent chemoradiotherapy and sequential chemotherapy with docetaxel plus cisplatin then being carried out, the carcinoma still progressed. The patient then obtained progression-free survival with continuous sintilimab, although he experienced the new onset of ICI-induced diabetes after 24 cycles of sintilimab and required sustained insulin treatment. He had negative type 1 diabetes-associated autoantibodies and the susceptible HLA genotype DR3-DQ2 haplotype. This is the first patient with radiation and multichemorefractory PSCC who has obtained the remarkable anti-tumor effect of partial regression exceeding 32 months during continuous sintilimab and anlotinib treatment.

Two-step artificial intelligence system for endoscopic gastric biopsy improves the diagnostic accuracy of pathologists.

Background: Endoscopic biopsy is the pivotal procedure for the diagnosis of gastric cancer. In this study, we applied whole-slide images (WSIs) of endoscopic gastric biopsy specimens to develop an endoscopic gastric biopsy assistant system (EGBAS). Methods: The EGBAS was trained using 2373 WSIs expertly annotated and internally validated on 245 WSIs. A large-scale, multicenter test dataset of 2003 WSIs was used to externally evaluate EGBAS. Eight pathologists were compared with the EGBAS using a man-machine comparison test dataset. The fully manual performance of the pathologists was also compared with semi-manual performance using EGBAS assistance. Results: The average area under the curve of the EGBAS was 0·979 (0·958-0·990). For the diagnosis of all four categories, the overall accuracy of EGBAS was 86·95%, which was significantly higher than pathologists (P< 0·05). The EGBAS achieved a higher κ score (0·880, very good κ) than junior and senior pathologists (0·641 ± 0·088 and 0·729 ± 0·056). With EGBAS assistance, the overall accuracy (four-tier classification) of the pathologists increased from 66·49 ± 7·73% to 73·83 ± 5·73% (P< 0·05). The length of time for pathologists to manually complete the dataset was 461·44 ± 117·96 minutes; this time was reduced to 305·71 ± 82·43 minutes with EGBAS assistance (P = 0·00). Conclusions: The EGBAS is a promising system for improving the diagnosis ability and reducing the workload of pathologists.

Adipose-Derived Stem Cells Exosomes Improve Fat Graft Survival by Promoting Prolipogenetic Abilities through Wnt/ß-Catenin Pathway.

Autologous fat grafting has been widely used in plastic surgery in recent years, but the unstable retention of fat graft has always been a key clinical problem. Adipose tissue has poor tolerant to ischemia, so the transplanted adipose tissue needs to rebuild blood supply at an early stage in order to survive stably. Our previous study has found that comparing to human foreskin fibroblast exosome (HFF-Exo), human adipose-derived stem cells exosome (hADSC-Exo) can significantly improve the proliferation of vascular endothelial cells and the angiogenic effect of artificial dermal preconstructed flaps. Therefore, the ability of hADSC-Exo to improve the retention of adipose grafts and its potential regenerative mechanism aroused our strong interest. In this study, we applied hADSC-Exo and HFF-Exo to adipose grafts and explored the potential regeneration mechanism through various means such as bioinformatics, immunofluorescence, immunohistochemistry, and adipogenic differentiation. The results showed that hADSC-Exo can significantly promote grafts angiogenesis and adipogenic differentiation of ADSC to improve the retention of fat grafts and may downregulate the Wnt/ß-catenin signaling pathway to promote the adipogenic differentiation. In summary, our results provide a theoretical basis for the clinical translation of hADSC-Exo in fat grafting.

Targeting RAS phosphorylation in cancer therapy: Mechanisms and modulators.

RAS, a member of the small GTPase family, functions as a binary switch by shifting between inactive GDP-loaded and active GTP-loaded state. RAS gain-of-function mutations are one of the leading causes in human oncogenesis, accounting for ∼19% of the global cancer burden. As a well-recognized target in malignancy, RAS has been intensively studied in the past decades. Despite the sustained efforts, many failures occurred in the earlier exploration and resulted in an 'undruggable' feature of RAS proteins. Phosphorylation at several residues has been recently determined as regulators for wild-type and mutated RAS proteins. Therefore, the development of RAS inhibitors directly targeting the RAS mutants or towards upstream regulatory kinases supplies a novel direction for tackling the anti-RAS difficulties. A better understanding of RAS phosphorylation can contribute to future therapeutic strategies. In this review, we comprehensively summarized the current advances in RAS phosphorylation and provided mechanistic insights into the signaling transduction of associated pathways. Importantly, the preclinical and clinical success in developing anti-RAS drugs targeting the upstream kinases and potential directions of harnessing allostery to target RAS phosphorylation sites were also discussed.

Anthrahydroquinone-2-6-disulfonate is a novel, powerful antidote for paraquat poisoning.

Paraquat (PQ) is a widely used fast-acting pyridine herbicide. Accidental ingestion or self-administration via various routes can cause severe organ damage. Currently, no effective antidote is available commercially, and the mortality rate of poisoned patients is exceptionally high. Here, the efficacy of anthrahydroquinone-2-6-disulfonate (AH2QDS) was observed in treating PQ poisoning by constructing in vivo and ex vivo models. We then explored the detoxification mechanism of AH2QDS. We demonstrated that, in a rat model, the PQ concentration in the PQ + AH2QDS group significantly decreased compared to the PQ only group. Additionally, AH2QDS protected the mitochondria of rats and A549 cells and decreased oxidative stress damage, thus improving animal survival and cell viability. Finally, the differentially expressed genes were analysed in the PQ + AH2QDS group and the PQ group by NextGen sequencing, and we verified that Nrf2's expression in the PQ + AH2QDS group was significantly higher than that in the PQ group. Our work identified that AH2QDS can detoxify PQ by reducing PQ uptake and protecting mitochondria while enhancing the body's antioxidant activity.

Observations of linear aggregation behavior in rotifers (Brachionus calyciflorus).

Linear aggregation is present in some animals, such as the coordinated movement of ants and the migration of caterpillars and spinylobsters, but none has been reported on rotifers. The rotifers were collected and clone cultured in the laboratory at 25 ± 1°C, under natural light (light intensity ~130 lx, L:D = 14:10). The culture medium(pH = 7.3) was formulated as described by Suga et al., and rotifers were fed on the micro algae Scenedesmus obliquus grown in HB-4 medium to the exponential growth stage. When density was high (150 individuals ml-1), the behavior of rotifers was observed using a stereo microscope (Motic ES-18TZLED). In this paper, linear aggregation in Brachionus calyciflorus was found for the first time, and experiments were carried out to verify the correlation between linear aggregation and culture density of B. calyciflorus. With the increase of density, the number of aggregations increase, the number of individuals in the aggregation increased, and the maintenance time of the aggregation was also increased. Therefore, we speculate that the formation of aggregates is related to density and may be a behavioral signal of density increase, which may transmit information between density increase and formation of dormant eggs.

Metformin regulates inflammation and fibrosis in diabetic kidney disease through TNC/TLR4/NF-κB/miR-155-5p inflammatory loop.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is significantly increasing worldwide, and the incidence of its complications is also on the rise. One of the main complications of T2DM is diabetic kidney disease (DKD). The glomerular filtration rate (GFR) and urinary albumin creatinine ratio (UACR) increase in the early stage. As the disease progresses, UACR continue to rise and GFR begins to decline until end-stage renal disease appears. At the same time, DKD will also increase the incidence and mortality of cardiovascular and cerebrovascular diseases. At present, the pathogenesis of DKD is not very clear. Therefore, exploration of the pathogenesis of DKD to find a treatment approach, so as to delay the development of DKD, is essential to improve the prognosis of DKD. AIM: To detect the expression of tenascin-C (TNC) in the serum of T2DM patients, observe the content of TNC in the glomerulus of DKD rats, and detect the expression of TNC on inflammatory and fibrotic factors in rat mesangial cells (RMCs) cultured under high glucose condition, in order to explore the specific molecular mechanism of TNC in DKD and bring a new direction for the treatment of DKD. METHODS: The expression level of TNC in the serum of diabetic patients was detected by enzyme-linked immunosorbent assay (ELISA), the protein expression level of TNC in the glomerular area of DKD rats was detected by immunohistochemistry, and the expression level of TNC in the rat serum was detected by ELISA. Rat glomerular mesangial cells were cultured. Following high glucose stimulation, the expression levels of related proteins and mRNA were detected by Western blot and polymerase chain reaction, respectively. RESULTS: ELISA results revealed an increase in the serum TNC level in patients with T2DM. Increasing UACR and hypertension significantly increased the expression of TNC (P < 0.05). TNC expression was positively correlated with glycosylated haemoglobin (HbA1c) level, body mass index, systolic blood pressure, and UACR (P < 0.05). Immunohistochemical staining showed that TNC expression in the glomeruli of rats with streptozotocin-induced diabetes was significantly increased compared with normal controls (P < 0.05). Compared with normal rats, serum level of TNC in diabetic rats was significantly increased (P < 0.05), which was positively correlated with urea nitrogen and urinary creatinine (P < 0.05). The levels of TNC, Toll-like receptor-4 (TLR4), phosphorylated nuclear factor-κB p65 protein (Ser536) (p-NF-κB p65), and miR-155-5p were increased in RMCs treated with high glucose (P < 0.05). The level of TNC protein peaked 24 h after high glucose stimulation (P < 0.05). After TNC knockdown, the levels of TLR4, p-NF-κB p65, miR-155-5p, connective tissue growth factor (CTGF), and fibronectin (FN) were decreased, revealing that TNC regulated miR-155-5p expression through the TLR4/NF-κB p65 pathway, thereby regulating inflammation (NF-κB p65) and fibrosis (CTGF and FN) in individuals with DKD. In addition, metformin treatment may relive the processes of inflammation and fibrosis in individuals with DKD by reducing the levels of the TNC, p-NF-κB p65, CTGF, and FN proteins. CONCLUSION: TNC can promote the occurrence and development of DKD. Interfering with the TNC/TLR4/NF-κB p65/miR-155-5p pathway may become a new target for DKD treatment.

An innovative technique of hydrosurgery in the treatment of osmidrosis.

BACKGROUND: We aimed at evaluating the effects of hydrosurgery and traditional surgical approach with two parallel incisions in the treatment of osmidrosis. METHODS: This prospective study enrolled patients with axillary osmidrosis between January 2015 and November 2016. For hydrosurgery, a 1-cm-long incision was made in the middle of the posterior long axis. The hand piece was turned upside down and processed in a 'W-O' way. For traditional method, two 3-cm-long parallel incisions were made transversely. Patient demographics, complications, duration of procedures and the outcomes were collected and compared. All patients had a follow-up period of 24-36 months. RESULTS: A total of 93 patients were included: 41 patients in hydrosurgery group and 52 patients in traditional method group. No severe complications occurred in the hydrosurgery group, while necrosis occurred in six sides of axillae of traditional surgical group. No recurrence occurred in both groups. Both groups showed similar odor and hair growth reduction rate. Only one in 82 sides occurred slight scar formation, while in traditional group, 22 sides of axillae formed scars (p < .001). CONCLUSIONS: The application of hydrosurgery in the treatment of osmidrosis is efficient and effective. Moreover, it has less postoperative complications, and high patient satisfaction rates.

VASH-1 Regulates Oxidative Stress and Fibrosis in Diabetic Kidney Disease via SIRT1/HIF1α and TGFß1/Smad3 Signaling Pathways.

Aims: To investigate the role of Vasohibin-1 (VASH-1), silence information adjustment factor 2-related enzyme 1 (SIRT1)/hypoxic-inducible factor 1α (HIF1α) and transforming growth factor-ß1 (TGFß1) /Smad3 signaling pathways in oxidative stress and fibrosis of diabetic kidney disease (DKD). Materials and Methods: A diabetic rat model was established in vivo and rat mesangial cells (RMCs) were cultured in vitro with high glucose via transfection with Vash1 small interfering RNA (siRNA), Hif1a siRNA, Sirt1 siRNA and TGFß1/Smad3 pathway inhibitor (SB431542). Renal histology was used to detect renal changes. Real-time PCR and western blot were used to analyze the expression of VASH-1, SIRT1, HIF1α, TGFß1, Smad3, vascular endothelial growth factor (VEGF), connective tissue growth factor (CTGF) and fibronectin (FN). Expression levels of tumor necrosis factor-α (TNFα), TGFß1, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), and malondialdehyde (MDA) in rat tissues and cell culture supernatant were detected by ELISA and chemiluminescence assay, while cell proliferation was detected by CCK-8. Results: The level of VASH-1 in renal tissues of diabetic rats was decreased, while both high glucose and Vash1 siRNA inhibited the expression of VASH-1 and SIRT1, increased the levels of HIF1α, TGFß1, and Smad3 in RMCs, thus up-regulating oxidative stress and fibrosis factors, and abnormally increasing cell proliferation activity (P < 0.05). However, inhibition of SIRT1/HIF1α signaling pathway only reduced TGFß1 and Smad3 (P < 0.05), while VASH-1 remained unchanged (P > 0.05). Conclusion: VASH-1 was under-expressed in renal tissues of diabetic rats and regulated the pathological process of oxidative stress and fibrosis in DKD via downstream SIRT1/HIF1α and TGFß1/Smad3 signaling pathways.

Vaginoplasty With Mesh Autologous Buccal Mucosa in Vaginal Agenesis: A Multidisciplinary Approach and Literature Review.

BACKGROUND: Vaginal agenesis, a rare condition, is treated by various surgical techniques to achieve neovaginal reconstruction. The main difference between the approaches lies in the graft material used to cover the newly formed cavity. OBJECTIVES: The purpose of this retrospective study was to describe the surgical procedure and outcomes of autologous buccal mucosal grafting in neovaginal reconstruction. METHODS: Sixteen patients with vaginal agenesis admitted to our department between January 2016 and January 2019 were included in our study. A reconstruction procedure, described in detail here, involving autologous buccal mucosa as graft material was successfully conducted in all of the patients. Long-term anatomic and functional outcomes were evaluated. RESULTS: The blood loss during operation was estimated to be 15 to 20 mL in all cases. No rectal or bladder injury occurred. The buccal mucosal wound completely healed 10 to 14 days after the operation. All patients had a well-formed neovagina 8 to 10 cm in length, with a mean diameter of >3 finger-breadths. CONCLUSIONS: The application of autologous buccal mucosa in neovaginal construction is a simple procedure. Autologous buccal mucosa is an ideal material to achieve excellent cosmetic and functional results in patients with vaginal agenesis.

Cytochrome P450 1A1 enhances inflammatory responses and impedes phagocytosis of bacteria in macrophages during sepsis.

The hydroxylase cytochrome P450 1A1 (CYP1A1) is regulated by the inflammation-limiting aryl hydrocarbon receptor (AhR), but CYP1A1 immune functions remain unclear. We observed CYP1A1 overexpression in peritoneal macrophages (PMs) isolated from mice following LPS or heat-killed Escherichia. coli (E. coli) challenge. CYP1A1 overexpression augmented TNF-α and IL-6 production in RAW264.7 cells (RAW) by enhancing JNK/AP-1 signalling. CYP1A1 overexpression also promoted 12S-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12(S)-HETE) production in activated RAW, while a 12(S)-HETE antibody attenuated and 12(S)-HETE alone induced inflammatory responses. Macrophages harbouring hydroxylase-deficient CYP1A1 demonstrated reduced 12(S)-HETE generation and LPS-induced TNF-α/IL-6 secretion. CYP1A1 overexpression also impaired phagocytosis of bacteria via decreasing the expression of scavenger receptor A (SR-A) in PMs. Mice injected with CYP1A1-overexpressing PMs were more susceptible to CLP- or E. coli-induced mortality and bacteria invading, while Rhapontigenin, a selective CYP1A1 inhibitor, improved survival and bacteria clearance of mice in sepsis. CYP1A1 and 12(S)-HETE were also elevated in monocytes and plasma of septic patients and positively correlated with SOFA scores. Macrophage CYP1A1 disruption could be a promising strategy for treating sepsis. Video abstract.

Correction to: Cytochrome P450 1A1 enhances inflammatory responses and impedes phagocytosis of bacteria in macrophages during sepsis.

An amendment to this paper has been published and can be accessed via the original article.

Long intergenic non-coding RNA 1939 eliminates proliferation and migration of human renal cell carcinoma (RCC) cells by down-regulation of miR-154.

Renal carcinoma (RCC) is widely accepted as a malignant tumour of urinary system. Long intergenic non-coding RNA 1939 (LINC01939) is a novel lncRNA which was found to be down-regulated in RCC. Thus, we set out to explore the effect and regulation mechanism of LINC01939 in RCC. LINC01939 and miR-154 in RCC tissues and cell lines were detected using qRT-PCR assay. To examine cellular viability of ACHN and CAKI-1 cells, cell counting kit-8 (CCK-8) assay was exploited here. Flow cytometric analysis was conducted to examine apoptosis. Cell mobility was valued through wound healing assays. Western blotting was applied for examination of proteins related to proliferation, apoptosis, migration and Wnt/ß-catenin/Notch. LINC01939 was down-regulated in RCC tissues. LINC01939 overexpression impeded proliferation and migration, and induced apoptosis. Further study found that the overexpression of LINC01939 strongly suppressed miR-154 expression. Then, the inhibiting effect of overexpressed LINC01939 on proliferation and mobility and the promoting role of LINC01939 in apoptosis were abolished by the combination of miR-154 mimic. Finally, we found that overexpressed LINC01939 inactivated Wnt/ß-catenin and Notch through suppressing miR-154. Up-regulation of LINC01939 inhibited proliferation and migration of RCC cells by down-regulating miR-154.

Artificial Dermis Composite Tissue Flaps versus Traditional Prefabricated Flaps.

OBJECTIVE: We compared the application of artificial dermis composite tissue flaps and traditional prefabricated flaps in a rat model of exposed bone and tendon injury. METHODS: Sprague Dawley rats were randomly divided into two groups (n = 40 per group). Group A rats received artificial dermis composite tissue flaps and group B rats received traditional prefabricated flaps. Flap appearance, range of motion, degree of swelling, tissue histologic results, and imaging findings were compared between groups at 7, 14, 21, and 28 days. RESULTS: There was no difference in flap appearance, range of motion, or degree of swelling between groups. However, blood perfusion of the artificial dermis composite tissue flap was better than that of the traditional prefabricated flap; the artificial dermis was also found to be thicker than the traditional prefabricated flap. CONCLUSIONS: The artificial dermis composite tissue flap is an ideal method for repairing exposed bone and tendon, and it displays repair effects comparable with those of the traditional prefabricated flap and may be a better alternative.

Metformin alleviates oxidative stress and enhances autophagy in diabetic kidney disease via AMPK/SIRT1-FoxO1 pathway.

Metformin, as the basic pharmacological therapy and the first preventive drug in type 2 diabetes mellitus (T2DM), is proved to have potential protection in diabetic kidney disease (DKD). Here, we established a diabetic rat model induced by high-fat diet and low dose streptozotocin, and high glucose cultured rat mesangial cells (RMCs) pre-treated with metformin or transfected with AMPK, SIRT1 and FoxO1 small interfering RNA, and detected oxidative stress and autophagy related factors to explore the molecular mechanisms of metformin on DKD via adenosine monophosphate-activated protein kinase (AMPK)/silent mating type information regulation 2 homolog-1 (sirtuin-1, SIRT1)-Forkhead box protein O1 (FoxO1) pathway. We found that metformin effectively alleviated the disorders of glycolipid metabolism, renal function injury in diabetic rats, and relieved oxidative stress, enhanced autophagy and slowed down abnormal cell proliferation in high glucose cultured RMCs through AMPK/SIRT1-FoxO1 pathway, indicating the protective role of metformin against the pathological process of DKD.