Reconstruction of perianal skin defect using modified keystone flap after perianal tumor resection.

Purpose: The large resection area of perianal tumor makes the skin defect hard to reconstruct. The keystone flap has demonstrated a growing application in skin defects. Herein, we aimed to explore the efficacy of keystone flap in the repair of skin defect after perianal tumor resection. Methods: This study is a retrospective review of patients diagnosed with perianal tumor from January 2010 to November 2021. A standardized data collection template was used to collect variables. The detailed process of the reconstructive surgery is carefully described in this article. After surgery, the healing process was closely observed. Results: Twenty patients underwent keystone flap repair. The average wound size before closure measured 3.5 × 4.9 cm2. Primary wound healing was achieved, and the flap survived during the follow up period, which ranged from 6 to 24 months. No severe complications occurred; slight edema was noticed in one patient. Conclusion: The application of keystone flap is a promising way to repair skin defect after tumor removal, and the complications rate was low after surgery. It can be concluded that this method is an effective and reliable way to repair perianal skin defect.

Exploring the landscape of stem cell extracellular vesicle research for angiogenesis: A bibliometric analysis from 2003 to 2023.

BACKGROUND: Exosomes and other secretory membrane vesicles are collectively referred to as extracellular vesicles (EVs). Relevant data indicate that stem cell-derived extracellular vesicles (SC-EVs) play a critical role in angiogenesis by transmitting crucial information such as proteins, second messengers, and genetic material between cells. Therefore, this study aimed to map current trends on SC-EVs for angiogenesis and provide directions for future research to advance this important field. METHODS: We conducted a thorough search for relevant studies on SC-EVs for angiogenesis from 2003 to 2023 using the Web of Science database. Subsequently, we used VOSviewer and CiteSpace to analyze the collected data. RESULTS: A total of 2359 relevant publications, which included original articles and reviews, related to the role of SC-EVs in angiogenesis were screened in this study based on the search strategy. China and the United States were leading in this field, with China having a higher output in terms of publications and citations (1172, 43681). Also, the top five universities were located in China, with Shanghai Jiao Tong University having the highest output. Stem Cell Research & Therapy and International Journal of Molecular Sciences, are prominent platforms for researchers in this field to share their findings and advancements, and they had most of published studies on SC-EVs for angiogenesis. The results derived from the cluster analysis suggested that future investigations should predominantly prioritize studying the involvement of SC-EVs in angiogenesis across various diseases, with a specific emphasis on skin wound healing. CONCLUSION: In this comprehensive review, global trends in SC-EVs for angiogenesis were analyzed. The analysis of journals, institutions, references, and keywords could assist researchers in deciding on the direction of research. The role of SC-EVs in promoting angiogenesis during wound healing and repair represents an emerging research focus.

Faecal hsa-miR-7704 inhibits the growth and adhesion of Bifidobacterium longum by suppressing ProB and aggravates hepatic encephalopathy.

Both gut microbiome and microRNAs (miRNAs) play a role in the development of hepatic encephalopathy (HE). However, the functional link between the microbiome and host-derived miRNAs in faeces remains poorly understood. In the present study, patients with HE had an altered gut microbiome and faecal miRNAs compared with patients with chronic hepatitis B. Transferring faeces and faecal miRNAs from patients with HE to the recipient mice aggravated thioacetamide-induced HE. Oral gavage of hsa-miR-7704, a host-derived miRNA highly enriched in faeces from patients with HE, aggravated HE in mice in a microbiome-dependent manner. Mechanistically, hsa-miR-7704 inhibited the growth and adhesion of Bifidobacterium longum by suppressing proB. B. longum and its metabolite acetate alleviated HE by inhibiting microglial activation and ammonia production. Our findings reveal the role of miRNA-microbiome axis in HE and suggest that faecal hsa-miR-7704 are potential regulators of HE progression.

Simplified and modified Limberg flap plus vacuum-assisted closure for treatment of sacrococcygeal pilonidal sinus disease.

BACKGROUND: Pilonidal sinus disease (PSD), a chronic inflammatory disease, affects the sacrococcygeal soft tissue, especially in young adults. The ideal treatment for PSD remains divergence. This study evaluated the application of a simplified modified Limberg flap combined with vacuum-assisted closure for treating PSD. METHODS: This prospective study was conducted from 1 June 2017 to 31 March 2022 in Changhai Hospital, Naval Military Medical University, Shanghai, China. The study included 88 male patients (91.7%) and 8 female patients (8.3%). The 96 patients ranged in age from 15 to 34 years (mean ± SD, 23 ± 4.4). Under general anaesthesia, all patients underwent simplified modified Limberg flap reconstruction with vacuum-assisted closure. The patient's weight, surgical time, extubation time, hospital stay, time to return to normal life or work, wound infection, wound dehiscence and recurrence rate were recorded. The visual analogue scale (VAS) score and the Vancouver scar score were used to score patients' pain and scars in the surgical area. RESULTS: The volume of resected diseased tissue was 13.5-120 (mean ± SD, 34.993 ± 24.406) cm2 . The average surgical time during the treatment period was 97.68 ± 18.72 min, and the average extubation time was (6.36 ± 1.55) days, the mean hospital stay was 19.4 days; no patients were lost to follow-up. None of the patients experienced post-operative recurrence, wound infection, seroma or hematoma. Six patients (6.3%) experienced wound dehiscence at the flap tip around the natal cleft. The mean time to the resumption of daily activities was 26.3 days. The average VAS pain score was (6.00 ± 1.53) points, and the average Vancouver scar score was (5.96 ± 1.51) points, 12 patients (12.5%) were dissatisfied with their aesthetic results, and the average beauty satisfaction score is (6.64 ± 1.28) points. CONCLUSIONS: Simplified modified Limberg flap reconstruction with vacuum-assisted closure surgery is an effective and innovative method for the treatment of PSD, with a low recurrence rate and rapid recovery.

Osteopontin May Improve Postinjury Muscle Repair Via Matrix Metalloproteinases And tgf-ß Activation in Regular Exercise.

Skeletal muscle injuries are commonly observed during sports and trauma. Regular exercise promotes muscle repair; however, the underlying mechanisms require further investigation. In addition to exercise, osteopontin (OPN) contributes to skeletal muscle regeneration and fibrosis following injury. However, whether and how OPN affects matrix proteins to promote post-injury muscle repair remains uncertain. We recruited regular exercise (RE) and sedentary control (SC) groups to determine plasma OPN levels. Additionally, we developed a murine model of muscle contusion injury and compared the extent of damage, inflammatory state, and regeneration-related proteins in OPN knockout (OPN KO) and wild-type (WT) mice. Our results show that regular exercise induced the increase of OPN, matrix metalloproteinases (MMPs), and transforming growth factor-ß (TGF-ß) expression in plasma. Injured muscle fibers were repaired more slowly in OPN-KO mice than in WT mice. The expression levels of genes and proteins related to muscle regeneration were lower in OPN-KO mice after injury. OPN also promotes fibroblast proliferation, differentiation, and migration. Additionally, OPN upregulates MMP expression by activating TGF-ß, which promotes muscle repair. OPN can improve post-injury muscle repair by activating MMPs and TGF-ß pathways. It is upregulated by regular exercise. Our study provides a potential target for the treatment of muscle injuries and explains why regular physical exercise is beneficial for muscle repair.

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.

Metformin promotes angiogenesis by enhancing VEGFa secretion by adipose-derived stem cells via the autophagy pathway.

Human adipose tissue-derived stem cell (ADSC) derivatives are cell-free, with low immunogenicity and no potential tumourigenicity, making them ideal for aiding wound healing. However, variable quality has impeded their clinical application. Metformin (MET) is a 5' adenosine monophosphate-activated protein kinase activator associated with autophagic activation. In this study, we assessed the potential applicability and underlying mechanisms of MET-treated ADSC derivatives in enhancing angiogenesis. We employed various scientific techniques to evaluate the influence of MET on ADSC, assess angiogenesis and autophagy in MET-treated ADSC in vitro, and examine whether MET-treated ADSC increase angiogenesis. We found that low MET concentrations exerted no appreciable effect on ADSC proliferation. However, MET was observed to enhance the angiogenic capacity and autophagy of ADSC. MET-induced autophagy was associated with increased vascular endothelial growth factor A production and release, which contributed to promoting the therapeutic efficacy of ADSC. In vivo experiments confirmed that in contrast to untreated ADSC, MET-treated ADSC promoted angiogenesis. Our findings thus indicate that the application of MET-treated ADSC would be an effective approach to accelerate wound healing by promoting angiogenesis at wound sites.

Pathogenic roles of long noncoding RNAs in melanoma: Implications in diagnosis and therapies.

Melanoma is one of the most dangerous types of cutaneous neoplasms, which are pigment-producing cells of neuroectodermal origin found all over the body. A great deal of research is focused on the mechanisms of melanoma to promote better diagnostic and treatment options for melanoma in its advanced stages. The progression of melanoma involves alteration in different levels of gene expression. With the successful implementation of next-generation sequencing technology, an increasing number of long noncoding RNAs (lncRNAs) sequences have been discovered, and a significant number of them have phenotypic effects in both in vitro and in vivo studies, implying that they play an important role in the occurrence and progression of human cancers, particularly melanoma. A number of evidence indicated that lncRNAs are important regulators in tumor cell proliferation, invasion, apoptosis, immune escape, energy metabolism, drug resistance, epigenetic regulation. To better understand the role of lncRNAs in melanoma tumorigenesis, we categorize melanoma-associated lncRNAs according to their cellular functions and associations with gene expression and signaling pathways in this review. Based on the mechanisms of lncRNA, we discuss the possibility of lncRNA-target treatments, and the application of liquid biopsies to detect lncRNAs in melanoma diagnosis and prognosis.

The Application of Double-Layer-Vacuum-Assisted Closure Therapy With Flap Repair of Soft Tissue Defects Near the Eyes or EarDL-VAC Therapy.

OBJECTIVE: We aimed to introduce and evaluate the safety of double-layer-vacuum-assisted closure (DL-VAC) therapy with flap repair of the wound near the eyes or ears. METHODS: This study is case reports of 2 patients who underwent DL-VAC therapy for tissue defects near the eyes or ears. The detailed process of the DL-VAC therapy is carefully described in this study. The postoperative wound healing process was closely observed. The biggest concern was the treatment outcome of DL-VAC therapy on the eyes and ears. RESULTS: Two patients underwent DL-VAC therapy due to their soft tissue defects close to the eyes or ears. Both patients achieved primary wound healing and the flaps survived during the follow-up period, which ranged from 1 to 24 months. Patients did not receive any dressing change until the VAC device was removed on the 5th to 7th postoperative day. No severe complications appeared and the patients were satisfied with both appearance and function. CONCLUSIONS: Double-layer-vacuum-assisted closure therapy is an effective and safe option for the treatment of wounds near the eyes and ears.

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.

Reconstruction of constricted ears by combing bilateral cartilage flaps bridging with V-Y advancement flap.

BACKGROUND: Despite a number of surgical procedures for the reconstruction of moderate to severe constricted ears described in the literature, a most cost-effective method remains to be explored. It is still a challenge to maximize the full use of the ear cartilage and surrounding skin while achieving the best results. METHODS: From 2011 to 2016, seven constricted ear patients were enrolled in this study. Five of them were moderate (type IIB Tanzer classification) deformities, and two were severe (type III Tanzer classification). All constricted ear patients were treated with bilateral cartilage flaps bridging and the V-Y advancement flap from preauricular skin, with the option of inserting a conchal cartilage graft if additional stability was required. Mean follow-up period was 4.0 ± 3.5years. RESULTS: All patients were satisfied with significant increase in the height of the constricted ears, also with the reconstruction of scapha and antihelix. The surgical scar was not obvious. No complications were observed. Long-term follow-up period revealed that the reconstructive procedure produced the long-lasting cosmetic results. CONCLUSION: Combination of bilateral cartilage flaps bridging with V-Y advancement of preauricular flap can make full use of its deformed tissue and surrounding skin. The method is effective and reliable in the reconstruction of moderate and some severe constricted ears.

zVAD alleviates experimental autoimmune hepatitis in mice by increasing the sensitivity of macrophage to TNFR1-dependent necroptosis.

BACKGROUND & AIMS: Autoimmune hepatitis (AIH) is characterized by hepatocyte destruction, leading to lymphocyte and macrophage accumulation in the liver. Macrophages are key drivers of AIH. A membrane-permeable pan-caspase inhibitor, Z-Val-Ala-DL-Asp-fluoromethylketone (zVAD), induces macrophage necroptosis in response to certain stimuli. However, the function of zVAD in the pathogenesis of autoimmune hepatitis remains elusive. In this study, we aimed to evaluate the effect and explore the underlying mechanisms of zVAD against AIH. METHODS: Murine acute autoimmune liver injury was established by concanavalin A (ConA) injection. Bone marrow-derived macrophages (BMDMs) were used in adoptive cell transfer experiments. The mechanism of action of zVAD was examined using macrophage cell lines and BMDMs. Phosphorylation of mixed lineage kinase domain-like proteins was used as a marker of necroptosis. RESULTS: Treatment with zVAD increased necroptosis, reduced inflammatory cytokine production, and alleviated liver injury in a ConA-induced liver injury mouse model. Regardless of zVAD treatment, macrophage deletion resulted in reduced neutrophil accumulation and relieved ConA-induced liver injury. In vitro studies have shown that zVAD pretreatment promotes lipopolysaccharide-induced macrophage necroptosis and leads to reduced pro-inflammatory cytokine and chemokine secretion. Transferring zVAD-pretreated BMDMs in mice notably reduced ConA-associated liver inflammation and injury, resulting in lower mortality than that observed after transferring normal BMDMs. Mechanistically, zVAD treatment increased the expression of tumour necrosis factor receptor (TNFR)-1 and interleukin (IL)-10 in macrophages. TNFR1 expression decreased upon transfection with IL-10-specific small interfering RNAs and blocking of TNFR1 decreased macrophage necroptosis. CONCLUSIONS: We found that zVAD alleviated ConA-induced liver injury by increasing the sensitivity of macrophages to necroptosis via IL-10-induced TNFR1 expression. This study provides new insights into the treatment of autoimmune hepatitis via zVAD-induced macrophage necroptosis.

Phospholipid metabolites of the gut microbiota promote hypoxia-induced intestinal injury via CD1d-dependent γδ T cells.

Gastrointestinal dysfunction is a common symptom of acute mountain sickness (AMS). The gut microbiota and γδ T cells play critical roles in intestinal disease. However, the mechanistic link between the microbiota and γδ T cells in hypoxia-induced intestinal injury remains unclear. Here, we show that hypoxia-induced intestinal damage was significantly alleviated after microbiota depletion with antibiotics. Hypoxia modulated gut microbiota composition by promoting antimicrobial peptides angiogenin-4 secretions. The abundance of Clostridium in the gut of mice after hypoxia significantly decreased, while the abundance of Desulfovibrio significantly increased. Furthermore, Desulfovibrio-derived phosphatidylethanolamine and phosphatidylcholine promoted γδ T cell activation. In CD1d-deficient mice, the levels of intraepithelial IL-17A and γδ T cells and intestinal damage were significantly decreased compared with those in wild-type mice under hypoxia. Mechanistically, phospholipid metabolites from Desulfovibrio are presented by intestinal epithelial CD1d to induce the proliferation of IL-17A-producing γδ T cells, which aggravates intestinal injury. Gut microbiota-derived metabolites promote hypoxia-induced intestinal injury via CD1d-dependent γδ T cells, suggesting that phospholipid metabolites and γδ T cells can be targets for AMS therapy.

LncNSPL facilitates influenza A viral immune escape by restricting TRIM25-mediated K63-linked RIG-I ubiquitination.

Long noncoding RNAs (lncRNAs) participate in host antiviral responses; however, how viruses exploit host lncRNAs for immune evasion remains largely unexplored. Functional screening of differentially expressed lncRNA profile in patients infected with influenza A virus (IAV) revealed that lncNSPL (Gene Symbol: LOC105370355) was highly expressed in monocytes. Deregulated lncNSPL expression in infected monocytes significantly increased type I interferon (IFN-I) production and inhibited IAV replication. Moreover, lncNSPL overexpression in mice increased the susceptibility to IAV infection and impaired IFN-I production. LncNSPL directly bound to retinoic acid-inducible gene I (RIG-I) and blocked the interaction between RIG-I and E3 ligase tripartite interaction motif 25 (TRIM25), reducing TRIM25-mediated lysine 63 (K63)-linked RIG-I ubiquitination and limiting the downstream production of antiviral mediators during the late stage of IAV infection. Our findings provide mechanistic insights into the means by which lncNSPL promotes IAV replication and immune escape via restricting the TRIM25-mediated RIG-I K63-linked ubiquitination. Thus, lncNSPL may represent a promising pharmaceutical target for anti-IAV therapy.

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.

Comparative Analysis of Long Non-Coding RNA Expression and Immune Response in Mild and Severe COVID-19.

Background: Coronavirus disease 2019 (COVID-19) is a worldwide emergency, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Long non-coding RNAs (lncRNAs) do not encode proteins but could participate in immune response. Methods: In our study, 39 COVID-19 patients were enrolled. The microarray of peripheral blood mononuclear cells from healthy and COVID-19 patients was applied to identify the expression profiles of lncRNAs and mRNAs. Identified differentially expressed (DE) lncRNAs were validated by qRT-PCR. Then, the lncRNA-mRNA network was constructed and visualized using Cytoscape (3.6.1) based on the Pearson correlation coefficient. The enrichment of DE mRNAs was analyzed using Metascape. The difference in frequencies of immune cells and cytokines was detected using CIBERSORT and ImmPort based on DE mRNAs. Results: All patients with COVID-19 displayed lymphopenia, especially in T cells, and hyper-inflammatory responses, including IL-6 and TNF-α. Four immune-related lncRNAs in COVID-19 were found and further validated, including AC136475.9, CATG00000032642.1, G004246, and XLOC_013290. Functional analysis enriched in downregulation of the T-cell receptor and the antigen processing and presentation as well as increased apoptotic proteins, which could lead to T-cell cytopenia. In addition, they participated in monocyte remodeling, which contributed to releasing cytokines and chemokines and then recruiting more monocytes and aggravating the clinical severity of COVID-19 patients. Conclusion: Taken together, four lncRNAs were in part of immune response in COVID-19, which was involved in the T-cell cytopenia by downregulating the antigen processing and presentation, the T-cell receptor, and an increased proportion of monocytes, with a distinct change in cytokines and chemokines.

Influenza A virus NS1 protein hijacks YAP/TAZ to suppress TLR3-mediated innate immune response.

The Hippo signaling pathway, which is historically considered as a dominator of organ development and homeostasis has recently been implicated as an immune regulator. However, its role in host defense against influenza A virus (IAV) has not been widely investigated. Here, we found that IAV could activate the Hippo effectors Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) through physical binding of the IAV non-structural protein 1 (NS1) with C-terminal domain of YAP/TAZ, facilitating their nuclear location. Meanwhile, YAP/TAZ downregulated the expression of pro-inflammatory and anti-viral cytokines against IAV infection, therefore benefiting virus replication and host cell apoptosis. A mouse model of IAV infection further demonstrated Yap deficiency protected mice against IAV infection, relieving lung injury. Mechanistically, YAP/TAZ blocked anti-viral innate immune signaling via downregulation of Toll-like receptor 3 (TLR3) expression. YAP directly bound to the putative TEADs binding site on the promoter region of TLR3. The elimination of acetylated histone H3 occupancy in the TLR3 promoter resulted in its transcriptional silence. Moreover, treatment of Trichostatin A, a histone deacetylases (HDACs) inhibitor or disruption of HDAC4/6 reversed the inhibition of TLR3 expression by YAP/TAZ, suggesting HDAC4/6 mediated the suppression function of YAP/TAZ. Taken together, we uncovered a novel immunomodulatory mechanism employed by IAV, where YAP/TAZ antagonize TLR3-mediated innate immunity.

Osteopontin aggravates acute lung injury in influenza virus infection by promoting macrophages necroptosis.

Infection with influenza A virus (IAV) can trigger pulmonary inflammation and lung damage. Osteopontin (OPN) is an essential regulator of cell death and immunity. However, the role and underlying mechanism of OPN in cell death in IAV-induced pulmonary injury remain poorly understood. Here, we demonstrated that OPN-deficient (OPN-/-) mice were insensitive to IAV, exhibiting decreased viral loads and attenuated lung injury after IAV infection compared to those in wild-type (WT) mice. Moreover, macrophage necroptosis was significantly reduced in OPN-/- mice infected with IAV compared to that in infected WT mice. OPN increased the expression of necroptosis-related genes and exacerbated macrophage necroptosis in IAV-infected THP1 cells. Notably, adoptive transfer of WT bone marrow-derived macrophages (BMDMs) or OPN-/- BMDMs into mice restored resistance to influenza infection, and the rescue effect of OPN-/- BMDMs was better than that of WT BMDMs. Collectively, these results suggest that OPN deficiency in macrophages reduces necroptosis, which leads to a decrease in viral titers and protects against IAV infection. Therefore, OPN is a potential target for the treatment of IAV infection.

The surgical strategies of vaginoplasty for vaginal agenesis patients with or without functional uterus.

BACKGROUND: Vaginal agenesis is a rare condition worldwide. Most reported cases were accompanied by the absence of uterus or uterine hypoplasia; for patients with functional endometrium, hysterectomy was most likely to be conducted to lower postoperative complications. OBJECTIVE: Based on our successful experience in vaginoplasty with autologous buccal mucosal, the purpose of this article is to discuss the surgical strategies in the reconstruction of neovaginal for vaginal agenesis patients with functional uterus and cervical hypoplasia. METHODS: The uterus was preserved in our procedure, and the cervicoplasty was performed to connect the uterine cavity with the neovagina. After the vaginal cavity was formed, the cervix was confirmed and fixed. With the assistance of laparoscope, the direction and angle of the cervix and the uterine body were observed and confirmed. An incision was made in cervix to connect the uterine cavity, and a Foley's catheter was inserted. The newly formed opening of cervix and neovagina was covered by autologous buccal mucosal. RESULTS: The connection between neovagina and cervix uteri was successfully conducted in patient with functional uterus. Unimpeded and regular menstrual was achieved, and the cyclic abdominal pain was disappeared. No complications were observed. CONCLUSION: For patients without functional uterus, vaginoplasty with autologous buccal mucosal can be conducted. However, fertility-preserving surgery should be the primary choice in patients with functional endometrium. It can be concluded from our experience that the utero-vaginal connection with the assistance of laparoscope and the use of autologous buccal mucosa is a promising way to achieve ideal outcomes.