[Treatment of Fournier's gangrene with "firebreak" drainage based on skin preservation].

Objective: To observe the clinical efficacy of a new type of "firebreak" drainage with skin preservation in the treatment of Fournier's gangrene. Methods: This technique is suitable for patients with perianal necrotizing fasciitis who can tolerate surgery without large area of skin blackness and necrosis. Procedure and key points: (1) The dividing line between inflammatory tissue and normal tissue was determined according to imaging examination and intraoperative exploration; (2) The abscess cavity was cut along the most obvious part of the abscess fluctuation, with a long diameter of 3~4 cm and a short diameter of 1~2 cm; (3) Necrotic tissue was discreetly separated and removed from the main incision to the outer edge of the infection. A fusiform incision was made every 3 to 5 cm, with a long diameter of 2 to 3 cm and a short diameter of 1 cm, and discreetly separated until the normal tissue, and a hose was hung between the adjacent incisions for drainage. (4) Each adjacent edge cut between the stealth separation and hanging hose drainage, forming a "firebreak"; (5) Rinse the wound repeatedly; (6) If the infection invades the rectum, colostomy is performed as required. The case data of 11 patients with perianal necrotizing fasciitis admitted to the Second Affiliated Hospital of Nanjing University of Chinese Medicine from July 2019 to February 2023 were retrospectively analyzed. All patients were treated with emergency surgical debridement by "firebreak" drainage with skin preservation. Results: All 11 cases were cured with 100%. One case underwent multiple operations. The hospitalization time was 11-46 days, with an average of 22 days. The wound healing time was 28-75 days, with an average of 43 days. Except for 1 patient with trauma, all the other patients had no significant anal function injury after surgery. All the 11 patients recovered and were discharged from hospital with a median follow-up of 136 (115-413) days. Conclusions: The "firebreak" drainage based on skin preservation has the advantages of less trauma and faster recovery, and do not cause obvious anal function damage.

[Clinical phenotype and genotype analysis of progressive familial intrahepatic cholestasis type 3 caused by novel ABCB4 gene mutation].

Objective: To investigate the pathogenic mechanism and clinical characteristics of the novel splicing variant of ATP-binding cassette subfamily B member 4 (ABCB4) and provide a basis for subsequent genetic diagnosis. Methods: The clinical data of a 5-year-old child with cholestatic liver disease admitted to the Beijing Children's Hospital of Capital Medical University was retrospectively analyzed. The pathogenic variations were detected by whole exome sequencing and verified by Sanger sequencing, and bioinformatics was used to predict the pathogenicity of the mutation sites. Possible pathogenic variations were verified in vitro by Minigene assay. The clinical outcome was followed after discharge from hospital. Results: The 5-year-old boy had developed cholestasis at the age of 11 months. His physical examination showed obvious enlargement of the liver and spleen. Cholestatic cirrhosis was diagnosed by liver function tests, abdominal ultrasonography, liver biopsy and pathology. The results of genetic analysis showed that the patient was a complex heterozygote of the ABCB4 gene, with a pathogenic mutation c.2860G>A and a novel mutation c.2065-8T>G, derived from the mother and father respectively. The conservative prediction of the c.2065-8T>G site showed that this region was highly conserved and may affect splicing. Minigene assay results confirmed that the c.2065-8T>G mutation resulted in a 7 bp retention of intron 16 in the mature mRNA. In the absence of nonsense-mediated mRNA decay, the amino acid frameshift forms a truncated protein, which is represented by p.Glu689ValfsTer19. The patient was diagnosed as progressive familial intrahepatic cholestasis type 3 (PFIC3) and treated with ursodeoxycholic acid (UDCA). His clinical symptoms improved during 18 months of follow-up. Conclusions: The c.2065-8T>G variant is confirmed to affect the splicing process and exhibits complex heterozygosity with c.2860G>A, which is identified as the cause of the disease. PFIC3 children with this variant showed cholestatic liver disease as the main manifestation with a slow progression and was sensitive to treatment with UDCA.

A multi-omics analysis reveals vitamin D supplementation since childhood modulates molecules for signal transductions in the mouse striatum.

Vitamin D is a critical fat-soluble vitamin for the nervous system. Research suggests a potential link between vitamin D deficiency and attention-deficit hyperactivity disorder (ADHD), particularly in children and adolescents. The core symptoms of ADHD are associated with deficits in striatal functions, and maintaining sufficient levels of vitamin D may help prevent or alleviate ADHD symptoms. However, the molecular changes in the striatum caused by vitamin D supplementation that may contribute to the brain processes linked to ADHD symptoms remain unclear. In this study, we established a mouse model fed diets with three different dose gradients of vitamin D3 (0, 500, and 2000 IU/kg·day) from postnatal day 21 (P21) to 14 weeks of age. Striatal tissues from mice with gradient vitamin D3 intake were subjected to reduced representation bisulfite sequencing (RRBS), RNA-sequencing, and neurotransmitter profiling by liquid chromatography-mass spectrometry (LC-MS). Our findings indicate that vitamin D supplementation since childhood influenced the overall landscape of DNA methylations and the expression of many genes involved in critical neurological functions in a dose-dependent manner. Additionally, our data demonstrate how vitamin D modulated neuropeptide signaling pathways, as well as cholinergic and dopaminergic synapses in the striatum, through an orchestrated mechanism involving epigenetic and transcriptional regulations. Furthermore, we observed a synergistic effect of vitamin D on dopamine release following acute methylphenidate injection into our mouse model. In summary, this study provides mechanistic insights into how dietary vitamin D supplementation since childhood can modulate specific signal transductions among striatal cells, underscoring the importance of vitamin D supplementation for ADHD management.

[Imaging risk factors for postoperative cerebral infarction in adults with ischemic Moyamoya disease].

Objective: To investigate the imaging factors associated with postoperative cerebral infarction in adult patients aged 18 and above with ischemic Moyamoya disease. Methods: The clinical data of adult patients who underwent surgeries for ischemic Moyamoya disease in the Department of Neurosurgery at Peking University International Hospital from October 2015 to October 2020 were retrospectively analyzed. Of the 239 patients, 120 were male and 119 were female, with ages ranging from 18 to 63 (41.7±10.3) years. A total of 239 patients(290 cases) underwent direct and indirect combined revascularization (CR).Gender, age, surgical side, preoperative transient ischemic attack (TIA), presence of old cerebral infarction, and imaging features were compared between the patients with (48 cases) and without (242 cases) cerebral infarction within 1 week after surgery. Multivariate logistic binary regression model was used to analyze the imaging risk factors of postoperative cerebral infarction. Results: Cerebral infarction occurred in 48 cases(16.5%) among the 290 CR group within 1 week after surgery. The proportion of patients with TIA, old cerebral infarction, ICA stenosis, A1 segment stenosis, M1 segment stenosis, abnormal posterior cerebral artery (PCA), and unstable compensation before CR in the cerebral infarction group was higher than that in the non-cerebral infarction group (P<0.05).Preoperative TIA (OR=4.514, 95%CI: 1.920-10.611), old cerebral infarction (OR=2.856,95%CI:1.176-6.936), A1 stenosis (OR=7.027,95%CI:1.877-26.308), M1 stenosis (OR=6.968,95%CI:2.162-22.459), abnormal PCA (OR=4.114,95%CI:1.330-12.728)and unstable compensation (OR=4.488,95%CI:1.194-16.865) were risk factors for cerebral infarction after CR surgery (all P<0.05). Conclusion: Among the imaging factors, TIA, old cerebral infarction, A1 stenosis, M1 stenosis, abnormal PCA and unstable compensation were risk factors for cerebral infarction in adult patients with ischemic Moyamoya disease treated by combined revascularization.

[Pathogenetic analysis of transfusion-related acute lung injury caused by human leukocytes antigen antibody against human leukocyte antigen].

From September 2019 to October 2020, pathogenetic analysis of three patients clinically diagnosed as transfusion-related acute lung injury (TRALI) caused by human leukocyte antibodies was conducted by Guangzhou Blood Centre, including 2 males and 1 female, aged 56, 50 and 20 years old, respectively. Solid phase agglutination, anti-human globulin test and flow cytometry method were used to detect the presence of antibodies against patients. Sequencing-based human leukocyte antigen (HLA-SBT) typing technique was used to detect the human leukocyte antigen (HLA) genotypes of patients. Lifecodes single antigen class Ⅰ/Ⅱ kit (LSA-Ⅰ/Ⅱ) were used to detect the specificity of HLA-class Ⅰ and class Ⅱ antibodies in donor blood by Luminex 200 liquid suspension chip system. The HLA specific antibodies and corresponding epitopes in donors were also analyzed. The results showed that　HLA class Ⅰ or class Ⅱ specific antibodies against TRALI patients were detected in the blood donors. The plasma of donor 3 received by patient 1 contained antibodies against the patient's HLA-DRB1*09∶01 antigen, and the epitopes mediating the antibody reaction of the donor and recipient were 70R, 31I, 70QA. There were antibodies against the HLA-A*11∶02, HLA-A*11∶01, DRB1*12∶02, and DRB1*09∶01 antigens of patient 2 in the plasma of donor 4, and the associated antigenic epitopes were 151AHA, 57V, and 16Y. Antibodies against the HLA-DRB1*14∶04, DRB1*11∶01, and DPB1*05∶01 antigens of patient 3 were present in the plasma of donor 6 and donor 7, and the associated epitopes were 96HK, 140TV, 13SE, and 111K.　Three cases of TRALI were confirmed to be caused by HLA antibodies through laboratory analysis, and human leukocyte antibody detection should be paid attention in clinically suspected cases of TRALI, and targeted diagnosis and treatment should be given.

[Ophthalmic surgical robot-assisted retinal puncture and injection for submacular hemorrhage caused by polypoid choroidal vasculopathy: a case report].

A 65-year-old man presented with decreased visual acuity in the left eye for 1 month. The diagnosis of hemorrhagic retinal detachment (submacular hemorrhage), which was caused by idiopathic polypoid choroidal vasculopathy, was confirmed by the ultra-wide-angle fundus examination, optical coherence tomography, and B-ultrasound. A vitrectomy combined with an ophthalmic surgical robot-assisted retinal puncture and injection was performed. The recombinant tissue plasminogen activator was injected accurately by the ophthalmic surgical robot between the retinal nerve epithelium and retinal pigment epithelium through a micro-injection needle. During the 2-month follow-up, the subretinal hemorrhage was significantly regressive, the visual acuity of the left eye was improved from hand movement to 0.1, and no other complications were observed. (This article was published ahead of print on the official website of Chinese Journal of Ophthalmology on March 15, 2024).

Disturbance of mitochondrial dynamics in myocardium of broilers with pulmonary hypertension syndrome.

1. The following study investigated the relationship between pulmonary hypertension syndrome (PHS) and mitochondrial dynamics in broiler cardiomyocytes.2. An animal model for PHS was established by injecting broiler chickens with CM-32 cellulose particles. Broiler myocardial cells were cultured under hypoxic conditions to establish an in vitro model. The ascites heart index, histomorphology, mitochondrial ultrastructure, and mitochondrial dynamic-related gene and protein expression were evaluated.3. The myocardial fibres from PHS broilers had wider spaces and were wavy and twisted and the number of mitochondria increased. Compared with the control group, the gene and protein expression levels were decreased for Opa1, Mfn1, and Mfn2 in the myocardium of PHS broilers. The gene and protein expression was significantly increased for Drp1 and Mff.4. This study showed that PHS in broilers may cause myocardial mitochondrial dysfunction, specifically by diminishing mitochondrial fusion and enhancing fission, causing disturbances in the mitochondrial dynamics of the heart.

A pivotal role for the IL-1ß and the inflammasome in preterm labor.

During labor, monocytes infiltrate massively the myometrium and differentiate into macrophages secreting high levels of reactive oxygen species and of pro-inflammatory cytokines (i.e. IL-1ß), leading to myometrial contraction. Although IL-1ß is clearly implicated in labor, its function and that of the inflammasome complex that cleaves the cytokine in its active form, has never been studied on steps preceding contraction. In this work, we used our model of lipopolysaccharide-induced preterm labor to highlight their role. We demonstrated that IL-1ß was secreted by the human myometrium during labor or in presence of infection and was essential for myometrial efficient contractions as its blockage with an IL-1 receptor antagonist (Anakinra) or a neutralizing antibody completely inhibited the induced contractions. We evaluated the implication of the inflammasome on myometrial contractions and differentiation stages of labor onset. We showed that the effects of macrophage-released IL-1ß in myometrial cell transactivation were blocked by inhibition of the inflammasome, suggesting that the inflammasome by producing IL-1ß was essential in macrophage/myocyte crosstalk during labor. These findings provide novel innovative approaches in the management of preterm labor, specifically the use of an inflammasome inhibitor to block the precursor stages of labor before the acquisition of the contractile phenotype.

[Research progress on AMPK activation in nonalcoholic fatty liver disease].

Nonalcoholic fatty liver disease (NAFLD) occurrence and progression are associated with lipid accumulation, insulin resistance, inflammation, liver damage, fibrosis, and other factors. AMP-dependent protein kinase (AMPK) is a key molecule that regulates bioenergy metabolism and participates in multiple biological processes, including lipid metabolism, autophagy, inflammation, and cell apoptosis. Promoting AMPK activation can reduce hepatic lipid accumulation and insulin resistance, alleviate the development of NAFLD, reduce liver inflammation and fibrosis, and inhibit the progression of NAFLD to nonalcoholic steatohepatitis.

Role of Cisplatin in Inducing Acute Kidney Injury and Pyroptosis in Mice via the Exosome miR-122/ELAVL1 Regulatory Axis.

Although cisplatin is an effective chemotherapy drug for the treatment of various cancers, its clinical use is limited due to its side effects, especially nephrotoxicity. Unfortunately, acute kidney injury (AKI) caused by cisplatin remains one of the main challenges in effective cancer treatment. Evidence increasingly suggests that renal inflammation and pyroptotic inflammatory cell death of renal tubular epithelial cells (RTECs) mainly determine the progression and outcome of cisplatin-induced AKI. However, it is not clear how cisplatin regulates the pyroptosis of RTECs cells in AKI. The current study aimed to determine the regulation mechanism of AKI induced by cisplatin. We used cisplatin to induce AKI in vivo. We performed H&E staining of mouse kidney tissue sections and evaluated serological indicators of kidney injury (including blood urea nitrogen (BUN), serum creatinine, and tumor necrosis factor-alpha (TNF-alpha)). We used immunohistochemistry and western blot to detect the important substrate protein gasdermin D (GSDMD) and key target caspase-1 of pyroptosis, respectively. Cisplatin induced mouse AKI and RTECs pyroptosis. HK2 cell-derived exosomes treated with cisplatin influenced pyroptosis of the surrounding HK2 cells. Cisplatin-treated HK2 cells exosome-derived miR-122 regulated pyroptosis in the surrounding cells. Exosome-derived miR-122 affected cisplatin-induced AKI and HK2 cells pyroptosis by regulating the expression of embryonic lethal abnormal vision (ELAVL1). These results suggest that exosome miR-122 inhibited pyroptosis and AKI by targeting ELAVL1 under cisplatin treatment, and this offers a potential target for the treatment of AKI.