OBJECTIVES: Sepsis-associated acute lung injury (S-ALI) is one of the major causes of death in intensive care unit (ICU) patients, yet its mechanisms remain incompletely understood and effective therapies are lacking. Lytic cell death of macrophages is a key driver of the inflammatory cascade in S-ALI. PANoptosis, a newly recognized form of lytic cell death characterized by PANoptosome assembly and activation, involves plasma membrane rupture (PMR) mediated by ninjurin-1 (NINJ1), a recently identified pore-forming protein. Itaconic acid is known for its anti-inflammatory effects, but its role in macrophage PANoptosis during S-ALI is unclear. This study aims to investigate the protective effect of itaconic acid on macrophage PANoptosis in S-ALI to provide new therapeutic insights. METHODS: Male specific-pathogen-free C57BL/6J mice (6-8 weeks, 18-20 g) received intraperitoneal lipopolysaccharide (LPS) to establish a classical S-ALI model. Western blotting was used to assess PANoptosome-related proteins and enzymes involved in the itaconic acid metabolic pathway, while real-time reverse transcription polymerase chain reaction and metabolomics quantified itaconic acid levels. Primary peritoneal macrophages (PMs) were pretreated with the itaconate derivative 4-octyl itaconate (4-OI) and then exposed to tumor necrosis factor alpha (TNF-α) plus interferon gamma (IFN-γ) to induce PANoptosis. Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. Western blotting was employed to quantify enzymes of the itaconate-metabolic pathway in PANoptotic macrophages, to evaluate the impact of 4-OI on PANoptosome-associated proteins, and to determine NINJ1 abundance in lung tissues from S-ALI mice and in PANoptotic macrophages. Fluorescent dye FM_4-64 was used to visualize 4-OI-mediated changes in PMR, whereas immunofluorescence staining mapped the effect of 4-OI on both the expression level and membrane localization of NINJ1 in PANoptotic macrophages. The effect of 4-OI on lactate dehydrogenase (LDH) release in culture supernatants and peripheal blood serum was assessed using a LDH assay kit, and non-denataring polyacylamide gel electrophoresis was used to assess the expression of NINJ1 in S-ALI mouse lung tissues and the impact of 4-OI on the expression of PANoptosis-associated NINJ1 multimeric reflected protein in macropahges. RESULTS: In S-ALI mouse lungs, PANoptosome components [NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Gasdermin D (GSDMD), Caspase-1, Z-DNA binding protein (ZBP1), and Caspase-3] and phosphorylated mixed lineage kinase domain-like protein (MLKL) S345 were significantly upregulated (all P<0.05), while metabolomics showed compensatory increases in itaconic acid and its key enzymes [aconitate decarboxylase 1 (ACOD1)/immunoresponsive gene 1 (IRG1)]. In macrophages, 4-OI obviously suppressed PANoptosome protein expression, reduced LDH release, restored plasma membrane integrity, and inhibited NINJ1 expression and oligomerization at the membrane (P<0.05). CONCLUSIONS Itaconic acid may alleviate macrophage PANoptosis in S-ALI by inhibiting NINJ1-mediated plasma membrane rupture. Targeting NINJ1 or enhancing itaconate pathways may offer a novel therapeutic strategy for S-ALI.
Animals ; Acute Lung Injury/pathology* ; Succinates/pharmacology* ; Sepsis/complications* ; Mice, Inbred C57BL ; Male ; Mice ; Macrophages/pathology* ; Cell Membrane/metabolism* ; Lipopolysaccharides ; Hydro-Lyases

Objective:To explore the association between cognitive function and the level of gamma-amino-butyric acid(GABA)in anterior cingulate cortex(ACC)before and after treatment in patients with major depres-sion disorder.Methods:Totally 31 medication-naive patients with major depression disorder meeting the criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5)and 33 normal controls were col-lected.Each eligible patient received treatment with selective serotonin reuptake inhibitor agents for 8 weeks.The MATRICS Consensus Cognitive Battery(MCCB)was used to evaluate the cognitive function.By means of 1H magnetic resonance spectroscopy,anterior cingulate cortex GABA concentrations were measured.Results:At base-line,the concentration of ACC GABA relative to water(GABA+/W)was lower in the patient group than in the control group(P＜0.05)and increased after treatment(P＜0.05).ACC GABA+/W was negatively associated with verbal learning and visual memory score in patient group at baseline(correlation coefficient and P value were r=-0.40,P＜0.05;r=-0.42,P＜0.05,respectively).The ACC GABA+/W difference resulted of treatment in patient group was positively associated with the difference of working memory score and the difference of reasoning and problem-solving score(correlation coefficient and P value were r=0.58,P＜0.05;r=0.66,P＜0.05,respec-tively).Conclusion:The cognitive dysfunction of patients with major depression disorder may not be related to the degree of depression and anxiety.And improvement of cognitive function may be associated with increase of ACC GABA concentrations.

Brucellosis is a common global zoonotic disease caused by Brucella, which has a variety of clinical manifestations. Fever, sweating and musculoskeletal pains appear in partial brucellosis patients. The most common complication of brucellosis is osteoarthritis, including spondylitis, sacroiliitis, and peripheral arthritis such as osteomyelitis, bursitis, and tenosynovitis. The spine and sacroiliac are the most frequent affected sites of brucellosis osteoarthritis; however, the reports of peripheral arthritis such as osteomyelitis, bursitis, and tenosynovitis are low. Early and proper treatment is vital for patients with brucellosis osteoarthritis. The therapy of drugs and surgery are two current options for treatment of brucellosis osteoarthritis. In this review, clinical manifestations and treatments of brucellosis osteoarthritis are discussed in detail, which are helpful to deepen clinicians' knowledge in brucellosis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the outbreak of coronavirus disease 2019 in Wuhan City, China. The SARS-CoV-2 is genetically similar to the coronavirus derived from bat. The SARS-CoV-2, the SARS-CoV and the Middle East respiratory syndrome coronavirus (MERS-CoV) all belong to beta coronavirus. Since the outbreak of the coronavirus disease 2019, effective antiviral drugs have become a hot issue in the world. Very little about SARS-CoV-2 is known and there is no precedent for treatment. The National Health Commission has repeatedly revised the diagnosis and treatment guide for the coronavirus disease 2019. The latest guide is "New Coronary Virus-Infected Pneumonia Diagnosis and Treatment Plan (Seventh Trial Version)"(short for Seventh Version of Diagnosis and Treatment Plan). But the use of antiviral drugs is still on trial and no rigorous clinical trials data is available. Hot anti-SARS-CoV-2 drugs include interferon α, ribavirin, lopinavir/ritonavir, chloroquine phosphate, abidol, as well as hydroxychloroquine sulfate and remdesivir. But the later 2 drugs aren't mentioned in the Seventh Version of Diagnosis and Treatment Plan.
Antiviral Agents ; therapeutic use ; Betacoronavirus ; China ; Coronavirus Infections ; drug therapy ; Humans ; Pandemics ; Pneumonia, Viral ; drug therapy ; Practice Guidelines as Topic

The clinical characteristics of the pneumonia includes hyperthermia, cough and pectoralgia, etc with simultaneous mixed signs of inflammatory infiltration, consolidation, cavity/air sac and abscess in pulmonary CT scan, and these signs change rapidly. Respiratory failure and septic shock frequently occur in severe such patients, resulting in refractory management and relatively long therapeutic course. The timely diagnosis, use of sensitive antibiotics, respiratory and nutritional support, etc comprehensive effective measures can elevate the rescue success rate with severe hematogenous staphylococcus aureus pneumonia.

Brucellosis is a common bacterial zoonotic disease that affects a variety of organs and tissues and causes a variety of clinical manifestations. Bone and joint are the most frequently involved parts, among which sacroiliac arthritis, spondylitis and peripheral arthritis are the most common osteoarticular disease. Brucella induces bone damage by affecting various cells of the skeletal system and the immune system, Brucella increases the expression of nuclear factor kappa B receptor activating factor ligand (RANKL), tumor necrosis factor (TNF)-α and interleukin (IL)-17 in osteoclasts and osteocytes, enhances the activity of osteoclasts. Brucella can proliferate in osteoblasts and osteocytes, induce apoptosis of osteoblasts and osteocytes, and inhibit the deposition of mineral and organic matrix in osteoblasts. After Brucella infection, inflammatory cells such as monocyte macrophages, neutrophils, T cells and B cells also participate in the inflammatory response, these inflammatory cells and bone system secrete more pro-inflammatory cytokines, chemokines and matrix metalloproteinases (MMPs), which enhance the inflammatory response and promote the degradation of extracellular matrix. Finally, the bone homeostasis is broken and the bone injury is aggravated. With the development of research on the molecular mechanism of Brucella osteoarthropathy, more and more people will understand the pathogenesis of chronic osteoarthropathy caused by Brucella.

Ganglioneuroma (GN) is a rare benign tumor of neural crest origin usually found in the abdomen, but may occasionally present at uncommon sites including the cervical, lumbar, or sacral spine. However, GNs of thoracic spine are extremely rare. In this report, we describe a 12-year-old girl with giant GN in the thoracic spine, who underwent successful resection (T1–4 level) of the tumor. Histopathological examination confirmed the diagnosis. GN should be considered in the differential diagnosis of any paraspinal mass. A high index of suspicion and correlation of clinico-radiological findings is necessary in differentiating a large benign tumor from a malignant growth. Complete surgical excision is the treatment of choice; however tumor size and location need to be considered for the surgical approach (one-step or multiple surgeries). Close follow-up after surgery is mandatory.
Abdomen ; Child ; Diagnosis ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Ganglioneuroma* ; Humans ; Neural Crest ; Spine*

BACKGROUND:Some studies have showed that the accuracy and surgery outcome of the percutaneous pedicle screw implantation was superior to open surgery, but the relationship between the angle of pedicle screws and screw stability is stil unclear in previous studies. OBJECTIVE:To investigate the effect of different angles of implanted screws on the stability of pedicle screw. METHODS:A total of 30 vertebral specimens of adult pigs were selected and screws were implanted respectively according to different coronal and sagittal angles. The maximum pul-out strength of screws from each specimen was tested by machine. Load-displacement curves were drew and statistical y analyzed. RESULTS AND CONCLUSION:The maximum pul-out strength and maximum energy of screw with 10° and 15° coronal and sagittal angles implantation were significantly better than those of 0° angle group (P<0.05). When the stress exceeded the maximum pul-out strength, the pul-out strength of screw decreased gradual y. The curves in coronal and sagittal 10° and 15° angle groups was similar, and the slope was better than 0° angle group (P<0.05). These results confirm that the angle of the implanted screw provides effective assistance to the stability of percutaneous pedicle screw. After the looseness of the screws, the pul out strength shows a steady downward trend.

Objective To investigate the role of the p38 MAPK pathway in the formation of cytoplasmic vacuoles .Methods Af-ter treated with Anisomycin ,SB203580 or SP600125 ,images of HepG2 ,LM3 ,QBC939 ,Hela and A549 cells were recorded by light microscopy and taken at a magnification of 400 × .The effects of anisomycin ,SB203580 and SP600125 on the activity of p38 and JNK were measured by Western blot .LM3 and A549 cells were stained with the ER-tracker red and the lyso-tracker red and subjec-ted to confocal microscopy analysis .Results (1)Anisomycin could abolish cytoplasmic vacuolization of HepG2 cells .(2)p38 MAPK activation was responsible for anisomycin-induced cytoplasmic vacuolization abolishment .(3)p38 MAPK blocking initiated cytoplas-mic vacuoles formation in various cancer cell lines .(4)p38 MAPK blocking-induced cytoplasmic vacuoles disrupted the integrity of endoplasmic reticulum .(5)p38 MAPK blocking reversibly induced cytoplasmic vacuoles formation .Conclusion These observations provide direct evidence for a role of p38 MAPK signaling in regulating the formation of cytoplasmic vacuoles .

To explore the clinical manifestations, diagnosis and treatment of pulmonary thromboembolism associated with protein C (PC)/protein S (PS) deifciency. Two male patients 29 and 26 years old diagnosed with PC deifciency and/or PS deifciency were retrospectively analyzed and related literatures were reviewed. The most common symptoms were pain in the lower limbs with chest pain or decreased vision. Color dopper lfow imaging (CDFI) showed lower deep venous phlebothrombosis. Multislice CT angiography (CTA) revealed pulmonary embolism. The level of serum homocysteine (HCY) increased and the level of plasma PC/PS content decreased to PC 57.4%, and PS 28.9%in patient 1, while PS 33.4%in patient 2. Poor routine anticoagulant response was observed. After the diagnosis of PC/PS deficiency, vitiamin B6 and B12 anticoagulant therapy was added, and the symptoms in the patients improved significantly. Congenital thrombophilia should be taken into consideration for young patients with lower deep venous thrombosis and pulmonary embolism which occur recurrently without obvious predisposing causes before 40. Plasma PC/PS concentrations or activity help a lot in the diagnosis and treatment.