Endoplasmic reticulum stress(ERS)is a subcellular pathological state formed by imbalance of environment in endoplasmic reticulum,and is regarded as an important pathway that mediates apoptosis.Recent studies have found that after ERS occurs in various immune tissues and cells,immunosuppressive effect that produced is involved in regulating body's immune homeo-stasis,affecting occurrence,outcome and prognosis of many diseases.This article reviews production of ERS,signal regulation and pathophysiological changes in immune organs and immune cells,and its role in development of inflammatory diseases and tumors.

The effect and mechanism of chronic stress on psychosomatic diseases are important topics in stress research.The establishment of animal models to simulate human chronic stress is of great significance to investigations of stress responses,the pathogenesis of related diseases,clinical treatment,and drug development.In this paper,animal models of chronic stress commonly used in China and abroad are reviewed;the classification of stressors,animal selection,model construction,pathological manifestations,and evaluation indexes are summarized;and the advantages and disadvantages and application of various models are discussed.The paper provides a reference for the study and selection of models of chronic stress response.

Ferroptosis is a non-apoptotic mode of cell death characterized by iron-dependent lipid-peroxide-accumulation-induced membrane lipid peroxidation and mitochondrial atrophy.It differs from other programmed cell deaths in its morphological and biochemical properties.Ferroptosis is regulated by a variety of metabolic pathways that are involved in the acute lung injury induced by hemorrhagic shock,ischemia-reperfusion,sepsis,and radiation.This article reviews the main regulatory mechanisms of ferroptosis and its role in the pathogenesis of acute lung injury in various animal models with the aim of providing new strategies for the prevention and treatment of acute lung injury.

The Nod-like receptor pyrin domain-associated protein 3(NLRP3)-mediated pyroptosis of pulmonary parenchymal and immune cells plays a key role in the pathogenesis of lung injury during sepsis.NF-κB,JAK2/STAT3 and MAPK signaling pathways are involved in NLRP3-mediated pyroptosis.Targeting NLRP3-pyroptosis and its related signaling pathways,pharmacological interventions with Physalin B,schisandrin,erythropoietin,and physical therapies such as acupuncture at Zusanli and Feishu points,as well as NLRP3-specific inhibitors like ergolide,have all shown effective anti-septic effects in treating lung injuries.This article reviewed the roles and mechanisms of NLRP3-pyroptosis in sepsis-induced lung injury,as well as the experimental progresses made in targeting NLRP3 pyroptosis as a therapy.We aim to highlight the importance of NLRP3-pyroptosis as a target,providing insights for the prevention and treatment of sepsis-induced lung injury.

Resveratrol is a polyphenolic plant extract with many biological activities such as anti-inflammation and anti-oxidative stress. Vascular endothelial cell (VEC) is the main sites for maintaining normal vascular permeability and participating in vasomotor regulation and substance exchange. VEC injury plays a key role in various diseases or pathological processes such as cardiovascular disease, chronic inflammation and sepsis. Studies have shown that resveratrol protects VEC and reduces endothelial damage by regulating nitric oxide (NO) and its related enzymes, reducing oxidative stress and inhibiting apoptosis, thereby exerting beneficial effects.

Sepsis is a syndrome of systemic inflammatory response in which the body′s response to infection is dysregulated, and is characterized by persistent infection, excessive inflammation and immunosuppression, etc. It often leads to organ dysfunction and can be life threatening, and also a common complication after trauma. The pathogenesis of post-traumatic sepsis is still unclear at present due to the complexity of its etiology, progression and prognosis. Multi-omics technology is a method to combine two or more single omics for comprehensive analysis, which can reveal the interaction network among the disease-associated molecules from multiple perspectives and aspects and is of great significance for the analysis of the pathogenesis of post-traumatic sepsis. To this end, the authors reviewed the research progress on the role of multi-omics technology in elucidating the pathogenesis of post-traumatic sepsis from the perspectives of genomics, transcriptomics, proteomics, metabolomics, single-cell transcriptomics and combination of multi-omics technologies, etc so as to provide a reference for the researches on post-traumatic sepsis.

Objective:To evaluate the efficacy of Janus kinase (JAK) inhibitors in the treatment of 5 children with severe alopecia areata, especially those with complicated nail damage.Methods:A total of 5 children with severe alopecia areata were enrolled and treated with oral JAK inhibitors (tofacitinib or baricitinib). The improvement of hair loss was assessed by using the severity of alopecia tool (SALT) at 12, 24, 36, and 48 weeks after the start of treatment. For 3 children with complicated nail damage, the improvement of diseased nails and toenails was evaluated by using the modified nail psoriasis severity index after treatment. During the treatment, adverse reactions were monitored.Results:The 5 children with severe alopecia areata were aged 2 - 11 years, with the disease duration ranging from 5 to 120 months, and the treatment with JAK inhibitors lasted 24 - 48 weeks. After 12-week treatment, 2 children achieved a 50% improvement in SALT (SALT50) ; after 24-week treatment, 3 achieved SALT95, and 1 achieved SALT75 and then withdrew baricitinib for personal reasons; after 36-week treatment, 3 achieved SALT99, and then received half-dose treatment; after 48-week treatment, 1, 1, 1 and 1 patient achieved SALT99, SALT83, SALT31, and SALT0, respectively, and 2 of them experienced gradually aggravated hair loss 1 - 2 months after the start of half-dose treatment. Among the 3 children with complicated nail damage, the improvement rates of nail severity index scores were 67.5%, 45.4%, and 25% respectively, and the improvement rates of toenail severity index scores were 42.5%, 71.4%, and 5% respectively after 12-week treatment; after 48-week treatment, the improvement rate of nail severity index scores were 100%, 100%, and 50% respectively, and the improvement rate of toenail severity index scores were 96.2%, 100%, 50% respectively. During the treatment, the uric acid level increased in 2 children, and one of them was accompanied by increased serum levels of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol; 1 suffered from respiratory tract infections twice during the treatment, and was recovered after symptomatic treatment; there were no adverse reactions leading to drug withdrawal.Conclusion:JAK inhibitors can be used as a treatment option for severe alopecia areata in children.

Objective:This study aims to compare the examination results of the vestibular evoked myogenic potential（VEMP） and video head impulse testing（vHIT） in patients with vestibular neuritis（VN）, thus exploring the methods to distinguish superior and inferior vestibular nerve damages in VN patients, and their feasibility. Methods:A total of 25 patients with unilateral VN treated in the Otology Department of the First Hospital of Qinhuangdao from May 2018 to July 2021 were recruited. They were respectively tested for ocular VEMP（oVEMP）, cervical VEMP（cVEMP） and vHIT, and the examination results were analyzed. Results:Examination results of oVEMP showed that 96%（24/25） patients had one-ear abnormalities with the amplitude decline or no waveform introduced, and 4%（1/25） patient had no waveform introduced of both ears. The overall abnormal rate examined by oVEMP was 100%（26/26）. Examination results of cVEMP showed that 36%（9/25） patients had one-ear abnormalities with the amplitude decline or no waveform introduced, and 4%（1/25） patients had no waveform introduced of both ears. The overall abnormal rate examined by cVEMP was 40%（10/25）, and 60%（15/25） patients had normal waveforms of both ears. Examination results of vHIT showed that 100%（25/25） patients had semicircular canal gain decline of one side, 92%（23/25） had anterior Semicircular canal decline of one side, and 36%（9/25） had posterior semicircular canal decline of one side. VEMP and vHIT results were compared. Examination results of VEMP showed that 60%（15/25） VN patients had superior vestibular nerve damage, and 40%（10/25） had both superior and inferior vestibular nerve damages. Examination results of vHIT showed that 64%（16/25） VN patients had superior vestibular nerve damage, and 36%（9/25） had both superior and inferior vestibular nerve damages. There was no significant difference in the ratio of VN patients with superior and inferior vestibular nerve damages examined by VEMP or vHIT（χ²=0.085, P>0.05）. The matching ratio of VEMP and vHIT results was 80%（20/25）, and the non-matching ratio was 20%（5/25）. Conclusion:Consistent results obtained from both VEMP and vHIT can preliminarily identify the type of vestibular nerve damage. If their results are not consistent, it is recommended not to identify the scope of the vestibular nerve damage.
Humans ; Vestibular Neuronitis/diagnosis* ; Vestibular Nerve ; Head Impulse Test/methods* ; Semicircular Canals ; Vestibular Evoked Myogenic Potentials/physiology*

Objective:To compare the efficacy and safety of biologics versus methotrexate in the treatment of severe pediatric plaque psoriasis.Methods:A retrospective matched case-control study was carried out. Twenty children with severe plaque psoriasis from Beijing Children′s Hospital, Capital Medical University from June 2016 to November 2021 were included in this study, and the patients treated with biologics (adalimumab or secukinumab) were matched with those treated with methotrexate at a ratio of 1∶1 according to the psoriasis area and severity index (PASI) score and age. PASI, physician′s global assessment (PGA) , and body surface area (BSA) scores were assessed at weeks 4, 8 and 12 after the start of treatment, and adverse drug reactions were recorded. Statistical analysis was mainly carried out by using Mann-Whitney U test, Fisher′s exact test and generalized estimating equations. Results:At weeks 4 and 8, the proportions of patients achieving PASI75 and PASI90 were significantly higher in the biologics group (PASI75: 7/10, 10/10, PASI90: 5/10, 9/10, respectively) than in the methotrexate group (PASI75: 1/10, 5/10, PASI90: 0, 1/10, respectively; all P < 0.05) , while there was no significant difference between the biologics group and methotrexate group at week 12 (PASI75: 10/10 vs. 8/10, PASI90: 9/10 vs. 4/10, both P > 0.05) . There were no significant differences in the PASI, BSA or PGA scores between the two groups at baseline (all P > 0.05) , while the biologics group showed significantly decreased PASI and BSA scores at weeks 4, 8 and 12, and significantly decreased PGA score at week 8 compared with the methotrexate group (PASI: Z = 2.50, 3.56, 2.63, respectively; BSA: Z = 2.87, 3.57, 2.40, respectively; PGA: Z = 2.81; all P<0.05) . Analysis of changes over time showed that the PASI, PGA and BSA scores in the biologics group significantly decreased at weeks 4, 8 and 12 compared with those at baseline (all P<0.01) ; the PASI and PGA scores significantly decreased at weeks 8 and 12 compared with the corresponding scores at week 4 (all P<0.05) ; however, there were no significant differences in the PASI, PGA or BSA scores between week 12 and 8 (all P>0.05) . In the methotrexate group, the PASI, PGA and BSA scores at weeks 4, 8 and 12 were all significantly lower than the corresponding scores at the previous adjacent time points (all P<0.05) . There was no significant difference in the incidence of adverse reactions between the two groups ( P = 0.650) , and no serious adverse reactions occurred in either group. The main adverse reaction was infection in the biologics group, while infection and elevation of transaminase levels were common in the methotrexate group. Conclusion:Biologics and methotrexate were both effective and safe for the treatment of severe pediatricplaque psoriasis, and biologics facilitated rapider achievement of PASI75 and PASI90 compared with methotrexate.

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.
Humans ; Benzydamine ; Esophageal Neoplasms/drug therapy* ; Esophageal Squamous Cell Carcinoma/drug therapy* ; Molecular Docking Simulation ; Phosphorylation ; Cell Proliferation ; Cell Line, Tumor ; Apoptosis ; Cyclin-Dependent Kinase 2