Endoplasmic reticulum is an important organelle in eukaryotic cells, which is responsible for the folding, processing and transportation of secretory proteins. A variety of stimuli inside and outside cells can lead to the accumulation of misfolded or unfolded proteins in the endoplasmic reticulum, resulting in abnormal structure and function of the endoplasmic reticulum, which is called endoplasmic reticulum stress (ERS). Endoplasmic reticulum autophagy is an important endogenous mechanism to alleviate ERS. It is often considered as a cell protective procedure, which participates in many important physiological processes, such as metabolism, immune response, inflammatory response and cell proliferation. Endoplasmic reticulum autophagy is an important endogenous protective mechanism to alleviate endoplasmic reticulum stress and restore the endoplasmic reticulum homeostasis, through eliminating redundant and disabled endoplasmic reticulum membrane and macromolecular protein complexes, which is critical to cell function and fate. This paper reviews the types of endoplasmic reticulum autophagy, related specific receptors, main regulatory mechanisms, and its role and significance in the related diseases.

Objective To explore the effects of different side tension pneumothorax on hemodynamics in pigs, providing data support for the optimization of on-site first-aid procedures for pneumothorax. Methods Twelve Bama pigs were randomly divided into left-sided tension pneumothorax group and right-sided tension pneumothorax group (6 in each group). During the occurrence of pneumothorax and as the pleural pressure gradually increases by 1 mmHg increments, the key indicators were collected using pulse indicator continuous cardiac output (PICCO) technology: hemodynamic indicators [global ejection fraction (GEF), cardiac output (CO), global end-diastolic volume (GEDV), intrathoracic blood volume (ITBV), stroke volume (SV), mean arterial pressure (MAP)], basic vital signs [heart rate (HR), diastolic blood pressure (DBP), systolic blood pressure (SBP)], and arterial blood gas parameters [partial pressure of oxygen (PO₂), partial pressure of carbon dioxide (PCO₂)]. Mediastinal localization was subsequently performed using radiographs. Differences were investigated through comparison between the two groups and within each group before and after the procedure. Results By comparing the hemodynamic changes and X-ray examination results, twelve Bama pigs tension pneumothorax models were successfully constructed. Hemodynamic analysis showed that in left-sided tension pneumothorax model when the pleural pressure reached 8 mmHg, SBP, DBP, MAP, CO, GEF, SV, GEDV and ITBV were significantly lower than those during the occurrence of ipsilateral pneumothorax (P<0.05). In right-sided tension pneumothorax model, when the pleural pressure reached about 3 mmHg, SBP, DBP, MAP, SV, GEDV, and ITBV were significantly lower than those during the occurrence of ipsilateral pneumothorax (P<0.05). Blood gas analysis showed that at 8 mmHg for left-sided and 3 mmHg for right-sided tension pneumothorax, compared with the occurrence of their respective ipsilateral pneumothorax, PO₂ was significantly lower (P<0.05) and PCO₂ was significantly higher (P<0.05). Conclusions There are different effects on hemodynamics in different side tension pneumothorax. Compared with left tension pneumothorax, right tension pneumothorax can lead to serious consequences under a smaller pleural pressure. Different side tension pneumothorax models can be constructed according to the actual situation when performing pneumothorax related experiments.

Objective To investigate the potential risk factors for immune checkpoint-related pneumonia (CIP) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), to identify high-risk patients with CIP at an early stage. Methods A total of 728 NSCLC patients treated with ICIs at the First Affiliated Hospital of Zhengzhou University from January 2020 to June 2023 were retrospectively selected, including 47 cases with CIP (CIP group), and 141 matched NSCLC patients without CIP (control group). Clinical data, laboratory tests, and CT images before the first immunotherapy were collected for all patients in two groups. The FACT medical imaging software was utilized for quantitative emphysema assessment in patients' CT scans. Univariate and multivariate logistic regression analyses were conducted to identify the risk factors associated with CIP. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive value of these factors for CIP occurrence in NSCLC patients. Results Among the 47 CIP patients, 40(85.1%) were male, with 25(53.0%) aged between 41 and 65 years. Grade 3 pneumonia according to the Common Terminology Criteria for Adverse Events (CTCAE) was found in 28(59.6%) cases, characterized by a predominant reticular radiographic pattern. Multivariate logistic regression analysis showed that a low albumin level (OR=0.889, 95%CI 0.808-0.979, P=0.017), targeted therapy (OR=9.204, 95%CI 1.678-50.486, P=0.011), anti-angiogenic therapy (OR=0.056, 95%CI 0.020-0.161, P<0.001), and a high percentage of low attenuation area (LAA%) (OR=1.227, 95%CI 1.053-1.430, P=0.009) were significant factors influencing CIP occurrence. The combined predictive model using these four factors showed an area under the ROC curve of 0.888 (95%CI 0.838-0.939), with a sensitivity of 0.894 and a specificity of 0.801 for predicting CIP in NSCLC patients. Conclusions Low serum albumin, first-line targeted therapy, and high LAA% are identified as risk factors for CIP occurrence, while anti-angiogenic therapy is a protective factor. The predictive model based on these four variables effectively predicts the risk of CIP in NSCLC patients.

Objective To investigate the predictive value of central venous oxygen saturation (ScvO₂) in elderly patients with acute kidney injury (AKI) after robot-assisted partial nephrectomy (RAPN). Methods Seventy-eight elderly patients who underwent RAPN in the Department of Urology, the Third Medical Center of Chinese PLA General Hospital from February to September 2022 were selected. AKI was diagnosed according to the International Nephropathy Improving Global Prognosis Criteria, and the patients were divided into AKI group (n=22) and non-AKI group (n=56) according to whether AKI occurred after surgery. Blood gas analysis of venous blood was taken after central venous puncture (T₀), 5 min after renal artery occlusion (T₁), 5 min after renal artery opening (T₂), and after surgery (T₃). Hemoglobin (Hb), arterial blood lactic acid (Lac), arterial oxygen partial pressure (PaO₂), ScvO₂ were recorded respectively. Oxygen uptake rate (O₂ER) were calculated. Multivariate logistic regression analysis was used to analyze the risk factors for postoperative AKI. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of ScvO₂ for AKI in elderly patients after RAPN. Results Compared with non-AKI group, fasting plasma glucose (FPG) level in AKI group significantly increased at T₁-T₂ (P<0.05). Compared with T₀, FPG level in two groups obviously increased at T₁-T₃ (P<0.01). Compared with T₁, the FPG level in T₃ significantly increased in non-AKI group (P<0.01). Compared with non-AKI group, ScvO₂ in AKI group significantly increased at T₁-T₂ (P<0.01), Lac level at T₂ significantly increased (P<0.05). There was no significant difference in O₂ER between the two groups at each time point (P>0.05). Compared with T₀, O₂ER in T₁-T₃ significantly decreased (P<0.01), and ScvO₂ in both groups significantly increased (P<0.01). Compared with T₁, ScvO₂ in non-AKI group significantly increased at T₂-T₃ (P<0.05 or P<0.01). Compared with T₂, ScvO₂ in non-AKI group significantly increased in T₃ (P<0.05). Multiple-factor analysis showed that T₁ ScvO₂ (OR=1.127, 95%CI 1.006-1.263, P=0.039) was an independent risk factor for AKI after RAPN. ROC curve analysis showed that T₁ ScvO₂ had a sensitivity of 77.3%, specificity of 71.4%, truncation value of 81%, and area under the curve (AUC) of 0.761 in predicting AKI after RAPN. Conclusion ScvO₂ has certain predictive value for the occurrence of short-term AKI after RAPN.

Objective To determine the effective dose of dexmedetomidine administered intranasally combined with oral midazolam sedation before pediatric magnetic resonance image (MRI). Methods This is a prospective modified sequential study. Children scheduled for MRI at the Children's Hospital of Zhejiang University School of Medicine from February to March 2023, aged 1 month to 6 years old, with a weight of 6.0-23.5 kg, were enrolled in this study. All children received 0.5 mg/kg oral midazolam, followed by intranasal dexmedetomidine. The initial dose of dexmedetomidine was 0.5 μg/kg, and the intranasal dose of dexmedetomidine was determined using the modified Dixon's up-and-down method with increments or decrements of 0.1 μg/kg. Probit analysis was used for calculating the half effective dose (ED₅₀), 95% effective dose (ED₉₅) and the corresponding 95% confidence interval (CI) of intranasal dexmedetomidine combined with oral midazolam for pediatric sedation during MRI. The sedation onset time, wake-up time, vital signs and adverse reactions were recorded. Results Among all the children,the sedation onset time of successful sedation children was (31.21±7.47) min, and the wake-up time was (81.21±26.04) min. The ED₅₀ for effective sedation with intranasal dexmedetomidine combined with oral medication at a dose of 0.5 mg/kg was calculated to be 0.392 μg/kg, with a 95%CI of 0.302-0.461 μg/kg; the ED₉₅ was 0.549 μg/kg, with a 95%CI of 0.473-0.996 μg/kg.There was a statistically significant difference (P<0.05) in heart rate and diastolic blood pressure after sedation compared to the baseline before medication. Two cases of restlessness during the awakening period were observed, but no other adverse reactions occurred. Conclusions The sedation regimen of intranasal dexmedetomidine combined with oral midazolam is non-invasive, easy to implement, safe, and effective. It can be widely used in pediatric MRI.

Uric acid, the end product of purine metabolism in human body, can lead to uric acid metabolism abnormality when its production and excretion are out of balance. This abnormality has emerged as one of the important risk factors for metabolic diseases, including diabetes, obesity, hypertension and metabolic syndrome. Recent studies have found that abnormal uric acid metabolism increases the risk of occurrence and development of type 2 diabetes mellitus (T2DM) and its complications, suggesting that uric acid metabolism could be a novel approach for intervening in T2DM. This review summarizes the research progress on how uric acid metabolism abnormality influences the occurrence, development and pathogenesis of T2DM, the beneficial effects of uric acid-lowering therapy, and the selection of hypoglycemic drugs on T2DM, which provide evidence for the early prevention and treatment of T2DM and its complications.

Objective To investigate the effects of astragaloside Ⅳ (AS-Ⅳ) on axon growth inhibitory factor A (Nogo-A) and its downstream pathway protein RHO-associated coiled spiral kinase 2 (ROCK2) in experimental autoimmune encephalomyelitis (EAE) mice, and to explore the mechanism by which it promotes axon repair and regeneration. Methods EAE model was induced in C57BL/6 female mice by subcutaneous injection of myelin oligodendrocyte glycoprotein 35-55 (MOG35-55). Mice were randomly divided into EAE group and AS-Ⅳ group (n=8 per group). EAE group received intraperitoneal injection of PBS on the 3rd day post-immunization, while AS-Ⅳ group was administered AS-Ⅳ at a dosage of 30mg/(kg.d) once daily, 0.2 ml per injection, for 25 consecutive days. On the 28th day post-immunization, the expression levels of growth-associated protein 43 (GAP-43), neuronal core antigen (NeuN), microtubule associated protein 2 (MAP-2), glial fibroacidic protein (GFAP), and Iba1 in the spinal cord were detected using immunofluorescence assay. Real-time fluorescence quantitative PCR (qRT-PCR) was conducted to detect mRNA expression levels of GAP-43, Nogo-A, and Nogo receptor (NgR) genes. Western blotting was utilized to determine the expression levels of GAP-43, Nogo-A, ROCK2, phosphorylated myosin phosphatase (p-MYPT1), B-lymphoblastoma-2 (Bcl-2), and Bcl-2 associated X protein (Bax). Results Compared with EAE group, AS-Ⅳ treatment significantly reduced the positive cell expression rates of Iba1 microglia and GFAP astrocyte in spinal cord (P<0.01 and P<0.001,respectively), while it also increased the positive expression rates of NeuN and MAP-2 (P<0.001 and P<0.05, respectively). The treatment also upregulated the expression level of anti-apoptotic factor Bcl-2 (P<0.001) and downregulated the expression level of pro-apoptotic factor Bax (P<0.05), leading to an increase in Bcl-2/Bax ratio (P<0.05). Furthermore, AS-Ⅳ enhanced the expression of GAP-43 protein (P<0.05) and decreased the mRNA expression levels of neuroregeneration inhibitor Nogo receptor (NgR) and ROCK2 gene (P<0.001, P<0.05, respectively); as well as decreased the expression levels of Nogo-A, ROCK2 and p-MYPT1 proteins (P<0.05, P<0.001). Conclusion AS-IV may inhibit the activation of microglia and astrocytes and neuronal apoptosis in EAE mice by inhibiting Nogo-A and downstream pathway ROCK2, thereby promoting the expression of GAP-43, NeuN and MAP-2, alleviating neuronal damage, and facilitating axon repair and regeneration.

Hemophagocytic syndrome (HPS), also known as hemophagocytic lymphohistiocytosis (HLH), is a rare and highly malignant hematologic disease with a poor prognosis. It can be divided into two categories: primary HLH and secondary HLH. HLH is characterized by a large number of abnormal immune cells that continuously activate and regulate out of control, leading to systemic inflammatory factor storm and multiple organ failure. Clinical manifestations mainly include persistent malignant hyperthermia, pancytopenia, hepatosplenomegaly, and hemophagocytosis in tissues and organs. The pathogenesis of adult HLH is complex, with rapid onset and rapid disease progression, and the fatality rate remains high. The main causes of death in HLH patients are multiple organ failure, abnormal coagulation and septic shock. Due to the specificity of HLH and the lack of effective understanding of the severity and prognosis in clinical practice, some HLH patients are misdiagnosed or overlooked, missing the best opportunity for diagnosis and treatment. Therefore, this review systematically explores and discusses the latest diagnostic and treatment progress of adult HLH, aiming to provide reference for clinical diagnosis, treatment and prognosis assessment of HLH.

Incompressible massive hemorrhage at the junction of trunk and limbs is the major cause of the potential preventable death in modern military conflicts, natural disasters and sudden trauma accidents. Because of the failure of direct compression hemostasis, aortic occlusion can reduce the amount of bleeding and provide a short time for injury recovery and accurate control of bleeding. As an effective assistant hemostasis method, resuscitative endovascular balloon occlusion of the aorta (REBOA) has shown initial potential in military and civilian hospitals and even pre-hospital trauma emergency treatment. With the continuous development of catheter guide technology, it is expected to achieve the emergency hemostasis treatment of war wound and massive hemorrhage. Basic and pre-clinical studies have been carried out in Europe and America, and the technology has been applied to the treatment of some patients with massive bleeding, but rarely reported in China. This paper reviews the history, scope, limitations and improvement of application and military application of REBOA in the treatment of traumatic hemorrhage, so as to promote the recognition of REBOA.

Objective To explore whether dexmedetomidine (DEX) can alleviate exertional heatstroke (EHS)-induced rhabdomyolysis (RM) in rats by activating adrenergic α2 receptors, and to explore its potential mechanism based on the reactive oxygen species (ROS)/NOD-like receptor protein 3 (NLRP3)/interleukin-1β (IL-1β) pathway. Methods Thirty-six male Sprague-Dawley (SD) rats, after a 7-day acclimatization training, were randomly divided into six groups: control group (CN group), EHS group, low-dose DEX group (EHS+low DEX group), high-dose DEX group (EHS+high DEX group), DEX combined with yohimbine (YOH) group (EHS+high DEX+YOH group), and YOH group (EHS+YOH), with six rats in each group. Before modeling, EHS+high DEX+YOH group and EHS+YOH group were intraperitoneally injected with YOH at 1 mg/kg, while the other four groups were injected intraperitoneally with an equal dose of physiological saline (0.9% NS). During modeling, except for CN group, the other 5 groups of rats were subjected to heat exercise in a high-temperature and high-humidity chamber to construct an EHS rat model. After successful modeling, EHS+low DEX group was intraperitoneally injected with DEX at 10 μg/kg, EHS+high DEX group and EHS+high DEX+YOH group were intraperitoneally injected with DEX at 30 μg/kg, and CN group, EHS group and DEX+YOH group were intraperitoneally injected with equal doses of saline. After 6 h of observation, all rats were anesthetized, and their blood from the abdominal aorta and gastrocnemius muscle tissue were taken. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β and myoglobin (MB) in rats; biochemical assay kit was used to measure the level of creatine kinase (CK) in rat serum; HE staining was used to observe pathological changes in rat gastrocnemius muscle tissues; transmission electron microscopy was used to observe ultrastructural changes in gastrocnemius muscle; 2′,7′-dichlorofluorescent yellow diacetate (DCFH-DA) fluorescent probe was used to detect the level of reactive oxygen species (ROS); and Western blotting was performed to detect the expression levels of NOD-like receptors 3 (NLRP3), aspartic protease-1 (caspase-1) and adrenergic α2A receptor (ADRA2A). Results Compared with CN group, the levels of serum IL-6, IL-1β, TNF-α, CK and MB in EHS group rats were significantly elevated (P<0.01). HE staining results revealed that the gastrocnemius muscle tissues of rats in EHS group had these pathological manifestations such as disarray of muscle fibrous structure, hemorrhage, edema, and infiltration of inflammatory cells. Transmission electron microscopy results showed that the ultrastructure of the gastrocnemius muscle in EHS group exhibited myofibroblasts with swelling and enlarging in size, cytoplasmic vacuolization, and mitochondria with obvious swelling, degranulation, and disappearance of double cristae. Compared with CN group, the expression levels of ROS, NLRP3, and caspase-1 in gastrocnemius of rats in EHS group significantly increased (P<0.01); Compared with EHS group, the levels of TNF-α, IL-6, IL-1β, CK, MB and the expression levels of ROS, NLRP3, caspase-1 in gastrocnemius tissue of rats in EHS+low DEX group and EHS+high DEX group decreased in a dose-dependent manner (P<0.05), and the pathological damage observed with HE staining and transmission electron microscopy was alleviated by DEX. After YOH pretreatment, compared with the EHS+high DEX group, the serum levels of TNF-α, IL-6, IL-1β, CK, MB and ROS, NLRP3 and caspase-1 in the gastrocnemius muscle tissue of rats in EHS+high DEX+YOH group relatively increased (P<0.05), and the pathological damage observed with HE staining and transmission electron microscopy was exacerbated. The expression of ADRA2A in gastrocnemius muscle of EHS group significantly decreased compared with CN group (P<0.01), and the expression of ADRA2A in muscle of rats in DES+low DEX group and EHS+high DEX group was higher than that in EHS group (P<0.05). Conclusions DEX can alleviate EHS-induced RM by activating ADRA2A, potentially through inhibiting the ROS-dependent NLRP3/IL-1β inflammatory pathway.