Review of methods for establishing limbal stem cell deficiency in animal model / 中华实验眼科杂志

Limbal stem cell deficiency (LSCD) is a common ocular surface disease.Severe LSCD can cause irreversible vision loss and the only effective treatment for severe LSCD is keratoplasty, which is limited by the number of donors.Exploring new effective treatments in lieu of keratoplasty remains a hot topic in current research.Since new treatments need to be critically evaluated in reliable animal models that reflect the pathological mechanisms of human LSCD, the establishment of an appropriate animal model is crucial in any experiment.Up to now, the main modeling methods for LSCD are mechanical method, thermal injury, chemical method, chemical method combined with surgery, and gene knock-down.Mechanical method is mature, reliable and widely used, but it can cause serious mechanical damage.Rotate burr tool could be the best mechanical method because of uniform damage and the small trauma, but it requires accumulation of experience.Cornea suffered from thermal injury performs stable, but the operation is complicated and uncontrollable.Chemical method is quick and simple, and the etiology is highly consistent with clinical cases, but the depth and extent of injury are uncontrollable.The chemical method combined with surgery could ensure the smoothness and flattening of the corneal surface, but the thickness of the central cornea and the limbus may be inconsistent, which affects neovascularization.The gene knockdown method is not widely used because of its complicated operations.Although there are different types of methods, the quality of modeling in different studies is not consistent.Therefore, selecting a reliable and efficient animal model of LSCD is not convenient for researchers.This review discussed current methods to establish LSCD model, including their advantages and disadvantages, therefore to provide inspiration for future model improvement.

Application of a closed-loop tracking system in the quality monitoring program for intravenous infusions / 中华护理杂志

Objective To monitor the quality of intravenous infusions in a constructed closed-loop tracking system,and to discuss its application effect.Methods The information program is reinvested in a team for the closed-loop tracking system of the intravenous infusion.There are modules of processing medical orders,pharmacy preparations,execution procedures with the doctor's orders,as well as the computing module.The system was put into clinical trial operation in November 2021 and officially applied in January 2022.Specifically,the number of infusion-related adverse events/red-light alert is recorded and compared before(January to December 2021)and after(January to December 2022)the application of the system.Random sampling method has been performed in a ward to investigate the amount of abnormal infusion for the comparison.Results It is shown that it occurred 3 times for the infusion-related adverse events before the operation of the system,and a time after that.In the neurological inpatients,we observe the amount of red-light alert as 5,120.25±775.82 before the system operation,and 1,518.25±74.77 after that.It is shown to decline by 70.35％on average with statistical significance on the total difference(P＜0.001).Monthly amount of infusion in the ward is 5,184 with 155 times of overfast(2.99％)for 775 minutes in total,and with 207 times of slow(3.99％)for 1,035 minutes in total.The average handling time per contact is 5 minutes.Conclusion The closed-loop tracking system for intravenous infusion quality monitoring can track and record the whole process of intravenous infusions.It is expected to provide accurate and objective data for closed-loop quality inspection on clinical nursing practice,which is conducive to nursing managers for any potential problems during infusion processing timely,to promote standardized nursing operations,and to further improve the safety of inpatients with intravenous infusion and medication.

Hypoxia-induced ROS aggravate tumor progression through HIF-1α-SERPINE1 signaling in glioblastoma / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Hypoxia, as an important hallmark of the tumor microenvironment, is a major cause of oxidative stress and plays a central role in various malignant tumors, including glioblastoma. Elevated reactive oxygen species (ROS) in a hypoxic microenvironment promote glioblastoma progression; however, the underlying mechanism has not been clarified. Herein, we found that hypoxia promoted ROS production, and the proliferation, migration, and invasion of glioblastoma cells, while this promotion was restrained by ROS scavengers N-acetyl-L-cysteine (NAC) and diphenyleneiodonium chloride (DPI). Hypoxia-induced ROS activated hypoxia-inducible factor-1α (HIF-1α) signaling, which enhanced cell migration and invasion by epithelial-mesenchymal transition (EMT). Furthermore, the induction of serine protease inhibitor family E member 1 (SERPINE1) was ROS-dependent under hypoxia, and HIF-1α mediated SERPINE1 increase induced by ROS via binding to the SERPINE1 promoter region, thereby facilitating glioblastoma migration and invasion. Taken together, our data revealed that hypoxia-induced ROS reinforce the hypoxic adaptation of glioblastoma by driving the HIF-1α-SERPINE1 signaling pathway, and that targeting ROS may be a promising therapeutic strategy for glioblastoma.

Survey on current status of noise hazards in key industries in Tianjin in 2020 / 公共卫生与预防医学

Objective To conduct a survey on the status of noise hazards in Tianjin in 2020, to analyze the main distribution characteristics of noise hazards, and to put forward corresponding preventive and control measures. Methods A unified questionnaire was used to investigate the city-wide enterprises with more than 5 employees, normal production and operation, and noise hazards. The χ2 test was used to analyze the survey results. Results There were 8 560 enterprises with noise hazards, which were concentrated in the five outer suburban districts, the four districts around the city and the Binhai New Area, mainly small and medium-sized enterprises. Totally, 223 800 people were exposed to noise. The rates of noise hazard detection and physical examination of workers were 25.88% and 17.66%, and the rate of over standard detection and the rate of abnormal physical examination were 13.09% and 1.62%, respectively. The differences in noise detection rate, over standard detection rate and physical examination rate were significant in different administrative regions, enterprise scales and industries. The detection rate and physical examination rate of enterprises in the five outer suburban districts, micro-scale enterprises, and paper products industries were the lowest, while the rate of exceeding standards was the highest in the railway, shipping, aerospace and other transportation equipment manufacturing industries. Conclusion Noise is a common occupational hazard in enterprises in Tianjin. There are a large number of people who are exposed to noise. The detection rate and physical examination rate of noise are at a low level. Individual industries have a high rate of exceeding the standard. The current situation of noise hazard prevention and control is not optimistic. It is recommended to pay attention to it and take effective intervention measures.

Neuroprotective effect of CDDO-Im on ischemic stroke in rats based on Nrf2/ARE signaling pathway / 中国免疫学杂志

Objective:To investigate the neuroprotective effect of synthetic triterpenoid(CDDO-Im)on ischemic stroke rats and its influence on inflammatory response by activating the nuclear factor 2-related factor 2(Nrf2)/antioxidant response elements(ARE)signaling pathway.Methods:SD rats were divided into sham group(S group),MCAO group(M group)and CDDO-Im inter-vention group(M+C group).The middle cerebral artery occlusion(MCAO)was used in M group and M+C group to establish ischemic stroke model in rats,and sham operation was used in S group to control.After operation,M+C group was injected with CDDO-Im(64 μg/300 g)every12 hours via caudal vein,S group and M group were given the same amount of normal saline.After 3 days,the nerve function of rats was measured by Longa score,and the area of cerebral infarction was evaluated by 2,3,5-triphenyltetrazolium chlo-ride(TTC)staining.The expressions of Nrf2,heme oxygenated-1(HO-1),ionic calcium binding adaptor molecule 1(Iba1),IL-1β and IL-4 protein were detected by Western blot.Results:Compared with S group,M group rats showed significant neurologic deficit and cerebral infarction area,and the expression of Nrf2 protein had no significant difference,and the expression levels of HO-1,Iba1,IL-1β and IL-4 protein were increased significantly(P<0.05).Compared with M group,the neurological deficit score,cerebral infarction area,the expression levels of Iba1 and IL-1β protein were decreased significantly(P<0.05),while Nrf2,HO-1 and IL-4 pro-tein expression increased significantly in M+C group(P<0.05).Conclusion:CDDO-Im may activate the Nrf2/ARE signaling pathway and play a neuroprotective role,which may be related to the modulation of microglia to M2 and the regulation of inflammatory response.

Correlation analysis of optic disc structure and fundus morphological markers in highly myopic eyes / 中华眼底病杂志

Objective:To observe the changes of optic disc structure in patients with high myopia and the correlation with the morphological markers of the fundus.Methods:A retrospective study. From July 2018 to January 2020, 90 patients (155 eyes) diagnosed as high myopia in Department of Ophthalmology of Beijing Friendship Hospital affiliated to Capital Medical University were included in the study. Among them, there were 31 males (52 eyes) and 59 females (103 eyes), with age of 57.1±14.2 years old and axial length (AL) of 28.5±2.6 mm. According to the classification of myopic macular degeneration, patients were divided into 4 groups based on forms and degree of lesions, including non-pathological myopia group, mild traction lesions group, severe traction lesions group and neovascular lesions group, 35, 58, 41, 21 eyes, respectively. The digitized fundus photographs and an Image J system were used to measure the horizontal, vertical, maximal, and minimal diameter of the optic disc, the horizontal and vertical diameter of the parapapillary δ zone and γ zone, ovality index, distance between the most superior point of the temporal superior arterial arcade and most inferior point of the temporal inferior arterial arcade (VDA), angle between the temporal arterial arcade and optic disc (angle kappa), distance between the optic disc center and the fovea (DFD), angle between the horizontal disc axis and the disc-fovea line (DFA). The correlation between the diameter of the optic disc and other parameters was analyzed. Univariate and multivariate analysis were used to compare differences between groups.Results:The horizontal diameter of the optic disc was positively correlated with the horizontal diameter of the δ zone ( r=0.300, P<0.001), Kappa angle ( r=0.260, P=0.003), and elliptic index ( r=0.650, P<0.001); it was negatively correlated with DFD ( r=-0.190, P=0.030). Optic disc vertical diameter and optic disc horizontal diameter ( r=0.280), δ-zone horizontal diameter ( r=0.330) and vertical diameter ( r=0.460), γ-zone horizontal diameter ( r=0.430) and vertical diameter ( r=0.390), DFD ( r=0.390) was positively correlated ( P<0.001); it was negatively correlated with DFA ( r=-0.210, P=0.001) and Kappa angle ( r=-0.210, P=0.004). Compared with the non-pathological myopia group, there were statistically significant differences in the horizontal and vertical diameters of the optic disc in the severe traction disease group ( P<0.05). Among them, the horizontal diameter difference did not depend on the eye axis and age difference; the vertical diameter difference was caused by the eye axis difference. Compared with the non-pathological myopia group, the difference in the horizontal diameter of the optic disc in the neovascular disease group was statistically significant ( P<0.05), and did not depend on the difference in the axis and age; the difference in the vertical diameter of the optic disc was not statistically significant ( P>0.05). Conclusion:The morphology of optic disc was related to several fundus morphological markers, which was differentiated according to the age, AL and the degree of disease in patients with high myopia.

The 486th case: chronic diarrhea and orthostatic hypotension / 中华内科杂志

A 57-year-old man was admitted to hospital with diarrhea for 10 months and dizziness for 4 months. The patient had 1-2 liters watery stool per day, without pyogenic blood or abnormality in gastroenteroscopy examination. The level of hemoglobin and albumin was generally normal, and fasting test was positive. At the same time, he was accompanied with hyperalgesia of lower limbs and orthostatic hypotension. After the discussion of multiple disciplinary teams, the patient was diagnosed with amyloidosis by sural nerve biopsy, myocardial MRI, and the assays of urine immunoelectrophoresis and serum free light chain. Light chain amyloidosis was confirmed after excluded the diagnosis of familial amyloidosis. The patient was improved after courses of chemotherapy with melphalan and dexamethasone.

Investigation and analysis of occupational hazards in dust related enterprises in Tianjin / 公共卫生与预防医学

Objective To understand the occupational hazards of dust related enterprises in Tianjin, and to provide a scientific basis for formulating regulatory policies and effectively curbing the high incidence of pneumoconiosis. Methods The basic situation of the enterprise, the occupational health management status, and the occupational health status of the workers were described and analyzed. Results Most of the enterprises exposed to dust in Tianjin were small and micro enterprises, manufacturing enterprises and private enterprises. The reporting rate of occupational hazard items was uneven (P < 0.01). As the scale of the enterprise decreased, the comprehensive training rate of occupational health, the training rate of enterprise leaders, the training rate of occupational health management personnel, the comprehensive implementation rate of occupational hazard detection and the detection rate decreased accordingly (P < 0.01). Conclusion Tianjin should focus on the supervision of small and micro enterprises, strengthen the occupational health training of small and micro enterprises, and implement hierarchical and effective supervision for enterprises of different sizes in different regions. Meanwhile, enterprises should bear the main responsibility of occupational health, so as to ensure the continuity of occupational health management measures such as occupational hazard detection and occupational health inspection.

Clinical Recommendations for Perioperative Immunotherapy-induced Adverse Events in Patients with Non-small Cell Lung Cancer / 中国肺癌杂志

BACKGROUND@#Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE).@*METHODS@#This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE.@*RESULTS@#This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively.@*CONCLUSIONS@#Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.

Prediction of prognosis of gastric cancer by a five-microRNA risk score model / 中华消化杂志

Objective:To analyze and screen microRNA (miRNA) related to the prognosis of gastric cancer(GC) by bioinformatics analysis, and to construct and validate a risk score model.Methods:The human genome miRNA sequencing data and corresponding clinicopathological data of the 491 samples (446 GC tissue samples and 45 normal gastric tissue samples) were downloaded from the cancer genome atlas (TCGA) database. The differentially expressed microRNA (DEM) was analyzed with edgeR package of R 4.0.2 software and the obtained DEM’s profile was randomly divided into training set and test set according to the ratio of 1∶1. The miRNA related to prognosis were analyzed and screened with univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression analysis was further performed to analyze the screened prognostic-related miRNA and then the prognostic risk score model was constructed. Kaplan-Meier curve, receiver operating characteristic curve (ROC), and dynamic area under the ROC were drawn to evaluate the predictive power of the model.Results:A total of 175 DEM in GC tissues were screened out based on the cut-off criteria of |log2 Fold Change|>1.5 and P<0.01. Six DEMs related to the overall survival rate of patients with GC were screened out by univariate Cox regression and LASSO regression analysis, and then a five-miRNA risk score model was successfully constructed by multivariate Cox regression. The risk score=0.183×hsa-miRNA-184+ 0.086×hsa-miRNA-675-0.231×hsa-miRNA-2115+ 0.548×hsa-miRNA-3943-1.455×hsa-miRNA-1246. In the training set, test set and overall data set, the cumulative survival rates of the patients with higher risk score were lower than those of the patients with lower risk score, respectively, and the differences were statistically significant ( χ2=18.90, 9.50 and 26.70, all P<0.05). The prediction power of the model was better than that of TNM stage. And the results of stratified analysis showed the predictive ability of the model in patients with early GC. The results of univariate Cox regression and multivariate Cox regression demonstrated that the risk score of the model, gae and M stage were independent risk factors for poor prognosis in patients with GC (hazard ratio(95% confidence interval)1.19(1.07 to 1.32), 1.20(1.06 to 1.40), 1.50(1.01 to 2.23), 1.90(1.28 to 2.90), 1.34(1.15 to 1.57), 2.10(1.05 to 4.40); all P<0.05). Conclusion:The 5-miRNA risk score model based on 5 miRNAs which was an independent prognostic factor had high accuracy in predicting the prognosis of patients with GC.

Analysis of silicosis surveillance data in Tianjin in 2017 / 中华劳动卫生职业病杂志

Objective@#Analyzes of the monitoring results of silicosis in key occupational disease monitoring in Tianjin in 2017, providing reference for continuous monitoring, and prevention and control work of silicosis.@*Methods@#Monitor and analyze the current state of silica dust hazard enterprises, the health status of silica dust workers, and the characteristics of newly developed silicosis cases in accordance with the national 2017 work plan for key occupational disease monitoring and occupational health risk assessment.@*Results@#In 2017, 210 enterprises have silica dust hazard in Tianjin, silica dust workplaces exceed the standard rate is 34.73%, 5 695 workers' health examination who contact with silica dust were collected. 2 were detected occupational contraindication, the abnormal detection rate of chest examination is 3.60%, the abnormal index of lung function mainly is FVC, the abnormal rate is 15.8%. The abnormal rate increases with working years. In 2017, 193 new cases of silicosis were reported most cases were developed after years of decontamination. Most enterprises with cases had already out of market, only 7 were still producing.@*Conclusion@#The key prevention and control in Tianjin was enterprises with silica dust excess of standard, as well as older and longer working years workers, adopting effective measures to reduce the concentration of silica dust in workplace is a fundamental measure to reduce the risk of silicosis.

Clinical Diagnosis and Treatment Recommendations for Immune Checkpoint Inhibitor-related Hematological Adverse Events / 中国肺癌杂志

Immune checkpoint inhibitors are able to reactivate the immune system therefore enhance the anti-tumor effects. However, over-activated T cells may induce immune related adverse events (irAEs). Hematological irAEs are rarely reported, which mainly represent as mono-lineage cytopenia or pancytopenia, including autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), neutropenia and aplastic anemia, sometimes even lethal, such as hemophagocytic lymphohistiocytosis. The clinical manifestations of hematological irAEs will be summarized and recommendations of diagnosis and treatment are proposed.

Management of Rheumatic Adverse Events Related to Immune Checkpoint Inhibitors / 中国肺癌杂志

Immune checkpoint inhibitors (ICIs) have made remarkable breakthroughs in cancer treatment. However, the widely use of ICIs is associated with a spectrum of immune-related adverse events (irAEs). These adverse events can affect any organ system. In this article, we have made a systemic review about the clinical characteristics of rheumatic irAEs, and also summarized irAEs in patients with pre-exsiting rheumatic disease. We also focus on the management of rheumatic irAEs.

Recommendation of Diagnosis and Management for the Infections Related to Immune Checkpoint Inhibitors / 中国肺癌杂志

Immune checkpoint inhibitors (ICIs) have been widely used in management of malignant tumor. Programmed death ligand 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors have been introduced to treat non-small cell lung cancer (NSCLC) in recent years. Currently, PD-1/PD-L1 inhibitors are considered to have minor side effects and do not independently increase the risk of infection. However, they may cause immune-related adverse events (irAEs) that can require immunosuppressive therapy with corticosteroids and/or immunosuppressants, leading to opportunistic infections. Furthermore, there were reports about reactivation of chronic/latent infections without irAEs. Thus, immune checkpoint inhibitor related infections have drawn more and more attention in the world. In this paper, we described the potential mechanism, available clinical data and recommendation of diagnosis and management for PD-1/PD-L1 inhibitor related infections.

Clinical Diagnosis and Treatment of Immune-related Adverse Events in Digestive System Related to Immune Checkpoint Inhibitors / 中国肺癌杂志

Immunotherapy for malignant tumors is a hot spot in current research and treatment of cancer. The activation of programmed cell death receptor-1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA)-4 relevant signaling pathway can inhibit the activation of T lymphocytes. Tumor cells can achieve immune escape by activating this signaling pathway. By inhibiting this signaling pathway, immune-checkpoint inhibitors (ICIs) activate T lymphocytes to clear the tumor cells. Therefore, the adverse effects of ICIs are mainly immune-related adverse events (irAEs). The digestive system, including gastrointestinal tract and liver are vital organs of digestion and absorption, metabolism and detoxification, as well as important immune related organs, which are the commonly affected system of irAEs. This review separately explains the incidence, clinical features, diagnosis and treatment of liver and gastrointestinal adverse events in ICIs.

Clinical Diagnosis and Treatment Recommendations for Ocular Toxicities of Target Therapy and Immune Checkpoint Inhibitor Therapy / 中国肺癌杂志

The increasing use of target therapy and immunocheckpoint inhibitors in cancers has brought new hope of survival to patients with advanced tumors. However, more and more adverse side-effects and toxicities of these medications had been reported, affect almost all human organs including the eye. These adverse effects may affect the entire ocular tissues, like eyelid, eye lashes, conjunctiva, cornea, uvea, retina, optic nerve and so on, which are always been ignored by patients and doctors. In this paper we will summarize the characteristics of the related ocular diseases and give our advice on how to diagnose and manage these diseases.

Clinical Diagnosis and Treatment of Immune-related Adverse Events of Edocrine System Related to Immune Checkpoint Inhibitors / 中国肺癌杂志

As a new type of anti-cancer drugs, immune checkpoint inhibitors (ICIs) have shown remarkable therapeutic effects in many malignant tumors. By virtue of their targets and mechanisms of action, ICIs can cause autoimmune and inflammatory effects, termed immune-related adverse events (irAEs). Unlike traditional therapies, irAEs are latent and unstable. Severe adverse reactions will force patients to discontinue treatment and even affect their survival. Therefore, with the wide application of ICIs in clinical practice, clinicians need to fully understand the possible adverse reactions of such drugs and appropriate treatment strategies, in order to improve the survival rate and treatment effect of patients receiving ICIs. In this article, we review the incidence, clinical features, diagnosis and treatment of immune-related endocrine events that may occur with administration of ICIs.

Management of Dermatologic Toxicities Related to Immune Checkpoint Inhibitors / 中国肺癌杂志

Immune checkpoint inhibitors (ICIs) represent a major breakthrough in cancer therapy. Immune-related adverse events (irAEs) may occur during treatment due to their unique mechanism of action. Dermatologic toxicities appear to be one of the most prevalent irAEs. The most common symptoms are maculopapular rash and pruritus. Serious dermatologic AEs, including Stevens-Johnson syndrome and toxic epidermal necrolysis, are rare. In this review, we summarized guidelines of management of immunotherapy-related toxicities and case reports, and proposed treatment recommendation.

Clinical Diagnosis and Treatment Recommendations for Cardiac Adverse Reactions Related to Immune Checkpoint Inhibitor / 中国肺癌杂志

Immunotherapy of malignant tumors has become a hot spot in the field of cancer research and treatment, bringing new hope to patients with advanced cancer. Activation of molecular programmer death protein-1 and T lymphocyte-associated antigen 4-related signaling pathways at the immunological checkpoint can inhibit T lymphocyte activation and thereby block the inflammatory response. Tumor cells achieve immune escape by activating the molecular pathways associated with immune checkpoints. The immune checkpoint inhibitor can wake up T lymphocytes and enhance the body's clearance of tumor cells. However, the role of immune checkpoint inhibitors is not specific to tumor cells, and it can cause side effects of multiple systems including the cardiovascular system while killing tumor cells. We will summarize the relevant cardiac side effects and give advice on how to manage it.

Clinical Diagnosis and Treatment Recommendations for the Pneumonitis Associated with Immune Checkpoint Inhibitor / 中国肺癌杂志

The increasing use of immunocheckpoint inhibitors in tumors has brought new hope of survival to patients with advanced tumors. However, the immune system activated by immunocheckpoint inhibitors, mainly activated T-cell immunity, may attack normal tissues and organs of the human body and lead to a variety of adverse effects. In the lung, they could induce checkpoint inhibitor associated pneumonitis (CIP). CIP is different from known pulmonary interstitial pneumonitis, and had a potentially fatal risk if it was not being properly treated. We will summarize the characteristics of CIP and give our advice on how to manage immunocheckpoint inhibitor associated pneumonitis.