Study on the efficacy of early treatment with pirfenidone on the lung function of patients with idiopathic pulmonary fibrosis

BACKGROUND Idiopathic pulmonary fibrosis(IPF)is classified under fibrotic interstitial pneumonia,characterized by a chronic and progressive course.The predominant clinical features of IPF include dyspnea and pulmonary dysfunction.AIM To assess the effects of pirfenidone in the early treatment of IPF on lung function in patients.METHODS A retrospective analysis was performed on 113 patients with IPF who were treated in our hospital from November 2017 to January 2023.These patients were divided into two groups:control group(n=53)and observation group(n=60).In the control group,patients received routine therapy in combination with methylprednisolone tablets,while those in the observation group received routine therapy together with pirfenidone.After applying these distinct treatment approaches to the two groups,we assessed several parameters,including the overall effectiveness of clinical therapy,the occurrence of adverse reactions(e.g.,nausea,vomiting,and anorexia),symptom severity scores,pulmonary function index levels,inflammatory marker levels,and the 6-min walk distance before and after treatment in both groups.RESULTS The observation group exhibited significantly higher rates than the control group after therapy,with a clear distinction(P<0.05).After treatment,the observation group experienced significantly fewer adverse reactions than the control group,with a noticeable difference(P<0.05).When analyzing the symptom severity scores between the two groups of patients after treatment,the observation group had significantly lower scores than the control group,with a distinct difference(P<0.05).When comparing the pulmonary function index levels between the two groups of patients after therapy,the observation group displayed significantly higher levels than the control group,with a noticeable difference(P<0.05).Evaluating the inflammatory marker data(C-reactive protein,interleukin-2[IL-2],and IL-8)between the two groups of patients after therapy,the observation group exhibited significantly lower levels than the control group,with significant disparities(P<0.05).Comparison of the 6-min walking distance data between the two groups of patients after treatment showed that the observation group achieved significantly greater distances than the control group,with a marked difference(P<0.05).CONCLUSION Prompt initiation of pirfenidone treatment in individuals diagnosed with IPF can enhance pulmonary function,elevate inflammatory factor levels,and increase the distance covered in the 6-min walk test.This intervention is conducive to effectively decreasing the occurrence of adverse reactions in patients.

PKHD1L1 blocks the malignant behavior of lung adenocarcinoma cells and restricts tumor growth by regulating CBX7

Objective:To explore the role of polycystic kidney and hepatic disease 1-like 1(PKHD1L1)in lung adenocarcinoma(LUAD).Methods:Bioinformatics tools were utilized to examine the clinical profile of PKHD1L1 and chromobox protein homolog 7(CBX7)in LUAD.The Cell Counting Kit-8,colony formation,terminal deoxynucleotidyl transferase dUTP nick end labeling,Transwell,and wound-healing assays were carried out to assess the proliferative,apoptotic,invasive,and migrative capacities of the cells.Furthermore,the interrelation between PKHD1L1 and CBX7 was validated using a co-immunoprecipitation assay.A LUAD mice model was constructed by subcutaneous injection of A549 cells.Finally,immunohistochemical staining was performed to evaluate CBX7 and Ki67 expression.Results:PKHD1L1 was downregulated in LUAD and predicted dismal outcomes in patients with LUAD.PKHD1L1 upregulation repressed the proliferative,invasive,and migrative capabilities of A549 cells and exacerbated the apoptotic rate.Additionally,PKHD1L1 may bind to CBX7 and positively modulate CBX7 expression.CBX7 deletion partly abrogated the effects of PKHD1L1 upregulation on the cellular biological activities in A549 cells.Furthermore,the PKHD1L1/CBX7 axis regulates the Hippo signaling pathway in A549 cells.PKHD1L1 restricted tumor growth in LUAD xenograft mice;this was partly abolished by CBX7 knockdown.Conclusion:PKHD1L1 can hinder LUAD progression by regulating CBX7-mediated Hippo signaling.

Polyunsaturated Fatty Acid Concentrations and Risk of Pneumoconiosis:A Two-sample Mendelian Randomization Study

Pneumoconiosis refers to a group of interstitial lung diseases that arise from the prolonged inhalation of occupational dust,resulting in chronic inflammation,immune dysregulation,and lung fibrosis[1].According to the 2019 Burden of Disease database,there are currently 3.1 million cases of pneumoconiosis worldwide,with developing countries such as China experiencing a particularly significant burden.The complex pathogenesis of pneumoconiosis,along with the irreversible nature of pulmonary fibrosis,has led to a scarcity of effective therapeutic options.While the aetiology of pneumoconiosis is well established,additional factors,including diet,genetic susceptibility,and lifestyle habits,may influence an individual’s risk of developing the disease or its progression.Notably,moderate intake of polyunsaturated fatty acids(PUFAs)has been associated with a reduced risk of chronic respiratory diseases and the modulation of lung inflammation through the regulation of antioxidant signaling pathways[2].However,the potential impact of PUFAs on pneumoconiosis remains an area requiring further investigation.

Role of diaphragmatic ultrasound in patients with acute exacerbation of chronic obstructive pulmonary disease

Assessing diaphragm function status is vital for diagnosing and treating acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Diaphrag-matic ultrasound has become increasingly important due to its non-invasive nature,absence of radiation exposure,widespread availability,prompt results,high accuracy,and repeatability at the bedside.The diaphragm is a crucial respiratory muscle.Decline or dysfunction of the diaphragm can lead to dyspnea and even respiratory failure in AECOPD patients.In this editorial,we comment on an article,retrospectively analyzed ninety-four acute exacerbations of chronic obstructive pulmonary disease patients who received mechanical ventilation from January 2022 to December 2023.The study found that the diaphragm thickening fraction,an index from diaphragm ultrasound,can better predict the outcome of non-invasive ventilation in patients with AECOPD.The value of non-invasive ventilation in treating respiratory failure caused by AECOPD has been widely acknowledged.Diaphragmatic dysfunction diagnosed with ultrasound is asso-ciated with prolonged mechanical ventilation and weaning times and higher mortality.

Prognostic and immunological roles of heat shock protein A4 in lung adenocarcinoma

BACKGROUND Heat shock protein A4(HSPA4)belongs to molecular chaperone protein family which plays important roles within variable cellular activities,including cancer initiation and progression.However,the prognostic and immunological significance of HSPA4 in lung adenocarcinoma(LUAD)has not been revealed yet.AIM To explore the prognostic and immunological roles of HSPA4 to identify a novel prognostic biomarker and therapeutic target for LUAD.METHODS We assessed the prognostic and immunological significance of HSPA4 in LUAD using data from The Cancer Genome Atlas database.The association between HSPA4 expression and clinical-pathological features was assessed through Kruskal-Wallis and Wilcoxon signed-rank test.Univariate/multivariate Cox regression analyses and Kaplan-Meier curves were employed to evaluate prognostic factors,including HSPA4,in LUAD.Gene set enrichment analysis(GSEA)was conducted to identify the key signaling pathways associated with HSPA4.The correlation between HSPA4 expression and cancer immune infiltration was evaluated using single-sample gene set enrichment analysis(ssGSEA).RESULTS Overexpressing HSPA4 was significantly related to advanced pathologic TNM stage,advanced pathologic stage,progression disease status of primary therapy outcome and female subgroups with LUAD.In addition,increased HSPA4 expression was found to be related to worse disease-specific survival and overall survival.GSEA analysis indicated a significant correlation between HSPA4 and cell cycle regulation and immune response,particularly through diminishing the function of cytotoxicity cells and CD8 T cells.The ssGSEA algorithm showed a positive correlation between HSPA4 expression and infiltrating levels of Th2 cells,while a negative correlation was observed with cytotoxic cell infiltration levels.CONCLUSION Our findings indicate HSPA4 is related to prognosis and immune cell infiltrates and may act as a novel prognostic biomarker and therapeutic target for LUAD.

Molecular Epidemiology and Clinical Characteristics of Hand, Foot and Mouth Disease in North Sichuan Region, China, 2018-2023: A Descriptive Study

Background: Hand, foot and mouth disease (HFMD) remains an important public health problem in China. Many studies on the epidemiological characteristics of HFMD have been reported, but studies in North Sichuan region have been neglected. Methods: HFMD-related enterovirus infected cases were clinically confirmed and underwent real-time RT-PCR (rRT-PCR) from May 2018 to October 2023 in Guangyuan Central Hospital. Results: During 2018-2023, other EV (437 cases, 81.08%) was the most predominant serotype followed by CV-A16 (94 cases, 17.44%), EV-A71 (8 cases, 1.48%) was the least predominant serotype. Peak infections occurred in July and October. There were no significant differences in gender, age and serotypes. HFMD was concentrated in children under 47 months of age, with the highest incidence in children aged 12 - 23 months and the highest proportion of other EV infections in the whole age group. COVID-19 did not cause significant changes in gender, age and serotype. Overall, there was a significant increase in the proportion of children aged 12 - 23 months infected with CV-A16, and an increase in the proportion of children aged over 36 months infected with other EVs. Conclusions: The incidence of HFMD caused by EV-A71 has decreased significantly, and other EVs have become the main pathogens of HFMD in North Sichuan region in recent years. In the prevention and control of CV-A16, more attention should be paid to children aged 12 - 23 months and the dominant serotype should be closely monitored. Our study highlights the importance of developing of new diagnostic reagents and vaccines for the prevention and control of enterovirus infection. This study for the first time provides insights into district interventions to local conditions.

Traumatic brain injury and variants of shock index

Traumatic Brain Injury is a major cause of death and long-term disability.The early identification of patients at high risk of mortality is important for both management and prognosis.Although many modified scoring systems have been developed for improving the prediction accuracy in patients with trauma,few studies have focused on prediction accuracy and application in patients with traumatic brain injury.The shock index(SI)which was first introduced in the 1960s has shown to strongly correlate degree of circulatory shock with increasing SI.In this editorial we comment on a publication by Carteri et al wherein they perform a retrospective analysis studying the predictive potential of SI and its variants in populations with severe traumatic brain injury.

The Value of γδ T Cells in Lung Infections and Advances in Diagnosis and Treatment

Lung infections are usually caused by pathogenic microorganisms and are a disease with high morbidity and mortality. In clinical practice, the use of broad-spectrum antibiotics has become increasingly common, but this has also led to the problem of antibiotic abuse and irrational use, which in turn has spawned the emergence of multidrug-resistant bacteria, making the treatment of lung infections more complex and difficult. In the human immune system, γδ T cells play a crucial role in defense against foreign pathogens and regulation of autoimmune responses. These cells act as a bridge between innate and adaptive immunity and can be rapidly activated in the early stages of infection to produce inflammatory factors and chemokines that attract other immune cells to the site of infection. Recent advances have shown that γδ T cells not only play a direct role in the innate immunity of pathogen infection, but are also involved in regulating the subsequent adaptive immune response. The aim of this review is to explore the mechanism of γδ T cells in lung infections and to summarize the current progress of clinical research, with the aim of providing new scientific basis and therapeutic strategies for the treatment of lung infections.

Analysis of the Effect of Continuous Nursing Care in Patients with COPD

Objective:to study the effect of continuous nursing intervention in patients with chronic obstructive pulmonary disease(COPD).Methods:In this paper,56 COPD patients were selected and grouped by drawing lots,with 28 cases in each group.The study group underwent continuous nursing intervention,while the control group underwent conventional care,and the parameters of both groups of patients were compared.Results:Compared with the control group,the patients in the study group had a significantly higher forced expiratory volume in one second to forced vital capacity ratio(FEV1/FVC),a significantly lower COPD Assessment Test(CAT)score,and Hamilton Depression(HAM-D)score,and a significantly higher 6-Minute Walk Test(6WMT)score after nursing care.Besides,their self-care ability score and SaO_(2)were significantly higher,while their PaCO_(2)and coagulation indexes were significantly lower(P<0.05).Conclusion:Continuous nursing intervention is beneficial for COPD patients.

Critical care practice in India:Results of the intensive care unit need assessment survey(ININ2018)

BACKGROUND A diverse country like India may have variable intensive care units(ICUs)practices at state and city levels.AIM To gain insight into clinical services and processes of care in ICUs in India,this would help plan for potential educational and quality improvement interventions.METHODS The Indian ICU needs assessment research group of diverse-skilled individuals was formed.A pan-India survey"Indian National ICU Needs"assessment(ININ 2018-I)was designed on google forms and deployed from July 23rd-August 25th,2018.The survey was sent to select distribution lists of ICU providers from all 29 states and 7 union territories(UTs).In addition to emails and phone calls,social medial applications-WhatsApp™,Facebook™and LinkedIn™were used to remind and motivate providers.By completing and submitting the survey,providers gave their consent for research purposes.This study was deemed eligible for category-2 Institutional Review Board exempt status.RESULTS There were total 134 adult/adult-pediatrics ICU responses from 24(83%out of 29)states,and two(28%out of 7)UTs in 61 cities.They had median(IQR)16(10-25)beds and most,were mixed medical-surgical,111(83%),with 108(81%)being adult-only ICUs.Representative responders were young,median(IQR),38(32-44)years age and majority,n=108(81%)were males.The consultants were,n=101(75%).A total of 77(57%)reported to have 24 h in-house intensivist.A total of 68(51%)ICUs reported to have either 2:1 or 2≥:1 patient:nurse ratio.More than 80%of the ICUs were open,and mixed type.Protocols followed regularly by the ICUs included sepsis care,ventilator-associated pneumonia(83%each);nutrition(82%),deep vein thrombosis prophylaxis(87%),stress ulcer prophylaxis(88%)and glycemic control(92%).Digital infrastructure was found to be poor,with only 46%of the ICUs reporting high-speed internet availability.CONCLUSION In this large,national,semi-structured,need-assessment survey,the need for improved manpower including;in-house intensivists,and decreasing patient-tonurse ratios was evident.Sepsis was the most common diagnosis and quality and research initiatives to decrease sepsis mortality and ICU length of stay could be prioritized.Additionally,subsequent surveys can focus on digital infrastructure for standardized care and efficient resource utilization and enhancing compliance with existing protocols.

Pulmonary sarcoidosis:A novel sequelae of drug reaction with eosinophilia and systemic symptoms:A case report

BACKGROUND Drug reaction with eosinophilia and systemic symptoms(DRESS)syndrome is an uncommon yet serious adverse drug hypersensitivity reaction with the presentations including rash,fever,lymphadenopathy,and internal organ involvement.Sarcoidosis is a systematic granulomatous disease with unknown etiology.We herein report a case of pulmonary sarcoidosis secondary to allopurinol-induced DRESS.CASE SUMMARY A 37-year-old man with a history of hyperuricemia was treated with allopurinol for three weeks at a total dose of 7000 milligrams before developing symptoms including anorexia,fever,erythematous rash,and elevated transaminase.The patient was diagnosed with DRESS and was treated with prednisone for 6 mo until all the symptoms completely resolved.Three months later,the patient presented again because of a progressively worsening dry cough.His chest computed tomography images showed bilateral lung parenchyma involvement with lymph node enlargement,which was confirmed to be nonnecrotizing granuloma by pathological examination.Based on radiologic and pathological findings,he was diagnosed with sarcoidosis and was restarted on treatment with prednisone,which was continued for another 6 mo.Reexamination of chest imaging revealed complete resolution of parenchymal lung lesions and a significant reduction in the size of the mediastinal and hilar lymph nodes.Following a 6-month follow-up of completion of treatment,the patient's clinical condition remained stable with no clinical evidence of relapse.CONCLUSION This is the first case in which pulmonary sarcoidosis developed as a late complication of allopurinol-induced DRESS.The case indicated that the autoimmune reaction of DRESS may play an important role in the pathogenesis of sarcoidosis.

Dantrolene in the Treatment of Refractory Hyperthermic Conditions in Critical Care: A Multicenter Retrospective Study

Purpose: To examine the use of intravenous dantrolene in hospitalized patients. Materials and Methods: Medical Records of patients treated with intravenous dantrolene between 2007 and 2012 at 6 teaching hospitals were reviewed. Temperature, muscle rigidity, creatine kinase levels, and mortality were assessed in association with dantrolene use. Results: Twenty-five patients received intravenous dantrolene, 9 patients with neuroleptic malignant syndrome (NMS), 8 with hyperthermia due to sepsis, 4 with NMS and sepsis, 2 for malignant hyperthermia (MH), and 2 with hypermetabolic syndrome associated with juvenile diabetic ketoacidosis. Dantrolene was administered as a bolus of 1 - 3 mg/kg. Core temperature decreased after dantrolene administration in all groups but significant only for MH, NMS cases (Pre 102.3 ± 0.9&degF vs. Post 99.5 ± 0.9&degF;p Conclusion: Dantrolene was associated with reductions in temperature and rigidity in hyperthermia of diverse origins in patients admitted to Intensive care settings.

Progress of Radix Astragali and Radix Angelicae Sinensis in the treatment of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis(IPF)is a chronic,progressive,fibrotic interstitial lung disease.Current treatment options for IPF are limited.Radix Astragali(RA)and Radix Angelicae Sinensis(RAS),according to 5:1 ratio composed of Danggui Buxue decoction(DGBXD),which have played an essential role in the treatment of IPF.This article reviewed the experimental research,clinical research,and progress of RA and RAS(DGBXD)treating IPF to provide a deeper scientific basis for the future experimental research and clinical research.

National survey of the awareness and implementation status of early pulmonary rehabilitation for patients with critical illness in departments of pulmonary and critical care medicine in 2019

To the Editor:The aim of early pulmonary rehabilitation(PR)in the intensive care unit(ICU)is to reduce the incidence of post-ICU syndrome,increase the number of ventilator-free days,reestablish and improve functional capacity,improve health-related life quality,promote mental health,and enhance participation in everyday life.PR in the ICU is highly effective and plays an important role in recovery of patients with reduced exercise endurance,functional capacity,and health-related life quality.Several surveys outside China have assessed the implementation of early rehabilitation in the ICU,[1]but there are few data from China.This study aimed to investigate the awareness and implementation of early PR in secondary-and tertiary-class hospitals with pulmonary and critical care medicine(PCCM)standardized certification.PCCM staff members were recruited to fill out a selfdesigned questionnaire.We defined early PR as PR within 5 days of ICU admission.

Metabolomic Analysis of Serum Glycerophospholipid Levels in Eosinophilic and Neutrophilic Asthma

Objective To compare the serum glycerophospholipid levels in the inflammatory subtypes of asthma by using targeted metabolomic analysis. Methods Demographic and clinical data were collected from 51 patients with asthma between January 2015 and December 2015. Routine blood and sputum induction tests were performed. Eosinophilic asthma was defined as induced sputum containing ≥ 3% eosinophils, and neutrophilic asthma, as induced sputum containing ≥ 71% neutrophils. Serum metabolic glycerophospholipid profile was determined by liquid chromatography-mass spectrometry. Differences in glycerophospholipid levels between eosinophilic and non-eosinophilic asthma and between neutrophilic and non-neutrophilic asthma were analyzed using partial least squares discriminant analysis. Results The serum lysophosphatidylglycerol level was significantly higher in the group with ≥ 3% eosinophils in sputum than in the group with < 3% eosinophils in sputum. The area under the receiver-operating characteristic curve was ≥ 70%. There was no significant difference in the serum metabolic glycerophospholipid profile between the group with sputum neutrophils ≥ 71% and the group with sputum neutrophils < 71%. Conclusion Serum lysophosphatidylglycerol is produced abundantly in eosinophilic asthma and may be a biomarker of eosinophilic asthma. This information is helpful for identifying and tailoring treatment for the common asthma subtypes.

Pulmonary embolism and deep vein thrombosis caused by nitrous oxide abuse: A case report

BACKGROUND Nitrous oxide(N2O)has gained increasing popularity as a recreational drug,causing hallucinations,excitation,and psychological dependence.However,side effects have been reported in recent years.Our case report proposes a correlation among N2O,pulmonary embolism(PE),and deep vein thrombosis(DVT)and emphasizes the role of homocysteine(Hcy)in thrombotic events.CASE SUMMARY A 29-year-old man with long-term N2O abuse sought evaluation after acute chest pain.A diagnostic workup revealed PE,DVT,and hyperhomocysteinemia.The patient was successfully treated with thrombolytic and anticoagulant therapy.Moreover,his Hcy level decreased and returned to normal after Hcy-lowering therapy.CONCLUSION Chronic N2O abuse might increase the risk of PE and DVT,although there have been few studies previously.

Clinical characteristics and risk factors of Talaromyces marneffei infection in human immunodeficiency virus-negative patients: A retrospective observational study

BACKGROUND: To investigate the clinical characteristics and risk factors of human immunodeficiency virus(HIV)-negative patients with Talaromyces marneffei(T. marneffei) infection.METHODS: We retrospectively collected the clinical information of HIV-negative patients with T. marneffei infection from January 1, 2010 to June 30, 2019, and analyzed the related risk factors of poor prognosis.RESULTS: Twenty-five cases aging 22 to 79 years were included. Manifestations of T. marneffei infection included fever, cough, dyspnea, chest pain or distress, lymphadenopathy, ear, nose, and throat(ENT) and/or skin lesions, bone or joint pain, edema and pain in the lower extremities, digestive symptoms, icterus, malaise, and hoarseness. Two cases had no comorbidity, while 23 cases suff ered from autoimmune disease, pulmonary disease, cancer, and other chronic diseases. Sixteen cases had a medication history of glucocorticoids, chemotherapy or immunosuppressors. Pulmonary lesions included interstitial infiltration, nodules, atelectasis, cavitary lesions, pleural effusion or hydropneumothorax, bronchiectasis, pulmonary fibrosis, pulmonary edema, and consolidation. The incidence of osteolytic lesions was 20%. Eight patients received antifungal monotherapy, and 11 patients received combined antifungal agents. Fifteen patients survived and ten patients were dead. The Cox regression analysis showed that reduced eosinophil counts, higher levels of blood urea nitrogen(BUN), alanine aminotransferase(ALT), aspartate aminotransferase(AST), lactic dehydrogenase(LDH), myoglobin(Mb), procalcitonin(PCT), and galactomannan were related to poor prognosis(hazard ratio [HR]>1, P<0.05).CONCLUSIONS: Bone destruction is common in HIV-negative patients with T. marneffei infection. Defective cell-mediated immunity, active infection, multiple system, and organ damage can be the risk factors of poor prognosis.

Metabolomic Profiling Differences among Asthma,COPD,and Healthy Subjects:A LC-MS-based Metabolomic Analysis

Objective Asthma and chronic obstructive pulmonary disease(COPD)feature different inflammatory and cellular profiles in the airways,indicating that the cellular metabolic pathways regulating these disorders are distinct.Methods We aimed to compare the serum metabolomic profiles among mild persistent asthmatic patients,individuals with stable COPD,and healthy subjects and to explore the potential metabolic biomarkers and pathways.The serum metabolomic profiles of 17 subjects with mild persistent asthma,17 subjects with stable COPD,and 15 healthy subjects were determined by an untargeted metabolomic an alysis utilizi ng liquid chromatography-mass spectrometry.A series of multivariate statistical an a lyses was subsequently used.Results Multivariate analysis indicated a distinct separation between the asthmatic patients and healthy controls in electrospray positive and negative ions modes,respectively.A total of 19 differential metabolites were identified.Similarly,a distinct separation between asthma and COPD subjects was detected in the two ions modes.A total of 16 differential metabolites were identified.Among the identified metabolites,the serum levels of hypoxanthine were markedly higher in asthmatic subjects compared with those in COPD or healthy subjects.Conclusions Patients with asthma present a unique serum metabolome,which can distinguish them from individuals with COPD and healthy subjects.Purine metabolism alteration may be distinct and involved in the pathogenesis of asthma.

Effects of Mitochondrial ATP-sensitive K^+ Channel on Protein Kinase C Pathway and Airway Smooth Muscle Cell Proliferation in Asthma

The effects of ATP-sensitive mitochondrial K + channel(mitoK ATP) on mitochondrial membrane potential(Δψm),cell proliferation and protein kinase C alpha(PKCα) expression in airway smooth muscle cells(ASMCs) were investigated.Thirty-six Sprague-Dawley(SD) rats were immunized with saline(controls) or ovalbumin(OVA) with alum(asthma models).ASMCs were cultured from the lung of control and asthma rats.ASMCs were treated with diazoxide(the potent activator of mitoK ATP) or 5-hydroxydencanote(5-HD,the inhibitor of mitoK ATP).Rhodamine-123(R-123) was used to detect Δψm.The expression of PKCα protein was examined by using Western blotting,while PKCα mRNA expression was detected by using real-time PCR.The proliferation of ASMCs was measured by MTT assay and cell cycle analysis.In diazoxide-treated normal ASMCs,the R-123 fluorescence intensity,protein and mRNA levels of PKCα,MTT A values and percentage of cells in S phase were markedly increased as compared with untreated controls.The ratio of G 0 /G 1 cells was decreased(P<0.05) in diazoxide-treated ASMCs from normal rats.However,there were no significant differences between the ASMCs from healthy rats treated with 5-HD and the normal control group.In untreated and diazoxide-treated ASMCs of asthmatic rats,the R-123 fluorescence intensity,protein and mRNA levels of PKCα,MTT A values and the percentage of cells in S phase were increased in comparison to the normal control group.Furthermore,in comparison to ASMCs from asthmatic rats,these values were considerably increased in asthmatic group treated with diazoxide(P<0.05).After exposure to 5-HD for 24 h,these values were decreased as compared with asthma control group(P<0.05).In ASMCs of asthma,the signal transduction pathway of PKCα may be involved in cell proliferation,which is induced by the opening of mitoK ATP and the depolarization of Δψm.

Identifying critically ill patients at risk of death from coronavirus disease

BACKGROUND:A pandemic of coronavirus disease(COVID-19)has been declared by the World Health Organization(WHO)and caring for critically ill patients is expected to be at the core of battling this disease.However,little is known regarding an early detection of patients at high risk of fatality.METHODS:This retrospective cohort study recruited consecutive adult patients admitted between February 8 and February 29,2020,to the three intensive care units(ICUs)in a designated hospital for treating COVID-19 in Wuhan.The detailed clinical information and laboratory results for each patient were obtained.The primary outcome was in-hospital mortality.Potential predictors were analyzed for possible association with outcomes,and the predictive performance of indicators was assessed from the receiver operating characteristic(ROC)curve.RESULTS:A total of 121 critically ill patients were included in the study,and 28.9%(35/121)of them died in the hospital.The non-survivors were older and more likely to develop acute organ dysfunction,and had higher Sequential Organ Failure Assessment(SOFA)and quick SOFA(qSOFA)scores.Among the laboratory variables on admission,we identifi ed 12 useful biomarkers for the prediction of in-hospital mortality,as suggested by area under the curve(AUC)above 0.80.The AUCs for three markers neutrophilto-lymphocyte ratio(NLR),thyroid hormones free triiodothyronine(FT3),and ferritin were 0.857,0.863,and 0.827,respectively.The combination of two easily accessed variables NLR and ferritin had comparable AUC with SOFA score for the prediction of in-hospital mortality(0.901 vs.0.955,P=0.085).CONCLUSIONS:Acute organ dysfunction combined with older age is associated with fatal outcomes in COVID-19 patients.Circulating biomarkers could be used as powerful predictors for the in-hospital mortality.