Overview of the immunological mechanisms in hepatitis B virus reactivation:Implications for disease progression and management strategies

Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.

Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population:An integrated genomic and transcriptional analysis

Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not been fully investigated.This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care.Methods:A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled.HRD status was assessed using the AmoyDx Genomic Scar Score(GSS),with a score of≥50 considered HRD-positive.Genomic,transcriptomic,tumor microenvironmental characteristics and prognosis between HRD-positive and HRDnegative patients were analyzed.Results:Of the patients,25.1%(89/355)were HRD-positive.Compared to HRD-negative patients,HRDpositive patients had more somatic pathogenic homologous recombination repair(HRR)mutations,higher tumor mutation burden(TMB)(P<0.001),and fewer driver gene mutations(P<0.001).Furthermore,HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes,MET and MYC in epidermal growth factor receptor(EGFR)/anaplastic lymphoma kinase(ALK)mutant NSCLC,and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC.HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity.HRD-negative NSCLC showed activated signatures of major histocompatibility complex(MHC)-II,interferon(IFN)-γand effector memory CD8+T cells.HRD-positive patients had a worse prognosis and shorter progressionfree survival(PFS)to targeted therapy(first-and third-generation EGFR-TKIs)(P=0.042).Additionally,HRDpositive,EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens.Conclusions:Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC.Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC.This study highlights potential actionable alterations in HRD-positive NSCLC,suggesting possible combinational therapeutic strategies for these patients.

Comparing the efficacy and safety of low,medium,and high dosages of selexipag for treating pulmonary hypertension:A systematic review and meta-analysis

Background:The maintenance dosage of selexipag is categorized as low,medium or high.In order to assess the efficacy and safety of different dosages of selexipag for the risk stratification of pulmonary arterial hypertension(PAH),we performed a sys-tematic review and meta-analysis.Methods:Studies assessing PAH risk stratification indices,such as the World Health Organization functional class(WHO-FC),six-minute walk distance(6MWD),N-terminal pro-B-type natriuretic peptide(NT-proBNP)level,right atrial pressure(RAP),cardiac index(CI)and mixed venous oxygen saturation(SvO2),were included.Results:Thirteen studies were included.Selexipag led to improvements in the 6MWD(MD:24.20 m,95%CI:10.74-37.67),NT-proBNP(SMD:-0.41,95%CI:-0.79-0.04),CI(MD:0.47 L/min/m^(2),95%CI:0.17-0.77)and WHO-FC(OR:0.564,95%CI:0.457-0.697).Subgroup analysis demonstrated that all three dosages improved the 6MWD.A moderate dosage led to improvements in the CI(MD:0.30 L/min/m^(2),95%CI:0.15-0.46)and WHO-FC(OR:0.589,95%CI:0.376-0.922).Within 6 months of treatment,only the WHO-FC and CI were significantly improved(OR:0.614,95%CI:0.380-0.993;MD:0.30 L/min/m^(2),95%CI:0.16-0.45,respectively).More than 6 months of treatment significantly improved the 6MWD,WHO-FC and NT-proBNP(MD:40.87 m,95%CI:10.97-70.77;OR:0.557,95%CI:0.440-0.705;SMD:-0.61,95%CI:-1.17-0.05,respectively).Conclusions:Low,medium,and high dosages of selexipag all exhibited good effects.When treatment lasted for more than 6 months,selexipag exerted obvious effects,even in the low-dosage group.This finding is important for guiding individualized treatments.

Diagnosis and therapy of tacrolimus toxicity in a liver transplant recipient during COVID-19 treatment

To the Editor:SARS-CoV-2,the pathogen responsible for the pandemic of coronavirus disease 2019(COVID-19),has had profound impacts on human health,and its antagonist Paxlovid is a commonly used treatment option[1].However,treatment selection for immunosuppressed patients,such as liver recipients,remains uncertain due to potential drug interactions and the risk of immunosuppressant dosage adjustment,which can cause liver injury[2].

Influence of blood glucose fluctuations on chemotherapy efficacy and safety in type 2 diabetes mellitus patients complicated with lung carcinoma

BACKGROUND Patients with type 2 diabetes mellitus(T2DM)have large fluctuations in blood glucose(BG),abnormal metabolic function and low immunity to varying degrees,which increases the risk of malignant tumor diseases and affects the efficacy of tumor chemotherapy.Controlling hyperglycemia may have important therapeutic implications for cancer patients.AIM To clarify the influence of BG fluctuations on chemotherapy efficacy and safety in T2DM patients complicated with lung carcinoma(LC).METHODS The clinical data of 60 T2DM+LC patients who presented to the First Affiliated Hospital of Ningbo University between January 2019 and January 2021 were retrospectively analyzed.All patients underwent chemotherapy and were grouped as a control group(CG;normal BG fluctuation with a mean fluctuation<3.9 mmol/L)and an observation group(OG;high BG fluctuation with a mean fluctuation≥3.9 mmol/L)based on their BG fluctuations,with 30 cases each.BGrelated indices,tumor markers,serum inflammatory cytokines and adverse reactions were comparatively analyzed.Pearson correlation analysis was performed to analyze the correlation between BG fluctuations and tumor markers.RESULTS The fasting blood glucose and 2-hour postprandial blood glucose levels in the OG were notably elevated compared with those in the CG,together with markedly higher mean amplitude of glycemic excursions(MAGE),mean of daily differences,largest amplitude of glycemic excursions and standard deviation of blood glucose(P<0.05).In addition,the OG exhibited evidently higher levels of carbohydrate antigen 19-9,carbohydrate antigen 125,carcinoembryonic antigen,neuron-specific enolase,cytokeratin 19,tumor necrosis factor-α,interleukin-6,and highsensitivity C-reactive protein than the CG(P<0.05).Pearson analysis revealed a positive association of MAGE with serum tumor markers.The incidence of adverse reactions was significantly higher in the OG than in the CG(P<0.05).CONCLUSION The greater the BG fluctuation in LC patients after chemotherapy,the more unfavorable the therapeutic effect of chemotherapy;the higher the level of tumor markers and inflammatory cytokines,the more adverse reactions the patient experiences.

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.

Klebsiella pneumoniae infections after liver transplantation:Drug resistance and distribution of pathogens,risk factors,and influence on outcomes

BACKGROUND Liver transplantation(LT)is the only curative treatment for end-stage liver disease.However,LT recipients are susceptible to infection,which is the leading cause of early mortality after LT.Klebsiella pneumoniae infections(KPIs)in the bloodstream are common in LT recipients.We hypothesized that KPIs and carbapenemresistant Klebsiella pneumoniae(CRKP)infections may affect the outcomes of LT recipients.AIM To assess KPI incidence,timing,distribution,drug resistance,and risk factors following LT and its association with outcomes.METHODS This retrospective study included 406 patients undergoing LT at The Third Xiangya Hospital of Central South University,a tertiary hospital,from January 2015 to January 2023.We investigated the risk factors for KPIs and assessed the impact of KPIs and CRKP infections on the prognosis of LT recipients using logistic regression analysis.RESULTS KPI incidence was 7.9%(n=32),with lung/thoracic cavity the most frequent site of infection;the median time from LT to KPI onset was 7.5 d.Of 44 Klebsiella pneumoniae isolates,43(97.7%)and 34(77.3%)were susceptible to polymyxin B or ceftazidime/avibactam and tigecycline,respectively;>70%were resistant to piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,meropenem,and levofloxacin.Female sex[odds ratio(OR)=2.827,95%confidence interval(CI):1.256-6.364;P=0.012],pre-LT diabetes(OR=2.794,95%CI:1.070-7.294;P=0.036),day 1 post-LT alanine aminotransferase(ALT)levels≥1500 U/L(OR=3.645,95%CI:1.671-7.950;P=0.001),and post-LT urethral catheter duration over 4 d(OR=2.266,95%CI:1.016-5.054;P=0.046)were risk factors for KPI.CRKP infections,but not KPIs,were risk factors for 6-month all-cause mortality post-LT.CONCLUSION KPIs occur frequently and rapidly after LT.Risk factors include female sex,pre-LT diabetes,increased post-LT ALT levels,and urethral catheter duration.CRKP infections,and not KPIs,affect mortality.

Analysis of the Efficacy,Progression-Free Survival,and Safety of Anlotinib in Advanced Lung Cancer Treatment

Objective:To analyze the clinical efficacy,progression-free survival,and safety of anlotinib in the treatment of advanced lung cancer.Methods:A retrospective analysis was conducted using data from 60 patients with advanced lung cancer treated with anlotinib from May 2019 to May 2021.This analysis aimed to comprehensively evaluate the clinical efficacy,progression-free survival,and adverse reactions of anlotinib.Results:The median progression-free survival(PFS)for the 60 patients was 5.79 months,with an overall response rate(ORR)of 21%and a disease control rate(DCR)of 90%.In the first-line group,the median PFS was 6.20 months,ORR was 76.92%,and DCR was 84.61%.The second-line group showed a median PFS of 6.30 months,ORR of 28.57%,and DCR of 90.48%.In the third-line group,the median PFS was 5.34 months,ORR was 19.23%,and DCR was 92.30%.The single-agent group exhibited a median PFS of 5.09 months,ORR of 23.33%,and DCR of 76.67%.In the combination group,the median PFS was 6.53 months,ORR was 46.67%,and DCR was 100%.The combination group demonstrated a significantly higher medication effect than the single-drug group,and adverse drug reactions were mostly grade 1-2.Conclusion:Anlotinib exhibits a better disease control rate and survival benefit in the treatment of advanced lung cancer.The combination effect is superior to monotherapy,with relatively controllable adverse effects.

Investigation and Analysis of Lung Cancer Risk Factors in the Health Check-Up Population

Objective: To investigate and analyze the risk factors of lung cancer in the population of health checkups. Methods: A total of 500 cases of the health check-up population were selected for data study. Surveyed showed that 19 cases of lung cancer were grouped as the lung cancer group and the remaining 481 cases made up the control group, and the risk factors were analyzed. Results: Among men, there was a significant proportion of individuals aged 60-69 years old, and women aged 30-39 years old. Additionally, individuals aged 60 and above were at increased risk of developing lung cancer. The results of the multifactorial analysis were that the risk factors affecting the detection of lung cancer in healthy people were smoking history, family history of lung cancer, secondhand smoke, history of respiratory diseases, psychosomatic factors, living environment, and kitchen fumes. Conclusion: People over 60 years of age were prone to early lung cancer, followed by individuals aged 30-39 years. It is important to identify the risk factors of lung cancer to strengthen the screening of high-risk groups for early detection and treatment.

Analysis of the Prevalence Characteristics of Lung Nodules and Their Influencing Factors in The Health Check-Up Population

Objective: To study the prevalence characteristics of pulmonary nodules and their influencing factors in the health check-up population. Methods: A total of 500 cases of health checkups were selected for the data study to analyze the detection and prevalence characteristics of pulmonary nodules. The influencing factors between the pulmonary nodules group and the no pulmonary nodules group were analyzed. Results: A total of 209 cases were detected, of which there were more males than females, and for female patients, the detection rate increased with age (P < 0.05). The distribution of gender, age, smoking, respiratory symptoms, and exposure to kitchen fumes between the two groups was compared (P < 0.05). The multifactorial analysis concluded that risk factors include, respiratory symptoms, older age, exposure to kitchen fumes, and smoking. In addition, patients who exercised more had a lower risk of developing lung nodules. Conclusion: The detection rate of pulmonary nodules was high in the health check-up population and the influencing factors analyzed involved the presence of respiratory symptoms, older age, kitchen fume exposure, and smoking, while the positive influencing factor was increased exercise.

Analysis of the Current Situation and Influencing Factors of Social Isolation Among the Elderly in the Community

Objective: To investigate the current situation of social isolation among the elderly in the community, and to analyze its influencing factors. Methods: A total of 265 elderly people were selected to conduct the survey using the general information questionnaire and the Chinese version of the social isolation scale for the elderly. Results: The social isolation score of the elderly was (20.15 ± 0.23). Factors such as age, education level, economic status, and social participation ability influenced the social isolation score (P < 0.05). Conclusion: The social isolation of the elderly is more serious, and the social isolation can be alleviated by improving the level of education and the economic situation and strengthening social participation.

Clinical Characteristics and Outcomes of Severe or Critical COVID-19 Patients Presenting No Respiratory Symptoms or Fever at Onset

It is difficult to identify suspected cases of atypical patients with coronavirus disease 2019(COVID-19),and data on severe or critical patients are scanty.This retrospective study presents the clinical,laboratory,and radiological profiles,treatments,and outcomes of atypical COVID-19 patients without respiratory symptoms or fever at onset.The study examined ten atypical patients out of 909 severe or critical patients diagnosed with COVID-19 in Wuhan Union Hospital West Campus between 25 January 2020 and 10 February 2020.Data were obtained from the electronic medical records of severe or critical patients without respiratory symptoms or fever at onset.Outcomes were followed up to discharge or death.Among 943 COVID-19 patients,909(96.4%)were severe or critical type.Of the severe or critical patients,ten(1.1%)presented without respiratory symptoms or fever at admission.The median age of the ten participants was 63 years(interquartile range(IQR):57–72),and seven participants were men.The median time from symptom onset to admission was 14 d(IQR:7–20).Eight of the ten patients had chronic diseases.The patients had fatigue(n=5),headache or dizziness(n=4),diarrhea(n=5),anorexia(n=3),nausea or vomiting(n=3),and eye discomfort(n=1).Four patients were found to have lymphopenia.Imaging examination revealed that nine patients had bilateral pneumonia and one had unilateral pneumonia.Eventually,two patients died and eight were discharged.In the discharged patients,the median time from admission to discharge lasted 24 d(IQR:13–43).In summary,some severe or critical COVID-19 patients were found to have no respiratory symptoms or fever at onset.All such atypical cases should be identified and quarantined as early as possible,since they tend to have a prolonged hospital stay or fatal outcomes.Chest computed tomography(CT)scan and nucleic acid detection should be performed immediately on close contacts of COVID-19 patients to screen out those with atypical infections,even if the contacts present without respiratory symptoms or fever at onset.

Inhibition of Bcl-6 Expression Ameliorates Asthmatic Characteristics in Mice

Objective The function of Bcl-6 in T follicular helper(Tfh)cell maturation is indispensable,and Tfh cells play a pivotal role in asthma.This study investigated the impact of Bcl-6 on asthmatic traits.Methods The microscopic pathological alterations,airway resistance(AR),and lung compliance(LC)were determined in asthmatic mice and Bcl-6 interference mice.The surface molecular markers of Tfh cells and the Bcl-6 mRNA and protein expression were determined by flow cytometry,RT-qPCR,and Western blotting,respectively.The relationships between the Tfh cell ratio and the IgE and IgG1 concentrations in peripheral blood mononuclear cells(PBMCs)and bronchoalveolar lavage fluid(BALF)were determined.Results Asthmatic inflammatory changes were observed in the lung tissue and were attenuated by Bcl-6 siRNA and dexamethasone(DXM).Asthmatic mice exhibited an increased AR and a decreased LC,while Bcl-6 siRNA or DXM mitigated these changes.The percentages of Tfh cells and eosinophils were significantly increased in the asthmatic mice,and they significantly decreased after Bcl-6 inhibition or DXM treatment.RT-qPCR and Western blotting analyses revealed that the Bcl-6 expression level in PBMCs was significantly higher in asthmatic mice,and it decreased following Bcl-6 inhibition or DXM treatment.The IgE expression in the serum and BALF and the B cell expression in PBMCs exhibited a similar trend.In asthmatic mice,the ratio of Tfh cells in the peripheral blood showed a strong positive correlation with the IgE levels in the serum and BALF,but not with the IgG1 levels.Conclusion The amelioration of airway inflammation and airway hyper-responsiveness is achieved through Bcl-6 suppression,which effectively hinders Tfh cell differentiation,ultimately resulting in a concurrent reduction in IgE production.

NCAPD2 serves as a potential prognostic biomarker for lung adenocarcinoma and promotes cell proliferation,migration,invasion and cell cycle in vitro

Objectives:The pro-oncogenic effects of NCAPD2 have been extensively studied across various tumor types;however,its precise role within the context of lung adenocarcinoma(LUAD)remains elusive.This study aims to elucidate the biological functions of NCAPD2 in LUAD and unravel the underlying mechanistic pathways.Methods:Utilizing bioinformatics methodologies,we explored the differential expression of NCAPD2 between normal and tumor samples,along with its correlations with clinical-pathological characteristics,survival prognosis,and immune infiltration.Results:In the TCGA-LUAD dataset,tumor samples demonstrated significantly elevated levels of NCAPD2 expression compared to normal samples(p<0.001).Clinically,higher NCAPD2 expression was notably associated with advanced T,N,and M stages,pathologic stage,gender,smoking status,and diminished overall survival(OS).Moreover,differentially expressed genes(DEGs)associated with NCAPD2 were predominantly enriched in pathways related to cell division.Immune infiltration analysis revealed that NCAPD2 expression levels were linked to the infiltration of memory B cells,naïve CD4+T cells,activated memory CD4+T cells,and M1 macrophages.In vitro experiments demonstrated that silencing NCAPD2 suppressed LUAD cell proliferation,migration,invasion,epithelial-mesenchymal transition(EMT),and cell cycle progression.Conclusions:In summary,NCAPD2 may represent a promising prognostic biomarker and novel therapeutic target for LUAD.

Biomaterials and tissue engineering in traumatic brain injury:novel perspectives on promoting neural regeneration

Traumatic brain injury is a serious medical condition that can be attributed to falls, motor vehicle accidents, sports injuries and acts of violence, causing a series of neural injuries and neuropsychiatric symptoms. However, limited accessibility to the injury sites, complicated histological and anatomical structure, intricate cellular and extracellular milieu, lack of regenerative capacity in the native cells, vast variety of damage routes, and the insufficient time available for treatment have restricted the widespread application of several therapeutic methods in cases of central nervous system injury. Tissue engineering and regenerative medicine have emerged as innovative approaches in the field of nerve regeneration. By combining biomaterials, stem cells, and growth factors, these approaches have provided a platform for developing effective treatments for neural injuries, which can offer the potential to restore neural function, improve patient outcomes, and reduce the need for drugs and invasive surgical procedures. Biomaterials have shown advantages in promoting neural development, inhibiting glial scar formation, and providing a suitable biomimetic neural microenvironment, which makes their application promising in the field of neural regeneration. For instance, bioactive scaffolds loaded with stem cells can provide a biocompatible and biodegradable milieu. Furthermore, stem cells-derived exosomes combine the advantages of stem cells, avoid the risk of immune rejection, cooperate with biomaterials to enhance their biological functions, and exert stable functions, thereby inducing angiogenesis and neural regeneration in patients with traumatic brain injury and promoting the recovery of brain function. Unfortunately, biomaterials have shown positive effects in the laboratory, but when similar materials are used in clinical studies of human central nervous system regeneration, their efficacy is unsatisfactory. Here, we review the characteristics and properties of various bioactive materials, followed by the introduction of applications based on biochemistry and cell molecules, and discuss the emerging role of biomaterials in promoting neural regeneration. Further, we summarize the adaptive biomaterials infused with exosomes produced from stem cells and stem cells themselves for the treatment of traumatic brain injury. Finally, we present the main limitations of biomaterials for the treatment of traumatic brain injury and offer insights into their future potential.

Mufangji tang ameliorates pulmonary arterial hypertension through improving vascular remodeling,inhibiting inflammatory response and oxidative stress,and inducing apoptosis

Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and Gypsum.In clinical settings,MFJT has been effectively employed in addressing a range of respiratory disorders,notably including pulmonary arterial hypertension(PAH).However,the mechanism of action of MFJT on PAH remains unknown.Methods:In this study,a monocrotaline-induced PAH rat model was established and treated with MFJT.The therapeutic effects of MFJT on PAH rat model were evaluated.Network pharmacology was conducted to screen the possible targets for MFJT on PAH,and the molecular docking between the main active components and the core targets was carried out.The key targets identified from network pharmacology were tested.Results:Results showed significant therapeutic effects of MFJT on PAH rat model.Analysis of network pharmacology revealed several potential targets related to apoptosis,inflammation,oxidative stress,and vascular remodeling.Molecular docking showed that the key components were well docked with the core targets.Further experimental validation results that MFJT treatment induced apoptosis(downregulated Bcl-2 levels and upregulated Bax levels in lung tissue),inhibited inflammatory response and oxdative stress(decreased the levels of IL-1β,TNF-α,inducible NOS,and malondialdehyde,and increased the levels of endothelial nitric oxide synthase,nitric oxide,glutathione and superoxide dismutase),reduced the proliferation of pulmonary arterial smooth muscle cells(downregulated ET-1 andβ-catenin levels and ERK1/2 phosphorylation,increased GSK3βlevels).Conclusion:Our study revealed MFJT treatment could alleviate PAH in rats via induction of apoptosis,inhibition of inflammation and oxidative stress,and the prevention of vascular remodeling.

Machine learning and bioinformatics to identify biomarkers in response to Burkholderia pseudomallei infection in mice

Objective:In the realm of Class I pathogens,Burkholderia pseudomallei(BP)stands out for its propensity to induce severe pathogenicity.Investigating the intricate interactions between BP and host cells is imperative for comprehending the dynamics of BP infection and discerning biomarkers indicative of the host cell response process.Methods:mRNA extraction from BP-infected mouse macrophages constituted the initial step of our study.Employing gene expression arrays,the extracted RNA underwent conversion into digital signals.The percentile shift method facilitated data processing,with the identification of genes manifesting significant differences accomplished through the application of the t-test.Subsequently,a comprehensive analysis involving Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway was conducted on the differentially expressed genes(DEGs).Leveraging the ESTIMATE algorithm,gene signatures were utilized to compute risk scores for gene expression data.Support vector machine analysis and gene enrichment scores were instrumental in establishing correlations between biomarkers and macrophages,followed by an evaluation of the predictive power of the identified biomarkers.Results:The functional and pathway associations of the DEGs predominantly centered around G protein-coupled receptors.A noteworthy positive correlation emerged between the blue module,consisting of 416 genes,and the StromaScore.FZD4,identified through support vector machine analysis among intersecting genes,indicated a robust interaction with macrophages,suggesting its potential as a robust biomarker.FZD4 exhibited commendable predictive efficacy,with BP infection inducing its expression in both macrophages and mouse lung tissue.Western blotting in macrophages confirmed a significant upregulation of FZD4 expression from 0.5 to 24 h post-infection.In mouse lung tissue,FZD4 manifested higher expression in the cytoplasm of pulmonary epithelial cells in BP-infected lungs than in the control group.Conclusion:Thesefindings underscore the upregulation of FZD4 expression by BP in both macrophages and lung tissue,pointing to its prospective role as a biomarker in the pathogenesis of BP infection.

Clinical evolution of antisynthetase syndrome-associated interstitial lung disease after COVID-19 in a man with Klinefelter syndrome:A case report

BACKGROUND This study presents a case of rapidly developing respiratory failure due to antisynthetase syndrome(AS)following coronavirus disease 2019(COVID-19)in a 33-year-old man diagnosed with Klinefelter syndrome(KS).CASE SUMMARY A 33-year-old man with a diagnosis of KS was admitted to the Department of Pulmonary and Critical Care Medicine of a tertiary hospital in China for fever and shortness of breath 2 wk after the onset of COVID-19.Computed tomography of both lungs revealed diffuse multiple patchy heightened shadows in both lungs,accompanied by signs of partial bronchial inflation.Metagenomic next-generation sequencing of the bronchoalveolar lavage fluid suggested absence of pathogen.A biopsy specimen revealed organizing pneumonia with alveolar septal thickening.Additionally,extensive auto-antibody tests showed strong positivity for anti-SSA,anti-SSB,anti-Jo-1,and anti-Ro-52.Following multidisciplinary discussions,the patient received a final diagnosis of AS,leading to rapidly progressing respiratory failure.CONCLUSION This study underscores the clinical progression of AS-associated interstitial lung disease subsequent to viral infections such as COVID-19 in patients diagnosed with KS.

Association of vitamin D and polymorphisms of its receptor with antiviral therapy in pregnant women with hepatitis B

BACKGROUND The interruption of mother-to-child transmission(MTCT)is considered important to decrease the individual and population morbidity of hepatitis B virus(HBV)infection as well as the global burden of hepatitis B.Serum vitamin D(VD)is associated with hepatitis B.AIM To assess whether baseline VD levels and single nucleotide polymorphisms of the VD receptor gene(VDR SNPs)are associated with the efficacy of tenofovir disoproxil fumarate(TDF)in the prevention of MTCT in pregnant women with high HBV viral loads.METHODS Thirty-eight pregnant women who were at high risk for MTCT of HBV(those with an HBV DNA level≥2×10^(5)IU/mL during 12-24 wk of gestation)receiving antiviral therapy of TDF between June 1,2019 and June 30,2021 in Mianyang were included in this retrospective study.The women received 300 mg TDF once daily from gestational weeks 24-28 until 3 mo after delivery.To further characterize the clinical relevance of maternal serum HBV DNA levels,we stratified patients according to HBV DNA level as follows:Those with levels<2×10_(5)(full responder group)vs those levels≥2×10^(5)IU/mL(partial responder group)at delivery.Serum levels of 25-hydroxyvitamin D[25(OH)D],liver function markers,virological parameters,VDR SNPs and other clinical parameters were collected to analyze their association with the efficacy of TDF.The Mann-Whitney U test or t test was used to analyze the serum levels of 25(OH)D in different groups.Multiple linear regressions were utilized to analyze the determinants of the maternal HBV DNA level at delivery.Univariate and multivariate logistic regression analyses were employed to explore the association of targeted antiviral effects with various characteristics at baseline and delivery.RESULTS A total of 38 pregnant women in Mianyang City at high risk for MTCT of HBV were enrolled in the study.The MTCT rate was 0%.No mother achieved hepatitis B e antigen or hepatitis B surface antigen(HBsAg)clearance at delivery.Twenty-three(60.5%)participants were full responders,and 15(39.5%)participants were partial responders according to antiviral efficacy.The present study showed that a high percentage(76.3%)of pregnant women with high HBV viral loads had deficient(<20 ng/mL)or insufficient(≥20 but<31 ng/mL)VD levels.Serum 25(OH)D levels in partial responders appeared to be significantly lower than those in full responders both at baseline(25.44±9.42 vs 17.66±5.34 ng/mL,P=0.006)and delivery(26.76±8.59 vs 21.24±6.88 ng/mL,P=0.044).Serum 25(OH)D levels were negatively correlated with maternal HBV DNA levels[log(10)IU/mL]at delivery after TDF therapy(r=-0.345,P=0.034).In a multiple linear regression analysis,maternal HBV DNA levels were associated with baseline maternal serum 25(OH)D levels(P<0.0001,β=-0.446),BMI(P=0.03,β=-0.245),baseline maternal log10 HBsAg levels(P=0.05,β=0.285)and cholesterol levels at delivery(P=0.015,β=0.341).Multivariate logistic regression analysis showed that baseline serum 25(OH)D levels(OR=1.23,95%CI:1.04-1.44),maternal VDR Cdx2 TT(OR=0.09,95%CI:0.01-0.88)and cholesterol levels at delivery(OR=0.39,95%CI:0.17-0.87)were associated with targeted antiviral effects(maternal HBV DNA levels<2×10^(5) at delivery).CONCLUSION Maternal VD levels and VDR SNPs may be associated with the efficacy of antiviral therapy in pregnant women with high HBV viral loads.Future studies to evaluate the therapeutic value of VD and its analogs in reducing the MTCT of HBV may be justified.

Clinical evaluation of ventilation mode on acute exacerbation of chronic obstructive pulmonary disease with respiratory failure

BACKGROUND At present,understanding of the most effective ventilation methods for treating chronic obstructive pulmonary disease(COPD)patients experiencing acute worsening symptoms and respiratory failure remains relatively limited.This report analyzed the efficiency and side effects of various ventilation techniques used for individuals experiencing an acute COPD exacerbation.AIM To determine whether pressure-controlled ventilation(PCV)can lower peak airway pressures(PAPs)and reduce the incidence of barotrauma compared to volume-controlled ventilation(VCV),without compromising clinical outcomes and oxygenation parameters.METHODS We have evaluated 600 patients who were hospitalized due to a severe COPD exacerbation,with 400 receiving mechanical ventilation for the respiratory failure.The participants were divided into two different groups,who were administered either VCV or PCV,along with appropriate management.We thereafter observed patients'attributes,clinical factors,and laboratory,radiographic,and arterial blood gas evaluations at the start and during their stay in the intensive care unit(ICU).We have also employed appropriate statistical methods for the data analysis.RESULTS Both the VCV and PCV groups experienced significant enhancements in the respiratory rate,tidal volume,and arterial blood gas values during their time in the ICU.However,no significant distinctions were detected between the groups in terms of oxygenation indices(partial pressures of oxygen/raction of inspired oxygen ratio)and partial pressures of carbon dioxide improvements.There was no considerable disparity observed between the VCV and PCV groups in the hospital mortality(32%vs 28%,P=0.53),the number of days of ICU stay[median interquartile range(IQR):9(6-14)d vs 8(5-13)d,P=0.41],or the duration of the mechanical ventilation[median(IQR):6(4-10)d vs 5(3-9)d,P=0.47].The PCV group displayed lower PAPs compared to the VCV group(P<0.05)from the beginning of mechanical ventilation until extubation or ICU departure.The occurrence of barotrauma was considerably lower in the PCV group in comparison to the VCV group(6%vs 16%,P=0.03).CONCLUSION Both VCV and PCV were found to be effective in treating patients with acute COPD exacerbation.However,PCV was associated with lower PAPs and a significant decrease in barotrauma,thus indicating that it might be a safer ventilation method for this group of patients.However,further large-scale study is necessary to confirm these findings and to identify the best ventilation approach for patients experiencing an acute COPD exacerbation.