Diabetic cardiomyopathy (DbCM) is a major complication of diabetes characterized by metabolic dysregulation in the heart. This study investigated the role of the long non-coding RNA Airn in the regulation of cardiac fatty acid metabolism during DbCM. Airn expression was markedly reduced in the hearts of diabetic mice. Cardiomyocyte-specific Airn overexpression improved cardiac structure and function, enhanced fatty acid oxidation (FAO), and reduced myocardial lipid accumulation, whereas Airn knockdown induced cardiac remodeling and dysfunction even under non-diabetic conditions. Mechanistically, Airn directly interacted with the RNA-binding protein quaking (QKI) and increased QKI protein stability. The present data further support the involvement of PSMD14, a deubiquitinating enzyme, in this process. In turn, QKI bound to QKI response elements (QREs) within the 3'UTR of Pparα mRNA and promoted its stability, while Airn preserved this regulatory pathway by maintaining QKI abundance. Functionally, activation of PPARα rescued the lipotoxic phenotype induced by Airn deficiency. Together, these findings identify an Airn-QKI-PPARα signaling axis that preserves cardiac FAO and limits lipotoxic remodeling, and highlight Airn as a potential therapeutic target in DbCM.

Background:The current status of nutritional support for patients in Respiratory ICU across mainland China remains inadequately characterized. This multi-center study, conducted in RICUs, was designed to investigate nutritional practices in this specific patient population, focusing on initiation timing, energy/protein adequacy, and associations with clinical outcomes. Methods:A prospective, observational study enrolled 1,026 patients (ICU stay >48 h) across 68 Chinese RICUs. We analyzed EN initiation rates (24 h/48 h), caloric/protein intake adequacy during the first 7 days, and outcomes via multivariable Cox regression. Results:EN initiation occurred in 36.8% (24 h) and 43.4% (48 h) of patients. Excluding patients who could take oral food, the proportion of patients who started EN within 24 and 48 h increased to 86.9 and 95.3%. Among 499 EN-fed patients, 26.1% developed EN complications. Caloric analysis (n = 317) identified three trajectories: underfeeding (<70% targets, 32.5%), adequate feeding (70-110, 43.2%), and overfeeding (>110, 24.3%). Overfeeding independently predicted higher non-social infections and significantly increased mortality risk in patients >50 years (HR = 1.83, 95% CI 1.02-3.28; p = 0.04). Mean protein intake was 0.9 g/kg/day, with no 28-day mortality benefit at higher thresholds (≥1.2 g/kg: p = 0.31; ≥1.3 g/kg: p = 0.42). Conclusion:This multicenter study demonstrates optimal early EN initiation rates in Chinese RICUs. Energy overfeeding was associated with increased mortality risk only in patients >50 years and non-social infections risk, whereas protein adequacy showed no outcome associations. Protocolized EN delivery balancing adequacy and overfeeding risks is urgently needed in RICUs. Clinical trial registration:Identifier, NCT04958447.

Background Existing asthma biomarkers are insufficient for comprehensive disease assessment. Exhaled volatile organic compounds (VOCs) offer a paradigm-shifting opportunity as non-invasive biomarkers for comprehensive clinical assessment in asthma. This study pioneers a holistic approach by systematically exploring the utility of exhaled VOC profiles for differentiating asthmatic patients (APs) from healthy individuals (HCs), evaluating disease control status, classifying asthma phenotypes, and predicting treatment response. Furthermore, it unravels critical correlations between exhaled VOC profiles and clinical parameters, thereby laying the groundwork for unprecedented precision in asthma diagnosis and management. Methods This single-center, cross-sectional and cohort study recruited 147 APs and 50 HCs over a 6-month period, and exhaled breath samples were analyzed using gas chromatography-mass spectrometry (GC-MS). Univariate and multivariate analyses identified potential VOC markers for classification. Subsequently, correlation analyses were performed between VOC biomarkers and clinical characteristics. Results We identified 10, 10, 1, 4, and 8 potential exhaled VOC biomarkers for differentiating APs from HCs, assessing disease control status, predicting treatment response, classifying asthma phenotypes, and characterizing pre- and post-treatment changes, respectively. Additionally, four VOCs demonstrated a significant degree of correlation with pulmonary function and clinical inflammatory markers. Conclusion This study identified discriminatory exhaled breath VOCs between asthmatic patients and healthy controls, with distinct profiles also observed in controlled versus uncontrolled asthma. Notably, significant VOC variations were additionally detected in patients undergoing conventional inhaled corticosteroid (ICS) or biological monoclonal antibody therapy. Upon validation, these findings advocate for breath analysis as a non-invasive, readily implementable technique for identifying airway inflammatory phenotypes and assessing treatment eligibility in asthma.

Background:Chemotherapy-induced myelosuppression (CIM) is a frequent complication in lung cancer, leading to treatment delays, dose reductions, and increased healthcare utilization. Trilaciclib, a first-in-class CDK4/6 inhibitor with myeloprotective properties, has been approved for extensive-stage small-cell lung cancer (ES-SCLC), but real-world evidence in broader lung cancer populations is limited. This retrospective real-world study aimed to evaluate the myeloprotection effects of trilaciclib in lung cancer patients undergoing chemotherapy. Methods:We conducted a retrospective analysis of lung cancer patients who received chemotherapy at the First Affiliated Hospital of Air Force Medical University between January 2023 and June 2024. Patients were categorized into trilaciclib group and non-trilaciclib group. Baseline characteristics, myelosuppression grades, drug dosages for myelosuppression treatment, chemotherapy delays, hospitalizations, and alopecia were collected and analyzed. Inverse probability of treatment weighting (IPTW) was applied to adjust for baseline imbalances. Results:A total of 108 patients were included (54 per group). Overall myelosuppression incidence did not differ significantly (74.1% vs. 87%, P=0.09), but grade ≥3 myelosuppression was markedly reduced in the trilaciclib group [40% vs. 66%, IPTW-adjusted odds ratio (OR) =2.90, P=0.02]. The trilaciclib group required fewer therapeutic granulocyte colony-stimulating factor (G-CSF) doses [median 2 vs. 6, IPTW-adjusted rate ratio (RR) =1.74, P=0.02] and had a lower incidence of grade ≥3 alopecia (77.8% vs. 93.2%, P=0.04), but not significant after IPTW adjustment. Myelosuppression-related hospitalization was significantly reduced (13% vs. 50%, IPTW-adjusted OR =7.77, P<0.001), while chemotherapy delays and other supportive medication use were similar. Conclusions:In a real-world cohort of patients with locally advanced or metastatic lung cancer receiving chemotherapy, trilaciclib was associated with a lower incidence of severe myelosuppression, reduced G-CSF utilization, and fewer hospitalizations. These findings should be considered exploratory, and may support the potential role of trilaciclib as a myeloprotective strategy to optimize treatment continuity and reduce healthcare burden.

Background:Patients with severe or critical coronavirus disease 2019 (COVID-19) remain at a high risk of mortality. Although nirmatrelvir/ritonavir has demonstrated efficacy in non-severe COVID-19 patients with high-risk factors, its effectiveness in hospitalized patients with severe or critical COVID-19 remains unclear. This study evaluates the effectiveness of nirmatrelvir/ritonavir in this specific population. Methods:In this multicenter retrospective cohort study, we included adults hospitalized with severe or critical COVID-19 at three tertiary hospitals in Shaanxi Province between December 2022 and November 2023. Participants were non-randomly categorized into either the nirmatrelvir/ritonavir group or the non-antiviral group based on whether they received nirmatrelvir/ritonavir during hospitalization. The primary outcome was 28-day mortality, and secondary outcomes included in-hospital mortality and post-baseline hospitalization duration. Results:Among the 386 patients (nirmatrelvir/ritonavir group, n = 173, and non-antiviral group, n = 213), those in the nirmatrelvir/ritonavir group had significantly lower 28-day mortality than those in the non-antiviral group (6.9% vs. 15.5%; p = 0.002). Additionally, the nirmatrelvir/ritonavir group had reduced in-hospital mortality rates (8.1% vs. 16.0%; p = 0.003). After multivariable adjustment, the use of nirmatrelvir/ritonavir remained independently associated with a reduced risk of 28-day mortality (adjusted hazard ratio (aHR) = 0.346, 95% confidence interval (CI): 0.175-0.687; p = 0.002) and in-hospital mortality (aHR = 0.374, 95% CI: 0.196-0.716; p = 0.003). Subgroup analyses suggested that the reduced mortality risk was particularly evident in patients aged ≥65 years, non-smokers, those without chronic lung disease or hypertension, those with critical illness, and those who initiated treatment within 5 days of symptom onset. The median post-baseline hospitalization duration was longer in the nirmatrelvir/ritonavir group than in the non-antiviral group (11.0 vs. 9.0 days; p = 0.019). Conclusion:Nirmatrelvir/ritonavir was associated with significantly reduced mortality in patients hospitalized with severe or critical COVID-19, supporting its clinical use in this population.

Meplazumab, a humanized CD147 antibody, showed favorable safety and clinical benefits in phase 1 and phase 2/3 seamless clinical studies. Further evaluation of its therapeutic efficacy in patients with severe COVID-19 is needed. In this phase 3 add-on study, we randomized patients with severe COVID-19 in a 1:1 ratio to receive 0.2 mg/kg meplazumab or placebo via intravenous injection, and evaluated efficacy and safety within 56 days. Between February 2023 and November 2023, 108 patients with severe COVID-19 were randomized to two groups, with their baseline characteristics generally balanced. The primary endpoint, 28-day all-cause mortality was 1.96% in the meplazumab group vs 7.69% in the placebo group (P = 0.1703). Supplementary analysis using composite strategy indicated a significant reduction of 28-day all-cause mortality in meplazumab compared to placebo (3.92% vs 15.38%, P = 0.044). Meplazumab also significantly reduced the mortality in smoking subjects on day 28 (P = 0.047) compared to placebo in supplementary analysis. The secondary endpoint, 56-day all-cause mortality, was 1.96% in the meplazumab group and 11.54% in the placebo group (P = 0.048), which was 3.92% and 15.38%, respectively (P = 0.044) by supplementary analysis. Additional secondary endpoints showed potential benefits, including increased hospital discharge rates, improved clinical outcomes, and improved viral nucleotide conversion rate. Meplazumab demonstrated good safety and tolerability, with no grade ≥ 3 TEAEs observed. These promising results indicate that meplazumab reduces mortality and enhances clinical benefits in severe COVID-19 patients with a good safety profile, providing effective and specific therapeutics for severe COVID-19 (the trial was registered at ClinicalTrials.gov (NCT05679479)).

In recent years, alternating epidemics of multiple respiratory pathogens have appeared globally, with recurrent infections in some individuals. However, there is a lack of evidence from clinical studies on the effects of the initial pathogen on the incidence, severity, and regression of infections with the subsequent pathogen. This study involved college students as survey respondents during the successive outbreaks of Mycoplasma pneumoniae (MP) and influenza epidemics to obtain evidence regarding MP–influenza interference. MP and influenza epidemics occurred successively between September 2023 and February 2024. Internet-based questionnaires were administered to all freshmen enrolled in August 2023 at three closed-management public universities in northern China after the end of the first wave of the MP epidemic and the second wave of the influenza epidemic, respectively. The participants self-rated their perceived severity for 16 symptoms, and the scores were summed to obtain a combined symptom score for each individual. Multiple logistic and linear regression analyses were used to investigate the effect of previous MP infection on the incidence and severity of subsequent influenza infection. A total of 1803 cases of MP-like illness and 2111 cases of influenza-like illness (ILI) were observed among 5790 freshmen across two waves of respiratory infection outbreaks. Moreover, 709 and 1244 cases were voluntarily tested for pathogens at the university clinic, of which 549 (77.4

As the prevalence of obesity continues to elevate, the effect of obesity on cardiovascular diseases (CVD) has received increasing attention in recent years. Obesity is not only related to CVD risk factors such as hypertension and diabetes but also directly impairs cardiomyocytes through various mechanisms. This article reviews the relationship and pathophysiological mechanisms between obesity and CVD occurrence from 3 perspectives: the direct impact of current obesity on CVD, the impact of previous obesity on CVD, and the impact of parental obesity on offspring CVD, along with different weight loss interventions. Multiple weight loss interventions serve as critical primary prevention for CVD in obese individuals. The latest research progress on the effect of weight loss interventions on CVD was also reviewed in this article, aiming to provide more references to understand the relationship between obesity and CVD and the effect of weight loss interventions.

PurposeThis study aimed to evaluate the regional ventilation distributions in A-B-E phenotypes among patients with chronic obstructive pulmonary disease (COPD). The feasibility to better distinguish the phenotypes combining global spirometry and regional ventilation parameters derived from electrical impedance tomography (EIT) was explored.MethodsA cohort undergoing pulmonary function testing was prospectively enrolled. Regional spatial and temporal ventilation parameters were calculated with EIT. Principal component analysis was used to visualize phenotypic clustering, while multinomial logistic regression evaluated discriminatory performance. Feature importance was interpreted using SHapley Additive exPlanations (SHAP).ResultsThis study enrolled 88 COPD patients (Group A n = 36, Group B n = 21, Group E n = 31). Spirometry and EIT parameters revealed significant intergroup differences in FEV1%pred (P < 0.001), FEV1/FVC (P < 0.001), GI-FEV1 (regional distribution of FEV1%pred in functional EIT; P = 0.004), GI-FEV1/FVC (regional distribution of FEV1/FVC; P = 0.001) and expiratory time constant (P = 0.017). Group A demonstrated the best pulmonary function (FEV1%pred: 77.67 ± 20.40), while Group E showed the most pronounced flow limitation (longest time required to exhale 75% of FVC, T75). The multinomial model showed optimal discrimination for Group A (AUC: 0.827), while differentiation between Groups B and E was less satisfactory (AUC: 0.749). SHAP analysis identified FEV1%pred as the most significant predictor (|SHAP| = 0.477), with EIT-derived parameters GI-FEV1/FVC (|SHAP| = 0.203) and regional T75 (|SHAP| = 0.189) providing substantial incremental value.ConclusionCOPD phenotypes showed differences in global and regional flow limitations. The combination of global and regional information helped with distinguishing phenotypes.

Tissue-resident memory CD8+ T cells (TRM cells) provide superior frontline defense against pathogens. While the role of costimulation in effector and memory CD8+ T-cell development is well characterized, how costimulatory signaling governs CD8+ TRM cells homeostasis at the memory phase remains poorly defined. Here it is revealed that the costimulatory receptors CD27 and ICOS coordinately sustain PD-1high CD8+ TRM cell populations following resolution of acute influenza infection. These costimulatory signals serve as critical targets for PD-1/PD-L1 blockade, thereby facilitating the rejuvenation of PD-1high TRM cells and influencing the progression of fibrotic sequelae during the memory phase. Mechanistic dissection identifies the nuclear receptor Nur77 (NR4A1) as the convergent transcriptional hub downstream of CD27/ICOS, governing proliferative renewal and maintenance of PD-1high TRM cells. Therapeutic administration of a CD27 agonist not only amplified this TRM cell subset in late-stage memory but also conferred cross-protective immunity against heterosubtypic viral challenges. Clinically, the expressions of CD27 and ICOS are enriched in CD8+ T cells within the lung tissues of patients with pulmonary fibrosis. Collectively, these findings establish the "CD27/ICOS-NR4A1-proliferation" axis as a linchpin of PD-1/PD-L1-mediated TRM cell homeostasis, revealing druggable targets for intercepting infection-associated fibrotic progression.

Figure S4. Polygenic risk scores based on tRFQTLs predict the risks of different cancer types. Hazard ratios (HR) for risks of different cancer types comparing the high PRS group (individuals with high polygenic risk scores, Top 33% group) and the low PRS group (individuals with low polygenic risk scores, Bottom 33% group, reference) of the population. CESC, cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL, cholangiocarcinoma; ESCA, esophageal carcinoma; HNSC, head and neck squamous cell carcinoma; STAD, stomach adenocarcinoma; THCA, thyroid carcinoma; UCEC, uterine corpus endometrial carcinoma.

Objectives: There is a scarcity of studies on multisite infections (MSIs) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). The primary objectives of this research were to determine the clinical characteristics of CRKP MSI, and the risk factors of infection and mortality. Methods: Patients with a CRKP bloodstream infection (BSI) were enrolled retrospectively between January 2017 and December 2021 in Xijing Hospital, China. The risk factors for CRKP MSI and mortality were evaluated. The demographic data, clinical and microbiological characteristics, therapy and outcomes were analyzed. Results: Among 101 patients, 74.3% (75/101) had a diagnosis of CRKP MSI, while 25.7% (26/101) of CRKP non-MSI. The overall case fatality rate was 42.6% (43/101). Multivariate analysis indicated that previous surgery (OR 3.971, 95% CI 1.504–10.480, p = 0.005) and ICU admission (OR 3.322, 95% CI 1.252–8.816, p = 0.016) were independent risk factors for CRKP MSI. ICU admission (OR 4.765, 95% CI 1.192–19.054, p = 0.027), a Pitt bacteremia score (PBS) > 4 (OR 3.820, 95% CI 1.218–11.983, p = 0.022) and thrombocytopenia (OR 8.650, 95% CI 2.573–29.007, p < 0.001) were independent risk factors for mortality due to CRKP MSI. Conclusions: Our findings confirmed that CRKP MSIs were associated with poorer outcomes. To improve prognosis, early screening of individuals at the highest risk is vital.

Background:SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4) encodes the BRG1 (Brahma-related gene 1) protein, which regulates chromatin remodeling and gene expression; its loss leads to chromatin reorganization and aberrant expression of tumor-related genes, and it has been detected in multiple aggressive malignancies. SMARCA4-deficient thoracic tumors (SMARCA4-dTTs) mainly include the highly malignant SMARCA4-deficient undifferentiated tumor [SMARCA4-dUT, recognized as a distinct entity in the 2021 World Health Organization (WHO) classification] and SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC). Currently, there is no standard treatment plan for SMARCA4-dTTs. platinum-based chemotherapy, targeted therapy, and immunotherapy have limited efficacy, underscoring the need for further investigation. This study aims to remind the clinicians and pathologists that they should raise their awareness of the existence of these rare subtypes of lung cancer, proactively conduct differential diagnosis to avoid misdiagnosis, and look for effective treatment options. Methods:This retrospective observational clinical study included 22 patients who diagnosed with SMARCA4-dTTs and attended in Xijing Hospital from January 2022 to June 2024. The clinical data of the patients were collected, including gender, age, smoking history, family history of tumors, symptoms, Eastern Cooperative Oncology Group performance status (ECOG-PS) score, programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS), distant metastasis status, treatment regimens, and survival. All the patients were pathologically diagnosed according to the WHO Classification of Thoracic Tumors (5th edition) and staged according to the Tumor-Node-Metastasis (TNM) Staging System for Lung Cancer (8th edition). The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used to compare survival differences between groups. Results:Among the 22 patients, 15 were diagnosed with SMARCA4-dNSCLC, and seven with SMARCA4-dUT. Most patients were male (95.5%) and smokers (90.9%), with mediastinal lymph node metastasis (81.8%) and distant metastasis (68.2%). The histopathological and immunohistochemical results showed significant tumor cell atypia, SMARCA4 expression loss, and high Ki-67 expression. The median overall survival (OS) of the 22 patients was 4 months. The main factors affecting survival were tumor staging (median OS, non-stage IV patients 12 months, stage IV patients 3 months, P<0.01) and undergoing treatment (median OS, treated patients 7 months, untreated patients 1 month, P<0.01). No significant survival differences were found among various drugs and combined treatment regimens. Conclusions:SMARCA4-dTTs are a rare, highly malignant group of tumors with an extremely poor prognosis. There is currently no standard drug treatment regimen for SMARCA4-dTTs, but patients who receive treatment derive some survival benefits. Future research is needed to explore more effective treatment strategies.

Background:During the influenza season, teachers have a higher infection rate of influenza than the general population. However, there has been no study on the clinical characteristics of this specific influenza in infection type-"class-acquired influenza," which means teachers acquire influenza infection from exposure to a substantial quantity of influenza virus aerosols in enclosed classrooms by teaching activities in a short period of time. Methods:In this study, teachers who had suffered from influenza during the 2024-2025 Seasonal Influenza from 12 schools in Xi'an, a city in northern China, were retrospectively collected through a questionnaire. They were divided into a class-acquired influenza group and a non-class-acquired influenza group, and then compared the clinical features and effects between these two groups. Results:Class-acquired cases showed higher incidence of symptoms, such as fever, cough, malaise, abdominal pain and diarrhea, and showed greater severity of symptoms like dry throat, runny nose and sputum. The class-acquired influenza group had longer recovery time [7.0 (5.0, 14.0) vs. 6.5 (5.0, 10.0) days, p = 0.003], and required more medical visits (69.9% vs. 52.3%, p = 0.004), medication (74.7% vs. 62.4%, p = 0.035), and sick leave (47.9% vs. 28.4%, p < 0.001). Incubation period (onset) showed no difference (p = 0.245). Conclusion:Class-acquired influenza is a specific type in teachers. Compared to non-class-acquired influenza, it involves worse symptoms, longer duration, higher healthcare needs, and more absenteeism, likely related to the unique working conditions and environment. Therefore, during the influenza season, schools and teachers should focus on rational prevention, early diagnosis and medication.

Early detection of lung function impairment is crucial. However, the sensitivity of spirometry in detecting early lung function deterioration is limited. In this study, lungs of 3180 healthy participants scheduled for annual health check were screened. Electrical impedance tomography measurements were conducted in 130 participants with normal spirometry for concept establishment phase and 105 for validation phase. A follow-up CT examination was suggested for participants with abnormal regional time constant or tobacco consumption ≥10 pack-years. Using CT as reference, the sensitivity and specificity of electrical impedance tomography-based screening were 81.3% and 50.0%, respectively in the concept establishment phase. In the validation phase, the sensitivity and specificity were 77.9% and 50.0%. In this study we show that conventional spirometry may not capture early changes that occur at a regional level. The regional time constant based on electrical impedance tomography can be a promising tool for early screening of lung function impairment. Clinical trial registration: ChiCTR2300076673, www.chictr.org.cn . The study explores the possibility of using electrical impedance tomography (EIT) as an early screening method to identify lung function impairment in participants with normal spirometry results. It identifies EIT-based regional τ values can be a promising tool for early screening of lung function impairment.

Background:After the cessation of the dynamic zero-coronavirus disease 2019 (COVID-19) policy in China, a large number of people were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) without being hospitalized, but few studies investigated the symptoms of this population. In this study, we aimed to describe the symptom characteristics of this population and to provide information for further understanding of COVID-19. Methods:An online nationwide anonymous survey questionnaire on symptoms was conducted through WeChat to probe participants infected with SARS-CoV-2 between December 2022 and January 2023. In order to guarantee the promptness of data collection while maximizing the coverage of diverse populations, we opted for the convenient sampling method. Demographic information, incidence and severity of main symptoms, and vaccination status were collected in the questionnaire. Descriptive analysis was utilized to elucidate the epidemiological characteristics of the overall population; comparative analysis was conducted to highlight the differences in symptom variations among distinct subgroups. Results:A total of 4,836 valid questionnaires were collected, with 64.8% testing positive for COVID-19 and 35.2% exhibiting symptoms but not having undergone testing. Among the COVID-19-positive respondents, 64.3% (n=2,016) were female, with a median age of 39.0 (33.0, 47.0) years, and 95.8% (n=3,002) had received multiple vaccine doses. The prevalent comorbidities included allergic rhinitis (10.1%), hypertension (6.1%), and diabetes (3.5%). The most frequently reported symptoms were fever (n=2,941, 93.9%), fatigue (n=2,871, 91.6%), expectoration (n=2,847, 90.8%), nasal congestion (n=2,735, 87.2%), and myalgia (n=2,712, 86.5%). Vaccinated individuals, non-smokers, and males exhibited significantly higher rates of respiratory symptoms. Myalgia (35.3%), fatigue (31.5%), and sore throat (30.9%) were the symptoms with the highest incidence of severe occurrence, and this varied between age groups. Except for sneezing, age of 60 years or older was negatively correlated with severe manifestations for all symptoms. Conversely, smoking was positively associated with severe symptoms for nearly all conditions. Conclusions:The study highlights common systemic and respiratory symptoms among non-hospitalized COVID-19 patients in China, varying by gender, age, and underlying diseases. These findings are clinically important for early identification, diagnosis, treatment evaluation, and global management of COVID-19.

Shortening the duration of the viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to controlling viral transmission, alleviating the burden on the healthcare system, and ultimately mitigating the impact of the pandemic. This randomized, single-blind, placebo-controlled clinical trial aimed to investigate the safety and efficacy of gargling with plasma-activated water (PAW) on prolonged viral shedding in patients infected with SARS-CoV-2 Delta and Omicron variants. Sixty-two subjects, aged 18-80 years and infected with SARS-CoV-2, were recruited at two coronavirus disease 2019 (COVID-19)-designated hospitals in Shaanxi from January to March 2022. Primary outcomes included cumulative conversion rates, incidence of adverse reactions, and biosafety parameters. Results suggested that PAW gargling treatment might contribute to reducing the duration of SARS-CoV-2 Delta and Omicron variant infections and alleviating symptoms. Plasma-activated water gargling shows promise in shortening severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta and Omicron variant infections. Our study highlights its potential to reduce viral shedding and ease symptoms, offering a safe and effective adjunct in managing coronavirus disease 2019 (COVID-19) transmission and impact.image

Background: Spontaneous respiratory mechanical force interacted with the primary lung injury and aggravated the progression of ARDS clinically. But the exact role and involved mechanism of it in the pathogenesis of ARDS animal model remained obscure. Aim: This study was to investigate the effect of spontaneous respiratory mechanical force on lung injury of ARDS in mice. Methods: Female C57BL/6 mice were subjected to resistive spontaneous breathing (RSB) by tracheal banding after 4-6 h of intranasal inhalation of LPS. Pulmonary function was examined by Buxco system, partial pressures of oxygen and carbon dioxide (PO2 and PCO2) were measured by a blood gas analyzer, and lung pathological changes were analyzed with hematoxylin and eosin staining. The levels of inflammatory markers were quantified by ELISA, total protein assay, and FACS analysis. The expression levels of mechanosensitive ion channels were detected by qRT-PCR and immunohistochemistry. Results: The airway resistance (Raw) was increased and the tidal volume (TV) was decreased remarkedly in RSB group. RSB treatment did not affect PO2, PCO2, pathology and inflammation levels of lung in mice. The Raw increased and ventilatory indicators decreased in RSB + ARDS compared to ARDS significantly. Besides, RSB treatment deteriorated the changes of PO2, PCO2 and level of lactic acid induced by LPS. Meanwhile, RSB significantly promoted LPS-induced pulmonary histopathological injury, and elevated the levels of IL-1 beta, IL-6, TNF-alpha and total proteins, increased neutrophils infiltration. The expression level of Piezo1 in RSB + ARDS group was remarkably reduced compared to ARDS group and consistent with the severity of pulmonary damage. Conclusion: RSB exacerbated LPS-induced ARDS hypoxemia and hypercapnia, inflammation and damage. The mechanosensitive protein Piezo1 expression decreased and may play an important role in the process.

We aimed to determine the clinical characteristics of patient self-inflicted lung injury (P-SILI)-associated pneumothorax/pneumomediastinum, to reveal its risk factors, and to assess its impact on severe COVID-19 cases. In total, 229 patients were included in this case-control study. They were randomly divided into either the case group or the control group as per the inclusion and exclusion criteria. The two groups were further analyzed to reveal the risk factors of spontaneous pneumothorax/pneumomediastinum (SP/P). Finally, risk factors for death were analyzed in the case group and the relationship between death and SP/P was also analyzed among all patients. The mean age of patients was 59.69 ± 17.01 years, most of them were male (74.2%), and 62.0% of them had comorbidities upon admission. A respiratory rate higher than 30 BPM was a risk factor for SP/P (OR 7.186, 95% CI 2.414–21.391, P < 0.001). Patients with delayed intubation due to early application of HFNC or NIV had a higher mortality rate when they developed SP/P (P < 0.05). Additionally, advanced age increased the risk of death (P < 0.05). Finally, SP/P may be a risk factor for death among patients with severe COVID-19 (OR 2.047). P-SILI occurs in severe COVID-19 with acute respiratory failure. It is necessary to identify the risk factors of P-SILI, the indicators of severe P-SILI, and the preventive measures.

The heart primarily derives its energy through lipid oxidation. In cardiomyocytes, lipids are stored in lipid droplets (LDs) and are utilized in mitochondria, although the structural and functional connections between these two organelles remain largely unknown. In this study, visible evidence have presented indicating that a complex is formed at the mitochondria-LD membrane contact (MLC) site, involving mitochondrion-localized Mfn2 and LD-localized Hsc70. This complex serves to tether mitochondria to LDs, facilitating the transfer of fatty acids (FAs) from LDs to mitochondria for β-oxidation. Reduction of Mfn2 induced by lipid overload inhibits MLC, hinders FA transfer, and results in lipid accumulation. Restoring Mfn2 reinstates MLC, alleviating myocardial lipotoxicity under lipid overload conditions both in-vivo and in-vitro. Additionally, prolonged lipid overload induces Mfn2 degradation through the ubiquitin-proteasome pathway, following Mfn2 acetylation at the K243 site. This leads to the transition from adaptive lipid utilization to maladaptive lipotoxicity. The experimental findings are supported by clinical data from patients with obesity and age-matched non-obese individuals. These translational results make a significant contribution to the molecular understanding of MLC in the heart, and offer new insights into its role in myocardial lipotoxicity.