A new integrative analysis of histopathology and single cell RNA-seq reveals the CCL5 mediated T and NK cell interaction with vascular cells in idiopathic pulmonary arterial hypertension.

BACKGROUND: Inflammation and dysregulated immunity play vital roles in idiopathic pulmonary arterial hypertension (IPAH), while the mechanisms that initiate and promote these processes are unclear. METHODS: Transcriptomic data of lung tissues from IPAH patients and controls were obtained from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA), differential expression analysis, protein-protein interaction (PPI) and functional enrichment analysis were combined with a hemodynamically-related histopathological score to identify inflammation-associated hub genes in IPAH. The monocrotaline-induced rat model of pulmonary hypertension was utilized to confirm the expression pattern of these hub genes. Single-cell RNA-sequencing (scRNA-seq) data were used to identify the hub gene-expressing cell types and their intercellular interactions. RESULTS: Through an extensive bioinformatics analysis, CXCL9, CCL5, GZMA and GZMK were identified as hub genes that distinguished IPAH patients from controls. Among these genes, pulmonary expression levels of Cxcl9, Ccl5 and Gzma were elevated in monocrotaline-exposed rats. Further investigation revealed that only CCL5 and GZMA were highly expressed in T and NK cells, where CCL5 mediated T and NK cell interaction with endothelial cells, smooth muscle cells, and fibroblasts through multiple receptors. CONCLUSIONS: Our study identified a new inflammatory pathway in IPAH, where T and NK cells drove heightened inflammation predominantly via the upregulation of CCL5, providing groundwork for the development of targeted therapeutics.

A case report of empyema caused by Enterococcus gallinarum.

BACKGROUND: Enterococcus gallinarum is an infrequently intestinal symbiotic pathogen associated with nosocomial infection in immunocompromised individuals. To date, rare cases of pulmonary infection attributable to Enterococcus gallinarum were reported. Herein, we presented the first case of empyema resulting from Enterococcus gallinarum infection. CASE PRESENTATION: An 81-year-old male presented with fever and dyspnea upon admission. Chest CT scan and thoracic ultrasonography confirmed the presence of right pleural effusion. Thoracoscopy revealed extensive adhesion, purulent fluid, and necrotic materials within the thoracic cavity. Enterococcus gallinarum was identified through pleural effusion culture. The patient underwent an intrathoracic injection of urokinase along with thoracic drainage. Following surgery, He took oral linezolid for over one month. Undergoing comprehensive treatment, the patient exhibited favorable recovery. CONCLUSIONS: We reported the first case of empyema due to Enterococcus gallinarum infection. It should be suspected in patients with impaired immune function and invasive therapies, without responding to conventional anti-infectious treatment.

Il34 rescues metronidazole-induced impairment of spinal cord regeneration in zebrafish central nervous system.

Metronidazole (MTZ), a commonly used anti-infective drug in clinical practice, has also been employed as a prodrug in cell-targeted ablation systems in scientific research, exhibiting significant application value. However, it has been demonstrated that MTZ can induce neurotoxic symptoms to some extent during its use, and there is currently a lack of effective means to circumvent its toxicity in both clinical and research settings, which limits its application. Therefore, exploring the specific mechanisms underlying MTZ-induced neurotoxic symptoms and elucidating countermeasures will enhance the practical value of MTZ. In this study, using a zebrafish spinal cord injury regeneration model, we confirmed that MTZ neurotoxicity leads to impaired axon regeneration in the central nervous system. By overexpressing il34 in the central nervous system of zebrafish, we eliminated the inhibitory effect of MTZ on axonal regeneration and demonstrated that the pro-regenerative effect against MTZ neurotoxicity is not caused by excessive macrophages/microglia chemoattracted by interleukin 34(Il34). Transcriptome sequencing analysis and GO enrichment analysis of differentially expressed genes between groups revealed that Il34 may counteract MTZ neurotoxicity and promote spinal cord injury repair through biological processes that enhance cellular adhesion and cell location. In summary, our work uncovers a possible cause of MTZ neurotoxicity and provides a new perspective for eliminating MTZ toxicity.

Enhancing Training Precision: Unveiling the Barbell Velocity's Role in Tailoring the Resistance Load for the China Badminton Team.

Velocity-based resistance training is a fundamental component of sports science, offering a systematic approach to investigating the load variables of resistance exercises. This research focused on assessing the load across various resistance exercises by examining the barbell velocity during the concentric phase. The study involved 11 male athletes representing the China badminton team, who underwent 1RM testing for bench press, hip thrust, back squat, and single leg press exercises and the maximum repetition testing at load intensities of 60%, 70%, 80%, and 90% of 1RM. Simultaneously, measurements were taken of the barbell's concentric phase velocity during each exercise. The findings revealed a robust negative correlation between barbell velocity and load intensity. Furthermore, exercises engaging greater muscle strength displayed smoother fitting curves. Analysis of velocity loss rates indicated that the hip thrust exhibited a higher completion percentage compared to the back squat and the bench press. Similarly, the non-dominant leg press showed a higher completion percentage than the dominant leg press. The study emphasizes the significance of delineating barbell velocity distributions in resistance training involving large muscle groups, as well as the accurate determination of load intensity. Precise load determination can be facilitated by employing fitting curves derived from distinct movement patterns and varying load intensities. The utilization of velocity data offers a quantifiable approach to achieving targeted training outcomes.

[The effect of narrow band imaging in CO2 laser therapy in early-stage glottic cancer].

Objective:To explore efficacy of narrow band imaging（NBI） technique in CO2laser therapy in Early-Stage Glottic cancer. Methods:The clinical data of patients with Early-Stage Glottic cancer who underwent CO2laser vocal cord resection from June 2011 to August 2022 were retrospectively analyzed. Among these, 27 patients who underwent surgery assisted by NBI were assigned to the observation group, while 25 patients who underwent conventional CO2 laser microsurgery with a suspension laryngoscope were assigned to the control group. The differences between the two groups were analyzed in terms of intraoperative frozen pathology results, postoperative recurrence rates, 5-year cumulative disease-free survival rates, complications, and voice recovery. Results:All 52 patients were operated successfully. Temporary tracheostomy and serious complications did not occur during the operation. The postoperative patient's pronunciation was satisfactory. One patient experienced vocal cord adhesion, but there were no severe complications such as breathing difficulties or bleeding, with an overall complication rate of 1.92%. Postoperative follow-up was 1-5 years. The 5 years recurrence free survival in the general group was 77.90％, and the 5 years recurrence free survival in the NBI group was 100％, the difference was statistically significant（P<0.05）. NBI endoscopy is safer and more accurate than the general group in determining the safe margin of tumor mucosal resection（P<0.05）. Among the patients who accepted the voice analysis, the difference was no statistically significant（P>0.05）. Conclusion:Compared with conventional CO2laser surgery under microscope, NBI guided laser resection of Early-Stage Glottic cancer is more accurate. NBI guided laser resection could improve 5 years recurrence free survival rate. In a word, narrow-band imaging endoscopy can has very high value in clinical application.

The association between indoor air pollution from solid fuels and cognitive impairment: a systematic review and meta-analysis.

This study aimed to comprehensively and methodically evaluate the correlation between cognitive impairment and indoor air pollution from solid fuel used for cooking/heating. PubMed, Web of Science, EMBASE, and Cochrane Library databases were searched up to December January 2023. 13 studies from three countries with a total of 277,001 participants were enrolled. A negative correlation was discovered between solid fuel usage for cooking and total cognitive score (ß=-0.73, 95 % CI: -0.90 to -0.55) and episodic memory score (ß=-0.23, 95 % CI: -0.30 to -0.17). Household solid fuel usage for cooking was considerably associated with a raised risk of cognitive impairment (HR=1.31, 95 % CI: 1.09-1.57) and cognitive decline (HR=1.24, 95 % CI: 1.18-1.30). Compared to continuous solid fuel use for cooking, sustained use of clean fuel and switching from solid fuel to clean fuel were associated with a lower risk of cognitive decline (OR=0.55, 95 % CI: 0.42-0.73; OR=0.81, 95 % CI: 0.71-0.93). A negative association was found between solid fuel usage for heating and total cognitive score (ß=-0.43, 95 % CI: -0.59 to -0.26) and episodic memory score (ß=-0.22, 95 % CI: -0.34 to -0.10). Our research provided evidence that exposure to indoor air pollution from solid fuel is a potential cause of cognitive impairment and cognitive decline. Making the switch from solid fuels to cleaner fuels could be an important step in preventing cognitive impairment in the elderly.

Exploration of Berberine Against Ulcerative Colitis via TLR4/NF-κB/HIF-1α Pathway by Bioinformatics and Experimental Validation.

Purpose: This study aimed to delineate the molecular processes underlying the therapeutic effects of berberine on UC by employing network pharmacology tactics, molecular docking, and dynamic simulations supported by empirical validations both in vivo and in vitro. Patients and Methods: We systematically screened potential targets and relevant pathways affected by berberine for UC treatment from comprehensive databases, including GeneCards, DisGeNET, and GEO. Molecular docking and simulation protocols were used to assess the interaction stability between berberine and its principal targets. The predictions were validated using both a DSS-induced UC mouse model and a lipopolysaccharide (LPS)-stimulated NCM460 cellular inflammation model. Results: Network pharmacology analysis revealed the regulatory effect of the TLR4/NF-κB/HIF-1α pathway in the ameliorative action of berberine in UC. Docking and simulation studies predicted the high-affinity interactions of berberine with pivotal targets: TLR4, NF-κB, HIF-1α, and the HIF inhibitor KC7F2. Moreover, in vivo analyses demonstrated that berberine attenuates clinical severity, as reflected by decreased disease activity index (DAI) scores, reduced weight loss, and mitigated intestinal inflammation in DSS-challenged mice. These outcomes include suppression of the proinflammatory cytokines IL-6 and TNF-α and downregulation of TLR4/NF-κB/HIF-1α mRNA and protein levels. Correspondingly, in vitro findings indicate that berberine decreases cellular inflammatory injury and suppresses TLR4/NF-κB/HIF-1α signaling, with notable effectiveness similar to that of the HIF-1α inhibitor KC7F2. Conclusion: Through network pharmacology analysis and experimental substantiation, this study confirmed that berberine enhances UC treatment outcomes by inhibiting the TLR4/NF-κB/HIF-1α axis, thereby mitigating inflammatory reactions and improving colonic pathology.

Sensitive sensing platform based on Co, Mo doped electrospun nanofibers for simultaneous electrochemical detection of dopamine and uric acid.

Abnormal levels of dopamine (DA) and uric acid (UA) in the human body are valuable indicators for monitoring human health, as they are associated with certain diseases. Therefore, it is crucial to develop sensitive and simultaneous analytical techniques for DA and UA in diagnosing the related diseases. Herein, the Co- and Mo- doped carbon nanofibers (Co, Mo@CNFs) electrochemical biosensor was developed successfully for the sensitive and accurate simultaneous detection of DA and UA. A straightforward electrospinning technique followed by a carbonization process was employed for the synthesis of Co, Mo@CNFs, and the encapsulation of Co and Mo within CNFs served to not only prevent nanoparticle agglomeration, thus providing more active sites, but also to facilitate rapid electron transfer. By incorporating Co and Mo into CNFs, the electrocatalytic activity of the modified electrode was greatly improved due to the beneficial conductivity and synergistic effects of transition metals. This enhancement effectively addressed issues such as the overlapping anodic peaks that occur when DA and UA are oxidized concurrently. Due to the mentioned synergistic contributions, the modified Co, Mo@CNFs electrode (Co, Mo@CNFs/GCE) achieved remarkable sensitivity for the simultaneous detection of DA and UA, while also exhibiting strong anti-interference ability. The detection limits for DA and UA were 2.35 nmol L-1 and 0.16 µmol L-1, respectively. We applied the developed Co, Mo@CNFs/GCE electrochemical biosensor to detect DA and UA in 50-fold diluted serum and urine samples. The results affirm the biosensor's reliability and precision. Moreover, the developed Co, Mo@CNFs/GCE biosensor demonstrated excellent performance in simultaneously detecting DA and UA, providing an efficient and dependable detection approach for clinical diagnosis and bioanalysis.

Evaluating the efficacy of balloon pulmonary angioplasty using quantitative analysis of SPECT pulmonary ventilation/perfusion scintigraphy in patients with chronic thromboembolic pulmonary hypertension.

Background: Single-photon emission computed tomography (SPECT) ventilation perfusion imaging is the main imaging method for the diagnosis of pulmonary embolism, and its application in the diagnosis and efficacy evaluation of chronic thromboembolic pulmonary hypertension (CTEPH) has been paid more and more attention. In recent years, with the development of computer software technology, ventilation/perfusion (V/Q) imaging quantitative analysis technology has become more and more mature. The objective of this study was to investigate the utility of quantitative analysis of pulmonary V/Q scintigraphy in evaluating the efficacy of balloon pulmonary angioplasty (BPA) in patients with CTEPH. Methods: In this retrospective analysis, we collected data of patients diagnosed with CTEPH who underwent BPA at the China-Japan Friendship Hospital from April 2018 to September 2020. The sample consisted of 23 males and 28 females, with an average age of 55.1±12.7 years. All patients underwent V/Q scintigraphy within one week before surgery, and we reviewed the pulmonary angiography within 1-3 months following the last BPA procedure. We repeated V/Q scintigraphy within 1 week before or after the pulmonary angiography, at the time of collecting clinical and hemodynamic parameters of these patients. We divided the patients into two groups based on the presence of residual pulmonary hypertension post-surgery and compared the pre- and post-operative quantitative pulmonary perfusion defect percentage scores (PPDs%) using the t-test. Results: In all, 102 V/Q scintigraphy scans were performed in 51 patients. The quantitative PPDs% were positively correlated with the hemodynamic indexes mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), and mean right ventricular pressure (RVP) (r=0.605, 0.391, and 0.464, respectively, all P<0.001) and negatively correlated with the 6-minute walking distance (6MWD) (r=-0.254, P=0.010). The average preoperative quantitative PPDs% were (49.0±15.6)% which significantly decreased to (33.5±13.9)% after surgery (t=11.249, P<0.001). The preoperative quantitative PPDs% were (54.7±15.7)% and (44.0±13.8)% in the residual pulmonary hypertension group and the non-residual pulmonary hypertension group, respectively (t=2.599, P=0.012). The postoperative quantitative PPDs% were (41.5±12.5)% and (26.3±11.0)%, in the residual pulmonary hypertension group and the non-residual pulmonary hypertension group, respectively (t=4.647, P<0.001). Conclusions: In this study, we found that quantitative analysis of SPECT pulmonary V/Q scintigraphy adequately reflected the pulmonary artery pressure and clinical status in patients with CTEPH. Our results demonstrate its definite utility in predicting residual pulmonary hypertension and in evaluating the postoperative efficacy of BPA in patients with CTEPH.

Safety and efficacy of balloon pulmonary angioplasty for technically operable chronic thromboembolic pulmonary hypertension.

Balloon pulmonary angioplasty (BPA) has been proven effective for addressing technically inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, the effectiveness of BPA in technically operable CTEPH patients who, for various reasons, did not undergo the procedure remains an area requiring exploration. This study sought to assess the safety and efficacy of BPA in such cases. We collected and reviewed data from CTEPH patients who underwent BPA in a consecutive manner. Following multidisciplinary team (MDT) decisions, patients were classified into two groups: technically inoperable (group A) and operable (group B). Group B comprised patients deemed technically suitable for pulmonary endarterectomy (PEA) but who did not undergo the procedure for various reasons. All patients underwent a comprehensive diagnostic work-up, including right heart categorization at baseline and the last intervention. This study compared changes in hemodynamic parameters, functional capacity, and quality of life between the two groups. In total, 161 patients underwent 414 procedures at our center, with Group A comprising 112 patients who underwent 282 BPA sessions and group B comprising 49 patients who underwent 132 BPA sessions. Significantly, both groups exhibited improvements in hemodynamics, functional capacity, and quality of life. The occurrence rate of complications, including hemoptysis and lung injury, was similar [12 (63.2%) vs. 7 (36.8%), p = 0.68]. BPA demonstrated favorable outcomes in patients with proximal CTEPH who did not undergo pulmonary endarterectomy. However, the clinical impact of BPA in technically operable CTEPH was found to be less significant than in inoperable cases.

Risk and related factors of elbow musculoskeletal diseases: a nationwide cross-sectional survey in China.

OBJECTIVES: Although studies have shown that work-related musculoskeletal disorders (WMSDs) are common and continue to be a major source of disability and work time loss, there are few reports about elbow WMSDs. The aim of this study was to explore the prevalence and associated factors of elbow WMSDs. METHODS: The valid questionnaires of 57501 workers from 15 different industries nationwide were collected and the c2 test and logistic regression analysis were applied to reveal the prevalence and risk factors of elbow WMSDs. RESULTS: The findings indicated that the overall prevalence of elbow WMSDs among workers was 7.3%. However, the prevalence of elbow WMSDs in toy manufacturing was 21.3%, which was significantly higher than that in other industries (P < .05). Logistic regression analysis showed that age 40 and above, married, very poor health, left-handedness, lifting weights (more than 20 kg each time), work requiring upper limb or hand force, work in an uncomfortable position, repetitive operations within 1 minute, using vibrating tools, work involving cold, cool draughts, or temperature changes, work being completed in the same workshop, work being done outdoors, frequent dealings with customers, 2 shifts, often working overtime, staff shortage, and often working for colleagues were risk factors for elbow WMSDs. A higer education level, monthly income, and enough rest time were protective factors for elbow WMSDs. CONCLUSIONS: Toy manufacturing is a high-risk industry for elbow WMSDs. Promotion of education about ergonomics should be strengthened, and workers' ergonomics awareness should be improved to reduce the impact of WMSDs.

Risk factors for venous thromboembolism in patients with pneumonia in the pre-COVID-19 era: a meta-analysis and systematic review.

Background: Elevated risk of venous thromboembolism (VTE) in patients with coronavirus disease 2019 (COVID-19) pneumonia has been recognized, while the risk factors associated with VTE in patients with non-COVID-19 pneumonia remain to be defined. This study aimed to conduct a meta-analysis and systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify potential risk factors for VTE in patients with pneumonia from the pre-COVID-19 era. Methods: PubMed, EMBASE, and Cochrane Library were searched. Two reviewers performed screening, full-text review, and extraction. Risk factors and odds ratio (OR) were estimated. Results: Of 595 articles identified, six studies were included. Pooled analysis suggested that age ≥60 years [OR =2.75, 95% confidence interval (CI): 2.55-2.97, P<0.001], mechanical ventilation (MV) (OR =9.48, 95% CI: 8.24-10.91, P<0.001), hypertension (OR =1.41, 95% CI: 1.09-1.83, P=0.010), diabetes (OR =1.49, 95% CI: 1.36-1.64, P<0.001), heart failure (OR =3.15, 95% CI: 1.05-9.41, P=0.040) and cancer (OR =2.86, 95% CI: 2.07-3.95, P<0.001) were associated with higher risk for deep vein thrombosis in patients with pneumonia. While age ≥60 years (OR =2.46, 95% CI: 2.21-2.73, P<0.001), bacterial pneumonia (OR =3.80, 95% CI: 1.65-8.73, P=0.002), hyperlipidemia (OR =1.55, 95% CI: 1.00-2.41, P=0.049), heart failure (OR =2.70, 95% CI: 2.05-3.56, P<0.001), chronic obstructive pulmonary disease (OR =4.73, 95% CI: 3.11-7.17, P<0.001) and cancer (OR =2.90, 95% CI: 2.39-3.53, P<0.001) were risk factors for pulmonary embolism in patients with pneumonia. Conclusions: Patients with non-COVID-19 pneumonia, particularly those with advanced age, MV, cardiovascular comorbidities or cancer, warrant individualized management during hospitalization. Our findings could contribute to refining risk prediction models and further risk stratification for VTE in patients with pneumonia in clinical practice.