Thymalfasin therapy accelerates COVID-19 pneumonia rehabilitation through anti-inflammatory mechanisms.

INTRODUCTION: Thymosin drugs are commonly used for the treatment of viral infections due to their immunomodulatory effects. The comprehensive clinical efficacy of Thymalfasin therapy for COVID-19 associated pneumonia is not yet fully researched, another issue, whether the use of thymosin drugs can reduce the rate of COVID-19 progression to severe pneumonia has not been well documented. The aim of the present study was to multi-angle evaluate the clinical efficacy of Thymalfasin therapy for COVID-19 pneumonia by retrospective review of the clinical data of 338 inpatients with common COVID-19 infection who received treatment in our hospital. METHODS: The primary index of observation was whether progression to severe pneumonia occurred within a week after admission, and the secondary indexes were the length of hospital stay, time of negative conversion of COVID-19 antigen, the number of peripheral lymphocytes and white blood cells (WBC), and C-reactive protein (CRP) and procalcitonin (PCT) levels,and the control of pneumonia related symptoms, for example, fever, listlessness, inflammatory exudate area shown on lung CT (%). RESULTS: The length of hospital stay of patients in Thymalfasin group was significantly shorter than that of patients in the control group (p < 0.01). The proportion of relief of pneumonia related symptoms (fever, fatigue) in the Thymalfasin therapy group was significantly higher than that in the control group, and the inflammatory exudate area shown on CT was significantly lower than that in the control group (p < 0.05). Multivariate logistic regression analysis showed that the use of Thymalfasin was an independent protective factor affecting the progression to severe pneumonia. Multifactorial Cox model analysis indicated that negative conversion of COVID-19 antigen was significantly faster in patients using Thymalfasin and younger patients. CONCLUSION: Thymalfasin therapy has shown excellent clinical efficacy in the treatment of COVID-19 pneumonia, it can reduce inflammatory reactions, promote the relief of COVID-19 pneumonia related symptoms such as fever and fatigue, facilitate effusion absorption, and accelerate COVID-19 pneumonia recovery. Thymalfasin can prevent progression of common COVID-19 infection to severe pneumonia via multiple immunity-enhancing and anti-inflammatory protective mechanisms.

Establishment of a malignancy and benignancy prediction model of sub-centimeter pulmonary ground-glass nodules based on the inflammation-cancer transformation theory.

Background: In recent years, Chinese clinicians are frequently encountered by patients with multiple lung nodules and these intensity ground-glass nodules (GGNs) are usually small in size and some of them have no spicule sign. In addition, early lung cancer is diagnosed in large numbers of non-heavy smokers and individuals with no caner history. Obviously, the Mayo model is not applicable to these patients. The aim of the present study is to develop a new and more applicable model that can predict malignancy or benignancy of pulmonary GGNs based on the inflammation-cancer transformation theory. Materials and methods: Included in this study were patients who underwent surgical resection or lung puncture biopsy of GGNs in Shanghai 10th People's Hospital between January 1, 2018 and May 31, 2021 with the inclusion criterion of the maximum diameter of GGN < 1.0 cm. All the included patients had their pulmonary GGNs diagnosed by postoperative pathology. The patient data were analyzed to establish a prediction model and the predictive value of the model was verified. Results: Altogether 100 GGN patients who met the inclusion criteria were included for analysis. Based on the results of logistic stepwise regression analysis, a mathematical predication equation was established to calculate the malignancy probability as follows: Malignancy probability rate (p) = ex/(1 + ex); p > 0.5 was considered as malignant and p ≤ 0.5 as benign, where x = 0.9650 + [0.1791 × T helper (Th) cell] + [0.2921 × mixed GGN (mGGN)] + (0.4909 × vascular convergence sign) + (0.1058 × chronic inflammation). According to this prediction model, the positive prediction rate was 73.3% and the negative prediction rate was 100% versus the positive prediction rate of 0% for the Mayo model. Conclusion: By focusing on four major factors (chronic inflammation history, human Th cell, imaging vascular convergence sign and mGGNs), the present prediction model greatly improves the accuracy of malignancy or benignancy prediction of sub-centimeter pulmonary GGNs. This is a breakthrough innovation in this field.

Psychological Impact During the First Outbreak of COVID-19 on Frontline Health Care Workers in Shanghai.

Background: The COVID-19 pandemic is a significant health threat. Health care worker (HCWs) are at a significant risk of infection which may cause high levels of psychological distress. The aim of this study was to investigate the psychological impact of the COVID-19 on HCWs and factors which were associated with these stresses during the first outbreak in Shanghai. Methods: Between February 9 and 21, 2020, a total of 3,114 frontline HCWs from 26 hospitals in Shanghai completed an online survey. The questionnaire included questions on their sociodemographic characteristics, 15 stress-related questions, and General Health Questionnaire-12 (GHQ-12). Exploratory factor analysis was applied to the 15 stress-related questions which produced four distinct factors for evaluation. Multiple linear regression models were performed to explore the association of personal characteristics with each score of the four factors. Binary logistic analysis was used to explain the association of personal characteristics and these four factors with the GHQ-12. Results: There were 2,691 valid surveys received. The prevalence of emotional distress (defined as GHQ-12 ≥ 12) was noted in 47.7% (95%CI:45.7-49.6%) HCWs. Females (OR = 1.43, 95%CI:1.09-1.86) were more likely to have a psychological distress than males. However, HCWs who work in secondary hospitals (OR = 0.71, 95% CI:0.58-0.87) or had a no contact history (OR = 0.45, 95%CI: 0.35-0.58) were less likely to suffer psychological distress. HCWs who were nurses, married, and had a known contact history were highly likely to have anxiety. HCWs working at tertiary hospitals felt an elevated anxiety regarding the infection, a lack of knowledge, and less protected compared to those who worked at secondary hospitals. Conclusions: Our study shows that the frontline HCWs had a significant psychosocial distress during the COVID-19 outbreak in Shanghai. HCWs felt a lack of knowledge and had feelings of being not protected. It is necessary for hospitals and governments to provide additional trainings and psychological counseling to support the first-line HCWs.

Investigating efficacy of "microbiota modulation of the gut-lung Axis" combined with chemotherapy in patients with advanced NSCLC: study protocol for a multicenter, prospective, double blind, placebo controlled, randomized trial.

BACKGROUND: Most NSCLCs metastasised out of the lungs at the time of diagnosis and cannot be surgically removed . Cytotoxic chemotherapy drugs have become the main treatment in recent decades, especially in patients with NSCLC without EGFR, ALK, and ROS gene mutations. The prognosis of lung cancer is poor, and the overall 5-year survival rate is only 9-13%. Therefore the treatment of advanced NSCLC remains a significant medical need. Recent studies have shown a significant relationship between the gut-lung axis microecology and malignant tumors. Intestinal probiotics are likely to play a role in inhibiting tumorigenesis through "intestinal-pulmonary axis microecological regulation". This study will seek to investigate the efficacy of "Microbiota modulation of the Gut-Lung Axis" combined with chemotherapy in patients with advanced NSCLC. METHODS: The research is a multicenter, prospective, double blind, placebo controlled, randomized trial. Based on the theoretical basis of "intestinal and lung axis microecological adjustment", combined with traditional platinum-containing two-drug chemotherapy, the efficacy of the new therapy on patients with advanced NSCLC was observed. Collect the basic information of the patient, and study the effect of platinum-based combined chemotherapy on the diversity of intestinal flora in patients with lung cancer after receiving chemotherapy treatment, feces before and after chemotherapy, and the status and extent of adverse reactions during chemotherapy . A total of 180 subjects were included, divided into a control group (platinum-containing dual-drug chemotherapy) and an intervention group (platinum-containing dual-drug chemotherapy combined with Bifico), and were randomly assigned to the group 1:1. DISCUSSION: As a result, intestinal-pulmonary microecological balance could become a new target for the treatment of lung cancer. This study explores the combination of intestinal microecological regulation and chemotherapy to provide new treatment strategies and basis for lung cancer patients. It can help prolong the survival time of lung cancer patients and improve the quality of life, thereby generating huge economic and social benefits. The results can be promoted and applied to units engaged in the treatment of lung cancer. TRIAL REGISTRATION NUMBER: NCT03642548, date: August 22, 2018, the first version protocol. The URL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT03642548?term=NCT03642548&draw=2&rank=1 .

Radiofrequency ablation vs. stereotactic body radiotherapy for stage IA non-small cell lung cancer in nonsurgical patients.

Background: Approximately 20% resectable non-small cell lung cancer (NSCLC) patients are treated non-surgically due to various reasons. The aim of the present study was to compare the effectiveness of radiofrequency ablation (RFA) and stereotactic body radiotherapy (SBRT) in patients with stage IA NSCLC who were ineligible for surgery using the surveillance, epidemiology and end-results (SEER) Database. Methods: Using the SEER registry, we identified a total of 6,195 IA NSCLC patients who received SBRT or RFA between 2004 and 2015 because of ineligibility for surgical resection due to various reasons. Complete clinical information was available in all these patients. Overall survival (OS) and cancer-specific survival (CSS) were compared between RFA and SBRT groups by using propensity score matching (PSM), inverse probability of treatment weight (IPTW), and overlap weighting analysis. Additionally, an exploratory analysis was conducted to determine the effectiveness of RFA treatment based on the subsets of clinically relevant patients. Results: Of the 6,195 nonsurgical IA NSCLC patients, 191 patients (3.1%) received RFA and the other 6,004 patients (96.9%) received SBRT. The one-, three- and five-year OS in the unmatched RFA and SBRT groups were 83.3%, 48.5%and 29.1% vs. 83.8%, 48.3% and 27.4%, respectively, there was similar results in the PSM, IPTW, overlap weighing analysis. Nonsurgical IA NSCLC patients receiving RFA seemed to have better five-year survival than those receiving SBRT, though the difference was not statistically significant (OS, HR; 0.986; 95% CI, 0.827-1.175, P=0.8738; CSS, HR; 0.965; 95% CI, 0.765-1.219, P=0.7663). We found that the odds of receiving RFA decreased with larger tumor size (>2, <3 cm, OR; 0.303; 95% CI, 0.191-0.479; >3 cm, OR; 0.153; 95% CI, 0.093-0.251) compared with tumor size <1 cm. In subgroup analysis, patients receiving RFA seemed to have better OS than those receiving SBRT, though the difference was not statistically significant. This specific trend was even more obvious in patients with tumors <1cm in diameter (P=0.1577). Conclusion: In comparison with SBRT, RFA did not seem to adversely affect CSS and OS of IA NSCLC patients who were not suitable for surgical treatment. In addition, RFA seemed to offer better survival to IA NSCLC patients, especially those with tumors <1 cm.

Comparative Analysis of Early-Stage Clinical Features Between COVID-19 and Influenza A H1N1 Virus Pneumonia.

Introduction: Influenza virus pneumonia and COVID-19 are two different types of respiratory viral pneumonia but with very similar clinical manifestations. The aim of the present study was to help clinicians gain a better understanding about differences between Influenza virus pneumonia and COVID-19 by comparative analysis of the early-stage clinical features. Methods: Clinical data of patients with confirmed diagnosis of COVID-19 and influenza A pneumonia identified in our hospital were collected and analyzed retrospectively to identify the clinical features that could differentiate between the two types of viral pneumonia. Results: The two types of viral pneumonia mainly affected adults, especially people over 50 years, with no gender difference between them. Fever, cough, sputum and muscle soreness were the most common symptoms of COVID-19. Some patients with COVID-19 may also exhibit digestive tract symptoms. Elevation of C-reactive protein (CRP) was a more common phenomenon in patients with COVID-19 than that in patients with influenza A H1N1 virus pneumonia. In addition, eosinophil count was decreased and the monocyte percentage was increased in COVID-19 patients. The grid-form shadow was a typical presentation of COVID-19 on the lung CT image, and the disease usually progressed quickly within a week. Conclusion: Influenza pneumonia and COVID-19 are two different types of respiratory viral pneumonia with very similar clinical manifestations. The percentage of monocytes is increased and the eosinophil count is decreased in COVID-19. Glass-ground density exudation shadow located peripherally is the typical sign of COVID-19 on the lung CT image, and the shadow often with grid-form sign. These features may not be typically observed in patients with influenza pneumonia. Chest CT scan combined with nucleic acid detection is an effective and accurate method for diagnosing COVID-19. Blood routine test has a limited diagnostic value in differentiating the two forms of pneumonia.

Immunomodulatory effects of intestinal lung axis microecology and other factors on the prognosis of advanced non-small cell lung cancer.

Overall survival (OS) of lung cancer varies greatly with individual patients in the global setting. Multiple factors may affect the prognosis. Different antibiotics have significant effects on the prognosis of lung cancer patients. The intestinal microbiome, nutritional status and inflammatory factors all have significant impact on OS of lung cancer patients.

CDK5 Functions as a Tumor Promoter in Human Lung Cancer.

Cyclin-dependent kinase 5 (CDK5), an atypical member of the cyclin-dependent kinase family, plays an important role in the nervous system. Recent studies have shown that CDK5 is also associated with tumors. However, few studies have been done to investigate the mechanism underlying the connection between CDK5 and cancers. To explore the role of CDK5 in cancers by using an extensive bioinformatics data mining process. We mined the transcriptional, survival, functions and structure of CDK5 gene through databases and in vitro experiments. We found that higher CDK5 expression levels in most cancer cell lines while lower expression in liver and brain cancer cell lines. High expression of CDK5 was associated with shorter overall survival (OS) in lung cancer. In addition, high expression level of CDK5 promoted lung cancer cells proliferation and metastasis. Inhibited CDK5 decreases CAP1 phosphorylation. CDK5 may prove to be a valid target of anticancer therapies.

Evaluation of the predictive value of red blood cell distribution width for onset of cerebral infarction in the patients with obstructive sleep apnea hypopnea syndrome.

Red blood cell distribution width (RDW) is a risk factor for the complications caused by obstructive sleep apnea hypopnea syndrome (OSAHS). This study was aimed to evaluate the predictive value of RDW for the occurrence of cerebral infarction in patients with OSAHS.We conducted a prospective study of 129 consecutive patients who were admitted to the Sleep Laboratory of in the Tenth People's Hospital of Shanghai (China) with complaints of snoring, apnea, or daytime sleepiness. All patients underwent polysomnography between June 2011 and May 2012. In total, 90 patients met the study criteria and were included in the study; there are 71 men and 19 women.RDW correlated positively with the apnea hypopnea index (AHI) (P = .00, r = 0.76). Logistic regression analysis showed correlations between each variation and cerebral infarction, high blood pressure (odds ratio [OR] = 4.72, P = .220), diabetes (OR = 2.67, P = .490), hyperlipidemia (OR = 7.42, P = .190), RDW (OR = 58.24, P = .020), and AHI (OR = 243.92, P = .001). RDW ≥ 15% showed a higher predictive value for the occurrence of cerebral infarction in patients with OSAHS (area under curve 0.837; sensitivity 0.919; specificity 0.755), with positive and negative predictive values of 0.697 and 0.938, respectively.RDW correlates positively with AHI. RDW values ≥15% are predictive for the occurrence of cerebral infarction in patients with OSAHS.

Systematic analysis of gene expression alterations and clinical outcomes of adenylate cyclase-associated protein in cancer.

Adenylate Cyclase-associated protein (CAP) is an evolutionarily conserved protein that regulates actin dynamics. Our previous study indicates that CAP1 is overexpressed in NSCLC tissues and correlated with poor clinical outcomes, but CAP1 in HeLa cells actually inhibited migration and invasion, the role of CAP was discrepancy in different cancer types. The present study aims to determine whether CAP can serve as a prognostic marker in human cancers. The CAP expression was assessed using Oncomine database to determine the gene alteration during carcinogenesis, the copy number alteration, or mutations of CAP using cBioPortal, International Cancer Genome Consortium, and Tumorscape database investigated, and the association between CAP expression and the survival of cancer patient using Kaplan-Meier plotter and PrognoScan database evaluated. Therefore, the functional correlation between CAP expression and cancer phenotypes can be established; wherein CAP might serve as a diagnostic marker or therapeutic target for certain types of cancers.

Overexpression of adenylate cyclase-associated protein 1 may predict brain metastasis in non-small cell lung cancer.

This study was designed to establish a biomarker risk model for predicting brain metastasis (BM) in non-small cell lung cancer (NSCLC). The model comprises 120 cases of NSCLC that were treated and followed up for 4 years. The patients were divided into the BM (n=50) and non-BM (other visceral metastasis and those without recurrence) (n=70) groups. Immunohistochemical and western blot analyses were performed in metastatic tissues of NSCLC. Multivariate regression analysis was performed to correlate the immunoreactive cyclase-associated protein 1 (CAP1) signal with BM. Survival analyses were performed by using the Kaplan-Meier method. CAP1 protein content and immunoreactivity were significantly increased in BM specimens compared to other-metastatic specimens. The survival analysis revealed that CAP1 overexpression was significantly associated with survival (P<0.05). The ROC test suggested that the area under the curve was 73.33% (P<0.001; 95% CI, 63.5-83.2%). When P=0.466, the sensitivity and specificity reached 79.5 and 67.1%, respectively. These findings suggested that CAP1 is involved in the BM of NSCLC, and that elevated levels of CAP1 expression may indicate a poor prognosis for patients with BM. The CAP1 molecular model may be useful in the prediction of the risk of BM in NSCLC.

Preparation of a nano emodin transfersome and study on its anti-obesity mechanism in adipose tissue of diet-induced obese rats.

OBJECTIVE: To describe the preparation of nano emodin transfersome (NET) and investigate its effect on mRNA expression of adipose triglyceride lipase (ATGL) and G0/G1 switch gene 2 (G0S2) in adipose tissue of diet-induced obese rats. METHODS: NET was prepared by film-ultrasonic dispersion method. The effects of emodin components at different ratios on encapsulation efficiency were investigated.The NET envelopment rate was determined by ultraviolet spectrophotometry. The particle size and Zeta potential of NET were evaluated by Zetasizer analyzer. Sixty male SD rats were assigned to groups randomly. After 8-week treatment, body weight, wet weight of visceral fat and the percentage of body fat (PBF) were measured. Fasting blood glucose and serum lipid levels were determined. The adipose tissue section was HE stained, and the cellular diameter and quantity of adipocytes were evaluated by light microscopy. The mRNA expression of ATGL and G0S2 from the peri-renal fat tissue was assayed by RT-PCR. RESULTS: The appropriate formulation was deoxycholic acid sodium salt vs. phospholipids 1:8, cholesterol vs. phospholipids 1:3, vitamin Evs. phospholipids 1:20, and emodin vs. phospholipid 1:6. Zeta potential was -15.11 mV, and the particle size was 292.2 nm. The mean encapsulation efficiency was (69.35 ± 0.25)%. Compared with the obese model group, body weight, wet weight of visceral fat, PBF and mRNA expression of G0S2 from peri-renal fat tissue were decreased significantly after NET treatment (all P < 0.05), while high-density lipoprotein cholesterol (HDL-C), the diameter of adipocytes and mRNA expression of ATGL from peri-renal fat tissue were increased significantly (all P < 0.05). CONCLUSION: The preparation method is simple and reasonable. NET with negative electricity was small and uniform in particle size, with high encapsulation efficiency and stability. NET could reduce body weight and adipocyte size, and this effect was associated with the up-regulation of ATGL, down-regulation of G0S2 expression in the adipose tissue, and improved insulin sensitivity.

Cryptogenic organizing pneumonia associated with invasive pulmonary aspergillosis: a case report and review of the literature.

BACKGROUND: Concomitant occurrence of invasive pulmonary aspergillosis (IPA) with cryptogenic organizing pneumonia (COP) is scarce. Here, we report a case where COP was a presenting feature in a patient with diagnosed IPA, and review additional 58 COP patients reported in the literature from 1988 through 2013. CASE OUTLINE: The study was reviewed and approved by the Institutional Ethics Committee of Shanghai Tenth People's Hospital of Tongji University and was conducted in compliance with the Helsinki Declaration. Written informed consent was obtained from patient. A 56-year-old man presenting with productive cough for several weeks and unremitting high fever for a week was hospitalized with an initial clinical diagnosis of pneumonia, for which antibiotics were prescribed but did not work. Seeing that the condition progressed both clinically and radiographically, bronchoscopy, bronchoalveolar lavage and lung biopsy were performed, and the diagnosis of cryptogenic organizing pneumonia (COP) and invasive pulmonary aspergillosis (IPA) co-existence was made. Initially, the patient responded to steroid pulse therapy and voriconazole treatment, and his condition was partially improved. However, the patient's condition deteriorated progressively 5 months after the disease onset and the patient died during the third admission due to respiratory failure and the adverse reactions of coriaceous hormone therapy. CONCLUSION: The diagnosis of cryptogenic organizing pneumonia (COP) and invasive pulmonary aspergillosis (IPA) co-occurrence depends on clinical, radiological and histological presentations. Similarities with other disease processes could lead to a delayed diagnosis or misdiagnosis. The present case suggests that clinicians should be alert to this disease in their clinical practices.