Esophageal carcinoma is a malignant disease with a high incidence rate and poor prognosis. The mitochondrial apoptosis pathway plays a pivotal role in the regulation of cell death and has become a focal point in current cancer therapeutics research. Various active components from traditional Chinese medicine （TCM） can target the mitochondrial apoptosis pathway to inhibit esophageal carcinoma， presenting as potential therapeutic agents for this disease. This paper summarizes relevant research on the inhibition of esophageal carcinoma by active components in TCM via targeting the mitochondrial apoptosis pathway. It has been found that flavonoids （casticin， icariin， luteolin， kaempferol， hesperetin， deguelin， etc.）， terpenoids （oridonin， Jaridonin， artesunate， ethyl acetate fraction of pleurotus ferulatus triterpenoid， etc.）， alkaloids （matrine， swainsonine， etc.）， polyphenols （curcumin， epigallocatechin-3-gallate， corilagin， etc.）， steroids （α-hederin， polyphyllin Ⅵ， etc.）， phenols （optimized scorpion venom peptide CT-K3K7， gecko active polypeptide， etc.）， volatile oils （cinnamaldehyde， α -asarone， etc.） and other active components from TCM can target the intrinsic mitochondrial apoptosis pathway， induce apoptosis in esophageal carcinoma cells， and inhibit their proliferation， invasion and migration by regulating oxidative stress， blocking the cell cycle， regulating signaling pathways such as PI3K/Akt and MAPK.

Objective To analyze the prognosis of children with severe mycoplasma pneumonia (MPP) and its correlation with serum SAA, PCT and SF levels, so as to provide a basis for evaluating the prognosis of children with MPP. Methods A total of 273 children with MPP admitted to our hospital from January 2020 to December 2020 were divided into mild MPP children (n=187) and severe MPP children (n=86) according to the severity of their disease. According to the prognosis, children with severe MPP were divided into survival group (n=65) and death group (n=21). Serum SAA, PCT and SF levels were determined. Pearson correlation analysis was used to analyze the correlation between serum SAA, PCT and SF levels and APACHE ⅱ score. ROC curve was used to analyze the predictive value of serum SAA, PCT and SF levels for poor prognosis of children with severe MPP. Results The levels of serum SAA, PCT and SF and APACHE II score in children with severe MPP were significantly higher than those in children with mild MPP (P<0.05). Serum SAA, PCT and SF levels and APACHE II score in death group were significantly higher than those in survival group (P<0.05). Pearson correlation analysis showed that APACHE II score was positively correlated with serum SAA, PCT and SF levels (r =0.474,0.519,0.446,P<0.05). The AUC, sensitivity and specificity of combined ROC curve analysis to predict the prognosis of severe MPP were 0.871, 85.9% and 93.6% respectively, which were higher than those of SAA, PCT and SF alone. Conclusion SAA, PCT and SF are closely related to the prognosis of severe MPP, and can be used as potential markers to predict poor prognosis of severe MPP children.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective To identify the potential long non-coding RNA (lncRNA) expressed in rheumatoid arthritis (RA) synovium key to RA onset and investigate its association with immune cell infiltration. Methods RA synovium data were downloaded from the GEO database and normalized. The lncRNAs key to RA onset were identified using multiple machine learning methods. Infiltration of 22 immune cell populations in RA synovium was measured by cell-type identification by estimating relative subsets of RNA transcripts (CIBER-SORT). The relationship between the key lncRNA and infiltrating immune cells was analyzed. Finally, real-time quantitative PCR was applied to validate the expression of the key lncRNA in RA synovial cells. Results lncRNA human leukocyte antigen complex P5(HCP5) was identified as the key lncRNA associated with RA onset. Infiltration analysis revealed increased abundance of CD8⁺ T cells, γδ T cells, and M1 macrophages while decreased abundance of M2 macrophages in RA synovial tissue. Correlation analysis demonstrated that the lncRNA HCP5 expression was positively associated with the infiltration abundance of CD8⁺ T cells, γδ T cells, and M1 macrophages in RA synovial tissue. Furthermore,the expression of lncRNA HCP5 in RA synovial cells was up-regulated. Conclusion lncRNA HCP5 expression is up-regulated in RA synovial tissue and potentially associated with immune cells infiltration.
Humans ; Arthritis, Rheumatoid ; CD8-Positive T-Lymphocytes ; HLA Antigens/metabolism* ; RNA, Long Noncoding/metabolism* ; Synovial Membrane/metabolism*

{L-End}Objective To investigate the current status of sleep quality and its influencing factors among coal miners in a company in Shanxi Province. {L-End}Methods A total of 1 047 coal miners from a coal mine company in Shanxi Province were selected as the study subjects by convenient sampling method. The occupational stress, occupational burnout and sleep quality of the study subjects were investigated using Occupational Stress Core Scale, Maslach Burnout Inventory-General Survey and Pittsburg Sleep Quality Index Scale. {L-End}Results The detection rates of occupational stress, occupational burnout, sleep disorder were 58.9%, 59.1% and 57.9%, respectively. The result of multivariate logistic regression analysis showed that education level, alcohol consumption, work shift, duration of dust-exposure, phase of respiratory symptoms, self-assessment of health, occupational stress and occupational burnout were independent influencing factors of sleep disorders in the coal miners (all P<0.05). Among them, the risk of sleep disorders in drinkers was higher than that in non-drinkers (P<0.05); the risk of sleep disorders was higher in miners working in a rotating work shift with two shifts than in those with three shifts (P<0.05); the higher the education level, the longer the duration of dust-exposure, the more serious the phase of respiratory symptoms, the worse the self-assessment of health, the higher the degree of occupational stress and the higher the degree of occupational burnout, the higher the risk of sleep disorders (all P<0.05). {L-End}Conclusion The incidence of sleep disorders in coal miners in this company is relatively high. Occupational stress, occupational burnout, education level, alcohol consumption, work shift, duration of dust-exposure, respiratory symptoms and health status are risk factors for sleep disorders in coal miners.

Background: Classical swine fever (CSF) is a severe infectious disease of pigs that causes significant economic losses to the swine industry. Objectives: This study developed a solid-phase blocking enzyme-linked immunosorbent assay (spbELISA) method for the specific detection of antibodies against the CSF virus (CSFV) in porcine serum samples. Methods: A spbELISA method was developed based on the recombinant E2 expressed in Escherichia coli. The specificity of this established spbELISA method was evaluated using reference serum samples positive for antibodies against other common infectious diseases.The stability and sensitivity were evaluated using an accelerated thermostability test. Results: The spbELISA successfully detected the antibody levels in swine vaccinated with the C-strain of CSFV. In addition, the detection ability of spbELISA for CSFV antibodies was compared with that of other commercial ELISA kits and validated using an indirect immunofluorescence assay. The results suggested that the spbELISA provides an alternative, stable, and rapid serological detection method suitable for the large-scale screening of CSFV serum antibodies. Conclusions The spbELISA has practical applications in assessing the vaccination status of large pig herds.

Organoid models are used to study kidney physiology, such as the assessment of nephrotoxicity and underlying disease processes. Personalized human pluripotent stem cell-derived kidney organoids are ideal models for compound toxicity studies, but there is a need to accelerate basic and translational research in the field. Here, we developed an automated continuous imaging setup with the "read-on-ski" law of control to maximize temporal resolution with minimum culture plate vibration. High-accuracy performance was achieved: organoid screening and imaging were performed at a spatial resolution of 1.1 μm for the entire multi-well plate under 3 min. We used the in-house developed multi-well spinning device and cisplatin-induced nephrotoxicity model to evaluate the toxicity in kidney organoids using this system. The acquired images were processed via machine learning-based classification and segmentation algorithms, and the toxicity in kidney organoids was determined with 95% accuracy. The results obtained by the automated "read-on-ski" imaging device, combined with label-free and non-invasive algorithms for detection, were verified using conventional biological procedures. Taking advantage of the close-to-in vivo-kidney organoid model, this new development opens the door for further application of scaled-up screening using organoids in basic research and drug discovery.
Humans ; Kidney ; Organoids ; Pluripotent Stem Cells

Purpose: Drug resistance is one of the main causes of chemotherapy failure in patients with small cell lung cancer (SCLC), and extensive biological studies into chemotherapy drug resistance are required. Materials and Methods: In this study, we performed lncRNA microarray, in vitro functional assays, in vivo models and cDNA microarray to evaluate the impact of lncRNA in SCLC chemoresistance. Results: The results showed that KCNQ1OT1 expression was upregulated in SCLC tissues and was a poor prognostic factor for patients with SCLC. Knockdown of KCNQ1OT1 inhibited cell proliferation, migration, chemoresistance and promoted apoptosis of SCLC cells. Mechanistic investigation showed that KCNQ1OT1 can activate transforming growth factor-β1 mediated epithelial-to-mesenchymal transition in SCLC cells. Conclusion Taken together, our study revealed the role of KCNQ1OT1 in the progression and chemoresistance of SCLC, and suggested KCNQ1OT1 as a potential diagnostic and prognostic biomarker in SCLC clinical management.

Objective:To investigate the efficacy and safety of less invasive surfactant administration(LISA) of neonatal respiratory distress syndrome(NRDS).Methods:From July 2017 to December 2018, 50 premature infants with birth weight ≤1 500 g and/or gestational age≤32 weeks diagnosed as NRDS at the Fifth Medical Center of PLA General Hospital were randomly divided into LISA group( n=25)and INSURE group( n=25). The patients in LISA group was inserted fine duct into the trachea through direct laryngoscope under nasal continuous positive airway pressure (nCPAP) and pulmonary surfactant was injected.The INSURE group adopts endotracheal intubation-pulmonary surfactant-nCPAP was performed after unplugging.The changes of vital signs, blood gas indexes, adverse reactions and the incidence of complications were compared between two groups at different time points. Results:There was no significant difference in respiration, heart rate, systolic blood pressure, diastolic blood pressure and PaO 2, PaCO 2, BE, SpO 2 between two groups at different administration time points.Although the pH value of LISA group was lower than that of INSURE group, it was within the normal range.There was no significant difference in bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leucomalacia and other complications between two groups, and there was no death, air leakage, retinopathy of prematurity and pulmonary hemorrhage in both two groups.In addition, there was no significant difference in hospitalization days, total medical expenses, oxygen use time between the two groups(all P>0.05). Conclusion:Compared with INSURE technology, LISA technology has its feasibility for premature infants with NRDS, but the effectiveness and safety in the practical application need to be further confirmed.

Objective:To identify the key genes related to rheumatoid arthritis (RA) by to the weighted gene co-expression network analysis (WGCNA) and experimental verification to find key genes related to RA.Methods:The microarray data of RA were downloaded from the Gene Expression Omnibus (GEO) database. Gene network was constructed, and the genes were classified into different modules using WGCNA. HUB genes in modules related to RA clinical symptoms were analyzed by gene ontology. Subsequently, different data sets of GEO were used to verify the expression profile and diagnostic capacity of the HUB gene [receiver operating characteristic curve (ROC)]. In addition, the expression of HUB gene in RA was verified by real time polymerase chain reaction (RT-PCR) and Western blot, and the relationship between key genes and disease activity score 28 joints (DAS28) was analyzed. Paired-sample t-test and Pearson's correlation analysis was used for statistical analysis. Results:A total of 5 413 differentially expressed genes were filtered. Weighted gene coexpression network was constructed and genes were classified into 23 modules. Among them, the black module is closely related to the clinical symptoms of RA, which contained 346 genes. Enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) signal pathway analysis showed that it was to be enriched in the positive regulation of interleukin 6, interleukin 1 beta secretion, osteoclast differentiation, NOD-like receptor signaling pathway, T helper cell 17 (Th17) cell differentiation and many other pathways closely related to RA. Motile sperm domain-containing protein 2 (MOSPD2) was significantly correlated with clinical symptoms. It was highly expressed in blood monocytes and bone marrow monocytes ( t=2.238, P=0.032; t=3.153, P=0.006), and positively correlated with blood expression in RA joint synovial fluid ( r=0.683, P=0.03). ROC curve analysis determined that MOSPD2 could distinguish RA from the control group (the area under the curve was 0.855 and 0.726) respectively. RT-PCR and Western blotting results showed that MOSPD2 was up-regulated in RA patients ( t=-3.96, P=0.02). MOSPD2 expression levels in blood were positively correlated with DAS28 in RA patients ( r=0.884 6, P=0.046 2). Conclusion:MOSDP2 is closely related to the clinical symptoms of RA patients, and may be one of the targets for the diagnosis and treatment of RA.