BACKGROUND: It is inaccurate to reflect the level of dust exposure through working years. Furthermore, identifying a predictive indicator for lung function decline is significant for coal miners. The study aimed to explored whether club cell secretory protein (CC16) levels can reflect early lung function changes. METHODS: The cumulative respiratory dust exposure (CDE) levels of 1,461 coal miners were retrospectively assessed by constructed a job-exposure matrix to replace working years. Important factors affecting lung function and CC16 were selected by establishing random forest models. Subsequently, the potential of CC16 to reflect lung injury was explored from multiple perspectives. First, restricted cubic spline (RCS) models were used to compare the trends of changes in lung function indicators and plasma CC16 levels after dust exposure. Then mediating analysis was performed to investigate the role of CC16 in the association between dust exposure and lung function decline. Finally, the association between baseline CC16 levels and follow-up lung function was explored. RESULTS: The median CDE were 35.13 mg/m³-years. RCS models revealed a rapid decline in forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁), and their percentages of predicted values when CDE exceeded 25 mg/m³-years. The dust exposure level (<5 mg/m³-years) causing significant changes in CC16 was much lower than the level (25 mg/m³-years) that caused changes in lung function indicators. CC16 mediated 11.1% to 26.0% of dust-related lung function decline. Additionally, workers with low baseline CC16 levels experienced greater reductions in lung function in the future. CONCLUSIONS CC16 levels are more sensitive than lung indicators in reflecting early lung function injury and plays mediating role in lung function decline induced by dust exposure. Low baseline CC16 levels predict poor future lung function.
Uteroglobin/blood* ; Humans ; Dust/analysis* ; Occupational Exposure/analysis* ; Male ; Middle Aged ; Adult ; Retrospective Studies ; Lung Injury/chemically induced* ; Coal Mining ; Biomarkers/blood* ; China/epidemiology* ; Air Pollutants, Occupational ; Female

OBJECTIVE To investigate the protective effect proanthocyanidin B2(PC-B2) on oxidative damage and apoptosis of mouse astrocytes(AS) induced by hydrogen peroxide(H2O2) and its mechanism. METHODS AS were isolated and cultured from neonatal C57BL/6 mice(1−3 d). The optimal concentration of H2O2 and PC-B2 was divided into four groups: normal group, normal+PC-B2 group(100 μg·mL‒1 PC-B2 treated for 24 h), H2O2 model group(200 μmol·L‒1 H2O2 treated for 24 h), PC-B2 group(200 μmol·L‒1 H2O2 and 100 μg·mL‒1 PC-B2 treated for 24 h). The cell viability of each group was detected by CCK-8 method. Cytotoxicity was detected by LDH method. The antioxidant capacity was detected by ABTS and DPPH. The content of MDA and the activity of SOD, CAT and GSH-Px were detected by ELISA kit. Detection of apoptosis in each group was done by TUNEL staining. The mRNA and protein expression levels of Bax, Bcl-2, Caspase-3, Akt/Stat3, p-Akt, p-Stat3 and Nrf2/HO-1 in AS were detected by RT-PCR and Western blotting, respectively. RESULTS PC-B2 could significantly enhance cell viability and inhibit AS apoptosis. Compared with the H2O2 model group, PC-B2 intervention could significantly reduce the content of LDH and MDA in AS, and increase the activity of SOD, CAT and GSH-Px. PC-B2 intervention could inhibit the mRNA and protein expression of Bax and Caspase-3, and up-regulate the mRNA and protein expression of Akt/Stat3, Bcl-2, Nrf2/HO-1. CONCLUSION PC-B2 can enhance the antioxidant capacity of AS through Akt/Stat3 and Nrf2/HO-1 pathways, therefore reduce H2O2-induced AS oxidative damage and apoptosis.

Objective To explore the relationship between the polymorphism of excision repair cross-complementation group 1 (ERCC1) C8092A locus and the efficacy and prognosis of platinum-based chemotherapy for lung cancer (LC), and to provide a theoretical basis for precision treatment of LC. Methods From January 2014 to October 2017, 120 patients from two tertiary hospitals in Haikou City, and with pathologically confirmed lung cancer treated with platinum-based chemotherapy were selected as the research objects. After informed consent was obtained, peripheral blood samples were collected for DNA extraction, and the genotype of ERCC1 C8092A locus was detected by mass spectrometry. WHO's Response Evaluation Criteria in Solid Tumours (RECIST) was used to judge patients' chemotherapy efficacy and patients' survival status was obtained by telephone follow-up and other means. Results Among the 120 LC patients, the genotype frequencies of ERCC1 C8092A locus were 67 cases of CC wildtype (55.8%), 45 cases of CA heterozygous type (37.5%), and 8 cases of AA rare mutation type (6.7%), which conformed to Hardy-Weinberg equilibrium (χ2=0.140, P>0.05). The total effective rate of chemotherapy was 32.5%, with the highest effective rate in patients with the CA genotype (42.2%) at the ERCC1 C8092A locus and the lowest in patients with the CC genotype (25.4%). The overall one-year survival rate was 68.3% and the three-year survival rate was 35.8%. The patients with ERCC1 C8092A AA genotype had the lowest survival rate, with a one-year survival rate of 50.0% and three-year survival rate of only 25.0%. However, there were no statistical differences in the overall survival rate among the three genotypes of carriers of ERCC1 C8092A (χ2=0.328, P=0.849). Conclusions The polymorphism of ERCC1 C8092A locus is associated with the efficacy of platinum-based chemotherapy for LC, and patients with CA genotype have the highest efficacy. The one-year and three-year survival rates of patients with CC genotype are significantly higher than those of CA and AA genotypes.

Alzheimer's disease(AD)is a severe threat to human health and one of the three major causes of human death.Double-stranded RNA-dependent protein kinase(PKR)is an interferon-induced protein kinase involved in innate immunity.In the occurrence and development of AD,PKR is upregulated and continu-ously activated.On the one hand,the activation of PKR triggers an integrated stress response in brain cells.On the other hand,it indirectly upregulates the expression of 3-site amyloid precursor protein cleaving enzyme 1 and facilitates the accumulation of amyloid-β protein(Aβ),which could activate PKR activator to further activate PKR,thus forming a sustained accumulation cycle of Aβ.In addition,PKR can promote Tau phosphorylation,thereby reducing microtubule stability in nerve cells.Inflammation in brain tissue,neurotoxicity resulted from Aβaccumulation,and disruption of microtubule stability led to the progression of AD and the declines of memory and cognitive function.Therefore,PKR is a key molecule in the development and progression of AD.Effective PKR detection can aid in the diagnosis and prediction of AD progression and provide opportunities for clinical treat-ment.The inhibitors targeting PKR are expected to control the activity of PKR,thereby controlling the progression of AD.Therefore,PKR could be a target for the development of therapeutic drugs for AD.

OBJECTIVE: To investigate the effectiveness of sacroiliac screw implantation assisted by three-dimensional (3D) printed faceted honeycomb guide plate in the treatment of posterior pelvic ring fracture. METHODS: The clinical data of 40 patients with posterior pelvic ring fractures treated with sacroiliac screw implantation between December 2019 and December 2022 were retrospectively analyzed. Among them, 18 cases were treated with sacroiliac screws fixation assisted by 3D printed faceted honeycomb guide plate (guide plate group), and 22 cases were treated with sacroiliac screws percutaneously fixation under fluoroscopy (conventional group). There was no significant difference in baseline data ( P>0.05) such as gender, age, time from injury to operation, and Dennis classification between the two groups. The implantation time, frequency of C-arm X-ray fluoroscopy, frequency of guide pin adjustment of each sacroiliac screw, and postoperative complications and bone healing were recorded. Majeed score was used to evaluate the functional recovery at 6 months after operation, and CT was used to observe whether the screw penetrated the bone cortex. The deviation between the virtual position and the actual position of the screw tip, the sacral foramen, and the screw entry point was measured on the sagittal CT images of the guide plate group. RESULTS: The number of screws implanted in S ₁ and S ₂ vertebral bodies was 14 and 16 respectively in the guide plate group, and 17 and 18 respectively in the conventional group. The implantation time of each sacroiliac screw, the frequency of C-arm X-ray fluoroscopy, and the frequency of guide pin adjustment in S ₁, S ₂, and all vertebrae in the guide plate group were significantly less than those in the conventional group ( P<0.05). Patients in both groups were followed up 8-48 months, with an average of 19.7 months. There was no incision infection, screw displacement, or internal fixation loosening in both groups. Callus growth was observed in all patients at 12 weeks after operation, and bone healing was achieved in all patients. The healing time ranged from 12 to 24 weeks, with an average of 15.7 weeks. No sacroiliac screw penetrated the bone cortex in the guide plate group; 2 patients in the conventional group had sacroiliac screws penetrating the bone cortex without damaging blood vessels or nerves. In the guide plate group, the deviation between the virtual position and the actual position of the screw tip, the sacral foramen, and the screw entry point were (2.91±1.01), (2.10±0.74), and (1.67±0.70) mm, respectively, with an average deviation of (2.19±1.22) mm. There was no significant difference in Majeed function evaluation between the two groups at 6 months after operation ( P>0.05). CONCLUSION The application of 3D printed faceted honeycomb guide plate in sacroiliac screw implantation for posterior pelvic ring fracture can shorten the screw implantation time, reduce the frequency of fluoroscopy and guide pin adjustment, and reduce the risk of screw penetration through the bone cortex.
Humans ; Fracture Fixation, Internal/instrumentation* ; Bone Screws ; Printing, Three-Dimensional ; Bone Plates ; Fractures, Bone/surgery* ; Pelvic Bones/surgery* ; Retrospective Studies ; Treatment Outcome ; Male ; Female ; Middle Aged ; Adult

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*

OBJECTIVE To comprehensively evaluate the quality of Eriobotrya japonica leaves from different producing areas. METHODS The contents of alcohol-soluble extracts were determined by hot-dipping method using 30 batches of E. japonica leaves from different producing areas as samples. The contents of total flavonoids and total triterpene acids were determined by ultraviolet spectrophotometry. The contents of five kinds of triterpenic acids （euscaphic acid，crataegolic acid，corosolic acid，oleanolic acid and ursolic acid） were determined by HPLC. The quality of E. japonica leaves from different producing areas was comprehensively evaluated by using entropy weight technique for order preference by similarity to an ideal solution （TOPSIS）. The bivariate correlation analysis of E. japonica leaves was conducted by SPSS 22.0 software in terms of weight， comprehensive evaluation value， the content of alcohol-soluble extract， the contents of total flavonoids， total triterpene acids and five triterpenic acids. RESULTS The contents of alcohol-soluble extract in 30 batches of E. japonica leaves were （24.56±0.08）%-（34.85±0.13）%； the contents of total flavonoids were （4.69±0.11）-（14.23±0.27） mg/g； the contents of total triterpene acid were （27.58±0.59）- （63.95±1.27） mg/g； the contents of euscaphic acid， crataegolic acid， corosolic acid， oleanolic acid and ursolic acid were （0.728± 0.011）-（6.064±0.063）， （0.526±0.013）-（3.245±0.022）， （1.222±0.025）-（8.807±0.094）， （0.856±0.021）-（2.931±0.075）， （4.704±0.087）-（11.806±0.283） mg/g， respectively. The analysis result of entropy weight TOPSIS method showed that the top three samples with comprehensive evaluation values （No.Kjcx-5） were S14 （Huotian Town， Yunxiao County， Zhangzhou，Fujian）， S19 （Qinnan District， Qinzhou， Guangxi） and S29 （Guoyang County， Bozhou， Anhui）. Comprehensive evaluation 0596-2559522。E-mail：jxrcwxp@163.com of E. japonica leaves was positively correlated with the contents of five kinds of triterpenic acids， such as euscaphic acid， crataegolic acid， corosolic acid， oleanolic acid and ursolic acid （P＜0.01）. The weight of E. japonica leaves was positively correlated with the comprehensive evaluation value （P＜0.01）. CONCLUSIONS The qualities of E. japonica leaves from different producing areas are very different. Among them， the qualities of E. japonica leaves from Huotian Town， Yunxiao County， Zhangzhou of Fujian， Qinzhou Qinnan District of Guangxi， and Bozhou Guoyang County of Anhui are relatively better. The weight of E. japonica leaves is positively correlated with their quality.

Objective:To explore the short-term efficacy of small dose omalizumab in refractory sinusitis with eosinophilia after extended sinus surgery.Methods:A total of 24 patients who met the diagnostic criteria for eosinophilic chronic rhinosinusitis and remained poorly controlled after multiple surgical treatments were included in this study. These patients were admitted to Hunan People′s Hospital between January 2020 and June 2022, and comprised 13 males and 11 females with an average age of (46.43±13.74) years. The patients were randomly divided into experimental group (12 cases) and control group (12 cases), both of which underwent extended sinus opening surgery. The experimental group received a small dose of omalizumab (150 mg/month) for 4 months, while no omalizumab was applied in the control group. All patients were followed up monthly, subjective and objective symptom scores were collected and compared between groups, which included visual analogue scale (VAS) score, sino-nasal outcome test (SNOT)-22 score, Lund-Mackay score, and Lund-Kennedy score. Statistical analysis was performed using SPSS 24.0 software.Results:The baseline was set at 1 month after surgery. There was no significant difference in baseline clinical characteristics between the two groups. After 4 months of treatment with omalizumab, the experimental group showed significant improvements in VAS scores for nasal obstruction, rhinorrhea, hyposmia, SNOT‐22 score, and Lund-Kennedy score (3.11±1.05 vs 6.44±1.13, 2.00±0.87 vs 6.55±1.33, 2.22±0.67 vs 7.00±1.22, 4.44±0.88 vs 15.22±1.20, 1.67±1.00 vs 7.44±0.88, respectively, all P<0.001). Compared to the control group at 4 months after baseline, the experimental group had significantly lower scores for nasal obstruction, rhinorrhea, hyposmia, SNOT-22, and Lund-Kennedy (3.11±1.05 vs 7.11±1.17, 2.00±0.87 vs 7.67±1.41, 2.22±0.67 vs 7.56±0.88, 4.44±0.88 vs 15.33±2.34, 1.67±1.00 vs 9.00±1.41, respectively, all P<0.001). During a 2-month follow-up period after drug withdrawal, the VAS, SNOT-22, and Lund-Kennedy scores of the experimental group were slightly higher than those before drug withdrawal but showed no significant difference (3.44±1.33 vs 3.11±1.05, 2.22±1.09 vs 2.00±0.86, 2.55±0.88 vs 2.22±0.66, 4.77±0.97 vs 4.44±0.88, 2.11±1.05 vs 1.67±1.00, respectively, all P>0.05). Conclusion:For patients of refractory sinusitis with eosinophilia, a combination of extended sinus surgery and postoperative small dosage of omalizumab can effectively control mucous inflammation, promote mucosal epithelization, and play an important role in the critical early stage of disease recovery.

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