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

Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*

Objective: To investigate the changes in the levels of interleukin-6 (IL-6) and let-7e in rats induced by coal mine dust, so as to provide the basis for the mechanism of coal worker's pneumoconiosis (CWP). Methods: Sixty-four clean and healthy male Sprague-Dawley rats were randomly divided into the control group, coal dust group, mixed dust group (mixed coal and silica dust) and quartz group. The rats in the control group were exposed to 1 mL physiological saline by non-exposure tracheal perfusion, and the rats in the dust-exposed groups were exposed to 1 mL dust suspension. Rats were sacrificed by anesthesia after 1 month and 6 months, lung tissue was observed using hematoxylin-eosin staining, the pathological change in the lungs was scored using the Szapiel scoring system, the levels of IL-6 in the bronchoalveolar lavage fluid were detected using enzyme-linked immunosorbent assay, and the expression of let-7e was determined by quantitative real-time PCR. Results: A month after exposure, a small amount of coal spots and inflammatory exudation were observed in the lung tissue of the coal dust group and the mixed dust group. The quartz group showed tissue structure destruction and mild fibrosis and thickening of alveolar septum. Six months after exposure, there were more coal spots and slightly thickened alveolar septum in the coal dust group, and hyperplasia of pulmonary interstitial fibers, destruction of alveolar structure and silica nodules were observed in the mixed dust group. In the quartz group, the alveolar structure was obviously destroyed, the interstitial fiber proliferation was significant and silica nodules were seen. Two-factor analysis of variance showed that the interaction between duration of exposure and dust type significantly influenced the pathological score of lung tissue, IL-6 levels, and let-7e expression levels (P<0.05). Under the same dust type, the pathological score of lung tissue and IL-6 levels were higher at 6 months after exposure than at 1 month, while the relative expression of let-7e was lower at 6 months after exposure than at 1 month (all P<0.05). Under the same duration of exposure, the pathological score of lung tissue and IL-6 levels were higher in the dust-exposed groups than in the control group, while the relative expression of let-7e was lower in the dust-exposed groups than in the control group (all P<0.05). Conclusions Coal dust can cause an increase in levels of IL-6 and a decrease in let-7e expression in rats. The type of dust and duration of exposure can interactively affect IL-6 and let-7e.

Objective To observe the value of intratumoral and peritumoral radiomics models combined with clinical and routine CT features for differentiating adenocarcinoma in situ(AIS)and microinvasive adenocarcinoma(MIA)of lung.Methods Totally 180 patients with isolated AIS and 180 with isolated MIA were retrospectively included,among them 160 AIS cases and 160 MIA cases were randomly selected into training set(n=320),while the other 20 AIS cases and 20 MIA cases were selected into test set(n=40).In training set,clinical and conventional CT features being statistically different between AIS and MIA were obtained to construct clinical model.Besides,radiomics features were extracted from intratumoral(CTi)ROI,intra-and peritumoral 2 mm(CTi+p2mm)ROI and intra-and peritumoral 4 mm(CTi+p4mm)ROI,and then CTi model,CTi+p2mm model and CTi+p4mm model for differentiating MIA and AIS were constructed.The optimal radiomics model for predicting MIA was selected using the area under the curve(AUC)of receiver operating characteristic(ROC)curve,and a combined model was built based on the optimal radiomics model combining with clinical and conventional CT features.The AUC,calibration and net benefit of the clinical model,the optimal radiomics model and the combined model were assessed.Results In training set,the larger nodular diameter,higher percentage of inhomogeneous density and ratio of nodules with vascular signals were observed in MIA compared with those in AIS(all P＜0.05).In test set,CTi+p2mm model had the highest efficacy(AUC=0.838)for differentiating MIA from AIS(P＜0.05),and the combined model had better efficacy(AUC=0.867,P＜0.05).The calibration of combined model was good,and the net benefit was high in 0.60-0.90 threshold probability range.Conclusion The radiomics model constructed with intratumoral and peritumoral 2 mm ROI based on plain CT was effective for differentiating MIA from AIS.Combining with clinical and routine CT features could furtherly improve differential diagnostic efficacy.

Objective:To investigate the effect of intensive lipid-lowering therapy on carotid artery intima-media thickness and plaque area in patients with acute cerebral infarction.Methods:Eighty-two patients with acute cerebral infarction who received treatment at the Changzhi Mental Health Center from July 2021 to July 2022 were included in this study. Using a randomized controlled trial design, the patients were randomly divided into an intensive treatment group ( n = 41) and a conventional treatment group ( n = 41) using the random number table method. All patients had surpassed the recommended time window for thrombolysis and were given conventional treatments, including antiplatelet aggregation and neuroprotection. The conventional treatment group received conventional lipid-lowering therapy, while the intensive treatment group underwent intensive lipid-lowering therapy. All treatments lasted 6 months. The levels of blood lipids (low-density lipoprotein cholesterol and total cholesterol), inflammatory factors (C-reactive protein and interleukin-6), and atherosclerosis indicators (carotid artery intima-media thickness and plaque area) were measured and compared between the two groups before and after treatment. Adverse reactions occurring during the treatment period, including myalgia, nausea, vomiting, and abnormal liver function were also recorded. Results:Before treatment, there were no significant differences in blood lipids, inflammatory factors or atherosclerosis indicators between the conventional treatment and intensive treatment groups (all P > 0.05). After treatment, the levels of low-density lipoprotein cholesterol and total cholesterol in the intensive treatment group were significantly lower than those in the conventional treatment group [(3.44 ± 0.42) mmol/L vs. (4.81 ± 0.53) mmol/L, (3.46 ± 0.35) mmol/L vs. (2.41 ± 0.27) mmol/L, t = 12.97, 15.21, both P < 0.05]. After treatment, serum levels of interleukin-6 and C-reactive protein in the intensive treatment group were significantly lower than those in the conventional treatment group [(4.79 ± 0.53) mg/L vs. (6.97 ± 0.81) mg/L, (38.45 ± 4.14) pg/L vs. (49.66 ± 5.07) pg/L, t = 14.42, 10.97, both P < 0.05]. Carotid artery intima-media thickness and plaque area in the intensive treatment group were significantly smaller than those in the conventional treatment group [(0.98 ± 0.10) mm vs. (1.17 ± 0.12) mm, (13.04 ± 1.37) mm 2vs. (17.96 ± 1.89 mm 2, t = 7.79, 13.50, both P < 0.001). There was no significant difference in the overall incidence of adverse reactions during treatment between the intensive treatment and conventional treatment groups ( P > 0.05). Conclusion:Intensive lipid-lowering therapy is highly effective in patients with acute cerebral infarction. It can reduce inflammatory reactions, delay the progression of atherosclerosis, and provide a safety profile similar to that of conventional lipid-lowering therapy.

We aimed to evaluate the effectiveness and safety of single-course initial regimens in patients with low-risk gestational trophoblastic neoplasia (GTN). In this trial (NCT01823315), 276 patients were analyzed. Patients were allocated to three initiated regimens: single-course methotrexate (MTX), single-course MTX + dactinomycin (ACTD), and multi-course MTX (control arm). The primary endpoint was the complete remission (CR) rate by initial drug(s). The primary CR rate was 64.4% with multi-course MTX in the control arm. For the single-course MTX arm, the CR rate was 35.8% by one course; it increased to 59.3% after subsequent multi-course MTX, with non-inferiority to the control (difference -5.1%,95% confidence interval (CI) -19.4% to 9.2%, P = 0.014). After further treatment with multi-course ACTD, the CR rate (93.3%) was similar to that of the control (95.2%, P = 0.577). For the single-course MTX + ACTD arm, the CR rate was 46.7% by one course, which increased to 89.1% after subsequent multi-course, with non-inferiority (difference 24.7%, 95% CI 12.8%-36.6%, P < 0.001) to the control. It was similar to the CR rate by MTX and further ACTD in the control arm (89.1% vs. 95.2%, P =0.135). Four patients experienced recurrence, with no death, during the 2-year follow-up. We demonstrated that chemotherapy initiation with single-course MTX may be an alternative regimen for patients with low-risk GTN.
Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Dactinomycin/adverse effects* ; Female ; Gestational Trophoblastic Disease/drug therapy* ; Humans ; Methotrexate/therapeutic use* ; Pregnancy ; Retrospective Studies

As one of the hallmarks of cancer, metabolic reprogramming leads to cancer progression, and targeting glycolytic enzymes could be useful strategies for cancer therapy. By screening a small molecule library consisting of 1320 FDA-approved drugs, we found that penfluridol, an antipsychotic drug used to treat schizophrenia, could inhibit glycolysis and induce apoptosis in esophageal squamous cell carcinoma (ESCC). Gene profiling and Ingenuity Pathway Analysis suggested the important role of AMPK in action mechanism of penfluridol. By using drug affinity responsive target stability (DARTS) technology and proteomics, we identified phosphofructokinase, liver type (PFKL), a key enzyme in glycolysis, as a direct target of penfluridol. Penfluridol could not exhibit its anticancer property in PFKL-deficient cancer cells, illustrating that PFKL is essential for the bioactivity of penfluridol. High PFKL expression is correlated with advanced stages and poor survival of ESCC patients, and silencing of PFKL significantly suppressed tumor growth. Mechanistically, direct binding of penfluridol and PFKL inhibits glucose consumption, lactate and ATP production, leads to nuclear translocation of FOXO3a and subsequent transcriptional activation of BIM in an AMPK-dependent manner. Taken together, PFKL is a potential prognostic biomarker and therapeutic target in ESCC, and penfluridol may be a new therapeutic option for management of this lethal disease.

Objective: To explore the feasibility of applying Omaha system theory to patients with coronary heart disease (CHD) through comparative analysis of nursing description. Methods: Using content extraction analysis method, the nursing records, nursing plans and nursing measures of discharged patients with CHD were retrieved from the medical records, and then the conceptual consistency of the extracted records and the problem classification system and intervention measures in the Omaha system were evaluated by cross mapping method. Results: A total of 2 609 nursing problems and intervention measures were extracted from the medical records of 68 patients with CHD. Among them, 1 844 (70.68%) records were labeled as "perfect fit", 608 records (23.30%) as "partial fit", and 157 (6.02%) recordsas "not fit at all". The total fit rate was 93.98% (perfect fit and partial fit). The most frequently reported problems were in physiological domain, followed by health-related behaviors domain, psychosocial domain and environmental domain. The nursing interventions extracted accounted for 26.67% (1 968 sentences) of directions and l00.00% (4 kinds) of categories in the intervention scheme of Omaha system. Conclusions The conceptual congruence between the medical records of patients with CHD and the Omaha System is quite high. It can help to improve nursing problems of patients of CHD in health-related behavioral domain, psychosocial domain and environmental domain, and can be applied to such patients after appropriate adjustment, so as to help clinical nursing staff to provide specialized and all-round guidance for patients with CHD.

Objective: To investigate the current situation of clinical nurses′ caring behavior and patients′ perception of caring, to understand the level of nursing care behavior and analyze the influencing factors, and to discuss the relationship between patients′ perception of caring and clinical nurses′ caring behavior. Methods: The convenience sampling method was used to investigate clinical nurses and inpatients from October to December 2018. The Caring Behavior Checklist was used to observe nurses' nursing care behavior, and the Client Perception of Caring Scale was used to investigate patients' perception of Caring. Results: A total of 132 clinical nurses were observed and 132 patients were investigated. The score of verbal caring behavior was (3.36±1.44) points (out of a possible 7 points), and the score of non-verbal caring behavior was (2.33±1.07) points (out of a possible 5 points).The overall score of Caring Behavior Checklist was (5.70±2.03) points (out of a possible 12 points). Nurses aged 26-35 (6.42±2.07) points had a higher level of nursing care behavior than nurses of other age groups, and the difference was statistically significant (F=3.902, P<0.05).N1 nurses had a higher level of nursing care behavior than nurses at other levels, it was (7.72±2.30) points, and the difference was significant (F=14.290, P<0.05). There was no significant difference in caring behavior level among nurses with different gender, departments, education backgrounds, academic titles and nursing ages (P>0.05). The overall score of Client Perception of Caring Scale was (43.49 ±3.84) (out of a possible 60 points), and there was a high positive correlation between client perception of caring and nursing care behavior (r=0.720, P<0.05). Conclusions The level of clinical nurses′ caring behavior is low, and the training of caring knowledge, belief and behavior should be carried out to promote nurses′ caring behavior, so as to further improve client perception of caring.

Objective? To investigate the effect of Team collaboration management program on the metabolic syndrome in schizophrenic patients. Methods? From March 2017 to March 2018, the schizophrenic patients with metabolic syndrome who were admitted in Shanghai Mental Health Center Affiliated to Shanghai Jiao Tong University School of Medicine were selected as the participants of this study and divided into observation group (n=45) and control group (n=47) according to the time of admission. The two groups were both given routine treatment and nursing care in psychiatric department. Besides of that, the team collaboration management program was implemented in the observation group. Assessments were done before intervention and 16 weeks after intervention using related metabolic parameters, the Brief Scale of World Health Organization Quality of Life (WHOQOL-BREF) and the Positive and Negative Symptoms Scale (PANSS). Results? There was no significant difference in metabolic parameters, WHOQOL-BREF and PANSS scores between the two groups before intervention (P＞0.05). After 16 weeks of intervention, patients' fasting blood sugar level, body weight, waist circumference, triglyceride, high density lipoprotein and systolic pressure in the observation group were lower than those in the control group, and the difference was statistically significant (P＜0.05). The scores of"physical health" and "psychological function" in WHOQOL-BREF in the observation group were higher than those in the control group, meanwhile, the scores of "positive and general pathological symptoms" in PANSS in the observation group were lower than those in the control group, both with statistical significance (P＜0.05). Conclusions? Team collaboration management program can help controlling the related metabolic parameters of the schizophrenic patients with metabolic syndrome effectively, improve their quality of life and promote recovery from their mental symptoms.