Objective: To explore the impacts of coal mine dust on lung function in rats, so as to provide the basis for the early prevention and treatment of coal worker's pneumoconiosis. Methods: Seventy-two SPF-grade 8-week-old male Sprague-Dawley rats were randomly divided into the coal dust group, the coal-silica dust group, the silica dust group and the control group. The rats in the first three groups of rats were administered 1 mL corresponding dust suspension into the lungs using non-exposure tracheal instillation, while the rats in the control group were administered 1 mL normal saline. Respiratory rate (f), forced vital capacity (FVC), peak expiratory flow (PEF) and dynamic pulmonary compliance (Cdyn) were measured at 1, 3 and 6 months after dust exposure. Lung tissues were collected to measure reactive oxygen species (ROS) and adenosine triphosphate (ATP) levels using corresponding ELISA kits and ATP assay kits, respectively. The relative mRNA expressions of peroxisome proliferators-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial transcription factor A (TFAM) were detected using real-time fluorescent quantitative polymerase chain reaction assay. The relative protein expressions of PGC-1α and TFAM were detected using Western blotting. Results: There was no interaction between dust type and exposure duration on f (P>0.05), but there were interactions on FVC, PEF and Cdyn (all P<0.05). Compared with the control group at 6 months after dust exposure, the f of the rats in the silica dust group were increased, while the FVC and PEF of the rats in the coal-silica dust and silica dust groups were decreased, and Cdyn of the rats in the coal dust, coal-silica dust and silica dust groups were decreased (all P<0.05). There were interactions between dust type and exposure duration on ROS and ATP levels, the relative mRNA and protein expressions of PGC-1α and TFAM (all P<0.05). Compared with the control group at 3 and 6 months after dust exposure, the ROS levels in the rats in the coal dust, coal-silica dust and silica dust groups were increased, while the ATP levels, the relative mRNA and protein expressions of PGC-1α and TFAM were decreased (all P<0.05). Conclusion The lung function impairment in rats caused by different types of coal mine dust is related to PGC-1α-mediated mitochondrial biogenesis dysfunction, which leads to increased ROS levels, decreased ATP and TFAM levels.

Objective: To investigate the trends in incidence and mortality of lung cancer in Huangpu District, Shanghai Municipality from 2002 to 2019, so as to provide the evidence for formulating lung cancer prevention and control measures. Methods: Data of lung cancer incidence and mortality among residents in Huangpu District from 2002 to 2019 were collected through the Shanghai Cancer Registration and Reporting Management System. The crude incidence and mortality of lung cancer was calculated, and standardized by the data from the Chinese Fifth National Population Census in 2000 (Chinese-standardized rate) and the Segi's world standard population in 1960 (world-standardized rate). The trends in incidence and mortality of lung cancer among residents by age and gender were evaluated using annual percent change (APC). Results: A total of 12 965 cases of lung cancer were reported in Huangpu District from 2002 to 2019, and the crude incidence rate was 80.66/105, the Chinese-standardized incidence rate was 34.54/105, and the world-standardized incidence rate was 31.30/105, all showing upward trends (APC=4.588%, 2.933% and 3.247%, all P<0.05). A total of 10 102 deaths of lung cancer were reported, and the crude mortality rate was 62.30/105, showing an upward trend (APC=0.959%, P<0.05); the Chinese-standardized mortality was 25.93/105, and the world-standardized mortality was 22.05/105, both showing downward trends (APC=-1.282% and -1.263%, both P<0.05). The crude incidence and mortality rates of lung cancer in males were higher than those in females (101.39/105 vs. 60.52/105, 85.45/105 vs. 39.87/105, both P<0.05). The crude incidence and mortality rates of lung cancer showed upward trends with age (both P<0.05), reaching their peaks in the age groups of 80-<85 years (341.37/105) and 85 years or above (355.97/105), respectively. Conclusions The incidence of lung cancer showed an upward trend, while the mortality showed a downward trend in Huangpu District from 2002 to 2019. Elderly men were the high-risk group for lung cancer incidence and mortality.

[Objective] To study on the genotyping of a sample with inconsistent forward and reverse serological tests, and to conduct a pedigree investigation and molecular biological mechanism study. [Methods] The ABO blood group of the proband and his family members were identified using blood group serological method. The ABO gene exon 1-7 of samples of the proband and his family were sequenced by Sanger and single molecule real-time sequencing (SMRT). DeepTMHMM was used to predict and analyze the transmembrane region of proteins before and after mutation. [Results] The proband and his mother have the Bw phenotype, while his maternal grandfather has ABw phenotype. The blood group results of forward and reverse typing of other family members were consistent. ABO gene sequencing results showed that there was B new mutation of c.3 G>C in exon 1 of ABO gene in the proband, his mother and grandfather, leading to a shift in translation start site. DeepTMHMM analysis indicated that the shift in the translation start site altered the protein topology. [Conclusion] The c.3G>C mutation in the first exon of the ABO gene leads to a shift in the translation start site, altering the protein topology from an α-transmembrane region to a spherical signaling peptide, reducing enzyme activity and resulting in the Bw serological phenotype.

BACKGROUND:Pinoresinol diglucoside promotes bone formation and bone matrix synthesis and accelerates bone tissue repair.However,the mechanism of action and effects of this compound in osteoblasts need to be further explored. OBJECTIVE:To investigate the effect and mechanism of action of pinoresinol diglucoside on dexamethasone-treated osteoblasts based on the Wnt/β-catenin signaling pathway. METHODS:Different concentrations of dexamethasone groups and pinoresinol diglucoside groups were set to treat osteoblasts for 24 hours,and the optimal intervention concentrations were screened.Osteoblasts were treated with dexamethasone,pinoresinol diglucoside and inhibitor XAV-939.Then,control group,dexamethasone group,XVA-939 group,pinoresinol diglucoside group,pinoresinol diglucoside+XVA-939 group were set up.Cell counting kit-8 assay was used to detect cell activity.Alkaline phosphatase activity and caspase3/7 enzyme activity in cells were detected.Annexin V/PI staining and EdU assay were used to detect cell apoptosis and proliferation.Real-time qPCR and western blot were used to detect the mRNA and protein expression levels of Wnt3a,β-catenin,c-myc,osteocalcin,and type I collagen,respectively. RESULTS AND CONCLUSION:After dexamethasone and pinoresinol diglucoside intervened in osteoblasts for 24 hours,10 μmol/L dexamethasone was found to be the optimal intervention concentration for cell inhibition,and cell proliferation was most pronounced at a concentration of pinoresinol diglucoside of 100 μmol/L.Compared with the dexamethasone group,alkaline phosphatase activity was significantly enhanced(P<0.05)and caspase3/7 enzyme activity was significantly reduced(P<0.05)in the pinoresinol diglucoside group.Annexin V/PI staining and cell proliferation assay by EdU method showed that pinoresinol diglucoside inhibited apoptosis and promoted proliferation of osteoblasts after dexamethasone intervention.The mRNA and protein expression levels of Wnt3a,β-catenin,c-myc,osteocalcin,and type I collagen were significantly higher in the pinoresinol diglucoside group and pinoresinol diglucoside+XVA-939 group compared with the dexamethasone and XVA-939 groups(P<0.05).To conclude,pinoresinol diglucoside can inhibit osteoblast apoptosis after dexamethasone intervention,protect osteoblast activity and promote osteoblast proliferation by activating the Wnt/β-catenin signaling pathway,which may play a role in delaying steroid-induced osteonecrosis of the femoral head.

Objective To establish a liquid chromatography method for the simultaneous determination of 13 aromatic amine compounds (AAs) in workplace air. Methods A total of 13 AAs in both vapor and aerosol phases were collected in workplace air using a new GDH-6 sampling tube. Samples were desorbed and eluted with methanol, separated using a Symmetry Shield™ RP₁₈ reversed-phase liquid chromatography column, and detected with a diode array detector. Quantification was performed using an external standard method. Results The linear range of the 13 AAs measured by this method was 0.02-373.60 μg/L with the correlation coefficients greater than 0.999 0. The minimum detection concentration was 0.09-14.37 μg/m³, and the minimum quantitative concentration was 0.31-47.90 μg/m³ (both calculated based on sampling 15.0 L of air and 3.0 mL of elution volume). The average desorption and elution efficiency ranged from 97.46% to 101.23%. The within-run relative standard deviation (RSD) was 0.10%-5.99%, and the between-run RSD was 0.17%-2.71%. Samples could be stably stored in sealed conditions at 2-8 ℃ for more than seven days. Conclusion This method is suitable for the simultaneous determination of 13 AAs in workplace air, including both vapor and aerosol phases.

Objective To establish a method for simultaneous determination of four high-molecular-weight thiol derivatives (TDs) in workplace air by gas chromatography. Methods The four kinds of vapor-phase macromolecular TDs (1-pentanethiol, 1-hexanethiol, 1-benzyl mercaptan, and n-octanethiol) in the workplace air were collected using the GDH-1 air sampling tubes, desorbed with anhydrous ethanol, separated on a DB-FFAP capillary column, and determined by flame ionization detector. Results The quantitation range of the four TDs was 0.30-207.37 mg/L, with the correlation coefficients greater than 0.999 00. The minimum detection mass concentrations and minimum quantitation mass concentrations were 0.18-0.32 and 0.60-1.05 mg/m³, respectively (both calculated based on the 1.5 L sample and 3.0 mL desorption solvent). The mean desorption efficiencies ranged from 87.07% to 103.59%. The within-run and between-run relative standard deviations were 1.92%-8.22% and 1.89%-8.45%, respectively. The samples can be stored at room temperature or 4 ℃ for three days and up to 7 days at -18 ℃. Conclusion This method is suitable for the simultaneous determination of four vapor-phase TDs in workplace air.

OBJECTIVE To explore the clinical effect and safety of nicorandil combined with different doses of tirofiban in the treatment of elderly patients with acute ST-segment elevation myocardial infarction （STEMI）. METHODS A total of 162 elderly patients with STEMI admitted to our hospital from June 1， 2022 to June 1， 2024 were retrospectively enrolled. All patients received percutaneous coronary intervention （PCI） and conventional treatment of STEMI， and used nicorandil （5 mg each time， tid） and tirofiban. According to the use of tirofiban， the patients were divided into conventional-dose group （n＝104） and half-dose group （n＝58）. Patients in the conventional-dose group received an intracoronary injection of 10 μg/kg tirofiban， followed by intravenous infusion of 0.1 μg/（kg·min） for 48 h； patients in the half-dose group received an intracoronary injection of 5 μg/kg tirofiban， followed by intravenous infusion of 0.05 μg/（kg·min） for 48 h. Related indexes of PCI （the proportion of patients with grade 3 of thrombolysis in myocardial infarction， no reflow in infarct related artery， percentage decrease in total ST-segment elevation ＞50% on electrocardiogram 2 hours after PCI）， cardiac function parameters before and after treatment （troponin I， N-terminal pro-brain natriuretic peptide contents and left ventricular ejection fraction）， bleeding events during treatment （gingival bleeding， epistaxis， mucosal bleeding， gastrointestinal bleeding） and other adverse events （all-cause death， non-fatal reinfarction， hypotension， ventricular fibrillation， acute heart failure） were compared between 2 groups. RESULTS There were no significant differences in related parameters of PCI， cardiac function parameters after treatment， the incidences of gingival bleeding， epistaxis and gastrointestinal bleeding， the total incidence of bleeding events， or the incidence of other adverse events during treatment between 2 groups （P＞0.05）， but the incidence of mucosal bleeding in the conventional-dose group was significantly higher than the half-dose group （P＜0.05）. CONCLUSIONS The clinical effect of nicorandil combined with half-dose tirofiban in the treatment of elderly patients with acute STEMI is comparable to that of nicorandil combined with conventional dose of tirofiban， but the mucosal bleeding risk of the former is lower than that of the latter. Therefore， patients at risk of mucosal bleeding are more suitable to use the previous regimen.

OBJECTIVE To establish a pharmaceutical management model for infusion safety in hospitalized inpatients and ensure the safety of drug use. METHODS Our hospital established the standardized management process for infusion scheme， formulated rules for compatibility contraindications in drug combinations. In the form of embedded hospital official account, the infusion scheme and medication guidance WeChat developed by pharmacists are pushed to the mobile phone of inpatients, providing electronic medication guidance services for patients, and forming a pharmaceutical management model for infusion safety of inpatients. RESULTS Our hospital provided a total of 45 291 inpatients with pharmaceutical services including the formulation of individualized infusion scheme and WeChat push infusion scheme and medication guidance as of December 2023. After the implementation of the management model， the intervention rate of pharmacists on the compatibility contraindications in drug combination of long-term medical orders for inpatients increased from 18.25% before implementation to 90.58% （P＜0.01）， and the satisfaction rate of inpatients increased from 87.50% to 94.50% （P＜0.05）. CONCLUSIONS The pharmaceutical management model for infusion safety of hospitalized patients integrates pharmaceutical services throughout the entire process of intravenous medication treatment. Pharmacists can participate in the management of infusion usage while providing qualified finished infusion products, achieving closed-loop management of pharmaceutical services, improving the hospital’s pharmaceutical service capabilities and patient satisfaction, and providing guarantees for the safety and effectiveness of patient medication.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.