BACKGROUND:Psoralen has a strong anti-osteoporotic activity and may have a restorative effect on chemotherapy-induced osteoporosis. OBJECTIVE:To explore the restorative effect of psoralen on the osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide and its mechanism. METHODS:C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured.Effect of psoralen on viability of bone marrow mesenchymal stem cells was detected by MTT assay.Osteogenic induction combined with alkaline phosphatase staining was used to determine the optimal dose of psoralen to restore the osteogenic differentiation of bone marrow mesenchymal stem cells inhibited by cyclophosphamide.The mRNA expression levels of Runx2,alkaline phosphatase,Osteocalcin,osteoprotegerin,and Wnt/β-catenin signaling pathway-related genes Wnt1,Wnt4,Wnt10b,β-catenin,and c-MYC were measured by RT-qPCR at different time points under the intervention with psoralen.The protein expression of osteogenic specific transcription factor Runx2 and Wnt/β-catenin signaling pathway related genes Active β-catenin,DKK1,c-MYC,and Cyclin D1 was determined by western blot assay at different time points under the intervention with psoralen. RESULTS AND CONCLUSION:(1)There was no significant effect of different concentrations of psoralen on the viability of bone marrow mesenchymal stem cells.The best recovery of the inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells caused by cyclophosphamide was under the intervention of psoralen at a concentration of 200 μmol/L.(2)Psoralen reversed the reduction in osteogenic differentiation marker genes Runx2,alkaline phosphatase,Osteocalcin and osteoprotegerin mRNA expression and Runx2 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(3)Psoralen reversed the decrease in Wnt/β-catenin pathway-related genes Wnt4,β-catenin,c-MYC mRNA and Active β-catenin,c-MYC,and Cyclin D1 protein expression and the increase in DKK1 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(4)The results showed that cyclophosphamide inhibited osteogenic differentiation of bone marrow mesenchymal stem cells in mice,and psoralen had a restorative effect on it.The best intervention effect was achieved at a concentration of 200 μmol/L psoralen,and this protective effect might be related to the activation of Wnt4/β-catenin signaling pathway by psoralen.

Objective: To analyze the disease burden of chronic obstructive pulmonary disease (COPD) and changes in its risk factors among residents in Zhejiang Province from 1990 to 2021, so as to identify key priorities for COPD prevention and control. Methods: Data on COPD mortality and disability-adjusted life years (DALY) for residents in Zhejiang Province from 1990 to 2021 were collected from the Global Burden of Disease (GBD) 2021 database. Standardized mortality and standardized DALY rate were calculated using the GBD 2021 world population standard structure. Premature mortality was computed via the life table method. The average annual percent change (AAPC) was applied to analyze trends in COPD mortality, DALY rate, and premature mortality. Changes in deaths of COPD risk factors were evaluated using population attributable fraction (PAF). Results: From 1990 to 2021, the standardized COPD mortality in Zhejiang Province decreased from 272.40/100 000 to 70.56/100 000 (AAPC=-4.395%), and the standardized DALY rate declined from 4 167.37/100 000 to 1 071.89/100 000 (AAPC=-4.396%). Similar downward trends were observed in both males (AAPC=-3.933%, -4.173%) and females (AAPC=-4.785%, -4.480%), all P<0.05. Crude mortality and DALY rates increased with age, and the crude mortality and DALY rates of various age groups in Zhejiang Province showed decreasing trends from 1990 to 2021 (all P<0.05). The premature mortality declined from 4.37% to 0.60% from 1990 to 2021 (AAPC=- 6.206%), with consistent trends across males and females (AAPC=- 6.144%, - 6.379%, all P<0.05). From 1990 to 2021, particulate matter pollution showed the largest reduction in PAF (- 56.76%), while ambient ozone pollution had the largest increase (103.07%) in Zhejiang Province. By 2021, smoking became the leading risk factor for deaths of COPD (PAF=43.32%). Conclusions The standardized mortality, standardized DALY rate, and premature mortality for COPD show consistent declining trends in Zhejiang Province from 1990 to 2021. However, risk factors such as smoking and ambient ozone pollution require intensified focus to further reduce disease burden of COPD.

ObjectiveTo explore the therapeutic effect and mechanism of Guipitang on rats with myocardial ischemia. MethodFifty SD rats were divided into five groups： a control group， a model group， low and high-dose Guipitang （7.52， 15.04 g·kg^-1） groups， and a trimetazidine group （0.002 g·kg^-1）. By intragastric administration of vitamin D₃ and feeding rats with high-fat forage and injecting isoproterenol， the rat model of myocardial ischemia was established. After drug treatment of 15 d， an electrocardiogram （ECG） was performed to analyze the degree of myocardial injury. A fully automatic biochemical analyzer was used to detect the changes in the serum levels of total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C）. Hematoxylin-eosin （HE） staining and Masson staining were used to observe myocardial histopathological changes. TdT-mediated dUTP nick end labeling （TUNEL） staining was used to detect cardiomyocyte apoptosis. Western blot was adopted to detect the protein levels of extracellular signal-regulated kinase 1/2 （ERK1/2）， phospho-ERK1/2 （p-ERK1/2）， p38 mitogen-activated protein kinase （p38 MAPK）， phospho-p38 MAPK （p-p38 MAPK）， B-cell lymphoma-2 （Bcl-2）-associated X （Bax）， Bcl-2， and cleaved cysteine aspartate proteolytic enzyme （cleaved Caspase-3）. ResultCompared with the control group， the ECG S-T segment decreased in the model group. The serum levels of TC， TG， and LDL-C were increased significantly （P<0.05）. The arrangement of myocardial tissue was disordered， and the proportion of cardiomyocyte apoptosis increased. The protein levels of cleaved Caspase-3， Bax， and p-p38 MAPK in the heart were increased， and the Bcl-2 expression was decreased （P<0.05）. Compared with the model group， the S-T segment downward shift was restored in the low and high-dose Guipitang groups and trimetazidine group， and the levels of TC， TG， and LDL-C were decreased. The protein expression of cleaved Caspase-3 and Bax in the heart dropped， and p-p38 MAPK and p-ERK1/2 protein expressions increased significantly （P<0.05）. The degree of myocardial injury was alleviated， and the proportion of cardiomyocyte apoptosis decreased. Bcl-2 protein expression was increased significantly in the low-dose Guipitang group （P<0.05）. ERK1/2 and p38 MAPK proteins had no significant difference among different groups. ConclusionGuipitang could alleviate myocardial injury and inhibit cardiomyocyte apoptosis in rats by activating the expression of ERK1/2 and p38 MAPK.

Objective: To analyze the disease burden and risk factors of colorectal cancer in Zhejiang Province from 1990 to 2019, so as to provide the basis for prevention and control of colorectal cancer. Methods: Based on data of 2019 Global Burden of Disease (GDB 2019), disease burden and risk factors of colorectal cancer in Zhejiang Province from 1990 to 2019 was assessed using years of life lost (YLL), years lived with disability (YLD), disability-adjusted life years (DALY). Results: In 2019, the YLL rate, YLD rate and DALY rate caused by colorectal cancer in Zhejiang Province were 496.15/105, 31.81/105 and 527.96/105, respectively. From 1990 to 2019, the YLL rate, YLD rate and DALY rate caused by colorectal cancer in Zhejiang Province increased by 114.90%, 482.60% and 123.38%, respectively, showing increasing trends (average annual percent change values were =2.663, 6.283 and 2.800, respectively,all P<0.05). From 1990 to 2019, the YLL rate, YLD rate and DALY rate in the age groups of 15 to 49 years, 50 to 69 years and 70 years and older showed increasing trends (all P<0.05). In 1990, the top ten risk factors for colorectal cancer in Zhejiang Province were diet low in calcium, diet low in milk, diet low in whole grains, smoking, alcohol use, low physical activity, high fasting plasma glucose, diet high in red meat, diet low in fiber and high body mass index. In 2019, the top ten risk factors for colorectal cancer in Zhejiang Province were diet low in milk, diet low in whole grains, diet low in calcium, alcohol use, diet high in red meat, high body mass index, high fasting plasma glucose, low physical activity, diet low in fiber and diet high in processed meat. Conclusions The disease burden of colorectal cancer in Zhejiang Province showed an upward trend from 1990 to 2019. The top ten risk factors for colorectal cancer remained between 1990 and 2019, while there was a slight change in ranking.

Objective:To investigate the impact of the birth of preterm infants on their family functioning, and to provide a reference for the formulation of targeted intervention programs.Methods:Based on the socio ecosystem theory, phenomenological research methods and objective sampling were used to conduct semi-structured interviews with 16 preterm infants in the neonatal intensive care unit (NICU) of Children′s Hospital of Soochow University from September 2023 to January 2024, who meet the inclusion and exclusion criteria, and the Colaizzi 7-step analysis method was used to analyze the interview data.Results:All 16 caregivers of the NICU preterm infants who participated in the interviews were the infants′ mothers, aged from 26 to 34 years. A total of 3 themes and 10 sub-themes were summarized. The micro system: physical and mental exhaustion coexisted with role growth of caregivers (physical and mental health was affected, positive experience after psychological adjustment, and adaptation to role change). The intermediate system: family relationship mode change (family satisfaction decreased, family difficulties affected family harmony, family communication content changed, family harmony and conflict coexisted, and family conflict resolution was actively resolved). The outer system: social support system needed to be improved (benefited from social support and not yet perceived external support).Conclusions:Medical staff can improve the multiple support system and provide continuous and personalized family support, so as to improve the family adjustment ability and improve the family functioning of preterm infants in the NICU.

Objective:To evaluate the diagnostic efficacy of the multiparametric MRI (mpMRI) deep learning artificial intelligence (AI) analysis system combined with 68Ga-prostate specific membrane antigen (PSMA) PET for prostate cancer. Methods:Data of 103 patients (age: 45-85 years) who underwent 68Ga-PSMA PET/MR at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from May 2018 to October 2023 for suspected or confirmed prostate cancer were retrospectively collected. ROI was delineated to measure SUV max of primary tumor or prostate, and a deep learning AI system was applied to analyze MR images of the prostate. The diagnostic efficacies of T 2 weighted imaging (WI), diffusion WI (DWI), mpMRI, PET SUV max, and PET/MR for prostate cancer were assessed, with using the pathological results as the gold standard. Results:Among 103 patients, 82 cases (79.61%) were with prostate cancer. PET unimodality demonstrated the best specificity (100%, 21/21), positive predictive value (100%, 58/58), and AUC (0.860, 95% CI: 0.777-0.920). The mpMRI AI analysis provided rapid diagnostic results and the sensitivity and accuracy were improved by combining with PET (sensitivities of PET, mpMRI and the combination of the two were 70.73%(58/82), 86.59%(71/82), and 92.68%(76/82), respectively; the accuracies were 76.70%(79/103), 81.55%(84/103) and 86.41%(89/103), respectively). Among 44 patients with negative PET, 30 patients received an accurate diagnosis when the results of mpMRI AI analysis were added. Conclusions:68Ga-PSMA PET demonstrates good specificity for prostate cancer and mpMRI AI analysis is time-saving. The combined application improves the diagnostic sensitivity and accuracy, which provides a valuable tool for 68Ga-PSMA PET/MR image analysis.

Objective:To evaluate the value of preoperative vascular ultrasound parameters in predicting the postoperative lower extremity deep venous thrombosis (DVT) in patients with gynecological malignant tumors.Methods:Ninety-nine patients with gynecological malignant tumors, aged>18 yr, with body mass index<30 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, scheduled for elective surgery under general anesthesia, were selected. Vascular ultrasound examination was performed before surgery. The flow velocity and diameter of common femoral vein (CFV), deep femoral vein (DFV), popliteal vein (POV), and intermuscular vein (IMV) were recorded. Ultrasound examination of lower limb veins (including anterior tibial vein, posterior tibial vein, IMV, CFV, DFV, POV) were conducted at 1-8 days after surgery to determine whether a DVT occurred. The receiver operating charcateristic curve was used to evaluate the accuracy of each indicator in predicting the lower extremity DVT, and the cut-off value was determined based on the maximum principle of Jorden index. Results:The incidence of lower extremity DVT was 13.1%. The area under the curve (95% confidence interval) of the preoperative CFV flow velocity and diameter, DFV flow velocity and diameter, POV flow velocity and diameter, IMV flow velocity and diameter in predicting the lower extremity DVT were 0.769 (0.616-0.923) and 0.800 (0.644-0.950), 0.797 (0.641-0.954) and 0.771 (0.596-0.945), 0.806 (0.645-0.968) and 0.754 (0.606-0.903), 0.764 (0.615-0.914) and 0.818 (0.645-0.990), respectively ( P<0.05), and the predicted cut-off values were 27.13 cm/s and 11.93 mm, 19.31 cm/s and 10.15 mm, 16.04 cm/s and 8.79 mm, 14.39 cm/s and 8.68 mm, respectively, and the sensitivity and specificity were 90.0%, 71.4% and 90.0%, 74.3%; 90.0%, 74.3% and 90.0%, 68.6%; 90.0%, 82.9% and 90.0%, 72.9%; 90.0%, 70.0% and 80.0%, 87.1%, respectively. Conclusions:Preoperative vascular vascular ultrasound parameters can accurately predict the occurrence of postoperative lower extremity DVT in patients with gynecological malignant tumors.

Objective:To investigate the expression of complement C3 in serums and tissues of lung adenocarcinoma patients with brain metastases and the mechanism of complement C3 in inducing epithelial mesenchymal transition (EMT).Methods:The retrospective case-control study, cell experiments and animal experiments were conducted. The serum samples from 20 healthy examinees, 20 advanced lung adenocarcinoma patients without brain metastases and 20 advanced lung adenocarcinoma patients with brain metastases at the First People's Hospital of Yancheng from January 2021 to January 2023 were collected, and the expression of complement C3 in serum samples was detected by immunoturbidimetry. At the same time, lung tissue samples were collected from 10 lung adenocarcinoma patients without brain metastases, and lung tissue and brain tissue samples were collected from 10 lung adenocarcinoma patients with brain metastases in the First People's Hospital of Yancheng. Immunohistochemistry was used to detect the expression of complement C3, C3aR, Kruppel like factor 5 (KLF5), and N-cadherin (N-cad) in the tissue samples. Using lentivirus to construct a human lung adenocarcinoma with brain metastases cell line PC14-C3 with stable overexpression of complement C3, with cells infected with empty vector virus as the control group (PC14-Ctrl). Western blotting was used to detect the expression of complement C3, KLF5, N-cad, and E-cadherin (E-cad) in PC14-C3 and PC14-Ctrl cells, and scratch assay was used to assess cell migration ability. Using the random number table method, 12 BALB/c nude mice were evenly divided into PC14-C3 group and PC14-Ctrl group. PC14-C3 cells and PC14-Ctrl cells were subcutaneously inoculated on the ventral side, and the body mass and tumor volume of the nude mice were recorded. Real-time fluorescence quantitative polymerase chain reaction was used to detect the expression of KLF5, N-cad and E-cad mRNA in various tumor cells and tumor tissues of nude mice.Results:The serum complement C3 levels in healthy individuals, lung adenocarcinoma patients without brain metastases and lung adenocarcinoma patients with brain metastases were (1.14±0.17) g/L, (1.20±0.15) g/L and (1.61±0.21) g/L, respectively. The serum complement C3 level in lung adenocarcinoma patients with brain metastases was higher than that in lung adenocarcinoma patients without brain metastases and healthy individuals, and the differences were statistically significant (both P < 0.001). The results of immunohistochemical testing showed that the proportions of positive expression areas of complement C3, C3aR, KLF5, and N-cad proteins in the lung primary lesions of lung adenocarcinoma patients with brain metastases were higher than those of patients without brain metastases, and the differences were statistically significant (all P < 0.05). The mRNA ( P < 0.05) and protein expression levels of complement C3 in PC14-C3 cells were higher than those in PC14-Ctrl cells, indicating successful transfection. The scratch assay results showed that the migration rate of PC14-Ctrl cells was (37.5±4.1)%, and the migration rate of PC14-C3 cells was (60.4±2.9)%, and the difference was statistically significant ( t = 7.86, P < 0.01). The relative expressions of EMT promoting molecules KLF5 and N-cad mRNA in PC14-C3 cells were higher than those in PC14-Ctrl cells, while the relative expression of EMT inhibiting molecule E-Cad mRNA was lower than that in PC14-Ctrl cells, and the differences were statistically significant (all P < 0.05). On the 26th day of tumor loading, the tumor volume of nude mice in PC14-C3 group was (610±10) mm 3, while that of PC14-Ctrl group was (321±30) mm 3; the body mass of nude mice in PC14-C3 group was lower than that in PC14-Ctrl group [(21.6±0.6) g vs. (23.2±0.6) g], and the differences were statistically significant (both P < 0.05). At the end of the experiment, 5 nude mice died and 1 survived in the PC14-C3 group; 1 nude mouse died and 5 survived in the PC14-Ctrl group. The relative expressions of KLF5 and N-cad mRNA in the tumor tissues of nude mice in PC14-C3 group were higher than those in PC14-Ctrl group, while the relative expression of E-Cad mRNA was lower than that in PC14-Ctrl group, and the differences were statistically significant (all P < 0.05). Conclusions:Lung adenocarcinoma patients with brain metastases have high levels of complement C3 in their serums and primary lesions. Complement C3 may induce EMT and promote the occurrence of lung adenocarcinoma brain metastases by affecting the expressions of KLF5, N-cad and E-cad.

Objective:To explore the efficacy of subcutaneous injection of granulocyte-macrophage colony-stimulating factor (GM-CSF) in preventing invasive fungal disease (IFD) in patients with multiple myeloma (MM).Methods:The clinical data of 222 patients who were admitted to the Second Hospital of Harbin Medical University from January 2015 to June 2021 were retrospectively analyzed. The patients was given GM-CSF (3-5 μg·kg -1·d -1, GM-CSF group) or granulocyte colony-stimulating factor (G-CSF, 2-5 μg·kg -1·d -1, G-CSF group) when neutrophils (ANC) ≤1.5×10 9/L after induction chemotherapy. Patients were discontinued when white blood cell count (WBC) ≥10.0×10 9/L. The incidence of IFD (including confirmed, clinical and proposed diagnosis) and breakthrough invasive fungal infections was compared between the two groups. Results:The incidence of IFD was 8.1% (18/222) in all patients. The incidence of IFD was 3.5% (3/85) and 10.9% (15/137) in the GM-CSF and G-CSF groups, respectively, and the difference between the two groups was statistically significant ( χ2 = 3.88, P = 0.049). In 9 patients of GM-CSF group receiving fungal infection prophylaxis and in 15 patients of G-CSF group receiving fungal infection prophylaxis, the incidence of breakthrough invasive fungal infections was 0 and 7 cases, respectively, and the difference between the two groups was statistically significant ( P = 0.022). Conclusions:GM-CSF application in MM patients can reduce the incidence of IFD and breakthrough invasive fungal infections.

Objective To analyze the risk factors of repeated admissions for community-acquired pneumonia(CAP)in adults,and to build a nomogram model to predict individual risk.Methods A total of 2 306 adult hospitalized patients with CAP in Beijing Shijitan Hospital affiliated to Capital Medical University from January 2018 to Decem-ber 2020 were retrospectively selected and divided into repeated admission group and control group according to whether they were readmitted within one year after discharge.Univariate logistic analysis and multivariate logistic a-nalysis were used to determine the risk factors.The risk factors were introduced into R 3.5.3 software to construct the nomogram prediction model.The calibration curve was drawn and the Hosmer-Lemeshow goodness of fit test was performed to evaluate the accuracy of the nomogram prediction model.The receiver operating characteristic(ROC)curve was drawn to evaluate the discrimination of the nomogram prediction model.The decision analysis curve was drawn to measure patient benefits.Results The age,gender,length of stay,total score of comorbidity index,use of special grade antibiotics,history of blood transfusion,and Vaccination history were risk factors of repeated hospi-tal admissions for CAP in adults.The nomogram prediction model of adult CAP repeated admission was constructed based on the above risk factors.The Hosmer-Lemeshow goodness of fit test showed that the fitting effect of the no-mogram prediction model was good(x2=8.873,P=0.353).The ROC curve analysis showed that the area under the curve of the test dataset was 0.775.The results of the decision analysis curve showed that when the threshold was 0.21,the model could generate a net profit of 0.104.Conclusion The nomogram model established in this study has good discrimination and accuracy in predicting the risk of adult CAP repeated admissions and has high clinical application value.