OBJECTIVE To explore and analyze the adverse drug event （ADE） signals of darolutamide and provide a reference for its clinical safe use. METHODS ADEs related to darotamide were collected based on the US FDA adverse event reporting system （FAERS） database from the third quarter of 2019 to the third quarter of 2022. Data mining and analysis were conducted by the report odds ratio （ROR） and proportional reporting ratio （PRR） methods. RESULTS A total of 565 ADE reports related to darolutamide were extracted， 356 ADE reports about darolutamide as the primary suspected drug were included， 38 ADE signals with darolutamide as the primary suspected drug were excavated， involving 15 system organ class （SOC）， mainly concentrated in patients over 65 years old. The SOC of darotamide ADE signal mainly focused on various examinations， systemic diseases and various reactions at the administration site， benign/malignant tumors or those with unknown nature （including cystic and polypoid）， kidney and urinary system diseases. A total of 13 ADE signals not mentioned in the instructions included increased prostate-specific antigen， dysphagia， cognitive impairment， erectile dysfunction， rhabdomyolysis， gynecomastia and decreased platelet count， etc. CONCLUSIONS When using darolutamide， in addition to ADE in the drug instruction， we should pay close attention to potential ADE， such as increased prostate-specific antigen， rhabdomyolysis， gynecomastia and decreased platelet count， so as to avoid drug withdrawal or organ damage caused by ADE.

Objective: To analyze the longitudinal association between mobile phone dependence and depressive symptoms in college students, so as to provide a theoretical basis for psychological health education among college students. Methods: From November 2021 to June 2023, 2 515 first year students from 2 universities in Yunnan Province were surveyed with a questionnaire by a cluster random sampling method, including baseline survey (November 2021, T1) and three follow up visits (June 2022, T2; November 2022, T3; June 2023, T4). The Self rating Questionnaire for Adolescent Problematic Mobile Phone Use and the Depression Anxiety Stress Scales-21 (DASS-21) were used to evaluate mobile phone dependence and depressive symptoms of college students. The χ 2 test was used to analyze the difference in depressive symptoms among different demographic groups, and a generalized estimation equation model was established to analyze the association between mobile phone dependence symptoms and depressive symptoms. Results: The detection rates of depressive symptoms among university students in Yunnan Province at time points T1, T2, T3, and T4 were 23.02%, 33.36%, 34.79% and 35.51%, respectively. There were statistically significant differences in the detection rates of depressive symptoms among college students with different sacademic burden (T1, T2, T3, T4), different number of close friends (T1, T2, T3), as well as their father s educational level (T1), mothers educational level (T2, T4), gender (T4), major (T3, T4), education (T2, T3, T4), family residency (T1, T2), and family economic conditions (T1, T2, T4) ( χ 2= 59.68 , 49.38, 16.70, 39.31; 55.35, 26.01, 16.69; 10.22; 14.87, 11.51; 14.90; 27.81, 50.28; 9.75, 7.42, 24.76; 6.06, 4.47 ; 15.88, 14.58, 15.85, P < 0.05 ). After controlling for demographic variables and confounding factors in the generalized estimation equation model, mobile phone dependence ( β =0.11), withdrawal symptoms of mobile phone dependence ( β =0.14), and the physical and mental effects of mobile phone dependence ( β =0.14) were all positively correlated with depressive symptoms ( P <0.01). Further gender analysis showed that depressive symptoms in both boys ( β =0.13, 0.13, 0.18) and girls ( β =0.10, 0.13, 0.13 ) were associated with mobile phone dependence, withdrawal symptoms of mobile phone dependence and the physical and mental effects of mobile phone dependence ( P <0.01). Conclusions Depressive symptoms of college students are positively correlated with mobile phone dependence, and family economic conditions, academic burden and number of close friends are factors that continued to affect depressive symptoms. College students should be guided to pay attention to the impact of excessive use of mobile phones on their physical and mental health, use mobile phones reasonably to reduce the incidence of depressive symptoms among college students.

Objective:To study the clinical characteristics and risk factors of nephrocalcinosis in preterm infants.Methods:From March 2021 to August 2021, all preterm infants admitted to NICU of our hospital were retrospectively analyzed. The infants were assigned into nephrocalcinosis group and non-nephrocalcinosis group according to urinary tract ultrasound. Clinical data including gestational age, birth weight(BW), nutritional support strategy and complications were reviewed.Results:A total of 40 preterm infants (<34 weeks) were enrolled. 9 cases were in the nephrocalcinosis group and 31 cases in the non-nephrocalcinosis group. The nephrocalcinosis group had lower BW[(1 167±214) g vs.(1 586±215) g], higher calcium [6.9 (5.1, 8.7) g vs.3.3 (2.1, 6.8) g] and vitamin D intake [3.2(2.5, 4.2)×10 4U vs.1.7(1.1, 3.2)×10 4U] during hospitalization. No significant differences existed between the two groups on the following items:blood calcium and phosphate, 25-hydroxyvitamin D, feeding strategy, time to reach full enteral feeding(TFF), furosemide dosage and respiratory support duration ( P>0.05). In the nephrocalcinosis group, the median age of diagnosing nephrocalcinosis was 40.0(30.0, 52.5)d after birth. 5 cases showed bilateral nephrocalcinosis. 5 cases in the nephrocalcinosis group received renal tubule function examination,4 cases had increased urine β2 microglobulin and 2 cases had increased urine α1 microglobulin. 7 cases had elevated urine calcium in the nephrocalcinosis group. Follow-up showed that nephrocalcinosis disappeared 3-9 months after birth. Conclusions:BW, total calcium and vitamin D intake are risk factors for nephrocalcinosis in preterm infants. Increased urine β2 microglobulin and calcium levels are common co-morbidities in preterm infants with nephrocalcinosis.

Objective To investigate the prognostic value of M2 macrophage-related genes(MRG)in hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC).Methods The transcriptome data of 73 patients with HBV-related HCC were obtained from TCGA database,and the MRG modules were identified by WGCNA.The MRG-based risk scoring model was constructed by LASSO regression analysis and validated using an external dataset.The correlation of the risk score with immune cell infiltration and drug sensitivity of HCC were analyzed with CIBERSORT and R.pRRophetic.The signaling pathways of the differential genes between the high-and low-risk groups were investigated using GSVA and GSEA enrichment analyses,and MRG expressions at the single cell level were validated using R.Seurat.The cell interaction intensity was analyzed by R.Cellchat to identify important cell types related to HCC progression.MRG expression levels were detected by RT-qPCR in THP-1 cells with HCC-conditioned medium-induced M2 polarization and in HBV-positive HCC cells.Results A high M2 macrophage infiltration level was significantly correlated with a poor prognosis of HCC,and 5 hub MRG(VTN,GCLC,PARVB,TRIM27,and GMPR)were identified.The overall survival of HCC patients was significantly lower in the high-risk than in the low-risk group.The high-and the low-risk groups showed significant enrichment of M2 macrophages and na?ve B cells,respectively,and were sensitive to BI.2536 and to AG.014699,AKT.inhibitor.Ⅷ,AZD.0530,AZD7762,and BMS.708163,respectively.The proliferation-related and metabolism-related pathways were enriched in the high-risk group,where monocytes showed the most active cell interactions during HCC progression.VTN was significantly upregulated in HCC cell lines,while GCLC,PARVB,TRIM27,and GMPR were upregulated in M2 THP-1 cells.Conclusion The MRG-based risk scoring model can accurately predict the prognosis of HBV-related HCC and reveal the differences in tumor microenvironment to guide precision treatment of the patients.

AIM:To clarify the effect of macrophage PKM2 deficiency on mucosal repair in ulcerative colitis(UC).METHODS:The gene expression and metabolic profiles in UC patients were first analyzed based on the following databases:PXD001608,GSE193677,and GSE214695.Using the macrophage-specific PKM2 elimination mice(PKM2ΔMAC),the functions of PKM2 in dextran sulfate sodium(DSS)-induced UC were clarified in vivo by analyzing the body weight,disease activity index(DAI)scores,HE staining,immunohistochemical staining,and expression of muco-sal barrier markers.The impact of PKM2 on macrophage polarization was also investigated by flow cytometry,RNA se-quencing and RT-qPCR in mouse bone marrow-derived macrophages(BMDMs)and THP-1 cells in vitro.RESULTS:Bioinformatic analysis suggested that the intestinal tissues of UC patients preferred glycolysis.The expression of PKM was parallel to the severity of UC in patients,and the expression of PKM2,but not PKM1,was elevated in macrophages of UC mice.In the DSS-induced UC mice,macrophage-specific PKM2 elimination significantly alleviates the body weight loss,diarrhea,rectal bleeding,colonic shorten,as well as decreased DAI scores and mucosal tissue damage.The BMDMs de-rived from the PKM2ΔMAC mice preferred the M2 polarization upon LPS or IL-4 stimulation to that derived from the wild-type mice,as indicated by the F4/80+CD45+CD86+and F4/80+CD45+CD206+population,as well as the expression of Ocln,F11r and Tjp-1.The RNA sequencing results indicated significant gene differential expression in PKM2 knockout mouse macrophages,which was enriched in biological processes such as leukocyte migration,tissue remodeling,and cytokine in-teractions.Macrophage PKM2 deficiency promoted the expression of mucosal repair factors(Il8,Cxcl1,Ptgs2 and Wnt6),which was further validated in PKM2 knockout THP-1 cells.CONCLUSION:The PKM2 deficiency in macro-phages benifits the mucosal repair in UC status via facilitating the wound-healing macrophage polarization.

Objective To investigate the prognostic value of M2 macrophage-related genes(MRG)in hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC).Methods The transcriptome data of 73 patients with HBV-related HCC were obtained from TCGA database,and the MRG modules were identified by WGCNA.The MRG-based risk scoring model was constructed by LASSO regression analysis and validated using an external dataset.The correlation of the risk score with immune cell infiltration and drug sensitivity of HCC were analyzed with CIBERSORT and R.pRRophetic.The signaling pathways of the differential genes between the high-and low-risk groups were investigated using GSVA and GSEA enrichment analyses,and MRG expressions at the single cell level were validated using R.Seurat.The cell interaction intensity was analyzed by R.Cellchat to identify important cell types related to HCC progression.MRG expression levels were detected by RT-qPCR in THP-1 cells with HCC-conditioned medium-induced M2 polarization and in HBV-positive HCC cells.Results A high M2 macrophage infiltration level was significantly correlated with a poor prognosis of HCC,and 5 hub MRG(VTN,GCLC,PARVB,TRIM27,and GMPR)were identified.The overall survival of HCC patients was significantly lower in the high-risk than in the low-risk group.The high-and the low-risk groups showed significant enrichment of M2 macrophages and na?ve B cells,respectively,and were sensitive to BI.2536 and to AG.014699,AKT.inhibitor.Ⅷ,AZD.0530,AZD7762,and BMS.708163,respectively.The proliferation-related and metabolism-related pathways were enriched in the high-risk group,where monocytes showed the most active cell interactions during HCC progression.VTN was significantly upregulated in HCC cell lines,while GCLC,PARVB,TRIM27,and GMPR were upregulated in M2 THP-1 cells.Conclusion The MRG-based risk scoring model can accurately predict the prognosis of HBV-related HCC and reveal the differences in tumor microenvironment to guide precision treatment of the patients.

Objective To investigate the expression of miR-30a-5p and miR-129-5p in the serum of patients with non-small cell lung cancer after EGFR targeted therapy and their relationship with the therapeutic effect.Methods A total of 186 patients with non-small cell lung cancer who received EGFR targeted therapy in our hospital from January 2020 to June 2022 were regarded as research objects.According to the efficacy of patients,they were separated into effective group(n=141)and ineffective group(n=45).The serum levels of miR-30a-5p and miR-129-5p were compared between the two groups;multivariate logistic regression was applied to analyze the factors influencing the efficacy of non-small cell lung cancer;receiver operating characteristic was applied to analyze the predictive value of serum miR-30a-5p,miR-129-5p levels for efficacy of non-small cell lung cancer.Results There were obvious differences in smoking history and TNM stage between the ineffective group and the effective group(P＜0.05).The expression levels of miR-30a-5p and miR-129-5p in the ineffective group were obviously lower than those in the effective group(P＜0.05).Multivariate logistic regression analysis showed that serum miR-30a-5p,miR-129-5p,smoking history,and TNM stage were all factors influencing the efficacy of non-small cell lung cancer(P＜0.05).Receiver operating characteristic showed that the AUC of the combination of serum miR-30a-5p and miR-129-5p to predict the efficacy of non-small cell lung cancer was 0.926,the sensitivity was 91.11％,and the specificity was 83.69％,which was better than their respective predictions(Z combination-miR-30a-5P=3.260,Zcombination-miR-129-5p=3.726,P=0.001,0.000).Conclusion The serum levels of miR-30a-5p and miR-129-5p in patients with non-small cell lung cancer who failed to respond to EGFR targeted therapy are obviously lower than those in the effective group;The combination of the two has a good predictive value for the efficacy of non-small cell lung cancer after EGFR targeted therapy.

Objective Idiopathic non-cirrhotic portal hypertension (INCPH) is a rare cause of portal hypertension, and this study aims to analyze the clinical features of patients with INCPH, and to assist in diagnosis and differential diagnosis. Methods A total of 74 patients who were hospitalized in Beijing YouAn Hospital from January 2019 to July 2022 and were diagnosed with INCPH were enrolled, and 332 patients with liver cirrhosis who were hospitalized during the same period of time were enrolled as control group. Demographic data, laboratory markers, gastroscopy, liver elasticity, pathological examination, and complications were recorded and compared between the two groups. The receiver operating characteristic (ROC) curve was used to investigate the ability of liver stiffness measurement (LSM), aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) in the differential diagnosis of INCPH, and the DeLong test was used to compare the area under the ROC curve (AUC). The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. Results Among the patients with INCPH, 46.55% had no obvious symptoms at disease onset and 43.24% were misdiagnosed with liver cirrhosis. Compared with the patients with liver cirrhosis, the patients with INCPH had a significantly higher proportion of patients with gastrointestinal bleeding (62.16% vs 41.27%, χ 2 =10.67, P < 0.01) and a significantly lower proportion of patients with moderate-to-severe ascites (16.21% vs 29.82%, χ 2 =34.98, P < 0.01), and there were few patients with hepatic encephalopathy. As for pathology, 89.19% (66/74) of the INCPH patients manifested as typical occlusive portal vein disease. The statistical analysis showed that compared with the patients with liver cirrhosis, the patients with INCPH had significantly better liver function parameters, MELD score, and Child-Pugh score and significantly lower LSM [9.05(7.18-12.33) vs 25.32(16.21-47.23), Z =-8.41, P < 0.01], APRI score [0.70(0.41-1.28) vs 1.35(0.80-2.39), Z =-6.21, P < 0.01], and FIB-4 index [2.99(1.62-4.81) vs 6.68(4.06-10.42), Z =-8.39, P < 0.01]. LSM, FIB-4, and APRI had a good ability in differentiating INCPH from liver cirrhosis, and in particular, LSM had an AUC of up to 0.92 (95% confidence interval: 0.87-0.96), with a sensitivity of 92.68% and a specificity of 81.60%. Conclusion INCPH patients tend to have an insidious onset, a relatively high incidence rate of portal hypertension-related complications, and relatively good liver function, especially the patients with LSM < 14.5 kPa. The possibility of INCPH should be considered for such patients in clinical practice.

Objective:To evaluate the value of dual-layer spectral detector CT (DLSDCT) in precise radiotherapy for central lung cancer (CLC) complicated with atelectasis.Methods:Clinical and imaging data (including DLSDCT, PET-CT, and radiotherapy simulation CT images) of 26 patients with pathologically confirmed CLC accompanied by atelectasis from the Third Affiliated Hospital of Shandong First Medical University and Shandong Cancer Hospital were analyzed retrospectively. There were 21 males and 5 females, aged 36-82 years. Two physicians assessed CLC identifiability on DLSDCT, PET-CT, and simulation localization CT images, respectively, and outlined the gross tumor volume (GTV) and measured GTV values (GTV DLSDCT, GTV PET-CT, GTV CT). Paired-sample Friedman test was used to compare the differences in GTV of the three images, and the SNK test with Bonferroni correction was used for a two-way comparison. The intra-class correlation coefficient (ICC) was used to compare the agreement of measured GTV between 2 physicians. Results:The differentiation rates on PET-CT, DLSDCT, and simulation CT images were 100% (26/26), 80.77% (21/26), and 11.54% (3/26), respectively. The differentiation rate of CLC on DLSDCT images was significantly higher than that on simulation CT images (χ 2=16.06, P<0.001). GTV CT, GTV PET-CT, and GTV DLSDCT measured on simulation localization CT images, PET-CT images, and DLSDCT images were 58.75 (22.57, 86.17) cm 3, 47.34 (18.13, 69.25) cm 3, and 51.40 (18.87, 71.31) cm 3, respectively, with statistically significant differences (χ 2=44.99, P<0.001). Both GTV DLSDCT and GTV PET-CT were significantly smaller than GTV CT (χ 2=4.23, 6.59, Bonferroni corrected P<0.001), and there was no significant difference between GTV DLSDCT and GTV PET-CT (χ 2=2.36, Bonferroni corrected P=0.055). The agreement between the two physicians was good for GTV values measured on both DLSDCT and PET-CT (ICC=0.86, 0.89). Conclusions:On DLSDCT images, most CLC and atelectasis can be identified. Compared to simulation localization CT, the tumor target areas outlined on DLSDCT are closer to PET-CT, and the tumor volumes outlined by different physicians are more consistent.

Medical microbiology is one of the compulsory courses of basic medical sciences, which lays an important theoretical foundation for the follow-up study of infectious diseases, contagions, tumors, and so on. The course of medical microbiology in our college adhered to the concept of student-centered, diversified teaching, scientific evaluation, and continuous improvement. Teaching design was a cross-link of general theories, specific chapters, clinical cases, theory and practice, and the ideological and political education throughout the curriculum. Lectures adopted the mode of offline teaching (such as flipped classroom, case analysis, and comprehensive experimental design), online assistance (such as classroom test, stage test, extracurricular homework, and questionnaire survey), and combined process evaluation. This teaching mode also reflected the deep integration of information technology and classroom teaching. With the development and construction in these years, medical microbiology has completed the renewal of curriculum resources, the construction of online question bank, the construction and design of ideological and political case bank, and process evaluation (10 points of usual score + 10 points of case study + 10 points of experimental performance + 100 points of final examination multiplied by 70%). There was no significant difference in the results of qustionnaire survey in terms of the improvement of independent learning ability, curriculum evaluation system and satisfaction feedback. Students in Batch 2019 were most satisfied with the teaching of keeping pace with the times and the guidance of positive outlook on life and values.