Objective To explore the mechanism by which zinc-regulated transporters, iron-regulated transporter-likeprotein 4 (ZIP4) regulates glycolysis and its impact on tumor progression in cholangiocarcinoma (CCA), providing a theoretical basis for targeted therapy of CCA. Methods ZIP4 expression in CCA was analyzed using the GEPIA database. Immuno-histochemistry (IHC) was used to detect ZIP4 expression in 20 paired CCA and adjacent non-tumor tissues. Stable ZIP4-overexpressing CCA cell lines (ZIP4-OE) were established. Gene set enrichment analysis was used to screen differentially expressed genes and pathways in ZIP-OE CCA cells. ZIP4, N-myc proto-oncogene protein (MYCN), and histone-lysine N-methyltransferase 2E (KMT2E) were knocked down using small interfering RNAs (siRNAs). The expression of glycolysis-related gene (glucose transporter 1 [Glut1], hexokinase 2 [HK2], and lactate dehydrogenase A [LDHA]) was measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Glycolytic activity was assessed by measuring the extracellular acidification rate (ECAR). Cell proliferation was evaluated using colony formation assays, and cell migration was assessed using Transwell assays. A xenograft mouse model was constructed to examine CCA tumor growth. Protein levels of ZIP4, KMT2E, H3K4me3 (tri-methylation of lysine 4 on histone H3), and MYCN were detected by Western blotting. Results GEPIA database analysis and IHC results confirmed significantly higher ZIP4 expression levels in CCA tissues compared to adjacent non-tumor tissues (P＜0.05). Compared to the control group, the ZIP4-OE group exhibited a significantly increased ECAR, along with significantly enhanced proliferation and migration abilities (P＜0.01). Conversely, knockdown of ZIP4 suppressed CCA cells proliferation and migration. GEPIA analysis indicated that ZIP4 upregulates the transcription of oncogene MYCN, as well as glycolysis-related genes. Knockdown of MYCN abolished the ZIP4 overexpression-induced upregulation of Glut1, HK2, and LDHA gene transcription, reduced glycolysis, and significantly inhibited CCA cell proliferation and migration (P＜0.05). Mechanistic studies demonstrated that ZIP4 increases H3K4me3 level via KMT2E, leading to MYCN transcription. Knockdown of KMT2E in CCA cells suppressed the ZIP4 overexpression-induced enhancement in H3K4me3 modification, resulting in MYCN downregulation and significantly reduced CCA cells proliferation and migration (P＜0.05). Conclusions ZIP4 upregulates H3K4me3 modification through KMT2E, which recruits transcription factors to activate the transcription of MYCN. This subsequently enhances cellular glycolysis and promotes the proliferation and migration of CCA cells.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To investigate the epidemic characteristics of influenza in children and the features of severe influenza.Methods:From January 2016 to September 2022, 1 600 samples from hospitalized cases of severe acute respiratory tract infection and 7 660 samples from outpatients with influenza-like illness were collected. Influenza virus was detected by real-time RT-PCR. Other respiratory viruses in the samples of severe hospitalized cases and some samples of outpatients were detected. Clinical features of influenza virus infection and co-infection were analyzed.Results:The positive rate of influenza virus in the 1 600 hospitalized cases of severe acute respiratory infection was 6.63% (106 cases). H1N1, H3N2, BV and BY were deteted in 49.06% (52 cases), 17.92% (19 cases), 29.25% (31 cases) and 3.77% (4 cases) of the 106 cases, respectively. The positive rate of influenza virus in the 7 660 out-patient cases was 15.01% (1 150 cases), and H1N1, H3N2, BV and BY were detected in 22.17% (255 cases), 30.96% (356 cases), 41.39% (476 cases) and 5.48% (63 cases) of the infected cases, respectively. Influenza A (H1N1) virus was more likely to cause severe influenza in children (χ 2=37.978, P<0.001), while seasonal H3N2 and BV strains were less likely to cause severe influenza in children (χ 2=7.871, P=0.005; χ 2=5.948, P=0.015). There was no statistically significant difference in the positive rates of BY lineage in the two groups. Severe influenza mainly occured in the peak season of influenza epidemic. There was no significant difference in the clinical manifestations between the children infected with the four different influenza viruses. In the 106 severe cases of influenza, the co-infection rate of influenza virus with other respiratory viruses was 17.92% (19 cases), while the co-infection rate reached 34.81% (47 cases) in 135 outpatient cases of influenza. The difference in the co-infection rates was statistically significant between outpatient and hospitalized cases (χ 2=10.734, P=0.001). Conclusions:Influenza A (H1N1) virus was more likely to cause severe influenza in infants and young children in comparison with seasonal H3N2 and BV. There was no significant difference in the clinical features of influenza caused by H1N1, H3N2, BV and BY. Co-infection of influenza virus with other respiratory viruses is not a major risk factor for severe influenza in infants.

Objective:To explore the effect of repetitive transcranial magnetic stimulation (rTMS) combined with cognitive behavioral therapies (CBT) on the cognitive function and alcohol craving in patients with alcohol dependence.Methods:From March 2019 to September 2021, a total of 150 patients with alcohol dependence were enrolled and randomly divided into rTMS treatment group (rTMS+ sham CBT, n=41), CBT treatment group (CBT+ sham rTMS, n=34), rTMS+ CBT treatment group( n=36) and control group (sham rTMS+ sham CBT, n=39). At baseline (before treatment), 2nd week, 8th week, 12th week and 24th week, alcohol dependence scale (ADS) was used to evaluate the degree of alcohol dependence, the obsessive compulsive drinking scale (OCDS) was used to assess patients' drinking craving, and Montreal cognitive assessment scale (MoCA) was used to assess the overall cognitive level of patients.SPSS 23.0 statistical software was used to compare the differences of ADS, OCDS and MoCA scale scores of the four groups by repeated measure ANOVA and simple effect analysis. Results:(1)The patients in the four groups were evaluated with ADS scale at baseline, 12th week and 24th week respectively.The interaction of group×time( F=1.279, P=0.279) and the main effect of group were not significant ( F=0.882, P=0.454), and the main effect of time was significant ( F=12.925, P<0.001) .Further simple effect analysis showed that the ADS score of rTMS+ CBT group was lower than that of baseline(14.48±5.70, 10.00±6.51) ( P=0.01) at 24th week.(2)Patients in the four groups were assessed with OCDs scale at baseline, 2nd week, 8th week, 12th week and 24th week, and the interaction of group×time was significant ( F=2.015, P=0.042). Further simple effect analysis showed that the OCDs scores of rTMS group and rTMS+ CBT group at each follow-up time node were lower than those at baseline period (all P<0.05). (3)Patients in the four groups were assessed with MoCA scale at baseline, 8th week, 12th week and 24th week, and the interaction of group×time was not significant ( F=1.660, P=0.106), and the main effect of group and the main effect of time were significant ( F=2.964, P=0.038; F=14.239, P<0.001). Further simple effect analysis showed that the score of MoCA scale in CBT group at the 24th week was higher than that at baseline (21.73±5.81, 24.60±3.98)( P=0.029), the score of MoCA scale in rTMS+ CBT group at the 24th week was higher than that at the 8th week (23.50±6.01, 25.95±2.87) ( P=0.006), and the score of MoCA scale in rTMS group at the 12th week was higher than that in control group (22.08±6.64, 26.64±2.46)( P=0.009). Conclusion:rTMS combined with CBT can be effective in improving alcohol craving and cognitive function in patients with alcohol dependence, and has a good long-term effect.

Objective:To study the pathogenic spectrum of enterovirus (EV) in the samples of child influenza-like(ILI)cases in Hangzhou city .Methods:In 2019, 1 060 throat swab specimens of ILI cases were collected for serotyping of influenza virus and EVs by real-time RT-PCR. The positive rates of influenza virus and EV in spring, summer, autumn and winter were compared by chi-square test with SPSS16.0 software. Specific primers were synthesized and used to amplify the VP1 fragments of EV. PCR products were sequenced and the results were compared with the reference sequences by using Basic Local Alignment Search Tool (BLAST) to identify the serotypes of isolated EV. The clinical diagnoses of EV positive cases were classified and analyzed.Results:A total of 1 060 specimens were collected and 283(26.70%) were positive for influenza virus, 75(7.08%) were positive for EV, 3(0.28%)were positive for influenza virus and EV. The comparison of positive detection rate of spring, summer, autumn and winter showed that influenza virus were prevalent in winter and spring. EV were mostly popular in the summer months. VP1 sequences of 51 EV were successfully amplified and BLAST analysis revealed that these strains belonged to 10 serotypes, including five serotypes of EV-A species, four serotypes of EV-B species and one serotype of EV-D. The ten serotypes of EV, including coxsackievirus (CV)A2, A4, A5, A6, A9, A10, and echovirus (ECHO)7, ECHO11, ECHO18, and EV-D68 were obtained and the percentages of positive were 16.00%, 16.00%, 5.33%, 12.00%, 5.33%, 1.33%, 1.33%, 5.33%, 4.00% and 1.33%, respectively. The phylogram of EV VP1 sequence showed that 51 EV strains in Hangzhou had different degrees of variation compared with the reference strains. Acute upper respiratory tract infection was the main clinical diagnosis in EV positive children, with 44 cases (58.67%). Acute tonsillitis was followed by 14 cases (18.67%). Followed by herpetic pharyngitis, acute bronchitis, asthmatic bronchitis, pneumonia, accounting for 12.00%, 8.00%, 1.33%, 1.33%, respectively.Conclusions:EV causing influenza-like illness in children in Hangzhou in 2019 belonged to 10 serotypes, CVA2 and CVA4 were the predominant serotypes, and the positive rate of EV detection was higher in summer.

Objective To investigate the health literacy level and health related behavior of high school students in Xuhui District of Shanghai, and to provide basis for health literacy intervention. Methods Using qualitative and quantitative methods, the quantitative part adopted the multi-stage stratified sampling method.A total of 355 aged 15-18 from senior high schools in Xuhui District were selected for face-to-face survey.The qualitative part adopted the form of group interviews, and 20 students from two senior high schools in Xuhui District were selected for interviews. Results The health literacy level of high school students in Xuhui District was 27.32%, which was lower than that of adults in the same period.Among the three dimensions, the level of basic knowledge and concept literacy was the highest, followed by the level of health basic skills literacy, the level of healthy lifestyle and behavior literacy was the lowest; among the six types of health problems, the level of infectious disease prevention literacy and basic medical literacy was at a low level.Statistical analysis of the correct answer rate showed that the answer rate of various questions in the health literacy survey was quite different.Further analysis of the health-related behavioral characteristics of high school students showed that most students had correct health concept and awareness of health change, but they encountered resistance in the process of knowledge transformation into action, which mainly came from academic burden, school education, peer influence and so on.The main channels for high school students to obtain health-related information were classroom, parents, school and various media.They had a high degree of trust in medical professionals and encountered difficulties in seeking health information. Conclusion The health literacy level of senior high school students in Xuhui District of Shanghai needs to be improved.We should explore a health intervention model more suitable for the behavioral characteristics of this group weak links in their health literacy.

Objective: To compare the results of invasive dual mitral and aortic valve replacement(DVR) through anterolateral minithoracotomy(RT) and partial upper hemistemotomy(PS) approaches. Methods: This was a retrospective, observational, cohort study of collected data on 30 patients undergoing dual mitral and aortic valve replacement between July 2009 and March 2018 at Department of Cardiovascular Surgery, Zhongshan Hospital, Fudan University. There were 10 male and 20 female patients, aging from 15 to 65 years with a mean age of(45.67±12.25) years. Of these, 8 were performed through right RT and 22 through PS. SPSS 23.0 was used to analysis gender, age, left ventricle ejection fraction, New York Heart Association class, perioperative complications, total operative duration, cardiopulmonary bypass duration, aortic cross clamp time, ICU monitoring time and postoperative hospital stay of the two groups. Results: Both groups successfully completed minimally invasive double-valve replacement surgery, without middle-opening thoracic surgery. Compared with PS group, patients in the RT group had longer aortic cross clamp time[(109.00±27.80)min vs.(81.23±14.10)min, P=0.026], cardiopulmonary bypass duration[(152.13±27.15)min vs.(129.55±26.36)min, P=0.049]and total operative duration[(4.81±0.77)h vs.(4.15±0.44)h, P=0.006]. In addition, the ICU monitoring time and postoperative hospital stay of patients in RT group were shorter than PS group[(24.63±11.55)h vs.(30.55±13.21)h; (5.50±0.93)day vs.(6.59±3.88)day] but there were no statistically significant(P=0.273; P=0.442). Conclusion Minimally invasive dual mitral and aortic valve replacement via RT and PS are both safe and effective. The incision of RT group is more concealed than the PS group as well as retaining sternal integrity. However, the total operative duration, cardiopulmonary bypass duration and aortic cross clamp time were longer than PS group and the requirements of the surgeon are higher. The PS group has a shorter operation time and does not change the habit of the surgeon. It is more suitable for the heart center that proposed to launch the minimally invasive dual mitral and aortic valve replacement.

Objective To develop and validate a mortality risk prediction model for patients infected with avian influenza A H 7N9 virus.Methods A stratified and random sampling method was adopted for selection of subjects .A total of 102 patients infected with avian influenza A H7N9 virus, who were admitted to the designated hospitals in Zhejiang Province during March 2013 and March 2015, were enrolled.Standard questionnaires were used to collect data about demographic , epidemiologic and clinical characteristics , and the data were retrospectively reviewed . Univariate analysis and stepwise logistic regression analysis were used to identify the mortality risk factors of patients infected with avian influenza A H7N9 virus, and nomogram was applied to develop the risk prediction model .The accuracy of the prediction model was assessed using Concordance index (C-index) and receiver operating characteristic (ROC) curve. Results Stepwise multiple logistic regression analysis showed that age ≥60 years (χ2 =3.98, OR=2.99, 95%CI:1.05-9.21, P<0.05), increased initial neutrophil count (χ2 =6.66,OR=5.06, 95%CI:1.56-18.83, P<0.05), C-reactive protein≥120mg/L (χ2 =8.63, OR=5.15, 95%CI:1.79-16.31, P<0. 01), poor hand hygiene (χ2 =6.83, OR =10.29, 95%CI:2.18-81.49, P <0.01) and 5 days of incubation period or shorter (χ2 =7.23, OR=4.75, 95%CI:1.59-15.80, P<0.01) were independent risk factors for mortality of patients .Based on the above study , a risk prediction model of nomogram was developed.Poor hand hygiene (grade A, 100.0 points) ranked on the top of all risk factors, followed by C-reactive protein≥120 mg/L (grade B, 76.5 points), increased initial neutrophil count (grade C, 70.5 points), 5 days of incubation period or shorter (grade D, 62.0 points) and age ≥60 years (grade E, 51.0 points).The C-index and the area under the curve were 0.833 and 0.817 for the nomogram model , respectively;and the nomogram model fitted well .Conclusion Nomogram model can effectively predict and estimate the risk of death for patients infected with avian influenza A H 7N9 virus.

Objective To investigate the risk factors related to mortality in human avian influenza A (H7N9)cases in Hangzhou.Methods The clinical and epidemiological data of 61 H7N9 patients whose diagnoses were confirmed by laboratory tests between 1st March,2013 and 2nd March,2014 in Hangzhou were collected.Descriptive analysis and univariate analysis were used to analyze the demographic,clinical and epidemiological characteristics and treatment outcomes.Patients were classified into improvement group and death group according to treatment outcomes,and risk factors for death were explored.Chi square test and t test were used for statistical analysis.Results A total of 61 patients were included in this study,among which 20(32.8%)patients died.The ratio of men to women for death attributed to H7N9 infection was three to one.The mean age of patients in death group was (63.6 ±3.8)years,which was older than that in improvement group ([55 .4±2.2]years,t =1 .97,P =0.05 ).The univariate analysis showed that the risk factors of mortality included over 60 years (χ2 =5 .16,P =0.02;OR =3.65 ,95 %CI :1 .19-11 .13 ),low education level (χ2 = 5 .42,P =0.02;OR =4.20,95 %CI :1 .24 - 14.00 ), chronic diseases (χ2 =4.67,P =0.03;OR=3.81 ,95 %CI :1 .12-12.69),bad hand hygiene (χ2 =4.05 , P =0.04;OR=4.67,95 %CI :1 .04 -11 .56 ),C-reactive protein (CRP)≥120 mg/L (χ2 =4.04,P =0.04;OR=6.00,95 %CI :1 .04-35 .33),increased initial neutrophil count (χ2 =3.90,P =0.05 ;OR=4.58,95 %CI :1 .01 -34.22)and decreased initial lymphocyte count (χ2 =7.12,P =0.01 ;OR =7.53, 95 %CI :1 .63 - 24.51 ).Conclusion Over 60 years,low education level,chronic diseases,bad hand hygiene,CRP≥ 120 mg/L,increased initial neutrophil count and decreased initial lymphocyte count are identified as risk factors for death in H7N9 cases in Hangzhou.

Objective To evaluate the use of endoscopy in assessment of invasion depth of colorectal flat lesions and in choice of treatment strategy. Methods The invasion depth of 222 colorectal flat lesions from 188 patients was endoscopically estimated by pit patterns, air-induced deformation testing and/or lifting sign. The lesion was endoscopically rosected if both tests were positive, otherwise, surgery was applied. The pathological evaluation of resected lesion was made according to WHO criteria and was used as a reference of tumor invasion depth. The sensitivity, specificity, positive and negative predictive value of airinduced deformation testing and lifting sign in prediction of invasion depth of tumors were calculated. Results The air-induced deformation testing and lifting sign were both positive in 212 cases, in which 192 were treated with endoscopic mucosal resection (EMR), 15 with endoscopic piecemeal mucosal resection (EPMR), 2 with additional surgery after EPMR and 3 with surgery only. Either air-induced deformation tesring or lifting sign was negative in 10, in which 4 cases underwent surgical resection. The sensitivity, specificity, positive and negative predictive value of air-induced deformation testing and lifting sign in prediction of invasion depth of tumors were 97.2%, 44. 4%, 97.6% and 40. 0%, respectively. Conclusion Endoscopic air-induced deformation testing and lifting sign can be used to predict invasion depth of colorectal flat tumors, which can guide instant therapeutic strategies and avoid excessive or insufficient treatments.