Background::Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods::We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results::GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions::GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.

Immunotherapy is an important breakthrough in canc-er treatment.Unfortunately,low drug concentration in tumor sites almost ineffectively initiates immune responses and thereby severely limits immune therapy applications in clinics.Nanoma-terials are well-recognized drug delivery system in cancer thera-py.Nanographene oxide(NGO)have shown immense perti-nence for anti-cancer drug delivery owing to their ultra-high sur-face area,chemical stability,good biocompatibility and excel-lent photosensitivity.In addition,functionalized modifications on the surface of NGO increase tumor targeting and minimize cy-totoxicity.This study focuses on reviewing the literature and up-dates on NGO in drug delivery and discussing the possibilities and challenges of NGO in cancer synergetic therapy.

Objective To explore clinical outcomes and bone resection of interlaminar fenestration decompression and u-nilateral biportal endoscopic(UBE)technique in treating lumbar disc herniation(LDH).Methods A retrospective study was performed on 105 patients with single-level LDH treated from December 2019 to December 2021.Fifty-four patients in UBE group,including 32 males and 22 females,aged from 18 to 50 years old with an average of(38.7±9.3)years old,were treated with UBE,29 patients withL4.5and 25 patients with L5S1.There were 51 patients in small fenestration group,including 27 males and 24 females,aged from 18 to 50 years old with an average of(39.9±10.0)years old,were treated with small fenestra-tion,25 patients with L4.5 and 26 patients with L5S1.Perioperative indexes,such as operation time,postoperative time of getting out of bed and hospital stay were observed and compared between two groups.Visual analogue scale(VAS)and Oswestry dis-ability index(ODI)were compared between two groups before operation and 1,3,6 and 12 months after operation,respective-ly;and modified MacNab evaluation criteria was used to evaluate clinical efficacy.Amount of bone resection and retention rate of inferior articular process laminoid complex were compared between two groups.Results All 105 patients were successfully completed operation.Both of two groups were followed up from 6 to 12 months with an average of(10.69±2.49)months.Oper-ation time,postoperative time of getting out of bed and hospital stay were(58.20±5.54)min,(2.40±0.57)dand(3.80±0.61)d in UBE group,and(62.90±7.14)min,(4.40±0.64)d and(4.40±0.64)d in small fenestrum group,respectively;and had sta-tistically difference between two groups(P＜0.05).Postoperative VAS of low back and leg pain and ODI in both groups were significantly lower than those before surgery(P＜0.05).VAS of lumbar pain in UBE group(1.37±0.49)score was lower than that of small fenestration group(2.45±0.64)score,and had statistically difference(t=9.745,P＜0.05).Postoperative ODI in UBE group at 1 and 3 months were(28.54±3.31)％and(22.87±3.23)％,respectively,which were lower than those in small fenestra group(36.31±9.08)％and(29.90±8.36)％,and the difference was statistically significant(P＜0.05).There were no significant difference in VAS and ODI between two groups at other time points(P＞0.05).According to the modified MacNab evaluation criteria at the latest follow-up,49 patients got excellent result,3 good,and 2 fair in UBE group.In small fenestration group,35 patients got excellent,12 good,and 4 fair.In UBE group,amount of bone resection on L4,5 segment was(0.45±0.08)cm3 and(0.31±0.08)cm3 on the segment of L5S1.In small fenestration group,amount of bone resection on L4.5 segment was(0.57±0.07)cm3 and(0.49±0.04)cm3 on the segment of L5S1,and amount of bone resection of lower articular process laminar complex on the same segment in UBE group was less than that in small fenestration group(P＜0.05).In UBE group,retention rate of laminoid complex on L4,5 segment was(0.73±0.04)and L5S1 segment was(0.83±0.03),whileL4,5segment was(0.68± 0.06)and L5S1 segment was(0.74±0.04)in small fenestration group,the lower articular process laminar complex retention rate in UBE group was higher than that in small fenestration group(P＜0.05).Conclusion Both unilateral double-channel endoscopy and small fenestration of laminae could achieve good clinical results in treating LDH,but UBE has advantages of less trauma,higher eficiency,faster postoperative recovery and less damage to bone structure.

Objective:To establish a mice model that is more in line with the human immunocompromised state,and to inves-tigate the regulatory effect of Rosa laevigata Michx.,probiotics and their combination on their immune function.Methods:Immunosup-pressive model of mice was established by using cyclophosphamide with different dosage,time and end point,and compared with im-munosuppressive model induced by hydrocortisone and cyclosporine A,immunosuppressive model of mice was established by injecting 25 mg/kg cyclophosphamide 7 times every other day,without recovery period;changes in the proportion of lymphocytes in spleen(CD4+T cells,CD8+T cells,CD19+B cells)were analyzed by flow cytometry;qRT-PCR was used to detect expression levels of inflam-matory factors(IL-1β and IL-6)mRNA in spleen.Results:After continuous injection of 80 mg/kg cyclophosphamide for 3 days,the thymus was atrophied,the spleen was significantly swelling,proportion of immune cells CD4+T cells,CD8+T cells and CD19+B cells in spleen were significantly decreased,while mRNA expressions of IL-1β and IL-6 were up-regulated.After 7 injections of 25 mg/kg cyclophosphamide every other day,the thymus and the spleen were significantly atrophied,proportion of CD4+T cells and CD8+T cells in spleen showed an increasing trend,and mRNA expressions of IL-1β and IL-6 were up-regulated;after 1 week or 2 weeks recovery period from cyclophosphamide injection,weight and index of immune organs,proportion of spleen lymphocytes and mRNA expres-sions of inflammatory cytokines in spleen were significantly reversed;Rosa laevigata Michx.combined with probiotics could signifi-cantly reverse the up-regulation of CD4+T cells and inflammatory factor IL-1β caused by cyclophosphamide.Conclusion:In this study,an immunocompromised mice model has been established with 7 injections of 25 mg/kg cyclophosphamide every other day and without recovery period.And a certain positive immunomodulatory effect of the combination of Rosa laevigata Michx.and probiotics has been found.

Objective:To study the reversal effect of NVP-BEZ235 on doxorubicin resistance in Burkitt lymphoma RAJI cell line.Methods:The doxorubicin-resistant cell line was induced by treating RAJI cells with a concentration gradient of doxorubicin.The levels of Pgp,p-AKT,and p-mTOR in cells were detected by Western blot.Cell viability was detected by MTT assay.IC50 was computed by SPSS.Results:The doxorubicin-resistant Burkitt lymphoma cell line,RAJI/DOX,was established successfully.The expression of Pgp and the phosphorylation levels of AKT and mTOR in RAJI/DOX cell line were both higher than those in RAJI cell line.NVP-BEZ235 downregulated the phosphorylation levels of AKT and mTOR in RAJI/DOX cell line.NVP-BEZ235 inhibited the proliferation of RAJI/DOX cell line,and the effect was obvious when it was cooperated with doxorubicin.Conclusion:The constitutive activation of PI3K/AKT/mTOR pathway of RAJI/DOX cell line was more serious than RAJI cell line.NVP-BEZ235 reversed doxorubicin resistance of RAJI/DOX cell line by inhibiting the PI3K/AKT/mTOR signal pathway.

Objectives:To investigate the feasibility of using bedside echocardiography on the evaluation of potential donors with different causes of brain death for adult heart transplantation. Methods:Bedside echocardiographic and clinical data of consecutive potential donors for adult heart transplantation evaluated by the team of our institution from February 2018 to December 2020 were retrospectively analyzed.Based on different causes of brain death,the potential donors were divided into stroke(ischemic or hemorrhagic,n=398)and non-stroke(head trauma,brain tumor,anoxia,n=272)groups.The clinical and echocardiographic features were compared between the two groups.A total of 350 donors were assigned to our hospital by the China Organ Transplant Response System and met the inclusion criteria for donor selection.There were 195 cases in the stroke group and 155 in the non-stroke group.Retrieval operations were performed and the retrieval rate of hearts for transplantation in stroke donors was compared to that in non-stroke donors. Results:(1)Among the 670 potential heart donors,compared with the non-stroke group,donors in the stroke group were significantly older,had higher body mass index,larger left ventricular end-diastolic diameter,thicker interventricular septum,higher rates of echocardiographic abnormalities,higher prevalence of hypertension(all P<0.001).Among the 670 potential heart donors,17.5%(117 cases)did not meet the echo selection criteria,the common causes were left ventricular hypertrophy(59 cases,50.4%),left ventricular ejection fraction<50%(27 cases,23.1%),wall motion abnormalities(21 cases,17.9%),and left ventricular dilation(14 cases,12.0%).(2)Among the 350 donors who had met the selection criteria and assigned to our hospital by the China Organ Transplant Response System and underwent retrieval operation,70.3%(246 cases)were successfully procured,110 cases(44.7%)in the stroke group and 136 cases(55.3%)in the non-stroke group.The retrieval rate of stroke donors(110/195,56.4%)was lower compared with that of non-stroke(136/155,87.7%,P<0.001),104 cases(29.7%)were not retrieved,and the leading cause of unsuccessful organ retrieval was the occlusion of at least one major coronary artery(91 cases,87.5%). Conclusions:Bedside echocardiography is of great value as a screening tool for cardiac donors.Cardiac structures of the potential donor with stroke as the cause of brain death were different from those with non-stroke causes.The retrieval rate of stroke donors was lower than that of non-stroke donors,even if the initial criteria for donor selection were fulfilled.

Cardiovascular surgery is still the preferred treatment for some congenital or acquired cardiovascular diseases.With the aging of China's population and the prevalence of unhealthy lifestyles brought about by the improvement of living standards,the burden of cardiovascular diseases is still steadily increasing and the volume of cardiovascular surgery continues to be at a high level,which puts forward a new demand for the prevention and treatment strategy of cardiovascular diseases and the allocation of medical resources.Cardiovascular surgery has many perioperative complications and high risk of mortality,a scientific surgical complexity scoring system can help clinicians fully assess the difficulty of surgery,stratify the risk of patient surgery,and formulate targeted and personalized diagnosis and treatment plans;meanwhile,it can help the health management department accurately grasp the overall diagnosis and treatment level of China's cardiovascular surgery,monitor the quality of medical care and provide a reference for the formulation and implementation of relevant medical policies.In this study,we systematically review the current status of evidence-based research on different cardiovascular surgical complexity assessment systems and summarize the application of machine learning in cardiovascular surgical assessment,with a view to contributing to the establishment of a cardiovascular surgical complexity assessment system applicable to the Chinese population.

Objective:To explore the expressions of zinc homeostasis-related proteins,G protein-coupled receptor 39(GPR39)and ANO1 mRNA in the sperm of patients with asthenozoospermia(AS),and analyze their correlation with sperm motility.Methods:We collected semen samples from 82 male subjects with PR+NP＜40％,PR＜32％and sperm concentration＞15 × 106/ml(the AS group,n=40)or PR+NP≥40％,PR≥32％and sperm concentration＞15 × 106/ml(the normal control group,n=42).We analyzed the routine semen parameters and measured the zinc content in the seminal plasma using the computer-assisted sperm analysis system,detected the expressions of zinc transporters(ZIP13,ZIP8 and ZNT10),metallothioneins(MT1G,MT1 and MTF),GPR39,and calcium-dependent chloride channel protein(ANO1)in the sperm by real-time quantitative PCR(RT qPCR),examined free zinc distribution in the sperm by laser confocal microscopy,and determined the expressions of GPR39 and MT1 proteins in the sperm by immunofluorescence staining,followed by Spearman rank correlation analysis of their correlation with semen parameters.Results:There was no statistically significant difference in the zinc concentration in the seminal plasma between the AS and normal control groups(P＞0.05).Compared with the controls,the AS patients showed a significantly reduced free zinc level(P＜0.05),relative expressions of MT1G,MTF,ZIP13,GPR39 and ANO1 mRNA(P＜0.05),and that of the GPR39 protein in the AS group(P＜0.05).No statistically significant differences were observed in the relative expression levels of ZIP8,ZNT10 and MT1 mRNA between the two groups(P＞0.05).The relative expression levels of GPR39,ANO1,MT1G and MTF mRNA were positively correlated with sperm motility and the percentage of progressively motile sperm(P＜0.05).Conclusion:The expressions of zinc homeostasis proteins(MT1G,MTF and ZIP13),GPR39 and ANO1 mRNA are downregulated in the sperm of asthenozoospermia pa-tients,and positively correlated with sperm motility.

Objective:To explore the trends and outcomes for heart transplantation (HT) in elderly recipients and further examine the related risk factors.Methods:Between June 2004 and December 2021, retrospective review was conducted for the relevant clinical data and age distribution of 1044 HT recipients aged ≥18 year at Fuwai Hospital. The study population was assigned into two groups of elder (≥60 year, n=877) and non-elder (<60 year, n=157). Subgroup analysis was made between recipients aged <65 year (n=107) and those aged ≥ 65 year (n=50) in elder group. Baseline demographic profiles, clinical data, in-hospital and one-year post-transplant mortality and long-term survival were compared between two groups. Then a further comparison of long-term survival was conducted among the groups of non-elder, elder aged <65 year and elder aged ≥65 year. Cox proportional risk regression and multivariate Logistic regression models were utilized for examining the relevant risk factors for cumulative survival rate and short-term mortality. Kaplan-Meier analysis was employed for plotting survival curves and Log-rank test for comparison. Multivariate Cox proportional risk regression model was utilized for examining the relevant risk factors for cumulative survival rate and multivariate Logistic regression model for analyzing the relevant risk factors for short-term mortality. After adjusting for other confounding factors, the impact of recipient age on survival post-HT was determined.Results:The number of elderly HT recipients spiked annually at our center while average age of adult recipients and average age of elderly recipients have remained relatively constant. The median follow-up period was 6.5 years. Regarding baseline data, statistically significant differences existed in ratio of males [84.7%(113/157) vs 77.5%(687/877)], hypertension history [20.4%(32/157) vs 8.9%(79/877)], smoking history [47.1%(74/157) vs 36.1%(320/877)], diabetic history [33.8%(53/157) vs 14.7%(130/877)], preoperative ICD/CRT/CRT-D implantation [28.0%(44/157) vs 18.0%(160/877)], value of creatinine [(105.3±25.3) vs (96.8±35.0) μmol/L], IMPACT score [(6.9±2.4) vs (4.2±2.9) point], serum total bilirubin [19.7(13.6, 30.3) vs 23.7(15.8, 36.8) μmol/L], mean pulmonary arterial pressure [(26.0±10.3) vs (29.7±11.0) mmHg (1 mmHg=0.133 kPa)] and ischemic duration [(274.7±105.6) vs (296.0±120.4) min] (all P<0.05). No significant inter-group difference existed in in-hospital mortality [4.5%(7/157) vs 4.7%(42/887)] or 1-year mortality [5.7%(9/157) vs 6.5%(58/887)] ( P=0.88, P=0.70); in-hospital mortality and 1-year postoperative mortality of recipients aged ≥65 years 10.0%(5/50) and 14.0%(7/50) were both higher than those aged <65 year [1.9%(2/107), 1.9%(2/107)]. The differences were both statistically significant ( P=0.02, P<0.01). Kaplan-Meier survival analysis indicated that long-term survival rate was lower in elder group than that in non-elder group and the difference was statistically significant ( P=0.046). Long-term survival rate of elders aged ≥65 year was lower than that of non-elders aged <65 year and the difference was statistically significant ( P<0.01). Regression analysis indicated that age of recipient ≥65 year, preoperative creatinine ≥133 μmol/L, preoperative total bilirubin ≥25.65 μmol/L and preoperative support of extracorporeal membrane oxygenation (ECMO) were independent risk factors for short/long-term mortality post-HT. Conclusion:Although long-term prognosis of elderly recipients is slightly worse than that of non-elderly ones, in-hospital mortality and one-year postoperative mortality are similar between two groups. For elderly recipients with fewer comorbidities and better preoperative status, they should not be excluded from HT based solely upon age. The long-term prognosis of recipients aged ≥65 year remains poor and HT decisions should be made carefully.

Objective To investigate the mechanism of mikanolide derivative LY19380b in inhibiting the growth of human leukemia cell HEL.Methods Methyl thiazolyl tetrazolium(MTT)assay was used to detect the effect of compound LY19380b on the proliferation of human tumor cells,flow cytometry was used to determine cell cycle,Annexin V-FITC/PI double staining and Hoechst 33258 staining were used to determine apoptosis.Western blot was used to analyze effects of LY19380b on cell cycle and apoptosis-related proteins.Results LY19380b had anti-proliferative activity on different human tumor cells,and significantly inhibited the growth of human leukemia cell HEL.It can also induce apoptosis and affect the cell cycle of HEL.In addition,LY19380b could significantly increase the expressions of P53,BIM,BID,BAD,BAX,FLIP,P21 and Cyclin B1 proteins,while decreased the expressions of Bcl-2,p-CDC25C,p-AKT,p-STAT3 and p-ERK proteins.Conclusion By increasing the expressions of pro-apoptotic proteins BIM,BID,BAD and BAX,decreasing the expression of anti-apoptotic protein Bcl-2,LY19380b induced the apoptosis of human leukemia cell HEL,and upregulated the expressions of P21 and Cyclin B1,thus leading to cell cycle arrest in HEL.