Objective:To explore the expression of transmembrane protein 9(TMEM9)as an oncogene in prostate cancer(PCa),and to examine its effect on the proliferation and invasion of PCa cells as well as on the Wnt/β-catenin signaling pathway and autophagy of PCa cells by intervening with its expression.Methods:The Cancer Genome Atlas was used for pan-cancer analysis of TMEM9 expres-sion levels in different tumors,and TMEM9 protein and messenger ribonucleic acid(mRNA)levels in clinical PCa and prostatic hyper-plasia specimens were analyzed.Real-time quantitative polymerase chain reaction and western blotting were used to analyze TMEM9 expression levels in different PCa cell lines.Cell counting,terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL),and Transwell assay were used to analyze cell proliferation,apoptosis,and PCa cell invasion,respectively.Subcutaneous tu-morigenesis in nude mice was used to analyze tumor proliferation in vivo.Western blotting was used to analyze the expression of autophagy-related pathway proteins,and transmission electron microscopy and immunofluorescence colocalization were used to deter-mine the colocalization of autophagosomes and lysosomes.Results:TMEM9 was highly expressed in PCa.The mRNA and protein ex-pression levels of TMEM9 were higher in PCa tissues than in prostatic hyperplasia tissues.The expression of TMEM9 was highest in PC3 cells(human PCa cells)(t=17.150,P<0.01).In TMEM9-knocked down PC3 cells,the proliferation(t=3.165,P<0.05)and inva-sion(F=76.620,P<0.01)significantly decreased,and apoptosis(t=13.530,P=0.010)significantly increased.After knockdown of TMEM9,the volume(F=1 699.000,P<0.01)and weight(t=9.057,P<0.01)of subcutaneous tumors in nude mice were reduced,and tu-mor growth was inhibited.TMEM9 regulated the Wnt/β-catenin signaling pathway and inhibited the AKT-mTOR signaling pathway to promote autophagy in PCa cells.Conclusion:TMEM9 inhibits the AKT-mTOR signaling pathway and promotes the proliferation and invasion of PCa cells through autophagy.

Hyaluronic acid (HA) possesses excellent biocompatibility, biodegradability, and non-immunogenicity, and exhibits active targeting capability to receptors such as cluster of differentiation 44 (CD44). Therefore, HA has become an important material for the design and preparation of drug delivery carriers in recent years. HA is rich in functional groups that can be chemically modified, but different modification methods and sites can affect its biological properties. This paper summarizes and discusses the effects of chemical modification on the biological properties of HA based on the formation mechanisms of such properties, as well as the derivatization and characterization methods of HA, so as to provide some reference for rational research on chemical modification of HA.

Objective To construct a risk prediction model of mild cognitive impairment(MCI)in the Chinese elderly population based on ensemble learning methods and verify it,to intervene in time and delay the progression of MCI.Methods A total of 8691 elderly people in the Chinese longitudinal health longevity study(CLHLS)from 2008 to 2018 were selected as the research objects,and the data from 2008 to 2014 were used as the training set.Data from 2014 to 2018 as a validation set.The Chinese version of the mini-mental state examination(CMMSE)was used to assess the cognitive status of the participants.Recursive feature elimination-random forest(RFE-RF),Boruta,mutual information(MI),and extra trees classifier(ETC)identified the predictors and screened out the common predictors.Use logistic regression(LR),random forest(RF),linear discriminant analysis(LDA),K-nearest neighbors(KNN),and na?ve bayes(NB)as the five single basic models,and a stacking ensemble model that integrates these basic models to predict the risk of mild cognitive impairment in elderly Chinese.Accuracy,precision,recall,and F1-score,as well as the area under the receiver operating characteristic(AUROC)and the area under the precision-recall curve(AUPRC),were used to evaluate the performance of the models.Results The performance of the stacking ensemble model under different feature selection algorithms is superior to any single base model,with AUROC greater than 0.9 in all cases.The feature selection algorithm ETC+stacking ensemble model performs best,and the AUROC and AUPRC in the test set are 0.912 and 0.872,respectively.Conclusion The stacking model shows superior performance in predicting MCI.This provides strong support for the strategy of healthy aging in China by timely identifying the high-risk groups of MCI,reducing the heavy burden of MCI brought by the elderly.

Objective To construct a risk prediction model of mild cognitive impairment(MCI)in the Chinese elderly population based on ensemble learning methods and verify it,to intervene in time and delay the progression of MCI.Methods A total of 8691 elderly people in the Chinese longitudinal health longevity study(CLHLS)from 2008 to 2018 were selected as the research objects,and the data from 2008 to 2014 were used as the training set.Data from 2014 to 2018 as a validation set.The Chinese version of the mini-mental state examination(CMMSE)was used to assess the cognitive status of the participants.Recursive feature elimination-random forest(RFE-RF),Boruta,mutual information(MI),and extra trees classifier(ETC)identified the predictors and screened out the common predictors.Use logistic regression(LR),random forest(RF),linear discriminant analysis(LDA),K-nearest neighbors(KNN),and na?ve bayes(NB)as the five single basic models,and a stacking ensemble model that integrates these basic models to predict the risk of mild cognitive impairment in elderly Chinese.Accuracy,precision,recall,and F1-score,as well as the area under the receiver operating characteristic(AUROC)and the area under the precision-recall curve(AUPRC),were used to evaluate the performance of the models.Results The performance of the stacking ensemble model under different feature selection algorithms is superior to any single base model,with AUROC greater than 0.9 in all cases.The feature selection algorithm ETC+stacking ensemble model performs best,and the AUROC and AUPRC in the test set are 0.912 and 0.872,respectively.Conclusion The stacking model shows superior performance in predicting MCI.This provides strong support for the strategy of healthy aging in China by timely identifying the high-risk groups of MCI,reducing the heavy burden of MCI brought by the elderly.

Background and purpose:Prostate-speciifc membrane antigen (PSMA), a cell surface protein with high expression in prostate carcinoma (PC) cells, is an attractive target for PC imaging and therapy. Small-molecule radiopharmaceuticals targeting PSMA can detect the location and extent of disease with high sensitivity and speciifcity. The aim of this study was to evaluate the value of technetium-99m-labelled small molecule against PSMA (HYNIC-Glu-Urea-A,99mTc-PSMA) for the detection of primary and metastatic prostate cancers.Methods:Twenty-four prostate cancer patients and 1 patient with benign prostate hyperplasia received whole-body scan followed by abdominopelvic SPECT/CT 2 h after intravenous injection of99mTc-PSMA. Tumor to muscle uptake ratio of99mTc-PSMA was calcu-lated using region of interest (ROI) technology. The sensitivity and specificity of99mTc-PSMA were evaluated. The relationships between positive99mTc-PSMA and prostate speciifc antigen (PSA) level and Gleason Score were analyzed. Results:Based on per patient, the sensitivity and speciifcity of99mTc-PSMA were 72.7% (16/22) and 100% (3/3), re-spectively. The level of PSA in patients with positive99mTc-PSMA imaging was signiifcantly higher than that in patients with negative99mTc-PSMA imaging [(PSA median 17.31 ng/mL, range: 2.26-3 239.0 ng/mL)vs(PSA median 0.49 ng/mL, range: 0.07-9.28 ng/mL)] (Z=-3.51,P<0.001). Among newly diagnosed patients and recurrent patients with PSA more than 2.0 nm/mL, it was apparent that99mTc-PSMA imaging was able to detect lesions with improved sensitivity of 94.1% (16/17). Gleason Scores between positive99mTc-PSMA patients and negative99mTc-PSMA patients were not significantly different (Z=-0.69,P=0.52).Conclusion:With the combination of whole-body scan and tomography, 99mTc-PSMA SPECT/CT can be an excellent and speciifc molecular imaging strategy to detect prostate cancer and its metastases.

Objective To improve the diagnosis and treatment of ACTH-independent macronodular adrenal hyperplasia(AIMAH).Methods A 51-year-old female patient with Cushing's syndrome caused by AIMAH was reported.Elevated early morning plasma cortisol levels,increased 24 h urinary free cortisol excretion,and loss of the normal circadian rhythm in cortisol secretion were presented.There was no suppression of cortisol secretion by administration of low-and high-dose overnight dexamethasone suppression test.Cardio-pulmonary function was very bad with the highest blood pressure reaching 300/120 mm Hg( 1 mm Hg=0.133 kPa).Initially,she was treated with mitotane(60 mg/d),but was not effective.After taking ketoconazole (800 mg/d)for 5 days,cardio-pulmonary function was not effectively improved with blood pressure only descending to 180/120 mm Hg.Orthopnoea appeared and Spo2fell once to 75％.The patient had to undergo right total adrenalectomy immediately.ResultsThe mass resected was 10 cm× 10 cm in size and weighted 67.5 g.Histological examination of the removed adrenal revealed nonpigmented macronodular cortical hyperplasia.The patient continued to take ketoconazole (400-800 mg/d)from the 6th day of the operation without steroid replacement therapy in that period.With normal cortisol levels( plasma cortisol at 8:00 was 18.65 μg/dl,24 h urinary free cortisol was 78.75 μmol),she left hospital after the general condition had been improved.During the following updated 10 months follow up,the indexes of her laboratory examination were maintained normal.ConclusionIndividualized therapy should be adopted for the patient with AIMAH.The medication is useful to suppress the adrenal gland cortisol production for those with progression of symptoms,very high blood pressure,hypokalemia and hypoproteinemia.Once the cardio-pulmonary function improves,the target organ should be resected as soon as possible.The supplement of cortisol is not appropriate during the perioperative period.The unilateral adrenalectomy is an effective treatment for AIMAH.