【Objective】 To investigate the risk factors and predictive effectiveness of prostate imaging reporting and data system (PI-RADS) score for patients with clinically significant prostate cancer (CsPCa) whose PI-RADS score was 3, so as to provide evidence for the diagnosis and treatment. 【Methods】 The clinical and multi-parameter magnetic resonance imaging (mpMRI) data of 153 CsPCa patients treated during Jan.2017 and Dec.2021 whose PI-RADS score was 3 were retrospectively analyzed. With PI-RADS score of 3 as the independent risk factor for CsPCa, the other relevant independent risk factors in predicting CsPCa were evaluated. 【Results】 Univariate and multivariate analyses showed that prostate-specific antigen (PSA) density and apparent dispersion coefficient (ADC) were independent risk factors for the diagnosis of CsPCa (P<0.05). Analysis of receiver operating characteristic (ROC) curve showed that combined PSA density and ADC were more effective than PSA density and ADC alone (P<0.05). 【Conclusion】 The combination of PSA density and ADC can guide clinicians to identify high-risk CsPCa patients from patients with PI-RADS score of 3 points.

Objective:To understand the relationship between the RNA shedding time of SARS-CoV-2 infected persons and the single nucleotide mutation of the virus, the population of infected persons, underlying diseases and other factors, so as to provide more clues for the study of SARS-CoV-2 infection dynamics.Methods:The data of epidemiology, clinical manifestations, and underlying diseases of infected persons in a cluster epidemic of COVID-19 in Jiangsu province from July to September 2021 were collected. Nasopharyngeal swab samples of cases were collected, and the whole genome of the virus was sequenced by second-generation sequencing technology. The online analysis platform was used to judge the virus type and analyze the mutation site, and Cox proportional risk model was used to analyze the relationship between the RNA shedding time of SARS-CoV-2 and various research factors.Results:There were 350 persons who finally obtained the whole genome sequence of the virus in this COVID-19 outbreak, of which 60.3% were female, the median age was 49 years old (interquartile range, IQR: 37-65 years old)), and the median time of virus shedding was 33 days ( IQR, 26-44 days). The whole-genome sequencing analysis showed that compared with the Wuhan reference strain sequence, the infected persons’ sequence had 34~41 nucleotide mutation sites, belonging to VOC/Delta variant (B.1.617.2 evolutionary branch), and C346T, C1060T, T2803C, T7513C, A29681C were the main single nucleotide polymorphisms (SNPs) of this epidemic. Cox regression analysis showed that age, underlying disease, clinical classification, vaccination, SNP T2803C and T7513C had an impact on the RNA shedding time of SARS-CoV-2. The adjusted multivariate Cox regression result showed that age [ HR=0.73, 95% CI (0.55, 0.95)] and T7513C [ HR=0.37, 95% CI (0.18, 0.77)] were still the risk factors for the extension of SARS-CoV-2 RNA shedding time. Conclusions:This study analyzed the effects of the individual factors and viral single nucleotide variations on the time of viral RNA shedding. Those who were older, suffered from hypertension, had more severe clinical symptoms, were not vaccinated or incompletely vaccinated, and had T7513C mutation in the infected virus, had a risk of a long RNA shedding time of SARS-CoV-2, which should be given special attention and follow-up after rehabilitation.

Objective:To investigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with oral paroxetine in the treatment of older adult patients with severe depression and its effects on the scores of the Hamilton Rating Scale for Depression (HAMD), the Mini-Mental State Examination (MMSE), and Activities of Daily Living (ADL).Methods:A total of 192 older adult patients with severe depression who received treatment in Shaoxing 7 th People's Hospital from January 2018 to December 2019 were included in this study. They were randomly assigned to receive either oral paroxetine (control group, n = 96) or rTMS + oral paroxetine (observation group, n = 96). All patients received 1 month of treatment. Clinical efficacy was compared between the two groups. HAMD, MMSE, and ADL scores pre- and post-treatment and the incidence of adverse events during the treatment were compared between the two groups. Results:Total response rate was significantly higher in the observation group than in the control group [96.88% (93/96) vs. 89.58% (86/96), χ2 = 4.04, P < 0.05]. HAMD scores post-treatment were significantly lower in the observation group than in the control group [(6.43 ± 2.33) points vs. (11.32 ± 2.02) points, t = 15.53, P < 0.05]. MMSE and ADL scores post-treatment in the observation group were (29.13 ± 3.01) points and (71.52 ± 5.32) points, respectively, which were significantly higher than those in the control group [(24.65 ± 2.79) points, (69.65 ± 5.17) points, t = 10.69, 2.47, P < 0.05]. There was no significant difference in the incidence of adverse events between the two groups ( P > 0.05). Conclusion:The combined therapy of rTMS and oral paroxetine is highly effective on severe depression in older adult patients. It can improve cognitive function and the activities of life living.

Objective : To investigate the effect of chemotherapeutic drug resistance induced by CLDN18⁃ARH⁃GAP26 fusion mutation gene in gastric cancer cells , and to investigate the sensitization effect of ginsenoside in the treatment of chemotherapeutic drug resistance caused by the expression of CLDN18⁃ARHGAP26 fusion mutation gene. Methods : The side population (SP) cells and non⁃side population ( NSP) cells of gastric cancer cell line BGC⁃823 were labeled with immunomagnetic bead antibody , and the lentiviral vector with overexpression of CLDN18⁃ARHGAP26 fusion mutation gene was selected for transfection with NSP cells. qPCR was used to detect the mRNA levels of CLDN18⁃ARHGAP26 fusion mutation and ATP Binding Cassette Subfamily G Member 2 (ABCG2) . The expression of EMT⁃related proteins E ⁃Cadherin and Vimentin was detected by Western blot. The sensitivity of transfected cells to oxaliplatin was detected by CCK⁃8. The effect of ginsenoside on drug resistance of transfected cells was detected by CCK ⁃ 8 . The expression of E ⁃ Cadherin and Vimentin in transfected cells was detected by Western blot after ginsenoside treatment. Results : qPCR detection showed that the expression of CLDN18⁃ARH⁃GAP26 fusion mutant gene in NSP cells transfected with overexpressed CLDN18⁃ARHGAP26 fusion mutant gene was significantly higher than that of the non⁃transfected group , and the expression of ABCG2 mRNA was significantly cells with over⁃expressed CLDN18⁃ARHGAP26 fusion mutation gene was lower than that in the non⁃transfected transfected cells to oxaliplatin was lower than that in the non⁃transfected group. The survival rate of transfected cells sion of E ⁃Cadherin protein in the transfected cells treated with ginsenoside was higher than that in the untreated group , and the expression of Vimentin protein was lower than that in the untreated group. Conclusion Ginsenoside can reverse cell EMT transformation and oxaliplatin resistance induced by CLDN18⁃ARHGAP26 fusion mutated gene expression in gastric cancer tissues.

Copy number variations (CNVs), which can affect the role of long non-coding RNAs (lncRNAs), are important genetic changes seen in some malignant tumors. We analyzed lncRNAs with CNV to explore the relationship between lncRNAs and prognosis in bladder cancer (BLCA). Messenger RNA (mRNA) expression levels, DNA methylation, and DNA copy number data of 408 BLCA patients were subjected to integrative bioinformatics analysis. Cluster analysis was performed to obtain different subtypes and differently expressed lncRNAs and coding genes. Weighted gene co-expression network analysis (WGCNA) was performed to identify the co-expression gene and lncRNA modules. CNV-associated lncRNA data and their influence on cancer prognosis were assessed with Kaplan-Meier survival curve. Multi-omics integration analysis revealed five prognostic lncRNAs with CNV, namely

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.

Objective To evaluate the clinical value of holographic image navigation in urological laparoscopic and robotic surgery.Methods The data of patients were reviewed retrospectively for whom accepted holographic image navigation laparoscopic and robotic surgery from Jan.2019 to Dec.2019 in Beijing United Family Hospital and other 18 medical centers,including 78 cases of renal tumor,2 cases of bladder cancer,2 cases of adrenal gland tumor,1 cases of renal cyst,1 case of prostate cancer,1 case of sweat gland carcinoma with lymph node metastasis,1 case of pelvic metastasis after radical cystectomy.All the patients underwent operations.In the laparoscopic surgery group,there were 27 cases of partial nephrectomy,1 case of radical prostatectomy,2 cases of radical cystectomy and 2 cases of adrenalectomy.In the da Vinci robotic surgery group of 54 cases,there were 51 cases of partial nephrectomy,1 case of retroperitoneal lymph node dissection,1 case of retroperitoneal bilateral renal cyst deroofing and 1 case of resection of pelvic metastasis.There were 41 partial nephrectomy patients with available clinical data for statistic,with a median age of 53.5 years (range 24-76),including 26 males and 15 females.The median R.E.N.A.L score was 7.8 (range 4-11).Before the operation,the engineers established the holographic image based on the contrast CT images and reports.The surgeon applied the holographic image for preoperative planning.During the operation,the navigation was achieved by real time fusing holographic images with the laparoscopic surgery images in the screen.Results All the procedures had been complete uneventfully.The holographic images helped surgeon in understanding the visual three-dimension structure and relation of vessels supplying tumor or resection tissue,lymph nodes and nerves.By manipulating the holographic images extracorporeally,the fused image guide surgeons about location vessel,lymph node and other important structure and then facilitate the delicate dissection.For the 41 cases with available clinical data including 23 cases of robotic-assisted partial nephrectomy and 18 cases of laparoscopic nephrectomy,the median operation time was 140 (range 50-225) min,the median warm ischemia time was 23 (range 14-60) min,the median blood loss was 80(range 5-1 200) ml.In the robotic surgery group,the median operation time was 140 (range 50-215)min,the median warm i schemia time was 21 (range 17-40)min,the median blood loss was 150(range 30-1 200)ml.In the laparoscopic surgery group,the median operation time was 160(range 80-225)min,the median warm ischemia time was 25 (range 14-60)min,the median blood loss was 50 (range 5-1 200) ml.All the patients had no adjacent organ injury during operation.There were 2 cases with Clavien Ⅱ complications.One required transfusion and the other one suffered hematoma post-operation.However,the tumors were located in the renal hilus for these 2 cases and the R.E.N.A.L scores were both 11.Conclusions Holographic image navigation can help location and recognize important anatomic structures during the surgical procedures..This technique will reduce the tissue injury,decrease the complications and improve the success rate of surgery.

AIM: To analyze the difference of endonuclease domain containing 1 (ENDOD1) expression be-tween benign prostatic hyperplasia ( BPH ) tissues and prostate cancer ( PCa ) tissues and to investigate the effect of ENDOD1 on the biological function of human prostate cancer cells .METHODS: The BPH samples ( n=20 ) and PCa samples (n=21) were processed and analyzed according to the instruction of immunohistochemical (IHC) staining.The mRNA and protein levels of ENDOD 1 in the normal prostate epithelial cells and prostate cancer cells were evaluated by RT -qPCR and Western blot , respectively .The recombinant plasmids pCMV-N-Flag-ENDOD1 was constructed and was trans-fected into the human prostate cancer cells .The proliferation , apoptosis , migration and invasion abilities of the prostate cancer cells were evaluated by MTT assay , flow cytometry, Transwell migration and Matrigel invasion assays , respectively. RESULTS:The analysis of variance of the immunoreactivity score showed that PCa tissues with high Gleason score dis -played significantly lower ENDOD1expression than that with low Gleason score and BPH (P<0.05).The expression of ENDOD1 at mRNA and protein levels in PC3 cells and DU145 cells was significantly lower than that in the LNCap cells (P<0.05).The proliferation of DU145 transfected with ENDOD1 was inhibited.The flow cytometry indicated that ENDOD1 over-expression in the DU145 cells resulted in a notable increase in G0/G1 phase arrest (P<0.05), but the ap-optotic rates showed no statistical difference .The results of Transwell assay showed that migration and invasion abilities of the cells were also inhibited after transfection with over-expressing ENDOD1 plasmid (P<0.05).CONCLUSION: The expression of ENDOD1 significantly decreased in prostate cancer with high Gleaon score .Meanwhile, the ENDOD1 is spe-cifically down-regulated in androgen independent prostate cancer (AIPC) cell lines.Over-expression of ENDOD1 remark-ably inhibits the proliferation , migration and invasion abilities of AIPC .

[Abstrict]Objective To explore the key points and clinical value of combined direct and indirect extracranial-in?tracranial (EC-IC) bypass in patients with adult moyamoya disease. Methods Retrospective analysis of combined revas?cularization surgery in 25 adult patients with moyamoya disease. The frontal branch and parietal branch of the superficial temporal artery (STA) were dissected. Combined revascularization surgery consisted of direct (anastomosis between the su?perficial temporal artery and cortical branch of the middle cerebral artery) and indirect (encephalodurogaleosynan-giosis EDAS) surgeries. Clinical status was evaluated using the modified Rankin Scale and NIHSS score at 1 day before, 1 week and 3 months after surgery. Results Thirty lateralities were successfully performed on 25 patients. Postoperative angiogra?phy or CTA and cranial computer tomography perfusion imaging(CTP) were conducted to examine the patency of the di?rect anastomosis and cerebral blood flow in 23 patientswithin 1 weeks after surgery . The results showed that the anasto?motic vascular patency was excellent and the cerebral blood flow increased in parallel to the relief of the patients’s isch?emic symptoms. The median mRS scores were 3 (1,3) before surgery, 2 (1,3) 1 week and 1 (0,3) 1 month after surgery.The median mRS scores were significantly improved (Z=15.14, P<0.01). The median NIHSS scores was 5 (4,8) preopera?tively and 4(2,7) postoperation 1 week and 3(1,4) 3 months. The median NIHSS scores were also significantly improved (Z=11.36, P<0.01). Unfortunately, two patients had complication and left hemiparesis. One patient complicated with con?tralateral hemisphere infarction and the another one complicated with ipsilateral hemispheric hemorrhage after operation. Conclusions Combined revascularization surgery may result in satisfying improvement in clinical, angiographic, and he?modynamic states and prevention of recurrent stroke. The stabilized hemodynamic is the key point in peroperative period for moyamoya patients.

OBJECTIVETo explore the subcellular localization of ataxin-3 and the effect of polyglutamine (polyQ) expansion mutation on the morphology of mitochondrion, golgi apparatus and endoplasmic reticulum.

METHODSTransient transfection was employed to build cell models expressing wild-type or mutant ataxin-3 proteins. Indirect immunofluorescence was applied to identify markers of organelle membrane. The results were observed under a laser scanning confocal microscope.

RESULTSNo co-localization was observed for ataxin-3 protein and mitochondrial marker TOM20, but the percentage of cells with mitochondrial fragmentation has increased in cells expressing mutant ataxin-3 (P<0.05). No co-localization was observed for ataxin-3 protein and golgi marker GM130, and mutant ataxin-3 did not cause golgi fragmentation. Wide type and polyQ-expanded ataxin-3 both showed partial co-localization with ER marker calnexin. The latter showed more overlap with calnexin, and the overlapping signals were mostly located in the places where aggregates were situated.

CONCLUSIONPolyQ-expanded ataxin-3 protein may indirectly affect the integrity of mitochondria, but may cause no effect on the structure and functions of golgi apparatus. Endoplasmic reticulum may be another place where extended ataxin-3 protein can induce cytotoxicity in addition to the nucleus.

Ataxin-3 ; Cytoplasm ; genetics ; metabolism ; Endoplasmic Reticulum ; genetics ; metabolism ; HeLa Cells ; Humans ; Machado-Joseph Disease ; genetics ; metabolism ; Mitochondria ; genetics ; metabolism ; Nerve Tissue Proteins ; genetics ; metabolism ; Nuclear Proteins ; genetics ; metabolism ; Protein Transport ; Repressor Proteins ; genetics ; metabolism