SciCombinator

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Journal: Zhonghua yi xue za zhi

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Objective: To compare the decolorization efficiency of lignin peroxidase (LiP), manganese peroxidase (MnP) and laccase on eumelanin and pheomelanin, and to investigate the effect of topical administration of LiP solution on hyperpigmented guinea pigs skin induced by 308 nm excimer light. Methods: Pheomelanin-enriched specimens were prepared from human hair and cutaneous melanoma tissue using alkaline lysis method.Synthetic eumelanin was purchased from a commercial supplier.The same amount (0.02%) of melanin was incubated with the equal enzyme activity (0.2 U/ml) of ligninolytic enzymes for 3 h respectively.The absorbance at 475 nm (A(475)) in the enzyme-catalyzed solution was measured using ELISA microplate reader.The experimental hyperpigmentation model was established in the dorsal skin of brownish guinea pigs using 308 nm excimer light radiation.LiP and heat-inactivated LiP solution were topically applied at each site.Meanwhile, 3% hydroquinone and vehicle cream were used as control.The skin color (L value) was recorded using a CR-10 Minolta chromameter.Corneocytes were collected using adhesive taping method.The amount and distribution of melanin in the corneocytes and skin tissues was visualized by Fontana-Masson staining. Results: All three ligninolytic enzymes showed various degree of eumelanin and pheomelanin decolorization activity.The decolorization activity of LiP, MnP and laccase was 40%-70%, 22%-42% and 9%-21%, respectively.The similar lightening was shown in the skin treated with LiP solution and 3% hydroquinone.The amount of melanin granules in the corneocytes was 199±11 by LiP, which was less than that in untreated control (923±12) and heat-inactive control (989±13). The amount of melanin was decreased in the whole epidermis treated with hydroquinone, the epidermis thickness was increased as well. In contrast, melanin of LiP group was decreased only in the superficial epidermis, the epidermis thickness seemed to be normal. Conclusion: LiP exerts a potent decolorization activity for hair- or skin-derived pheomelanin as well as eumelanin.It remains to be further investigated whether LiP serves as a substitute for hydroquinone in skin lightening products.

Concepts: Enzyme, Skin, Melanin, Epidermis, Human skin color, Melanocyte, Ligninase, Skin whitening

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Objective: To systematically compare the differences in the detection rate of prostate cancer with fusion targeting biopsy and systemic biopsy. Methods: A computer-based search of PubMed, Medline, China Biomedical Literature Database and Wanfang database (from the beginning of establishment of library to October 2016) on the detection rate of prostate cancer by fusion targeting biopsy and systemic biopsy was performed manually.The inclusion and exclusion criteria were formulated by 2 reviewers, and the data were extracted and evaluated respectively. RevMan5.3 software was used to analyze the detection rate of prostate cancer by two biopsy methods. Results: A total of 15 related clinical studies were included, 5 337 cases were enrolled in the study, including 2 667 cases of targeted fusion biopsy and 2 670 cases of routine systemic biopsy. The results showed that the overall detection rate of prostate cancer in targeting fusion biopsy was significantly higher than that of conventional systemic biopsy (OR=1.16, 95% CI 1.04-1.30, P=0.007). The detection rates of prostate cancer with different risk grades by two biopsy methods were conducted. We found that targeted fusion biopsy had a significant advantage compared with conventional system biopsy (OR=1.37, 95% CI 1.19-1.58, P<0.05) in middle and high risk prostate cancer with Gleason ≥ 7 points. In low-risk prostate cancer patients with Gleason score <7, the detection rate of prostate cancer by targeted fusion biopsy was lower (OR=0.76, 95% CI 0.65-0.89, P<0.05) than that of conventional systemic biopsy. Conclusions: Targeted fusion biopsy was significantly better than systemic biopsy in the overall detection rate of prostate cancer and the detection rate of the middle and high risk prostate cancer with Gleason ≥7 points. However, systemic biopsy performed better in patients with Gleason<7 points of low-risk prostate cancer.

Concepts: Cancer, Metastasis, Oncology, Obesity, Prostate cancer, Radiation therapy, BRCA2, Screening

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Objective: To explore the minimally invasive techniques and outcome of carotid ophthalmic artery aneurysms clipping via a frontolateral approach. Methods: The clinical data of 95 patients with carotid ophthalmic artery aneurysms treated via frontolateral approach in the last 1.5 years in Beijing Tiantan Hospital and Beijing Anzhen Hospital were analyzed retrospectively.Before the operation, digital subtraction angiogram (DSA) was performed among all patients.The patients were divided into two groups by the lateral approach.According to preoperative classification, surgical characteristics and prognosis were summarized. Results: Ninety-five cases of ophthalmic aneurysms were divided into type Ⅰ of 44 cases (46.3%), type Ⅱ of 34 cases (35.7%) and type Ⅲ of 17cases (17.9%), according to the results of DSA.The diameter of aneurysm was <10 mm (35 cases), 10-25 mm (34 cases), and >25 mm (26 cases). In the 17 cases of subarachnoid hemorrhage (SAH), 8 cases were ruptured carotid-ophthalmic artery aneurysms.Among those 95 patients, 93 were clipped successfully, 2 was trapped.Multiple aneurysms in 5 cases were treated in one surgical session through the same approach.No aneurysm residual was found after postoperative CTA review.Ipsilateral vision of 3 cases were decline.Cerebral infarction was appeared in 9 cases.All the others had a good recovery. Conclusions: The carotid-ophthalmic artery aneurysms could be well exposed. Microsurgery through frontolateral approach has the advantages such as minimal invasion, less effect on the patients' look and simple procedure.The frontolateral approach is safe and effective in surgery for ophthalmic segment of the internal carotid artery aneurysms.

Concepts: Atherosclerosis, Stroke, Surgery, Internal carotid artery, Common carotid artery, Subarachnoid hemorrhage, Arteries of the head and neck, Ophthalmic artery

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Objective: To investigate the therapeutic efficacy of tonsillectomy for patients with recurrence of IgA nephropathy (IgAN) after kidney transplantation. Methods: From May 2014, tonsillectomy was performed in 11 renal transplant patients with biopsy-proved recurrent IgAN. In a median follow-up of 14 (4-38) months, data of proteinuria, hematuria, estimated glomerular filtration rate (eGFR), and serum levels of IgA in these patients were compared before and after tonsillectomy.Patient’s survival and renal graft survival were also summarized. Results: A remission of proteinuria was observed in 8 patients after tonsillectomy, and this status maintained well in the subsequent follow-up.Three patients had no or minimal reduction of proteinuria after tonsillectomy and returned to dialysis within 1 year after tonsillectomy.Possible causes could be severe primary IgAN of crescentric glomerulonephritis, IgAN recurrence in kidney retransplantation, and late tonsillectomy after IgAN recurrence.Serum levels of IgA significant decreased and no patients developed acute rejection or infection after tonsillectomy.In the 1-year follow-up, no patients died and grafts survived well in 8 out of 11 patients. Conclusions: Tonsillectomy may represent an effective and reliable way to treat recurrence IgAN after kidney transplantation, and may be applied widely in the future clinical management. However, early intervention is critical and effects may depend on the pathological features of primary IgAN.

Concepts: Renal failure, Chronic kidney disease, Kidney, Nephrology, Organ transplant, Kidney transplantation, Glomerulonephritis, IgA nephropathy

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Objective: To analyze the risk factors of postoperative intestinal obstruction (POI) in patients undergoing robot-assisted laparoscopic radical prostatectomy (RARP). Methods: The clinical data of 573 patients receiving RARP from January to December 2019 in Nanjing Drum Tower Hospital were analyzed retrospectively. According to the occurrence of POI, the cases were divided into the occurrence group and the non-occurrence group. The clinical data of the two groups were compared and the risk factors of POI were investigated by multivariate logistic regression. Results: Forty-five of 573 patients (7.9%) had POI. Between the two groups, preoperative underlying diseases (cardiopathy, COPD, hypoalbuminemia), preoperative chemotherapy, preoperative WBC, operation time, blood loss, blood transfusion rate, postoperative early fever, length of stay were statistically significant (P<0.05). Multivariable logistic regression analysis showed that heart disease (OR=2.331, P=0.036), COPD (OR=4.285, P=0.001), hypoalbuminemia(OR=2.142, P=0.026), blood loss (≥4.26 ml/kg) (OR=2.388, P=0.010), operative time (≥225 min) (OR=4.200, P<0.001), and postoperative early fever (OR=2.773, P=0.004) were independent risk factors for POI after RARP. Conclusions: The incidence of POI following RARP is related to multiple perioperative factors. Improving the preoperative heart and lung function, correcting hypoalbuminemia, reducing intraoperative bleeding, shortening the operation time, and preventing early postoperative infection may be important measures to reduce the risk of POI in RARP patients.

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Objective: To investigate the feasibility and safety of minimally invasive radical prostatectomy for prostate cancer patients without preoperative prostate biopsy in the new era of the continuous development of comprehensive new imaging diagnostic mode and minimally invasive surgery technology. Methods: From August 2018 to October 2019, 17 patients with prostate cancer were enrolled in this study in the Cancer Hospital, Chinese Academy of Medical Sciences. All patients were highly suspected of prostate cancer by PSMA-PET/CT-based imaging diagnostic techniques and underwent 3D laparoscopic radical prostatectomy without prostate biopsy. The perioperative data, postoperative pathology, postoperative complications and follow-up results were recorded and analyzed. Results: The average age of 17 patients with prostate cancer was (65±7) years. The body mass index (BMI) average was (24.4±3.0) kg/m(2). The American Society of Anesthesiologists (ASA) score was 1 (1-2) and the Charlson comorbidity index (CCI) score was 1 (0-4). The preoperative value of PSA was (19±11) μg/L. The PSMA PET/CT showed abnormally high expression foci and the great possibility of prostate cancer for all the 17 patients. Prostate puncture biopsy: the results of prostate biopsy were negative in 3 cases. The digital rectal examination found that the prostate volume was Ⅰ or Ⅱ degree large, 10 cases touched hard and the nodule was touched in two cases. Three patients had undergone a previous prostate biopsy, but prostate cancer was not found. All the 17 operations were successfully performed without conversion to open surgery. The surgery time was (85±21) (range from 45 to 120) min, the estimated blood loss was (25±18) (range from5 to 100) ml, the time of intake of liquid diet was (14.3±4.4) h, the intestinal recovery time was (23±10) h, the postoperative activity time was (22±7) h, the drainage duration was (3.7±0.8) d, the postoperative hospital stay was (4.9±1.2) days, and the catheter removal time was (7.4±1.5) days. In the early postoperative period (within 30 days after surgery), no obvious complications occurred. The postoperative final pathology confirmed that all the 17 specimens were prostate cancer. After a median follow-up of 6.5 months, the patient’s urinary control rate reached 81.3% at postoperative 1 month, 92.3% at postoperative 3 months after surgery, and the urinary control rate reached 100% at postoperative 6 months. Postoperative PSA value was (0.08±0.08) μg/L, significantly lower than preoperative PSA level (P<0.001). There was significant difference between the preoperative and postoperative QOL (Quality of life) score (57±5 and 47±5 respectively, P<0.001) which indicated that the patients' postoperative quality of life was greatly improved. Conclusions: It is safe and feasible to perform minimally invasive radical prostatectomy without preoperative prostate biopsy for patients with highly suspected prostate cancer by comprehensive diagnostic mode based on modern new imaging technology.

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Objective: To explore the correlation between prostate imaging report and data system (PI-RADS) score and international society of uological pathology (ISUP) grade of prostate cancer (PCa) and the role of PI-RADS score in predicting the pathological features of clinically significant PCa (csPCa), positive surgical margin and pathological upgrade. Methods: The pathologically positive patients with multi-parameter magnetic resonance image (mpMRI) were included in this study. The patients with prostate specific antigen (PSA)<100 μg/L were divided into two groups: biopsy group (n=523) and RP group (n=215). The correlation between PI-RADS score and ISUP grade and the accuracy of predicting csPCa in the two groups were evaluated. In the RP group, the correlation between PI-RADS score and postoperative pathological grade or degradation and positive incisal margin was further discussed. The patients with PSA≥100 μg/L (171cases in biopsy group and 6 cases in RP group) were not included in the statistical analysis, and the results were simply described. Results: The age, prostate volume, and PSA level of biopsy group and RP group was (72±8) years vs (68±7) years, 48.3 (32-57) cm(3) vs 47.2 (32-54) cm(3), and 26.3(10.2-34.2)μg/L vs 21.7 (9.24-23.95)μg/L, respectively. The PI-RADS scores ≤ 3,4, and 5 in the biopsy group were 109,97, and 317 respectively, and those in the RP group were 61,55, and 99 respectively. There were significant differences in the composition of ISUP grades of different PI-RADS scores between the two groups (P<0.001), and there was a positive correlation between the two groups (r=0.493 in the biopsy group, r=0.671 in the RP group, both P<0.001). Using PI-RADS score to predict csPCa, biopsy group (AUC=0.764, P<0.001, 95%CI:0.710-0.819) and RP group (AUC=0.807, P<0.001, 95%CI:0.735-0.879) had certain accuracy. The PI-RADS score combined with PSA could improve the accuracy of csPCa prediction in the biopsy group (AUC=0.795,P<0.001, 95% CI:0.746-0.843) and the RP group (AUC=0.852, P<0.001, 95%CI:0.789-0.915). Compared with the pathological results of biopsy in the RP group, 52.6% of the patients showed upgrade and degrade of ISUP, and there was insignificant difference in the composition of PI-RADS scores between upgraded and degraded patients (P>0.05). However, 41.7%(27/65) of the patients with ISUP grade 1 biopsies had pathological upgrades that the patients with PI-RADS ≤ 3 accounted for 33.3%, while the patients with PI-RADS>3 accounted for 66.7%, and there was significant difference between the two groups (P<0.05). After RP, 43.3% of the patients had positive surgical margins, and the patients with PI-RADS score ≤ 3, 4 and 5 were 13 (14%), 24 (25.8%) and 56 (60.2%), respectively, while the PI-RADS scores of patients with negative surgical margin were 48 (39.3%), 31(25.4%) and 43(35.2%), respectively. There was significant difference between the two groups (P<0.001). The higher the PI-RADS score, the greater the possibility of the positive surgical margin. For the patients with PSA ≥ 100 μg/L, 98.8% (169/171) patients in the biopsy group had a PI-RADS score 5. The pathological results of all patients were csPCa, of which 85.4% (146/171) had ISUP grade ≥ 4. Among them, 6 cases underwent RP, 5 cases had ISUP grade ≥ 4, all surgical margin were positive, 5 cases had seminal vesicle invasion, 3 cases had capsule invasion and 3 cases had positive pelvic lymph nodes. Conclusion: ThePI-RADS score is correlated with the ISUP grade of PCa. Combined with PSA can accurately predict csPCa. At the same time, the higher PI-RADS score, the more likely the patients with positive incisal margin after RP and Gleason score of 3+3=6 at the time of puncture will be upgraded pathologically.

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Objective: To investigate Notch receptor expression in CD8(+) T cells in patients with prostate cancer, and to assess the influence of Notch signaling pathway on the function of CD8(+)T cells inpatients with prostate cancer. Methods: Forty-five patients with prostate cancer, forty-one patients with nonbacterial prostatitis, and thirty healthy controls who were hospitalized or followed-up in Shanxi Provincial People’s Hospital between November 2017 and June 2018 were enrolled. CD8(+)T cells were purified, and mRNA relative levels of Notch1-4 were semi-quantified by reverse transcriptional real-time PCR. CD8(+)T cells were stimulated with Notch signaling inhibitor γ-secretase inhibitor (GSI). mRNA relative levels of perforin, granzyme B, and FasL were semi-quantified by reverse transcriptional real-time PCR. Percentages of PD-1 and CTLA-4 positive cells were investigated by flow cytometry. Direct contact and indirect contact coculture systems were set up between CD8(+)T cells and prostate cancer cell line LAPC4 cells. The influence of Notch signaling inhibition to CD8(+)T cell cytotoxicitywas assessed by measuringtarget cell death and cytokine secretion. One-Way ANOVA, LSD-t test, and paired t test was used for comparison. Results: mRNA relative levels of Notch1~4 were elevated in CD8(+)T cells from prostate cancer patients when compared with those from healthy controls and nonbacterial prostatitis patients (all P<0.05). There was CD8(+)T cell exhaustion in prostate cancer patients, which presented as decreased mRNA relative levels of perforin, granzyme B, and FasL (all P<0.000 1), as well as increased percentage of PD-1(+)CD8(+) (19.3%±5.4%) and CTLA-4(+)CD8(+)(11.7%±3.9%) cells. CD8(+)T cells from prostate cancer patients induced LAPC cell death was downregulated in direct contact coculture system (28.8%±6.4% vs 37.2%±2.6%, P=0.015). IFN-γsecretion was also reduced ((61.7±10.6)ng/L vs (88.6±20.2)ng/L, P=0.003 2). Inhibition of Notch signaling by GSI increased mRNA of perforin, granzyme B, and FasL in CD8(+)T cells from prostate cancer patients (all P<0.01), while reduced percentage of PD-1(+)CD8(+)(12.6%±2.5% vs 17.4%±4.7%, P=0.005 9) and CTLA-4(+)CD8(+) (12.0%±1.0% vs 14.1%±3.1%, P=0.011)cells. Notch signaling inhibition promoted LAPC4 cell death (34.3%±7.2%, P=0.000 2) which induced by prostate cancer derived CD8(+)T cells, and increased IFN-γ production ((88.4±33.6)ng/L, P=0.008 3). Conclusion: Elevated Notch receptors induced CD8(+)T cells exhaustion in prostate cancer patients.

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Objective: To explore the relationship between insomnia phenotype and mild cognitive impairment (MCI) in young and middle-aged patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: Those patients admitted due to snoring and examined by polysomnography (PSG) in the Sleep Center of the Second Affiliated Hospital of Soochow University from January 2014 to January 2019 were screened. They were between 30 and 60 years old, and their cognitive function was assessed by the Montreal cognitive assessment (MoCA) and their sleep quality was assessed by the Pittsburgh sleep quality index (PSQI). According to the sleep apnea hypopnea index (AHI), the patients were divided into three groups: snoring group (AHI<5 times/h), mild/moderate OSAHS group (5≤AHI≤30 times/h) and severe OSAHS group (AHI>30 times/h). According to the results of PSQI score, the patients were further divided into non-insomnia group (PSQI total score<8) and insomnia group (PSQI total score≥8). The differences of parameters in different groups were compared, and the relationship between OSAHS insomnia phenotype and MCI was analyzed by binary logistic regression model. Results: A total of 2 098 patients with the average age of (42.7±8.4) years old and the average BMI of (26.3±3.6) kg/m(2) were enrolled in the study, including 398 cases in snoring group (including 254 cases in non-insomnia group and 144 cases in insomnia group), 754 cases in mild/moderate OSAHS group (including 446 cases in non-insomnia group and 308 cases in insomnia group) and 946 cases in severe OSAHS group (including 722 cases in non-insomnia group and 224 cases in insomnia group). In the mild/moderate OSAHS group, compared with the non-insomnia group, the proportion of women in the insomnia group was higher with lighter degree of obesity, lighter severity of illness and lighter degree of hypoxia (all P<0.05). In the severe OSAHS group, the general characteristics of insomnia patients were similar to those of the mild/moderate OSAHS group, and the MoCA score of the insomnia group was lower than that of the non-insomnia group [(26.3±2.7) vs (25.5±2.9) points] (P=0.001). In the evaluation of each item of PSQI, the total score and daytime dysfunction score of insomnia patients in mild/moderate OSAHS group and severe OSAHS group was higher than those in snoring group [(11.2±1.9) points, (12.8±2.2) points vs (10.9±2.1) points and (1.5±0.4) points, (1.9±0.8) points vs (0.5±0.5) points], but the score in sleep latency was lower than that in snoring group [(1.5±0.5) points, (1.5±0.5) points vs (2.1±0.8) points] (all P<0.05). After correcting the effects of OSAHS disease severity, hypoxia, awake times, education, age, gender, hypnagogue, BMI, smoking and drinking history, the risk of MCI in insomnia group of severe OSAHS patients was significantly higher than that of non-insomnia group by 49% (OR=1.49, 95%CI: 1.05-2.11). Conclusion: Insomnia phenotype is a common clinical phenotype of OSAHS, and it is a risk factor for MCI in young and middle-aged patients with severe OSAHS.

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Objective: The aim of present study was to investigate the influence of genetic variation of programmed death-ligand 1 (PD-L1) on the prognosis of patients with non-small cell lung cancer (NSCLC) who received platinum-based adjuvant chemotherapy. Methods: This study was designed as a retrospective analysis, and a total of 278 patients with postoperative NSCLC who received platinum-based adjuvant chemotherapy from January 2012 to December 2018 in the Department of Respiratory Medicine of the First affiliated Hospital of Zhengzhou University were included in this study. Biological specimens of the patients were collected during hospitalization. Recurrence status and adverse reactions were evaluated in the hospital during adjuvant chemotherapy. Survival data of the patients were obtained through telephone follow-up after completing the fixed cycle of adjuvant chemotherapy. DNA extracted from the collected hematological specimens was genotyped for PD-L1 gene polymorphism. Additionally, postoperative cancer tissue specimens from 68 patients were collected for RNA extraction in order to perform the PD-L1 mRNA expression analysis. The univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis. Results: Prognostic results indicated that the median disease-free survival (DFS) of the 278 patients with NSCLC was 3.2 years and the median overall survival (OS) was 4.9 years. The prevalence of -1813G>C polymorphism were: GG genotype 173 cases (62.23%), GC genotype 92 cases (33.09%), CC genotype 13 cases (4.68%), the minor allele frequency was 0.21, the distribution of the three genotypes was in accordance with Hardy-Weinberg Equilibrium (P=0.864). In view of the rare frequency of CC genotype, GC and CC genotype were merged in the following analysis. The survival analysis results of the two genotype groups suggested that the median DFS of patients with GG and GC/CC genotype was 2.7 and 4.0 years, which was statistically significant (P=0.013). Furthermore, the median OS of patients with GG and GC/CC was 4.0 and 5.4 years respectively, which was statistically significant as well (P=0.009). However, the safety analysis failed to find the significant association between the polymorphism and adverse events (P>0.05). Interestingly, expression analysis of RNA extracted from cancer tissues specimens indicated that the PD-L1 mRNA expression of the patients with GG genotype were significantly higher than those of the GC/CC genotype (3.67±0.65 vs 2.69±0.78, P<0.001). Conclusion: The prognosis of patients with postoperative non-small cell lung cancer who received platinum-based adjuvant chemotherapy is influenced by -1813G>C polymorphism of PD-L1 gene.