ABSTRACT Purpose Targeted biopsy (TB) combined with systematic biopsy (SB) is an optimized mode of prostate biopsy but can often lead to oversampling and overdiagnosis accompanied by potential biopsy-related complications and patient discomfort. Here, we attempted to reasonably stratify the patient population based on multi-parameter indicators with the aim of avoiding unnecessary SB. Methods In total, 340 biopsy-naïve men with suspected lesions, prostate-specific antigen (PSA) < 20 ng/mL and prostate imaging-reporting and data system (PI-RADS) ≥ 3 enrolled for study underwent both TB and SB. The primary outcome was to determine independent predictors for a valid diagnosis, assuming that only TB was performed and SB omitted (defined as mono-TB), taking TB + SB as the reference standard. The secondary outcomes were exploration of the predictive factors of mono-TB and TB + SB in detection of prostate cancer (PCa) and clinically significant PCa (csPCa). Results The mean PSA density (PSAD) of patient group was 0.27 ng/mL/mL. Multiparametric MRI PI-RADS scores were 3-5 in 146 (42.94%), 105 (30.88%), and 89 (26.18%) cases, respectively. PCa and csPCa were detected in 178/340 (52.35%) and 162/340 (47.65%) patients, respectively. Overall, 116/178 (65.17%) patients diagnosed with PCa displayed pathological consistencies between mono-TB and TB + SB modes. PSAD and PI-RADS were independent predictors of valid diagnosis using mono-TB. Conclusions PSAD combined with PI-RADS showed utility in guiding optimization of the prostate biopsy mode. Higher PSAD and PI-RADS values were associated with greater confidence in implementing mono-TB and safely omitting SB, thus effectively balancing the benefits and risks.

Abstract Previous studies have shown that peripheral nerve injury can lead to abnormal dendritic spine remodeling in spinal dorsal horn neurons. Inhibition of abnormal dendritic spine remodeling can relieve neuropathic pain. Electroacupuncture (EA) has a beneficial effect on the treatment of neuropathic pain, but the specific mechanism remains unclear. Evidence has shown that slit-robo GTPase activating protein 3 (srGAP3) and Rho GTPase (Rac1) play very important roles in dendritic spine remodeling. Here, we used srGAP3 siRNA and Rac1 activator CN04 to confirm the relationship between SrGAP3 and Rac1 and their roles in improving neuropathic pain with EA. Spinal nerve ligation (SNL) was used as the experimental model, and thermal withdrawal latency (TWL), mechanical withdrawal threshold (MWT), Western blotting, immunohistochemistry and Golgi-Cox staining were used to examine changes in behavioral performance, protein expression and dendritic spines. More dendritic spines and higher expression levels of srGAP3 were found in the initial phase of neuropathic pain. During the maintenance phase, dendritic spines were more mature, which was consistent with lower expression levels of srGAP3 and higher expression levels of Rac1-GTP. EA during the maintenance phase reduced the density and maturity of dendritic spines of rats with SNL, increased the levels of srGAP3 and reduced the levels of Rac1-GTP, while srGAP3 siRNA and CN04 reversed the therapeutic effects of EA. These results suggest that dendritic spines have different manifestations in different stages of neuropathic pain and that EA may inhibit the abnormal dendritic spine remodeling by regulating the srGAP3/Rac1 signaling pathway to alleviate neuropathic pain.

Abstract Background: Bungarus multicinctus is one of the most dangerous venomous snakes prone to cardiopulmonary damage with extremely high mortality. In our previous work, we found that glutamine (Gln) and glutamine synthetase (GS) in pig serum were significantly reduced after Bungarus multicinctus bite. In the present study, to explore whether there is a link between the pathogenesis of cardiopulmonary injury and Gln metabolic changes induced by Bungarus multicinctus venom. We investigated the effect of Gln supplementation on the lung and heart function after snakebite. Methods: We supplemented different concentrations of Gln to mice that were envenomated by Bungarus multicinctus to observe the biological behavior, survival rate, hematological and pathological changes. Gln was supplemented immediately or one hour after the venom injection, and then changes in Gln metabolism were analyzed. Subsequently, to further explore the protective mechanism of glutamine on tissue damage, we measured the expression of heat-shock protein70 (HSP70), NF-κB P65, P53/PUMA by western blotting and real-time polymerase in the lung and heart. Results: Gln supplementation delayed the envenoming symptoms, reduced mortality, and alleviated the histopathological changes in the heart and lung of mice bitten by Bungarus multicinctus. Additionally, Gln increased the activity of glutamine synthetase (GS), glutamate dehydrogenase (GDH) and glutaminase (GLS) in serum. It also balanced the transporter SLC7A11 expression in heart and lung tissues. Bungarus multicinctus venom induced the NF-κB nuclear translocation in the lung, while the HO-1 expression was suppressed. At the same time, venom activated the P53/PUMA signaling pathway and the BAX expression in the heart. Gln treatment reversed the above phenomenon and increased HSP70 expression. Conclusion: Gln alleviated the glutamine metabolism disorder and cardiopulmonary damage caused by Bungarus multicinctus venom. It may protect lungs and heart against venom by promoting the expression of HSP70, inhibiting the activation of NF-κB and P53/PUMA, thereby delaying the process of snake venom and reducing mortality. The present results indicate that Gln could be a potential treatment for Bungarus multicinctus bite.

Abstract Objective To investigate the value of a nomogram based on multiparametric and multiregional MR images to predict Isocitrate Dehydrogenase-1 (IDH1) gene mutations in glioma. Data and methods The authors performed a retrospective analysis of 110 MR images of surgically confirmed pathological gliomas; 33 patients with IDH1 gene Mutation (IDH1-M) and 77 patients with Wild-type IDH1 (IDH1-W) were divided into training and validation sets in a 7:3 ratio. The clinical features were statistically analyzed using SPSS and R software. Three glioma regions (rCET, rE, rNEC) were outlined using ITK-SNAP software and projected to four conventional sequences (T1, T2, Flair, T1C) for feature extraction using AI-Kit software. The extracted features were screened using R software. A logistic regression model was established, and a nomogram was generated using the selected clinical features. Eight models were developed based on different sequences and ROIs, and Receiver Operating Characteristic (ROC) curves were used to evaluate the predictive efficacy. Decision curve analysis was performed to assess the clinical usefulness. Results Age was selected with Radscore to construct the nomogram. The Model 1 AUC values based on four sequences and three ROIs were the highest in these models, at 0.93 and 0.89, respectively. Decision curve analysis indicated that the net benefit of model 1 was higher than that of the other models for most Pt-values. Conclusion A nomogram based on multiparametric and multiregional MR images can predict the mutation status of the IDH1 gene accurately.

Abstract Introduction: Long QT Syndrome (LQTS) is an inherited disease with an abnormal electrical conduction system in the heart that can cause sudden death as a result of QT prolongation. LQT2 is the second most common subtype of LQTS caused by loss of function mutations in the potassium voltage-gated channel subfamily H member 2 (KCNH2) gene. Although more than 900 mutations are associated with the LQTS, many of these mutations are not validated or characterized. Methods and results: Sequencing analyses of genomic DNA of a family with LQT2 identified a putative mutation. i.e., KCNH2(NM_000238.3): c.3099_3112del, in KCNH2 gene which appeared to be a definite pathogenic mutation. The family pedigree information showed a gender difference in clinical features and T-wave morphology between male and female patients. The female with mutation exhibited recurring ventricular arrhythmia and syncope, while two male carriers did not show any symptoms. In addition, T-wave in females was much flatter than in males. The female proband showed a positive reaction to the lidocaine test. Lidocaine injection almost completely blocked ventricular arrhythmia and shortened the QT interval by ≥30 ms. Treatment with propranolol, mexiletine, and implantation of cardioverter-defibrillators prevented the sustained ventricular tachycardia, ventricular fibrillation, and syncope, as assessed by a 3-year follow-up evaluation. Conclusions: A putative mutation c.3099_3112del in the KCNH2 gene causes LQT2 syndrome, and the pathogenic mutation mainly causes symptoms in female progeny.

Resumen: Cuando se habla del renacimiento del budismo a finales de la dinastía Ming, los estudiosos echan en falta el estudio de ricos registros locales, regiones específicas y casos típicos. El templo de Jingshan, en Hangzhou, proporciona una muestra de este tipo. Una manifestación destacada del templo de Jingshan a finales de la dinastía Ming es la emergencia de todo un conjunto de anales. Diferentes grupos, como los monjes, los magistrados y la alta burguesía, participaron en la redacción de la historia de Jingshan de forma diacrónica en el mismo espacio. Las diferentes versiones de los Anales de Jingshan revelan el entrelazamiento de los acontecimientos históricos, las tendencias de la época y los deseos de varios grupos en distintas regiones, lo que arroja luz sobre el desarrollo que los registros históricos budistas empezaron a tener con otros clásicos ajenos al budismo en lugar de centrarse únicamente en los sutras budistas. Este proceso pone de manifiesto que el renacimiento del budismo a finales de la dinastía Ming es también un estado activo diacrónico alcanzado por las actividades de personas con diferentes propósitos en un área específica.

Abstract: When discussing the revival of Buddhism in the late Ming Dynasty, scholars lack the study of rich local records, specific regions and typical cases. Jingshan temple in Hangzhou provides such a sample. An outstanding manifestation of Jingshan Temple in the late Ming Dynasty is the emergency of a whole bunch of annals. Different groups such as monks, magistrates, and gentry all participated in the writing of the history of Jingshan diachronically in the same space. Different versions of Jingshan Annals reveal the interweaving of historical events, trends of the times, and the wishes of various groups in distinct regions, shedding light on the development that Buddhist historical records began to involve other classics outside Buddhism instead of only focusing on Buddhist sutras. This process manifests that the revival of Buddhism in the late Ming Dynasty is also a diachronic active state achieved by the people’s activities with different purposes in a specific area.

Abstract To investigate the imaging features and clinic value of magnetic resonance imaging (MRI) and computed tomography (CT) in the diagnosis of clear cell renal cell carcinoma (ccRCC). 139 RCC patients underwent MRI and CT examination before surgery, and the sensitivity, specificity, accuracy, positive and negative predictive values of MRI and CT in diagnosing ccRCC were analyzed and compared. There were 93 true-positive, 11 false-positive, 11 false-negative and 24 true-negative in MRI screening with sensitivity, specificity, accuracy, positive predictive value and negative predictive value of 89.42%, 68.57%, 84.17%, 89.42% and 68.57% respectively. Whereas there were 72 true-positive, 4 false-positive, 32 false-negative and 31 true-negative in CT screening with the sensitivity, specificity, accuracy, positive predictive value and negative predictive value of 69.23%, 88.57%, 74.10%, 94.74% and 49.21% respectively. The sensitivity and negative predictive value of MRI were better than those of CT, while the specificity of CT was better than that of MRI. MRI and CT have respective advantages in the diagnosis of ccRCC. The sensitivity and negative predictive value of MRI are superior to those of CT, while the specificity of CT is superior to that of MRI. Clinically, different examinations are selected according to different situations.

Abstract To investigate structure-property relationship of polymer-based curcumin solid dispersion (SD), three acrylic polymers were used to formulate curcumin SD by solvent evaporation method. Curcumin Eudragit EPO SD (cur@EPO), curcumin Eudragit RS PO SD (cur@RSPO) and curcumin Eudragit RL PO SD (cur@RLPO) showed deep red, golden orange and reddish orange color, respectively. Cur@RSPO entrapped 15.42 wt% of curcumin followed by cur@RL PO and cur@EPO. FTIR spectra indicated that in cur@EPO, curcumin may transfer hydrogen to the dimethylaminoethyl methacrylate group and thus change its color to red. In contrast, curcumin may form hydrogen bonding with Eudragit RS PO and Eudragit RL. Curcumin exists in amorphous state in three SDs as proved by differential scanning calorimetry and X-Ray diffraction measurement. In vitro digestion presented that lower pH value in simulated gastric fluid (SGF) stimulates the curcumin release from cur@EPO while permeability influences the release profile in other two SDs. When in simulated intestinal fluid (SIF), first order release model governs the release behaviors of all three SDs which showed sustained release pattern. Our results are helpful to elucidate how structure of polymer may impact on the major properties of curcumin contained SD and will be promising to broaden its therapeutic applications.

Abstract To illuminate changes in the secondary metabolic spectrum and hypoglycemic activity between Rose roxburghii fruit fermented (RRFF) by Chinese traditional distiller’s yeast and R. roxburghii fruit (RRF) using UPLC–MS/MS and streptozotocin-induced diabetic mice. Secondary metabolomics in the RRFF apparently differs from those in RRF; 32 pentacyclic triterpenoids were identified first, and ursolic acid-substituted roxburix acids were found to be the marker compounds. Testing of HepG2 cells indicated that RRFF had good glucose consumption capacity. Additionally, fasting blood glucose levels, glucose tolerance tests, plasma insulin levels and insulin resistance in diabetic mice indicated that RRFF was better than RRF. More importantly, RRFF exhibited good structure in pancreatic tissue. These results indicate that the fermentation process is beneficial for increasing the content of triterpenoids and enhancing hypoglycemic activity. Traditional fermentation with Chinese traditional distiller’s yeast can provide a way to expand the application of nutritious fruits with short shelf life.

Abstract Background Importin 7 (IPO7) belongs to the Importin β family and is implicated in the progression of diverse human malignancies. This work is performed to probe the role of IPO7 in pancreatic cancer development and its potential downstream mechanisms. Methods IPO7 expression in PC and paracancerous tissues were measured using Immunohistochemistry (IHC) staining and qRT-PCR. Western blotting was utilized to detect the expression level of IPO7 in PC cells and immortalize the pancreatic ductal epithelial cell line. After constructing the IPO7 overexpression and knockdown models, the effect of IPO7 on the proliferation of PC cells was analyzed by the CCK-8 and EdU assay. The migration and invasion of PC cells were examined by wound healing assay and Transwell experiment. The apoptosis rate of PC cells was analyzed by flow cytometry and TUNEL assay. The Gene Set Enrichment Analysis (GSEA) was used to determine the enrichment pathways of IPO7. The effect of IPO7 on the ERBB2 expression was determined using Western blotting. A xenograft mouse model was applied to investigate the carcinogenic effect of IPO7 in vivo. Results IPO7 expression was remarkably elevated in the cancer tissues of PC patients. IPO7 overexpression remarkably enhanced PC cell proliferation, migration and invasion and suppressed apoptosis, while knockdown of IPO7 exerted the opposite effect. Mechanistically, IPO7 facilitated the malignant phenotype of PC cells by up-regulating ERBB2 expression. In addition, knockdown of IPO7 inhibited tumor growth and lung metastasis in vivo. Conclusion IPO7 can act as an oncogenic factor and accelerate PC progression by modulating the ERBB pathway.

ABSTRACT Purpose: To explore the potential impact of traditional Chinese herb FuZhengHuaYuJiangZhuTongLuo recipe (FZHY) on renal interstitial fibrosis (RIF) in chronic kidney disease (CKD) at cellular and molecular levels. Methods: Unilateral ureteral obstruction (UUO) rats were established as the RIF model in vivo. The rats were given intragastric administration with FZHY once a day for consecutive 7, 14 and 21 days, respectively. The renal function parameters and inflammation indicators in kidney tissues were measured using enzyme-linked immunosorbent assay, the CD4+/CD8+ T cells in peripheral blood was detected using flow cytometry, the renal fibrosis degree was estimated using Masson’s staining, and the fibrosis-related genes’ expression was detected using quantitative polymerase chain reaction, western blotting, and immunohistochemistry analyses. Results: FZHY prescription reduced the serum creatinine and blood urea nitrogen, decreased the levels of c-reactive protein, interleukin-1, interleukin-6 and tumor necrosis factor-α in kidney tissues, and increased the ratio of CD4+/CD8+ T cells in peripheral blood. FZHY prescription suppressed the renal tissue fibrosis and reduced the levels of laminin, fibronectin, collagen I and collagen III. Conclusions: FZHY prescription suppressed the renal fibrosis and improved the condition of “Healthy Qi Deficiency and Evil Qi Excess” in rats with UUO, which may provide an effective method for CKD treatment.

Abstract Objective: To investigate the impact of recombinant human interferon α1b (rhIFNα1b) treatment in infants hospitalized with lower respiratory tract infections on subsequent wheezing. Methods: The clinical data of infants (n = 540) with viral pneumonia, wheezy bronchitis, or bronchiolitis hospitalized in 19 Chinese hospitals from June 2009 to June 2015 were retrospectively analyzed. The parameters relevant to wheezing episodes within the last year were collected by telephone and questionnaires. The rhIFNα1b treatment group (n = 253) and control group (n = 287) were compared in terms of wheezing episodes within the last year. Moreover, the wheezing group (95 cases) and non-wheezing group (445 cases) were compared. Results: Out of 540 cases, 95 (17.6%) experienced wheezing episodes, 13.8% (35/253) cases treated with rhIFNα1b, and 20.9% (60/287) cases without rhIFNα1b experienced wheezing episodes within the last year. The rhIFNα1b treatment significantly improved wheezing episodes within the last year, compared with the control peers (p = 0.031). Single-factor regression showed statistically significant differences between the wheezing and non-wheezing groups in terms of age, rhIFNα1b use, childhood and family history of allergy, housing situation, and feeding history (p < 0.05). Binary logistic regression showed a childhood history of allergy (OR = 2.14, p = 0.004), no rhIFNα1b use (OR = 1.70, p = 0.028), and living in a crowded house (OR = 1.92, p = 0.012) might be risk factors of subsequent wheezing. Accordingly, breastfeeding (OR = 0.44, p = 0.008) and hospitalization age of 1-year-old (OR = 0.58, p = 0.024) were protective factors. Conclusions: Early use of rhIFNα1b in infants hospitalized with lower respiratory tract infections and breastfeeding could prevent subsequent wheezing. Living in a crowded house could promote subsequent wheezing.

ABSTRACT In order to provide the basis for the design and control of a citrus picking robot clamp and cutter, and find the optimal combination of cutting parameters, this study used a self-made citrus stem cutting test-bed to study the effects of the citrus stem diameter, blade cutting speed, blade cutting clearance, and tool sliding cutting angle on the peak cutting force of citrus stems through a single-factor experiment. Based on the single-factor test, the blade cutting speed, blade cutting clearance, and tool sliding angle are selected as the influencing factors, and a multi-factor test is carried out with the target of the peak cutting force, and the regression model is established. The results showed that the peak cutting force increased linearly with the diameter of the fruit stalk, decreased with the increase of the blade cutting speed and sliding cutting angle, and first decreased and then increased with the increase of the blade cutting clearance. Through the optimisation analysis of the regression model, it is found that the optimal cutting parameter combination is the blade cutting speed of 40 mm/min, blade cutting gap of 1 mm, tool sliding cutting angle of 20°, and the peak cutting force under this combination is 168.23 N. The deviation between the predicted value of the peak cutting force and the measured value is less than 2%, and the optimisation result of the cutting parameters is reliable. This study provides a theoretical basis for the optimal design and control of the clamping and cutting mechanism of the citrus picking robot.

Resumo: Introdução: A doença diverticular do apêndice vermiforme (DDA) tem uma incidência de 0,004 a 2,1% em peças de apendicectomia. DDA está de forma variável associada a perfuração e malignidade. Reportamos uma experiência unicêntrica de DDA. O objectivo primário é validar a associação de DDA com apendicite complicada ou malignidade, e o objectivo secundário é validar os critérios de Systemic Inflammatory Response Syndrome (SIRS) e o score de quick Sepsis-related Organ Failure Assessment (qSOFA). Métodos: Os relatórios histopatológicos de 2,305 peças de apendicectomia de Janeiro 2011 a Dezembro de 2015 foram revistos. Apendicite aguda foi verificada em 2,164 (93,9%) peças. A histologia das restantes 141 (6,1%) revelou: apêndice normal (n = 110), DDA (n = 22), endometriose do apêndice (n = 6) e apêndice ausente (n = 3). As características demográficas dos doentes, perfil clínico, dados cirúrgicos e perioperatórios dos doentes com DDA foram avaliados. Modified Alvarado score, Andersson score, SIRS criteria, e o qSOFA scores foram calculados retrospectivamente. Resultados: A incidência de DDA foi de 0,95%. Dez doentes (45,5%) tinham diverticulite. A idade média dos doentes com DDA foi de 39,5 anos (âmbito 23-87) com predominância masculina (n = 12, 54,5%). A mediana do Modified Alvarado score foi de 8 (âmbito 4-9), e a mediana do Andersson score foi de 5 (âmbito 2-8). Quatorze doentes (63,6%) tinham SIRS e nenhum tinha um qSOFA score alto. Oito doentes (36,4%) tinham apendicite complicada (perfuração n = 2; abcesso n = 6). Onze (50%) doentes foram submetidos a apendicectomia laparoscópica. Verificaram-se 3 readmissões aos 30 dias e nenhuma morte. Conclusão: DDA é uma entidade clínica e patológica distinta e está associada a apendicite complicada.

Abstract: Introduction : Diverticular disease of the vermiform appendix (DDA) has an incidence of 0.004 to 2.1% in appendicectomy specimens. DDA is variably associated with perforation and malignancy. We report a single-center experience of DDA. The primary aim is to validate the association of DDA with complicated appendicitis or malignancy, and the secondary aim is to validate systemic inflammatory response syndrome (SIRS) criteria and quick Sepsis-related Organ Failure Assessment (qSOFA) scores. Methods: The histopathology reports of 2,305 appendicectomy specimens from January 2011 to December 2015 were reviewed. Acute appendicitis was found in 2,164 (93.9%) specimens. Histology of the remaining 141 (6.1%) patients revealed: normal appendix (n = 110), DDA (n = 22), endometriosis of appendix (n = 6), and an absent appendix (n = 3). Patient demographics, clinical profile, operative data, and perioperative outcomes of DDA patients are studied. Modified Alvarado score, Andersson score, SIRS criteria, and qSOFA scores were retrospectively calculated. Results: The incidence of DDA was 0.95%. Ten patients (45.5%) had diverticulitis. The mean age of DDA patients was 39.5 years (range 23-87), with male preponderance (n = 12, 54.5%). The median Modified Alvarado score was 8 (range 4-9), and the median Andersson score was 5 (range 2-8). Fourteen patients (63.6%) had SIRS, and none had a high qSOFA score. Eight patients (36.4%) had complicated appendicitis (perforation [n = 2] or abscess [n = 6]). Eleven (50%) patients underwent laparoscopic appendicectomy. There were three 30-day readmissions and no mortality. Conclusion: DDA is a distinct clinical pathology associated with complicated appendicitis.

Abstract Zinc is one of the most important trace elements and deficiency can lead to significant clinical complications. Microbial transformation is one of the most important methods used to supplement organic zinc and there may be some naturally occurring microorganisms that have both higher zinc tolerances and transformation capabilities. In this study, microorganisms which displayed such characteristics were widely screened, and a strain designated T-A was found. Morphological and molecular determination demonstrated that T-A is closely related to Candida tropicalis with 87% of 18S rDNA homology, with a G+C content measured by RP-HPLC of 88.42%. Candida tropicalis sp. T-A strains were shown to grow and transform zinc best at pH5 in medium with a zinc ion concentration of 8000 μg/mL at 28 °C for 121 hours. Our results showed C. tropicalis sp. T-A’s zinc content was 19.153 mg/g dry weight, with a relative bioavailability in rats of 173% when compared with traditional zinc supplements. Our study suggests that C. tropicalis sp. T-A could be exploited for use as a potential zinc supplement.