Multimodal data integration for predicting progression risk in castration-resistant prostate cancer using deep learning: a multicenter retrospective study.

Purpose: Patients with advanced prostate cancer (PCa) often develop castration-resistant PCa (CRPC) with poor prognosis. Prognostic information obtained from multiparametric magnetic resonance imaging (mpMRI) and histopathology specimens can be effectively utilized through artificial intelligence (AI) techniques. The objective of this study is to construct an AI-based CRPC progress prediction model by integrating multimodal data. Methods and materials: Data from 399 patients diagnosed with PCa at three medical centers between January 2018 and January 2021 were collected retrospectively. We delineated regions of interest (ROIs) from 3 MRI sequences viz, T2WI, DWI, and ADC and utilized a cropping tool to extract the largest section of each ROI. We selected representative pathological hematoxylin and eosin (H&E) slides for deep-learning model training. A joint combined model nomogram was constructed. ROC curves and calibration curves were plotted to assess the predictive performance and goodness of fit of the model. We generated decision curve analysis (DCA) curves and Kaplan-Meier (KM) survival curves to evaluate the clinical net benefit of the model and its association with progression-free survival (PFS). Results: The AUC of the machine learning (ML) model was 0.755. The best deep learning (DL) model for radiomics and pathomics was the ResNet-50 model, with an AUC of 0.768 and 0.752, respectively. The nomogram graph showed that DL model contributed the most, and the AUC for the combined model was 0.86. The calibration curves and DCA indicate that the combined model had a good calibration ability and net clinical benefit. The KM curve indicated that the model integrating multimodal data can guide patient prognosis and management strategies. Conclusion: The integration of multimodal data effectively improves the prediction of risk for the progression of PCa to CRPC.

Deep learning algorithm-based multimodal MRI radiomics and pathomics data improve prediction of bone metastases in primary prostate cancer.

PURPOSE: Bone metastasis is a significant contributor to morbidity and mortality in advanced prostate cancer, and early diagnosis is challenging due to its insidious onset. The use of machine learning to obtain prognostic information from pathological images has been highlighted. However, there is a limited understanding of the potential of early prediction of bone metastasis through the feature combination method from various sources. This study presents a method of integrating multimodal data to enhance the feasibility of early diagnosis of bone metastasis in prostate cancer. METHODS AND MATERIALS: Overall, 211 patients diagnosed with prostate cancer (PCa) at Gansu Provincial Hospital between January 2017 and February 2023 were included in this study. The patients were randomized (8:2) into a training group (n = 169) and a validation group (n = 42). The region of interest (ROI) were segmented from the three magnetic resonance imaging (MRI) sequences (T2WI, DWI, and ADC), and pathological features were extracted from tissue sections (hematoxylin and eosin [H&E] staining, 10 × 20). A deep learning (DL) model using ResNet 50 was employed to extract deep transfer learning (DTL) features. The least absolute shrinkage and selection operator (LASSO) regression method was utilized for feature selection, feature construction, and reducing feature dimensions. Different machine learning classifiers were used to build predictive models. The performance of the models was evaluated using receiver operating characteristic curves. The net clinical benefit was assessed using decision curve analysis (DCA). The goodness of fit was evaluated using calibration curves. A joint model nomogram was eventually developed by combining clinically independent risk factors. RESULTS: The best prediction models based on DTL and pathomics features showed area under the curve (AUC) values of 0.89 (95% confidence interval [CI], 0.799-0.989) and 0.85 (95% CI, 0.714-0.989), respectively. The AUC for the best prediction model based on radiomics features and combining radiomics features, DTL features, and pathomics features were 0.86 (95% CI, 0.735-0.979) and 0.93 (95% CI, 0.854-1.000), respectively. Based on DCA and calibration curves, the model demonstrated good net clinical benefit and fit. CONCLUSION: Multimodal radiomics and pathomics serve as valuable predictors of the risk of bone metastases in patients with primary PCa.

Enhancement of TKI sensitivity in lung adenocarcinoma through m6A-dependent translational repression of Wnt signaling by circ-FBXW7.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) that specifically target mutational points in the EGFR gene have significantly reduced suffering and provided greater relief to patients with lung adenocarcinoma (LUAD). The third-generation EGFR-TKI, Osimertinib, has been successfully employed in clinical treatments to overcome resistance to both original and acquired T790M and L858R mutational points. Nevertheless, the issue of treatment failure response has emerged as an insurmountable problem. METHODS: By employing a combination of multiple and integrated approaches, we successfully identified a distinct population within the tumor group that plays a significant role in carcinogenesis, resistance, and recurrence. Our research suggests that addressing TKI resistance may involve targeting the renewal and repopulation of stem-like cells. To investigate the underlying mechanisms, we conducted RNA Microarray and m6A Epi-Transcriptomic Microarray analyses, followed by assessment of transcription factors. Additionally, we specifically designed a tag to detect the polypeptide circRNA-AA, and its expression was confirmed through m6A regulations. RESULTS: We initially identified unique molecular signatures present in cancer stem cells that contributed to poor therapeutic responses. Activation of the alternative Wnt pathway was found to sustain the renewal and resistant status of these cells. Through bioinformatics analysis and array studies, we observed a significant decrease in the expression of circFBXW7 in Osimertinib-resistant cell lines. Notably, the abnormal expression pattern of circFBXW7 determined the cellular response to Osimertinib. Functional investigations revealed that circFBXW7 inhibits the renewal of cancer stem cells and resensitizes both resistant LUAD cells and stem cells to Osimertinib. In terms of the underlying mechanism, we discovered that circFBXW7 can be translated into short polypeptides known as circFBXW7-185AA. These polypeptides interact with ß-catenin in an m6A-dependent manner. This interaction leads to reduced stability of ß-catenin by inducing subsequent ubiquitination, thereby suppressing the activation of canonical Wnt signaling. Additionally, we predicted that the m6A reader, YTHDF3, shares common binding sites with hsa-Let-7d-5p. Enforced expression of Let-7d post-transcriptionally decreases the levels of YTHDF3. The repression of Let-7d by Wnt signaling releases the stimulation of m6A modification by YTHDF3, promoting the translation of circFBXW7-185AA. This creates a positive feedback loop contributing to the cascade of cancer initiation and promotion. CONCLUSIONS: Our bench study, in vivo experiments, and clinical validation have unequivocally shown that circFBXW7 effectively inhibits the abilities of LUAD stem cells and reverses resistance to TKIs by modulating Wnt pathway functions through the action of circFBXW7-185AA on ß-catenin ubiquitination and inhibition. The regulatory role of circRNA in Osimertinib treatment has been rarely reported, and our findings reveal that this process operates under the influence of m6A modification. These results highlight the tremendous potential of this approach in enhancing therapeutic strategies and overcoming resistance to multiple TKI treatments.

Multiparametric MRI radiomics in prostate cancer for predicting Ki-67 expression and Gleason score: a multicenter retrospective study.

PURPOSE: Prostate cancer (PCa) with high Ki-67 expression and high Gleason Scores (GS) tends to have aggressive clinicopathological characteristics and a dismal prognosis. In order to predict the Ki-67 expression status and the GS in PCa, we sought to construct and verify MRI-based radiomics signatures. METHODS AND MATERIALS: We collected T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) images from 170 PCa patients at three institutions and extracted 321 original radiomic features from each image modality. We used support vector machine (SVM) and least absolute shrinkage and selection operator (LASSO) logistic regression to select the most informative radiomic features and built predictive models using up sampling and feature selection techniques. Using receiver operating characteristic (ROC) analysis, the discriminating power of this feature was determined. Subsequent decision curve analysis (DCA) assessed the clinical utility of the radiomic features. The Kaplan-Meier (KM) test revealed that the radiomics-predicted Ki-67 expression status and GS were prognostic factors for PCa survival. RESULT: The hypothesized radiomics signature, which included 15 and 9 selected radiomics features, respectively, was significantly correlated with pathological Ki-67 and GS outcomes in both the training and validation datasets. Areas under the curve (AUC) for the developed model were 0.813 (95% CI 0.681,0.930) and 0.793 (95% CI 0.621, 0.929) for the training and validation datasets, respectively, demonstrating discrimination and calibration performance. The model's clinical usefulness was verified using DCA. In both the training and validation sets, high Ki-67 expression and high GS predicted by radiomics using SVM models were substantially linked with poor overall survival (OS). CONCLUSIONS: Both Ki-67 expression status and high GS correlate with PCa patient survival outcomes; therefore, the ability of the SVM classifier-based model to estimate Ki-67 expression status and the Lasso classifier-based model to assess high GS may enhance clinical decision-making.

Phylogeny and taxonomy of three species of Blastospora (Pucciniales) from East Asia.

Three species of the rust fungus genus Blastospora, Bl. betulae, Bl. itoana, and Bl. smilacis, have been reported in East Asia. Although their morphological characteristics and life cycles have been investigated, their phylogenetic positions have not been clarified sufficiently. Phylogenetic analysis showed that these three species were included into Zaghouaniaceae of Pucciniales. However, Bl. betulae was phylogenetically distinct from Bl. itoana and Bl. smilacis and different from other genera. Based on this result, and applying recent International Code of Nomenclature decisions/recommendations/requirements, Botryosorus, gen. nov., and Bo. deformans,, comb. nov., were applied for Bl. betulae. Two new combinations, Bl. radiata for Bl. itoana and Bl. makinoi for Bl. smilacis, were also applied. Their host plants and distribution were described based on literature records. Zaghouania yunnanensis, comb. nov., was proposed for Cystopsora yunnanensis as a result of this analysis.

A retrospective study on the relationship between 5 modified frailty index (5-mFI) and postoperative complications of gynecological elderly patients undergoing abdominal surgery.

INTRODUCTION: Aim to evaluate the application of 5 modified frailty index (5-mFI) in predicting postoperative complications in elderly gynecological patients undergoing abdominal surgery. METHODS: A total of 294 elderly gynecological patients who were hospitalized in the affiliated Hospital of North Sichuan Medical College and underwent abdominal surgery from November 2019 to May 2022 were collected from the Union Digital Medical Record (UniDMR) Browser of the hospital. According to whether postoperative complications (infection, hypokalemia, hypoproteinemia, poor wound healing and intestinal obstruction) occurred, the patients were divided into complication group (n = 98) and non-complication group (n = 196). Univariate and multivariate logistic regression analysis were used to analyze the risk factors of complications in elderly gynecological patients undergoing abdominal surgery. The receiver operating characteristic (ROC) curve was used to determine the predictive value of the frailty index score in elderly gynecological patients with postoperative complications after abdominal surgery. RESULTS: Postoperative complications occurred in 98 of 294 elderly gynecological patients undergoing abdominal surgery, accounting for 33.3%, 5-mFI (OR1.63, 95%CI 1.07-2.46,P = 0.022), age (OR1.08,95%CI 1.02-1.15, P = 0.009), operation time (OR 1.01, 95%CI 1.00-1.01). P < 0.001) were independent risk factors for postoperative complications in elderly patients undergoing abdominal surgery, and the area under the curve of postoperative complications in elderly gynecological patients was 0.60. (95%CI: 0.53-0.67, P = 0.005) CONCLUSION: Five modified frailty index can effectively predict the occurrence of postoperative complications in elderly gynecological patients.

Preterm neonate with a large congenital hemangioma on maxillofacial site causing thrombocytopenia and heart failure: A case report.

BACKGROUND: We report a rare case of a large congenital hemangioma (CH) in the maxillofacial region in a female neonate that caused thrombocytopenia and heart failure. With close multidisciplinary collaboration, the congenital hemangioma was successfully resected with good results. CASE SUMMARY: The patient was delivered at gestational age of 36 wk by cesarean section due to cephalopelvic disproportion and lack of onset of labor (birth weight: 2630 g). A right-sided facial tumor was detected in the fetus during routine antenatal ultrasound examination of the mother at 32 wk of gestation. Physical examination revealed a 7 cm × 7 cm × 3 cm hard, dull purple-colored mass on the right maxillofacial region. The mass was tense and had prominent surface telangiectasias. Laboratory investigations revealed reduced hemoglobin and platelet count, and increased activated partial thromboplastin time, prothrombin time, and thrombin time. International normalized ratio, fibrin degradation products, and D-Dimer levels were significantly increased. Thromboelastography showed increased alpha angle, mean amplitude, and the clot formation speed. Thyroid-stimulating hormone level was significantly elevated. The patient was administered prednisone, propranolol, euthyrox, vitamin K1, milrinone, and digoxin. After operation, cefepime was administered for anti-infection and propranolol was prescribed at discharge. CONCLUSION: We report a rare case of CH in the right maxillofacial region causing thrombocytopenia and heart failure.

Three-dimensional digital measurement of the facet joint in normal individual and lumbar intervertebral disc herniation patients aged 13 - 18 years.

BACKGROUND: Lumbar facet joint is an important element of spinal "three-joint complex". Whether there is a relationship between strange structure of facet joint and adolescent lumbar disc herniation (ALDH) is nonetheless controversial, and the current research is mainly centered on adults. OBJECTIVE: To find out the normal lumbar facet joints between 13 and 18 years old to provide anatomical basis for early diagnosis and therapy of lumbar disc herniation. METHODS: CT imaging information of 32 sufferers with lumbar disc herniation aged from 13 to 18 years old in Inner Mongolia have been collected as the ALDH group, and 62 wholesome subjects in the equal period had been chosen as the normal group. Uncooked records of continuous scanning lumbar tomography pix were imported into MIMICS 21.0 for evaluation and size in DICOM format. The parameters include facet joint height, facet joint width, et al. RESULTS: 1. The left and right transverse angle of L5S1 segment in the ALDH group were (52.41 ± 9.2) ° and (55.99 ± 10.91) ° (P < 0.05), and the differences were statistically significant. The right side is larger than the left side. 2. Facet joint thickness in L3-L5 segment of the normal group was significantly higher than that of male (1.63 ± 0.32) mm than that of female (1.38 ± 0.25) mm; In 16-18 years old group, comparison of facet joint cross-sectional area was statistically significant (22.1 ± 3.04) mm2 in male than (18.92 ± 3.71) mm2 in female. 3. In comparison between normal and ALDH group, there was significant difference in L3-4 transverse angle (P < 0.05), L4-5 facet joint height and facet joint thickness (P < 0.05), L5S1 facet joint thickness and transverse angle (P < 0.05). CONCLUSION: When ALDH occurs in the L5S1 segment, there is a substantial difference between the left and right sides of the transverse angle, and there is a difference in the thickness and the facet joint cross-sectional area between males and females, which is generally larger in males than in females. Facet joint height is larger, transverse angle of left and right is asymmetric, inferior articular process is larger, and facet joint thickness is smaller can indicate that lumbar disc herniation is effortless to occur.

Effect of low-concentration carbohydrate on patient-centered quality of recovery in patients undergoing thyroidectomy: a prospective randomized trial.

BACKROUND: At present, low-concentration carbohydrate is rarely used in minor trauma surgery, and its clinical efficacy is unknown. The aim of the study was to evaluate the effect of preoperative oral low-concentration carbohydrate on patient-centered quality of recovery in patients undergoing thyroidectomy using Quality of Recovery - 15 (QoR-15) questionnaire. METHODS: One hundred twenty patients were randomized to oral intake of 300 ml carbohydrate solution (CH group) or 300 ml pure water (PW group) 2 h before surgery or fasting for 8 h before surgery (F group). The QoR-15 questionnaire was administered to compare the quality of recovery at 1d before surgery (T0), 24 h, 48 h, 72 h after surgery (T1, T2, T3), and perioperative blood glucose was recorded. RESULTS: Compared to the F group, the QoR-15 scores were statistically higher in the CH and PW group at T1 (P < 0.05), and the enhancement of recovery quality reached the clinical significance at T1 in the CH group compared with the F group. Among the five dimensions of the QoR-15 questionnaire, physical comfort, physiological support and emotional dimension in the CH group were significantly better than the F group (P < 0.05) at T1. Besides, blood glucose of CH group was significantly lower than the PW group and F group at each time point after surgery. CONCLUSIONS: Low-concentration carbohydrate could decrease the incidence of postoperative hyperglycemia and improve the patient-centered quality of recovery on patients undergoing open thyroidectomy at the early stage postoperatively. TRIAL REGISTRATION: ChiCTR1900024731 . Date of registration: 25/07/2019.

Computed tomography-guided localization for lung nodules: methylene-blue versus coil localization.

PURPOSE: To compare the relative clinical efficacy of preoperative computed tomography (CT)-guided methylene-blue (MB) and coil localization for lung nodules (LNs). MATERIAL AND METHODS: Between January 2013 and December 2018, a total of 89 patients with LNs underwent CT-guided MB or coil localization and subsequent video-assisted thoracoscopic surgery (VATS)-guided wedge resection in our hospital. We compared the technical success of localization and wedge resection between two groups. RESULTS: In MB group, 47 LNs in 39 patients were localized, with successful localization and wedge resection rates of 97.9% and 97.9%, respectively. In the coil group, 64 LNs in 50 patients were localized, with successful localization and wedge resection rates of 96.9% and 96.9%, respectively. There were no significant differences in technical success rates of localization and wedge resection between the two groups (p = 1.000 and 1.000). The coil group sustained a longer duration between localization and VATS relative to the MB group (14.4 h vs. 1.6 h, p = .001). CONCLUSION: Both MB and coil localization were safe and effective techniques to establish a high success rate of VATS-guided wedge resection for LNs. Relative to MB localization, coil localization might be compatible with a longer delay between localization and VATS.

Antinociceptive effects of magnesium sulfate for monitored anesthesia care during hysteroscopy: a randomized controlled study.

BACKGROUND: Opioids are the most effective antinociceptive agents, they have undesirable side effects such as respiratory depressant and postoperative nausea and vomiting. The purpose of the study was to evaluate the antinociceptive efficacy of adjuvant magnesium sulphate to reduce intraoperative and postoperative opioids requirements and their related side effects during hysteroscopy. METHODS: Seventy patients scheduled for hysteroscopy were randomly divided into 2 groups. Patients in the magnesium group (Group M) received intravenous magnesium sulfate 50 mg/kg in 100 ml of isotonic saline over 15 min before anesthesia induction and then 15 mg/kg per hour by continuous intravenous infusion. Patients in the control group (Group C) received an equal volume of isotonic saline as placebo. All patients were anesthetized under a BIS guided monitored anesthesia care with propofol and fentanyl. Intraoperative hemodynamic variables were recorded and postoperative pain scores were assessed with verbal numerical rating scale (VNRS) 1 min, 15 min, 30 min, 1 h, and 4 h after recovery of consciousness. The primary outcome of our study was total amount of intraoperative and postoperative analgesics administered. RESULTS: Postoperative serum magnesium concentrations in Group C were significantly decreased than preoperative levels (0.86 ± 0.06 to 0.80 ± 0.08 mmol/L, P = 0.001) while there was no statistical change in Group M (0.86 ± 0.07 to 0.89 ± 0.07 mmol/L, P = 0.129). Bradycardia did not occur in either group and the incidence of hypotension was comparable between the two groups. Total dose of fentanyl given to patients in Group M was less than the one administered to Group C [100 (75-150) vs 145 (75-175) µg, median (range); P < 0.001]. In addition, patients receiving magnesium displayed lower VNRS scores at 15 min, 30 min, 1 h, and 4 h postoperatively. CONCLUSIONS: In hysteroscopy, adjuvant magnesium administration is beneficial to reduce intraoperative fentanyl requirement and postoperative pain without cardiovascular side effects. Our study indicates that if surgical patients have risk factors for hypomagnesemia, assessing and correcting magnesium level will be necessary. TRIAL REGISTRATION: ChiCTR1900024596 . date of registration: July 18th 2019.

ß-Lactams as promising anticancer agents: Molecular hybrids, structure activity relationships and potential targets.

ß-Lactam, commonly referred as azetidin-2-one, is a multifunctional building block for synthesizing ß-amino ketones, γ-amino alcohols, and other compounds. Besides its well known antibiotic activity, this ring system exhibits a wide range of activities, attracting the attention of researchers. However, the structurally diverse ß-lactam analogues as anticancer agents and their different molecular targets are poorly discussed. The purpose of this review is 3-fold: (1) to explore the molecular hybridization approach to design ß-lactams hybrids as anticancer agents; (2) the structure activity relationship of the most active anticancer ß-lactams and (3) to summarize their antitumor mechanisms.

Effects of epidural combined with general anesthesia versus general anesthesia on quality of recovery of elderly patients undergoing laparoscopic radical resection of colorectal cancer: A prospective randomized trial.

STUDY OBJECTIVES: The aim of the present study was to assess the quality of recovery from anesthesia on patients subjected to laparoscopic radical resection of colorectal cancer under epidural block combined with general anesthesia or general anesthesia by means of Quality of Recovery-15 (QoR-15) questionnaire. DESIGN: Prospective randomized trial. SETTING: The setting is at an operating room, a post-anesthesia care unit, and a hospital ward. PATIENTS: Seventy patients, aging from 65 to 79 years with an American Society of Anesthesiologists physical status II or III, were scheduled to undergo laparoscopic radical resection of colorectal cancer. INTERVENTIONS: Epidural block combined with general anesthesia or general anesthesia. MEASUREMENTS: The QoR-15 was administered by an investigator blind to group allocation before surgery (T0), at 24 and 72h after surgery (T1 and T2), and on postoperative day 7 (T3). The quality of recovery, as assessed by the score on the QoR-15, was compared between the groups. Besides, the consumption of anesthetics, respiratory recovery time, response time, extubation time, flatus time, the incidence of nausea or vomiting, the consumption of antiemetic and analgesic agents, and the duration of the hospital stay were also recorded. MAIN RESULTS: The QoR-15 scores at T1 and T2 were significantly higher in the E + G group compared with the G group (P < 0.05). Among the five dimensions of the QoR-15, physiological comfort, physiological independence, pain, and emotional dimension were significantly better at T1 in the E + G group, and physiological comfort and pain were significantly better at T2 in the E + G group. CONCLUSION: This study demonstrates that epidural block combined with general anesthesia can improve the early recovery of elderly patients after laparoscopic radical resection of colorectal cancer from the perspective of patients.

Aquaporin 4 regulation by ginsenoside Rb1 intervenes with oxygen-glucose deprivation/reoxygenation-induced astrocyte injury.

BACKGROUND: Spinal cord ischemia-reperfusion injury (SCII) is a common complication of spinal surgery as well as thoracic and abdominal surgery. Acute cytotoxic edema is the key pathogenic alteration. Therefore, avoiding or decreasing cellular edema has become the major target for SCII treatment. METHODS: The antiedema activity of ginsenoside Rb1 on aquaporin (AQP) 4, nerve growth factor (NGF), and brain-derived neurotrophic factor expression was detected by western blot and real-time polymerase chain reaction under conditions of oxygen-glucose deprivation/reoxygenation (OGD/R) in a rat astrocyte model in vitro. In addition, the cellular membrane permeability of AQP4 overexpressing cells or AQP4 small interfering RNA-transfected cells was detected. RESULTS: Ginsenoside Rb1 significantly prevented OGD/R-induced AQP4 downregulation in rat astrocytes. In addition, ginsenoside Rb1 treatment or AQP4 overexpression in rat astrocytes significantly attenuated the OGD/R-induced increase of cellular membrane permeability. Moreover, ginsenoside Rb1 obviously prevented the OGD/R-induced decrease of NGF and BDNT expression in rat astrocytes. CONCLUSION: These findings demonstrate that ginsenoside Rb1 can relieve spinal cord edema and improve neurological function by increasing AQP4 expression.

What is the most relevent factor causing pain during ALA-PDT? A multi-center, open clinical pain score research trial of actinic keratosis, acne and condylomata acuminata.

BACKGROUND: To date, it has been reported that the intrinsic factors(lesions location, lesions area, disease tynpes) and extrinsic factors(fluence rate) contribute to the pain during 5-aminolevulinic acid photodynamic therapy (ALA-PDT). But there are few studies on pain during ALA-PDT and lack of sufficient clinical evidence related to the pain intensity. OBJECTIVE: To investigate pain intensity and its relative factors during ALA-PDT and to provide clinical implication. METHODS: The pain numeric rating scale (PNRS) score was used to evaluate the patients' pain intensity at different times during ALA-PDT irradiation from 0 to 10 min during treatment. Gender, age, lesions location, lesions area, ALA concentration and fluence rate were recored. RESULTS: The trial enrolled 274 patients in total, including 118 acne patients (in face), 30 actinic keratosis(AK)patients(in face), 126 Condylomatata acuminate patients(in genitalia). The average pain score in PDT was highest in the patients with actinic keratosis(7.3 ± 0.7), and that of condylomata acuminata was the lowest (4.5 ± 1.1) (p < 0.05). The highest pain score in patients with AK, acne and condylomata acuminata was 8, 6 and 6 respectively which occurred at 4 min, 4 min and 6 min respectively. The pain score of males was higher compared with females in all of the three diseases (p < 0.05). The pain score of facial diseases (5.6 ± 1.2) was higher than that of the genitalia (4.5 ± 1.1) (p < 0.05). The lesions area was positively correlated with the pain score (p < 0.05). In facial diseases, the pain score of patients with high fluence rate (7.3 ± 0.7) was higher than patients with low fluence rate (5.1 ± 0.9) (p < 0.05). CONCLUSIONS: Intrinsic and extrinsic factors both correlate with pain during PDT. Intrinsic factors are difficult to change, so extrinsic factors are the key point to control. We can reduce the fluence rate and extend the treatment time, relieving pain intensity while still ensuring equivalent efficacy.

MicroRNA-29 enhances autophagy and cleanses exogenous mutant αB-crystallin in retinal pigment epithelial cells.

Retinal pigment epithelial cells (RPEs), a pigmented cell layer in the outer retina, are constantly exposed to photo-oxidative stress. Autophagy relieves the stress by removing oxidative protein adducts, protein aggregates, and damaged mitochondria. We previously found that miR-29 is downregulated in choroid/RPE tissue in a model of exudative age-related macular degeneration (AMD), suggesting that miR-29 deficiency may contribute to autophagy inhibition and AMD progression. Here we wanted to test whether overexpression of miR-29 in RPEs could enhance autophagy, thereby facilitating removal of drusen components. Indeed, overexpression of miR-29 in the RPEs increased autophagy, assessed by decreased protein levels of p62, increased lipid form of microtubule-associated protein light chain (LC3-II), and elevated autophagy flux. Furthermore, overexpression of miR-29 mitigated the formation of mutant αB-crystallin (R120G) protein aggregates. In probing the mechanism, we demonstrated that miR-29 post-transcriptionally repressed LAMPTOR1/p18 via targeting its 3'-UTRs of messenger RNA. MiR-29 overexpression and knockdown of LAMPTOR1/p18 led to limited mTORC1 recruitment to lysosomes and inhibition of mTORC1 activity. Altogether, miR-29 enhances autophagy which aids in removal of protein aggregates. These findings reveal a novel role of miR-29, which has the potential of being a therapeutic strategy for rescuing RPE degeneration in ocular disorders.

[Two new polypeptides from extract of deer bone extract].

Two new polypeptides were isolated and purified from the extract of deer bone (constitutive part of Cucumis and Cervus polypeptide injection) by various column chromatography including C4 300Å and Sephadex G-50, as well as semipreparative HPLC. Their N-terminal amino acid sequences were identified by De Novo sequencing on the basis of MALDI-TOF-MS data and Explorer™ software. The N-terminal amino acid sequences of polypeptides were identified as NH2-Gly-Pro-Val-Gly-Pro-Thr-Gly-Pro-Val-Gly-Ala-Ala-Gly-Pro-Ser-Gly-Pro-Asp (Mei18 peptide, 1) and NH2-Ala-Gly-Pro-Ala-Gly-Pro-Leu-Gly-Pro-Leu-Gly-Pro-Leu-Gly-Pro-Leu-Gly-Pro-Pro-Asp-Ser-Try-Asp (Mei23 peptide, 2), respectively. Mei18 and Mei 23 peptides are new polypeptides.

Value of Adjuvant Radiotherapy for Thymoma with Myasthenia Gravis after Extended Thymectomy.

BACKGROUND: The co-existence of myasthenia gravis (MG) and thymoma makes the surgical treatment more complicated and adjuvant radiation more controversial. The aim of this study was to investigate adjuvant radiotherapy for thymoma with MG after extended thymectomy. METHODS: A total of 181 patients with both MG and thymoma were recruited between 2003 and 2014 at Tongren Hospital, China. Among all the patients, 157 patients received radiation therapy after surgery (Group A); whereas the other 24 patients did not receive radiation therapy (Group B). According to the time that patients started mediastinal radiation therapy, we subdivided the 157 patients in Group A into subgroups (1-month subgroup, n = 98; 2-month subgroup, n = 7; and 3-month subgroup, n = 52). We then compared the effect of the mediastinal radiation therapy across these different groups using the survival rate, the rate of postoperative myasthenic crisis, and the complete stable remission (CSR) rate as the primary endpoints. RESULTS: There was a significant difference in the occurrence of postoperative myasthenic crisis between 1-month subgroup and Group B (χ2 = 4.631, P = 0.031). The rates of reaching CSR were 32.6% in 1-month subgroup, 25% in 3-month subgroup, and 22.7% in Group B, respectively. The overall survival rates of 1-month subgroup, 3-month subgroup, and Group B were 88.8%, 83.3%, and 77.3%, respectively. Analysis on the Kaplan-Meier survival curves demonstrated that within 8 years after surgery, there was no significant difference in aspects of overall survival and disease-free survival between 1-month subgroup and Group B, and between 3-month subgroup and Group B; over 8 years after surgery, the disease-free survival rates in 1-month subgroup, 3-month subgroup and Group B were 79.4%, 70.6%, and 55.3%, respectively. CONCLUSIONS: Adjuvant radiation within 1 month after extended thymectomy may be helpful in controlling postoperative MG, such as decreasing the possibility of postoperative myasthenic crisis, and raising cumulative probabilities of reaching CSR.

Serine racemase deficiency attenuates choroidal neovascularization and reduces nitric oxide and VEGF levels by retinal pigment epithelial cells.

Choroidal neovascularization (CNV) is a leading cause of blindness in age-related macular degeneration. Production of vascular endothelial growth factor (VEGF) and macrophage recruitment by retinal pigment epithelial cells (RPE) significantly contributes to the process of CNV in an experimental CNV model. Serine racemase (SR) is expressed in retinal neurons and glial cells, and its product, d-serine, is an endogenous co-agonist of N-methyl-d-aspartate receptor. Activation of the receptor results in production of nitric oxide (. NO), a molecule that promotes retinal and choroidal neovascularization. These observations suggest possible roles of SR in CNV. With laser-injured CNV mice, we found that inactivation of SR-coding gene (Srrnull ) significantly reduced CNV volume, neovascular density, and invading macrophages. We exploited the underlying mechanism in vivo and ex vivo. RPE from wild-type (WT) mice expressed SR. To explore the possible downstream target of SR inactivation, we showed that choroid/RPE homogenates extracted from laser-injured Srrnull mice contained less inducible nitric oxide synthase and decreased phospho-VEGFR2 compared to amounts in WT mice. In vitro, inflammation-primed WT RPEs expressed more inducible NOS, produced more. NO and VEGF than did inflammation-primed Srrnull RPEs. When co-cultured with inflammation-primed Srrnull RPE, significantly fewer RF/6A-a cell line of choroidal endothelial cell, migrated to the opposite side of the insert membrane than did cells co-cultured with pre-treated WT RPE. Altogether, SR deficiency reduces RPE response to laser-induced inflammatory stimuli, resulting in decreased production of a cascade of pro-angiogenic cytokines, including. NO and VEGF, and reduced macrophage recruitment, which contribute synergistically to attenuated angiogenesis.