An approach combining bioinformatics and machine learning to identify eight autophagy-related biomarkers and construct molecular mechanisms underlying COVID-19 and major depressive disorders.

OBJECTIVE: A lack of objective biomarkers is preventing the screening and diagnosis of COVID-19 combined with major depression disorder (COVID-19-MDD). The purpose of this study was to identify diagnostic biomarkers and gene regulatory mechanisms associated with autophagy; a crucial process significantly involved in the pathogenesis of COVID-19-MDD. MATERIALS AND METHODS: In this study, differentially expressed genes (DEGs) were screened using GSE98793 from the GEO2R analysis (GEO) database, and intersected with the COVID-19-related gene (CRGs) and autophagy-related genes (ARGs) to obtain common genes involved in. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of these common genes were performed. Subsequently, the transcription factor (TF)-gene regulatory network and comorbidity network were constructed. In addition, 10 drug candidates were screened using the DSigDB database. To identify diagnostic markers, we used LASSO regression. RESULTS: In total, 13 common genes were screened, which were primarily enriched in lysosomes, endoplasmic reticulum membranes, and other endomembrane systems also associated with autophagy. Additionally, these genes were involved in neurological cell signaling and have a functional role in pathways related to vascular endothelial growth factor, tyrosine kinase, autophagy, inflammation, immunity, and carcinogenesis. Tumors and psychiatric disorders were the most highly linked diseases to COVID-19. Finally, ten drug candidates and eight diagnostic markers (STX17, NRG1, RRAGD, XPO1, HERC1, HSP90AB1, EPHB2, and S1PR3) were screened. CONCLUSIONS: This is the first study to screen eight diagnostic markers and construct a gene regulatory network for COVID-19-MDD from the perspective of autophagy. The findings of our study provide novel insights into the diagnosis and treatment of COVID-19-MDD.

[Retrospective analysis of factors affecting patency rates and causes of failure in use of single-armed two-suture microsurgical vasoepididymostomy].

Objectives: To analyze the factors affecting the patency rate of microsurgical single-stitch longitudinal intussusception vasoepididymostomy and to explore the possible causes of failure. Methods: The clinical data of 87 patients with epididymal obstructive azoospermia who underwent microsurgical vasoepididymostomy from January 2015 to February 2018 in the First Affiliated Hospital of Fujian Medical University were analyzed retrospectively. We observed the patency rate postoperatively and evaluated several factors that possibly related to the patency rates. Preoperative examinations included peripheral blood chromosomes, Y chromosome microdeletions, sex hormones, seminal plasma, etc. After admission, microsurgical single-stitch longitudinal intussusception vasoepididymostomy was performed. During the follow-up, the semen was evaluated to assess the patency rate and the time to patency. Results: The patient's age ranged from 21 to 42 years and the mean age was(25±3) years. Infertility lasted for 1-8 years and the mean infertility time was(2.2±1.1) years. The longitudinal intussusception vasoepididymostomy was successfully completed in 80 patients , 5 cases gave up the anastomosis surgery because of multiple segment obstruction of the vas deferens, complete obstruction of the epididymis or testicular obstruction. Two cases underwent crossed vasovasostomy( sperm was present in the ejaculate in 1 case postoperatively). Of all the patients, 72 were successfully followed up. The follow-up time was 3-29 months, with an average of (12.0±1.7)months. Excluding 3 cases of follow-up time less than 12 months who still had no sperm in the ejaculate, 69 patients' data were in cluded in the final statistics, of which 50 cases with return of sperm in the ejaculate, the overall patency rate was 72.5%(50/69), concentration of sperm was 0.1-137.2 million/ml, and the mean concentration was(29±21) million/ml; with the progressive motile sperm rate ranging from 0-57.9%, the mean rate was(29.9±21.1)%. The patency rates of motile sperm and immobile sperm found in epididymal fluid during surgery were 82.2%(37/45) and 54.2%(13/24), respectively. The patency rate of bilateral and unilateral anastomoses was 77.6%(45/58) and 45.5%(5/11), respectively; the patency rate of caput anastomosis was 47.8%(11/23), and 84.8%(39/46) for corpus or caudal anastomosis. 17 patients achieved natural pregnancy postoperatively, the rate was 34.0%(17/50). Conclusions: The therapeutic effect of microsurgical single-stitch longitudinal intussusception vasoepididymostomy is satisfactory. The motile spermatozoa in epididymal fluid, bilateral surgery and corpus or caudal anastomosis can improve the patency rate postoperatively.

[Clinicopathologic analysis of primary carcinoid of the ovary].

Objective: To describe the clinicopathologic features, diagnosis and differential diagnosis of ovarian carcinoid tumors. Methods: A retrospective chart review was performed of all patients diagnosed with primary ovarian carcinoid tumors at Fudan University Shanghai Cancer Centre from 2007 to 2017. Results: The histologic analysis of these carcinoid tumors revealed 3 were insular, 1 was trabecular, 1 was mucinous, and 10 were strumal. Histologic features of insular and trabecular carcinoid were similar to other parts of the neuroendocrine tumor. Strumal carcinoid was composed of thyroid tissue intimately admixed with carcinoid tumor, showing trabecular pattern. Mucinous carcinoid was resembles Krukenberg tumor. Most ovarian carcinoid tomours were diffusely positive with at least one neuroendocrine marker, especially synaptophysin (14/14) and CD56(9/10). The median follow-up time was 53 months, 1 patient with squamous-cell carcinoma of cervixrecur rence in vaginal after 37 months, and only 1 patient died of disease. The remaining patients were disease-free survival. Conclusions: Primary carcinoid of the ovary is a very rare low grade malignant monodermal teratomas and somatic-type tumours arising from a dermoid. The diagnosis and differential diagnosis mainly relies on the histopathologic characteristics and the immuno-phenotype. Primary ovarian carcinoid almost always exhibit a benign clinical behavious except mucinous carcinoid.

[Correlation between androgen receptor expression and surrogate molecular subtypes in invasive breast carcinoma].

Objective: To investigate androgen receptor(AR)expression in invasive breast carcinoma and the correlation with surrogate molecular breast carcinoma subtypes. Methods: Immunohistochemical staining of AR and other biomarkers was performed in a cohort of 870 cases of primary invasive breast carcinomas collected from August to December, 2016. The association of AR expression with different histological and surrogate molecular subtypes was analyzed. Results: The positive expression rate of AR in the immunohistochemistry-based surrogate subtypes was 96.3%(207/215) for Luminal A, 89.8%(378/421) for Luminal B, 82.4%(75/91) for HER2 overexpression and 37.1%(53/143) for triple negative breast carcinoma, with significant differences among the four groups (P<0.01). AR correlated positively with the expression of ER(P<0.01), PR(P<0.01), HER2(P=0.007), GATA3(P<0.01), GCDFP15(P<0.01)and mammaglobin(P<0.01), while negatively with the expression of Ki-67(P<0.01), CK5/6(P<0.01)and CK14(P<0.01). Conclusions: AR exhibits a high expression in invasive breast carcinoma, which is mainly correlated with ER-positive breast carcinoma. Regardless of the relatively low expression rate, AR is a potential therapeutic target in triple negative breast carcinoma.

[Clinicopathologic study of seromucinous carcinoma of ovary].

Objective: To elucidate the clinicopathologic characteristics, immunophenotype and differential diagnosis of ovarian seromucinous carcinoma. Methods: The clinical and pathological characteristics of 7 cases of ovarian seromucinous carcinoma were analyzed. Immunohistochemical study of selected markers was performed employing the EnVision method. Literature of ovarian seromucinous carcinoma were also reviewed. Results: The age of the 7 ovarian seromucinous carcinoma patients ranged from 27 to 70 years of age (mean=48 years). Two patients had bilateral ovarian tumors. The complaint of most patients was abdominal distention. The serum concentration of CA125 and/or CA19-9 was elevated in most patients.Four patients were found to have ascites during surgery, of whom 2 were also found to have malignant cells in their ascites or peritoneal washings. The maximum dimension of these tumors ranged from 6.0 to 15.0 cm (mean=9.3 cm). Grossly, 6 of 9 tumors were predominantly cystic with protrusions of papillae from the inside wall of the cysts. Among these 6 tumors, 2 had brown viscous material in the cyst. The other 3 tumors were predominantly solid. Microscopically, all 9 tumors contained endocervical-like mucinous cells and other Mullerian cells. The tumor cells had intermediate or severe atypia. A lot of acute inflammatory cells especially neutrophil polymorphs could be seen in the stroma and lumens of all the 9 tumors, which is an apparent feature for ovarian seromucinous tumors. Architecturally, the tumors mainly exhibited complex papillary architectures, compactly back-to-back glandular lumensforming cribriform, labyrinthine formations, or solid growth pattern, with immunophenotype of Mullerian tumors. Mucin stain was performed in 1 tumor with AB positive, PAS positive and D-PAS positive, highlighting intracytoplasmicmucin secretions. Follow-up (3-86 months with a mean of 21 month) data revealed that except 1 patient dying of the tumor at 81 months after surgery, the other 6 patients all survived the malignancy. Conclusions: Seromucinous carcinoma of the ovary possesses relatively special clinicopathologic features, with some morphological and immunophenotypical overlap with endometrioid carcinoma and low grade serous carcinoma of the ovary. It is necessary to thoroughly investigate the pathogenesis and molecular changes involved in the type of tumor to determine whether it is a convincingly distinctive category of ovarian carcinoma.

[Effectiveness of transurethral seminal vesiculoscopy in the treatment of persistent hematospermia, and oligoasthenozoospermia and azoospermia from ejaculatory duct obstruction].

Objective: To analyze the effectiveness of transurethral seminal vesiculoscopy in the treatment of persistent hematospermia, and oligoasthenozoospermia and azoospermia from ejaculatory duct obstruction. Methods: The clinical date of 56 cases of persistent hematospermia, or azoospermia/oligoasthenozoospermia from ejaculatory duct obstruction treated with transurethral seminal vesiculoscopy between November 2013 and January 2016 in the First Affiliated Hospital of Fujian Medical University were reviewed. A total of 30 cases were persistent hematospermia for 6 months to 3 years, with no response to routine antibiotic therapy for >4 weeks; 24 cases were obstructive azoospermia; and the other 2 cases were extreme oligoasthenozoospermia. Transrectal ultrasound of the prostate and seminal vesicles, and pelvic magnetic resonance imaging (MRI) were performed before the surgery, finding seminal vesicle dilation in 28 cases, ejaculatory duct dilation in 18 cases, seminal vesicle and ejaculatory duct dilation in 7 cases, seminal vesicle dilation with ejaculatory duct cyst in 2 cases, and bilateral ejaculatory duct dilation with prostatic utricle cyst in 1 case. After the transurethral seminal vesiculoscopy, follow-up examinations were performed to assess the effectiveness of the surgery for ≥3 months. Results: The surgery was successful in all the patients, with the duration of surgery ranging from 30 to 148 minutes. Among the 30 patients with hematospermia, calculi in ejaculatory duct or seminal vesicle was found in 20 cases, while inflammation or dark red jelly-like substances in seminal vesicle was seen in all cases. In the follow-up of 9.7 months (3.0-13.0 months), hematospermia in 26 (26/30, 86.7%)patients was relieved or cured after 1-6 times of ejaculation; the other 4 (4/30, 13.3%)cases still had hematospermia. In postoperative semen analysis for the 24 cases of azoospermia from ejaculatory duct obstruction, sperms were detected in 16(16/24, 66.7%)cases, but sperms were not found after 6 months following the surgery in 1 of the 16 case, thus re-obstruction was suspected; in the other 8 (8/24, 33.3%)cases, sperms could not be found in multiple semen analyses in >12 months after the surgery. The 2 cases of extreme oligoasthenozoospermia had obvious improvement in routine semen analysis in 1 and 3 months after the surgery. Except for 1 case of scrotum swelling after surgery, no postoperative complications (retrograde ejaculation, urinary incontinence, or rectal injury) were observed. Conclusions: Transurethral seminal vesiculoscopy was an effective therapy for persistent hematospermia. More strict operation indication and careful performance are necessary for azoospermia oligoasthenozoospermia from ejaculatory duct obstruction.

[Endometrioid carcinoma with sex cord-like formations and hyalinization of the uterine corpus: a clinicopathologic analysis of 5 cases].

OBJECTIVE: Endometrioid carcinoma with sex cord-like formations and hyalinization of the uterine corpus is a rare morphological variant of endometrioid carcinoma. The biphasic morphological features may cause confusion with carcinosarcoma of the uterus, leading to misdiagnosis. The aim of this article is to elucidate the clinicopathological characteristics of such endometrial carcinoma to avoid misdiagnosis. METHODS: The clinical and pathological data of 5 cases of endometrioid carcinoma with sex cord-like formations and hyalinization of the uterine corpus were collected and analyzed. RESULTS: The age of the 5 patients ranged from 29 to 39 years, with a mean age of 33 years. Four patients underwent surgery of radical hysterectomy, the other dilation and curettage biopsy. Among the former, 3 patients were at FIGO stageⅠA, the other ⅢC1. Microscopically, all 5 tumors contained endometrioid carcinoma components, 4 of which were FIGO gradeⅠ, the remaining one was grade Ⅱ. Each tumor was of variable proportions of corded and hyalinized areas ranging from 10% to 60%. The cells in the corded and hyalinized areas were epithelioid, fusiform and spindle in morphology, admixed with the endometrioid carcinoma component, resulting in a biphasic pattern. The corded and hyalinized component exhibited distinctively different immunophenotypical feature from that by the conventional endometrioid carcinoma component. The results of follow-up for 4 patients of 7 to 68 months (mean=26.5 months) revealed that all patients were alive without recurrence of the malignancy. CONCLUSIONS: Endometrioid carcinoma with sex cord-like formations and hyalinization of the uterine corpus presents unique morphology, and the patients are usually young with relatively favorable prognosis. The definite mechanism for the pathogenesis of the sex cord-like formations and hyalinization needs further investigation.

Epithelial discrimination of commensal and pathogenic Candida albicans.

All mucosal surfaces are lined by epithelial cells and are colonised by opportunistic microbes. In health, these opportunistic microbes remain commensal and are tolerated by the immune system. However, when the correct environmental conditions arise, these microbes can become pathogenic and need to be controlled or cleared by the immune system to prevent disease. The mechanisms that enable epithelial cells to initiate the 'danger' signals activated specifically by pathogenic microbes are critical to mucosal defence and homeostasis but are not well understood. Deciphering these mechanisms will provide essential understanding to how mucosal tissues maintain health and activate immunity, as well as how pathogens promote disease. This review focuses on the interaction of the human fungal pathogen Candida albicans with epithelial cells and the epithelial mechanisms that enable mucosal tissues to discriminate between the commensal and pathogenic state of this medically important fungus.

Effect of tea catechins on regulation of cell proliferation and antioxidant enzyme expression in H2 O2 -induced primary hepatocytes of goat in vitro.

Tea catechins (TC) are polyphenols that have potent antioxidant activity. The objectives of this study were to determine the effects of TC on antioxidant status of hepatocytes challenged with H2 O2 . Primary hepatocytes of goat were exposed to 1 mm H2 O2 without or with 5, 50 and 500 µg/ml TC. The cells were harvested at 48 h post-treatment to determine effects of TC on proliferation, apoptotic features and membrane integrity of cells, and expression of genes and activities of antioxidant enzymes. H2 O2 exposure caused damage to cells (p < 0.001). A lower concentration of TC (5 µg/ml) displayed a protective effect by inhibiting exorbitant cell proliferation and DNA degradation. Both H2 O2 exposure and TC pre-incubation affected expression of antioxidant enzymes at mRNA and protein levels (p < 0.001). The activities of catalase (CAT) (p = 0.027), CuZn-superoxide dismutase (CuZn-SOD) (p < 0.001) and glutathione peroxidase (GPx) (p < 0.001) increased with TC pre-incubation followed by H2 O2 challenge. Changes of CuZn-SOD activity induced by H2 O2 and TC basically paralleled the changes in the corresponding mRNA and protein levels, but the correlation in CAT and GPx expression displayed slightly different patterns at different concentrations of TC. These findings infer that oxidative stress can induce deleterious cellular responses and this unfavourable condition may be alleviated by treatment with TC.

Effects of maternal protein or energy restriction during late gestation on antioxidant status of plasma and immune tissues in postnatal goats.

Maternal malnutrition can have temporary or long-lasting effects on development and physiological function of offspring. Our objective was to investigate whether maternal protein or energy restriction in late gestation affects the antioxidant status of plasma, immune organs (thymus and spleen), and natural barrier organs (jejunum) in neonatal goats and whether the effects could be reversed after nutritional recovery. Forty-five pregnant goats (Liuyang Blacks) of similar age (2.0 ± 0.3 yr) and BW (22.2 ± 1.5 kg at d 90 of gestation) were assigned to 3 dietary treatments during late gestation: control (ME = 9.34 MJ/kg and CP = 12.5%, DM basis), 40% protein restricted (PR), and 40% energy restricted (ER) until parturition, after which offspring received the normal diet for nutritional recovery. Plasma and tissues of kids were sampled to determine antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), and catalase (CAT)] and gene expression of antioxidant enzymes (Cu/Zn-SOD [SOD1], CAT, and peroxiredoxin 2 [PRDX2]). Maternal protein or energy restriction decreased (P < 0.05) SOD activities in plasma, liver, thymus, and spleen and SOD1 expression in thymus, and maternal energy restriction also decreased (P < 0.05) plasma GSH-Px activity and expressions of SOD1 and CAT in liver at birth. After nutritional recovery of 6 wk, SOD activities in thymus (both in PR and ER) and spleen (only in PR) were greater (P < 0.05), but CAT activity of thymus (both in PR and ER) and CAT expression (only in ER) were less (P < 0.01) than those in control. After nutritional recovery of 22 wk, SOD1 and PRDX2 expression in thymus (both in PR and ER) and SOD1 expression in liver (only in ER) were greater (P < 0.05) whereas CAT expression in thymus (both in PR and ER) was less (P < 0.001) than in control. The current results indicate that maternal protein or energy restriction can decrease the antioxidant capacity of the neonatal kids and result in an imbalance of SOD and hydrogen peroxide-inactivating systems in thymus, even after 6 or 22 wk of nutritional recovery.

Milk powder induced lipid peroxidation reduction using Ku Ding tea (Lactuca taiwaniana Maxim) in rats.

The effects of Ku Ding tea (Lactuca taiwaniana Maxim) and milk powder on biochemical and immunological parameters of Sprague-Dawley rats were investigated and the possibility of use of Ku Ding tea to reduce physiological discomfort of drinking milk powder was assessed. Eighty rats were randomly assigned to four treatments: basal diet (control), basal diet plus whole milk powder (WM), basal diet plus Ku Ding tea (KD) and basal diet plus whole milk powder and Ku Ding tea (MK). Data was collected on animals' final body weight, hematological values, blood biochemical parameters, antioxidation parameters and immune organ weight index. Results showed that final body weight of male KD was significantly lower than that of WM. White blood cell count, monocyte count and granulocyte count of KD rats were significantly lower than those of WM. Compared to the control, single milk powder supplementation numerically increased plasma malondialdehyde. The malondialdehyde in the male KD and MK rats were lower than those in WM and control, although the differences were not significant. No significant differences were found in Na(+)K(+)-adenosine triphosphatase activity, spleen and thymus index in each group. Consumption of Ku Ding tea appeared to lower lipid peroxidation that was induced by milk powder in the rats.

Bioactivities of nerve growth factor from Chinese cobra venom.

The nerve growth factor, NGF, from Chinese cobra Naja naja atra venom was isolated by gel-filtration and ion-exchange chromatography. Cobra NGF was characterized by analytical HPLC techniques as well as SDS-PAGE, and was proven to be a glycoprotein with a mol. wt. of 23 (+/- 2) kD and a pI of 9.2. The amino acid analysis and N-terminal sequencing were performed using conventional methods. Bioassays with cultured chick embryos ganglia and rat pheochromocytoma PC-12 cells revealed a promotion of fiber outgrowth, which is typical of NGF activity. Absence of enzymatic, toxicological, and teratogenic activities were shown by quality inspection. Since 1994, many clinical cases about volunteers receiving NGF treatment have been reported in mainland China. Bioactivities of NGF deal with a wide range of disciplines and technologies. In this paper we will discuss neuronal and non-neuronal effects of NGF treatment. Does the NGF cross the blood-brain barrier by transcytosis into the brain tissue? How is NGF important in wound healing, especially in peripheral nerve injury and diabetic neuritis? NGF may also be useful for male volunteers suffering from sterility, because it is possible that the sexual cells of testis can be promoted to maturity.