OBJECTIVES: To evaluate the therapeutic effect of gastrodin against hypoxic-ischemic brain damage (HIBD) in neonatal mice and explore the role of GPX4/SLC7A11/FTH1 signaling in mediating its effect. METHODS: Twenty-four 9- to 11-day-old C57BL/6J mice were randomized equally into 4 groups for sham operation, HIBD modeling by right common carotid artery ligation and subsequent exposure to hypoxia for 1 h, or gastrodin treatment at 100 or 200 mg/kg before and at 1 and 2 days after modeling. The mice then underwent neurological assessment (Zea-Longa scores), and the cerebral cortical penumbra tissue were collected for HE and Nissl staining, detection of ferroptosis biomarkers and protein expressions of GPX4, SLC7A11, and FTH1 with Western blotting and immunofluorescence co-localization, and observation of mitochondrial ultrastructure with electron microscopy. In cultured HT22 neuronal cells with oxygen-glucose deprivation (OGD) for 2 h, the effects of pretreatments with 0.5 mmol/L gastrodin, 10 μmol/L RSL3 (a GPX4 inhibitor), alone or in combination, were analyzed on expressions of ferroptosis-related proteins, cellular Fe²⁺, ROS, lipid peroxidation, MDA, and GSH levels, mitochondrial membrane potential (JC-1), and cell viability. RESULTS: Gastrodin treatment at the two doses both significantly ameliorated HIBD and neurological deficits of the mice, reduced mitochondrial damage and Fe²⁺, MDA and ROS levels, increased GSH level, and upregulated GPX4, SLC7A11, and FTH1 protein expressions. In HT22 cells, gastrodin pretreatment obviously attenuated OGD-induced ferroptosis and improved cell viability and mitochondrial function. Co-treatment with RSL3 potently abrogated the inhibitory effects of gastrodin on Fe²⁺, ROS, BODIPY-C11, and MDA levels and attenuated its protective effects on GSH level, cell viability, and mitochondrial membrane potential. CONCLUSIONS Gastrodin provides neuroprotective effects in neonatal mice with HIBD by suppressing neuronal ferroptosis via upregulating the GPX4/SLC7A11/FTH1 signaling pathway.
Animals ; Ferroptosis/drug effects* ; Hypoxia-Ischemia, Brain/drug therapy* ; Mice ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Glucosides/pharmacology* ; Animals, Newborn ; Benzyl Alcohols/pharmacology* ; Amino Acid Transport System y+/metabolism*

【Objective】 To investigate the suicidal attitude, ideation of adolescent patients with depression, and to analyze their relationships with family environment, in order to provide evidence for the clinical treatment of adolesent depression and to reduce the suicide rate. 【Methods】 Totally 376 adolescents diagnosed with depression in Lu′an area from March 2019 to October 2021 were selected as the case group, and 376 normal adolescents were selected as the control group.The suicide attitude questionnaire (QSA), Beck scale for suicide ideation (BSS) and family environment scale (FES-CV) were used to investigate the suicide attitude, suicidal ideation and family environment of adolescents in two groups. Logistic regression analysis was used to analyze the influencing factors of suicide attitude and ideation of adolescent depression patients.Pearson correlation test was used to analyze the correlations between suicidal attitude, ideation and family environment of adolescent patients with depression. 【Results】 The scores of QSA and BSS in the case group were significantly higher than those in the control group (t=43.352, 96.527, P<0.001).The scores of intimacy, emotional expression, knowledge and entertainment in FES-CV of the case group were lower than those of the control group (t=25.487, 14.573, 22.160, 18.906), the score of contradiction was higher than that of the control group (t=30.311), and the differences were statistically significant (P<0.001).Logistic regression analysis showed that age of 20 - 25 years old (OR=2.016,2.261), severe illness (OR=2.115, 2.192), dwelling in city (OR=2.442, 2.557) were all risk factors for suicidal attitude and ideation in adolescent depression patients (P<0.05).The scores of QSA and BSS in the case group were negatively correlated with the scores of intimacy, emotional expression, knowledge and entertainment in FES-CV (QSA: r=-0.891,-0.933,-0.788,-0.698, BSS: r=-0.901,-0.832,-0.725,-0.637, P<0.05), but they were positively correlated with the score of contradiction (r=0.848, 0.883, P<0.05). 【Conclusions】 The suicidal attitude, ideation of adolescents with depression are higher than those of normal adolescents. Age, illness and growth environment are all influencing factors for suicidal attitudes and ideation in adolescent depression patients, of which the suicide attitude, ideation of patients are closely related to family environment.

Background::To date, there is no effective medicine to treat coronavirus disease 2019 (COVID-19), and the antiviral efficacy of arbidol in the treatment for COVID-19 remained equivocal and controversial. The purpose of this study was to evaluate the efficacy and safety of arbidol tablets in the treatment of COVID-19.Methods::This was a prospective, open-label, controlled and multicenter investigator-initiated trial involving adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients were stratified 1:2 to either standard-of-care (SOC) or SOC plus arbidol tablets (oral administration of 200 mg per time, three times a day for 14 days). The primary endpoint was negative conversion of SARS-CoV-2 within the first week. The rates and 95% confidential intervals were calculated for each variable.Results::A total of 99 patients with laboratory-confirmed SARS-CoV-2 infection were enrolled; 66 were assigned to the SOC plus arbidol tablets group, and 33 to the SOC group. The negative conversion rate of SARS-CoV-2 within the first week in patients receiving arbidol tablets was significantly higher than that of the SOC group (70.3% [45/64] vs. 42.4% [14/33]; difference of conversion rate 27.9%; 95% confidence interval [CI], 7.7%-48.1%; P = 0.008). Compared to those in the SOC group, patients receiving arbidol tablets had a shorter duration of clinical recovery (median 7.0 days vs. 12.0 days; hazard ratio [HR]: 1.877, 95% CI: 1.151-3.060, P = 0.006), symptom of fever (median 3.0 days vs. 12.0 days; HR: 18.990, 95% CI: 5.350-67.410, P < 0.001), as well as hospitalization (median 12.5 days vs. 20.0 days; P < 0.001). Moreover, the addition of arbidol tablets to SOC led to more rapid normalization of declined blood lymphocytes (median 10.0 days vs. 14.5 days; P > 0.05). The most common adverse event in the arbidol tablets group was the elevation of transaminase (5/200, 2.5%), and no one withdrew from the study due to adverse events or disease progression. Conclusions::SOC plus arbidol tablets significantly increase the negative conversion rate of SARS-CoV-2 within the first week and accelerate the recovery of COVID-19 patients. During the treatment with arbidol tablets, we find no significant serious adverse events.Trial registration::Chinese Clinical Trial Registry, NCT04260594, www.clinicaltrials.gov/ct2/show/NCT04260594?term= NCT04260594&draw=2&rank=1

Objective:To analyze the potential influencing factors of depression among chronic heart failure (CHF) patients systematically, so as to provide reference for effective intervention.Methods:We searched the databases of CNKI, WanFang Data, VIP, CBM, PubMed, Cochrane library, Web of Science, Embase, PsycINFO and PsyARTICLE database for relevant articles. The literature was screened according to the inclusion and exclusion criteria. The quality of the included literature was evaluated and the data was extracted by 2 researchers independently. Review Manager 5.3 was used to analyze the data.Results:A total of 25 articles were included. The combined effect size OR/ SD (95% CI) of each influencing factor in descending order were: sedentary behavior 2.75 (1.62 to 4.66) , long duration 2.58 (2.09 to 3.07) , EF values -2.29 (-3.44 to -1.13) , NYHAⅢ/Ⅳ 2.28 (1.70 to 3.08) , the combination of anemia 1.72 (1.30 to 2.28) , solitary 1.48 (1.16 to 1.88) , the combination of Chronic renal insufficiency 1.46 (1.16 to 1.85) and COPD 1.44 (1.04 to 2.00) , low BMI -1.13 (-1.64 to -0.98) , good knowledge of heart failure 0.67 (0.47 to 0.95) , male 0.63 (0.53 to 0.76) , married 0.57 (0.47 to 0.69) . Conclusions:The influencing factors of chronic heart failure combined with depression are diverse. Medical staff can identify the heart failure patients with high prevalence of depression early according to the related influencing factors, and can also intervene the controllable influencing factors to reduce the occurrence of depression.

Objective To investigate dermoscopic features of onychomycosis and nail psoriasis.Methods From March 2017 to March 2018,128 patients with onychomycosis and 128 with nail psoriasis were enrolled from Department of Dermatology,Xiangyang Central Hospital.Dermoscopic images of the lesional nails were compared.Enumeration data were analyzed by chi-square test and Fisher's exact test.Results There were 7 kinds of dermoscopic patterns in onychomycosis,including jagged edge (69/128,53.91％),longitudinal striae (72/128,56.25％),cone-shaped keratosis (30/128,23.44％),nail plate thickening (21/128,16.41％),black dots (5/128,3.91％),onycholysis (26/128,20.31％),and nail discoloration (23/128,17.97％).The jagged edge and longitudinal striae occurred more frequently in distal/ lateral subungual onychomycosis (DLSO) than in the other 3 clinical subtypes of onychomycosis (all P ＜ 0.001),and cone-shaped keratosis occurred more frequently in total dystrophic onychomycosis (TDO) than in the other 3 clinical subtypes of onychomycosis (x2 =42.020,P ＜ 0.001).There were no significant differences in the prevalance of nail plate thickening,black dots,onycholysis and nail discoloration among the 4 clinical subtypes of onychomycosis (all P ＞ 0.05).There were 7 kinds of dermoscopic patterns in nail psoriasis,including pitting corrosion (61/128,47.66％),oil drop sign (41/128,32.03％),splinter hemorrhage (41/128,32.03％),dilated hyponychial capillaries (23/128,17.97％),nail plate thickening (20/128,15.63％),onycholysis (20/128,15.63％),and nail discoloration (13/128,10.16％).The oil drop sign occurred more frequently in psoriasis vulgaris and psoriasis arthropathica than in the other 2 clinical subtypes of psoriasis (P =0.019).The dilated hyponychial capillaries occurred more frequently in pustular psoriasis than in the other 3 clinical subtypes of psoriasis (P =0.047).There were no significant differences in the prevalance of pitting corrosion,splinter haemorrhage,nail plate thickening and nail discoloration among the 4 clinical subtypes of psoriasis (all P ＞ 0.05).Conclusions The dermoscopic features of onychomycosis include jagged edge,longitudinal striae,cone-shaped keratosis and black dots,and the dermoscopic features of nail psoriasis include pitting corrosion,oil drop sign,splinter haemorrhage and dilated hyponychial capillaries.Their common dermoscopic features include nail plate thickening,onycholysis and nail discoloration.

Objective To investigate the role and significance of neuropilin-2(NRP2)for regulating the angiogenesis of pancreatic neuroendocrine tumors(PNETs).Methods The NRP2 expression in pancreatic neuroendocrine tumer BON-1 cell line was intevened.The BON-1 cells cultural supernatants in the control group and interference group were used to treat human umbilical vein endothelial cells(HUVEC).CCK-8 was used to detect the cell proliferation,Transwell was used to detected the cell migration and the tubule formation test was used detect the pro-angiogenesis.Results The CCK-8 detection showed that there was no statistically significant difference in the supernatant treated HUVEC proliferations between the interference group and control group medium(P>0.05):the absorbancy in the control group was 0.35±0.04,while which in the interference group was 0.32±0.04.The Transwell test showed that the invasion ability of HUVEC treated with cultural supernatants in the interference group was weakened compared with the control group,the control group was(203±13)/hole,while the interference group was(100±10)/hole(P＜0.01);the tubule formation test showed that HUVEC tubular formation treated by cultural supernatant in the interference group was decreased,the control group was 40±5,while the interference group was 24±3(P＜0.01).Conclusion Interfering NRP2 expression of BON-1 cells can inhibit the vessel formation ability of co-cultured HUVEC,suggesting that NRP2 may have the pro-angiogenesis effect of PNETs,and may be a potential new target for the treatment of PNETs.

Objective To study the effect of Jingyebaidu granules on treating cytomegalovirus ( CMV) infection during mid-pregnancy. Methods The sexually mature guinea pigs with no CMV infection history served as the subjects. Put the male and female ones in the same cages. Then the female ones were randomly divided into three groups during mid-pregnancy. Model control group:15 guinea pigs which were inoculated 1 mL suspension of GPCMV intraperitoneally. Jingyebaidu Medicine group:15 guinea pigs which were treated with Jingyebaidu(3. 09 mL·kg-1 ) through stomach perfusion after inoculation for 14 days. Normal control group:15 normal mid-pregnant guinea pigs. Viremia rates were examined 7 days after infection. All animals were sacrificed 20 days after infection. The placenta infection rate, pup infection rate, still-born rate were examined. Results Compared with the normal controls, the still-born rate was increased in model control group(8. 33% vs 34. 55%, P<0. 05). In comparison to the model control group, the GPCMV maternal infection rate(86. 67% vs 33. 33%), placenta infection rate (91. 67% vs 61. 22%), pup infection rate(90. 91% vs 48. 28%), still-born rate(34. 55% vs 15. 52%) were significantly decreased in the Jinyebaidu group (all P<0. 05). Conclusion Jinyebaidu granules could reduce maternal infection,pup loss, and placenta infection caused by CMV inoculation during mid-pregnancy.

The link between nonresolving inflammation and cancer is well documented. On the one hand, epidemiologic evidence supports that approximately 25% of all human cancer worldwide is caused by nonresolving inflammation. On the other hand, inflammatory cells are found in the microenvironment of most, if not all, tumors. In the tumor micro-environment, inflammatory cells and molecules influence almost every aspect of cancer. MicroRNAs (miRNAs) participate in the initiation and progression of nonresolving inflammation-related cancer by regulating the key genes and related signaling pathways. Further investigation into the molecular mechanisms by which miRNAs carry out their functions will be of great value in the prevention, early diagnosis, and treatment of tumors.
Chronic Disease ; Humans ; Inflammation ; complications ; genetics ; immunology ; Inflammation Mediators ; immunology ; MicroRNAs ; genetics ; Neoplasms ; etiology ; genetics ; Tumor Microenvironment

The research team on the National Key Scientific Program of China: "Transcriptomic regulation and molecular mechanism research of polygenic tumor at different stages" has focused on the field of transcriptomics of 4 common polygenic tumors, including nasopharyngeal carcinoma(NPC), breast cancer, colorectal cancer, and glioma. Extensive laboratory work has been carried out on the expression and regulation of tumor transcriptomics; identification of tumor suppressor/susceptible genes; mechanism of tumor epigenetics including miRNAs, and comparative study of specific gene/protein cluster of tumor transcriptomics and proteomics. Genes including SPLUNC1, LTF, BRD7, NOR1, BRCA1/2, PALB2, AF1Q, SOX17, NGX6, SOX7, and LRRC4 have been identified as the key transcriptional regulation genes during the stage of tumor initiation and invasion. Accordingly,the NPC gene signal regulation network of "SPLUNC1-miR-141-target genes", the breast cancer interaction signal pathway of "miR-193b-uPA",the glioma signal network of "miR-381- LRRC4-MEK/ERK/AKT", and the miRNA-target gene network of colorectal cancer metastasis related gene NGX6 have been thoroughly elucidated. These fruitful Results imply that the changes of key molecules in crucial signal pathway will cause severe dysfunction in signal transduction and gene regulation network in polygenic tumors, indicating that in the category of pathogenesis,these tumors may further classify as the "Disease of gene signal transduction and gene regulation network disorder". The researches have laid solid foundation for revealing the molecular mechanism and transcriptomic regulation of polygenic tumors at different stages.
Animals ; Brain Neoplasms ; genetics ; pathology ; Breast Neoplasms ; genetics ; pathology ; Colorectal Neoplasms ; genetics ; pathology ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Glioma ; genetics ; pathology ; Humans ; MicroRNAs ; genetics ; Multifactorial Inheritance ; Nasopharyngeal Neoplasms ; genetics ; pathology ; Neoplasm Proteins ; genetics ; Neoplasm Staging ; Neoplasms ; genetics ; Transcription, Genetic ; Transcriptome ; Tumor Suppressor Proteins ; genetics

Objective To investigate and assess 13C-methacetin breath test as a method to quantitatively evaluate the liver function of non-alcoholic fatty liver. Methods Twenty-four male Wistar rats were randomly divided into the following 2 groups, control group given a standard chow and model group given high-fat diet (88 % standard chow + 10% lard +2% cholesterol). At the 8th week and 12th week, the isotope-selective nondispersive infrared spectrometer (NDIRS) was applied to 13C-methacetin breath test. Peak value of breathing (DOB), the duration to peak (T), and cumulative expiration within 60 min (CUM60min) were determined. Then, the two groups of rats were executed respectively. The level of endotoxin in the portal vein and abdominal aorta was detected respectively, and the specific tissue of liver was fixed in 10% buffered formalin, processed, and embedded in paraffin for hematoxylin eosin (H&E). Results Compared with the control group, DOB increased in the model group at the 12th week but not at the 8th week. The trend was corresponded to the degree of path-ological lesion in the liver of rats. At the 8th week and 12th week, endotoxin levels in the portal vein of model group were significantly in-creased compared with control group. The breath test results were positively related to emlotoxin levels in the portal vein. Conclusion 13C-methacetin breath test may be a non-invasive method to evaluate the pathological changes of non-alcoholic fatty liver.