[Diaphragmatic dysfunction post-COVID-19 infection: report of two cases].

Following the global outbreak of COVID-19, many patients have suffered from multi-system complications and long-term sequelae caused by the virus. Diaphragm dysfunction is an obscure post-COVID-19 symptom. Although a few cases of diaphragm dysfunction caused by COVID-19 infection have been reported abroad, there are no relevant reports in China. Herein, we present two cases of patients with respiratory distress after COVID-19 infection. On admission, dynamic chest radiographs revealed diaphragm dysfunction in these patients. Further investigations including diaphragm ultrasound, neurophysiological examinations, transdiaphragmatic pressure measurements cranial MRI, and antibody testing for autoimmune diseases, were conducted. The final diagnoses were severe myasthenia gravis induced by COVID-19 infection and diaphragmatic nerve and muscle involvement caused by COVID-19 infection. Both patients showed improvement in symptoms after treatment. Therefore, we summarized our case, with a review of the relevant literature to improve the understanding of the disease and to provide clinical evidence for future diagnosis and treatment.

[Psychological problems in breast cancer patients should be taken seriously].

With the transformation of the biopsychosocial medical model, psychological problems and related interventions for breast cancer patients have received more and more attention. Patients often have various psychological problems, in diagnosis, treatment, and even in the state of disease-free survival, such as anxiety and depression, which not only seriously reduces the quality of life, but also affects the follow-up treatment and increases the risk of recurrence and metastasis. Therefore, physicians should perform routine psychological screening and appropriate intervention for patients. In recent years, psychological intervention has gradually become an important part of comprehensive breast cancer treatment, in which cognitive behavior therapy can alleviate patients' anxiety and sleep disorders, mindfulness therapy can treat patients' anxiety, depression and fear of cancer recurrence, and psychoeducational support is mainly used to address patients' mood disorders and sexual dysfunction. Improving patients' compliance with treatment and quality of life is the main goal of psychological intervention for breast cancer patients.

[An analysis of breast cancer patients with ultrasound BI-RADS 3 lesions after minimally invasive excision in clinicopathological features and influencing factors of residual tumor].

Objectives: To examine the clinicopathological characteristics and the influencing factors of the residual tumor of patients with Breast Image Report and Data System (BI-RADS) grade 3 lesions diagnosed with malignancy after minimally invasive excision. Methods: In this retrospective case-control study, clinicopathological data of 69 cases, which had been evaluated as BI-RADS 3 lesions by ultrasound (4 151 cases) diagnosed with breast cancer by minimally invasive excision pathology, were analyzed between May 2012 and June 2016 at the Department of Breast Surgery of the Second Hospital of Shandong University and Linyi People's Hospital. All patients were female, aged (43.4±8.2) years (range: 22 to 70 years). Based on residual tumor after minimally invasive excision, patients were classified into two subgroups: tumor residual group (n=39) and non-tumor residual group (n=30). The clinicopathological features between the two groups were compared. The differences in clinicopathological characteristics were compared in different groups using the χ2 test and the t test. Potential variables identified in the univariate analysis and other relevant variables will be analyzed multivarially using Logistic regression models. The Kaplan-Meier method was applied for survival analysis and survival curves. Results: The breast cancer detection rate of ultrasound BI-RADS 3 lesions was 1.66% (69/4 151), and their maximum diameter of the masses was (1.27±0.45) cm (range: 0.5 to 2.3 cm). Among them, the maximum diameter were ≤1 cm in 28 cases and >1 cm in 41 cases. Histopathological results showed carcinoma in situ in 24 cases and invasive carcinoma in 41 cases, positive expression of the estrogen receptor in 47 cases, positive expression of the progesterone receptor in 43 cases, Ki-67 proliferation index elevated in 26 cases. Axillary metastasis positive rate was 10.1% (7/69). Residual tumor after minimally invasive surgery was found in 39 cases (56.5%). Univariate analysis showed that the tumour residual group showed a significantly increased rate of positive expression of the estrogen receptor (91.9%(34/37) vs. 61.9%(13/21), χ2=7.838, P=0.012). In multivariate analysis, the only variable found to significantly affect the residual tumor was the positive expression of the estrogen receptor (OR=16.852, 95%CI: 1.819 to 156.130, P=0.013). The 5-year disease-free survival rate of breast cancer patients with breast ultrasound BI-RADS 3 lesions was 97.1% and the overall survival rate was 98.6%. Conclusions: BI-RADS 3 lesions diagnosed by ultrasound undergoing ultrasound-guided minimally invasive excision have a certain risk of detected malignancy, approximately 1.66%. Patients with positive expression of the estrogen receptor are more likely to develop residual tumor. A secondary operation should be considered to ensure that no tumor residues remain in the cavity.

Gamma-Ray Observation of the Cygnus Region in the 100-TeV Energy Region.

We report observations of gamma-ray emissions with energies in the 100-TeV energy region from the Cygnus region in our Galaxy. Two sources are significantly detected in the directions of the Cygnus OB1 and OB2 associations. Based on their positional coincidences, we associate one with a pulsar PSR J2032+4127 and the other mainly with a pulsar wind nebula PWN G75.2+0.1, with the pulsar moving away from its original birthplace situated around the centroid of the observed gamma-ray emission. This work would stimulate further studies of particle acceleration mechanisms at these gamma-ray sources.

[The influence of dihydrotestosterone on cytokine releases in male mice model with Graves disease].

Objective: To study the influences of dihydrotestosterone (DHT) on the development of experimental autoimmune Graves disease (EAGD), and to observe the effect of DHT on cytokines in male BALB/c mice model. Methods: Male BALB/c mice aged 6-8 weeks were divided into 4 groups using random number table: (1) control group; (2) EAGD group; (3) placebo group; (4) DHT group. EAGD mice were induced with an adenovirus expressing the human thyroid stimulating hormone receptor antibody A-subunit (Ad-TSHR289). DHT (5mg) or a matching placebo were implanted one week before the first immunization. Thyroid hormones were detected with radioimmunoassay kit.. Cytokines [such as interferonγ (IFNγ), interleukin (IL)-4, IL-10, IL-9, and IL-17] producing cells from the spleen were detected using flow cytometry. Results: As expected Ad-TSHR289 treatment increased total thyroxine [EAGD group vs. control group: (117.76±32.69) nmol/L vs. (33.08±12.61) nmol/L, P<0.0001] and free thyroxine [EAGD group vs. control group: (15.01±11.55) pmol/L vs. (3.55±1.88) pmol/L, P<0.0001]. Treatment of DHT slightly lowered thyroid hormones [DHT group vs. placebo group: total thyroxine (114.80±44.27) nmol/L vs. (123.17±77.73) nmol/L; free thyroxine (13.48±6.01) pmol/L vs. (14.19±12.65) pmol/L], without significant difference (all P>0.05)]. However, the percentage of IL-10, but not IFN γ, IL-4, IL-9 and IL-17, secreted spleen cells increased in DHT group than in the placebo group [(7.11±3.29)% vs. (3.51±1.36)%, P<0.05]. Conclusion: The effects of DHT on thyroid hormone are mild. It might play an immunomodulatory role in the male mouse Graves disease model by up-regulating the cytokine IL-10.

[Relationship between morphological characteristics and prognosis of non-nasopharyneal EBV-associated carcinoma].

Objective: To analyze the pathological features and their influence on the clinical outcome of non-nasopharyngeal EBV-associated carcinomas. Methods: One hundred and twenty cases of non-nasopharyngeal EBV-associated carcinoma confirmed by in situ hybridization were identified at Zhejiang Cancer Hospital from January 1, 2006 to May 1, 2018, and the clinicopathological data were collected and analyzed using Kaplan-Meier survival analysis, Cox univariate and multivariate analysis. Results: One hundred and twenty cases were involved in the study; the male to female ratio was 1∶1; patients' age range was 24 to 89 years (median 50 years). The primary sites were large parotid glands (62 cases), lung(26 cases), stomach(15 cases), and others (oral, oropharynx, larynx, cervix, liver; totally 17cases). Non-nasopharyngeal EBV-associated cancer could be divided into two histological types according to the amount of interstitial lymphocytes: type Ⅰ was "lymphoepithelial-like carcinoma" and rich in stromal lymphocytes; type Ⅱ lacked lymphocytic infiltration. Ninety-eight primary tumor samples could be classified morphologically: 43 cases were as type Ⅰ and 55 cases as typeⅡ; the distribution of type Ⅰ was 57.4% (27/47) in large parotid glands, 20.8% (5/24) in lung, 4/13 in stomach, and 7/14 in other sites. Complete treatment and survival data were obtained for 114 patients. According to the TNM staging criteria of WHO, 52 patients were at early stages (Ⅰ-Ⅱ) and 62 were at advanced stages (Ⅲ-Ⅳ); 102 patients underwent surgery. Seventy-four patients received adjuvant chemotherapy before or after surgery, and 52 patients received local radiotherapy. Kaplan-Meier survival analysis showed that patients with type Ⅱ EBV-associated carcinoma had a worse prognosis than patients with type Ⅰtumors (P=0.010 2). In addition, vascular invasion(P=0.021 8),neural recidivism(P=0.000 1),advanced stage(P=0.017 1),lymph node metastasis (P=0.005 0) and chemotherapy (P=0.013 2) were poor prognostic factors; female patients had better survival than male (P=0.028 4). Cox multivariate regression analysis found that lymph node metastasis (95%CI: 1.489-13.830, P=0.007 6) and neural recidivism (95%CI: 1.228-6.544, P=0.014 7) were independent adverse prognostic factors. Cox multivariate regression analysis after stratification by site revealed that radiotherapy was a preferable prognostic factor for EBV-associated carcinoma of the large salivary glands (95%CI: 0.003-0.569, P=0.016 8). Conclusion: EBV associated carcinoma can be divided into two types, for which type Ⅰ was with abundant interstitial lymphocytes and type Ⅱ was lack of interstitial lymphocytes. TypeⅡ EBV-associated carcinoma has a worse prognosis than type Ⅰ. Radiation therapy can prolong the survival time of patients with primary EBV-associated carcinoma of large salivary glands.

Detection of combined procalcitonin and c-reactive protein applied in the diagnosis of bacterial infections.

In recent years, procalcitonin and C-reactive protein have been used as important indexes in the detection of inflammation. In order to analyze the combined detection of procalcitonin and C-reactive protein in infected patients, 57 subjects in the Clinical Laboratory of Zhengzhou Maternal and Child Health Hospital with a bacterial infection were selected as the observation group. Correspondingly, 57 non-infected subjects were selected for the control group. The procalcitonin and C-reactive protein levels in the included cases were analyzed and compared by extracting peripheral blood. The results showed that the two indexes of C-reactive protein (46.13±8.24 mg/L) and procalcitonin (6.61±3.45 ug/L) of the observation group were significantly higher than those of the control group (P less than 0.05). The positive rates of C-reactive protein (71.93%) and procalcitonin (91.23%) of the observation group were significantly higher than those of the control group (P less than0.05). Within the observation group, the C-reactive protein and procalcitonin levels in the infected patients after 2 and 3 days of treatment, decreased significantly (P less than 0.05). This study indicates that the combined detection of procalcitonin and C-reactive protein in patients with bacterial infections is effective and can be used in clinical settings.

Response of Chrysoperla nipponensis (Okamoto) (Neuroptera: Chrysopidae) Under Long and Short Photoperiods.

C. NIPPONENSIS: Photoperiod is an important factor influencing many biological processes including population dynamics of many insect species in temperate zones. To determine the population response of Chrysoperla nipponensis under altered conditions (high temperature and short photoperiod) and to test whether the short photoperiod was suitable for artificial storage, the life table data of were collected at 25 °C under a long photoperiod, 15:9 h (L:D), and a short photoperiod, 9:15 h (L:D) and analyzed using the age-stage, two-sex life table approach. We found that developed faster under long photoperiod than under the short photoperiod. The shorter developmental time, higher fecundity, and higher proportion of females found during the long photoperiod resulted in higher intrinsic and net reproductive rates, but a shorter mean generation time and life expectancy compared to those reared during the short photoperiod. Individuals reared under the short photoperiod also had a high reproductive value. Population projection demonstrated that reared at long photoperiod would complete four generations in 150 d, while reared under short photoperiod would just be entering the second generation. Our results demonstrated that the different fitness values obtained for individuals by varying photoperiod lengths, were readily distinguishable when using the age-stage, two-sex life table.

The association between clinical periodontal parameters and free haem concentration within the gingival crevicular fluid: a pilot study.

OBJECTIVES: To investigate the concentration of local free haem in gingival crevicular fluid at periodontally healthy compared with diseased sites in relation to clinical periodontal parameters. The second objective is to investigate for any correlation between smoking and haem concentration. MATERIAL AND METHODS: Clinical parameters were recorded for two healthy and two diseased sites from 22 patients with untreated periodontitis. Gingival crevicular fluid samples were collected from the same sites. Haem assay analysis was undertaken to determine haem concentration at these sites. RESULTS: Gingival crevicular fluid haem concentration was higher at periodontally diseased sites compared to healthy sites (mean 46.6 ± 70.6 nM in healthy vs. 1116.6 ± 2007.0 nM in diseased sites, p < 0.001) and positively correlated with probing pocket depth, attachment level and radiographic bone loss. Gingival crevicular fluid haem concentration was higher in non-smokers compared with smokers. However, no significant difference in correlation between haem concentration and clinical parameters were seen between smokers and non-smokers (p > 0.3). CONCLUSION: The higher concentration of gingival crevicular fluid haem at diseased compared with healthy sites indicates that there is an association between increased levels of local free haem and periodontal disease. This may be through the pro-inflammatory actions of free haem. Further study on a larger scale is required to determine the influence of smoking between haem concentration and clinical parameters.

Characterization, expression analysis and localization pattern of toll-like receptor 1 (tlr1) and toll-like receptor 2 (tlr2) genes in grass carp Ctenopharyngodon idella.

In this study, the toll-like receptor 1 (tlr1) and toll-like receptor 2 (tlr2) genes of grass carp Ctenopharyngodon idella were cloned and characterized. tlr1 and tlr2 were found to be highly expressed in immune system organs such as spleen, middle kidney and heart kidney. The expression level of tlr1 and tlr2 was found to be up-regulated at the later stage of viral challenge process. Moreover, subcellular localization indicated that Tlr1 and Tlr2 shared similar localization pattern and both of them may locate in the plasma membrane of transfected cells.

Notch signaling mediates granulocyte-macrophage colony-stimulating factor priming-induced transendothelial migration of human eosinophils.

BACKGROUND: Priming with cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances eosinophil migration and exacerbates the excessive accumulation of eosinophils within the bronchial mucosa of asthmatics. However, mechanisms that drive GM-CSF priming are incompletely understood. Notch signaling is an evolutionarily conserved pathway that regulates cellular processes, including migration, by integrating exogenous and cell-intrinsic cues. This study investigates the hypothesis that the priming-induced enhanced migration of human eosinophils requires the Notch signaling pathway. METHODS: Using pan Notch inhibitors and newly developed human antibodies that specifically neutralize Notch receptor 1 activation, we investigated a role for Notch signaling in GM-CSF-primed transmigration of human blood eosinophils in vitro and in the airway accumulation of mouse eosinophils in vivo. RESULTS: Notch receptor 1 was constitutively active in freshly isolated human blood eosinophils, and inhibition of Notch signaling or specific blockade of Notch receptor 1 activation during GM-CSF priming impaired priming-enhanced eosinophil transendothelial migration in vitro. Inclusion of Notch signaling inhibitors during priming was associated with diminished ERK phosphorylation, and ERK-MAPK activation was required for GM-CSF priming-induced transmigration. In vivo in mice, eosinophil accumulation within allergic airways was impaired following systemic treatment with Notch inhibitor, or adoptive transfer of eosinophils treated ex vivo with Notch inhibitor. CONCLUSIONS: These data identify Notch signaling as an intrinsic pathway central to GM-CSF priming-induced eosinophil tissue migration.

Seasonal concentrations, contamination levels, and health risk assessment of arsenic and heavy metals in the suspended particulate matter from an urban household environment in a metropolitan city, Beijing, China.

The levels and health risks of arsenic and heavy metals (As, Ba, Cd, Co, Cr, Cu, Mn, Ni, Pb, and Zn) in the suspended particulate matter (SPM) collected from an urban household environment in Beijing of China for 12 months were investigated. The mean concentrations of the studied toxic elements were higher and lower than crustal abundance and PM2.5 in the urban outdoors of Beijing. The concentrations of the studied elements displayed significant seasonality. The highest concentrations of the total elements occurred in winter, followed by autumn, while the lowest concentrations were recorded in summer. Based on the calculated values of enrichment factor (EF) and geoaccumulation index (Igeo), the levels for As and Cu were heavily contaminated, while those for Cd, Pb, and Zn were extremely contaminated. As and Pb might pose risks to children and adults via ingestion exposure. The accumulative risks of multi-elements resulted from dermal contact and inhalation exposures were not negligible. More attention should be paid to reducing the non-carcinogenic and carcinogenic health risks posed by the toxic elements bound to urban household SPM particles via ingestion, inhalation, and dermal contact exposure.

Defining the anti-inflammatory activity of a potent myxomaviral chemokine modulating protein, M-T7, through site directed mutagenesis.

Viral chemokine modulating proteins provide new and extensive sources for therapeutics. Purified M-T7, a poxvirus-derived secreted immunomodulatory protein, reduces mononuclear cell invasion and atheroma in rodent models of angioplasty injury as well as aortic and renal transplant, improving renal allograft survival. M-T7 is a rabbit species-specific interferon gamma receptor (IFNγR) homolog, but also inhibits chemokine/glycosaminoglycan (GAG) interactions for C, CC and CXC chemokines, with cross-species specific inhibitory activity. M-T7 anti-atheroma activity is blunted in GAG deficient mouse aortic transplants, but not in CC chemokine receptor deficient transplants, supporting M-T7 interference in chemokine/GAG interactions as the basis of the atheroma-inhibitory activity. We have assessed point mutants of M-T7 both in vivo in a mouse angioplasty model and in vitro in tissue culture and binding assays, in order to better define the primary mechanism of anti-atheroma activity. Of these M-T7 mutants, the R(171)E and E(209)I M-T7 mutants lost inhibitory activity for plaque growth in hyperlipidemic ApoE(-/-) mice after angioplasty injury and R(171)E, moreover, greatly exacerbated plaque growth and inflammation. F(137)D retained some inhibitory activity for plaque growth. In contrast, for cell migration assays, M-T7-His6X, F(137)D, R(171)E, and E(209)I all inhibited CC chemokine (RANTES) mediated cell migration. For the ligand binding assays, R(171)E and E(209)I had significantly reduced binding to RANTES and IFNγ, whereas F(137)D retained wild-type binding activity. Heparin treatment further reduced RANTES binding of all three M-T7 mutants. In summary, point mutations of M-T7, R(171)E and E(209)I, exhibited reduced anti-inflammatory properties in vivo after mouse angioplasty with a loss of in vitro binding to RANTES and IFNγ, indicating these point mutations partially disrupt M-T7 ligand-binding activities. Unexpectedly, the M-T7 mutants all retained inhibitory activity for human monocyte THP-1 cell migration ex vivo, suggesting additional inhibitory properties against human monocyte THP-1 cells that are independent of chemokine inhibition.

Detection of a novel single nucleotide polymorphism and imprinted status analysis of the Ras protein-specific guanine nucleotide-releasing factor 1 gene in domestic pigs.

The aim of this study was to determine the imprinting status of the Ras protein-specific guanine nucleotide-releasing factor 1 (Rasgrf1) gene in domestic pigs. In this study, a 228-bp partial sequence located in exon 14 and a 193-bp partial sequence located in exon 1 of the Rasgrf1 gene in domestic pigs were obtained. A novel single nucleotide polymorphism, a G/A transition, was identified in Rasgrf1 exon 14, and then the reciprocal Berkshire x Wannan black F1 hybrid model and the reverse transcription-polymerase chain reaction-restriction fragment length polymorphism method were used to detect the imprinting status of the porcine Rasgrf1 gene at the 1-day-old developmental stage. Imprinting analysis showed that, compared to the imprinted expression of the Rasgrf1 gene in mouse and rat, a variable imprinting status was observed in domestic pigs. In principle, the porcine Rasgrf1 gene was maternally expressed in the liver and small intestine, paternally expressed in the lung, and biallelically expressed in brain, heart, spleen, kidney, stomach, pancreas, fat, testis, ovary, longissimus dorsi, and pituitary tissues. In conclusion, our results indicated that the Rasgrf1 gene shows both species- and tissue-specific variation in imprinted expression.

The effect of dietary protein levels on the expression of genes coding for four selected protein translation initiation factors in muscle tissue of Wujin pig.

The objective of this study was to investigate the regulatory mechanism underlying the increased muscle protein accumulation in pigs while were fed a high protein diet. The eukaryotic initiation factors (eIFs) have been reported to involve in muscle protein synthesis. We investigated the mRNA and protein expression levels of eIF2B1, 4A1, 4B and 4E in Wujin pigs fed either a high protein (HP: 18%) or a low protein (LP: 14%) diet at 30, 60 or 100 kg body weight, based on real-time PCR and western blotting analyses. Our results indicated that the expression levels of eIF2B1 mRNA and protein were increased by HP diet at all body weight. The HP diet showed higher mRNA and protein levels of eIF4B gene at 60 and 100 kg. The protein expression of eIF4E phosphorylation was increased by HP diet only at 30 kg. These data suggested that the HP diet promoted porcine muscle protein accumulation mainly by up-regulating eIF2B1, 4B and 4E rather than 4A1 expression along the growth stages.

[Effects of applying human umbilical cord mesenchymal stem cell exosomes through different pathways to treat full-thickness skin defect wounds in mice].

Objective: To investigate the effects of human umbilical cord mesenchymal stem cell (hUCMSC) exosomes in the treatment of full-thickness skin defect wounds in mice through local wound application, subcutaneous injection at the wound margin, and tail vein injection, and to explore the optimal administration route of hUCMSC exosomes for wound treatment. Methods: This study was an experimental study. hUCMSC exosomes were extracted from the discarded umbilical cord tissue of three normal delivery women aged 25-35 years in the Department of Obstetrics and Gynecology of Baogang Hospital of Inner Mongolia and successfully identified. Totally 120 male BALB/c mice aged 6-8 weeks were selected, and full-thickness skin defect wounds were prepared on the back of them. According to the random number table, the injured mice were divided into control group (without drug administration), local wound application group, wound margin subcutaneous injection group, and tail vein injection group (with 30 mice in each group). Mice in the latter three groups were given 0.2 mL phosphate buffer solution containing 200 µg hUCMSC exosomes by local wound application, subcutaneous injection at the wound margin, and tail vein injection, respectively. On post injury day (PID) 7, 14, and 21, the general condition of the wound was observed, and the wound healing rate was calculated; the wound tissue was collected, the pathological changes and collagen fibers were observed respectively by hematoxylin-eosin staining and Masson staining, the number of new microvessels was observed by CD31 immunohistochemical staining, and the content of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) was detected by enzyme-linked immunosorbent assay. The sample number was 10 in each group at each time point. Results: On PID 7, 14, and 21, the wounds of mice in the 4 groups all healed gradually, and the wound healing of the mice in wound margin subcutaneous injection group was the best; the wound healing rates of mice in the three administration groups were significantly higher than those in control group (P<0.05), the wound healing rates of mice in wound margin subcutaneous injection group and tail vein injection group were significantly higher than those in local wound application group (P<0.05), and the wound healing rates of mice in wound margin subcutaneous injection group were significantly higher than those in tail vein injection group (P<0.05). On PID 7, 14, and 21, the growth and epithelialization speed of the wound tissue of mice in the three administration groups were significantly accelerated, and the collagen fibers in the wounds of mice in the three administration groups were larger in number and more neatly arranged in comparison with the control group. On PID 7, 14, and 21, under every 200-fold visual field, the number of new microvessels in the wound tissue of mice in local wound application group was 24.1±2.5, 50.7±4.1, and 44.2±2.3, respectively, the number of new microvessels in the wound tissue of mice in wound margin subcutaneous injection group was 32.2±2.9, 67.5±4.9, and 53.6±3.7, respectively, and the number of new microvessels in the wound tissue of mice in tail vein injection group was 27.8±2.4, 59.1±3.7, and 49.6±2.6, respectively, which was significantly more than 20.6±1.7, 46.7±3.4, and 40.9±2.8 in control group (P<0.05); the number of new microvessels in the wound tissue of mice in wound margin subcutaneous injection group and tail vein injection group was significantly more than that in local wound application group (P<0.05); the number of new microvessels in the wound tissue of mice in wound margin subcutaneous injection group was significantly more than that in tail vein injection group (P<0.05). On PID 7, 14, and 21, the content of TNF-α and IL-6 in the wound tissue of mice in the three administration groups was significantly less than that in control group (P<0.05), the content of TNF-α and IL-6 in the wound tissue of mice in wound margin subcutaneous injection group and tail vein injection group was significantly less than that in local wound application group (P<0.05), and the content of TNF-α and IL-6 in the wound tissue of mice in wound margin subcutaneous injection group was significantly less than that in tail vein injection group (P<0.05). Conclusions: Local wound application, subcutaneous injection at the wound margin, and tail vein injection of hUCMSC exosomes can all promote the wound healing of full-thickness skin defects in mice through alleviating excessive inflammatory response and promoting angiogenesis. Among them, subcutaneous injection at the wound margin has a better therapeutic effect, indicating subcutaneous injection at the wound margin is the optimal administration route for hUCMSC exosomes in wound treatment.

MECP2 promotes cell proliferation by activating ERK1/2 and inhibiting p38 activity in human hepatocellular carcinoma HEPG2 cells.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide and currently represents the leading cause of death amongst cirrhotic patients, but the mechanisms remain unknown. In this experiment, we investigated the expression of Methyl CpG-binding protein 2 (MeCP2) in HCC, the effect of MeCP2 on the proliferation of human HCC HepG2 cells, and the activation of mitogen-activated protein kinases (MAPKs) signaling pathways. The results showed that MeCP2 expression levels was higher in human HCC tissue than normal hepatocellular tissue, and MeCP2 siRNA reduced the proliferation of HCC HepG2 cells by decreasing cell activity and cell division in vitro. After MeCP2 siRNA treatment, the proportion of G1/G0 phase cells increased, but the proportion of S and G2/M phase cells decreased, indicative of G1/G0 cell cycle arrest. Furthermore, the proportions of early and late apoptosis in HCC HepG2 cells were enhanced after MeCP2 siRNA treatment. It was also found that activation of extracellular signal-regulated protein kinase (ERK) and p38 signaling pathways were involved in the proliferation of HepG2 cells. After MeCP2 siRNA treatment, p-ERK1/2 levels decreased, but p-p38 levels increased. Our findings demonstrated that MeCP2 promoted the proliferation of human HCC HepG2 cells with activation of ERK1/2 signaling pathways, suggesting a novel mechanism for pharmacological study of treatment for human HCC.

5-Aza-2'-deoxycytidine may influence the proliferation and apoptosis of cervical cancer cells via demethylation in a dose- and time-dependent manner.

The methylation of tumor suppressor genes has been shown to be involved in many human cancers. 5-Aza-2'-deoxycytidine (5-Aza-CdR) can reactivate the expression of methylated tumor suppressor genes. In our study, 2 human cervical cancer cell lines, HeLa and SiHa, were treated with different concentrations (20, 10, 5, and 2.5 µM) of 5-Aza-CdR for 24, 48, and 72 h. After incubation, cells were analyzed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay and flow cytometry. The expression of RASSF1A and APAF-1 was detected by RT-PCR. 5-Aza-CdR inhibited the growth of HeLa and SiHa cells at different concentrations. The strongest inhibition and apoptosis rates were obtained after incubation for 72 h (5.63 ± 1.38 and 8.24 ± 2.40%, respectively). No significant difference in the expression of RASSF1A was found upon drug treatment, while APAF-1 expression increased in HeLa cells after treatment (0.790 ± 0.056%). Our results suggest that the tumor-suppressive effect of 5-Aza-CdR may result from the reactivation of silenced APAF-1 through demethylation.