BACKGROUND: Muscle-derived stem cells (MDSCs) have been accepted as seeding cells in tissue engineered artificial nerves. Tacrolimus exhibits anti-immunologic rejection and promotes nerve regeneration and recovery. Whether can combine these factors with acellular nerve to form a new bridge that can inhibit immunologic rejection and promote nerve regeneration is uncertain. OBJECTIVE: Using the freeze-thawing combined optimized acellular nerve hypotonic-chemical detergent to prepare acellular nerveallograft scaffold. To explore the effect of co-application of MDSCs and FK-506 on nerve regeneration and function recovery following acellular nerve ailograft implantation.METHODS: The sciatic nerve derived from SD rats was prepared nerve bridge after acallular disposal. Gel containing FK-506 and MDSCs was injected into acellular nerveallograft scaffold with 100 μL microsyringe to repair defects. A total of 32 SD rats were randomly divided into 4 groups, with 8 animals in each group. Agap of 10 mm of left sciatic nerve was removed. And then the defects were repaired by extracted nerve graft containing FK-506+MDSCs, MDSCs and FK-506, respectively. In the control group, only hyaluronic acid gel was injected. Sciatic nerve function index (SFI) and electrophysiological exam were performed at weeks 8 and 12 after operation. Gross observation, neurohistological and ultrastructure were observed at week 12 after operation.RESULTS AND CONCLUSION: Compared with the same time point, the SFI, recovery rate of the motor nerve conduction velocities (MNCV), and myelinated nerve fibers in grafting part and in its distal part in the FK-506+MDSCs group were superior to other groups (P < 0.05). The nerve grafts were in normal size with considerabie blood vessels and slightly connected to peripheral Ussues. Compared to other groups, the regenerated nerve fiber in the FK-506+MDSCs group was more density with well-arranged order. A great quantity of Schwann cells proliferated in grafting. The density end diameter of myelinated fiber in the middle and distal part of the grafting were all greater than that of MDSCs and FK-506 groups, and there were few connective tissues between microfascicles, which was close to normal level. The co-application of MDSCs and FK-506 enhances peripheral nerve regeneration and functional recovery in acelluler nerve allograft graft. Therefore, MDSCs and FK-506 are synergistic factors in peripheral nerve injury repair.

Human adenovirus ( HAdV ) is the most widely used vector of gene drugs . Its applications range from oncolytic therapy to vaccination , besides , HAdV is one of the most important pathogen causing acute respiratory infections in infants and young children .How the human innate immune system protects against HAdV has always been the focus of its application as a vaccine carrier .In patients with immunodeficient and hematopoietic stem cell transplant , specific T cell immunotherapy is also one of the hotspots in recent years .Although some HAdV vector vaccines have entered clinical trials , the immune mechanism remains controversial .This article describes how the human innate immune system and the adaptive immune system defend against HAdV and the escape mechanism of HAdV for human immune responses ,in order to indicate directions for vaccine research and deepen clinicians 'understanding of HAdV severe infections .

Hepatitis B virus(HBV)infection is the main cause of chronic liver diseases in China. The clearance of HBV is important for patients with chronic hepatitis B.Current antiviral therapy includes interferon and nucleotide analogues.The adverse reactions of interferon are common which restrict its application.Nucleotide analogues need long-term maintenance treatment.Kupffer cells (KCs) are the main innate immune cells in the liver.Studies have shown that KCs play an important role in hepatitis B virus infection.It can inhibit virus replication effectively , but may also result in immune dysfunction , causing HBV persistence.Understanding the mechanism related to the role of KCs in hepatitis B virus infection may lead to a new approach of antiviral therapy.

Objective:To investigate the association of FAT atypical cadherin 1 (FAT1) with clinicopathological parameters and prognosis in esophageal squamous cell carcinoma (ESCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 124 patients with ESCC who were admitted to Shanxi Cancer Hospital from January 2011 to December 2015 were collected. There were 85 males and 39 females, aged from 40 to 72 years, with a median age of 60 years. The ESCC tissues surgically removed and adjacent tissues specimens were collected to prepare tissue microarray for immunohistochemical staining. The 5 cases of ESCC tissues and adjacent tissues were analyzed by real-time quantitative polymerase chain reaction (qRT-PCR). Observation indicators: (1) the expression of FAT1 protein in ESCC and adjacent tissues; (2) the expression of FAT1 RNA in ESCC and adjacent tissues; (3) the expression of FAT1 protein in ESCC tissues and its association with clinicopathological parameters; (4) follow-up and survival. Follow-up using outpatient examination and telephone interview was conducted to detect survival of patients up to February 13, 2019. The survival time was from surgical date to tumor-related death or endpoint of follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M (range). Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Comparison of ordinal data was analyzed using the non parameter rank sum test. The Kaplan-Meier method was used to calculate survival time, and Log-rank test was used for survival analysis. Results:(1) The expression of FAT1 protein in ESCC and adjacent tissues: of 124 specimens, the 107 cases of ESCC tissues and 93 cases of adjacent tissues were finally obtained because of exfoliative tissues. There were 76 cases of ESCC tissues and corresponding adjacent tissues matched. Results of immuno-histochemical staining showed that FAT1 protein was expressed in both ESCC and adjacent tissues and was brown after staining. FAT1 was located in cytomembrane, with high expression of FAT1 as ≥75 and low expression as <75. The relative expression levels of FAT1 protein in ESCC and adjacent tissues were 68±42 and 77±37, showing a significant difference between ESCC and adjacent tissues ( t=2.380, P<0.05). (2) The expression of FAT1 RNA in ESCC and adjacent tissues: results of qRT-PCR showed that the relative expression levels of FAT1 RNA in 5 cases of ESCC and adjacent tissues were 1.6±0.4 and 2.5±0.3, with a significant difference between them ( t=3.560, P<0.05). (3) The expression of FAT1 protein in ESCC tissues and its association with clinicopathological parameters: of the 107 ESCC patients, 58 cases had high expression of FAT1. There were 42 and 16 cases with high expression of FAT1 in 65 non-drinking patients and 42 drinking patients, respectively, showing a significant difference between them ( χ2=7.229, P<0.05). (4) Follow-up and survival: 96 of 107 ESCC patients were followed up for 38.0?94.9 months, with a median follow-up time of 45.9 months. Survival analysis showed that the survival time of patients with high FAT1 expression was 24 months, versus 22 months of patients with low FAT1 expression, indicating no significant difference between them ( χ2=1.773, P>0.05). Results of subgroup analysis showed that the survival time was 24 months and 21 months of female patients with high and low FAT1 expression, 23 months and 22 months of non-smoking patients with high FAT1 expression and low FAT1 expression, 23 months and 21 months of non-drinking patients with high FAT1 expression and low FAT1 expression, respectively, showing significant differences between them ( χ2=8.769, 12.827, 10.724, P<0.05). Conclusions:The expression of FAT1 in ESCC tissues is low. Female, non-smoking and non-drinking ESCC patients with high FAT1 expression have good survival.

BACKGROUND: Despite the progress in perinatal-neonatal medicine, complications of extremely preterm infants continue to constitute the major adverse outcomes in neonatal intensive care unit. Human umbilical cord Wharton’s Jellyderived mesenchymal stem cells (HUMSCs) may offer new hope for the treatment of intractable neonatal disorders. This study will explore the functional differences of HUMSCs between extremely preterm and term infants. METHODS: UMSCs from 5 extremely preterm infants(weeks of gestation: 22+5 w,24+4 w,25+3 w,26 w,28 w) and 2 term infants(39 w,39+2 w) were isolated, and mesenchymal markers, pluripotent genes, proliferation rate were analyzed.HUVECs were injured by treated with LPS and repaired by co-cultured with HUMSCs of different gestational ages. RESULTS: All HUMSCs showed fibroblast-like adherence to plastic and positively expressed surface marker of CD105,CD73 and CD90, but did not expressed CD45,CD34,CD14,CD79a and HLA-DR; HUMSCs in extremely preterm exhibited significant increase in proliferation as evidenced by CCK8, pluripotency markers OCT-4 tested by RT-PCR also showed increase. Above all, in LPS induced co-cultured inflame systerm, HUMSCs in extremely preterm were more capable to promote wound healing and tube formation in HUVEC cultures, they promoted TGFb1 expression and inhibited IL6 expression. CONCLUSIONS Our results suggest that HUMSCs from extremely preterm infants may be more suitable as candidates in cell therapy for the preterm infants.

ObjectiveTo investigate the mechanism of gamma-chain (γC) cytokines in regulating the expression of T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) in CD8+ T cells of chronic hepatitis B (CHB) patients. MethodsA total of 23 CHB patients who attended Tangdu Hospital, Fourth Military Medical University, from January to May, 2017, were enrolled. Peripheral blood was collected from all patients, and Ficoll density gradient centrifugation was used to isolate peripheral blood mononuclear cells (PBMCs). PBMCs were stimulated with interleukin-7 (IL-7), interleukin-15 (IL-15), and interleukin-21, respectively, and then anti-γC antibody and/or anti-IL-7Rα, anti-IL-2Rβ, and anti-IL-21R were added to the culture solution. After 96 hours of culture, flow cytometry was used to measure the expression of TIM-3, interleukin-2 (IL-2), interleukin-10 (IL-10), and interferon-γ (IFNγ) and the phosphorylation level of signal transducer and activator of transcription (STAT) in CD8+ T cells. A one-way analysis of variance and the least significant difference t-test were used for comparison of continuous data. ResultsThe CD8+ T cells stimulated by IL-7 and IL-15 had a significantly higher percentage of TIM-3-positive CD8+ T cells than those without stimulation (t=9.966 and 9074, P＜0.05), as well as significantly higher expression levels of IL-2, IL-10, and IFN-γ and phosphorylation levels of STAT-5 and STAT-1 (all P＜0.05). Stimulation with anti-IL-7Rα and anti-γC antibody significantly reduced the elevated expression levels of TIM-3, IL-2, and IL-10 in the IL-7 stimulation group (t=5.537, 6.224, and 4.500, P＜0.05). Stimulation with anti-IL-2Rβ alone or in combination with anti-γC antibody significantly reduced the expression levels of TIM-3 and IL-2 and the phosphorylation level of STAT-1 in the IL-15 stimulation group (P ＜0.05). ConclusionIL-7 and IL-15 can upregulate the expression of TIM-3 in CD8+ T cells of CHB patients, possibly via the γC receptor-mediated STAT-cytokine signaling pathway.

Objective:To investigate the expression of miRNA-34b (miR-34b) in non-small cell lung cancer (NSCLC) tissues and its effect on proliferation and invasion of human NSCLC A549 cells in vitro.Methods:The specimens of cancer tissues and paracancerous normal epithelial tissues (more than 5 cm from the edge of the tumor) were collected from 40 NSCLC patients in Shanxi Province Cancer Hospital from June 2015 to March 2017. A549 cells were transfected with miR-34b mimics (experimental group) and irrelevant sequences (negative control group), respectively. The expression of miR-34b in tissues and each group of A549 cells was detected by reverse transcription real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). The proliferation activity of A549 cells in the experimental group and the negative control group was detected by methyl thiazolyl tetrazolium (MTT) assay, and the invasion ability of A549 cells in the two groups was detected by Transwell assay.Results:The relative expression of miR-34b in NSCLC tissues was lower than that in paracancerous normal epithelial tissues (0.52±0.06 vs. 1.05±0.17), and the difference was statistically significant ( P < 0.001). The relative expression of miR-34b in A549 cells of the experimental group was higher than that in the negative control group, and the difference was statistically significant ( P < 0.05). MTT assay showed that the cell proliferation ability (absorbance value) of A549 cells in the experimental group was lower than that in the negative control group after cultured for 24 and 48 hours (both P < 0.01). Transwell assay showed that the number of invaded A549 cells in the experimental group was less than that in the negative control group [(49.53±5.03) cells vs. (121.00±12.06) cells, P < 0.01]. Conclusions:The expression of miR-34b is low in NSCLC tissues, and the up-regulation of miR-34b expression can inhibit the proliferation and invasion of NSCLC A549 cells.

Objective:To analyze the clinical epidemiological characteristics and the prognostic risk factors of patients with hemorrhagic fever with renal syndrome (HFRS).Methods:A total of 2 245 HFRS patients who were admitted to the Second Affiliated Hospital of Air Force Medical University from September 2008 to December 2021 were enrolled. Clinical epidemiological data (including gender, age, onset season, onset region, case fatality rate, et al) of HFRS patients were analyzed. The clinical epidemiological characteristics of patients with HFRS in the 2008 to 2012, 2013 to 2017, and 2018 to 2021 groups were compared. Statistical comparisons were performed using chi-square test. The Bonferroni adjusted P-value method was used for pairwise comparisons between groups, and logistic regression analysis was used to screen and evaluate the risk factors associated with the prognosis of HFRS patients. Results:The age of 2 245 HFRS patients was (42.3±15.9) years old. Most of them were male (79.24%(1 779/2 245)), and the main incidence area was Xi′an City (69.53%(1 561/2 245)). There were 132 deaths with an overall case fatality rate of 5.88%. There were 1 088 patients (48.46%) from 2008 to 2012, 647 patients (28.82%) from 2013 to 2017, and 510 patients (22.72%) from 2018 to 2021, with a mortality rate of 7.17%(78/1 088), 5.10%(33/647) and 4.12%(21/510), respectively. From 2008 to 2021, both the number of HFRS cases and the case fatality rate had shown a fluctuating downward trend. There were significant differences in case fatality rate, age distribution, onset season, and onset region among patients in the different year groups ( χ2=6.84, 49.22, 83.47 and 19.29, respectively, all P<0.05). The results of pairwise comparisons showed that the proportion of patients aged >60 years in the 2018 to 2021 group (23.33%(119/510)) was higher than those in the 2008 to 2012 group (12.13%(132/1 088)) and the 2013 to 2017 group (12.36%(80/647)), and the differences were statistically significant (both P<0.05). The proportions of patients at large peak (October to December) were 62.35%(318/510) in the 2018 to 2021 group and 56.26%(364/647) in the 2013 to 2017 group, which were both lower than that in the 2008 to 2012 group (75.18%(818/1 088)), and the differences were both statistically significant (both P<0.05). The case fatality rate of patients aged >60 years was 9.67%(32/331), which was higher than those of patients aged <30 years (2.86%(16/559)) and patients aged 30 to 60 years (6.20%(84/1 355)), with statistically significant differences (both P<0.05). Univariate analysis showed that age 30 to 60 years, age >60 years, smoking, complicated with hypertension, hypotensive shock and hypoxemia were significantly correlated with the prognosis of HFRS patients (odds ratio ( OR)=2.243, 3.632, 1.484, 3.532, 79.422 and 143.955, respectively, all P<0.05). The results of multivariate logistic regression analysis indicated that complicated with hypertension ( OR=2.467, P=0.004), hypotensive shock ( OR=11.658, P=0.001), and hypoxemia ( OR=67.767, P<0.001) were the independent risk factors affecting the prognosis of HFRS patients. Conclusions:The prevalence of HFRS has shown new changing characteristics from 2008 to 2021. The numbers of HFRS patients and the case fatality rates show a downward trend, and the proportion of HFRS patients aged >60 years increases. Complicated with hypertension, hypotensive shock and development with hypoxemia are the independent risk factors for the prognosis of HFRS.

Objective To observe the proliferation and apoptosis of oxaliplatin-resistant colon cancer cell lines and the expression of estrogen receptor related receptor(ERR)α when tetrasoanin was down-regulated. Methods Western blot and quantitative real-time polymerase chain reaction(qRT-PCR)were used to detect the expression of tetrasoanin and ERRα of colon cancer cells and oxaliplatin resistant cells in mRNA and protein levels. ERRα inhibitor XCT790 was used to down-regulate ERRα expression, The expression of ERRα was down regulated by ERR α inhibitor XCT790,and the level of tetrasoanin,apoptosis and proliferation of L-OHP-SW620 cells were detected by Western blot, flow cytometry and MTT.Tetrasoanin expression was down regulated by siRNA, the expression, apoptosis and proliferation of L-OHP-SW620 cells AKT, p-AKT, tetrasoanin and ERRα were detected by Western blot,qRT-PCR,flow cytometry and MTT assay.Results The expression of tetrasoanin and ERRα protein in L-OHP-SW620 cell lines were higher than those in SW620 cells (t=6.127,P<0.01,t=12.579,P<0.01),The expression of tetrasoanin mRNA in L-OHP-SW620 cell line was higher than that in SW620 cell line(t=9.085,P< 0.01). The early apoptosis rate of L-OHP-SW620 cells in XCT790 group after XCT790 inhibited ERR -αexpression was higher than that in NC group(t=3.297, P< 0.01). The survival rate of XCT790 group after 72 h culture was(45.264±6.249)%,lower than that of NC group((63.364 ± 9.472)%)(t=4.537, P<0.01). Compared with NC group,p-AKT protein was up-regulated(t=8.139,P<0.01),ERRα protein was down-regulated(t=6.452,P<0.01),the apoptosis rate was(17.541±2.317)%,lower than that in the sitetrasoanin group((32.892±3.296)%)(t=4.526,P<0.01), the survival in sitetrasoanin group after 72 h culture was(49.653 ± 5.945)%, lower than that in NC group ((67.376±7.934)%)(t=3.109,P<0.05).Conclusion Tetrasoanin down-regulation and p-AKT protein up-regulation decreases ERRα protein and OHP-resistant colon cell proliferation is decreased, apoptosis is increased and drug resistance is decreased.

Objective: To investigate the clinical features, diagnosis and treatment of osteomyelitis of the jaw caused by an actinomycotic infection and to provide a reference for clinical diagnosis and treatment. Methods: A case of osteomyelitis in the bilateral maxilla and the left zygomatic bone and arch caused by a mixed bacterial infection dominated by Actinomycetes was reviewed and analyzed in combination with the literature. Results : The patient had left upper posterior tooth pain with repeated left facial swelling for 7 months. The patient's left face was swollen before surgery, the left maxillary alveolar bone was necrotic, and the upper palate showed fistula discharge. A maxillofacial magnetic resonance imaging scan excluded tumors and other space-occupying lesions. According to CBCT images, the initial diagnoses were left infraorbital space infection and osteomyelitis of the bilateral maxillary, the left zygomatic bone, the left zygomatic arch and the lateral orbital wall. Necrosis of the left maxilla and the zygomatic bone was excised, the focus was cleared and the focal tooth was extracted under general anesthesia. Histopathological results confirmed osteomyelitis and actinomycotic infection. Anti-inflammatory therapy with penicillin sodium was given before surgery, and piperacillin sodium and tazobactam sodium, dexamethasone sodium phosphate, tranexamic acid and mecobalamine were given after surgery. The patients' 6-month follow-up results showed that the maxillofacial shape was basically symmetrical; no ulceration, pus or abnormal secretion was found in the skin or intraoral mucosa; and the surgical area showed good recovery. A review of the relevant literature showed that Actinomyces is an opportunistic pathogen, and factors such as trauma and dental infection have been implicated in the pathogenesis of osteomyelitis. In addition to surgery, antibiotics are used to treat the disease and multidisciplinary symptomatic treatment combined with supportive treatment is required to achieve a better prognostic effect. Conclusion Actinomycotic osteomyelitis occurring in the maxilla and the zygomatic bone is an extremely rare disease that can be diagnosed by clinical manifestations, bacteriological examination and biopsy. Appropriate and effective penicillin drugs should be given at the initial stage of treatment, more sensitive antibiotics should be selected according to the results of the drug sensitivity test, and the lesions should be surgically removed when the patient's condition improves. Active symptomatic and supportive treatment should be performed during the treatment period.