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Objective·To construct an mRNA vaccine encoding hemagglutinin(HA)of influenza A H1N1 virus,and explore the protective effects of different booster vaccination strategies.Methods·Firefly luciferase(Fluc)was used as the reporter gene to construct Fluc mRNA vaccine enveloped in lipid nanoparticles(LNP).The in vivo expression of Fluc mRNA-LNP after intramuscular injection was determined by live imaging assay in mice.Furthermore,M15-HA mRNA-LNP derived from H1N1 subtype(A/Michigan/45/2015)was constructed.Mice were immunized with 20,10,5,or 1 μg doses of M15-HA mRNA-LNP twice(with an interval of 3 weeks)through intramuscular injection.Serum antibody titers were measured by enzyme-linked immunosorbent assay(ELISA)at 2 weeks and 4 weeks after the second immunization,and functional antibody levels were detected by hemagglutination inhibition test.The third booster vaccination was performed 40 d after the second immunization in 1 μg dose group with 1 μg M15-HA mRNA-LNP or 10 μg HA subunit vaccine.The levels of specific antibody and functional antibody were detected by ELISA and hemagglutination inhibition test,respectively 2 weeks and 4 weeks later.Results·Live imaging assay showed that luciferase activity could be detected in mice 1 d after injection of Fluc mRNA-LNP.At 2 weeks and 4 weeks after the second immunization of M1 5-HA mRNA-LNP,HA-specific antibodies were significantly higher than those before the immunization in all vaccination groups at different doses(P=0.000).The hemagglutination inhibition test showed that the levels of functional antibodies in the 20 μg dose and 10 μg dose groups were significantly higher than those in the PBS control group(P＜0.05).After 1 μg dose group mice were immunized with HA protein or M15-HA mRNA-LNP,higher levels of HA-specific antibody and functional antibody were induced and maintained for a long time.There was no significant difference between the two different booster immunization strategies.Conclusion·M15-HA mRNA-LNP vaccine is constructed with immunogenicity and antibody neutralization activity.Low-dose mRNA priming vaccination followed by both homologous mRNA vaccine and heterologous protein subunit vaccine booster vaccination can induce stronger immune recall responses.
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Depsides and depsidones have attracted attention for biosynthetic studies due to their broad biological activities and structural diversity. Previous structure‒activity relationships indicated that triple halogenated depsidones display the best anti-pathogenic activity. However, the gene cluster and the tailoring steps responsible for halogenated depsidone nornidulin ( 3) remain enigmatic. In this study, we disclosed the complete biosynthetic pathway of the halogenated depsidone through in vivo gene disruption, heterologous expression and in vitro biochemical experiments. We demonstrated an unusual depside skeleton biosynthesis process mediated by both highly-reducing polyketide synthase and non-reducing polyketide synthase, which is distinct from the common depside skeleton biosynthesis. This skeleton was subsequently modified by two in-cluster enzymes DepG and DepF for the ether bond formation and decarboxylation, respectively. In addition, the decarboxylase DepF exhibited substrate promiscuity for different scaffold substrates. Finally, and interestingly, we discovered a halogenase encoded remotely from the biosynthetic gene cluster, which catalyzes triple-halogenation to produce the active end product nornidulin ( 3). These discoveries provide new insights for further understanding the biosynthesis of depsidones and their derivatives.
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Objective Using network pharmacology to explore the mechanism of action of tripterygium wilfordii-white peony in the treatment of rheumatoid arthritis(RA)and validating it using an adjuvant arthritis rat model.Methods Obtain the effective ingredients of tripterygium wilfordii and white peony through TCMSP database and predict the action targets;Obtain the disease targets of RA using DisGeNET and GeneCards online database;Draw the network of"tripterygium wilfordii-white peony-active ingredient-RA"and screen the core effective components using the software Cytoscape 3.9.1;Construct the protein-protein interaction(PPI)network using String database and screen the core targets using the CytoNCA plug-in,using the Metascape database for gene enrichment analysis of common targets,and using Auto Dock Tools and Pymol software for molecular docking of core active ingredients and targets.Enzyme linked immunosorbent assay(ELISA)detection of serum tumor necrosis factor-α(TNF-α),interleukin(IL)-4,IL-6,and IL-17 levels in adjuvant arthritis rats,Western blot was used to detect the expression of phosphorylated phosphatidylinositol 3-hydroxy kinase(p-PI3K)and phosphorylated AKT protein(p-AKT),validate the results of network pharmacology analysis.Results There were a total of 61 effective ingredients in the treatment of RA with tripterygium wilfordii-white peony,with 116 targets and 191 signaling pathways involved.Animal experiments have shown that compared with the model group rats,the serum cytokine TNF-α,IL-6 and IL-17 of rats in tripterygium wilfordii-white peony group and tripterygium wilfordii extract group were significantly decreased(P<0.05),IL-4 significantly increased(P<0.05);The expression of p-PI3K and p-AKT in synovial tissue was significantly reduced(P<0.05);Compared with rats in tripterygium wilfordii extract group,the TNF-α,IL-6,IL-17,p-PI3K and p-AKT of rats in tripterygium wilfordii-white peony group were significantly reduced(P<0.05),while IL-4 was significantly increased(P<0.05).Conclusion Tripterygium wilfordii-white peony can inhibit the overexpression of phosphatidylinositol 3-hydroxy kinase(PI3K)/protein kinase B(AKT)signaling pathway,regulate cytokine release,exert anti-inflammatory effects,and ultimately treat RA through multiple active ingredients and targets.
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Objective:To explore the value of conventional ultrasonography combined with cervical compression in the diagnosis of orbital venous malformation (OVM).Methods:A total of 43 patients with suspected OVM were admitted in sequentially from January 2019 to July 2022 in the Third Medical Center of PLA General Hospital. All patients were examined by ultrasonography combined with cervical compression and demonstrated by operation or digital subtraction angiography (DSA). The conventional ultrasound features of OVM were summarized, and the value of conventional ultrasonography combined with cervical compression in the diagnosis of OVM was discussed.Results:The features of the conventional ultrasound combined with cervical compression for diagnosis of OVM were as follows: the interior of lesion was mainly tubular structure, and the compression test was positive. After cervical compression, the lesion enlarged and the inner diameter of the internal tubular structure widened. Doppler flow imaging showed that the interior of lesion was mainly venous blood flow. Compared with the results of postoperative pathology or DSA, the sensitivity, specificity, accuracy and positive predictive value of ultrasonography combined with cervical compression were 0.952, 1.000, 95.3% and 100%, respectively. The results of Fisher exact diagnosis showed that there was no significant difference between ultrasonography and operation or DSA of OVM( P>0.05). Conclusions:Conventional ultrasound combined with cervical compression can be used as an effective method for the diagnosis of OVM.
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ObjectiveTo investigate the effect of Xinfeng capsules on immunoinflammatory indicators in patients with rheumatoid arthritis （RA） due to spleen deficiency and dampness exuberance. MethodA total of 102 patients were randomly divided into control group and observation group according to the random number table method， with 51 cases in each group. All patients were treated with methotrexate tablets， while those in the observation group received additional Xinfeng capsules. The course of treatment in both groups was 12 weeks. The 28-joint disease activity score （DAS28）， visual analogue scale （VAS） scores， morning stiffness time， erythrocyte sedimentation rate （ESR）， high-sensitivity C-reactive protein （hs-CRP）， rheumatoid factor （RF）， anti-cyclic citrullinated peptide （anti-CCP） antibody， vascular endothelial growth factor （VEGF）， and serum amyloid A （SAA） of the two groups before and after treatment were compared. The efficacy and incidence of adverse events were compared between the two groups. The Apriori association rule model and random walk model were constructed to evaluate the effect of Xinfeng capsules in improving hs-CRP， ESR， RF， SAA， VEGF， and anti-CCP. ResultThere were no dropouts in this study. There was no statistical difference in the indicators between the two groups before treatment. After 12 weeks of treatment， the total effective rate in the observation group was 90.19% （46/51）， which was higher than 74.51% （38/51） in the control group （χ2＝4.320，P<0.05）. DAS28， VAS score， and morning stiffness time in the observation group were improved compared with those in the control group （P<0.05）. Apriori association rule model results showed that the application of Xinfeng capsules in the observation group had a strong correlation with the reduction of RF， ESR， hs-CRP， SAA， and VEGF. The results of the random walk model showed that the improvement coefficients of hs-CRP， ESR， RF， SAA， and VEGF in the observation group were all better than those of the control group， and the improvement coefficient of anti-CCP in the control group was better than that of the observation group. The improvement degree of hs-CRP， ESR， RF， SAA， and VEGF in the observation group was superior to that of the control group （P<0.05）. The incidence of adverse reactions in the observation group was lower than in the control group （χ2＝4.057，P<0.05）. ConclusionOn the basis of the treatment with methotrexate tablets， Xinfeng capsules can effectively improve the immunoinflammatory level in RA due to spleen deficiency and dampness exuberance and reduce the incidence of adverse reactions.
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Objective:To investigate the clinical features and prognosis of B-cell acute lymphoblastic leukemia (B-ALL) children with intrachromosomal amplification of chromosome 21 (iAMP21).Methods:The data of 233 children diagnosed with B-ALL who received chemotherapy according to Chinese Children Cancer Group (CCCG) - acute lymphoblastic leukemia -2015 (CCCG-ALL-2015) protocol in the Affiliated Union Hospital of Fujian Medical University from January 2019 to December 2020 were retrospectively analyzed. These patients were divided into iAMP21 group and non-iAMP21 group according to whether iAMP21 was positive in the bone marrow fluid of children before chemotherapy based on ETV6-RUNX1 probe fluorescence in situ hybridization. Children in iAMP21 group received CCCG-ALL-2015 intermediate-risk group regimen induction chemotherapy, while children in non-iAMP21 group received different intensities of chemotherapy according to the clinical risk classification. The clinicopathological characteristics of patients were compared in both groups, the therapeutic efficacy and prognosis of B-ALL children with iAMP21 was analyzed.Results:iAMP21 was found in 5 (2.1%) of 233 B-ALL children. The median hemoglobin concentration in iAMP21 group was higher than that in non-iAMP21 group [99 g/L (71-148 g/L) vs. 74 g/L (30-156 g/L); U = 268.50, P = 0.043]; there were 4 cases (80%) with bone pain in iAMP21 group (5 cases) and 53 cases (23.2%) with bone pain in non-iAMP21 group (228 cases),and the difference in the osteoarticular pain incidence of both groups was statistically significant ( χ2 = 8.53, P = 0.017). There were no significant differences in the proportion of patients with different gender, age, white blood cell counts, platelet counts, hepatosplenomegaly between the two groups (all P > 0.05). Among 5 children with iAMP21, 1 patient was detected with high CRLF2 expression and 1 patient with IKZF1 1-8 exon loss of heterozygosity. The above mentioned two children with iAMP21, whose minimal residual disease (MRD) were still positive after consolidation therapy, and then they received chimeric antigen receptor T-cell treatment and hematopoietic stem cell transplantation. MRD of the other 3 children with iAMP21 turned negative after induction therapy. Up to the last follow-up in October 2021, 5 patients with iAMP21 had disease-free survival. Conclusions:The incidence of B-ALL children with iAMP21 is about 2%. These patients are prone to osteoarticular pain and have relatively mild anemia. The curative effect of some children is still poor after active treatment,which needs to be further clarified with more samples.
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Objective:To explore the value of 5G-based robotic remote ultrasound diagnosis system in musculoskeletal joint injuries.Methods:From March to December 2020, 58 volunteers at a training base who felt musculoskeletal pain or paresthesia were selected and performed both robotic remote ultrasound (remote ultrasound group) and conventional ultrasound (portable ultrasound group). The two types of examinations were compared, the consistency of the two diagnosis results was analyzed by the Kappa test, and the the difference of the diagnosis results was compared by McNemar test.Results:Among the 58 volunteers, 40 cases were positive by both methods and 11 volunteers had 2-3 positive results. There were 59 positive results in the remote ultrasound group and 64 positive results in the portable ultrasound group. The positive rate of the examination sites from high to low was knee joint>foot and ankle joint >hand and wrist joint >shoulder joint>elbow joint, calf and hip. The diagnosis results of the two groups were in good consistency (Kappa=0.782, P<0.001), and there was no statistically significant difference in the diagnosis results between the two groups (χ 2=3.2, P=0.063). Five more diseases with positive results were detected in the portable ultrasound group: 1 meniscus injury, 1 medial collateral ligament injury, 1 soft tissue injury around the metatarsal, 1 biceps tendinitis with effusion and 1 cubital ulnar nerve subluxation. Conclusions:The 5G-based robotic remote ultrasound system has good consistency with conventional ultrasound in the diagnosis of musculoskeletal injures. It can be applied to the ultrasound diagnosis of musculoskeletal joint injuries in remote areas.
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Objective:To explore the value of 5G robotic remote ultrasound in the diagnosis of plateau pulmonary edema(HAPE).Methods:A total of 27 patients who quickly entered Nagqu, Tibet at an altitude of 4 600 m-5 600 m from March to December 2021 and developed one of the clinical symptoms of HAPE were collected. All patients were examined by 5G remote robotic ultrasound and lung CT respectively. Kappa test was used to analyze the consistency of the two diagnostic results, and McNemar test was used to compare the difference in diagnostic results. The ROC curve was used to analyze the sensitivity and specificity of remote lung ultrasound scores in the diagnosis of HAPE.Results:Among the 27 patients, 16 showed thickening of pleural line, increasing of B line, lung consolidation, pleural effusion, etc. Meanwhile, 11 showed no abnormality. Additionally, 8 cases had diffuse pulmonary fluid in both lungs, and 8 cases had localized pulmonary fluid. ROC curve showed that the area under the curve of lung ultrasound score for the diagnosis of HAPE was 0.947 (95% CI=0.78-0.99, P<0.001). The sensitivity and specificity were 0.933 and 0.917, respectively. Lung CT diagnosis was positive in 15 cases. Lung CT showed thickening of lung texture, ground glass, small nodular shadow, fine reticulate shadow, etc. The diagnostic results of the two techniques were in good agreement (Kappa=0.924, P<0.001), and there was no significant difference between the two methods ( P>0.05). Conclusions:5G remote robotic ultrasound has high consistency with CT in the diagnosis of HAPE and is an alternative early diagnosis method for HAPE. It may have clinical application value in scattered medical resources and remote plateau areas.
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Objective:To analyze the categories, scoring methods and effects of dietary patterns in heart failure patients, systematically.Methods:The databases such as Medline, Embase, and Cochrane were searched to obtain articles on dietary patterns of heart failure patients up to December 31, 2019. Arksey and O′Malley's scoping review method was applied to analyze the articles.Results:A total of 1 500 studies were identified, 21 of them met the inclusion criteria. These studies mainly studied Mediterranean diet(11 articles), Dietary Approaches to Stop Hypertension Diet(7 articles), Palaeolithic diet(1 article), low fat diet(1 article), High-protein Diet(1 article).Conclusions:The Mediterranean and DASH dietary patterns have a positive protective effect on heart failure disease prevention and treatment, but more randomized controlled trials are needed to improve the reliability of the conclusions.
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Objective:To evaluate the effects of oropharyngeal administration of colostrum on feeding intolerance in preterm infants.Methods:A total of 87 preterm infants from December 2016 to December 2017 in the Second Affiliated Hospital of Wenzhou Medical University were distributed to the study group(41 cases) and the control group(46 cases) by random digits table method. The study group got oropharyngeal administration of 0.4 ml of own mother’s colostrum three times a day for 5 days. The control group got sterile water. The research data included early gastric residual volumes(the first to fourteenth day), gastric residual times and feeding status.Results:The gastric residual volumes on the eighth day, the eleventh day, the twelfth day were 8.5(0, 18.25), 0(0, 13.50), 2.5(0, 5.00) ml in the control group and 0(0,9.00), 0(0,1.00), 0(0,2.50) ml in the study group, the differences were statistically significant ( t values were -2.001, -1.987, -2.061, all P<0.05). The gastric residual times on the eighth day, the eleventh day were 1.5(0, 4.0), 0(0, 2.0) times in the control group, and 0(0, 1.0), 0(0, 0.5) times in the study group, the differences were statistically significant ( t values were -1.984, -2.267, all P<0.05).The vomiting times on the tenth day, the twelfth day were 0(0, 1.0), 0(0, 1.0) times in the control group and 0(0, 0.0), 0(0, 0.0) times in the study group, the differences were statistically significant ( t values were -3.149, -2.098, P<0.01 or 0.05). The time reaching full enteral feeding was (17.45±10.44) d in the study group, and (21.62±5.52) d in the control group, the difference was statistically significant ( t value was -2.022, P<0.05). Conclusions:Oropharyngeal administration of colostrum can better the condition of feeding intolerance.
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Intestinal mucosal barrier is the first line of defense against exogenous substances. A complete mechanical barrier can separate the body from the contents of the intestines and prevent the translocation of bacteria and microorganisms in the intestines, playing an important role in maintaining the homeostasis of the human body. If the intestinal mechanical barrier function is damaged, it will cause the intestinal endotoxin and bacterial translocation, leading to systemic inflammatory response syndrome and multiple organ dysfunction diseases. The barrier function of intestinal mucosa is a key link in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Therefore, the maintenance of intestinal mucosal barrier function is of great value for the diagnosis and treatment of NAFLD. In this paper, the research progress in intestinal mechanical barrier function of NAFLD was reviewed, and the main factors maintaining intestinal permeability of NAFLD were introduced, such as apoptosis, autophagy, apical junctional complex, cytoskeleton, main signal pathway, to provide reference for the diagnosis and treatment of NAFLD.
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Objective:To investigate the application of Aptima high-risk human papillomavirus (HR-HPV) E6/E7 mRNA (AHPV) and its genotyping (GT) in the risk assessment of low-grade squamous intraepithelial lesions (LSIL).Methods:The AHPV and its genotype (AHPV-GT) incervical exfoliated cells were detectedin 529 women with LSIL.The DNA-Based Hybrid Capture 2 HPV Test (HC2-HPV), colposcopy and cervical biopsy were performedsimultaneously.Results:① In 529 patients with LSIL, the positive rate of HC2-HPV in the group of ＜30 years old was significantly higher than that in the group of ≥30 years old (92.2％ vs 83.6％, P=0.026).There was no significant difference in AHPV positive rate among different age groups (82.5％ vs 77.7％, P=0.284).No significant difference of the genotyping (AHPV-GT) was detected between the two groups, either.In the 529 cases, 83 cases of HSIL+were confirmed by histology.81 cases (97.6％) were AHPV positive in the patients with HSIL+;② Compared with other 11 positive types of HR-HPV, the incidence of HSIL+in GT+ women increased significantly (P＜0.05).In the group ≥30 years old, the OR value of HSIL+exposure risk of AHPV16 positive women was the highest (141.00), which was significantly higher than that of 18/45+, GT +, AHPV + (P=0.005, 0.000, 0.000).However, in the group of ＜30 years old, the OR value of HSIL+exposure risk of AHPV16 positive women was 8.50, which showed no significant difference from that of 18/45+ and AHPV-(P=1.000, 0.070).③ In group over 30 years old, the specificity of detecting HSIL+by AHPV was higher than that by HC2-HPV (P＜0.05).There was no significant difference in detection specificity between AHPV and HC2-HPV in women under 30 years old.Conclusions:AHPV and its GT detection are reliable methods for colposcopic screening and risk stratification in women aged over 30 years old with LSIL, more attention should be focused on AHPV16 positive.Better biological markers should be explored for younger women.
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Objective To investigate the effect of acupoint catgut embedding combined with Ziwu-Liuzhu theory based acupuncture on the clinical efficacy and sleep quality of depressive patients. Methods A total of 64 patients who met the inclusion criteria were randomly divided into two groups, 32 in each group. The control group was treated with routine electro-acupuncture, while the observation group was treated with acupoint catgut embedding combined with Ziwu-Liuzhu theory based acupuncture. Both groups were treated for 8 weeks. Sleep quality was assessed by Pittsburgh Sleep Quality Index (PSQI), and depression was assessed by Hamilton Depression Scale (HAMD) to evaluate the clinical efficacy. Results After treatment, the HAMD score (11.3 ± 2.4 vs. 14.5 ± 2.6, t=4.986) and PSQI index (9.6 ± 2.3 vs. 11.8 ± 2.5, t=3.307) in the observation group were significantly lower than those in the control group (P<0.01). The quality of life (12.9 ± 2.3 vs. 11.3 ± 2.5, t=2.598) and mental health score (13.5 ± 2.4 vs. 11.3 ± 2.6, t=3.413) of WHOQOL-BREF scale in the observation group were significantly higher than those in the control group (P<0.01). The total effective rate was 93.8％ (30/32) in the observation group and 75.0％ (24/32) in the control group. There were significant differences between the two groups (χ2=4.246, P=0.038). Conclusions Acupoint catgut embedding combined with Ziwu-Liuzhu theory based acupuncture can effectively improve depressive state, sleep quality and quality of life in patients with depression, and the curative effect is better than conventional electro- acupuncture treatment.
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BACKGROUND: Nasal mucosa fibroblasts are reported to involve in inflammation and wound repair of various nasal diseases by secreting a variety of cytokines and chemokines. Guinea pig is a most suitable experimental animal for the study of allergic diseases. OBJECTIVE: To investigate the effective methods of isolation, culture, purification and identification of guinea pig nasal mucosa fibroblasts. METHODS: Guinea pig nasal mucosa fibroblasts were isolated by collagenase digestion, and purified by differential velocity adherence. The morphology of fibroblasts was observed by inverted phase contrast microscope, fibroblasts were identified by vimentin immunocytochemical staining, and the cell growth was detected by MTT assay to draw the growth curve. RESULTS AND CONCLUSION: (1) Under inverted phase contrast microscope, there were cells with different shapes in the primary nasal mucosa fibroblasts, most of which showed spindle-like and applanate shape, and cells were scattered distribution in cluster. The purified fibroblasts were homogeneous, mainly were long spindle-shaped, and distributed in fish shoal-like and radial-like. (2) Immunocytochemical staining indicated that fibroblasts were positive for vimentin. (3) The cell growth curve appeared to be typical S-shaped. (4) To conclude, the isolated and cultured cells exhibit typical biological characteristics of fibroblasts.
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Objective To evaluate the diagnostic value of acetic acid spray combined with narrow-band imaging ( NBI) for early gastric cancer and precancerous lesion. Methods A total of 136 gastric cancers and precancerous lesions from 132 patients detected by screening endoscopy from November 2015 to November 2017 in Guangming Chinese Medicine Hospital of Pudong New Area, Shanghai were enrolled in this study, and were divided into NBI group, acetic acid spray group, and acetic acid spray combined with NBI group ( combination group) . The image clarity, microsurface pattern, microvascular pattern, demarcation line, and mucosal whitening time were observed, and value of the 3 methods in diagnosis of early gastric cancer and precancerous lesions was analyzed. Results Image clarity of micro glandular in combination group was significantly better than that in NBI group and acetic acid spray group (χ2=8. 766, P=0. 003;χ2=5. 273, P=0. 022) , and image clarity of microvascular in combination group was significantly better than that in NBI group (χ2=7. 457, P=0. 006) . The overall diagnostic coincidence rate with pathology of combination group, NBI group, and acetic acid spray group was 91. 9％(125/136), 85. 3％(116/136), and 89. 7％(122/136), respectively. The diagnostic sensitivity of irregular or missing microsurface, irregular or missing microvascular, obvious demarcation line, mucosal whitening time <30 s for carcinoma ( including high grade intraepithelial neoplasia, early carcinoma and infiltrating carcinoma ) were 92. 3％, 91. 3％, 92. 3％ and 90. 4％, respectively, in the combination group, and the diagnostic specificity of above indicators were 93. 8％, 93. 8％, 96. 9％ and 90. 6％, respectively, accuracy were 92. 6％, 91. 9％, 93. 4％ and 90. 4％, respectively. For observation of microsurface, the combination group was superior to the NBI group (χ2 =7. 378, P=0. 007) , but there was no significant difference compared with the acetic acid spray group (χ2=0. 427, P=0. 513);the acetic acid spray group was superior to the NBI group (χ2=4. 405, P=0. 036) . For observation of microvascular, the combination group was not significantly better than the NBI group (χ2=2. 398, P=0. 122). For observation of demarcation line, the combination group was not significantly better than the NBI group (χ2=2. 722,P=0. 099) and the acetic acid spray group (χ2=0. 216, P=0. 642). There was no difference between the acetic acid spray group and the NBI group (χ2=1. 433, P=0. 231) in observation of demarcation line. Conclusion Acetic acid spray combined with NBI has a good consistency with pathological results with high diagnostic sensitivity and specificity, and can clearly show microsurface of early gastric cancers and precancerous lesions compared to single NBI.
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Objective To explore the clinical characteristics and related background diseases of type 1 gastric neuroendocrine tumor (g-NET) and to provide reference information for clinical diagnosis and treatment.Methods From Januayy 2011 to February 2019,at the First Affiliated Hospital of Sun Yat-sen University and China-Japan Friendship Hospital,the clinical features and related background diseases of type 1 g-NET patients (41 cases and 93 cases respectively)were retrospectively analyzed.The clinical symptoms,serological indicators,gastroscopic and pathological features,tumor location,metastasis and treatment,and concomitant diseases were statistically described.Results Among 134 patients with type 1 g-NET,there were 53 males (39.6％) and 81 females (60.4 ％);and the mean diagnosed age was (51 ± 11) years (21 to 76 years).Main clinical manifestations were non-specific gastrointestinal symptoms.The mean level of serum chromogranin A was (237.7 ± 176.8) μg/L.The endoscopic findings of 97.8％ (131/134) of the patients were polypoid or protuberant lesions at gastric fundus or gastric body.And 75.0％ (96/128) of the patients had multiple tumors.65.7％ (88/134) of the patients had the tumors with the maximum diameter less than 1 cm (77.2％,88/114) and the lesions mainly located in mucosa (59.8％,52/87) and submucosa (40.2％,35/87).The pathological classification of 79.3％ (96/121) of the tumors was G1 grade and 20.7％ (25/121) were G2 grade.The rate of local lymph node metastasis was 1.4％ (1/73) and no distant metastasis was found.About 70.9％ (95/134) of the patients received endoscopic treatment.Among the patients,93.6％ (103/110) of the patients had chronic atrophic gastritis confirmed by endoscopy or pathology,45.6％ (47/103) were confirmed by both endoscopy and pathology.Among the patients with chronic atrophy gastritis,serum gastrin levels of 93.2％ (96/103) patients were twice higher than the upper limit of the normal value.The positive rates of antiparietal cells antibody (PCA) and intrinsic factor (IFA) were 78.5％ (73/93) and 51.9％ (14/27),respectively.The incidence of Helicobacter pylori (H.pylori) infection was 28.1％ (16/57).The incidence of autoimmune atrophy gastritis was 80.6％ (75/93).The percentage of patients with deficiency of serum vitamin B12 and ferritin was 70.8％ (63/89) and 30.7％ (27/88),respectively.Patients with anemia accounted for 27.8％ (25/90).The patients with microcytic anemia,normocyticanemia and macrocytic anemia were 28.0％ (7/25),56.0％ (14/25) and 16.0％ (4/25),respectively.46.9％ (45/96) of the patients had increased thyroid autoantibodies and 17.9％ (17/95) patients had changes of thyroid hormone level.Conclusions Type 1 g-NET is more common in women and mainly caused by autoimmune atrophic gastritis.The level of serum PCA and IFA increase in more than half of the patients.And it is often accompanied by vitamin B12 deficiency and autoimmune thyroid disease.
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Objective To investigate the distribution differences of human papillomavirus(HPV) genotypes in the patients with cervical intraepithelial neoplasia grade Ⅱ/Ⅲ and the patients with cervical cancer. Methods 260 cases of cervical cancer and 280 cases of cervical intraepithelial neoplasia grade Ⅱ /Ⅲ patients who were admitted to our hospital from January 2010 to October 2017 were selected and divided into cancer group and neoplasia group respectively. The HPV infection of patients was detected and typing identification was performed. The distribution differences of HPV genotypes in cancer group and neoplasia group were compared. The differences of genotypes of HPV infection in different types of tissues in cancer group were also compared. Results The negative constituent ratio of HPV infection in cancer group was lower than that in neoplasia group(P＜0. 05), and the constituent ratio of all the high-risk types in single infection was significantly higher than that in the neoplasia group(P＜0. 05). The constituent ratio of all the low-risk types in single infection was significantly similar to that in the neoplasia group(P＞0. 05). The constituent ratio of multiple infections in cancer group was significantly higher than that in neoplasia group(P＜0. 05); the constituent ratios of negative HPV infections and 18 types of single infections in cervical squamous cell carcinoma was much lower than that of cervical adenocarcinoma(P＜0. 05). The constituent ratios of 16 types of HPV and multiple infections in cervical squamous cell carcinoma were much higher than that of cervical adenocarcinoma(P＜0. 05). Conclusion The risk of HPV infection in cervical cancer patients is significantly higher than that of cervical intraepithelial neoplasia grade Ⅱ /Ⅲ, the infection rate of cervical cancer high-risk type HPV is higher, and the risk of multiple infections is also higher. The tissue types of cervical cancer can be determined according to HPV typing.
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Background:Cerebellar fastigial nucleus (FN)is involved in regulation of visceral activities such as cardiovascular, ingestion,respiratory,and acute gastric mucosal injury,yet it is unclear whether it participates in the regulation of visceral hypersensitivity and what is the possible mechanism. Aims:To investigate the effect and possible mechanism of glutamic acid (Glu ) injection into cerebellar FN on chronic visceral hypersensitivity in rats. Methods: Chronic visceral hypersensitivity rat model was established by neonatal colorectal distension (CRD). After 8 weeks,the rats were divided into CRD group,solvent group (0. 2 μL 0. 9% NaCl solution injection into cerebellar FN),high-,medium-,low-dose Glu groups (12,6,3 μg Glu injection into cerebellar FN,respectively),3-MPA +Glu group (12 μg Glu injection after glutamate decarboxylase inhibitor 3-MPA injection into cerebellar FN),Bic + Glu group (12 μg Glu injection into cerebellar FN after GABAAreceptor blocker Bic injection into lateral hypothalamic area). Pain threshold,abdominal withdrawal reflex (AWR)score and abdominal external oblique muscle electromyography (EMG)were used to detect visceral sensitivity,and malondialdehyde (MDA)content and superoxide dismutase (SOD)activity were measured. Results:Chronic visceral hypersensitivity rat model was successfully established. Compared with CRD group,pain threshold was significantly increased (P＜0. 05),AWR score,EMG amplitude,MDA content were significantly decreased (P＜0. 05 ),and SOD activity was significantly increased in a dose-dependent manner in Glu group (P ＜0. 05 ). Compared with 12 μg Glu group,pain threshold was significantly decreased (P＜0. 05),AWR score,EMG amplitude, MDA content were significantly increased (P ＜0. 05),and SOD activity was significantly decreased in 3-MPA +Glu group,Bic+Glu group (P＜0. 05). Conclusions:Glu injection into cerebellar FN can significantly reduce the visceral sensitivity in rats. The mechanism may be that Glu in cerebellar FN produces GABA via glutamate decarboxylase,and then binding GABAAreceptor in lateral hypothalamic area,resulting in increased intestinal mucosal antioxidant capacity, thereby reducing visceral hypersensitivity.
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Objective To investigate the antigen-specific T cell functionality in type 2 diabetes mellitus patients. Methods Peripheral blood from 38 type 2 diabetes mellitus patients and 47 health controls (control group) have been collected. The proportions of CD4+and CD8+T cell as well as the ratio of CD4+/CD8+were monitored by flow cytometry. Meanwhile, antigen- nonspecific and specific Th1 responses were compared between two groups through detecting interferon (IFN)-γ, interleukin 2 (IL-2), and tumor necrosis factor (TNF)-α producing cells upon propylene glycol monomethyl ether acetate (PMA)/ionomycine and epstein-barr virus ( EBV) peptides stimulation, respectively followed by an intracellular cytokine staining. Results Compared to control group, the proportion of CD4+T cell and the ratio of CD4+/CD8+were significantly increased in type 2 diabetes mellitus group (P＜0.05) whereas CD8+T cells exhibited no significant difference between two groups. Antigen-nonspecific Th1 responses in type 2 diabetes mellitus patients were significantly decreased, demonstrated by lower percentages of IFN-γ, IL-2, and TNF-α producing CD4+T cells when compared to control group , while CD8+T cells in type 2 diabetes mellitus patients exhibited similar cytokine production patterns. However, when stimulated by EBV specific peptides, the percentages of IFN-γ, IL-2, and TNF-α producing CD8+T cells were significantly higher in type 2 diabetes mellitus patients than those in control group (P＜0.05). HbA1Cwas positively correlated with the percentage of EBV-specific TNF-α producing CD8+T cells (P＜0.05). Conclusion In type 2 diabetes mellitus, the secretion capacity of CD4+and CD8+T cell was significantly decreased and the antigen-specific responses represent the presence of an abnormal activated status, which indicates that chronic hyperglycemia may damage T cells function and aggravate chronic inflammation.
ABSTRACT
A 22-year-old male patient visited the Department of Dermatology of the First Affiliated I Iospital of Zbengzhou University on October 31,2016 due to dark red papules,nodules,pustules and cysts on the face,neck,back and in the axillary and inguinal regions for 6 years,and multiple dark purple plaques and ulcers on bilateral lower limbs for 1 year.Six years ago,the patient was diagnosed with acne in other hospital,and no treatment was given.One year ago,multiple purple plaques occurred on the bilateral lower limbs,which then ruptured and progressed into ulcers with diameters of 1-12 cm.On May 9,2002,the patient visited the Department of Pediatric Medicine of the First Affiliated Hospital of Zhengzhou University due to the left knee joint swelling and pain for half a year.Laboratory examination showed negative rheumatoid factor,and smear examination of the left knee joint effusions revealed that there were neutrophils and a small amount of lymphocytes and monocytes in the joint effusions,and no abnormal cells were observed.Then,the patient was diagnosed with pyogenic arthritis of the left knee.Physical examination at admission showed poor general condition,walking difficulty,slightly increased blood pressure of 142/92 mmHg (1 mmHg =0.133 kPa),multiple purple plaques on the bilateral lower limbs with central ulcer formation.Histopathological examination of ulcer margin on the lower limbs showed ulceration,intercellular edema and infiltrating neutrophils in the epidermis,and edema,focal erythrocyte extravasation,diffuse infiltration of neutrophils,lymphocytes and histiocytes in the superficial and middle dermis.Clinical manifestations and pathological features confirmed a diagnosis of pyoderma gangrenosum.There were extensive inflammatory papules,pustules,abscesses and cysts on the face,neck,waist and back,and a small amount of dark red nodules on the axillary and inguinal regions,which were consistent with cystic acne and hidradenitis suppurativa.As PSTPIP1 gene sequencing showed,no mutations were found in exon fragments,while compound heterozygous mutations c.36 + 68 G ＞ A,c.137 + 47 G ＞ C and c.562 + 114 C ＞ G her were found in intron fragments.Among 100 healthy controls,45 carried the same mutations.So,these mutation sites were considered to be polymorphic sites,and the pathogenicity of these mutations was still unclear.Finally,the patient was diagnosed with PAPASH syndrome.The patient was treated with methylprednisolone,cefminox,isotretinoin and thalidomide,and the lesions were markedly improved after 2 weeks.Now the patient was still followed up.