Crohn's disease (CD) is a chronic transmural inflammatory bowel disease that can affect the entire digestive tract. The etiology is unknown, but it is mainly considered to be caused by a variety of factors such as environment, genetic susceptibility, and gut microbiota, leading to immune-inflammatory reactions in the gastrointestinal mucosa. Studies have found that the interleukin 23 (IL-23) /T helper cell 17 (Th17) inflammatory axis in CD bridges innate immunity and adaptive immunity, promoting the differentiation of naive T cells into Th17 through the IL-23p19-JAK-STAT3 pathway, producing a large amount of pro-inflammatory cytokines represented by IL-17, thereby maintaining intestinal inflammation. This axis is regulated by genetic genes, gut microbiota, and bile acid metabolism. Drugs targeting some signaling molecules of the IL-23/Th17 inflammatory axis have been developed and have achieved good therapeutic effects. In the future, further development of potential target drugs for this axis will be beneficial to personalized treatment of CD.

Crohn's disease (CD) is a chronic transmural inflammatory bowel disease that can affect the entire digestive tract. The etiology is unknown, but it is mainly considered to be caused by a variety of factors such as environment, genetic susceptibility, and gut microbiota, leading to immune-inflammatory reactions in the gastrointestinal mucosa. Studies have found that the interleukin 23 (IL-23) /T helper cell 17 (Th17) inflammatory axis in CD bridges innate immunity and adaptive immunity, promoting the differentiation of naive T cells into Th17 through the IL-23p19-JAK-STAT3 pathway, producing a large amount of pro-inflammatory cytokines represented by IL-17, thereby maintaining intestinal inflammation. This axis is regulated by genetic genes, gut microbiota, and bile acid metabolism. Drugs targeting some signaling molecules of the IL-23/Th17 inflammatory axis have been developed and have achieved good therapeutic effects. In the future, further development of potential target drugs for this axis will be beneficial to personalized treatment of CD.

Subphrenic splenic implantation is a rare disease, usually occurred followed the splenic trauma and splenectomy. Surgeries are often necessary for diagnosing and treating it. A 46-year-old male post-splenectomy patient, tolerating abdominal bloating and pain for more than 1 year, was admitted to the Second Xiangya Hospital, Central South University. Fundus bulge suggested a possibility of stromal tumors originating from the muscularispropria layer with endoscopic ultrasound. Slightly stomachic thickness was detected using enhanced computed tomography (CT). Without any improvement for symptoms after medication, the patient strongly requested to undergo an endoscopic therapy. Natural orifice transluminal endoscopic surgery (NOTES) result confirmed it as subphrenic splenic implantation with postoperative pathology. In this case, NOTES helped us to confirm the diagnosis, relieve the symptoms, as well as prevent secondary surgery injury, which would be helpful to other clinicians.
Endoscopy ; Gastric Fundus ; Humans ; Intraoperative Complications ; Male ; Middle Aged ; Splenectomy/adverse effects* ; Tomography, X-Ray Computed

To analyze the clinical features, diagnosis and treatment in patients with immunoglobulin 4 (IgG4)-related diseases.
 Methods: The clinical data (including general situation, clinical manifestations, laboratory examination, imaging examination, pathological examination, treatment and follow-up) in 21 patients, who were diagnosed with IgG4-related diseases in Second Xiangya Hospital of Central South University from June 2014 to February 2018, were retrospectively analyzed.
 Results: Among the 21 patients, including men 16 (76.2%) and women 5 (23.8%), the age was 37.00-78.00 (59.19±12.93) years old. Multi-organ involvement was discovered in 10 patients (47.6%), among which the lung (42.9%), pancreas (38.1%), kidney (33.3%), bile duct (19.0%) and liver (14.3%) were the main organs involved. The serum IgG4 levels in 19 patients (90.5%) were increased [8.63 (1.13-36.50) g/L]. The condition of 16 patients (84.2%) was improved after glucocorticoid therapy.
 Conclusion: IgG4-related diseases are mostly found in middle-aged and elderly men. Multiple organs or tissues of the body can be involved. Affected organs are mostly seen in lung, pancreas, kidney and bile duct, with diverse clinical manifestations. Glucocorticoid and immunosuppressive therapy are effective.
Adult ; Aged ; Female ; Humans ; Immunoglobulin G ; Immunoglobulin G4-Related Disease ; Lung ; Male ; Middle Aged ; Pancreas ; Retrospective Studies

Objective To explore the changes and their clinical significance of peripheral blood myeloid-derived suppressor cells (MDSC)and their subtypes in patients with inflammatory bowel disease (IBD).Methods From April 2016 to April 2017,99 hospitalized IBD patients in 2nd Xiangya Hospital of Central South University were enrolled as observation group one,which included 84 Crohn's disease (CD) (70 in active phase and 14 in remission phase)and 15 patients with ulcerative colitis(UC).At the same period,32 healthy controls were enrolled as healthy control group one.The proportion of peripheral blood MDSC and subtypes of CD patients,UC patients and healthy controls were examined.Observation group two including 62 IBD patients (47 CD and 15 UC)were selected from observation group one and 21 healthy individuals were selected from healthy control group one as healthy control.The serum levels of tumor necrosis factorα(TNF-α)and interleukin 8 (IL-8)were detected.Chi square test,t test and one-way analysis of variance were performed for statistical analysis.Pearson correlation was performed for correlation analysis.Results The proportion of MDSC in peripheral blood mononuclear cells of CD and UC patients of observation group one were both higher than that of healthy control group one ((6 .30 ± 3.97)% and (7.50±3.12)% vs.(3.94±2.25)%,respectively),and the differences were statistically significant (t＝-3.22 and -3.21,both P＜0.01).The proportion of granulocytic MDSC in peripheral blood mononuclear cells of CD patients was higher than that of UC patients and healthy control group one ((65.69±20.45)% vs.(50.93±13.56)% and (51.50±11.61)%,respectively),and the differences were statistically significant (t＝2 .93 and 3 .79 ,both P＜0 .01 ).The proportion of monocytic MDSC in peripheral blood mononuclear cells of UC patients was higher than that of CD patients and healthy control group one ((28.41±18.33)% vs.(18.38±17.43)% and (28.17±10.22)%,respectively),and the differences were statistically significant (t＝2.22 and 2.93,both P＜0.05 ).The proportion of granulocytic MDSC was higher and the proportion of monocytic MDSC was lower in peripheral blood mononuclear cells of CD patients in active phase than those of CD patients in remission phase ((67 .36 ± 2.27)% vs.(46.49±6.32)%,and (17.19±2.02)% vs.(34.33±6.12)%),and the differences were statistically significant (t＝3.60 and 3.26,both P＜0.01).The serum level of TNF-αof CD patients of observation group two was higher than that of UC patients and healthy control group two ((7.83± 6.54)ng/L vs.(4.77±2.12)ng/L and (4.40±2.05)ng/L),and the differences were statistically significant (t＝2.01 and 2.53,both P＜0.05).The serum level of IL-8 of UC patients of observation group two was higher than that of CD patients and healthy control group two ((65.80±45.14)ng/L vs. (25.80±22.32)ng/L and (26.40±22.37)ng/L),and the differences were statistically significant (t＝4.87 and 4.21,both P＜0.01).Granulocytic MDSC was positively correlated with TNF-α(r＝0.319, P＝0 .0 1 1 )and was negatively correlated with IL-8 (r＝-0 .2 9 6 ,P＝0 .0 1 9 ).Monocytic MDSC was negatively correlated with TNF-α(r＝-0.260,P＝0.040)and was positively correlated with IL-8 (r＝0.306,P＝0.016).Conclusions The proportion of granulocytic MDSC in peripheral blood mononuclear cells significantly increases in active CD patients,while the proportion of monocytic MDSC significantly increases in UC and CD patients in remission phase.Detection of MDSC and their subtypes maybe helpful in the differentiation of CD and UC as well as the diagnosis and treatment of CD.

OBJECTIVE: To study the association of TNFRSF1B +676 gene (rs1061622) polymorphism with the risk of rheumatoid arthritis (RA ) in Han Chinese population of Hunan. METHODS: A total of 112 patients with RA from Han Chinese population in Hunan were recruited, along with 129 healthy controls. TNFRSF1B +676 (rs1061622) gene polymorphisms were examined by PCR-RFLP. Serum levels of soluble TNFR II were analyzed by ELISA. RESULTS: RA patients displayed a similar TNFRSF1B +676 genotype to controls (GG/TG/TT: 5/62/45 vs 9/56/64, P=0.167), but signifi cant diff erence was found between female RA patients and female controls (GG/TG/TT: 3/49/24 vs 8/28/48, P<0.001). No significant difference was found in the frequency of TNFRSF1B +676 T or G allele between RA patients and controls (P>0.05). RA patients showed a signifi cantly higher level of serum soluble tumor necrosis factor receptor II (sTNFR II) than controls [(7.83±2.61) ng/mL vs (4.32±1.67) ng/mL, P<0.001], but there was no diff erence among the three genotypes (P>0.05). No association was found between TNFRSF1B+676 gene polymorphism and RA clinical characteristics. CONCLUSION In Han Chinese population of Hunan province, TNFRSF1B+676 gene polymorphisms are not associated with the genetic risk of RA .
Alleles ; Arthritis, Rheumatoid ; ethnology ; genetics ; Asian Continental Ancestry Group ; Female ; Gene Frequency ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Polymorphism, Genetic ; genetics ; Polymorphism, Single Nucleotide ; Receptors, Tumor Necrosis Factor, Type II ; blood ; genetics ; Risk Factors

OBJECTIVE: To investigate the association of TNF-α-308 gene polymorphism with the risk of RA in Hunan's Han Chinese population.
 METHODS: A total of 112 patients with RA from Han Chinese population in Hunan were recruited, along with 129 healthy controls. TNF-α-308 (rs1800629) gene polymorphisms were analyzed by PCR-RFLP. Serum levels of TNF-α were detected by ELISA.
 RESULTS: TNF-α-308 A allele carrier was 3.6% in RA patients and 10.5% in controls (P=0.004); male RA patients displayed noticeably lower rates of TNF-α-308 A allele than that in the male controls (2.8% vs 15.6%, OR=0.179, P=0.007). Patients containing both HLA-DRB1*04 and TNF-α-308 GG genotype showed a significant increase in risk for RA (OR=6.107), no matter they were male (OR=7.273) or female (OR=5.029). Female RA patients with both HLA-DRB1*04 and TNF-α-308 GG showed earlier disease onset and higher TNF-α level.
 CONCLUSION In Han Chinese population from Hunan, susceptibility of RA was increased in patients with TNF-α-308 G allele, especially in the female carrier of genotypes; TNF-α-308 A allele may play a positive role in reduction of RA risk in males.
Alleles ; Arthritis, Rheumatoid ; ethnology ; genetics ; Asian Continental Ancestry Group ; Case-Control Studies ; China ; Female ; Genetic Predisposition to Disease ; Genotype ; HLA-DRB1 Chains ; genetics ; Humans ; Male ; Polymorphism, Single Nucleotide ; Tumor Necrosis Factor-alpha ; genetics

OBJECTIVE: To investigate the potential effect of NALP3 inflammasome on the occurrence and development of nonalcoholic steatohepatitis (NASH). METHODS: THP-1 macrophages were cultured for 24 h by palmitic acid at various concentrations. The THP-1 macrophages were pretreated with N-acetyl-cysteine at different doses for 24 h before the palmitic acid cultivation. ROS production was determined by flow cytometry. The expression of IL- 1β was detected by ELISA; the expressions of NALP3 protein and caspase-1 protein were detected by immunofluorescence; NALP3, ASC, and caspase-1 mRNA were measured by real-time PCR. RESULTS: Compared with the THP-1 macrophages without palmitic acid, the level of ROS, NALP3 protein and caspase-1 protein, and the expression of IL-1β were increased after palmitic acid treatment in a dose dependent manner (P<0.05). Compared with the THP-1 macrophages with palmitic acid (400 μmol/L), the level of NALP3 mRNA (P<0.05), the level of NALP3 protein and caspase-1 protein (P<0.05), the expression of IL-1β (P<0.05) were decreased after preadministration of N-acetyl-cysteine in a dose dependent manner. CONCLUSION ROS induced by free fatty acid can regulate the activation of NALP3 inflammasome signaling pathway leading to the release of inflammatory cytokines. This pathway may be the possible mechanism of NASH.
Carrier Proteins ; metabolism ; Caspase 1 ; metabolism ; Cell Line ; Fatty Acids, Nonesterified ; chemistry ; Humans ; Inflammasomes ; metabolism ; Interleukin-1beta ; metabolism ; Macrophages ; cytology ; NLR Family, Pyrin Domain-Containing 3 Protein ; Reactive Oxygen Species ; metabolism ; Real-Time Polymerase Chain Reaction ; Signal Transduction

Objective To investigate the effect of emodin on insulin resistance and leptin in rat with nonalcoholic fatty liver disease (NAFLD) and to explore the mechanisms of emodin treating NAFLD.Methods Forty two Spraque-Dawley rats were numbered according to their body weights,and were randomly divided into two groups(group A:8 rats; group M:34 rats) by random number table method.The rats in group A was fed with ordinary diets and Group M with improved high fat diets.Four weeks later,when hepatic steatosis in group M were identified,the remaining 32 rats in group M were numbered according to their body weights,and were divided randomly into 4 subgroups (group M1,M2,M3 and M4) by random number table method,with 8 rats in each subgroup.The feeding of all rats was unchanged.The rats in group M2,M3 and M4 were separately intervened with emodin by low doses,emodin by high doses and metformin.Emodin and metformin were dissolved by 0.5％ sodium carboxymethyl cellulose.The rats in group A and M1 was fed with 0.5％ sodium carboxymethyl cellulose by gavage.Four weeks later,all rats were executed.The serum glucose was measured with automatic biochemical analyzer.The serum insulin and leptin were measured by radioimmunoassay (RIA).Insulin resistance was estimated by insulin resistance index of homeostasis model assessment (HOMA-IR) and insulin sensitivity index (ISI).Liver biopsy tissues were treated by Hematoxylin-eosin (HE) staining to evaluate the degree of steatosis and inflammation of liver.Results Compared with group M1,the low and high dosage emodin improved insulin resistance which was represent by serum insulin,HOMA-IR,and ISI(P ＜0.05,P ＜0.01).The serum leptin in group M1 was higher than that in group A (P ＜0.01).The serum leptin in groups M2 and M3 was lower than that in group M1(P ＜0.05,P ＜0.01).Correlation analysis showed that the serum leptin was positively correlated with HOMA-IR(r =0.746,P ＜0.05),and negatively correlated with ISI(r =-0.731,P ＜ 0.05)in group M1.Compared with group M1,the low and high dosage emodin together had the respective effect of ameliorating steatosis(P ＜0.05,P ＜0.01),and they also reduced the hepatic inflammatory activity(P ＜ 0.01).Conclusions Reducing serum leptin and improving insulin resistance may be the mechanisms of emodin treating NAFLD.

OBJECTIVE: To study the role of Novaferon on TNF-α production and expression of NF-κB mRNA in monocytes isolated from normal human peripheral blood and to provide theoretical basis for treatment of immunological diseases with Novaferon. METHODS: Monocytes were isolated from the peripheral blood in 30 healthy volunteers and divided into 5 groups: group A was blank control, group B was stimulated by LPS without Novaferon intervention, group C by LPS together with Novaferon intervention, group D by LPS before Novaferon intervention, which group E by LPS after Novaferon intervention. We detected the concentration of TNF-α after LPS stimulation and Novaferon intervention in the supernatant by ELISA and expression of NF-κB mRNA by RT-PCR. RESULTS: Novaferon inhibited TNF-α production by monocytes isolated from healthy volunteers induced by LPS in vitro in group D compared with group B [(1446.76±72.36) pg/mL vs (946.46±46.12) pg/mL, P<0.01], and the rate was 29.7%. There was no significant change in TNF-α concentration in group C and E compared with group B [(1446.76±72.36) pg/mL vs (1275.62±87.75) pg/mL, P>0.05; (1446.76±72.36) pg/mL vs (1383.62±86.96) pg/mL, P>0.05]. There was significant change in NF-κB mRNA expression in group D compared with group B (0.2829±0.0365 vs 0.4994±0.0604, P<0.01). There was no significant change in NF-κB mRNA expression in group C and group E compared with group B (0.4716±0.0616 vs 0.4994±0.0604, P>0.05; 0.4767±0.0600 vs 0.4994±0.0604, P>0.05). CONCLUSION Novaferon can suppress TNF-α secretion by monocytes induced by LPS in vitro, and it can affect the immunity function of monocytes, which may be associated with the downregulation of NF-κB mRNA expression in monocytes.
Humans ; Lipopolysaccharides ; pharmacology ; Monocytes ; drug effects ; metabolism ; NF-kappa B ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Recombinant Proteins ; pharmacology ; Tumor Necrosis Factor-alpha ; antagonists & inhibitors ; metabolism