Objective To observe the effects of aging on liver and heat shock protein (HSP)70 expression in rats,and explore the role of HSP 70 in the changes of aging liver. Methods 24 healthy Sprague Dawley rats were divided into 4 groups according to age:21-day-old group,3-monthold group,12-month-old group and 18-month-old group (n=6 per group).Routine blood tests and biochemical tests were tested. Liver tissues were observed under light microscopy. The mRNA expression of HSP70 was detected by real-time PCR. Results The ratios of liver weight to body weight were decreased gradually with aging in 4 groups (0.073,0.050,0.025,0.019,respectively,t=78.016,P =0.000).Compared with those of young rats (21-day-old and 3-month-old),serum albumin levels of aged rats (12-months and 18-months) were declined [(35.0±2.7) g/L and (39.8±3.5) g/L vs.(27.3±9.3) g/L and (20.6± 1.7) g/L,t=12.233,P=0.000].Nevertheless serum alkaline phosphatase (ALP) levels were increased with aging [(68.8± 23.3) U/L,(71.6 ± 19.2)U/L,( 185.9 ± 41.5) U/L,(418.6 ± 140.6) U/L,respectively,t =35.454,P=0.000].The differences in other routine biochemical indexes were not found among the age groups (P＞0.05).Liver histological changes including hepatocytes disordered and vacuolization or fatty changes were detected with aging,especially in 18 month-old rats. Real-time PCR results indicated that the expression level of HSP70 mRNA was much lower in 18-month-old rats than in 12-month-old and 3-month-old rats (0.218 vs.0.220 and 0.230,P=0.000). Conclusions HSP70,as a stress protein,may play an important role in the procedure of injury and senescence of liver cell,and then can serve liver aging as one of the influential markers.

ObjectiveThis study is aimed to investigate the association of human leukocyte antigen (HLA)-DRB1 with rheumatoid arthritis (RA) in Chinese Han population.MethodsA total of 281 Chinese Han patients with RA and 202 healthy controls were recruited.DNA was extracted from PBMC and HLA typing was performed by sequence based typing and PCR-Sequence Specific Primer.The frequency of HLADRB1 was compared between patients and controls using x2 test with continuity correction.ResultsThe susceptible HLA-DRB1 alleles were * 0101,* 0102,*0404,* 0405,and * 0410 which belonged to QRRAA.DRRAA and DERAA were protective alleles.At genotypic level,The association of S3P and S3D was detected.However,the protective effect of S3D was shown to be in a recessive mode.ConclusionOur results have shown that there are racial differences in RA susceptibility between Chinese Han population and Caucasians.

Objective:To summarize the characteristics of clinical, muscle pathology and gene mutation of late-onset reducing body myopathy caused by FHL1 gene mutation, in order to improve clinicians′ understanding of this disorder. Methods:The clinical, muscle pathology and muscle magnetic resonance imaging data of the proband from a family diagnosed as reducing body myopathy in Jiaozuo People′s Hospital in December 2021 were collected. Genetic tests and pedigree verification were conducted on the proband and her son.Results:The proband was a 59-year-old female with progressive, asymmetrical limb weakness and muscular atrophy. Her mother, sister and brother had similar symptoms. Electromyography showed myogenic and neurogenic damage. Muscle magnetic resonance imaging indicated that the lesion mainly involved the posterior muscles of the thigh and calf, as well as the gluteus maximus. The muscle pathology showed eosinophilic granular inclusion bodies and rimmed vacuoles in the muscle fibers of the lesion. The structure of myofibrils was disordered and abnormal protein deposition was observed. The gene sequencing showed the FHL1 gene p.C150S heterozygous variation. Conclusions:Late-onset reducing body myopathy is characterized by progressive asymmetric proximal limb muscle weakness, partially involving distal limb muscles and gluteus maximus. Muscle pathology shows the characteristic pathological changes of many kinds of myofibrillar myopathies. FHL1 gene mutation is an important basis for diagnosis.

Objective To investigate the influencing factors for rebleeding and 5-year survival rate after treatment in patients with liver cirrhosis and spontaneous splenorenal shunt(SSRS),and to provide a basis for clinical prognostic assessment.Methods A total of 95 patients with liver cirrhosis and SSRS who were admitted to Zhongshan Hospital and Xiamen Branch of Fudan University from June 2014 to June 2018 were enrolled,and all patients were followed up for at least 5 years.According to the presence or absence of gastrointestinal bleeding during follow-up,the patients were divided into rebleeding group with 27 patients and non-rebleeding group with 68 patients.The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous between two groups,and the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.Univariate and multivariate Cox regression analyses were used to investigate the influencing factors for the prognosis of patients with SSRS,and the Kaplan-Meier method was used to describe survival outcomes.A Pearson or Spearman correlation analysis was performed.Results Compared with the non-rebleeding group,the rebleeding group had significantly higher splenorenal shunt diameter[4.60(3.20—5.90)mm vs 3.45(2.10—5.45)mm,Z=1.973,P=0.048]and hepatic venous pressure gradient(18.57±6.60 mmHg vs 15.06±5.82 mmHg,t=2.280,P=0.026)and a significantly lower portal vein diameter(14.04±2.90 mm vs 15.45±2.90 mm,t=2.138,P=0.035).The correlation analysis showed that splenorenal shunt diameter was negatively correlated with portal vein diameter(rs=-0.211,P=0.040).Adverse events within 5 years after treatment included rebleeding(27.4%),portal vein thrombosis(11.6%),infection(4.2%),cerebral hemorrhage(1.1%),and cerebral infarction(1.1%).Splenorenal shunt diameter(risk ratio[RR]=1.173,95%confidence interval[CI]:1.001—1.374,P=0.048)and superior mesenteric vein diameter(RR=0.844,95%CI:0.746—0.956,P=0.007)were independent influencing factors for gastrointestinal rebleeding within 5 years after treatment.Bilirubin(RR=1.028,95%CI:1.010—1.046,P=0.002)and blood urea nitrogen(RR=1.347,95%CI:1.116—1.625,P=0.002)were independent risk factors for 5-year survival rate after treatment.Conclusion Splenorenal shunt diameter is closely associated with the prognosis of cirrhotic patients,and it is recommended to enhance imaging follow-up of splenorenal shunt diameter for cirrhotic patients with SSRS.

Objective:To analyze the clinical characteristics, muscle imaging and pathological features of patients with anti-signal recognition particle positive immune-mediated necrotizing myopathy (SRP-IMNM).Methods:Nine patients with SRP-IMNM were collected in the Neuromuscular Disease Center of Jiaozuo People′s Hospital from May 2018 to May 2023, who were confirmed by skeletal muscle pathology and myositis-specific autoantibodies detection, and their clinical manifestations, muscle imaging and muscle pathology characteristics were systematically summarized.Results:Among the 9 patients with SRP-IMNM, there were 7 females and 2 males. The age of onset ranged from 18 to 59 years. All the patients presented proximal muscle weakness. Seven patients experienced neck weakness, and dysphagia was present in 5 patients. Laboratory examinations showed elevated serum creatine kinase levels in all 9 patients (1 866-6 725 U/L). Eight patients were combined with other antibodies positivity, except for anti-SRP antibody. Among them, 7 patients were combined with anti-Ro-52 antibody positivity, 4 patients combined with anti-Ro-52 antibody positivity alone, and 3 patients combined with 3 or more positive antibodies simultaneously. Those patients who presented with interstitial lung disease and cardiac involvement were all combined with other antibodies positivity. Seven patients completed thigh muscle magnetic resonance imaging (MRI), which showed diffuse skeletal muscle oedema, partial muscle atrophy and fatty replacement, primarily affecting the posterior thigh muscle group. Two patients underwent shank muscle MRI. The soleus involvement was evident, while the tibialis anterior muscle and gastrocnemius muscles were involved in 1 patient. All 9 patients showed varying degrees of scattered muscle fiber necrosis and regeneration on muscle biopsies. In 1 patient, a small amount of inflammatory cell infiltration was observed. Pipestem capillaries were observed in 4 patients. Immunohistochemical staining revealed a small number of CD68-positive lymphocytes in 8 patients. Additionally, 5 patients showed upregulation of major histocompatibility complex Ⅰ expression on the muscle fiber membrane, while 6 patients showed deposition of membrane attack complex (C5b-9) on non-necrotic muscle fibers and capillaries. P62 staining showed homogeneous fine-granular in sarcoplasm in 6 patients.Conclusions:In addition to proximal muscle weakness, patients with SRP-IMNM often experience neck weakness and dysphagia. Those with multiple antibodies are more likely to develop interstitial lung disease and cardiac involvement. SRP-IMNM patients have diffuse oedema in the affected muscles, and the posterior thigh muscles are more prone to atrophy and fatty tissue formation. C5b-9 deposition and pipestem capillaries are significant pathological features of SRP-IMNM, which provide additional evidence for clinical diagnosis.

Objective To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma(ESCC).Methods We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients.GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog,and TIMER online tool was used to analyze the correlations among TβR1,MMP-2,and MMP-9 in esophageal cancer.Results Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated.Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age,gender,or tumor differentiation.The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time.Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-β signaling pathway,and the expressions of MMP-2/MMP-9 and TβR1 were positively correlated.In cultured ESCC cells,Nanog knockdown significantly decreased the expression of TβR1,p-Smad2/3,MMP-2,and MMP-9 and strongly inhibited cell migration.Conclusion The high expressions of Nanog,MMP-2,and MMP-9,which are positively correlated,are closely related with invasion depth,lymph node metastasis,and prognosis of ESCC.Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-β signaling pathway,and its high expression promotes migration of ESCC cells.

Objective To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma(ESCC).Methods We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients.GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog,and TIMER online tool was used to analyze the correlations among TβR1,MMP-2,and MMP-9 in esophageal cancer.Results Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated.Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age,gender,or tumor differentiation.The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time.Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-β signaling pathway,and the expressions of MMP-2/MMP-9 and TβR1 were positively correlated.In cultured ESCC cells,Nanog knockdown significantly decreased the expression of TβR1,p-Smad2/3,MMP-2,and MMP-9 and strongly inhibited cell migration.Conclusion The high expressions of Nanog,MMP-2,and MMP-9,which are positively correlated,are closely related with invasion depth,lymph node metastasis,and prognosis of ESCC.Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-β signaling pathway,and its high expression promotes migration of ESCC cells.