[Correlation between the mutation spectrum of the UGT1A1 gene and clinical phenotype in patients with inherited hyperunconjugated bilirubinemia].

Objective: To analyze the distribution characteristics of UGT1A1 mutant genes (including enhancers, promoters, and exons 1-5) and further explore the correlation between UGT1A1 genotype and clinical phenotypes in patients with inherited hyperunconjugated bilirubinemia. Methods: Patients diagnosed with hereditary hyperunconjugated bilirubinemia at Nanjing Second Hospital from June 2015 to December 2022 were retrospectively analyzed. The UGT1A1 gene was examined using Sanger sequencing in all patients. Complete blood count, liver function, and abdominal imaging examinations were performed. Comparison of categorical variable data using χ(2) testor Fisher percision tests. Comparison of continaous veriable data with normal distribution using t-test. Results: 112 cases (male:female ratio 81:31, aged 9-70 years) had inherited hyperunconjugated bilirubinemia, with a total of 14 mutation sites identified, of which seven were confirmed mutations, and the frequency ranged from high to low: (TA)n accounted for 50%, c.211G>A (p.G71R) accounted for 49.10%, 1456T>G (p.Y486D) accounted for 16.96%, c.686C>A (p.R229W) accounted for 12.5%, 1091C>T (p.P364L) accounted for 8.04%, and c- 3279T>G accounted for 0.982%. Simultaneously, all patients had one to four mutations, of which only one mutation was the most common (55.36%), followed by two mutations (37.5%), and rare three and four mutations (5.36% and 1.78%). There was no statistical significance in total bilirubin (TBil) levels among the four groups (F=0.652, P=0.583). One mutation was most common in (TA)n and c.211G>A (p.G71R), among which TA6/TA7 (n=10) and TA7/TA7 (n=14) mutations were statistically significant in TBil (t=2.143, P=0.043). The c.211G>A (p.G71R) heterozygous (n=9) and isolated (n=15) mutation had no statistical significance in TBil (t=0.382, P=0.706). The GS group accounted for 75%, the intermediate group accounted for 16.9%, and the CNS-Ⅱ group accounted for 8%. TBil was statistically significant among the three groups (F=270.992, P<0.001). There was no statistically significant difference (χ(2)=3.317, P=0.19) between mutation 1 (44 cases, 14 cases, and 4 cases, respectively) and mutations ≥ 2 (40 cases, 5 cases, and 5 cases, respectively) in the GS group, intermediate group, and CNS-II group. Conclusion: The number of UGT1A1 gene mutation sites may have no synergistic effect on TBil levels in patients with inherited hyperunconjugated bilirubinemia. TA7/TA7 mutations are not uncommon, and TBil levels are relatively high.

[Granulomatous disease with liver injury as the main manifestation].

Hepatic granuloma is a kind of disease caused by both infection or non-infection etiologies, and it is found in approximately 2% to 15% of liver biopsies. Some of which could be identified by the pathological morphology. This article reviews the common etiology, pathological manifestations, diagnosis, and differential diagnosis of hepatic granuloma, which is hopeful to improve clinicians' and pathologists' awareness.

Manganese promoted wheat straw decomposition by regulating microbial communities and enzyme activities.

AIMS: This study investigated the dose-effect of manganese (Mn) addition on wheat straw (WS) decomposition, and explored the potential mechanisms of Mn involved in the acceleration of WS decomposition in regards to the soil microbial communities and enzyme activities. METHODS AND RESULTS: A 180-day incubation experiment was performed to examine the decomposition of WS under four Mn levels, that is, 0, 0.25, 1 and 2 mg g-1 . The effects of microbial communities and enzyme activities were evaluated using control (0 mg g-1 ) and Mn (0.25 mg g-1 ) treatments. Our results revealed that Mn (0.25 mg g-1 ) addition significantly increased WS decomposition, and enhanced the release of carbon and nitrogen. Optimal Mn addition (0.25 mg g-1 ) also caused significant increases in the activity of neutral xylanase (NEX), laccase (Lac), manganese peroxidase (MnP) and lignin peroxidase (LiP) within the incubation period. Mn (0.25 mg g-1 ) addition also enriched some operational taxonomic units (OTUs) that, in turn, had the potential ability to decompose crop straw, such as secreting lignocellulolytic enzymes. CONCLUSIONS: Mn (0.25 mg g-1 ) could promote WS decomposition through enrichment of the microbial species involved in biomass decomposition, which enhanced the lignocellulose-degrading enzyme activity. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides evidence for Mn to promote WS biodegradation after Mn application, opening new windows to improve the utilization efficiency of crop residues.

Risk factors for death from hand-foot-mouth disease: a meta-analysis.

In recent years, outbreaks of hand-foot-mouth disease (HFMD) in China, Singapore and other Western Pacific Region, involving millions of children, have become a big threat to public health. This study aimed to quantitatively assess all qualified studies and identify the risk factors for HFMD death. A systematic search of the databases PubMed, Medline, Embase and the Cochrane Library was performed. Study heterogeneity and publication bias were estimated. Seven case-control studies involving 1641 participants (634 died and 1007 survived) were included in the meta-analysis. Human enterovirus 71 infection, male, age ⩽3 years, vomiting, cyanosis, convulsion, duration of fever ⩾3 days, atypical rashes and abdominal distention were not significantly related to HFMD death (P ⩽ 0.05). Lethargy (odds ratio (OR) = 6.62; 95% CI 3.61-12.14; I2 = 0%; P < 0.0001), pneumonoedema/pneumorrhagia (OR = 4.09; 95% CI 2.44-6.87; I2 = 0%; P < 0.0001), seizures (OR = 6.85; 95% CI 2.37-19.74; I2 = 0%; P = 0.0004), dyspnoea (OR = 8.24; 95% CI 2.05-33.19; I2 = 83%; P = 0.003) and coma (OR = 3.76; 95% CI 1.85-7.67; I2 = 0%; P = 0.0003) were significantly associated with HFMD death, which were risk factors for HFMD death.

[Open hepatectomy versus laparoscopic in the treatment of primary left-sided hepatolithiasis: a propensity, long-term follow-up analysis at a single center].

To compare short-term and long-term efficacy after laparoscopic left hepatectomy(LLR) to open left hepatectomy(OLH) for primary left-sided hepatolithiasis. Methods: Clinical data of 187 patients with left-sided hepatolithiasis and underwent laparoscopically or open left-sided hepatectomy from October 2014 to October 2019 at the Second Affiliated Hospital of Anhui Medical University were retrospectively analyzed in this propensity score matching (PSM) study and were matched in terms of age, sex, body mass index, liver function, ASA score, comorbidities, history of biliary surgery, and smoking history on the ratio of 1∶1.There were 47 cases in each group and the mean age were (54.7±12.3)years old(range:34 to 75 years old) and (53.2±12.6) years old (range: 34 to 75 years old) in open and laparoscopically group respectively. The data of operation time, intraoperative blood loss, postoperative hospital-stay, complication rate, biliary fistula rate, stone clearance rate, and stone recurrence rate were compared. The quantitative data were compared using t-test or rank-sum test. Count data were analyzed with χ(2) test or Fisher test. Results: No significant difference was observed in the clinical characteristics of included 94 patients in this study(all P>0.05).The length of the postoperative hospital-stay after OLH was significantly higher than that in the LLH group((10.8±3.1) days vs.(8.5±2.2)days, t=4.085, P=0.000). LLR significantly decreased the incidence of postoperative biliary fistula compared with the OLH (6.3% vs.21.2%, χ(2)=4.374, P=0.036) and the rates of postoperative complications in the OLH group was significantly higher than that in the LLH group (48.9% vs.27.6%, χ(2)=4.502, P=0.034). Moreover, the stone recurrence rates in the LLH group was significantly lower than that after OLR (4.2% vs. 17.0%, χ(2)=4.029, P=0.045). OLH (95% CI: 1.55 to 10.75, P=0.004) and postoperative complications (95% CI: 1.29 to 9.52, P=0.013) were independent risk factors for prolonged hospital stay. OLH (95% CI: 1.428 to 44.080, P=0.018) and residual stones (95% CI: 1.580 to 62.379, P=0.014) were independent risk factors for the occurrence of postoperative biliary fistula. Biliary fistula (95% CI: 1.078 to 24.517, P=0.040) was an independent risk factor for the recurrence of stones. Conclusion: Compared with OLH, LLH is safe and effective for the treatment of the primary left-sided hepatolithiasis with the clinical benefits of shorter hospital stay, fewer morbidity and biliary fistula occurrence, and lower stone recurrence rates.

[Etiological analysis of hepatopathy of unknown etiology in 470 cases undergoing routine liver biopsy examination].

Objective: To understand the etiology of hepatopathy of unknown etiology in patients undergoing liver biopsy. Methods: Demographic data and pathological examination reports of patients with hepatopathy of unknown etiology who underwent liver biopsy examination at outpatient and inpatient of the Second Hospital of Nanjing between January 2017 and June 2018 were retrospectively collected. All liver histopathological sections combined with clinical and pathological features based on liver biopsy examinations were diagnosed by a reputed clinician and a pathologist. Results: A total of 470 cases with hepatopathy of unknown etiology who underwent liver biopsy were enrolled. Of these, 425 cases (90.4%) had a definite diagnosed disease after comprehensive analysis of pathological and clinical data. The diagnosis of hepatopathy of unknown etiology included 11 diseases: 90 cases with autoimmune hepatitis had autoimmune liver disease (19.1%), 38 cases had primary biliary cholangitis (8.1%), 43 cases with overlap syndrome of autoimmune hepatitis had primary biliary cholangitis (9.1%), 118 cases had drug-induced liver injury (25.1%), 75 cases had nonalcoholic fatty liver disease (NAFLD) (16.0%), 12 cases had alcoholic liver disease (2.6 cases) %), 15 cases (3.2%) had vascular liver disease, 7 cases (1.5%) had hereditary metabolic liver disease, 5 cases (1.1%) had other systemic diseases, 16 cases (3.4%) had more than two kinds of liver diseases, and 6 cases (1.3%) had others rare liver diseases. Conclusion: Over 90% cause of the hepatopathy of unknown etiology in the long run can be determined, and the main causes are autoimmune liver disease, drug-induced liver injury, and nonalcoholic fatty liver disease, which needs multidisciplinary cooperation to diagnose, and clinicians need to master the basic and clinical knowledge of liver diseases as well as liver pathology, hepatobiliary imaging, and genetics.

Association of serum fibroblast growth factor 19 levels with visceral fat accumulation is independent of glucose tolerance status.

BACKGROUND AND AIMS: Recent studies suggested that circulating fibroblast growth factor (FGF) 19 levels might be associated with the fat content and distribution, and varied with different glucose tolerance status. This study aimed to investigate the association of serum FGF19 levels with obesity and visceral fat accumulation in a Chinese population with differing glucose tolerance status. METHODS AND RESULTS: The 2383 participants were divided into subgroups of glucose tolerance status: normal glucose tolerance (NGT, n = 1754), impaired glucose regulation (IGR, n = 499), and newly diagnosed diabetes mellitus (DM, n = 130). They were further stratified into quartiles of serum FGF19 levels (Q1-Q4). Visceral fat area (VFA) and subcutaneous fat area were measured using magnetic resonance imaging. FGF19 were detected via quantitative sandwich enzyme-linked immunosorbent assay. Serum FGF19 levels showed a downtrend across the NGT, IGR, and DM groups (P for trend = 0.016). VFA was an independent and negative factor of serum FGF19 levels (standardized ß = -0.108, P = 0.001). After adjustment for glucose tolerance status, VFA differed significantly among FGF19 quartiles (P < 0.001), showing a downtrend from Q1-Q4. The associations of serum FGF19 levels and glucose tolerance status with VFA were independent of each other. After adjustment for insulin resistance and secretory function separately, VFA still decreased significantly from Q1-Q4 (all P < 0.001). CONCLUSION: Serum FGF19 levels were related to visceral fat accumulation. Independent of glucose tolerance status, serum FGF19 levels were inversely associated with VFA.

High-level expression and characterization of a new κ-carrageenase from marine bacterium Pedobacter hainanensis NJ-02.

A novel κ-carrageenase gene (CgkB) has been cloned from Pedobacter hainanensis NJ-02 and expressed heterologously in Escherichia coli BL21 (DE3). It consisted of 1935 bp and encoded 644 amino acid residues with a molecular weight of 71·61 kDa. The recombinant enzyme showed maximal activity of 2458 U mg-1 at 40°C and pH 8·0. Additionally, it could retain more than 70% of its maximal activity after being incubated at pH of 5·5-10·0 below 40°C. K+ and a broad range of NaCl can activate the enzyme. The Km and Vmax of CgkB was 2·4 mg ml-1 and 126 mmol mg-1  min-1 . The ESI-MS analysis of hydrolysates indicated that the enzyme can endolytically depolymerize the carrageenan into tetrasaccharides and hexasaccharides. The results indicated that the enzyme with high activity could be a valuable enzyme tool to produce carrageenan oligosaccharides with various activities. SIGNIFICANCE AND IMPACT OF THE STUDY: Enzymatic preparation of carrageenan oligosaccharides has drawn increased attention due to their various physiological activities. It is urgent to explore enzyme tools with higher activity and better stability. In this work, a novel κ-carrageenase was identified and characterized from marine bacterium Pedobacter hainanensis NJ-02. The enzyme with high activity could be a valuable tool to produce carrageenan oligosaccharides with various activities.

[Histopathological features and diagnostic considerations for genetic metabolic liver disease].

There are many kinds of genetic metabolic diseases, the causes are complicated, and both children and adults can develop diseases. Its diagnosis counts on finding clues from clinical data, and making diagnosis based on family history, symptoms and signs, laboratory examination, pathological examination and gene analysis. This article reviews the proper method of handling liver biopsy, histopathological pattern and characteristics as well as pathological and clinical diagnosis reports of genetic metabolic liver disease.

[Study on spectrum of UGT1A1 mutations in connection with inherited non-hemolytic unconjugated hyperbilirubinemia].

Objective: To compare and analyze patient's general condition, changes in laboratory parameters, and the spectrum of UGT1A1 mutations in patients with inherited non-hemolytic unconjugated hyperbilirubinemia. Methods: A retrospective study was conducted at Nanjing Second Hospital from January 2015 to July 2018 and patients' demographic characteristics, liver function test, and UGT1A1 gene were analyzed. The categorical variable data were compared by χ (2) test. The normal distribution continuous variable data were compared by t-test and the non-normal distribution continuous variable data were compared using Mann-Whitney U test. Results: Of the 51 patients with inherited non-hemolytic unconjugated hyperbilirubinemia, 44 (86.3%) were Gilbert's syndrome (GS) and seven (13.7%) were Crigler-Najjar syndrome type II (CNS- II). The male to female ratio was 2.9:1 and the average age was 36.11 ± 13.17 years. Six variant types were detected: C. -40_-39insTA, C. -3279T > G, c.211G > A (p.G71R), c.686C > A (p.P229Q), c.1091C > T (p.P364L), c.1456T > G (P.Y486D). Among them, c.211G > A accounted for 58.82% (30/51), c.-40_-39insTA accounted for 27.5% (14/51), and c.1456T > G accounted for 25.5% (13/51). The total bilirubin(TB) and unconjugated bilirubin (UCB) in CNS-II patients were significantly higher than GS patients[155.91 (130 ~ 207) vs. 38.25(29 ~ 52.15) µmol/L, U = 0, P < 0.01; 144.13 (120.8 ~ 197) vs. 30.00 (21.7 ~ 46.75) µmol/L, U = 0.00, P < 0.01, respectively]. Exon mutations of c.1091C > T and c.1456T > G were statistically significant(P < 0.01).There were no differences in age, TB, UCB, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) between the c.211G > A homozygous variants and heterozygous variants (P > 0.05). Conclusion: The common pathogenic mutations of UGT1A1 gene were c.211G > A, c.-40_-39insTA, c.1456T > G. c.211G > A. The mutation has little effect on the level of total bilirubin, but c.1091C > T, c.1456T > G mutations has great influence on the level of total bilirubin.

Contribution of fibroblast growth factor 23 to Framingham risk score for identifying subclinical atherosclerosis in Chinese men.

BACKGROUND AND AIMS: Fibroblast growth factor 23 (FGF23) was demonstrated to be involved in the occurrence and development of cardiovascular disease (CVD). The goal of the present study was to investigate the relationship between serum FGF23 levels and carotid intima-media thickness (C-IMT) in men with a low-to-moderate CVD risk. METHODS AND RESULTS: Subjects with normal kidney function were selected from the Shanghai Obesity Study. Serum FGF23 levels were determined by sandwich enzyme-linked immunosorbent assay. C-IMT was measured by ultrasonography. The Framingham risk score (FRS) was used to assess CVD risk. A total of 392 men with low CVD risk and 372 men with moderate CVD risk were enrolled. The recognition rate of an elevated C-IMT was 85.66% with the combination of a moderate CVD risk and high serum FGF23 levels, which was greater than that with either parameter alone (65.44% and 61.03%, respectively). Subjects with high serum FGF23 levels, and either low or moderate CVD risk, were more likely to have elevated C-IMT than those with low serum FGF23 levels and low CVD risk (P = 0.014 and 0.001, respectively). The serum FGF23 levels were independently and positively associated with C-IMT in subjects with low or moderate CVD risk (both P = 0.007). CONCLUSION: In men with low-to-moderate CVD risk, serum FGF23 levels were associated independently and positively with C-IMT. As a complementary index, serum FGF23 levels strengthen the capacity of the FRS to identify subclinical atherosclerosis.

[Recurrent syncope related to catecholaminergic polymorphic ventricular tachycardia due to de novo RyR2-R2401H mutation].

Objective: To explore the clinical and molecular genetic features of a Chinese patient with catecholaminergic polymorphic ventricular tachycardia (CPVT). Methods: Clinical data including resting electrocardiography, echocardiography and treadmill exercise testing of a patient with CPVT admitted to our department in March 2013 were analyzed, and the peripheral venous blood samples of the patient and his family members and 400 ethnicity-matched healthy controls were obtained. All exons and exon-intron boundaries of the six CPVT-related genes including RYR2, CASQ2, TRDN, CALM1, KCNJ2 and ANKB were sequenced to detect the variants related to CPVT. The relationship between the genotypes and phenotypes was analyzed to direct the target therapy. Results: Recurrent syncope induced either by exercise or extreme frightened fear was observed in this patient. There was no positive family history of syncope or sudden death. The resting electrocardiography and echocardiography of the patient were normal, while the exercise testing revealed bidirectional and polymorphic ventricular tachycardia. A cardiac ryanodine receptor gene mutation (R2401H) was identified in this patient, while this mutation was absent in his parents and sister and 400 controls. No variant was detected in the remaining five candidate genes. Treatment with high dose of metoprolol succinate (118.75 mg/d) was effective and patient was free of syncopal attack during the 2 years follow-up. Conclusion: This is the first report on RyR2-R2401H mutation in Chinese patient with CPVT, and high dose of metoptolol is the effective therapy option for CPVT related to RyR2 mutation.

Contribution of a first-degree family history of diabetes to increased serum adipocyte fatty acid binding protein levels independent of body fat content and distribution.

BACKGROUND/OBJECTIVES: First-degree relatives of patients with diabetes bear an increased risk of diabetes, overweight/obesity and cardiovascular disease. Accumulating evidence indicates that circulating concentrations of adipokines are altered in individuals with a first-degree family history of diabetes (FHD), but the adipokine adipocyte fatty acid binding protein (A-FABP) has been rarely studied in this population. The present study explored the association between a first-degree FHD and serum A-FABP levels. SUBJECTS/METHODS: A total of 1962 normoglycemic participants were divided into subgroups of men, premenopausal women and postmenopausal women. Serum A-FABP levels were measured using a sandwich enzyme-linked immunoabsorbent assay. Abdominal fat distribution, including visceral fat area and subcutaneous fat area, was assessed by magnetic resonance imaging. RESULTS: Totals of 792 men, 544 premenopausal women and 626 postmenopausal women were enrolled. Serum A-FABP levels were much higher in subjects with a first-degree FHD than in those without an FHD in all subgroups (all P<0.05). Logistic regression analysis revealed an independent and positive relationship between a first-degree FHD and serum A-FABP levels in men (P=0.029), premenopausal women (P=0.036) and postmenopausal women (P=0.008). Multiple stepwise regression analysis showed that a first-degree FHD was an independent factor positively associated with serum A-FABP levels in men (standardized ß=0.068, P=0.029), premenopausal women (standardized ß=0.090, P=0.018) and postmenopausal women (standardized ß=0.102, P=0.004). CONCLUSIONS: Serum A-FABP levels were increased significantly in normoglycemic individuals with a first-degree FHD. The contribution of the first-degree FHD to the elevated serum A-FABP levels was independent of total body fat content and abdominal fat distribution. Thus, use of serum A-FABP as a biomarker in the first-degree relatives of patients with diabetes may result in overestimation of the risk of obesity-induced metabolic disease and cardiovascular disease.

Laboratory assessment of anti-thrombotic therapy in heart failure, atrial fibrillation and coronary artery disease: insights using thrombelastography and a micro-titre plate assay of thrombogenesis and fibrinolysis.

As heart failure, coronary artery disease and atrial fibrillation all bring a risk of thrombosis, anti-thrombotic therapy is recommended. Despite such treatment, major cardiovascular events such as myocardial infarction and stroke still occur, implying inadequate suppression of thrombus formation. Accordingly, identification of patients whose haemostasis remains unimpaired by treatment is valuable. We compared indices for assessing thrombogenesis and fibrinolysis by two different techniques in patients on different anti-thrombotic agents, i.e. aspirin or warfarin. We determined fibrin clot formation and fibrinolysis by a microplate assay and thromboelastography, and platelet marker soluble P selectin in 181 patients with acute or chronic heart failure, coronary artery disease who were taking either aspirin or warfarin. Five thromboelastograph indices and four microplate assay indices were different on aspirin versus warfarin (p < 0.05). In multivariate regression analysis, only microplate assay indices rate of clot formation and rate of clot dissolution were independently related to aspirin or warfarin use (p ≤ 0.001). Five microplate assay indices, but no thrombelastograph index, were different (p < 0.001) in aspirin users. Three microplate assay indices were different (p ≤ 0.002) in warfarin users. The microplate assay indices of lag time and rate of clot formation were abnormal in chronic heart failure patients on aspirin, suggesting increased risk of thrombosis despite anti-platelet use. Soluble P selectin was lower in patients on aspirin (p = 0.0175) but failed to correlate with any other index of haemostasis. The microplate assay shows promise as a tool for dissecting thrombogenesis and fibrinolysis in cardiovascular disease, and the impact of antithrombotic therapy. Prospective studies are required to determine a role in predicting thrombotic risk.

A replicating plasmid-based vector for GFP expression in Mycoplasma hyopneumoniae.

Mycoplasma hyopneumoniae (M. hyopneumoniae) causes porcine enzootic pneumonia (PEP) that significantly affects the pig industry worldwide. Despite the availability of the whole genome sequence, studies on the pathogenesis of this organism have been limited due to the lack of a genetic manipulation system. Therefore, the aim of the current study was to generate a general GFP reporter vector based on a replicating plasmid. Here, we describe the feasibility of GFP reporter expression in M. hyopneumoniae (strain 168L) controlled by the p97 gene promoter of this mycoplasma. An expression plasmid (pMD18-TOgfp) containing the p97 gene promoter, and origin of replication (oriC) of M. hyopneumoniae, tetracycline resistant marker (tetM), and GFP was constructed and used to transform competent M. hyopneumoniae cells. We observed green fluorescence in M. hyopneumoniae transformants under fluorescence microscopy, which indicates that there was expression of the GFP reporter that was driven by the p97 gene promoter. Additionally, an electroporation method for M. hyopneumoniae with an efficiency of approximately 1 x 10(-6) transformants/µg plasmid DNA was optimized and is described herein. In conclusion, our data demonstrate the susceptibility of M. hyopneumoniae to genetic manipulation whereby foreign genes are expressed. This work may encourage the development of genetic tools to manipulate the genome of M. hyopneumoniae for functional genomic analyses.

[The influence of lumbar sympathetic ganglion radiofrequency thermocoagulation on the activation of microglia in rats with diabetic neuropathic pain].

OBJECTIVE: To observe the influence of lumbar sympathetic ganglion radiofrequency thermocoagulation on the activation of spinal microglia in rats with diabetic neuropathic pain (DNP). METHODS: Thirty-six painful diabetic Sprague-Dawley rats induced by 60 mg/kg streptozotocin (STZ) intraperitoneal injection were randomly divided into diabetic neuropathic pain group (group DNP, n=12), Sham operation group (group Sham, n=12) and radiofrequency thermocoagulation group (group R, n=12). Meanwhile another 12 age-matched rats were allocated as normal control group (group N), rats in group N received intraperitoneal injection of equal volume of normal saline. Twenty-eight days after STZ injection, rats in group R received L3 lumbar sympathetic ganglia radiofrequency thermocoagulation on the left side under X-ray guideline after anesthesia with damage time 60 s and damage temperature 60 ℃. Rats in group Sham received puncture positioning, but not thermocoagulation therapy. The mechanical paw withdrawal threshold (PWT) were performed before STZ injection, 7, 14, 21, 28 days after STZ injection and 1, 3, 5, 7, 14 days after radiofrequency thermocoagulation, respectively. Blood glucose were performed before STZ injection, 3, 28 days after STZ injection and 1, 14days after radiofrequency thermocoagulation. After the final behavioral testing, L3-L5 spinal cord tissues were removed to exam the expression of microglia marker OX42 by Western blotting and immunofluorescence technique, and the changes in the expression of inflammation factor IL-1ß, IL-6, TNF-α were detected by ELISA technique. RESULTS: Compared with group N, after 14, 21, 28 days of STZ injection and 1, 3, 5, 7, 14 days of radiofrequency thermocoagulation, the PWT of group DNP and group Sham decreased significantly (P<0.05); Before radiofrequency thermocoagulation, the PWT of rats in group DNP was (3.84±0.83) g, the PWT of rats in group R was (4.45±0.88) g, there was no statistically significant difference between group DNP and group R (t=1.514, P>0.05), but after radiofrequency thermocoagulation, compared with DNP group, the PWT of rats in group R increased significantly (P<0.05), and lasted to 14 d after radiofrequency thermocoagulation. The ratio of spinal microglia marker OX42 and GAPDH, the expression of inflammation factor IL-1ß, IL-6, and TNF-α in group N were 0.074±0.023, (35.93±6.16) pg/ml, (92.11±13.23) pg/ml, and (169.50±22.64) pg/ml, respectively. The ratio of spinal microglia marker OX42 and GAPDH, the expression of inflammation factor IL-1ß, IL-6, and TNF-α in group DNP were 1.023±0.185, (73.82±9.25) pg/ml, (155.33±21.82) pg/ml, and (298.30±33.21) pg/ml, respectively. The ratio of spinal microglia marker OX42 and GAPDH, the expression of inflammation factor IL-1ß, IL-6, and TNF-α in group Sham were 0.951±0.103, (73.00±7.54) pg/ml, (151.02±24.26) pg/ml, and (294.01±36.37) pg/ml, respectively. The ratio of spinal microglia marker OX42 and GAPDH, the expression of inflammation factor IL-1ß, IL-6, and TNF-α in group R were 0.563±0.019, (51.81±7.36) pg/ml, (123.24±16.13) pg/ml, and (229.23±29.16) pg/ml, respectively. Compared with group N, the expression of spinal microglia marker OX42 and inflammation factor IL-1ß, IL-6, and TNF-α in group DNP, group Sham and group R increased significantly (F=7.501, 348.698, 568.021, 145.110, all P<0.05). Compared with DNP group, the expression of spinal microglia marker OX42 and inflammation factor IL-1ß, IL-6, and TNF-α of group R reduced significantly (all P<0.05). CONCLUSION: The lumbar sympathetic ganglion radiofrequency thermocoagulation can alleviate diabetic neuropathic pain. The mechanism may relate with the inhibition of spinal microglia activation and the lower expression of inflammation factor.

[Diagnosis and treatment of orbit solitary fibrous tumor: a report of 4 cases].

OBJECTIVE: To investigate the diagnosis, treatment and prognosis of orbital solitary fibrous tumor. METHODS: Clinical data of 4 cases with orbital solitary fibrous tumor from January 2001 to June 2014 in the Second Affiliated Hospital of Xi'an Jiaotong University was retrospectively analyzed and the image, pathologic and immunohistochemical findings were reviewed. RESULTS: In the 4 cases, 3 were males and 1 was female, aged from 48 to 67 years. The main symptoms were unilateral progressive proptosis, orbital tumor and decreased vision. Two cases involved the left orbit and 2 in right. The locations of the tumor were in the lateral (2 cases) or inferior orbit (2 cases). Encapsulated smooth round shadow was shown in imaging examination and a homogeneous enhancement strengthening was seen by CT scanning. All cases underwent surgical resection and the removed tumors, appeared as round or irregular oval with fibrous capsule, were 1.5-5.0 cm in size. Three cases were pathological benign and 1 was malignant. Microscopically, the tumors were composed of a large number of spindle tumor cells and varying amounts of interstitial collagen deposition and angiogenesis. There was no atypia in benign tumor, while there was atypia in malignant tumor. Moreover, the tumor was invasive, capsuleless and shown hyperplasia area by light microscope in the case with malignant disease. CD34 and Vimentin were positive in 4 cases and Bcl-2 positive in 2 cases by immunohistochemistry staining. One patient with malignant pathology showed strong positive staining of Ki-67 (>70%) and died of tumor recurrence 10 months after he received the second operation. No metastasis or recurrence occurred by a follow-up of 2 months to 5 years in other 3 cases. CONCLUSIONS: Orbital SFT is characteristic of unilateral progressive proptosis in symptom. Imaging examination is an important diagnostic tool and a complete surgical resection of the tumor is the primary treatment method. Diagnosis depends on pathological and immunohistochemical staining. Malignant transformation may be occurred from benign lesion, hence postoperative follow-up is essential for confirmed patients.(Chin J Ophthalmol, 2016, 52: 268-272).