[Correlation analysis between Pirani score and talo-navicular angle,calcaneo-cuboid angle and tibio-calcaneall angle of infant clubfoot under ultrasound].

Objective: To explore the evaluation effect of ultrasonography and Pirani score on tarsal deformity, treatment effect and pseudo-correction of congenital clubfoot in infants and young children, and the correlation between the two methods. Methods: This is a retrospective case series study. The clinical data of 26 children (40 feet) with congenital clubfoot who were evaluated by ultrasonography in the Third Affiliated Hospital of Zhengzhou University from January 2020 to January 2023 were retrospectively collected. There were 16 males and 10 females. The age at the first ultrasound examination was (M(IQR)) 9.0 (18.0) days (range: 1 to 46 days). All patients were treated with Ponseti method by the same physician. The Pirani scores before and after treatment and at the last examination, and the talonavicular angle, calcaneocuboid angle and tibiocalcaneal angle measured by ultrasound were collected, and the treatment and follow-up were recorded. Paired sample t test, repeated measures analysis of variance or Kruskal-Wallis test were used for data comparison, and Spearman correlation analysis was used for correlation analysis. The receiver operating characteristic curve was used to calculate the efficacy of ultrasound in evaluating different Pirani scores. Results: The number of plaster fixation in 26 children was 4.0 (1.0) times (range: 2 to 8 times). The medial talonavicular angle and posterior tibiocalcaneal angle were significantly improved after treatment and at the last follow-up compared with those before treatment, and the differences were statistically significant (all P<0.01). There was no difference in lateral calcaneocuboid angle before and after treatment and at the last follow-up (F=1.971, P>0.05). Pseudo-correction occurred in 2 cases (2 feet) during the treatment, with an incidence of 5%. Correlation analysis showed that there was a moderate positive correlation between talonavicular angle and Pirani midfoot score (r=0.480, P<0.01). There was no correlation between calcaneocuboid angle and Pirani midfoot score (r=0.114, P=0.105). There was a moderate negative correlation between tibial heel angle and Pirani hindfoot score (r=-0.566, P<0.01). The cut-off point of Pirani midfoot score of 1.5 was 38.78°, the sensitivity was 0.90, the specificity was 0.56, and the area under the curve was 0.75. The cut-off value of angle was 27.51 °, the sensitivity was 0.16, the specificity was 0.92, and the area under the curve was 0.44.The cut-off points of Pirani midfoot score of 3.0 were 45.08°and 9.96°, the sensitivity was 0.94 and 0.91, the specificity was 0.37 and 0.42, and the area under the curve was 0.59 and 0.62, respectively. The cut-off values of Pirani hindfoot score of 2.0 and 3.0 were 167.46° and 160.15°, respectively. The sensitivity was 0.75 and 0.67, the specificity was 0.81 and 0.83, and the area under the curve was 0.78 and 0.71, respectively. Conclusion: Ultrasound can complement with Pirani score, visually and dynamically observe the morphology and position changes of talonavicular joint, calcaneocuboid joint and tibiotalocalcaneal joint, monitor the recovery and pseudo-correction of tarsal bones, and better evaluate the therapeutic effect.

[Analysis of the efficacy of the Ponseti method for treatment of secondary clubfoot in young children with tethered cord syndrome].

Objective: To explore the feasibility of Ponseti method in treatment of secondary clubfoot in young children with Tethered Cord Syndrome(TCS). Methods: The clinical data of 53 young children with clubfeet treated with Ponseti method from March 2014 to March 2017 at Department of Pediatric Orthopedics, the Third Affiliated Hospital of Zhengzhou University were analyzed retrospectively. These patients were divided into TCS group and Idiopathic group according to the etiology. There were 19 patients (33 feet) in TCS group,with an mean age of 2.8 months(range:0.2 to 24.0 months), including 13 males and 6 females, 5 patients with unilateral clubfeet and 14 patients with bilateral clubfeet. There were 34 patients (45 feet) in idiopathic group, with an mean age of 3.1 months(range: 0.1 to 21.0 months), including 18 males and 16 females, 23 patients with unilateral clubfeet and 11 patients with bilateral clubfeet. All the children received casts correction according to Ponseti method, and were followed up at 3 weeks, 3 months, 6 months and every 6 months after the Achilles tendon tenotomy or the last cast correction. Complications were recorded and therapeutic effect was evaluated of these children by Dimeglio Scoring System and the International Clubfoot Study Group (ICFSG) at the last follow-up. Independent t test, Mann-Witney U test or χ(2) test were used to compare the indicators of the two groups. Results: The number of plaster fixation in TCS group was (6.1±2.0) times, and that of idiopathic group was (4.8±1.0) times(t=3.482, P<0.01).In TCS group, 22 feet treated with Achilles tendon transection and that of idiopathic group was 40 feet(χ(2)=0.279, P=0.598). There were 18 cases recurrence in TCS group and 8 cases in Idiopathic group (t=11.149, P<0.01). In TCS group, 16 cases (27 feet) completed the initial correction, the success rate was 60.6% (27/33), 3 cases (6 feet) could not correct the deformity after 9 to 10 times of plaster fixation, and then underwent soft tissue release.In idiopathic group, 34 cases (45 feet) achieved initial correction after Ponseti treatment(χ(2)=6.488, P=0.011).At the last follow up, there were 5 cases (9 feet) in TCS group and 2 cases (2 feet) in idiopathic group underwent soft tissue release(χ(2)=6.110, P=0.013). The classification grade of ICFSG score of the two groups without soft tissue release were (2.1±0.6) and (1.8±0.7), the difference was not statistically significant (t=1.765, P=0.082). All the children had no skin ulceration, bedsores, skin allergy and other complications. Conclusion: Ponseti method is effective in the treatment of clubfoot secondary to TCS, and the functional recovery is similar to that of children with idiopathic clubfoot.

[Phenotype and mechanism of inducible ppp2r1a knockout mouse model].

Objective: Investigate the effects of inducible ppp2r1a knockout on main physiological function in adult mice and study the mechanism. Methods: Ppp2r1a(flox/flox) mice and CAGG-CreER mice were hybridized to obtain 20 CAGG-CreER ppp2r1a(flox/flox) and 20 mice in homozygous group. Two groups of mice were divided into 4 groups respectively, finally we got 8 groups with 5 mice in each group. Tamoxifen was injected intraperitoneally to acquire inducible ppp2r1a knockout mice. The knockout efficiency of PP2A Aα in vital organs was measured by Western blot. At 0, 2, 4 and 6 days after injection, we measured body weight, histopathological change, peripheral blood cell counts and blood biochemical. Real-time PCR was performed to measure expression of liver glucolipid metabolism genes. Results: After tamoxifen injection for 6 days, the knockout efficiency of PP2A Aα in vital organs was 35%, 12%, 15%, 60%, 69% and 72%, respectively in heart, liver, spleen, lung, kidney and brain. After tamoxifen injection for 6 days, the weight of homozygous mice was lower than that of wild type mice, with values of (17.42±1.76) g and (21.69±1.82) g, respectively (P<0.05). Moreover, the activity level, abdominal and renal fat were significantly decreased in homozygous mice. Homozygous mice survived no more than 7 days. Compared with wild type mice, the organ coefficient of spleen of homozygous mice was decreased at the 6th day, with values of (0.59±0.10)% and (0.36±0.05)% respectively (P<0.05). Obvious spleen atrophy and marked decrease of nucleated cells were showed by performing HE staining. Tunel staining revealed increased apoptosis ratio of splenic lymphocytes in homozygous mice. The levels of alanine aminotransferase (ALT) and aspartate transaminase (AST) of homozygous mice were higher than wild type mice (P<0.05). The values of ALT and AST in homozygous mice were (153.68±62.80) U/L and (193.2±44.28) U/L. The corresponding values in wild type mice were (41.02±12.91) U/L and (69.40±9.55) U/L. The above results indicated that ppp2r1a knockout caused liver damage. Blood sugar level of homozygous mice was lower than in wild type mice (P<0.05), with values of (4.20±1.99) mmol/L and (8.88±0.65) mmol/L respectively. Plasma total cholesterol (TC), high density lipoprotein (HDL) and ß-hydroxybutyric acid (ß-HB) level of homozygous mice were higher than those of wild type mice (P<0.05). The values of TC, HDL and ß-HB in homozygous mice were (3.12±0.39), (1.53±0.38) and (2.49±0.89) mmol/L. The corresponding values in wild type mice were (1.69±0.92), (0.78±0.50) and (0.45±0.30) mmol/L respectively. The above results indicated that ppp2r1a loss interfered glucose and cholesterol metabolism. In addition, we also found that the white blood cell count (WBC) and lymphocyte count (LYM) of homozygous mice were lower than in wild type mice (P<0.05). The values of WBC and LYM in homozygous mice were (1.88±0.89)×10(9)/L and (0.92±0.37)×10(9)/L respectively. The corresponding values in wild type mice were (3.91±0.80)×10(9)/L and (2.74±0.52)×10(9)/L respectively. The mRNA levels of glucose-6-phosphatase (G6P) and phosphoenolpyruvate carboxykinase (PEPCK) of homozygous were lower than wild type mice (P<0.05). The fold change of G6P and PEPCK in homozygous mice was 0.46±0.11 and 0.72±0.07 respectively. The corresponding fold change in wild type mice was 1.02±0.07 and 1.02±0.06 respectively. Conclusion: Whole body ppp2r1a is essential for the survival of adult mice, due to the important role in maintaining the metabolism of glucose and cholesterol of liver.

miR-383 inhibits ovarian cancer cell proliferation, invasion and aerobic glycolysis by targeting LDHA.

MicroRNAs (miRNAs) are differentially expressed in various cancers and act as oncogenes or tumor suppressors. MiR-383 has been characterized as a cancer suppressor in several cancers. However, the exact expression patterns of miR-383 and the precise molecular mechanisms underlying its role in ovarian cancer have not been investigated thoroughly. In this study, we found that the expression of miR-383 was significantly downregulated in ovarian cancer tissues and ovarian cancer cell lines. Ectopic expression of miR-383 remarkably suppressed the ovarian cancer cell proliferation by enhancing cell apoptosis and significantly inhibited the invasion of ovarian cancer cells, while low expression of miR-383 exhibited the opposite effect. Bioinformatics analysis suggested LDHA as a novel target of miR-383, and miR-383 suppressed the expression level of LDHA mRNA by direct binding to its 3'-untranslated region (3'UTR). Expression of miR-383 was negatively correlated with LDHA in ovarian cancer tissues. In addition, modulation of miR-383 expression could affect the aerobic glycolysis in the ovarian cancer cells. Furthermore, Silencing of LDHA counteracted the effects of miR-383 suppression, while its overexpression reversed tumor inhibitory effects of miR-383. In conclusion, our study demonstrated that miR-383 regulated LDHA expression in ovarian cancer cells, thereby stunting glycolysis, cell proliferation and invasion.

[The relationship between histone H3Ser10 phosphorylation and DNA damage in periphery blood lymphocytes of polycyclic aromatic hydrocarbons exposed workers].

Objective: To investigate the effect of polycyclic aromatic hydrocarbons (PAHs) exposure on the level of histone H3Ser10 phosphorylation (p-H3S10) and DNA damage degree in peripheral blood lymphocyte (PBLCs). Method: 75 coke oven workers from Benxi steel plant in Liaoning Province of China (PAHs-exposed group) and local 50 hot rolling workers (control group) were recruited in this study with age, working years, labor intensity and high temperature for matching factors using cluster sampling method in 2014. HPLC-fluorescence was performed to determine the level of urinary 1-hydroxypyrene (1-OHP), DNA damage and specific histone modification were measured in PBLCs of the subjects through comet assay and ELISA assay, respectively. Linear regression model analysis was used to analyze the differences among PAHs exposure, DNA damage and p-H3S10 level in two groups. The Mediation analysis was used to analyze the regulated relationships between urinary 1-OHP, DNA damage and histone modification through the bootstrap method. Results: Age of the control and the exposed group were (45.32±8.32) and (43.87±5.67) years old (P=0.284). The concentration of urinary 1-OHP, OTM value, Tail DNA% and p-H3S10 level in exposure group were higher than that in control group, while the M (P(5)-P(95)) of p-H3S10 levels in control and exposed group were 2.21 (0.68-4.71), 4.54 (1.85-23.91) (P<0.001). The degree p-H3S10 level was increased after the subgroups which were (2.59±1.19)%, (3.24±2.81)%, (5.55±3.25)%, (8.77±7.84)%, respectively, divided by quantitated 1-OHP concentration as P(0)-P(25), P(26)-P(50), P(51)-P(75) and P(76)-P(100) (P<0.001). We also found the correlations between urinary 1-OHP and p-H3S10 level or OTM value or Tail DNA%, ß (95%CI) were 0.264 (0.167-0.360), 0.500 (0.299-0.702), and 0.510 (0.384-0.671), respectively (P<0.001). Similar result was also observed between p-H3S10 level and OTM value or Tail DNA%, ß (95%CI) were 0.149 (0.073-0.226) and 0.220 (0.132-0.308) (P<0.001). Moreover, the mediation effect value of DNA damage on PAHs induced p-H3S10 alteration was 0.054(P=0.040). Conclusion: The results suggested that PAHs exposure could induce DNA damage and an increase in histone H3Ser10 phosphorylation in PBLCs. Particularly, the alteration of H3S10 phosphorylation may play an important role in regulating cell DNA damage repair.

Enhanced high-mobility group box 1 (HMGB1) modulates regulatory T cells (Treg)/T helper 17 (Th17) balance via toll-like receptor (TLR)-4-interleukin (IL)-6 pathway in patients with chronic hepatitis B.

High-mobility group box 1 (HMGB1) proteins are substantially up-regulated in acute and chronic hepatitis. However, the immunopathogenic role of HMGB1 in patients with chronic hepatitis B (CHB) has not been elucidated. In this study, using a cohort of 36 CHB patients, we demonstrated a crucial role for HMGB1 to modulate balance between regulatory T (Treg) and T helper 17 (Th17) cells via the toll-like receptor (TLR)-4-interleukin (IL)-6 pathway. Serum HMGB1 levels were dramatically higher in CHB patients and increased along with liver injury, inflammation and fibrosis. Notably, HMGB1 increased along with decreased Treg/Th17 cells ratios in the periphery or intrahepatic microenvironment, which provides a clue for HMGB1 to favour Th17 responses whereas inhibit Treg responses. For in vitro studies, serum pools were constructed with serum from CHB patients at an advanced stage, whereas peripheral blood mononuclear cells (PBMC) pools were constructed with cells from those at an early stage. CHB-serum significantly enhanced retinoic acid-related orphan receptor-γt (RORγt), whereas they inhibited forkhead box P3 (Foxp3) expression in CHB-PBMC, which could be reversed by blocking of HMGB1, TLR4, or IL-6. Besides, recombinant HMGB1 (rHMGB1) dose-dependently up-regulated RORγt whereas down-regulated Foxp3 expression in CHB-PBMC, and meanwhile, rHMGB1 enhanced TLR4 and IL-6 expression in CHB-PBMC. Moreover, the axis of HMGB1-TLR4-IL-6-Treg/Th17 required noncontact interactions between CD4 and non-CD4 cells. In addition, rHMGB1 down-regulated anti-inflammatory proteins on CD4(+) CD25(+) cells whereas up-regulated pro-inflammatory cytokines in CD4(+) CD25(-) cells. In summary, enriched HMGB1 in CHB patients shifts Treg/Th17 balance to Th17 dominance via the TLR4-IL-6 pathway, which exacerbates liver injury and inflammation.

Diameter-controlled synthesis of α-Mn2O3 nanorods and nanowires with enhanced surface morphology and optical properties.

Single crystalline α-Mn(2)O(3) nanorods, and nanowires with and without nanoparticles on them have been successfully synthesized by a template-free hydrothermal route. The variation in hydrothermal temperature has not only affected the diameter of the nanostructure but also noticeably affected the morphology and optical properties of the α-Mn(2)O(3) nanostructure. The influence of temperature on the diameter, crystallinity, surface morphology and optical properties of the α-Mn(2)O(3) nanostructure have been characterized by x-ray diffraction, scanning electron microscopy, energy dispersive x-ray analysis, transmission electron microscopy, high resolution transmission electron microscopy, Raman spectroscopy and UV-visible spectroscopy and photoluminescent (PL) spectroscopy. The results showed in our experimental conditions that single crystalline nanorods of the α-Mn(2)O(3) were obtained at a temperature of 180 °C, while single crystalline nanowires were obtained by increasing the temperature to 240 and 300 °C. Nanowires with nanoparticles on them were obtained by increasing the temperature to 240 °C and nanowires without nanoparticles on them were obtained by increasing the temperature to 300 °C. The nanorods and nanowires obtained had a well-defined morphology. The nanowires synthesized at 300 °C exhibited an intense orange band PL spectrum.

Long noncoding RNA OIP5-AS1 exhibits oncogenic activity in bladder cancer through miR-217 and MTDH.

OBJECTIVE: The aim of this study was to investigate the role of long non-coding Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) in bladder cancer (BCa), and the mechanism of OIP5-AS1/microRNA-217 (miR-217)/metadherin (MTDH) in promoting the progression of BCa. PATIENTS AND METHODS: OIP5-AS1, miR-217 and MTDH expressions in BCa tissues and cells were detected by qRT-PCR or Western blot. CCK-8 and transwell assays were used to determine the proliferation and invasion of BCa cells. The correlation between OIP5-AS1 and miR-217, miR-217 and MTDH, and OIP5-AS1 and MTDH were studied by Luciferase reporter assay and Spearman correlation analysis. Statistical analysis of test data was performed using t-test. RESULTS: OIP5-AS1 was upregulated in BCa tissues and cells, and OIP5-AS1 knockdown could inhibit the proliferation and invasion of BCa cells. MiR-217 was a direct-acting target of OIP5-AS1, and MTDH was a target of miR-217. OIP5-AS1 knockdown inhibits human BCa cell proliferation and invasion through miR-217/MTDH axis. CONCLUSIONS: This study systematically explored the effect of OIP5-AS1 in human BCa. MiR-217/MTDH pathway mediated the promotion of OIP5-AS1 in BCa cells proliferation and invasion. OIP5-AS1, as an oncogene, could be used as a biomarker for the treatment of BCa.

Pharmacokinetics and safety of bromotetrandrine (BrTet, W198) after single-dose intravenous administration in healthy Chinese volunteers.

OBJECTIVE: To investigate the safety and pharmacokinetics of bromotetrandrine (BrTet, W198), a novel inhibitor of P-glycoprotein (P-gp), after single-dose i.v. infusion in healthy Chinese volunteers. METHODS: We conducted a randomized, dose-escalating, phase I clinical study for that purpose. Thirty healthy subjects received BrTet at the doses of 10, 20 or 30 mg/m(2) by i.v. infusion. Plasma and urine concentrations of bromotetrandrine were determined by using a liquid chromatography-tandem mass spectrometric (LC/MS/MS) method. AUC was calculated by the trapezoidal rule extrapolation method. C(max), T(max), t(1/2alpha), t(1/2beta), Cl and V(d) were compiled from the plasma concentration-time data. RESULTS: Bromotetrandrine was generally well tolerated at all doses. No serious or severe adverse events were found in the study. The pharmacokinetic parameters of BrTet after single i.v. infusion doses of BrTet 10, 20 and 30 mg/m(2) were as follows: T(max) were 1.5 h in three groups, C(max) were 24.79, 39.59 and 64.31 microg/L, t(1/2alpha) were 0.37, 0.29 and 0.30 h, t(1/2beta) were 62.88, 56.45 and 52.20 h. AUC(0-194h) were 345.83, 688.15 and 1096.28 microg h/L, Cl were 23.68, 25.69 and 25.66 L h/m(2), V(d) were 157.73,156.96 and 140.73 L/m(2). In urine, the total eliminate rate of originate compound was 0.61 +/- 0.19%. CONCLUSIONS: This study suggested that bromotetrandrine was well tolerated in healthy volunteers within the dose range evaluated. The pharmacokinetics parameters of bromotetrandrine indicated that the compound was rapidly distributed and accumulated in the tissues, and slowly cleared from plasma, which supported the use of BrTet for a once or twice dosing per chemotherapy cycle.

MiR-377-3p inhibits cell metastasis and epithelial-mesenchymal transition in cervical carcinoma through targeting SGK3.

OBJECTIVE: In cervical carcinoma (CC), microRNAs (miRNAs) were reported to be involved in its development. In this study, we explored how miR-377-3p regulates cell metastasis and epithelial-mesenchymal transition (EMT) in CC. PATIENTS AND METHODS: Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), Dual-Luciferase Assay, transwell assays, and Western blot analysis were performed to explore the dysregulation of miR-377-3p. RESULTS: MiR-377-3p expression was decreased in CC, and the downregulation of miR-377-3p could predict poor prognosis in CC patients. Moreover, miR-377-3p overexpression repressed cell invasion and migration in CC. Similarly, miR-377-3p overexpression also inhibited EMT in CC cells. Furthermore, miR-377-3p directly targeted SGK3 in CC cells. SGK3 silence had the same function as miR-377-3p overexpression in CC. Especially, the upregulation of SGK3 abolished the inhibitory action of miR-377-3p in CC. CONCLUSIONS: Taken together, miR-377-3p inhibited cell metastasis and EMT by suppressing SGK3 expression. Moreover, the high miR-377-3p expression could predict good prognosis of CC patients.

[Analysis of clinical characteristics and drug treatment of inflammatory bowel disease in children: a single center study].

Objective: To analyze the clinical characteristics and efficacy of drug treatment in children with inflammatory bowel disease (IBD) at different ages of onset. Methods: The clinical data of 87 children with IBD admitted to Department of Gastroenterology in Children's Hospital, Capital Institute of Pediatrics from January 2009 to December 2018 were collected. The patients were divided into four groups according to the age of onset: 0 -<2 years old group (36 cases), 2 -<6 years old group (10 cases), 6 -<10 years old group (12 cases) and 10 -<18 years old group (29 cases). The clinical manifestations, laboratory examination, endoscopic findings, pathologic and genetic changes, and treatment were compared among different age groups with chi-square test or Fisher's exact text. Results: (1) A total of 87 patients were diagnosed with IBD, including 50 Crohn's disease (CD) (57%), 25 ulcerative colitis (UC) (29%) and 12 unclassified inflammatory bowel disease (IBD-U) (14%). (2) Patients with fever accounted for 78% (28/36) and 8/10 in the 0 -<2 years old group and 2 -<6 years old group, respectively. Patients with abdominal pain and perianal diseases accounted for 6% (2/36) and 47% (17/36) in the 0 -<2 years old group, and their proportions were significantly different among the four groups (χ(2)=8.369, 40.317 and 13.130, all P<0.05). (3) Leukocytosis, thrombocytosis and anemia were more common in the 0-<2 years old group, seen in 72% (26/36), 31% (11/36) and 81% (29/36), respectively. There were significant differences in the changes of complete blood count among the four groups (χ(2)=21.919, 8.095 and 11.520, all P<0.05). (4) Colonic involvement accounted for 85% (17/20) in the 0 -<2 years old CD patients. While in the CD patients over 6 years old, 61% (14/23) had inflammation of ileum and colon, with a significant difference compared to that in patients under 6 years old (19% (5/27) , χ(2)=9.455, P=0.003). Also, the location of bowel inflammation among the four groups were significantly different (χ(2)=21.120, P<0.01). (5) Noncaseating granulomas were found in 15 (30%) CD patients, and crypt abscess was found in 11 (44%) UC patients. (6) Among the 24 patients whose genes were analyzed by high throughput sequencing, 12 had pathogenic single gene mutation. (7) There were 25 patients treated with total enteral nutrition. Among the 25 patients treated with thalidomide, 20 (80%) had clinical remission or partial remission. Among the 19 CD patients treated with infliximab (IFX), 14 had clinical remission at the 6(th) week of treatment, and the proportion of remission maintenance at the 30(th) week of treatment was 12/14. (8) The rate of clinical remission or partial remission was 64% (23/36) in the 0 -<2 years old group, 8/10 in the 2 -<6 years old group, 11/12 in the 6 -<10 years old group, and 83% (24/29) in the 10 -<18 years old group. Conclusions: The proportion of CD was higher than that of UC in this study. Infant onset inflammatory bowel disease was more likely to present with perianal lesions, and was usually associated with leukocytosis, thrombocytosis and anemia, and has high possibility of single gene mutation. IFX may be effective in treating CD.

[Clinical and genotypic characteristics of infantile inflammatory bowel disease].

Objective: To analyze the clinical and genotypic characteristics of infantile inflammatory bowel disease (IBD). Methods: The age of onset, family history, clinical manifestations, and treatment effect were retrospectively analyzed in 39 infants (male 23 cases, female 16 cases) with IBD who were admitted to the Department of Gastroenterology in Children's Hospital, Capital Institute of Pediatrics from January 2007 to December 2017. Next generation sequencing (NGS) based on target gene panel was used for gene analysis in 17 patients. Results: The median age of onset was 0.5 (0.5, 1.0) month. The most common clinical symptoms included diarrhea (39, 100%), malnutrition (38, 97%), hematochezia (34, 87%), fever (25, 64%), and perianal diseases (24, 61%). Four children had associated family history. Among the 17 patients whose gene was analyzed, 10 were found to have the pathogenic gene variation, within whom 7 had interleukin-10 receptor α subunit (IL-10RA) mutation, 2 had CYBB heterozygous mutation, 1 had interleukin-10 receptor ß subunit (IL-10RB) mutation. The therapeutic medicine included mesalazine, steroids, and thalidomide. Eighteen children (46%) reached clinical remission (10 cases) or partial remission (8 cases). Conclusions: The incidence of single gene mutation in infants with IBD is high, with IL-10RA mutation as the most common. Refractory diarrhea and malnutrition may indicate infantile IBD.

[Interleukin-10 receptor gene mutations induced very early onset inflammatory bowel disease in 6 infants].

Objective: To analyze the clinical features and interleukin-10 receptor gene mutations in six infants with very early onset inflammatory bowel disease (VEO-IBD). Methods: Four girls and two boys with VEO-IBD admitted to Children's Hospital Affiliated to Capital Institute of Pediatrics from June 2016 to September 2017 were reviewed. The clinical data including general condition, clinical symptoms, laboratory tests, and colonoscopy and pathological results were collected and analyzed. Interleukin-10 receptor α subunit (IL-10RA) gene was examined in all patients. Results: Persistent diarrhea and fever were the most common symptoms and were found within 1 month after birth in all 6 patients. Anemia, oral ulcer or perianal lesions and growth retardation were common concomitant symptoms. All patients had colonoscopy examination and the results showed multiple ulcers affecting the colon with biopsies revealing acute and chronic inflammation. Three patients were found to have cryptitis and crypt abscesses. Gene sequencing revealed IL-10RA gene mutations in all six patients, including 3 cases with homozygous mutations (one with c.537G>A and two with c.301C>T) and 3 heterozygous mutations (paternal c.301C>T in all cases; maternal c.299T>G, c.350G>A and c.537G>A, respectively) . After conventional treatment, one got clinical and pathological improvement according to colonoscopy, three improved clinically, one worsened and died, and one died of septic shock secondary to intestinal perforation. Conclusions: VEO-IBD is associated with IL-10RA mutation, usually with severe intestinal symptoms and significant extra-intestinal symptoms, as well as varied responses to conventional treatment. In our study, c.301C>T and c.537G>A are the most common mutations.

Separate acquisition rest thallium-201/stress technetium-99m sestamibi dual-isotope myocardial perfusion single-photon emission computed tomography: a clinical validation study.

OBJECTIVES: This study assessed the validity of a novel approach to myocardial perfusion scintigraphy that provides the opportunity to avoid the drawbacks of standard same-day rest/stress technetium-99m sestamibi myocardial perfusion studies by using separate-acquisition dual-isotope rest thallium-201 and exercise technetium-99m sestamibi single-photon emission computed tomography (SPECT). BACKGROUND: Standard same-day rest/stress technetium-99m sestamibi myocardial perfusion studies are cumbersome, associated with a potential decrease in perceived stress defect severity compared with thallium-201 due to the presence of rest technetium-99m sestamibi and may be unable to differentiate hibernating from infarcted myocardium. METHODS: The dual-isotope procedure was performed in 63 patients without previous myocardial infarction undergoing coronary angiography to evaluate sensitivity and specificity for coronary artery disease and in 107 patients with a low (< 5%) likelihood of coronary artery disease to evaluate normalcy rate. To validate defect reversibility, the dual-isotope SPECT study was compared with stress/rest technetium-99m sestamibi SPECT studies in a separate group of 31 patients with previous documented myocardial infarction who underwent a rest technetium-99m sestamibi study in addition to the dual-isotope SPECT study. RESULTS: In angiographic correlations, dual-isotope SPECT demonstrated high sensitivity for detecting patients with > or = 50% stenosis (91%, 55 patients) and > or = 70% stenosis (96%, 52 patients). In a small group of patients, high specificity was also observed (75% for < 50% stenosis [8 patients] and 82% for < 70% stenosis [11 patients]). A very high normalcy rate of 95% was also found. In the patient group assessed for defect reversibility, in zones with no previous myocardial infarction, segmental agreement for defect type between rest thallium-201 and rest technetium-99m sestamibi studies was 97% (kappa = 0.79, p < 0.001). In myocardial infarct zones, segmental agreement for defect type was 98% (kappa = 0.93, p < 0.001). Image quality was generally good to excellent. CONCLUSIONS: Our findings demonstrate that separate-acquisition dual-isotope myocardial perfusion SPECT is accurate for coronary artery disease detection, correlates well with rest-stress sestamibi studies for assessment of defect reversibility and results in good to excellent image quality. This approach provides an excellent method for the combined assessment of stress myocardial perfusion and myocardial viability.

Incremental value of prognostic testing in patients with known or suspected ischemic heart disease: a basis for optimal utilization of exercise technetium-99m sestamibi myocardial perfusion single-photon emission computed tomography.

OBJECTIVES: This study assessed the incremental prognostic implications of normal and equivocal exercise technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) and sought to determine its incremental prognostic value, impact on patient management and cost implications. BACKGROUND: The prognostic implications of Tc-99m sestamibi SPECT are not well defined, and risk stratification using this test has not been explored. METHODS: We studied 1,702 patients referred for exercise Tc-99m sestamibi SPECT who were followed up for a mean (+/- SD) of 20 +/- 5 months. Patients with previous percutaneous transluminal coronary angioplasty or coronary artery bypass surgery were excluded. The SPECT studies were assessed using semiquantitative visual analysis. Cardiac death and myocardial infarction were considered "hard" events, and coronary angioplasty and bypass surgery > 60 days after testing were considered "soft" events. RESULTS: Of the 1,702 patients studied, 1,131 had normal or equivocal scan results. A total of 10 events occurred in this group (1 cardiac death and 1 myocardial infarction [0.2% hard events]; 4 coronary angioplasty and 4 bypass surgery procedures [0.7% soft events]). The rates of hard events and referral to catheterization after SPECT were similarly low in patients with a low (< 0.15), intermediate (0.15 to 0.85) and high (> 0.85) post-exercise treadmill test (ETT) likelihood of coronary artery disease. With respect to scan type, patients with normal, probably normal or equivocal scan results had similarly low hard event rates. In the 571 patients with abnormal scan results, there were 43 hard events (7.5%) and 42 soft events (7.4%) (p < 0.001 vs. 1,131 patients with normal scan results for both). When the complete spectrum of scan responses was considered, SPECT provided incremental prognostic value in all patient subgroups analyzed. However, the nuclear scan was cost-effective only in patients with interpretable exercise ECG responses and an intermediate to high post-ETT likelihood of coronary artery disease and in those with uninterpretable exercise ECG responses and an intermediate to high pre-ETT likelihood of coronary artery disease. CONCLUSIONS: Normal or equivocal exercise Tc-99m sestamibi study results are associated with a benign prognosis, even in patients with a high likelihood of coronary artery disease. Although incremental prognostic value is added by nuclear testing in all patient subgroups, a testing strategy incorporating nuclear testing proved to be cost-effective only in the groups with an intermediate to high likelihood of coronary artery disease before scanning.

The C-terminal module of Chi1 from Aeromonas caviae CB101 has a function in substrate binding and hydrolysis.

The chitinase gene chi1 of Aeromonas caviae CB101 encodes an 865-amino-acid protein (with signal peptide) composed of four domains named from the N-terminal as an all-beta-sheet domain ChiN, a triosephosphate isomerase (TIM) catalytic domain, a function-unknown A region, and a putative chitin-binding domain (ChBD) composed of two repeated sequences. The N-terminal 563-amino-acid segment of Chi1 (Chi1DeltaADeltaChBD) shares 74% identity with ChiA of Serratia marcescens. By the homology modeling method, the three-dimensional (3D) structure of Chi1DeltaADeltaChBD was constructed. It fit the structure of ChiA very well. To understand fully the function of the C-terminal module of Chi1 (from 564 to 865 amino acids), two different C-terminal truncates, Chi1DeltaChBD and Chi1DeltaADeltaChBD, were constructed, based on polymerase chain reaction (PCR). Comparison studies of the substrate binding, hydrolysis capacity, and specificity among Chi1 and its two truncates showed that the C-terminal putative ChBD contributed to the insoluble substrate-protein binding and hydrolysis; the A region did not have any function in the insoluble substrate-protein binding, but it did have a role in the chitin hydrolysis: Deletion of the A region caused the enzyme to lose 30-40% of its activity toward amorphous colloidal chitin and soluble chitin, and around 50% toward p-nitrophenyl (pNP)-chitobiose pNP-chitotriose, and its activity toward low-molecular-weight chitooligomers (GlcNAc)3-6 also dropped, as shown by analysis of its digestion processes. This is the first clear demonstration that a domain or segment without a function in insoluble substrate-chitinase binding has a role in the digestion of a broad range of chitin substrates, including low-molecular-weight chitin oligomers. The reaction mode of Chi1 is also described and discussed.

Quantitative stress-redistribution thallium-201 SPECT using prone imaging: methodologic development and validation.

Prone 201Tl myocardial perfusion SPECT has been shown to improve left ventricular inferior wall counts compared to supine imaging, thus minimizing diaphragmatic attenuation. Prone SPECT quantitative normal limits were developed and prospectively applied to 36 patients who had coronary angiography. The prone imaging table used had a cut-out under cardiac area which increased the average myocardial counts by 10.7% compared to prone SPECT through the standard table. Overall specificity and sensitivity were 80% and 93%, respectively. For the right, left circumflex and left anterior descending coronary arteries, the specificities were 94%, 71%, and 94%; and sensitivities were 88%, 89% and 78%, respectively. The normalcy rate in 55 normal patients was 89%. Incidence and the severity of patients motion in 200 prone SPECT studies were compared to 200 supine SPECT studies. Mild and severe motion occurred in 12% and 4% of the supine studies and in only 3.5% and none of the prone studies, respectively. When compared to supine SPECT, prone SPECT had higher (p less than 0.01) regional counts/pixel in the inferior wall and septum, but required an average increase of 2.9 +/- 1.0 cm in camera to chest wall distance and resulted in a reduction of total myocardial counts. Prone SPECT provides an alternative approach for patients who cannot tolerate supine imaging. It should be considered when inferior wall defects on supine imaging pose a diagnostic dilemma and when motion on supine imaging necessitates repeat acquisition.

Comparative feasibility of separate or simultaneous rest thallium-201/stress technetium-99m-sestamibi dual-isotope myocardial perfusion SPECT.

UNLABELLED: Separate or simultaneous rest 201Tl/stress 99mTc-sestamibi dual-isotope SPECT are potentially efficient myocardial perfusion imaging protocols which combine the use of a high-resolution 99mTc tracer for stress perfusion assessment and 201Tl, the current single-photon agent of choice, for viability assessment. METHODS: To investigate the feasibility of dual-isotope myocardial perfusion SPECT protocols using rest 201Tl and stress sestamibi, 201Tl crosstalk into the 99mTc acquisition window (Group 1, n = 26 patients) and 99mTc crosstalk into 201Tl windows (Group 2, n = 25) were studied. For Group 1, treadmill exercise with sestamibi injection and poststress SPECT ("virgin" sestamibi images) were performed, followed by rest 201Tl injection and SPECT acquisition using dual-isotope windows (contaminated or "dual" images). For Group 2, the order was reversed: rest 201Tl SPECT (virgin 201Tl images) was performed first, followed by exercise sestamibi injection and dual-isotope SPECT. RESULTS: The contribution of 201Tl scatter to the dual sestamibi images (Group 1) was measured to be 2.9% +/- 2.1%, while 99mTc crosstalk contributed 26.7% +/- 13.0% to the dual 201Tl images (Group 2). Image quality was considered good to excellent in 92% of the sestamibi (virgin and dual) images and 88% of the virgin 201Tl SPECT, but only in 23% of the dual 201Tl studies. CONCLUSIONS: Technetium-99m crosstalk into 201Tl windows is substantial; therefore, simultaneous dual-isotope protocols, which involve assessment of 201Tl images contaminated by 99mTc, are not recommended. On the other hand, because of the small amount of 201Tl crosstalk into the 99mTc window, a separate acquisition dual-isotope approach employing the rest 201Tl (virgin)/stress sestamibi sequence is acceptable.

Dual-isotope myocardial perfusion SPECT with rest thallium-201 and stress Tc-99m sestamibi.

The commercial availability of Tc-99m-labeled myocardial perfusion agents had added choices in the noninvasive clinical assessment of coronary artery disease. Preferential use of Tc-99m sestamibi has been advocated principally due to improved image quality, which results from the combined physical and biological characteristics of this agent. This article reports upon the investigation of another approach for Tc-99m sestamibi SPECT--dual-isotope rest-stress myocardial perfusion SPECT, which takes advantage of the Anger camera's ability to collect date in different energy windows. For the dual-isotope approach, separate radiopharmaceuticals are employed for the rest injection and the stress injection.

[Studies on the chemical components of Rhodiola crenulata].

Six chemical components I-IV were isolated from the roots of Rhodiola crenulata (Crassulaceae). Five (I-V) of them were identified as known salidroside (I), p-tyrosol(II), pyrogallol, gallic acid, and beta-sitosterol, based on comparison of its Rf(TLC), mmp and spectral data with those of authentic samples. The sixth component was found to be a new delta 1-isopentenyl-3-O-beta-D-glucopyranoside and named crenulatin(VI). Its structure was confirmed on the basis of its spectral data (IR, MS, 1H- and 13C-NMR).