Objective: To investigate the clinicopathological and molecular characteristics of hepatic fibrinogen storage disease (FSD) in children. Methods: The clinical, histopathologic, immunophenotypic, ultrastructural and gene sequencing data of 4 FSD cases were collected from September 2019 to January 2021 in the Children's Hospital of Fudan University, Shanghai, China. Retrospective analysis and literature review were conducted. Results: There were 4 cases of FSD, 3 males and 1 female, aged 3 years and 3 months to 6 years (median age, 3 years and 4 months). The clinical manifestations were abnormal liver function and abnormal blood coagulation function, for which 2 cases had family genetic history. Liver biopsies revealed that, besides liver steatosis, fibrosis and inflammation, there were single or multiple eosinophilic inclusion bodies of various sizes and surrounding transparent pale halo in hepatocytes. Immunohistochemistry showed that the inclusion bodies were positive for anti-fibrinogen. Under the electron microscope, they corresponded to the dilated cisternae of the rough endoplasmic reticulum, which were occupied by compactly packed tubular structures and arranged into a fingerprint-like pattern with curved bundles. Gene sequencing revealed that the 2 cases of FGG mutation were located in exon 8 c.1106A>G (p.His369Arg) and c.905T>C (p.Leu302Pro), and 1 case was located in exon 9 c.1201C>T (p.Arg401Trp). No pathogenic variant was detected in the other case. Conclusions: FSD is a rare genetic metabolic disease and clinically manifests as abnormal liver function with hypofibrinogenemia. In the background of liver steatosis, fibrosis and inflammation, there are eosinophilic inclusions with pale halo in the hepatocytic cytoplasm, which can be identified by anti-fibrinogen immunohistochemical staining. The fingerprint-like structures under electron microscope are helpful for the diagnosis, while FGG sequencing detects the pathogenic mutation of exon 8 or 9 that can clearly explain the phenotype. However, the diagnosis of FSD cannot be completely ruled out if the relevant mutations are not detected.
Child ; Child, Preschool ; China ; Female ; Fibrinogen/chemistry* ; Humans ; Liver/pathology* ; Liver Diseases/pathology* ; Male ; Metabolic Diseases/pathology* ; Retrospective Studies

Objective To investigate the prevalence and influencing factors of intestinal protozoan infections among rural children in Henan Province. Methods A total of 104 survey sites were sampled from 35 counties (cities) in Henan Province using the stratified cluster sampling method to investigate the prevalence of intestinal protozoan infections among rural children from 2014 to 2015. The trophozoites and cysts of intestinal protozoa were identified using the iodine staining method and the physiological saline direct smear method (one detection for one stool sample). The prevalence of intestinal protozoan infections was compared among rural children with different characteristics, and the factors affecting intestinal protozoan infections among rural children were identified. Results The overall prevalence of intestinal protozoan infections was 0.60% (40/6 771) among rural children in Henan Province from 2014 to 2015. There were 7 species of intestinal protozoa identified, and there was no species-specific prevalence (χ² = 37.732, P = 0.000). No significant differences were found in prevalence of intestinal protozoan infections among rural children in terms of gender (χ² = 1.793, P = 0.181), age (χ² = 1.443, P = 0.486), occupation (χ² = 0.219, P = 0.896) or ecological region (χ² = 1.700, P = 0.637). In addition, terrain (χ² = 2.311, P = 0.510), economic level (χ² = 4.322, P = 0.229), source of drinking water (χ² = 0.731, P = 0.393), eating raw vegetables (χ² = 1.134, P = 0.287) and deworming (χ² = 1.089, P = 0.297) had no remarkable effects on the prevalence of intestinal protozoan infections among rural children in Henan Province; however, the prevalence of intestinal protozoan infections varied significantly among rural children living in regions with different coverage of non-harmless toilets (χ² = 10.050, P = 0.018). Conclusion The prevalence of intestinal protozoan infections is low among rural children in Henan Province.

Objective: To evaluate the efficiency of left cardiac sympathetic denervation (LCSD) in inherited arrhythmia patients with adrenergic activity-induced malignant ventricular arrhythmia, and observe exercise-stress test features before and after LCSD. Methods: This retrospective observational study included catecholaminergic polymorphic ventricular tachycardia(CPVT) and long QT syndromes(LQTS) patients who underwent video-assisted LCSD at Beijing Tsinghua Changgung Hospital and Peking University People's Hospital from September 2006 to May 2020. The indications for LCSD surgery were intolerant or refractory to beta-blocker medication. Clinical and exercise-stress tests data of included patients were collected before and 1 month after LCSD. Heart rate, exercise tolerance, atrial and ventricular arrhythmia, QTc interval and predictors for sudden cardiac death were analyzed. Patents were regularly followed up at 1, 3, 6, and 12 months after LCSD and then once every year thereafter. Cardiac events and medication adjustment records were collected. Results: Five patients (2 CPVT, 1 LQT1, and 2 LQT2)were included in the study. All patients experienced syncope as first symptom at the median age of 12(10, 16)years, and underwent LCSD at the median age of 21(16, 26)years, Baseline heart rate was similar before and after LCSD ((65.6±6.5) beats/min vs. (68.0±11.1) beats/min, P=0.57); while maximum workload tended to be lower after LCSD ((12.1±2.8) metabolic equivalents (METS) before surgery vs. (10.5±2.4) METS after surgery, P=0.07). Incidence of atrial and ventricular arrhythmia were significantly reduced post LCSD, and the ventricular arrhythmia score was decreased after LCSD in CPVT patients (4 points before LCSD vs. 3 points after LCSD in case 1;5 points before LCSD vs. 3 points after LCSD in case 2). QTc interval was shortened significantly in three LQTs patients (QTc interval at baseline heart rate: (546.6±72.3) ms before surgery vs. (493±61.1) ms after LCSD, P=0.047; QTc interval at maximal exercise heart rate: (516.3±73.7) ms before surgery vs. (486.7±64.2)ms after LCSD, P=0.035). Additionally, sudden cardiac death risk indicator ΔHRR1 (heart rate decreasing value within the first 1 min during recovery phase) decreased from (51.5±21.1) beats/min before surgery to (32.0±13.9) beats/min after surgery (P=0.035). During a median follow-up of 1(1, 4) year, all five patients were on low dosage of propranolol (37.0±21.7) mg/d. Cardiac events free survival was achieved in four out of 5 patients (80%) after sympathectomy, while 1 case suffered from sudden cardiac death after emotional stress. Conclusion: LCSD surgery can be safely and effectively performed in most hereditary arrhythmia patients with adrenergic activity-induced life-threatening cardiac events. Exercise stress test results show that LCSD could reduce malignant arrhythmias and improve sudden cardiac death risk indicators without decreasing heart rate.

Objective To understand the epidemic status and influencing factors of intestinal parasitic diseases among rural children in Henan Province. Methods According to the Scheme for The National Survey on Current Status of Major Human Parasitic Diseases in China, the survey counties were selected based on the ecological zones and economic levels in Henan Province between 2014 and 2015. Then, the included counties were stratified according to the topography and economic levels. A township was randomly sampled from each stratum, and a village was randomly sampled from each township as the study site. Finally, a total of 104 study sites from 35 counties were enrolled for the survey of intestinal parasitic diseases in children. At least 250 fresh stool samples were collected from each study site for detection of intestinal helminth eggs with the Kato-Katz technique, for the identification of Necator americanus and Ancylostoma duodenale with the fecal culture method, and for the detection of intestinal protozoa trophozoite and cyst with the physiological saline smear and iodine staining techniques. In addition, the Enterobius vermicularis and tapeworm eggs were detected in children aged 3 to 6 years using the adhesive cellophane-tape perianal swab method. Results The overall prevalence of intestinal parasitic infections was 3.21% (214/6 671) among rural children in Henan Province, and the prevalence of intestinal helminthes (2.62%, 175/6 671) was higher than that of intestinal protozoa (0.60%, 40/6 671). A total of 12 species of intestinal parasites were found, including 4 nematodes species, one trematode species, and 7 protozoa species, and the highest infection was seen in E. vermicularis (2.47%, 161/6 671). Among the four ecological zones in Henan Province, the greatest prevalence of intestinal parasitic infections was detected among children in the Qinba Mountain Ecological Zone (5.85%, 90/1 538). There was no gender-specific difference in the prevalence of intestinal parasitic infections in children (P > 0.05); however, there were age- (χ² = 32.762, P < 0.05) and education level-specific differences in the prevalence of intestinal parasitic infections in children (χ² = 67.507, P < 0.05), with the greatest prevalence of E. vermicularis infection seen in all species of intestinal parasites in children at all age groups. Multivariate non-conditional logistic regression analysis showed that high education level, high coverage of harmless toilets, drinking tap water and deworming were protective factors for intestinal parasitic infections in children in Henan Province. The overall prevalence of intestinal parasitic infections appeared a tendency towards a gradual decline among children in Henan Province as compared to the previous two surveys. Conclusions The overall prevalence of intestinal parasitic infections shows a tendency towards a remarkable decline among children in Henan Province. E. vermicularis infection should be given a priority for future parasitic disease control activities among rural children in Henan Province.

OBJECTIVE: To study the value of fast spin-echo diffusion weighted imaging (TSE-DWI) apparent diffusion coefficient (ADC) in children aged 2-12 years with intellectual disability (ID)/global developmental delay (GDD) who have normal conventional brain MRI findings. METHODS: A total of 578 children with normal conventional brain MRI findings who met the diagnostic criteria for ID/GDD and 375 normal children were enrolled. Their imaging and clinical data were collected. All children underwent scanning with brain TSE-DWI sequence and routine sequence. ADC values of each brain region were compared between normal children with different ages, as well as between children with different degrees of ID/GDD in each age group. The influence of Adaptive Behavior Assessment System-II (ABAS-II) score on ADC values of each brain region was analyzed. RESULTS: For the normal children, the ADC values of the frontal and temporal white matter, the corpus callosum, the inner capsule, the centrum semiovale, the cerebellar dentate nucleus, the optic radiation, the thalamus, the lenticular nucleus, and the caudate nucleus gradually decreased with age (P<0.05). ADC values of the deep white matter, the shallow white matter, the deep gray matter nuclei, and the shallow gray matter increased with the increase in the degree of ID/GDD in the ID/GDD children aged 4-6 years (P<0.05). In the children with ID/GDD, the ADC values of the deep white matter, the shallow white matter, and the deep gray matter nuclei decreased with age (P<0.05). The ADC values of the children with ID/GDD decreased with the increase in ABAS-II score (P<0.05). CONCLUSIONS ADC can reflect the subtle structural changes of brain regions in children with ID/GDD who have normal conventional brain MRI findings. It may be associated with social adaptation. It can provide an objective basis for the quantitative diagnosis of ID/GDD in children.
Brain ; Child ; Child, Preschool ; Diffusion Magnetic Resonance Imaging ; Humans ; Intellectual Disability ; diagnostic imaging ; Magnetic Resonance Imaging ; White Matter

Hydrophobic medicine carbendazim,come into inclusion compounds with β-cyclodextrin(β-CD),2-hydroxypropyl-β-CD (2-Hp-β-CD) and 2,6-dimethyl-β-CD(Me-β-CD),were made by solvent method.By investigating the inclusion behaviors of these three cyclodextrins combined with carbendazim using 1H NMR,2D rotating frame overhause effect spectroscopy (ROESY) and diffusion ordered spectroscopy,the possible ways of combinations and the recognition ratio of this three inclusion compounds,Dβ-CD=2.516×10-10m2/s,D2-Hp-β-CD=1.676×10-10m2/s,DMe-β-CD=2.046×10-10m2/s,were obtained.According to X-ray power diffraction,thermogravimetric analysis,infrared spectroscopy and scanning electron spectroscopy characterization,it was found that the characteristic diffraction peaks changed after carbendazim and cyclodextrin formed into inclusion compounds,and the characteristic diffraction peak of carbendazim at 10.4°,21.2°,25.8°,31.5°(2θ) lost or disappear.The pyrolysis temperature of carbendazim was 197.5℃,and would be higher than 260℃ after it formed inclusion complex.The infrared spectrum also showed that the oscillation peaks of inner cyclodextrin cavum apparently reduced after carbendazim combined,which demonstrated that the position of water molecules inside cyclodextrin cavum were occupied by the carbendazim molecules.With the help of SEM,the appearances of inclusion were different from a single carbendazim molecule,which manifested a new structure appeared.

Objective To study the correlation of patellar stability with age ,knee Kellgren-Lawrence grading and patellar Wiberg typing of adults with Kaschin-Beck disease (KBD) .Methods Through cross-sectional study , we asked 143 adult patients with KBD from several villages in Gansu Province to receive digital radiographic x-ray (DR) which included lateral slice of knee joint and axis slice of patellar .Meanwhile ,each patient had to undergo patellar stability measurement on the DR film which included some indexes such as Insall index , lateral patellofemoral angle ,sulcus angle ,congruence angle ,lateral migrating ratio of patella ,and patellofemoral index . Then ,all the participants were divided into four groups based on the patella Wiberg typing and three groups based on KBD clinical grading .Last ,we analyzed the correlation of patellar stability with patellar Wiberg typing ,clinical KBD grading ,and Kellgren-Lawrence grading of the patients by Spearman test .Results ① By ANOVA test on the patella Wiberg typing ,lateral patellofemoral angle decreased with increased level of patella Wiberg typing ,but congruence angle ,lateral migrating ratio of patella ,and patellofemoral index were increased with increased level of patella Wiberg typing . P values of the six indexes were all <0 .05 ,which indicated that these differences between groups were significant .By ANOVA test on the KBD clinical grading ,lateral patellofemoral angle decreased with increased level of KBD clinical grading ,but congruence angle ,lateral migrating ratio of patella ,sulcus angle ,and patellofemoral index increased with increased level of KBD clinical grading .Besides that P value of Insall index was>0 .05 , P value of the other five indexes were all <0 .05 ,which indicated these differences between groups were significant .② Spearman test :a strong correlation lay between Wiberg patellar typing and other indexes including age ,lateral patellofemoral angle ,congruence angle ,lateral migrating ratio of patella ,and patellofemoral index ( R=0 .684 ,0 .752 ,0 .582 ,0 .533 ,0 .735 , P< 0 .05) .However ,there was no correlation between Wiberg patellar typing and K-L photographical grading (R=0 .030 ,P>0 .05) .K-L grading was strongly correlated with age (R=0 .782 , P< 0 .05 ) , weakly correlated with lateral migrating ratio of patella ( R = 0 .104 , P> 0 .05 ) , but not correlated with the others ( R < 0 .1 , P> 0 .05 ) . Age was strongly correlated with K-L grading and lateral patellofemoral angle (R=0 .782 ,0 .506 ,P<0 .05) ,moderately correlated with congruence angle ,lateral migrating ratio of patella ,and patellofemoral index (R=0 .403 ,0 .361 ,0 .475 , P< 0 .05) ,but not correlated with Wiberg typing ,sulcus angle ,or Insall index ( R=0 .024 ,0 .074 ,0 .053 , P>0 .05) .Conclusion Patellar Wiberg typing is the key factor which influences latellar stability ;age has a limited influence ,while K-L grading does not affect patellar stability .

Objective To study the correlation between knee biomechanics and clinical manifestation in adults with Kaschin-Beck disease(KBD). Methods Three hundred and eighty-nine digital radiographic X-ray (DR)anteroposterior keen films of adult KBD patients diagnosed at the Center for Disease Control and Prevention of Gansu Province from Sep 2012 to Sep 2016 were taken as subjects of observation and were retrospectively reviewed. Every patient must undergo a WOMAC function evaluation for knee joint and biomechanic angle measure for the lower limbs on the DR film which included femur angle, tibial angle, femur-tibial angle and joint space angle, Insall-Salvati index (LT/LP), and LT/HI index. Then, the regression equation was built and the correlation analysis was made with multiple linear regression test. Results Three hundred and eighty-nine patients' average scores of femur angle(X1),tibial angle(X2),joint space angle(X3),femur-tibial angle(X4),LT/LP index(X5),LT/HI index (X6) and WOMAC evaluation were (76.32 ± 2.05)°, (110.65 ± 4.68)°, (4.73 ± 0.91)°, (137.56 ± 2.29)°, 0.98 ± 0.12, 1.73 ± 0.11, and (61.35 ± 7.68) scores. By multiple linear regression test, femur angle, tibial angle, femur-tibial angle,LT/LP index, and LT/HI index were selected to enter into the equation; while, joint space angle was rejected. The multiple linear regression equation was as follows: Y = - 77.307 - 6.327X6+ 1.360X1+ 1.310X5+ 0.331X4-0.147X2.The adjusted determination coefficient (R2) of the equation was 0.958. Through variance analysis, the fitted equation had statistical significance (F = 1 790.391, P < 0.05). Through two- tailed significance test, the above-mentioned 5 indexes that were adopted to enter this question were in significant correlation with WOMAC scores(P<0.05).Conclusion There is a significant correlation between knee biomechanic angle and WOMAC scoring in adults with KBD,which is reflected with the following parameters from big to small in turn:femur angle,tibial angle, LT/LP index,femur-tibial angle,LT/HI index,.

We employed a multiplex polymerase chain reaction (PCR) coupled with capillary electrophoresis (mPCR-CE) targeting six Clostridium difficile genes, including tpi, tcdA, tcdB, cdtA, cdtB, and a deletion in tcdC for simultaneous detection and characterization of toxigenic C. difficile directly from fecal specimens. The mPCR-CE had a limit of detection of 10 colony-forming units per reaction with no cross-reactions with other related bacterial genes. Clinical validation was performed on 354 consecutively collected stool specimens from patients with suspected C. difficile infection and 45 isolates. The results were compared with a reference standard combined with BD MAX Cdiff, real-time cell analysis assay (RTCA), and mPCR-CE. The toxigenic C. difficile species were detected in 36 isolates and 45 stool specimens by the mPCR-CE, which provided a positive rate of 20.3% (81/399). The mPCR-CE had a specificity of 97.2% and a sensitivity of 96.0%, which was higher than RTCA (x = 5.67, P = 0.017) but lower than BD MAX Cdiff (P = 0.245). Among the 45 strains, 44 (97.8%) were determined as nonribotype 027 by the mPCR-CE, which was fully agreed with PCR ribotyping. Even though ribotypes 017 (n = 8, 17.8%), 001 (n = 6, 13.3%), and 012 (n = 7, 15.6%) were predominant in this region, ribotype 027 was an important genotype monitored routinely. The mPCR-CE provided an alternative diagnosis tool for the simultaneous detection of toxigenic C. difficile in stool and potentially differentiated between RT027 and non-RT027.
Clostridium Infections ; diagnosis ; Clostridium difficile ; genetics ; Electrophoresis, Capillary ; Feces ; microbiology ; Genes, Bacterial ; Humans ; Polymerase Chain Reaction ; Ribotyping ; Sensitivity and Specificity