[Clinical and genetic analysis of pulmonary embolism induced by a novel gene mutation of the antithrombin â ¢ gene].

Objective: To improve the clinical management of acute pulmonary embolism caused by antithrombin Ⅲ (AT Ⅲ) deficiency through gene sequence analysis of the SERPINC1 gene. Methods: The diagnosis and treatment of a 33-year-old male patient with chest pain was reviewed. All exon sequences and flanking regions of 7 related genes of thrombophilia were subjected to detection by high-throughput next generation sequencing technology. The gene mutation was inquired in the gene database and the pathogenic probability of the mutant gene was predicted by Mutation Taster software. Results: The patient was diagnosed with acute pulmonary embolism (intermediate-low risk), with the ATⅢ activity less than 50%. Anticoagulation with nadroparin calcium combined with warfarin was administrated, but hemoptysis was aggravated, and then the medication was replaced by anticoagulant of rivaroxaban. In the end, the embolus was gradually absorbed. A heterozygous missense mutation of c.1148T>A (p.L383H) in the SERPINC1 gene was detected. The gene database and Mutation Taster confirmed the mutation as a new pathogenic mutation with the pathogenic probability of 0.999 999 851 200 991. Conclusions: C.1148T>A (p.L383H) is a novel pathogenic mutation in SERPINC1 gene that complements and updates the gene mutation spectrum of hereditary AT Ⅲ deficiency. The new oral anticoagulant rivaroxaban may be used as the first-line treatment for these patients.

[Prevalence of Spirometra mansoni infections in hosts in Jiangsu Province].

OBJECTIVE: To investigate the prevalence of Spirometra mansoni infections in hosts in Jiangsu Province, so as to provide the scientific basis for the management of sparganosis mansoni. METHODS: From 2018 to 2019, nine counties (cities, districts) were randomly selected from Jiangsu Province as the survey sites, and 100 healthy individuals were randomly selected to perform the serological test of S. mansoni infections and the detection of S. mansoni eggs. The procercoids were detected in the intermediate host Cyclops, and the S. mansoni eggs were identified in the stool samples of the definitive hosts cats and dogs. RESULTS: The prevalence of S. mansoni human infections was 0 (0/900) in the 9 survey sites of Jiangsu Province, and the sero-prevalence of the specific IgG antibody against S. mansoni was 1.22% (11/900). The positive rate of procercoids was 0.33% (3/900) in Cyclops. In addition, the S. mansoni egg-positive rate was 1.48% (2/135) in cats and dogs. CONCLUSIONS: Sparganosis mansoni is prevalent in Jiangsu Province. Health education pertaining to the damages of sparganosis mansoni and the route of S. mansoni infections should be improved.

[Status of child health services in less developed areas in Sichuan province, 2014-2018].

Objective: To understand the status of child health services by primary medical institutions in less developed areas in Sichuan province and provide evidence for the development of health policy for poverty alleviation. Methods: Annual child health records in the primary medical institutions selected through multistage stratified sampling in 21 prefectures in Sichuan were extracted during 2014-2018. Field survey and telephone interview were used to evaluate the performance of child health services provided and the child guardian's satisfaction degree. Sample descriptive statistics, pair sample t-test, χ(2) test, trend χ(2) test, Pearson correlation analysis were used for statistical analysis. Results: Except child system management rate, the other indicators reflecting the status of child health service in less developed areas in Sichuan were on rise (P<0.05), and close to average level of whole province in 2018. Except child system management rate, the other indicators reflecting the status of child health management in less developed counties were lower than those in developed counties in Sichuan, most differences were significant (P<0.05). Except child health management rate of traditional Chinese medicine, the other indicators reflecting the status of child health management in less developed counties were higher than those in poverty-stricken counties in Sichuan, most differences were not significant (P≥0.05). Except child systematic management rate, the gap in indicators reflecting child health service status between less developed area and developed area was in reduction, some difference were significant (P<0.05). The child guardian satisfaction degree was associated with true child health management rates (r=0.947, P=0.015), and child health management rate of traditional Chinese medicine (r=0.996, P<0.001). Conclusions: Some achievements have been made in child health services provided by primary medical institutions in less developed areas in Sichuan. To achieve the 2020 poverty alleviation goal, it is necessary to take measures to increase input and improve service level.

[Clinical analysis of cervical intraepithelial lesion in postmenopausal women].

Objective: To investigate the pathological escalation after cervical cone resection in postmenopausal women, and analyze the related influencing factors. Methods: A retrospective cohort study was conducted at the Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University between July 2013 and January 2015. Seven hundred and fifty cases of cervical cone-cut were enrolled in this study, 129 cases of them were postmenopausal women, and 621 were premenopausal women. All results of patients' liquid-based thin-layer cytology (TCT) , HPV test, colposcopy and biopsy pathology, cervical cone resection and postoperative pathological examination were collected. Then the compliance with the pathological examination results after colposcopic cervical biopsy and cervical cone resection, and the related factors affecting the pathological escalation after cervical cone resection were analyzed. The pathological escalation of patients with different menopausal conditions after cervical cone resection was also analyzed. Results: (1) Of the 750 patients, there were 329 patients had the same pathological examination results after colposcopic cervical biopsy and cervical cone resection, which accounted for 43.9% (329/750) . And 216 cases demonstrated pathological escalation after cervical cone resection, which accounted for 28.8% (216/750) . The results of TCT examination and menopause were significantly correlated with the pathological escalation after cervical cone resection (P<0.05) . However, the condition of HPV infection was unrelated to pathological escalation after cervical cone resection (P>0.05) . (2) Compared with the different results of TCT examination [including non-intrusive load monitoring (NILM) , atypical squamous cell of undetermined signification (ASCUS) , low-grade squamous intraepithelial lesion (LSIL) , high-grade squamous intraepithelial lesion (HSIL) ], the ratio of pathological escalation after cervical cone resection was not statistically significant difference between postmenopausal and non-menopausal patients (P>0.05) . The proportion of pathological escalation of patients with >5 years of menopause was significantly higher than that of patients with menopause time ≤5 years (40.3% vs 27.7%, OR=1.8, 95%CI: 1.1-2.8, P=0.029) . Among them, when the result of TCT examination was LSIL, the rate of pathological escalation in patients > 5 years of menopause was significantly higher than that in menopause time ≤5 years (6/10 vs 26.3%, OR=4.2, 95%CI: 1.1-15.8, P=0.033) . While the results of TCT examination were NILM, ASCUS or HSIL showed there was no statistically significant difference between two groups (P>0.05) . (3) Among the 143 cases, of which the result of TCT examination was LSIL, 9 cases of the pathological examination results after cervical resection were escalated to cervical cancer, which accounted for 6.3% (9/143) . Among 10 cases of menopause time >5 years, 2 cases (2/10) of the pathological examination results after cervical cone resection were escalated to cervical cancer. Among 133 cases with menopause time ≤ 5 years, 7 cases (5.3%) were upgraded to cervical cancer after cervical cone resection. The ratio of pathological escalation to cancer in postmenopausal patients with >5 years was higher than that of menopause time ≤5 years. Due to the data volume limitation, the comparison was not statistically significant difference (χ2=0.460, P>0.05) . Conclusions: In postmenopausal women, especially when menopausal time is > 5 years, the proportion of pathological escalation after cervical cone resection following colposcopic cervical biopsy is increased. And the pathological escalation after cervical cone resection is significantly correlated with the results of TCT examination and menopausal status. Therefore, doctors should treat the colposcopic biopsy pathological results with caution during clinic. Depending on TCT results, loop electrosurgical excision procedure (LEEP) sampling could be administrated directly in case of avoid missing diagnosis.

The Dlk1 and Gtl2 genes are linked and reciprocally imprinted.

Genes subject to genomic imprinting exist in large chromosomal domains, probably reflecting coordinate regulation of the genes within a cluster. Such regulation has been demonstrated for the H19, Igf2, and Ins2 genes that share a bifunctional imprinting control region. We have identified the Dlk1 gene as a new imprinted gene that is paternally expressed. Furthermore, we show that Dlk1 is tightly linked to the maternally expressed Gtl2 gene. Dlk1 and Gtl2 are coexpressed and respond in a reciprocal manner to loss of DNA methylation. These genes are likely to represent a new example of coordinated imprinting of linked genes.

Genomic imprinting is disrupted in interspecific Peromyscus hybrids.

Genomic imprinting, the unequal expression of gene alleles on the basis of parent of origin, is a major exception to mendelian laws of inheritance. By maintaining one allele of a gene in a silent state, imprinted genes discard the advantages of diploidy, and for this reason the rationale for the evolution of imprinting has been debated. One explanation is the parent-offspring conflict model, which proposes that imprinting arose in polyandrous mammals as the result of a parental conflict over the allocation of maternal resources to embryos. This theory predicts that there should be no selection for imprinting in a monogamous species. Crosses between the monogamous rodent species Peromyscus polionotus and the polyandrous Peromyscus maniculatus yield progeny with parent-of-origin growth defects that could be explained if imprinting was absent in the monogamous species. We find, however, that imprinting is maintained in P. polionotus, but there is widespread disruption of imprinting in the hybrids. We suggest that the signals governing genomic imprinting are rapidly evolving and that disruptions in the process may contribute to mammalian speciation.

Multiple mechanisms regulate imprinting of the mouse distal chromosome 7 gene cluster.

Genomic imprinting is an epigenetic process that results in the preferential silencing of one of the two parental copies of a gene. Although the precise mechanisms by which genomic imprinting occurs are unknown, the tendency of imprinted genes to exist in chromosomal clusters suggests long-range regulation through shared regulatory elements. We characterize a 800-kb region on the distal end of mouse chromosome 7 that contains a cluster of four maternally expressed genes, H19, Mash2, Kvlqt1, and p57(Kip2), as well as two paternally expressed genes, Igf2 and Ins2, and assess the expression and imprinting of Mash2, Kvlqt1, and p57(Kip2) during development in embryonic and extraembryonic tissues. Unlike Igf2 and Ins2, which depend on H19 for their imprinting, Mash2, p57(Kip2), and Kvlqt1 are unaffected by a deletion of the H19 gene region, suggesting that these more telomeric genes are not regulated by the mechanism that controls H19, Igf2, and Ins2. Mutations in human p57(Kip2) have been implicated in Beckwith-Wiedemann syndrome, a disease that has also been associated with loss of imprinting of IGF2. We find, however, that a deletion of the gene has no effect on imprinting within the cluster. Surprisingly, the three maternally expressed genes are regulated very differently by DNA methylation; p57(Kip2) is activated, Kvlqt1 is silenced, and Mash2 is unaffected in mice lacking DNA methyltransferase. We conclude that H19 is not a global regulator of imprinting on distal chromosome 7 and that the telomeric genes are imprinted by a separate mechanism(s).

Two dominant mutations in the mouse fused gene are the result of transposon insertions.

The mouse Fused locus encodes a protein that has been implicated in the regulation of embryonic axis formation. The protein, which has been named Axin to distinguish it from the product of the unrelated Drosophila melanogaster gene fused, contains regions of similarity to the RGS (regulators of G-protein signaling) family of proteins as well as to dishevelled, a protein that acts downstream of Wingless in D. melanogaster. Loss-of-function mutations at Fused lead to lethality between days 8 and 10 of gestation. Three dominant mutations result in a kinked tail in heterozygotes. Two of the dominant mutations, Fused and Knobbly, result from insertion of intracisternal A particle retrotransposons into the gene. The insertion in Fused, within the sixth intron, creates a gene that produces wild-type transcripts as well as mutant transcripts that initiate at both the authentic promoter and the 3'-most long terminal repeat of the insertion. Knobbly, an insertion of the retrotransposon into exon 7, precludes the production of wild-type protein. Thus the Fused homozygote is viable whereas Knobbly is a recessive embryonic lethal. In both mutants the dominant kink-tailed phenotype is likely to result from the synthesis of similar amino-terminal fragments of Axin protein that would contain the RGS domain, but lack the dishevelled domain.

Enhancement of glucocorticoid receptor-mediated gene expression by cellular stress: evidence for the involvement of a heat shock-initiated factor or process during recovery from stress.

Recent reports have demonstrated the ability of cellular stress to cause a large increase in the maximal levels of steroid receptor-mediated gene expression, a process we refer to as the heat shock potentiation effect (HSPE). In the present work, we have analyzed the time of appearance of the HSPE on the glucocorticoid receptor (GR) of L929 cells stably-transfected with the MMTV-CAT reporter plasmid (LMCAT2 cells). In LMCAT2 cells exposed to heat shock (43 degrees C, 2-h) before addition of 1 microM dexamethasone, the first appearance of HSPE (CAT levels greater than hormone-alone) occurred at 8 h of recovery and continued to increase by 24 h of recovery. Treatment of LMCAT2 cells with 1 microM dexamethasone for 2 h before heat or chemical shock (sodium arsenite) resulted in the same delayed onset pattern for the HSPE. Based on a [35S]methionine assay and tests of L929 cells stably transfected with the constitutive pSV2-CAT reporter, evidence is provided that the delayed appearance of the HSPE is not due to the heat shock block of general protein synthesis or to specific repression of CAT mRNA expression or translation. By using short-term incubations (4 h) with dexamethasone during the recovery period, the peaks of HSPE expression during recovery were determined to be 12-16 h for CAT enzyme activities, and 4-8 h for CAT mRNA expression. Taken together, these results provide evidence that the timing of the HSPE is not dependent on the rate of GR activation, or on the type of stress, but rather on a factor or process that is either synthesized or activated during the recovery period following stress.

Linkage between vitamin D-binding protein and alpha-fetoprotein in the mouse.

The albumin gene family consists of four evolutionarily related genes that code for serum transport proteins. In rodents, the genes for albumin, alpha-fetoprotein, and alpha ALB are physically linked within 100 kilobases of DNA. The fourth gene, Gc, encoding vitamin D-binding protein or group-specific component, maps to the same chromosome as the other family members, but linkage has not been established. This report describes the genetic and physical mapping of Gc in mouse and establishes that, although Gc is genetically linked to the other genes, its physical distance from them extends beyond the resolution range of yeast artificial chromosome cloning and pulsed-field gel electrophoresis.

Effects of triazolodiazepine on the production of interleukin-6 from murine spleen cells and rabbit synovial cells in vitro.

Interleukin-6 (IL-6) is a multifunctional cytokine that regulates the immune response, acute phase anaphylactic reaction, and haematopoiesis. Lipopolysaccharide (6-24 mug/ml) significantly induced IL-6 release from murine spleen cells. In cultured rabbit synovial cells interleukin-1 (IL-1, 1-10 U/ml) induced IL-6 production in a concentration-dependent manner. Triazolodiazepine (Tri) is a hetrazepine platelet-activating factor antagonist. In this study we found that Tri (0.1-10 mumol/l) exerted strong inhibitory effects on LPS stimulated IL-6 production in murine spleen cells. Kinetic studies showed that the inhibition of IL-6 release was time-independent. In rabbit synovial cells Tri also reduced IL-6 release induced by IL-1 and tumour necrosis factor. Inhibition of cytokine production by Tri may partially explain its wide and strong anti-inflammatory effects.

[Inhibitory effects of esculentoside A on mouse macrophages and antibody production].

Esculentoside A (EsA) is a kind of saponin isolated from Phytolacca esculenta Van Houtte. It was shown to significantly inhibit phagocytic activity, intracellular and extracellular production of interleukin-1 by thioglycollate primed murine peritoneal macrophages in vitro at the concentration 0.01-1.0 mumol.L-1. In vivo experiments showed that EsA 2.5-5 mg.kg-1 markedly decreased serum hemolysin concentration in sensitized mice challenged with sheep red blood cells. Inhibition of antibody production by B lymphocytes, phagocytosis and the production of inflammatory mediators by macrophages may partially explain the wide and strong anti-inflammatory effect of EsA.

[Experimental studies on the significance of processing Eucommia ulmoides Oliv].

The inhibitory action on isolated uterus of middle-pregnancy mice have been compared in Eucommia ulmoides and its salt water processed product. It has been found that after processing the inhibitory action on the automatic contraction of isolated uterus, the antagonism on spasmodis contraction caused by acetylcholine are increased, but the antagonism on spasmodis contraction caused by pituitarium posterius and the Pb content are decreased.

[Comparison of some trace element contents of Eucommia ulmoides Oliv. and its processed products].

A comparison of the contents of 7 trace elements (Zn, Mn, Cu, Fe, Ca, P, Pb) in Eucommia ulmoides and its processed products has been made, and the significance of processing Eucommia ulmoides is discussed in light of the experimental results.