[Clinical and genetic characteristics of children with primary dilated cardiomyopathy]. / å„¿ç«¥åŽŸå‘æ€§æ‰©å¼ åž‹å¿ƒè‚Œç— çš„ä¸´åºŠç‰¹å¾åŠé—ä¼ å­¦åˆ†æž.

OBJECTIVES: To study the genetic characteristics, clinical characteristics, and prognosis of children with primary dilated cardiomyopathy (DCM). METHODS: A retrospective analysis was performed on the medical data of 44 children who were diagnosed with DCM in Hebei Children's Hospital from July 2018 to February 2023. According to the genetic testing results, they were divided into two groups: gene mutation-positive group (n=17) and gene mutation-negative group (n=27). The two groups were compared in terms of clinical data at initial diagnosis and follow-up data. RESULTS: Among the 44 children with DCM, there were 21 boys (48%) and 23 girls (52%). Respiratory symptoms including cough and shortness of breath were the most common symptom at initial diagnosis (34%, 15/44). The detection rate of gene mutations was 39% (17/44). There were no significant differences between the two groups in clinical characteristics, proportion of children with cardiac function grade Ⅲ or Ⅳ, brain natriuretic peptide levels, left ventricular ejection fraction, and left ventricular fractional shortening at initial diagnosis (P>0.05). The median follow-up time was 23 months, and 9 children (20%) died, including 8 children from the gene mutation-positive group, among whom 3 had TTN gene mutation, 2 had LMNA gene mutation, 2 had TAZ gene mutation, and 1 had ATAD3A gene mutation. The gene mutation-positive group had a significantly higher mortality rate than the gene mutation-negative group (P<0.05). CONCLUSIONS: There is no correlation between the severity of DCM at initial diagnosis and gene mutations in children. However, children with gene mutations may have a poorer prognosis.

Visible-Light-Induced Regio- and Stereoselective C(sp2)-H Trifluoroethylation of Enamides with 2,2,2-Trifluoroethyl Iodide.

A photoredox-catalyzed regio- and stereoselective trifluoroethylation reaction of enamides using commercially available 2,2,2-trifluoroethyl iodide as trifluoroethylating agents has been developed, furnishing geometrically defined and synthetically and physiochemically pivotal ß-trifluoroethylated enamides bearing a diverse range of functional groups.

Incidence of iatrogenic pneumothorax following acupuncture treatments in Taiwan.

BACKGROUND: Pneumothorax is a rare complication of acupuncture and the risk factors are unclear. OBJECTIVE: This study analysed the incidence of post-acupuncture pneumothorax requiring hospitalisation in a one-million-sample cohort derived from Taiwan's National Health Insurance Research Database. METHODS: We tracked this cohort between 1997 and 2012 and recorded all medical insurance information. Subjects were categorised according to gender, insurance amount, comorbidities, residential area, and number of acupuncture treatments. Pneumothorax risk was evaluated according to different demographic and medical variables by logistic regression analysis using an adjusted odds ratio (aOR) with a 95% confidence interval (95% CI). RESULTS: Overall, 411 734 patients undergoing 5 407 378 acupuncture treatments were identified with data collected over the first 7 days after acupuncture. The incidence rates of iatrogenic pneumothorax were 0.87 per 1 000 000 acupuncture treatments overall and 1.75 per 1 000 000 acupuncture treatments in "at-risk" anatomical areas. Multivariate logistic regression demonstrated that a history of thoracic surgery (aOR 7.85, 95% CI 3.49 to 9.25), chronic bronchitis (aOR 2.61, 95% CI 1.03 to 6.87), emphysema (aOR 4.87, 95% CI 1.03 to 7.96), pneumonia (aOR 2.09, 95% CI 1.44 to 2.72), tuberculosis (aOR 3.65, 95% CI 1.39 to 9.56), and lung cancer (aOR 3.85, 95% CI 1.53 to 9.73) may increase the post-acupuncture risk of iatrogenic pneumothorax. Men had a higher risk of pneumothorax than women (aOR 3.41, 95% CI 1.36 to 8.57). The number of treatments was not associated with risk of pneumothorax. CONCLUSIONS: Patients with a history of lung disease including chronic bronchitis, emphysema, tuberculosis, lung cancer and pneumonia, and a history of thoracic surgery, might have an increased post-acupuncture risk of pneumothorax. This information may possibly help physicians avoid post-acupuncture pneumothorax.

Correlation of HLA-DQ and TNF-α gene polymorphisms with ocular myasthenia gravis combined with thyroid-associated ophthalmopathy.

The present study aims to explore the correlation of human leucocyte antigen (HLA)-DQ and tumour necrosis factor (TNF)-α gene polymorphisms with ocular myasthenia gravis (OMG) combined with thyroid-associated ophthalmopathy (TAO). From March 2009 to March 2015, 56 OMG patients complicated with TAO (OMG + TAO group), 134 patients diagnosed with OMG only (OMG group) and 236 healthy individuals (control group) were enrolled in the present study. PCR-sequence specific primer (PCR-SSP) was used for HLA-DQ genotyping and PCR-restriction fragment length polymorphism (PCR-RFLP) for TNF-α genotyping. ELISA kit was applied to detect acetylcholine receptor antibody (AchRAb) level and chemiluminescence immunoassay (CLIA) to measure thyroid-associated antibody (T-Ab) level. Logistic regression analysis was carried out to analyse the risk factors for OMG combined with TAO. DQA1*0103 showed lower frequency in the OMG group than in the control group. DQA1*0301 showed increased and DQB1*0601 showed decreased frequency in the OMG + TAO group. DQB1*0501 showed higher frequency in the OMG and OMG + TAO groups than in the control group. Patients carrying TNF-α -863C > A (CA + AA) might confront with greater risks of OMG combined with TAO. Frequency of DQA1*0103/*0301 and DQB1*0501/*0601, and TNF-α -863C > A, -238G > A and -308G > A were associated with the levels of AchRAb and T-Ab. TNF-α -863C > A (CA + AA) and high level of T-Ab were risk factors for OMG combined with TAO. Our results demonstrate that TNF-α -863 polymorphism is possibly correlated with the risk of OMG combined with TAO.

Insulin-like growth factor binding protein-3 is a new predictor of radiosensitivity on esophageal squamous cell carcinoma.

Insulin-like growth factor binding protein-3 (IGFBP-3) plays an essential role in radiosensitivity of esophageal squamous cell carcinoma (ESCC). However, the underlying mechanism is not completely understood. Here, we observed that IGFBP-3 had favorable impact on the tumorigenicity of ESCC cells in nude mice by using an in vivo imaging system (IVIS) to monitor tumor growth treated with ionizing radiation (IR). Downregulation of IGFBP-3 expression enhanced tumor growth, inhibited anti-proliferative and apoptotic activity and result in IR resistance in vivo. Cell cycle antibody array suggested that silencing IGFBP-3 promoted transition from G0/G1 to S phase, perhaps though influencing Smad3 dephosphorylation and retinoblastoma protein (Rb) phosphorylation. Downregulation of P21 and P27, and upregulation of p-P27 (phospho-Thr187), cyclin-dependent kinase 2 (CDK2), and cyclin E1 might contribute to the G0/G1 to S phase transition promoted by IGFBP-3. Our results suggest that Smad3-P27/P21-cyclin E1/CDK2-phosphorylated retinoblastoma protein pathways might be involved in this IGFBP-3 mediated radiosensitivity transition in ESCC.

Association between E-cadherin (CDH1) polymorphisms and pancreatic cancer risk in Han Chinese population.

This study was designed to investigate the associations between E-cadherin (CDH1) gene polymorphisms and pancreatic cancer (PC) risk predisposition. We undertook a case-control study to analyze three E-cadherin polymorphisms (+54T>C, -160C>A and -347G→GA) in an Han Chinese population, by extraction of genomic DNA from the peripheral blood of 368 patients with PC and 376 control participants and performed E-cadherin genotyping using DNA sequencing. Overall, no statistically significant association was observed in +54T>C. Nevertheless, -347G→GA genotype was at increased risk of PC (P=0.022; odds ratio (OR)=1.128, CI 95%: 1.017-1.251). Furthermore, -347GA/GA genotype pancreatic cancers were more significantly common in cases of advanced T stage, lymph node metastasis and clinical pathological stage than G or G/GA genotypes PC. However, -160C>A genotype demonstrated a protective effect in PCs (P=0.017; OR=0.883, CI 95%: 0.798-0.977). In conclusion, polymorphism in -347G→GA was observed to be associated with susceptibility of PC. However, -160C>A polymorphism indicated to play a protective role in susceptibility to PC. Nevertheless, further investigation with a larger sample size is needed to support our results.

[Effects of Nutrient Inputs on Changes of Phosphorus Forms and Phytoplankton Growth in Taihu Lake].

In order to determine the effects of nutrient inputs on changes of phosphorus forms and phytoplankton growth in large shallow lakes, an enrichment bioassay was conducted using surface lake water collected from the Meiliang Bay of Taihu Lake in spring. The concentration of different phosphorus forms, phytoplankton biomass (chlorophyll a) and alkaline phosphatase activity (APA) was analyzed after the addition of different concentrations of inorganic nutrients. The results showed that the phytoplankton biomass increased significantly with the addition of phosphorus (P), but with no primary effect from nitrogen (N), which suggested the phytoplankton growth was mainly limited by P. The maximum growth rate and the highest concentration of chlorophyll both occurred in the SRP 0.015 mg x L(-1) treatment. Nitrate addition could improve the bioavailability of phosphorus, accelerate the phosphorus cycling process and promote the growth of APA. There was an induction-repression mechanism resulting in a negative relationship between APA and orthophosphate concentration. The APA was obviously stimulated under PO4(3-) -P ≤ 0.025 mg x L(-1). This paper researches the transformation and cycling process of phosphorus in water and the induction-repression mechanism between the APA and orthophosphate concentration. The result can help to reveal the compensation path of nutrients in algae growth process and provide a theoretical basis for the further reveal of the mechanism of algae outbreaks.

Long non-coding RNA HOTTIP is correlated with progression and prognosis in tongue squamous cell carcinoma.

Long non-coding RNAs (lncRNAs) have been demonstrated to be a critical role in cancer progression and prognosis. However, little is known about the pathological role of lncRNA HOXA transcript at the distal tip (HOTTIP) in tongue squamous cell carcinoma (TSCC) patients. The aim of this study is to measure the expression of lncRNA HOTTIP in TSCC patients and to explore the clinical significance of the lncRNA HOTTIP. The expression of lncRNA HOTTIP was measured in 86 TSCC tissues and 14 adjacent non-malignant tissues using qRT-PCR. In our study, results indicated that lncRNA HOTTIP was highly expressed in TSCC compared with adjacent non-malignant tissues (P < 0.001) and positively correlated with T stage (T1-2 vs. T3-4, P = 0.023), clinical stage (I-II stages vs. III-IV stages, P = 0.018), and distant metastasis (absent vs. present, P = 0.031) in TSCC patients. Furthermore, we also found that lncRNA HOTTIP overexpression was an unfavorable prognostic factor in TSCC patients (P < 0.001), regardless of T stage, distant metastasis, and clinical stage. Finally, overexpression of lncRNA HOTTIP was supposed to be an independent poor prognostic factor for TSCC patients through multivariate analysis (P = 0.023). In conclusion, increased lncRNA HOTTIP expression may be serve as an unfavorable prognosis predictor for TSCC patients. Nevertheless, further investigation with a larger sample size is needed to support our results.

The association between the Survivin A9194G exon polymorphisms and papillary thyroid carcinoma risk in the Han Chinese population.

The dysregulation of apoptosis plays a key role in carcinogenesis. This study was designed to investigate the association of apoptosis-related gene survivin A9194G single-nucleotide polymorphisms (SNPs) with papillary thyroid carcinoma (PTC) susceptibility. A case-control study of 126 patients and 198 controls was performed to investigate the association between Survivin A9194G polymorphisms and PTC susceptibility by polymerase chain reaction (PCR) following DNA sequencing methods. Moreover, the distribution of genotype frequency and the association of genotype with clinicopathologic characteristics were analyzed. We found that the survivin A9194G genotype was at a decreased risk of PTC (P=0.003; odds ratio (OR)=0.56). Furthermore, compared to the PTCs of the AA and AG phenotypes, the GG genotype thyroid cancers were significantly more common in younger patients and in cases of lower pathologic stages. In conclusion, the survivin (A9194G) polymorphism was found to play a protective role in the susceptibility to PTC. Nevertheless, further investigation with a larger sample size is needed to support our results.

Antiproliferative effects of selective cyclooxygenase-2 inhibitor modulated by nimotuzumab in estrogen-dependent breast cancer cells.

Breast cancer is the most common malignancy in women, and many breast cancer patients fail conventional treatment strategies of chemotherapy, radiation, and antiestrogen therapy. Research into the molecular pathways and biomarkers involved in the development of breast cancer should yield information that will guide therapeutic decisions. Epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) are involved in the carcinogenesis of breast cancer and exist tight crosstalk with estrogen receptor (ER) pathway. Combination of EGFR and COX-2 inhibitors, therefore, could be an effective strategy for reducing cell growth in estrogen-dependent breast cancer. In order to verify the effects of EGFR and COX-2 inhibitors, breast cancer cells MCF-7 and SKBR-3 were characterized for receptors status and then treated with respective inhibitors (nimotuzumab and celecoxib) alone and in combination. Both cell lines were sensitive to celecoxib, but not to nimotuzumab. However, combination of two drugs demonstrated synergistic effects on cell killing. Moreover, association of two drugs resulted in SKBR-3 cells, a further G0/G1 phase arrest than one drug alone. Downregulation of p-EGFR, p-Akt, p-mTOR, and amplified in breast cancer 1 (AIB1) were observed in both cell lines, and upregulation of E-cadherin was only found in MCF-7, after treatment with single agent or in combination. These studies suggest that nimotuzumab and celecoxib exert synergistic antiproliferation effects in breast cancer, which partly correlates with ER status. Due to Akt/mTOR, EMT and AIB1 pathways participate in this process, therefore, E-cadherin and AIB1 may be considered as possible biomarkers to predict response in ER-positive breast cancer cells treated with EGFR and COX-2 inhibitors.

Role of Caspase 8, Caspase 9 and Bcl-2 polymorphisms in papillary thyroid carcinoma risk in Han Chinese population.

Dysregulation of apoptosis plays a key role in carcinogenesis. This study was designed to investigate the association of apoptosis-related gene Caspase 8, Caspase 9 and Bcl-2 polymorphisms with papillary thyroid carcinoma (PTC) susceptibility. We undertook a case-control study of 118 patients and 213 controls to investigate the association between Caspase 8 (-652 6 N ins/del), Caspase 9 (-1263 A>G) and Bcl-2 (-938 C>A) polymorphisms and PTC susceptibility by polymerase chain reaction restriction-fragment length polymorphism and DNA sequencing methods. We further analyzed the distribution of genotype frequency, as well as the association of genotype with clinicopathological characteristics. Overall, no statistically significant association was observed in Caspase 8 (-652 6 N ins/del). Nevertheless, Caspase 9 -1263 GG genotype was at increased risk of PTC (P=0.045; odds ratio (OR)=1.12). Furthermore, GG genotype thyroid cancers were significantly more common in older patients than AA or AG genotypes PTC and in cases of advanced pathological stages. However, Bcl-2 -938 AA genotype demonstrated a protective effect in PTCs (P=0.004; OR=0.35). Polymorphism in Caspase 9 (-1263 A>G) was observed to be associated with susceptibility of PTC. However, Bcl-2 (-938 C>A) polymorphism indicated to play a protective role in susceptibility to PTC. Nevertheless, further investigation with a larger sample size is needed to support our results.

Association between E-cadherin (CDH1) polymorphisms and papillary thyroid carcinoma risk in Han Chinese population.

The aim of this study is to investigate the associations between E-cadherin gene (CDH1) polymorphisms and papillary thyroid carcinoma (PTC) risk predisposition. We undertook a case-control study to analyze three CDH1 polymorphisms (+54T>C, -160C>A, and -347G→GA) in an Han Chinese population, by extraction of genomic DNA from the peripheral blood of 98 patients with PTC and 176 control participants, and performed CDH1 genotyping using DNA sequencing. The obtained results indicated that overall, no statistically significant association was observed in +54T>C. Nevertheless, -347G→GA genotype was at increased risk of PTC (P = 0.001; odds ratio (OR) = 2.12, CI 95%:1.24-3.34). Furthermore, -347GA/GA genotype thyroid cancers were more significantly common in patients with tumor size of ≥20 mm than G or G/GA genotypes PTC and in cases of advanced T stage. However, -160C>A genotype demonstrated a protective effect in PTCs (P = 0.006; OR = 0.59, CI 95%: 0.42-0.87). These findings led us to conclude that polymorphism in -347G→GA was observed to be associated with susceptibility of PTC. However, -160C>A polymorphism indicated to play a protective role in susceptibility to PTC. Nevertheless, further investigation with a larger sample size is needed to support our results.

[In vitro activation of bone marrow natural killer T cells of aplastic anemia patients].

OBJECTIVE: To investigate the quantitative and qualitative changes of TCRVα24(+)Vß11(+) natural killer T (NKT) cells from bone marrow (BM) of aplastic anemia (AA) after in vitro stimulation of α-galactosylceramide (α-Galcer). METHODS: NKT cells in the bone marrow mononuclear cells (BMMNCs) from either AA patients or healthy controls were enumerated with flow cytometry. BMMNCs were cultured in RPMI1640 medium supplemented with either α-Galcer and rhIL-2 or α-Galcer, rhIL-2 and rhG-CSF. The proliferative capacity of NKT cells was determined by NKT cell numbers before and after in vitro culture. Expression of intracellular IFNγ and IL-4 in activated NKT cells was analyzed with flow cytometry. RESULTS: In AA group, the percentage of NKT cells in BMMNCs was (0.19 ± 0.09)%. Addition of rhG-CSF into the α-Galcer/rhIL-2 culture medium resulted in significantly reduced expansion of NKT cells (67.45 ± 29.42-fold vs 79.91 ± 40.56 fold, P < 0.05). Meanwhile, addition of rhG-CSF reduced IFNγ positive NKT cells \[(37.45 ± 7.89)% vs (62.31 ± 14.67)%, P < 0.01\] and increased IL-4 positive NKT cells \[(55.11 ± 12.13)% vs (27.03 ± 9.88)%, P < 0.01\]. In healthy control group, the percentage of NKT cells in BMMNCs was (0.25 ± 0.12)%. Addition of rhG-CSF into the α-Galcer/rhIL-2 culture medium also significantly reduced expansion of NKT cells (97.91 ± 53.22-fold vs 119.58 ± 60.49-fold, P < 0.05), reduced IFNγ positive NKT cells \[(28.65 ± 10.63)% vs (50.87 ± 12.66)%, P < 0.01\], and increased IL-4 positive NKT cells \[(66.53 ± 14.96)% vs (31.11 ± 10.07)%, P < 0.01\]. CONCLUSION: Compared to those from healthy controls, BMMNCs from AA patiants have a reduced fraction of NKT cells, which possesses a decreased potential to expand in vitro in response to α-Galcer stimulation, and produce more IFNγ(+) NKT1 cells. rhG-CSF, in combination with α-Galcer, confers polarization of NKT cells towards IL-4(+) NKT2 subpopulation.

[The relevance of tumor necrosis factor-alpha gene-863C/A polymorphism with thyroid-associated ophthalmopathy].

OBJECTIVE: To investigate the relevance of tumor necrosis factor-alpha (TNF-alpha) gene -863C/A polymorphism with thyroid-associated ophthalmopathy (TAO). METHODS: TNF-alpha gene polymorphism at position -863 was determined by PCR-RFLP in 76 normal people, 54 patients with TAO and 60 patients with autoimmune thyroid disease (AITD) who had no ophthalmopathy. All the subjects were collected from July 2002 to December 2003 in out-patient department of endocrinology in the hospital. The difference of genotype and the variation of allele frequencies were analyzed by Chi-square test. RESULTS: (1) Frequencies distribution of CA + AA genotype in TAO, non-ophthalmopathy and control groups were 46.3%, 30.0%, 25.0% respectively, and allele A were 27.8%, 15.0%, 12.5% for those three groups respectively. (2) Frequencies of allele A in TAO group were significantly higher than those in non-ophthalmopathy and control groups (P = 0.018 and 0.002 respectively). (3) When the three groups were stratified according to sex, frequencies of -863 CA + AA genotype and allele A in male TAO patients were significantly higher than those in control group (OR = 4.31, P = 0.019; OR = 4.81, P = 0.003) and non-ophthalmopathy group (OR = 4.87, P = 0.027; OR = 5.38, P = 0.008). No significant difference was found in female patients (P > 0.05). (4) Frequencies of CA + AA genotype and allele A in TAO patients with 5 + 6 grade were significantly higher than those in non-ophthalmopathy group (CA + AA genotype: OR = 20.68, P = 0.021; allele A: OR = 39.67, P < 0.001). CONCLUSION: Allele A of TNF-alpha gene at position -863 may be associated with TAO especially in male patients.

[A preliminary experience of treatment of severe aplastic anemia with murine anti-human CD3 T lymphocyte monoclonal antibody].

OBJECTIVE: To investigate the efficacy of the specific murine anti-human CD(3) T lymphocyte monoclonal antibody (CD(3) MoAb) for severe aplastic anemia (SAA). METHODS: 13 SAA patients were chosen with a medium age of 22 years, including 4 untreated patients and 9 nonresponding to previous management. They were treated with 5 mg of CD(3) MoAb per day for a total 10 days. RESULTS: The response rate was 11/13, including 2 cured and 2 remission cases during a follow up of 3 to 15 months. As compared with the pretreatment condition the proliferation of bone marrow in 8 cases become better; the leukocytes, granulocytes, hemoglobin and platelets of peripheral blood increased 1.59 x 10(9)/L, 0.72 x 10(9)/L, 40 g/L and 47 x 10(9)/L respectively (P < 0.01, respectively); the ratio of CD(4)/CD(8) of T cell subsets increased from 1.12 to 1.42 while the expression of HLA-DR antigen decreased from 29.2 to 15.2 (P < 0.01, respectively); TNF alpha, IFN gamma and IL-2 secreted by peripheral blood mononuclear cells (PBMNCs) decreased obviously from 267, 784 and 92 to 152, 570 and 51 U/ml on the average respectively (P < 0.01, respectively). The main side effects were fever in all the patients and shortness of breath in 4 cases, but none died during the therapy. CONCLUSIONS: In contrast to other kinds of common immune suppressor, CD(3) MoAb showed better response and probably higher efficacy and safety for SAA. It is necessary to have more cases and to follow up longer to estimate its long term effect and side effects.