RESUMO
Objective: To explore the effect and molecular mechanism of circ_0000263 on HeLa cell activity, apoptosis, telomerase activity, and radiosensitivity. Methods: The Hela cells were divided into si-NC, si-circ, vector, circ_0000263, anti-NC, anti-miR-338-3p, miR-NC, miR-338-3p, si-circ+anti-NC, si-circ+ anti-miR-338-3p, si-circ+vector, si-circ+TERT, sh-NC, sh-circ groups. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expressions of circ_0000263 and miR-338-3p. Cell clone formation array was used to detect cell survival; cell counting kit-8 (CCK-8) to detect cell proliferation; flow cytometry to detect apoptosis; western blot method to detect the expressions of proliferating cell nuclear antigen (PCNA), Cleaved-casp3, telomerase reverse transcriptase (TERT) proteins; double luciferase assay to detect the targeting relationships of circ_0000263 and miR-338-3p, miR-338-3p and TERT; telomere repeat amplification enzyme linked immunosorbent assay (TRAR-ELISA) to detect telomerase activity. Results: Circ_0000263 was highly expressed in Hela cells, miR-338-3p was low expressed, and TERT was highly expressed; circ_0000263 was also highly expressed in Hela cells treated with radiation (Pï¼0.05). Knockdown of circ_0000263 inhibited the clone formation and cell proliferation ability of HeLa cells, and enhanced the radiosensitivity and apoptosis of HeLa cells. In contrast, knockdown of circ_0000263 decreased PCNA protein expression level and enhanced Cleaved-casp3 protein expression level in HeLa cells (Pï¼0.05). The apoptosis rate in the si-circ group was (13.19±1.12)%, which was higher than (6.80±0.62)% of si-NC group (Pï¼0.05). The apoptosis rate in the si-circ+4 Gy group was (24.82±1.57)%, which was higher than (17.00±0.96)% of si-NC+4 Gy group (Pï¼0.05). Circ_0000263 targeted regulated miR-338-3p, and miR-338-3p targeted regulated TERT. MiR-338-3p was lowly expressed in HeLa cells, and knockdown of circ_0000263 elevated miR-338-3p expression level in HeLa cells. Circ_0000263 regulated TERT expression and inhibited telomerase activity through miR-338-3p. MiR-338-3p/TERT can restore the effect of circ_0000263 on the radiosensitivity of Hela cells. The apoptosis rate in the si-circ+anti-NC group was (27.37±0.89)%, which was higher than (18.22±1.18)% of the si-circ+anti-miR-338-3p group (Pï¼0.05). The apoptosis rate in the si-circ+vector group was (27.55±0.48)%, which was higher than (20.10±0.68)% of si-circ+TERT group (Pï¼0.05). After 72 hours of radiation by 4 Gy, the cell survival fraction of si-circ+anti-NC group was 0.41±0.02, which was lower than 0.66±0.03 of the si-circ+anti-miR-338-3p group (Pï¼0.05); the cell survival fraction of si-circ+vector group was 0.42±0.05, which was lower than 0.70±0.03 of si-circ+TERT group (Pï¼0.05). Conclusion: Inhibiting the expression of circ_0000263 supresses the proliferation of Hela cells by regulating miR-338-3p/TERT, promotes apoptosis, inhibits telomerase activity, increases the radiosensitivity of cancer cells, and provides a theoretical basis for improving the radiosensitivity of Hela cells.
Assuntos
Apoptose , Proliferação de Células , MicroRNAs , Tolerância a Radiação , Telomerase , Humanos , Células HeLa , MicroRNAs/metabolismo , MicroRNAs/genética , Telomerase/genética , Telomerase/metabolismo , Apoptose/efeitos da radiação , RNA Circular/genética , RNA Circular/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Antígeno Nuclear de Célula em Proliferação/genéticaRESUMO
Objective: To establish and validate a prediction model for early-stage epithelial ovarian cancer based on least absolute shrinkage and selection operator (LASSO) regression. Methods: A total of 509 cases ovarian mass patients who underwent surgical treatment in Tianjin Medical General Hospital from January 2018 to March 2023 were retrospectively analyzed. The patients were randomly divided into modeling group [n=356, M(Q1,Q3) for age were 43 (31, 61) years] and internal validation group [n=153, age 42 (31, 60) years] by 7â¶3 ratio. In addition, 86 patients [age 44 (33, 61) years] who underwent surgical treatment for ovarian mass in Tianjin Medical University General Hospital from April to November 2023 were collected as external validation group. The variables were screened by LASSO regression. The nomogram model was established and plotted by multivariate logistic regression. Internal and external validation were then conducted. The model performance and clinical applicability were evaluated using receiver operating characteristic (ROC) curve, calibration curve and decision curve. Results: Five variables including age (OR=1.040,95%CI:1.000-1.050,P=0.002), carbohydrate antigen 125 (CA125) (OR=1.001, 95%CI: 1.000-1.010, P=0.017), human epididymis protein 4 (HE4) (OR=1.020, 95%CI: 1.000-1.030, P=0.002), carbohydrate antigen 199 (CA199) (OR=1.001, 95%CI:1.000-1.020, P=0.023) and lactate dehydrogenase (LDH) (OR=1.020, 95%CI: 1.010-1.022, P=0.001) were screened as risk factors for early-stage epithelial ovarian cancer. The nomogram model was constructed based on these above five risk factors to predict early-stage epithelial ovarian cancer. ROC curves showed the area under curve (AUC) were 0.915(95%CI:0.910-0.932)for modeling group, 0.891(95%CI:0.874-0.905) for internal validation group, and 0.924(95%CI:0.907-0.942) for external verification. The calibration curves and clinical decision curves showed the model exhibited good consistency and clinical practicability. Conclusions: The nomogram model built includes age, CA125, HE4, CA199, and LDH. It can effectively predict early-stage epithelial ovarian cancer and has strong clinical practicability.
Assuntos
Carcinoma Epitelial do Ovário , Nomogramas , Neoplasias Ovarianas , Humanos , Feminino , Pessoa de Meia-Idade , Carcinoma Epitelial do Ovário/patologia , Neoplasias Ovarianas/patologia , Adulto , Estudos Retrospectivos , Antígeno Ca-125/sangue , Curva ROC , Estadiamento de Neoplasias , Modelos Logísticos , Fatores de Risco , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/análiseRESUMO
Apart from individual genetic background, unhealthy lifestyle and diet, etc., nutrition also plays an important role in the occurrence and progression of gastrointestinal tumors. Although some patients with gastrointestinal tumors can be satisfied with the traditional nutritional support, it is apparently inadequate for the systemic management of all patients. Precision nutrition support, also known as personalized nutrition support, refers to safe and efficient individualized nutrition intervention based on the investigation of individual genetic background, life characteristics, metabolic indicators, intestinal microbial characteristics, and physiological status factors through big data analysis for the prevention and treatment of chronic diseases. This review focuses on the relationship between nutrition and gastrointestinal tumors and discusses the progress of precision nutrition support therapy in the gastrointestinal tumors. Based on this, we hope to achieve effective personalized intervention protocols, and improve the clinical outcome and the overall oncology care of gastrointestinal tumors.
Assuntos
Neoplasias Gastrointestinais , Apoio Nutricional , Humanos , Estado Nutricional , Doença CrônicaRESUMO
Objective: To analyze the efficacy of second-line regimens and prognostic factors in patients with first-relapsed multiple myeloma (MM) treated with bortezomib, cyclophosphamide, and dexamethasone (BCD). Methods: A retrospective cohort study. Clinical data were collected in first-relapsed MM patients after BCD treatment from three tertiary hospitals in north China from July 2009 to October 2022. Patients were classified according to the second-line regimen into the immunotherapy group, single novel agent group [either proteasome inhibitor (PI) or immunomodulatory drug (IMiD)], combination treatment group (both PI+IMiD), and traditional treatment group. Responses to second-line regimens and survival data were analyzed. The Kaplan-Meier method was used for survival analysis and the Cox proportional risk model was used for univariate and multivariate analyses. Results: A total of 217 patients were enrolled including 8.8% (19/217) in the immunotherapy group, 48.4% (105/217) in the PI/IMiD group, 29.9% (65/217) in the PI+IMiD group, and 12.9% (28/217) in the traditional treatment group. The median age was 62 years (range 31-83 years) and 56.2% (122/217) were males. The overall response rates (ORRs) in the four groups were 94.7% (18/19) vs. 56.2% (59/105) vs. 73.8% (48/65) vs. 32.1% (9/28) (χ2=24.55; P<0.001), respectively. The progression-free survival (PFS) of the second-line regimens (2ndPFS) was 17.7 vs. 9.0 vs. 9.2 vs. 4.6 months (χ2=22.74; P<0.001), respectively, among which patients in the PI/IMiD and PI+IMiD groups had comparable 2ndPFS (χ2=1.76; P=0.923). Patients with high-risk cytogenetic abnormalities (HRCAs) achieved the longest 2ndPFS of 22.0 months in the immunotherapy group (χ2=15.03; P=0.002). Multivariate analysis suggested that immunotherapy (HR=0.11, 95%CI 0.05-0.27), achievement of efficacy of partial response or better (HR=0.47, 95%CI 0.34-0.66), and non-aggressive relapse (HR=0.25, 95%CI 0.17-0.37) were independent prognostic factors of 2ndPFS. Conclusion: In this real-world study, immunotherapy was associated with a more favorable efficacy and PFS for first-relapsed MM patients after BCD treatment, with similar outcomes in patients with HRCAs.
Assuntos
Mieloma Múltiplo , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Mieloma Múltiplo/tratamento farmacológico , Bortezomib/uso terapêutico , Prognóstico , Estudos Retrospectivos , Recidiva Local de Neoplasia/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Dexametasona/uso terapêuticoRESUMO
Objective: Polyethylene glycol-modified gold nanostar particles (GNS-PEG) were constructed to investigate whether the degradation of extracellular matrix in triple-negative breast cancer could improve the tumor delivery of GNS-PEG and enhance the efficacy of photothermal therapy. Methods: GNS-PEG were constructed and characterized for physicochemical properties as well as photothermal properties. At the cellular level, the cytotoxicity of halofuginone (HF) and the effect of photothermal therapy were detected. Mouse model of triple negative breast cancer was established by subcutaneous inoculation of 4T1 cells in BALB/c nude mice. Five injections of HF were given via tail vein (HF group), and tumor sections were stained with Masson stain and immunohistochemical staining for transforming growth factor ß1 (TGFß1), α-smooth muscle actin (α-SMA) and CD31 to observe the effect of tumor stromal degradation. Five injections of HF via tail vein followed by GNS-PEG (HF+ GNS-PEG group) were applied to determine the content of gold in tumor tissues by inductively coupled plasma mass spectrometry. The tumor sites of the mice in the GNS-PEG and HF+ GNS-PEG groups were irradiated with NIR laser and the temperature changes were recorded with an IR camera. The tumour growth and weight changes of mice in each group were observed. Ki-67 immunohistochemical staining, TdT-mediated dUTP nick-end labeling and HE staining were performed on tumor tissue sections from each group to observe tumor proliferation, apoptosis and necrosis. HE staining was performed on heart, liver, spleen, lung and kidney tissues from each group to observe the morphological changes of cells. Results: GNS-PEG nanoparticles showed a multi-branched structure with a particle size of 73.5±1.4 nm. The absorption peak of GNS was 810 nm, which is in the near infrared region. The photothermal conversion rate of GNS-PEG was up to 79.3%, and the photothermal effect could be controlled by the laser energy. HF has a concentration-dependent cytotoxicity, with a cell survival rate being as low as (22.8±2.6)% at HF concentration of up to 1 000 nmol/L. The photothermal effect of GNS-PEG was significant in killing tumor cells, with a cell survival rate of (32.7±5.2)% at the concentration of 25 pmol/L. The collagen area fraction, TGFß1 integrated optical density and α-SMA integrated optical density in the tumor tissues of mice in the HF group were (2.1±0.2)%, 3.1±0.4 and 5.2±1.9, respectively, which were lower than those of the control group (all P<0.01), and the vessel diameter was 8.6±2.9 µm, which was higher than that of the control group (P<0.05). In the HF+ GNS-PEG group, the concentration of gold in tissues was 52.4 µg/g, higher than that in the GNS-PEG group (15.9 µg/g, P<0.05). After laser irradiation, the temperature of the tumor site in the HF+ GNS-PEG group was significantly higher than that in the GNS-PEG group. At the 4th minute, the temperatures of the tumor site in the GNS-PEG and HF+ GNS-PEG groups were 51.5 â and 57.7 â respectively; the tumor volume in the HF+ GNS-PEG group was effectively suppressed. The body weights of the mice in each group did not change significantly during the monitoring period. No significant abnormalities were observed in the main organs of the mice in the GNS-PEG group, but some hepatocytes in the HF and HF+ GNS-PEG groups showed edema and degeneration. Conclusion: The remodeling of extracellular matrix in triple-negative breast cancer could significantly improve the intratumoral delivery of GNS-PEG and thus achieve better photothermal therapy effect.
Assuntos
Hipertermia Induzida , Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Fototerapia/métodos , Terapia Fototérmica , Neoplasias de Mama Triplo Negativas/patologia , Hipertermia Induzida/métodos , Camundongos Nus , Ouro/química , Linhagem Celular TumoralRESUMO
Objective: To investigate the effect of blocking P21 activated kinase 1 (PAK1) activity on the proliferation, differentiation, and apoptosis of acute megakaryocytic leukemia (AMKL) cell lines (CHRF and CMK) . Methods: Cell counts were used to detect the effects of PAK1 inhibitors (IPA-3 and G5555) on AMKL cell proliferation inhibition and colony formation, and flow cytometry was used to detect its effects on AMKL cell cycle. The effect of PAK1 inhibitor on the expression of cyclin D1 and apoptosis-related protein Cleaved caspase 3 was detected using Western blot, while interference with the protein expression level of PAK1 in AMKL cells was assessed using lentivirus-mediated shRNA transfection technology. Flow cytometry was used to detect the effects of knockdown of PAK1 kinase activity on the ability of polyploid DNA formation and cell apoptosis in AMKL cells. Results: PAK1 inhibitors inhibited the proliferation of AMKL cells in a dose-dependent manner and reduced the ability of cell colony formation, and the difference was statistically significant when compared with the control group (P<0.05) . Moreover, they also reduced the percentage of AMKL cells in S phase, and Western blot detection showed that the expression levels of phosphorylated PAK1 and cyclin D1 decreased significantly. Finally, PAK1 inhibitors induced AMKL cell apoptosis by up-regulating Cleaved caspase 3 and showed different abilities to increase the content of polyploid DNA in megakaryocytes. Only high concentrations of IPA-3 and low doses of G5555 increased the number of polyploid megakaryocytes, while knockdown of PAK1 kinase activity promoted AMKL cell differentiation and increased the apoptosis rate. Conclusion: PAK1 inhibitor significantly arrests AMKL cell growth and promotes cell apoptosis. Knocking down the expression of PAK1 promotes the formation of polyploid DNA and induces AMKL cell apoptosis. The above findings indicate that inhibiting the activity of PAK1 may control AMKL effectively.
Assuntos
Leucemia Megacarioblástica Aguda , Quinases Ativadas por p21 , Apoptose , Caspase 3/metabolismo , Diferenciação Celular , Linhagem Celular Tumoral , Ciclina D1/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Leucemia Megacarioblástica Aguda/tratamento farmacológico , Leucemia Megacarioblástica Aguda/genética , Leucemia Megacarioblástica Aguda/metabolismo , Poliploidia , Quinases Ativadas por p21/antagonistas & inibidores , Quinases Ativadas por p21/genética , Quinases Ativadas por p21/metabolismoRESUMO
Objective: Functional near-infrared spectroscopy (fNIRS) was used to study the effect of aging on the neuroimaging characteristics of cerebral cortex in the process of speech perception. Method: Thirty-four adults with normal hearing were recruited from March 2021 to June 2021, including 17 in the young group, with 6 males, 11 females, age (32.1±5.0) years, age range 20-39 years. and 17 in the elderly group, with 6 males, 11 females, age (63.2±2.8) years, age range 60-70 years. The test material was the sentence table of the Mandarin Hearing Test in Noise (MHINT). The task state block experiment design was adopted, and the temporal lobe, Broca's area, Wernicke's area, motor cortex were used as regions of interest. Objective brain imaging technology (fNIRS) combined with subjective psychophysical testing method was used to analyze the activation area and degree of cerebral cortex related to auditory speech perception in the elderly and young people under different listening conditions (quiet, signal-to-noise ratio of 10 dB, 5 dB, 0 dB, -5 dB). SPSS 23 software was used for statistical analysis. Result: The activation area and degree of activation in the elderly group were lower than those in the young group under each task condition; The number of activation channels in the young group were significantly more than those in the old group, and the number of activation channels in the left hemisphere were more than those in the right hemisphere, but there was no difference in the number of activation channels. There were more channels affected by age in the left hemisphere than in the right hemisphere. The activation degree of the young group when the signal-to-noise ratio was 0 dB was significantly higher than that of other signal-to-noise ratio conditions (P<0.05), but there was no significant difference in the old group under the five conditions (P>0.05). The speech recognition score of the young group was higher than that of the old group under all conditions. When the quiet and signal-to-noise ratio was 10 dB, the correct score of the two groups was equal or close to 100%. With the gradual decrease of signal-to-noise ratio, there was a significant difference between the two groups when the signal-to-noise ratio was 5 dB. The speech recognition accuracy of the young group decreased significantly when the signal-to-noise ratio was 0 dB, while that of the old group decreased significantly when the signal-to-noise ratio was 5 dB. Conclusions: With the increase of age, the speech perception in noisy environment and the activity of cerebral cortex gradually deteriorate, and the speech dominance hemisphere (left hemisphere) will be significantly affected by aging. The overall activation area and activation degree of the elderly under different speech tasks are lower than those of the young.
Assuntos
Córtex Auditivo , Percepção da Fala , Estimulação Acústica/métodos , Adolescente , Adulto , Idoso , Córtex Auditivo/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espectroscopia de Luz Próxima ao Infravermelho , Percepção da Fala/fisiologia , Tecnologia , Adulto JovemRESUMO
Objectives: To investigate the prevalence and associated risk factors of tinnitus in Sichuan and Chongqing. Methods: We designed a tinnitus epidemiological questionnaire. The multi-stage stratified cluster random sampling methods was applied to obtain study subjects in six areas (Nanchong, Jiangjin, Fengdu, Yunyang, Suining and Ya'an), which were selected for epidemiological investigation. Home visit completion of epidemiological questionnaires was conducted. The trained investigators guided the respondents to fill in the tinnitus epidemiological questionnaires, and the epidemiological status of six areas on prevalence and risk factor was investigated. SPSS 22.0 software was used for statistical analysis. Results: Sampling population were 10 289, in which 9 273 were valid questionnaires. There were 4 281 males and 4 992 females, with an average age of 47.3 years, among which 34.83% (3 230/9 273) had tinnitus. 3.99% (370/9 273) were diagnosed with bothersome tinnitus. In a multivariable logistic regression mod, the following factors were associated with onsetting of tinnitus: sleep disorder [Odds Ratio(OR)=3.74] and noise exposure(OR=1.99). The risk of disease was lowest in the age of 30-40 years old, while the risk of disease was higher for people under 30 and over 40. In another multivariable logistic regression mode, the following factors were associated with having bothersome tinnitus: older people were more likely to suffer from tinnitus, sleep disorders (OR=4.68) and noise exposure (OR=1.56). Conclusions: The prevalence of tinnitus in Sichuan and Chongqing is about 34.83%, but most of the tinnitus is short-lived and has low loudness, which will not affect the patients. Only a small number of patients with tinnitus (3.99%) persist and affect their health and need treatment. The occurrence and exacerbation of tinnitus may be related to sleep, age, and noise exposure.
Assuntos
Zumbido , Adulto , Idoso , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Inquéritos e Questionários , Zumbido/epidemiologiaRESUMO
Objective: To analyze the characteristics of magnetic resonance imaging (MRI) and clinical etiology of ovarian infertility. Methods: The data of infertile women who underwent 3.0T MRI and magnetic resonance hysterosalpingography (MR-HSG) examination in the Affiliated Hospital of Nanjing University of Chinese Medicine from September 2017 to March 2020 were collected. The ovarian factors of infertility, as well as the abnormalities of bilateral fallopian tubes and uterus, were evaluated. Etiologies assessed by MRI were finally confirmed by hysteroscopy, laparoscopy, surgery, or a comprehensive clinical diagnosis. Results: Among 1 351 patients, 1 296 cases were eligible and included for further analysis. Evaluated by MRI and MR-HSG, 494(38.12%) cases had ovarian abnormalities, including 239(48.38%) cases of ovarian endometriosiss, 116(23.48%) cases of polycystic ovary syndrome (PCOS), 37(7.49%) cases of diminished ovarian reserve (DOR), 33(6.68%) cases of ovarian mass, 28(5.67%) cases of ovarian injury, and 41(8.30%) cases who had at least two kinds of ovarian diseases. Unilateral and bilateral ovarian abnormalities accounted for 52.02% (257/494) and 47.98%(237/494), respectively.In total, 453 of 494(91.7%) patients had only one kind of ovarian disease. Among the 494 patients, 103(20.85%) cases had abnormal ovary with normal uterus and fallopian tubes, and the other 391(79.15%) cases had abnormalities not only in ovary, but in fallopian tube and/or uterus. Conclusion: Infertility-related ovarian diseases have certain characteristics of MRI findings. 3.0T MRI is useful for comprehensive analysis of etiology in ovarian infertility. Combined with MR-HSG, it provides one-stop assessments of the pelvic factors in female infertility.
Assuntos
Infertilidade Feminina , Laparoscopia , Tubas Uterinas , Feminino , Humanos , Histerossalpingografia , Infertilidade Feminina/diagnóstico por imagem , Infertilidade Feminina/etiologia , Imageamento por Ressonância Magnética , Ovário/diagnóstico por imagemRESUMO
Objective: To summarize survival outcomes and prognostic factors in esophageal cancer (EC) patients treated with intensity-modulated radiotherapy (IMRT). Methods: A retrospective analysis was performed on the clinical and follow-up data of 1 637 patients with EC who were admitted to our hospital from January 2005 to December 2017 and met the inclusion criteria.The 5-year overall survival (OS), progression-free survival (PFS) and pattern of recurrence were analyzed. The Kaplan-Meier method was used to calculate survival rates, Log-rank test for univariate analysis and Cox method for multivariate analysis were used to detect survival difference. Results: 1-year, 3-year and 5-year OS and PFS of the entire group were 65.9% and 45.8%, 34.2% and 25.0%, 27.0% and 18.5%, respectively. Median OS and PFS were 19.4 months (95% CI=18.0-20.7 months) and 10.4 months (95% CI=9.3-11.3 months), respectively. Univariate analysis showed that the sex, KPS, tumor location, T stage, N stage, M stage, TNM stage, radiation dose and treatment modality were prognostic factors for 5-year OS and PFS of EC patients (P<0.05). Multivariate analysis indicated that the sex, KPS, TNM stage, radiation dose and treatment modality were independent prognostic factors for 5-year OS and PFS (P<0.05). Conclusions: EC patients treated with IMRT can obtain a promising survival. The sex, KPS, TNM stage, radiation dose and treatment modality are independent prognostic factors for prognosis.
Assuntos
Neoplasias Esofágicas , Radioterapia de Intensidade Modulada , Intervalo Livre de Doença , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/radioterapia , Humanos , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
Objective: To analyze the clinical characteristics and identify the causative gene of a case with congenital deafness. Methods: Detailed medical history and clinical examination of a 4-year-old male child with congenital deafness were conducted in the First Affiliated Hospital of Army Military Medical University in June 2016. He was diagnosed with sensorineural deafness. The venous blood of the child and his parents was drawn, and genomic DNA was extracted. Proband's DNA was performed with targeted capture of high-throughput sequencing, then Sanger sequencing was used to verify the suspected mutation and segregation in this pedigree. According to the genetic diagnosis of the proband's deafness, ophthalmic examinations were performed. Genetic prenatal diagnosis was performed when the proband's mother was pregnant again. Results: The patient was detected with p.Trp1466Ter/p.Tyr2042Ter compound heterozygous mutations of MYO7A gene with targeted high-throughput sequencing. The mutation of p.Trp1466Ter was a reported mutation, while p.Tyr2042Ter has not been reported. In addition to congenital deafness, retinitis pigmentosa was also found by ophthalmologic examination, and the patient was clinically diagnosed with Usher syndrome type 1. Amniocentesis and fetal DNA sequencing were performed on the repregnancy fetus of this family at 18 weeks of gestation. The heterozygous mutation of MYO7A gene p.Tyr2042Ter was found, and the other allele was the wild type, indicating that the child will not exhibit clinical manifestations of Usher syndrome type 1. Indeed, the second child passed neonatal hearing screening. Conclusions: The clinical features and genetic variants were delineated in this family with Usher syndrome type 1. The results of the current study have enriched the phenotype and genotype data of the disease and provided a basis for genetic counseling.
Assuntos
Síndromes de Usher , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Mutação , Miosina VIIa , Miosinas/genética , Linhagem , Gravidez , Diagnóstico Pré-Natal , Síndromes de Usher/genéticaRESUMO
Objective: To study the orthopedic treatment strategy for hemophilia complicated with musculoskeletal disorders as well as the peri-operative consumption of clotting factor. Methods: Total 338 orthopedic surgeries were performed for 261 patients, average age of 30.6 y (6-65 y) , with hemophilia between January 1996 and December 2019 at our institute. Two hundred and twenty-six patients presented with bleeds within the joints. Sixty-one patients presented with intramuscular bleeds, 45 presented with hemophilic pseudotumors, and six presented with miscellaneous complaints. Strategy of clotting factor replacement therapy was designed as per differences in the level of the operation procedure. Information regarding clinical manifestation, operative strategy, clotting factor consumption, and re-operation for complications was retrospectively recorded. The costs for multiple joint procedure and single joint procedure were studied. Results: We found that 270 of the 338 surgical procedures were major surgical procedures (79.9%) . There were 203 procedures of joint arthroplasty (60%) . Fourteen patients underwent reoperations for local recurrence (4.2%) . The average factor â § consumption before the surgery was 44.4 ± 8.1 IU/kg. The average Fâ § consumption within postoperative 2 weeks was 40 962 IU (647±177 IU/kg) . Seven type A hemophilic patients developed F â § inhibitor following the surgical procedure, with an average level of 13.7±11.2 BU/mL. Sixty-eight patients underwent multiple joint procedures under one anesthesia session (26%) . There was no significant difference in the factor consumption between the multiple joint procedure and single joint procedure. Conclusions: Surgical treatment was found to be effective for hemophilic arthropathy and lesion of the musculoskeletal apparatus, with the clotting factor replacement therapy. Multiple joint procedures under one anesthesia were more cost effective for patients with hemophilia, with less factor consumption than staged single joint procedure.
Assuntos
Hemofilia A , Doenças Musculoesqueléticas/complicações , Adulto , Artrite , Fatores de Coagulação Sanguínea , Hemofilia A/complicações , Humanos , Manipulação Ortopédica , Estudos RetrospectivosRESUMO
OBJECTIVE: To evaluate the clinical efficacy of short-term halo-pelvic traction (HPT) combined with surgery in the treatment of severe spinal deformities. METHODS: In the study, 24 patients diagnosed as severe spinal deformity accepted the treatment of one-stage short-term HPT and two-stage surgery from January 2015 to May 2018 in our orthopedics department. 24 cases (9 males and 15 females) were retrospectively reviewed. The average age of the cohort was (28.8±10.0) years (12ï¼48 years). The height, scoliosis angle, kyphosis angle, the height difference of shoulders, the height difference of crista iliaca, C7PL-CSVL and the perpendicular distance of S1 and the convex point of the patients were assessed at pre-traction, post-traction and post-surgery. The paired t test was used to analyze the difference among pre-traction, post-traction and post-surgery. RESULTS: The average traction time of 24 cases was (2.5±1.1) weeks (1ï¼5 weeks). The height of pre-traction and post-traction were (141.7±11.2) cm (116-167 cm) and (154.1±9.5) cm (136ï¼176 cm) respectively, showing significant difference (P < 0.05), and the increased height was (12.4±4.6) cm (4ï¼20 cm). The average scoliosis angle before traction was 104.9°±35.0°(25°ï¼158°), and it was significantly decreased in post-traction[64.8°±21.0°(19°ï¼92°)] and post-surgery[39.3°±17.0° (10°-70°)] (P < 0.05). The traction's coronal correction rate was 37.2%±10.9% (11.9%ï¼51.2%) and the total coronal correction rate was 61.9%±12.6%(26.9%-79.0%). The average kyphosis angle before traction was 106.9°±29.2°(54°ï¼163°), and it was significantly decreased in post-traction [63.1°±17.1°(32°ï¼92°)] and post-surgery [39.0°±16.8°(10°ï¼68°)](P < 0.05). The traction's sagittal correction rate was 40.0%±10.7%(16.7%ï¼55.5%) and the total sagittal correction rate was 64.3%±10.7%(49.0%ï¼87.5%). The average C7PL-CSVL before traction was (3.2±2.8) cm, and it was significantly decreased in post-traction [(2.5±2.5) cm] (P < 0.05). The perpendicular distance of S1 and the convex point before traction was (10.5±4.8) cm, and it was significantly decreased in post-traction[(8.4±3.5) cm] (P < 0.05). CONCLUSION: The one-stage short-term HPT combined with two-stage surgery is a safe and effective procedure for severe spinal deformities. The clinical efficacy is satisfactory and the complication is relatively less.
Assuntos
Cifose , Escoliose , Adolescente , Adulto , Feminino , Humanos , Cifose/cirurgia , Masculino , Estudos Retrospectivos , Escoliose/cirurgia , Tração , Resultado do Tratamento , Adulto JovemRESUMO
Objective: To establish a clustered management plan for pulmonary care of massive burn casualties (hereinafter referred to as the clustered management plan for pulmonary care), and to explore its application effects. Methods: (1) A clustered care intervention group was established, including the medical and nursing staff from the Department of Burns and Plastic Surgery, Department of Respiratory Medicine, and Department of Infection Control at the Fourth Medical Center of PLA General Hospital (hereinafter referred to as our hospital). Four major links, including pulmonary care assessment, chest and lung physical therapy, artificial airway management, and specialized infection control were sorted out according to the key points and difficulties in pulmonary care for massive burn casualties. Evidence-based nursing methods were employed to retrieve articles related to the above-mentioned four links from PubMed, Chinese Journal Full-Text Database, VIP Database and Wanfang Data using terms of " mass burn, respiratory management and airway management" and terms of ",," , and the clustered management plan for pulmonary care was established based on reading and discussion in combination with clinical practice and experience. (2) In this non-randomized controlled study, the clustered management plan for pulmonary care was applied to 73 massive burn patients (48 males and 25 females, aged 32 (25, 38) years) who were admitted to our hospital from January 2016 to December 2019 and met the inclusion criteria, and they were included into the clustered care group; 43 massive burn patients (25 males and 18 females, aged 35 (17, 45) years) who were admitted to our hospital from January 2013 to December 2015, received routine care and met the inclusion criteria were retrospectively included into routine care group. The pulmonary infection rate and mortality of patients in the two groups were recorded during the hospital stay. Data were statistically analyzed with chi-square test, Mann-Whitney U test, and independent sample t test. Results: (1) The clustered management plan for pulmonary care included a total of 12 specific measures covering four aspects of pulmonary care. The contents in pulmonary care assessment clearly stated to include the previous medical history, history of injury, respiratory status, hoarseness, pulmonary auscultation, etc. Chest and lung physical therapy included how to guide patients to effectively cough and do pursed lip breathing and abdominal breathing exercise, etc. Artificial airway management specified the preparation for the establishment of artificial airway at clinical reception, the observation index and frequency after tracheotomy, the method of humidification, the method and frequency of sputum suction, and the management of mechanical ventilation, etc. Specialized infection control required to strengthen hand hygiene and ventilator management. (2) The pulmonary infection rate and mortality of patients in the clustered care group were 2.74% (2/73) and 4.11% (3/73), respectively, significantly lower than 25.58% (11/43) and 18.60% (8/43) in routine care group (χ(2)=11.986, 5.043, P<0.05 or P<0.01). Conclusions: The clustered management plan for pulmonary care developed for massive burn casualties focuses on the major links and key points. The measures are systemic and comprehensive, simple but precise, and highly operable, covering the entire process of massive burn care, hereby reducing the pulmonary infection rate significantly and improving the success rate of treatment.
Assuntos
Queimaduras , Adolescente , Adulto , Manuseio das Vias Aéreas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Respiração Artificial , Estudos Retrospectivos , Traqueotomia , Adulto JovemRESUMO
Objective: To explore the possible pathogenesis of central paroxysmal positional vertigo (CPPV) by analyzing its clinical manifestations and characteristics. Methods: The clinical data of 3 patients with CPPV, including 1 male and 2 females, aged 36, 14 and 70 years old respectively, were collected from the Department of Otorhinolaryngology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences from June 2014 to June 2018. The clinical symptoms, nystagmus, other central ocular motor abnormalities, MRI, PET-CT, and laboratory findings were analyzed retrospectively. Results: All patients showed transient vertigo and nystagmus induced by head changes relative to gravity, but the characteristics of nystagmus did not conform to the typical characteristics of nystagmus in benign paroxysmal positional vertigo. None of patients response to repositioning maneuvers, and all patients presented with the signs of abnormal visual oculomotor system or other symptoms of central system. MRI, PET-CT and blood biochemical tests confirmed that the causes of CPPV in the patients were chronic hemorrhage, inflammation and paraneoplastic cerebellar degeneration. Although the etiology of the three cases is different, the lesion site is involved in the central velocity storage mechanism. Conclusion: The damage of central velocity storage mechanism may lead to the damage of feedback rotation signal correction pathway, and CPPV appears when the head position changes relative to gravity.
Assuntos
Nistagmo Patológico/diagnóstico , Nistagmo Patológico/etiologia , Vertigem/diagnóstico , Vertigem/etiologia , Adolescente , Adulto , Idoso , Encefalopatias/sangue , Encefalopatias/complicações , Encefalopatias/diagnóstico , Encefalopatias/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Nistagmo Patológico/sangue , Nistagmo Patológico/diagnóstico por imagem , Posicionamento do Paciente/efeitos adversos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos , Vertigem/sangue , Vertigem/diagnóstico por imagemRESUMO
Objective: To investigate the clinical characteristics and imaging manifestations of primary bone lymphoma (PBL) located in the jaw. Methods: Clinical data of 14 PBL patients admitted to The First Affiliated Hospital of Zhengzhou University from January 2014 to April 2019 were retrospectively analyzed, which including age, gender, location, chief complaint, laboratory test, imaging manifestations and so on. Results: Among the 14 PBL patients, 10 were male and 4 were female. Age range from 4 to 79 years, median age was 56 years old. There were 6 cases involved maxillary, 7 cases involved mandible and 1 case involved mandible and maxillary simultaneously. Twelve patients were admitted with local mass as the chief complaint, 3 had a history of toothache, 4 had loosen tooth and 2 had numbness of lips and cheeks. Two cases of oral mass with mucosal surface ulcer or abscess formation. One case complained of fever, night sweats and other systemic symptoms. The imaging findings showed 8 cases of osteolytic lesions, 1 case of sclerosis, 4 cases of mixed lesions and 1 case of cystic lesions. One case had periosteum reaction. In 12 cases, there was an obvious mass, which was characterized by the large soft-tissue mass and marrow changes were associated with surprisingly little cortical destruction. Conclusions: PBL is more common in middle aged male. The upper and lower jaw bones can be involved. Clinical and imaging manifestations lack characteristics, and common dental or periodontal symptoms such as toothache, tooth loosening, and paresthesia may occur. However, the imaging characteristics of large soft tissue masses with small degree of bone destruction can be used as an important basis for the differential diagnosis of osteomyelitis, squamous cell carcinoma, osteosarcoma and other diseases.
Assuntos
Neoplasias Ósseas , Linfoma/diagnóstico por imagem , Osteólise , Osteossarcoma , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Objective: To investigate the role of CD40/CD40L Pathway in the formation of silicosis fibrosis. Methods: Totally 64 inpatients were recruited and assigned to the silicosis group and the control group, 23 in each group. The alveolar lavage fluid was collected from all patients and isolated. The expression of CD40L protein was detected by Flow Cytometry. The level of IL-8ãThe IL-6ãINF-γ and MCP-1 was detected by ELISA. Two groups of BALF were co-cultured with HFL-1 cells, the expression of Collagen I and α-SMA was detected by Immunohistochemistry. Results: Compared with the control group, CD40L was highly expressed on T lymphocyte cells in silicosis group (P<0.05) , and the contents of IL-8ãThe IL-6ãINF-γand MCP-1 in Silicosis group were significantly higher than those in control group (P<0.05) . After co-culture of BALF and HFL-1 cells, the expression levels of Collagen I and α-SMA in Silicosis group were significantly higher than those in control group (P<0.05) . Conclusion: CD40-CD40L cross-linking system can promote the activation of T cells, release inflammatory factors, promote the synthesis of collagen I and α-SMA by fibroblasts, make the lung fibrous tissue proliferate, and lead to the formation of silicosis fibrosis.