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AIMS: Assess rates of true pseudoprogression in unconfirmed progressive disease (iUPD) in a pool of immunotherapy clinical trials for different cancers, analyze tumor characteristics that drive iUPD classification, and investigate potentials predictors of pseudoprogression. MATERIALS AND METHODS: Retrospective interpretation of prospectively acquired data. Patients from 18 immunotherapy clinical trials with two arms (RECIST 1.1, iRECIST), of 10 cancer types were selected. Pooled rate of true pseudoprogression among iUPD was estimated using a common effect meta-analysis. Target, Non-target, and new lesions as the trigger of confirmed-vs pseudo-progression were compared using Chi-Square and Fisher exact tests. Conditional logistic regression was used to investigate the association between age, sex, tumor burden at baseline, and number of follow ups and pseudoprogression. RESULTS: 60/287 (21%) patients (17 women) were classified as iUPD with at least one subsequent confirmatory timepoint. The overall pooled estimate of pseudoprogression was 15% (95%CI: 8%--26%). Nontarget lesions were significantly more frequent the cause of iUPD than change in Target lesions size (p< 0.001). Most observations of true pseudoprogression occurred in the first follow-up (77%), whereas confirmed progression occurred in later time points during the trial. Pseudoprogression was not significantly associated with age, sex, tumor burden at baseline, or number of timepoints. CONCLUSION: In a pool of immunotherapy trials, the rate of true pseudoprogression was 15%, most often in the first timepoint after baseline than later in treatment. iUPD categorization was mostly driven by changes in NT lesions rather than objective changes in measurements of target lesions.
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Objective: To investigate the expression of DARS2 and its clinical significance in colorectal cancer. Methods: In this study, bioinformatics tools, especially gene expression profile interactive analysis 2 (GEPIA2), were used to conduct an in-depth analysis of DARS2 expression in colorectal cancer tissues. Immunohistochemical staining was carried out in 108 colorectal cancer specimens and 30 normal colorectal tissues obtained from the First Affiliated Hospital of Nanchang University, Nanchang, China. Colorectal cancer cell lines (HCT116 and SW480) were transfected with small interfering RNA (siRNA) and DARS2 overexpression plasmid to examine the effects of DARS2 knockdown and overexpression on cell function. To assess the effects on cell function, CCK8 and transwell migration assays were used to assess proliferation and cell motility, respectively. Additionally, protein immunoblotting was employed to scrutinize the expression of proteins associated with the epithelial-mesenchymal transition of colorectal cancer cells. Results: DARS2 exhibited a pronounced upregulation in expression within colorectal cancer tissues compared to their normal epithelial counterparts. Furthermore, DARS2 expression was higher in colorectal cancer of stage â ¢-â £ than those of stage â -â ¡, exhibiting a significant correlation with N staging, M staging, and pathological staging (P<0.05). Kaplan-Meier analyses showed a decreased overall survival rate in colorectal cancer with DARS2 expression compared to those without DARS2 expression (P<0.05). In the siRNA transfection group, there was a significant reduction in cell proliferation and migration (P<0.01 and P<0.05, respectively). Conversely, the transfection of DARS2 overexpression plasmids substantially increased both cell proliferation and migration (P<0.05). Additionally, immunoblotting revealed that DARS2 knockdown led to an upregulation of E-cadherin expression and a downregulation of N-cadherin and vimentin expression. In contrast, DARS2 overexpression resulted in increased N-cadherin and vimentin expression, coupled with reduction in E-cadherin expression. Conclusions: There is a strong association between DARS2 expression and colorectal cancer progression. Silencing DARS2 inhibits cell proliferation and migration, exerting a discernible influence on the epithelial-mesenchymal transition process.
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Movimento Celular , Proliferação de Células , Neoplasias Colorretais , Transição Epitelial-Mesenquimal , RNA Interferente Pequeno , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/genética , RNA Interferente Pequeno/genética , Linhagem Celular Tumoral , Vimentina/metabolismo , Vimentina/genética , Caderinas/metabolismo , Caderinas/genética , Taxa de Sobrevida , Células HCT116 , Estadiamento de Neoplasias , Regulação para Cima , Regulação Neoplásica da Expressão Gênica , Relevância ClínicaRESUMO
Objective: To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice. Methods: Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate's parents used the JCard to measure jaundice at the neonate's cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson's correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis. Results: Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) µmol/L, with a range of 23.7-717.0 µmol/L. The JCard level was (221.4±77.0) µmol/L and the TcB level was (252.5±76.0) µmol/L. Both the JCard and TcB values showed good correlation (r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2 µmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0 µmol/L. The TcB value of 205.2 µmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 µmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 µmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 µmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 µmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 µmol/L (both P<0.05). Conclusions: JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 µmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 µmol/L).
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Bilirrubina , Hiperbilirrubinemia Neonatal , Icterícia Neonatal , Sensibilidade e Especificidade , Humanos , Recém-Nascido , Bilirrubina/sangue , Estudos Prospectivos , Feminino , Masculino , Hiperbilirrubinemia Neonatal/diagnóstico , Hiperbilirrubinemia Neonatal/sangue , Icterícia Neonatal/diagnóstico , Icterícia Neonatal/sangue , Curva ROC , Triagem Neonatal/métodos , Idade Gestacional , PaisRESUMO
Single crystals of GaKCu(PO4)2were synthesized using the hydrothermal method, and subsequent measurements of specific heat, magnetic susceptibility, and high-field magnetization were performed. A broad peak is observed in the magnetic susceptibility and specific heat curves, with the maximum values appearing at about 11.5 K and 5.29 K, respectively. The highest maximum peak value of susceptibility is observed when the magnetic field is applied along thec-axis, followed by thea-axis,b-axis, and polycrystalline samples. These indicate that the system exhibits one-dimensional magnetism and the magnetic easy axis is thecaxis. The magnetization at 2 K reveals the occurrence of a field-induced Bose-Einstein condensation (BEC) phase within the magnetic field range of approximately 8-12 T. High-field magnetization up to 40 T indicates that the compound reaches magnetization saturation as the field exceedsHs= 12 T. Through systematic measurements, a field-temperature (H-T) phase diagram was constructed, and dome-like phase boundaries were observed. The findings suggest that GaKCu(PO4)2is a spin gap system and a promising candidate for studying BEC of magnons due to its phase transition boundary occurring at low magnetic fields.
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Rabies is one of the important zoonotic infectious diseases, with a mortality rate of almost 100%. Rabies is a vaccine preventable disease, and proper rabies exposure prophylaxis can effectively prevent the occurrence of human rabies. In recent years, there has been significant progress in clinical research on the rabies exposure prophylaxis both domestically and internationally. World Health Organization (WHO) released the Rabies Vaccine: WHO Position Paper-April 2018. In order to guide medical institutions of all levels in rabies exposure prophylaxis, the National Administration of Disease Prevention and Control, in conjunction with the National Health Commission of the People's Republic of China, organized the Rabies Vaccine Working Group of the National Immunization Program Technical Working Group and invited experts to revise and issue the National Regulation for the Rabies Exposure Prophylaxis (2023 Edition). This article compares the National Regulation for the Rabies Exposure Prophylaxis (2009 Edition) and interprets the updated key points and supporting basis of the new version of the guidelines to guide clinical application and implementation.
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Vacina Antirrábica , Raiva , Humanos , Raiva/prevenção & controle , Raiva/epidemiologia , Vacina Antirrábica/uso terapêutico , Profilaxia Pós-Exposição , Organização Mundial da Saúde , ChinaRESUMO
Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7â¶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.
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Asparaginase , Linfoma Extranodal de Células T-NK , Masculino , Humanos , Pessoa de Meia-Idade , Asparaginase/uso terapêutico , Prognóstico , Estudos Retrospectivos , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Etoposídeo , Ciclofosfamida , Metotrexato/uso terapêutico , DNA/uso terapêutico , Resultado do TratamentoRESUMO
Rabies is a severe infectious disease caused by the rabies virus, which seriously damages the central nervous system. Once it occurs, the fatality rate is close to 100%. The World Health Organization's position paper on rabies vaccines recognizes that rabies immunoglobulin (RIG) should be used for post-exposure prophylaxis (PEP) in all category â ¢ exposure for the first time, as well as in category â ¡ exposure that suffer from severe immune deficiency, long-term massive use of immunosuppressants, and head and face exposure. The anti-rabies virus monoclonal antibody has high purity and specific activity, can be produced on a sustainable scale, and has no risk of blood source virus contamination. Preclinical pharmacodynamic studies and clinical trial results of the anti-rabies virus monoclonal antibody preparation have confirmed that the preparation has a broad-spectrum neutralization effect on the rabies virus. Additionally, its combined application with the vaccine has little impact on the active immunity of the vaccine. Therefore, the anti-rabies virus monoclonal antibody preparation shows great potential for clinical application in PEP.
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Vacina Antirrábica , Vírus da Raiva , Raiva , Humanos , Raiva/prevenção & controle , Imunossupressores , Anticorpos Monoclonais/uso terapêutico , Anticorpos AntiviraisRESUMO
Objective: To evaluate the application value of metagenomic next-generation sequencing (mNGS) in the diagnosis and treatment of pulmonary infection in immunocompromised patients. Methods: A total of 78 patients with immunocompromised pulmonary infection [55 males and 23 females, aged (50.3±16.9) years] and 61 patients with non-immunocompromised pulmonary infection [42 males and 19 females, aged (63.6±15.9) years] in the Intensive Care Unit of the First Medical Center of College of the Pulmonary & Critical Care Medicine, Chinese PLA General Hospital from November 2018 to May 2022 were retrospectively selected. Patients in both groups received bronchoalveolar lavage fluid (BALF) mNGS and conventional microbiological tests (CMTs) while clinically diagnosed with pulmonary infection. The diagnostic positive rate, pathogen detection rate and clinical coincidence rate of the two methods were compared. At the same time, the difference of adjustment rate of anti-infective treatment strategy based on the results of mNGS detection was compared between the two groups. Results: The positive rates of mNGS in patients with pulmonary infection were 94.9% (74/78) and 82.0% (50/61) in the immunocompromised group and the non-immunocompromised group, respectively. The positive rates of CMTs in patients with pulmonary infection were 64.1% (50/78) and 75.4% (46/61) in the immunocompromised group and the non-immunocompromised group, respectively. The positive rates of mNGS and CMTs in patients with pulmonary infection in immunocompromised group showed a statistically significant difference (P<0.001). The detection rates of mNGS in the immunocompromised group for pneumocystis jirovecii and cytomegalovirus were 41.0% (32/78) and 37.2% (29/78), respectively, and the detection rates of Klebsiella pneumoniae, chlamydia psittaci and Legionella pneumophila were 16.4% (10/61), 9.8% (6/61) and 8.2% (5/61) in the non-immunocompromised patients, respectively, which were higher than those of CMTs [1.3% (1/78), 7.7% (6/78), 4.9% (3/61), 0 and 0] (all P<0.05). In the immunocompromised group, the clinical coincidence rates of mNGS and CMTs and were 89.7% (70/78) and 43.6% (34/78), respectively, with a statistically significant difference (P<0.001). In the non-immunocompromised group, the clinical coincidence rates of mNGS and CMTs were 83.6% (51/61) and 62.3% (38/61), with a statistically significant difference (P=0.008). In the immunocompromised group, according to the results of the etiology of mNGS, the adjustment rate of anti-infection treatment strategy was 87.2% (68/78), while in the non-immunocompromised group, the adjustment rate of anti-infective treatment strategy was 60.7% (37/61), with a statistically significant difference (P<0.001). Conclusion: In patients with immunocompromised pulmonary infection, mNGS has more advantages than CMTs in diagnostic positive rate, diagnosis rate of mixed infection, pathogen detection rate and guidance of anti-infection treatment strategy adjustment, which is worthy of clinical promotion and application.
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Pneumocystis carinii , Pneumonia , Feminino , Masculino , Humanos , Estudos Retrospectivos , Sequenciamento de Nucleotídeos em Larga Escala , Hospitais Gerais , Sensibilidade e EspecificidadeRESUMO
We report the single-crystal growth of Mn2V2O7and the results of magnetic susceptibility, high-field magnetization up to 55 T and high-frequency electric spin resonance (ESR) measurements for its low-temperatureαphase. Two antiferromagnetic (AFM) ordering at 17.5 K and 3 K and obvious magnetic anisotropy are observed inα-Mn2V2O7upon cooling. In pulsed high magnetic fields, the compound reaches the saturation magnetic moment of â¼10.5µBfor each molecular formula at around 45 T after two undergoing AFM phase transitions atHc1≈ 16 T,Hc2≈ 34.5 T forH//[11-0] andHsf1= 2.5 T,Hsf2= 7 T forH//[001]. In these two directions, two and seven resonance modes are detected by ESR spectroscopy, respectively. Theω1andω2modes ofH//[11-0] can be well described by two-sublattice AFM resonance mode with two zero-field gaps at 94.51 GHz and 169.28 GHz, indicating a hard-axis feature. The seven modes forH//[001] are partially separated by the critical fields ofHsf1andHsf2, displaying the two signs of spin-flop transition. The fittings ofωc1andωc2modes yield zero-field gaps at 69.50 GHz and 84.73 GHz forH//[001], confirming the axis-type anisotropy. The saturated moment and gyromagnetic ratio indicate the Mn2+ion inα-Mn2V2O7is in a high spin state with orbital moment completely quenched. A quasi-one-dimensional magnetism with a zig-zag-chain spin configuration is suggested inα-Mn2V2O7, due to the special neighbor interactions caused by a distorted network structure with honeycomb layer.
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Clonidina , Hematúria , Criança , Humanos , Clonidina/farmacologia , Clonidina/uso terapêutico , ArgininaRESUMO
OBJECTIVE: Synthetic hydroxyapatite (HA) and its related materials have made great progress in basic research and clinical application in spinal repair and reconstruction. However, the effect of HA and its composites used in spinal fusion still remained controversial. This meta-analysis aimed at evaluating the efficacy and safety of HA compared with autologous bone. MATERIALS AND METHODS: A systematic search in PubMed, MEDLINE, China National Knowledge Internet, EMBASE, and the Cochrane Library was conducted for relevant studies from inception until May 2021. Studies investigating the application of HA and its related composites in spinal fusion were selected for analysis. RESULTS: The operation time of patients treated with artificial bone containing HA was less than that of patients with autologous bone (p = 0.02). The amount of operative blood loss in patients in the HA group was less than that in the autograft group (p = 0.007). Patients treated with autologous bone got a more significant advantage in fusion rate at 6 months (p = 0.009). Nevertheless, there was no significant difference in the fusion rate between patients in the two groups at 12 months or no less than 24 months postoperatively (p = 0.24; p = 0.87). Compared to the autograft group, the HA group significantly decreased postoperative adverse events (p = 0.03). Furthermore, there was no significant difference in the Oswestry Disability Index (p = 1.00) nor the Visual Analogue Scale score (p = 0.94) between the two groups. CONCLUSIONS: This meta-analysis suggests that the clinical application of HA and its related composite materials in spinal reconstruction is comparable to that of autologous bone, with satisfactory efficacy and safety.
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Durapatita , Fusão Vertebral , Transplante Ósseo , Durapatita/efeitos adversos , Humanos , Vértebras Lombares/cirurgia , Coluna Vertebral , Resultado do TratamentoRESUMO
Objective: To investigate the relationship between body mass index (BMI) and sexual development in Chinese children. Methods: A nationwide multicenter and population-based large cross-sectional study was conducted in 13 provinces, autonomous regions and municipalities of China from January 2017 to December 2018. Data on sex, age, height, weight were collected, BMI was calculated and sexual characteristics were analyzed. The subjects were divided into four groups based on age, including ages 3-<6 years, 6-<10 years, 10-<15 years and 15-<18 years. Multiple Logistic regression models were used for evaluating the associations of BMI with sexual development in children. Dichotomous Logistic regression was used to compare the differences in the distribution of early and non-early puberty among normal weight, overweight and obese groups. Curves were drawn to analyze the relationship between the percentage of early puberty and BMI distribution in girls and boys at different Tanner stages. Results: A total of 208 179 healthy children (96 471 girls and 111 708 boys) were enrolled in this study. The OR values of B2, B3 and B4+ in overweight girls were 1.72 (95%CI: 1.56-1.89), 3.19 (95%CI: 2.86-3.57), 7.14 (95%CI: 6.33-8.05) and in obese girls were 2.05 (95%CI: 1.88-2.24), 4.98 (95%CI: 4.49-5.53), 11.21 (95%CI: 9.98-12.59), respectively; while the OR values of G2, G3, G4+ in overweight boys were 1.27 (95%CI: 1.17-1.38), 1.52 (95%CI: 1.36-1.70), 1.88 (95%CI: 1.66-2.14) and in obese boys were 1.27 (95%CI: 1.17-1.37), 1.59 (95%CI: 1.43-1.78), and 1.93 (95%CI: 1.70-2.18) (compared with normal weight Tanner 1 group,all P<0.01). Analysis in different age groups found that OR values of obese girls at B2 stage and boys at G2 stage were 2.02 (95%CI: 1.06-3.86) and 2.32 (95%CI:1.05-5.12) in preschool children aged 3-<6 years, respectively (both P<0.05). And in the age group of 6-10 years, overweight girls had a 5.45-fold risk and obese girls had a 12.54-fold risk of B3 stage compared to girls with normal BMI. Compared with normal weight children, the risk of early puberty was 2.67 times higher in overweight girls, 3.63 times higher in obese girls, and 1.22 times higher in overweight boys, 1.35 times higher in obese boys (all P<0.01). Among the children at each Tanner stages, the percentage of early puberty increased with the increase of BMI, from 5.7% (80/1 397), 16.1% (48/299), 13.8% (27/195) to 25.7% (198/769), 65.1% (209/321), 65.4% (157/240) in girls aged 8-<9, 10-<11 and 11-<12 years, and 6.6% (34/513), 18.7% (51/273), 21.6% (57/264) to 13.3% (96/722), 46.4% (140/302), 47.5% (105/221) in boys aged 9-<10, 12-<13 and 13-<14 years, respectively. Conclusions: BMI is positively correlated with sexual development in both Chinese boys and girls, and the correlation is stronger in girls. Obesity is a risk factor for precocious puberty in preschool children aged 3-<6 years, and 6-<10 years of age is a high risk period for early development in obese girls.
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Sobrepeso , Puberdade Precoce , Adolescente , Índice de Massa Corporal , Criança , Pré-Escolar , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Puberdade , Desenvolvimento SexualRESUMO
Youth is the core force of social and economic development, once the occurrence of youth stroke will place a heavy burden on society and family. However, the prevention and control of stroke in China is mainly aimed at middle-aged and elderly patients, the part of young stroke is relatively easy to be ignored. This article focuses on the characteristics, research progress, prevention and control status of young stroke, pointing out the importance of centering on the prevention and treatment of young stroke. At the same time, it hopes that the industry can concentrate on the prevention and treatment of young stroke, making precise policies in the future, and developing secondary prevention guidelines for the causes or risk factors of young stroke, so as to improve comprehensive stroke prevention and control system. On this basis, the health level of the whole population will be improved, and the life expectancy of residents will be extended, thus promoting the realization of the strategic goal of "Healthy China 2030".
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Expectativa de Vida , Acidente Vascular Cerebral , Adolescente , Idoso , China/epidemiologia , Nível de Saúde , Humanos , Pessoa de Meia-Idade , Políticas , Acidente Vascular Cerebral/prevenção & controleRESUMO
Objective: To explore the risk factors and preventive strategies of pancreatitis after percutaneous transhepatic biliary drainage (PTBD) in patients with pancreatic cancer and obstructive jaundice. Methods: A total of 241 patients were retrospectively analyzed from May 2001 to October 2014 in Tianjin Medical University Cancer Institute and Hospital. The possibly correlated 9 factors were analyzed, including gender, age, hemoglobin level, total bilirubin level, degree of pancreatic duct dilatation, degree of pancreatic atrophy, degree of biliary stenosis, the pancreatic duct visualization, and drainage mode. Results: Univariate analysis suggested that pancreatic duct dilatation, pancreatic atrophy, visualized pancreatic duct and drainage mode were associated with the incidence of pancreatitis after PTBD (P<0.05). Logistic regression analysis showed that visualization of pancreatic duct (OR=6.33) was a risk factor for pancreatitis, while pancreatic duct dilatation (OR=0.14), pancreatic atrophy (OR=0.12) and external drainage (OR=0.11) were protective factors for pancreatitis. Conclusion: In pateints with pancreatic cancer and obstructive jaundice, pancreatic duct dilatation and pancreatic atrophy predict low risk of pancreatitis after PTBD,while intraoperative pancreatic duct visualization and internal or external drainage may increase the incidence of postoperative pancreatitis.
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Icterícia Obstrutiva , Neoplasias Pancreáticas , Pancreatite , Drenagem , Humanos , Icterícia Obstrutiva/etiologia , Neoplasias Pancreáticas/complicações , Estudos Retrospectivos , Fatores de RiscoRESUMO
Objective: To clarify the molecular basis of patients with Bartter syndrome type I and explore the therapeutic effect of trafficking-defective variations by chemical chaperone 4-Phenylbutyric acid(4-PBA). Methods: The clinical characteristics, laboratory findings and genetic data of 3 patients diagnosed with Bartter syndrome type I who were admitted to Department of Nephrology, Children's Hospital of Nanjing Medical University from 2017 to 2018 were retrospectively analyzed. Wild type and variant SLC12A1 gene constructs were transiently overexpressed in HEK293 cells. Western blotting was used to detect the expression levels of Na+-K+-2Cl-cotransporter(NKCC2) protein. Immunofluorescent staining was applied to investigate the subcellular localization of NKCC2 protein. In addition, the effect of the chemical chaperone 4-PBA on the expression and localization of the SLC12A1 gene variants was investigated. Unpaired t test was used for statistical analysis of 4-PBA treatment. Results: All the 3 patients (2 males and 1 female), aged 3.0, 4.0 and 1.2 years, respectively. All patients had antenatal onset with polyhydramnios and were born prematurely. After birth, all patients presented with hypochlorine alkalosis accompanied by hypokalemia and hyponatremia. Sequencing analysis revealed that the 3 patients were homozygotes or compound heterozygotes for variants in the SLC12A1 gene. In HEK293 cells, the surface expression of NKCC2 in 3 variants (p.L463S, p.L479V, p.507-510del) are all lower than in wild type (0.718±0.039, 0.287±0.081, 0.025±0.156 vs. 1.001±0.028, t=5.92, 8.35, 30.49, all P<0.01). Moreover, the total protein expression of p.L479V and p.507-510del group were all lower than that in wild type group (0.630±0.032, 0.043±0.003 vs. 1.000±0.111, t=3.21, 8.65, all P<0.05). 4-PBA treatment increased the mature protein expression level of the p.L463S and p. L479V group in 4-PBA treatment group are all higher than the untreated group (0.459±0.018 vs. 1.123±0.024, 0.053±0.012 vs. 1.256±0.037, t=2.75, 18.35, all P<0.05). Cytoplasmic retention of the L479V and 507-510del variants were observed by immunofluorescent staining. 4-PBA treatment could rescue a number of NKCC2 L479V variants to the membrane. Conclusions: The 3 SLC12A1 variants cause expression or subcellular localization defects of the protein. The findings that plasma membrane expression and activity can be rescued by 4PBA might help to develop novel therapeutic strategy for Bartter syndrome type â .
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Síndrome de Bartter , Síndrome de Bartter/genética , Pré-Escolar , Feminino , Células HEK293 , Homozigoto , Humanos , Lactente , Masculino , Gravidez , Estudos Retrospectivos , Membro 1 da Família 12 de Carreador de Soluto/genéticaRESUMO
Insulin-like growth factor 1 (IGF-1) is considered to be a crucial gene in the animal development of bone and body size. In this study, a unique synonymous mutation (c.258 A > G) of the IGF-1 gene was modified with an adenine base editor to observe the growth and developmental situation of mutant mice. Significant expression differences and molecular mechanisms among vectors with different alanine synonymous codons were explored. Although modification of a single synonymous codon rarely interferes with animal phenotypes, we observed that the expression and secretion of IGF-1 were different between 8-week-old homozygous (Ho) and wild-type (WT) mice. In addition, the IGF-1 with optimal codon combinations showed a higher expression content than other codon combination modes at both transcription and translation levels and performed proliferation promotion. The gene stability and translation initiation efficiency also changed significantly. Our findings illustrated that the synonymous mutation altered the IGF-1 gene expression in individual mice and suggested that the synonymous mutation affected the IGF-1 expression and biological function through the transcription and translation processes.
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Objective: To investigate the status of height and weight of 3-18-year-old children and adolescents in urban China, and to provide a basis for establishing puberty phase specific curves for age-specific height and age-specific weight. Methods: A cross-sectional survey of 218 185 children and adolescents aged 3-18 years in urban China was conducted by using the method of stratified random cluster sampling from January 2017 to December 2019. The sampling areas included 12 provinces municipalities in China and autonomous regions in total. Data were collected on weight, height, waist circumference, hip circumference and secondary sexual characteristics. The generalized additive model for location, scale, and shape (GAMLSS) was employed to establish percentile reference values and growth curves of height and weight for boys and girls aged 3-18 years. Wilcoxon rank sum test was applied to compare the P50 value of height and weight between children of each Tanner stage and children of the same age ignoring the different puberty phase. Results: The 3rd, 50th, and 97th percentile curves for height and weight for age were developed for boys and girls aged 3-18 years. The 3rd, 50th, and 97th percentile curves for age-specific height and age-specific weight for each puberty phase were developed for boys and girls. Compared with all children ignoring the different puberty phase, boys aged 9 and over and girls aged 7 and over who are at Tanner stage 1 showed shorter height and lighter weight than those of the same age group (all P<0.01), the difference ranges of height at P50 are -4.0 to -0.6 cm for boys, and -4.4 to 0.5 cm for girls; the difference ranges of weight are -4.8 to 0.4 kg for boys, and -4.0 to -0.3 kg for girls; children at Tanner stage 2 & 3 initially were taller and heavier than those of the same age group; and later grew shorter and lighter than those of the same age group, the two sets of curves cross over; boys aged 16 and under and girl aged under 14 who are at Tanner stage 4 were taller and heavier than those of the same age group (all P<0.01), the difference ranges of height at P50 are 0.2 to 10.0 cm for boys, and 0.2 to 9.4 cm for girls; the difference ranges of weight at P50 are 0.7 to 10.9 kg for boys, and 1.0 to 11.2 kg for girls, and the differences showed narrowing trend with age. Conclusion: The puberty phase specific growth curves of age-specific height and age-specific weight for boys and girls aged 3-18 years are established, it is useful for clinical work to evaluate physical development of children at different puberty phases.
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Estatura , Adolescente , Índice de Massa Corporal , Peso Corporal , Criança , Pré-Escolar , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Inquéritos e QuestionáriosRESUMO
Objective: Factors influencing the prognosis of hemophagocytic lymphohistiocytosis (HLH) in adults were analyzed based on multicentric data. Methods: Clinical data of 124 adult patients with HLH diagnosed in eight medical centers in the Huaihai Lymphoma Working Group from March 2014 to July 2020 were collected. The optimal truncation value of continuous variables was obtained based on the Maxstat algorithm, X-Tile software, and restricted cubic spline. Cox proportional risk regression model was used to construct the adult HLH risk prediction model, and the visualization of the model was realized through the histogram. The bootstrap resampling method was used to verify the model, C-index and calibration curve was used to verify the histogram, and the prediction accuracy was checked. Kaplan-Meier analysis was used to calculate the survival rate and draw the survival curve. Furthermore, the differences between groups were tested by log-rank. Results: The median age of the 124 patients was 55 (18-84) years, including 61 (49.19%) males. The most common etiology was infection. Serum ferritin increased in 110 cases (88.71%) , hepatosplenomegaly in 57 cases (45.97%) . Of the 124 patients, 77 (62.10%) died, and the median survival time of the patients was 7.07 months. Univariate results showed that the prognosis of adult HLH was influenced by sex, age, fibrinogen, serum creatinine, alanine aminotransferase, and albumin (P<0.05) . The results of multivariate analysis showed that gender, platelet, albumin, alanine aminotransferase, and treatment regimens were independent influencing factors for prognosis. Based on the above five risk factors, the prediction model of the histogram was established, and the C-index of the model was 0.739. Finally, the calibration chart showed good consistency between the observed and predicted values of HLH. Conclusion: The prognosis of the adult hemophagocytic syndrome is influenced by many factors. Gender, platelet, albumin, alanine aminotransferase, and treatment regimens are independent risk factors. Therefore, the established histogram provides a visual tool for clinicians to evaluate the prognosis of adult HLH.
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Linfo-Histiocitose Hemofagocítica , Linfoma , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
Objective: To establish a multilocus sequence typing (MLST) assay for Corynebacterium (C.) striatum, explore the population structure and evolution relationship of clinical isolates of C. striatum. Methods: Seven housekeeping genes (gyrA, gyrB, hsp65, sodA, secA1, rpoB, 16S rRNA) were amplified with PCR by using self-designed specific primers and sequenced. Then, the sequences were assembled with software SeqMan. The gene diversity and gene recombination characteristics were evaluated by using software DnaSP 5.10.01 and Splits tree 4.14.2. The phylogenetic tree and the minimum spanning tree were constructed based on the sequence types (ST) characteristics by using software MEGA 7.0.14 and BioNumerics, respectively. In addition, the genetic evolutionary relationship among STs were analyzed by using software eBURST 3.0. Results: The expected amplification products of seven sites selected in all the test strains were obtained. Splits tree showed that the clustering of all C. striatum strains was consistent, suggesting that gene recombination is the potential driving force for the evolution of C. striatum. All of the 344 C.striatum strains were divided into 72 STs by MLST and 85.7% of the strains formed clonal complexes. CC19 was the predominant clonal complex, whereas ST16 in the clonal complex was detected in the most strains. ST had a certain geographic clustering and a certain correlation with the isolation time. Conclusions: C. striatum showed high genetic diversity in China and CC19 was the predominant clonal complex. The MLST assay established in this study can be used for the typing of C. striatum, but further improvement is needed.
Assuntos
Corynebacterium , Variação Genética , Humanos , Tipagem de Sequências Multilocus , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNARESUMO
Objective: To analyze the trends of overweight and obesity prevalence in Chinese children, aged from 6 to 15 years old among 4 provinces and cities from 2009 to 2019. Methods: Reviewed the national multi-center epidemiological survey data of children from the National Key Technology R&D Program of China during the Eleventh Five-Year Plan (2009 to 2010) and the National Key Research and Development Program of China during the Thirteenth Five-Year Plan (2017 to 2019). The participants' data were selected from four provinces,municipalities and autonomous region,including Beijing, Tianjin (Northern region), Zhejiang (Eastern region), and Guangxi (Southern region). Totally 14 597 pairs of 6-15 year-old children were surveyed. According to the body mass index (BMI) and standard deviation score (SDS) of children among different genders, ages, and regions, t test or chi-square test was used to evaluate the changes in overweight and obesity over a 10-year span. Results: Totally 7 721 pairs of boys and 6 876 pairs of girls were collectted in this study, whose mean age was (10.7±2.5) years. In the past 10 years, the overall BMISDS were 0.39±1.24 and 0.36±1.31 and the overall obesity rate were 11.8% (n=1 773) anel 12.5% (n=1 813) of children in the 4 administrative regions did not have statistically significant differences (all P>0.05). However, the overall overweight rate rose from 17.1% (n=2 496) to 19.1% (n=2 781) (χ²=18.657, P<0.01), and the average annual growth rate was 0.20%. The BMISDS in the Eastern region increased from 0.10±1.07 to 0.19±1.22 (t=-4.095, P<0.01), and the overweight rate and obesity rate increased by 3.8% (n=202) and 3.1% (n=169) respectively (both P<0.01); the BMISDS in the Northern region and the obesity rate did not have statistically significant differences(all P>0.05), but the overweight rate rose from 20.5% (n=1 233) to 22.8% (n=1 365) significantly (χ²=7.431, P<0.01); BMISDS in the Southern region was significantly decreased from 0.30±1.19 to 0.09±1.25 (t=1.426, P<0.01), and the rate of obesity decreased from 9.8% (n=315) to7.9% (n=256) (χ²=6.46, P<0.05), the overweight rate was not stafistically significant (P=0.10), respectively. The obesity rate of boys had risen from 16.4% (n=1 265) to 18.2% (1 407) (χ²=8.997, P<0.01) in the past 10 years, and the overweight rate had risen from 18.0% (n=1 393) to 20.5% (n=1 579) (χ²=14.26, P<0.01). The overweight+obesity rate rose from 34.4% (n=2 658) to 38.7% (n=2 986) (χ²=29.859, P<0.01), and the weight problem in the age group of 8 to 11 years was particularly severe (all P<0.01). The obesity rate of girls dropped from 6.8% (n=468) to 5.9% (n=406) (χ²=4.546, P<0.05), the overweight rate rose from 16.0% (n=1 103) to 17.5% (n=1 202) (χ²=5.006, P<0.05), and the overall overweight+obesity rate rose from 22.8% (n=1 571) to 23.4% (n=1 608) (χ²=0.53, P>0.05). Conclusions: The growth rate of obesity among children in China had slowed down from 2009 to 2019, but the overweight rate was still on the rise. The overall base of overweight and obesity population continued to expand. The weight problem of peri-adolescent boys was particularly prominent. The current status of obesity epidemics in different regions, ages, and genders are significantly different and had their own characteristics. It is necessary to establish a personalized prevention and control strategy.