RESUMO
To analyze the clinical efficacy and its influencing factors of ustekinumab (UST) in the treatment of patients with Crohn's disease (CD). From January 2021 to January 2024, CD patients who received UST treatment were retrospectively collected from the Second Affiliated Hospital of Wenzhou Medical University. Harvey-Bradshaw index were applied to assess clinical activity of CD patients, C-reactive protein was used to evaluate biochemical remission rate, and simplified Crohn's disease endoscopy score was used to evaluate the degree of intestinal inflammation. Logistic regression model was used to analyze the influencing factors for the clinical response rate at week 8, as well as the clinical remission rate and endoscopic remission rate at week 32. A total of 138 CD patients were included, including 93 males and 45 females. The age of diagnosis [M (Q1, Q3)] was 24 (19, 32) years old. At week 8, the clinical response rate and biochemical remission rate was 58.0% and 49.3%, respectively. Multivariate logistic regression model analysis showed that disease behavior (stenosis or penetration) was the risk factor of the clinical response rate at week 8 (OR=0.46, 95%CI: 0.23-0.95). The clinical remission rate and endoscopic remission rate at week 32 were 56.5% and 37.7%, respectively. Multivariate logistic regression model analysis showed that disease behavior (stenosis or penetration) was the risk factor of the clinical remission rates (OR=0.18, 95%CI: 0.08-0.42) and endoscopic remission rates (OR=0.25, 95%CI: 0.11-0.55) at week 32. Failure to achieve clinical response at week 8 was the risk factor of the clinical remission rates (OR=0.21, 95%CI: 0.09-0.52) and endoscopic remission rates (OR=0.19, 95%CI: 0.07-0.50) at week 32. UST treatment has good clinical efficacy in CD patients. CD patients with intestinal stenosis or penetrating lesions can decrease the efficacy of UST treatment. Failure to achieve clinical response at week 8 can decrease the efficacy at week 32.
Assuntos
Doença de Crohn , Indução de Remissão , Ustekinumab , Humanos , Doença de Crohn/tratamento farmacológico , Ustekinumab/uso terapêutico , Masculino , Feminino , Adulto , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem , Modelos Logísticos , Proteína C-Reativa/análiseRESUMO
Objective: To analyze the clinical efficacy and its influencing factors of vedolizumab (VDZ) in the treatment of ulcerative colitis (UC). Methods: The patients with moderately-to-severely active UC, who underwent VDZ treatment at the Second Affiliated Hospital of Wenzhou Medical University from November 2020 to November 2023 were retrospectively included. Based on whether 5-aminosalicylic acid (5-ASA) was used in combination with VDZ treatment, the patients were divided into combination group (received combination therapy of VDZ and 5-ASA) and monotherapy group (received monotherapy of VDZ). The clinical response rate and biological remission rate were analyzed at week 14. The clinical remission rate and mucosal healing rate were analyzed at week 38. The differences in efficacy of VDZ between the two groups were compared at week 14 and week 38, respectively. Multivariate logistic regression model was applied to analyze the influencing factors of clinical remission rate and mucosal healing rate in UC patients. Results: A total of 137 patients were included, including 74 males and 63 females, aged 18-76 (44±14) years old; Seventy-six cases in combination group and 61 cases in monotherapy group. At week 14 of VDZ treatment, the clinical response rate and biological remission rate were 79.6% (109/137) and 80.5% (33/41), respectively. At week 38, the clinical remission rate and mucosal healing rate were 78.8% (108/137) and 47.9% (57/119), respectively. There was no significant difference in clinical response rate and biological remission rate between combination group and monotherapy group at week 14 (both P>0.05). The clinical remission rate [85.5% (65/76) vs 70.5% (43/61), P=0.032] and mucosal healing rate [56.5% (39/69) vs 36.0% (18/50), P=0.027] were higher in combination group than those in monotherapy group at week 38. Multivariate logistic regression analysis showed that the combination therapy of VDZ and 5-ASA (OR=2.48, 95%CI: 1.02-6.03) and the clinical response at week 14 (OR=5.05, 95%CI: 1.98-12.85) were influencing factors of clinical remission rate of UC patients at week 38. Moreover, the baseline serum albumin (Alb) level ≥42.5 g/L was the influencing factor for the mucosal healing rate of UC patients at week 38 (OR=4.60, 95%CI: 2.06-10.24). Conclusions: VDZ is effective in treating UC patients. Both the combination of 5-ASA and the clinical response at week 14 are the influencing factors of the clinical remission rate at week 38. In addition, the baseline serum Alb level ≥42.5 g/L is the influencing factor of the mucosal healing rate at week 38.
Assuntos
Anticorpos Monoclonais Humanizados , Colite Ulcerativa , Colite Ulcerativa/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Estudos Retrospectivos , Mesalamina/uso terapêutico , Resultado do Tratamento , Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Albumina Sérica Humana/análiseAssuntos
Fundo Gástrico , Hiperplasia , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Fundo Gástrico/patologia , Fundo Gástrico/metabolismo , Transformação Celular Neoplásica , Mucina-5AC/metabolismo , Mucina-6/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/diagnóstico , Proteínas Proto-Oncogênicas p21(ras)/genética , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/metabolismo , Masculino , Mucosa Gástrica/patologia , Mutação , Pessoa de Meia-Idade , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , FemininoRESUMO
From June 16 to 30, 2023, men who have sex with men (MSM) who had visited Voluntary Counseling Testing (VCT) clinics in the Luohu, Futian and Nanshan districts of Shenzhen were included in this study to analyze their awareness of Mpox and the influencing factors. The mean age of the 262 MSM was (34.78±8.94) years, with the majority being unmarried (75.2%) and 79.0% confirmed to be infected with HIV. The awareness rates for five primary indicators, current status of Mpox, pathogen and source of infection, mode of transmission, population susceptibility, clinical manifestations and treatment were 68.4%, 84.7%, 60.3%, 87.8%, and 52.5%, respectively. The awareness rates for five secondary indicators, earliest transmission location (44.7%), main mode of transmission (54.2%), role of masks (46.9%), drug accessibility (46.6%), and self-limiting nature (38.2%) were all below 60%. The MSM population in Shenzhen perceived their likelihood of being infected (2.76±1.32) and discriminated against (3.87±1.26) as relatively low. The logistic analysis showed that the high school or vocational school education (OR:3.094, 95%CI:1.180-9.299), college or above education (OR:5.360, 95%CI:2.159-15.501), and higher scores on questions affecting learning or work (OR:2.196, 95%CI:1.409-3.599) were promoting factors for Mpox awareness, while higher scores on questions concerning the possibility of Mpox mortality (OR:0.591, 95%CI:0.432-0.791) was the hindering factor for Mpox awareness.
Assuntos
Infecções por HIV , Conhecimentos, Atitudes e Prática em Saúde , Homossexualidade Masculina , Masculino , Humanos , Adulto , China/epidemiologia , Infecções por HIV/epidemiologia , Inquéritos e Questionários , Pessoa de Meia-Idade , Adulto JovemRESUMO
The clinical characteristics, auxiliary examinations, skin and neuropathological features of 7 patients who had reticular cyanosis with peripheral neuropathy from the Department of Neurology, Huashan Hospital, Fudan University from January 2019 to December 2022 were retrospectively analyzed. Among the 7 patients, 5 were female and 2 were male.The age of onset of peripheral neuropathy was (39.8±21.3) years and the disease duration of peripheral neuropathy was (2.7±2.3) years. Three patients had acute onset and 4 patients had chronic onset. All the patients had limb numbness, with limb weakness in 6 patients and pain in 5 cases. Neuroelectrophysiological examination revealed 1 case of mononeuropathy, 2 cases of polyneuropathy, 2 cases of peripheral neuropathy, and 2 cases of sensory neuron neuropathy. Skin biopsy was performed in 3 patients, which presented hyperplasia and expansion of blood vessels in the dermis with lymphocyte infiltration. Nerve biopsy was performed in 3 patients, indicating axonal damage. Reticular cyanosis with peripheral neuropathy characterizes with numbness and weakness of limbs, most of which were accompanied by pain. Electrophysiological changes are in various forms. The pathological changes are dominated by the damage of axonal.
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Livedo Reticular , Doenças do Sistema Nervoso Periférico , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Cianose/complicações , Hipestesia/complicações , Livedo Reticular/complicações , Dor , Estudos RetrospectivosRESUMO
Wastewater-based epidemiology (WBE) is an emerging discipline, which has been applied to drug abuse tracking and infectious disease pathogen surveillance. During the COVID-19 epidemic, WBE has been applied to monitor the epidemic trend and SARS-CoV-2 variants etc. In order to detect hidden COVID-19 cases and prevent transmission in the community, wastewater surveillance system for monitoring SARS-CoV-2 RNA was developed in Shenzhen. The sewage sampling sites were set up in key places such as the port areas, urban villages and residential communities of Futian, Nanshan, Luohu and Yantian districts. From July 26 to November 30, 2022, a total of 369 sewage sampling sites were set up, covering 1.93 million people. Continuous sampling was carried out for 3 hours in the peak period of water use every day. Sewage virus enrichment and SARS-CoV-2 nucleic acid detection were carried out by polyethylene glycol precipitation method and RT-qPCR, and a positive water sample disposal process was molded. This article aims to introduce the case of source tracing of COVID-19 infected patients based on urban sewage in Shenzhen. The sewage monitoring of Honghu water treatment plant in Luohu District played an early warning role, and the source of infection was traced. In the disposal of positive water samples in Futian South Road, Futian District, the important experience of monitoring point layout was obtained. In the sewage monitoring of Nanshan village, Nanshan District, the existence of occult infection was revealed. Sharing the experience of tracing the source of COVID-19 patients to avoid the spread of COVID-19 in the community based on wastewater surveillance of SARS-CoV-2 RNA in Shenzhen, and summarizing the advantages and application prospects of sewage surveillance can provide new ideas for monitoring emerging or re-emerging pathogens that are known to exhibit gastrointestinal excretion in the future.
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COVID-19 , SARS-CoV-2 , Humanos , Vigilância Epidemiológica Baseada em Águas Residuárias , RNA Viral , Esgotos , Águas ResiduáriasRESUMO
Objective: To explore the epidemiological characteristic of a COVID-19 outbreak caused by 2019-nCoV Omicron variant BF.7 and other provinces imported in Shenzhen and analyze transmission chains and characteristics. Methods: Field epidemiological survey was conducted to identify the transmission chain, analyze the generation relationship among the cases. The 2019-nCoV nucleic acid positive samples were used for gene sequencing. Results: From 8 to 23 October, 2022, a total of 196 cases of COVID-19 were reported in Shenzhen, all the cases had epidemiological links. In the cases, 100 were men and 96 were women, with a median of age, M (Q1, Q3) was 33(25, 46) years. The outbreak was caused by traverlers initial cases infected with 2019-nCoV who returned to Shenzhen after traveling outside of Guangdong Province.There were four transmission chains, including the transmission in place of residence and neighbourhood, affecting 8 persons, transmission in social activity in the evening on 7 October, affecting 65 persons, transmission in work place on 8 October, affecting 48 persons, and transmission in a building near the work place, affecting 74 persons. The median of the incubation period of the infection, M (Q1, Q3) was 1.44 (1.11, 2.17) days. The incubation period of indoor exposure less than that of the outdoor exposure, M (Q1, Q3) was 1.38 (1.06, 1.84) and 1.95 (1.22, 2.99) days, respcetively (Wald χ2=10.27, P=0.001). With the increase of case generation, the number and probability of gene mutation increased. In the same transmission chain, the proportion of having 1-3 mutation sites was high in the cases in the first generation. Conclusions: The transmission chains were clear in this epidemic. The incubation period of Omicron variant BF.7 infection was shorter, the transmission speed was faster, and the gene mutation rate was higher. It is necessary to conduct prompt response and strict disease control when epidemic occurs.
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COVID-19 , Epidemias , Masculino , Humanos , Feminino , SARS-CoV-2 , COVID-19/epidemiologia , Surtos de Doenças , China/epidemiologiaRESUMO
Objective: To explore the effects of circTNPO1 on the proliferation and metastasis of osteosarcoma (OS) by sponging miR-338-3p. Methods: The expression of circTNPO1 on osteoblasts and multiple OS cell lines were detected by qRT-PCR. CircTNPO1 stable knockdown 143B cell line was constructed by sh-circTNPO1. Cell count kit 8 (CCK-8) assay and wound healing assay were applied to evaluate the proliferation and metastasis of this cell. Luciferase reporter assay was used to explore the binding between circTNPO1 and miR-338-3p. In xenograft tumor model, miR-338-3p inhibitor or its control was injected into the circTNPO1 knockdown tumors. The weight and size of the tumors were evaluated and Ki-67 expression was detected by immunohistochemistry. Results: The RNA expression of circTNPO1 in OS cell lines U2OS, HOS, MG63, 143B, ZOS and ZOSM were 2.73±0.27, 3.18±0.54, 4.33±0.52, 5.75±0.65, 4.50±0.49 and 3.96±0.35, respectively, higher than 1.00±0.09 in hFOB1.19 (P<0.001). CCK-8 assay revealed that after 48 h and 72 h, the absorbance of sh-circTNPO1 #1 was 0.81±0.05 and 1.09±0.06, while sh-circTNPO1 #2 143B cells was 0.84±0.04 and 1.2±0.04, which were sharply reduced compared with the control (1.00±0.06 and 1.49±0.06, P<0.001); after 48 h and 72 h, the absorbance of 143B cells transfected with circTNPO1 #1 and miR-338-3p (0.92±0.06 and 1.32±0.07) were higher than those of cells transfected with sh-circTNPO1 cells and miR NC (0.92±0.06 and 1.32±0.07, P<0.050). Wound healing assay demonstrated that the 24 hour-migration rates of sh-circTNPO1 #1 and sh-circTNPO1 #2 cells were (24.43±2.15)% and (39.70±4.20)% respectively, which were significantly lower than that of the control [(56.51±3.27)%, P<0.010]; the migration rates of sh-circTNPO1 #1+ miR NC and sh-circTNPO1 #1+ miR-338-3p inhibitor were (26.70±2.21)% and (46.10±5.71)%, with a significant difference (P<0.005). In xenograft tumor model, the weight and size of tumors in control, sh-circTNPO1 #1+ miR NC and sh-circTNPO1 #1+ miR-338-3p inhibitor mice were (458.80±158.10) mg, (262.50±82.09) mg, (395.40±137.60) mg and (593.00±228.40) mm(2,) (203.30±144.20) mm(2,) (488.60±208.60) mm(2,) respectively. Compared with control, sh-circTNPO1 tumors were significantly smaller (P<0.01). Injection with miR-338-3p inhibitor significantly reversed both the weight and size of tumors (P<0.05). Conclusion: CircTNPO1 promotes the proliferation and metastasis of OS by sponging miR-338-3p, which could be a new target for OS treatments.
Assuntos
Neoplasias Ósseas , MicroRNAs , Osteossarcoma , RNA Circular , Animais , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Antígeno Ki-67/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Osteossarcoma/secundário , RNA Circular/metabolismoRESUMO
Objective: To explore the effect of neoadjuvant immunotherapy on pulmonary function and the efficacy in patients with resectable non-small cell lung cancer. Methods: Data of 30 patients with non-small cell lung cancer (NSCLC) who received neoadjuvant immunotherapy before surgery in the Chest Hospital of Shanghai Jiaotong University from March 2018 to September 2021 were retrospectively collect. The efficacy and safety of neoadjuvant immunotherapy in the perioperative period and changes in pulmonary function of patients before and after neoadjuvant treatment were valuated. Results: The patients were all-male with age of (61±8)years old, The major pathological response (MPR) rate of patients receiving neoadjuvant immunotherapy was 43%(13 cases), the pathologic complete response (pCR) rate was 37% (11 cases), disease control rate (DCR) was 97% (29 cases), objective response rate (ORR) was 67% (20 cases). The forced expiratory volume in one second (FEV1) after treatment was (2.59±0.63) L, and the ratio of FEV1 to the predicted value (FEV1%pred) was 85.27%±15.86%, which were significantly higher than those before treatment [(2.48±0.59)L, 81.73%±15.94%, respectively] (P=0.013, 0.022, respectively). Forced vital capacity (FVC) after treatment was (3.59±0.77) L, which was also significantly higher than before [(3.47±0.76) L,P=0.036]; while there were no statistical difference in FEV1/FVC and FVC accounted for the proportion of predicted values (FVC%pred) between before and after treatment (P=0.084, 0.344, respectively). The ratio of carbon monoxide dispersion (DLCO) to the predicted value (DLCO%pred) decreased from 83.61%±13.10% to 78.69%±13.85% after treatment (P=0.023). There was no significant difference in the incidence of postoperative complications between the DLCO%pred decreased group and the non-decreased group (3/18 vs 0/6; P=0.546). Conclusions: Neoadjuvant immunotherapy can increase the rate of MPR and PCR, significantly increase FEV1 and FEV1%pred, but also lead to a decrease in DLCO%pred; neoadjuvant immunotherapy does not increase the incidence of postoperative complications.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Idoso , Carcinoma Pulmonar de Células não Pequenas/terapia , China , Volume Expiratório Forçado , Humanos , Imunoterapia , Pulmão , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estudos RetrospectivosRESUMO
Objective: To investigate the influencing factors of pneumoconiosis complicated with tuberculosis in order to provide the scientific evidence for formulating the preventive strategies. Methods: From July 2019 to January 2020, all occupational pneumoconiosis patients reported in Guangzhou from 1958 to 2018 were investigated retrospectively (n=1155) . The basic data (including gender, diagnosis time, diagnosis age, dust exposure duration, period, pneumoconiosis disease type, work type and industry) were obtained from pneumoconiosis case card and network report database. The data of pulmonary tuberculosis were collected from the occupational disease diagnosis files of Guangzhou Occupational Disease Prevention and Control Hospital, and were supplemented by telephone follow-up. The distribution of pneumoconiosis and tuberculosis in Guangzhou was analyzed. Binary logistic regression analysis model was used to analyze the influencing factors of pneumoconiosis complicated with pulmonary tuberculosis. Results: Among the 1155 new cases of pneumoconiosis, 357 cases were pneumoconiosis tuberculosis, and the complication rate of tuberculosis was 30.9%. Year of diagnosis, age of diagnosis, dust exposure duration, pneumoconiosis caused by mineral dust and construction industry were influencing factors for pneumoconiosis complicated with pulmonary tuberculosis (OR=0.948, 1.048, 0.972, 3.112, 2.815, P<0.05) . After the adjustment of gender, diagnosis year, diagnosis age, dust exposure duration and diagnosis period, the risk of pulmonary tuberculosis in rock drilling workers was 1.462 times higher than that in other types of work (P<0.05) . Conclusion: The complication rate of tuberculosis in patients with pneumoconiosis is relatively high. The main influencing factors are the year of diagnosis, age of diagnosis, dust exposure duration, the type of pneumoconiosis and the industry. The importance of occupational health examination and health education on prevention and treatment of tuberculosis should be emphasized among dust-exposed workers and pneumoconiosis patients. People with susceptibility factors are the top priority.
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Doenças Profissionais , Exposição Ocupacional , Pneumoconiose , Tuberculose Pulmonar , Poeira , Humanos , Pneumoconiose/complicações , Pneumoconiose/epidemiologia , Estudos Retrospectivos , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/epidemiologiaRESUMO
BACKGROUND: Accumulating evidence have shown that the intestinal microbiota plays an important role in prevention of host obesity and metabolism disorders. Recent studies also demonstrate that early life is the key time for the colonization of intestinal microbes in host. However, there are few studies focusing on possible association between intestinal microbiota in the early life and metabolism in adulthood. Therefore the present study was conducted to examine whether the short term antibiotic and/or probiotic exposure in early life could affect intestinal microbes and their possible long term effects on host metabolism. RESULTS: A high-fat diet resulted in glucose and lipid metabolism disorders with higher levels of visceral fat rate, insulin-resistance indices, and leptin. Exposure to ceftriaxone in early life aggravated the negative influences of a high-fat diet on mouse physiology. Orally fed TMC3115 protected mice, especially those who had received treatment throughout the whole study, from damage due to a high-fat diet, such as increases in levels of fasting blood glucose and serum levels of insulin, leptin, and IR indices. Exposure to ceftriaxone during the first 2 weeks of life was linked to dysbiosis of the fecal microbiota with a significant decrease in the species richness and diversity. However, the influence of orally fed ceftriaxone on the fecal microbiota was limited to 12 weeks after the termination of treatment. Of note, at week 12 there were still some differences in the composition of intestinal microbiota between mice provided with high fat diet and antibiotic exposure and those only fed a high fat diet. CONCLUSIONS: These results indicated that exposure to antibiotics, such as ceftriaxone, in early life may aggravate the negative influences of a high-fat diet on the physiology of the host animal. These results also suggest that the crosstalk between the host and their intestinal microbiota in early life may be more important than that in adulthood, even though the same intestinal microbes are present in adulthood.
Assuntos
Dieta Hiperlipídica , Disbiose/complicações , Microbioma Gastrointestinal , Doenças Metabólicas/etiologia , Doenças Metabólicas/microbiologia , Animais , Biodiversidade , Dieta Hiperlipídica/efeitos adversos , Disbiose/microbiologia , Camundongos , Obesidade/etiologia , Obesidade/microbiologiaRESUMO
OBJECTIVE: To examine the longitudinal associations of fetal growth with adverse child growth outcomes and to assess whether maternal metabolic factors modify the associations. DESIGN: Prospective cohort study. SETTING: Born in Guangzhou Cohort Study, China. POPULATION: A total of 4818 mother-child pairs. METHODS: Fetal growth was assessed according to estimated fetal weight (EFW) from 22 weeks of gestation until birth and the measurement of the birthweight. Fetal growth Z-scores were computed from random effects in the multilevel linear spline models to represent fetal size in early pregnancy (22 weeks of gestation) and growth in mid-pregnancy (22-27 weeks of gestation), early third trimester (28-36 weeks of gestation) and late third trimester (≥37 weeks of gestation). MAIN OUTCOME MEASURES: Z-scores for childhood stunting, low weight, overweight or obesity, length/height for age (LAZ/HAZ), weight for age (WAZ) and body mass index for age (BMIZ) at the age of 3 years. Adjusted associations were examined using multiple Poisson or linear regression models. RESULTS: Increased Z-scores of fetal size in early pregnancy and growth in mid-pregnancy and early third trimester were associated with a higher risk of childhood overweight or obesity (risk ratios 1.25-1.45). Fetal growth in each period was negatively associated with stunting and low weight, with the strongest associations observed for fetal size in early pregnancy and growth in mid-pregnancy. The results for continuous outcomes (LAZ/HAZ, WAZ and BMIZ) were similar. The associations of fetal growth with overweight or obesity in childhood were stronger among mothers who were underweight and who were overweight or obese than among mothers of normal weight. CONCLUSIONS: Accelerated fetal growth before 37 weeks of gestation is associated with children who are overweight or obese, whereas the critical period for stunting and low weight occurs before 28 weeks of gestation. TWEETABLE ABSTRACT: Fetal growth during different periods is differentially associated with childhood stunting, underweight and overweight or obesity.
Assuntos
Recém-Nascido Pequeno para a Idade Gestacional/crescimento & desenvolvimento , Obesidade Infantil/epidemiologia , Adulto , Pré-Escolar , China/epidemiologia , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Estudos Longitudinais , Masculino , Obesidade Infantil/etiologia , Gravidez , Estudos ProspectivosRESUMO
Alzheimer's disease (AD) is characterized by memory dysfunction, Aß plaques together with phosphorylated tau-associated neurofibrillary tangles. Unfortunately, the present existing drugs for AD only offer mild symptomatic cure and have more side effects. As such, developments of effective, nontoxic drugs are immediately required for AD therapy. Present study demonstrates a novel role of Chinese medicine prescription Yuan-Hu Zhi Tong (YZT) in treating AD, and it has substantiated the in vivo effectiveness of YZT in two different transgenic mice models of AD, namely P301S tau and 3XTg-AD mice. Oral treatment of YZT significantly ameliorates motor dysfunction as well as promotes the clearance of aggregated tau in P301S tau mice. YZT improves the cognitive function and reduces the insoluble tau aggregates in 3XTg-AD mice model. Furthermore, YZT decreases the insoluble AT8 positive neuron load in both P301S tau and 3XTg-AD mice. Using microarray and the "Connectivity Map" analysis, we determined the YZT-induced changes in expression of signaling molecules and revealed the potential mechanism of action of YZT. YZT might regulate ubiquitin proteasomal system for the degradation of tau aggregates. The research results show that YZT is a potential drug candidate for the therapy of tau pathogenesis and memory decline in AD.
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Objective: To evaluate the clinical characteristics and prognosis of gallbladder cancer (GBC) patients in China. Methods: This retrospective multicenter cohort study enrolled 3 528 consecutive GBC patients diagnosed between January 2010 to December 2017 in 15 hospitals from 10 provinces. There were 1 345 (38.12%) males and 2 183 (61.88%) females.The age of diagnosis was (63.7±10.8) years old (range: 26 to 99 years old) .There were 213 patients (6.04%) in stage 0 to â , whereas 1 059 (30.02%) in stage â ¡ to â ¢, 1 874 (53.12%) in stage â £, and 382 (10.83%) unavailable. Surgery was performed on 2 255 patients (63.92%) . Three hundred and thirty-six patients received chemotherapy or radiotherapy (9.52%; of which 172 were palliative); 1 101 (31.21%) received only supportive treatment.The patient source, treatment and surgery, pathology, concomitant gallstone, and prognosis were analyzed. Results: Among the 3 528 GBC patients, 959 (27.18%) were from East China, 603 (17.09%) from East-North China, 1 533 (43.45%) from Central China, and 433(12.27%) from West China. Among the 1 578 resectable tumor, 665 (42.14%) underwent radical surgery, 913 (57.86%) underwent surgery that failed to follow the guidelines.Eight hundred and ninety-one (56.46%) patients were diagnosed before surgery, 254 (16.10%) during surgery, and 381 (24.14%) after surgery (time point of diagnosis couldn't be determined in 52 patients) .Among the 1 578 patients with resectable tumor, 759 (48.10%) had concomitant gallstone.Among the 665 patients underwent radical surgery, 69 (10.4%) showed positive resection margin, 510 (76.7%) showed negative resection margin, and 86 (12.9%) unreported margin status.The 5-year overall survival rate (5yOS) for the 3 528-patient cohort was 23.0%.The 5yOS for patients with resectable tumor was 39.6%, for patients with stage â £B tumor without surgery was 5.4%, and for patients with stage â £B tumor underwent palliative surgery was 4.7%. Conclusions: More than half GBC patients in China are diagnosed in stage â £.Curative intent surgery is valuable in improving prognosis of resectable GBC.The treatment of GBC needs further standardization.Effective comprehensive treatment for GBC is in urgent need.
Assuntos
Neoplasias da Vesícula Biliar/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Neoplasias da Vesícula Biliar/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
Objective: To compare the efficacy between thymectomy plus prednisone and prednisone alone in patients with non-thymoma myasthenia gravis (MG). Methods: Thirty generalized MG patients without thymoma who underwent thymectomy were collected as the operation group, and thirty-nine patients without thymectomy who were treated with prednisone alone were matched as the control group. The start point was the enrollment time and the endpoint event was the "clinical remission" (including complete stabilization remission, drug remission, and poor performance). The survival curve was used to analyze the difference of endpoint event time between the two groups. Besides, a 12-month follow-up study was conducted to compare relevant clinical indicators between the two groups. Results: There was no significant difference in the occurrence time of endpoint events between the two groups (P=0.614). After 6-month follow-up, no significant differences were found in clinical remission rate, the dosage of pyridostigmine bromide and prednisone, the peak dosage of prednisone, the use of other immunosuppressive medications and the rate of hospitalization for exacerbation of disease between the two groups (all P>0.05). After 12-month follow-up, the dosage of prednisone and pyridostigmine in the operation group was significantly lower than that in the control group (5(0,10)mg/d vs 7.5(5,10)mg/d and 30(0,105)mg/d vs 90(15,180)mg/d; P=0.038, 0.032). Conclusion: In patients with mild to moderate non-thymoma generalized MG, thymectomy does not achieve faster remission, but it does reduce the long-term dosage of prednisone and bromopyrazine.
Assuntos
Miastenia Gravis , Timoma , Neoplasias do Timo , Seguimentos , Humanos , Timectomia , Resultado do TratamentoRESUMO
Objectives: This study aimed to evaluate the effect of the strategies on COVID-19 outbreak control in Shenzhen, and to clarify the feasibility of these strategies in metropolitans that have high population density and strong mobility. Methods: The epidemic feature of COVID-19 was described by different phases and was used to observe the effectiveness of intervention. Hierarchical spot map was drawn to clarify the distribution and transmission risk of infection sources at different time points. The Susceptible-Exposed-Infectious-Asymptomatic-Recovered model was established to estimate case numbers without intervention and compare with the actual number of cases to determine the effect of intervention. The positive rate of the nucleic acid test was used to reflect the risk of human exposure. A survey on COVID-19 related knowledge, attitude and behaviors were used to estimate the abilities of personal protection and emergency response. Results: The epidemic of COVID-19 in Shenzhen experienced the rising, plateau and decline stage. The case number increased rapidly at the beginning, with short duration of peak period. Although the epidemic curve showed human-to-human transmission, the "trailing" was not obvious. From the spot map, during the intervention period, the source of infection was widely distributed. More cases and higher transmission risk were observed in areas with higher population density. After the effective intervention measures, both infection sources and the risk of transmission decreased. After compared with the estimated case numbers without intervention, actual number proved the COVID-19 control strategies were effective. The positive rate of nucleic acid test for high risk populations decreased and no new cases reported since February 16. Shenzhen citizens had high knowledge, attitude and behavior level, and high protection ability and emergency response. Conclusions: Although the response initiated by the health administration department played a key role at the early stage of the epidemic, it was not enough to contain the outbreak of COVID-19. The first-level emergency response initiated by provincial and municipal government was effective and ensured the start of work resumption after the Spring Festival. Metropolitans like Shenzhen can also achieve the goals of strategies and measures for containment and mitigation of COVID-19.
Assuntos
Betacoronavirus , Controle de Doenças Transmissíveis/métodos , Infecções por Coronavirus/epidemiologia , Planejamento em Desastres , Transmissão de Doença Infecciosa/prevenção & controle , Serviços Médicos de Emergência/organização & administração , Pandemias , Pneumonia Viral/epidemiologia , COVID-19 , China/epidemiologia , Socorristas , Humanos , Pneumonia Viral/prevenção & controle , SARS-CoV-2RESUMO
Objective: To evaluate the clinical characteristics of myelin oligodendrocyte glycoprotein antibody (MOG-IgG) associated myelitis in a cohort of Chinese Han adults. Methods: From January 2016 to December 2017, 70 patients with MOG-IgG associated disorders (MOGAD) and 120 patients with aquaporin 4 antibody (AQP4-IgG) positive neuromyelitis optica spectrum disorders (NMOSD) visited the NMO/MS clinic or the neurology ward of Huashan Hospital, and the neurophthalmology clinic of Eye and ENT hospital, Shanghai Medical College, Fudan University were enrolled. The clinical and paraclinical data of the patients were retrospectively reviewed. The characteristics of MOG-IgG associated myelitis were further clarified. Results: Sixteen of the 70 patients with MOGAD had ever experienced myelitis. The frequency of myelitis was 18.6% at the first attack and 22.9% throughout the disease duration. The onset age of MOG-IgG associated myelitis was 9-57(30±11) years, and the female to male ratio was 0.6â¶1. Compared with AQP4-IgG positive myelitis attacks, MOG-IgG associated myelitis attacks were more common to be accompanied by feverish prodromal symptom (30.8%) while less common to exhibit painful tonic (12.5%). Longitudinally extensive myelitis (>3 vertebral segments) was less frequent (56.3%), and short-segment myelitis and multiple short-segment myelitis could also be seen. MRI showed that MOGAD patients had more lower spinal cord lesions (20%), fewer cervical cord lesions (40%) and less transverse lesions (52%). Axial H sign was a distinct feature (36%). MOG-IgG associated myelitis attack also demonstrated a lower EDSS score after treatment. Conclusion: MOG-IgG associated myelitis should be recognized as an important clinical component of MOGAD.
Assuntos
Mielite , Adulto , Aquaporina 4 , Autoanticorpos , China , Feminino , Humanos , Imunoglobulina G , Masculino , Glicoproteína Mielina-Oligodendrócito , Neuromielite Óptica , Estudos RetrospectivosRESUMO
Gastric cardia adenocarcinoma (GCA) is one of the most common types of cancer and the incidence is increasing globally. MicroRNAs (miRNAs) have been reported to play critical roles in the progression of GCA. However, the exact role of miR-638 in GCA and its underlying mechanism remain largely unknown. The expression levels of miR-638 and metastasis-associated in colon cancer 1 (MACC1) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis, migration and invasion were detected by Cell Counting Kit-8 (CCK-8) assay, flow cytometry and transwell assay, respectively. Western blot analysis was performed to determine the protein levels of cleaved-caspase 3 (C-caspase 3) and MACC1. The possible binding sites of miR-638 and MACC1 were predicted by TargetScan online software and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. A xenograft model was established to investigate the roles of MACC1 in GCA in vivo. The expression of miR-638 was evidently reduced and MACC1 expression was obviously enhanced in GCA tissues and cells. Overexpression of miR-638 or knockdown of MACC1 inhibited cell proliferation, migration and invasion but increased apoptosis in GCA cells. Moreover, MACC1 was a direct target of miR-638 and its upregulation attenuated the inhibitory effect of miR-638 overexpression on the progression of GCA. In addition, overexpression of miR-638 significantly decreased tumor growth by downregulating MACCI in vivo. In conclusion, miR-638 overexpression suppressed cell proliferation, migration and invasion but induced cell apoptosis by targeting MACC1 in GCA cells, providing a potential therapeutic strategy for the treatment of GCA.
Assuntos
Adenocarcinoma/patologia , Cárdia/patologia , MicroRNAs/genética , Neoplasias Gástricas/patologia , Transativadores/genética , Adenocarcinoma/genética , Animais , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Gástricas/genéticaRESUMO
The present paper analyzes the typical unified lattice Boltzmann (LB) models for different convection-diffusion (CD) problems in multiphase systems. The CD problems in multiphase systems can be roughly classified into three groups: CD problems with a continuous scalar value and a continuous flux, a discontinuous scalar value and a continuous flux, a continuous scalar value and a discontinuous flux. The characteristics of the corresponding unified LB models for the three kinds of CD problems are analyzed and the equivalence between the LB models based on different perspectives or numerical schemes is revealed. Finally, a comprehensive multiphase LB model (CMLBM) capable of solving different isotropic and anisotropic CD problems in multiphase systems is proposed. Four typical CD problems in multiphase systems are calculated to validate the CMLBM; the results show that it performs well against the typical isotropic and anisotropic CD problems in multiphase systems.