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1.
Appl Opt ; 60(21): 6030-6043, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34613267

RESUMO

White light interferometry is a well-established surface recovery technique. In this paper, a white light signal processing algorithm based on phase error compensation using spectrum selection is proposed. The derived nonlinear phase distribution from the correlogram is modeled as the combination of random errors and systemic deviations. By developing a new, to the best of our knowledge, recovery algorithm, the phase noise can be separated from the linear map and significantly attenuated. Based on the proposed algorithm, the spectrum features of white light LEDs and halogen lamps are investigated in detail. The inner products defined by three selected points are employed to generate a coefficient to evaluate the linearity of an unwrapped phase map within a certain spectrum region. The optimal spectrum range corresponding to the best measurement performance can then be located where the coefficient approximates 1 and the spectrum energy stays relatively high. The simulations are carried out under different levels of SNR and scan step noises, which show that the new method can effectively reduce additional disturbance from the recovered topography. In experiments, the system with the proposed method is first calibrated by a step height standard (VLSI, 182.7±2.0nm) with the repeatability of 0.44 nm. A silicon wafer and three roughness standards are also tested to further verify the robustness of the new method.

2.
Resuscitation ; 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34624410

RESUMO

OBJECTIVE: This study aimed to investigate the predictive value of pulse oximetry plethysmography (POP) for the return of spontaneous circulation (ROSC) in cardiac arrest (CA) patients. METHODS: This was a multicenter, observational, prospective cohort study of patients hospitalized with cardiac arrest at 14 teaching hospitals cross China from December 2013 through November 2014. The study endpoint was ROSC, defined as the restoration of a palpable pulse and an autonomous cardiac rhythm lasting for at least 20 minutes after the completion or cessation of CPR. RESULTS: 150 out-of-hospital cardiac arrest (OHCA) patients and 291 in-hospital cardiac arrest (IHCA) patients were enrolled prospectively. ROSC was achieved in 20 (13.3%) and 64 (22.0%) patients in these cohorts, respectively. In patients with complete end-tidal carbon dioxide (ETCO2) and POP data, patients with ROSC had significantly higher levels of POP area under the curve (AUCp), wave amplitude (Amp) and ETCO2 level during CPR than those without ROSC (all p<0.05). Pairwise comparison of receiver operating characteristic (ROC) curve analysis indicated no significant difference was observed between ETCO2 and Amp (p=0.204) or AUCp (p=0.588) during the first two minutes of resuscitation. CONCLUSION: POP may be a novel and effective method for predicting ROSC during resuscitation, with a prognostic value similar to ETCO2 at early stage.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34601149

RESUMO

OBJECTIVES: Post-treatment recurrence remains a challenge for the global control of tuberculosis (TB). This study investigated longitudinal data on pulmonary TB recurrence rates and its risk factors among successfully treated smear-positive tuberculosis cases in China. METHODS: From 1 January 2009 to 31 December 2016, we evaluated 33,441 treatment-naïve patients diagnosed with sputum smear-positive, non-multidrug-resistant TB in Hangzhou, China. We included the data of 9,828 patients with TB who were successfully treated. RESULTS: A total of 4.9% were recurrent cases (479/9,828), identified within a median observation period lasting 1,565 days. Altogether, 51.1% (245/479) of the recurrences occurred within one year. The cumulative 2- and 5-year recurrence rates were 3.90% (95% confidence interval [CI], 3.3%-4.5%) and 5.4% (95% CI, 4.8%-6.0%), respectively. Prolonged treatment (over 7 months) was occurred in 64.7% (6,363/9,828), with median treatment duration of 242 (interquartile range, 195-348) days. Male sex (adjusted hazard ratio [aHR] [95% CI] = 1.61 [1.30-2.00], P<0.001), ≥ 60-years age (aHR [95% CI] = 2.03 [1.70-2.44], P<0.001), pulmonary cavity (aHR [95% CI] = 1.51 [1.25-1.82], P<0.001) and sputum positive at 2 months (aHR [95% CI] =1.39 [1.05-1.81], P=0.02) increased the risk of TB recurrence. Prolonged treatment was associated with reduced TB recurrence (aHR [95% CI] =0.73 [0.61-0.88], P=0.001). CONCLUSIONS: Recurrence remains a problem for successfully treated patients with sputum smear-positive pulmonary TB, especially those with independent risk factors. Further analysis of prolonged treatment is required.

4.
Phys Rev Lett ; 127(8): 087203, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34477416

RESUMO

The magnon cat state represents a macroscopic quantum superposition of collective magnetic excitations of large number spins that not only provides fundamental tests of macroscopic quantum effects but also finds applications in quantum metrology and quantum computation. In particular, remote generation and manipulation of Schrödinger cat states are particularly interesting for the development of long-distance and large-scale quantum information processing. Here, we propose an approach to remotely prepare magnon even or odd cat states by performing local non-Gaussian operations on the optical mode that is entangled with the magnon mode through pulsed optomagnonic interaction. By evaluating key properties of the resulting cat states, we show that for experimentally feasible parameters, they are generated with both high fidelity and nonclassicality, as well as with a size large enough to be useful for quantum technologies. Furthermore, the effects of experimental imperfections such as the error of projective measurements and dark count when performing single-photon operations have been discussed, where the lifetime of the created magnon cat states is expected to be t∼1 µs.

5.
World J Surg Oncol ; 19(1): 271, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34503530

RESUMO

BACKGROUND: The safety and efficacy of indocyanine green (ICG) imaging navigational laparoscopic gastrectomy remain controversial. This study is to evaluate the short-term and long-term outcomes of ICG-guided laparoscopic radial gastrectomy in patients with gastric cancer. METHODS: Consecutive patients with definitive diagnosis of gastric cancer that underwent laparoscopic radical gastrectomy were collected retrospectively. Propensity score matching (PSM) at 1:1 ratio was performed to compare the outcomes of two groups. RESULTS: A total of 122 qualified patients were divided into ICG group (n = 34) and non-ICG group (n = 88). PSM yielded 28 patients with comparable baseline characteristics into each group. The number of retrieved lymph node in ICG group was significantly higher than that in non-ICG group (P = 0.0196). There was no statistical difference of perioperative, short-term, and long-term complications between the two groups. CONCLUSION: ICG-guided laparoscopic radical gastrectomy is safe and effective, and ICG-navigated lymphadenectomy improves the number of retrieved lymph nodes for patients with gastric cancer.


Assuntos
Laparoscopia , Neoplasias Gástricas , Gastrectomia , Humanos , Verde de Indocianina , Excisão de Linfonodo , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
6.
Brain Behav ; : e32366, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34520636

RESUMO

BACKGROUND: Sleep disorders are highly prevalent among stroke survivors and impede stroke recovery. It is well established that melatonin has neuroprotective effects in animal models of ischemic stroke. However, as a modulator of endogenous physiological circadian rhythms, the effects of melatonin on poststroke sleep disorders remain unclear. In the present study, we investigated how melatonin delivered intraperitoneally once daily in the subacute phase after stroke onset, influencing neuronal survival, motor recovery, and sleep-wake profiles in rats. METHODS: Transient ischemic stroke in male Sprague-Dawley rats was induced with 30 min occlusion of the middle cerebral artery. Melatonin or vehicle was delivered intraperitoneally once daily in the subacute phase, from 2 to 7 days after stroke. Electroencephalogram and electromyogram recordings were obtained simultaneously. RESULTS: Compared to the effects observed in the vehicle-treated ischemic group, after 6 daily consecutive treatment of melatonin at 10 mg/kg starting at ischemic/reperfusion day 2, the infarct volume was significantly decreased (from 39.6 to 26.2%), and the degeneration of axons in the ipsilateral striatum and the contralateral corpus callosum were significantly alleviated. Sensorimotor performances were obviously improved as evidenced by significant increases in the latency to falling off the wire and in the use of the impaired forelimb. In addition to those predictable results of reducing brain tissue damage and mitigating behavioral deficits, repeated melatonin treatment during the subacute phase of stroke also alleviated sleep fragmentation through reducing sleep-wake stage transitions and stage bouts, together with increasing stage durations. Furthermore, daily administration of melatonin at 9 a.m. significantly increased the nonrapid eye movement sleep delta power during both the light and dark periods and decreased the degree of reduction of the circadian index. CONCLUSIONS: Melatonin promptly reversed ischemia-induced sleep disturbances. The neuroprotective effects of melatonin on ischemic injury may be partially associated with its role in sleep modulation.

7.
Aging (Albany NY) ; 13(17): 21712-21728, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518442

RESUMO

Clear cell renal cell carcinoma (ccRCC) is a common and fatal malignancy. Long noncoding RNAs (lncRNAs) have emerged as crucial biomarkers and regulators in many cancers, warranting the detailed investigation of their biological functions and molecular mechanisms. In this study, we explored the role and mechanism of plasmacytoma variant translocation 1 (PVT1), a competitive endogenous RNA (ceRNA) in ccRCC tissues in vitro and in vivo. We found that PVT1 is upregulated in ccRCC cells and promoted cell proliferation. Bioinformatic analysis, dual-luciferase reporter assays, argonaute 2-RNA immunoprecipitation (AGO2-RIP), quantitative PCR arrays, western blot assay, and rescue experiments were conducted to explore the underlying mechanisms of PVT1. Our analyses revealed that miR-328-3p was a direct target of PVT1 and that FAM193B was a direct target of miR-328-3p. FAM193B is upregulated in ccRCC tissues and promotes cell proliferation by activating the MAPK/ERK and PI3K/AKT pathways. Our results indicated that PVT1 promotes ccRCC cells proliferation by sponging miR-328-3p to upregulate FAM193B and activate the MAPK/ERK and PI3K/AKT pathways. Collectively, these results suggest that PVT1- miR-328-3p-FAM193B loop could serve as a potential biomarker and therapeutic target for ccRCC.

8.
Clin Genet ; 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34564849

RESUMO

DUOX2 is the most frequently mutated gene in patients with congenital hypothyroidism (CH) in China. However, no reliable genotype-phenotype relationship has been found in patients with DUOX2 mutations. In this study, DUOX2 mutations were screened in 266 CH patients, and the enzymatic activity of 89 DUOX2 variants was determined in vitro. Furthermore, the DUOX2 residual activity in 76 CH patients caused by DUOX2 biallelic mutations was calculated. The thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels were found to be higher and lower in patients with DUOX2 residual activity ≤22%, respectively, compared to patients with residual enzymatic activity >22%. Moreover, we interpreted the pathogenicity of DUOX2 variants by applying the ACMG classification criteria with or without PS3/BS3 evidence. The results indicated that residual DUOX2 enzymatic activity was closely related to the clinical phenotypes of CH patients caused by DUOX2 biallelic mutations. These findings suggest that the residual enzymatic activity of 22% may be a cutoff value for estimating the severity of hypothyroidism in CH patients with biallelic DUOX2 mutations. Well-established functional studies are useful and necessary to evaluate the pathogenicity of DUOX2 variants, improving the accuracy and scope of genetic consultations.

9.
Infect Dis Ther ; 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34586592

RESUMO

INTRODUCTION: There have been no prospective clinical studies investigating adherence and tolerability of HIV post-exposure prophylaxis (PEP) in China. Tolerability, adherence, and transmitted drug resistance are concerns, especially when single-tablet regimen (STR) usage is low. The present study aimed to explore the safety, tolerability, and adherence of regimens containing albuvirtide (ABT) compared with recommended non-STR antiretrovirals for HIV PEP. METHODS: This was a prospective, open-label, multicenter cohort study. The subjects were stratified into 3 groups based on their preference: ABT + Dolutegravir (DTG) (Group 1), ABT + Tenofovir disoproxil fumarate (TDF) + Lamivudine (3TC) (Group 2), and DTG + TDF + 3TC (Group 3). All enrolled subjects received PEP within 72 h after exposure and continued for 28 days, and were followed-up for 12 weeks. RESULTS: A total of 330 participants were enrolled in the three groups. Most participants were male (87.2%). Sexual contact was the most frequent mode of exposure (91.9%). The average time from exposure to treatment was 26.8 ± 19.5 h. There were no statistically significant differences between the three study groups with respect to completion of oral medication at 28 days. The 28-day completion rate was shown to be significantly higher with ABT versus oral (88.9% vs. 64.0%; p < 0.0001), and adherence with ABT was 94.4% compared to 75.7% with oral PEP (p < 0.0001). Subjects in ABT-containing Group 1 exhibited higher adherence than those in Group 3 (87.3% vs. 72.9%; p < 0.05). None of the participants reported serious adverse drug reactions which led to withdrawal from the study. All the drug regimens were found to be safe and well tolerated. No HIV incident case was observed during the study period. CONCLUSIONS: ABT-containing regimens (ABT + DTG or ABT + TDF + 3TC) offer a good option for HIV PEP due to higher completion rates and adherence than the DTG + TDF + 3TC regimen. The overall safety was comparable and acceptable among the three groups. REGISTRATION: The study was registered in Chinese Clinical Trial Registry with registration number (ChiCTR1900022881, http://www.chictr.org.cn/showprojen.aspx?proj=37395 ).

10.
Technol Cancer Res Treat ; 20: 15330338211041191, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34520284

RESUMO

Lung cancer is listed as the most common reason for cancer-related death all over the world despite diagnostic improvements and the development of chemotherapy and targeted therapies. MicroRNAs control both physiological and pathological processes including development and cancer. A microRNA-9 to 1 (miR-9 to 1) overexpression model in lung cancer cell lines was established and miR-9 to 1 was found to significantly suppress the proliferation rate in lung cancer cell lines, colony formation in vitro, and tumorigenicity in nude mice of A549 cells. Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) was then identified to direct target of miR-9 to 1. The inhibition of UHRF1 by miR-9 to 1 causes G1 arrest and p15, p16, and p21 were re-expressed in miR-9 to 1 group in mRNA level and protein level. Silence of UHRF1 expression in A549 cells resulted in the similar re-expression of p15, p16, p21 which is similar with miR-9 to 1 infection. Therefore, we concluded that UHRF1 is a new target for miR-9 to 1 to suppress cell proliferation by re-expression of tumor suppressors p15, p16, and p21 mediated by UHRF1.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34469370

RESUMO

OBJECTIVES: This study aimed to estimate the safety and efficacy of endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) and endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) for malignant biliary obstruction. METHODS: We conducted a literature search using PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. Studies that compared EUS-CDS and EUS-HGS were included in this study. RESULTS: Thirteen studies were eligible for inclusion. The technical [odds ratio (OR): 0.95; 95% confidence interval (CI): 0.51-1.74) and clinical (OR: 1.13; 95%CI: 0.66-1.94) success rates of EUS-CDS were comparable to those of EUS-HGS. However, EUS-CDS had less reintervention (OR: 0.31; 95%CI: 0.16-0.63) and stent obstruction (OR: 0.48; 95%CI: 0.21-0.94) than EUS-HGS. Both groups had similar adverse events (OR: 1.00; 95%CI: 0.70-1.43) and overall survival (hazard ratio: 1.07; 95%CI: 0.58-1.97). CONCLUSIONS: EUS-CDS and EUS-HGS have comparable technical and clinical success rates, adverse events, and overall survival. However, EUS-CDS has less reintervention and stent obstruction.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34545167

RESUMO

Objective: Defects in the human solute carrier family 26 member 4 (SLC26A4) gene are reported to be one of the causes of congenital hypothyroidism (CH). We aimed to identify SLC26A4 mutations in Chinese patients with CH and analyze the function of the mutations. Methods: 273 patients with primary CH were screened for 21 CH candidate genes mutations by targeted next-generation sequencing. All the exons and exon-intron boundaries of SLC26A4 were found and analyzed. The function of 6 missense mutation in SLC26A4 were further investigated in vitro. Results: Among 273 patients with CH, 7 distinct SLC26A4 heterozygous mutations (p.S49R, p.I363L, p.R409H, p.T485M, p.D661E, p.H723R, c.919-2A>G) were identified in 10 patients (3.66%, 10/273). In vitro experiments showed that mutation p.I363L, p.R409H,p.H723R affect the membrane location and ion transport of SLC26A4, ,while p.S49R did not.Mutation p.T485M and p.D661E only affect the ion transport, but has no effect on the membrane location. Conclusion: Our study indicated that the prevalence of SLC26A4 mutations was 3.66% in the Chinese patients with CH. Five mutations (p.I363L, p.R409H, p.T485M, p.D661E and p.H723R) impaired the membrane location or ion transport function of SLC26A4,which revealed important role of the Ile363,Arg409, Thr485, Asp661, His723 residues in function of SLC26A4. Because these mutations are heterozygous mutations, the pathogenesis of these patients cannot be explained, and the pathogenesis of these patients needs further study.

13.
Immun Inflamm Dis ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34525267

RESUMO

INTRODUCTION: The development of pancreatic ductal adenocarcinoma (PDAC) is closely tied with the immune system. C-C motif chemokine ligands (CCL) were proved to lead to immune recruitment and training. Thus, we reckoned CCL2 to be the kernel of immune suppression in PDAC tissues. METHODS: We compared normal pancreatic tissues with PDAC tissues according to The Cancer Genome Atlas (TCGA) and clinical samples. Flow cytometry was used to identify M-MDSCs. We further demonstrated immune suppression of M-MDSCs according to proliferation rates of CD8+ T cells/CD4+ T cells. Levels of reactive oxygen species (ROS) and Arginase were also tested by flow cytometry, enzyme-linked immunosorbent assay, and western blot analysis. We also analyzed the specific mechanisms by cluster analysis after CCL2 stimulating M-MDSCs. RESULTS: We found that CCL2 highly increased in PDAC tissues. CCL2 is positively related to CD33 and CD14, markers of monocytic myeloid-derived suppressor cells (M-MDSCs). We have demonstrated that CCL2 recruited M-MDSCs into PDAC tissues both in vitro and in vivo. M-MDSCs recruitment is accompanied by sustained immune suppression. Furthermore, we have found that M-MDSCs impeded T cell proliferation and produced high levels of ROS and Arginase, which can be enhanced by CCL2. Mechanistically, CCL2 stimulated M-MDSCs led to a significant upregulation of genes, a large part of which accumulated in the mitogen-activated protein kinase signaling pathway. Treatment of aloesin, MAPK signaling inhibitor, relieved the associated immunosuppressive phenotype induced by CCL2. CONCLUSIONS: Our study indicates that PDAC cells produced CCL2, which promoted localized M-MDSC recruitment and immune suppression, thereby promoting tumor progression.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34444540

RESUMO

BACKGROUND: The frail elderly are prone to falls and fractures, which can result in dependency, disability, admission to institutions, and even death. They are at increased risk of frailty due to decreased physical activity, cognitive decline, and depression. Some evidence suggests that music therapy with physical activities may be particularly beneficial. OBJECTIVE: This study aimed to investigate the intervention effect of music therapy with physical activities (MTPA) on frail elderly in the community. METHODS: A quasi-experimental design was adopted. We selected 10 community care centers in southern Taiwan, in which elderly people over the age of 65 were assigned to a MTPA group and a comparison group after obtaining their informed consent. The MTPA group performed group music activities once a week for 120 min for 12 weeks, while the comparison group only continued with their daily activities. Instruments in this study included the Kihon Checklist, Senior Fitness Test (with Body Mass Index (BMI) and seven physical fitness items), Mini-Mental Status Examination (MMSE), and Geriatric Depression Scale Short Form (GDS-SF). RESULTS: A total of 132 community elders agreed to participate in this study, and 122 completed both the pretest and posttest, with 62 in the music therapy group and 60 in the comparison group. The results of ANCOVA showed that after intervention, except for BMI, the Kihon frailty assessment, seven fitness scores individually and in total, MMSE, and depression showed significant improvements in the music therapy group relative to the comparison group (all p < 0.05). CONCLUSION: MTPA can improve the frailty index, cognitive function, depression, and physical fitness index in the community elderly. The results of this study can be used as a reference for the design of activities for the community elderly, to provide them with appropriate activities, improve their physical functions, and improve or delay their disability.


Assuntos
Fragilidade , Musicoterapia , Música , Atividades Cotidianas , Idoso , Exercício Físico , Idoso Fragilizado , Fragilidade/prevenção & controle , Avaliação Geriátrica , Humanos , Vida Independente
15.
J Evid Based Med ; 14(3): 218-231, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34463038

RESUMO

In the past years, network meta-analysis (NMA) has been widely used among clinicians, guideline makers, and health technology assessment agencies and has played an important role in clinical decision-making and guideline development. To inform further development of NMAs, we conducted a bibliometric analysis to assess the current status of published NMA methodological studies, summarized the methodological progress of seven types of NMAs, and discussed the current challenges of NMAs.

16.
Curr Med Res Opin ; : 1-6, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34376068

RESUMO

BACKGROUND: Pharmacovigilance is a science that plays a significant role in reducing ADRs and helps predict adverse reactions to drugs in community. To safely use drugs in treatment and prevention of disease, adverse drug reaction has been paid more attention. OBJECTIVES: To evaluate the future needs of existing systems, the paper investigated the current state of pharmacovigilance and the reporting of ADR in Chinese hospitals. METHODS: This cross-sectional, questionnaire-based study involved 10,063 pharmacists, doctors, and nurses from primary, secondary, and tertiary hospitals in all 31 provinces of China. It was commissioned by the National Centre for ADR Monitoring of China and conducted in March 2020. Three areas were assessed: sociodemographic characteristics of participants, awareness of the pharmacovigilance system, and the current state of hospitals' reporting of ADRs. Chi-square tests were used to calculate P values. RESULTS: Health care professionals had heard the term "pharmacovigilance" previously (89.40%) and knew the reporting object (68.47%), content (65.94%), and range (64.83%) of pharmacovigilance. Most hospitals dispatched responsible professionals (87.64%) and departments (86.25%) to monitor ADR reporting. A total of 58.66% of tertiary medical, 45.25% of secondary, and 38.90% of primary hospitals extracted ADRs from a hospital information system. Moreover, 53.09% of tertiary medical, 38.93% of secondary, and 23.89% of primary hospitals had established a prescription automatic screening system to warn about risks for ADRs. Health care professionals' reports (99.92%) and patient feedback (77.99%) were included in most hospitals' ADR reporting. CONCLUSIONS: Chinese health care professionals generally have good awareness of pharmacovigilance, and pharmacovigilance is relatively more advanced in China compared to other developing countries.

17.
Artigo em Inglês | MEDLINE | ID: mdl-34374102

RESUMO

OBJECTIVE: Congenital hypothyroidism (CH) is known to be due to thyroid dyshormonogenesis (DH), which is mostly inherited in an autosomal recessive inheritance pattern or thyroid dysgenesis (TD), whose inheritance pattern is controversial and whose molecular etiology remains poorly understood. DESIGN AND METHODS: The variants in 37 candidate genes of CH, including 25 genes related to TD, were screened by targeted exon sequencing in 205 Chinese patients whose CH cannot be explained by biallelic variants in genes related to DH. The inheritance pattern of the genes was analyzed in family trios or quartets. RESULTS: Of the 205 patients, 83 patients carried at least one variant in 19 genes related to TD, and 59 of those 83 patients harbored more than two variants in distinct candidate genes for CH. Biallelic or de novo variants in the genes related to TD in Chinese patients are rare. We also found nine probands carried only one heterozygous variant in the genes related to TD that were inherited from a euthyroid either paternal or maternal parent. These findings did not support the monogenic inheritance pattern of the genes related to TD in CH patients. Notably, in family trio or quartet analysis, of 36 patients carrying more than two variants in distinct genes, 24 patients carried these variants inherited from both their parents, which indicated that the oligogenic inheritance pattern of the genes related to TD should be considered in CH. CONCLUSIONS: Our study expanded the variant spectrum of the genes related to TD in Chinese CH patients. It is rare that CH in Chinese patients could be explained by monogenic germline variants in genes related to TD. The hypothesis of an oligogenic origin of the CH should be considered.

18.
Int J Infect Dis ; 111: 138-147, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34454119

RESUMO

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) patients have been suffering long, ineffective, and toxic treatment until short-course injectable-free regimens emerged. However, the new WHO-recommended regimens might be less feasible in the real-world setting. Here, we evaluated two optimized all-oral short-course regimens in China. METHODS: From April 2019 to August 2020, we conducted a prospective nonrandomized controlled trial and consecutively included 103 MDR-TB patients diagnosed with pulmonary MDR-TB in Shenzhen, China. A 4-5 drug regimen of 9-12 months was tailored to the strain's resistance patterns, patients' affordability, and tolerance to drugs. This was an interim analysis, focusing on the early treatment period. RESULTS: 53.4% (55/103) of patients were prescribed linezolid, fluoroquinolone (FQ), clofazimine, cycloserine, and pyrazinamide, followed by a regimen in which clofazimine was replaced by bedaquiline (35/103, 34.0%). The culture conversion rate was 83.1% and 94.4% at two and four months, respectively, with no significant difference between bedaquiline-free and bedaquiline-containing cases and between FQ-susceptible and FQ-resistant cases. Among 41 patients who completed treatment, 40 (97.6%) patients had a favorable outcome and no relapse was observed. Peripheral neuropathy and arthralgia/myalgia were the most frequent AEs (56.3%, 58/103). 18 AEs caused permanent discontinuation of drugs, mostly due to pyrazinamide and linezolid. CONCLUSION: Optimized all-oral short-course regimens showed satisfactory efficacy and safety in early treatment stage. Further research is needed to confirm these results.


Assuntos
Antituberculosos , Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos/efeitos adversos , Diarilquinolinas/efeitos adversos , Humanos , Estudos Prospectivos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
19.
BMC Infect Dis ; 21(1): 786, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376147

RESUMO

BACKGROUND: Cryptococcal meningitis (CM) remains a leading cause of death in HIV-infected patients, despite advances in CM diagnostic and therapeutic strategies. This study was performed with the aim to develop and validate a novel scoring model to predict mortality risk in HIV-infected patients with CM (HIV/CM). METHODS: Data on HIV/CM inpatients were obtained from a Multicenter Cohort study in China. Independent risk factors associated with mortality were identified based on data from 2013 to 2017, and a novel scoring model for mortality risk prediction was established. The bootstrapping statistical method was used for internal validation. External validation was performed using data from 2018 to 2020. RESULTS: We found that six predictors, including age, stiff neck, impaired consciousness, intracranial pressure, CD4+ T-cell count, and urea levels, were associated with poor prognosis in HIV/CM patients. The novel scoring model could effectively identify HIV/CM patients at high risk of death on admission (area under curve 0.876; p<0.001). When the cut-off value of 5.5 points or more was applied, the sensitivity and specificity was 74.1 and 83.8%, respectively. Our scoring model showed a good discriminatory ability, with an area under the curve of 0.879 for internal validation via bootstrapping, and an area under the curve of 0.886 for external validation. CONCLUSIONS: Our developed scoring model of six variables is simple, convenient, and accurate for screening high-risk patients with HIV/CM, which may be a useful tool for physicians to assess prognosis in HIV/CM inpatients.


Assuntos
Infecções por HIV , Meningite Criptocócica , Estudos de Coortes , Infecções por HIV/complicações , Humanos , Programas de Rastreamento , Meningite Criptocócica/diagnóstico , Fatores de Risco
20.
Chin Med J (Engl) ; 134(16): 1920-1929, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34320566

RESUMO

BACKGROUND: The global pandemic coronavirus disease 2019 (COVID-19) has become a major public health problem and presents an unprecedented challenge. However, no specific drugs were currently proven. This study aimed to evaluate the comparative efficacy and safety of pharmacological interventions in patients with COVID-19. METHODS: Medline, Embase, the Cochrane Library, and clinicaltrials.gov were searched for randomized controlled trials (RCTs) in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/SARS-CoV. Random-effects network meta-analysis within the Bayesian framework was performed, followed by the Grading of Recommendations Assessment, Development, and Evaluation system assessing the quality of evidence. The primary outcome of interest includes mortality, cure, viral negative conversion, and overall adverse events (OAEs). Odds ratio (OR) with 95% confidence interval (CI) was calculated as the measure of effect size. RESULTS: Sixty-six RCTs with 19,095 patients were included, involving standard of care (SOC), eight different antiviral agents, six different antibiotics, high and low dose chloroquine (CQ_HD, CQ_LD), traditional Chinese medicine (TCM), corticosteroids (COR), and other treatments. Compared with SOC, a significant reduction of mortality was observed for TCM (OR = 0.34, 95% CI: 0.20-0.56, moderate quality) and COR (OR = 0.84, 95% CI: 0.75-0.96, low quality) with improved cure rate (OR = 2.16, 95% CI: 1.60-2.91, low quality for TCM; OR = 1.17, 95% CI: 1.05-1.30, low quality for COR). However, an increased risk of mortality was found for CQ_HD vs. SOC (OR = 3.20, 95% CI: 1.18-8.73, low quality). TCM was associated with decreased risk of OAE (OR = 0.52, 95% CI: 0.38-0.70, very low quality) but CQ_HD (OR = 2.51, 95% CI: 1.20-5.24) and interferons (IFN) (OR = 2.69, 95% CI: 1.02-7.08) vs. SOC with very low quality were associated with an increased risk. CONCLUSIONS: COR and TCM may reduce mortality and increase cure rate with no increased risk of OAEs compared with standard care. CQ_HD might increase the risk of mortality. CQ, IFN, and other antiviral agents could increase the risk of OAEs. The current evidence is generally uncertain with low-quality and further high-quality trials are needed.


Assuntos
COVID-19 , Humanos , Medicina Tradicional Chinesa , Metanálise em Rede , Pandemias , SARS-CoV-2
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