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1.
Influenza Other Respir Viruses ; 18(5): e13310, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38725276

RESUMEN

BACKGROUND: A variety of viruses can cause acute respiratory infections (ARIs), resulting in a high disease burden worldwide. To explore the dominant viruses and their prevalence characteristics in children with ARIs, comprehensive surveillance was carried out in the Pudong New Area of Shanghai. METHODS: Between January 2013 and December 2022, the basic and clinical information, and respiratory tract specimens of 0-14 years old children with ARIs were collected in five sentinel hospitals in Shanghai Pudong. Each specimen was tested for eight respiratory viruses, and the positive rates of different age groups, case types (inpatient or outpatient) were analyzed. RESULTS: In our study, 30.67% (1294/4219) children with ARIs were positive for at least one virus. Influenza virus (IFV) was the most commonly detected respiratory virus (349/4219, 8.27%), followed by respiratory syncytial virus (RSV) (217/4219, 5.14%), para-influenza virus (PIV) (215/4219, 5.10%), and human coronavirus (HCoV, including 229E, OC43, NL63, and HKU1) (184/4219, 4.36%). IFV was the leading respiratory virus in outpatients aged 5-14 years (201/1673, 12.01%); RSV was the most prevalent respiratory virus in both inpatients (61/238, 25.63%) and outpatients (4/50, 8.00%) for ARI patients aged <6 months old. For PIV, HMPV, HCoV, and HRV, the risk of infection usually was higher among young children. Co-infection with more than two viruses was seen in 3.25% (137/4219). CONCLUSIONS: IFV and RSV played important roles in ARIs among children, but the risk populations were different. There are needs for targeted diagnosis and treatment and necessary immunization and non-pharmaceutical interventions.


Asunto(s)
Infecciones del Sistema Respiratorio , Humanos , China/epidemiología , Preescolar , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Niño , Lactante , Masculino , Adolescente , Femenino , Prevalencia , Recién Nacido , Virus/aislamiento & purificación , Virus/clasificación , Virosis/epidemiología , Virosis/virología , Coinfección/epidemiología , Coinfección/virología , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/virología , Enfermedad Aguda/epidemiología
2.
Hepatobiliary Surg Nutr ; 13(2): 214-228, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38617480

RESUMEN

Background: Colorectal liver metastasis (CRLM) exhibits highly heterogeneity, with clinically and molecularly defined subgroups that differ in their prognosis. The aim of this study is to explore whether left-sided tumors is clinically and gnomically distinct from right-sided tumors in CRLM. Methods: This retrospective study included 1,307 patients who underwent primary tumor and metastases resection at three academic centers in China from January 1, 2012, to December 31, 2020. Propensity score matching with 1:1 ratio matching was performed. The prognostic impact of tumor sidedness was determined after stratifying by the KRAS mutational status. Moreover, whole-exome sequencing (WES) of 200 liver tumor tissues were performed to describe the heterogeneity across the analysis of somatic and germline profiles. Results: The median follow-up was 68 months. Matching yielded 481 pairs of patients. Compared to right-sided CRLM, left-sided patients experienced with better 5-year overall survival (OS) in surgery responsiveness, with a 14.6 lower risk of death [hazard ratio (HR), 1.36, 95% confidence interval (CI), 1.10-1.69, P=0.004]. Interaction between tumor sidedness and KRAS status was statistically significant: left-sidedness was associated with better prognosis among KRAS wild-type patients (HR 1.71; 95% CI: 1.20-2.45; P=0.003), but not among KRAS mutated-type patients. Integrated molecular analyses showed that right-sided tumors more frequently harbored TP53, APC, KRAS, and BRAF alterations, and identified a critical role of KRAS mutation in correlation with their survival differences. Higher pathogenic germline variants were identified in the right-sided tumors compared with left-sided tumors (29.3% vs. 15.5%, P=0.03). Conclusions: We demonstrated that the prognostic impacts of tumor sidedness in CRLM is restricted patients with KRAS wild-type tumors. Tumor sidedness displays considerable clinical and molecular heterogeneity that may associate with their therapy benefits and prognosis.

3.
Hum Genomics ; 18(1): 42, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38659038

RESUMEN

BACKGROUND: The integration of transcriptomic, proteomic, druggable genetic and metabolomic association studies facilitated a comprehensive investigation of molecular features and shared pathways for cancers' development and progression. METHODS: Comprehensive approaches consisting of transcriptome-wide association studies (TWAS), proteome-wide association studies (PWAS), summary-data-based Mendelian randomization (SMR) and MR were performed to identify genes significantly associated with cancers. The results identified in above analyzes were subsequently involved in phenotype scanning and enrichment analyzes to explore the possible health effects and shared pathways. Additionally, we also conducted MR analysis   to investigate metabolic pathways related to cancers. RESULTS: Totally 24 genes (18 transcriptomic, 1 proteomic and 5 druggable genetic) showed significant associations with cancers risk. All genes identified in multiple methods were mainly enriched in nuclear factor erythroid 2-related factor 2 (NRF2) pathway. Additionally, biosynthesis of ubiquinol and urate were found to play an important role in gastrointestinal tumors. CONCLUSIONS: A set of putatively causal genes and pathways relevant to cancers were identified in this study, shedding light on the shared biological processes for tumorigenesis and providing compelling genetic evidence to prioritize anti-cancer drugs development.


Asunto(s)
Neoplasias , Humanos , Neoplasias/genética , Neoplasias/patología , Neoplasias/tratamiento farmacológico , Estudio de Asociación del Genoma Completo , Proteómica , Transcriptoma/genética , Análisis de la Aleatorización Mendeliana , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Metabolómica/métodos , Redes y Vías Metabólicas/genética , Predisposición Genética a la Enfermedad , Multiómica
4.
Comput Methods Programs Biomed ; 248: 108122, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38507960

RESUMEN

BACKGROUND AND OBJECTIVE: Most of the existing machine learning-based heart sound classification methods achieve limited accuracy. Since they primarily depend on single domain feature information and tend to focus equally on each part of the signal rather than employing a selective attention mechanism. In addition, they fail to exploit convolutional neural network (CNN) - based features with an effective fusion strategy. METHODS: In order to overcome these limitations, a novel multimodal attention convolutional neural network (MACNN) with a feature-level fusion strategy, in which Mel-cepstral domain as well as general frequency domain features are incorporated to increase the diversity of the features, is proposed in this paper. In the proposed method, DilationAttenNet is first utilized to construct attention-based CNN feature extractors and then these feature extractors are jointly optimized in MACNN at the feature-level. The attention mechanism aims to suppress irrelevant information and focus on crucial diverse features extracted from the CNN. RESULTS: Extensive experiments are carried out to study the efficacy of the feature level fusion in comparison to that with early fusion. The results show that the proposed MACNN method significantly outperforms the state-of-the-art approaches in terms of accuracy and score for the two publicly available Github and Physionet datasets. CONCLUSION: The findings of our experiments demonstrated the high performance for heart sound classification based on the proposed MACNN, and hence have potential clinical usefulness in the identification of heart diseases. This technique can assist cardiologists and researchers in the design and development of heart sound classification methods.


Asunto(s)
Cardiopatías , Ruidos Cardíacos , Humanos , Aprendizaje Automático , Redes Neurales de la Computación
5.
Hum Vaccin Immunother ; 20(1): 2287294, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38299510

RESUMEN

The vaccination rate for seasonal influenza remains low in most regions of China. It is essential to understand the factors that associated with the low influenza vaccination rate in various populations after the COVID-19 pandemic. A cross-sectional survey was conducted with residents in Pudong New Area, Shanghai, China. Respondents' vaccination condition during the 2021-2022 flu season and the reasons for receiving or not receiving influenza vaccine were investigated. Binary logistic regression was conducted to explore potential factors influencing vaccination uptake. 2,476 of 14,001 respondents received an influenza vaccine, with a total coverage of 17.68% (95% CI: 17.05%, 18.32%). Children had the highest vaccination coverage (35.68%; 95% CI: 34.02, 37.33), followed by adults (12.75%; 95% CI: 11.91%, 13.58%) and elderly individuals (11.70%, 95% CI: 10.78%, 12.62%). For children, lower household income was an significant promoting factor. For adults, factors significantly associated with vaccination were household income, sex, and education level. For elderly, factors significantly associated with vaccination were household income, education level, living state, and having underlying diseases. (P < .05)The main reason for vaccine hesitancy among children was worried about side effects (21.49%), for adults and elderly was self-rated good health (adults: 37.14%, elderly people: 30.66%). The overall influenza vaccination coverage rate in Shanghai, especially among elderly individuals, is lower than many developed countries. Appropriate strategies and programs targeting different populations need to be implemented to enhance influenza vaccine coverage.


The vaccination rate for seasonal influenza remains low in most regions of China. However, the COVID-19 pandemic has resulted in an increase in public awareness regarding the prevention and control of infectious diseases and changes in people's health behaviors thus may leading to changes in influenza vaccination rates and vaccination willingness. We conducted a survey on the medical service utilization behavior of community residents in Shanghai, the biggest city in eastern China. The vaccination status of respondents during the 2021­2022 flu season and the reasons for receiving or not receiving the vaccine were investigated among 14,001 local residents. The influenza vaccination rate in 2021­2022 season (17.68%) was higher than that in 2018­2019 season (11.8%) in the same area. And this trend was found in population of different age groups. However, the overall influenza vaccination coverage rate in Shanghai is still low, especially among elderly, it remains inadequate to establish an immune barrier and lags behind other developed regions. For children, lower household income was an independent promoting factor. For adults, factors significantly associated with vaccination were  household income, sex, and education level. For elderly, factors significantly associated with vaccination were household income, education level, living state, and having underlying diseases. (P < .05) The main reason for vaccine hesitancy among children was worried about side effects (21.49%), for adults and elderly was self-rated good health (adults: 37.14%,elderly people: 30.66%).Efforts should be made to increase awareness of influenza vaccines according to the characteristics of different population.


Asunto(s)
COVID-19 , Vacunas contra la Influenza , Gripe Humana , Adulto , Niño , Humanos , Anciano , Vacunas contra la Influenza/uso terapéutico , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Gripe Humana/tratamiento farmacológico , COVID-19/epidemiología , COVID-19/prevención & control , Estudios Transversales , Pandemias/prevención & control , China/epidemiología , Vacunación
6.
Artículo en Inglés | MEDLINE | ID: mdl-38381354

RESUMEN

OBJECTIVES: The concurrent impact of COVID-19 and influenza on disease burden is a topic of great concern. This discussion delves into the epidemiological characteristics of seasonal influenza activity in Shanghai within the context of the SARS-CoV-2 epidemic. METHODS: From 2017 to 2023, a total of 11,081 patients having influenza-like illness (ILI) were included in this study for influenza virus detection. Reverse transcription polymerase chain reaction (RT-PCR) assays were conducted according to standardised protocols to identify the types and subtypes of influenza viruses. The positivity rate of the influenza virus among the sampled ILI cases served as a surrogate measure for estimating various influenza seasonal characteristics, such as periodicity, duration, peak occurrences, and the prevalent subtypes or lineages. Epidemiological aspects across different years and age groups were subjected to comprehensive analysis. For categorical variables, the Chi-square test or Fisher's exact test was employed, as deemed appropriate. RESULTS: A total of 1553 (14.0%) tested positive for influenza virus pathogens. The highest positivity rate for influenza was observed in adults aged 25-59 years (18.8%), while the lowest rate was recorded in children under 5 years (3.8%). The influenza circulation patterns in Shanghai were characterised: (1) 2 years exhibited semiannual periodicity (2017-2018, 2022-2023); (2) 3 years displayed annual periodicity (2018-2019, 2019-2020, and 2021-2022); and (3) during 2020-2021, epidemic periodicities of seasonal influenza viruses disappeared. In terms of influenza subtypes, four subtypes were identified during 2017-2018. In 2018-2019 and 2019-2020, A/H3N2, A/H1N1, and B/Victoria were circulating. Notably, one case of B/Victoria was detected in 2020-2021. The epidemic period of 2021-2022 was attributed to B/Victoria, and during 2022-2023, the influenza A virus was the dominant circulating strain. CONCLUSIONS: The seasonal epidemic period and the predominant subtype/lineage of influenza viruses around the SARS-CoV-2 epidemic period in Shanghai city are complex. This underscores the necessity for vigilant influenza control strategies amidst the backdrop of other respiratory virus pandemics.

7.
FEBS J ; 291(7): 1575-1592, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38243371

RESUMEN

Ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) is a common clinical syndrome with high morbidity and mortality. Ferroptosis, a newly discovered form of oxidative cell death, is involved in the pathogenesis of renal I/R injury; however, the underlying mechanism remains to be explored. Here, we reported that site 1 protease (S1P) promotes ischemic kidney injury by regulating ferroptotic cell death of tubular epithelial cells. S1P abundance was measured in hypoxia/reoxygenation (H/R)-treated Boston University mouse proximal tubular (BUMPT) cells and I/R-induced murine kidney tissue. S1P expression in BUMPT cells and kidneys was initially activated by hypoxic stimulation, accompanied by the ferroptotic response. Blocking S1P blunted H/R-induced ferroptotic cell death, which also restored sirtuin 3 (SIRT3) expression and superoxide dismutase 2 (SOD2) activity in BUMPT cells. Next, inhibition of S1P expression restored I/R-suppressed SIRT3 abundance, SOD2 activity and reduced the elevated level of mitochondria reactive oxygen species (mtROS), which attenuated tubular cell ferroptosis and renal I/R injury. In conclusion, S1P promoted renal tubular epithelial cell ferroptosis under I/R status by activating SIRT3-SOD2-mtROS signaling, thereby accelerating kidney injury. Thus, targeting S1P signaling may serve as a promising strategy for I/R kidney injury.


Asunto(s)
Lesión Renal Aguda , Ferroptosis , Daño por Reperfusión , Serina Endopeptidasas , Sirtuina 3 , Superóxido Dismutasa , Animales , Ratones , Lesión Renal Aguda/genética , Lesión Renal Aguda/patología , Células Epiteliales/metabolismo , Ferroptosis/genética , Riñón/metabolismo , Péptido Hidrolasas/metabolismo , Daño por Reperfusión/metabolismo , Sirtuina 3/genética , Sirtuina 3/metabolismo , Serina Endopeptidasas/metabolismo , Proproteína Convertasas/metabolismo , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismo
8.
Ren Fail ; 45(2): 2285873, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38044852

RESUMEN

OBJECTIVE: Peritoneal dialysis-related peritonitis (PDRP) presents a significant challenge for nephrologists. Continuous intraperitoneal cefazolin and ceftazidime are recommended for the treatment of peritonitis. However, some pharmacokinetic studies have shown that doses of 15-20 mg/kg/d may not achieve sufficient therapeutic levels. In this study, we investigated the pharmacokinetics of ceftazidime and cefazolin in patients with continuous ambulatory peritoneal dialysis-related peritonitis and compared the pharmacokinetic characteristics between traditional and modified treatment groups. METHODS: From February 2017 to December 2019, 42 PDRP patients (17 males, 25 females; mean age: 50.7 ± 12.1 years; mean body weight: 60.9 ± 11.8 kg) were recruited for the study, all participants were anuric. Twenty patients were enrolled in the traditional group and treated with cefazolin (1.0 g) and ceftazidime (1.0 g) via intraperitoneal administration once daily for 14 days. Twenty-two patients were enrolled in the modified group and received the same dose of antibiotics twice daily for the initial five days, followed by once daily for the subsequent nine days. Serum and dialysate samples were collected after days 1, 2, 3, 5, 7, 10, and 14 and analyzed via liquid chromatography-mass spectrometry. RESULTS: In the traditional group, the highest and lowest serum concentrations of ceftazidime were 35.9 and 21.7 µg/mL, respectively. The highest concentration of cefazolin was 54.6 µg/mL on day 5 and the lowest concentration was 30.4 µg/mL on day 1. In the modified group, the highest and lowest serum concentrations of ceftazidime were 102.2 and 54.8 µg/mL, respectively. The highest concentration of cefazolin was 141.7 µg/mL and the lowest concentration was 79.8 µg/mL. All antibiotic concentrations were above the minimum inhibitory concentration (MIC) level (8 µg/mL of ceftazidime and 2 µg/mL of cefazolin) throughout the treatment period. However, on day 1, the concentration of ceftazidime in the third bag of dialysate effluent from the traditional group fell below the MIC level. Despite remaining above the MIC, cefazolin concentration was consistently lower in the third bag of dialysate effluent from the traditional group throughout the treatment period. CONCLUSIONS: Intraperitoneal administration of cefazolin and ceftazidime at a dose of 1 g twice daily for 5 days and then once daily for the rest of the treatment period ensured adequate therapeutic levels of antibiotics for treating anuric PDRP patients.


Asunto(s)
Anuria , Diálisis Peritoneal Ambulatoria Continua , Peritonitis , Masculino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Cefazolina , Ceftazidima/farmacocinética , Ceftazidima/uso terapéutico , Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Diálisis Peritoneal Ambulatoria Continua/métodos , Estudios Prospectivos , Antibacterianos/uso terapéutico , Peritonitis/tratamiento farmacológico , Peritonitis/etiología , Soluciones para Diálisis , Anuria/etiología
9.
Nanotechnology ; 35(6)2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-37922540

RESUMEN

This paper proposes a Whipple structure to enhance the impact resistance of graphene/aluminum alloy composites by varying the interlayer spacing between graphene and aluminum alloy. The increased interlayer spacing provides more deformation space for the graphene to absorb more deformation energy, and enables the formation of a debris cloud from the bullet fragments and graphene fragments, significantly reducing the impact energy per unit area of the next material. The impact limit serves as a critical metric for assessing the impact resistance of the Whipple structure. Based on molecular dynamics simulations, we developed a machine learning model to predict the protection of aluminum alloy, and quickly determined the impact limits of velocity, bullet radius, and interlayer spacing by using the machine learning model. An empirical equation for the impact limit of interlayer spacing was established. The results showed that non-zero interlayer spacing can significantly improve the impact resistance of the hybrid structure; to fully exploit the superior impact resistance of this Whipple structure, the number of graphene layers should be at least 3. Furthermore, at high impact velocities and large bullet radii, the impact limit of the interlayer spacing exhibits a substantial correlation with the number of graphene layers. These results provide valuable information for the design of the impact resistance of the graphene/aluminum alloy composites.

10.
Environ Sci Pollut Res Int ; 30(47): 103947-103957, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37697190

RESUMEN

The objective of this study is to investigate the association between military spending and environmental sustainability within the N-11 countries. There exists a strong correlation between sustainable economic expansion and energy consumption, which in turn results in the generation of elevated levels of carbon emissions. Moreover, it is plausible that a correlation exists between military spending and the degradation of the environment. The primary objective of this study is to examine the emissions of carbon and emissions of greenhouse gases in the N-11 countries, as these nations exhibit comparatively elevated levels of such emissions. Therefore, this study examines the correlation among economic growth, militarization, renewable energy, and environment in the Next Eleven nations from 1990 to 2022. The cross-section autoregressive distributed lag (CS-ARDL) model is employed to analyze the enduring and immediate connections between variables. Empirical evidence indicates that a country's environment is positively influenced by GDP and militarization. The escalation of military capital intensity has exacerbated the environmental damage. Increasing the adoption of renewable energy sources can mitigate negative environmental impacts over time. This study proposes policy recommendations for sustainable development, including reducing militarization and improving the use of clean energy.


Asunto(s)
Gases de Efecto Invernadero , Personal Militar , Humanos , Desarrollo Económico , Energía Renovable , Carbono , Dióxido de Carbono
11.
Vaccines (Basel) ; 11(7)2023 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-37514962

RESUMEN

Reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants due to immune escape is challenging for the global response to the pandemic. We estimated the Omicron reinfection prevalence among people who had a previous SARS-CoV-2 infection in Shanghai, China. We conducted a telephone survey in December 2022 with those who had previously been infected with Omicron between March and May 2022. Information on their demographics, coronavirus disease 2019 (COVID-19) testing, and vaccination history was collected. The overall and subgroup reinfection rates were estimated and compared. Among the 1981 respondents who were infected between March and May 2022, 260 had positive nucleic acid or rapid antigen tests in December 2022, with an estimated reinfection rate of 13.1% (95% confidence interval [95% CI]: 11.6-14.6). The reinfection rate for those who had a booster vaccination was 11.4% (95% CI: 9.2-13.7), which was significantly lower than that for those with an incomplete vaccination series (15.2%, 95% CI: 12.3-18.1) (adjusted odds ratio [aOR]: 0.579; 95% CI: 0.412-0.813). Reinfection with the Omicron variant was lower among individuals with a previous SARS-CoV-2 infection and those who had a booster vaccination, suggesting that hybrid immunity may offer protection against reinfection with Omicron sublineages.

12.
Adv Healthc Mater ; 12(28): e2301084, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37219912

RESUMEN

Most solid tumors are clinically treated using surgical resection, and the presence of residual tumor tissues at the surgical margins often determines tumor survival and recurrence. Herein, a hydrogel (Apt-HEX/Cp-BHQ1 Gel, termed AHB Gel) is developed for fluorescence-guided surgical resection. AHB Gel is constructed by tethering a polyacrylamide hydrogel and ATP-responsive aptamers together. It exhibits strong fluorescence under high ATP concentrations corresponding to the TME (100-500 µm) but shows little fluorescence at low ATP concentrations (10-100 nm) such as those in normal tissues. AHB Gel can rapidly (within 3 min) emit fluorescence after exposure to ATP, and the fluorescence signal only occurs at sites exposed to high ATP, resulting in a clear boundary between the ATP-high and ATP-low regions. In vivo, AHB Gel exhibits specific tumor-targeting capacity with no fluorescence response in normal tissue, providing clear tumor boundaries. In addition, AHB Gel has good storage stability, which is conducive to its future clinical application. In summary, AHB Gel is a novel tumor microenvironment-targeted DNA-hybrid hydrogel for ATP-based fluorescence imaging. It can enable the precise imaging of tumor tissues, showing promising application in fluorescence-guided surgeries in the future.


Asunto(s)
Hidrogeles , Neoplasias , Humanos , Microambiente Tumoral , Imagen Óptica/métodos , Adenosina Trifosfato
13.
Cancer Med ; 12(11): 12263-12271, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37039263

RESUMEN

AIM: This study was aimed to evaluate the safety and the efficacy of gemcitabine and oxaliplatin (GEMOX) combined with donafenib plus tislelizumab as the first-line treatment for patients with unresectable biliary tract cancer (BTC). METHODS: This is a prospective single-center exploratory study. Eligible patients (Stage III/IV BTC, at least one measurable disease according to RECIST v1.1, etc.) received gemcitabine 1000 mg/m2 IV Q3W, oxaliplatin 100 mg/m2 IV Q3W, donafenib 200 mg PO BID, and tislelizumab 200 mg IV Q3W until disease progression, unacceptable toxicity, or withdrawal of consent whichever occurred first. The primary endpoint was safety and secondary endpoints included disease control rate (DCR), objective response rate (ORR), conversion rate, and overall survival (OS). RESULTS: A total of 13 patients were enrolled. The median follow-up time was 420 days (range 345-487). The median duration of treatment was four cycles (range 1-15). The incidence of ≥Grade 3 treatment-related adverse events (TRAEs) was 53.8% and no Grade 5 TRAE. The most frequent Grade 3-4 TRAEs were rash (4/13, 30.8%), platelet count decreased (2/13, 15.4%), and fatigue (2/13, 15.4%). Tumor response was assessed in eight evaluable patients; ORR was 25.0% (95% CI, 3.2%-65.1%) and DCR 87.5% (95% CI, 47.3%-99.7%). The median PFS was 4.8 months (95% CI, 1.25-NE). Three Stage III patients underwent subsequent surgery with a conversion rate of 23.1%. The median OS was not estimable. CONCLUSIONS: GEMOX combined with donafenib plus tislelizumab as the first-line therapy for unresectable BTC showed manageable toxicity and encouraging efficacy especially in terms of promising conversion rate in Stage III patients.


Asunto(s)
Neoplasias de los Conductos Biliares , Neoplasias del Sistema Biliar , Humanos , Oxaliplatino , Gemcitabina , Estudios Prospectivos , Neoplasias del Sistema Biliar/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
14.
J Org Chem ; 88(9): 5248-5253, 2023 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-37023248

RESUMEN

Direct para-selective C(sp2)-H alkylation of electron-deficient arenes based on the electroreduction-enabled radical addition of alkyl bromides has been developed under mild conditions. In the absence of any metals and redox agents, the simple electrolysis system tolerates a variety of primary, secondary, and tertiary alkyl bromides and behaves as an important complement to the directed alkylation of the C(sp2)-H bond and the classic Friedel-Crafts alkylation. This electroreduction process provides a more straightforward, environmentally benign, and effective alkylation method for electron-deficient arenes.

16.
Open Med (Wars) ; 18(1): 20230648, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36820062

RESUMEN

Nephrolithiasis is a highly prevalent disease worldwide that is associated with significant suffering, renal failure, and cost for the healthcare system. A patient with nephrolithiasis was found to have SLC6A20 variation. SLC6A20 gene in human is located on chromosome 3p21.3, which is a member of SLC6 family of membrane transporters and the product of this gene expression is transporter protein of sub-amino acid transporter system. The previous studies have reported that the mutation of SLC6A20 may cause hyperglycinuria or iminoglycinuria which may lead to nephrolithiasis. The object was to investigate the relationship between nephrolithiasis and SLC6A20 through pedigree genetic analysis. To explore whether the SLC6A20 mutation can cause hereditary nephrolithiasis, and provide evidence for further research. The urine and blood were collected from the patients for compositional analysis. DNA sequencing was applied to analyze the gene mutation. Labial gland and kidney biopsy were conducted for pathological analysis. As a result we reported a rare family case of nephrolithiasis accompanied by primary Sjogren's syndrome and investigated it by examining the family members with whole exome gene sequencing technology and detecting 20 different amino acids and 132 kinds of organic acids in the urine with gas chromatography-mass spectrometry. We discovered that the proband and her mother had hyperglycinuria and the proband (Ⅱ2), her sister (Ⅱ3), and mother (Ⅰ1) were found to carry the SLC6A20 gene exon NM_020208.3 sequence c.1072T > C heterozygous mutation, and the other family members (Ⅰ2, Ⅱ1, Ⅱ4, Ⅲ1, Ⅲ2) did not carry the genetic mutation. As a conclusion, the heterozygous mutation of SLC6A20 (c.1072T > C) might be contributed to hyperglycinuria and the formation of nephrolithiasis.

17.
J Colloid Interface Sci ; 640: 41-51, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-36827847

RESUMEN

Multimodal synergistic therapy based on nanomedicine drug delivery systems can achieve accurate cancer treatment. The anisotropy of gold nanorods (AuNRs) allows the adjustment of the longitudinal localized surface plasmon resonance absorption to the near-infrared band, which shows potential application in the field of photothermal therapy of cancer. Here, we report a new type of thermal-sensitive gold nanorod drug-loaded vesicles (UGRV-DOX) via the self-assembly of AuNRs modified with the amphiphilic polymer (PEG45-b-PS150) and upper critical solution temperature (UCST) polymer (P(AAm-co-AN)). The hollow structure of the vesicle can increase the drug loading capacity, and the polymers on its surface are intertwined to reduce drug leakage. As-prepared UGRV-DOX vesicles exhibits excellent photothermal conversion efficiency and can achieve light-controlled drug release. In vivo anti-tumor experiments showed that UGRV-DOX could ablate HepG2 transplanted tumors significantly under 808 nm laser irradiation, and the inhibition rate was as high as 99.3 %. These tumor-specific nanovesicles prefigure great potentials for high-precision cancer treatment.


Asunto(s)
Hipertermia Inducida , Nanotubos , Terapia Fototérmica , Fototerapia , Doxorrubicina/farmacología , Oro/farmacología , Oro/química , Temperatura , Línea Celular Tumoral , Nanotubos/química , Polímeros/química , Rayos Infrarrojos , Rayos Láser
19.
Vaccines (Basel) ; 10(12)2022 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-36560519

RESUMEN

BACKGROUND: Seasonal influenza may overlap with the COVID-19 pandemic, and children are one of the priority populations for influenza vaccination in China, yet vaccine coverage has been low. This study aimed to investigate the extent of parental influenza vaccine hesitancy (IVH) and to explore the associated factors. METHODS: The study was conducted in Shanghai, China, from 1 June 2022 to 31 July 2022, using an anonymous questionnaire to survey a random sample of parents of children aged six months to 14 years. Binary logistic regression models were used to identify factors associated with IVH. RESULTS: Of the 5016 parents, 34.05% had IVH. Multivariate analysis showed that after adjustment for non-modifiable markers (i.e., sociodemographic, health status, and past vaccination status), being affected by negative influenza vaccine news and having higher "complacency" were positively associated with parental IVH. Higher knowledge of influenza vaccination, being recommended by healthcare workers (HCWs), people around having a positive attitude toward influenza vaccine and having higher levels of "confidence" and "convenience" were negatively associated with parental IVH. CONCLUSIONS: In China, public health education aimed at modifying vaccination-related attitudes and beliefs, as well as knowledge and societal influences, could help reduce influenza vaccination hesitancy.

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