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1.
JAMA Oncol ; 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33792623

RESUMO

Importance: This study demonstrates that tislelizumab in combination with chemotherapy is associated with improved progression-free survival (PFS) in patients with advanced squamous non-small-cell lung cancer (sq-NSCLC). Objective: To assess the efficacy and safety/tolerability of tislelizumab plus chemotherapy vs chemotherapy alone as first-line treatment for patients with advanced sq-NSCLC. Design, Setting, and Participants: This open-label, randomized phase 3 clinical trial was conducted at 46 sites in China between July 2018 and June 2019 and included patients with treatment-naive, histologically confirmed stage IIIB/IV sq-NSCLC. The data cutoff for these analyses was December 6, 2019; data extraction occurred on January 7, 2020. Interventions: Patients were randomized (1:1:1) to receive 1 of the following regimens intravenously on a 21-day cycle: tislelizumab (200 mg, day 1) plus paclitaxel (175 mg/m2, day 1) and carboplatin (area under the concentration of 5, day 1) (arm A); tislelizumab plus nab-paclitaxel (100 mg/m2, days 1, 8, and 15) and carboplatin (arm B); and paclitaxel and carboplatin (arm C). Patients were stratified by disease stage and tumor programmed cell death 1 ligand 1 (PD-L1) expression (<1% vs 1%-49% vs ≥50%). Main Outcomes and Measures: The primary end point was progression-free survival (PFS) assessed by an independent review committee (IRC). Secondary end points included overall survival, investigator-assessed (INV) PFS, IRC-assessed objective response rate (ORR), and IRC-assessed duration of response, as well as the incidence and severity of adverse events (AEs). Results: Overall, 355 patients (median [range] age, 62 [34-74] years; 330 men [91.7%]) with sq-NSCLC received treatment. After a median study follow-up of 8.6 months (95% CI, 8.1-9.0 months), IRC-assessed PFS was significantly improved with tislelizumab plus chemotherapy (arm A, 7.6 months; arm B, 7.6 months) vs chemotherapy alone (arm C, 5.5 months; hazard ratios were 0.524 (95% CI, 0.370-0.742; P < .001 [A vs C]) and 0.478 (95% CI, 0.336-0.679; P < .001 [B vs C]). Higher IRC-assessed ORR and longer IRC-assessed duration of response were observed in arms A (72.5%; 8.2 months) and B (74.8%; 8.6 months) vs C (49.6%; 4.2 months). No association was observed between PD-L1 expression and IRC-assessed PFS or ORR. Discontinuation of any treatment because of AEs was reported in 15 (12.5%; arm A), 35 (29.7%; arm B), and 18 (15.4%; arm C) patients. In each arm, the most common grade of 3 or greater AE was decreased neutrophil levels, which aligned with known chemotherapy toxic effects. Six treatment-related AEs leading to death occurred; however, no deaths were solely attributed to tislelizumab. Conclusions and Relevance: In this phase 3 randomized clinical trial, adding tislelizumab to chemotherapy was associated with significantly prolonged IRC-assessed PFS, higher IRC-assessed ORRs, and a manageable safety/tolerability profile in patients with advanced sq-NSCLC, regardless of PD-L1 expression. Trial Registration: ClinicalTrials.gov Identifier: NCT03594747.

2.
J Pharm Pharmacol ; 73(2): 145-151, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33793805

RESUMO

OBJECTIVES: To assess the effect of sildenafil on monocrotaline-induced right ventricular (RV) remodeling and investigate the possible mechanism. METHODS: Rats were subcutaneously injected with monocrotaline to establish an RV remodeling model and then administered sildenafil (25 mg/kg) from days 1 to 28. After 28 days of administration, the RV systolic pressure and the RV hypertrophy index (RVHI) were measured. The morphology of the right ventricle was observed by H&E staining. The ultrastructure of the right ventricle was observed using a transmission electron microscope. The myocardial apoptosis of the right ventricle was evaluated by TUNEL staining. The protein expression of apoptosis-related proteins and PPARs were examined by western blotting. KEY FINDINGS: The results indicated that sildenafil decreased the RV systolic pressure and RVHI, and improved the microstructure and ultrastructure of the right ventricle in monocrotaline-induced rats. In addition, sildenafil suppressed myocardial apoptosis and promoted the protein expression of PPARs of the right ventricle in monocrotaline-induced rats. CONCLUSION: Sildenafil inhibits RV remodeling in monocrotaline-induced rats, which might be partially mediated by reducing myocardial apoptosis and activating PPARs.

3.
Anal Chim Acta ; 1157: 338396, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33832593

RESUMO

Exosomal microRNAs (miRNAs) derived from different cells are proposed to be important noninvasive biomarkers for the diagnosis of cardiovascular disease. Recently, sensitive and reliable sensing of exosomal miRNAs has been garnered significant attention. Herein, a novel electrochemical biosensor based on a step polymerization catalytic hairpin assembly (SP-CHA) circuit is designed for exosomal miR-181 detection. Exosomal miR-181 as a trigger, induced SP-CHA process and generated a large number of T shaped concatemers with different length on the electrode surface. These ultra-concatemers could provide a much enhanced signal-to-noise ratio with the linear range from 10 fM to 100 nM and the detection limit of 7.94 fM. Furthermore, this assay was successfully applied to the detection of exosomal miR-181 in serum samples of normal healthy controls and patients with coronary heart disease (CHD) and the results were consistent with those analysis collected from qRT-PCR. The assembly demonstrated great performance in differentiating CHD patients from healthy controls (AUC:0.9867). Collectively, this sensing system possessed high stability and sensitivity with ease of operation and cost efficiency, leading to great potential for exosomal miRNAs detection in cardiovascular disease.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33835201

RESUMO

African swine fever, a serious infectious disease, has been found in many countries around the world over the last nearly 100 years, and causes untold damage to the economy wherever it occurs. Diagnosis is currently performed by real-time PCR, which is highly sensitive but can only be carried out in a diagnostic laboratory environment with sophisticated equipment and expertise. A sensitive, rapid diagnostic method that can be implemented in agricultural settings is thus urgently needed for the detection and control of African swine fever virus (ASFV) infection. In this study, we developed an isothermal amplification technology to achieve molecular diagnosis of ASFV in clinical samples, using recombinase-aided amplification (RAA) assay combined with a portable instrument. This assay method avoids the limitations of traditional real-time PCR and offers detection times within 20 min, enabling detection of as few as 10 copies of ASFV DNA molecules per reaction without cross-reaction with other common swine viruses. We evaluated clinical performance using 200 clinical blood samples. The coincidence rate of the detection results between rt-RAA and RT-qPCR was 96.94% positive, 100% negative, and 97.50% total. We have also developed an rt-RAA system for the detection of ASFV targeting the EP402R gene, with detection of as few as 10 copies of DNA per reaction; this offers the possibility of DIVA (differentiating infected from vaccinated animals) diagnosis, because CD2V gene-deleted ASFV could soon be approved to be the leading candidate for live attenuated vaccine in China. The rt-RAA assay is a reliable, rapid, highly sensitive method, and it offers a reasonable alternative to RT-qPCR for point-of-care detection of ASFV. KEY POINTS: • The RT-RAA assay can detect as few as 10 copies of ASFV genome per reaction within 20 min. • The rt-RAA assay system targeting different genes can achieve differentiating infected from vaccinated diagnosis.

5.
DNA Cell Biol ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33781092

RESUMO

The abnormal proliferation of vascular smooth muscle cells (VSMCs) is crucial in the atherosclerosis. Although long noncoding RNAs (lncRNAs) are implicated in a variety of diseases, their roles in activation of VSMCs proliferation and vascular disorder diseases are not well understood. In addition, heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) was reported to participate in lncRNAs-mediated function. Herein, we propose to investigate the role of lncRNA AC105942.1 and hnRNPA2/B1 in pathological VSMCs proliferation and the possible mechanisms in vitro. We have identified that lncRNA AC105942.1 was downregulated and hnRNPA2/B1 was upregulated in atherosclerotic plaques compared with normal artery tissues. Enhanced lncRNA AC105942.1 could noticeably inhibit Ang II-induced VSMCs proliferation. Further investigation suggested that lncRNA AC105942.1 could downregulate the expression of hnRNPA2/B1 and then regulate the level of CDK4 and p27. Taken together, our study indicated that lncRNA AC105942.1 downregulated hnRNPA2B1 to protect against the atherosclerosis by suppressing VSMCs proliferation. LncRNA AC105942.1 and hnRNPA2/B1 could represent potential therapeutic and diagnostic targets to atherosclerosis-related diseases.

6.
Zhongguo Zhong Yao Za Zhi ; 46(5): 1205-1210, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33787116

RESUMO

To explore the effect of Baihe Dihuang Decoction on the synaptic plasticity of hippocampal neurons in rats with anxious depression. Fifty SD rats were randomly divided into normal group, model group, venlafaxine group(6.75 mg·kg~(-1)), high-dose Baihe Dihuang Decoction group(8.64 g·kg~(-1)) and low-dose Baihe Dihuang Decoction group(4.32 g·kg~(-1)). Chronic restraint stress(6 h) combined with corticosterone(ih, 30 mg·kg~(-1)) was used to establish an anxious depression model, and 7 days after modeling, the administration started and continued for 21 days. The anxiety and depression-like behaviors of the rats were evaluated. Golgi-Cox staining and electron microscopy were used to observe the morphology and ultrastructural changes of synaptic dendrites. Immunofluorescence was used to detect the expression of hippocampal synaptic plasticity protein synapsin-1 and postsynaptic density protein 95(PSD-95). Western blot method was used to detect the expression of functional protein synaptophysin(SYP) and synaptic Ras GTPase activating protein(SynGap). The results showed that the rats in the model group had obvious anxiety and depression-like behaviors, the hip-pocampal dendritic spine density and branch length were reduced, the number of synapses was cut, and the internal structure was da-maged. The average fluorescence intensity of synapsin-1 and PSD-95 was significantly reduced and the expression of SYP and SynGap also decreased. High-dose Baihe Dihuang Decoction could significantly improve the anxiety and depression-like behaviors of model rats, relieve synaptic damage, and increase the expression of synapsin-1, PSD-95, SYP, and SynGap proteins. Therefore, we believe that Baihe Dihuang Decoction can improve anxiety and depression behaviors by regulating the synaptic plasticity of hippocampal neurons.


Assuntos
Depressão , Plasticidade Neuronal , Animais , Depressão/tratamento farmacológico , Hipocampo , Ratos , Ratos Sprague-Dawley , Sinapses
7.
Nanoscale ; 13(11): 5706-5713, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33683263

RESUMO

Living organisms use interconnected chemical reaction networks (CRNs) to exchange information with the surrounding environment and respond to diverse external stimuli. Inspired by nature, numerous artificial CRNs with a complex information processing function have been recently introduced, with DNA as one of the most attractive engineering materials. Although much progress has been made in DNA-based CRNs in terms of controllable reaction dynamics and molecular computation, the effective integration of signal translation with information processing in a single CRN remains to be difficult. In this work, we introduced a stimuli-responsive DNA reaction network capable of integrated information translation and processing in a stepwise manner. This network is designed to integrate sensing, translation, and decision-making operations by independent modules, in which various logic units capable of performing different functions were realized, including information identification (YES and OR gates), integration (AND and AND-AND gates), integration-filtration (AND-AND-NOT gate), comparison (Comparator), and map-to-map analysis (Feynman gate). Benefitting from the modular and programmable design, continuous and parallel processing operations are also possible. With the innovative functions, we show that the DNA network is a highly useful addition to the current DNA-based CRNs by offering a bottom-up strategy to design devices capable of cascaded information processing with high efficiency.

8.
Food Res Int ; 141: 110146, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33642012

RESUMO

Hong Qu glutinous rice wine (HQ wine) is a traditional alcoholic beverage produced in China by fermenting cooked rice using a fermentation starter prepared with the fungus Monascus purpureus. This starter (Hong Qu, HQ) is made empirically by open spontaneous fermentation that is hard to control and standardize, resulting in inconsistent wine quality. This study investigates representative HQ samples from a large geographic region. It explores fungal microbiome compositions, identifies characteristic differences important for the production of various HQ wine styles, and reveals the key fungi responsible for HQ wine fermentation characteristics. The source of the HQ inoculum was found to be the main factor influencing fungal community composition and diversity, followed by processing technology and geographical distribution. Linear discriminant analysis effect size (LEfSe) uncovered 14 genera as potential biomarkers to distinguish regional varieties of HQ. Significant differences were also found in fermentation characteristics such as liquefying power (LP), saccharifying power (SP), fermenting power (FP), total acid content (TA) and liquor-producing power (LPP). The key fungi responsible for LP (5 genera), SP (3 genera), FP (1 genera), LPP (4 genera), and TA (4 genera) were determined using redundancy correlation analysis. Finally, Spearman's correlation analysis indicated that LPP shows a strong positive correlation with FP and LP, while TA displays a strong negative correlation with FP. The results of this study may be utilized to prepare consistently high quality, next-generation HQ by better controlling fungal community structures, and to design fermentation processes for HQ wines with desirable oenological characteristics.

9.
Aging (Albany NY) ; 13(5): 7259-7283, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33658400

RESUMO

The fuzzy planar cell polarity protein (Fuz) is an effector component of the planar cell polarity (PCP) signaling. Together with other core and effector proteins, the PCP pathway controls polarized cell movements. Fuz was also reported as a negative regulator of cell survival. In this study, we performed a pan-cancer survey to demonstrate the role of Fuz in multiple types of cancer. In head-neck squamous cell carcinoma and lung adenocarcinoma tumor samples, a reduction of Fuz transcript expression was detected. This coincides with the poor overall survival probabilities of these patients. We further showed that Fuz promoter hypermethylation contributes to its transcriptional downregulation. Meanwhile, we also identified a relatively higher mutation frequency at the 404th arginine amino acid residue in the coding sequence of Fuz locus, and further demonstrated that mutant Fuz proteins perturb the pro-apoptotic function of Fuz. In summary, our study unveiled an intriguing relationship between Fuz dysregulation and cancer prognosis, and further provides mechanistic insights of Fuz's involvement in carcinogenesis.

10.
Cancer Med ; 10(8): 2865-2876, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33724715

RESUMO

BACKGROUND: Cancer is an important focus of public health worldwide. This study aims to provide a comprehensive overview of temporal trends in incidence and mortality of leading cancer in Guangzhou, China from 2004 to 2015. METHODS: Data were collected from the population-based registry in Guangzhou. Age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) were calculated and Joinpoint regression was used for evaluating the average annual percent changes (AAPC) among the entire study period and the estimated annual percent changes (EAPC) in time segments. The effects of age, period, and birth cohort were assessed by the age-period-cohort model. RESULTS: The age-standardized incidence and mortality by the world standard population decreased significantly among males with AAPC of -1.7% (95% CI: -3.0%, 0.2%) and -2.7% (95% CI: -4.3%, -1.1%) for all malignancies during 2004-2015, while among females, the age-standardized incidence had a non-significant reduction with AAPC of -1.3% (95% CI: -2.8%, 0.2%) and the age-standardized mortality demonstrated a remarkable decline (AAPC -2.0%, 95% CI: -3.6%, -0.3%). For males, the most commonly diagnosed cancers were trachea, bronchus, and lung (TBL), liver, colorectal, nasopharyngeal, stomach, and prostate cancer. For females, breast, TBL, colorectal, liver stomach, and thyroid cancer ranked the top. Unfavorable trends were observed in ASIR of colorectal, thyroid, and prostate cancer. APC models yielded different ages, periods, and birth cohort effect patterns by cancer sites. CONCLUSIONS: Cancer burden remained a public health challenge in Guangzhou as the aging population and lifestyles changes, despite declines in incidence and mortality rates in some cancers. Surveillance of cancer trends contributed to valuable insights into cancer prevention and control.

11.
Nat Plants ; 7(2): 198-208, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33574576

RESUMO

Late blight caused by Phytophthora infestans greatly constrains potato production. Many Resistance (R) genes were cloned from wild Solanum species and/or introduced into potato cultivars by breeding. However, individual R genes have been overcome by P. infestans evolution; durable resistance remains elusive. We positionally cloned a new R gene, Rpi-amr1, from Solanum americanum, that encodes an NRC helper-dependent CC-NLR protein. Rpi-amr1 confers resistance in potato to all 19 P. infestans isolates tested. Using association genomics and long-read RenSeq, we defined eight additional Rpi-amr1 alleles from different S. americanum and related species. Despite only ~90% identity between Rpi-amr1 proteins, all confer late blight resistance but differentially recognize Avramr1 orthologues and paralogues. We propose that Rpi-amr1 gene family diversity assists detection of diverse paralogues and alleles of the recognized effector, facilitating durable resistance against P. infestans.

12.
Int Immunopharmacol ; 93: 107402, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33540246

RESUMO

Aberrant expression of long non-coding RNA (lncRNA) H19 is tightly linked to multiple steps of tumorigenesis via the modulation of cell proliferation and apoptosis; however, the pathological significance and regulatory mechanisms of lncRNA H19 in macrophages remain obscure. To investigate whether lncRNA H19 modulates macrophage activation in rheumatoid arthritis (RA), lncRNA H19 levels in PMA-induced PBMC from patients with RA and healthy volunteers were assessed. In addition, the distribution of macrophage subsets, macrophage phenotypic characteristics, and pro-inflammatory gene expression were examined in lncRNA H19 smart silencer- or pcDNA 3.1- H19-transfected macrophages and AAV8-mediated H19 overexpression in a Freund' s complete adjuvant-induced arthritis mouse model. The level of lncRNA H19 was higher in RA patients than in healthy volunteers. Silencing of lncRNA H19 altered lipopolysaccharide plus interferon-induced M1 macrophage polarization and decreased IL-6, CD80, CCL8, and CXCL10 expression in macrophages of RA patients. LncRNA H19 overexpression markedly induced IL-6, CD80, HLA-DR, KDM6A, STAT1, IRF5, CCL8, CXCL9, CXCL10, and CXCL11 expression in macrophages and promoted macrophage migration. AAV8-mediated H19 overexpression aggravated arthritis in mice by promoting M1 macrophage polarization along with iNOS, IL-6, CCL8, CXCL9, CXCL10, CXCL11, MMP3, MMP13 and COX-2 expression in mononuclear cells isolated from the swollen ankle. GSK-J4, an inhibitor of KDM6A, suppressed the activity of lncRNA H19 in macrophages and ameliorated lncRNA H19-aggravated arthritis. In summary, the current study demonstrated that lncRNA H19 is upregulated in RA patients and arthritic mice. LncRNA H19 promotes M1 macrophage polarization and aggravates arthritis by upregulating KDM6A expression.

13.
Mol Psychiatry ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542468

RESUMO

Pandemics have become more frequent and more complex during the twenty-first century. Posttraumatic stress disorder (PTSD) following pandemics is a significant public health concern. We sought to provide a reliable estimate of the worldwide prevalence of PTSD after large-scale pandemics as well as associated risk factors, by a systematic review and meta-analysis. We systematically searched the MedLine, Embase, PsycINFO, Web of Science, CNKI, WanFang, medRxiv, and bioRxiv databases to identify studies that were published from the inception up to August 23, 2020, and reported the prevalence of PTSD after pandemics including sudden acute respiratory syndrome (SARS), H1N1, Poliomyelitis, Ebola, Zika, Nipah, Middle Eastern respiratory syndrome coronavirus (MERS-CoV), H5N1, and coronavirus disease 2019 (COVID-19). A total of 88 studies were included in the analysis, with 77 having prevalence information and 70 having risk factors information. The overall pooled prevalence of post-pandemic PTSD across all populations was 22.6% (95% confidence interval (CI): 19.9-25.4%, I2: 99.7%). Healthcare workers had the highest prevalence of PTSD (26.9%; 95% CI: 20.3-33.6%), followed by infected cases (23.8%: 16.6-31.0%), and the general public (19.3%: 15.3-23.2%). However, the heterogeneity of study findings indicates that results should be interpreted cautiously. Risk factors including individual, family, and societal factors, pandemic-related factors, and specific factors in healthcare workers and patients for post-pandemic PTSD were summarized and discussed in this systematic review. Long-term monitoring and early interventions should be implemented to improve post-pandemic mental health and long-term recovery.

14.
Chin J Traumatol ; 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33549392

RESUMO

PURPOSE: Treatment of irreducible femoral intertrochanteric fractures often requires open reduction. However, the technique unavoidably causes patients to suffer greater trauma. As such, minimally invasive techniques should be employed to reduce the surgical-related trauma on these patients and maintain a stable reduction of the fractures. Herein, a minimally invasive wire introducer was designed and used for the treatment of femoral intertrochanteric fractures. The effectiveness of using a wire-guided device to treat irreducible femoral intertrochanteric fractures was evaluated. METHODS: Between 2013 and 2018, patients with femoral intertrochanteric fractures who were initially treated by intramedullary nail fixation but had difficult reduction using the traction beds were retrospectively reviewed. Decision for an additional surgery was based on the displacement of the fracture. The patients were then divided into two groups: those in the control group received an open reduction surgery while those in the observation group received a closed reduction surgery using a minimally invasive wire introducer to guide the wire that could assist in fracture reduction. The operation time, blood loss, visual analogue scale scores, angulation, reduction, neck-shaft angle, re-displacement, limb length discrepancy, and union time were then recorded and analyzed to determine the efficiency of the wire introducer technique. Categorical variables were analyzed by using Chi-square test, while continuous variables by independent t-test and the Mann-Whitney test accordingly. RESULTS: There were 92 patients included in this study: 61 in the control group and 31 in the observation group. There were no significant differences in baseline demographic factors between the two groups. All surgeries were successful with no deaths within the perioperative period. The average follow-up time for the patients was 23.8 months. However, the observation group had a significantly shorter operation time, lower visual analogue scale score, less intraoperative bleeding, and shorter fracture healing time. There were no significant differences in the angulation, reduction, neck-shaft angle, and limb length discrepancy between the two groups. CONCLUSION: The minimally invasive wire guide achieved a similar effect to that of open reduction in the treatment of intertrochanteric fractures with difficult reduction. Moreover, the minimally invasive wire introducer is a good technology that accurately guides the wire during reduction. Indeed, it is an effective technique and achieves good clinical outcomes in restoration of irreducible femoral intertrochanteric fractures.

15.
Jpn J Clin Oncol ; 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33537721

RESUMO

OBJECTIVE: This study was aimed at exploring whether miR-30a enhanced sensitivity of non-small-cell lung cancer (NSCLC) cells against neoadjuvant chemotherapy through an autophagy-dependent way. METHODS: We totally recruited 304 NSCLC patients who have underwent chemotherapy, as well as 185 NSCLC patients who did not receive chemotherapy. NSCLC cell lines (i.e. H1299 and H460) were also purchased, and they were transfected by miR-30a mimic/inhibitor. Furthermore, cisplatin (DDP)/pemetrexed (PEM) resistance of NSCLC cells was assessed utilizing MTT assay, and autophagic proteins isolated from NSCLC tissues and cells were quantitated by western blotting. RESULTS: Lowly expressed miR-30a was reflective of lymph node metastasis, advanced TNM stage and poor 5-year survival among NSCLC patients treated by neoadjuvant chemotherapy (i.e. combined treatment of DDP and PEM) (P < 0.05). Moreover, DDP combined with PEM attenuated viability and proliferation, but, on the contrary, promoted autophagy of H1299 and H460 cell lines (P < 0.05). However, miR-30a undermined resistance of NSCLC cells against DDP and PEM (P < 0.05), and it suppressed DDP/PEM-induced autophagy and promoted DDP/PEM-triggered apoptosis of NSCLC cells (P < 0.05). CONCLUSIONS: Intentionally elevating miR-30a expression was conducive to improving NSCLC prognosis after neoadjuvant chemotherapy, for its depressing drug-caused autophagy and resistance.

16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 137-144, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33554810

RESUMO

OBJECTIVE: To investigate the short-term efficacy and safety of generic bortezomib in the treatment of Chinese patients with multiple myeloma (MM). METHODS: Clinical data of 62 MM patients (median age of 62 years) who had accepted at least 2 cycles of chemotherapy based on generic bortezomib in our center from December 2017 to July 2019 were retrospectively analyzed, including 47 newly diagnosed patients and 15 with disease recurrence or progression. RESULTS: Anemia, renal dysfunction, hypoproteinemia and high level of ß 2-microglobulin were all improved rapidly after induction treatment. In 56 patients who had completed at least 4 cycles of chemotherapy, the overall response rate (ORR) was 85.7%, and 64.3% of the patients achieved very good partial response (VGPR) or better, and 28.6% achieved complete remission (CR) or better. In the 19 patients who had already completed all planned induction and consolidation treatment (9 cycles of chemotherapy or 4-6 cycles of chemotherapy plus autologous hematopoietic stem cell transplantation), 84.2% achieved VGPR or better, and 57.9% achieved CR or stringent complete remission (sCR). Median follow-up time was 300 days with data cut-off date of September 20, 2019, and the progression-free survival (PFS) rate and overall survival (OS) rate were 62.1% and 85.3%, respectively. The possible adverse reactions associated with bortezomib were grade 1-2, the most common hematologic adverse reaction was thrombocytopenia (27.4%), and the most common non-hematologic adverse reaction was peripheral neuropathy (43.5%), followed by asthenia (37.1%). CONCLUSION: The disease severity can be rapidly alleviated after generic bortezomib-based chemotherapy, and a favorable short-term efficacy and survival have been observed with a generally acceptable toxicity profile. However, the long-term outcomes will be examined through further follow-up.


Assuntos
Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/uso terapêutico , Dexametasona/uso terapêutico , Intervalo Livre de Doença , Humanos , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento
17.
Org Lett ; 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33599508

RESUMO

Diboron-mediated rhodium-catalyzed transfer hydrogenation of functionalized arenes is reported. In addition to good functional group tolerance, the reaction features operational simplicity and controllable chemoselectivity. The general applicability of this procedure is demonstrated by the selective hydrogenation of a range of arenes, including functionalized benzenes, biphenyls, and polyaromatics.

18.
Anim Sci J ; 92(1): e13527, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33615637

RESUMO

Non-alcoholic fatty liver disease (NAFLD) occurs in humans, domestic animals and poultry. Different from upregulation of complement C3 in human NAFLD, C3 expression is inhibited in goose fatty liver (GFL), implying a specific role of C3 in GFL. This study was mainly focused on uncovering the uniqueness of goose liver cells in the regulation of C3 expression and identifying the downstream genes of C3 to improve understanding on the specific role of C3 in GFL. The results showed that C3 expression was inhibited in the liver, muscle and fat tissues of the overfed versus control (normally fed) geese. Oleate and insulin could inhibit C3 expression in goose primary hepatocytes but induce it in mouse primary hepatocytes. A total of 1,123 differentially expressed genes (DEGs) were affected by C3 overexpression and were mainly enriched in immune response/inflammation and catabolism-related KEGG pathways. Additionally, the representative downstream genes (FASN and ETNK1) of C3 could mediate the role of C3 in the development of GFL. In conclusion, the suppression of C3 in GFL is at least partially attributed to hyperinsulinemia, hyperlipidemia and uniqueness of goose liver cells. Complement C3 does not only affect hepatic steatosis but also affect inflammation/immune response in GFL.

19.
Sci Total Environ ; 774: 145707, 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33611009

RESUMO

BACKGROUND: The association of ambient fine particulate pollution with daily outpatient clinic visits (OCV) for hypertension in China remains to be investigated. OBJECTIVES: This study aimed to examine short-term impacts of exposure to fine particulate matter of aerodynamic diameter < 2.5µm (PM2.5) on daily OCV for hypertension, using a large-scale multi-center community database in Guangzhou, one of the most densely-populated cities in Southern China. METHODS: We collected a total of 28,548 individual records of OCV from 22 community healthcare facilities in Guangzhou from January 1st to May 7th 2020. Hourly data on air pollutants and daily information on meteorological factors were obtained. According to the World Health Organization air-quality guidelines, daily excessive concentration hours (DECH) was calculated. PM2.5 daily mean, hourly-peak concentration and DECH were used as the exposure variables. Based on a case-time-control design, the Cox regression model was applied to evaluate the short-term relative risks (RR) of daily OCV for hypertension. Sensitivity analyses were conducted, with nitrogen dioxide, sulfur dioxide, carbon monoxide, and ozone being adjusted. RESULTS: Daily mean and hourly-peak of PM2.5 were significantly associated with daily OCV for hypertension, while weaker associations were observed for DECH. The estimated RRs at lag day 0 were 1.039 (95% confidence interval [CI]: 1.037, 1.040), 1.851 (95%CI: 1.814, 1.888), and 1.287 (95%CI: 1.276, 1.298), respectively, in association with a 1-unit increase in DECH, daily mean, and hourly-peak concentration of PM2.5. For the lagged effect, lag4 models estimated the greatest RRs for PM2.5 DECH and hourly-peak, whereas a lag2 model produced the highest for PM2.5 daily mean. DISCUSSION: This study consolidates the evidence for a positive correlation between ambient PM2.5 exposure and risks of hypertensive OCV. It also provides profound insight regarding planning for health services needs and establishing early environmental responses to the worsening air pollution in the communities.

20.
Obstet Gynecol Sci ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33631068

RESUMO

Objective: To determine the risk factors for occult endometrial atypia and malignancy in patients diagnosed with non-atypical endometrial hyperplasia (NEH) on endometrial biopsy. Methods: All new cases of NEH diagnosed between April 2015 and March 2016 at KK Women's and Children's Hospital, who underwent hysterectomy as first-line treatment, were included in the study. Patients with a history of endometrial hyperplasia or malignancy were excluded from the study. Patient demographics (e.g., age, parity, body mass index [BMI]), medical history, and clinical presentation were obtained for analysis. Results: In total, 262 patients were diagnosed with NEH, of which 18.3% (n=48) underwent hysterectomy as first-line management. The average time to surgery was 77.0±35.7 days. All cases were diagnosed by dilation and curettage, and hysteroscopy. The mean age was 51 years, and the mean BMI was 26.9±5.8 kg/m2. Histology from the hysterectomy specimen showed 9 (18.8%) patients with atypical hyperplasia and 2 (4.2%) with grade 1, stage 1A endometrioid adenocarcinoma. Patients with higher grade final pathology had significantly lower median parity (1 vs. 2, P=0.039), higher mean BMI (30.1±6.5 vs 25.9±5.3 kg/m2, P=0.033), and BMI ≥30 kg/m2 (54.5% vs. 13.5%, P=0.008, odds ratio 7.68), compared to patients whose final histology showed NEH or no residual hyperplasia. Conclusion: Occult endometrial atypia and malignancy were found in 18.8% and 4.2% of patients with an initial diagnosis of NEH, respectively. High BMI and low parity were identified as significant risk factors for high-grade endometrial lesions in patients with NEH.

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