Publications by authors named "Dan Cao"

250 Publications

Anterior-posterior hippocampal dynamics support working memory processing.

J Neurosci 2021 Nov 23. Epub 2021 Nov 23.

Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China

The hippocampus is a locus of working memory (WM) with anterior and posterior subregions that differ in their transcriptional and external connectivity patterns. However, the involvement and functional connections between these subregions in WM processing are poorly understood. To address these issues, we recorded intracranial EEG from the anterior and the posterior hippocampus in human (7 females and 7 males) who maintained a set of letters in their WM. We found that WM maintenance was accompanied by elevated low-frequency activity in both the anterior and posterior hippocampus and by increased theta/alpha band (3-12 Hz) phase synchronization between anterior and posterior subregions. Cross-frequency and Granger prediction analyses consistently showed that the correct WM trials were associated with theta/alpha band-coordinated unidirectional influence from the posterior to the anterior hippocampus. In contrast, WM errors were associated with bidirectional interactions between the anterior and posterior hippocampus. These findings imply that theta/alpha band synchrony within the hippocampus may support successful WM via a posterior to anterior influence. A combination of intracranial recording and a fine-grained atlas may be of value in understanding the neural mechanisms of WM processing.Working memory (WM) is crucial to everyday functioning. The hippocampus has been proposed to be a subcortical node involved in WM processes. Previous studies suggest that the anterior and posterior hippocampus differ in their external connectivity patterns and gene expression. However, it remains unknown whether and how human hippocampal subregions are recruited and coordinated during WM tasks. Here, by recording intracranial electroencephalography simultaneously from both hippocampal subregions, we found enhanced power in both areas and increased phase synchronization between them. Furthermore, correct WM trials were associated with a unidirectional influence from the posterior to the anterior hippocampus, whereas error trials were correlated with bidirectional interactions. These findings indicate a long-axis specialization in the human hippocampus during WM processing.
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http://dx.doi.org/10.1523/JNEUROSCI.1287-21.2021DOI Listing
November 2021

Whether high government subsidies reduce the healthcare provision of township healthcare centers in rural China.

BMC Health Serv Res 2021 Oct 30;21(1):1184. Epub 2021 Oct 30.

School of Public Policy and Administration, Xi'an Jiaotong University, Xi'an, 710049, China.

Background: China's government launched a large-scale healthcare reform from 2009. One of the main targets of this round reform was to improve the primary health care system. Major reforms for primary healthcare institutions include increasing government investment. However, there are insufficient empirical studies based on large sample to catch long-term effect of increased government subsidy and lack of sufficient incentives on township healthcare centers (THCs), therefore, this study aims to provide additional empirical evidence on the concern by conducting an empirical analysis of THCs in Shaanxi province in China.

Methods: We collected nine years (2009 to 2017) data of THCs from the Health Finance Annual Report System (HFARS) that was acquired from the Health Commission of Shaanxi Province. We applied two-way fixed effect model and continue difference-in-difference (DID) model to estimate the effect of percentage of government subsidy on medical provision.

Results: A clear jump of the average percentage of government subsidy to total revenue of THCs can be found in Shaanxi province in 2011, and the average percentage has been more than 60% after 2011. Continue DID models indicate every 1% percentage of government subsidy to total revenue increase after 2011 resulted in a decrease of 1.1 to 3.5% in THCs healthcare provision (1.9% in medical revenue, 1.2% in outpatient visit, 3.5% in total occupy beds of inpatient, 1.1% in surgery revenue, 2.1% in sickbed utilization rate). The results show that the THCs with high government subsidy reduce the number of medical services after 2011.

Conclusions: We think that it is no doubt that the government should take more responsibility for the financing of primary healthcare institutions, the problem is when government plays a central role in the financing and delivery of primary health care services, more effective incentives should be developed.
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http://dx.doi.org/10.1186/s12913-021-07201-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8557613PMC
October 2021

Understanding parental self-medication with antibiotics among parents of different nationalities: a cross-sectional study.

Glob Health Res Policy 2021 10 25;6(1):42. Epub 2021 Oct 25.

School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, China.

Background: There is an increasing trend on the practices of parental self-medication with antibiotics (PSMA) around world, accelerating the antibiotic abuse. This study aims to examine the nationality differences in the practices of PSMA and knowledge, attitudes and practices (KAP) toward antibiotic use, and understand the practices of PSMA among parents of various nationalities in China.

Methods: A cross-sectional study based on a structured questionnaire survey was conducted in Xi'an, Shaanxi Province, China, from September 2018 to October 2018. A total of 299 respondents participated in. The practices of PSMA (a dichotomous variable) and KAP toward antibiotic use (a continuous variable) served as dependent variables. Participant's nationality was regarded as the independent variable. Binary logistic regression and ordinary least square regression were employed to examine the association between parent's nationality and the practices of PSMA, and KAP toward antibiotic use, respectively.

Results: 121 (40.88%) Chinese, 100 (33.76%) other Asians and 75 (25.34%) Occidentals were included in final analysis, with a sample size of 296. Chinese were more likely to practice PSMA (OR = 7.070; 95% CI 1.315, 38.01), with worse knowledge (Coef. = - 0.549; 95% CI - 1.021, - 0.078), attitudes (Coef. = - 3.069; 95% CI - 4.182, - 1.956) and practices (Coef. = - 1.976; 95% CI - 3.162, - 0.790) toward antibiotic use, compared to their Occidental counterparts. The main reasons for the practices of PSMA were enough previous medication experience (80.49%) and same ailments with no need to see a doctor (39.02%), with common symptoms such as fever (60.98%) and cough (58.54%). Purchasing antibiotics at pharmacies (92.08%) and using leftover antibiotics (26.83%) were usual approaches.

Conclusions: The study highlights the gaps in the practices of PSMA and KAP toward antibiotic use among parents of different nationalities. The access to obtain antibiotics from pharmacies reflects the pharmacists' unaware of laws on prescription of antibiotics, fierce competition in the pharmacy market, and the government's lax supervision in China. It suggests the need to improve pharmacists' training, enforce current legislations on pharmacy market regarding the sale of antibiotics, and provide practical and effective educational interventions for residents about antibiotic use.
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http://dx.doi.org/10.1186/s41256-021-00226-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8543833PMC
October 2021

Construction of a Pearson- and MIC-Based Co-expression Network to Identify Potential Cancer Genes.

Interdiscip Sci 2021 Oct 25. Epub 2021 Oct 25.

Hunan Engineering and Technology Research Center for Agricultural Big Data Analysis and Decision-Making, Hunan Agricultural University, Changsha, 410128, Hunan, China.

The weighted gene co-expression network analysis (WGCNA) method constructs co-expressed gene modules based on the linear similarity between paired gene expressions. Linear correlations are the main form of similarity between genes, however, nonlinear correlations still existed and had always been ignored. We proposed a modified network analysis method, WGCNA-P + M, which combines Pearson's correlation coefficient and the maximum information coefficient (MIC) as the similarity measures to assess the linear and nonlinear correlations between genes, respectively. Taking two real datasets, GSE44861 and liver hepatocellular carcinoma (TCGA-LIHC), as examples, we compared the gene modules constructed by WGCNA-P + M and WGCNA from four perspectives: the "Usefulness" score, GO enrichment analysis on genes in the gray module, prediction performance of the top hub gene, survival analysis and literature reports on different hub genes. The results showed that the modules obtained by WGCNA-P + M are more biological meaningful, the hub genes obtained from WGCNA-P + M have more potential cancer genes.
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http://dx.doi.org/10.1007/s12539-021-00485-wDOI Listing
October 2021

Gender differences in depressive symptoms of rural Chinese grandparents caring for grandchildren.

BMC Public Health 2021 10 11;21(1):1838. Epub 2021 Oct 11.

School of Public Policy and Administration, Xi'an Jiaotong University, No. 28 Xianning West Road, Xi'an, 710049, Shaanxi, China.

Background: Caring for grandchildren is regarded as one of the principle roles of middle- and old-aged adults, especially among rural Chinese grandparents. This study aims to examine the gender differences in depressive symptoms of rural Chinese grandparents caring for grandchildren, based on the gender differences in grandparental role engagement and the theories of role strain and role enhancement.

Methods: A total of 4833 rural citizens with one or more grandchildren were selected from the China Health and Retirement Longitudinal Study (CHARLS) conducted in 2015. Grandchild care was measured by continuous variable (duration) and categorical variable (no care, low intensity, moderate intensity, high intensity). Depressive symptoms were assessed by the Center for Epidemiologic Studies Depression Scale (CES-D). We used coarsened exact matching (CEM) to balance the covariates of caregivers and non-caregivers. Following CEM, 1975 non-caregivers and 2212 caregivers were identified (N = 4187). Multilevel linear regression was employed to examine the gender differences in depressive symptoms. We also tested for the moderating role of gender on the association between grandchild care and depressive symptoms.

Results: Grandmothers were more likely to provide grandchild care (54.42% vs 51.43%) at high intensity (61.46% vs 51.01%), with longer duration (39.24 h vs 33.15 h) than that given by grandfathers. Grandmothers suffered more from depressive symptoms than grandfathers, and such gap increased when grandparents were involved in high-intensity care. Grandmothers providing grandchild care, particularly at moderate intensity, were associated with fewer depressive symptoms (Coef. = - 0.087, 95%CI: - 0.163, - 0.010; Coef. = - 0.291, 95%CI: - 0.435, - 0.147), compared with non-caregivers. Grandmothers giving moderate intensity of grandchild care were also associated with fewer depressive symptoms (Coef. = - 0.171, 95% CI: - 0.313, - 0.029), compared with those with low-intensity care. However, such associations were not significant among grandfathers.

Conclusions: Our findings highlight the gender differences in depressive symptoms of rural Chinese grandparents caring for grandchildren. Grandparents should be encouraged to engage in grandchild care, but at moderate intensity. The health status of middle- and old-aged adults, particularly females, should be monitored closely. Humanistic care, preventive care and curative treatment strategies focusing on such populations should be developed and refined.
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http://dx.doi.org/10.1186/s12889-021-11886-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507248PMC
October 2021

Effects of Oral Vitamin C Supplementation on Liver Health and Associated Parameters in Patients With Non-Alcoholic Fatty Liver Disease: A Randomized Clinical Trial.

Front Nutr 2021 14;8:745609. Epub 2021 Sep 14.

Department of Nutrition and Food Safety of School of Public Health, Xi'an Jiaotong University, Xi'an, China.

Non-alcoholic fatty liver disease (NAFLD) is now recognized as the most prevalent hepatic disorder worldwide, and an unhealthy lifestyle is the leading risk factor for its occurrence. Vitamin C (VC) has been suggested to protect NAFLD, whereas evidence from randomized controlled trials (RCTs) is sparse. In this study, we aimed to investigate the potential benefits of VC supplementation daily on liver health and associated parameters in patients with NAFLD. In this double-blind, RCT, 84 patients with NAFLD, aged 18-60 years old, were assigned to 12 weeks of oral treatment with either low (250 mg/day, = 26), medium (1,000 mg/day, = 30), or high (2,000 mg/day, = 28) doses of VC supplements. After the intervention, the Medium group had a more significant decrease in aspartate aminotransferase [Medium, -5.00 (-10.25, -1.75) vs. High, -2.50 (-7.75, 0.00), = 0.02] and alanine aminotransferase [Medium, -8.00 (-18.00, -1.75) vs. High, -3.50 (-13.75, 4.25), = 0.05; Medium vs. Low, -3.00 (-9.00, 5.50), = 0.031]. The levels of other indicators of liver health, such as gamma-glutamyl transferase, alkaline phosphatase, total bilirubin, and direct bilirubin were decreased after the intervention but comparable among the three groups and so did the parameters of glucose metabolism, such as fasting insulin, fasting glucose, and homeostasis model assessment for insulin resistance. The plasma level of VC in patients and total adiponectin and high molecular weight (HMW) adiponectin levels were also elevated but not in a dose-dependent manner. Meanwhile, analysis of fecal microbiota composition showed an increase in the alpha diversity (Abundance-based Coverage Estimator (ACE), Shannon, chao1, and Simpson) both in the Low and the Medium groups. A total of 12 weeks of VC supplementation, especially 1,000 mg/day, improved liver health and glucose metabolism in patients with NAFLD. The elevated plasma levels of VC, total and HMW adiponectin, and the improvement of intestinal microbiota may have made some contributions.
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http://dx.doi.org/10.3389/fnut.2021.745609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478121PMC
September 2021

CAR-T therapy: Prospects in targeting cancer stem cells.

J Cell Mol Med 2021 Nov 28;25(21):9891-9904. Epub 2021 Sep 28.

Basic Laboratory, Suining Central Hospital, Suining, China.

Cancer stem cells (CSCs), a group of tumour cells with stem cell characteristics, have the ability of self-renewal, multi-lineage differentiation and tumour formation. Since CSCs are resistant to conventional radiotherapy and chemotherapy, their existence may be one of the root causes of cancer treatment failure and tumour progression. The elimination of CSCs may be effective for eventual tumour eradication. Because of the good therapeutic effects without major histocompatibility complex (MHC) restriction and the unique characteristics of CSCs, chimeric antigen receptor T-cell (CAR-T) therapy is expected to be an important method to eliminate CSCs. In this review, we have discussed the feasibility of CSCs-targeted CAR-T therapy for cancer treatment, summarized current research and clinical trials of targeting CSCs with CAR-T cells and forecasted the challenges and future direction from the perspectives of toxicity, persistence and potency, trafficking, infiltration, immunosuppressive tumour microenvironment, and tumour heterogeneity.
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http://dx.doi.org/10.1111/jcmm.16939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8572776PMC
November 2021

Intrahepatic cholangiocyte regeneration from an Fgf-dependent extrahepatic progenitor niche in a zebrafish model of Alagille Syndrome.

Hepatology 2021 Sep 27. Epub 2021 Sep 27.

Human Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, United States.

Alagille Syndrome (ALGS) is a congenital disorder caused by mutations in the Notch ligand gene, JAGGED1, leading to neonatal loss of intrahepatic duct (IHD) cells and cholestasis. Cholestasis can resolve in certain ALGS patients, suggesting regeneration of IHD cells. However, the mechanisms driving IHD cell regeneration following Jagged loss remains unclear. Here, we show that cholestasis due to developmental loss of IHD cells can be consistently phenocopied in zebrafish with compound jagged1b and jagged2b mutations or knockdown. Leveraging the transience of jagged knockdown in juvenile zebrafish, we find that resumption of Jagged expression leads to robust regeneration of IHD cells via a Notch-dependent mechanism. Combining multiple lineage tracing strategies with whole liver 3D-imaging, we demonstrate that the extrahepatic duct (EHD) is the primary source of multipotent progenitors that contribute to the regeneration, but not to the development, of IHD cells. Hepatocyte-to-IHD cell transdifferentiation is possible, but rarely detected. Progenitors in the EHD proliferate and migrate into the liver with Notch signaling loss and differentiate into IHD cells if Notch signaling increases. Tissue-specific mosaic analysis with an inducible dominant-negative Fgf receptor suggests that Fgf signaling from the surrounding mesenchymal cells maintains this extrahepatic niche by directly preventing premature differentiation and allocation of EHD progenitors to the liver. Indeed, transcriptional profiling and functional analysis of adult mouse EHD organoids uncover their distinct differentiation and proliferative potential relative to IHD organoids. CONCLUSION: Our data show that IHD cells regenerate upon resumption of Jag/Notch signaling, from multipotent progenitors originating from an Fgf-dependent extrahepatic stem cell niche. We posit that if Jagged/Notch signaling is augmented, via normal stochastic variation, gene therapy, or a Notch agonist, regeneration of IHD cells in ALGS patients may be enhanced.
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http://dx.doi.org/10.1002/hep.32173DOI Listing
September 2021

Authors' response.

Am J Orthod Dentofacial Orthop 2021 09;160(3):336-337

Nanjing, China.

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http://dx.doi.org/10.1016/j.ajodo.2021.06.005DOI Listing
September 2021

Effects of hyperventilation with face mask on brain network in patients with epilepsy.

Epilepsy Res 2021 10 15;176:106741. Epub 2021 Aug 15.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China; Beijing Key Laboratory of Neuromodulation, Beijing, 100053, China; Center of Epilepsy, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, 100053, China. Electronic address:

Objectives: During the ongoing pandemic of COVID-19, wearing face masks was recommended, including patients with epilepsy doing the hyperventilation (HV) test during electroencephalogram (EEG) examination somewhere. However, evidence was still limited about the effect of HV with face mask on cortical excitability of patients with epilepsy. The motivation of this work is to make use of the graph theory of EEG to characterize the cortical excitability of patients with epilepsy when they did HV under the condition wearing a surgical face mask.

Methods: We recruited 19 patients with epilepsy and 17 normal controls. All of participants completed two HV experiments, including HV with face mask (HV+) and HV without a mask (HV). The interval was 30 min and the sequence was random. Each experiment consisted of three segments: resting EEG, EEG of HV, and EEG of post-HV. EEG were recorded successively during each experiment. Participants were asked to evaluate the discomfort degree using a questionnaire when every HV is completed.

Results: All of the participants felt more uncomfortable after HV + . Moreover, not only HV decreased small-worldness index in patients with epilepsy, but also HV + significantly increased the clustering coefficient in patients with epilepsy. Importantly, the three-way of Mask*HV*Epilepsy showed interaction in the clustering coefficient in the delta band, as well as in the path length and the small-worldness index in the theta band.

Conclusions: The results of this study indicated that patients with epilepsy showed the increased excitability of brain network during HV + . We should pay more attention to the adverse effect on brain network excitability caused by HV + in patients with epilepsy. In the clinical practice under the COVID-19 pandemic, it is important that the wearing face mask remain cautious for the individuals with epilepsy when they carried out HV behavior such as exercise (e.g., running, etc.).
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http://dx.doi.org/10.1016/j.eplepsyres.2021.106741DOI Listing
October 2021

Investigation of cell wall proteins of C. sinensis leaves by combining cell wall proteomics and N-glycoproteomics.

BMC Plant Biol 2021 Aug 20;21(1):384. Epub 2021 Aug 20.

Fruit and Tea Research Institute, Hubei Academy of Agricultural Sciences, No. 10 Nanhu Road, Wuhan, 430064, Hubei, People's Republic of China.

Background: C. sinensis is an important economic crop with fluoride over-accumulation in its leaves, which poses a serious threat to human health due to its leaf consumption as tea. Recently, our study has indicated that cell wall proteins (CWPs) probably play a vital role in fluoride accumulation/detoxification in C. sinensis. However, there has been a lack in CWP identification and characterization up to now. This study is aimed to characterize cell wall proteome of C. sinensis leaves and to develop more CWPs related to stress response. A strategy of combined cell wall proteomics and N-glycoproteomics was employed to investigate CWPs. CWPs were extracted by sequential salt buffers, while N-glycoproteins were enriched by hydrophilic interaction chromatography method using C. sinensis leaves as a material. Afterwards all the proteins were subjected to UPLC-MS/MS analysis.

Results: A total of 501 CWPs and 195 CWPs were identified respectively by cell wall proteomics and N-glycoproteomics profiling with 118 CWPs in common. Notably, N-glycoproteomics is a feasible method for CWP identification, and it can enhance CWP coverage. Among identified CWPs, proteins acting on cell wall polysaccharides constitute the largest functional class, most of which might be involved in cell wall structure remodeling. The second largest functional class mainly encompass various proteases related to CWP turnover and maturation. Oxidoreductases represent the third largest functional class, most of which (especially Class III peroxidases) participate in defense response. As expected, identified CWPs are mainly related to plant cell wall formation and defense response.

Conclusion: This was the first large-scale investigation of CWPs in C. sinensis through cell wall proteomics and N-glycoproteomics. Our results not only provide a database for further research on CWPs, but also an insight into cell wall formation and defense response in C. sinensis.
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http://dx.doi.org/10.1186/s12870-021-03166-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377857PMC
August 2021

Comparative safety and tolerability of approved PARP inhibitors in cancer: A systematic review and network meta-analysis.

Pharmacol Res 2021 10 11;172:105808. Epub 2021 Aug 11.

Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China; Research Laboratory of Tumor Epigenetics and Genomics for General Surgery, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address:

Background: We aimed to evaluate comparative safety and tolerability of the approved PARP inhibitors in people with cancer.

Methods: Eligible studies included randomized controlled trials comparing an approved PARP inhibitor (fluzoparib, olaparib, rucaparib, niraparib, or talazoparib) with placebo or chemotherapy in cancer patients. Outcomes of interest included: serious adverse event (SAE), discontinuation due to adverse event (AE), interruption of treatment due to AE, dose reduction due to AE, and specific grade 1-5 AEs.

Results: Ten trials including 3763 participants and six treatments (olaparib, rucaparib, niraparib, talazoparib, placebo, and protocol-specified single agent chemotherapy) were identified. SAE and discontinuation of treatment did not differ significantly among the four approved PARP inhibitors. Regarding interruption of treatment and dose reduction due to AE, statistically significant differences and statistically non-significant trend were observed. Talazoparib is associated with a higher risk of interruption of treatment and dose reduction (excluding rucaparib) due to AE as compared with the other drugs. Niraparib showed a trend of lower risk of AE related dose reduction as compared with the other drugs. Furthermore, there were significant differences in specific grade 1-5 AE among the four drugs.

Conclusion: The safety profile of the four approved PARP inhibitors is comparable in terms of SAE and AE-related discontinuation of treatment. Statistically significant differences in the AEs spectrum and AEs related dose interruption and dose reduction demonstrated the prompt identification of AE and dose personalization seem mandatory to obtain maximal benefit from PARP inhibitors.
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http://dx.doi.org/10.1016/j.phrs.2021.105808DOI Listing
October 2021

Correction to: The germline/somatic DNA damage repair gene mutations modulate the therapeutic response in Chinese patients with advanced pancreatic ductal adenocarcinoma.

J Transl Med 2021 Aug 12;19(1):345. Epub 2021 Aug 12.

Department of Abdominal Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

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http://dx.doi.org/10.1186/s12967-021-02997-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361738PMC
August 2021

Enzyme-free fluorescence determination of uric acid and trace Hg(II) in serum using Si/N doped carbon dots.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Dec 16;263:120182. Epub 2021 Jul 16.

West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China. Electronic address:

A new fluorescence probe method for the detection of Hg(II) in serum was established, which has the detection limit of 3.57 nM and quantification limit of 5 nM, based on the electrostatic induced agglomeration quenching and complexation between Hg(II) and silicon-nitrogen-doped carbon nanodots (Si/N-CDs). Furthermore, the fluorescence probe also showed the satisfactory results in the determination of Hg(II) in human serum. Subsequently, take advantage of the uric acid (UA) to recover the fluorescence of the Si/N-CDs-Hg(II) complex probe, another enzyme-free ways to determine UA was developed. The complex probe can selectively detect the UA content in the 0.5-30 μM range, and its detection limit can reach 0.14 μM, which has successfully detected the UA in total serum, and the results were no significant difference comparing with the controls.
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http://dx.doi.org/10.1016/j.saa.2021.120182DOI Listing
December 2021

The germline/somatic DNA damage repair gene mutations modulate the therapeutic response in Chinese patients with advanced pancreatic ductal adenocarcinoma.

J Transl Med 2021 07 12;19(1):301. Epub 2021 Jul 12.

Department of Abdominal Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with molecular heterogeneity, inducing differences in biological behavior, and therapeutic strategy. NGS profiles of pathogenic alterations in the Chinese PDAC population are limited. We conducted a retrospective study to investigate the predictive role of DNA damage repair (DDR) mutations in precision medicine.

Methods: The NGS profiles were performed on resected tissues from 195 Chinese PDAC patients. Baseline clinical or genetic characteristics and survival status were collected. The Kaplan-Meier survival analyses were performed by the R version 3.6.1.

Results: The main driver genes were KRAS, TP53, CDKN2A, and SMAD4. Advanced patients with KRAS mutation showed a worse OS than KRAS wild-type (p = 0.048). DDR pathogenic deficiency was identified in 30 (15.38%) of overall patients, mainly involving BRCA2 (n = 9, 4.62%), ATM (n = 8, 4.10%) and RAD50 genes (n = 3, 1.54%). No significance of OS between patients with or without DDR mutations (p = 0.88). But DDR mutation was an independent prognostic factor for survival analysis of advanced PDAC patients (p = 0.032). For DDR mutant patients, treatment with platinum-based chemotherapy (p = 0.0096) or olaparib (p = 0.018) respectively improved the overall survival. No statistical difference between tumor mutation burden (TMB) and DDR mutations was identified. Treatment of PD-1 blockades did not bring significantly improved OS to DDR-mutated patients than the naive DDR group (p = 0.14).

Conclusions: In this retrospective study, we showed the role of germline and somatic DDR mutation in predicting the efficacy of olaparib and platinum-based chemotherapy in Chinese patients. However, the value of DDR mutation in the prediction of hypermutation status and the sensitivity to the PD-1 blockade needed further investigation.
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http://dx.doi.org/10.1186/s12967-021-02972-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273977PMC
July 2021

METTL9 mediated N1-histidine methylation of zinc transporters is required for tumor growth.

Protein Cell 2021 Jul 4. Epub 2021 Jul 4.

Department of Gastroenterology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, China.

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http://dx.doi.org/10.1007/s13238-021-00857-4DOI Listing
July 2021

Genome-wide identification and characterization of phosphate transporter gene family members in tea plants (Camellia sinensis L. O. kuntze) under different selenite levels.

Plant Physiol Biochem 2021 Sep 26;166:668-676. Epub 2021 Jun 26.

Key Laboratory of Tea Science of Ministry of Education, National Research Center of Engineering and Technology for Utilization of Botanical Functional Ingredients & Co-Innovation Center of Education Ministry for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha, Hunan, 410128, China. Electronic address:

Selenium (Se) is an essential element for human health and an important nutrient for plant growth. Selenite is the main form of Se available to plants in acidic soils. Previous studies have shown that phosphate transporters (PTHs) participate in selenite uptake in plants. Research on the PHT gene family is therefore vital for production of Se-rich products. Here, 23 CsPHT genes were identified in the tea (Camellia sinensis) genome and renamed based on homology with AtPHT genes in Arabidopsis thaliana. The CsPHT genes were divided into four subfamilies: PHT1, PHT3, PHT4, and PHO, containing nine, three, six, and five genes, respectively. Phylogenetic analysis indicated that fewer duplication events occurred in tea plants than in A. thaliana, rice, apple, and poplar. Genes in the same subfamily tended to share similar gene structures, conserved motifs, and potential functions. CsPHT genes were differentially expressed in various tissues and in roots under different Se levels, suggesting key roles in selenite uptake, translocation, and homeostasis. The results illuminate the contributions of CsPHT genes to selenite supply in tea plants, and lay a foundation for follow-up studies on their potential functions in this plant species.
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http://dx.doi.org/10.1016/j.plaphy.2021.06.038DOI Listing
September 2021

Analysis of the intestinal microbiota in COVID-19 patients and its correlation with the inflammatory factor IL-18.

Med Microecol 2020 Sep 28;5:100023. Epub 2020 Sep 28.

The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

The ongoing global pandemic of COVID-19 disease, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mainly infect lung epithelial cells, and spread mainly through respiratory droplets. However, recent studies showed potential intestinal infection of SARS-CoV-2, implicated the possibility that the intestinal infection of SARS-CoV-2 may correlate with the dysbiosis of gut microbiota, as well as the severity of COVID-19 symptoms. Here, we investigated the alteration of the gut microbiota in COVID-19 patients, as well as analyzed the correlation between the altered microbes and the levels of intestinal inflammatory cytokine IL-18, which was reported to be elevated in the serum of in COVID-19 patients. Comparing with healthy controls or seasonal flu patients, the gut microbiota showed significantly reduced diversity, with increased opportunistic pathogens in COVID-19 patients. Also, IL-18 level was higher in the fecal samples of COVID-19 patients than in those of either healthy controls or seasonal flu patients. Moreover, the IL-18 levels were even higher in the fecal supernatants obtained from COVID-19 patients that tested positive for SARS-CoV-2 RNA than those that tested negative in fecal samples. These results indicate that changes in gut microbiota composition might contribute to SARS-CoV-2-induced production of inflammatory cytokines in the intestine and potentially also to the onset of a cytokine storm.
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http://dx.doi.org/10.1016/j.medmic.2020.100023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832617PMC
September 2020

Neural Mechanism of Noise Affecting Face Recognition.

Neuroscience 2021 08 18;468:211-219. Epub 2021 Jun 18.

Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing 100049, China; Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; Key Laboratory for Neuro Information of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China; Queensland Brain Institute, University of Queensland, 4072 Brisbane, Australia. Electronic address:

Face recognition is one of the most important cognitive functions for humans in social activities. The ability will be negatively affected when the face images deteriorate. However, the neural process of extracting facial information under challenging conditions is still poorly understood. Therefore, it is necessary to further understand the neurophysiological relevance of this effect. We examined patients with multiple subdural electrodes (ECoG) monitored for clinical purposes. During the experimental task, the patients were presented with face and house images with different noise levels and were asked to recognize the faces. We found a striking increase in high gamma band power (HGP; 60-160 Hz) when face images were shown. We localized the face-specific electrodes to the fusiform gyrus (FG) and surrounding cortices. For each subject, the behavioral performance and magnitudes of the HGP for the face-specific sites significantly both fit a sigmoid function and showed similar changes. Additionally, the curve profile of the average HGP magnitude across the face-specific sites was almost equal to the average behavior curve; the former could precisely track the behavioral performance. In general, these results suggest that the HGP in the FG is closely related to the performance of face image recognition.
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http://dx.doi.org/10.1016/j.neuroscience.2021.06.017DOI Listing
August 2021

Evaluating global ecosystem water use efficiency response to drought based on multi-model analysis.

Sci Total Environ 2021 Jul 11;778:146356. Epub 2021 Mar 11.

State Key Laboratory of Urban and Regional Ecology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China; College of Resources and Environment, University of Chinese Academy of Sciences, China.

Drought has serious consequences on terrestrial ecosystems, particularly for their carbon and water processes. As an important indicator to examine the balance of ecosystem water and carbon cycles, ecosystem water use efficiency (WUE) has been widely used to investigate ecosystem responses to drought. However, the response of WUE to drought and the role of different ecosystem processes in controlling the response of WUE to drought are not well studied. In this paper, we used four WUE datasets from different remote sensing-driven (RS-driven) models and three drought indices (Standardized Precipitation Evapotranspiration Index, soil moisture anomaly index and water storage anomaly-based drought index) to comprehensively investigate the response of WUE to drought and its dominant ecosystem processes during the period of 2001-2018. The results showed the WUE datasets from four different RS-driven models had discrepancies in WUE temporal trends, particularly in tropical and subtropical forest and semi-arid regions. The Spearman correlation analysis revealed that the positive correlations between WUE and drought accounted for more than half of global vegetated lands, while negative relationship mainly occurred in the high latitude regions. We further explored the dominant ecosystem processes (represented by GPP and ET) in controlling WUE response to drought, and found ET controlled WUE-drought relationship in the high latitude areas and semi-arid/sub-humid regions, while GPP dominated it in tropical forest regions. Additionally, the effects of GPP and ET on controlling WUE response to drought were examined to change with different drought indices, especially in the semi-arid regions. Our study suggests multi-model analysis tend to reduce uncertainties in analyzing WUE response to drought caused by a single WUE data. Moreover, our results highlight the different role of ecosystem processes in controlling WUE response to drought and provide new information for the underlying mechanism of drought impacts on ecosystem water and carbon cycles.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146356DOI Listing
July 2021

Combination of gemcitabine, nab-paclitaxel, and S-1(GAS) as the first-line treatment for patients with locally advanced or advanced pancreatic ductal adenocarcinoma: study protocol for an open-label, single-arm phase I study.

BMC Cancer 2021 May 13;21(1):545. Epub 2021 May 13.

Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, No.37 Guoxue Alley, Chengdu, 610041, Sichuan, China.

Background: Pancreatic ductal adenocarcinoma (PDAC) is still a highly fatal malignancy among the most common cancers. More powerful treatments are expecting to bring hope for patients. Biweekly gemcitabine/nab-paclitaxel/S-1 (GAS) was proved safe and effective for patients with locally advanced pancreatic cancer in Japan. The objective of this study is to evaluate the feasibility and toxicity of GAS (repeated every 3 weeks) in the treatment of locally advanced or advanced pancreatic cancer and determine the recommended dose of S-1 in this combination.

Methods: This is an open-label, single-arm, and single-center phase I trial. Patients who have been diagnosed with locally advanced or advanced PDAC pathologically without previous systemic treatments will be enrolled and be treated with GAS chemotherapy every 3 weeks (nab-paclitaxel 125 mg/m , ivgtt, day1, 8; gemcitabine 1000 mg/m, day1, 8; different doses of S-1 within a dose escalation scheme) until the presence of disease progression (PD), intolerable adverse events (AEs), or requirement of patients and researchers. The primary endpoints are maximum tolerated dose (MTD) and dose-limiting toxicity (DLT). The secondary endpoints include safety, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS).

Discussion: This trial will adjust the administration of GAS to make it more effective for Chinese patients, while exploring the toxicity and feasibility of this adjustment.

Trial Registration: ChiCTR, ( ChiCTR1900027833 ). Registered 30 November 2019.
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http://dx.doi.org/10.1186/s12885-021-08275-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117556PMC
May 2021

Volar locking plate versus external fixation for unstable distal radius fractures: a systematic review and meta-analysis based on randomized controlled trials.

BMC Musculoskelet Disord 2021 May 12;22(1):433. Epub 2021 May 12.

Department of Orthopedics, The First People's Hospital of Longquanyi District, 610100, Chengdu, China.

Background: The outcomes for volar locking plate (VLP) and external fixation (EF) in distal radius fracture cases remain controversial. The current study of randomized controlled trials (RCTs) aimed to assess VLP and EF, which might benefit distal radius fracture cases.

Methods: RCTs comparing VLP and EF in distal radius fracture cases, until 18 March 2020, were systematically reviewed and summarized. The functional and radiographic outcomes, together with complications, for distal radius fracture cases, were evaluated.

Results: In total, 12 studies comprising 1205 distal radius fracture cases were included. The VLP group had observed lower disability in the arm shoulder and hand score (DASH) at 3rd, 6th, and 12th -month post-operation, with the mean differences (MDs) of - 10.43 (95 % CI = - 15.77 to - 5.08, P < 0.01), - 3.48 (95 % CI = - 6.37 to - 0.59, P = 0.02), and - 4.13 (95 % CI = - 6.94 to - 1.33, P < 0.01), respectively. The VLP group also had lower visual analog scale scores (VAS) compared to the EF group, with MDs of - 0.10 (95 % CI = - 0.18 to - 0.03, P < 0.01) for the former at 6th -month post-operation. Also, the EF group exhibited better grip strength than that in the VLP group, with MD of 12.48 (95 % CI = 7.00-17.95, P < 0.01) at the 3rd month and 4.54 (95 % CI = 0.31-8.76, P = 0.04) at 6th month. No significant differences in radiographic outcomes were observed between the VLP and EF groups (P > 0.05). The VLP group had a lower complication rate than that in the EF group.

Conclusions: VLP had a lower DASH score and VAS score but with lower grip strength. No significant differences in radiographic outcomes were observed. VLP had a lower complication rate than that of EF.
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http://dx.doi.org/10.1186/s12891-021-04312-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117612PMC
May 2021

An improved algorithm for the maximal information coefficient and its application.

R Soc Open Sci 2021 Feb 10;8(2):201424. Epub 2021 Feb 10.

Hunan Engineering and Technology Research Centre for Agricultural Big Data Analysis and Decision-making, Hunan Agricultural University, Changsha 410000, People's Republic of China.

The maximal information coefficient (MIC) captures both linear and nonlinear correlations between variable pairs. In this paper, we proposed the BackMIC algorithm for MIC estimation. The BackMIC algorithm adds a searching back process on the equipartitioned axis to obtain a better grid partition than the original implementation algorithm ApproxMaxMI. And similar to the ChiMIC algorithm, it terminates the grid search process by the -test instead of the maximum number of bins B(, ). Results on simulated data show that the BackMIC algorithm maintains the generality of MIC, and gives more reasonable grid partition and MIC values for independent and dependent variable pairs under comparable running times. Moreover, it is robust under different in B(, ). MIC calculated by the BackMIC algorithm reveals an improvement in statistical power and equitability. We applied (1-MIC) as the distance measurement in the K-means algorithm to perform a clustering of the cancer/normal samples. The results on four cancer datasets demonstrated that the MIC values calculated by the BackMIC algorithm can obtain better clustering results, indicating the correlations between samples measured by the BackMIC algorithm were more credible than those measured by other algorithms.
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http://dx.doi.org/10.1098/rsos.201424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074658PMC
February 2021

Olaparib Treatment in a Patient with Advanced Gallbladder Cancer Harboring Mutation.

Onco Targets Ther 2021 22;14:2815-2819. Epub 2021 Apr 22.

Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.

Gallbladder cancer is a highly aggressive malignancy with an extremely poor prognosis. Germline mutation in gallbladder cancer is very rare. Herein, we present a case of a 73-year-old Asian patient diagnosed with lymph nodes and peritoneal metastases just two months after surgery for primary gallbladder cancer. The patient had a past history of early-stage breast cancer and received a left radical mastectomy 27 years ago. Next-generation sequencing (NGS) was performed as the patient refused to receive systemic chemotherapy. According to NGS result of germline mutation, the patient was administered first-line Olaparib and obtained a progression-free survival of about 6 months. Furthermore, we briefly summarized the current targeted treatment of gallbladder cancer. To the best of our knowledge, this is the first report of germline p. S451Lfs*20 mutation and first-line Olaparib treatment in a metastatic gallbladder cancer patient. As a highly heterogeneous and aggressive malignancy, we suggest making clinical decisions according to a precision medicine concept based on gene sequencing in advanced gallbladder cancer.
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http://dx.doi.org/10.2147/OTT.S303594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075353PMC
April 2021

Rural and urban differences in patient experience in China: a coarsened exact matching study from the perspective of residents.

BMC Health Serv Res 2021 Apr 13;21(1):330. Epub 2021 Apr 13.

School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, China.

Background: Patient experience is a key measure widely used to evaluate quality of healthcare, yet there is little discussion about it in China using national survey data. This study aimed to explore rural and urban differences in patient experience in China.

Methods: Data regarding this study were drawn from Chinese General Social Survey (CGSS) 2015, with a sample size of 9604. Patient experience was measured by the evaluation on healthcare services. Coarsened exact matching (CEM) method was used to balance covariates between the rural and urban respondents. Three thousand three hundred seventy-two participants finally comprised the matched cohort, including 1592 rural residents and 1780 urban residents. Rural and urban differences in patient experience were tested by ordinary least-squares regression and ordered logistic regression.

Results: The mean (SD) score of patient experience for rural and urban residents was 72.35(17.32) and 69.45(17.00), respectively. Urban residents reported worse patient experience than rural counterparts (Crude analysis: Coef. = - 2.897, 95%CI: - 4.434, - 1.361; OR = 0.706, 95%CI: 0.595, 0.838; Multivariate analysis: Coef. = - 3.040, 95%CI: - 4.473, - 1.607; OR = 0.675, 95%CI: 0.569, 0.801). Older (Coef. = 2.029, 95%CI: 0.338, 3.719) and healthier (Coef. = 2.287, 95%CI: 0.729, 3.845; OR = 1.217, 95%CI: 1.008, 1.469) rural residents living in western area (Coef. = 2.098, 95%CI: 0.464, 3.732; OR = 1.276, 95%CI: 1.044, 1.560) with higher social status (Coef. = 1.158, 95%CI: 0.756, 1.561; OR = 1.145, 95%CI: 1.090, 1.204), evaluation on adequacy (Coef. = 7.018, 95%CI: 5.045, 8.992; OR = 2.163, 95%CI: 1.719, 2.721), distribution (Coef. = 4.464, 95%CI: 2.471, 6.456; OR = 1.658, 95%CI: 1.312, 2.096) and accessibility (Coef. = 2.995, 95%CI: 0.963, 5.026; OR = 1.525, 95%CI: 1.217, 1.911) of healthcare resources had better patient experience. In addition, urban peers with lower education (OR = 0.763, 95%CI: 0.625, 0.931) and higher family economic status (Coef. = 2.990, 95%CI: 0.959, 5.021; OR = 1.371, 95%CI: 1.090,1.723) reported better patient experience.

Conclusions: Differences in patient experience for rural and urban residents were observed in this study. It is necessary to not only encourage residents to form a habit of seeking healthcare services in local primary healthcare institutions first and then go to large hospitals in urban areas when necessary, but also endeavor to reduce the disparity of healthcare resources between rural and urban areas by improving quality and capacity of rural healthcare institutions and primary healthcare system of China.
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http://dx.doi.org/10.1186/s12913-021-06328-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042990PMC
April 2021

Bevacizumab Combined with S-1 and Raltitrexed for Patients with Metastatic Colorectal Cancer Refractory to Standard Therapies: A Phase II Study.

Oncologist 2021 08 30;26(8):e1320-e1326. Epub 2021 Apr 30.

Department of Abdominal Cancer, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.

Lessons Learned: Bevacizumab combined with S-1 and raltitrexed demonstrated positive antitumor efficacy and acceptable toxicity. This combination might represent a treatment option for refractory metastatic colorectal cancer.

Background: In patients with metastatic colorectal cancer (mCRC) refractory to standard therapies, S-1 plus raltitrexed showed a good objective response rate (ORR) and significant survival benefit in our previous study. In the present study, we assessed the activity and safety of bevacizumab combined with S-1 and raltitrexed.

Methods: This investigator-initiated, open-label, single-arm, phase II trial was performed at West China Hospital in China. Patients with mCRC who had disease progression after fluoropyrimidine, irinotecan, and oxaliplatin and had at least one measurable lesion were eligible for this trial. Anti-epidermal growth factor receptor (EGFR) (for tumors with wild-type RAS) and anti-vascular endothelial growth factor (VEGF) therapy in the first or second line was allowed, but patients who had been treated with bevacizumab across two consecutive chemotherapy regimens were excluded. Patients received bevacizumab (7.5 mg/kg on day 1), oral S-1 (80-120 mg per day for 14 days), and raltitrexed (3 mg/m on day 1) every 3 weeks. The primary endpoint was ORR. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity.

Results: From September 2015 to November 2019, 44 patients were enrolled. Tumor response evaluation was available in 44 patients at the time of the analysis. There were no complete responses; the ORR was 15.9%, and the disease control rate was 54.5%. Median PFS and OS were 110 days (95% confidence interval [CI], 65.0-155.0) and 367 days (95% CI, 310.4-423.6), respectively. The combination was well tolerated.

Conclusion: Bevacizumab combined with S-1 and raltitrexed showed promising antitumor activity and safety in refractory mCRC.
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http://dx.doi.org/10.1002/onco.13778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342567PMC
August 2021

Case Report: Trastuzumab Treatment in Adenosquamous Carcinoma of the Extrahepatic Biliary Tract With Her-2 Amplification.

Front Oncol 2021 25;11:538328. Epub 2021 Feb 25.

Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.

Extrahepatic cholangiocarcinoma (ECC) is an uncommon and devastating malignancy that mainly consists of adenocarcinoma. Adenosquamous carcinoma is a rare histologic type and accounts for 2-5% of ECC. It reports that 3.6-8.5% of ECC patients carry Her-2 amplification. A 45-year-old woman was admitted to our hospital because of jaundice. Abdominal computerized tomography (CT) suggested extrahepatic biliary tract mass. The patient received surgery and pathological examination confirmed adenosquamous carcinoma. Fluorescence in Situ Hybridization (FISH) and Next-generation sequencing showed the tumor had Her-2 amplification. One month after the operation, CT demonstrated distant lymph nodes metastases (cT3N1M1, stage IV). The patient received gemcitabine and cisplatin combined with targeted therapy of trastuzumab. After three cycles of treatment, the evaluation of response was stable disease (SD). The progression-free survival of 1st line treatment (PFS1) reached 5 months with five cycles of treatment. After progression, the patient received three cycles of albumin-bound paclitaxel combined with S-1 and trastuzumab and concurrent chemoradiotherapy (S-1) because of serious backache. Now, the disease is stable, and the PFS of 2nd line treatment (PFS2) has reached 7 months.
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http://dx.doi.org/10.3389/fonc.2021.538328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983672PMC
February 2021

Functional specificity of the left ventrolateral prefrontal cortex in positive reappraisal: A single-pulse transcranial magnetic stimulation study.

Cogn Affect Behav Neurosci 2021 08 9;21(4):793-804. Epub 2021 Mar 9.

Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200030, China.

Neuroimage studies have yielded evidence for a correlation between the left ventrolateral prefrontal cortex (VLPFC) and a specific type of cognitive reappraisal strategy, positive reappraisal. However, evidence is still lacking for a direct relation. We used single-pulse transcranial magnetic stimulation (TMS) over the left VLPFC at different time points to investigate the functional specificity of the left VLPFC in the success of positive reappraisal and the timing at which the left VLPC was involved in positive reappraisal. Fifteen participants engaged in a baseline experiment and in TMS experiments. All participants successfully reduced their negative emotional ratings using positive reappraisal in the baseline experiment. In the TMS experiments, participants performed the same task as in the baseline experiment but single-pulse TMS was applied over the left VLPFC at 300 ms or/and 3,300 ms after stimulus onset, as well as over the vertex as a control stimulation. Valence ratings of negative stimuli increased (unpleasantness reduction) when participants reappraised negative stimuli with TMS stimulation over the left VLPFC, regardless of the timing of the stimulation at 300 ms or/and at 3,300 ms after the stimulus onset, relative to the vertex stimulation and the baseline experiment. Our study provided evidence of the functional specificity of the left VLPFC in regulation of negative emotions using positive reappraisal. The left VLPFC was believed to be involved in different stages of positive reappraisal. The prominent facilitation effect of TMS over the left VLPFC makes it possible to consider potential applications in clinical practice for mood disorders.
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http://dx.doi.org/10.3758/s13415-021-00881-1DOI Listing
August 2021

The efficacy of aprepitant in salvage treatment of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy for patients with gastrointestinal cancer.

Int J Clin Oncol 2021 Jun 22;26(6):1091-1098. Epub 2021 Mar 22.

Department of Abdominal Oncology, Cancer Center of West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.

Purpose: To evaluate the efficacy of aprepitant and its effect on the quality of life when added to standard antiemetic therapy as salvage therapy.

Patients And Methods: This is an open-label, noncomparative prospective phase II clinical trial. A total of 224 patients receiving initial moderately emetogenic chemotherapy (MEC) were enrolled. Patients received standard antiemetic treatment (5-hydroxytryptamine (5-HT) antagonists + dexamethasone) in the first cycle. Patients failing to achieve a complete response (CR) during cycle 1 entered cycle 2 with the addition of aprepitant as salvage treatment.

Results: Of the 224 patients eligible for cycle 1, 159 (71.0%, 95% CI 65.0-77.0) had a CR, and 65 patients with a noncomplete response (NCR) proceeded to cycle 2 to receive aprepitant-based salvage therapy. Then, 49 (75.4%, 95% CI 64.6-84.1) of these patients achieved a CR. The Functional Living Index-Emesis (FLIE) questionnaire showed that NCR patients in cycle 1 had an improved quality of life after receiving aprepitant-based salvage therapy in cycle 2 (cycle 1 and 2: 80.3 vs 114.0, P < 0.001). Failing to achieve a CR had a significant impact on the quality of life in both cycle 1 (FLIE score of NCR and CR patients: 80.3 vs 119.7, P < 0.001) and cycle 2 (FLIE score of NCR and CR patients: 88.3 vs 122.4, P < 0.001).

Conclusion: The addition of aprepitant as salvage therapy for patients with gastrointestinal cancer is effective and has a positive effect on quality of life.
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http://dx.doi.org/10.1007/s10147-021-01898-9DOI Listing
June 2021

Regulation of connective tissue growth factor expression by miR-133b for the treatment of renal interstitial fibrosis in aged mice with unilateral ureteral obstruction.

Stem Cell Res Ther 2021 03 10;12(1):171. Epub 2021 Mar 10.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, 28 Fuxing Road, Beijing, China.

Introduction: Renal interstitial fibrosis, an important pathological feature of kidney aging and chronic renal failure, is regulated by mesenchymal stem cells (MSCs). We have previously demonstrated low expression of miR-133b in MSC-derived extracellular vesicles (MSC-EVs) in aged rats. However, miR-133b can mediate the inhibition of epithelial-mesenchymal transition (EMT) of renal tubules induced by transforming growth factor-β1 (TGF-β1). We investigated the effect of miR-133b for the treatment of geriatric renal interstitial fibrosis and evaluated its target genes.

Methods: We performed real-time polymerase chain reaction to detect miR-133b expression induced during EMT of HK2 cells by TGF-β1 at different concentrations (0, 6, 8, and 10 ng/mL) and at different time points (0, 24, 48, and 72 h). The target genes of miR-133b were validated using the dual-luciferase reporter assay. In vitro experiments were performed to evaluate mRNA and protein expression of miR-133b targets, E-cadherin, α-smooth muscle actin (SMA), fibronectin, and collagen 3A1 (Col3A1), in HK2 cells transfected with miR-133b under TGF-β1 stimulation. A 24-month-old unilateral ureteral obstruction (UUO) mouse model was established and injected with transfection reagent and miR-133b into the caudal vein. The target gene of miR-133b and other parameters mentioned above such as mRNA and protein expression levels and renal interstitial fibrosis were detected at 7 and 14 days.

Results: miR-133b expression gradually decreased with an increase in TGF-β1 concentration and treatment time, and the miR-133b mimic downregulated connective tissue growth factor (CTGF) expression. The dual-luciferase reporter assay confirmed CTGF as a direct target of miR-133b. Transfection of the miR-133b mimic inhibited TGF-β1-induced EMT of HK2 cells; this effect was reversed by CTGF overexpression. miRNA-133b expression significantly increased (approximately 70-100 times) in mouse kidney tissues after injection of the miRNA-133b overexpression complex, which significantly alleviated renal interstitial fibrosis in mice with UUO.

Conclusion: miR-133b exerted targeted inhibitory effects on CTGF expression, which consequently reduced TGF-β1-induced EMT of HK2 cells and renal interstitial fibrosis in aged mice with UUO.
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http://dx.doi.org/10.1186/s13287-021-02210-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944614PMC
March 2021
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