Publications by authors named "Cheng Zhou"

607 Publications

Severe inflammation in new-borns induces long-term cognitive impairment by activation of IL-1β/KCC2 signaling during early development.

BMC Med 2022 07 27;20(1):235. Epub 2022 Jul 27.

Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital of Sichuan University, Chengdu, 610041, China.

Background: Neonatal sepsis can induce long-term cognitive impairment in adolescence or adulthood, but the underlying molecular mechanism is not fully understood. The expression of K-Cl co-transporter 2 (KCC2) plays a pivotal role in the GABAergic shift from depolarizing to hyperpolarizing during early postnatal development. In this study, we aimed to determine whether neonatal severe inflammation-induced cognitive impairment was associated with the expression of KCC2 during early development.

Methods: Neonatal severe inflammation was established by intraperitoneal injection of high dose lipopolysaccharide (LPS, 1 mg kg) in postnatal day 3 (P3) rats. The Morris water maze task and fear conditioning test were used to investigate long-term cognitive functions. ELISA, RT-PCR and Western blotting were used to examine the expression levels of proinflammatory cytokines and KCC2. Perforated patch-clamping recordings were used to determine the GABAergic shift.

Results: Neonatal severe inflammation led to long-term cognitive impairment in rats. Meanwhile, sustained elevation of interleukin-1 beta (IL-1β) levels was found in the hippocampus until P30 after LPS injection. Elevated expression of KCC2 and hyperpolarized GABA reversal potential (E) were observed in CA1 hippocampal pyramidal neurons from the P7-P10 and P14-P16 rats after LPS injection. Specific knockdown of IL-1β mRNA expression rescued the elevated expression of KCC2 and the hyperpolarized E at P7-P10 and P14-P16. Accordingly, specific knockdown of IL-1β or KCC2 expression improved the cognitive impairment induced by neonatal severe inflammation.

Conclusions: Sustained elevation of IL-1β in the hippocampus may induce cognitive impairment by upregulation of KCC2 during early development.
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http://dx.doi.org/10.1186/s12916-022-02434-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9327322PMC
July 2022

Flooding-induced rhizosphere Clostridium assemblage prevents root-to-shoot cadmium translocation in rice by promoting the formation of root apoplastic barriers.

J Hazard Mater 2022 Jul 16;439:129619. Epub 2022 Jul 16.

Key Lab of Bio-Organic Fertilizer Creation, Ministry of Agriculture and Rural Affairs, Anhui Science and Technology University, Bengbu 233100, China; Jiangsu Provincial Key Lab of Solid Organic Waste Utilization, Jiangsu Collaborative Innovation Center of Solid Organic Wastes, Educational Ministry Engineering Center of Resource-Saving Fertilizers, Nanjing Agricultural University, Nanjing 210095, China. Electronic address:

Water managements are the most effective agricultural practices for restraining cadmium (Cd) uptake and translocation in rice, which closely correlated with rhizosphere assembly of beneficial microbiome. However, the role of the assemblage of specific microbiota in controlling root-to-shoot Cd translocation in rice remains scarcely clear. The aim of this study was to ascertain how water managements shaped rhizosphere microbiome and mediated root-to-shoot Cd translocation. To disentangle the acting mechanisms of water managements, we performed an experiment monitoring Cd uptake and transport in rice and changes in soil microbial communities in response to continuously flooding and moistening irrigation. Continuously flooding changed rhizosphere microbial communities, leading to the increased abundance of anaerobic bacteria such as Clostridium populations. Weighted gene co-expression network analysis (WGCNA) showed that a dominant OTU163, corresponding to Clostridium sp. CSP1, exhibited a strong negative correlation with root-to-shoot Cd translocation. An integrated analysis of transcriptome and metabolome further indicated that the Clostridium-secreted butyric acid was involved in the regulation of phenylpropanoid pathway in rice roots. The formation of endodermal suberized barriers and lignified xylems was remarkably enhanced in the Clostridium-treated roots, which led to more Cd retained in root cell wall and less Cd in the xylem sap. Collectively, our results indicate that the development of root apoplastic barriers can be orchestrated by beneficial Clostridium strains that are assembled by host plants grown under flooding regime, thereby inhibiting root-to-shoot Cd translocation.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129619DOI Listing
July 2022

Inhibition of BTK improved APAP-induced liver injury via suppressing proinflammatory macrophages activation by restoring mitochondrion function.

Int Immunopharmacol 2022 Jul 15;110:109036. Epub 2022 Jul 15.

The State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China. Electronic address:

Background: Acetaminophen (APAP) overdose can cause severe liver injury and APAP-induced liver injury (AILI) is one of the leading causes of acute liver failure (ALF). Bruton's tyrosine kinase (BTK) is a key tyrosine kinase in immune responses, which plays an important role in many inflammatory diseases. However, its effect on AILI is still not clear. Here, we aimed to assess the effect of BTK on AILI and explore its underlying mechanism.

Methods: In our study, western blot and immunohistochemistry were used to detect the expression of BTK in AILI. The C57BL/6 mice were used to check the protective effect of BTK inhibition on AILI and the activation of BTK was confirmed in mice macrophages treated with APAP. Immunofluorescence, immunohistochemistry, oxygen consumption rate (OCR) detection, polymerase chain reaction (PCR), flow cytometry and western blot were used to determine the role of BTK in mitochondrial dynamics and function of macrophages and the underlying mechanisms in AILI.

Results: Our results showed that BTK upregulated in AILI. BTK inhibition protected mice from AILI and BTK was activated in mice macrophages in response to APAP. Mechanically, BTK inhibition promoted mitochondrial fusion and restored mitochondrial function through phospholipase C gamma 2 (PLCγ2)-reactive oxygen species (ROS)-Optic Atrophy 1(OPA1) pathway in macrophages and finally suppressed the release of proinflammatory cytokines.

Conclusions: In conclusion, we found that BTK inhibition protected mice from AILI by restoring the mitochondrial function of macrophages through the improvement of the mitochondrial dynamic imbalance via PLCγ2-ROS-OPA1 signaling pathway, which indicated that BTK might be a potential therapeutic target of AILI.
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http://dx.doi.org/10.1016/j.intimp.2022.109036DOI Listing
July 2022

Hymeglusin Enhances the Pro-Apoptotic Effects of Venetoclax in Acute Myeloid Leukemia.

Front Oncol 2022 29;12:864430. Epub 2022 Jun 29.

Department of Hematology, Xiangya Hospital, Central South University, Changsha, China.

Venetoclax is used for the priority treatment of elderly patients with acute myeloid leukemia (AML). Resistance or intolerance to venetoclax offsets its clinical benefits in some patients. Combination strategies with other drugs are promising alternatives to overcome the current complications associated with venetoclax use. Hymeglusin, a specific inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A synthase 1 (HMGCS1), regulates the mevalonate pathway, which is vital for AML growth and chemosensitivity. The effects of the combination of venetoclax and hymeglusin on AML were explored in this study. The correlations between HMGCS1 and apoptosis-related genes were analyzed using the Gene Expression Profiling Interactive Analysis 2 and The Cancer Genome Atlas databases. Apoptosis and cell viability were detected in HL-60 and KG-1 cells after treatment with gradient concentrations of venetoclax or hymeglusin. The transcriptomic profiles of HL-60 and KG-1 cells were compared RNA-Seq analysis. The effects of venetoclax and hymeglusin on apoptosis were validated in primary cells. The results showed that HMGCS1 expression was closely associated with apoptosis-related genes based on the data from large clinical databases. B cell lymphoma (BCL)-2 expression was elevated in AML and negatively associated with overall survival. Hymeglusin decreased BCL2 expression levels in HL-60 and KG-1 cells. Venetoclax and hymeglusin inhibited cell viability in both cell lines, but induced apoptosis in HL-60 cells. This discrepancy in sensitivity to hymeglusin may be attributed to the positive increase in the expression levels of HMGCS1 and multiple upregulated pro-leukemia genes in KG-1 cells. Combination treatment with venetoclax and hymeglusin significantly increased the apoptotic rates compared to single-agent treatment in both AML cell lines and primary AML cells. Furthermore, the combination strategy did not result in remarkably enhanced toxicity in normal mononuclear cells. Collectively, hymeglusin enhanced the effects of venetoclax on apoptosis. This combination strategy showed enhanced antileukemic activity with acceptable toxicity in AML.
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http://dx.doi.org/10.3389/fonc.2022.864430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277771PMC
June 2022

Elevated D-Dimer levels correlate with the development of hepatorenal syndrome and a poor outcome in patients with cirrhosis.

Scand J Gastroenterol 2022 Jul 14:1-8. Epub 2022 Jul 14.

State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Objectives: Whether hemostatic status was correlated with the diverse types of acute kidney injury in cirrhotic patients is unclear. The present study aimed to investigate the relationship between hemostatic markers and the diverse types of acute kidney injury (AKI) in liver cirrhosis.

Patients And Methods: Cirrhotic patients with consecutive treatment at the First Affiliated Hospital of Medicine School, Zhejiang University, were pooled in a cohort. Their demographic and clinical data, biochemistry parameters and hemostatic markers were assessed to identify risk factors for the development and prognosis of AKI.

Results: A total of 773 cirrhotic patients were included in this cohort. Patients with hepatorenal syndrome (HRS) had significantly higher D-Dimer than those with the other types of AKI. In univariate COX regression, APTT, TT, INR, D-Dimer and Fib were correlated with the development of AKI, HRS and acute tubular necrosis (ATN), however, only D-Dimer remained independently associated with the development of AKI and HRS in multivariate COX regression. The area under the ROC curve of D-Dimer was 0.755 (95%CI, 0.718-0.793) in predicting the development of AKI, 0.879 (95%CI, 0.791-0.967) in predicting the development of HRS, respectively. D-Dimer was used for diagnosis of HRS with a sensitivity of 87.3% and specificity of 72.9% at the cutoff of 3.7 (mg/L FEU). Survival rates differed significantly between groups by D-Dimer level.

Conclusions: Hemostatic markers were significantly associated with the diverse types of AKI. D-Dimer was an independent risk factor for HRS and correlated with a poor outcome in cirrhotic patients.
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http://dx.doi.org/10.1080/00365521.2022.2098051DOI Listing
July 2022

Ultra-High-Sensitivity Humidity Fiber Sensor Based on Harmonic Vernier Effect in Cascaded FPI.

Sensors (Basel) 2022 Jun 25;22(13). Epub 2022 Jun 25.

School of Electronic and Information Engineering, Harbin Institute of Technology, Shenzhen 518055, China.

In this study, an ultra-high-sensitivity fiber humidity sensor with a chitosan film cascaded Fabry-Perot interferometer (FPI) based on the harmonic Vernier effect (HVE) is proposed and demonstrated. The proposed sensor can break the limitation of the strict optical path length matching condition in a traditional Vernier effect (TVE) FPI to achieve ultra-high sensitivity through the adjustment of the harmonic order of the HVE FPI. The intersection of the internal envelope tracking method allows spectra demodulation to no longer be limited by the size of the FSR of the FPI. The sensitivity of the proposed sensor is -83.77 nm/%RH, with a magnification of -53.98 times. This work acts as an excellent guide in the fiber sensing field for the further achievement of ultra-high sensitivity.
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http://dx.doi.org/10.3390/s22134816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9269540PMC
June 2022

Retraction notice to "Ginsenoside Rg3 inhibits growth and epithelial-mesenchymal transition of human oral squamous carcinoma cells by down-regulating miR-221" [Eur. J. Pharmacol. 853 (2019) 353-363].

Eur J Pharmacol 2022 08 5;928:175123. Epub 2022 Jul 5.

Department of Stomatology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, China.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Given the comments regarding this article https://pubpeer.com/publications/917A4D8593F06C8E5ADC7AA0A30136, particularly regarding the background of the Western Blots from Figure 2B, the journal requested the authors to provide the raw data. However, the authors were not able to fulfil this request and therefore the Editor-in-Chief decided to retract the article.
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http://dx.doi.org/10.1016/j.ejphar.2022.175123DOI Listing
August 2022

Oral Tofacitinib and Systemic Corticosteroids, Alone or in Combination, in Patients With Moderate-to-Severe Alopecia Areata: A Retrospective Study.

Front Med (Lausanne) 2022 21;9:891434. Epub 2022 Jun 21.

Department of Dermatology, Peking University People's Hospital, Beijing, China.

Introduction: Alopecia areata (AA) is an autoimmune hair loss mediated by CD8 + T cells. Treatment for moderate-to-severe AA is still challenging. Janus kinase inhibitors, such as tofacitinib, have been recently investigated as a promising treatment option for AA. Evidence on the combination use of oral tofacitinib and systemic corticosteroids (SCs) for AA is still lacking.

Objective: To compare the efficacy and safety of monotherapy of oral tofacitinib and SCs, as well as their combination in patients with moderate-to-severe AA.

Methods: Patients with moderate-to-severe AA, who have been treated with at least 3 months of monotherapy of tofacitinib or SCs, or in their combination, were included in this study. The efficacy and adverse events of these treatments were retrospectively analyzed.

Results: Sixty-one patients with moderate-to-severe AA were included in this study. There were 12 (66.7%) of 18 patients in the SCs group, 12 (60.0%) of 20 patients in the tofacitinib group, and 18 (78.3%) of 23 patients achieved SALT, with no significant difference among the three groups. The ratio of patients who achieved SALT was significantly higher in patients with a short duration of current hair loss episode (≤2 years) than in those with a duration of current hair loss episode (>2 years) in all the three groups. There were 66.7% patients in the SCs group, 35.0% patients in the tofacitinib group, and 56.5% patients in the combined group that showed adverse effects.

Conclusion: Tofacitinib was an effective treatment for patients with moderate-to-severe AA, and it was more tolerated than SCs. A combination of tofacitinib and SCs may have higher efficacy than SCs alone. Efficacy significantly decreased in patients with a current episode of disease for more than 2 years.
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http://dx.doi.org/10.3389/fmed.2022.891434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255896PMC
June 2022

The protective role of cigarette smoking against Parkinson's disease via moderation of the interaction between iron deposition in the nigrostriatal pathway and clinical symptoms.

Quant Imaging Med Surg 2022 Jul;12(7):3603-3624

Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: Although cigarette smoking is a risk factor for multiple disorders, it has long been thought to protect against Parkinson's disease (PD). Quantitative susceptibility mapping (QSM) is a novel magnetic resonance imaging (MRI)-based technique for assessing iron accumulation that has been widely applied in PD studies. This study aimed to investigate how cigarette smoking affects clinical performance of PD using quantified iron deposition as a proxy for PD pathology.

Methods: In this observational study, we enrolled 35 male PD patients and 47 male healthy controls (HCs) and divided them into four groups. We performed an enhanced T2 star-weighted angiography (ESWAN) MRI sequence to measure the iron content of the nuclei within the nigrostriatal pathway. With the age and total intracranial volume (TIV) controlled as covariates, we performed inter-group comparisons of QSM values and moderation analyses for PD patients using smoking status and the smoking index (SI), respectively, as moderator variables.

Results: The 2-way multivariate analysis of covariance (MANCOVA) results showed higher QSM values in the left red nucleus (P=0.024) in PD patients compared with those in HCs, and in the bilateral globi pallidi [left/right (L/R): P=0.009/0.003], substantia nigra pars compacta (SNc; L/R: P=0.001/0.037), and right substantia nigra pars reticulata (SNr; P=0.002) in non-smokers compared with smokers, with no marked interaction effect between PD and smoking status observed when applying the Bonferroni adjustment for multiple comparisons. Using cigarette smoking status and the SI as separate moderator variables, the moderation was shown up by a significant interaction effect in a disordinal and double-edged form. In our results, smoking-moderated protection for PD movement deficits emerged when PD was progressed. Among the affected deep brain nuclei, the nuclei most moderated by the impact of cigarette smoking on the interaction between brain iron and PD symptoms were the thalamus [smoking status associated with the Unified Parkinson's Disease Rating Scale (UPDRS) total score, P=0.04 (L); rigidity, P=0.03 (L); SI associated with UPDRS-III, P (L/R) =0.049/0.0497; rigidity, P (L/R) =0.01/0.02; bradykinesia, P (L/R) =0.048/0.04], the right red nucleus (SI associated with rigidity, P=0.04; bradykinesia, P=0.02), and the left SNc [smoking status associated with the Hoehn and Yahr (H&Y) stage, P=0.01].

Conclusions: This was the first study investigating the impacts of current cigarette smoking on PD using quantified iron deposition. Our study confirmed the protective role of cigarette smoking against PD, consistent with the findings of previous studies. Furthermore, neuroprotection was present only when the PD pathology had progressed to a certain extent. In the interaction between iron deposition and clinical PD symptoms, our findings suggest that the thalamus, red nucleus, and SNc are likely to be the most affected nuclei moderated by cigarette smoking.
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http://dx.doi.org/10.21037/qims-21-1090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9246741PMC
July 2022

Effects of polyamide microplastic on the transport of graphene oxide in porous media.

Sci Total Environ 2022 Jun 28;843:157042. Epub 2022 Jun 28.

Guangdong Provincial Research Center for Environment Pollution Control and Remediation Materials, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.

With the rapid development of the nano-material and chemical industry, more and more microplastic (MP) and nano-material were discharged into the environment. In this study, a two-dimensional (2D) surface of Extended Darjaguin-Landau-Verwe-Overbeek (XDLVO) is proposed to quantitatively investigate the effect of polyamide (PA) on the transport of graphene oxide (GO) in porous media. The influences of mass fraction of PA, flow rate, GO concentration, ionic type and strength on the migration of GO in saturated porous media are investigated by column experiments and numerical models. The two-dimensional (2D) surfaces of XDLVO interaction energy between GO and GO, GO and QS, GO and PA, are firstly calculated to analyze the transport of GO in saturated porous media. Experimental results suggest the mobility of GO is enhanced when flow velocity and initial concentration of GO are increased. However, the mobility of GO is inhibited when the mass fraction of PA and ionic strength are increased. More important, the inhibitory effect of divalent cations on GO migration is stronger than that of monovalent cations. Simultaneously, XDLVO results suggest that ionic types and strengths are important factors affecting the mobility of GO in porous media, and the critical ionic strength is observed from the continuous variation of the secondary minimum trap of XDLVO interaction energy. Model results show that there is a linear relationship between the logarithm of the secondary minimum trap of XDLVO interaction energy and the parameters related to GO mobility, which suggests XDLVO energy surface has an important application significance in the accurate quantification of GO mobility in porous media. These findings contribute to GO transport affected by microplastic in porous media, thus laying a significant foundation for the environmental risk and contamination remediation.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157042DOI Listing
June 2022

Wogonin Ameliorated Obesity-Induced Lipid Metabolism Disorders and Cardiac Injury via Suppressing Pyroptosis and Deactivating IL-17 Signaling Pathway.

Am J Chin Med 2022 Jun 30:1-12. Epub 2022 Jun 30.

Department of Paediatrics, Changzhou Second People's Hospital Affiliated to Nanjing Medical University, Changzhou, Jiangsu 213164, P. R. China.

Obesity leads to structural and functional changes in the heart and has become a global burden of disease. Wogonin is a natural flavonoid which possesses cardioprotective, neuroprotective, and anti-cancer properties. However, the effects of wogonin on obesity-induced cardiac injury remain unclear. In this study, the high-fat diet (HFD)-induced obese mice model was successfully established. Moreover, HFD induced a fat mass and cardiac injury in mice. More importantly, wogonin treatment reduced fat mass and improved cardiac function of HFD mice. Consistently, wogonin ameliorated myocardial lipid metabolism in HFD-induced obese mice by reducing triglyceride (TC), total cholesterol (TG), and non-esterified fatty acid (NEFA) levels in serum, as well as the TG and free fatty acids (FFA) levels in heart tissues. Interestingly, wogonin treatment alleviated myocardial pyroptosis in HFD-induced obese mice. Through bioinformatic analysis, the IL-17 signaling pathway was predicted to be modulated by wogonin. Results showed that wogonin deactivated the IL-17 signaling pathway in HFD mice. These findings suggested that wogonin ameliorated obesity-induced disorders of lipid metabolism and cardiac injury via suppressing pyroptosis and deactivating the IL-17 signaling pathway, which provided a novel therapeutic strategy for HFD-induced cardiac injury.
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http://dx.doi.org/10.1142/S0192415X22500653DOI Listing
June 2022

Characterization of highly expressed novel hub genes in hepatitis E virus chronicity in rabbits: a bioinformatics and experimental analysis.

BMC Vet Res 2022 Jun 23;18(1):239. Epub 2022 Jun 23.

Division I of In Vitro Diagnostics for Infectious Diseases, Institute for In Vitro Diagnostics Control, National Institutes for Food and Drug Control, 2 Tiantanxili Rd, Dongcheng District, 100050, Beijing, China.

Background: Hepatitis E virus (HEV), which is the leading cause of acute viral hepatitis worldwide, usually causes self-limited infections in common individuals. However, it can lead to chronic infection in immunocompromised individuals and its mechanisms remain unclear. Rabbits are the natural host of HEV, and chronic HEV infections have been observed in rabbits. Therefore, we aimed to investigate potential key genes in HEV chronicity process in rabbits. In this study, both bioinformatics and experimental analysis were performed to deepen the understanding of hub genes in HEV chronic infection in rabbits.

Results: Ninety-four candidate differentially expressed genes (DEGs) and the pathways they enriched were identified to be related with HEV chronicity. A total of 10 hub genes were found by protein-protein interaction (PPI) network construction. Rabbits of group P (n = 4) which showed symptoms of chronic HEV infection were selected to be compared with HEV negative rabbits (group N, n = 6). By detecting the identified hub genes in groups P and N by real-time PCR, we found that the expressions of MX1, OAS2 and IFI44 were significantly higher in group P (P < 0.05).

Conclusions: In this work, we presented that MX1, OAS2 and IFI44 were significantly upregulated in HEV chronic infected rabbits, indicating that they may be involved in the pathogenesis of HEV chronicity.
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http://dx.doi.org/10.1186/s12917-022-03337-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219159PMC
June 2022

A Novel Method for the Preparation of Poly (Acrylamide-co-Acrylonitrile) Upper Critical Solution Temperature Thermosensitive Hydrogel by the Partial Dehydration of Acrylamide Grafted Polypropylene Sheets.

Gels 2022 May 31;8(6). Epub 2022 May 31.

Department of Chemical Engineering and Technology, School of Environmental and Chemical Engineering, Shanghai University, Shangda Road 99, Shanghai 200444, China.

In an attempt to find a potential application of cell culture harvesting, a novel method for the preparation of an upper critical solution temperature (UCST) thermosensitive hydrogel was studied. An electron accelerator was used as the electron beam (EB) radiation source, and acrylamide (AAm) was first grafted onto the pre-irradiated polypropylene (PP) sheet. Then, the grafting layer of poly (acrylamide-co-acrylonitrile) (P (AAm-co-AN)) was obtained by the partial dehydration of the acylamino group into the cyano group in the solution mixture of sulfoxide chloride (SOCl) and dimethyl formamide (DMF). The effects of the absorbed dose, AAm concentration, reaction time, and temperature on the degree of grafting were studied, respectively. The effect of the SOCl concentration on the conversion degree of the cyano group from the acylamino group was studied, followed by the temperature of the UCST. The UCST properties of the grafted samples with P (AAm-co-AN) were studied by quartz crystal microbalance (QCM) and atomic force microscope (AFM), respectively. The cytotoxicities of the hydrogels against cells were verified by CCK-8 studies.
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http://dx.doi.org/10.3390/gels8060345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9222357PMC
May 2022

Normalization effect of levodopa on hierarchical brain function in Parkinson's disease.

Netw Neurosci 2022 Jun 1;6(2):552-569. Epub 2022 Jun 1.

Department of Radiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Hierarchical brain organization, in which the rich club and diverse club situate in core position, is critical for global information integration in the human brain network. Parkinson's disease (PD), a common movement disorder, has been conceptualized as a network disorder. Levodopa is an effective treatment for PD. Whether there is a functional divergence in the hierarchical brain system under PD pathology, and how this divergence is regulated by immediate levodopa therapy, remains unknown. We constructed a functional network in 61 PD patients and 89 normal controls and applied graph theoretical analyses to examine the neural mechanism of levodopa short response from the perspective of brain hierarchical configuration. The results revealed the following: (a) PD patients exhibited disrupted function within rich-club organization, while the diverse club preserved function, indicating a differentiated brain topological organization in PD. (b) Along the rich-club derivate hierarchical system, PD patients showed impaired network properties within rich-club and feeder subnetworks, and decreased nodal degree centrality in rich-club and feeder nodes, along with increased nodal degree in peripheral nodes, suggesting distinct functional patterns in different types of nodes. And (c) levodopa could normalize the abnormal network architecture of the rich-club system. This study provides evidence for levodopa effects on the hierarchical brain system with divergent functions.
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http://dx.doi.org/10.1162/netn_a_00232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9208001PMC
June 2022

Signatures of Thalamocortical Alpha Oscillations and Synchronization With Increased Anesthetic Depths Under Isoflurane.

Front Pharmacol 2022 3;13:887981. Epub 2022 Jun 3.

Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital of Sichuan University, Chengdu, China.

Electroencephalography (EEG) recordings under propofol exhibit an increase in slow and alpha oscillation power and dose-dependent phase-amplitude coupling (PAC), which underlie GABA potentiation and the central role of thalamocortical entrainment. However, the exact EEG signatures elicited by volatile anesthetics and the possible neurophysiological mechanisms remain unclear. Cortical EEG signals and thalamic local field potential (LFP) were recorded in a mouse model to detect EEG signatures induced by 0.9%, 1.5%, and 2.0% isoflurane. Then, the power of the EEG spectrum, thalamocortical coherence, and slow-alpha phase-amplitude coupling were analyzed. A computational model based on the thalamic network was used to determine the primary neurophysiological mechanisms of alpha spiking of thalamocortical neurons under isoflurane anesthesia. Isoflurane at 0.9% (light anesthesia) increased the power of slow and delta oscillations both in cortical EEG and in thalamic LFP. Isoflurane at 1.5% (surgery anesthesia) increased the power of alpha oscillations both in cortical EEG and in thalamic LFP. Isoflurane at 2% (deep anesthesia) further increased the power of cortical alpha oscillations, while thalamic alpha oscillations were unchanged. Thalamocortical coherence of alpha oscillation only exhibited a significant increase under 1.5% isoflurane. Isoflurane-induced PAC modulation remained unchanged throughout under various concentrations of isoflurane. By adjusting the parameters in the computational model, isoflurane-induced alpha spiking in thalamocortical neurons was simulated, which revealed the potential molecular targets and the thalamic network involved in isoflurane-induced alpha spiking in thalamocortical neurons. The EEG changes in the cortical alpha oscillation, thalamocortical coherence, and slow-alpha PAC may provide neurophysiological signatures for monitoring isoflurane anesthesia at various depths.
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http://dx.doi.org/10.3389/fphar.2022.887981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204038PMC
June 2022

Targeting PCSK9 Ameliorates Graft Vascular Disease in Mice by Inhibiting NLRP3 Inflammasome Activation in Vascular Smooth Muscle Cells.

Front Immunol 2022 26;13:894789. Epub 2022 May 26.

Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Graft vascular disease (GVD), which limits the long-term survival of patients after solid-organ transplantation, is associated with both immune responses and nonimmune factors, including dyslipidemia. Recent studies have shown that inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9), a U.S. Federal Drug Administration-approved treatment for hyperlipidemia, reduces cardiovascular events, regulates inflammatory responses, and enhances the efficacy of immune checkpoint therapy in cancer treatment through a cholesterol-independent mechanism. However, whether targeting PCSK9 is a potential therapeutic strategy for GVD remains unknown.

Methods: Serum samples and grafts were harvested from male mice undergoing abdominal aortic transplantation. The pathological alterations in the aortic grafts were detected by hematoxylin and eosin staining, Verhoeff's Van Gieson staining, and Masson staining. Inflammatory cell infiltration and proinflammatory cytokine expression in the aortic grafts were detected by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. The regulatory effects of PCSK9 on vascular smooth muscle cell (VSMC) migration and proliferation were examined by transwell, EdU, and western blot assays. The effect of Evolocumab, a PCSK9 inhibitor, on GVD in humanized PCSK9 mice was also evaluated.

Results: PCSK9 was upregulated in the serum, grafts, and liver of mice in the allograft group subjected to abdominal aortic transplantation. knockout significantly reduced vascular stenosis, the intimal hyperplasia area and collagen deposition. depletion also inhibited macrophage recruitment and the mRNA expression of proinflammatory cytokines in aortic grafts. Furthermore, knockout suppressed the migration and proliferation of VSMCs, which was related to the inhibition of NLRP3 inflammasome activation. Meanwhile, Evolocumab significantly ameliorated GVD in humanized PCSK9 mice.

Conclusion: PCSK9 is upregulated in a mouse model of GVD, and knockout reduces vascular occlusion, suggesting that PCSK9 may be a promising target for the treatment of GVD.
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http://dx.doi.org/10.3389/fimmu.2022.894789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204514PMC
May 2022

Spatial-temporal characteristics and driving factors of the chemical fertilizer supply/demand correlation network in China.

Environ Sci Pollut Res Int 2022 Jun 20. Epub 2022 Jun 20.

Key Laboratory of JiangHuai Arable Land Resources Protection and Eco-restoration, Anhui Agricultural University, Hefei, 230036, China.

The rational allocation of chemical fertilizer resources is of strategic importance in mitigating agricultural source pollution and achieving agricultural green development. The spatiotemporal correlation of chemical fertilizer supply/demand and its determinants remains unclear. In this study, based on the inter-provincial chemical fertilizer supply/demand panel data of China from 1994 to 2018, an improved gravity model was employed to determine provincial chemical fertilizer supply/demand correlations. Finally, the chemical fertilizer supply/demand evolution and its driving factors were analyzed using social network analysis and a quadratic assignment procedure. The results indicated that (1) the intensity of the spatial relationship of inter-provincial chemical fertilizer supply/demand increased in a fluctuating fashion, but there was still room for improvement. The network structure presented good stability, and the spillover effect exhibited multiple superposition characteristics; (2) the spatial correlation network of inter-provincial chemical fertilizer supply/demand presented a "core-periphery" distribution pattern of the supply, demand, and balance areas. The division of blocks in the network changed in time and space, and some provinces changed their roles and positions in the network during development; (3) chemical fertilizer-related policies (e.g., Exemption Agricultural Tax, Notice on the resumption of value added tax policy on fertilizers, and Rural Revitalization Strategy) have played a positive role in the formation and development of the interprovincial spatial correlation network of chemical fertilizer supply/demand in China; (4) natural conditions and socioeconomic factors interact to promote the formation of the spatial correlation network of chemical fertilizer supply/demand. The differences in the scale of the rural labor force, the scale of agricultural mechanization, the agricultural planting structure, the populations, and urbanization levels all had a significant impact on it. The identification of the spatial characteristics of chemical fertilizer supply/demand correlation networks offers a new perspective on taking various measures to realize the cross-regional coordination of chemical fertilizer resources, strengthen the protection and utilization of agricultural resources, and promote green agricultural development.
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http://dx.doi.org/10.1007/s11356-022-21387-4DOI Listing
June 2022

SERPINA5 may promote the development of preeclampsia by disruption of the uPA/uPAR pathway.

Transl Res 2022 Jun 15. Epub 2022 Jun 15.

Department of Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. Electronic address:

Preeclampsia (PE) is the leading cause of maternal and fetal morbidity or mortality but lacks reliable methods for early diagnosis. In a previous study, serum SERPINA5 levels were higher in women with PE before the clinical manifestation of the disease. This study aimed to evaluate the efficacy of SERPINA5 in predicting PE and investigate its role in trophoblast cell biology. A multicenter, 2-stage observational case-control study was performed to develop and validate an early predictive PE model based on SERPINA5, maternal characteristics, and inflammatory factors. To further understand the relationship between SERPINA5 and PE, SERPINA5 was overexpressed or knocked down in extravillous trophoblast cells (EVT) and a pregnant rat model. After development and initial validation, a model that combined SERPINA5 and inflammatory factors had a high predictive ability for PE before 20 weeks gestation with an AUC of 0.90 (95% CI 0.83-0.96). It also demonstrated that SERPINA5 inhibited primary EVT cell invasion by disrupting the urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor (uPA/uPAR) pathway, in turn, is involved in the development of PE. In vivo experiments also proved that overexpression of SERPINA5 induced a PE-like syndrome (hypertension and proteinuria) in pregnant rats. Therefore, serum SERPINA5 is a promising early biomarker of PE, suggesting that it may be involved in placental development through its action on the uPA/uPAR system prior to the clinical manifestation of PE.
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http://dx.doi.org/10.1016/j.trsl.2022.06.011DOI Listing
June 2022

Axillary channel-assisted TOETVA: An effective way to prevent mental nerve from iatrogenic injury?

J Minim Access Surg 2022 Jul-Sep;18(3):450-458

Department of General and Transplant Surgery, PHM, Munich, Germany.

Aim: To evaluate the protective effect of axillary channel-assisted (ACA) transoral endoscopic thyroidectomy vestibular approach on mental nerve.

Materials And Methods: From August 2018 to December 2020, 126 cases of thyroid micro-carcinoma patients who underwent endoscopic thyroidectomy were recruited retrospectively. Of those, 74 cases were performed with ACA trans-oral endoscopic thyroidectomy vestibular approach (ACA_TOETVA) (V and A group), 52 cases received standard TOETVA (V group). On postoperative day 1 (POD1), nylon monofilament test and numbness visual analogue scale score were conducted to evaluate the severity of numbness within the mental area, facial expression was tested to determine the motor function of lower mandible and the thickness of cutaneous and subcutaneous layers was measured with ultrasound. The other observation parameters including the time for operation and intraoperative blood loss were carefully collected.

Results: On POD1, nylon monofilament test showed that scores in the V and A group (2.9 ± 0.3) were significantly higher than V group (1.7 ± 0.5), P < 0.01, u = 254. The completion percentage of facial expression in the V and A group was 90.5% (67/74) and significantly higher than in V group (21.2%, 11/52), P < 0.01, χ = 62.35. The thickness increment of cutaneous and subcutaneous layer was 2.2 ± 1.2 mm in the V and A group, which was significantly less than in the V group (4.0 ± 1.2 mm), P < 0.01, u = 605. Compared with V group, the operation time (113.4 ± 22.3 min vs. 127.7 ± 25.6 min, u = 1262) and intraoperative blood loss (43.5 ± 13.4 ml vs. 51.0 ± 14.1 ml, u = 1355) were also significantly less in the V and A group.

Conclusions: The ACA transoral endoscopic thyroidectomy possesses the protective effect on mental nerve and motor function of lower mandible and facilitates the operative procedures of TOETVA.
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http://dx.doi.org/10.4103/jmas.jmas_263_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9306113PMC
June 2022

A new method for simultaneous determination of 14 phenolic acids in agricultural soils by multiwavelength HPLC-PDA analysis.

RSC Adv 2022 May 18;12(23):14939-14944. Epub 2022 May 18.

Department of Resources and Environment, Anhui Science and Technology University Fengyang 233100 China

There are phenolic acids with allelopathy in the rhizosphere soil of plants. At present, the identification and quantification of phenolic acids in different matrix mixtures is usually analysed by high performance liquid chromatography, but the detection of phenolic acids in soil has rarely been studied. As well as, previous studies have evaluated a limited number of target compounds. In this work, we proposed and verified a method for quantitative determination of 14 phenolic acids, including gallic acid, vanillic acid, -hydroxybenzoic acid, protocatechuic acid, caffeic acid, syringic acid, -coumaric acid, ferulic acid, chlorogenic acid, benzoic acid, salicylic acid, 2-methoxycinnamic acid, 3-methoxycinnamic acid, and cinnamic acid, which are widely present in rhizosphere soil of plants and have allelopathy. This method used multiwavelength HPLC-PDA analysis for simultaneous determination of these compounds. The detection wavelengths selected 254 nm, 280 nm, 300 nm, and 320 nm. Chromatographic separation of all compounds was achieved using a column of Shim-pack VP-ODS (250 mm × 4.6 mm, 5 μm), kept at 30 °C. Mobile phase A was acetonitrile, B was a 0.5% acetic acid aqueous solution, and the flow rate was 1.0 mL min. Under the condition of gradient elution, the mobile phase A was acetonitrile, B was a 0.5% acetic acid aqueous solution, and the flow rate was kept constant at 1.0 mL min. The 14 target phenolic acids were completely separated within 45 min. All the calibration curves showed good linearity, and the correlation coefficient was 0.9994-0.9999. With the detection limit varying from 0.003 mg L to 0.239 mg L. The recovery rates and the RSD of 14 phenolic acids were 80.54∼107.0% and 1.43-4.35%, respectively. This method has the characteristics of high sensitivity, high accuracy, and high recovery rate. This method is a novel technical means for the simultaneous analysis of compound phenolic acids in soil.
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http://dx.doi.org/10.1039/d1ra09433eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9116113PMC
May 2022

Deep-learning-based analysis of preoperative MRI predicts microvascular invasion and outcome in hepatocellular carcinoma.

World J Surg Oncol 2022 Jun 8;20(1):189. Epub 2022 Jun 8.

Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, People's Republic of China.

Background: Preoperative prediction of microvascular invasion (MVI) is critical for treatment strategy making in patients with hepatocellular carcinoma (HCC). We aimed to develop a deep learning (DL) model based on preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict the MVI status and clinical outcomes in patients with HCC.

Methods: We retrospectively included a total of 321 HCC patients with pathologically confirmed MVI status. Preoperative DCE-MRI of these patients were collected, annotated, and further analyzed by DL in this study. A predictive model for MVI integrating DL-predicted MVI status (DL-MVI) and clinical parameters was constructed with multivariate logistic regression.

Results: Of 321 HCC patients, 136 patients were pathologically MVI absent and 185 patients were MVI present. Recurrence-free survival (RFS) and overall survival (OS) were significantly different between the DL-predicted MVI-absent and MVI-present. Among all clinical variables, only DL-predicted MVI status and a-fetoprotein (AFP) were independently associated with MVI: DL-MVI (odds ratio [OR] = 35.738; 95% confidence interval [CI] 14.027-91.056; p < 0.001), AFP (OR = 4.634, 95% CI 2.576-8.336; p < 0.001). To predict the presence of MVI, DL-MVI combined with AFP achieved an area under the curve (AUC) of 0.824.

Conclusions: Our predictive model combining DL-MVI and AFP achieved good performance for predicting MVI and clinical outcomes in patients with HCC.
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http://dx.doi.org/10.1186/s12957-022-02645-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178852PMC
June 2022

Gray and white matter alterations in different predominant side and type of motor symptom in Parkinson's disease.

CNS Neurosci Ther 2022 Sep 7;28(9):1372-1379. Epub 2022 Jun 7.

Department of Radiology, The Second Affiliated Hospital, Zhejiang University of Medicine, Hangzhou, China.

Background: Parkinson's disease (PD) is highly heterogeneous reflected by different affected side of body and type of motor symptom. We aim to explore clinical characteristics and underlying brain structure alterations in PD with different predominant sides and motor types.

Methods: We recruited 161 PD patients and 50 healthy controls (HC). Patients were classified into four subtypes according to their predominant side and motor type: left akinetic/rigid-dominant (LAR), left tremor-dominant (LTD), right akinetic/rigid-dominant (RAR), and right tremor-dominant (RTD). All participants assessed motor and cognitive performances, then underwent T1-weighted and diffusion tensor imaging scanning. A general linear model was used to compare neuroimaging parameters among five groups.

Results: Among four PD subtypes, patients of LAR subtype experienced the worst motor impairment, and only this subtype showed worse cognitive performance compared with HC. Compared with HC and other subtypes, LAR subtype showed a significant reduction in cortical thickness of the right caudal-anterior-cingulate gyrus and fractional anisotropy of the right cingulum bundle.

Conclusions: We demonstrated that LAR subtype had the worst clinical performance, which the severer damage in the right cingulate region might be the underlying mechanism. This study underscores the importance of classifying PD subtypes based on both the side and type of motor symptom for clinical intervention and research to optimize behavioral outcomes in the future.
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http://dx.doi.org/10.1111/cns.13877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344082PMC
September 2022

APOBEC-mediated mutagenesis is a favorable predictor of prognosis and immunotherapy for bladder cancer patients: evidence from pan-cancer analysis and multiple databases.

Theranostics 2022 16;12(9):4181-4199. Epub 2022 May 16.

Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

The APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) family-mediated mutagenesis is widespread in human cancers. However, our knowledge of the biological feature and clinical relevance of APOBECs and APOBEC mutagenesis in cancers remains limited. In this study, with a series of bioinformatic and statistical approaches, we performed a comprehensive analysis of multiple levels of data, including whole-exome sequencing (WES) and targeted next-generation sequencing (NGS), transcriptome (bulk RNA-seq and single-cell RNA-seq), immune signatures and immune checkpoint blockade (ICB) potential, patient survival and drug sensitivity, to reveal the distribution characteristics and clinical significance of APOBECs and APOBEC mutagenesis in pan-cancer especially bladder cancer (BLCA). APOBEC mutagenesis dominates in the mutational patterns of BLCA. A higher enrichment score of APOBEC mutagenesis correlates with favorable prognosis, immune activation and potential ICB response in BLCA patients. APOBEC3A and 3B play a significant role in the malignant progression and cell differentiation within the tumor microenvironment. Furthermore, using machine learning approaches, a prognostic APOBEC mutagenesis-related model was established and validated in different BLCA cohorts. Our study illustrates the characterization of APOBECs and APOBEC mutagenesis in multiple cancer types and highlights its potential value as a promising biomarker for prognosis and immunotherapy in BLCA.
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http://dx.doi.org/10.7150/thno.73235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9169361PMC
June 2022

A multiple-tissue-specific magnetic resonance imaging model for diagnosing Parkinson's disease: a brain radiomics study.

Neural Regen Res 2022 Dec;17(12):2743-2749

Department of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.

Brain radiomics can reflect the characteristics of brain pathophysiology. However, the value of T1-weighted images, quantitative susceptibility mapping, and R2* mapping in the diagnosis of Parkinson's disease (PD) was underestimated in previous studies. In this prospective study to establish a model for PD diagnosis based on brain imaging information, we collected high-resolution T1-weighted images, R2* mapping, and quantitative susceptibility imaging data from 171 patients with PD and 179 healthy controls recruited from August 2014 to August 2019. According to the inclusion time, 123 PD patients and 121 healthy controls were assigned to train the diagnostic model, while the remaining 106 subjects were assigned to the external validation dataset. We extracted 1408 radiomics features, and then used data-driven feature selection to identify informative features that were significant for discriminating patients with PD from normal controls on the training dataset. The informative features so identified were then used to construct a diagnostic model for PD. The constructed model contained 36 informative radiomics features, mainly representing abnormal subcortical iron distribution (especially in the substantia nigra), structural disorganization (e.g., in the inferior temporal, paracentral, precuneus, insula, and precentral gyri), and texture misalignment in the subcortical nuclei (e.g., caudate, globus pallidus, and thalamus). The predictive accuracy of the established model was 81.1 ± 8.0% in the training dataset. On the external validation dataset, the established model showed predictive accuracy of 78.5 ± 2.1%. In the tests of identifying early and drug-naïve PD patients from healthy controls, the accuracies of the model constructed on the same 36 informative features were 80.3 ± 7.1% and 79.1 ± 6.5%, respectively, while the accuracies were 80.4 ± 6.3% and 82.9 ± 5.8% for diagnosing middle-to-late PD and those receiving drug management, respectively. The accuracies for predicting tremor-dominant and non-tremor-dominant PD were 79.8 ± 6.9% and 79.1 ± 6.5%, respectively. In conclusion, the multiple-tissue-specific brain radiomics model constructed from magnetic resonance imaging has the ability to discriminate PD and exhibits the advantages for improving PD diagnosis.
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http://dx.doi.org/10.4103/1673-5374.339493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9165377PMC
December 2022

Axillary channel-assisted TOETVA: An effective way to prevent mental nerve from iatrogenic injury?

J Minim Access Surg 2022 May 27. Epub 2022 May 27.

Department of General and Transplant Surgery, PHM, Munich, Germany.

Aim: To evaluate the protective effect of axillary channel-assisted (ACA) transoral endoscopic thyroidectomy vestibular approach on mental nerve.

Materials And Methods: From August 2018 to December 2020, 126 cases of thyroid micro-carcinoma patients who underwent endoscopic thyroidectomy were recruited retrospectively. Of those, 74 cases were performed with ACA trans-oral endoscopic thyroidectomy vestibular approach (ACA_TOETVA) (V and A group), 52 cases received standard TOETVA (V group). On postoperative day 1 (POD1), nylon monofilament test and numbness visual analogue scale score were conducted to evaluate the severity of numbness within the mental area, facial expression was tested to determine the motor function of lower mandible and the thickness of cutaneous and subcutaneous layers was measured with ultrasound. The other observation parameters including the time for operation and intraoperative blood loss were carefully collected.

Results: On POD1, nylon monofilament test showed that scores in the V and A group (2.9 ± 0.3) were significantly higher than V group (1.7 ± 0.5), P < 0.01, u = 254. The completion percentage of facial expression in the V and A group was 90.5% (67/74) and significantly higher than in V group (21.2%, 11/52), P < 0.01, χ = 62.35. The thickness increment of cutaneous and subcutaneous layer was 2.2 ± 1.2 mm in the V and A group, which was significantly less than in the V group (4.0 ± 1.2 mm), P < 0.01, u = 605. Compared with V group, the operation time (113.4 ± 22.3 min vs. 127.7 ± 25.6 min, u = 1262) and intraoperative blood loss (43.5 ± 13.4 ml vs. 51.0 ± 14.1 ml, u = 1355) were also significantly less in the V and A group.

Conclusions: The ACA transoral endoscopic thyroidectomy possesses the protective effect on mental nerve and motor function of lower mandible and facilitates the operative procedures of TOETVA.
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http://dx.doi.org/10.4103/jmas.jmas_263_21DOI Listing
May 2022

Gene alternation of cerebrospinal fluid in patients with leptomeningeal metastases of lung adenocarcinoma using next-generation sequencing.

BMC Cancer 2022 May 25;22(1):580. Epub 2022 May 25.

Department of Oncology, Shanghai Pulmonary Hospital &Thoracic Cancer Institute, School of Medicine, Tongji University, Shanghai, 200092, China.

Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) provide a better prognosis in EGFR-mutant non-small cell lung cancer (NSCLC). Nevertheless, the outcome of leptomeningeal metastasis (LM) remains poor. In addition, due to limited access to intracranial tumour tissue, gene alterations associated with leptomeningeal metastasis from lung adenocarcinoma (LM-LUAD) are unclear.

Methods: Forty-five patients with LM-LUAD from May 2019 to June 2021 in Guangdong Sanjiu Brain Hospital were enrolled in this study. Seventy-five percent (34/45) of patients with LM harbored EGFR mutations, and patients with progressive disease (PD) of LM had 3rd-generation EGFR-TKI therapy and were defined as Cohort 1; those without 3rd-generation EGFR-TKI therapy were defined as Cohort 2. Next-generation targeted panel sequencing (NGS) was performed in each cerebrospinal fluid (CSF) sample of the two cohorts, and 9/45 LM-LUAD patients had matched plasma (PLA).

Results: The common gene alterations discovered in the CSF of LM-LUAD were EGFR mutation (34/45, 75%), TP53 (25/45, 56%), CDKN2A (9/45, 20%), ALK (7/45, 16%), CTNNB1 (6/45, 13%), MET (5/45, 11%), APC (4/45, 9%), FGF4 (4/45, 9%), FGF3 (4/45, 9%), ERBB2 (4/45, 9%), and PIK3CG (4/45, 9%). Cooccurring mutations of TP53 and EGFR were found in 49% (22/45) of patients and correlated with poor prognosis. CDKN2A was identified in 20% (9/45) of patients and presented slightly shorter overall survival (OS) than those without (7.1 versus 8.8 months, p = 0.2). Cohort 1 had more genes associated with poor prognosis, consisting of CDK4, CDKN2A, PIK3CG, or PIK3CA, and YES1 and MET were more likely to be detected in cohort 2. The alteration of EGFR was comparable between CSF and matched PLA. Incidences of gene alterations such as CDK4, CDKN2A, MET, SOX2, JAK2, BRAF, and PIK3CG were more likely to be identified in CSF. All mutant allele frequencies (MAF) were much higher in CSF than in matched PLA.

Conclusions: CSF could be a potential candidate for the genetic profiling of LM-LUAD, demonstrating the genetic characteristics of LM in EGFR-mutated lung adenocarcinoma on diverse EGFR-TKI therapies.
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http://dx.doi.org/10.1186/s12885-022-09597-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9131527PMC
May 2022

A Single-Arm Phase 2 Trial on Induction Chemotherapy Followed by Concurrent Chemoradiation in Nasopharyngeal Carcinoma Using a Reduced Cumulative Dose of Cisplatin.

Front Oncol 2022 27;12:842281. Epub 2022 Apr 27.

Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Background: We conducted this study to evaluate if a reduced cumulative dose of induction and concurrent cisplatin conferred similar favorable outcomes when compared to trial NPC-0501.

Methods: Newly diagnosed nasopharyngeal carcinoma (NPC) with stage III-IVA were prospectively recruited from January 2015 to September 2019. Induction chemotherapy (IC) consisted of cisplatin 80mg/m on day 1 and capecitabine 1000mg/m twice daily from day 1 to 14 every 3 weeks for 3 cycles followed by concurrent chemoradiotherapy (CCRT) with 2 cycles of cisplatin 100mg/m given every 3 weeks. Tumor response was evaluated according to RECIST v1.1. Acute and late adverse events (AEs) were graded with CTCAE v4.0 and Late Radiation Morbidity Scoring of the RTOG, respectively.

Results: 135 patients were recruited. At 16 weeks after CCRT, all 130 patients who completed the entire course of radiotherapy (RT) had a complete response upon final assessment. With a median follow-up of 36.2 months, 22 treatment failures and 8 deaths were observed. The 3-year progression-free survival, overall survival, locoregional recurrence-free survival, and distant recurrence-free survival were 83.7%, 94.1%, 94.1%, and 85.9%, respectively. Our survival data outcomes were similar to those reported in the cisplatin and capecitabine (PX) induction arm of the 0501 trial. 103 patients (76.3%) reported acute grade 3-4 AEs. Two patients (1.5%) had late grade 3-4 complications, numerically fewer than those reported in the NPC-0501 trial.

Conclusions: Induction PX and concurrent cisplatin with a reduced cumulative cisplatin dose yield survival outcomes comparable to those reported in the NPC-0501 trial with excellent tolerability. Therefore, a reduced cumulative dose of cisplatin is a promising treatment scheme for nasopharyngeal carcinoma.
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http://dx.doi.org/10.3389/fonc.2022.842281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9092977PMC
April 2022

Efficacy and Safety of Qili Qiangxin Capsule on Dilated Cardiomyopathy: A Systematic Review and Meta-Analysis of 35 Randomized Controlled Trials.

Front Pharmacol 2022 28;13:893602. Epub 2022 Apr 28.

First Affiliated Hospital of Henan University of CM, Zhengzhou, China.

Qili Qiangxin Capsule (QQC), a Chinese patent medicine, is clinically effective in treating dilated cardiomyopathy (DCM). However, the meta-analysis of QCC combined with conventional western medicine (CWM) on DCM remains unexplored. This study aimed to systematically evaluate the efficacy and safety of QCC in the treatment of DCM. Searched the studies of the combination of QQC and CWM in the treatment of DCM, from databases like PubMed, Cochrane Library, Web of Science, Wan Fang Databases, Chinese Biomedical Literature Database, China Science and Technology Journal Database, China National Knowledge Infrastructure, prior to 15 January 2022. Two reviewers respectively regulated research selection, data extraction, and risk of bias assessment. Review Manager Software 5.4 was used for meta-analysis. Furthermore, GRADE pro3.6.1 software was selected to grade the current evidence in our findings. This meta-analysis has been registered in PROSPERO (CRD42022297906). There were 35 studies pertaining to 3,334 patients included. The meta-analysis showed compared with CWM alone, the combination therapy had significant advantages in improving the clinical efficiency rate (RR = 1.24, 95% CI: 1.19 to 1.29, < 0.00001), 6 min walking distance (6MWD) (MD = 41.93, 95%CI: 39.82 to 44.04, < 0.00001), superior in ameliorating the left ventricular ejection fraction (LVEF) (MD = 5.73, 95%CI: 4.70 to 6.77, < 0.00001), left ventricular end-diastolic dimension (LVEDD) (MD = -4.09, 95%CI: -4.91 to -3.27), < 0.00001), left ventricular end-systolic diameter (LVESD) (MD = -4.73, 95%CI: -5.63 to -3.84), < 0.00001) and BNP (MD = -101.09, 95%CI: -132.99 to -69.18), < 0.00001), and also superior in reducing hypersensitive-C-Reactive Protein (hs-CRP) (MD = -3.78, 95%CI: -4.35 to -3.21), < 0.00001), Interleukin- 6 (IL-6) (MD = -25.92, 95%CI: -31.35 to -20.50), < 0.00001), tumor necrosis factor-α (TNF-α) (MD = -5.04, 95%CI: -6.13 to -3.95), < 0.00001), high mobility group protein B1 (HMGB1) (MD = -4.34, 95%CI: -5.22 to -3.46), < 0.00001), and adverse reactions (ARs) (RR = 0.70, 95%CI: 0.51-0.97), = 0.03). The GRADE evidence quality rating presented with moderate or low quality of evidence for the available data. Compared with the control group, QQC combined with CWM may be effective in treating DCM. However, the conclusion of this study must be interpreted carefully due to the inferior quality and ambiguity of bias in the included trials. : https://www.crd.york.ac.uk/prospero, identifier [CRD42022297906].
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http://dx.doi.org/10.3389/fphar.2022.893602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9095857PMC
April 2022

Structurally Resemblant Dopants Enhance Organic Room-Temperature Phosphorescence.

Adv Mater 2022 Jul 12;34(29):e2201569. Epub 2022 Jun 12.

Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore, 117585, Singapore.

Doping has shown very promising potential in endowing room-temperature phosphorescence (RTP) properties of organic phosphors with minimal effort. Here, a new isomer design and doping strategy is reported that is applicable to dibenzothiophene (DBT) and its derivatives. Three isomers are synthesized to study the dopant effect on enhancing RTP of DBT derivatives. It is found that isomer dopants bearing close resemblance to the host with matched highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy levels and small energy difference between singlet- and triplet-excited states can yield efficient RTP for the doped system. Meanwhile, phosphorescence color from yellow to red is achieved by varying isomer dopants used for doping the DBT derivatives. This work represents an RTP enhancement strategy based on isomer design and doping to construct luminescent organic phosphors.
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http://dx.doi.org/10.1002/adma.202201569DOI Listing
July 2022

Dissecting Intra-Tumoral Changes Following Immune Checkpoint Blockades in Intrahepatic Cholangiocarcinoma Single-Cell Analysis.

Front Immunol 2022 26;13:871769. Epub 2022 Apr 26.

Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China.

Purpose: To dissect the tumor ecosystem following immune checkpoint blockades (ICBs) in intrahepatic cholangiocarcinoma (ICC) at a single-cell level.

Methods: Single-cell RNA sequencing (scRNA-seq) data of 10 ICC patients for the ICB clinical trial were extracted from GSE125449 and systematically reanalyzed. Bulk RNA-seq data of 255 ICC patients were analyzed. Infiltration levels of SPP1CD68 tumor-associated macrophages (TAMs) were examined by dual immunofluorescence (IF) staining in 264 resected ICC samples. The correlation between SPP1 TAMs and clinicopathological features as well as their prognostic significance was evaluated.

Results: Among the 10 patients, five received biopsy at baseline, and others were biopsied at different timings following ICBs. Single-cell transcriptomes for 5,931 cells were obtained. A tighter cellular communication network was observed in ICB-treated ICC. We found a newly emerging VEGF signaling mediated by PGF-VEGFR1 between cancer-associated fibroblasts (CAFs) and endothelial cells in ICC following ICBs. SPP1 expression was dramatically upregulated, and SPP1 TAM gene signatures were enriched in TAMs receiving ICB therapy. We also identified SPP1 TAMs as an independent adverse prognostic indicator for survival in ICC.

Conclusion: Our analyses provide an overview of the altered tumor ecosystem in ICC treated with ICBs and highlight the potential role of targeting CAFs and SPP1TAMs in developing a more rational checkpoint blockade-based therapy for ICC.
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http://dx.doi.org/10.3389/fimmu.2022.871769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9088915PMC
April 2022
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