Publications by authors named "Rong Zeng"

549 Publications

Case report of a rare giant bone island in a vertebral body combined with hemangioma.

J Int Med Res 2021 May;49(5):3000605211010699

Department of Orthopaedics, The First People's Hospital of Longquanyi District, Chengdu, Sichuan, China.

This case report describes a rare giant bone island combined with hemangioma diagnosed in a patient with osteolytic vertebral metastases. The bone island's greatest diameter was 3.15 cm, and bone islands of this size are rare in the literature. This article aims to provide clinicians with information about the diagnosis and relevant literature of bone islands.
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http://dx.doi.org/10.1177/03000605211010699DOI Listing
May 2021

Establishment of predicting equation for individual sufentanil dosage postoperatively based on gene polymorphisms.

Pain Pract 2021 May 12. Epub 2021 May 12.

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

Background: Postoperative analgesia is widely used for patients undergoing major surgeries. Individual differences in genetic polymorphisms may be obstructive factors for accurately anesthetics using. However, the equation for predicting sufentanil dosage postoperatively based on genetic design has been established yet. Our aim was to establish sufentanil dosage postoperatively prediction equation based on patients' genetic polymorphisms.

Methods: 140 patients with total gastrectomy and radical resection of pulmonary carcinoma were included. To establish sufentanil dosage postoperatively for gastric cancer patients, we collected patients' basic information and CYP3A4*1G, COMTVal158Met, OPRM1A118G and ABCB1C3435T gene sequencing results. To verify this equation, we put lung cancer surgeries patients' information into it.

Results: The sufentanil dosage prediction equation postoperatively was y = 4.104 - 0.222 × [gender] + 0.021 × [OPRM1A118G] + 0.249 × [ABCB1C3435T]. Lung cancer surgeries patients' information were substituted into it. The results showed no significant differences between predicted and actual sufentanil dosage (P > 0.05).

Conclusion: We established the prediction equation for individual sufentanil dosage postoperatively based on gene polymorphisms. The results showed this prediction equation was valid, which might be used for different types of surgeries.
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http://dx.doi.org/10.1111/papr.13030DOI Listing
May 2021

[Risk Factors for Patients Using Intraoperative Vasopressor Infusions During Carotid Body Tumor Excision].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2021 Apr;43(2):199-204

Department of Vascular Surgery,PUMC Hospital,CAMS and PUMC,Beijing 100730,China.

Objective To investigate the risk factors for patients using intraoperative vasopressor infusions during carotid body tumor(CBT)excision.Patients' mean arterial pressure(MAP)and heart rate(HR)fluctuations as well as their requirements for vasoactive agents during surgery were assessed. Methods The patients receiving CBT excision in Peking Union Medical College Hospital from May 1,2013 to July 31,2017 were included for a retrospective cohort study.The potential factors of intraoperative requirement for vasopressor infusions were investigated using univariate analysis and Logistic multivariate analysis.Furthermore,the relationships of Shamblin types of CBT with intraoperative MAP/HR fluctuations and requirements for vasoactive agents were analyzed. Results A total of 108 patients with 116 CBTs were included.Univariate analysis revealed that maximum tumor diameter >4 cm,intraoperative internal carotid artery injury,internal carotid artery reconstruction,malignant pathology,advanced Shamblin types(type Ⅱ and Ⅲ),estimated blood loss ≥400 ml,and operation duration >4 hours were associated with intraoperative requirements for vasopressor infusions.Logistic analysis showed that Shamblin type Ⅲ(OR=2.286,95% CI=1.324-14.926,P=0.016)and operation duration >4 hours(OR=3.874,95% CI=1.020-14.623,P=0.046)were risk factors for intraoperative requirements for vasopressor infusions during CBT surgery.In addition,Shamblin type Ⅲ was associated with intraoperative abnormal HR elevation and requirements for vasopressors.Conclusions Shamblin type Ⅲ and operation duration>4 hours are risk factors for intraoperative requirements of patients for using vasopressor infusions during CBT surgery.Shamblin type Ⅲ is associated with intraoperative abnormal HR elevation and requirements for vasopressors.
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http://dx.doi.org/10.3881/j.issn.1000-503X.12976DOI Listing
April 2021

Effects of Itraconazole and Micafungin on Aspergillus fumigatus Biofilms.

Mycopathologia 2021 May 6. Epub 2021 May 6.

Institute of Dermatology, Chinese Academy of Medical Science and Peking Union Medical College, 12 Jiangwangmiao Street, Nanjing, 210042, Jiangsu, China.

Aspergillus fumigatus (A. fumigatus) is the most common airborne opportunistic fungal pathogen. Biofilm formation is one of the main pathogenic mechanisms of A. fumigatus. During the past decades, A. fumigatus azole resistance has become prevalent due to the medical and agricultural use of antifungal drugs and fungicides. Until now, the role of fungal biofilms in azole resistance of A. fumigatus remains unclear. In the present study, we compared biofilm drug susceptibility and biofilm formation under itraconazole of azole-resistant strains, sensitive strains, and standard strains, separately. The biofilm viability and matrix thickness at the early and the late stage were measured by XTT assay and Calcofluor white. Our results showed that the sessile minimum inhibitory concentration of itraconazole, which describing the inhibition of drugs on fungi sessile with biofilm, was much higher than the traditional minimal inhibitory concentration of itraconazole. Additionally, low concentrations of itraconazole inhibited biofilm formation of A. fumigatus strains. Notably, biofilm formation by azole-resistant strains could not be inhibited by high concentrations of itraconazole but could be effectively restrained by low concentrations of micafungin, revealing the efficacy of a cell-wall inhibitor to disrupt A. fumigatus biofilm formation. However, late-stage biofilms of both azole-resistant strains and standard strains were hard to disrupt using itraconazole. We found that itraconazole was effective to prevent A. fumigatus biofilm formation at the early stage. For the treatment of A. fumigatus biofilm, our findings suggest that an early-stage preventive strategy is preferred and micafungin is effective to control the azole-resistant strain infection.
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http://dx.doi.org/10.1007/s11046-021-00534-4DOI Listing
May 2021

The effect of epidural analgesia on maternal-neonatal outcomes: a retrospective study.

Ginekol Pol 2021 Apr 29. Epub 2021 Apr 29.

Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizho, China.

Objectives: Epidural analgesia is commonly used for relieving labor pain incontemporary clinical practice. The rate of pregnant women who request epiduralanalgesia during labor has been increasing annually, leading to a debate on the effectof epidural analgesia on maternal or neonatal outcomes.

Material And Methods: The medical records of nulliparous women with a term singletonpregnancy from January to December 2019 at the Affiliated Hospital of ZunyiMedical University were retrospectively reviewed. The women were divided intothose who received epidural analgesia during delivery and those who did not receiveit. Maternal and neonatal outcomes were assessed.

Results: A total of 528 women met the inclusion criteria. The overall labor analgesiarate was 43.0% (227). Women with epidural analgesia had a significantly longersecond stage [34.5 (22.8-65.3) vs 27.0 (18.0-41.3) min, p < 0.001] and total durationof labor [698.5 (493.5-875.0) vs 489.5 (344.0-676.3) min, p < 0.001] compared withthose without epidural. There were no significant relationships between epiduralanalgesia and the normal vaginal delivery rate, the incidence of episiotomy, and otheradverse maternal or neonatal outcomes (p > 0.05).

Conclusions: Epidural analgesia can prolong the second stage of labor, but this is no increased risk for both mother and neonate.
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http://dx.doi.org/10.5603/GP.a2021.0007DOI Listing
April 2021

Resveratrol Alleviates Vascular Endothelial Damage Caused by Lower-Extremity Ischemia Reperfusion (I/R) through Regulating Keap1/Nrf2 Signaling-Mediated Oxidative Stress.

Evid Based Complement Alternat Med 2021 24;2021:5556603. Epub 2021 Mar 24.

Department of Vascular Surgery, Peking Union Medical College Hospital, Beijing 100730, China.

The present study aims to investigate the protective effects of Resveratrol (RSV) against vascular endothelial damage caused by lower-extremity I/R and the underlying preliminary mechanism. The in vitro hypoxia reoxygenation (HR) model was established on HUVECs. Lower-extremity I/R model was established on rats followed by being treated with RSV and the pathological state of artery was evaluated by HE and EVG staining, while the apoptotic state of artery was detected by TUNEL assay. The cell viability was detected by MTT assay and the apoptotic state of cells was determined by Hoechst test and flow cytometry assay. DCFH-DA staining was used to measure the level of ROS and the production of MDA and SOD was measured by commercial kits. The expression level of Nrf2, Keap1, HO-1, Bcl-2, Bax, and Caspase-3 in cells was determined by Western blot. Nrf2 was knocked down by siRNA technology. Overall, our data indicated that increased cell viability, declined apoptotic rate, and alleviated oxidative stress were observed in RSV treated HR HUVECs, which were significantly reversed by knocking down Nrf2. Animal experiment revealed that the pathological and apoptotic state of femoral artery were dramatically ameliorated by the treatment of RSV, accompanied by the alleviated oxidative stress, which were abolished by the co-administration of ML385, an inhibitor of Nrf2. Taken together, our data revealed that RSV might alleviate vascular endothelial injury induced by lower-extremity I/R injury through regulating Keap1/Nrf2 signaling-mediated oxidative stress.
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http://dx.doi.org/10.1155/2021/5556603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016569PMC
March 2021

Plasma glycerophospholipid profile, erythrocyte n-3 PUFAs, and metabolic syndrome incidence: a prospective study in Chinese men and women.

Am J Clin Nutr 2021 Apr 7. Epub 2021 Apr 7.

CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

Background: Animal studies have highlighted critical roles of glycerophospholipid (GP) metabolism in various metabolic syndrome (MetS)-related features such as dyslipidemia, obesity, and insulin resistance. However, human prospective studies of associations between circulating GPs and risks of MetS are scarce.

Objectives: We aimed to investigate whether GPs are associated with incidence of MetS in a well-established cohort.

Methods: A total of 1243 community-dwelling Chinese aged 50-70 y without MetS at baseline and followed up for 6 y were included in current analyses. A total of 145 plasma GPs were quantified by high-throughput targeted lipidomics. MetS was defined using the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian Americans.

Results: After 6 y, 429 participants developed MetS. Eleven GPs, especially those with long-chain polyunsaturated fatty acids (LCPUFAs) or very-long-chain polyunsaturated fatty acids (VLCPUFAs) at the sn-2 position, including 1 phosphatidylcholine (PC) [PC(18:0/22:6)], 9 phosphatidylethanolamines (PEs) [PE(16:0/22:6), PE(18:0/14:0), PE(18:0/18:1), PE(18:0/18:2), PE(18:0/20:3), PE(18:0/22:5), PE(18:0/22:6), PE(18:1/22:6), and PE(18:2/22:6)], and 1 phosphatidylserine (PS) [PS(18:0/18:0)], were positively associated with incident MetS (RRs: 1.16-1.30 per SD change; Bonferroni-corrected P < 0.05). In network analysis, the strongest positive association for MetS incidence was evidenced in a module mainly composed of PEs containing C22:6 and PSs [RR: 1.21; 95% CI: 1.12, 1.31 per SD change; Bonferroni-corrected P < 0.05]. This association was more pronounced in participants with lower erythrocyte total n-3 PUFA concentrations [Bonferroni-corrected Pinter(P value for the interaction)< 0.05].

Conclusions: Elevated plasma concentrations of GPs, especially PEs with LCPUFAs or VLCPUFAs at the sn-2 position, are associated with higher risk of incident MetS. Future studies are merited to confirm our findings.
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http://dx.doi.org/10.1093/ajcn/nqab050DOI Listing
April 2021

First Report of Strawberry Crown Rot Caused by Xanthomonas fragariae in China.

Plant Dis 2021 Apr 2. Epub 2021 Apr 2.

Shanghai Academy of Agricultural Sciences, Eco-Environmental Protection Research Institute, Shanghai, China;

Strawberry (Fragaria × ananassa Duch.) is a kind of fruit with great economic importance and widely cultivated in the world. From 2019 to 2020, a serious crown rot disease was sporadically observed in several strawberry cultivars including 'Zhang Ji', 'Hong Yan' and 'Yue Xiu' in Shanghai, China. Initially, water-soaked rot appeared in inner tissue of strawberry crown, then progressed into browning and hollowing symptoms accompanied with yellow discolorations of young leaves. To isolate and identify the causal agent, small pieces of tissue taken from ten diseased crowns were sterilized by 70% alcohol. The cut-up pieces were macerated and serially diluted. The dilutions were placed on nutrient agar (NA) medium. After incubation at 25°C for 4-5 days, the yellow bacterial colonies were tiny and were streaked on NA plate for purification. The colonies were yellow, mucoid, smooth-margined, and five independent representative colonies were used for further confirmation. To confirm the species identity of the bacterial, genomic DNA was extracted from the five representative isolates, and 16S rRNA gene was amplified and sequenced using universal primers 27F/1492R. The 16S rRNA sequence was deposited in GenBank (MW725235) and showed 99% nucleotide similarity with Xanthomonas fragariae strain LMG 708 (NR_026318). The isolate's identity was further confirmed by X. fragariae-specific primers XF9/XF12 (Roberts et al. 1996). All five isolates could be detected by XF9/XF12 primer. To confirm Koch's postulates, five healthy strawberry plants were placed in 1000 ml glass beakers by submerging the cutting wound in 50 ml the bacterial suspension of 108 CFU/ml. Five additional strawberry plants treated with sterilized water served as a control. The beakers containing inoculated plants were sealed with plastic film at 25°C. Water-soaked rot appeared on internal tissue of crown similar to those observed in the field within 10-12 days after inoculation, while the control samples remained healthy. The bacteria were re-isolated from rot of inoculated crowns, and confirmed by X. fragariae-specific primers XF9/XF12. X. fragariae has been reported to cause angular leaf spot on strawberry in China (Wang et al. 2017; Wu et al., 2020). It's also found that X. fragariae could systematically infect crown tissue (Milholland et al. 1996; Mahuku and Goodwin, 1997). To our knowledge, this is the first report of X. fragariae causing strawberry crown rot in China. This report increased our understanding of X. fragariae, and showed that the spread of this disease might seriously threaten the development of strawberry industry in the future.
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http://dx.doi.org/10.1094/PDIS-03-21-0574-PDNDOI Listing
April 2021

Discovery of sertraline and its derivatives able to combat drug-resistant gastric cancer cell via inducing apoptosis.

Bioorg Med Chem Lett 2021 Jun 26;41:127997. Epub 2021 Mar 26.

Department of Medicinal Chemistry, School of Pharmacy, Third Military Medical University, Chongqing 40038, China. Electronic address:

Resistance phenomena during chemotherapy of tumor has been severely hampering the applications of chemotherapeutics. Due to advantage of drug repurposing, discovery of new chemosensitizers based on approved drugs is an effect strategy to find new candidates. Herein, we found antidepressant drug - sertraline, could sensitize drug-resistant gastric cancer cell (SGC-7901/DDP) with the IC value of 18.73 μM. To understand the structure-activity relationship and improve the activity, 30 derivatives were synthesized and evaluated. The IC value of the best compound was improved to 5.2 μM. Moreover, we found apoptosis induction and cell cycle arrest was the reason for the cell death of the drug-resistant cells after treatment of sertraline and derivatives, and PI3K/Akt/mTOR pathway was involved.
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http://dx.doi.org/10.1016/j.bmcl.2021.127997DOI Listing
June 2021

Proposed modification to the Shamblin's classification of carotid body tumors: A single-center retrospective experience of 116 tumors.

Eur J Surg Oncol 2021 Mar 20. Epub 2021 Mar 20.

Department of Vascular Surgery, Peking Union Medical College Hospital, Shuaifuyuan 1, Dongcheng District, Beijing, 100730, China. Electronic address:

Objectives: Carotid body tumors (CBTs) are rare head and neck neoplasms, we aimed to propose a modification to the Shamblin's classification of CBTs.

Materials And Methods: This retrospective study included 105 patients (116 CBTs) operated at our institution from March 2013 to July 2020. CBTs were divided by a modified Shamblin's classification into five subtypes (type I-V) based on the radiographic features. Correlations between modified classification and intraoperative bleeding, internal carotid artery (ICA) bypass and postoperative neural complications, as main outcomes, as well as other outcomes were analyzed.

Results: Surgeries for type V and type I CBTs had the most (median: 700 ml, IQR: 375-1575 ml) and least (median: 20 ml, IQR: 20-50 ml) bleeding, respectively. Intraoperatively, ICA bypass was needed in 41.7% (10/24) type V, 18.2% (8/44) type IV and 5.9% (1/17) type III lesions, but not in other subtypes (p = .001). Postoperatively, overall cranial nerve deficits (CND) were found most frequently in type V tumors (17/24, 70.8%) (p = .016). Permanent CND were found in 33.3% (8/24) type V and 4.5% (2/44) type IV lesions, but not in other subtypes (p = .001). Other outcomes including external carotid artery ligation, operation time, blood transfusion, postoperative intensive unit care and postoperative hospitalization also showed significant difference among different subtypes. Patients recovered uneventfully during a follow-up of 23.5 ± 16.2 months except for one ipsilateral recurrence at 42 months after surgery.

Conclusions: The modified classification was correlated with surgical outcomes of CBTs and will be helpful for making surgical plans.
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http://dx.doi.org/10.1016/j.ejso.2021.03.244DOI Listing
March 2021

Successful treatment of oral pigmented spots in Chinese subjects with Peutz-Jeghers syndrome using a 755-nm picosecond laser.

Indian J Dermatol Venereol Leprol 2021 Mar-Apr;87(2):288-289

Institute of Dermatology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

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http://dx.doi.org/10.25259/IJDVL_151_20DOI Listing
February 2020

Oxidative α-C-C Bond Cleavage of 2° and 3° Alcohols to Aromatic Acids with O at Room Temperature via Iron Photocatalysis.

Org Lett 2021 Apr 26;23(8):2915-2920. Epub 2021 Mar 26.

The selective α-C-C bond cleavage of unfunctionalized secondary (2°) and tertiary alcohols (3°) is essential for valorization of macromolecules and biopolymers. We developed a blue-light-driven iron catalysis for aerobic oxidation of 2° and 3° alcohols to acids via α-C-C bond cleavages at room temperature. The first example of oxygenation of the simple tertiary alcohols was reported. The iron catalyst and blue light play critical roles to enable the formation of highly reactive O radicals from alcohols and the consequent two α-C-C bond cleavages.
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http://dx.doi.org/10.1021/acs.orglett.1c00556DOI Listing
April 2021

Myogenin suppresses apoptosis induced by angiotensin II in human induced pluripotent stem cell-derived cardiomyocytes.

Biochem Biophys Res Commun 2021 May 17;552:84-90. Epub 2021 Mar 17.

Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510100, China. Electronic address:

Background: Angiotensin II (Ang II), an important component of the renin-angiotensin system (RAS), plays a critical role in the pathogenesis of cardiovascular disorders. In addition, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been considered as a promising platform for studying personalized medicine for heart diseases. However, whether Ang II can induce the apoptosis of hiPSC-CMs is not known.

Methods: In this study, we treated hiPSC-CMs with different concentrations of Ang II [0 nM (vehicle as a control), 1 nM, 10 nM, 100 nM, 1 μM, 10 μM, 100 μM, and 1 mM] for various time periods (24 h, 48 h, 6 days, and 10 days) and analyzed the viability and apoptosis of hiPSC-CMs.

Results: We found that treatment with 1 mM Ang II for 10 days reduced the viability of hiPSC-CMs by 41% (p = 2.073E-08) and increased apoptosis by 2.74-fold, compared to the control group (p = 6.248E-12). MYOG, which encodes the muscle-specific transcription factor myogenin, was also identified as an apoptosis-suppressor gene in Ang II-treated hiPSC-CMs. Ectopic MYOG expression decreased the apoptosis and increased the viability of Ang II-treated hiPSC-CMs. Further analysis of the RNA sequencing (RNA-seq) data illustrated that myogenin ameliorated Ang II-induced apoptosis of hiPSC-CMs by downregulating the expression of proinflammatory genes.

Conclusion: Our findings suggest that Ang II induces the apoptosis of hiPSC-CMs and that myogenin attenuates Ang II-induced apoptosis.
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http://dx.doi.org/10.1016/j.bbrc.2021.03.031DOI Listing
May 2021

Circulating Glycerolipids, Fatty Liver Index and Incidence of Type 2 Diabetes: A Prospective Study among Chinese.

J Clin Endocrinol Metab 2021 Mar 12. Epub 2021 Mar 12.

CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

Context: Few lipidomic studies have specifically investigated the association of circulating glycerolipids and type 2 diabetes (T2D) risk, especially among Asian populations. It remains unknown whether or to what degree fatty liver could explain the glycerolipids-T2D associations.

Objective: We aimed to assess associations between plasma glycerolipids and incident T2D, and explore a potential role of liver fat accumulation in the associations.

Design: A prospective cohort study with 6-year of follow-up.

Participants: This work included 1,781 Chinese aged 50-70 years.

Main Outcome Measures: T2D.

Results: At 6-year resurvey, 463 participants developed T2D. At the false-discovery rate (FDR) of 5%, 43 of 104 glycerolipids were significantly associated with incident T2D risk after multivariate adjustment for conventional risk factors. After further controlling for glycated hemoglobin (HbA1c), 9 of the 43 glycerolipids remained significant, including 2 diacylglycerols (DAGs)(16:1/20:4, 18:2/20:5) and 7 triacylglycerols (TAGs)(46:1, 48:0, 48:1, 50:0, 50:1, 50:2, and 52:2), with relative risks (RRs) (95% confidence intervals [CIs]) ranging from 1.16 (1.05 to 1.27) to 1.23 (1.11 to 1.36) per SD increment of glycerolipids. However, additional adjustment for fatty liver index (FLI) largely attenuated these findings (RRs [95% CIs] were 0.88 [0.81 to 0.95] to 1.10 [1.01 to 1.21]). Mediation analyses suggested that the FLI explained 12%-28% glycerolipids-T2D associations (all p < 0.01).

Conclusions: Higher plasma levels of DAGs and TAGs were associated with increased incident T2D risk in this Chinese population, which might be partially explained by liver fat accumulation.
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http://dx.doi.org/10.1210/clinem/dgab165DOI Listing
March 2021

Serum BDNF levels and the antidepressant effects of electroconvulsive therapy with ketamine anaesthesia: a preliminary study.

PeerJ 2021 5;9:e10699. Epub 2021 Feb 5.

The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.

Objective: To firstly examine the relationship between serum brain-derived neurotrophic factor (BDNF) levels and antidepressant response to ketamine as an anaesthesia in electroconvulsive therapy (ECT) in Chinese patients with treatment-refractory depression (TRD).

Methods: Thirty patients with TRD were enrolled and underwent eight ECT sessions with ketamine anaesthesia (0.8 mg/kg) alone. Depression severity, response and remission were evaluated using the 17-item Hamilton Depression Rating Scale (HAMD-17). Enzyme-linked immunosorbent assay (ELISA) was applied to examine serum BDNF levels in patients with TRD at baseline and after the second, fourth and eighth ECT sessions. Baseline serum samples were also collected for 30 healthy controls.

Results: No significant differences were observed in serum BDNF levels between patients with TRD and healthy controls at baseline ( > 0.05). The remission rate was 76.7% (23/30) after the last ECT treatment, although all patients with TRD obtained antidepressant response criteria. Serum BDNF levels were not altered compared to baseline, even between remitters and nonremitters (all > 0.05), despite the significant reduction in HAMD-17 and Brief Psychiatric Rating Scale (BPRS) scores after ECT with ketamine anaesthesia (all < 0.05). The antidepressant effects of ECT with ketamine anaesthesia were not correlated with changes in serum BDNF levels (all > 0.05).

Conclusion: This preliminary study indicated that serum BDNF levels do not appear to be a reliable biomarker to determine the antidepressant effects of ketamine as an anaesthesia in ECT for patients with TRD. Further studies with larger sample sizes are warranted to confirm these findings.
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http://dx.doi.org/10.7717/peerj.10699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869666PMC
February 2021

Development and Validation of a Nomogram for the Estimation of Response to Platinum-Based Neoadjuvant Chemotherapy in Patients with Locally Advanced Cervical Cancer.

Cancer Manag Res 2021 11;13:1279-1289. Epub 2021 Feb 11.

Department of Breast Surgery, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology and Hubei Provincial Clinical Research Center for Breast Cancer, Wuhan, Hubei, 430079, People's Republic of China.

Purpose: Non-response to platinum-based neoadjuvant chemotherapy (non-rNACT) reduces the surgical outcomes of patients with locally advanced cervical cancer (LACC). The development of an accurate preoperative method to predict a patient's response to NACT (rNACT) could help surgeons to manage therapeutic intervention in a more appropriate manner.

Patients And Methods: We recruited a total of 341 consecutive patients who underwent platinum-based NACT followed by radical surgery (RS) at the Hubei Cancer Hospital between January 1, 2010 and April 1, 2020. All patients had been diagnosed with stage Ib2-IIa2 cervical cancer in accordance with the 2009 International Federation of Gynecology and Obstetrics (FIGO) classification system. First, we created a training cohort of patients who underwent NACT+RS (n=239) to develop a nomogram. We then validated the performance of the nomogram in a validation cohort of patients who underwent NACT+RS (n=102). Data analysis was conducted from October 1, 2020. First, we determined overall survival (OS) and progression-free survival (PFS) after NACT+RS. Multivariate logistic regression was then used to identify independent risk factors that were associated with the response to rNACT; these were then incorporated into the nomogram.

Results: The analysis identified several significant differences between the rNACT and non-rNACT groups, including neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), lymphocyte monocyte ratio (LMR), platelet count, and FIGO stage. The performance of the rNACT nomogram score exhibited a robust C-index of 0.76 (95% confidence interval [CI]: 0.65 to 0.87) in the training cohort and high C-index of 0.71 (95% CI: 0.62 to 0.78) in the validation cohort. Clinical impact curves showed that the nomogram had good predictive ability.

Conclusion: We successfully established an accurate and optimized nomogram that could be used preoperatively to predict rNACT in patients with LACC. This model can be used to evaluate the risk of an individual patient experiencing rNACT and therefore facilitate the choice of treatment.
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http://dx.doi.org/10.2147/CMAR.S293268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884956PMC
February 2021

An indirect comparison by Bayesian network meta-analysis of drug-coated devices versus saphenous vein graft bypass in femoropopliteal arterial occlusive disease.

J Vasc Surg 2021 Feb 16. Epub 2021 Feb 16.

Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address:

Objective: To compare the efficacy and safety between drug-coated devices (DCDs) and bypass surgery with saphenous vein graft (BSV) in femoropopliteal arterial occlusive disease.

Methods: A Bayesian network meta-analysis and indirect comparison were performed. Randomized controlled trials of BSV, bypass surgery with prosthetic graft, bare metal stents, endoluminal bypass (covered stent), percutaneous transluminal angioplasty, and DCDs treating femoropopliteal arterial occlusive disease were collected. The primary end point was target lesion revascularization/target vessel revascularization, and secondary end points were all-cause mortality, limb salvage, and early complications (PROSPERO registry number: CRD42019136530).

Results: Forty-two trials and 6867 patients were included. The comparison of DCDs and BSV revealed no significant difference in the 1-year target lesion revascularization/target vessel revascularization (DCDs vs BSV: odds ratio [OR], 0.60; 95% credible interval [CrI], 0.16-2.39). Total early complications from BSV were significantly higher than those from DCDs (DCDs vs BSV: OR, 0.14; 95% CrI, 0.05-0.45), and the main complications of BSV were not death related. There was also no significant difference in systemic early complications (DCDs vs BSV: OR, 0.19; 95% CrI, 0.00-7.82) and 1-year amputation rate (DCDs vs BSV: OR, 2.81; 95% CrI, 0.16-89.53). The 30-day (DCDs vs BSV: OR, 0.38; 95% CrI, 0.00-110.46), 1-year (DCDs vs BSV: OR, 0.96; 95% CrI, 0.24-3.29), 2-year (DCDs vs BSV: OR, 1.60; 95% CrI, 0.64-4.95), and 5-year all-cause mortality rates (DCDs vs BSV: OR, 2.05; 95% CrI, 0.92-4.39) showed no significant differences between DCDs and BSV, although there was a noticeable tendency toward significant results of a higher 5-year mortality rate.

Conclusions: There is no significant difference between DCDs and BSV in short-term efficacy or short- and long-term mortality. Despite traditional BSV remaining the gold standard, DCDs provide a reasonable alternative therapy. In addition, the DCDs have a lower short-term morbidity associated with the procedure at the cost of the possible risk of higher long-term mortality. Clinical trials with more validity are required for a direct comparison between BSV and DCDs.
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http://dx.doi.org/10.1016/j.jvs.2020.11.054DOI Listing
February 2021

Treatment of venous thromboembolism in cancer patients: a systematic review and meta-analysis on the efficacy and safety of different direct oral anticoagulants (DOACs).

Ann Transl Med 2021 Jan;9(2):162

Department of Vascular Surgery, Peking Union Medical College Hospital, Beijing, China.

Background: To evaluate the efficacy and safety of different direct oral anticoagulants (DOACs) compared with low molecular weight heparins (LMWHs) in the treatment of venous thromboembolism (VTE) in cancer patients.

Methods: Literature was searched in databases including Cochrane Library, EMBASE (Ovid), and MEDLINE (PubMed). Eligible studies were included, and data were collected independently by 2 reviewers. We conducted a systematic review of the efficacy and safety of DOACs in the treatment of VTE in cancer patients. The odds ratios (ORs) of different DOACs compared with LMWHs for VTE, deep vein thrombosis (DVT), pulmonary embolism (PE) recurrence, major bleeding, and clinically relevant non-major bleeding (CRNMB), were calculated in meta-analyses and subgroup analyses.

Results: A total of 18 articles were eligible for analyses, including 4 randomized controlled trials (RCTs) and 14 retrospective studies. Both RCTs and retrospective studies confirmed that DOACs decreased the risk of VTE recurrence [RCTs: OR, 0.60; 95% confidence interval (CI), 0.45-0.80; retrospective studies: OR, 0.73; 95% CI, 0.59-0.90] and DVT recurrence (RCTs: OR, 0.54; 95% CI, 0.36-0.80; retrospective studies: OR, 0.20; 95% CI, 0.06-0.63), but not PE recurrence or fatal PE in cancer patients. Subgroup analyses revealed an important role of rivaroxaban in decreasing recurrent VTE. Meanwhile, major bleeding events were not increased in the DOAC group, but the risks of CRNMBs were significantly elevated. Subgroup analyses confirmed the role of rivaroxaban in increasing the risk of major bleeding events and CRNMBs.

Conclusions: Compared with LMWHs, DOACs (especially rivaroxaban) significantly reduce the risk of VTE and DVT, but not PE recurrence, in patients with cancer. Although DOACs did not increase the major bleeding events in pooled analysis, rivaroxaban showed an elevated risk of this adverse effect in subgroup analysis. In addition, the risk of CRNMB events was increased after the application of DOACs including rivaroxaban.
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http://dx.doi.org/10.21037/atm-20-8156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867886PMC
January 2021

Dynamically remodeled hepatic extracellular matrix predicts prognosis of early-stage cirrhosis.

Cell Death Dis 2021 Feb 8;12(2):163. Epub 2021 Feb 8.

State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, 200031, Shanghai, China.

Liver cirrhosis remains major health problem. Despite the progress in diagnosis of asymptomatic early-stage cirrhosis, prognostic biomarkers are needed to identify cirrhotic patients at high risk developing advanced stage disease. Liver cirrhosis is the result of deregulated wound healing and is featured by aberrant extracellular matrix (ECM) remodeling. However, it is not comprehensively understood how ECM is dynamically remodeled in the progressive development of liver cirrhosis. It is yet unknown whether ECM signature is of predictive value in determining prognosis of early-stage liver cirrhosis. In this study, we systematically analyzed proteomics of decellularized hepatic matrix and identified four unique clusters of ECM proteins at tissue damage/inflammation, transitional ECM remodeling or fibrogenesis stage in carbon tetrachloride-induced liver fibrosis. In particular, basement membrane (BM) was heavily deposited at the fibrogenesis stage. BM component minor type IV collagen α5 chain expression was increased in activated hepatic stellate cells. Knockout of minor type IV collagen α5 chain ameliorated liver fibrosis by hampering hepatic stellate cell activation and promoting hepatocyte proliferation. ECM signatures were differentially enriched in the biopsies of good and poor prognosis early-stage liver cirrhosis patients. Clusters of ECM proteins responsible for homeostatic remodeling and tissue fibrogenesis, as well as basement membrane signature were significantly associated with disease progression and patient survival. In particular, a 14-gene signature consisting of basement membrane proteins is potent in predicting disease progression and patient survival. Thus, the ECM signatures are potential prognostic biomarkers to identify cirrhotic patients at high risk developing advanced stage disease.
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http://dx.doi.org/10.1038/s41419-021-03443-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870969PMC
February 2021

Smart Responsive Quercetin-Conjugated Glycol Chitosan Prodrug Micelles for Treatment of Inflammatory Bowel Diseases.

Mol Pharm 2021 03 1;18(3):1419-1430. Epub 2021 Feb 1.

State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, P. R. China.

The incidence and progression of inflammatory bowel disease are closely related to oxidative stress caused by excessive production of reactive oxygen species (ROS). To develop an efficacious and safe nanotherapy against inflammatory bowel diseases (IBD), we designed a novel pH/ROS dual-responsive prodrug micelle as an inflammatory-targeted drug, which was comprised by active quercetin () covalently linked to biocompatible glycol chitosan () by aryl boronic ester as a responsive linker. The optimized micelles exhibited well-controlled physiochemical properties and stability in a physiological environment. Time-dependent NMR spectra traced the changes in the polymer structure in the presence of HO, confirming the release of the drug. The drug release studies indicated a low release rate (<20 wt %) in physiological conditions, but nearly complete release (>95 wt % after 72 h incubation) in a pH 5.8 medium containing 10 μM HO, exhibiting a pH/ROS dual-responsive property and sustained release behavior. Importantly, the negligible drug release in a simulated gastric environment in 1 h allowed us to perform intragastric administration, which has potential to achieve the oral delivery by mature enteric-coating modification in future. Further activities and biodistribution experiments found that the micelles tended to accumulate in intestinal inflammation sites and showed better therapeutic efficacy than the free drugs (quercetin and mesalazine) in a colitis mice model. Typical inflammatory cytokines including TNF-α, IL-6, and iNOS were significantly suppressed by micelle treatment. Our work promoted inflammatory-targeted delivery and intestinal drug accumulation for active single drug quercetin and improved the therapeutic effect of IBD. The current study also provided an alternative strategy for designing a smart responsive nanocarrier for a catechol-based drug to better achieve the target drug delivery.
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http://dx.doi.org/10.1021/acs.molpharmaceut.0c01245DOI Listing
March 2021

iTRAQ-based proteomic profiling reveals protein alterations after traumatic brain injury and supports thyroxine as a potential treatment.

Mol Brain 2021 01 27;14(1):25. Epub 2021 Jan 27.

Emergency Center, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.

Traumatic brain injury (TBI) is a primary cause of disability and death across the world. Previously, RNA analysis was widely used to study the pathophysiological mechanisms underlying TBI; however, the relatively low correlation between the transcriptome and proteome revealed that RNA transcription abundance does not reliably predict protein abundance, which led to the emergence of proteomic research. In this study, an iTRAQ proteomics approach was applied to detect protein alterations after TBI on a large scale. A total of 3937 proteins were identified, and 146 proteins were significantly changed after TBI. Moreover, 23 upregulated proteins were verified by parallel reaction monitoring (PRM), and fold changes in 16 proteins were consistent with iTRAQ outcomes. Transthyretin (Ttr) upregulation has been demonstrated at the transcriptional level, and this study further confirmed this at the protein level. After treatment with thyroxine (T4), which is transported by Ttr, the effects of T4 on neuronal histopathology and behavioral performance were determined in vivo (TBI + T4 group). Brain edema was alleviated, and the integrity of the blood brain barrier (BBB) improved. Escape latency in the Morris water maze (MWM) declined significantly compared with the group without T4 treatment. Modified neurological severity scores (mNSS) of the TBI + T4 group decreased from day 1 to day 7 post-TBI compared with the TBI + saline group. These results indicate that T4 treatment has potential to alleviate pathologic and behavioral abnormalities post-TBI. Protein alterations after T4 treatment were also detected by iTRAQ proteomics. Upregulation of proteins like Lgals3, Gfap and Apoe after TBI were reversed by T4 treatment. GO enrichment showed T4 mainly affected intermediate filament organization, cholesterol transportation and axonal regeneration. In summary, iTRAQ proteomics provides information about the impact of TBI on protein alterations and yields insight into underlying mechanisms and pathways involved in TBI and T4 treatment. Finally, Ttr and other proteins identified by iTRAQ may become potential novel treatment targets post-TBI.
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http://dx.doi.org/10.1186/s13041-021-00739-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839205PMC
January 2021

Construction of a Benzo[]azepine Skeleton through Decarboxylative Ylide [6+1] Annulations with Modified Vinyl Benzoxazinanones.

Org Lett 2021 Feb 27;23(3):814-818. Epub 2021 Jan 27.

Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu 610052, China.

A Lewis acid-promoted [6+1] annulation between sulfur ylides and modified vinyl benzoxazinanones was described. In this reaction, the newly designed vinyl benzoxazinanones could serve as a novel six-atom synthon, and the key to success is the installation of an electron-withdrawing group on the alkene moiety of the benzoxazinanones. A broad range of substrates are compatible with this mild reaction system, thereby providing a facile and practical approach for constructing a benzo[]azepine skeleton.
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http://dx.doi.org/10.1021/acs.orglett.0c04041DOI Listing
February 2021

Kinase-substrate Edge Biomarkers Provide a More Accurate Prognostic Prediction in ER-negative Breast Cancer.

Genomics Proteomics Bioinformatics 2021 Jan 13. Epub 2021 Jan 13.

CAS Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Department of Life Sciences, ShanghaiTech University, Shanghai 201210, China. Electronic address:

The estrogen receptor (ER)-negative breast cancer subtype is aggressive with few treatment options available. To identify specific prognostic factors for ER-negative breast cancer, this study included 705,729 and 1034 breast invasive cancer patients from the Surveillance, Epidemiology, and End Results (SEER) and The Cancer Genome Atlas (TCGA) databases, respectively. To identify key differential kinase-substrate node and edge biomarkers between ER-negative and ER-positive breast cancer patients, we adopted a network-based method using correlation coefficients between molecular pairs in the kinase regulatory network. Integrated analysis of the clinical and molecular data revealed the significant prognostic power of kinase-substrate node and edge features for both subtypes of breast cancer. Two promising kinase-substrate edge features, CSNK1A1-NFATC3 and SRC-OCLN, were identified for more accurate prognostic prediction in ER-negative breast cancer patients.
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http://dx.doi.org/10.1016/j.gpb.2019.11.012DOI Listing
January 2021

Pathogen Infection and Host-Resistance Interactively Affect Root-Associated Fungal Communities in Watermelon.

Front Microbiol 2020 17;11:605622. Epub 2020 Dec 17.

Institute of Eco-Environmental Protection, Shanghai Academy of Agricultural Sciences, Shanghai, China.

Interactions of pathogen infection, host plant resistance, and fungal communities are poorly understood. Although the use of resistant watermelon cultivars is an effective control measure of watermelon wilt disease, fungal communities may also have significant effects on the development of the soil-borne pathogen complexes. We characterized the root and rhizosphere fungal communities associated with healthy and diseased watermelons of three different cultivars with different susceptibilities toward wilt disease by paired-end Illumina MiSeq sequencing. Thirty watermelon plants including highly wilt-resistant, moderately resistant, and susceptible cultivars were collected from a greenhouse, half of which showing clear wilt symptoms and the other half with no symptoms. Patterns of watermelon wilt disease and the response of the fungal communities varied among the three cultivars. The amount of the pathogen f. sp. was higher in diseased root and rhizosphere samples, particularly in the susceptible cultivar, and was significantly positively correlated with the disease index of Fusarium wilt. Plant health had significant effects on root-associated fungal communities, whereas only the highly resistant cultivar had significant effects only on the rhizosphere fungal communities. Co-occurrence networks revealed a higher complexity of fungal communities in the symptom-free roots compared to diseased roots. In addition, networks from roots of the highly resistant plants showing symptoms had a higher complexity compared to the susceptible cultivars. Keystone species were identified for the plants with different symptom severity and the different cultivars in the root and rhizosphere, such as , and . Overall, the most important factor determining fungal communities in the roots was plant symptom severity, whereas in the rhizosphere, plant genotype was the most important factor determining fungal communities.
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http://dx.doi.org/10.3389/fmicb.2020.605622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793699PMC
December 2020

Rolling-translated EGFR variants sustain EGFR signaling and promote glioblastoma tumorigenicity.

Neuro Oncol 2021 May;23(5):743-756

Department of Neurosurgery, Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou, Guangdong, China.

Background: Aberrant epidermal growth factor receptor (EGFR) activation is observed in over 50% of cases of adult glioblastoma (GBM). Nevertheless, EGFR antibodies are ineffective in clinical GBM treatment, suggesting the existence of redundant EGFR activation mechanisms. Whether circular RNA (circRNA) encodes a protein involved in EGFR-driven GBM remains unclear. We reported an unexpected mechanism in which circular EGFR RNA (circ-EGFR) encodes a novel EGFR variant to sustained EGFR activation.

Method: We used RNA-seq, Northern blot, and Sanger sequencing to confirm the existence of circ-EGFR. Antibodies and a liquid chromatograph tandem mass spectrometer were used to identify circ-EGFR protein products. Lentivirus-transfected stable cell lines were used to assess the biological functions of the novel protein in vitro and in vivo. Clinical implications of circ-EGFR were assessed using 97 pathologically diagnosed GBM patient samples.

Results: The infinite open reading frame (iORF) in circ-EGFR translated repeating amino acid sequences via rolling translation and programmed -1 ribosomal frameshifting (-1PRF) induced out-of-frame stop codon (OSC), forming a polymetric novel protein-complex, which we termed rolling-translated EGFR (rtEGFR). rtEGFR directly interacted with EGFR, maintained EGFR membrane localization and attenuated EGFR endocytosis and degradation. Importantly, circ-EGFR levels correlated with the EGFR signature and predicted the poor prognosis of GBM patients. Deprivation of rtEGFR in brain tumor-initiating cells (BTICs) attenuated tumorigenicity and enhanced the anti-GBM effect.

Conclusion: Our findings identified the endogenous rolling-translated protein and provided strong clinical evidence that targeting rtEGFR could improve the efficiency of EGFR-targeting therapies in GBM.
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http://dx.doi.org/10.1093/neuonc/noaa279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099477PMC
May 2021

A CRISPR/Cas12a Based Universal Lateral Flow Biosensor for the Sensitive and Specific Detection of African Swine-Fever Viruses in Whole Blood.

Biosensors (Basel) 2020 Dec 10;10(12). Epub 2020 Dec 10.

School of Food Science and Engineering, Foshan University, Foshan 528231, China.

Cross-border pathogens such as the African swine fever virus (ASFV) still pose a socio-economic threat. Cheaper, faster, and accurate diagnostics are imperative for healthcare and food safety applications. Currently, the discovery of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) has paved the way for the diagnostics based on Cas13 and Cas12/14 that exhibit collateral cleavage of target and single-stranded DNA (ssDNA) reporter. The reporter is fluorescently labeled to report the presence of a target. These methods are powerful; however, fluorescence-based approaches require expensive apparatuses, complicate results readout, and exhibit high-fluorescence background. Here, we present a new CRISPR-Cas-based approach that combines polymerase chain reaction (PCR) amplification, Cas12a, and a probe-based lateral flow biosensor (LFB) for the simultaneous detection of seven types of ASFV. In the presence of ASFVs, the LFB responded to reporter trans-cleavage by naked eyes and achieved a sensitivity of 2.5 × 10 M within 2 h, and unambiguously identified ASFV from swine blood. This system uses less time for PCR pre-amplification and requires cheaper devices; thus, it can be applied to virus monitoring and food samples detection.
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http://dx.doi.org/10.3390/bios10120203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763806PMC
December 2020

Associations among circulating sphingolipids, β-cell function, and risk of developing type 2 diabetes: A population-based cohort study in China.

PLoS Med 2020 12 9;17(12):e1003451. Epub 2020 Dec 9.

Key Laboratory of Systems Biology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou, China.

Background: Animal studies suggest vital roles of sphingolipids, especially ceramides, in the pathogenesis of type 2 diabetes (T2D) via pathways involved in insulin resistance, β-cell dysfunction, and inflammation, but human studies are limited. We aimed to evaluate the associations of circulating sphingolipids with incident T2D and to explore underlying mechanisms.

Methods And Findings: The current study included 826 men and 1,148 women who were aged 50-70 years, from Beijing and Shanghai, and without T2D in 2005 and who were resurveyed in 2011. Cardiometabolic traits were measured at baseline and follow-up surveys. A total of 76 sphingolipids were quantified using high-coverage targeted lipidomics. Summary data for 2-sample Mendelian randomization were obtained from genome-wide association studies of circulating sphingolipids and the China Health and Nutrition Survey (n = 5,731). During the 6-year period, 529 participants developed T2D. Eleven novel and 3 reported sphingolipids, namely ceramides (d18:1/18:1, d18:1/20:0, d18:1/20:1, d18:1/22:1), saturated sphingomyelins (C34:0, C36:0, C38:0, C40:0), unsaturated sphingomyelins (C34:1, C36:1, C42:3), hydroxyl-sphingomyelins (C34:1, C38:3), and a hexosylceramide (d18:1/20:1), were positively associated with incident T2D (relative risks [RRs]: 1.14-1.21; all P < 0.001), after multivariate adjustment including lifestyle characteristics and BMI. Network analysis further identified 5 modules, and 2 modules containing saturated sphingomyelins showed the strongest associations with increased T2D risk (RRQ4 versus Q1 = 1.59 and 1.43; both Ptrend < 0.001). Mediation analysis suggested that the detrimental associations of 13 sphingolipids with T2D were largely mediated through β-cell dysfunction, as indicated by HOMA-B (mediation proportion: 11.19%-42.42%; all P < 0.001). Moreover, Mendelian randomization evidenced a positive association between a genetically instrumented ceramide (d18:1/20:1) and T2D (odds ratio: 1.15 [95% CI 1.05-1.26]; P = 0.002). Main limitations in the current study included potential undiagnosed cases and lack of an independent population for replication.

Conclusions: In this study, we observed that a panel of novel sphingolipids with unique structures were positively associated with incident T2D, largely mediated through β-cell dysfunction, in Chinese individuals.
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http://dx.doi.org/10.1371/journal.pmed.1003451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725305PMC
December 2020

Aerobic, resistance and combined training for adults with chronic kidney disease: A protocol for a systematic review and network meta-analysis.

Medicine (Baltimore) 2020 Dec;99(49):e23518

Department of Nephrology, the Second Hospital.

Background: Chronic kidney disease (CKD) as a disease that poses a great threat to human health, which has become a public health issue of great concern. Studies have found that exercise training has a positive effect on improving the condition of chronic kidney disease. We will conduct a network meta-analysis to assess the effects of aerobic training, resistance training and combined aerobic and resistance training in treating CKD patients.

Methods: We will search PubMed, EMBASE, Medline, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of science to identify randomized control trails (RCTs) that assessed the effect of different exercise training for CKD patients. Cochrane Handbook will be used to evaluate the risk of bias of included articles. We will use Stata or R software to perform data analysis.

Results And Conclusion: Our systematic review and network meta-analysis will be the first study that investigates the effect of different exercise training for CKD patients, and will provide evidence for management of chronic kidney disease.

Ethics And Dissemination: The data involved in this study are from published articles. For this reason, there is no need for ethical approval or patient consent.

Trial Registration: the registration number was: CRD42020157280.
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http://dx.doi.org/10.1097/MD.0000000000023518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717791PMC
December 2020

Development and Biodegradation of Biomimetic Zwitterionic Phosphorylcholine Chitosan Coating on Zn1Mg Alloy.

ACS Appl Mater Interfaces 2020 Dec 24;12(49):54445-54458. Epub 2020 Nov 24.

Institute of Advanced Wear & Corrosion Resistant and Functional Materials, Jinan University, Guangzhou 510632, China.

Zinc (Zn) alloys are promising alternatives to magnesium (Mg)- and iron (Fe)-based alloys because of their moderate corrosion rate and superior biocompatibility. To reduce the mass release of Zn and improve the biocompatibility of Zn implants, the biomimetic zwitterionic polymer layer (phosphorylcholine chitosan-PCCs) was immobilized on the plasma-treated Zn1Mg surface. It is the chemical bonds between the -NH groups of the PCCs chain and O-C═O (C═O) groups on the plasma-treated Zn1Mg (Zn1Mg-PP) that contributes to the strong bonding strength between the film and the substrate, by which the PCCs (approx. 200 nm thick) layer can bear a 5.93 N normal load. The electrochemical impedance spectroscopy (EIS) results showed that the PCCs layer remarkably increased the resistance against corrosion attack, protecting substrates from over-quick degradation, and the protective effect of the layer with a thickness of 200 nm lasts for about 24 h. The corrosion products of Zn1Mg-PP-PCC in NaCl solution were determined as Zn(OH)Cl·HO and Zn(PO). Besides, the bulk Zn1Mg can trigger more aggressive macrophage activity, while the surface of Zn1Mg-PP and Zn1Mg-PP-PCC and their corrosion products (Zn(PO)) tend to promote the differentiation of macrophages into the M2 phenotype, which is beneficial for implant applications.
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http://dx.doi.org/10.1021/acsami.0c16662DOI Listing
December 2020

Elevated CXorf67 Expression in PFA Ependymomas Suppresses DNA Repair and Sensitizes to PARP Inhibitors.

Cancer Cell 2020 12 12;38(6):844-856.e7. Epub 2020 Nov 12.

State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China. Electronic address:

Ependymoma is the third most common pediatric tumor with posterior fossa group A (PFA) being its most aggressive subtype. Ependymomas are generally refractory to chemotherapies and thus lack any effective treatment. Here, we report that elevated expression of CXorf67 (chromosome X open reading frame 67), which frequently occurs in PFA ependymomas, suppresses homologous recombination (HR)-mediated DNA repair. Mechanistically, CXorf67 interacts with PALB2 and inhibits PALB2-BRCA2 interaction, thereby inhibiting HR repair. Concordantly, tumor cells with high CXorf67 expression levels show increased sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors, especially when combined with radiotherapy. Thus, our findings have revealed a role of CXorf67 in HR repair and suggest that combination of PARP inhibitors with radiotherapy could be an effective treatment option for PFA ependymomas.
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http://dx.doi.org/10.1016/j.ccell.2020.10.009DOI Listing
December 2020