Publications by authors named "Rong Shi"

366 Publications

Pharmacokinetics-based comprehensive strategy to identify multiple effective components in Huangqi decoction against liver fibrosis.

Phytomedicine 2021 Feb 18;84:153513. Epub 2021 Feb 18.

Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai Key Laboratory of Compound Chinese Medicines, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address:

Background: Huangqi decoction (HQD) has been used to treat chronic liver diseases since the 11th century, but the effective components in HQD against liver fibrosis have not been definitively clarified.

Purpose: To investigate and identify multiple effective components in HQD against liver fibrosis using a pharmacokinetics-based comprehensive strategy.

Methods: The absorbed representative components in HQD and their metabolites were detected in human plasma and urine using high-resolution mass spectrometry combined with a database-directed method, and then pharmacokinetics in multiple HQD components in human plasma was analyzed by ultra-performance liquid chromatography coupled with triple-quadruple mass spectrometry. Furthermore, the anti-fibrotic effect of potential effective HQD components was studied in LX-2 cells and that of a multi-component combination of HQD (MCHD) was verified in a mouse CCl-induced hepatic fibrosis model.

Results: Twenty-four prototype components in HQD and 17 metabolites were identified in humans, and the pharmacokinetic characteristics of 14 components were elucidated. Among these components, astragaloside IV, cycloastragenol, glycyrrhizic acid, glycyrrhetinic acid, liquiritigenin, and isoliquiritigenin downregulated the mRNA expression of α-SMA; cycloastragenol, calycosin-7-O-β-D-glucoside, formononetin, glycyrrhetinic acid, liquiritin, and isoliquiritin downregulated the mRNA expression of Col I; and calycosin, liquiritigenin, isoliquiritigenin, cycloastragenol, and glycyrrhetinic accelerated the apoptosis of LX-2 cells. MCHD reduced serum aminotransferase activity and hepatic collagen fibril deposition in mice with CCl-induced hepatic fibrosis.

Conclusion: Using the pharmacokinetics-based comprehensive strategy, we revealed that multiple effective HQD components act together against liver fibrosis.
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http://dx.doi.org/10.1016/j.phymed.2021.153513DOI Listing
February 2021

Use of transmuscular quadratus lumborum block for postoperative analgesia after laparoscopic nephrectomy.

Reg Anesth Pain Med 2021 Feb 25. Epub 2021 Feb 25.

Department of Anesthesia and Pain Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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http://dx.doi.org/10.1136/rapm-2021-102478DOI Listing
February 2021

Differential impact of various substitutions at codon 715 in region II of HSV-1 and HCMV DNA polymerases.

Antiviral Res 2021 Feb 12;188:105046. Epub 2021 Feb 12.

Research Center in Infectious Diseases, CHU de Québec- Laval University, Quebec City, QC, Canada. Electronic address:

This study aimed at understanding the impact of different substitutions at codon 715 localized in the region II of the palm domain of herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV) DNA polymerases (pol). Here, we report a new theoretical mutation V715S that confers resistance of HSV-1 to foscarnet/acyclovir (5.6- and 9.2-fold increases EC values compared to wild type, respectively) and of HCMV to foscarnet/ganciclovir (2.8- and 2.9-fold increases in EC values compared to wild type, respectively). To further analyze the importance of this amino acid, we investigated the impact of the already known mutations V715M and V715G on the replicative capacities and drug susceptibilities of both viruses as well as on the activity and drug inhibition of the DNA pol. The V715G recombinant HSV-1 mutant was resistant to foscarnet and acyclovir (3.4- and 4.6-fold EC increase, respectively) whereas the V715M mutant was susceptible to foscarnet and resistant to acyclovir (3.4-fold EC increase). The V715G recombinant HCMV mutant did not grow and the V715M mutant was resistant to foscarnet (3.7-fold EC increase) and susceptible to ganciclovir. Finally, we showed by three-dimensional modeling that the differential impact of these mutations on the viral replicative capacity and drug resistance profile was related to different hydrophobic local environments for V715 in the DNA pol of the two viruses. Furthermore, we hypothesize that the DNA pol of HSV-1 is more tolerant to changes at this residue compared to that of HCMV because of a more hydrophobic environment stabilizing the region.
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http://dx.doi.org/10.1016/j.antiviral.2021.105046DOI Listing
February 2021

Dermatomal coverage of single-injection ultrasound-guided parasagittal approach to anterior quadratus lumborum block at the lateral supra-arcuate ligament.

J Anesth 2021 Feb 7. Epub 2021 Feb 7.

Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China.

The subcostal quadratus lumborum (QL) block is used in postoperative analgesia for abdominal surgery. However, only a small portion of local anesthetic can spread into the thoracic paravertebral space from the injection site via the lateral arcuate ligament, due to the barrier action of the ligament. In this study, we determined the effectiveness of a new ultrasound-guided parasagittal approach to anterior QL block at the lateral supra-arcuate ligament. Twenty six patients scheduled for laparoscopic renal surgery were enrolled. The parasagittal approach to the anterior QL block at the lateral supra-arcuate ligament was carried out preoperatively. Our data showed that at 5 and 10 min after injection, the patients achieved the sensory block of dermatomes T9-T12 and T7-L1, respectively. Some patients achieved coverage as cephalad as T5 and as caudal as L3. Four patients (16.7%) developed quadriceps weakness after the blocks. The parasagittal technique provides a new choice for postoperative analgesia of abdominal surgery with rapid onset and reliable dermatomal coverage.Trial registration: Chinese Clinical Trial Registry: ChiCTR2000029211.
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http://dx.doi.org/10.1007/s00540-021-02903-1DOI Listing
February 2021

Transincisional Ultrasound-Guided Quadratus Lumborum Block in Open Renal Surgeries.

Pain Physician 2021 Jan;24(1):E127-E128

Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.

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January 2021

Nomogram Based on Risk Factors for Type 2 Diabetes Mellitus Patients with Coronary Heart Disease.

Diabetes Metab Syndr Obes 2020 18;13:5025-5036. Epub 2020 Dec 18.

School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.

Introduction: This study aimed to study risk factors for coronary heart disease (CHD) in type 2 diabetes mellitus (T2DM) patients and establish a clinical prediction model.

Research Design And Methods: A total of 3402 T2DM patients were diagnosed by clinical doctors and recorded in the electronic medical record system (EMRS) of six Community Health Center Hospitals from 2015 to 2017, including the communities of Huamu, Jinyang, Yinhang, Siping, Sanlin and Daqiao. From September 2018 to September 2019, 3361 patients (41 patients were missing) were investigated using a questionnaire, physical examination, and biochemical index test. After excluding the uncompleted data, 3214 participants were included in the study and randomly divided into a training set (n = 2252) and a validation set (n = 962) at a ratio of 3:1. Through lead absolute shrinkage and selection operator (LASSO) regression analysis and logistic regression analysis of the training set, risk factors were determined and included in a nomogram. The C-index, receiver operating characteristic (ROC) curve, calibration plot and decision curve analysis (DCA) were used to validate the distinction, calibration and clinical practicality of the model.

Results: Age, T2DM duration, hypertension (HTN), hyperuricaemia (HUA), body mass index (BMI), glycosylated haemoglobin A1c (HbA1c), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) were significant factors in this study. The C-index was 0.750 (0.724-0.776) based on the training set and 0.767 (0.726-0.808) based on the validation set. Through ROC analysis, the set area was 0.750 for the training set and 0.755 for the validation set. The calibration test indicated that the S:P of the prediction model was 0.982 in the training set and 0.499 in the validation set. The decision curve analysis showed that the threshold probability of the model was 16-69% in the training set and 16-73% in the validation set.

Conclusion: Based on community surveys and data analysis, a prediction model of CHD in T2DM patients was established.
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http://dx.doi.org/10.2147/DMSO.S273880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756175PMC
December 2020

Indoor volatile organic compounds exposures and risk of childhood acute leukemia: a case-control study in shanghai.

J Environ Sci Health A Tox Hazard Subst Environ Eng 2021 26;56(2):190-198. Epub 2020 Dec 26.

Department of Environmental Health, School of Public Health, Shanghai Jiao Tong University school of Medicine, Shanghai, China.

A case-control study was conducted to investigate the relationship between indoor air pollution and childhood acute leukemia (AL) in Shanghai. 97 cases and 148 gender-, age-, and residence-matched controls were included. Indoor air pollution was evaluated by questionnaires and quantitative measurement including 14 volatile organic compounds (VOCs) and nitrogen dioxide (NO) in the homes of the two groups. The levels of individual VOCs, VOC families, TVOC (sum of the concentrations of the individual VOCs) and NO were compared between the two groups. Exposure to styrene and butyl alcohol were associated with an increased risk of childhood AL (styrene: odds ratio (=2.33, 95% confidence interval (: 1.07-5.07; butyl alcohol:  = 2.51, 95%: 1.19-5.28); 4th quartile of chlorinated hydrocarbons ( = 2.52, 95% 1.02-6.26) and 3rd quartile of TVOC ( = 4.03, 95% 1.06-6.81) had significant higher s for childhood AL compared with that in the lowest quartiles. Elevated levels of individual VOCs, VOC families and TVOC were also associated with self-reported risk factors. Our findings suggest that VOCs exposure was associated with an elevated risk of childhood AL, underscore that more attention should be paid to indoor air pollution as a risk factor of childhood AL.
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http://dx.doi.org/10.1080/10934529.2020.1861903DOI Listing
February 2021

Da-Huang-Xiao-Shi decoction protects against3, 5-diethoxycarbonyl-1,4-dihydroxychollidine-induced chronic cholestasis by upregulating bile acid metabolic enzymes and efflux transporters.

J Ethnopharmacol 2021 Apr 18;269:113706. Epub 2020 Dec 18.

Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Shanghai Key Laboratory of Compound Chinese Medicines, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address:

Ethnopharmacological Relevance: Chronic cholestasis is a usual clinical pathological process in hepatopathy and has few treatment options; it is classified under the category of jaundice in Chinese medicine. Da-Huang-Xiao-Shi decoction (DHXSD) is a classic Chinese prescription which is used to treat jaundice.

Aim Of The Study: We aimed to examine the protective effect of DHXSD on liver and its potential mechanism of action against chronic cholestasis.

Materials And Methods: Chronic cholestasis was induced using 3, 5-diethoxycarbonyl-1,4-dihydroxychollidine (DDC) in mice. Mice were then administered DHXSD intragastrically at doses of 3.68, 7.35, and 14.70 g/kg for four weeks followed by further analyses. Serum biochemical indices and liver pathology were explored. Eighteen individual bile acids (BAs) in mice serum and liver were quantified using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The expression of BA related metabolic enzymes, transporters, along with nuclear receptor farnesoid X receptor (FXR) was detected by real-time qPCR and Western blot.

Results: DHXSD treatment reduced the serum biochemical indices, ameliorated pathological injury, and improved the disordered BA homeostasis. Mice treated with DHXSD showed significantly upregulated expression of the metabolic enzymes, cytochrome P450 2b10 (Cyp2b10), Cyp3a11, and UDP-glucuronosyltransferase 1a1 (Ugt1a1); and the bile acid transporters, multidrug resistance protein 2 (Mdr2), bile salt export pump (Bsep), and multidrug resistance-associated protein 3 (Mrp3). DHXSD treatment also significantly upregulated FXR expression in mice with DDC-induced chronic cholestasis.

Conclusions: DHXSD exerted protective effects on chronic cholestasis in DDC-treated mice by alleviating the disordered homeostasis of BAs through increased expression of BA related metabolic enzymes and efflux transporters.
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http://dx.doi.org/10.1016/j.jep.2020.113706DOI Listing
April 2021

Ultrasound-Guided Lumbar Paravertebral Block After Pre-Designed Route on X-Ray Film for Radicular Pain Following Failed Back Surgery Syndrome: A Case Report.

J Pain Res 2020 8;13:3331-3336. Epub 2020 Dec 8.

Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People's Republic of China.

Background: Persistent or recurring radicular pain after lumbar surgery is a clinical condition of failed back surgery syndrome (FBSS) that seriously affects the life quality of patients. Conventional medication and physiotherapy do not fully relieve this pain. A simpler, safer, and less invasive option is lumbar selective nerve root block or paravertebral block. Here, we share our experience regarding lumbar paravertebral block for a patient with FBSS, which successfully alleviated radicular pain after lumbar surgery.

Case Presentation: An 80-year-old man with left lower limb radicular pain diagnosed as L4-5, L5-S1 intervertebral disc protrusion, spinal canal stenosis, and degenerative scoliosis underwent lumbar surgery. Four months after surgery, he experienced left lower limb radicular pain. After designing the puncture route based on X-ray film, we performed a combined ultrasound-guided L4 and L5 paravertebral block. With his improved pain control, his functional status and ability to perform daily activities also markedly improved.

Conclusion: Real-time ultrasound-guided lumbar paravertebral block performed with a pre-designed route on X-ray film can provide a simple and safe way to relieve radicular pain in FBSS.
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http://dx.doi.org/10.2147/JPR.S280541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733463PMC
December 2020

Application of a Two-Analyte Integrated Population Pharmacokinetic Model to Evaluate the Impact of Intrinsic and Extrinsic Factors on the Pharmacokinetics of Polatuzumab Vedotin in Patients with Non-Hodgkin Lymphoma.

Pharm Res 2020 Dec 1;37(12):252. Epub 2020 Dec 1.

Department of Clinical Pharmacology, Genentech, Inc, South San Francisco, California, USA.

Purpose: The established two-analyte integrated population pharmacokinetic model was applied to assess the impact of intrinsic/extrinsic factors on the pharmacokinetics (PK) of polatuzumab vedotin (pola) in patients with non-Hodgkin lymphoma (NHL) following bodyweight-based dosing.

Methods: Model simulations based on individual empirical Bayes estimates were used to evaluate the impact of intrinsic/extrinsic factors as patient subgroups on Cycle 6 exposures. Intrinsic factors included bodyweight, age, sex, hepatic and renal functions. Extrinsic factors included rituximab/obinutuzumab or bendamustine combination with pola and manufacturing process. The predicted impact on exposures along with the established exposure-response relationships were used to assess clinical relevance.

Results: No clinically meaningful differences in Cycle 6 pola exposures were found for the following subgroups: bodyweight 100-146 kg versus 38-<100 kg, age ≥ 65 years versus <65 years, female versus male, mild hepatic impairment versus normal, mild-to-moderate renal impairment versus normal. Co-administration of rituximab/obinutuzumab or bendamustine, and change in the pola manufacturing process, also had no meaningful impact on PK.

Conclusions: In patients with NHL, bodyweight-based dosing is adequate, and no further dose adjustment is recommended for the heavier subgroup (100-146 kg). In addition, no dose adjustments are recommended for other subgroups based on intrinsic/extrinsic factors evaluated.
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http://dx.doi.org/10.1007/s11095-020-02933-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708381PMC
December 2020

Physiologically Based Pharmacokinetic Model-Informed Drug Development for Polatuzumab Vedotin: Label for Drug-Drug Interactions Without Dedicated Clinical Trials.

J Clin Pharmacol 2020 Oct;60 Suppl 1:S120-S131

Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, California, USA.

Model-informed drug development (MIDD) has become an important approach to improving clinical trial efficiency, optimizing drug dosing, and proposing drug labeling in the absence of dedicated clinical trials. For the first time, we developed a physiologically based pharmacokinetic (PBPK) model-based approach to assess CYP3A-mediated drug-drug interaction (DDI) risk for polatuzumab vedotin (Polivy), an anti-CD79b-vc-monomethyl auristatin E (MMAE) antibody-drug conjugate (ADC). The model was developed and verified using data from the existing clinical DDI study for brentuximab vedotin, a similar vc-MMAE ADC. Analogous to the brentuximab vedotin clinical study, polatuzumab vedotin at the proposed labeled dose was predicted to have a limited drug interaction potential with strong CYP3A inhibitor and inducer. Polatuzumab vedotin was also predicted to neither inhibit nor induce CYP3A. The present work demonstrated a high-impact application using a PBPK MIDD approach to predict the CYP3A-mediated DDI to enable drug labeling in the absence of any dedicated clinical DDI study. The key considerations for the PBPK report included in the Biologics License Application/Marketing Authorization Application submission, as well as the strategy and responses to address some of the critical and challenging questions from the health authorities following the submission are also discussed. Our experience and associated perspective using a PBPK approach to ultimately enable a drug interaction label claim for polatuzumab vedotin in lieu of a dedicated clinical DDI study, as well as the interactions with the regulatory agencies, further provides confidence in applying MIDD to accelerate the registration and approval of new drug therapies.
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http://dx.doi.org/10.1002/jcph.1718DOI Listing
October 2020

A Case Report of an Ultrasound-Guided and Fluoroscopy-Assisted Posterior Approach for Celiac Plexus Neurolysis in a Patient with Pancreatic Cancer-Associated Abdominal Pain.

J Pain Res 2020 13;13:2561-2566. Epub 2020 Oct 13.

Department of Anesthesia and Pain Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, People's Republic of China.

Background: Imaging-guided celiac plexus neurolysis using ultrasound (US) guidance via a transabdominal approach and endoscopic-ultrasound (EUS) has been increasingly applied for the treatment of pancreatic cancer-associated abdominal pain.

Objective: To investigate the application of ultrasound-guided and fluoroscopy-assisted celiac plexus neurolysis in a patient with advanced pancreatic cancer suffering from refractory abdominal pain for which oral opioid treatment was ineffective.

Case Report: We report a case of ultrasound-guided and fluoroscopy-assisted celiac plexus neurolysis in a patient with advanced pancreatic cancer with refractory abdominal pain. With the patient in the prone position, celiac plexus neurolysis was performed under real-time US guidance. The transducer was placed below the costal margin and a puncture needle with an ultrasound enhancement tip was inserted in-plane aiming for the lateral anterior end of the vertebral body. The correct needle tip position was confirmed by the C-arm with contrast material located anterior to the vertebral body and posterior to the diaphragm.

Conclusion: We highlight the use of an US-guided and fluoroscopy-assisted posterior approach for use in celiac plexus neurolysis procedures, particularly in patients suffering from contraindications from the US or EUS-guided anterior approaches.
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http://dx.doi.org/10.2147/JPR.S270343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568612PMC
October 2020

A new mutation causes female infertility and total fertilization failure.

Gynecol Endocrinol 2020 Oct 19:1-2. Epub 2020 Oct 19.

The ART Center, Northwest Women and Children's Hospital, Xi'an, China.

Objective: The genetic reasons of total fertilization failure (TFF), especially regarding suspected oocyte-related factors, are largely unknown. Only , and mutations have been shown to result in human fertilization failure. The aim of this study is to report a new mutation which causes female infertility and total fertilization failure.

Methods: A patient presenting TFF after two failed cycles was included. In the first cycle, 13 oocytes were obtained, all of which were inseminated by IVF, but there was no sign of fertilization. In the second cycle, 11 oocytes were obtained, 8 of which were matured; however, none were fertilized upon ICSI and ICSI-AOA. Peripheral blood samples were taken from the patient and her family members. The whole-exome sequencing was performed on them.

Results: We identified two heterozygous missense variants (NM_153447.4: c.1598G > C and 1919 T > G; p.Arg533Pro and Leu640Arg) which could cause the incidence of TFF. The first mutation of c.1598G > C (p.Arg533Pro) was inherited from her father and the second mutation of c.1919T > G (Leu640Arg) was inherited from her mother. The sister with normal fertility did not carry these variants.

Conclusions: A new mutation causes female infertility and the incidence of TFF.
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http://dx.doi.org/10.1080/09513590.2020.1832069DOI Listing
October 2020

Study on the Risk Factors for Hyperuricaemia and Related Vascular Complications in Patients with Type 2 Diabetes Mellitus.

Risk Manag Healthc Policy 2020 21;13:1661-1675. Epub 2020 Sep 21.

School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.

Purpose: The study aimed to identify diseases that exhibit significant differences between hyperuricaemia (HUA) and non-hyperuricaemia (NHUA) groups and analyse the risk factors for HUA based on the related diseases in type 2 diabetes mellitus (T2DM).

Methods: A total of 3264 T2DM patients were investigated from 2013 to 2017 in the Jinyang and Sanlin communities by obtaining basic data from the electronic medical record system (EMRS). From September 2018 to July 2019, 3000 patients (264 patients were missing during follow-up) were investigated with questionnaires, physical examinations and biochemical index tests. After removing missing values, 2899 patients were divided into HUA and NHUA groups. The chi-square test was used to identify diseases with differences. Using Lasso analysis and logistic regression analysis, risk factors for HUA based on the related diseases were obtained. The C-index, receiver operating characteristic (ROC) curve and calibration plot were used to validate the discrimination and accuracy of the factors.

Results: The chi-square test showed that there were significant differences in coronary heart disease (CHD) and diabetic nephropathy (DN) between the HUA group and the NHUA group. Through Lasso regression, glycosylated haemoglobin A1c (HbA1c), triglyceride (TG), blood urea nitrogen (BUN) and serum creatinine (SCR) were screened in the CHD group. Body mass index (BMI), HbA1c, total cholesterol (TC), TG, BUN, SCR and urine microalbumin (UMA) were screened in the DN group. The P-value of all the variables was less than 0.05. Through the C-index, calibration, and ROC curve analyses, these risk factors had medium accuracy.

Conclusion: HUA was significantly related to CHD and DN. The level of UA was correlated with HbA1c, TG, BUN, and SCR based on CHD. The level of UA was associated with BMI, HbA1c, TC, TG, BUN, SCR, and UMA based on DN.
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http://dx.doi.org/10.2147/RMHP.S255042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518772PMC
September 2020

Sirtuin 3 Inhibits Airway Epithelial Mitochondrial Oxidative Stress in Cigarette Smoke-Induced COPD.

Oxid Med Cell Longev 2020 11;2020:7582980. Epub 2020 Sep 11.

Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Mitochondrial damage in airway epithelial cells plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Sirtuin 3 (Sirt3) is a mitochondrial deacetylase regulating mitochondrial function, but its role in the pathogenesis of COPD is still unknown. The aim of the present study was to investigate the effect of Sirt3 on airway epithelial mitochondria in cigarette smoke-induced COPD. Our present study has shown serious airway inflammation, alveolar space enlargement, and mitochondrial damage of the airway epithelium in COPD rats. Compared to the control rats, Sirt3 protein expression was significantly decreased in the airway epithelium and lung tissue homogenate from COPD rats. In airway epithelial cells (BEAS-2B), cigarette smoke extract (CSE) treatment significantly decreased mRNA and protein expression of Sirt3 and manganese superoxide dismutase (MnSOD), as well as MnSOD activity in a concentration and time-dependent manner. Sirt3 siRNA further significantly intensified the decreases in MnSOD expression and activity and aggravated mitochondrial oxidative stress and cell injury when airway epithelial cells were treated with 7.5% CSE. In contrast, Sirt3 overexpression significantly prevented the decrease of MnSOD expression and activity and improved mitochondrial oxidative stress and cell injury in CSE-treated airway epithelial cells. These data suggest that Sirt3 inhibits airway epithelial mitochondrial oxidative stress possibly through the regulation of MnSOD, thereby contributing to the pathogenesis of COPD.
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http://dx.doi.org/10.1155/2020/7582980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503124PMC
September 2020

Establishment of Clinical Prediction Model Based on the Study of Risk Factors of Stroke in Patients With Type 2 Diabetes Mellitus.

Front Endocrinol (Lausanne) 2020 25;11:559. Epub 2020 Aug 25.

School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Stroke has sparked global concern as it seriously threatens people's life, bringing about dramatic health burdens on patients, especially for type 2 diabetes mellitus (T2DM) patients. Therefore, a risk scoring model is urgently valuable for T2DM patients to predict the risk of stroke incidence and for positive health intervention. We randomly divided 4,335 T2DM patients into two groups, training set ( = 3,252) and validation set ( = 1,083), at the ratio of 3:1. Characteristic variables were then selected based on the data of training set through least absolute shrinkage and selection operator regression. Three models were established to verify predictive ability. Foundation model was composed of basic information and physical indicators. Biochemical model consisted of biochemical indexes. Integrated model combined the above two models. Data of three models were then put into logistic regression analysis to form nomogram prediction models. Tools including index, calibration plot, and curve analysis were implemented to test discrimination, calibration, and clinical use. To select the best predicting model, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were put into effect. Eleven risk factors were determined, including age, duration of T2DM, estimated glomerular filtration rate, systolic blood pressure, diastolic blood pressure, low-density lipoprotein, high-density lipoprotein, triglyceride, body mass index, uric acid, and glycosylated hemoglobin A, all with significant -values through logistic regression analysis. In the training set, areas under the curve of three models were 0.810, 0.819, and 0.884, whereas in the validation set, they were 0.836, 0.832, and 0.909. Through calibration plot, the S:P values in the training set were 0.836, 0.754, and 0.621 and were 0.918, 0.682, and 0.666 separately in the validation set. In terms of the decision curve analysis, the risk thresholds were, respectively, 8-73%, 8-98%, and 8%~ in the training set and 8-70%, 8-90%, and 8-95% in the validation set. With the aid of NRI and IDI, integrated model is proved to be the best model in training set and validation set. Besides, internal validation was conducted on all the subjects in this study, and the index was 0.890 (0.873-0.907). This study established a model predicting risk of stroke for T2DM patients through a community-based survey.
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http://dx.doi.org/10.3389/fendo.2020.00559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479835PMC
August 2020

Generation of Glycosyl Radicals from Glycosyl Sulfoxides and Its Use in the Synthesis of C-linked Glycoconjugates.

Angew Chem Int Ed Engl 2021 01 27;60(1):385-390. Epub 2020 Oct 27.

Department of Emergency, State Key Laboratory of Biotherapy, West China Hospital, and School of Chemical Engineering, Sichuan University, No. 17 Renmin Nan Road, Chengdu, 610041, China.

We here report glycosyl sulfoxides appended with an aryl iodide moiety as readily available, air and moisture stable precursors to glycosyl radicals. These glycosyl sulfoxides could be converted to glycosyl radicals by way of a rapid and efficient intramolecular radical substitution event. The use of this type of precursors enabled the synthesis of various complex C-linked glycoconjugates under mild conditions. This reaction could be performed in aqueous media and is amenable to the synthesis of glycopeptidomimetics and carbohydrate-DNA conjugates.
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http://dx.doi.org/10.1002/anie.202009828DOI Listing
January 2021

Quantification of prostaglandins E and D using liquid chromatography-tandem mass spectrometry in a mouse ear edema model.

Anal Methods 2020 Jun;12(22):2865-2871

Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

A sensitive, specific, and accurate high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed and validated for the quantification of prostaglandins D2 (PGD2) and E2 (PGE2) in a mouse ear edema model. We used activated charcoal to obtain PG-free ear samples. The chromatographic separation was performed using a Hypersil Gold C18 column. The limit of detection of each PG was 0.4 ng mL-1, and the intra- and inter-assay estimates of precision and accuracy were <14.5 and 94.2-102.9%, respectively. Stability studies showed that all analytes were stable under various storage conditions and analytical processes. The developed and validated method was successfully used to investigate the anti-inflammatory effects of cultured bear bile powder (CBBP) by quantitatively determining PGE2 and PGD2 levels in mouse ear edema samples. These results showed that CBBP significantly inhibited the xylene-induced ear edema in mice and reversed the xylene-induced elevation of PGE2 and PGD2 levels. These results provide useful data about the anti-inflammatory bioactivities in tissues, mediated by the reduction of PGE2 and PGD2 levels, and may further encourage research and development studies of CBBP for its use as an anti-inflammatory agent.
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http://dx.doi.org/10.1039/d0ay00506aDOI Listing
June 2020

Evaluation of intrahepatic manifestation and distant extrahepatic disease in alveolar echinococcosis.

World J Gastroenterol 2020 Aug;26(29):4302-4315

Department of Internal Medicine I, University Hospital Ulm, Ulm 89081, Germany.

Background: The main endemic areas of alveolar echinococcosis (AE) are in Central Europe and Western China. Both the infiltration of intrahepatic vascular and bile duct structures as well as extrahepatic disease can lead to further complications and may increase morbidity in patients with AE.

Aim: To evaluate vascular/biliary involvement in hepatic AE and its distant extrahepatic disease manifestations in an international collective was the aim.

Methods: Consecutively, five experienced examiners evaluated contrast-enhanced abdominal computed tomography (CT) scans for 200 patients with hepatic AE of each of four locations ( 50) in Germany, France and China. Therefore, we retrospectively included the 50 most recent abdominal contrast-enhanced CT examinations at each center, performed because of hepatic AE from September 21, 2007 to March 21, 2018. AE liver lesions were classified according to the echinococcosis multilocularis Ulm classification for CT (EMUC-CT). Distant extrahepatic manifestations were documented either by whole body positron emission tomography-CT or with the addition of thoracic CT and cranial magnetic resonance imaging. Vascular/biliary involvement of the hepatic disease as well as the presence of distant extrahepatic manifestations were correlated with the EMUC-CT types of liver lesion. Statistical analysis was performed using SAS Version 9.4 (SAS Institute Inc., Cary, NC, United States).

Results: Distant extrahepatic AE manifestations were significantly more frequent in China than in Europe ( 0.0091). A significant relationship was found between the presence of distant extrahepatic disease and AE liver lesion size ( 0.0075). Vascular/biliary structures were involved by the liver lesions significantly more frequently in China than in Europe ( 0.0001), and vascular/biliary involvement depended on lesion size. Different morphological types of AE liver lesions led to varying frequencies of vascular/biliary involvement and were associated with different frequencies of distant extrahepatic manifestations: Vascular/biliary involvement as a function of lesions primary morphology ranged from 5.88% of type IV liver lesions to 100% among type III lesions. Type IV differed significantly in these associations from types I, II, and III ( 0.0001). With respect to extrahepatic disease, the primary morphology types IV and V of liver lesions were not associated with any case of distant extrahepatic disease. In contrast, distant extrahepatic manifestations in types I-III were found to varying degrees, with a maximum of 22% for type III.

Conclusion: Different CT morphological patterns of hepatic AE lesions influence vascular/biliary involvement and the occurrence of distant extrahepatic manifestations. There are intercontinental differences regarding the characteristics of AE manifestation.
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http://dx.doi.org/10.3748/wjg.v26.i29.4302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422544PMC
August 2020

Intrahepatic manifestation and distant extrahepatic disease in alveolar echinococcosis: a multicenter cohort study.

Acta Radiol 2020 Aug 26:284185120951958. Epub 2020 Aug 26.

Department of Internal Medicine I, University Hospital Ulm, Ulm, Germany.

Background: The main endemic areas of alveolar echinococcosis (AE) are in central Europe and western China. The infiltration of intrahepatic vascular and bile ducts as well as extrahepatic disease can lead to complications and may increase morbidity in AE.

Purpose: To evaluate the vascular/biliary involvement of hepatic alveolar echinococcosis (HAE) and distant extrahepatic disease at each of four locations in Germany, France, and China.

Material And Methods: Contrast-enhanced abdominal magnetic resonance imaging (MRI) scans of patients with HAE, 200 in total, were evaluated by five examiners. AE liver lesions were classified according to Kodama's classification. Furthermore, distant extrahepatic manifestations were documented with additionally performed imaging modalities. Vascular/biliary involvement of hepatic manifestations as well as the presence of extrahepatic manifestations were correlated with the respective Kodama type of the liver lesion.

Results: Distant extrahepatic AE manifestations were significantly more frequent in China than in Europe (12/100 vs. 3/100; Fisher's exact test: =0.0286). A significant relationship exists between presence of distant extrahepatic disease manifestation and size of the AE liver lesion (132.53 ± 48.65 vs. 92.49 ± 50.06;  = 0.0030). Vascular/biliary involvement is significantly more frequent in China than in Europe (86/100 vs. 65/100; χ = 11.92;  = 0.0006). Vascular/biliary involvement depends on lesion size (111.10 ± 47.44 vs. 47.36 ± 24.36; <0.0001). Different types of AE liver lesions are associated with differences in vascular/biliary involvement and extrahepatic manifestations.

Conclusion: Vascular/biliary involvement and presence of distant extrahepatic manifestations depend on size of the HAE lesions and are more frequently detected in China. Different MRI morphological patterns influence vascular/biliary involvement and the occurrence of distant extrahepatic manifestations.
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http://dx.doi.org/10.1177/0284185120951958DOI Listing
August 2020

Asian race and origin have no clinically meaningful effects on polatuzumab vedotin pharmacokinetics in patients with relapsed/refractory B-cell non-Hodgkin lymphoma.

Cancer Chemother Pharmacol 2020 09 8;86(3):347-359. Epub 2020 Aug 8.

Genentech Inc., South San Francisco, CA, USA.

Purpose: The CD79b-targeted antibody-drug conjugate polatuzumab vedotin (pola), alone and with chemoimmunotherapy, has clinical efficacy and a tolerable safety profile in B-cell non-Hodgkin lymphoma (B-NHL). We assessed (a) whether exposure from global studies of pola is comparable to Asian patients, and (b) if the recommended pola dose is appropriate in Asian patients based on exposure.

Methods: The pharmacokinetics (PK) of pola in Asian and global populations was characterized for three analytes (antibody-conjugated monomethyl auristatin E (MMAE) [acMMAE], total antibody, and unconjugated MMAE) in five phase 1b/2 single-agent and combination studies in B-NHL patients (JO29138 [JAPICCTI-142580], DCS4968g [NCT01290549], GO27834 [NCT01691898], GO29044 [NCT01992653], and GO29365 [NCT02257567]). PK data were compared between Japanese phase 1 JO29138 (JAPICCTI-142580) and global phase 1 DCS4968g (NCT01290549) studies and between Asian and non-Asian patients in the randomized relapsed/refractory B-NHL cohorts of the phase 1b/2 study GO29365 (NCT02257567). A population PK (popPK) model was used to assess the effects of Asian race and region on acMMAE and unconjugated MMAE exposure.

Results: PK non-compartmental analysis (NCA) parameters for the key analyte acMMAE in the Japanese JO29138 (JAPICCTI-142580) and global phase 1 DCS4968g (NCT01290549) studies were similar. In GO29365 (NCT02257567), the phase 1b/2 combination study, mean exposure to the analytes was generally lower in Asian patients (by ~ 9.9 to 17.5%), but not to a clinically meaningful extent. Overall, the popPK model further suggested comparable PK in Asian patients with B-NHL (race or region) versus non-Asian patients.

Conclusion: Race has no clinically meaningful effect on pola PK. These results (and observations from efficacy/safety exposure-response analyses) support no pola dose adjustments are warranted for Asian patients with DLBCL.
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http://dx.doi.org/10.1007/s00280-020-04119-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478950PMC
September 2020

Combining Computed Tomography and Histology Leads to an Evolutionary Concept of Hepatic Alveolar Echinococcosis.

Pathogens 2020 Aug 4;9(8). Epub 2020 Aug 4.

Department of Diagnostic and Interventional Radiology, University Hospital of Ulm, 89081 Ulm, Germany.

Alveolar echinococcosis (AE) is caused by the intermediate stage of . We aimed to correlate computed tomography (CT) data with histology to identify distinct characteristics for different lesion types. We classified 45 samples into five types with the Ulm Classification for Computed Tomography (EMUC-CT). The various CT lesions exhibited significantly different histological parameters, which led us to propose a progression model. The initial lesion fit the CT type IV classification, which comprises a single necrotic area with the central located laminated layer, a larger distance between laminated layer and border zone, a small fibrotic peripheral zone, and few small particles of (spems). Lesions could progress through CT types I, II, and III, characterized by shorter distances between laminated layer and border zone, more spems inside and surrounding the lesion, and a pronounced fibrotic rim (mostly in type III). Alternatively, lesions could converge to a highly calcified, regressive state (type V). Our results suggest that the CT types mark sequential stages of the infection, which progress over time. These distinct histological patterns advance the understanding of interactions between AE and human host; moreover, they might become prognostically and therapeutically relevant.
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http://dx.doi.org/10.3390/pathogens9080634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459611PMC
August 2020

Establishment of a Risk Prediction Model for Non-alcoholic Fatty Liver Disease in Type 2 Diabetes.

Diabetes Ther 2020 Sep 28;11(9):2057-2073. Epub 2020 Jul 28.

School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.

Introduction: Non-alcoholic fatty liver disease (NAFLD) is becoming more prevalent in patients with type 2 diabetes mellitus (T2DM) and can contribute to serious liver damage in this patient population. The aim of this study was to develop a risk nomogram for NAFLD in a Chinese population with T2DM.

Methods: A questionnaire survey, physical examination and biochemical indicator testing were performed on 874 patients with T2DM, and the collected data were used to evaluate the risk to develop NAFLD in T2DM patients. The least absolute shrinkage and selection operator (LASSO) regression analysis method was used to optimize variable selection by running cyclic coordinate descent with k-fold (tenfold in this case) cross-validation. Multivariable logistic regression analysis was applied to build a predictive model by introducing the predictors selected from the LASSO regression analysis. The nomogram was developed based on the selected variables visually. A calibration plot, receiver operating characteristic curve (ROC) and decision curve analysis (DCA) were used to validate the model, with further assessment by external validation.

Results: A total of nine predictors, namely sex, age, total cholesterol (TC), body mass index (BMI), waistline, diastolic blood pressure (DBP), serum uric acid (SUA), course of disease and high-density lipoprotein-cholesterol (HDL-C), were identified by LASSO regression analysis from a total of 24 variables studied. The model constructed using these nine predictors displayed medium prediction ability, with an area under the ROC of 0.848 in the training set and 0.809 in the validation set. The DCA curve showed that the nomogram could be applied clinically if the risk threshold was between 48 and 91%, which was found to be between 44 and 82% in the external validation.

Conclusion: Introducing sex, age, TC, BMI, waistline, DBP, SUA, course of disease and HDL-C into the risk nomogram increased its usefulness for predicting NAFLD risk in patients with T2DM.
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http://dx.doi.org/10.1007/s13300-020-00893-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434817PMC
September 2020

A Lactococcal Phage Protein Promotes Viral Propagation and Alters the Host Proteomic Response During Infection.

Viruses 2020 07 24;12(8). Epub 2020 Jul 24.

Département de biochimie, de microbiologie, et de bio-informatique, Faculté des sciences et de génie and PROTEO, Québec City, QC G1V 0A6, Canada.

The lactococcal virulent phage p2 is a model for studying the genus, the most prevalent group of phages causing milk fermentation failures in cheese factories worldwide. This siphophage infects MG1363, a model strain used to study Gram-positive lactic acid bacteria. The structural proteins of phage p2 have been thoroughly described, while most of its non-structural proteins remain uncharacterized. Here, we developed an integrative approach, making use of structural biology, genomics, physiology, and proteomics to provide insights into the function of ORF47, the most conserved non-structural protein of unknown function among the genus. This small phage protein, which is composed of three α-helices, was found to have a major impact on the bacterial proteome during phage infection and to significantly reduce the emergence of bacteriophage-insensitive mutants.
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http://dx.doi.org/10.3390/v12080797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472136PMC
July 2020

Exposure-safety and exposure-efficacy analyses of polatuzumab vedotin in patients with relapsed or refractory diffuse large B-cell lymphoma.

Leuk Lymphoma 2020 12 24;61(12):2905-2914. Epub 2020 Jul 24.

Genentech, Inc, South San Francisco, CA, USA.

Exposure-response relationships were investigated to assess the risk/benefit of polatuzumab vedotin (pola) + bendamustine-rituximab (pola + BR) in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Analyses were conducted in pivotal study GO29365 (NCT02257567; BR/pola + BR/pola + BG [BG: bendamustine-obinutuzumab]; 1.8 mg/kg pola, every 3 weeks [Q3W], six cycles), and supportive studies DCS4968g (NCT01290549) and GO27834 (NCT01691898) (pola/pola + R/pola + G; 0.1-2.4 mg/kg pola Q3W; eight-cycle landmark), separately. Exposure was characterized as simulated cycle-6 AUC and for antibody-conjugated mono-methyl auristatin E (acMMAE) and unconjugated MMAE. Supportive studies showed response rate and safety risk (grade ≥2 peripheral neuropathy; grade ≥3 anemia) increased with exposure, suggesting not to dose below 1.8 mg/kg (up to eight-cycle) for balancing safety and efficacy. Pivotal study with limited exposure range showed no exposure-safety relationship and slightly positive exposure (acMMAE)-efficacy relationship for overall survival. The exposure-response analyses and the observed risk/benefit characteristics in pivotal study supported pola (1.8 mg/kg) +BR Q3W for six cycles in R/R DLBCL patients.
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http://dx.doi.org/10.1080/10428194.2020.1795154DOI Listing
December 2020

Hepatic alveolar echinococcosis: correlation between computed tomography morphology and inflammatory activity in positron emission tomography.

Sci Rep 2020 07 16;10(1):11808. Epub 2020 Jul 16.

Department of Internal Medicine III, Ulm University Hospital, Albert-Einstein-Allee 23, 89081, Ulm, Germany.

Positron emission tomography-computed tomography (PET-CT) with 18F-fluorodesoxyglucose (FDG) is the imaging modality of choice for assessing inflammation surrounding hepatic alveolar echinococcosis (AE) lesions. This study is the first to evaluate FDG uptake in hepatic AE (n = 51) based on the standardized uptake value (SUV) and to correlate the SUVs with primary morphology and calcification patterns, based on the Echinococcus multilocularis Ulm Classification for Computed-Tomography (EMUC-CT). Our results show that the SUVs were increased for lesions with EMUC-CT types I-IV primary morphology, compared to the surrounding healthy liver tissue (SUV = 2.5 ± 0.4; p < 0.05). Type IV lesions included, by far, the highest number of PET-negative lesions. A comparison of lesions with different primary morphologies showed clear differences. The highest SUVs were found for types I and III, and the lowest was found for type IV. Type IV lesions (SUV, 3.8 ± 1.5) showed significantly lower uptake compared to type I (SUV, 6.9 ± 3.5; p = 0.030) and type III (SUV, 7.4 ± 3.9; p = 0.031) lesions. For type II lesions, the results showed only a statistical trend (SUV, 6.1 ± 3.1; p = 0.073). Due to the small number of cases, an evaluation of type V (n = 1) lesions was not possible. The different SUVs of lesions with different primary morphologies, particularly the lower FDG uptake observed in type IV lesions, suggested that these SUVs might reflect different stages of the disease.
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http://dx.doi.org/10.1038/s41598-020-68624-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366930PMC
July 2020

Nomogram-Based Prediction of the Risk of Diabetic Retinopathy: A Retrospective Study.

J Diabetes Res 2020 7;2020:7261047. Epub 2020 Jun 7.

School of Public Health, Shanghai University of Traditional Chinese Medicine, 201203, China.

Objectives: This study is aimed at developing a risk nomogram of diabetic retinopathy (DR) in a Chinese population with type 2 diabetes mellitus (T2DM).

Methods: A questionnaire survey, biochemical indicator examination, and physical examination were performed on 4170 T2DM patients, and the collected data were used to evaluate the DR risk in T2DM patients. By operating R software, firstly, the least absolute shrinkage and selection operator (LASSO) regression analysis was used to optimize variable selection by running cyclic coordinate descent with 10 times cross-validation. Secondly, multivariable logistic regression analysis was applied to build a predicting model introducing the predictors selected from the LASSO regression analysis. The nomogram was developed based on the selected variables visually. Thirdly, calibration plot, receiver operating characteristic (ROC) curve, and decision curve analysis were used to validate the model, and further assessment was running by external validation.

Results: Seven predictors were selected by LASSO from 19 variables, including age, course of disease, postprandial blood glucose (PBG), glycosylated haemoglobin A1c (HbA1c), uric creatinine (UCR), urinary microalbumin (UMA), and systolic blood pressure (SBP). The model built by these 7 predictors displayed medium prediction ability with the area under the ROC curve of 0.700 in the training set and 0.715 in the validation set. The decision curve analysis curve showed that the nomogram could be applied clinically if the risk threshold is between 21% and 57% and 21%-51% in external validation.

Conclusion: Introducing age, course of disease, PBG, HbA1c, UCR, UMA, and SBP, the risk nomogram is useful for prediction of DR risk in T2DM individuals.
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http://dx.doi.org/10.1155/2020/7261047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298262PMC
June 2020

Follow-up in hepatic alveolar echinococcosis under benzimidazole therapy using computed tomography.

Chin Med J (Engl) 2020 06;133(12):1507-1509

Qinghai University, Qinghai University Affiliated Hospital, Xining, Qinghai 810001, China.

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http://dx.doi.org/10.1097/CM9.0000000000000874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339307PMC
June 2020

Epidemic Characteristics of Carbapenem-Resistant in the Pediatric Intensive Care Unit of Yanbian University Hospital, China.

Infect Drug Resist 2020 18;13:1439-1446. Epub 2020 May 18.

Department of Respiratory Medicine, Yanbian University Hospital, Yanji, People's Republic of China.

Introduction: Carbapenem-resistant (CRE) pose a serious threat to clinical patient management and public health, as they are generally resistant to most antibiotics and cause infections with high mortality rates. ranks second among species that cause nosocomial infections. In this study, we investigated the epidemic characteristics of carbapenem-resistant (CRKP) in the pediatric intensive care unit (PICU) of Yanbian University Hospital.

Materials And Methods: A total of 14 non-duplicate CRKP strains, collected from March 2015 to November 2019, were subjected to automated microbial identification and antimicrobial susceptibility tests using the Phoenix-100 ID/AST system. The strains were also subjected to genotypic resistance testing, polymerase chain reaction assays to detect genes encoding carbapenemases and other β-lactamases, multi-locus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE)-based homology analysis.

Results: Two carbapenemase genes, KPC-2 and NDM-1 (in eight and six strains, respectively), were detected. MLST enabled the division of the strains into two sequence types, ST11 and ST1224 (containing eight and six strains, respectively). PFGE results classified the 14 strains into clonotypes A-D, of which clonotypes A and B belonged to ST11, while clonotypes C and D belonged to ST1224.

Conclusion: Our study reveals that epidemics of the KPC-2-ST11 and NDM-1-ST1224 strains occurred in the PICU of Yanbian University Hospital. Surveillance and strict implementation of prevention and control measures are crucial to prevent the occurrence and rapid spread of nosocomial infections.
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http://dx.doi.org/10.2147/IDR.S245397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244351PMC
May 2020

Identification novel mutations in TUBB8 in female infertility and a novel phenotype of large polar body in oocytes with TUBB8 mutations.

J Assist Reprod Genet 2020 Aug 10;37(8):1837-1847. Epub 2020 Jun 10.

Institute of Pediatrics, Children's Hospital of Fudan University and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology and Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China.

Purpose: We aimed to identify novel variants in TUBB8 and corresponding new abnormal phenotypes in oocytes/fertilization/ embryonic development responsible for female infertility.

Methods: Sanger sequencing of TUBB8 was performed in infertile women with abnormalities in oocyte maturation or embryonic development. The effects of the variants were evaluated in patients' oocytes by morphological observations and immunofluorescence.

Results: We identified 34 novel variants of TUBB8 in 51 patients who were diagnosed with abnormalities in oocyte maturation or early embryonic development. We found a novel phenotype in which large polar bodies were present in three independent patients possibly associated with a recurrent variant. Moreover, we identified a novel type of TUBB8 variant consisting of an in-frame deletion-insertion, which has not been previously reported.

Conclusions: Our present study identified 34 novel variants in TUBB8 in 51 patients. These patients show oocyte maturation arrest, oocytes with large polar body, fertilization failure, early embryonic arrest or embryonic implantation failure. These results expand the kinds of variants and phenotypic spectrum of TUBB8 variants with regard to female infertility.
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http://dx.doi.org/10.1007/s10815-020-01830-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468027PMC
August 2020