Publications by authors named "Hao Pan"

332 Publications

An emerging role of Prevotella histicola on estrogen deficiency-induced bone loss through the gut microbiota-bone axis in postmenopausal women and in ovariectomized mice.

Am J Clin Nutr 2021 Jun 10. Epub 2021 Jun 10.

Department of Orthopaedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Background: The gut microbiota (GM)-bone axis has emerged as a crucial mediator of bone homeostasis. Estrogen deficiency-induced bone loss is closely associated with an altered GM. However, the underlying mechanisms remain unclear.

Objectives: We sought to explore the putative effects of GM on estrogen deficiency-induced bone loss and determine a potential mechanism.

Methods: Fecal samples collected from postmenopausal women with osteoporosis (PMO) and with normal bone mass (PMN) were examined by 16S ribosomal RNA (rRNA) gene sequencing and analysis. Prevotella histicola, a typical species of Prevotella, was orally given to female C57BL6/J mice after ovariectomy [ovariectomized (OVX)]. The primary outcomes were changes in bone microstructures as measured by micro-computed tomography scanning and bone histomorphometry analysis. Secondary outcomes included changes in osteoclast activity, the expression of osteoclastogenic cytokines, and gut permeability, which were measured by ELISA, qRT-PCR, western blot, and immunofluorescence.

Results: As demonstrated through 16S rRNA gene sequencing and analysis, the GM in the PMO group featured a significantly decreased proportion of the genus Prevotella in comparison with that in the PMN group (∼60%, P < 0.05). In animal experiments, P. histicola-treated OVX mice maintained a relatively higher bone volume than OVX controls. Mechanistically, the protective effects of P. histicola on bone mass were found to be associated with its modulation of gut permeability as well as its inhibitory effects on osteoclast activity which function by attenuating osteoclastogenic cytokine expression.

Conclusions: The GM diversity and composition between the PMN and PMO groups were significantly different. In particular, the proportion of the genus Prevotella was notably higher in the PMN group, demonstrating its potential bone-protective effects on osteoporosis. Further animal study using osteoporotic mice showed P. histicola could prevent estrogen deficiency-induced bone loss through the GM-bone axis. Thus, P. histicola may serve as a therapeutic agent or target for osteoporosis treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajcn/nqab194DOI Listing
June 2021

Viral mimetic poly(I:C) induces neutrophil extracellular traps via PAD4 to promote inflammation and thrombosis.

Biochem Biophys Res Commun 2021 Aug 4;565:64-71. Epub 2021 Jun 4.

Department of Cardiology, The 2nd Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. Electronic address:

Neutrophil extracellular traps (NETs) are extracellular webs of DNA, histones and granular contents that are released by neutrophils to control infections. However, NETs that is not properly regulated can propagate inflammation and thrombosis. It was recognized that viruses can induce NETs. As a synthetic analog of viral double-stranded (ds) RNA, polyinosinic-polycytidylic acid [poly(I:C)] is known to induce inflammation and thrombosis. However, whether and how poly(I:C) modulates NETs remains unclear. Here, we have demonstrated that poly(I:C) induced extracellular DNA traps in human neutrophils in a dose-dependent manner. Further, poly(I:C) or dsRNA virus elevated the levels of myeloperoxidase-DNA complexes and citrullinated histone H3, which are specific markers of NETs, in both neutrophil supernatants and mouse plasma. Interestingly, a potent peptidylarginine deiminase 4 (PAD4) inhibitor, BB-CL-Amidine (BB-CLA) or PAD4 knockdown effectively prevented poly(I:C)-induced NETs formation and release. In addition, BB-CLA abrogated poly(I:C)-triggered neutrophil activation and infiltration, and vascular permeability in lungs. BB-CLA also attenuated poly(I:C)-induced thrombocytopenia in circulation, fibrin deposition and thrombus formation in tissues. Taken together, these results suggest that viral mimetic poly(I:C) may induce NETs-dependent inflammation and thrombosis through PAD4, and that inhibiting PAD4 may become a good strategy to protect against viral infection-caused inflammation/thrombosis-related pathological conditions of diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2021.05.091DOI Listing
August 2021

Whole-genome resequencing of large yellow croaker (Larimichthys crocea) reveals the population structure and signatures of environmental adaptation.

Sci Rep 2021 May 27;11(1):11235. Epub 2021 May 27.

National Engineering Research Center of Marine Facilities Aquaculture, Zhejiang Ocean University, Zhoushan, 316022, China.

Large yellow croaker is an economically important fish in China and East Asia. Despite its economic importance, genome-wide adaptions of domesticated large yellow croaker are largely unknown. Here, we performed whole-genome resequencing of 198 individuals of large yellow croaker obtained in the sea or from farmers in Zhoushan or Ningde. Population genomics analyses revealed the genetic population structure of our samples, reflecting the living environment. Each effective population size is estimated to be declining over generations. Moreover, we identified genetically differentiated genomic regions between the sea-captured population in the Zhoushan Sea area and that of the Ningde Sea area or between the sea-captured population and the farmed population in either area. Gene ontology analyses revealed the gene groups under selective sweep for the adaptation to the domesticated environment. All these results suggest that individuals of the large yellow croaker populations show genomic signatures of adaptation to different living environments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-90645-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159941PMC
May 2021

Small-molecule inhibitor targeting the Hsp70-Bim protein-protein interaction in CML cells overcomes BCR-ABL-independent TKI resistance.

Leukemia 2021 May 18. Epub 2021 May 18.

State Key Laboratory of Fine Chemicals, Zhang Dayu School of Chemistry, Dalian University of Technology, Dalian, Liaoning, China.

Herein, we screened a novel inhibitor of the Hsp70-Bim protein-protein interaction (PPI), S1g-2, from a Bcl-2 inhibitor library; this compound specifically disrupted the Hsp70-Bim PPI by direct binding to an unknown site adjacent to that of an allosteric Hsp70 inhibitor MKT-077, showing binding affinity in sub-μM concentration range. S1g-2 exhibited overall 5-10-fold higher apoptosis-inducing activity in CML cells, primary CML blasts, and BCR-ABL-transformed BaF3 cells than other cancer cells, normal lymphocytes, and BaF3 cells, illustrating Hsp70-Bim PPI driven by BCR-ABL protects CML through oncoclient proteins that enriched in three pathways: eIF2 signaling, the regulation of eIF4E and p70S6K signaling, and the mTOR signaling pathways. Moreover, S1g-2 progressively enhanced lethality along with the increase in BCR-ABL-independent TKI resistance in the K562 cell lines and is more effective in primary samples from BCR-ABL-independent TKI-resistant patients than those from TKI-sensitive patients. By comparing the underlying mechanisms of S1g-2, MKT-077, and an ATP-competitive Hsp70 inhibitor VER-155008, the Hsp70-Bim PPI was identified to be a CML-specific target to protect from TKIs through the above three oncogenic signaling pathways. The in vivo activity against CML and low toxicity endows S1g-2 a first-in-class promising drug candidate for both TKI-sensitive and resistant CML.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41375-021-01283-5DOI Listing
May 2021

A novel alginate/gelatin sponge combined with curcumin-loaded electrospun fibers for postoperative rapid hemostasis and prevention of tumor recurrence.

Int J Biol Macromol 2021 May 14;182:1339-1350. Epub 2021 May 14.

School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address:

Surgical resection of the tumor remains the preferred treatment for most solid tumors at an early stage, but surgical treatment often leads to massive bleeding and residual tumor cells. Therefore, a novel alginate/gelatin sponge combined with curcumin-loaded electrospun fibers (CFAGS) for rapid hemostasis and prevention of tumor recurrence was prepared by using an electrospinning and interpenetrating polymer network (IPN) strategy. The present results show that alginate/gelatin sponge display excellent hemostatic properties and possess more advantages than commercial gelatin hemostasis sponge. More importantly, CFAGS could control the release of curcumin, inducing curcumin to accumulate at the surgical site of the tumor, thereby inhibiting local tumor recurrence in the subcutaneous postoperative recurrence model. In addition, the sponge was safe to implant in the body and did not cause toxicity to normal tissues and organs. This approach represents a new strategy to implant a dual functional sponge at the postoperative site as an adjuvant to the surgical treatment of cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijbiomac.2021.05.074DOI Listing
May 2021

Fabrication and Characterization of Taurine Functionalized Graphene Oxide with 5-Fluorouracil as Anticancer Drug Delivery Systems.

Nanoscale Res Lett 2021 May 13;16(1):84. Epub 2021 May 13.

School of Pharmacy, Liaoning University, Shenyang, 110036, China.

Recently, nanocarrier systems for cancer drugs, especially GO-based drug delivery systems, have become a boon for cancer patients. In this study, we choose Tau to functionalize the GO surface to improve its biocompatibility. Firstly, nano-scale GO was synthesized by the modified Hummer's method and ultrasonic stripping method. The taurine-modified graphene oxide carrier (Tau-GO) was synthesized by chemical method to obtain Tau-GO that has a good dispersibility and stability in water, with a zeta potential of - 38.8 mV and a particle size of 242 nm. Based on the encapsulation efficiency evaluation criteria, the optimal formulation was determined to combine Tau-GO and 5-FU by non-covalent bonding. The 5-FU-Tau-GO was more stable in neutral environment than in acidic environment, and with a certain PH response and sustained release effect. In vivo, we compared oral and intravenous administrations of 5-FU and 5-FU-Tau-GO, respectively, using pharmacokinetic tests and related parameters and showed that 5-FU-Tau-GO oral or intravenous administration prolongs the action time of 5-FU in the body and improves its bioavailability. In addition, the inhibition of HepG2 cells that was measured by the MTT assay, showed that the IC value of 5-FU was 196 ± 8.73 μg/mL, and the IC value of 5-FU-Tau-GO was 65.2 ± 0.7 μg/mL, indicating that 5- FU-Tau-GO is more potent against HepG2 cells and has a stronger inhibitory effect on cancer cells. The effect on cell morphology that was measured using the AO/EB staining also showed that 5-FU-Tau-GO not only disrupted cells, but also significantly induced apoptosis compared to 5-FU. We also verified by computer aided design that Tau-GO can bind better to 5-FU than to the unmodified GO, and that the formed 5-FU-Tau-GO system is more stable, and conducive to the transfer and release of 5-FU in vivo.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s11671-021-03541-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119561PMC
May 2021

Controlled release of KGF-2 for regulation of wound healing by KGF-2 complexed with "lotus seedpod surface-like" porous microspheres.

J Mater Chem B 2021 05;9(19):4039-4049

Department of Intensive Care, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.

Keratinocyte growth factor-2 (KGF-2) can regulate the proliferation and differentiation of keratinocyte, which plays a remarkable role in maintaining normal tissue structure and promoting wound healing. As an effective strategy, KGF-2 solution is widely used in the treatment of wounds in clinical applications. However, KGF-2 in solution cannot achieve sustained release, which results in drug loss and unnecessary waste. Polysaccharide hemostasis microspheres (PHMs) are an ideal drug loading platform due to their special "lotus seedpod surface-like" morphology and structure. Herein, to realize the controllable release of KGF-2, PHMs loaded with KGF-2 ([email protected]) were prepared. It was found that the bioavailability of KGF-2 was improved greatly. Most importantly, [email protected] can reduce inflammation and accelerate the wound healing process due to the controlled release of KGF-2. [email protected] might be a potential alternative strategy for wound healing in future clinical applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1tb00148eDOI Listing
May 2021

Diagnostic Role of Four-Dimensional Computed Tomography for Preoperative Parathyroid Localization in Patients with Primary Hyperparathyroidism: A Systematic Review and Meta-Analysis.

Diagnostics (Basel) 2021 Apr 7;11(4). Epub 2021 Apr 7.

Department of Radiology, Beijing Luhe Hospital, Capital Medical University, No 82 Xinhua South Road, Tongzhou District, Beijing 101149, China.

We sought to systematically evaluate diagnostic performance of four-dimensional computed tomography (4D-CT) in the localization of hyperfunctioning parathyroid glands (HPGs) in patients with primary hyperparathyroidism (pHPT). We calculated the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratios (DOR) of 4D-CT on a per-lesion level, as well as pooled sensitivity and positive predictive value (PPV) on a per-patient level with 95% confidence intervals (CIs). Additionally, we plotted summary receiver operating characteristic (SROC) curves and evaluated the areas under the curves (AUC). A total of 16 studies were included in the analysis. Their pooled sensitivity, specificity, PLR, NLR, and DOR of 4D-CT on per-lesion level were 75% (95%CI: 66-82%), 85% (95%CI: 50-97%), 4.9 (95%CI: 1.1-21.3), 0.30 (95%CI: 0.19-0.45), and 17 (95%CI: 3-100), respectively, with an AUC of 81% (95%CI: 77-84%). We also observed heterogeneity in sensitivity (I = 79%) and specificity (I = 94.7%), and obtained a pooled sensitivity of 81% (95%CI: 70-90%) with heterogeneity of 81.9% ( < 0.001) and PPV of 91% (95%CI: 82-98%) with heterogeneity of 80.8% ( < 0.001), based on a per-patient level. Overall, 4D-CT showed moderate sensitivity and specificity for preoperative localization of HPG(s) in patients with pHPT. The diagnostic performance may improve with 4D-CT's promotion to first-line use on a lesion-based level, further research is needed to confirm the results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/diagnostics11040664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068020PMC
April 2021

A novel Hsp70 inhibitor specifically targeting the cancer-related Hsp70-Bim protein-protein interaction.

Eur J Med Chem 2021 Aug 14;220:113452. Epub 2021 Apr 14.

State Key Laboratory of Fine Chemicals, Zhang Dayu School of Chemistry, Dalian University of Technology, Dalian, Liaoning, 116024, China. Electronic address:

Targeting cancer-related Hsp70-Bim protein-protein interactions (PPIs) offers a new strategy for the design of Hsp70 inhibitors. Herein, we discovered a novel Hsp70 inhibitor, S1g-6, based on the established BH3 mimetics. S1g-6 exhibited sub-μM binding affinity toward Hsp70 and selectively disrupted Hsp70-Bim PPI. The target specificity of S1g-6in situ was validated by affinity-based protein profiling, co-immunoprecipitation, and cell-based shRNA assays. S1g-6 specifically antagonized the ATPase activity of Hsp70 upon recruiting Bim and showed selective apoptosis induction in some cancer cell lines over normal ones through suppression of some oncogenic clients of Hsp70, representing a new class of antitumor candidates. Hsp70-Bim PPI exhibited cancer-dependent role as a potential anti-cancer target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmech.2021.113452DOI Listing
August 2021

Sustainable stabilization/solidification of the Pb, Zn, and Cd contaminated soil by red mud-derived binders.

Environ Pollut 2021 Apr 19;284:117178. Epub 2021 Apr 19.

Institute of Construction Materials, Technische Universität Dresden, 01062, Dresden, Germany. Electronic address:

Red mud and phosphogypsum are voluminous industrial by-products worldwide. They have long been disposed of in landfills or open storage, leading to a waste of resource and environmental pollution. This study provides a novel approach to recycle these industrial by-products as sustainable red mud-phosphogypsum-Portland cement (RPPC) binders for stabilization/solidification (S/S) of multimetal-contaminated soil. The physical strength, metal leachability and microstructure of S/S soil were investigated after 7-day and 28-day curing, as well as freezing-thawing (F-T) cycle and wetting-drying (W-D) cycle. The results show that the strength of soil treated by all binders fulfilled the uniaxial compressive strength requirement (350 kPa) of S/S waste in landfills. Microstructural analyses show that the main hydration products of the RPPC S/S soil are ilmenite, ettringite, anhydrite and hydrated calcium silicate. The 10% and 15% RPPC binders have a competitive metal immobilization ability compared with 10% PC, but the immobilization priority is different: Pb > Zn > Cd in RPPC system and Zn > Cd > Pb in PC system, respectively, probably due to the precipiataion of Pb with the abundant SO in phosphogypsum in RPPC system. The strength of RPPC and PC treated soil was still higher than 350 kPa except for RPPC7.5 after 10 freeze-thaw or 10 wetting-drying cycles. The RPPC binder performed worse than PC binder after both freeze-thaw and wetting-drying cycles, especially at a lower dosage. Only the metal leaching concentrations of samples treated by RPPC15 and PC10 could fulfil the Chinese standards for hazardous wastes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2021.117178DOI Listing
April 2021

Amino acids functionalized dendrimers with nucleus accumulation for efficient gene delivery.

Int J Pharm 2021 Jun 24;602:120641. Epub 2021 Apr 24.

School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address:

Gene therapy is a promising approach to many diseases, however, the barriers in the gene delivery restrict its application. Therefore, in the present study, an efficient non-viral gene vector (PRHF/N/D) for overcoming the barriers in gene delivery was prepared. The synthesized PRHF integrated the advantages of PAMAM and amino acids, which could improve the cellular uptake, enhance the endosomal escape ability and minimize cytotoxicity. To further enhance nuclear entry of carrier, the nuclear localization signal (NLS) peptide was selected to add in the PRHF/D polyplexes. The PRHF/N/D polyplexes demonstrated good condensation capacity, wonderful pDNA protection and low toxicity. Moreover, the PRHF/N/D polyplexes showed the excellent transfection efficiency than P/D. PRHF/N/D further improve transfection capability than PRHF/D in the presence of NLS. After 4 h of incubation, the mean fluorescence intensity of PRHF/N/D was also higher than the P/D and PRHF/D complexes. We then investigated the intracellular dissociation, the DNA is able to disassemble from PRHF/N/D gene carriers. Taken together, we exhibited that this PRHF/N/D polyplexes has the potential for use in the gene delivery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2021.120641DOI Listing
June 2021

Development and Evaluation of Nomograms to Predict the Cancer-Specific Mortality and Overall Mortality of Patients with Hepatocellular Carcinoma.

Biomed Res Int 2021 29;2021:1658403. Epub 2021 Mar 29.

Department of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.

Hepatocellular carcinoma (HCC) is the most common type among primary liver cancers (PLC). With its poor prognosis and survival rate, it is necessary for HCC patients to have a long-term follow-up. We believe that there are currently no relevant reports or literature about nomograms for predicting the cancer-specific mortality of HCC patients. Therefore, the primary goal of this study was to develop and evaluate nomograms to predict cancer-specific mortality and overall mortality. Data of 45,158 cases of HCC patients were collected from the Surveillance, Epidemiology, and End Results (SEER) program database between 2004 and 2013, which were then utilized to develop the nomograms. Finally, the performance of the nomograms was evaluated by the concordance index (C-index) and the area under the time-dependent receiver operating characteristic (ROC) curve (td-AUC). The categories selected to develop a nomogram for predicting cancer-specific mortality included marriage, insurance, radiotherapy, surgery, distant metastasis, lymphatic metastasis, tumor size, grade, sex, and the American Joint Committee on Cancer (AJCC) stage; while the marriage, radiotherapy, surgery, AJCC stage, grade, race, sex, and age were selected to develop a nomogram for predicting overall mortality. The C-indices for predicted 1-, 3-, and 5-year cancer-specific mortality were 0.792, 0.776, and 0.774; the AUC values for 1-, 3-, and 5-year cancer-specific mortality were 0.830, 0.830, and 0.830. The C-indices for predicted 1-, 3-, and 5-year overall mortality were 0.770, 0.755, and 0.752; AUC values for predicted 1-, 3-, and 5-year overall mortality were 0.820, 0.820, and 0.830. The results showed that the nomograms possessed good agreement compared with the observed outcomes. It could provide clinicians with a personalized predicted risk of death information to evaluate the potential changes of the disease-specific condition so that clinicians can adjust therapy options when combined with the actual condition of the patient, which is beneficial to patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/1658403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024067PMC
May 2021

PEG-interpenetrated genipin-crosslinked dual-sensitive hydrogel/nanostructured lipid carrier compound formulation for topical drug administration.

Artif Cells Nanomed Biotechnol 2021 Dec;49(1):345-353

Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.

PEG-interpenetrated dual-sensitive hydrogels that load nano lipid carrier (NLC) were researched and developed for topical drug administration. Natural antioxidant α-lipoic acid (ALA) was selected as our model drug. The α-lipoic acid (ALA) nano lipid carrier was successfully prepared by hot melt emulsification and ultrasonic dispersion method, and the physicochemical properties of the nano lipid carrier were investigated, including morphology, particle distribution, polydispersity coefficient, zeta potential and encapsulation efficiency. Carboxymethyl chitosan and poloxamer 407 contributed to pH- and temperature-sensitive properties in the hydrogel, respectively. Natural non-toxic cross-linking agent genipin reacted with carboxymethyl chitosan to form the hydrogel. Poly ethylene glycol (PEG), a polymer compound with good water solubility and biocompatibility, interpenetrated the hydrogel and influenced the mechanical strength and drug release behaviour. FI-IR test verified the successful synthesis of the hydrogel. The rheological parameters indicated that the mechanical strength of the hydrogel was positively correlated with the amount of PEG, and the dissolution profiles demonstrated that the increasement of PEG could accelerate the drug release rate. The compatibility of the drug delivery system was verified with cells and mice model. Topical delivery of ALA in solution, NLC and NLC-gel was investigated in-vitro.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21691401.2021.1879104DOI Listing
December 2021

Predictive model for the 5-year survival status of osteosarcoma patients based on the SEER database and XGBoost algorithm.

Sci Rep 2021 Mar 10;11(1):5542. Epub 2021 Mar 10.

Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, China.

Osteosarcoma is the most common bone malignancy, with the highest incidence in children and adolescents. Survival rate prediction is important for improving prognosis and planning therapy. However, there is still no prediction model with a high accuracy rate for osteosarcoma. Therefore, we aimed to construct an artificial intelligence (AI) model for predicting the 5-year survival of osteosarcoma patients by using extreme gradient boosting (XGBoost), a large-scale machine-learning algorithm. We identified cases of osteosarcoma in the Surveillance, Epidemiology, and End Results (SEER) Research Database and excluded substandard samples. The study population was 835 and was divided into the training set (n = 668) and validation set (n = 167). Characteristics selected via survival analyses were used to construct the model. Receiver operating characteristic (ROC) curve and decision curve analyses were performed to evaluate the prediction. The accuracy of the prediction model was excellent both in the training set (area under the ROC curve [AUC] = 0.977) and the validation set (AUC = 0.911). Decision curve analyses proved the model could be used to support clinical decisions. XGBoost is an effective algorithm for predicting 5-year survival of osteosarcoma patients. Our prediction model had excellent accuracy and is therefore useful in clinical settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-85223-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970935PMC
March 2021

Exploration and evaluation of dynamic dose-control platform for pediatric medicine based on Drop-on-Powder 3D printing technology.

Int J Pharm 2021 Mar 1;596:120201. Epub 2021 Feb 1.

Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, China. Electronic address:

Patient responses to doses vary widely, and affording limited doses to such a diverse population will inevitably yield unsatisfactory therapeutic effects and even adverse effects. In Particular, there is an urgent demand for a dynamic dose-control platform for pediatric patients, many of whom require diverse doses and flexible dose adjustments. The aim of this study was to explore the possibility of using a drop-on-powder (DoP) technology-based desktop 3D printer to build a dynamic dose-control platform for theophylline (TP) and metoprolol tartrate (MT). In addition, the impact of drug loading patterns on the accuracy of dose regulation was also assessed. All of the printed tablets exhibited good mechanical properties and satisfactory structural integrity. On printing tablets with target drug doses, the accuracy was in the range of 91.2~108% with a small variation coefficient in the range of 0.5~3.2%. Compared with traditional divided-dose methods, drop-on-powder 3D printing technology exhibited higher accuracy in dose regulation, but had less impact on the in vitro drug release behavior. The results in this work clearly indicate the possibility and ability of DoP technology as a promising method for constructing a dynamic dose-control platform for the fabrication of personalized medicines for pediatric patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2021.120201DOI Listing
March 2021

New molecular prognostic factors of adult diffuse lower-grade gliomas in post-2016 molecular era: a retrospective analysis from single center.

Br J Neurosurg 2021 Feb 4:1-8. Epub 2021 Feb 4.

Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.

Background And Objective: Several studies have examined the prognostic significance of IDH1/2 mutation, 1p/19q codeletion and MGMT promoter methylation in lower-grade gliomas but most of these used the 2007 fourth edition of the WHO classification. We evaluate prognostic significance of these indicators in the 2016 WHO updated fourth edition of CNS tumor classification.

Methods: A total of 180 intracranial glioma patients diagnosed according WHO 2016 edition between December 2016 and December 2018 Jinling Hospital (Nanjing, China) were reviewed retrospectively. We performed survival analysis on 109 patients with complete molecular pathology and follow-up data.

Results: Histologically, 52 were diagnosed as astrocytoma (WHO grade II and III), 17 as oligodendrogliomas (WHO grade II and III) and 40 as GBMs. At last follow-up, 50.5% patients had experienced tumor progression and 34.9% had died. Among grade II and III cases 36.2% experienced tumor progression and 27.5% died. In univariate Kaplan-Meier analysis, multifocal tumor, EGFR mutation or amplification, PIK3CA mutation and IDHwt/TERTpwt group were associated with shorter PFS ( < 0.001,  = 0.003,  = 0.005,  < 0.001, respectively) and OS ( = 0.010,  = 0.020,  = 0.018,  < 0.001, respectively) as were older age (≥55 years), multifocal tumor, IDH1/2 wild type, 1p/19q non-codeletion and negative methylation in the MGMT promoter region. A Cox proportional hazards model was created demonstrating that single tumor (HR = 0.180,  = 0.04), MGMTp methylation (HR = 0.095,  = 0.003) and chemoradiotherapy (HR = 0.006,  = 0.002) were independent prognostic factors for OS.

Conclusions: Beyond histological classification as well as IDH1/2 mutation, 1p/19q codeletion status, we could incorporate IDH1/2mt combined with TERTpmt, EGFR mutation or amplification and PIK3CA mutation into the diagnostic criteria for DLGGs to supplement WHO 2016 pathological criteria.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02688697.2020.1847249DOI Listing
February 2021

Genipin-cross-linked hydrogels based on biomaterials for drug delivery: a review.

Biomater Sci 2021 Mar;9(5):1583-1597

School of Pharmacy, Liaoning University, Shenyang 110036, China.

Genipin is a naturally occurring nontoxic cross-linker, which has been widely used for drug delivery due to its excellent biocompatibility, admirable biodegradability and stable cross-linked attributes. These advantages led to its extensive application in the fabrication of hydrogels for drug delivery. This review describes the physicochemical characteristics and pharmacological activities of genipin and attempts to elucidate the detailed mechanisms of the cross-linking reaction between genipin and biomaterials. The current article entails a general review of the different biomaterials cross-linked by genipin: chitosan and its derivatives, collagen, gelatin, etc. The genipin-cross-linked hydrogels for various pharmaceutical applications, including ocular drug delivery, buccal drug delivery, oral drug delivery, anti-inflammatory drug delivery, and antibiotic and antifungal drug delivery, are reported. Finally, the future research directions and challenges of genipin-cross-linked hydrogels for pharmaceutical applications are also discussed in this review.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0bm01403fDOI Listing
March 2021

Three-Dimensional (3D)-Printed Zero-Order Released Platform: a Novel Method of Personalized Dosage Form Design and Manufacturing.

AAPS PharmSciTech 2021 Jan 6;22(1):37. Epub 2021 Jan 6.

School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China.

In 2017, there are 451 million people with diabetes worldwide. These figures were expected to increase to 693 million by 2045. The research and development of hypoglycemic drugs has become a top priority. Among them, sulfonylurea hypoglycemic drugs such as glipizide are commonly used in non-insulin-dependent type II diabetes. In order to adapt to the wide range of hypoglycemic drugs and the different individual needs of patients, this topic used glipizide as a model drug, and prepared glipizide preparations with 3D printing technology. The purpose of this study was to investigate the prescription applicability and control-release behavior of structure and explore the application prospects of 3D printing personalized drug delivery formulations. This article aims to establish a production process for personalized preparations based on 3D printing technology. The process is easy to obtain excipients, universal prescriptions, flexible dosages, exclusive customization, and integrated automation. In this paper, the UV method was used to determine the in vitro release and content analysis method of glipizide; the physical and chemical properties of the glipizide were investigated. The established analysis method was inspected and evaluated, and the experimental results met the methodological requirements. Glipizide controlled-release tablets were prepared by the semisolid extrusion (SSE) method using traditional pharmaceutical excipients combined with 3D printing technology. The formulation composition, in vitro release, and printing process parameters of the preparation were investigated, and the final prescription and process parameters (traveling speed 6.0-7.7 mm/s and extruding speed 0.0060-0.0077 mm/s) were selected through comprehensive analysis. The routine analysis results of the preparation showed that the performance of the preparation meets the requirements. In order for 3D printing technology to play a better role in community medicine and telemedicine, this article further explored the universality of the above prescription and determined the scope of application of prescription drugs and dosages. Glipizide, gliclazide, lornoxicam, puerarin, and theophylline were used as model drugs, and the range of drug loading percentage was investigated. The results showed when the solubility of the drug is 9.45 -8.34 mg/mL, and the drug loading is 3-43%; the release behavior is similar.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1208/s12249-020-01886-8DOI Listing
January 2021

Molecular Characterization and Evolution Analysis of Two Forms of TLR5 and TLR13 Genes Base on Genome Data.

Int J Genomics 2020 9;2020:4895037. Epub 2020 Dec 9.

National Engineering Research Center for Facilitated Marine Aquaculture, Zhejiang Ocean University, No. 1, South Haida Road, Dinghai District, Zhoushan, China.

TLRs (Toll-like receptors) are essential in host defense against pathogens. There are two types of TLR5, namely, membrane form of TLR5 (TLR5M) and soluble form of TLR5 (TLR5S), both of which perform a crucial role in flagellin response. TLR13 is a TLR that localizes to endosomes and recognizes nucleic acids released by internal microorganisms, including viruses, bacteria, and fungi. Here, the full-length coding sequence (CDS), protein structure, and immune response and subcellular localization of TLR5 (TLR5S) and TLR13 were characterized in large yellow croaker (). These TLRs share high sequence homology with other ichthyic TLRs, while also having their own characters; qtPCR was determined and the results found that the three genes were constitutively expressed in all examined tissues: TLR5M was highly expressed in the spleen and liver; TLR13 expression was high in the kidney, liver, and spleen. And TLRs were upregulated following stimulation with in the liver, spleen, and kidney. Immunofluorescence staining revealed that TLR5M were localized in the cytoplasm, while TLR5S and TLR13 were in the endosome. The evolutionary analysis has shown that TLR13 was clustered with TLR11, 19, 20, 21, and 22, while TLR5 and TLR3 were classified into a group; these results suggest that TLRs are vital in the defense of against bacterial infection and further increase our understanding of TLR function in innate immunity in teleosts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/4895037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744196PMC
December 2020

Gallic Acid Alleviates Gouty Arthritis by Inhibiting NLRP3 Inflammasome Activation and Pyroptosis Through Enhancing Nrf2 Signaling.

Front Immunol 2020 7;11:580593. Epub 2020 Dec 7.

Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.

Gallic acid is an active phenolic acid widely distributed in plants, and there is compelling evidence to prove its anti-inflammatory effects. NLRP3 inflammasome dysregulation is closely linked to many inflammatory diseases. However, how gallic acid affects the NLRP3 inflammasome remains unclear. Therefore, in the present study, we investigated the mechanisms underlying the effects of gallic acid on the NLRP3 inflammasome and pyroptosis, as well as its effect on gouty arthritis in mice. The results showed that gallic acid inhibited lactate dehydrogenase (LDH) release and pyroptosis in lipopolysaccharide (LPS)-primed and ATP-, nigericin-, or monosodium urate (MSU) crystal-stimulated macrophages. Additionally, gallic acid blocked NLRP3 inflammasome activation and inhibited the subsequent activation of caspase-1 and secretion of IL-1β. Gallic acid exerted its inhibitory effect by blocking NLRP3-NEK7 interaction and ASC oligomerization, thereby limiting inflammasome assembly. Moreover, gallic acid promoted the expression of nuclear factor E2-related factor 2 (Nrf2) and reduced the production of mitochondrial ROS (mtROS). Importantly, the inhibitory effect of gallic acid could be reversed by treatment with the Nrf2 inhibitor ML385. NRF2 siRNA also abolished the inhibitory effect of gallic acid on IL-1β secretion. The results further showed that gallic acid could mitigate MSU-induced joint swelling and inhibit IL-1β and caspase 1 (p20) production in mice. Moreover, gallic acid could moderate MSU-induced macrophages and neutrophils migration into joint synovitis. In summary, we found that gallic acid suppresses ROS generation, thereby limiting NLRP3 inflammasome activation and pyroptosis dependent on Nrf2 signaling, suggesting that gallic acid possesses therapeutic potential for the treatment of gouty arthritis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2020.580593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750458PMC
December 2020

Desktop-Stereolithography 3D Printing of a Polyporous Extracellular Matrix Bioink for Bone Defect Regeneration.

Front Bioeng Biotechnol 2020 6;8:589094. Epub 2020 Nov 6.

Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, China.

Introduction: Decellularized tendon extracellular matrix (tECM) perfectly provides the natural environment and holds great potential for bone regeneration in Bone tissue engineering (BTE) area. However, its densifying fiber structure leads to reduced cell permeability. Our study aimed to combine tECM with polyethylene glycol diacrylate (PEGDA) to form a biological scaffold with appropriate porosity and strength using stereolithography (SLA) technology for bone defect repair.

Methods: The tECM was produced and evaluated. Mesenchymal stem cell (MSC) was used to evaluate the biocompatibility of PEGDA/tECM bioink . Mineralization ability of the bioink was also evaluated . After preparing 3D printed polyporous PEGDA/tECM scaffolds (3D-pPES) via SLA, the calvarial defect generation capacity of 3D-pPES was assessed.

Results: The tECM was obtained and the decellularized effect was confirmed. The tECM increased the swelling ratio and porosity of PEGDA bioink, both cellular proliferation and biomineralization of the bioink were significantly optimized. The 3D-pPES was fabricated. Compared to the control group, increased cell migration efficiency, up-regulation of osteogenic differentiation RNA level, and better calvarial defect repair in rat of the 3D-pPES group were observed.

Conclusion: This study demonstrates that the 3D-pPES may be a promising strategy for bone defect treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fbioe.2020.589094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677189PMC
November 2020

An inherently kidney-targeting near-infrared fluorophore based probe for early detection of acute kidney injury.

Biosens Bioelectron 2021 Jan 22;172:112756. Epub 2020 Oct 22.

The Fourth Affiliated Hospital, College of Pharmaceutical Sciences, School of Medicine, Zhejiang University, Hangzhou, 310058, PR China. Electronic address:

Acute kidney injury (AKI) is common in hospital patients. Delayed diagnosis and treatment of AKI due to the lack of efficient early diagnosis is an important cause of its high mortality. While fluorescence imaging seems promising to non-intrusively interrogate AKI-related biomarkers, the low kidney contrast of many fluorophores conferred by their relatively low abundance of distribution in the kidney limits their application for AKI detection. Herein, we discovered a near-infrared fluorophore with inherent kidney-targeting ability. Based on this fluorophore, a fluorogenic probe (KNP-1) was developed by targeting peroxynitrite (ONOO), which is upregulated at the early onset of AKI. KNP-1 exhibits desirable kidney distribution after intravenous administration and is fluorescent only after activation by ONOO. These properties lead to excellent kidney contrast imaging results. KNP-1 is capable of detecting both nephrotoxin-induced and ischemia-reperfusion injury-induced AKI in live mice. Temporally resolved imaging of AKI-disease model mice with KNP-1 suggests a gradual increase in renal ONOO levels with disease progression. Notably, the upregulation of ONOO can be observed at least 24 h earlier than the clinically popular sCr and BUN methods. Blocking ONOO generation also proves beneficial. These results highlight the applicability of this inherently tissue targeting-based strategy for designing probes with desirable imaging contrast; potentiate ONOO as a biomarker and target for AKI early diagnosis and medical intervention; and imply the clinical relevance of KNP-1 for AKI early detection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bios.2020.112756DOI Listing
January 2021

Hierarchical Toughening of a Biomimetic Bulk Cement Composite.

ACS Appl Mater Interfaces 2020 Nov 10;12(47):53297-53309. Epub 2020 Nov 10.

Jiangsu Key Laboratory of Construction Materials, School of Materials Science and Engineering, Southeast University, Nanjing 211189, China.

Because of the inherent quasibrittleness and heterogeneity, matrix-directed toughening of concrete and cement composites remains to be a huge challenge. Herein, inspired by nacre materials, a novel biomimetic bulk cement composite is fabricated via a facile and efficient process based on compacting prefabricated multisized cement-polymer hybrid prills. This method combines with the three-dimensional "brick-bridge-mortar" structure design and synchronously the intrinsic and extrinsic toughening strategies. Such an approach shows the remarkable maximum toughness enhancement of 27-fold with 71% increase in flexural strength via cooperation with only 4 wt % organic matter. More attractively, it alters the traditional brittle fracture of cement composites to a distinct ductile fracture. In addition, such a biomimetic composite demonstrates the long-term ever-increasing strength and toughness, performing the excellent ductile-fracture retention ability. The hierarchical toughening mechanisms are further revealed with the synergy of microscopic characterizations and simulation methods. This strategy provides a new route for the development of high toughness biomimetic cement-based materials for potential applications in civil engineering domain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.0c15313DOI Listing
November 2020

Study of accumulation behaviour of tungsten based composite using electron probe micro analyser for the application in bone tissue engineering.

Saudi J Biol Sci 2020 Nov 23;27(11):2936-2941. Epub 2020 Jul 23.

Department of Trauma Center, Central Hospital Affiliated to Shandong First Medical University, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250013, China.

In this research, a proto-type study we have conducted, where we have synthesized tungsten based composite materials which are tungsten along with combined oxides of other elements like calcium, scandium, barium, and aluminium in the form of powder with bones powder of mice devised by high energy ball mill and later on fabricating high dense pellets by sintering by spark plasma. The particle sizes of the composite materials are found to be 1-2 µm, as evidenced by the electron microscope, suggesting synthesized materials are of micron size. The quantitative and qualitative analysis of sintered pellets are well confirmed by electron probe micro analyzer (EPMA) and energy dispersive X-ray spectrometer (EDS) which illustrate the greater percentage of tungsten presents in the profound scan areas with other elements of the composite. The absence of pores across the 3D geometry suggesting dense sample, which is quite revealed by the X-ray tomography inspection. The prepared sintered pellets from the tungsten based composites are found to be ≈ 99.5% density with the observation of tungsten to be accumulated uniformly across the scan regions along with focussed hot spots as implied by EPMA. This study paves the way, to examine how the tungsten accumulation and the distribution with the other elements for future understanding in bone tissue engineering application and the in vivo specification of tungsten.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.sjbs.2020.07.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569116PMC
November 2020

Epidemiological and clinical characteristics of 161 discharged cases with coronavirus disease 2019 in Shanghai, China.

BMC Infect Dis 2020 Oct 20;20(1):780. Epub 2020 Oct 20.

Shanghai Municipal Center for Disease Control and Prevention, No. 1380, West Zhongshan Road, Shanghai, 200336, China.

Background: In December 2019, the outbreak of coronavirus disease 2019 (COVID-19) began in Wuhan, China, and rapidly spread to other regions. We aimed to further describe the epidemiological and clinical characteristics of discharged COVID-19 cases and evaluate the public health interventions.

Methods: We collected epidemiological and clinical data of all discharged COVID-19 cases as of 17 February 2020 in Shanghai. The key epidemiological distributions were estimated and outcomes were also compared between patients whose illness were before 24 January and those whose illness were after 24 January.

Results: Of 161 discharged COVID-19 cases, the median age was 45 years, and 80 (49.7%) cases were male. All of the cases were categorized as clinical moderate type. The most common initial symptoms were fever (85.7%), cough (41.0%), fatigue (19.3%), muscle ache (17.4%), sputum production (14.9%), and there were six asymptomatic cases. 39 (24.2%) cases got infected in Shanghai, and three of them were second-generation cases of Shanghai native cases. The estimated median of the time from onset to first medical visit, admission, disease confirmation, and discharge for 161 cases was 1.0 day (95% CI, 0.6-1.2), 2.0 days (95% CI, 1.5-2.6), 5.2 days (95% CI, 4.6-5.7), 18.1 days (95% CI, 17.4-18.8), respectively. The estimated median of the time from admission to discharge was 14.0 days (95% CI, 13.3-14.6). The time from onset to first medical visit, admission and disease confirmation were all shortened after the Shanghai's first-level public health emergency response. In Cox regression model, the significant independent covariates for the duration of hospitalization were age, the time from onset to admission and the first-level public health emergency response.

Conclusions: Local transmission had occurred in Shanghai in late January 2020. The estimated median of the time from onset to discharge of moderate COVID-19 was 18.1 days in Shanghai. Time intervals from onset to first medical visit, admission and disease confirmation were all shortened after the Shanghai's first-level public health emergency response. Age, the first-level public health emergency response and the time from onset to admission were the impact factors for the duration of hospitalization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12879-020-05493-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573864PMC
October 2020

Accelerated degradation of HAP/PLLA bone scaffold by PGA blending facilitates bioactivity and osteoconductivity.

Bioact Mater 2021 Feb 10;6(2):490-502. Epub 2020 Sep 10.

Department of Periodontics & Oral Mucosal Section, Xiangya Stomatological Hospital, Central South University, Changsha, 410013, China.

The incorporation of hydroxyapatite (HAP) into poly-l-lactic acid (PLLA) matrix serving as bone scaffold is expected to exhibit bioactivity and osteoconductivity to those of the living bone. While too low degradation rate of HAP/PLLA scaffold hinders the activity because the embedded HAP in the PLLA matrix is difficult to contact and exchange ions with body fluid. In this study, biodegradable polymer poly (glycolic acid) (PGA) was blended into the HAP/PLLA scaffold fabricated by laser 3D printing to accelerate the degradation. The results indicated that the incorporation of PGA enhanced the degradation rate of scaffold as indicated by the weight loss increasing from 3.3% to 25.0% after immersion for 28 days, owing to the degradation of high hydrophilic PGA and the subsequent accelerated hydrolysis of PLLA chains. Moreover, a lot of pores produced by the degradation of the scaffold promoted the exposure of HAP from the matrix, which not only activated the deposition of bone like apatite on scaffold but also accelerated apatite growth. Cytocompatibility tests exhibited a good osteoblast adhesion, spreading and proliferation, suggesting the scaffold provided a suitable environment for cell cultivation. Furthermore, the scaffold displayed excellent bone defect repair capacity with the formation of abundant new bone tissue and blood vessel tissue, and both ends of defect region were bridged after 8 weeks of implantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioactmat.2020.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493133PMC
February 2021

Commentary: Metabolites released from apoptotic cells act as tissue messengers.

Front Immunol 2020 20;11:1878. Epub 2020 Aug 20.

Institute of Tissue Transplantation and Immunology, Department of Immunobiology, Jinan University, Guangzhou, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2020.01878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468377PMC
March 2021

Dielectric films for high performance capacitive energy storage: multiscale engineering.

Nanoscale 2020 Oct 23;12(38):19582-19591. Epub 2020 Sep 23.

Department of Materials Science and Metallurgy, University of Cambridge, 27 Charles Babbage Road, Cambridge, CB3 0FS, UK.

Dielectric capacitors are fundamental components in electronic and electrical systems due to their high-rate charging/discharging character and ultrahigh power density. Film dielectrics possess larger breakdown strength and higher energy density than their bulk counterparts, holding great promise for compact and efficient power systems. In this article, we review the very recent advances in dielectric films, in the framework of engineering at multiple scales to improve energy storage performance. Strategies are summarized including atomic-scale defect control, nanoscale domain and grain engineering, as well as mesoscale composite design. Challenges and remaining concerns are also discussed for further performance improvement and practical application of dielectric films.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0nr05709fDOI Listing
October 2020

Aggressive Quarantine Measures Reduce the High Morbidity of COVID-19 in Patients on Maintenance Hemodialysis and Medical Staff of Hemodialysis Facilities in Wuhan, China.

Kidney Dis (Basel) 2020 Jul 25;6(4):271-283. Epub 2020 May 25.

Department of Nephrology, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Introduction: Maintenance hemodialysis (MHD) patients are highly vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Medical staff of dialysis facilities without sufficient biosecurity protection are susceptible once exposed to asymptomatic coronavirus disease 2019 (COVID-19) patients. This study evaluated the epidemiological characteristics of COVID-19 in all MHD patients and medical staff of dialysis facilities in Wuhan, China.

Methods: We collected COVID-19 morbidity and mortality data from MHD patients and medical staff from 52 hemodialysis centers in Wuhan. Then, we analyzed the symptoms and signs of patients and staff in our hospital (Tongji Hospital in Wuhan), and chest CT, SARS-CoV-2 nucleic acid detection and laboratory tests were performed. After aggressive quarantine of the COVID-19 patients, we followed up on the prognosis of them.

Results: We analyzed the hemodialysis data from Wuhan and found that 10% of MHD patients and 6.0% of medical staff were suspected of COVID-19. Further detection of SARS-CoV-2 nucleic acid showed that 1.7% of MHD patients and 2.9% of medical staff were confirmed as having COVID-19. In our facility, 18.9% (46/244) of patients and 9.5% (6/63) of medical staff were suspected of COVID-19. Among them, 2.9% (7/244) of MHD patients and 4.8% (3/63) of medical staff tested positive for SARS-CoV-2 were confirmed as having COVID-19. Interestingly, 87.0% of MHD patients suspected of COVID-19 did not have obvious symptoms, but the CT screening showed features of viral pneumonia. There were no significant differences in symptoms, CT findings, comorbidity and laboratory findings of SARS-CoV-2 nucleic-acid-positive and -negative patients. We followed up these patients and found that 57 patients with COVID-19 died (COVID-19 mortality 8.9%). Two patients from our dialysis center with COVID-19 (mortality 4.3%) died. No new infections occurred in our dialysis center after aggressive quarantine was initiated.

Conclusions: The SARS-CoV-2 infection rates in MHD patients and medical staff in dialysis facilities were both high in Wuhan. Frequent chest CT and SARS-CoV-2 nucleic acid detection were needed to screen COVID-19 patients in dialysis facilities. Through the lessons of this experience on the aggressive diagnosis and quarantine measures of COVID-19 patients, we hope medical staff avoid more infections in serious epidemic areas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000508579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316663PMC
July 2020

Three infection clusters related with potential pre-symptomatic transmission of coronavirus disease (COVID-19), Shanghai, China, January to February 2020.

Euro Surveill 2020 08;25(33)

Department of Infectious Disease Control and Prevention, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.

We report three clusters related with potential pre-symptomatic transmission of coronavirus disease (COVID-19) between January and February 2020 in Shanghai, China. Investigators interviewed suspected COVID-19 cases to collect epidemiological information, including demographic characteristics, illness onset, hospital visits, close contacts, activities' trajectories between 14 days before illness onset and isolation, and exposure histories. Respiratory specimens of suspected cases were collected and tested for SARS-CoV-2 by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) assay. The interval between the onset of illness in the primary case and the last contact of the secondary case with the primary case in our report was 1 to 7 days. In Cluster 1 (five cases), illness onset in the five secondary cases was 2 to 5 days after the last contact with the primary case. In Cluster 2 (five cases) and Cluster 3 (four cases), the illness onset in secondary cases occurred prior to or on the same day as the onset in the primary cases. The study provides empirical evidence for transmission of COVID-19 during the incubation period and indicates that pre-symptomatic person-to-person transmission can occur following sufficient exposure to confirmed COVID-19 cases. The potential pre-symptomatic person-to-person transmission puts forward higher requirements for prevention and control measures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2807/1560-7917.ES.2020.25.33.2000228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441604PMC
August 2020