Publications by authors named "Bin Shen"

556 Publications

Preoperative bacteriuria positivity on urinalysis increases wound complications in primary total hip arthroplasty regardless of the urine culture result.

BMC Musculoskelet Disord 2021 Sep 29;22(1):834. Epub 2021 Sep 29.

Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, 37# Guoxue Road, Chengdu, 610041, Sichuan Province, China.

Background: Current evidence does not recommend screening urine culture and curing asymptomatic bacteriuria (ASB) before joint arthroplasty. The bacteriuria count on pre-operative urinalysis is a more common clinical parameter. We aimed to investigate whether the bacteriuria count on preoperative urinalysis can increase postoperative wound complications in primary total hip arthroplasty (THA).

Methods: We conducted a retrospective study that included patients who underwent primary THA in our institution from 2012 to 2018. We obtained preoperative urinalysis results before THA during the same hospitalization and identified patients with abnormal urinalysis. Receiver operating characteristic (ROC) curves were first generated to evaluate the predicted value of leukocyte esterase (LE), nitrite, bacteriuria, and pyuria in the urinalysis for superficial wound infection. Then, all included patients were divided into two groups according to the preoperative urinalysis: a bacteriuria-positive group and a bacteriuria-negative group. The primary outcome was the superficial wound infection rate within 3 months postoperatively, and the secondary outcomes included wound leakage, prosthetic joint infection (PJI), pulmonary infection, urinary tract infection (UTI), readmission rate within 3 months postoperatively, and length of stay (LOS) during hospitalization. We utilized univariable analyses to compare the outcomes between the two groups. A multivariable logistic regression model was generated to explore the potential association between bacteriuria and the risk of superficial wound infection, wound leakage, and readmission rate controlling for baseline values.

Results: A total of 963 patients were included in the study. One hundred sixty patients had abnormal urinalysis. The AUCs for LE, nitrite, bacteriuria, and pyuria were 0.507 (95% confidence interval (CI), 0.315 to 0.698), 0.551 (0.347 to 0.756), 0.675 (0.467 to 0.882), and 0.529 (0.331 to 0.728), respectively. Bacteriuria was diagnostically superior to LE, nitrite, and pyuria. Among the 963 patients, 95 had a positive bacteriuria on preoperative urinalysis, and only 9 (9.5%) had a positive urine culture. Compared with the bacteriuria-negative group, the bacteriuria-positive group had a higher superficial wound infection rate (4.2% vs. 0.6%, P = 0.008), higher wound leakage rate (11.6% vs. 4.5%, P = 0.007), higher readmission rate (5.3% vs. 1.3%, P = 0.015) within 3 months postoperatively and longer LOS (6.19 ± 2.89 days vs. 5.58 ± 2.14 days, P = 0.011). After adjustment, the bacteriuria-positive group had a significantly increased risk of superficial wound infection (OR = 7.587, 95%CI: 2.002 to 28.755, P = 0.003), wound leakage (OR = 3.044, 95%CI: 1.461 to 6.342, P = 0.003), and readmission (OR = 4.410, 95%CI: 1.485 to 13.097, P = 0.008).

Conclusion: Preoperative bacteriuria positivity on urinalysis significantly increased the risk of postoperative wound complications, readmission, and LOS in primary THA regardless of the result of the urine culture. Urinalysis is a fast and cost-acceptable test whose advantages have been underestimated.

Level Of Evidence: Level III, observational study.
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http://dx.doi.org/10.1186/s12891-021-04725-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480008PMC
September 2021

Measurement of the Total Lung Volume Using an Adjusted Single-Breath Helium Dilution Method in Patients With Obstructive Lung Disease.

Front Med (Lausanne) 2021 8;8:737360. Epub 2021 Sep 8.

Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.

Whole-body plethysmography (WBP) is the gold standard for measuring lung volume, but its clinical application is limited as it requires expensive equipment and is not simple to use. Studies have shown that the single-breath helium dilution (SBHD) method, which is commonly used in clinical practice, significantly underestimates lung volume in patients with obstructive lung disease (OLD). By comparing the differences in lung volume measured using SBHD and WBP, we aimed to establish a correction equation for the SBHD method to determine the total lung volume in patients with OLD of different severities. From 628 patients with OLD simultaneously subjected to SBHD and WBP, 407 patients enrolled between January 2018 and November 2019 were in the training group and 221 enrolled between December 2019 and December 2020 were in the prospective verification cohort. The multiple linear regression equation was used for data in the training group to establish a correction equation for SBHD to determine the total lung volume, and this was validated in the prospective validation cohort. There was a moderate positive correlation between total lung capacity (TLC) determined using the SBHD [TLC (SBHD)] and WBP methods [TLC (WBP)] (r = 0.701; < 0.05), and the differences between TLC (SBHD) and TLC (WBP) (ΔTLC) were related to the severity of obstruction. As the severity of obstruction increased, the TLC was underestimated by the SBHD method. We established the following correction equation: () () = -0.669 + 0.756*()() - 0.047* +0.039* ()-0.009*()(r2 = 0.753 and adjusted r2 = 0.751). Next, we validated this equation in the validation cohort. With the correction equation, no statistical difference was observed between TLC (adjusted SBHD) and TLC (WBP) among the obstruction degree groups ( > 0.05). The SBHD method is correlated with WBP to measure the total lung volume, but the SBHD method presents limitations in determining the total lung volume in patients with obstructive lung disease. Here, we established an effective and reliable correction equation in order to accurately assess the total lung volume of patients with OLD using the SBHD method.
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http://dx.doi.org/10.3389/fmed.2021.737360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455942PMC
September 2021

[Comparison of unicompartmental knee arthroplasty and total knee arthroplasty in the treatment of severe medial compartment osteoarthritis].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Sep;35(9):1125-1132

Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China.

Objective: To compare the effectiveness of unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA) in the treatment of severe medial compartment osteoarthritis (OA).

Methods: A clinical data of 69 patients (69 knees), who underwent joint replacement due to severe medial compartment OA between February 2015 and September 2018 and met the selection criteria, was retrospectively analyzed. Among them, 38 cases were treated with UKA (UKA group) and 31 cases with TKA (TKA group). There was no significant difference in gender, age, body mass index, course of disease, lesion side, and preoperative visual analogue scale (VAS) score, Hospital for Special Surgery (HSS) score, Western Ontario and McMaster University Osteoarthritis Index (WOMAC) score, Feller score, range of motion of knee, physiological and psychological scores of short-form 12 health survey scale (SF-12) between the two groups ( >0.05). The femorotibial angle (FTA) of TKA group was bigger than that of UKA group, and hip-knee-ankle angle (HKA) was smaller, showing significant differences ( <0.05). The operative time, incision length, blood loss, time for flexion 90°, ambulation time, hospital stay, and incidence of deep venous thrombosis of lower extremity were recorded and compared between the two groups. The VAS score, HSS score, WOMAC score, Feller score, range of motion, and physiological and psychological scores of SF-12 were used to evaluate patients' quality of life. FTA, HKA, and prosthesis looseness were observed by X-ray films. Kaplan-Merier survival analysis was used to evaluate the survival rate of prosthesis.

Results: All operations were successfully completed in both groups. Compared with TKA group, UKA group had shorter incision length, longer operative time, and less blood loss ( <0.05). There was no significant difference in time for flexion 90°, ambulation time, hospital stay, and the incidence of deep venous thrombosis of lower extremity between the two groups ( >0.05). The incisions in both groups healed by first intention. During follow-up, 3 patients in the UKA group and 1 patient in the TKA group developed mild anterior knee pain. Patients were followed up (30.7±9.6) months in the UKA group and (34.9±8.7) months in the TKA group, and the difference was not significant ( =-1.832, =0.071). At last follow-up, there were significant differences in the HSS score, Feller score, WOMAC score, range of motion, VAS score, and physiological and psychological scores of SF-12 between pre- and post-operation ( <0.05). The range of motion in the UKA group was bigger than that in the TKA group ( =-2.666, =0.008), and there was no significant difference in the other indexes between the two groups ( >0.05). X-ray films showed that the alignment of the two groups recovered well, and the FTA and HKA of the two groups were improved at 1 week after operation ( <0.05). No radiolucency was found around the prosthesis during follow-up, no prosthesis loosening and meniscal bearing dislocation occurred. The survival rates of the prostheses in the two groups were 100%.

Conclusion: For severe medial compartment OA, the early survival rates of the two prostheses are similar, but UKA has less traumatic, can preserve the normal structure of the knee, and the range of motion of the knee after operation is significantly better than TKA.
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http://dx.doi.org/10.7507/1002-1892.202103181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444138PMC
September 2021

The trajectories of depression symptoms and comorbidity in knee osteoarthritis subjects.

Clin Rheumatol 2021 Sep 6. Epub 2021 Sep 6.

Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, 37# Guoxue Road, Chengdu, 610041, People's Republic of China.

Background: Previous cross-sectional studies have demonstrated the high prevalence of depression and comorbidity in knee osteoarthritis (KOA), and KOA or its impact on lifestyle was seen as a potential trigger factor of depression and comorbidity. However, the exact onset and progression pattern of depression and comorbidity in KOA was still unknown.

Methods: Group-based trajectory modeling (GBTM) analysis was conducted in the 2833 subjects selected from the osteoarthritis initiative (OAI) database. Eight-year trajectories were determined and described. Baseline characteristics were investigated in multi-variable regression to detect the risk factors of the unfavored trajectory.

Results: Stable trajectory (70.4%) and worsening trajectory (29.6%) were identified in comorbidity. The risk factors for the worsening trajectory membership were the obesity (OR = 1.47 CI = [1.20, 1.79], P < 0.001), older age (OR = 1.74, CI = [1.41, 2.16], P < 0.001), and smoke (OR = 1.30, CI = [1.08, 1.57], P < 0.01) at baseline. Stable trajectory (52.0%), slow-worsening trajectory (40.5%), and fast-worsening trajectory (7.5%) were identified in depression symptoms. The risk factors for the fast-worsening trajectory membership were female (OR = 1.51 CI = [1.03, 2.20], P < 0.05), lower income (OR = 1.52, CI = [1.01, 2.27], P < 0.05), and smoke (OR = 1.30, CI = [1.08, 1.57], P < 0.01) at baseline.

Conclusion: A significant amount of KOA subjects tends to develop depression symptoms and comorbidity. Managing related risk factors, like weight loss or smoking cessation, might have considerable significance in preventing or delaying depression symptoms and comorbidity in KOA. Key Points • The first study investigating the trajectory of comorbidity progression in KOA. • Approximately 7.5% of KOA patients tend to develop depression symptoms quite rapidly, and 30% of KOA patients tend to develop comorbidity • Risk factors of worsening trajectories were identified: obesity, older age, smoking, female, and lower income.
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http://dx.doi.org/10.1007/s10067-021-05847-9DOI Listing
September 2021

Precision modeling of mitochondrial diseases in zebrafish via DdCBE-mediated mtDNA base editing.

Cell Discov 2021 Sep 3;7(1):78. Epub 2021 Sep 3.

State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.

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http://dx.doi.org/10.1038/s41421-021-00307-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417030PMC
September 2021

Identification of a prognostic 4-mRNA signature in laryngeal squamous cell carcinoma.

J Cancer 2021 3;12(19):5807-5816. Epub 2021 Aug 3.

Department of Otorhinolaryngology-head and neck surgery, Shanghai General Hospital, Shanghai, China.

Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignancy in the respiratory tract and could reduce the quality of life seriously like dyspnea, dysphonia and dysphagia. Moreover, 5-year survival rate has decreased over the past 40 years. This study was designed to identify mRNAs that related to prognosis in LSCC to enable early detection and outcome improvement. Gene expression profiles from Gene Expression Omnibus (GEO) (GSE59102, GSE84957) and The Cancer Genome Atlas (TCGA) were analyzed to identify differentially expressed genes (DEGs) with the help of bioinformatics tools. Functional enrichment analyses including Gene Ontology (GO) and pathway analysis were carried out to investigate the role of those genes and underlying molecular mechanisms in LSCC. Cox's regression analyses (univariate, LASSO and multivariate in order) were utilized to identify DEGs related with patients' overall survival and a 4-mRNA-based prognostic risk score model was established. Univariate and multivariate Cox's regression analyses were then performed on LSCC data (90 patients left) to identify independent predictors of OS, including the signature and clinicopathologic variables. The prognostic value of the gene signature was further validated and the genes were analyzed by GEPIA to get pan-cancer expression profiles. 444 differentially expressed mRNAs (250 up-regulated, 194 down-regulated) were identified based on the threshold of fold change > 2 and adjusted p value < 0.05. Univariate Cox's regression analysis showed that high risk score (HR: 3.056, 95% confidence interval [CI]: 0.135-0.649, p<0.001) and female (HR: 0.296, 95% CI: 2.020-4.624, p=0.002) were associated with relatively poor prognosis. Further multivariate Cox's regression analysis indicated that risk score and gender were independent prognostic factors (p<0.05). The risk score model could stratify patients into high- and low‑risk groups, which presents significantly differential overall survival (p= 8.252e-04). The AUCs of 1-, 3- and 5-year OS were 0.724, 0.783 and 0.818, respectively. Our study provides evidence that the four-mRNA signature could serve as a biomarker to predict prognosis in LSCC, especially in long-term.
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http://dx.doi.org/10.7150/jca.47557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408111PMC
August 2021

A Clinical PET Imaging Tracer ([F]DASA-23) to Monitor Pyruvate Kinase M2-Induced Glycolytic Reprogramming in Glioblastoma.

Clin Cancer Res 2021 Sep 2. Epub 2021 Sep 2.

Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, California.

Purpose: Pyruvate kinase M2 (PKM2) catalyzes the final step in glycolysis, a key process of cancer metabolism. PKM2 is preferentially expressed by glioblastoma (GBM) cells with minimal expression in healthy brain. We describe the development, validation, and translation of a novel PET tracer to study PKM2 in GBM. We evaluated 1-((2-fluoro-6-[F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([F]DASA-23) in cell culture, mouse models of GBM, healthy human volunteers, and patients with GBM.

Experimental Design: [F]DASA-23 was synthesized with a molar activity of 100.47 ± 29.58 GBq/μmol and radiochemical purity >95%. We performed initial testing of [F]DASA-23 in GBM cell culture and human GBM xenografts implanted orthotopically into mice. Next, we produced [F]DASA-23 under FDA oversight, and evaluated it in healthy volunteers and a pilot cohort of patients with glioma.

Results: In mouse imaging studies, [F]DASA-23 clearly delineated the U87 GBM from surrounding healthy brain tissue and had a tumor-to-brain ratio of 3.6 ± 0.5. In human volunteers, [F]DASA-23 crossed the intact blood-brain barrier and was rapidly cleared. In patients with GBM, [F]DASA-23 successfully outlined tumors visible on contrast-enhanced MRI. The uptake of [F]DASA-23 was markedly elevated in GBMs compared with normal brain, and it identified a metabolic nonresponder within 1 week of treatment initiation.

Conclusions: We developed and translated [F]DASA-23 as a new tracer that demonstrated the visualization of aberrantly expressed PKM2 for the first time in human subjects. These results warrant further clinical evaluation of [F]DASA-23 to assess its utility for imaging therapy-induced normalization of aberrant cancer metabolism.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-0544DOI Listing
September 2021

Knockdown of lncRNA SNHG15 Ameliorates Oxygen and Glucose Deprivation (OGD)-Induced Neuronal Injury via Regulating the miR-9-5p/TIPARP Axis.

Biochem Genet 2021 Aug 28. Epub 2021 Aug 28.

Jiangsu Vocational College of Medicine, No. 283 Jiefang South Road, Yancheng City, 224005, Jiangsu Province, China.

Stroke is a cerebrovascular disease with impaired nerve function. Long non-coding RNA (lncRNA) is considered to be an important regulator of various diseases. Nevertheless, the role of lncRNA small nucleolar RNA host gene 15 (SNHG15) in cerebral ischemia injury induced by stroke is still unclear. Cell-counting kit 8 assay and flow cytometry were used to detect cell viability and apoptosis, respectively. The caspase3 activity of cells was measured using Caspase3 Activity Assay Kit. Besides, the protein levels of apoptosis markers and TCCD-induced poly (ADP)-ribose polymerase (TIPARP) were determined using western blot analysis. Moreover, quantitative real-time polymerase chain reaction was employed to examine the relative expression of SNHG15 and miR-9-5p. Furthermore, dual-luciferase reporter assay was used to assess the interaction between miR-9-5p and SNHG15 or TIPARP. In addition, biotin-labeled RNA pull-down assay was performed to evaluate the interaction between miR-9-5p and SNHG15 further. Middle cerebral artery occlusion (MCAO) model was constructed to further explore the role of SNHG15 in neuronal injury in vivo. Our data showed that oxygen and glucose deprivation (OGD) could induce N-2a cell injury and enhance SNHG15 expression. Silenced SNHG15 could promote the viability and suppress the apoptosis of OGD-induced N-2a cells. Also, SNHG15 knockdown also could alleviate the neuronal injury of MCAO mice. Mechanistically, SNHG15 could sponge miR-9-5p, and miR-9-5p could target TIPARP. Further experiments revealed that miR-9-5p inhibition or TIPARP overexpression could reverse the suppressive effect of SNHG15 knockdown on OGD-induced N-2a cell injury. Our findings indicated that SNHG15 knockdown inhibited neuronal injury through the miR-9-5p/TIPARP axis, suggesting that SNHG15 might be a potential target for cerebral ischemia injury induced by stroke.
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http://dx.doi.org/10.1007/s10528-021-10121-3DOI Listing
August 2021

Correction to: Nuclear m6A reader YTHDC1 regulates the scaffold function of LINE1 RNA in mouse ESCs and early embryos.

Protein Cell 2021 Aug 25. Epub 2021 Aug 25.

Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200120, China.

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http://dx.doi.org/10.1007/s13238-021-00853-8DOI Listing
August 2021

Identification and characterization of the c-type lysozyme gene from a marine fish, Bostrychus sinensis.

Dev Comp Immunol 2021 Dec 13;125:104232. Epub 2021 Aug 13.

National Engineering Research Center of Marine Facilities Aquaculture, Zhejiang Ocean University, Zhoushan, 316004, China. Electronic address:

In this study, a c-type lysozyme gene (BsLyzC) was identified and characterized from a marine fish, Bostrychus sinensis. The BsLyzC encodes 154 amino acids and contains a signal peptide of 17 amino acids, two catalytic residues and eight cysteine residues. The genomic DNA of BsLyzC consists of four exons and three introns. The BsLyzC shares high sequence similarity with c-type lysozyme from other fish species. The qPCR assays indicated that the BsLyzC exhibited a constitutive expression pattern in eleven examined tissues of healthy B. sinensis individuals. The transcripts of BsLyzC could be significantly induced after infection of Vibrio parahemolyticus in blood, spleen and head kidney. The optimal temperature and pH for recombinant BsLyzC (rBsLyzC) were found to be 50 °C and 6.0, respectively. The rBsLyzC exhibited antibacterial activities against two Gram-positive bacteria and two Gram-negative bacteria. These results indicate that the BsLyzC is involved in the antibacterial immunity of B. sinensis.
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http://dx.doi.org/10.1016/j.dci.2021.104232DOI Listing
December 2021

Correction to: A small-molecule/cytokine combination enhances hematopoietic stem cell proliferation via inhibition of cell differentiation.

Stem Cell Res Ther 2021 Aug 17;12(1):458. Epub 2021 Aug 17.

Biopharmaceutical R&D Center, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, China.

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http://dx.doi.org/10.1186/s13287-021-02535-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369768PMC
August 2021

miR-582-5p inhibits migration and chemo-resistant capabilities of colorectal cancer cells by targeting TNKS2.

Genes Genomics 2021 Aug 6. Epub 2021 Aug 6.

Department of Hepatobiliary Surgery, Jiaxing Hospital of Traditional Chinese Medicine, No. 1501 Zhongshan East Road, Jiaxing, 314000, Zhejiang, China.

Background: Metastasis and chemo-resistance are still important factors that limit the overall efficacy of colorectal cancer treatment. Understanding the detailed molecular mechanism and identifying potential biomarkers are of great value in prognosis prediction and risk stratification.

Objective: We investigated the role of miR-582-5p in colorectal cancer pathogenesis, progression and chemo-resistance. Furthermore, we explored the underlying molecular mechanism of miR-582-5p in modulation of malignant behaviors of colorectal cancer cells.

Methods: Clinical samples and colorectal cancer cell lines were applied to explore miR-582-5p expression level and its significance on tumor cell metastasis and chemo-resistance. Transwell study and cellular survivability study were performed to explore the influences of miR-582-5p expression modulation on tumor cell chemo-resistance and invasion/migration. Dual-luciferase reporter gene assay was conducted to explore the influences of miR-582-5p on its target gene TNKS2.

Results: Colorectal cancer patients with lymph node or distal organ metastatic diseases exhibited significantly lower level of miR-582-5p. In vitro studies have indicated that miR-582-5p inhibition significantly increased migration and chemo-resistant capabilities of tumor cells. And dual-luciferase reporter gene assay demonstrated that miR-582-5p exhibited its influences on the biological behavior of tumor cells by targeting TNKS2.

Conclusions: Our study demonstrated for the first time that miR-582-5p played an important role for colorectal tumor cell metastasis and chemo-resistance. Our research also indicated that miR-582-5p and its target gene TNKS2 could be novel biomarkers for metastatic disease prediction, overall prognosis evaluation, as well as potential therapeutic target for colorectal cancer patients.
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http://dx.doi.org/10.1007/s13258-021-01141-9DOI Listing
August 2021

An Ultra-Stretchable Sensitive Hydrogel Sensor for Human Motion and Pulse Monitoring.

Micromachines (Basel) 2021 Jul 1;12(7). Epub 2021 Jul 1.

Guangdong Provincial Key Laboratory of Functional Supramolecular Coordination Materials and Applications, Guangdong Engineering & Technology Research Centre of Graphene-Like Materials and Products, College of Chemistry and Materials Science, Jinan University, Guangzhou 510632, China.

Ionic hydrogels with intrinsic conductivity and stretchability show great potential in flexible electronics. However, it remains a great challenge to achieve hydrogels with mechanical stretchability, ionic conductivity, optical transparency, and a self-healing ability at the same time. In this paper, we developed a hydroxyethylidene diphosphonic acid (HEDP) assisted poly(vinyl alcohol) (PVA) composite hydrogel to achieve high-performance stretch-sensitive sensor. Through a facile freeze-thaw strategy, the hydrogel could achieve large stretchability (up to 950% strain), good conductivity (10.88 S/m), excellent linear sensitivity (GF = 2.72, within 100% strain), high transparency, and significant self-healing ability. The PVA-HEDP hydrogel-based strain sensor is capable of monitoring various human movements from small scale (e.g., laryngeal vibration while speaking) to large scale (e.g., knee joint movement). Moreover, the multisite sensor array is capable of detecting the subtle differences between the pulse wave features from Cun, Guan and Chi positions, mimicking the three-finger palpation in Traditional Chinese Medicine. This work demonstrates that the composite hydrogel-based flexible sensor provides a promising solution for multifunctional human activities and health monitoring.
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http://dx.doi.org/10.3390/mi12070789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305011PMC
July 2021

Long non-coding RNA ZFAS1 exerts a protective role to alleviate oxygen and glucose deprivation-mediated injury in ischemic stroke cell model through targeting miR-186-5p/MCL1 axis.

Cytotechnology 2021 Aug 24;73(4):605-617. Epub 2021 Jun 24.

Jiangsu Vocational College of Medicine, Jinhua Garden, Chaosheng Road, Tinghu District, Yancheng, 224005 Jiangsu China.

In recent years, accumulating articles have revealed that long non-coding RNAs (lncRNAs) play crucial roles in ischemic stroke (IS). A previous study found that lncRNA zinc finger antisense 1 (ZFAS1) was down-regulated in IS patients compared with healthy controls. However, the precise function of ZFAS1 in IS and its associated mechanism remain unclear. Cell viability was assessed by cell counting kit-8 (CCK8) assay. Cell apoptosis was analyzed by flow cytometry. Western blot assay and quantitative real-time polymerase chain reaction (qRT-PCR) were conducted to measure protein and RNA expression. The interaction between microRNA-186-5p (miR-186-5p) and ZFAS1 or MCL1 apoptosis regulator, BCL2 family member (MCL1) was confirmed by dual-luciferase reporter assay, RNA-pull down assay and RNA immunoprecipitation (RIP) assay. IS cell model was established through exposing N2a cells to oxygen and glucose deprivation (OGD). OGD exposure restrained the viability and induced the apoptosis of N2a cells. OGD exposure down-regulated the expression of ZFAS1 and up-regulated the level of miR-186-5p in a time-dependent manner. ZFAS1 overexpression alleviated OGD-mediated injury in IS cell model. MiR-186-5p was identified as a direct target of ZFAS1, and OGD-induced injury in IS cell model was attenuated by the silence of miR-186-5p. MiR-186-5p interacted with the 3' untranslated region (3'UTR) of MCL1 messenger RNA (mRNA). ZFAS1 positively regulated MCL1 mRNA expression by sequestering miR-186-5p in N2a cells. ZFAS1 overexpression-mediated protective effects in IS cell model were partly overturned by the overexpression of miR-186-5p. MCL1 silencing partly counteracted the protective effects mediated by miR-186-5p silencing in IS cell model. In conclusion, ZFAS1 overexpression exerted a protective role in IS cell model to attenuate OGD-induced injury through targeting miR-186-5p/MCL1 axis. ZFAS1/miR-186-5p/MCL1 signaling might be a novel diagnostic marker and promising treatment target for IS patients.

Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-021-00481-4.
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http://dx.doi.org/10.1007/s10616-021-00481-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319279PMC
August 2021

Analgesic efficacy of adding the iPACK to adductor canal block in the presence or absence of periarticular local anesthetic infiltration in total knee arthroplasty.

Authors:
Min Yi Bin Shen

Reg Anesth Pain Med 2021 Aug 3. Epub 2021 Aug 3.

Department of Orthopaedic Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China

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http://dx.doi.org/10.1136/rapm-2021-102898DOI Listing
August 2021

Hippocampal subfield imaging and fractional anisotropy show parallel changes in Alzheimer's disease tau progression using simultaneous tau-PET/MRI at 3T.

Alzheimers Dement (Amst) 2021 28;13(1):e12218. Epub 2021 Jul 28.

Department of Radiology Stanford University Stanford California USA.

Introduction: Alzheimer's disease (AD) is the most common form of dementia, characterized primarily by abnormal aggregation of two proteins, tau and amyloid beta. We assessed tau pathology and white matter connectivity changes in subfields of the hippocampus simultaneously in vivo in AD.

Methods: Twenty-four subjects were scanned using simultaneous time-of-flight F-PI-2620 tau positron emission tomography/3-Tesla magnetic resonance imaging and automated segmentation.

Results: We observed extensive tau elevation in the entorhinal/perirhinal regions, intermediate tau elevation in cornu ammonis 1/subiculum, and an absence of tau elevation in the dentate gyrus, relative to controls. Diffusion tensor imaging showed parahippocampal gyral fractional anisotropy was lower in AD and mild cognitive impairment compared to controls and strongly correlated with early tau accumulation in the entorhinal and perirhinal cortices.

Discussion: This study demonstrates the potential for quantifiable patterns of F-PI2620 binding in hippocampus subfields, accompanied by diffusion and volume metrics, to be valuable markers of AD.
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http://dx.doi.org/10.1002/dad2.12218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319659PMC
July 2021

[Biomechanical research on effects of pseudo-patella baja on stress of patellofemoral joint after total knee arthroplasty].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Jul;35(7):841-846

Department of Orthopaedics, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China.

Objective: To investigate biomechanical effects of pseudo-patella baja on stress of patellofemoral joint after total knee arthroplasty (TKA) by using finite element analysis (FEA).

Methods: A series of CT and MRI of the left knee joint of two healthy volunteers and three-dimensional (3D) scanned data of TKA prosthesis were taken, and the 3D models of knee before and after TKA were established. The finite element model of pseudo-patella baja, normal patella, and alta patella after TKA were constructed by Insall-Salvafi (IS) ratio and Blackburne-Peel (BP) ratio. The load was applied along the direction of quadriceps femoris. After testing the validity of the finite element model, the high contact stress of patellofemoral joint was measured on the von Mise stress nephogram of pseudo-patella baja, normal patella, and alta patella after TKA when the knee flexion was 30°, 60°, and 90°. The average contact area was calculated according to two volunteers' data.

Results: On the finite element model of the normal patella after TKA with knee flexion 30°, 475 N pressure was applied along the direction of quadriceps femoris. The contact stress of patellofemoral joint was (1.29±0.41) MPa, which was similar to the results reported previously. The finite element model was valid. The von Mise stress nephogram showed that the stress mainly focused on the medial patellofemoral articular surface during knee flexion, and the contact point gradually moved up with the knee flexion deepened. The stress on the medial and lateral patellofemoral articular surface increased with the knee flexion deepened but decreased with the increase of patellar height. The effects of patellar height and knee flexion on the high contact stress of patellofemoral joint were similar among the finite element models after TKA based on the data of two volunteers. The high contact stress of patellofemoral joint increased with the knee flexion deepened in the same patellar height models ( <0.05), but decreased with the increase of patellar height in the same knee flexion models ( <0.05). The high contact stress of patellofemoral joint of pseudo-patella baja model was significantly higher than normal and alta patella models ( <0.05). The average contact area of patellofemoral joint of pseudo-patella baja was bigger than normal and alta patella models with the knee flexion deepened.

Conclusion: The pseudo-patella baja after TKA has an important effect on the biomechanics of patellofemoral joint. Reserving the joint line and avoiding the occurrence of pseudo-patella baja can decrease the risk of anterior knee pain, patellar arthritis, and other complications caused by the increasing of contact stress of patellofemoral joint.
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http://dx.doi.org/10.7507/1002-1892.202101166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311199PMC
July 2021

Metabolic engineering of Saccharomyces cerevisiae for enhanced production of caffeic acid.

Appl Microbiol Biotechnol 2021 Aug 20;105(14-15):5809-5819. Epub 2021 Jul 20.

Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, People's Republic of China.

As a natural phenolic acid product of plant source, caffeic acid displays diverse biological activities and acts as an important precursor for the synthesis of other valuable compounds. Limitations in chemical synthesis or plant extraction of caffeic acid trigger interest in its microbial biosynthesis. Recently, Saccharomyces cerevisiae has been reported for the biosynthesis of caffeic acid via episomal plasmid-mediated expression of pathway genes. However, the production was far from satisfactory and even relied on the addition of precursor. In this study, we first established a controllable and stable caffeic acid pathway by employing a modified GAL regulatory system to control the genome-integrated pathway genes in S. cerevisiae and realized biosynthesis of 222.7 mg/L caffeic acid. Combinatorial engineering strategies including eliminating the tyrosine-induced feedback inhibition, deleting genes involved in competing pathways, and overexpressing rate-limiting enzymes led to about 2.6-fold improvement in the caffeic acid production, reaching up to 569.0 mg/L in shake-flask cultures. To our knowledge, this is the highest ever reported titer of caffeic acid synthesized by engineered yeast. This work showed the prospect for microbial biosynthesis of caffeic acid and laid the foundation for constructing biosynthetic pathways of its derived metabolites. KEY POINTS: Genomic integration of ORgTAL, OHpaB, and HpaC for caffeic acid production in yeast. Feedback inhibition elimination and Aro10 deletion improved caffeic acid production. The highest ever reported titer (569.0 mg/L) of caffeic acid synthesized by yeast.
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http://dx.doi.org/10.1007/s00253-021-11445-1DOI Listing
August 2021

Discovery of Highly Potent and Selective IRAK1 Degraders to Probe Scaffolding Functions of IRAK1 in ABC DLBCL.

J Med Chem 2021 08 19;64(15):10878-10889. Epub 2021 Jul 19.

Discovery Sciences, Janssen (China) Research & Development, Shanghai 201210, P.R. China.

MyD88 gene mutation has been identified as one of the most prevalent driver mutations in the activated B-cell-like diffuse large B-cell lymphoma (ABC DLBCL). The published literature suggests that interleukin-1 receptor-associated kinase 1 (IRAK1) is an essential gene for ABC DLBCL harboring MyD88 mutation. Importantly, the scaffolding function of IRAK1, rather than its kinase activity, is required for tumor cell survival. Herein, we present our design, synthesis, and biological evaluation of a novel series of potent and selective IRAK1 degraders. One of the most potent compounds, (), effectively degraded cellular IRAK1 protein with a DC of 3 nM in HBL-1 cells. Furthermore, potently inhibited IRAK1 downstream signaling pathways and demonstrated strong anti-proliferative effects in ABC DLBCL cells with MyD88 mutation. This work suggests that IRAK1 degraders have the potential for treating cancers that are dependent on the IRAK1 scaffolding function.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00103DOI Listing
August 2021

Molecular Markers of MDR of Chemotherapy for HSCC: Proteomic Screening With High-Throughput Liquid Chromatography-Tandem Mass Spectrometry.

Front Oncol 2021 28;11:687320. Epub 2021 Jun 28.

Department of Otolaryngology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Background: Hypopharyngeal squamous cell cancer (HSCC) is a head and neck tumor with a poor prognosis. Chemotherapy lacks effectiveness because of multidrug resistance (MDR), which has increased toxic side effects. Thus, there is an urgent need to identify the molecular markers of MDR of chemotherapy for HSCC.

Methods: Fifty clinical samples of HSCC were derived from patients including 12 sensitive or resistant to chemotherapy drugs. Proteomic screening was performed using liquid chromatography-tandem mass spectrometry (LC-MS), which was based on data-independent acquisition. Molecular markers of MDR of chemotherapy in patients with HSCC were identified with clinical data and validated with ELISA.

Results: A total of 673 differentially expressed proteins were identified in HSCC samples, where 172 were upregulated and 501 were downregulated. A total of 183 differentially expressed proteins including 102 upregulated and 81 downregulated proteins, were identified by comparing cancer sensitive to chemotherapy with cancer resistant to chemotherapy. Clinical HSCC samples had significantly higher expression of FADD and significantly lower expression of RIPK1. Expressions of FADD and RIPK1 proteins were significantly lower in the chemotherapy-sensitive group. These expression differences were not correlated with clinical data. RIPK1 and FADD are involved in necroptosis and the signaling pathway of PRRs. Using ELISA, the low expression of RIPK1 and FADD was found in the patients sensitive to chemotherapy.

Conclusion: LC-MS proteomics is an effective method to identify the molecular markers of HSCC. FADD and RIPK1 can act as molecular markers of MDR of chemotherapy in patients with HSCC and may function through necroptosis and the PRR signaling pathway.
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http://dx.doi.org/10.3389/fonc.2021.687320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274423PMC
June 2021

A Critical Role of Nuclear m6A Reader YTHDC1 in Leukemogenesis by Regulating MCM Complex-Mediated DNA Replication.

Blood 2021 Jul 13. Epub 2021 Jul 13.

University of Florida, Gainesville, Florida, United States.

YTHDC1 has distinct functions as a nuclear N6-methyladenosine (m6A) reader in regulating RNA metabolism. Here we show that YTHDC1 is overexpressed in Acute Myeloid Leukemia (AML) and that it is required for proliferation and survival of human AML cells. Genetic deletion of Ythdc1 markedly blocks AML development and maintenance as well as self-renewal of leukemia stem cells (LSCs) in vivo in mice. We find that Ythdc1 is also required for normal hematopoiesis and hematopoietic stem/progenitor cell (HSPC) maintenance in vivo. Notably, Ythdc1 haploinsufficiency reduces self-renewal of LSCs, but not HSPCs in vivo. YTHDC1 knockdown has a strong inhibitory effect on proliferation of primary AML cells. Mechanistically, YTHDC1 regulates leukemogenesis through MCM4, which is a critical regulator of DNA replication. Our study provides the compelling evidence to show an oncogenic role and a distinct mechanism of YTHDC1 in AML.
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http://dx.doi.org/10.1182/blood.2021011707DOI Listing
July 2021

gene mutation by pair truncated sgRNA/Cas9-D10A in cynomolgus monkeys.

Zool Res 2021 Jul;42(4):469-477

Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.

Mutations of () cause early-onset Parkinson's disease (PD) with selective neurodegeneration in humans. However, current knockout mouse and pig models are unable to recapitulate the typical neurodegenerative phenotypes observed in PD patients. This suggests that generating disease models in non-human primates (NHPs) that are close to humans is essential to investigate the unique function of PINK1 in primate brains. Paired single guide RNA (sgRNA)/Cas9-D10A nickases and truncated sgRNA/Cas9, both of which can reduce off-target effects without compromising on-target editing, are two optimized strategies in the CRISPR/Cas9 system for establishing disease animal models. Here, we combined the two strategies and injected Cas9-D10A mRNA and two truncated sgRNAs into one-cell-stage cynomolgus zygotes to target the gene. We achieved precise and efficient gene editing of the target site in three newborn cynomolgus monkeys. The frame shift mutations of in mutant fibroblasts led to a reduction in mRNA. However, western blotting and immunofluorescence staining confirmed the PINK1 protein levels were comparable to that in wild-type fibroblasts. We further reprogramed mutant fibroblasts into induced pluripotent stem cells (iPSCs), which showed similar ability to differentiate into dopamine (DA) neurons. Taken together, our results showed that co-injection of Cas9-D10A nickase mRNA and sgRNA into one-cell-stage cynomolgus embryos enabled the generation of human disease models in NHPs and target editing by pair truncated sgRNA/Cas9-D10A in gene exon 2 did not impact protein expression.
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http://dx.doi.org/10.24272/j.issn.2095-8137.2021.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317192PMC
July 2021

Single-cell RNA-Seq reveals a highly coordinated transcriptional program in mouse germ cells during primordial follicle formation.

Aging Cell 2021 07 26;20(7):e13424. Epub 2021 Jun 26.

Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing, China.

The assembly of primordial follicles in mammals represents one of the most critical processes in ovarian biology. It directly affects the number of oocytes available to a female throughout her reproductive life. Premature depletion of primordial follicles contributes to the ovarian pathology primary ovarian insufficiency (POI). To delineate the developmental trajectory and regulatory mechanisms of oocytes during the process, we performed RNA-seq on single germ cells from newborn (P0.5) ovaries. Three cell clusters were classified which corresponded to three cell states (germ cell cyst, cyst breakdown, and follicle) in the newborn ovary. By Monocle analysis, a uniform trajectory of oocyte development was built with a series of genes showed dynamic changes along the pseudo-timeline. Gene Ontology term enrichment revealed a significant decrease in meiosis-related genes and a dramatic increase in oocyte-specific genes which marked the transition from a germ cell to a functional oocyte. We then established a network of regulons by using single-cell regulatory network inference and clustering (SCENIC) algorithm and identified possible candidate transcription factors that may maintain transcription programs during follicle formation. Following functional studies further revealed the differential regulation of the identified regulon Id2 and its family member Id1, on the establishment of primordial follicle pool by using siRNA knockdown and genetic modified mouse models. In summary, our study systematically reconstructed molecular cascades in oocytes and identified a series of genes and molecular pathways in follicle formation and development.
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http://dx.doi.org/10.1111/acel.13424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282241PMC
July 2021

BLZ945 derivatives for PET imaging of colony stimulating factor-1 receptors in the brain.

Nucl Med Biol 2021 Sep-Oct;100-101:44-51. Epub 2021 Jun 23.

Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University, School of Medicine, Stanford, CA, USA. Electronic address:

Background: The kinase colony stimulating factor-1 receptor (CSF-1R) has recently been identified as a novel therapeutic target for decreasing tumor associated macrophages and microglia load in cancer treatment. In glioblastoma multiforme (GBM), a high-grade cancer in the brain with extremely poor prognosis, macrophages and microglia can make up to 50% of the total tumor mass. Currently, no non-invasive methods are available for measuring CSF-1R expression in vivo. The aim of this work is to develop a PET tracer for imaging of CSF-1R receptor expression in the brain for future GBM patient selection and treatment monitoring.

Methods: BLZ945 and a derivative that potentially allows for fluorine-18 labeling were synthesized and evaluated in vitro to determine their affinity towards CSF-1R. BLZ945 was radiolabeled with carbon-11 by N-methylation of des-methyl-BLZ945 using [C]CHI. Following administration to healthy mice, metabolic stability of [C]BLZ945 in blood and brain and activity distribution were determined ex vivo. PET scanning was performed at baseline, efflux transporter blocking, and CSF-1R blocking conditions. Finally, [C]BLZ945 binding was evaluated in vitro by autoradiography on mouse brain sections.

Results: BLZ945 was the most potent compound in our series with an IC value of 6.9 ± 1.4 nM. BLZ945 was radiolabeled with carbon-11 in 20.7 ± 1.1% decay corrected radiochemical yield in a 60 min synthesis procedure with a radiochemical purity of >95% and a molar activity of 153 ± 34 GBq·μmol. Ex vivo biodistribution showed moderate brain uptake and slow wash-out, in addition to slow blood clearance. The stability of BLZ945 in blood plasma and brain was >99% at 60 min post injection. PET scanning demonstrated BLZ945 to be a substrate for efflux transporters. High brain uptake was observed, which was shown to be mostly non-specific. In accordance, in vitro autoradiography on brain sections revealed high non-specific binding.

Conclusions: [C]BLZ945, a CSF-1R PET tracer, was synthesized in high yield and purity. The tracer has high potency for the target, however, future studies are warranted to address non-specific binding and tracer efflux before BLZ945 or derivatives could be translated into humans for brain imaging.
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http://dx.doi.org/10.1016/j.nucmedbio.2021.06.005DOI Listing
June 2021

Therapeutic effect and potential mechanisms of intra-articular injections of miR-140-5p on early-stage osteoarthritis in rats.

Int Immunopharmacol 2021 Jul 28;96:107786. Epub 2021 May 28.

Orthopedic Research Institute & Department of Orthopedics, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address:

MicroRNAs (miRs) receive extensive attention in osteoarthritis (OA) pathogenesis in recent years, and our previous study confirmed that an intra-articular injection (IAJ) of miR-140-5p alleviates early-stage OA (EOA) progression in rats. This study aims to investigate the therapeutic effect and potential mechanisms of single IAJ (SIAJ) of miR-140-5p on different stage OA and multiple IAJs (MIAJ) of miR-140-5p on EOA. Firstly, the OA model was surgically induced in rats, nine were treated with IAJ of Cy5-miR-140-5p at one week after surgery, and fluorescence distribution was analyzed at different times. Then, 72 rats were treated with SIAJ of miR-140-5p at different stages or MIAJ of miR-140-5p at one week after surgery, and OA progression was evaluated macroscopically and histologically at different times. Finally, the downstream targets and underlying molecular mechanisms of miR-140-5p were predicted by bioinformatics and partially validated. As a result, the intra-articularly injected miR-140-5p entered cartilage and could be taken up by chondrocytes rapidly. IAJ(s) of miR-140-5p improved the behavioral scores, chondrocyte number, cartilage thickness, and pathological scores to varying degrees. Specifically, the earlier a SIAJ of miR-140-5p was administrated, the better the therapeutic effect; meanwhile, MIAJ of miR-140-5p exhibited a better therapeutic effect than SIAJ on EOA. Eighty-four potential target genes and mechanisms of rno-miR-140-5p were predicted, and the effect of miR-140-5p on the potential target genes VEGFA and JAG1 was experimentally validated. Collectively, IAJs of miR-140-5p effectively alleviate EOA progression by modulating multiple biological processes and pathways in rats, representing a promising therapeutic for EOA.
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http://dx.doi.org/10.1016/j.intimp.2021.107786DOI Listing
July 2021

[Research progress on finite element analysis of unicompartmental knee arthroplasty in medial knee compartmental osteoarthritis].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Jun;35(6):781-785

Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China.

Objective: To review the research progress on finite element analysis (FEA) of unicompartmental knee arthroplasty (UKA) in medial knee compartmental osteoarthritis.

Methods: The FEA research literature on the medial knee UKA at home and abroad was reviewed, and the progress on the aspects of the influences of the prosthesis arrangement and the postoperative joint line on the mechanical distribution of the knee joint, the improvement of the UKA prosthesis, and the related research of different types of prostheses were summarized.

Results: At present, scholars have conducted a large number of FEA studies on UKA in the medial knee compartmental osteoarthritis. The results of the study show that the recommended coronal alignment and the tibial slope angle of tibial component in medial fixed-bearing UKA are 0° and 5°-7°, respectively; and the coronal alignment and the tibial slope angle of tibial component in mobile-bearing UKA are 4° varus to 4° valgus and 5°-7°, respectively. The femoral component is arranged in the neutral position of the distal femur. The joint line is recommended to be the primary alignment. The anatomical UKA prosthesis can restore the biomechanical properties of the normal knee joint.

Conclusion: FEA research can clarify the best arrangement and joint line of the medial knee UKA prosthesis based on the mechanical distribution results, and guide the design of UKA prostheses that are more suitable for patients.
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http://dx.doi.org/10.7507/1002-1892.202101028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218186PMC
June 2021

Same-day discharge arthroplasty has a higher overall complications rate than fast-track arthroplasty: a systematic review and meta-analysis.

Arch Orthop Trauma Surg 2021 Jun 15. Epub 2021 Jun 15.

Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, 37# Guoxue Road, 610041, Chengdu, Sichuan, People's Republic of China.

Background: Published studies have reported many inconsistent results regarding the comparison of same-day discharge total joint arthroplasty (TJA) and inpatient TJA. More notably, many recent studies comparing same-day discharge TJA with fast-track TJA presented higher rates of complications for same-day discharge TJA, which raises concerns about the safety of same-day discharge TJA.

Methods: We systematically searched the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases up to June 2020 for studies comparing mortality, readmission, and complications in same-day discharge and inpatient total hip or knee arthroplasty. Studies that used inpatient TJA as the control could be further divided into fast-track inpatient TJA (length of stay [LOS] ≤ 2 days) and traditional inpatient TJA (no restrictions on LOS). Relative risks were pooled to compare the outcomes of the same-day discharge group and the control group.

Results: According to selection criteria and quality assessment, 14 studies including 222,766 cases were identified. There was no significant difference in the risk of mortality (RR = 1.42, CI [0.67, 3.01]) or readmission (RR = 0.93, CI [0.79, 1.10]) between same-day discharge TJA and inpatient TJA. Compared with fast-track TJA, the rate of overall complications in same-day discharge TJA was significantly higher (RR = 1.67, CI [1.45, 1.93]), while the rates of overall complications were similar between same-day discharge and traditional inpatient TJA (RR = 0.83, CI [0.67, 1.03]).

Conclusion: The overall safety of same-day discharge TJA is satisfactory; however, more complications were detected in same-day discharge TJA than that in fast-track TJA. Complications in same-day discharge TJA might be underestimated in some previous studies taking long-staying inpatient TJA as control. Being more cautious about complications is necessary in the care of same-day discharge TJA, and extensive prospective studies are needed to explore the optimized option that weighs both cost and complications.
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http://dx.doi.org/10.1007/s00402-021-03883-3DOI Listing
June 2021

Evaluation of carbon-11 labeled 5-(1-methyl-1H-pyrazol-4-yl)-N-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenyl)nicotinamide as PET tracer for imaging of CSF-1R expression in the brain.

Bioorg Med Chem 2021 Jul 30;42:116245. Epub 2021 May 30.

Stanford University, School of Medicine, Department of Radiology, Molecular Imaging Program at Stanford (MIPS), 1201 Welch Road, PS049, Stanford, CA 94305-5484, USA. Electronic address:

Pharmacological targeting of tumor associated macrophages and microglia in the tumor microenvironment is a novel therapeutic strategy in the treatment of glioblastoma multiforme. As such, the colony stimulating factor-1 receptor (CSF-1R) has been identified as a druggable target. However, no validated companion diagnostic marker for these therapies exists to date. Towards development of a CSF-1R PET tracer, a set of six compounds based on recently reported CSF-1R inhibitor 5-(1-methyl-1H-pyrazol-4-yl)-N-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenyl)nicotinamide (Compound 5) was designed, synthesized and evaluated in vitro for potency and selectivity. The highest affinity for CSF-1R was found for compound 5 (IC: 2.7 nM). Subsequent radiosynthesis of [C]5 was achieved in 2.0 ± 0.2% yield (decay corrected to start of synthesis) by carbon-11 carbon monoxide aminocarbonylation in 40 min after end of bombardment. In vitro autoradiography with [C]5 on rat brain sections demonstrated high specific binding, but also strong off-target binding. Ex vivo, only intact tracer was observed in blood plasma at 90 min post injection in healthy rats. PET scanning results demonstrated negligible brain uptake under baseline conditions and this brain uptake did not increase by blocking of efflux transporters using Tariquidar. To conclude, [C]5 was successfully synthesized and evaluated in healthy rats. However, the inability of [C]5 to cross the blood-brain-barrier excludes its use for imaging of CSF-1R expression in the brain.
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http://dx.doi.org/10.1016/j.bmc.2021.116245DOI Listing
July 2021

Cementless femoral stems with lower canal fill ratio have similar mid-term to long-term outcomes to those with adequate fill ratio in Dorr type C femurs.

Arch Orthop Trauma Surg 2021 Jun 12. Epub 2021 Jun 12.

Department of Orthopedics, Orthopedic Reseach Institute, West China Hospital, Sichuan University, 37# Guoxue Road, Chengdu, 610041, Sichuan, China.

Background: Lower canal fill ratio was reported to correlate with aseptic loosening in many studies. However, the most widely used standard of fill ratio seemed inapplicable to Dorr type C femurs. We aimed to adapt the method of measuring the fill ratio in Dorr type C femurs and compare the outcomes among patients with different fill ratios.

Methods: Twenty patients with Corail stems implanted in their Dorr type C femurs received spectrum CT to evaluate the whole-stem's fill ratio. Pearson Correlation Coefficient was calculated to assess the correlation between the fill ratio in X-ray film and spectrum CT. Then 87 THAs were involved in this study, divided into the fill ratio ≤ 80% group and the fill ratio > 80% group. Clinical and radiological outcomes were evaluated with a mean follow-up of 8.2 years.

Results: Fill ratio at 2 cm below the lesser trochanter in anterior-posterior X-ray film correlated with the whole-stem's fill ratio (r = 0.50, P = 0.02). Survival rate of stem, function scores, and radiological outcomes between the two groups showed no significant difference. In the fill ratio > 80% group, intraoperative fracture was significantly higher (19% VS 5%, P < 0.05).

Conclusion: Patients with lower fill ratios at 2 cm below the lesser trochanter did not have poorer functional scores or more subsidence, but had a lower intraoperative fracture rate. The revision rates of the two groups presented no significant difference, but this result need to be confirmed in larger cohort in the future. In Dorr type C femurs, risk of fracture and the special morphology of the femur should be noted, and high fill ratio is not the most decisive factor for stem size selecting.
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http://dx.doi.org/10.1007/s00402-021-03916-xDOI Listing
June 2021

Anisotropic c-f Hybridization in the Ferromagnetic Quantum Critical Metal CeRh_{6}Ge_{4}.

Phys Rev Lett 2021 May;126(21):216406

Center for Correlated Matter and Department of Physics, Zhejiang University, Hangzhou 310058, China.

Heavy fermion compounds exhibiting a ferromagnetic quantum critical point have attracted considerable interest. Common to two known cases, i.e., CeRh_{6}Ge_{4} and YbNi_{4}P_{2}, is that the 4f moments reside along chains with a large interchain distance, exhibiting strong magnetic anisotropy that was proposed to be vital for the ferromagnetic quantum criticality. Here, we report an angle-resolved photoemission study on CeRh_{6}Ge_{4} in which we observe sharp momentum-dependent 4f bands and clear bending of the conduction bands near the Fermi level, indicating considerable hybridization between conduction and 4f electrons. The extracted hybridization strength is anisotropic in momentum space and is obviously stronger along the Ce chain direction.The hybridized 4f bands persist up to high temperatures, and the evolution of their intensity shows clear band dependence. Our results provide spectroscopic evidence for anisotropic hybridization between conduction and 4f electrons in CeRh_{6}Ge_{4}, which could be important for understanding the electronic origin of the ferromagnetic quantum criticality.
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http://dx.doi.org/10.1103/PhysRevLett.126.216406DOI Listing
May 2021
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