Publications by authors named "Yun Cai"

263 Publications

Development and validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of voriconazole in human cerebrospinal fluid.

Anal Methods 2021 Sep 17. Epub 2021 Sep 17.

Center of Medicine Clinical Research, Department of Pharmacy, Chinese PLA General Hospital, 28 Fu Xing Road, Beijing 100853, China.

: A liquid chromatography-tandem mass spectrometry (LC-MS/MS). : For the quantification of voriconazole in human cerebrospinal fluid (CSF) was developed and validated, to guide the clinical use of voriconazole in the treatment of central nervous system infections. CSF samples were treated by protein precipitation with methanol containing fluconazole as the internal standard (IS). The supernatant was analyzed by LC-MS/MS using an Agilent EclipsePlus C18 column eluted with a methanol and water mobile phase at a flow rate of 0.4 mL min. Quantification was performed by multiple-reaction monitoring using the precursor and product ion pair 350/280.9 for voriconazole and 307/219.9 for fluconazole. s: The calibration curve was linear over the range of 0.1-10.0 μg mL ( = 0.9991). The inter-day and intra-day precisions were <4.20% and <9.97%, respectively. The recoveries for the three concentrations (0.2, 1.0, and 8.0 μg mL) were 99.96%, 107.00%, and 99.85%, and the matrix effects were 99.35%, 103.41%, and 99.64%, respectively. The stability under various conditions was also acceptable. The study also demonstrated that the CSF matrix could be replaced by plasma and artificial CSF. : A simple and accurate method for the determination of voriconazole concentrations in human CSF was developed and validated, which can be used for drug monitoring in the treatment of central nervous system infections.
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http://dx.doi.org/10.1039/d1ay01103kDOI Listing
September 2021

Genkwanin suppresses MPP-induced cytotoxicity by inhibiting TLR4/MyD88/NLRP3 inflammasome pathway in a cellular model of Parkinson's disease.

Neurotoxicology 2021 Sep 2;87:62-69. Epub 2021 Sep 2.

Department of Neurology, Affiliated Hospital of Hebei University, Baoding, 071030, China.

Parkinson's disease (PD) is a complicated multifactorial neurodegenerative disorder. Oxidative stress, neuroinflammatory response, and activation of apoptosis have been proposed to be tightly involved in the pathogenesis of PD. Genkwanin is a typical bioactive non-glycosylated flavonoid with anti-inflammatory and anti-oxidant activities. However, the effect of genkwanin on PD remains unclear. Cell viability, lactate dehydrogenase (LDH) release, caspase-3/7 activity, and apoptosis was evaluated by MTT, LDH release assay, caspase-3/7 activity assay, and TUNEL assay, respectively. The secretion of prostaglandin E (PGE), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were measured by respective commercial ELISA kits. The mRNA expression of TNF-α, IL-1β, and IL-6 was detected by qRT-PCR. The protein levels of cycloxygenase-2 (COX-2), toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and NOD-like receptor (NLR) protein: 3 (NLRP3) were determined by western blot analysis. Genkwanin at concentrations less than 40 μM had no impact on cell viability and LDH release. Genkwanin suppressed MPP-induced neuroinflammation in SH-SY5Y cells. MPP treatment inhibited cell viability, increased LDH release, apoptosis, and ROS generation, and reduced superoxide dismutase (SOD) activity in SH-SY5Y cells, which were abolished by genkwanin treatment. Genkwanin suppressed MPP-induced activation of TLR4/MyD88/NLRP3 inflammasome pathway in SH-SY5Y cells. TLR4 overexpression weakened the anti-inflammatory and anti-neurotoxicity of genkwanin in SH-SY5Y cells. In conclusion, genkwanin attenuated neuroinflammation and neurotoxicity by inhibiting TLR4/MyD88/NLRP3 inflammasome pathway in MPP-induced cellular model of PD.
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http://dx.doi.org/10.1016/j.neuro.2021.08.018DOI Listing
September 2021

Interferon-Induced Transmembrane Protein 3 Shapes an Inflamed Tumor Microenvironment and Identifies Immuno-Hot Tumors.

Front Immunol 2021 11;12:704965. Epub 2021 Aug 11.

Department of Oncology, Nantong Third People's Hospital Affiliated to Nantong University, Nantong, China.

Interferon-induced transmembrane protein 3 (IFITM3) is an interferon-induced membrane protein, which has been identified as a functional gene in multiple human cancers. The role of IFITM3 in cancer has been preliminarily summarized, but its relationship to antitumor immunity is still unclear. A pancancer analysis was conducted to investigate the expression pattern and immunological role of IFITM3 based on transcriptomic data downloaded from The Cancer Genome Atlas (TCGA) database. Next, correlations between IFITM3 and immunological features in the bladder cancer (BLCA) tumor microenvironment (TME) were assessed. In addition, the role of IFITM3 in estimating the clinical characteristics and the response to various therapies in BLCA was also evaluated. These results were next confirmed in the IMvigor210 cohort and a recruited cohort. In addition, correlations between IFITM3 and emerging immunobiomarkers, such as microbiota and N6-methyladenosine (m6A) genes, were assessed. IFITM3 was enhanced in most tumor tissues in comparison with adjacent tissues. IFITM3 was positively correlated with immunomodulators, tumor-infiltrating immune cells (TIICs), cancer immunity cycles, and inhibitory immune checkpoints. In addition, IFITM3 was associated with an inflamed phenotype and several established molecular subtypes. IFITM3 expression also predicted a notably higher response to chemotherapy, anti-EGFR therapy, and immunotherapy but a low response to anti-ERBB2, anti-ERBB4, and antiangiogenic therapy. In addition, IFITM3 was correlated with immune-related microbiota and m6A genes. In addition to BLCA, IFITM3 is expected to be a marker of high immunogenicity in most human cancers. In conclusion, IFITM3 expression can be used to identify immuno-hot tumors in most cancers, and IFITM3 may be a promising pancancer biomarker to estimate the immunological features of tumors.
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http://dx.doi.org/10.3389/fimmu.2021.704965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385493PMC
August 2021

Risk Factors and Prognosis of Carbapenem-Resistant Infections in Respiratory Intensive Care Unit: A Retrospective Study.

Infect Drug Resist 2021 19;14:3297-3305. Epub 2021 Aug 19.

Centre of Medicine Clinical Research, Department of Pharmacy, Chinese PLA General Hospital, Beijing, 100853, People's Republic of China.

Purpose: Carbapenem-resistant (CRKP) infections have become a serious threat with high morbidity and mortality. Early identification of risk factors for CRKP infections is important, but these factors are still controversial. Therefore, we aimed to identify the risk factors and clinical outcomes of CRKP infections.

Patients And Methods: The retrospective, single-center study was carried out in the respiratory intensive care unit of the Chinese People's Liberation Army General Hospital from 2017 to 2020. Patients infected with were included and categorized into the CRKP group and carbapenem-sensitive (CSKP) group based on the susceptibility to carbapenems. The independent risk factors were investigated by univariate analysis and multivariate logistic regression analysis. The clinical outcomes were also evaluated between the two groups.

Results: A total of 138 eligible patients were included in our study, with a median age of 80.5 years (interquartile range: 62.0-86.3), and 78.3% of them were males. Of the 138 patients, there were 97 patients in the CRKP group, and the other 41 were assigned into the CSKP group. Multivariate analysis showed that exposure to ≥three types of comorbidities (OR = 5.465, = 0.003), previous hospitalization (OR = 4.279, = 0.006), use of quinolones (OR = 5.872, = 0.012), and indwelling urinary catheter (OR = 5.035, = 0.000) were independent risk factors for CRKP infections. The in-hospital mortality rate of the CRKP group was 42.1%, which was higher compared with the CSKP group (17.5%, = 0.006).

Conclusion: Exposure to ≥three types of comorbidities, previous hospitalization, use of quinolones, and indwelling urinary catheter were independent risk factors for CRKP infections, which had higher mortality compared with CSKP infections. Early detection of high-risk patients and timely control measures should be implemented to prevent the emergence of CRKP infections and thereby improve the clinical outcomes.
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http://dx.doi.org/10.2147/IDR.S317233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382964PMC
August 2021

Non-carbapenem β-lactam/β-lactamase inhibitors versus carbapenems for urinary tract infections caused by extended-spectrum β-lactamase-producing Enterobacteriaceae: a systematic review.

Int J Antimicrob Agents 2021 Oct 30;58(4):106410. Epub 2021 Jul 30.

Centre of Medicine Clinical Research, Department of Pharmacy, PLA General Hospital, Beijing 100853, China. Electronic address:

This systematic review was conducted to compare the efficacy of non-carbapenem β-lactam/β-lactamase inhibitors (BLBLIs) versus carbapenems for the treatment of urinary tract infections (UTIs) caused by extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE). A comprehensive search of the Cochrane Library, PubMed and Embase was conducted from January 1979 to December 2020. Clinical success, microbiological success, clinical and microbiological success, and mortality were assessed as efficacy outcomes. Heterogeneity was assessed using the I statistic, and a fixed-effects or random-effects model was applied for estimation of the risk ratio (RR). A total of 1612 patients from three randomised clinical trials (RCTs) and seven cohort studies were included in the meta-analysis. There was no statistically significant difference between BLBLIs and carbapenems in clinical success (RR = 0.99; P = 0.71), clinical and microbiological success (RR = 0.97; P = 0.46) and mortality (RR = 0.63; P = 0.22). A slightly higher rate of microbiological success was observed in BLBLI group (RR = 1.06; P = 0.01), which was mainly attributed to the efficacy of ceftazidime/avibactam based on a single RCT. BLBLIs were not inferior to carbapenems, with higher microbiological success, indicating an effective alternative non-carbapenem option for the treatment of UTIs caused by ESBL-PE. More high-quality and large-scale RCTs are required to further validate these findings. [Trial registration: PROSPERO ID: CRD42021233706].
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http://dx.doi.org/10.1016/j.ijantimicag.2021.106410DOI Listing
October 2021

Clinical efficacy of thyroid-stimulating immunoglobulin detection for diagnosing Graves' disease and predictors of responsiveness to methimazole.

Clin Biochem 2021 Jul 28. Epub 2021 Jul 28.

Department of Endocrinology and Metabolism, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. Electronic address:

Background: As thyroid-stimulating immunoglobulins (TSI) are a sign of Graves' disease (GD), measuring TSI titers is becoming increasingly important for GD diagnosis. This study evaluated the diagnostic accuracy of a new fully automated TSI immunoassay (Immulite™ TSI assay) in GD patients and compared it to the third generation thyroid-stimulating hormone receptor antibody (TRAb) electrochemiluminescence assay (Elecsys Anti-TSHR assay). Additionally, clinical characteristics associated with responsiveness to methimazole in patients with newly diagnosed GD were preliminarily explored.

Methods: This study involved 324 subjects, comprising patients with untreated GD (GD-UT), Graves' ophthalmopathy (GO) patients, GD patients who had been treated for > 12 months (GD-T), autoimmune thyroiditis (AIT) patients, and healthy subjects (HS). The Immulite™ TSI and Elecsys Anti-TSHR assay were performed on all samples. According to their responsiveness to methimazole, the GD-UT patients were divided into rapid and slow responder groups, and their clinical characteristics were compared.

Results: A receiver operating characteristic (ROC) curve analysis of GD-UT patients showed that the optimal TSI cut-off value was 0.57 IU/L. Logistic regression revealed that age and initial FT4 and TSI levels in the middle-dose methimazole group were related to a rapid response, while the initial FT4 level, but not TSI, in the high-dose group was also associated with a rapid response.

Conclusions: The clinical diagnostic performance of the Immulite™ TSI assay for diagnosing GD was comparable to that of the Elecsys Anti-TSHR assay. The initial FT4 and TSI levels can be used as predictors of the responsiveness to methimazole in patients with newly diagnosed GD.
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http://dx.doi.org/10.1016/j.clinbiochem.2021.07.014DOI Listing
July 2021

AAV Delivery of shRNA Against TRPC6 in Mouse Hippocampus Impairs Cognitive Function.

Front Cell Dev Biol 2021 13;9:688655. Epub 2021 Jul 13.

Department of Military Cognitive Psychology, School of Psychology, Third Military Medical University (Army Medical University), Chongqing, China.

Transient Receptor Potential Canonical 6 (TRPC6) has been suggested to be involved in synapse function and contribute to hippocampal-dependent cognitive processes. Gene silencing of TRPC6 was performed by injecting adeno-associated virus (AAV) expressing TRPC6-specific shRNA (shRNA-TRPC6) into the hippocampal dentate gyrus (DG). Spatial learning, working memory and social recognition memory were impaired in the shRNA-TRPC6 treated mice compared to control mice after 4 weeks. In addition, gene ontology (GO) analysis of RNA-sequencing revealed that viral intervention of TRPC6 expression in DG resulted in the enrichment of the process of synaptic transmission and cellular compartment of synaptic structure. KEGG analysis showed PI3K-Akt signaling pathway were significantly down-regulated. Furthermore, the shRNA-TRPC6 treatment reduced dendritic spines of DG granule neurons, in terms of spine loss, the thin and mushroom types predominated. Accompanying the spine loss, the levels of PSD95, pAkt and CREB in the hippocampus were decreased in the shRNA-TRPC6 treated animals. Taken together, our results suggest that knocking down TRPC6 in the DG have a disadvantageous effect on cognitive processes.
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http://dx.doi.org/10.3389/fcell.2021.688655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313999PMC
July 2021

Sex-based clinical and immunological differences in COVID-19.

BMC Infect Dis 2021 Jul 5;21(1):647. Epub 2021 Jul 5.

Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, China.

Background: Males and females differ in their immunological responses to foreign pathogens. However, most of the current COVID-19 clinical practices and trials do not take the sex factor into consideration.

Methods: We performed a sex-based comparative analysis for the clinical outcomes, peripheral immune cells, and severe acute respiratory syndrome coronavirus (SARS-CoV-2) specific antibody levels of 1558 males and 1499 females COVID-19 patients from a single center. The lymphocyte subgroups were measured by Flow cytometry. The total antibody, Spike protein (S)-, receptor binding domain (RBD)-, and nucleoprotein (N)- specific IgM and IgG levels were measured by chemiluminescence.

Results: We found that male patients had approximately two-fold rates of ICU admission (4.7% vs. 2.7% in males and females, respectively, P = 0.005) and mortality (3% vs. 1.4%, in males and females, respectively, P = 0.004) than female patients. Survival analysis revealed that the male sex is an independent risk factor for death from COVID-19 (adjusted hazard ratio [HR] = 2.22, 95% confidence interval [CI]: 1.3-3.6, P = 0.003). The level of inflammatory cytokines in peripheral blood was higher in males during hospitalization. The renal (102/1588 [6.5%] vs. 63/1499 [4.2%], in males and females, respectively, P = 0.002) and hepatic abnormality (650/1588 [40.9%] vs. 475/1499 [31.7%], P = 0.003) were more common in male patients than in female patients. By analyzing dynamic changes of lymphocyte subsets after symptom onset, we found that the percentage of CD19+ B cells and CD4+ T cells was generally higher in female patients during the disease course of COVID-19. Notably, the protective RBD-specific IgG against SARS-CoV-2 sharply increased and reached a peak in the fourth week after symptom onset in female patients, while gradually increased and reached a peak in the seventh week after symptom onset in male patients.

Conclusions: Males had an unfavorable prognosis, higher inflammation, a lower percentage of lymphocytes, and indolent antibody responses during SARS-CoV-2 infection and recovery. Early medical intervention and close monitoring are important, especially for male COVID-19 patients.
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http://dx.doi.org/10.1186/s12879-021-06313-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256650PMC
July 2021

Therapeutic Drug Monitoring of Tigecycline in 67 Infected Patients and a Population Pharmacokinetics/Microbiological Evaluation of Study.

Front Microbiol 2021 16;12:678165. Epub 2021 Jun 16.

Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center of Chinese PLA General Hospital, Beijing, China.

Background: The widespread use of antibiotics has led to the emergence of multidrug-resistant (MDR) bacteria such as multidrug-resistant (AB). Tigecycline (TGC), as the first glycylcycline antibiotic approved by FDA, is a broad-spectrum antibiotic which remains highly effective to treat AB infections.

Objective: To confirm the TGC treatment dosage and effectiveness to treat AB infections in the Chinese population by performing therapeutic drug monitoring (TDM).

Methods: This study was performed from October 2018 through March 2019 at the PLA General Hospital. A high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was validated and employed to determine the plasma concentrations of TGC in patients with infectious diseases. The minimum inhibitory concentration (MIC) of TGC to clinically isolated AB was determined by broth microdilution method, agar dilution method, and disk diffusion method. Moreover, a model of population pharmacokinetics/pharmacodynamics (PPK/PD) was constructed.

Results: A total of 186 plasma samples from 67 patients were detected by the validated HPLC-MS/MS method. The MIC values determined by the broth microdilution method were more sensitive and accurate than the other two methods. The microbial and clinical PK/PD breakpoints were reached when the maintenance dose of TGC was 100 mg.

Conclusion: Our study established a validated HPLC-MS/MS method to monitor the plasma concentrations of TGC. In view of the MIC range to AB isolates in our hospital and the PPK/PD modeling results, we recommend a relatively high dose of 100 mg q12h regimen to achieve the optimal clinical efficacy and antimicrobial response.
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http://dx.doi.org/10.3389/fmicb.2021.678165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241901PMC
June 2021

Upregulated osteoprotegerin expression promotes lung cancer cell invasion by increasing miR-20a expression.

Exp Ther Med 2021 Aug 7;22(2):846. Epub 2021 Jun 7.

Department of Respiratory Diseases, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.

Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor superfamily and a major regulatory factor in osteoclast development. OPG has been previously associated with the malignant behavior of various types of cancer, particularly that of cancer metastasis. However, information on the link between the expression profile of OPG and lung cancer metastasis remained elusive. In the present study, the expression levels of OPG in the serum samples of patients with non-small cell lung cancer (NSCLC) was measured using ELISA. The expression of miRNAs was assessed using reverse transcription-quantitative PCR. A549 or H3122 cell invasion was assessed using Transwell invasion assays. The effect of OPG on the invasiveness of lung cancer cells was evaluated using an experimental mouse lung metastasis model. OPG expression was found to be upregulated in the serum of patients with NSCLC compared with that in healthy individuals. The serum levels of OPG in patients with distant metastasis were observably higher compared with those in patients without metastasis. Functionally, overexpression of OPG in NSCLC cells markedly promoted cell invasion. Mechanistically, increased expression of OPG resulted in upregulation of microRNA (miR)-20a in NSCLC cells. Furthermore, miR-20a promoted NSCLC cell invasion, whilst miR-20a inhibition partially abrogated the effect of OPG on NSCLC cell invasion. Taken together, the present results demonstrated that the OPG/miR-20a axis serve an important role in lung cancer metastasis, which potentially provide an additional novel target for lung cancer treatment.
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http://dx.doi.org/10.3892/etm.2021.10278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210324PMC
August 2021

Identification of a nomogram based on an 8-lncRNA signature as a novel diagnostic biomarker for childhood acute lymphoblastic leukemia.

Aging (Albany NY) 2021 06 9;13(11):15548-15568. Epub 2021 Jun 9.

Medical Research Center, The Third People's Hospital of Chengdu, The Second Chengdu Hospital Affiliated to Chongqing Medical University, Chengdu 610031, China.

Childhood acute lymphoblastic leukemia (cALL) still represents a major cause of disease-related death in children. This study aimed to explore the prognostic value of long non-coding RNAs (lncRNAs) in cALL. We downloaded lncRNA expression profiles from the TARGET and GEO databases. Univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses were applied to identify lncRNA-based signatures. We identified an eight-lncRNA signature (LINC00630, HDAC2-AS2, LINC01278, AL356599.1, AC114490.1, AL132639.3, FUT8.AS1, and TTC28.AS1), which separated the patients into two groups with significantly different overall survival rates. A nomogram based on the signature, BCR ABL1 status and white blood cell count at diagnosis was developed and showed good accuracy for predicting the 3-, 5- and 7-year survival probability of cALL patients. The C-index values of the nomogram in the training and internal validation set reached 0.8 (95% CI, 0.757 to 0.843) and 0.806 (95% CI, 0.728 to 0.884), respectively. The nomogram proposed in this study objectively and accurately predicted the prognosis of cALL. experiments suggested that LINC01278 promoted the proliferation of leukemic cells and inhibited leukemic cell apoptosis by targeting the inhibition of miR-500b-3p in cALL, and LINC01278 may be a biological target for the treatment of cALL in the future.
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http://dx.doi.org/10.18632/aging.203116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221355PMC
June 2021

Adjunctive clindamycin therapy in invasive β-haemolytic streptococcal infections.

Authors:
Huan Zhang Yun Cai

Lancet Infect Dis 2021 06;21(6):762

Centre of Medicine Clinical Research, Department of Pharmacy, PLA General Hospital, Beijing 100853, China. Electronic address:

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http://dx.doi.org/10.1016/S1473-3099(21)00198-5DOI Listing
June 2021

Analysis of the Sagittal Motion Posture of the Acromioclavicular Joint Using Image Registration and Axial Angle Representation.

Int J Gen Med 2021 20;14:1975-1981. Epub 2021 May 20.

Department of Orthopaedics, Teaching Hospital of Capital Medical University, Beijing Shijingshan Hospital, Beijing, People's Republic of China.

Objective: This study aimed to directly and accurately measure the range of motion of the acromioclavicular joint through 3D reconstruction and image registration.

Methods: Thirteen healthy volunteers participated in the study. Computerized tomography (CT) was used to measure the acromioclavicular joint in four different motion poses. The images were integrated using reconstruction and registration technology, and the rotation angle range of the acromioclavicular joint was measured using 3D reconstruction. The measurements were expressed by axial angle representation. The dominant and the non-dominant sides were compared, and the difference in the axial angle of the acromioclavicular joint was compared in different postures.

Results: The difference between the dominant and non-dominant sides in acromioclavicular motion was not significant. In the sagittal motion of the upper limb, the rotation angle of the acromioclavicular joint was greatest in a resting horizontal position, with an average of 26.1°. In this position, 34.6% of flexion and extension movements of the upper limb were completed by the acromioclavicular joint, which was the highest level of engagement. The rotation angle was lowest in the resting posteroinferior position, with an average of 8.2°. In this position, 24.9% of the flexion and extension movements of the upper limb were completed by the acromioclavicular joint.

Conclusion: Combining 3D reconstruction and image registration is a direct and accurate method of measuring the motion of the acromioclavicular joint. The rotational motions of the acromioclavicular joint are bilaterally symmetrical and can be used as a reference for comparative study. The maximum range of motion of the acromioclavicular joint during rotation was found in the resting horizontal position. The clinical examination and post-treatment evaluation of the acromioclavicular joint's rotation function can therefore be targeted in this range.
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http://dx.doi.org/10.2147/IJGM.S302938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144179PMC
May 2021

Efficacy and safety of oritavancin for the treatment of acute bacterial skin and skin-structure infections: a systematic review and meta-analysis.

J Glob Antimicrob Resist 2021 06 11;25:380-389. Epub 2021 May 11.

Centre of Medicine Clinical Research, Department of Pharmacy, PLA General Hospital, Beijing 100853, China. Electronic address:

Objectives: This study aimed to evaluate the efficacy and safety of oritavancin (ORI) versus comparators for the treatment of acute bacterial skin and skin-structure infections (ABSSSIs) based on available clinical studies.

Methods: PubMed, Cochrane Library and Embase were searched from database inception to 28 July 2020 to identify clinical studies assessing the efficacy and safety of ORI and comparator antibiotics for the treatment of ABSSSIs. Primary efficacy outcome, investigator-assessed clinical cure, lesion size reduction ≥20%, additional post-treatment antibiotics, and 30-day emergency room (ER) visits and readmission were assessed as efficacy outcomes. Adverse events (AEs) and mortality were assessed as safety outcomes. I statistic was calculated for heterogeneity, and a fixed-effects or random-effects model was used for estimation of the risk ratio (RR).

Results: A total of 9213 patients from two randomised clinical trials (RCTs) and four cohort studies were included in this meta-analysis. ORI was statistically non-inferior to control agents in all efficacy and safety outcomes. Moreover, ORI significantly reduced the occurrence of 30-day readmission (RR = 0.42; P = 0.0004) and drug-related AEs (RR = 0.78; P = 0.002). In the subgroup analysis, ORI also had a lower rate of 30-day ER visits in the outpatient setting (RR = 0.34; P < 0.00001).

Conclusion: ORI was not inferior to comparators for the treatment of ABSSSIs. Meanwhile, it showed advantages in reducing the rate of readmission and drug-related AEs. More high-quality and large-scale RCTs are required to further confirm the efficacy and safety of ORI. [Trial registration: PROSPERO ID: CRD42020201942].
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http://dx.doi.org/10.1016/j.jgar.2021.04.013DOI Listing
June 2021

Characterization of the Clinical Significance of PD-1/PD-Ls Expression and Methylation in Patients With Low-Grade Glioma.

Technol Cancer Res Treat 2021 Jan-Dec;20:15330338211011970

Department of Oncology, 261546Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, China.

Background: Immune checkpoints play crucial roles in the immune escape of cancer cells. However, the exact prognostic values of expression and methylation of programmed-death 1 (PD-1), programmed-death-ligand 1 (PD-L1) and PD-L2 in low-grade glioma (LGG) have not been well-defined yet.

Methods: A total 514 LGG samples from the Cancer Genome Atlas (TCGA) dataset containing gene expression, DNA methylation, and survival data were enrolled in our study. Besides, a total of 137 primary LGG samples from the Chinese Glioma Genome Atlas (CGGA) database were also extracted for the survival analysis of the prognostic values of PD-1/PD-Ls expression.

Results: PD-1/PD-Ls had distinct co-expression patterns in LGG tissues. The expression and methylation level of PD-1/PD-Ls seemed to be various in different LGG subtypes. Besides, overexpression and hypo-methylation of PD-1/PD-Ls were associated with worse prognosis. In addition, PD-1/PD-Ls expression was positively associated with TIICs infiltration, while their methylation was negatively associated with TIICs infiltration. Moreover, PD-1/PD-Ls and their positively correlated gene mainly participated in immune response related biological processes.

Conclusion: To conclude, overexpression and hypo-methylation of PD-1/PD-Ls predicted unfavorable prognosis in LGG patients, suggesting those patients may benefit from PD1/PD-Ls checkpoint inhibitors treatment.
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http://dx.doi.org/10.1177/15330338211011970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111557PMC
May 2021

Autoimmune thyroid disease correlates to islet autoimmunity on zinc transporter 8 autoantibody.

Endocr Connect 2021 May 19;10(5):534-542. Epub 2021 May 19.

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

Objective: The most common coexisting organ-specific autoimmune disease in patients with type 1 diabetes mellitus (T1DM) is autoimmune thyroid disease (AITD). However, there have been few clinical reports based on a large population about the prevalence of zinc transporter 8 autoantibody (ZnT8A) and other islet autoantibodies in AITD patients. We aimed to explore the presence of islet autoantibodies, ZnT8A, glutamic acid decarboxylase autoantibodies (GADA) and insulinoma-associated antigen 2 autoantibodies (IA-2A) compared with thyroid autoantibodies, thyroid peroxidase autoantibodies (TPOAb) and thyroglobulin autoantibodies (TGAb) and thyrotropin receptor autoantibodies (TRAb) in patients with Graves' disease (GD), Hashimoto's thyroiditis (HT) and T1DM patients with AITD.

Methods: Totally, 389 patients with GD, 334 patients with HT, 108 T1DM patients with AITD and 115 healthy controls (HC) were recruited in the study. Islet autoantibodies (ZnT8A, GADA and IA-2A) were detected by radioligand binding assay. Thyroid autoantibodies, TPOAb and TGAb were detected by chemiluminescence assay, and TRAb was detected by RIA.

Results: The prevalence of ZnT8A, GADA and IA-2A was higher in GD and HT patients than that of HC (ZnT8A: GD 8.48%, HT 10.8% vs HC 1.74%; GADA: GD 7.46%, HT 7.74% vs HC 0.870%; IA-2A: GD 4.88%, HT 3.59% vs HC 0%; All P < 0.05) but lower than that of T1DM subjects with AITD (ZnT8A: 42.6%; IA-2A: 44.4%; GADA: 74.1%; all P < 0.0001).

Conclusions: An increased prevalence of ZnT8A as well as GADA and IA-2A was found in both GD and HT patients, indicating that there is a potential link between thyroid autoimmunity and islet autoimmunity.
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http://dx.doi.org/10.1530/EC-20-0650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183620PMC
May 2021

Examining Barriers and Facilitators to Palliative Care Access in Rural Areas: A Scoping Review.

Am J Hosp Palliat Care 2021 Apr 28:10499091211011145. Epub 2021 Apr 28.

School of Nursing, 311308Purdue University, West Lafayette, IN, USA.

Background: Despite the growth of palliative care (PC), access to PC remains challenging for rural Americans living with chronic diseases. Given the demand and benefits of PC, a comprehensive view of PC access would inform policymakers in developing PC services in rural areas.

Objective: This scoping review aimed to understand the barriers and facilitators to PC access in rural areas from the voices of service users and service providers during the past decade.

Methods: A scoping literature review was conducted from 2010 to 2020 using MEDLINE, CINAHL, and PsychINFO databases. Results: Twenty-eight studies met inclusion criteria. Barriers to PC access in rural areas mostly arose in structural issues: (1) the inadequate knowledge and awareness of PC among both service users and providers and (2) the poorly structured PC system. Other barriers included communication gaps/challenges between providers and patients/families and cultural barriers. The facilitators mainly originated in patients/families' connectedness with local providers and with other social networks such as friends.

Conclusions: These findings highlight the need for funding support to increase provider competency, service availability and accessibility, and the public knowledge and awareness of PC in rural areas. A holistic and tailored PC model that standardizes care delivery, referral and coordination, including family caregiver support programs, can improve care access. Future practice and research are warranted to implement and evaluate innovative approaches, such as a coordinated community-based approach, to the successful integration of PC in rural communities.
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http://dx.doi.org/10.1177/10499091211011145DOI Listing
April 2021

Evaluation of the Potential Effect of Iptakalim Hydrochloride on the QT Interval in Single- and Multiple-Ascending-Dose Studies Using Concentration-QTc Analysis.

Clin Pharmacol Drug Dev 2021 Apr 14. Epub 2021 Apr 14.

Chinese People's Liberation Army General Hospital, Medicine Clinical Research Center, Beijing, China.

Cardiotoxicity has been one of the most common causes of withdrawal of drugs from the market, and prolongation of the QT interval is one of the manifestations of drug cardiotoxicity. Iptakalim hydrochloride (ITKL) is a selective ATP-sensitive potassium channel opener used to treat hypertension. It is crucial to assess the risk of cardiac repolarization of ITKL in clinical trials. This study was conducted to determine the effect of ITKL on corrected QT (QTc) interval. A randomized, double-blind, placebo-controlled single- and multidose regimen was carried out to investigate the QTc and ITKL concentration correlation. ITKL was administered at doses of 5, 10, 15, and 20 mg with single oral administration and 10 and 20 mg with multiple oral administration, along with placebo, in 83 healthy subjects. Electrocardiograms (ECGs) and blood samples were collected on a preset time schedule. A ΔΔQTcF effect above 10 milliseconds was excluded at all observed plasma levels. Among them, the highest dose was 20 mg, which is twice the therapeutic dose. We concluded that ITKL did not prolong the QT interval in healthy subjects within the therapeutic dose. Retrospectively registered: The study was registered at Chinese Clinical Trial Registry with registration number ChiCTR1800014466.
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http://dx.doi.org/10.1002/cpdd.945DOI Listing
April 2021

A New Therapeutic Candidate for Cardiovascular Diseases: Berberine.

Front Pharmacol 2021 17;12:631100. Epub 2021 Mar 17.

Laboratory of Cardiovascular Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China.

Cardiovascular diseases (CVD) are the leading cause of death in the world. However, due to the limited effectiveness and potential adverse effects of current treatments, the long-term prognosis of CVD patients is still discouraging. In recent years, several studies have found that berberine (BBR) has broad application prospects in the prevention and treatment of CVD. Due to its effectiveness and safety for gastroenteritis and diarrhea caused by bacterial infections, BBR has been widely used in China and other Asian countries since the middle of the last century. The development of pharmacology also provides evidence for the multi-targets of BBR in treating CVD. Researches on CVD, such as arrhythmia, atherosclerosis, dyslipidemia, hypertension, ischemic heart disease, myocarditis and cardiomyopathy, heart failure, etc., revealed the cardiovascular protective mechanisms of BBR. This review systematically summarizes the pharmacological research progress of BBR in the treatment of CVD in recent years, confirming that BBR is a promising therapeutic option for CVD.
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http://dx.doi.org/10.3389/fphar.2021.631100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010184PMC
March 2021

Design, reliability, and validity of a portable electronic device based on ergonomics for early screening of adolescent scoliosis.

J Orthop Translat 2021 May 9;28:83-89. Epub 2021 Mar 9.

Department of Orthopaedics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.

Background/objective: The reported incidence of scoliosis among adolescents in China differs according to screening method owing to the lack of uniformity and limitations of certain techniques. We aimed to design, develop, and validate a non-invasive, accurate, portable, fast, and automated tool that would enable the measurement and storage of data during scoliosis screening.

Methods: We designed a new portable electronic scoliosis screening device (PESSD)-for the identification of adolescent scoliosis based on ergonomics theory. The device measured the axial deflection angle of the trunk of the human body using a built-in angle sensor. Data obtained using the PESSD, a traditional scoliometer manual ruler, and X-ray measurement of the Cobb angle were compared.

Results: The PESSD exhibited more sensitive detection of small-angle scoliosis and improved repeatability compared with the scoliometer. The data obtained using the PESSD showed good correlation with Cobb angle data measured from X-ray images. All patients who were indicated to be positive for scoliosis using the PESSD were found to have clinically identifiable scoliosis from X-ray examination.

Conclusions: The PESSD may be able to achieve early detection of scoliosis in adolescents. It is non-invasive, highly precise, portable, easy to use, and offers automated data storage and traceability. This study is a pilot or preliminary validation study. With further, more in depth studies, the PESSD has excellent potential for transformation into an effective tool for use in large-scale screening programs for adolescent scoliosis in schools and communities.

The Translational Potential Of This Article: This article is about designing a new portable electronic scoliosis screening device based on ergonomics theory. Because there are currently no uniform screening methods and standards, the results in this article could facilitate the adoption of a uniform screening tool into large-scale screening programs for adolescent scoliosis in schools and communities, preliminary examination in hospitals, and self-testing at home after parent training.
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http://dx.doi.org/10.1016/j.jot.2020.10.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972962PMC
May 2021

Pharmacokinetics, Bioequivalence and Safety Evaluation of Two Ticagrelor Tablets Under Fasting and Fed Conditions in Healthy Chinese Subjects.

Drug Des Devel Ther 2021 15;15:1181-1193. Epub 2021 Mar 15.

Center of Medicine Clinical Research, Department of Pharmacy, PLA General Hospital, Beijing, 100853, People's Republic of China.

Purpose: To evaluate the pharmacokinetics (PK), bioequivalence and safety profiles of test drug and reference drug of 90 mg ticagrelor tablets and their main active metabolite AR-C124910XX under fasting and fed conditions.

Methods: This was a randomized, open-label, single-dose, two-period, two-sequence, and two-treatment crossover study. Subjects were randomized and evenly administered with a single dose of test drug or reference drug of 90 mg ticagrelor tablets orally under fasting or fed conditions with a 7-day washout period. The primary PK parameters were calculated with non-compartmental model, including peak concentration (C), area under the curve (AUC) from zero to last quantifiable concentration (AUC), and AUC from zero to infinity (AUC). Bioequivalence was judged by whether the 90% confidence intervals (CIs) of the geometric mean ratio (GMR) of the test/reference drugs were within the predefined range of 80-125%. Adverse events (AEs) were assessed as safety endpoints.

Results: Eighty healthy Chinese subjects (fasting condition: n=40; fed condition: n=40) were enrolled, but two withdrew for personal reasons. As for PK parameters, there was no statistical difference (P>0.05) between the test and reference drugs under both conditions. As for bioequivalence, the 90% CIs of GMR for C AUC and AUC all fell within 80%-125% regardless of food intake or not. No severe adverse events were observed in the study. Chinese clinical trial registration number is ChiCTR1800015091 (http://www.chictr.org.cn).

Conclusion: Our results demonstrated that the test drug and the reference drug of ticagrelor tablets were bioequivalent. The PK and safety profiles were also similar regardless of food intake or not in healthy Chinese subjects.
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http://dx.doi.org/10.2147/DDDT.S297918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979338PMC
March 2021

Genome Mining Discovery of a C-Alkylated Dihydroisocoumarin Pathway in Fungi.

Authors:
Yun Cai Li Rao Yi Zou

Org Lett 2021 03 10;23(6):2337-2341. Epub 2021 Mar 10.

College of Pharmaceutical Sciences, Medical Research Institute, Southwest University, Chongqing 400715, China.

A fungal C-alkylated dihydroisocoumarin pathway was discovered and elucidated. This pathway includes the following (1) a nonreducing polyketide synthase and a P450 collaboratively synthesize hydroxylated C-methylated isocoumarin ; (2) a methyltransferase methylates to ; and (3) importantly, an esterase specifically catalyzes a ring reconstruction process of to C-alkylated dihydroisocoumarin . Our discovery fills the gap in the enzymatic transformation process of natural C-alkylated isocoumarin derivates.
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http://dx.doi.org/10.1021/acs.orglett.1c00458DOI Listing
March 2021

Evaluation of bioequivalence of two flurbiprofen axetil injections: A randomized, open-label, double-cycle, and crossover study.

Clin Exp Pharmacol Physiol 2021 05 20;48(5):660-667. Epub 2021 Feb 20.

Department of Pharmacy, Center of Medicine Clinical Research, Chinese PLA General Hospital, Beijing, China.

Flurbiprofen is a non-steroidal anti-inflammatory drug. We evaluated the bioequivalence of a new formulation of flurbiprofen axetil for injection and the reference drug ROPION (another kind of flurbiprofen axetil injection marketed for use) in healthy Chinese subjects. This is a single-centre, randomized, open-label, single-dose, two period crossover bioequivalence study. Each subject received a single intravenous injection at the dose of 50 mg under fasting. The drug was dissolved in 100 mL normal saline, and the injection was completed in 15 minutes. There was a 7-day washout period between the two administrations. The plasma concentrations of flurbiprofen were measured by LC-MS/MS, and descriptive statistics were used to describe the safety outcomes including adverse events (AEs) and adverse drug reactions (ADRs). Twenty-four subjects were enrolled in this study. Mean values of primary PK parameters (T , C , AUC , AUC , λ , T ) were similar (P > 0.05). T for both products is 0.3 hours. The 90% confidence intervals (CIs) for peak concentration C ranged between 96.87% and 100.42%, and the area under curve AUC and AUC ranged between 99.09% and 104.29% and 98.97% and 104.29%, respectively. The 90% CIs for the geometric means and ratios of primary PK endpoints of flurbiprofen axetil injection to reference drug ranged between 98.97% and 104.29%. The adverse event rate of the test product was 8.3% and no serious adverse events (SAE) occurred in this clinical study. We concluded that the test product and the reference drug were bioequivalent and the safety was high in healthy Chinese subjects.
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http://dx.doi.org/10.1111/1440-1681.13479DOI Listing
May 2021

Immunomodulatory Effect of Colistin and its Protective Role in Rats with Methicillin-Resistant induced Pneumonia.

Front Pharmacol 2020 20;11:602054. Epub 2021 Jan 20.

Department of Pharmacy, Center of Medicine Clinical Research, Medical Supplies Center of PLA General Hospital, Beijing, China.

Colistin is the last resort of antimicrobials against multi-drug resistant Gram-negative pathogens. Previous studies in and macrophages of rats have suggested that colistin possesses the immunomodulatory properties by acting p38/MAPK pathway. Here, we aimed to confirm the immunomodulatory role of colistin in animal models. Rat model of Methicillin-resistant (MRSA)-induced pneumonia was established. Plasma concentrations of proinflammatory cytokines, quantitative bacteriology, histology and immunohistochemistry of lungs were assessed to compare the immunomodulatory properties of colistin pre-administration. The numbers of white blood cells and granulocytes were significantly increased in the 9 mg/kg colistin pre-administration group at 72 h after infection. Levels of TNF-α, IL-6 and IL-1β in plasma after colistin pre-administration were lower compared with the infected group without treatment. Colistin pre-treatment resulted in lower bacterial counts, a dramatic decrease of cytokines and improved histopathological injury in infected lung tissues compared with the untreated animals. However, p38/MAPK inhibitor SB203580 did not fully block the above-mentioned effects caused by colistin. Pre-administration of colistin could attenuate an excessive inflammatory reaction and protect the lungs from MRSA-associated damages. However, these effects could not be reversed by blocking the p38/MAPK pathway alone. Collectively, the mechanism underlying the immunoregulatory effects of colistin in mammals needs to be further explored.
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http://dx.doi.org/10.3389/fphar.2020.602054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854386PMC
January 2021

Novel Beta-Lactam/Beta-Lactamase Plus Metronidazole vs Carbapenem for Complicated Intra-abdominal Infections: A Meta-analysis of Randomized Controlled Trials.

Open Forum Infect Dis 2021 Jan 8;8(1):ofaa591. Epub 2020 Dec 8.

Center of Medicine Clinical Research, Department of Pharmacy, PLA General Hospital, Beijing, People's Republic of China.

Background: Complicated intra-abdominal infections (cIAIs) remain a leading cause of death in surgical wards, in which antibiotic treatment is crucial. We aimed to compare the efficacy and safety of novel β-lactam/β-lactamase inhibitors (BL/BLIs) in combination with metronidazole and carbapenems in the treatment of cIAIs.

Methods: A comprehensive search of randomized controlled trials (RCTs) was performed using Medline, Embase, and Cochrane Library, which compared the efficacy and safety of novel BL/BLIs and carbapenems for the treatment of cIAIs.

Results: Six RCTs consisting of 2254 patients were included. The meta-analysis showed that novel BL/BLIs in combination with metronidazole had a lower clinical success rate (risk difference [RD], -0.05; 95% CI, -0.07 to -0.02;  = 0%) and a lower microbiological success rate (RD, -0.04; 95% CI, -0.08 to -0.00;  = 0%). No difference was found between the 2 groups in incidence of adverse events (RD, 0.02; 95% CI, -0.01 to 0.06;  = 0%), serious adverse events (SAEs; RD, 0.01; 95% CI, -0.02 to 0.03;  = 0%), or mortality (RD, 0.01; 95% CI, -0.00 to 0.02). However, ceftazidime/avibactam had a higher risk of vomiting (RD, 0.03; 95% CI, 0.01 to 0.05;  = 47%), and the ceftolozane/tazobactam subgroup showed a higher incidence of SAEs (RD, 0.12; 95% CI, 0.01 to 0.03).

Conclusions: The efficacy of novel BL/BLIs in combination with metronidazole was not as high as that of carbapenems. Although no significant differences were found with respect to overall adverse events, SAEs, or mortality, the novel BL/BLIs has a higher risk of vomiting. We still need to be cautious about the clinical application of a new anti-infective combination.

Trial Registration: PROSPERO ID: 42020166061.
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http://dx.doi.org/10.1093/ofid/ofaa591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813193PMC
January 2021

Bimodal Stimulation in Children With Bilateral Profound Sensorineural Hearing Loss: A Suitable Intervention Model for Children at the Early Developmental Stage.

Otol Neurotol 2020 12;41(10):1357-1362

Department of Otolaryngology-Head and Neck Surgery, Ninth People's Hospital.

Objective: To evaluate the auditory and speech benefit of bimodal stimulation for prelingual deafened cochlear implantation recipients.

Study Design: Retrospective and comparative study.

Setting: Tertiary referral center.

Patients: Fifty-six children with bilateral prelingual profound sensorineural hearing loss were enrolled, including 28 consecutive children with unilateral cochlear implantation (CI group), and 28 consecutive children with bimodal stimulation (BI group) who used an additional hearing aid (HA) in the contralateral ear.

Main Outcome Measures: Hearing assessments included the Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) and Categories of Auditory Performance (CAP). Speech evaluations included the Meaningful Use of Speech Scale (MUSS), and Speech Intelligibility Rating (SIR). These measurements were evaluated at the first mapping of cochlear implants and 0.5, 1, 3, 6, 12, 18, 24 months after. Data were analyzed by repeated measures analysis.

Results: The mean ages of BI and CI groups were similar (17.6 ± 6.87 vs 19.0 ± 8.10 months, p = 0.497). The initial scores for hearing and speech assessments showed no differences between the two groups, apart from IT-MAIS (2.46 ± 0.631 in BI group vs 0.50 ± 0.279 in CI group, p = 0.004). The auditory and speech development over time were different in the two groups as seen in IT-MAIS (p < 0.001), CAP (p = 0.029), MUSS (p < 0.001), and SIR (p < 0.001). A continuing but stable difference was observed in CAP, MUSS, and SIR at 3, 18, and 12 months after the first mapping, respectively. In addition, the BI group had better IT-MAIS scores at 3 and 6 months compared with the CI group; however, the difference was not significant after 12 months.

Conclusion: Bimodal stimulation is beneficial for prelingually deafened CI recipients who have minimal contralateral residual hearing when bilateral CIs are not available. Hearing aid use in the contralateral ear might be recommended for children after unilateral cochlear implantation to facilitate the development of auditory and speech skills.
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http://dx.doi.org/10.1097/MAO.0000000000002812DOI Listing
December 2020

Minimizing salinity accumulation via regulating draw solute concentration in a bioelectrochemically assisted osmotic membrane bioreactor.

Chemosphere 2021 Jun 11;272:129613. Epub 2021 Jan 11.

School of Environment, Nanjing Normal University, Wenyuan Road 1, Nanjing, 210023, China. Electronic address:

A suitable draw solute (DS) concentration in bioelectrochemically assisted osmotic membrane bioreactor (BEA-OMBR) can convert the "negative effect" of salinity accumulation into a "beneficial effect" by using the reverse-fluxed DS as a buffer agent or a carbon source supplement. Herein, the effect of DS concentration from acid buffer solution (i.e., ammonium chloride, NHCl), alkaline buffer solution (i.e., sodium bicarbonate, NaHCO), and organic solution (i.e., sodium acetate, NaOAc) on salinity accumulation was systematically investigated. Salinity accumulation with NaHCO DS mainly derived from reversal fluxed sodium ion (Na, major contributor with DS concentration ≤0.25 M) and bicarbonate ion (main contributor with DS concentration ≥0.50 M): Na accumulation could be mitigated by Na transport dominant by electrically driven migration (i.e., 21.3-62.1% of reverse-fluxed Na), and bicarbonate accumulation could be reduced by buffer system. A medium-low concentration of 0.25 M NHCl DS had a better performance on current density of 165.0 ± 23.0 A m and COD removal efficiency of 91.5 ± 3.4% by taking advantage that 77.7 ± 1.3% of reverse-fluxed ammonium could be removed by biological treatment and ammonium transport. A high NaOAc DS concentration (i.e., ≥0.05 M) exhibited a higher current density of 145.3-146.0 A m but a lower COD removal efficiency due to the limited carbon source utilization capacity of anaerobic bacteria. Both concentration diffusion (20.9-28.3%) and electrically driven migration (29.5-39.4%) promoted reverse-fluxed Na transport to catholyte and thus mitigated Na accumulation in the feed/anolyte. These findings have provided an optimal DS concentration for BEA-OMBR operation and thus encourage its further development.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129613DOI Listing
June 2021

Formation of disinfection by-products during sodium hypochlorite cleaning of fouled membranes from membrane bioreactors.

Front Environ Sci Eng 2021 10;15(5):102. Epub 2021 Jan 10.

Shandong Key Laboratory of Water Pollution Control and Resource Reuse, School of Environmental Science and Engineering, Shandong University, Qingdao, 266237 China.

Periodic chemical cleaning with sodium hypochlorite (NaClO) is essential to restore the membrane permeability in a membrane bioreactor (MBR). However, the chlorination of membrane foulants results in the formation of disinfection by-products (DBPs), which will cause the deterioration of the MBR effluent and increase the antibiotic resistance in bacteria in the MBR tank. In this study, the formation of 14 DBPs during chemical cleaning offouled MBR membrane modules was investigated. Together with the effects of biofilm extracellular polymeric substances (EPS), influences of reaction time, NaClO dosage, initial pH, and cleaning temperature on the DBP formation were investigated. Haloacetic acids (HAAs) and trichloromethane (TCM), composed over 90% of the DBPs, were increasingly accumulated as the NaClO cleaning time extended. By increasing the chlorine dosage, temperature, and pH, the yield of TCM and dichloroacetic acid (DCAA) was increased by up to a factor of 1-14, whereas the yields of haloacetonitriles (HANs) and haloketones (HKs) were decreased. Either decreasing in the chlorine dosage and cleaning temperature or adjusting the pH of cleaning reagents toward acidic or alkaline could effectively reduce the toxic risks caused by DBPs. After the EPS extraction pretreatment, the formation of DBPs was accelerated in the first 12 h due to the damage of biofilm structure. Confocal laser scanning microscopy (CLSM) images showed that EPS, particularly polysaccharides, were highly resistant to chlorine and might be able to protect the cells exposed to chlorination.

Electronic Supplementary Material: Supplementary material is available in the online version of this article at 10.1007/s11783-021-1389-3 and is accessible for authorized users.
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http://dx.doi.org/10.1007/s11783-021-1389-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797181PMC
January 2021

Image registration analysis of the motion characteristics of sternoclavicular joints in sagittal motion of the upper limbs.

Technol Health Care 2021 ;29(5):1011-1019

Department of Orthopaedics, Beijing Shijingshan Hospital, Teaching Hospital of Capital Medical University, Beijing, China.

Objective: This study aims to accurately measure the range of motion of the sternoclavicular (SC) joint using 3D reconstruction and image registration. The motion of the SC joint is analyzed by means of axial angle representation to identify the kinematical characteristics of this joint.

Methods: A total of 13 healthy volunteers were enrolled in the study. The limit postures of four SC joint movements were scanned by computerized tomography. The images were integrated with reconstruction and registration techniques. The range of motion of the SC joint was measured using 3D modelling. The axial angle was used to indicate the range of motion of the SC joint. The difference between the dominant side and non-dominant side was compared and the differences in axial angle of the SC joint in different postures were compared.

Results: The active axial angle of the SC joint on the dominant side was approximately 1∘ higher than that of the non-dominant side when the upper limb moved from a rest position to a posteroinferior position. In the sagittal motion of the upper limbs, the axial angle of the SC joint was greatest when moving from a horizontal position to a posterosuperior position, with an average of 23.55∘. Of the flexion and extension movements of the upper limbs from a rest position to a horizontal position, 13.66% (the smallest proportion) were completed by the SC joint.

Conclusion: The combination of 3D reconstruction and image registration is a direct and accurate method of measuring the motion of the SC joint. Axial angle representation is an intuitive method of expressing rotation in a 3D space that allows for more convenient comparison; it is also more in line with the characteristics of human anatomy and kinesiology and therefore more accurately reflects the characteristics of joint motion. It is therefore useful for guiding clinical practice. In a physical examination, the extension of the upper limb from the horizontal position to the posterosuperior position and from the rest position to the posteroinferior position can best reflect the rotation function of the SC joint in the combined motion of shoulder joints.
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http://dx.doi.org/10.3233/THC-202675DOI Listing
September 2021

Partial deficiency of HIF-1α in chondrocytes effected bone repair of mandibular condylar neck.

Arch Oral Biol 2021 Feb 8;122:105023. Epub 2020 Dec 8.

Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China. Electronic address:

Objectives: This study aimed to explore the expression of hypoxia-inducible factor 1α (HIF-1α) in chondrocytes with the healing process after unilateral mandibular condylar neck osteotomy and to verify its effect on bone repair.

Methods: Models of mandibular condylar neck osteotomy were established in mice. Transgenic mice with heterozygous deficiency in HIF-1α gene in chondrocytes were used. Radiographic evaluation, quantitative reverse transcription polymerase chain reaction and histomorphometric analyses were used to compare the difference in capacities of chondrogenesis, vasifaction, osteogenesis, and bone resorption.

Results: HIF-1α was expressed in the chondrocytes of calluses. Decreased expression of HIF-1α in chondrocytes promoted the proliferation of chondrocytes and upregulated the expression of apoptosis markers. However, the density and thickness of newly formed trabecula in transgenic mice were reduced on post-osteotomy day 28, and some expression of angiogenic, osteogenic, and osteoclastogenic markers was impaired.

Conclusions: These results demonstrated the importance of HIF-1α to chondrocytes and bone repair during the healing process after osteotomy of the mandibular condylar neck. Decreased HIF-1α promoted the chondrocyte proliferation, and effected endochondral ossification.
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http://dx.doi.org/10.1016/j.archoralbio.2020.105023DOI Listing
February 2021
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