Publications by authors named "Shanshan Xu"

172 Publications

Red blood cell distribution width and tumor necrosis factor-α for the early prediction of coronary artery lesion in Kawasaki disease: a retrospective study.

Eur J Pediatr 2021 Sep 7. Epub 2021 Sep 7.

Department of Infectious, Xinhua Hospital Affiliated to Shanghai Jiaotong University Medical College, No. 1665 Kongjiang Road, Shanghai, 200092, China.

We aimed to identify novel risk factors for the early prediction of coronary artery lesion (CAL) in children with Kawasaki disease (KD). We retrospectively analyzed data from hospitalized children newly diagnosed with KD between January 1, 2018, and December 31, 2020, with the following inclusion criteria: (1) diagnosis of KD, (2) first onset of CAL after admission, (3) with complete clinical records. Demographic and laboratory data were collected and analyzed. The independent risk factors of KD combined with CAL were identified by multivariate logistic regression analysis, followed by receiver operating characteristic (ROC) curve analysis to calculate the efficacy of identified risk factors in predicting KD combined with CAL. Among 241 initially recruited patients, 226 were eligible to be included in the study. Based on echocardiographic indications of CAL, 104 patients (46%) were assigned to the CAL (KD-CAL) group and 122 (54%) patients were assigned to the non-CAL (KD-nCAL) group. The levels of red blood cell count, red blood cell distribution width (RDW), C-reactive protein, tumor necrosis factor-α (TNF-α), and interleukin-6 were significantly higher in the KD-CAL group than those in the KD-nCAL group (all p < 0.05). RDW and TNF-α were found as independent risk factors of CAL occurrence. The sensitivity and specificity of RDW, TNF-α, and RDW + TNF-α in predicting KD with CAL were 67.31% and 79.51%, 74.04% and 73.77%, and 79.81% and 80.33%, respectively.Conclusion: In conclusion, alterations in RDW and TNF-α levels can be used as novel biomarkers for early prediction of CAL in KD patients, although the differences in their absolute values were small and might not give any added value to echocardiography. What is Known: •Known risk factors of CAL in children with KD include male gender and delayed use of intravenous immune globulin. What is New: •Our current study identified that red blood cell distribution width (RDW) and tumor necrosis factor-α (TNF-α) are novel independent risk factors for predicting CAL combined with KD among patients. •The combination of these RDW and TNF-α together shows higher sensitivity and specificity than either one used alone.
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http://dx.doi.org/10.1007/s00431-021-04252-3DOI Listing
September 2021

A risk-scoring predictive model for synchronous multiple early gastric cancers or gastric dysplasia before initial endoscopic resection.

J Dig Dis 2021 Sep 4. Epub 2021 Sep 4.

School of Medicine, Nankai University, Nankai University, Tianjin, China.

Aims: To establish a novel and easy-to-use risk-scoring predictive model to help endoscopists identify high-risk patients with synchronous multiple gastric neoplasms (SMGNs), including early gastric cancer (EGC) and gastric dysplasia (GD), before initial endoscopic resection (ER).

Methods: We retrospectively enrolled 1361 patients with EGC or GD who underwent ER from November 2006 to September 2019. All patients were randomly divided into the training (n = 681) or validation cohorts (n = 680). In the training phase, a prediction score was constructed to assess the independent predictors of SMGNs based on multivariable logistic regression analysis. The performance of the prediction model was evaluated using the receiver operating characteristic (ROC) curve and the Hosmer-Lemeshow test.

Results: Of the 1361 patients, 122 (9.0%) had SMGNs. Three predictors for SMGNs were scored and weighted, as follows: elderly male (≥ 65 y, 3 points); family history of gastric cancer (2 points); and surface redness (2 points). Accordingly, patients were divided into the low- (risk score, 0-3 points) or high-risk groups (risk score, 4-7 points). In the validation cohort, the incidence of SMGNs in the low-risk and high-risk groups were 6.1% and 32.0%, respectively (P < 0.001). Our risk-scoring predictive model had good discrimination (the area under the ROC curve, 0.719; 95% confidence interval, 0.634-0.794, P < 0.001) and calibration ability (Hosmer-Lemeshow, χ = 6.539, P = 0.587) in the validation group CONCLUSIONS: This risk-scoring model demonstrated good performance in predicting SMGNs before the initial ER. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/1751-2980.13050DOI Listing
September 2021

Monitoring temporal trends of dioxins, organochlorine pesticides and chlorinated paraffins in pooled serum samples collected from Northern Norwegian women: The MISA cohort study.

Environ Res 2021 Aug 30:111980. Epub 2021 Aug 30.

Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, 7491, Norway; Department of General Hygiene I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, 119992, Russia. Electronic address:

The ubiquitous presence of legacy and emerging persistent organic pollutants (POPs) in the environmental matrices poses a potential hazard to the humans and creating public health concerns. The present study aimed to evaluate dioxins, dioxin-like polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs) and chlorinated paraffins (CPs) concentrations in serum of women (postpartum, pregnant and non-pregnant) from Northern Norway to better understand their exposure and contamination status as well as temporal trends across 2007-2009 (MISA 1) to 2019 (MISA 2). Sixty-two blood samples from the MISA 1 cohort and 38 samples from MISA 2 were randomly selected in this study (n = 100). Ninety samples from postpartum (MISA 1) and pregnant women (MISA 2) were randomly combined into 9 pools, with 9-11 individual samples contributing to each pool keeping the groups of pregnant and postpartum women. Remaining 10 samples from non-pregnant women (MISA 2) were allocated into separate group. Geometric mean, minimum and maximum were used to describe the serum concentrations of pooled POPs in MISA cohort. Mann-Whitney U test and independent sample t-test were applied for trend analysis of blood levels of POPs between MISA 1 and MISA 2. We found the serum concentrations of selected POPs in this study to be at lower range. Serum concentrations of dibenzo-p-dioxins (PCDDs) (p = 0.010), polychlorinated dibenzofurans (PCDFs) (p = 0.002), dioxins-like PCBs (p = 0.001), hexachlorobenzene (HCB) (p < 0.001) and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) (p = 0.002) were decreased between the studied time. In contrast, the serum concentrations of medium chain chlorinated paraffins showed an increasing trend between 2007 and 2009 and 2019 (p = 0.019). Our findings report a particular concern of emerging contaminant medium chain chlorinated paraffin exposure to humans. Future observational studies with repeated measurements of chlorinated paraffins in general populations worldwide and large sample size are warranted.
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http://dx.doi.org/10.1016/j.envres.2021.111980DOI Listing
August 2021

Quality chemical analysis of crush-tear-curl (CTC) black tea from different geographical regions based on UHPLC-Orbitrap-MS.

J Food Sci 2021 Sep 13;86(9):3909-3925. Epub 2021 Aug 13.

State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, Hefei, Anhui, China.

Crush-tear-curl (CTC) black tea is a popular beverage, owing to its unique taste characteristics and health benefits. However, differences in the taste quality and chemical profiles of CTC black tea from different geographical regions remain unclear. In this study, 28 CTC black tea samples were collected from six geographical regions and analyzed using electronic tongue and ultrahigh performance liquid chromatography-Orbitrap-mass spectroscopy. The e-tongue analysis indicated that each region's CTC black tea has its own relatively prominent taste characteristics: Sri Lanka (more umami and astringent), North India (more umami), China (more sweetness and astringent), South India (moderate umami and sweetness), and Kenya (moderate umami and astringent). Based on multivariate statistical analysis, 78 metabolites were tentatively identified and used as potential markers for CTC black tea of different origins, mainly including amino acids, flavone/flavonol glycosides, and pigments. Different metabolites, which contributed to the taste characteristics of CTC black tea, were clarified by partial least squares regression correlation analysis. Our findings may serve as useful references for future studies on origin traceability and quality characteristic determination of CTC black teas. PRACTICAL APPLICATION: This study provides useful references for future studies on the origin traceability and taste characteristic determination of CTC black teas from different geographical regions.
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http://dx.doi.org/10.1111/1750-3841.15871DOI Listing
September 2021

Effect of Exercise on Fatigue in Multiple Sclerosis Patients: A Network Meta-analysis.

Int J Sports Med 2021 Aug 10. Epub 2021 Aug 10.

Department of Epidemiology and Biostatistics, Anhui Medical University, Hefei, Anhui, China.

Few studies have directly compared the effects of different exercise therapies on reducing fatigue in patients with multiple sclerosis. Thus, we conducted a Frequentist network meta-analysis to analyze and compare the effectiveness of different types of exercise on reducing multiple sclerosis-related fatigue. Relevant randomized controlled trials were searched in PubMed, Web of Science and Cochrane Library databases from the date of their inception up to April 1, 2021. In total, 27 articles involving 1470 participants and 10 types of interventions met the inclusion criteria. The results indicated that aquatic exercise ranked as the most effective among these interventions, and aerobic exercise had small-to-moderate effect sizes. Most of the interventions were shown to be better than the control group, except for climbing. Climbing was the only intervention that ranked worse than the controls. All of these findings merit further investigation in future clinical trials.
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http://dx.doi.org/10.1055/a-1524-1935DOI Listing
August 2021

Long-term low-dose oxytetracycline potentially leads to neurobehavioural changes.

Ecotoxicol Environ Saf 2021 Oct 27;223:112546. Epub 2021 Jul 27.

Department of Infectious Disease, Xinhua Children's Hospital, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. Electronic address:

Trace levels of oxytetracycline (OTC)-a veterinary antibiotic and feed additive-are widespread in the environment. Studies revealed that OTC potentially impairs thyroid function, which may affect neurobehaviour; however, the impact of exposure to environmental concentrations of OTC on adult neurobehaviour is unknown. In this study, the effects of OTC on zebrafish after 30-day exposure were investigated. The total swimming distance was significantly increased under vibration and light/dark stimulation, while time spent in the white area was prolonged during the black/white preference test, indicating that the zebrafish became bolder and more impulsive under low OTC exposure. Additionally, monoamine neurotransmitter (5-hydroxytryptamine, dopamine, norepinephrine) levels were decreased and gene expression of monoamine oxidase (mao) involved in neurotransmitter metabolism was upregulated at the transcription level after OTC exposure. Because triiodothyronine (T3) levels were enhanced following exposure to OTC, we speculated that T3 may mediate OTC damage to the nervous system. Our simulated molecular docking analysis showed that OTC combined with the sodium iodide cotransporter protein may result in excessive T3 synthesis. We further exposed zebrafish to T3, and they exhibited similar behaviour to the OTC exposure group. In conclusion, environmental OTC may activate monoamine oxidase and enhance the metabolism of monoaminergic neurotransmitters via T3, thereby inducing abnormal neurobehaviour.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112546DOI Listing
October 2021

Association of FOXO3a gene polymorphisms and ankylosing spondylitis susceptibility in Eastern Chinese Han population.

Gene 2021 Oct 16;800:145832. Epub 2021 Jul 16.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China; The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China. Electronic address:

Objective: To investigate the association of FOXO3a polymorphisms and ankylosing spondylitis (AS) susceptibility in Eastern Chinese Han population.

Methods: FOXO3a polymorphisms rs12206094, rs12212067, rs2253310, rs3800232, and rs4946933 were genotyped in 650 AS patients and 646 controls by the improved Multiple Ligase Detection Reaction.

Results: The distribution of genotype in rs12212067 polymorphism was significantly different between AS patients and controls (P = 0.020), especially in male population (P = 0.009). There was significant difference of the genotype frequency distribution at rs3800232 between patients and controls in male population. The results of binary regression analysis showed that the rs12212067 GG genotype and rs3800232 TT genotype were obviously correlated with elevated AS risk, and the associations were still significant after being adjusted by age and gender (all P < 0.05). Interestingly, rs12212067 and rs3800232 genotypes were associated with disease activity of patients. Additionally, haplotype block rs12212067- rs3800232 (OR = 1.403, 95%CI = 1.011-1.949) was further shown to confer promoting effect on developing AS.

Conclusion: Among Eastern Chinese Han population, FOXO3a polymorphism rs12212067 and rs3800232 may contribute to increased risk of developing AS, but well-designed multicenter studies are needed to further confirm these preliminary findings in the future.
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http://dx.doi.org/10.1016/j.gene.2021.145832DOI Listing
October 2021

Mitophagy in Cerebral Ischemia and Ischemia/Reperfusion Injury.

Front Aging Neurosci 2021 8;13:687246. Epub 2021 Jun 8.

Zhejiang University-University of Edinburgh Institute, School of Medicine, Zhejiang University, Haining, China.

Ischemic stroke is a severe cerebrovascular disease with high mortality and morbidity. In recent years, reperfusion treatments based on thrombolytic and thrombectomy are major managements for ischemic stroke patients, and the recanalization time window has been extended to over 24 h. However, with the extension of the time window, the risk of ischemia/reperfusion (I/R) injury following reperfusion therapy becomes a big challenge for patient outcomes. I/R injury leads to neuronal death due to the imbalance in metabolic supply and demand, which is usually related to mitochondrial dysfunction. Mitophagy is a type of selective autophagy referring to the process of specific autophagic elimination of damaged or dysfunctional mitochondria to prevent the generation of excessive reactive oxygen species (ROS) and the subsequent cell death. Recent advances have implicated the protective role of mitophagy in cerebral ischemia is mainly associated with its neuroprotective effects in I/R injury. This review discusses the involvement of mitochondria dynamics and mitophagy in the pathophysiology of ischemic stroke and I/R injury in particular, focusing on the therapeutic potential of mitophagy regulation and the possibility of using mitophagy-related interventions as an adjunctive approach for neuroprotective time window extension after ischemic stroke.
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http://dx.doi.org/10.3389/fnagi.2021.687246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217453PMC
June 2021

The next generation therapy for lung cancer: taking medicine by inhalation.

Nanotechnology 2021 Jul 9;32(39). Epub 2021 Jul 9.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, People's Republic of China.

The inhalation administration method which has been applied to treat respiratory diseases has the characteristics of painlessness high efficiency and non-invasiveness, and the drug can also be targeted at the organ level first to reduce the loss of drug during circulation. Therefore, delivering medicine by inhalation administration has brought a new turnaround for lung cancer treatment. Herein from the perspective of combining traditional drug delivery design strategies with new drug delivery methods how to improve lung targeting efficiency and treatment efficacy is discussed. We also discuss the comparative advantages of inhaled drug delivery and traditional administration in the treatment of lung cancer such as intravenous injection. And the researches are divided into different forms of inhalation administration studied in the treatment of lung cancer in recent years, such as single-component loaded and multi-component loaded systems and their advantages. Finally, the obstacles of the application of carrier materials for inhalation administration and the prospects for improvement of lung cancer treatment methods are presented.
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http://dx.doi.org/10.1088/1361-6528/ac0e68DOI Listing
July 2021

Pathogen identification of root-knot nematode disease in Yulong, China.

J Nematol 2021 12;53. Epub 2021 Jun 12.

School of Landscape and Horticulture, Southwest Forestry University, Yunnan, Kunming 650233, China.

In September 2020, samples of galled roots with rhizosphere soil were collected from declining in Yulong County, China. The pathogenic nematodes were identified by observing morphological characteristics of females, second-stage juveniles and perineal pattern, sequence alignments, and specific amplification of sequence characterized amplified region (SCAR). The results showed that the perineal pattern of this nematode was round or oval, the dorsal arch was moderately high or low, one side or both of the lateral field extended to form a wing shape, the tail region had punctations, and the morphological characteristics and morphometric values of second-stage juveniles and females were similar to those of . The ITS region fragment of this nematode were highly similar to those of in NCBI database, with a similarity of over 99.35%. Using the SCAR specific primers, a specific band with an expected size of approximately 440 bp was amplified from this nematode. Morphological and molecular identification supports the nematode species found on Gentiana macrophylla as . This is the first report of this regulated root-knot nematode on in China.
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http://dx.doi.org/10.21307/jofnem-2021-056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204197PMC
June 2021

Impact and barriers of a pharmacist-led practice with computerized reminders on intravenous to oral antibiotic conversion for community-acquired pneumonia inpatients.

J Clin Pharm Ther 2021 Aug 7;46(4):1055-1061. Epub 2021 Jun 7.

Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

What Is Known And Objective: Intravenous to oral (IV-PO) antibiotic conversion, one of the critical elements in antimicrobial stewardship (AMS), is not well implemented in China. Studies on the strategy to apply the IV-PO conversion are needed. Our objective was to evaluate the impact and its barriers of a pharmacist-led practice with computerized reminders on IV-PO antibiotic conversion for community-acquired pneumonia (CAP) inpatients.

Method: This was a retrospective, observational pre- and post-intervention study. Interventions were introduced in 2 sequential 12-month phases: Phase 1: pharmacists implemented the conventional practice of reviewing patient charts and medication records every 24 h and verbally informed the prescribers on eligible IV-PO conversions; Phase 2: pharmacists implemented a new intervention practice to inform the prescribers with a computerized reminder in electronic medical record system on eligible IV-PO conversions.

Main Outcome Measures: The primary outcome was the proportion of patients who converted to oral therapy on the day patients were eligible for the conversion. The secondary outcomes were length of IV antibiotic therapy days, total length of antibiotic therapy days and length of hospital stay.

Results: A total of 524 patients were studied (256 in phase 1 and 268 in phase 2). The proportion of patients who converted to oral therapy on the day patients were eligible for the conversion was significantly increased from 34.77% (89/256) in phase 1 to 62.69% (168/268) in phase 2 (p < 0.05). Length of IV antibiotic therapy days in phase 2 was shortened by 1.23 days, which was 5.52 days compared to 6.75 days in phase 1 (p < 0.05). Total length of antibiotic therapy days was 12.05 days in Phase 1, compared to 10.75 days in phase 2 (p > 0.05). Length of hospital stay for patients in phase 2 was significantly shorter, with a difference of 1.38 days (6.02 days vs. 7.40 days, p < 0.05). The most common barrier of not converting IV-PO was the presence of co-morbidity.

Conclusion: The pharmacist-led IV-PO antibiotic conversion practice with computerized reminders was successful and feasible in Chinese hospitals. More IV-PO intervention studies in patients with other infections are needed in the future.
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http://dx.doi.org/10.1111/jcpt.13397DOI Listing
August 2021

Neurophysiological evidence of how quiet eye supports motor performance.

Cogn Process 2021 Jun 4. Epub 2021 Jun 4.

College of Life and Environmental Sciences, University of Exeter, Exeter, UK.

Prolonged quiet eye (QE) duration is associated with greater performance in various types of targeting and interceptive tasks. However, the mechanism by which QE affects performance remains debatable. This study aimed to test the validity of the pre-programming and online control hypotheses using electromyography (EMG), electrooculography (EOG) and electroencephalography (EEG) during a golf putting task. Twenty-one college students were recruited for this study. Each participant performed 100 golf putting trials during which the putting performance, EMG, EOG, and EEG signals were recorded. The QE duration including the pre- and post-movement initiation components, and movement-related cortical potentials (MRCPs) were analyzed off-line. We found that successful putts were associated with longer QEtotal (the total QE duration from QE onset to QE offset), QEpre (QE occurring before movement initiation), and QEpost (QE occurring after movement initiation) durations than failed putts. Greater cortical activation in the MRCPs was observed within the prefrontal, premotor, and parietal cortices during successful putts compared with failed putts. These findings suggest that QE serves both pre-programming and online control roles in supporting golf putting performance.
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http://dx.doi.org/10.1007/s10339-021-01036-3DOI Listing
June 2021

Association of methylation level and transcript level in TRAF5 gene with ankylosing spondylitis: a case-control study.

Genes Immun 2021 Jun 21;22(2):101-107. Epub 2021 May 21.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China.

To explore the association between methylation level and transcript level of TNF receptor-associated factor 5 (TRAF5) gene with ankylosing spondylitis (AS) in Chinese Han population. Methylation and mRNA expression level of the TRAF5 gene were tested in 98 patients and 98 healthy controls. Among the 21 CpG sites, methylation levels at eight sites were significantly different between AS patients and healthy controls. However, only three sites remained significantly different after the correction by the Benjamini-Hochberg method. Compared with controls, the CpG island of TRAF5 gene promoter was highly methylated in AS patients, and the relative mRNA expression level of TRAF5 was significantly reduced in AS patients. And the mRNA level was negatively correlated with the methylation level of TRAF5 gene in AS patients (r = -0.453, P < 0.001). Subgroup analyses indicated that there was no significant difference in the level of methylation between groups of different status of HLA-B27 and medications in AS patients. Multiple linear regression showed that disease-modifying antirheumatic drugs could reduce methylation levels of AS patients after adjusting for the effects of other drugs. In conclusion, the hypermethylation of the TRAF5 might contribute to the pathogenesis of AS, but many open questions remain.
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http://dx.doi.org/10.1038/s41435-021-00135-7DOI Listing
June 2021

Nanotechnology: Breaking the Current Treatment Limits of Lung Cancer.

Adv Healthc Mater 2021 06 21;10(12):e2100078. Epub 2021 May 21.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, 100190, P. R. China.

Lung cancer is one of the most rapidly growing malignancies in terms of morbidity and mortality. Although traditional treatments have been used for more than 50 years, it is still far from solving the problems of postoperative risks and systemic toxicity. Emerging targeting and immunotherapy are developing continuously and are gaining recognition; eventually, they face the inevitable challenge of drug resistance. Nanotechnology has several important effects on lung cancer treatment, owing to its unique properties. Several nanoparticle-based treatments have successfully become cancer treatments. Good biocompatibility with higher specific surface area can carry substantial amounts of lung cancer treatment medications while avoiding medication toxicity; editable and modified characteristics give rise to multifunctional nanomedicines; excellent photoelectric effects make lung cancer a multimodal treatment. This article summarizes the breakthroughs achieved by nanotechnology, targeted therapy, and immunotherapy, reflecting the importance and necessity of nanotechnology in the treatment of lung cancer.
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http://dx.doi.org/10.1002/adhm.202100078DOI Listing
June 2021

Prognostic value of MTA1, SOX4 and EZH2 expression in esophageal squamous cell carcinoma.

Exp Ther Med 2021 Jul 3;22(1):722. Epub 2021 May 3.

Department of Pathology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China.

Esophageal cancer has always been one of the major malignant tumor types affecting the health of the Chinese population. Metastasis-associated protein 1 (MTA1), SOX4 and enhancer of zeste homolog 2 (EZH2) are all potent inducers of invasion and metastasis in esophageal squamous cell carcinoma (ESCC). However, the role of these signaling molecules and their implication in ESCC have remained largely elusive. In the present study, the effects of MTA1, SOX4 and EZH2 on the prognosis of patients with ESCC were explored. Immunohistochemistry was used to examine the expression levels of MTA1, SOX4 and EZH2. The χ test was used to analyze the association between protein expression and clinicopathological parameters. Kaplan-Meier curves and Cox proportional hazards model survival analysis was performed to investigate the effects of the three proteins examined on disease prognosis. The results indicated that MTA1 may be used as a prognostic and diagnostic marker for ESCC. To the best of our knowledge, the present study was the first to demonstrate that MTA1-SOX4 signaling is associated with prognosis in ESCC. However, no significant association was noted between SOX4 and EZH2 in the present study, which was inconsistent with previously reported findings. The function of the MTA1-SOX4-EZH2 axis and the interactions of the proteins involved require further investigation.
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http://dx.doi.org/10.3892/etm.2021.10154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120658PMC
July 2021

Genetic Association Study Revealed Three Loci Were Associated Risk of Myopia Among Minors.

Pharmgenomics Pers Med 2021 11;14:547-551. Epub 2021 May 11.

Nanjing Tongren Hospital, School of Medicine, Southeast University, Nanjing, 211102, People's Republic of China.

Background: Myopia has raised a predominant public concern among minors. A recent genome-wide association study (GWAS) identified six novel loci in Asian adults. Whether these genetic loci works for myopia in minors remains unknown and worthy of exploration.

Methods: In order to validate the findings, here we performed a case-control study (600 myopia minors, 110 high myopia (HM) minors, and 800 non-myopia minors as controls) utilizing the TaqMan single nucleotide polymorphism (SNP) genotyping assays. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) was adopted.

Results: The median ages in controls, myopia, and HM were 15.1, 15.0, and 15.1, respectively, while the means ± standard deviations for them were 0.32±0.41, - 3.2 ±1.6, and -9.8±2.2, respectively. We found rs2246661 (allelic OR: 1.29; 95% CI: 1.09-1.52; P =0.003), rs74633073 (allelic OR: 1.41; 95% CI: 1.12-1.78; P =0.004), and rs76903431 (allelic OR: 1.42; 95% CI: 1.11-1.81; P =0.005) were significantly associated with increased risk of myopia. Rs2246661 was also significantly associated with increased risk of HM in minors (OR: 1.37; 95% CI: 1.02-1.84; P =0.035).

Conclusion: We identified three loci contributed to myopia in minors and these findings gave new insight into the genetic susceptibility mechanisms of myopia at the molecular level.
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http://dx.doi.org/10.2147/PGPM.S296444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124010PMC
May 2021

Single nucleotide polymorphisms of TRAF2 and TRAF5 gene in ankylosing spondylitis: a case-control study.

Clin Exp Med 2021 May 17. Epub 2021 May 17.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China.

Objective To investigate the role of eight locus polymorphisms of tumor necrosis factor receptor-associated factor 2 (TRAF2) and TRAF5 gene and their interaction in the susceptibility to ankylosing spondylitis (AS) in Chinese Han population. Methods Eight single nucleotide polymorphisms (SNPs) of TRAF2 (rs3750511, rs10781522, rs17250673, rs59471504) and TRAF5 (rs6540679, rs12569232, rs4951523, rs7514863) gene were genotyped in 673 AS patients and 687 controls. Results The SNPs of TRAF2 and TRAF5 do not indicate a correlation with the susceptibility of AS in Chinese Han population. Genotype frequencies of rs3750511 were statistically significant in females between patients and controls. The allele frequencies of rs10781522 and genotype frequencies of rs3750511 were statistically significant between groups of different diseases activity. One three-locus model, TRAF2 (rs10781522, rs17250673) and TRAF5 (rs12569232), had a maximum testing accuracy of 52.67% and a maximum cross-validation consistency (10/10) that was significant at the level of P = 0.0001, after determined empirically by permutation testing. As to environmental variables, only marginal association was found between sleep quality and AS susceptibility. Conclusion TRAF2 rs3750511 polymorphism may be associated with the susceptibility and severity of AS. Besides, the interaction of TRAF2 and TRAF5 genes may be associated with AS susceptibility, but many open questions remain.
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http://dx.doi.org/10.1007/s10238-021-00719-7DOI Listing
May 2021

The Expression Level of FOXO3a in Patients With Autoimmune Diseases: A Meta-analysis.

J Clin Rheumatol 2021 Apr 28. Epub 2021 Apr 28.

From the Department of Epidemiology and Biostatistics, School of Public Health The Key Laboratory of Major Autoimmune Diseases Department of Health Toxicology, School of Public Health, Anhui Medical University Department of Rheumatism and Immunity, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.

Numerous studies have investigated the expression of forkhead box O3a (FOXO3a) in autoimmune diseases, but the results were inconsistent. This meta-analysis aims to synthetically evaluate the levels of FOXO3a in autoimmune diseases.

Methods: PubMed, Web of Science, and China National Knowledge Infrastructure were used to retrieve relevant articles. The pooled standard mean difference with 95% confidence interval was calculated.

Results: Totally, 10 studies from 7 publications were included. The levels of FOXO3a were significantly decreased in patients with autoimmune diseases compared with healthy controls (standard mean difference, -1.045; 95% confidence interval, -1.892 to -0.197). When stratified by disease, FOXO3a levels were significantly decreased in rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), but were significantly increased in systemic lupus erythematosus. FOXO3a levels of specific tissues or cells in patients with autoimmune diseases were significantly decreased, but no significant difference was observed in the subgroup of peripheral blood mononuclear cells. In the subgroup analysis combining disease and sample, significant differences of FOXO3a were observed in non-PMBCs of RA and IBD patients.

Conclusions: Our study indicated that FOXO3a were significantly decreased in patients with autoimmune diseases. FOXO3a levels was a potential therapeutic target of autoimmune diseases.
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http://dx.doi.org/10.1097/RHU.0000000000001675DOI Listing
April 2021

Physical Activity and Resilience among College Students: The Mediating Effects of Basic Psychological Needs.

Int J Environ Res Public Health 2021 04 2;18(7). Epub 2021 Apr 2.

School of Physical Education, Shandong University, Jinan 250061, China.

Considering the significance of resilience in coping with adversity, how to improve college students' resilience is worthy of attention. Previous studies have revealed that physical activity can promote resilience; however, few studies examined the mediating factors between them. The purpose of this study was to investigate the effect of physical activity on resilience, as well as the mediating effects of competence need, autonomy need, and relatedness need between physical activity and resilience. The study involved 2375 college students (1110 males and 1265 females), with an average age of 20.25 years ( = 2.04). Participants completed the International Physical Activity Questionnaire Short Form, Basic Needs Satisfaction in General Scale, and Connor-Davidson Resilience Scale. Results showed that physical activity was positively associated with resilience, and the three basic needs played significant mediating roles between physical activity and resilience. The indirect effect of competence need was significantly greater than that of autonomy need and relatedness need. To conclude, physical activity plays an important role in resilience among college students, and the satisfaction of competence, autonomy, and relatedness needs mediates the relationship between physical activity and resilience, among which, competence need appears as the strongest mediator.
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http://dx.doi.org/10.3390/ijerph18073722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038173PMC
April 2021

The role of RNA mA methylation in the regulation of postnatal hypoxia-induced pulmonary hypertension.

Respir Res 2021 Apr 26;22(1):121. Epub 2021 Apr 26.

Department of Neonatology, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, People's Republic of China.

Background: Pulmonary hypertension (PH) is a complex pulmonary vascular disease characterized by an imbalance in vasoconstrictor/vasodilator signaling within the pulmonary vasculature. Recent evidence suggests that exposure to hypoxia early in life can cause alterations in the pulmonary vasculature and lead to the development of PH. However, the long-term impact of postnatal hypoxia on lung development and pulmonary function remains unknown. N-methyladenosine (mA) regulates gene expression and governs many important biological processes. However, the function of mA in the development of PH remains poorly characterized. Thus, the purpose of this investigation was to test the two-fold hypothesis that (1) postnatal exposure to hypoxia would alter lung development leading to PH in adult rats, and (2) mA modification would change in rats exposed to hypoxia, suggesting it plays a role in the development of PH.

Methods: Twenty-four male Sprague-Dawley rats were exposed to a hypoxic environment (FO: 12%) within 24 h after birth for 2 weeks. PH was defined as an increased right ventricular pressure (RVP) and pathologic changes of pulmonary vasculature measured by α-SMA immunohistochemical staining. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) was performed to analyze mA modification changes in lung tissue in 2- and 9-week-old rats that were exposed to postnatal hypoxia.

Results: Mean pulmonary arterial pressure, lung/body weight ratio, and the Fulton index was significantly greater in rats exposed to hypoxia when compared to control and the difference persisted into adulthood. mA methyltransferase and demethylase proteins were significantly downregulated in postnatal hypoxia-induced PH. Distinct mA modification peak-related genes differed between the two groups, and these genes were associated with lung development.

Conclusions: Our results indicate postnatal hypoxia can cause PH, which can persist into adulthood. The development and persistence of PH may be because of the continuous low expression of methyltransferase like 3 affecting the mA level of PH-related genes. Our findings provide new insights into the impact of postnatal hypoxia and the role of mA in the development of pulmonary vascular pathophysiology.
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http://dx.doi.org/10.1186/s12931-021-01728-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074209PMC
April 2021

Zinc finger protein 91 accelerates tumour progression by activating β-catenin signalling in pancreatic cancer.

Cell Prolif 2021 May 23;54(5):e13031. Epub 2021 Mar 23.

Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Objectives: ZFP91, an E3 ligase, has been reported to possess cancer-promoting functions. This study aimed to elucidate the exact role of ZFP91 in tumour progression of pancreatic cancer and underlying mechanisms.

Materials And Methods: We analysed the correlation between ZFP91 expression and pancreatic cancer through TCGA and GEO data sets. Growth curve, colony formation, wound healing and transwell invasion assays were conducted to evaluate proliferation, migration and invasion of lentivirus transfected pancreatic cancer cells. GSEA and Western blot analysis were performed to validate the regulatory effect of ZFP91 on β-catenin. Drug response curve and orthotopic implantation model reflected the sensitivity of chemotherapies.

Results: ZFP91 overexpression is prevalent in pancreatic cancer and negatively correlated with overall survival. ZFP91 knock-down attenuated proliferation, migration and invasion of pancreatic cancer cells. β-catenin was a downstream gene of ZFP91, and its agonist could reverse the phenotype. ZFP91 promoted EMT and chemoresistance in pancreatic cancer.

Conclusions: We demonstrated that ZFP91 promoted pancreatic cancer proliferation, migration and invasion through activating β-catenin signalling. EMT and chemoresistance were also regulated by ZFP91. ZFP91 might be a potential therapeutic target for pancreatic cancer.
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http://dx.doi.org/10.1111/cpr.13031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088462PMC
May 2021

Aspirin "Allergy"-Induced Thrombocytopenia: A Case Report.

J Asthma Allergy 2021 9;14:201-205. Epub 2021 Mar 9.

Department of Allergology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.

Aspirin is clinically widely used to inhibit platelet aggregation after coronary intervention. Herein we describe a case of aspirin-induced thrombocytopenia that may be related to allergy to aspirin. A 47-year-old man developed a delayed hypersensitivity reaction to aspirin, with pruritus, purpura and thrombocytopenia, increased peripheral blood eosinophils and enlarged inguinal lymph node. All the symptoms disappeared in 2 years after stopping aspirin. Aspirin-induced thrombocytopenia related to allergy is rarely reported. Aspirin hypersensitivity should be taken into consideration in case of unexplained thrombocytopenia in patients taking aspirin. Aspirin "allergy"-induced thrombocytopenia may involve both aspirin related IgG and IgE antibodies.
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http://dx.doi.org/10.2147/JAA.S292567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955731PMC
March 2021

Exposure to 50 Hz Extremely-Low-Frequency Magnetic Fields Induces No DNA Damage in Cells by Gamma H2AX Technology.

Biomed Res Int 2021 15;2021:8510315. Epub 2021 Feb 15.

Bioelectromagnetics Laboratory, Zhejiang University School of Medicine, Hangzhou City, 310058 Zhejiang Province, China.

The current results for extremely-low-frequency magnetic fields (ELF-MF) on DNA damage are still debated. A sensitive indicator and systematic research are needed to assess the effects of ELF-MF. In this study, we used H2AX as an early and sensitive molecular marker to evaluate the DNA damage effects of ELF-MF in vitro. Human amnion epithelial cells (FLs), human skin fibroblast cells (HSFs), and human umbilical vein endothelial cells (HUVECs) were exposed to 50 Hz ELF-MF at 0.4, 1, and 2 mT for 15 min, 1 h, and 24 h, respectively. After exposure, cells were subjected to H2AX immunofluorescence and western blot. The results showed no significant difference in the average number of foci per cell, the percentage of H2AX foci-positive cells, or the expression of H2AX between the sham and 50 Hz ELF-MF exposure groups ( > 0.05). In conclusion, 50 Hz ELF-MF did not induce DNA damage in FLs, HSFs, or HUVECs, which was independent of the intensity or duration of the exposure.
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http://dx.doi.org/10.1155/2021/8510315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899753PMC
May 2021

Comparisons of adipogenesis- and lipid metabolism-related gene expression levels in muscle, adipose tissue and liver from Wagyu-cross and Holstein steers.

PLoS One 2021 24;16(2):e0247559. Epub 2021 Feb 24.

Key Laboratory of Combining Farming and Animal Husbandry of Ministry of Agriculture, Institute of Animal Husbandry, Heilongjiang Academy of Agricultural Sciences, Harbin, China.

The intramuscular fat (IMF) content and fatty acid composition are important meat quality traits that are mostly affected by the cattle breed. Muscle, adipose tissue and liver are important organs involved in the development of intramuscular adipose tissue. Thus, we hypothesized that there were marked differences in the adipogenesis and lipid metabolism of these tissues between Wagyu-cross and Holstein steers during the finishing phases. To test this hypothesis, we analyzed the expression levels of adipogenesis- and lipid metabolism-related genes in longissimus muscle (LM), subcutaneous fat (SCF) and liver from Wagyu-cross and Holstein steers at 26 months of age. The IMF content and fatty acid profile of LM were determined. Wagyu-cross steers had a higher IMF content and MUFA percentages in the LM than Holstein steers (P<0.05). The relative expression of FGF2, COL1A1, SREBP1c, SCD1, GRP78 and LEP was greater in the LM of Wagyu-cross steers than in Holstein steers (P<0.05). In contrast, Holstein steer SCF had higher (P<0.05) mRNA expression levels of FABP4 and ADIPOQ than Wagyu-cross steers. In the liver, the expression of SREBP1c and GRP78 in Wagyu-cross steers was significantly higher than that in Holstein steers (P<0.05). The results demonstrate that both intramuscular adipogenesis and fibrogenesis are enhanced in Wagyu-cross steers compared with Holstein steers during the finishing phase and that IMF deposition is positively correlated with the maturity of SCF and hepatic lipid accumulation in Wagyu-cross steers.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247559PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904217PMC
August 2021

Characterizing volatile metabolites in raw Pu'er tea stored in wet-hot or dry-cold environments by performing metabolomic analysis and using the molecular sensory science approach.

Food Chem 2021 Jul 6;350:129186. Epub 2021 Feb 6.

State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, 130 Changjiang West Road, Hefei, Anhui 230036, China. Electronic address:

The aroma profile of raw pu'er tea (RPT) depends on its storage duration (2-10 years) and storage conditions (wet-hot or dry-cold environment). We analyzed the major odorants of RPT samples by performing metabolomic analysis and by using the molecular sensory science approach. Under dry-cold storage conditions, tea leaves had more carotenoid derivatives, glycoside-derived volatiles, and phenolic volatiles, resulting in "fresh," "floral," and "sweet" aroma. Under wet-hot storage conditions, tea leaves had more methoxybenzenes, which contributed considerably to their "stale" and "woody" aroma. We identified 11 and 4 compounds as the odor markers of RPTs when stored in dry-cold and wet-hot environments, respectively. Our findings provide a scientific basis for optimal storage that yields the desired aroma profile.
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http://dx.doi.org/10.1016/j.foodchem.2021.129186DOI Listing
July 2021

Epigenetics of ankylosing spondylitis: Recent developments.

Int J Rheum Dis 2021 Apr 19;24(4):487-493. Epub 2021 Feb 19.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China.

Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease which mainly affects the spine, sacroiliac joint and peripheral joints. To date, the exact causes and pathogenesis of AS still remain unknown. It is considered that the pathogenesis of AS is associated with genetic, infection, environment, immunity and other factors. Among them, the role of genetic factors in the pathogenesis of AS has been studied most deeply. However, over the past few years, the function of environmental predisposition and epigenetic modification in the pathogenesis of AS has received extensive attention. This paper summarizes the recent progress in the epigenetics of AS, including abnormal epigenetic modifications at AS-associated genomic loci, such as DNA methylation, histone modification, microRNA, and so on. In summary, the findings of this review attempt to explain the role of epigenetic modification in the occurrence and development of AS. Nevertheless, there are still unknown and complicated aspects worth exploring to deepen our understanding of the pathogenesis of AS.
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http://dx.doi.org/10.1111/1756-185X.14080DOI Listing
April 2021

Expression of Twist, Slug and Snail in esophageal squamous cell carcinoma and their prognostic significance.

Oncol Lett 2021 Mar 6;21(3):184. Epub 2021 Jan 6.

Department of Pathology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China.

Esophageal cancer is one of the most common types of malignancy worldwide. At present, surgical resection is the main treatment for esophageal cancer, but recurrence and distant metastasis are the main causes of mortality. The transcription factors Twist, Slug and Snail regulate epithelial-mesenchymal transition and thereby participate in tumor invasion and metastasis. The aim of the present study was to investigate the expression of Twist, Slug and Snail in esophageal squamous cell carcinoma (ESCC) and their prognostic significance. The expression of Twist, Slug and Snail in 229 paraffin-embedded ESCC and matched normal mucosal tissues was detected by immunohistochemistry. The expression differences of Twist, Slug and Snail in the ESCC and normal tissues were compared by χ test, and the associations between the three proteins and the clinicopathological parameters of ESCC were analyzed. The expression levels of Twist, Slug and Snail in 29 fresh frozen ESCC and matched normal mucosal tissues were detected by reverse transcription-quantitative PCR. The correlations among Twist, Slug and Snail in ESCC were examined by Pearson's correlation analyses. In addition, single factor and multivariate Cox regression analyses were used to analyze the influence of Twist, Slug and Snail on the prognosis of ESCC. Twist was found to be highly expressed in ESCC. The difference of Slug expression in ESCC was associated with differentiation degree, TNM stage and vascular invasion, but no significant association was observed between Snail expression and any clinicopathological parameters. In ESCC, there were significant differences in protein expression between Twist and Snail, and Slug and Snail. The mRNA expression level of Twist in ESCC was significantly higher than that in normal esophageal mucosa. However, the mRNA expression of Slug in normal esophageal mucosa was higher than that in ESCC, and the mRNA expression levels of Twist and Snail were positively correlated in ESCC. Kaplan-Meier analysis of 229 patients with ESCC revealed that Snail influenced the overall survival, as did the co-expression of Twist and Snail. Nerve invasion was also identified as an independent factor affecting the progression-free survival of ESCC. The results indicate that Twist is highly expressed, Slug may be a tumor suppressor, and Snail is an independent prognostic factor in ESCC. Twist and Snail are positively correlated, and the simultaneous inhibition of Twist and Snail protein expression may be beneficial for prolonging the overall survival of patients with ESCC.
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http://dx.doi.org/10.3892/ol.2021.12445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816285PMC
March 2021

The increased risk of atrial fibrillation in inflammatory arthritis: a systematic review and meta-analysis of cohort studies.

Immunol Invest 2021 Feb 10:1-13. Epub 2021 Feb 10.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China.

: Atrial fibrillation (AF) is the most common cardiac arrhythmia contributing to stroke and sudden cardiac death. Numbers of studies indicated that patients with inflammatory arthritis have an increased risk of AF. The present study aims to assess the risk of AF in inflammatory arthritis patients.: We systematically searched cohort studies regarding the risk of AF in patients with rheumatoid arthritis, or spondyloarthritis through PubMed, Web of Science, Cochrane Library, Clinical Trials Registry, and China National Knowledge from inception to August 1, 2019. Meta-analysis was performed using fixed effect model, estimating both crude and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Subgroup analysis and meta-regression based on geographic characteristics, comorbidities, and medication use were conducted to explore the source of heterogeneity.: Literature search identified 388 potentially relevant studies, and five studies containing seven cohorts of rheumatoid arthritis or spondyloarthritis were included in the meta-analysis. The AF risk of inflammatory arthritis patients was significantly increased compared with health controls (HR = 1.42, 95% CI: 1.36 to 1.49, = 14.17, < .001), and the pooled HR of studies adjusted factor, like demographic characteristics, medications use, and comorbidities, was 1.37 (95% CI: 1.29 to 1.46; Z = 9.82, < .001).: Patients with inflammatory arthritis have increased risk of AF, probably due to the underlying chronic inflammation. Although various confounders have been adjusted like medications use and comorbidities, the risk of AF is still significantly increased in inflammatory arthritis patients. AF: Atrial fibrillation; AS: Ankylosing spondylitis; CI: Confidence interval; HR: Hazard ratio; NOS: Newcastle-Ottawa scale; NSAIDs: Non-steroid anti-inflammatory drugs; PsA: Psoriatic arthritis; RA: Rheumatoid arthritis; SpA: Spondyloarthritis; TNFi: Tumor necrosis factors inhibitor; uSpA: Undifferentiated spondyloarthritis.
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http://dx.doi.org/10.1080/08820139.2021.1884091DOI Listing
February 2021

Controlled drug release: On the evolution of physically entrapped drug inside the electrospun poly(lactic-co-glycolic acid) matrix.

J Control Release 2021 03 4;331:472-479. Epub 2021 Feb 4.

Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, MD 20899, USA; Department of Physics, Georgetown University, Washington, D. C., 20057, USA. Electronic address:

The drug loading and releasing properties of poly(lactic-co-glycolic acid) (PLGA) were approached with the application of neutron techniques. The neutron reflection (NR) study on the response of PLGA material to vapor and to bulk water revealed that the hydration of PLGA origins from the molecular compatibility between water and PLGA. Hydration is reversible with regard to the change in humidity and temperature. Capecitabine as drug was embedded in the electrospun PLGA fibers. Small angle neutron scattering (SANS) was able to disclose the domain of entrapped drug inside the fibers and trace its evolution over time when the electrospun membrane was incubated in DO buffer solution. The evolution of drug domains is discussed in terms of the concentration dependence, the temperature dependence, and the relevance between the drug diffusion inside the polymer matrix and the drug release out to the medium. It was observed that, at 20 °C the drug-related domains are relatively small (~ 100 Å) and relax extremely slow while at 37 °C the drug-related domains are relatively larger (~ 200 Å) and relax faster. These behaviors can be related to the glassy property of structural material. The transportation of drug through the polymer matrix relies on the global relaxation of PLGA chains. The variation of fiber diameter vs. incubation time was followed by ultra-small angle neutron scattering (USANS). The bi-phasic or tri-phasic release kinetics from a series of fibers with different drug loading (2%, 5%, 10%, 20%, 30%, 40%, 50%) were discussed based on the SANS and USANS discovery.
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http://dx.doi.org/10.1016/j.jconrel.2021.01.038DOI Listing
March 2021

Vergleich der Wirksamkeit und Sicherheit von Biologika bei mittelstark bis stark ausgeprägter Plaque-Psoriasis: Metaanalyse multipler Therapien.

J Dtsch Dermatol Ges 2021 Jan;19(1):47-57

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China.

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http://dx.doi.org/10.1111/ddg.14308_gDOI Listing
January 2021
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