[Impact of autologous hematopoietic stem cell transplantation on the efficacy of CAR-T treatment of relapsed/refractory multiple myeloma].

Objective: To evaluate the effect of autologous hematopoietic stem cell transplantation (ASCT) on the treatment of relapsed/refractory multiple myeloma (RRMM) with chimeric antigen receptor T cell (CAR-T) therapy. Methods: A retrospective cohort study. The clinical data of 168 patients with RRMM who underwent CAR-T therapy at the Department of Hematology, Xuzhou Medical University Hospital from 3 January 2020 to 13 September 2022 were analyzed. Patients were classified into a transplantation group (TG; n=47) and non-transplantation group (NTG; n=121) based on whether or not they had undergone ASCT previously. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and the levels of CD3, CD4, CD8, CD19, CD56 and natural killer (NK) cells before CAR-T infusion were analyzed by χ2 test, Kaplan-Meier method and independent sample t-test. Results: Among 168 patients with RRMM, 98 (58.3%) were male. The median age of onset was 57 (range 30-70) years. After CAR-T therapy, the ORR of patients was 89.3% (92/103) in the NTG and 72.9% (27/73) in the TG. The ORR of the NTG was better than that of the TG (χ2=5.71, P=0.017). After 1 year of CAR-T therapy, the ORR of the NTG was 78.1% (75/96), and that of the TG was 59.4% (19/32). The ORR of the NTG was better than that of the TG (χ2=4.32, P=0.038). The median OS and PFS in the NTG were significantly longer than those in the TG (OS, 30 vs. 20 months; PFS, 26 vs. 12 months; both P<0.05). The CD4 level before CAR-T infusion in the TG was significantly lower than that in the NTG (25.65±13.56 vs. 32.64±17.21; t=-2.15, P=0.034), and there were no significant differences in the counts of CD3, CD8, CD19, CD56, and NK cells between the TG and NTG (all P>0.05). Conclusion: Among patients suffering from RRMM who received CAR-T therapy, patients who did not receive ASCT had significantly better outcomes than those who had received ASCT previously, which may have been related to the CD4 level before receiving CAR-T therapy.

[Effect of corneal e-value on myopia control in children and adolescents with orthokeratology].

Objective: To investigate the influence of corneal e-value on the effectiveness of orthokeratology in controlling myopia in children and adolescents. Methods: A retrospective cohort study was conducted, involving the data from 1 563 myopic patients (1 563 eyes) who underwent orthokeratology at the Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine from June 2015 to August 2021 and adhered to lens wear for at least 2 years. The cohort consisted of 737 males and 826 females with an average age of (10.84±2.13) years. Based on corneal e-value parameters obtained from corneal topography, patients were categorized into a low e-value group (n=425) and a high e-value group (n=1 138). Data on gender, age, parental myopia history, and baseline measures such as spherical equivalent (SE), axial length, and corneal e-value were collected. Differences in axial length change and corneal fluorescein staining rates were compared between the two groups at 1 and 2 years after the start of lens wear. A generalized linear mixed model was established with axial length change as the dependent variable to analyze the correlation between axial length change and baseline corneal e-value. Results: The initial age of the 1 563 myopic patients was (10.84±2.13) years, with a baseline SE of (-3.05±1.30) D. After 1 year of lens wear, the axial length change was (0.20±0.19) mm in the low e-value group and (0.24±0.20) mm in the high e-value group. After 2 years, the changes were (0.38±0.25) mm and (0.43±0.27) mm, respectively, with statistically significant differences (all P<0.05). The incidence of corneal staining after 1 year of lens wear was 9.2% (39/425) in the low e-value group and 14.1% (160/1 138) in the high e-value group. After 2 years, the rates were 15.8% (67/425) and 21.8% (248/1 138), respectively, with statistically significant differences (all P<0.05). After adjusting for parental myopia history, age, SE, and baseline axial length, the baseline corneal e-value was positively correlated with axial length change at 1 and 2 years after lens wear (all P<0.05). Conclusions: Corneal e-value is an independent factor influencing the effectiveness of orthokeratology in controlling myopia. A smaller corneal e-value is associated with slower axial length growth after orthokeratology, indicating better control of myopia in treated eyes.

[Disease burden and risk factors of chronic respiratory diseases in Jiangsu Province from 1990 to 2019].

Objective: To analyze the prevalence and the trend of the disease burden of chronic respiratory diseases and relevant risk factors in Jiangsu province from 1990 to 2019 and provide evidence for the prevention and treatment of chronic respiratory diseases. Methods: The data from the 2019 Global Burden of Disease Study (GBD2019) were used to calculate the prevalence rate, mortality rate and disability-adjusted life year (DALY) rate. Software Joinpoint was used to calculate the annual percent change (APC) and average annual percent change (AAPC) of the standardized prevalence rate, standardized mortality rate and standardized DALY rate. The population attributable fractions (PAF) were used to estimate the proportion of chronic respiratory disease caused by different risk factors. Results: In 1990 and 2019, the prevalence rates of chronic respiratory diseases were 4.83% and 5.45%. The mortality rates were 134.91/100 000 and 80.99/100 000 respectively, and the DALY rates were 2 678.52/100 000 and 1 534.31/100 000 respectively. From 1990 to 2019, the age-standardized prevalence rate, mortality rate and DALY rate in Jiangsu showed a significant downward trend (AAPC values were -0.90%, -5.28% and -4.70% respectively, P<0.05). Tobacco use was the leading cause of chronic respiratory diseases, followed by air pollution, occupational exposure, suboptimal temperature and high BMI. Compared with 1990, the proportion of DALYs of chronic respiratory diseases attributable to tobacco use and high BMI increased in 2019. Conclusion: The overall burden of chronic respiratory diseases in Jiangsu shows a downward trend. Prevention and health education should be focused on the population with a smoking history and high BMI. At the same time, environmental management, attention to suboptimal temperature and control of occupational exposure factors should also be adopted as important means to prevent and control chronic respiratory diseases.

[An occupational acute poisoning incident of diethylene glycol monobutyl ether].

Objective: To analyze the causes and clinical characteristics of 9 cases of occupational acute poisoning with diethylene glycol monobutyl ether, and provide a basis for clinical diagnosis, treatment, prognosis, and prevention. Methods: The leakage accident of diethylene glycol monobutyl ether occurred in an electronic company in Janvary 2021, in Weihai City was analyzed. The clinical manifestations, laboratory examinations, diagnosis, treatment and prognosis of 9 cases of diethylene glycol monobutyl ether poisoning were summarized. Results: All 9 patients had moderate chemical eye burns and chemical conjunctivitis, and were immediately given symptomatic treatment. They fully recovered after 14 days. Conclusion: Patients who inhale diethylene glycol monobutyl ether for a short time have obvious eye burns, but early detection and timely treatment can achieve better prognosis.

Effects of wearing personal protective equipment during COVID-19 pandemic on composition and diversity of skin bacteria and fungi of medical workers.

BACKGROUND: During the COVID-19 pandemic, wearing PPE can induce skin damage such as erythema, pruritus, erosion, and ulceration among others. Although the skin microbiome is considered important for skin health, the change of the skin microbiome after wearing PPE remains unknown. OBJECTIVE: The present study aimed to characterize the diversity and structure of bacterial and fungal flora on skin surfaces of healthcare workers wearing personal protective equipment (PPE) during the COVID-19 pandemic using metagenomic next-generation sequencing (mNGS). METHODS: A total of 10 Chinese volunteers were recruited and the microbiome of their face, hand, and back were analysed before and after wearing PPE. Moreover, VISIA was used to analyse skin features. RESULTS: Results of alpha bacterial diversity showed that there was statistically significant decrease in alpha diversity indice in the skin samples from face, hand, and three sites after wearing PPE as compared with the indice in the skin samples before wearing PPE. Further, the results of evaluated alpha fungal diversity show that there was a statistically significant decrease in alpha diversity indices in the skin samples from hand after wearing PPE as compared with the indices in the skin samples before wearing PPE (P < 0.05). Results of the current study found that the main bacteria on the face, hand, and back skin samples before wearing the PPE were Propionibacterium spp. (34.04%), Corynebacterium spp. (13.12%), and Staphylococcus spp. (38.07%). The main bacteria found on the skin samples after wearing the PPE were Staphylococcus spp. (31.23%), Xanthomonas spp. (26.21%), and Cutibacterium spp. (42.59%). The fungal community composition was similar in three skin sites before and after wearing PPE. CONCLUSION: It was evident that wearing PPE may affect the skin microbiota, especially bacteria. Therefore, it was evident that the symbiotic microbiota may reflect the skin health of medical workers during the COVID-19 pandemic.

[Application of cold flowable gutta-percha in root canal obturation after apexification].

OBJECTIVE: To evaluate the clinical effect of root canal obturation therapy using cold flowable gutta-percha on young permanent teeth after apexification. METHODS: Ninety cases of young permanent teeth with pulp necrosis or periapical periodontitis treated by apexification were randomly divided into two groups. The cases in each group were divided into single root canal and multiple root canal according to the number of the root canal, and divided into classifications Ⅰ, and Ⅱ/Ⅲ/Ⅳ according to Frank's classification of root development after apexification. Cold flowable gutta-percha and warm gutta-percha obturation techniques were used for root canal obturation of the two groups. The operation time was recorded, and the patients' therapy pain degree was evaluated by visual analog scale (VAS) immediately after operation. Periapical X-ray was performed after operation to evaluate the effect of the root canal filling. The total length of the root was divided into equal three parts on the X-ray film, and three-dimensional tightness of the apical, middle, and coronal region of the root canals were statistically analyzed respectively. Clinical examinations and X-ray examination were performed 6 and 12 months after the operation to evaluate the treatment success rate. RESULTS: The operation time of cold flowable gutta-percha group was significantly lower than that of the control group, which were 51 s and 74 s (P < 0.05); The percentages of pain and discomfort in the two groups were 26.67% and 40.00%, respectively. There were two cases of underfilling and no overfilling in both groups. The percentages of proper filling and tight three-dimensional obturation in the experimental and control groups were 71.11% and 60.00% respectively; and the percentages of tight three-dimensional obturation in the apical third areas were 86.67% and 66.67%, the difference was significant (P < 0.05). There was no significant difference in the three-dimensional tightness between the two groups in the middle and coronal third areas. The percentages of tight three-dimensional obturation in classification Ⅰ groups were 86.67%, 83.33%, 93.33% and 76.67%, 90.00%, 96.67% in experimental and control group, respectively; The percentages of classification Ⅱ/Ⅲ/Ⅳ groups were 86.67%, 86.67%, 100.00% and 46.67%, 86.67%, 100.00%, respectively, and the difference was significant (P < 0.05). There were no apical lesions that occurred in either group during the one-year review period. CONCLUSION: The application of cold flowable gutta-percha on young permanent teeth root canal obturation after apexification can achieve good obturation effect. The root obturation effect in the apical third area is significantly better than that of warm gutta-percha obturation techniques. Cold flowable gutta-percha can shorten the clinical treatment time and ameliorate the patients' therapy comfort.

[Clinical characteristics and prognosis of seizures in 75 children with acute lymphoblastic leukemia].

OBJECTIVE: To investigate the clinical characteristics, treatment, and prognosis of seizures in children with acute lymphoblastic leukemia (ALL) during chemotherapy. METHODS: Children with ALL with seizures during chemotherapy admitted to the Department of Pediatrics, Peking University People's Hospital from January 2010 to March 2022 were retrospectively analyzed. Clinical data including the incidence of seizure, time at seizure onset, causes, management, and prognosis were collected retrospectively. RESULTS: A total of 932 children with ALL were admitted during the study period, of whom, 75 (8%) were complicated with seizures during the period of chemotherapy. There were 40 males and 35 females, with a median age of 7.5 (1-17) years, and 43 cases (57.3%) occurred within the first 2 months of chemotherapy. The underlying diseases were reversible posterior encephalopathy syndrome (n=15), cerebral hemorrhage (n=10, one of whom was complicated with venous sinus thrombosis), intrathecal or systemic methotrexate administration (n=11), brain abscess (n=7, fungal infection in 3 cases, and bacterial in 4), viral encephalitis (n=2), febrile seizure (n=7), hyponatremia (n=7), hypocalcemia (n=2), and unknown cause (n=14). Sixty-four children underwent neuroimaging examination after seizure occurrence, of whom 37 (57.8%) were abnormal. The electroencephalograhpy (EEG) was performed in 44 cases and was abnormal in 24 (54.4%). Fifty-five patients remained in long-term remission with regular chemotherapy, 8 patients received hematopoietic stem cell transplantation, 9 died and 3 lost to follow-up. Symptomatic epilepsy was diagnosed in 18 cases (24%), and was well controlled in 16 with over 1 year of seizure-free. Whereas 2 cases were refractory to anti-seizure medications. CONCLUSION: Seizures are relatively common in children with ALL, most commonly due to reversible posterior encephalopathy syndrome, methotrexate-related neurotoxicity, and cerebral hemorrhage. Seizures occurred within 2 months of chemotherapy in most cases. Neuroimaging and EEG should be performed as soon as possible after the first seizure onset to identify the etiology and to improve the treatment regimen. Some cases developed symptomatic epilepsy, with a satisfactory outcome of seizure remission mostly after concurrent antiseizure medication therapy.

[Establishment of a mutation prediction model for evaluating the efficacy of immunotherapy in renal carcinoma].

OBJECTIVE: To establish a mutation prediction model for efficacy assessment, the genomic sequencing data of renal cancer patients from the MSKCC (Memorial Sloan Kettering Cancer Center) pan-cancer immunotherapy cohort was used. METHODS: The genomic sequencing data of 121 clear cell renal cell carcinoma patients treated with immune checkpoint inhibitors (ICI) in the MSKCC pan-cancer immunotherapy cohort were obtained from cBioPortal database (http://www.cbioportal.org/) and they were analyzed by univariate and multivariate Cox regression analysis to identify mutated genes associated with ICI treatment efficacy, and we constructed a comprehensive prediction model for drug efficacy of ICI based on mutated genes using nomogram. Survival analysis and time-dependent receiver operator characteristic curves were performed to assess the prognostic value of the model. Transcriptome and genomic sequencing data of 538 renal cell carcinoma patients were obtained from the TCGA database (https://portal.gdc.cancer.gov/). Gene set enrichment analysis was used to identify the potential functions of the mutated genes enrolled in the nomogram. RESULTS: We used multivariate Cox regression analysis and identified mutations in PBRM1 and ARID1A were associated with treatment outcomes in the patients with renal cancer in the MSKCC pan-cancer immunotherapy cohort. Based on this, we established an efficacy prediction model including age, gender, treatment type, tumor mutational burden (TMB), PBRM1 and ARID1A mutation status (HR=4.33, 95%CI: 1.42-13.23, P=0.01, 1-year survival AUC=0.700, 2-year survival AUC=0.825, 3-year survival AUC=0.776). The validation (HR=2.72, 95%CI: 1.12-6.64, P=0.027, 1-year survival AUC=0.694, 2-year survival AUC=0.709, 3-year survival AUC=0.609) and combination (HR=2.20, 95%CI: 1.14-4.26, P=0.019, 1-year survival AUC=0.613, 2-year survival AUC=0.687, 3-year survival AUC=0.526) sets confirmed these results. Gene set enrichment analysis indicated that PBRM1 was involved in positive regulation of epithelial cell differentiation, regulation of the T cell differentiation and regulation of humoral immune response. In addition, ARID1A was involved in regulation of the T cell activation, positive regulation of T cell mediated cyto-toxicity and positive regulation of immune effector process. CONCLUSION: PBRM1 and ARID1A mutations can be used as potential biomarkers for the evaluation of renal cancer immunotherapy efficacy. The efficacy prediction model established based on the mutation status of the above two genes can be used to screen renal cancer patients who are more suitable for ICI immunotherapy.

Emerging salt marshes as a source of Trichoderma arenarium sp. nov. and other fungal bioeffectors for biosaline agriculture.

AIMS: Sustainable agriculture requires effective and safe biofertilizers and biofungicides with low environmental impact. Natural ecosystems that closely resemble the conditions of biosaline agriculture may present a reservoir for fungal strains that can be used as novel bioeffectors. METHODS AND RESULTS: We isolated a library of fungi from the rhizosphere of three natural halotolerant plants grown in the emerging tidal salt marshes on the south-east coast of China. DNA barcoding of 116 isolates based on the rRNA ITS1 and 2 and other markers (tef1 or rpb2) revealed 38 fungal species, including plant pathogenic (41%), saprotrophic (24%) and mycoparasitic (28%) taxa. The mycoparasitic fungi were mainly species from the hypocrealean genus Trichoderma, including at least four novel phylotypes. Two of them, representing the taxa Trichoderma arenarium sp. nov. (described here) and T. asperelloides, showed antagonistic activity against five phytopathogenic fungi, and significant growth promotion on tomato seedlings under the conditions of saline agriculture. CONCLUSIONS: Trichoderma spp. of salt marshes play the role of natural biological control in young soil ecosystems with a putatively premature microbiome. SIGNIFICANCE AND IMPACT OF THE STUDY: The saline soil microbiome is a rich source of halotolerant bioeffectors that can be used in biosaline agriculture.

[Advances and controversies of statins application in prevention and treatment of hepatocellular carcinoma].

Statins, as lipid-regulating drugs, have been widely used in the treatment for hyperlipidemia and the primary and secondary prevention of cardio-cerebrovascular diseases. Hepatocellular carcinoma (HCC) is a serious burden of liver disease in China with poor prognosis, thus effective adjuvant drug used for HCC treatment has attracted much attention. Statins can suppress tumor growth, decrease the risk of tumorigenesis and postoperative recurrence of HCC, extend the survival time and improve the therapeutic effect of other treatment, therefore might increase the benefit obtained by the HCC patients. Statins also can impact the expression of MAPK/ERK signaling pathway, promote the apoptosis of malignant cells and ameliorate the HCC risk of hepatitis B virus infected patients. Statins not only prevents the HCC, but also has part therapeutic effect on the different stage of HCC. Although it can't replace the operation, radiofrequency ablation, molecular targeted treatment and immunotherapy currently, statins may be a potential adjuvant drug to provide clinical benefit for HCC patients. The advancement of statins application in the prevention and treatment of HCC has attracted more attention recently, however, discussion and controversy also existed about whether it can eventually become an adjuvant therapy for HCC. The purpose of this paper is to summarize and comment on the new development and disputes of statins application in the prevention and treatment of HCC in recent years, to provide help for the future clinical practice.

[Establishment and application of HPLC-MS/MS method for detecting m6A level in RNA].

Objective: Explore the establishment of a fast, stable and sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for detecting the level of m6A modification in RNA and its application. Methods: The degree of m6A in RNA can be expressed as the ratio of m6A and adenosine (A) in concentration, which can be determined by ESI source positive ion multiple reaction monitoring (MRM) mode. The established method was verified by analyzing three quality control samples (m6A: 4, 40, 400 nmol/L; A: 40, 400, 4 000 nmol/L) with three different concentrations of low, medium, and high. The method was used to detect the degree of m6A in RNA from mouse spleen T cells treated in different ways. The t test was used to compare the differences between the two groups of data. Results: The established method had a good Linearity (R2>0.99) in a range of 1-500 nmol/L for m6A and 10-5 000 nmol/L for A. The limit of detection (LOD) was 1 nmol/L for m6A and 10 nmol/L for A. The recoveries were between 98.9% and 116.5%. The intra-day (n=5) RSDs and the inter-day (n=15, 5 days) RSDs were 2.4%-9.5% and 4.4%-9.6%, respectively. And this method was used to detect the degree of m6A in the RNA from mouse spleen T cells cultured in different conditions. The results showed that the m6A modification level in the RNA of primary CD8+T cell was 0.271 5±0.017 9, and the m6A modification level in the RNA of primary CD8+T cell with IL-27 was 0.251 7±0.015 0, indicating that primary CD8+T cells have a higher level of RNA methylation. Conclusion: This research has established a fast, simplemethylation degree in RNA with HPLC-MS/MS. This method is easy to be popularized and is suitable for the detection of large quantity of samples, and of great significance in analyzing the relationship between methylation and diseases.

[Clinical value of TDI combined with 2D-STI on evaluating the microcirculation dysfunction and left ventricular dysfunction in patients with non-obstructive coronary angina].

Objective: To explore the value of tissue Doppler imaging (TDI) combined with two-dimensional speckle tracking imaging (2D-STI) at rest on evaluating microcirculation dysfunction and left ventricular dysfunction in patients with angina and no obstructive coronary artery disease(ANOCA). Methods: This retrospective study recruited 78 ANOCA patients, who hospitalized in the People's Hospital of Liaoning Province from August 2019 to July 2021. These patients underwent conventional echocardiography examination, including TDI and 2D-STI, to evaluate the left ventricular dysfunction, and adenosine stress echocardiography (SE) to evaluate the coronary flow velocity reserve (CFVR). ANOCA patients were divided into coronary microcirculation dysfunction CMD group (CFVR<2) and control group (CFVR≥2) according to CFVR. Clinical data, routine echocardiographic parameters, TDI parameters including isovolumic contraction time (IVCT), isovolumic relaxation time (IVRT), ejection time (ET), and STI parameters including global longitudinal peak strain (GLS), time to peak (TTP); peak strain dispersion (PSD) were compared between the two groups. Binary logistic regression was used to analyze the risk factors of CMD and the predictive value of each parameter to construct a joint prediction model for the diagnosis of CMD in this patient cohort. Results: The mean age was (55.5±11.2) years, 43 (55%) patients were females in this patient cohort, 38 (49%) patienst were didvided into the CMD group and 40 (51%) into the control group. Age, prevalence of hypertension, diabetes, dyslipidemia, and smokers were significantly higher in the CMD group than in the control group (all P<0.05). Tei index was higher, IVCT and TTP were longer, PSD was higher, ET was shorter, and absolute GLS was lower in the CMD group than in the control group (all P<0.05). The results of logistic regression analysis showed that longer IVCT, higher Tei index, higher time to PSD and lower absolute GLS were the independent risk factors of CMD. The ROC curve revealed that the predicting efficacy on CMD was satisfactiory with the combined predictors: AUC=0.884, sensitivity of 82% and specificity of 80%. Conclusions: TDI combined with 2D-STI is associated with a good diagnostic value on the diagnosis of CMD and left ventricular dysfunction in patients with ANOCA, which provides a feasible non-invasive tool for the diagnosis of CMD and risk stratification of patients with ANOCA.

ADAR1p150 regulates the biosynthesis and function of miRNA-149* in human melanoma.

Melanoma is an aggressive malignant skin tumor. Study found that miR-149* was abnormally expressed in melanoma. Adenosine deaminases acting on the RNA1 (ADAR1) is an RNA editing enzyme. It can change the structure and function of miRNA. In this study, we investigate the role of ADAR1 in regulation of miRNA-149* in melanoma. Western-blot analysis was used to analyze the expression of ADAR1p150, ADAR1p110 and GSK3α at protein level. The expression of ADAR1p150, miR-149* and GSK3α at mRNA level were detected using qRT-PCR. Co-immunoprecipitation test was then performed to determine the interaction between ADAR1 and Dicer. Target verification of miRNA-149*/GSK3α was carried out using luciferase reporter assay. CCK-8 was used to detect cell proliferation. Cell apoptosis was tested using Tunel assays. The expression level of ADAR1p150 was found to be increased in human melanoma tissues, but not ADAR1p110. There was a direct interaction between ADAR1p150 and Dicer in melanoma cells. MiRNA-149* was significantly up-regulated in melanoma tissues and melanoma cells. Luciferase reporter assay suggested that GSK3α was a directly target of miR-149*. The expression level of miR-149* showed a positive correlation with ADAR1p150. At the same time, ADAR1p150 expression was negatively correlated with the expression of GSK3α. ADAR1p150 promoted proliferation of melanoma cells and inhibited cell apoptosis. ADAR1p150 can promote the biosynthesis and function of miRNA-149* in melanoma cells which makes it be considered as both a bio-marker and a therapeutic target for treatment of melanoma.

Characterization of a P18 protein in the S1 segment of the novel duck reovirus genome.

Novel duck reovirus (NDRV), the prototype strain of avian orthoreoviruses, continues to circulate among ducks. Analysis of its genome suggested that a putative second open reading frame in the S1 segment encodes a 162-amino acid nonstructural protein with size of 18 kDa, provisionally designated P18. This protein is different from the 17 kDa nonstructural protein encoded in the same open reading frame in other avian orthoreoviruses, which is designated P17 and consists of 146 amino acids. There is no corresponding protein in Muscovy duck reovirus. Antibodies raised to the purified recombinant protein reacted with viral P18 both in vitro and in vivo. In cells, P18 was located predominantly in the nucleus at 6-12 h post-infection, with negligible levels in the cytoplasm. However, the protein accumulated both in the nucleus and cytoplasm at 24 to 36 h post-infection. Immunohistochemistry indicated that P18 strongly accumulates in spleen tissues of infected ducklings. Collectively, the data provide the direct experimental evidence that P18 is expressed by novel duck reovirus both in vivo and in vitro. Keywords: duck reovirus; expression; characterization; novel P18 protein.

[Associated factors of different fatigue dimensions in elderly patients with rheumatoid arthritis].

Objective: To investigate the associated factors of different dimensions of fatigue in elderly patients with rheumatoid arthritis (RA). Methods: A cross-sectional analysis was performed in the elderly outpatients with RA (age ≥ 60 years) in the First Affiliated Hospital of Sun Yat-sen University from January 2018 to June 2019. Fatigue was measured by Multidimensional Fatigue Inventory-20 (MFI-20) and 36-item Short Form Health Survey-Vitality (SF-36-VT). Physical fatigue and mental fatigue were subsequently measured by MFI-20 subscales. Results: A total of 104 patients were included. Male-to-female ratio was 1∶3.3. The average age was (68±6) years. The MFI-20 score and SF-36-VT score were 60±14 and 64±20, respectively. The score of physical fatigue measured by MFI-20 was 14±3, and mental fatigue scored 10±4 (P<0.001). Arthralgia, disease activity, disability, insomnia, depression and anxiety were correlated with fatigue assessed by MFI-20 (correlated coefficient: 0.48-0.62). Multivariable regression analysis showed that arthralgia and depression were associated with physical fatigue (Standardized regression coefficients were 0.44 and 0.38, respectively). Insomnia, depression and anxiety were associated factors of mental fatigue (Standardized regression coefficients were 0.20, 0.32 and 0.24, respectively). Conclusions: Elderly patients with RA experiencehigh level of fatigue, mainly presenting as physical fatigue. Arthralgia and depression mainly affect physical fatigue, and arthralgia is a critical factor. Insomnia, depression and anxiety are associated with mental fatigue.

Integrating transcriptome-wide association study and mRNA expression profiling identifies novel genes associated with bone mineral density.

To scan novel candidate genes associated with osteoporosis, a two-stage transcriptome-wide association study (TWAS) of bone mineral density (BMD) was conducted. The BMD-associated genes identified by TWAS were then compared with the gene expression profiling of BMD in bone cells, B cells, and mesenchymal stem cells. We identified multiple candidate genes and gene ontology (GO) terms associated with BMD. INTRODUCTION: Osteoporosis (OP) is a metabolic bone disease characterized by decrease in BMD. Our objective is to scan novel candidate genes associated with OP. METHODS: A transcriptome-wide association study (TWAS) was performed by integrating the genome-wide association study (GWAS) summary of bone mineral density (BMD) with two pre-computed mRNA expression weights of peripheral blood and muscle skeleton. Then, another independent GWAS data of BMD was used to verify the discovery results. The BMD-associated genes identified between discovery and replicate TWAS were further subjected to gene ontology (GO) analysis implemented by DAVID. Finally, the BMD-associated genes and GO terms were further compared with the mRNA expression profiling results of BMD to detect the common genes and GO terms shared by both DNA-level TWAS and mRNA expression profile analysis. RESULTS: TWAS identified 95 common genes with permutation P value < 0.05 for peripheral blood and muscle skeleton, such as TMTC4 in muscle skeleton and DDX17 in peripheral blood. Further comparing the genes detected by discovery-replicate TWAS with the differentially expressed genes identified by mRNA expression profiling of OP patients found 18 overlapped genes, such as MUL1 in muscle skeleton and SPTBN1 in peripheral blood. GO analysis of the genes identified by discovery-replicate TWAS detected 12 BMD-associated GO terms, such as negative regulation of cell growth and regulation of glycogen catabolic process. Further comparing the GO results of discovery-replicate TWAS and mRNA expression profiles found 6 overlapped GO terms, such as membrane and cell adhesion. CONCLUSION: Our study identified multiple candidate genes and GO terms for BMD, providing novel clues for understanding the genetic mechanism of OP.

Invasive fungal disease in patients with systemic lupus erythematosus from Southern China: a retrospective study.

OBJECTIVE: To investigate the characteristics and associated factors of invasive fungal disease in patients with systemic lupus erythematosus from Southern China. METHODS: A retrospective study was performed. Demographic and clinical characteristics, laboratory data, and radiographic manifestations were recorded. RESULTS: A total of 45 lupus patients with invasive fungal disease (incidence 1.1%) were included. Twenty-three cases (51.1%) were infected with mold and 22 cases (48.9%) with yeast. Aspergillus spp. (44.4%) and Cryptococcus spp. (33.3%) were common. Aspergillosis mainly occurred in the lung. Cryptococcosis developed in the lung (40.0%), meninges (46.7%) and bloodstream (13.3%). Compared with yeast infection, mold infection tended to develop in patients with active lupus nephritis (65.2% vs. 31.8%, P = 0.03) and the mortality rate was higher (20.0% vs. 0%, P = 0.001). Co-infection with bacteria, virus or superficial fungi occurred in 12 patients (26.7%). Multivariate logistic regression analysis indicated that lymphopenia (odds ratio 2.65, 95% confidential interval 1.14-6.20, P = 0.02) and an accumulated dose of glucocorticoid (odds ratio 1.58, 95% confidence interval 1.10-2.25, P = 0.01) was associated with invasive fungal disease in lupus patients. CONCLUSION: Mold infection tended to develop in patients with active lupus disease with high mortality. Co-infection is not rare. Lymphopenia and an accumulated dose of glucocorticoid are associated with invasive fungal disease in lupus patients.

Mid-term outcome of percutaneous thermal ablation for intrahepatic recurrent hepatocellular carcinoma after liver transplantation.

AIM: To evaluate the safety and mid-term outcome of percutaneous thermal ablation (PTA) for the treatment of intrahepatic recurrent hepatocellular carcinoma (r-HCC) after liver transplantation (LT). MATERIALS AND METHODS: Between October 2010 and March 2017, a total of 52 cases with 120 r-HCCs after LT treated with PTA as a first-line option were enrolled. Overall survival (OS), recurrence free survival (RFS), and the incidence of complications were comprehensively analysed. RESULTS: Major complications occurred in four of 52 (7.7%) patients and minor complications occurred in 19 patients (36.5%). Median OS time was 21.6 months (95% confidence interval [CI]:16.4-26.7 months), with 1-, 2-, and 3-year cumulative survival rates of 74.5%, 45.6%, and 26.2%, respectively. Multivariate analysis revealed that tumour number, the time to recurrence after LT, and serum alpha fetoprotein (AFP) level were found as independent predictors of OS. The estimated of median RFS time was 6 months (95% CI: 3.1-9 months) with the estimated 1-year recurrence-free survival rates of 28.8%. Cox proportional hazards regression analysis indicated tumour number and the time to recurrence after LT were found as independent predictors of RFS. CONCLUSION: PTA is a safe and effective treatment for intrahepatic r-HCCs after LT, with a favourable mid-term outcome. Single tumour, late recurrence after LT (>12 months), and serum AFP level ≤200 ng/ml were independent predictors for longer OS time.

Clinical outcomes of ultrasound-guided radiofrequency ablation for the treatment of primary papillary thyroid microcarcinoma.

AIM: To evaluate the safety, efficacy, and long-term outcomes of ultrasound-guided radiofrequency ablation (RFA) for the treatment of primary papillary thyroid microcarcinoma (PTMC). MATERIALS AND METHODS: A total of 37 patients with 38 PTMC nodules underwent RFA at a power of 20 W between September 2014 and December 2017. The clinical data of these patients were reviewed retrospectively and analysed. Imaging studies of the nodules were conducted, and the patients' thyroid function was assessed before RFA; 1, 3, 6, and 12 months after RFA; and every 6 months thereafter. The volumes and volume reduction rate (VRR) of the nodules were also calculated. RESULTS: RFA with a low power of 20 W was used in the treatment of 37 patients with 38 PTMC nodules. All nodules achieved complete ablation, no complications occurred, and thyroid function was not affected. During follow-up, the volume of the nodules gradually decreased. Twelve months after ablation, the mean volumes of the nodules significantly decreased to 0.01±0.03 ml with a VRR of 99.34±3.49%. At a median follow-up of 6 (range: 1-18) months, 37 of the 38 nodules were completely absorbed, and no recurrence was observed in all 37 patients. CONCLUSIONS: Low-power RFA showed good safety and promising efficacy outcomes for the treatment of PTMC. In addition to surgery and active surveillance, RFA may be an alternative treatment option for patients with PTMC.

Neural response to working memory demand predicts neurocognitive deficits in HIV.

Human immunodeficiency virus (HIV) continues to have adverse effects on cognition and the brain in many infected people, despite a reduced incidence of HIV-associated dementia with combined antiretroviral therapy (cART). Working memory is often affected, along with attention, executive control, and cognitive processing speed. Verbal working memory (VWM) requires the interaction of each of the cognitive component processes along with a phonological loop for verbal repetition and rehearsal. HIV-related functional brain response abnormalities during VWM are evident in functional MRI (fMRI), though the neural substrate underlying these neurocognitive deficits is not well understood. The current study addressed this by comparing 24 HIV+ to 27 demographically matched HIV-seronegative (HIV-) adults with respect to fMRI activation on a VWM paradigm (n-back) relative to performance on two standardized tests of executive control, attention and processing speed (Stroop and Trail Making A-B). As expected, the HIV+ group had deficits on these neurocognitive tests compared to HIV- controls, and also differed in neural response on fMRI relative to neuropsychological performance. Reduced activation in VWM task-related brain regions on the 2-back was associated with Stroop interference deficits in HIV+ but not with either Trail Making A or B performance. Activation of the posterior cingulate cortex (PCC) of the default mode network during rest was associated with Hopkins Verbal Learning Test-2 (HVLT-2) learning in HIV+. These effects were not observed in the HIV- controls. Reduced dynamic range of neural response was also evident in HIV+ adults when activation on the 2-back condition was compared to the extent of activation of the default mode network during periods of rest. Neural dynamic range was associated with both Stroop and HVLT-2 performance. These findings provide evidence that HIV-associated alterations in neural activation induced by VWM demands and during rest differentially predict executive-attention and verbal learning deficits. That the Stroop, but not Trail Making was associated with VWM activation suggests that attentional regulation difficulties in suppressing interference and/or conflict regulation are a component of working memory deficits in HIV+ adults. Alterations in neural dynamic range may be a useful index of the impact of HIV on functional brain response and as a fMRI metric in predicting cognitive outcomes.