[Safety of umeclidinium/vilanterol in Chinese patients in a real-world setting: a prospective, multicenter, single-arm, observational study].

Objective: To evaluate the safety of umeclidinium/vilanterol in Chinese participants in a real-world setting. Methods: This was a 24-week, prospective, multicenter, single-arm, observational study that enrolled participants treated with umeclidinium/vilanterol in real-world settings from 14 sites in China from 14 December 2020 to 30 January 2022. The primary outcomes were the incidence of adverse events (AEs) and serious adverse events (SAEs) at week 24. Results: A total of 887 participants on umeclidinium/vilanterol were enrolled. The mean (±SD) age of these participants was 67.5 (±9.6) years, with more men (77.7%) enrolled. The majority of the participants (98.1%) had been diagnosed with chronic obstructive pulmonary disease, and 67.6% of them reported comorbidities. More than half of the participants (52.8%) were taking concomitant medication in addition to the study treatment. AEs were reported in 59 (6.7%) participants and were predominantly mild to moderate in severity. SAEs were reported in 21 (2.4%) participants, including 9 fatal SAEs, 10 reported non-fatal SAEs, and 2 reported both non-fatal and fatal SAEs. None of the SAEs, including the fatal events, were considered by the investigators to be related to umeclidinium/vilanterol. Adverse drug reactions (ADRs) were reported in 6 (0.7%) participants with 4 preferred terms (PTs), all of which were considered mild in severity. Of these PTs, 2 were known ADRs of umeclidinium/vilanterol. Three participants (0.3%) reported AEs that were part of serious identified/potential hazards, all of which were considered by the investigators to be unrelated to umeclidinium/vilanterol. Conclusion: The results of this study showed that umeclidinium/vilanterol was well tolerated in Chinese participants in a real-world setting and no new drug-related safety signals were observed.

[Clinical diagnosis and treatment of multiple pulmonary nodules].

CT screening has markedly reduced the lung cancer mortality in high-risk population and increased the detection of early-stage pulmonary neoplasms, including multiple pulmonary nodules, especially those with a ground-glass appearance on CT. Multiple primary lung cancer (MPLC) constitutes a specific subtype of lung cancer with indolent biological behaviors, which is predominantly early-stage adenocarcinoma. Although MPLC progresses slowly with rare lymphatic metastasis, existence of synchronous lesions and distributed location of these nodules still pose difficulty for the management of such patients. One single operation is usually insufficient to eradicate all neoplastic lesions, whereas repeated surgical procedures bring about another dilemma: whether clinical benefits of surgical treatment outweigh loss of pulmonary function following multiple operations. Therefore, despite the anxiety for treatment among MPLC patients, whether and how to treat the patient should be assessed meticulously. Currently there is a heated discussion upon the timing of clinical intervention, operation mode and the application of local therapy in MPLC. Based on clinical experience of our multiple disciplinary team, we have summarized and commented on the evaluation, surgical treatment, non-surgical local treatment, targeted therapy and immunotherapy of MPLC in this article to provide further insight into this field.

[Mediating effect of self-efficacy on self-management ability and self-management behavior in patients with type 2 diabetes mellitus].

OBJECTIVE: To investigate the mechanism of self-efficacy between self-management ability and self-management behavior and its differences among patients with different disease courses through mediation tests. METHODS: In the study, 489 patients with type 2 diabetes who attended the endocrinology departments of four hospitals in Shanxi Province and Inner Mongolia Autonomous Region from July to September 2022 were enrolled as the study population. They were investigated by General Information Questionnaire, Diabetes Self-Management Scale, Chinese version of Diabetes Empowerment Simplified Scale, and Diabetes Self-Efficacy Scale. Mediation analyses were performed using the linear regression model, Sobel test, and Bootstrap test in the software Stata version 15.0 and divided the patients into different disease course groups for subgroup analysis according to whether the disease course was > 5 years. RESULTS: In this study, the score of self-management behavior in the patients with type 2 diabetes was 6.16±1.41, the score of self-management ability was 3.99±0.74, and the score of self-efficacy was 7.05±1.90. The results of the study showed that self-efficacy was positively correlated with self-management ability (r=0.33) as well as self-management behavior (r=0.47) in the patients with type 2 diabetes (P < 0.01). The mediating effect of self-efficacy accounted for 38.28% of the total effect of self-management ability on self-management behaviors and was higher in the behaviors of blood glucose monitoring (43.45%) and diet control (52.63%). The mediating effect of self-efficacy accounted for approximately 40.99% of the total effect for the patients with disease course ≤ 5 years, while for the patients with disease course > 5 years, the mediating effect accounted for 39.20% of the total effect. CONCLUSION: Self-efficacy enhanced the effect of self-management ability on the behavior of the patients with type 2 diabetes, and this positive effect was more significant for the patients with shorter disease course. Targeted health education should be carried out to enhance patients' self-efficacy and self-management ability according to their disease characteristics, to stimulate their inner action, to promote the development of their self-management behaviors, and to form a more stable and long-term mechanism for disease management.

[Joint association of sedentary behavior and physical activity on anxiety tendency among occupational population in China].

OBJECTIVE: To investigate the status and influencing factors of anxiety tendency among occupational population in China and to examine the joint association between sedentary behavior and physical activity with anxiety tendency. METHODS: The data were from the 2021 Asia Best Workplace (Chinese mainland) program. The Generalized Anxiety Tendency scale was used to assess employees' anxiety status, and Logistic regression was used to analyze the factors influencing anxiety tendency and calculate the odds ratio (OR) within different groups. The OR of sitting for each sitting-physical activity (PA) combination group and within PA strata were calculated to explore the joint association. RESULTS: A total of 11 903 workers with an average age of 32.9 years were included in this study. Among them, 3 562 workers had anxiety tendency (29.9%) and the prevalence of those under 40 years old (30.6%) was significantly higher than the other age group (26.7%). 41.0% of the respondents had the moderated to vigorous physical activity. Their average daily sitting time was 9.4 h, and the percentage of those who exceeded 8 h sitting reached 73.9% in the past week. The analysis of Logistic regression showed that smoking (OR=1.24, 95%CI: 1.23-1.39), longer sedentary time and lower physical activity level were risk factors for anxiety tendency, and longer average daily sleep time (OR=0.56, 95%CI: 0.51-0.61) was a protective factor. The joint association analysis and stratified analysis of physical activity and sedentary behavior with anxiety tendency showed that increased sedentary time combined with decreased physical activity intensity was significantly associated with increased risk of anxiety tendency (range of OR: 1.64-3.14). The threshold for sedentary time in total as a risk factor for anxiety tendency gradually decreased as physical activity intensity increased. CONCLUSION: The anxiety tendency and sedentary behavior among the occupational population should recieve more attention. Lack of physical activity and sedentary behavior are both risk factors for anxiety tendency, and strengthening the intensity of physical activity can attenuate the harmful effects of sedentary behavior on anxiety tendency.

[The prevalence and influence factors of work-related musculoskeletal disorders of dental nurse].

Objective: To investigate the prevalence and Influence factors of work-related musculoskeletal disorders (WMSDs) among dental nurses in tertiary stomatology hospitals. Methods: From June to July 2020, 1321 dental nurses from 18 tertiary stomatology hospitals in 18 provinces of China were enrolled as research subjects through a phased sampling method. The cross-sectional study was performed with validated instruments including the basic information questionnaire, Effort-Reward Imbalance Questionnaire, Nurse-Physician Collaboration Scale, and Chinese Musculoskeletal Questionnaire, so as to get the information about the social demography information, nursing-physician cooperation, work stress and the incidence of WMSDs. The influenang factors of WMSDs was analyzed. Results: The past prevalence, annual prevalence, and weekly prevalence of WMSDs were 80.8% (1067/1321) , 68.7% and 43.7% (575/1321) . 58.4% (771/1321) of nurses had WMSDs in three or more body parts. Neck (51.4%) , waist (42.2%) and shoulder (41.6%) were the top three body regions in the past year. The absenteeism rate due to musculoskeletal disorders ranged from 3.5% to 9.0%, waist (8.9%) and neck (8.0%) were the top two body regions. Working more than 40 hours per week (OR=1.74, P<0.001) and effect/reward>1 (OR=1.50, P=0.002) were risk factors of WMSDs (OR=1.74, 95% CI: 1.32~2.30; OR=1.50, 95%CI: 1.17~1.92, P<0.05) , while regular physical exercise every week (≥30 min per times) was the protective factor (OR=0.74, 95%CI: 0.56~0.97, P=0.030) . Conclusion: The prevalence rate of WMSDs of dental nurses in China was high, and most of the nurses suffered with many body parts. Thus, we should reduce controllable occupational stresso, ensuring adequate rest and strengthening physical exercise to reduce the incidence of WMSDs.

Oxygen Electromigration and Energy Band Reconstruction Induced by Electrolyte Field Effect at Oxide Interfaces.

Electrolyte gating is a powerful means for tuning the carrier density and exploring the resultant modulation of novel properties on solid surfaces. However, the mechanism, especially its effect on the oxygen migration and electrostatic charging at the oxide heterostructures, is still unclear. Here we explore the electrolyte gating on oxygen-deficient interfaces between SrTiO_{3} (STO) crystals and LaAlO_{3} (LAO) overlayer through the measurements of electrical transport, x-ray absorption spectroscopy, and photoluminescence spectra. We found that oxygen vacancies (O_{vac}) were filled selectively and irreversibly after gating due to oxygen electromigration at the amorphous LAO/STO interface, resulting in a reconstruction of its interfacial band structure. Because of the filling of O_{vac}, the amorphous interface also showed an enhanced electron mobility and quantum oscillation of the conductance. Further, the filling effect could be controlled by the degree of the crystallinity of the LAO overlayer by varying the growth temperatures. Our results reveal the different effects induced by electrolyte gating, providing further clues to understand the mechanism of electrolyte gating on buried interfaces and also opening a new avenue for constructing high-mobility oxide interfaces.

The structure of schizotypal personality traits: a cross-national study.

BACKGROUND: Schizotypal traits are considered a phenotypic-indicator of schizotypy, a latent personality organization reflecting a putative liability for psychosis. To date, no previous study has examined the comparability of factorial structures across samples originating from different countries and cultures. The main goal was to evaluate the factorial structure and reliability of the Schizotypal Personality Questionnaire (SPQ) scores by amalgamating data from studies conducted in 12 countries and across 21 sites. METHOD: The overall sample consisted of 27 001 participants (37.5% males, n = 4251 drawn from the general population). The mean age was 22.12 years (s.d. = 6.28, range 16-55 years). The SPQ was used. Confirmatory factor analysis (CFA) and Multilevel CFA (ML-CFA) were used to evaluate the factor structure underlying the SPQ scores. RESULTS: At the SPQ item level, the nine factor and second-order factor models showed adequate goodness-of-fit. At the SPQ subscale level, three- and four-factor models displayed better goodness-of-fit indices than other CFA models. ML-CFA showed that the intraclass correlation coefficients values were lower than 0.106. The three-factor model showed adequate goodness of fit indices in multilevel analysis. The ordinal α coefficients were high, ranging from 0.73 to 0.94 across individual samples, and from 0.84 to 0.91 for the combined sample. CONCLUSIONS: The results are consistent with the conceptual notion that schizotypal personality is a multifaceted construct and support the validity and utility of SPQ in cross-cultural research. We discuss theoretical and clinical implications of our results for diagnostic systems, psychosis models and cross-national mental health strategies.

mRNA and protein expression levels of four candidate genes for ear size in Erhualian and Large White pigs.

Porcine ear size is an important characteristic for distinguishing among pig breeds. In a previous genome-wide association study of porcine ear size, LEM domain-containing 3 (LEMD3), methionine sulfoxide reductase B3 (MSRB3), high mobility group AT-hook 2 (HMGA2), and Wnt inhibitory factor 1 (WIF1) were implicated as important candidate genes for ear size. This study investigated the expression levels of four candidate genes for ear size in Erhualian and Large White pigs. Ten Erhualian pigs with large ears and eight Large White pigs with small ears at 60 days of age were examined. The mRNA expression levels of the four candidate genes were quantified by real-time polymerase chain reaction. WIF1 mRNA expression was significantly higher in Large White than in Erhualian pigs (P < 0.05), whereas the expression levels of the other three genes were not significantly different between the two breeds. The protein expression levels of the four genes were analyzed using western blot. WIF1 protein expression was significantly higher in Large White than in Erhualian pigs (P < 0.01), whereas MSRB3 protein expression was significantly higher in Erhualian than in Large White pigs (P < 0.05). There were no significant differences between the two breeds in residual protein expression. These results suggest that WIF1 is the main causal gene for ear size in pigs.

Application of retrograde dissection method for isolation of bone marrow cells from rat femurs and tibiae.

Currently, there is no practical and efficient method for the isolation of bone marrow cells (BMCs) from rat femurs and tibiae. Here, we attempted to develop a rapid, simple, effective, and non-contaminating method for the isolation of BMCs from rat femurs and tibiae. Rat femurs and tibiae were dissected from the ankle to the hip joint; subsequently, a three-step "locate-slide-twist" procedure was performed using scissors and forceps to remove the femurs and tibiae completely, from the surrounding musculature. The bones were flushed with phosphate-buffered saline to harvest BMCs. The femurs and tibiae were dissected in 1.8 ± 0.6 min, and the BMC suspension preparation time was 13.1 ± 2.3 min. The bone marrow cavities did not incur any fractures or injuries during the isolation. Culture of harvested BMCs for 72 h led to a significant increase in cell number from 4.4 ± 0.3 x 106 to 6.9 ± 0.7 x 10(6) (P < 0.01) with no significant decrease in viability (98.1 ± 0.6% vs 96.2 ± 1.1%; P > 0.05). Microscopic examination of the isolated BMCs after the 72-h incubation period revealed the no-microbial or muscle cell contamination. Furthermore, flow cytometry revealed that cultured BMCs (72-h culture) grew well. Here, we have reported a rapid, simple, effective, and non-contaminating method for the isolation of BMCs from rat femurs and tibiae by using retrograde dissection. This method can be used to harvest a large number of viable BMCs without the risk of contamination from muscle and connective tissues.

Molecular cloning, tissue expression pattern, and copy number variation of porcine SCUBE3.

The signal peptide CUB EGF-like domain-containing protein 3 (SCUBE3) gene is a member of SCUBE gene family and plays important roles in bone cell biology and the determination of limb bone length. In this study, the full-length transcript of porcine SCUBE3 was cloned using reverse transcription-polymerase chain reaction and rapid amplification of cDNA ends. The full-length sequence of porcine SCUBE3 cDNA was 4131 base pairs and included 21 exons. The SCUBE3 gene contained a 2895-base pair open reading frame that encoded a peptide of 965 amino acids. Comparison of the deduced amino acid sequences of porcine SCUBE3 with those of human, mouse, zebrafish, and rat showed 96, 95, 73, and 95% identities, respectively. Porcine SCUBE3 mRNA expression levels were highest in the backfat, bone marrow, and cartilage tissues. Copy number variation was detected in porcine SCUBE3 and validated by real-time quantitative polymerase chain reaction. Different copy number variations were present in randomly selected individuals and may, therefore, be a good marker for identifying phenotypic traits. Our findings provide a basis for further investigation of the functions and regulatory mechanisms of SCUBE3 in pigs.

Porcine MAP3K5 analysis: molecular cloning, characterization, tissue expression pattern, and copy number variations associated with residual feed intake.

Mitogen-activated protein kinase kinase kinase 5 (MAP3K5) is essential for apoptosis, proliferation, differentiation, and immune responses, and is a candidate marker for residual feed intake (RFI) in pig. We cloned the full-length cDNA sequence of porcine MAP3K5 by rapid-amplification of cDNA ends. The 5451-bp gene contains a 5'-untranslated region (UTR) (718 bp), a coding region (3738 bp), and a 3'-UTR (995 bp), and encodes a peptide of 1245 amino acids, which shares 97, 99, 97, 93, 91, and 84% sequence identity with cattle, sheep, human, mouse, chicken, and zebrafish MAP3K5, respectively. The deduced MAP3K5 protein sequence contains two conserved domains: a DUF4071 domain and a protein kinase domain. Phylogenetic analysis showed that porcine MAP3K5 forms a separate branch to vicugna and camel MAP3K5. Tissue expression analysis using real-time quantitative polymerase chain reaction (qRT-PCR) revealed that MAP3K5 was expressed in the heart, liver, spleen, lung, kidney, muscle, fat, pancrea, ileum, and stomach tissues. Copy number variation was detected for porcine MAP3K5 and validated by qRT-PCR. Furthermore, a significant increase in average copy number was detected in the low RFI group when compared to the high RFI group in a Duroc pig population. These results provide useful information regarding the influence of MAP3K5 on RFI in pigs.

[Phenotypic characteristics of LAP(+) CD4(+) T lymphocytes in colorectal cancer tissues].

OBJECTIVE: To analyze the phenotypic characteristics of LAP(+) CD4(+) T lymphocytes and investigate their molecular mechanisms in colorectal cancer (CRC) microenvironment. METHODS: Fifty colorectal cancer patients treated in our two hospitals from January 2014 to May 2014 were included in this study. Their tumor tissues and adjacent normal tissues, peripheral blood samples, and peripheral blood samples of 25 healthy donors (HD) were collected to isolate the lymphocytes. The different expressions of CCR7, CD45RA, Foxp3, CTLA-4, CCR4 and CCR5 in LAP(+) CD4(+) T and LAP(-)CD4(+) T lymphocytes were analyzed by flow cytometry (FCM). RESULTS: The FCM assay detected that the percentage of LAP(+) CD4(+) T cells in peripheral blood of the CRC patients were significantly higher than that of HD [(9.44±3.18)% versus (1.49±1.00)%, P<0.001]. In addition, significantly more LAP(+) CD4(+) T cells were also recruited into tumor tissue than those in the tumor-adjacent normal tissue [(11.76±3.74)% versus (3.87±1.64)%, P<0.001]. LAP(+) CD4(+) T cells in the tumor-adjacent normal tissue and peripheral blood of both HDs and CRC patients mainly displayed a central memory phenotype. However, effector memory lymphocytes were predominant in the tumor tissue.In the tumor tissue, the expression of Foxp3 in the LAP(+) CD4(+) T cells was (3.87±1.12)%, significantly lower than that in the LAP(-)CD4(+) T cells (16.70±2.61)%, (P<0.001); the expression of CTLA-4 in the LAP(+) CD4(+) T cells was (36.36±19.14)%, significantly higher than the (19.60±8.91)% in the LAP(-)CD4(+) T cells (P<0.001); the expression of CCR4 in the LAP(+) CD4(+) T cells was (37.72±11.14)%, significantly higher than the (30.06±9.14)% in the LAP(-)CD4(+) T cells (P<0.001); and the expression of CCR5 in the LAP(+) CD4(+) T cells was (18.86±7.10)%, significantly higher than the (13.92±3.31)% in the LAP(-)CD4(+) T cells (P<0.001). CONCLUSIONS: LAP(+) CD4(+) T cells with low expression of Foxp3 and high expressions of CTLA-4, CCR4 and CCR5 are tend to be enriched and accumulated in the tumor tissue. The unique phenotypic characteristics make these cells a distinct subset of lymphocytes, apparently different from the traditional CD4(+) CD25(+) Treg cells.

Efficacy and safety of pregabalin for treating painful diabetic peripheral neuropathy: a meta-analysis.

BACKGROUND: Pregabalin is considered to be an effective treatment for painful diabetic peripheral neuropathy (DPN), but controversy exists about its efficacy and safety. We performed a meta-analysis to systematically assess the efficacy and safety of pregabalin for managing pain associated with DPN. METHODS: Medline, EMBASE, and the Cochrane Central Register were searched in July 2014 for randomized, double-blind, placebo-controlled trials published in English on the use of pregabalin to treat DPN-associated pain. Principal outcomes were mean pain score after pregabalin treatment and the proportions of patients showing a pain reduction of at least 50%. RESULTS: Nine trials involving a total of 2056 participants were identified. Pooled analysis showed that pregabalin was significantly superior to placebo for improving mean pain scores [mean difference (MD) = -0.79, P < 0.001]. Pregabalin reduced pain below baseline by at least 50% in a significantly greater proportion of patients than placebo did [relative risk = 1.54, P < 0.001]. Patients were more likely to self-report their status as 'improved' after taking pregabalin than placebo (relative risk = 1.38, P < 0.001). Pregabalin also improved sleep quality more than placebo (MD = -0.88, P < 0.001). On the other hand, patients receiving pregabalin were more likely to experience mild side effects than were patients receiving placebo. CONCLUSIONS: Our meta-analysis indicates that pregabalin is more effective than placebo for managing DPN-associated pain and other symptoms that reduce quality of life. The drug is also reasonably well tolerated.

Association between polymorphisms in insulin-like growth factor-1 and risk of osteoporosis.

We conducted a case-control study to assess the relation-ship between rs35767, rs2288377, and rs5742612 insulin-like growth factor-1 (IGF-1) and osteoporosis risk in a Chinese female population. The genotypes of rs35767, rs2288377, and rs5742612 of IGF-1 were determined by polymerase chain reaction-restriction fragment length polymorphism. Patients with osteoporosis were more likely to have drinking and smoking habits and have lower bone mineral density in the L2-L4 vertebrae, femoral neck, and total hip. According to conditional regression analysis, individuals carrying the TT genotype of rs35767 had an increased risk of osteoporosis, with an adjusted odds ratio (95% confidence interval) of 2.29 (1.35-4.97). In conclusion, our results sug-gest that the TT genotype of IGF-I rs35767 was associated with an in-creased risk of osteoporosis, suggesting that this polymorphism can be used as a predictive factor for osteoporosis risk.

[Radiographic analysis of treatment of inter-trochanteric fractures using proximal femoral nails].

OBJECTIVE: To establish a reliable approach for measuring proximal femoral 3 dimensional anatomy, and to compare post-operative differences of proximal femoralanatomy in the inter-trochanter fractures with two kinds of antegrade nailings. METHODS: Some computer assisted design (CAD) softwares, e.g. Mimics, were used to establish a reliable approach for measuring proximal femoral 3 dimensional (3D) anatomy. Intra-class correlation coefficient (ICC) was used to test the reliability of intra- and inter-observers. The post-operative pelvic CT data of 19 cases of inter-trochanter fracture patients treated with InterTAN nailing and 21 cases of inter-trochanter fracture patients treated with proximal femoral nail anti-rotation (PFNA) were retrospectively analysed and used to measure bilateral proximal femoral anatomical parameters, including 2D and 3D femoral neck-shaft (NS) angle and femoral neck anteversion (NA) angle, and 2D and 3D anteversion angles of the intramedullary (IM) nailings. ICC was used to test the consistency of the NA angles in the different groups, and the paired student T-test was used to test the differences of the paired quantitative data. RESULTS: The established measurement method hasdexcellent consistency within the intra- and inter-observers, with all the ICCs higher than 0.9. The paired student T-test showed no significant difference between the post-operative bilateral 2D or 3D NA angles. The ICCs results showed that there were no consistency between the post-operative bilateral 2D or 3D NA angles (P values were 0.099 and 0.055, respectively), but the excellent consistency between the 2D injured side NA angle and 2D IM nailing's NA angle, or between the 3D injured side NA angle and 3D IM nailing's NA angle (the ICCs were 0.81 and 0.8, respectively, P values < 0.001). In PFNA group, 57% of the differences between the 2D post-operative injured side's and intact side's NA angles were higher than 15°, which was more than 15.78% in InterTAN group. The paired student T-test showed no significant difference between the post-operative injured side's 2D or 3D NS angles and the intact side's respective 2D or 3D angles in PFNA group (P values were 0.925 and 0.367, respectively), but in InterTAN group, the post-operative injured side's 2D or 3D NS angles were significantly smaller than the intact side's respective angles (P values were 0.033 and 0.009, respectively). CONCLUSION: By analyzing and comparing bilateral proximal femoral anatomical parameters after two kinds of IM nailings procedures, the differences between the bilateral post-operative NA angles in PFNA group were significantly larger than those in InterTAN group. There was significant correlation between the NA angles of the injured sides and NA angles of IM nailings in both the groups.

Association of CAST gene polymorphisms with carcass and meat quality traits in Yanbian cattle of China.

Bovine calpastatin (CAST) gene polymorphisms have been associated with meat tenderness traits; however, little is known about how the CAST gene affects beef quality traits. In this study, 25 single nucleotide polymorphisms were detected in the CAST gene using polymerase chain reaction with single-strand conformation polymorphism and gene sequencing. Different preponderant genotypes were found at the corresponding gene locus. The E1-1, E1-2, and C3-1 loci were correlated with meat tenderness height and highly correlated with the fatty acid content and the amino acid content. The E4-2 locus was not correlated with meat tenderness, but it was correlated with cooking loss, brightness, and yellowness, among others. The CAST gene is a potential marker for these meat quality traits, but further research is required.

[Analysis of relationship between distribution of pathogenic microorganisms in olfactory cleft and olfactory disorders among patients with upper respiratory inflammation during the prevention and control of COVID-19].

Objective: To explore the relationship between pathogens in the olfactory cleft area and olfactory disorders in patients with upper respiratory inflammation (URI) during the prevention and control of 2019 novel coronavirus disease (COVID-19). Methods: A total of 234 URI patients including acute upper respiratory infection, chronic rhinosinusitis (CRS), allergic rhinitis (AR) were continuously selected from September 2020 to March 2021 in Beijing Anzhen Hospital and 98 healthy adults were enrolled as controls. The secretions from the olfactory cleft of all subjects were collected with nasal swabs under nasal endoscopy. Multiple real-time fluorescent quantitative polymerase chain reaction detection method was used to detect nucleic acids of 33 types of respiratory pathogenic microorganism. Sniffin' Sticks olfactory test was performed on all patients with URI. URI patients with olfactory dysfunction were followed up for 9 (8, 10) months (M (Q1, Q3)). SPSS 20.0 software was used for statistical analysis. Results: Among the 98 controls, 9 (9.18%) were positive for pathogenic microorganisms, including 1 (1.02%) rhinovirus, 1 (1.02%) parainfluenza virus type 3, 3 (3.06%) enterovirus, 1 (1.02%) staphylococcus aureus and 3 (3.06%) Moraxella catarrhalis. Among the 234 URI patients, 111 (47.44%) had olfactory disorders and 123 (52.56%) had normal sense of smell. In the olfactory disorder group (111 cases), 38 cases (34.23%) were positive for pathogenic microorganisms, and 4 cases (3.60%) were mixed infection, including 11 cases of rhinovirus (9.91%), 5 cases of coronavirus 229E (4.50%), 2 cases of coronavirus OC43/NL63 (1.80%), 3 cases of parainfluenza virus type 1 (2.70%), 2 cases of enterovirus (1.80%), 1 case of influenza B virus type BV (0.90%), 11 cases of Staphylococcus aureus (9.91%), 7 cases of Moraxella catarrhalis (6.31%), and 1 case of Klebsiella pneumoniae (0.90%). In the normal smell group (123 cases), 18 cases (14.63%) were positive for pathogenic microorganisms, and 1 case (0.81%) was mixed infection, including 3 cases of rhinovirus (2.44%), 4 cases of coronavirus 229E (3.25%), 1 case of Influenza virus type 3 (0.81%), 3 cases of enterovirus (2.44%), 3 cases of Staphylococcus aureus (2.44%), 4 cases of Moraxella catarrhalis (3.25%), and 1 case of Klebsiella pneumoniae (0.81%). Univariate analysis between the two groups found that there were significant differences in the detection rate of pathogenic microorganisms, rhinovirus and Staphylococcus aureus between the groups (all P<0.05). The detection rate of parainfluenza virus type 1, Staphylococcus aureus, and rhinovirus were different between the patients with olfactory disorder and normal olfactory function in the three subgroups of acute upper respiratory tract infection, CRS and AR, respectively (χ2 value was 3.88, 4.53 and 4.73, respectively, all P<0.05). During the follow-up period, among the 111 patients with olfactory disorder, 71 (63.96%) patients' olfactory function returned to normal, 32 (28.83%) patients' olfactory function improved but not completely returned to normal, 8 (7.21%) patients' olfactory function did not improve. Conclusions: During the prevention and control of COVID-19, rhinovirus or Staphylococcus aureus infection or colonization of URI patients is closely related to olfactory disorders. Parainfluenza virus type 1 infection can cause relatively persistent olfactory disorders in patients with acute upper respiratory tract infection. Staphylococcus aureus and rhinovirus colonization are related to the occurrence of olfactory dysfunction in CRS and AR patients respectively.

Circle RNA circCSPP1 promotes human osteosarcoma cell proliferation and increases glucose metabolism by suppressing miR-200c maturation.

INTRODUCTION: MiR-200c plays a central role in glucose metabolism in cancer cells. However, its upstream regulators in this process are unknown. CircRNA CSPP1 (circCSPP1) was predicted to bind to premature miR-200c, an oncogenic miRNA. Therefore, we explored their interaction in osteosarcoma (OS). METHODS: Differential circCSPP1 and miR-200c expression in OS was analyzed using RT-qPCR. Glucose metabolism was analyzed by glucose uptake assay. Subcellular circCSPP1 location in OS cells was detected using cellular fractionation assay. The direct interaction between circCSPP1 and miR-200c was explored using RNA-RNA pull-down assay. The role of circCSPP1 in miR-200c maturation was investigated by analyzing both mature and premature miR-200c levels in OS cells with circCSPP1 overexpression. RESULTS: CircCSPP1 and premature miR-200c levels were increased while mature miR-200c level was decreased in OS. CircCSPP1 was detected in both the nuclear and cytoplasm fractions of OS cells. CircCSPP1 directly interacted with premature miR-200c. CircCSPP1 overexpression increased premature miR-200c level, glucose uptake, and cell proliferation, but decreased mature miR-200c level. MiR-200c overexpression suppressed the role of circCSPP1 in OS cells. CONCLUSIONS: CircCSPP1 promotes OS cell proliferation and increases glucose metabolism by suppressing miR-200c maturation.