Abstract Background Sensorineural hearing loss (SNHL) poses a major threat to both physical and mental health; however, there is still a lack of effective drugs to treat the disease. Recently, novel biological therapies, such as mesenchymal stem cells (MSCs) and their products, namely, exosomes, are showing promising therapeutic potential due to their low immunogenicity, few ethical concerns, and easy accessibility. Nevertheless, the precise mechanisms underlying the therapeutic effects of MSC-derived exosomes remain unclear. Results Exosomes derived from MSCs reduced hearing and hair cell loss caused by neomycin-induced damage in models in vivo and in vitro. In addition, MSC-derived exosomes modulated autophagy in hair cells to exert a protective effect. Mechanistically, exogenously administered exosomes were internalized by hair cells and subsequently upregulated endocytic gene expression and endosome formation, ultimately leading to autophagy activation. This increased autophagic activity promoted cell survival, decreased the mitochondrial oxidative stress level and the apoptosis rate in hair cells, and ameliorated neomycin-induced ototoxicity. Conclusions In summary, our findings reveal the otoprotective capacity of exogenous exosome-mediated autophagy activation in hair cells in an endocytosis-dependent manner, suggesting possibilities for deafness treatment. SNHL (SNHL health however disease Recently therapies (MSCs products namely immunogenicity concerns accessibility Nevertheless MSCderived MSC unclear neomycininduced neomycin induced vitro addition effect Mechanistically formation survival ototoxicity summary exosomemediated exosome mediated endocytosisdependent endocytosis dependent manner treatment

Abstract There is growing evidence that the COVID-19 pandemic has had an impact on the mental health and professional identity of nursing students. This study aimed to explore the trajectories of psychological distress and professional identity and examine their causal relationship among graduate nursing students. A prospective longitudinal study was conducted with 556 graduate nursing students in China who were asked to complete the Questionnaires for Emergent Events of Public Health and the Professional Identity Questionnaire for Nursing Students at three timepoints during the pandemic (T1 = onset of the outbreak, T2 = state-wide isolation, T3 = school reopening). The results showed that psychological distress and psychological identity changed over time, with the lowest psychological distress and highest professional identity at T3. The cross-lagged analysis showed that professional identity at T1 and T2 negatively predicted psychological distress at T2 and T3. We concluded that nurse educators should develop programs and strategies to cultivate professional identity in graduate nursing education to improve mental health during public health crises.

Resumen: Cada vez hay más evidencia de que la reciente epidemia de que la COVID-19 puede afectar a la salud mental y la identidad profesional de los estudiantes de posgrado en enfermería. Es por ello que el propósito de este estudio fue explorar las trayectorias del estrés psicológico y la identidad ocupacional y examinar su relación causal de dichos estudiantes de posgrado durante la nueva epidemia. Se llevó a cabo un estudio prospectivo longitudinal con 556 estudiantes de posgrado en enfermería en China, a los que se les pidió que completaran los cuestionarios de emergencia de salud pública y el de identidad ocupacional para estudiantes de enfermería en tres etapas del brote (T1 = brote, T2 = aislamiento estatal, T3 = reapertura escolar). Los resultados mostraron que estrés psicológico y la identidad psicológica de los estudiantes universitarios habían cambiado con el tiempo. En T3, la perturbación emocional fue la más baja y la identidad ocupacional la más alta. El análisis de retraso cruzado mostró que la identidad ocupacional de T1 y T2 tenía un efecto predictivo negativo sobre la perturbación psicológica de T2 y T3. Conclusión: los educadores de enfermería deberían formular programas y estrategias que cultiven la identidad profesional de sus estudiantes a fin de mejorar la salud mental en emergencias públicas.

Abstract Objective: The aim of this study was to report 6 cases of sinonasal/basicranial myxofibrosarcoma and review demographic data, clinical symptoms, diagnostic methods, therapeutic methods, and prognosis on this subject in the literature. Methods: We conducted a retrospective analysis of six patients referred to our hospital during a 10-year period from 2010 to 2020. Results: In this series, there were four males and two females. The tumours originated from the maxillary sinus in all six cases. The symptoms were nonspecific, and all patients underwent endoscopic resection alone or combined with open resection. The postoperative period was uneventful. All patients were diagnosed with myxofibrosarcoma. After a median follow-up period of 36 (6–52) months, the recurrence rate of MFS was 66.7% (4/6), and the mortality rate was 50% (3/6). Conclusion: Sinonasal/basicranial MFS is a rare neoplasm, and the most common primary site is the maxillary sinus. When diagnosing MFS, osteolysis may help rule out benign lesions. So far surgery is the mainstay of treatment for sinonasal/basicranial MFS. Our surgical strategy using endoscopic resection or endoscopic resection combined with open resection to achieve a negative surgical margin and using re-excision operations to treat relapsed cases may be recommended to rhinologists who treat MFS. Prospective randomised trials are needed to study the role of chemotherapy, radiotherapy, and our surgical strategy for sinonasal/basicranial MFS. Diagnosing patients at an earlier stage and better patient compliance with follow-up plans may improve the prognosis of patients.

Abstract In order to explore the effects of thymol on the antimicrobial activity, structure, physical properties and fresh-keeping application of starch/PBAT composite films, different contents of thymol (0, 1%, 3% and 5%) were used to prepare antimicrobial composite films by extrusion blow molding. The results indicated that tourier transform infrared spectroscopy showed there was intermolecular hydrogen bonding force among starch/PBAT and thymol. The inhibition effect on Botrytis cinerea and the preservation effect of cherry tomato of the composite film were significantly improved, the hardness and nutritional characteristics of cherry tomato were maintained, and the fruit decay rate was reduced. The addition of thymol increased the water vapor permeability of the starch based composite films, but reduced the interaction between the composite film and water. Although thymol reduced the mechanical properties of the composite film, high concentration of thymol further improved the mechanical properties. In conclusion, the high concentration of thymol improved the comprehensive properties of starch composite film, and proved the application prospect of the film as active food packaging material.

Abstract Quinoa starch microparticles (QSMs) fabricated with unhydrolyzed quinoa starch (QS) by inverse microemulsion technology could be used as medicine delivery and cosmetic accessories. The size distribution of QSMs was uniform at 28.5 μM, and the adsorption capacity of methylene blue was 0.82 mg/ g. The optimum preparation process was as follows: a QS mass fraction of 9%, an epoxy chloropropane content of 1%, an amount of oil phase of 100 mL, a span 80 of 3 mg/mL, and a stirring speed of 400 r/min for 3 h at room temperature and pressure. The QSMs were spherical, ellipsoidal in shape with the specific surface area of 1.676 m2/g. The crystallinity of the QSMs increased from 1.24% to 16.8% after crosslinking. The maximum thermal degradation temperature of the QSMs rose slightly than QS. It will be a promising material for application as a drug carrier and in cosmetics.

Abstract The research constructs a novel structure by integrating two parts of online object detection pipelines into the current state-of-the-art Mask R-CNN algorithm to improve the detection performance. The DJI Mavic Air drone is used to collect low-altitude sensing images of strawberry plant canopies. The data augmentation method is employed to feed more instances into the original image dataset to boost the generalization and robustness of the detection model in the training procedure. A ResNet50 backbone combined with a feature pyramid network is presented to extract the features of strawberry plant canopies. The online hard example mining algorithm is introduced to mine hard samples to learn rich features and update model weights. Soft non-maximum suppression based on recursive application on the remaining detection boxes within the predefined overlap threshold is proposed to improve the performance of identifying the large complex overlapping area of strawberry plant canopies. The qualitative results demonstrate that the improved detection model had an AP50 of 96.9 and an AR of 78.5 on the test set, which are approximately 30% higher than the original values.

Dexmedetomidine (DEX) is known to provide neuroprotection against cerebral ischemia and reperfusion injury (CIRI), but the exact mechanisms remain unclear. This study was conducted to investigate whether DEX pretreatment conferred neuroprotection against CIRI by inhibiting neuroinflammation through the JAK2/STAT3 signaling pathway. Middle cerebral artery occlusion (MCAO) was performed to establish a cerebral ischemia/reperfusion (I/R) model. Specific-pathogen-free male Sprague-Dawley rats were randomly divided into Sham, I/R, DEX, DEX+IL-6, and AG490 (a selective inhibitor of JAK2) groups. The Longa score, TTC staining, and HE staining were used to evaluate brain damage. ELISA was used to exam levels of TNF-α. Western blotting was used to assess the levels of JAK2, phosphorylated-JAK2 (p-JAK2), STAT3, and phosphorylated-STAT3 (p-STAT3). Our results suggested that both pretreatment with DEX and AG490 decreased the Longa score and cerebral infarct areas following cerebral I/R. After treatment with IL-6, the effects of DEX on abrogating these pathological changes were reduced. HE staining revealed that I/R-induced neuronal pathological changes were attenuated by DEX application, consistent with the AG490 group. However, these effects of DEX were abolished by IL-6. Furthermore, TNF-α levels were significantly increased in the I/R group, accompanied by an increase in the levels of the p-JAK2 and p-STAT3. DEX and AG490 pretreatment down-regulated the expressions of TNF-α, p-JAK2, and p-STAT3. In contrast, the down-regulation of TNF-α, p-JAK2, and p-STAT3 induced by DEX was reversed by IL-6. Collectively, our results indicated that DEX pretreatment conferred neuroprotection against CIRI by inhibiting neuroinflammation via negatively regulating the JAK2/STAT3 signaling pathway.

Resumo Introdução: A fenda labial não sindrômica, com ou sem fenda palatina, é um defeito congênito comum em todo o mundo, devido a uma combinação de fatores ambientais e genéticos. O genome-wide association studies relatou que o polimorfismo rs7078160 do Vax1 está intimamente relacionado à fenda labial não sindrômica, com ou sem fenda palatina em populações europeias. Estudos subsequentes mostraram os mesmos resultados nas populações mongol, japonesa, filipina e vietnamita etc. No entanto, pesquisas conflitantes foram relatadas na população chinesa. Objetivo: Investigar a associação entre o polimorfismo rs7078160 e fenda labial não sindrômica, com ou sem fenda palatina, em pacientes do sul da China. Método: Tentamos investigar a distribuição do polimorfismo rs7078160 em 100 trios completos de pacientes (39 pacientes com fenda labial e palatina não sindrômica; 36 pacientes com fenda labial somente, não sindrômica; 25 com fenda palatina somente, não sindrômica e seus pais), da etnia Han do sul da China, e em 60 trios saudáveis selecionados como controle. Reação de polimerase em cadeia e o sequenciamento de Sanger foram uszados para genotipar o polimorfismo rs7078160 do Vax1 e tanto os casos-controle quanto as associações baseadas na família foram analisadas. Resultados: As análises de caso-controle revelaram que o polimorfismo rs7078160 estava significativamente associado a fenda labial não sindrômica, com ou sem fenda palatina (p = 0,04) e fenda labial e palatina não sindrômica (p = 0,01), mas não estava associado a pacientes com fenda labial somente não sindrômica e fenda palatina somente não sindrômica. A composição do genótipo de rs7078160 compreende AA homozigoto mutado, AG heterozigoto e GG homozigoto selvagem. Casos com genótipos AG + AA comparados com GG homozigotos mostraram um risco aumentado de fenda labial não sindrômica, com ou sem fenda palatina (p = 0,04, OR = 2,05, IC de 95%: 1,01 ± 4,16) e fenda labial e palatina não sindrômica (p = 0,01, OR = 3,94, IC 95%: 1,34-11,54). Além disso, não detectamos desequilíbrio de transmissão em rs7078160 (p = 0,68). Conclusão: Este estudo sugere que o polimorfismo rs7078160 foi um fator de risco para fenda labial não sindrômica, com ou sem fenda palatina, e o gene Vax1 está fortemente associado com fenda labial não sindrômica, com ou sem fenda palatina em populações da etnia Han do sul da China.

Abstract Introduction: Non-syndromic cleft lip with or without cleft palate is a common worldwide birth defect due to a combination of environmental and genetic factors. Genome-wide association studies reported the rs7078160 of Vax1 is closely related to non-syndromic cleft lip with or without cleft palate in European populations. The following studies showed the same results in Mongolian, Japanese, Filipino, Vietnamese populations etc. However, conflicting research had been reported in Chinese population, Objective: The aim of this study was to investigate the association between the rs7078160 polymorphism and non-syndromic cleft lip with or without cleft palate in Southern Chinese patients. Methods: In this study, we investigated the polymorphism distribution of rs7078160 in 100 complete patient trios (39 patients with non-syndromic cleft lip and palate; 36 patients with non-syndromic cleft lip only; 25 had non-syndromic cleft palate only; and their parents) from Southern ethnic Han Chinese. 60 healthy trios were selected as control. Polymerase chain reaction and Sanger sequencing were used to genotype rs7078160 in Vax1; both case-control and family-based associations were analyzed. Results: The case-control analyses revealed the rs7078160 polymorphism was significant, associated with non-syndromic cleft lip with or without cleft palate (p = 0.04) and non-syndromic cleft lip and palate (p = 0.01), but not associated with non-syndromic cleft lip only and nonsyndromic cleft palate only patients. The genotype composition of rs7078160 comprises mutated homozygous AA, heterozygous AG and wild homozygous GG. Cases with AG + AA genotypes compared with GG homozygotes showed an increased risk of non-syndromic cleft lip with or without cleft palate (p = 0.04, OR = 2.05, 95% CI: 1.01-4.16) and non-syndromic cleft lip and palate (p = 0.01, OR = 3.94, 95% CI: 1.34-11.54). In addition, we did not detect any transmissiondisequilibrium in rs7078160 (p = 0.68). Conclusion: This study suggests that rs7078160 polymorphism is a risk factor of non-syndromic cleft lip with or without cleft palate, and Vax1 is strongly associated with non-syndromic cleft lip with or without cleft palate in Southern Chinese Han populations.

Abstract To evaluate the effect of medical nutritional therapy (MNT) combined with low glycaemic index (LGI) formula at breakfast for 4 weeks on the glycaemic control of patients with type 2 diabetes mellitus (T2DM). Ninety-six participants were recruited and randomly equally divided into two groups. The intervention group was offered with 40g LGI formula at breakfast adjusted according to MNT, and the control group with regular MNT. After 4 weeks, fasting blood glucose, glycated albumin (GA), insulin, C-peptide levels and metabolic index were compared between the two groups. Compared to the intervention group, the total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and the change of FBG (–0.64 ± 1.4 vs. 0.3 ± 2.2; p < 0.05) and 2h-PBG (–1.8 ± 3.6 vs.0.8 ± 3.2; p < 0.01) in the control group were significantly decreased. The LGI formulations, having a significant effect on controlling glucose and lipid metabolism, could be used as a non-pharmacological intervention for T2DM self-management.

SUMMARY OBJECTIVE: This study analyzes the suboptimal health status (SHS) and influencing factors of nurses in Wuhan Hospital, China during the coronavirus disease 2019 (COVID-19) outbreak. METHODS: This study was conducted through an online survey, from March 1–7, 2020, in Wuhan, China. The data collection tools, such as Suboptimal Health Status Questionnaires, Generalized Anxiety Disorder, and Chinese version of the Perceived Stress Scale, were used. RESULTS: The average value of suboptimal health status was 28.44 (standard deviation=15.15). The overall prevalence of SHS was 35.1%. Suboptimal health status of the nurses was significantly different based on their gender, age, whether they directly care for COVID-19 patients, anxiety level, and stress perception expect education. Multivariate analysis found that average sleep times per day, female, age, directly participate in the rescue of COVID-19, self-infection, and anxiety were the influencing factors of suboptimal health status. CONCLUSIONS: First-line nurses have poor suboptimal health status in Wuhan.

ABSTRACT Purpose: Radical nephrectomy (RN) is the standard surgical type for pathological stage T3a (pT3a) renal cell carcinoma (RCC). Recently, some studies have suggested equivalence between partial nephrectomy (PN) and RN for oncologic control and have shown the benefits of PN for better renal function. We conducted this meta-analysis to assess oncologic outcomes, perioperative outcomes and renal function between two groups among patients with pT3a RCC. Materials and methods: PubMed, Scopus, Web of Science, Science Direct, Ovid MEDLINE, The Cochrane Library, Embase and Google Scholar were searched for eligible articles. The endpoints of the final analysis included overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), surgical complications, operative time, estimated blood loss (EBL), serum creatinine and estimated glomerular filtration rate (eGFR). Results: Twelve studies of moderate to high quality, including 14.152 patients, were examined. PN showed superiority for renal functional preservation, providing higher eGFR (WMD=12.48mL/min; 95%CI: 10.28 to 14.67; P <0.00001) and lower serum creatinine (WMD=-0.31mg/dL; 95%CI: −0.40 to −0.21; P <0.00001). There were no significant differences between PN and RN regarding operative time, EBL, surgical complications, OS, RFS and CSS. Despite inherent selection bias, most pooled estimates were consistent in sensitivity analysis and subgroup analysis. More positive margins were found in the PN group (RR=2.42; 95%CI: 1.25-4.68; P=0.009). Conclusions: PN may be more suitable for treating pT3a RCC than RN because it provides a similar survival time (OS or RFS) and superior renal function. Nevertheless, this result is still disputed, and more high-quality studies are required.

Genomic studies have provided insights into molecular subgroups and oncogenic drivers of pediatric brain tumors (PBT) that may lead to novel therapeutic strategies. Participants of the cohort Pediatric Brain Tumor Atlas: CBTTC (CBTTC cohort), were randomly divided into training and validation cohorts. In the training cohort, Kaplan-Meier analysis and univariate Cox regression model were applied to preliminary screening of prognostic genes. The LASSO Cox regression model was implemented to build a multi-gene signature, which was then validated in the validation and CBTTC cohorts through Kaplan-Meier, Cox, and receiver operating characteristic curve (ROC) analyses. Also, gene set enrichment analysis (GSEA) and immune infiltrating analyses were conducted to understand function annotation and the role of the signature in the tumor microenvironment. An eight-gene signature was built, which was examined by Kaplan-Meier analysis, revealing that a significant overall survival difference was seen, either in the training or validation cohorts. The eight-gene signature was further proven to be independent of other clinic-pathologic parameters via the Cox regression analyses. Moreover, ROC analysis demonstrated that this signature owned a better predictive power of PBT prognosis. Furthermore, GSEA and immune infiltrating analyses showed that the signature had close interactions with immune-related pathways and was closely related to CD8 T cells and monocytes in the tumor environment. Identifying the eight-gene signature (CBX7, JADE2, IGF2BP3, OR2W6P, PRAME, TICRR, KIF4A, and PIMREG) could accurately identify patients' prognosis and the signature had close interactions with the immunodominant tumor environment, which may provide insight into personalized prognosis prediction and new therapies for PBT patients.

Hypertrophic scar (HS) formation is a common complication that develops after skin injury; however, there are few effective and specific therapeutic approaches for HS. Emodin has previously been reported to inhibit mechanical stress-induced HS inflammation. Here, we investigated the molecular mechanisms underlying the inhibitory effects of emodin on HS formation. First, we conducted in vitro assays that revealed that emodin inhibited M1 and M2 polarization in rat macrophages. We subsequently established a combined rat model of tail HS and dorsal subcutaneous polyvinyl alcohol (PVA) sponge-induced wounds. Rats were treated with emodin or vehicle (DMEM). Tail scar specimens were harvested at 14, 28, and 42 days post-incision and subjected to H&E staining and Masson's trichrome staining. Histopathological analyses confirmed that emodin attenuated HS formation and fibrosis. Macrophages were separated from wound cells collected from the PVA sponge at 3 and 7 days after implantation. Flow cytometry analysis demonstrated that emodin suppressed in vivo macrophage recruitment and polarization at the wound site. Finally, we explored the molecular mechanisms of emodin in modulating macrophage polarization by evaluating the expression levels of selected effectors of the Notch and TGF-β pathways in macrophages isolated from PVA sponges. Western blot and qPCR assays showed that Notch1, Notch4, Hes1, TGF-β, and Smad3 were downregulated in response to emodin treatment. Taken together, our findings suggested that emodin attenuated HS formation and fibrosis by suppressing macrophage polarization, which is associated with the inhibition of the Notch and TGF-β pathways in macrophages.

Abstract Background: Knowledge of plant population structure facilitates conservation, management, and utilization of endangered plants. Research question: What is the current status of the natural populations of Tetracentron sinense in Leigong Mountain Nature Reserve (LMNR) and what future population development trends can be predicted? Studied species: Tetracentron sinense. Study site and period of research: T. sinense populations in LMNR in China in 2018. Methods: The population structure and quantity dynamics of four typical patches were studied using static life tables, survival curves, survival analyses, and time series analyses. Results: The age structures of the T. sinense populations were spindle-shaped, with few seedlings and saplings, and Deevey type II and III survival curves. The mortality rate (q x ) of each patch increased quickly, and then plateaued, finally increasing again. Survival rate (S x ) showed a contrary trend to q x . Trends in cumulative mortality rate (F (i) ), killing power (K x ), mortality density (f (ti) ), and hazard rate (λ (ti) ) with increasing age class were similar: increasing at a younger age, gradually stabilizing in middle age, and then increasing slightly in older age. The number of individuals in these T. sinense populations was predicted to decrease sharply in future, with younger individuals being seriously deficient. The results showed that the natural populations of T. sinense in the LMNR were relatively stable but were in an early stage of decline. Conclusions: The lack of younger individuals might reflect a bottleneck for regeneration of T. sinense populations, leading to a decline in population size.

Resumen Antecedentes: El conocimiento de la estructura poblacional de una planta facilita su conservación, manejo y utilización. Pregunta de investigación: ¿Cuál es el estado actual de las poblaciones naturales de Tetracentron sinense en la Reserva Natural de la Montaña Leigong (LMNR) y qué tendencias futuras de desarrollo de la población se pueden predecir? Especies estudiadas: Tetracentron sinense. Sitio y período de investigación: Poblaciones en LMNR, China, 2018. Métodos: Se usaron tablas de vida estáticas, curvas de supervivencia, análisis de supervivencia y análisis de series de tiempo para el análisis de la estructura poblacional y dinámica de parches. Resultados: Las estructuras de edad de las poblaciones de T. sinense mostraron forma de huso, con pocas plántulas y juveniles. Curvas de supervivencia Deevey tipo II y III. La tasa de mortalidad (q x ) de cada parche aumentó rápidamente, para estabilizarse y finalmente aumentar nuevamente. La tasa de supervivencia (S x ) mostró una tendencia contraria a q x . Las tendencias en las tasas de mortalidad acumulada (F (i) ), mortalidad (K x ), densidad de mortalidad (f (ti) ), y tasa de riesgo (λ (ti) ) fueron similares con el aumento de la clase de edad. Las poblaciones naturales de T. sinense en el LMNR eran relativamente estables, aunque en etapa temprana de disminución. El número de individuos en poblaciones de T. sinense disminuirá drásticamente en el futuro, donde los más jóvenes mostrarán serias deficiencias. Conclusiones: La ausencia de individuos más jóvenes podría reflejar un cuello de botella para la regeneración de las poblaciones de T. sinense, lo que lleva a una disminución en el tamaño de la población.

Abstract Circulating miRNAs presenting in plasma in a stable manner have been demonstrated their potential role as a promising biomarkers in many human diseases, such as Alzheimer’s disease, melanoma and ovarian carcinoma. However, few circulating miRNAs could be used for breast ductal cancer diagnosis. Here, we identified miR-1273g-3p as a biomarker for detecting breast ductal cancer. We detected miR-1273g-3p levels in the plasma of 39 sporadic breast ductal cancer patients and 40 healthy donors by Stem-loop Quantitative Real-time PCR (qRT-PCR). The results showed the plasma miR-1273g-3p level were significantly up-regulated in breast ductal cancer patients compared with healthy donors (p=0.0139). Receiver operating characteristic (ROC) curve also revealed the significantly diagnostic ability of miR-1273g-3p in patients (p=0.0414). In addition, the plasma level of miR-1273g-3p was closely related to IIIB-IIIC TNM stage. We also confirmed the higher expression level of miR-1273g-3p in breast cancer cell lines MCF-7 (4.872±0.537) than normal breast cells (Hs 578Bst). Taken together, miR-1273g-3p could represent as a potential biomarker for early breast ductal cancer diagnosis.