A 3-month-old neonatal rhesus macaque HFMD model caused by coxsackievirus B1 infection and viral tissue tropism.

Coxsackievirus B1 (CVB1), an enterovirus with multiple clinical presentations, has been associated with potential long-term consequences, including hand, foot, and mouth disease (HFMD), in some patients. However, the related animal models, transmission dynamics, and long-term tissue tropism of CVB1 have not been systematically characterized. In this study, we established a model of CVB1 respiratory infection in rhesus macaques and evaluated the clinical symptoms, viral load, and immune levels during the acute phase (0-14 days) and long-term recovery phase (15-30 days). We also investigated the distribution, viral clearance, and pathology during the long-term recovery period using 35 postmortem rhesus macaque tissue samples collected at 30 days postinfection (d.p.i.). The results showed that the infected rhesus macaques were susceptible to CVB1 and exhibited HFMD symptoms, viral clearance, altered cytokine levels, and the presence of neutralizing antibodies. Autopsy revealed positive viral loads in the heart, spleen, pancreas, soft palate, and olfactory bulb tissues. HE staining demonstrated pathological damage to the liver, spleen, lung, soft palate, and tracheal epithelium. At 30 d.p.i., viral antigens were detected in visceral, immune, respiratory, and muscle tissues but not in intestinal or neural tissues. Brain tissue examination revealed viral meningitis-like changes, and CVB1 antigen expression was detected in occipital, pontine, cerebellar, and spinal cord tissues at 30 d.p.i. This study provides the first insights into CVB1 pathogenesis in a nonhuman primate model of HFMD and confirms that CVB1 exhibits tissue tropism following long-term infection.

Function of a non-enzymatic hexokinase LcHXK1 as glucose sensor in regulating litchi fruit abscission.

Fruit abscission is a severe hindrance to commercial crop production, and a lack of carbohydrates causes fruit abscission to intensify in a variety of plant species. However, the precise mechanism by which carbohydrates affect fruit setting potential has yet to be determined. In the current study, we noticed negative correlation between hexose level and fruit setting by comparing different cultivars, bearing shoots of varying diameters, and girdling and defoliation treatments. The cumulative fruit-dropping rate was significantly reduced in response to exogenous glucose dipping. These results suggested that hexose, especially glucose, is the key player in lowering litchi fruit abscission. Moreover, five putative litchi hexokinase genes (LcHXKs) were isolated and the subcellular localization as well as activity of their expressed proteins in catalyzing hexose phosphorylation were investigated. LcHXK2 was only found in mitochondria and expressed catalytic protein, whereas the other four HXKs were found in both mitochondria and nuclei and had no activity in catalyzing hexose phosphorylation. LcHXK1 and LcHXK4 were found in the same cluster as previously reported hexose sensors AtHXK1 and MdHXK1. Furthermore, VIGS-mediated silencing assay confirms that LcHXK1 suppression increases fruit abscission. These findings revealed that LcHXK1 functions as hexose sensor, negatively regulating litchi fruit abscission.

Application of whole-process management mode based on "Internet + nursing service" in the management of children with concealed penis / 中国实用护理杂志

Objective:To explore the effect of whole-process management mode based on "Internet + nursing service" in the management of children with concealed penis.Methods:This study adopted a quasi-experimental research method. A total of 383 children with concealed penis who were hospitalized in the Third Department of Urology of Hunan Provincial People′s Hospital from January 2018 to August 2021 were convenient selected. According to the sequence of admission, 195 children admitted from January 2018 to May 2020 were set as the control group, and 188 children admitted from June 2020 to August 2021 were set as the observation group. The control group was received conventional treatment and nursing, but the observation group was received whole-process management mode based on "Internet + nursing service". The length of hospitalization, incidence of complications after discharge, anxiety of the children′s parents and satisfaction of the doctors, the specialist & nurse sharing and the children′s parents were compared between the two groups.Results:Finally, 186 and 193 children were included in the observation group and the control group, respectively After the intervention, in the observation group, the length of hospitalization, anxiety score of the children′s parents, difference of anxiety score of the children′s parents, satisfaction content of the doctors, satisfaction effect of the doctors, satisfaction content of the specialist & nurse sharing, satisfaction effect of the specialist & nurse sharing, satisfaction content of the children′s parents and satisfaction effect of the children′s parents were (4.30 ± 1.35) d, (35.08 ± 3.17) points, (19.14 ± 4.35) points,(4.57 ± 0.54) points, (4.71 ± 0.49) points, (4.75 ± 0.50) points, (5.00 ± 0.00) points, (4.60 ± 0.49) points, (4.65 ± 0.49) points; in the control group, the scores were (5.50 ± 1.41) d, (44.79 ± 3.30) points, (9.22 ± 3.67) points, (3.71 ± 0.49) points, (4.00 ± 0.58) points, (3.50 ± 0.58) points, (3.25 ± 0.50) points, (3.54 ± 0.59) points, (3.64 ± 0.67) points. The differences between the two groups were statistically significant ( t values were -23.94-29.19, all P<0.05). The complication rates of the observation group and the control group were not statistically significant ( χ2=0.64, P>0.05). Conclusions:The whole-process management mode based on "Internet + nursing service" is beneficial to shorten the length of hospitalization, relieve the degree to anxiety of the children′s parents, improve the satisfaction of the doctors, the specialist & nurse sharing and the children′s parents, and accelerate the rehabilitation of children, which is worthy of clinical promotion.

Anticancer Activity of Diosgenin and Its Molecular Mechanism / 中国结合医学杂志

Diosgenin, a steroidal sapogenin, obtained from Trigonella foenum-graecum, Dioscorea, and Rhizoma polgonati, has shown high potential and interest in the treatment of various cancers such as oral squamous cell carcinoma, laryngeal cancer, esophageal cancer, liver cancer, gastric cancer, lung cancer, cervical cancer, prostate cancer, glioma, and leukemia. This article aims to provide an overview of the in vivo, in vitro, and clinical studies reporting the diosgenin's anticancer effects. Preclinical studies have shown promising effects of diosgenin on inhibiting tumor cell proliferation and growth, promoting apoptosis, inducing differentiation and autophagy, inhibiting tumor cell metastasis and invasion, blocking cell cycle, regulating immunity and improving gut microbiome. Clinical investigations have revealed clinical dosage and safety property of diosgenin. Furthermore, in order to improve the biological activity and bioavailability of diosgenin, this review focuses on the development of diosgenin nano drug carriers, combined drugs and the diosgenin derivatives. However, further designed trials are needed to unravel the diosgenin's deficiencies in clinical application.

Effects of extramedullary disease on patients with newly diagnosed multiple myeloma / 中华血液学杂志

Objective: To summarize the characteristics of patients with newly diagnosed multiple myeloma (NDMM) admitted at Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine. We compared the clinical characteristics and prognoses among patients with non-extramedullary disease (EMD), bone-related extramedullary (EM-B) disease, and extraosseous extramedullary (EM-E) disease and further explored the effects of autologous hematopoietic stem cell transplantation (ASCT) for EMD. Methods: From January 2015 to January 2022, data of 114 patients (22%) with EMD out of 515 patients with NDMM were retrospectively analyzed; 91 (18%) and 23 (4%) patients comprised the EM-B and EM-E groups, respectively. The clinical characteristics of patients in all groups were compared with the Chi-square test. Progression-free survival (PFS) and overall survival (OS) of patients were analyzed by the Kaplan-Meier method. Independent prognostic factors were determined using multivariate Cox proportional hazard model. Results: There were no significant differences in age, gender, ISS stage, light chain, creatinine clearance, cytogenetic risk, 17p deletion, ASCT, and induction regimens among the three groups. Overall, 13% of EM-E patients had IgD-type M protein, which was significantly higher than that in EM-B patients (P=0.021). The median PFS of patients in the non-EMD, EM-B, and EM-E groups was 27.4, 23.1, and 14.0 months; the median OS was not reached, 76.8 months, and 25.6 months, respectively. The PFS (vs non-EMD, P=0.004; vs EM-B, P=0.036) and OS (vs non-EMD, P<0.001; vs EM-B, P=0.002) were significantly worse in patients with EM-E, while those were not significantly different between patients with EM-B and those with non-EMD. In the multivariate analysis, EM-E was an independent prognostic factor for OS in patients with NDMM (HR=8.779, P<0.001) and negatively impacted PFS (HR=1.874, P=0.050). In those who did not undergo ASCT, patients with EM-B had significantly worse OS than those with non-EMD (median 76.8 months vs. not reached, P=0.029). However, no significant difference was observed in the PFS and OS of patients with EM-B and those with non-EMD who underwent ASCT. Conclusions: Compared to patients with either non-EMD or EM-B, those with EM-E had the worst prognosis. EM-E was an independent risk factor for OS in patients with NDMM. ASCT can overcome the poor prognosis of EM-B.

Anticancer Activity of Diosgenin and Its Molecular Mechanism / 中国结合医学杂志

Diosgenin, a steroidal sapogenin, obtained from Trigonella foenum-graecum, Dioscorea, and Rhizoma polgonati, has shown high potential and interest in the treatment of various cancers such as oral squamous cell carcinoma, laryngeal cancer, esophageal cancer, liver cancer, gastric cancer, lung cancer, cervical cancer, prostate cancer, glioma, and leukemia. This article aims to provide an overview of the in vivo, in vitro, and clinical studies reporting the diosgenin's anticancer effects. Preclinical studies have shown promising effects of diosgenin on inhibiting tumor cell proliferation and growth, promoting apoptosis, inducing differentiation and autophagy, inhibiting tumor cell metastasis and invasion, blocking cell cycle, regulating immunity and improving gut microbiome. Clinical investigations have revealed clinical dosage and safety property of diosgenin. Furthermore, in order to improve the biological activity and bioavailability of diosgenin, this review focuses on the development of diosgenin nano drug carriers, combined drugs and the diosgenin derivatives. However, further designed trials are needed to unravel the diosgenin's deficiencies in clinical application.

Cloning and functional analysis of IPI gene from Fritillaria unibracteata Hsiao et K. C. Hsia / 药学学报

An open reading frame (ORF) of isopentenyl-diphosphate delta isomerase gene (FuIPI) was cloned from Fritillaria unibracteata Hsiao et K. C. Hsia. (F. unibracteata). Furthermore, the bioinformatics and functional analyses of FuIPI were performed in this study. The result showed that, the ORF of FuIPI gene was 825 bp, encoding a polypeptide of 274 amino acids in length, with a relative molecular mass of about 31 kD and a theoretical isoelectric point of 5.61. Sequence analysis showed that FuIPI contained conserved structural domains and key residues involved in the catalyzing process. The phylogenetic analysis exhibited that FuIPI was closely related to IPIs of Dendrobium officinale and Musa acuminate. Real-time PCR analysis showed that FuIPI was distributed in different tissues of F. unibracteata, but had the highest transcriptional level in leaves, followed by stems, bulbs, and flowers. Furthermore, the FuIPI protein was successfully expressed in Escherichia coli BL21(DE3). The purified FuIPI protein successfully catalyzed the conversion from isopentenyl diphosphate (IPP) to dimethylallyl pyrophosphate (DMAPP). The above results provided a theoretical basis for further investigation of the molecular role of FuIPI in the biosynthesis of alkaloids.

How adverse and benevolent childhood experiences influence depression and suicidal ideation in Chinese undergraduates: a latent class analysis

BACKGROUND@#There has been minimal research on the role of benevolent childhood experiences (BCEs) and how such events may offer protection from the insidious effects of adverse childhood experiences (ACEs) or later in life.@*OBJECTIVES@#This research aims to learn how BCEs and ACEs interact to affect adolescents' psychological distress.@*METHODS@#Cross-sectional survey was conducted in three cities (Xuzhou, Nanjing, and Wuhan) in China from March 2021 to May 2021. Latent class analysis (LCA) was used to classify the patterns of ACEs and BCEs. We adopted hierarchical multivariable regression to examine the influences of ACEs and BCEs on depression and suicidal ideation.@*RESULTS@#To explore the relationship between childhood experience and suicidal ideation and depression, LCA revealed three patterns of ACEs: (1) emotional abuse (10.57%); (2) high ACEs (0.55%); and (3) low ACEs classes (88.88%). Adolescents with emotional abuse (depression: OR = 3.82, 95%CI = 2.80-5.22, P < 0.001; suicidal ideation: OR = 5.766, 95%CI = 3.97-8.38, P < 0.001) and high ACEs class (suicidal ideation: OR = 5.93, 95%CI = 1.19-29.66, P < 0.05) had an increased risk of psychological distress (reference: low ACEs). LCA revealed four patterns of BCEs: (1) relationship support (14.54%); (2) low BCEs (4.85%); (3) high BCEs (55.34%); and (4) high quality of life classes (25.28%). Adolescents with a high quality of life (depression: OR = 0.09, 95%CI = 0.05-0.16, P < 0.001; suicidal ideation: OR = 0.22, 95%CI = 0.12-0.40, P < 0.001) and high BCEs (depression: OR = 0.05, 95%CI = 0.03-0.09, P < 0.001; suicidal ideation: OR = 0.15, 95%CI = 0.09-0.26, P < 0.001) protected the mental health of adolescents (reference: low BCEs).@*CONCLUSIONS@#High ACEs and emotional abuse classes were significantly associated with poorer mental health symptoms, including suicidal ideation and depression. In contrast, high BCEs and high quality of life classes were associated with better mental health. These findings point out that it is more necessary to identify and support victims of ACEs, and it is urgent to increase BCEs in early childhood.

Moxibustion as an adjunctive treatment for rheumatoid arthritis and its effects on the serum levels of SOST and β-catenin / 中国针灸

OBJECTIVES@#To observe the clinical efficacy of moxibustion as an adjunctive treatment for rheumatoid arthritis (RA) based on conventional medication and its effects on serum sclerostin (SOST) and β-catenin levels, exploring the potential mechanisms by which moxibustion may protect joint bones in RA patients.@*METHODS@#Seventy-six RA patients were randomly divided into an observation group (38 cases, 3 cases dropped out) and a control group (38 cases, 4 cases were eliminated, 2 cases dropped out). The patients in the control group were treated with conventional oral medication; based on the treatment of the control group, the patients in the observation group were treated with moxibustion. The direct moxibustion was applied at Zusanli (ST 36) on both sides and ashi points around small joints, and indirect moxibustion was applied at Shenshu (BL 23) on both sides and ashi points around large joints. The treatment was given three times a week for a total of 5 weeks. The count of pain and swollen joint, morning stiffness score, disease activity score of 28 joints (DAS28), visual analogue scale (VAS) score, health assessment questionnaire (HAQ) score, and serum levels of SOST, β-catenin, and tumor necrosis factor-α (TNF-α) were evaluated before and after treatment in the two groups.@*RESULTS@#Compared those before treatment, after treatment, both groups showed a reduction in pain and swollen joint count (P<0.01, P<0.05), morning stiffness, DAS28, VAS, and HAQ scores (P<0.01, P<0.05), with the observation group having lower scores than the control group (P<0.01). Serum levels of SOST, β-catenin, and TNF-α after treatment in the observation group were lower than those in both before treatment and the control group (P<0.01, P<0.05). There was a positive correlation between the difference in serum β-catenin levels before and after treatment and the difference in serum SOST (r=0.578, P<0.001) and TNF-α (r=0.403, P<0.05) levels in the observation group.@*CONCLUSIONS@#In addition to medication, moxibustion as an adjunctive treatment could significantly alleviate joint pain and reduce disease activity in RA patients, suggesting a potential role in joint protection. This mechanism may be related to the inhibition of the inflammatory factor TNF-α, regulation of β-catenin levels, and reduction in the production of the endogenous negative regulator protein SOST within the Wnt/β-catenin signaling pathway.

The Effect of Allograft Inflammatory Factor-1 on Inflammation, Oxidative Stress, and Autophagy via miR-34a/ATG4B Pathway in Diabetic Kidney Disease.

Increasing evidence suggests that disorders of inflammation, oxidative stress, and autophagy contribute to the pathogenesis of diabetic kidney disease (DKD). This study attempted to clarify the effect of allograft inflammatory factor-1 (AIF-1), miR-34a, and ATG4B on inflammation, oxidative stress, and autophagy in DKD both in vitro and in vivo experiments. In vivo, it was found that the levels of AIF-1, miR-34a, oxidative stress, and inflammatory factors were significantly increased in blood and urine samples of DKD patients and mouse models and correlated with the level of urinary protein. In vitro, it was also found that the expressions of AIF-1, miR-34a, ROS, and inflammatory factors were increased, while ATG4B and other autophagy related proteins were decreased in human renal glomerular endothelial cells (HRGECs) cultured with high concentration glucose medium (30 mmol/L). When AIF-1 gene was overexpressed, the levels of miR-34a, ROS, and inflammatory factors were significantly upregulated, and autophagy-related proteins such as ATG4B were downregulated, while downregulation of AIF-1 gene had the opposite effect. In addition, miR-34a inhibited the expression of ATG4B and autophagy-related proteins and increased the levels of ROS and inflammation. Furthermore, the result of luciferase reporter assay suggested that ATG4B was the target gene of miR-34a. When ATG4B gene was overexpressed, the level of autophagy was upregulated, and inflammatory factors were downregulated. Conversely, when ATG4B gene was inhibited, the level of autophagy was downregulated, and inflammatory factors were upregulated. Then, autophagy inducers inhibited the levels of inflammation and ROS, whereas autophagy inhibitors had the opposite function in HRGECs induced by glucose (30 mmol/L). In conclusion, the above data suggested that AIF-1 regulated the levels of inflammation, oxidative stress, and autophagy in HRGECs via miR-34a/ATG4B pathway to contribute to the pathogenesis of diabetic kidney disease.

Effect of 52 % low-sodium salt applied to CM-DASH diet on atherosclerotic cardiovascular disease risks in patients with hypertension and type-2 diabetes / Efecto de un 52 % de sal baja en sodio en la dieta CM-DASH sobre el riesgo de enfermedad cardiovascular aterosclerótica en pacientes con hipertensión arterial y diabetes de tipo 2

Introduction: hypertension and diabetes are chronic disorders associated with an increased risk of cardiovascular disease.Objectives:to evaluate the effect of 52 % low-sodium salt applied to the Chinese-modified DASH (CM-DASH) diet on risk of atherosclerotic cardiovascular disease (ASCVD) in patients with hypertension and type-2 diabetes.Methods:the low-sodium salt group (LSSG) took 5 g/day of 52 % low-sodium salt plus CM-DASH diet for 8 weeks, while the normal-sodium salt group (NSSG) took the same dose of normal-sodium salt plus CM-DASH diet for 8 weeks. Blood tests, 24-hour urine tests, anthropometric measurements, and 10-year risk of ASCVD prediction were assessed.Results:compared with baseline, both LSSG and NSSG showed a significant reduction in 10-year risk of ASCVD, but we did not find any statistically significant differences in 10-year risk of ASCVD between LSSG and NSSG.Conclusions:our study shows that salt limits and DASH diets reduce the risk of cardiovascular disease whereas low-sodium salt containing 52 % sodium chloride did not significantly lower the risk of cardiovascular disease when compared to regular salt. Due to the limitations of the research, additional studies will be necessary to confirm our findings. (AU)

Introducción: la hipertensión y la diabetes son trastornos crónicos asociados a un mayor riesgo de enfermedad cardiovascular.Objetivos:evaluar el efecto de la sal baja en sodio (52 %) aplicada a la dieta DASH modificada en China (CM-DASH) sobre los riesgos de enfermedad cardiovascular aterosclerótica (ECA) en pacientes con hipertensión arterial y diabetes de tipo 2.Métodos:el grupo de sal baja en sodio (LSSG) tomó 5 g/día de sal baja en sodio al 52 % más dieta CM-DASH durante 8 semanas, mientras que el grupo de sal normal en sodio (NSSG) tomó la misma dosis de sal normal en sodio más dieta CM-DASH durante 8 semanas. Se evaluaron los análisis de sangre, los análisis de orina de 24 horas, las mediciones antropométricas y los riesgos de predicción de ECVA a 10 años.Resultados:en comparación con el valor basal, tanto el LSSG como el NSSG mostraron una reducción significativa de los riesgos a 10 años de ECVA, mientras que no se encontraron diferencias estadísticamente significativas en los riesgos a 10 años de ECVA entre el LSSG y el NSSG.Conclusiones:nuestro estudio muestra que los límites de sal y las dietas DASH reducen el riesgo de enfermedad cardiovascular mientras que la sal baja en sodio con un 52 % de cloruro sódico no redujo significativamente el riesgo de enfermedad cardiovascular en comparación con la sal normal. Debido a las limitaciones de la investigación, serán necesarios estudios adicionales para confirmar nuestros hallazgos. (AU)

Effect of sodium reduction based on the DASH diet on blood pressure in hypertensive patients with type 2 diabetes / Efecto de la reducción de sodio basada en la dieta DASH sobre la presión arterial en pacientes hipertensos con diabetes de tipo 2

Objectives: to evaluate the effect of sodium reduction based on a modified DASH diet on blood pressure in hypertensive patients with type 2 diabetes. Material and methods: sixty-one hypertensive patients with type 2 diabetes were selected from the community and randomly allocated to a common salt group and low sodium salt group receiving the 8-week dietary intervention, in which weeks 1-2 was the dietary guidance phase, weeks 3-4 was the centralized feeding phase, and weeks 5-8 was the home medical care phase. Participants were followed up in the hospital once a week to collect information on outpatient blood pressure, salt, and drug use. Physical examinations were conducted at 4 weeks and the end of the intervention, as well as at baseline. Results: after the intervention, the blood pressure of both the low sodium group (SBP: -14.32 mmHg, p < 0.001; DBP: -6.32mmHg, p < 0.001) and the common salt group (SBP: -10.98 mmHg, p < 0.001; DBP: -5.24 mmHg, p = 0.001) decreased significantly with a more pronounced decrease in the low sodium group but no statistically significant differences between the two groups (SBP: -0.28 mmHg, p = 0.929; DBP: -3.32 mmHg, p = 0.093). At the end of the intervention, sodium intake was significantly decreased, but potassium intake was increased in the low sodium group (p < 0.05); however, the common salt group had no significant change. Conclusion: reducing sodium intake based on the modified DASH diet had a good effect on systolic and diastolic blood pressure in hypertensive patients with type 2 diabetes. Sodium reduction based on the modified DASH diet is safe and effective, and can be used as a guide for healthy living in hypertensive patients (AU)

Objetivos: evaluar el efecto de la reducción de sodio basada en una dieta DASH modificada sobre la presión arterial en pacientes hipertensos con diabetes de tipo 2. Material y métodos: sesenta y un pacientes hipertensos con diabetes de tipo 2 fueron seleccionados de la comunidad y asignados aleatoriamente a un grupo de sal común y un grupo de sal baja en sodio, que recibieron una intervención dietética de 8 semanas en la que las semanas 1-2 fueron la fase de orientación dietética, las semanas 3-4 fueron la fase de alimentación centralizada, y las semanas 5-8 fueron la fase de atención médica domiciliaria. Los participantes fueron seguidos en el hospital una vez por semana para recopilar información sobre la presión arterial, la sal y el uso de drogas en pacientes ambulatorios. Los exámenes físicos se realizaron a las 4 semanas y al final de la intervención, así como al inicio del estudio. Resultados: después de la intervención, la presión arterial tanto del grupo bajo en sodio (PAS: -14,32 mmHg, p < 0,001; PAD: -6,32 mmHg, p < 0,001) como del grupo de sal común (PAS: -10,98 mmHg, p < 0,001; PAD: -5,24 mmHg, p = 0,001) disminuyó significativamente con una disminución más pronunciada en el grupo bajo en sodio pero sin diferencias estadísticamente significativas entre los dos grupos (PAS: -0,28 mmHg, p = 0,929; PAD: -3,32 mmHg, p = 0,093). Al final de la intervención, la ingesta de sodio disminuyó significativamente, pero la ingesta de potasio aumentó en el grupo bajo en sodio (p < 0,05); sin embargo, el grupo de la sal común no tuvo cambios significativos. Conclusión: la reducción de la ingesta de sodio basada en la dieta DASH modificada tuvo un buen efecto sobre la presión arterial sistólica y diastólica en pacientes hipertensos con diabetes de tipo 2. La reducción de sodio basada en la dieta DASH modificada es segura y eficaz, por lo que puede utilizarse como guía para una vida saludable en pacientes hipertensos (AU)

Respiratory mucosal vaccination of peptide-poloxamine-DNA nanoparticles provides complete protection against lethal SARS-CoV-2 challenge

The ongoing SARS-CoV-2 pandemic represents a brutal reminder of the continual threat of mucosal infectious diseases. Mucosal immunity may provide robust protection at the predominant sites of SARS-CoV-2 infection. However, it remains unclear whether respiratory mucosal administration of DNA vaccines could confer protective immune responses against SARS-CoV-2 challenge due to the insurmountable barriers posed by the airway. Here, we applied self-assembled peptide-poloxamine nanoparticles with mucus-penetrating properties for pulmonary inoculation of a COVID-19 DNA vaccine (pSpike/PP-sNp). Not only displays the pSpike/PP-sNp superior gene-transfection and favorable biocompatibility in the mouse airway, but pSpike/PP-sNp promotes a tripartite immunity consisting of systemic, cellular and mucosal immune responses that are characterized by mucosal IgA secretion, high levels of neutralizing antibodies, and resident memory phenotype T-cell responses in the lungs of mice. Most importantly, pSpike/PP-sNp completely eliminates SARS-CoV-2 infection in both upper and lower respiratory tracts and enables 100% survival rate of mice following lethal SARS-CoV-2 challenge. Our findings indicate PP-sNp might be a promising platform in mediating DNA vaccines to elicit all-around mucosal immunity against SARS-CoV-2.

In Situ Grown Co-Based Interstitial Compounds: Non-3d Metal and Non-Metal Dual Modulation Boosts Alkaline and Acidic Hydrogen Electrocatalysis.

Interfacial engineering and elemental doping are the two parameters to enhance the catalytic behavior of cobalt nitrides for the alkaline hydrogen evolution reaction (HER). However, simultaneously combining these two parameters to improve the HER catalytic properties of cobalt nitrides in alkaline media is rarely reported and also remains challenging in acidic media. Herein, it is demonstrated that high-valence non-3d metal and non-metal integration can simultaneously achieve Co-based nitride/oxide interstitial compound phase boundaries on stainless steel mesh (denoted Mo-Co5.47 N/N-CoO) for efficient HER in alkaline and acidic media. Density functional theory (DFT) calculations show that the unique structure does not only realize multi-active sites, enhanced water dissociation kinetics, and low hydrogen adsorption free energy in alkaline media, but also enhances the positive charge density of hydrogen ions (H+ ) to effectively allow H+ to receive electrons from the catalysts surface toward promoting the HER in acidic media. As a result, the as-prepared Mo-Co5.47 N/N-CoO demands HER overpotential of -28 mV@10 mA cm-2 in an alkaline medium, and superior to the commercial Pt/C at a current density > 44 mA cm-2 in acidic medium. This work paves a useful strategy to design efficient cobalt-based electrocatalysts for HER and beyond.

Effect of hierarchical and phased teaching method on the teaching of neurosurgery interns / 中华医学教育探索杂志

Objective:To explore the teaching effect of hierarchical and phased teaching method on the teaching of neurosurgery interns.Methods:Thirty-five interns of the Department of Neurosurgery of The First People's Hospital of Liangshan Yi Autonomous Prefecture from July 2019 to March 2020 were selected as the control group, and received the traditional clinical teaching method. Another 34 interns from June 2020 to February 2021 were selected as the research group, and adopted the hierarchical and phased teaching method. The graduation examination results were compared, and the scores of mini-clinical evaluation exercise (Mini-CEX) scale before and after practice and the recognition of teaching methods by interns were compared. SPSS 24.0 was used for t test and chi-square test. Results:The results of theoretical knowledge of neurosurgery [(90.15±4.47) points], operation skills [(91.12±3.68) points] and clinical case analysis ability [(87.32±5.41) points] in the study group were higher than those in the control group [(85.26±5.19) points, (86.14±5.25) points and (80.94±4.26) points], and the differences were statistically significant ( P<0.001). The scores of Mini-CEX scale in the two groups after internship were both higher than those before internship ( P<0.001), which in the study group after internship were higher than those in the control group ( P<0.001). The recognition of the teaching method in improving the learning interest and enthusiasm, strengthening the ability to master knowledge, improving the ability to analyze and deal with clinical problems, improving the ability to combine theoretical knowledge with practice and improving the clinical thinking ability of interns in the study group were higher than those in the control group ( P<0.05). Conclusion:In the clinical teaching of neurosurgery interns, the application of hierarchical and phased teaching method can significantly improve the comprehensive assessment ability and professional quality of interns, and can also improve their recognition of this teaching method.

Comparison between Ultrasonography and CT in Diagnosis of Cervical Lymph Node Metastasis of Papillary Thyroid Carcinoma / 中国医学科学院学报

Objective To evaluate the efficacy of ultrasound and computed tomography (CT) in diagnosing cervical lymph node metastasis (CLNM) of papillary thyroid carcinoma (PTC). Methods The patients with PTC treated by surgery in the Chinese PLA General Hospital from January 2016 to January 2021 were selected for analysis.All the patients underwent preoperative ultrasound and CT examinations,the diagnostic values of which for CLNM were retrospectively analyzed. Results A total of 322 PTC patients were enrolled in this study,including 242 with CLNM and 80 with non-CLNM.The CLNM group and non-CLNM group had significant differences in age,tumor size,and maximum size of lateral CLNM (χ2=20.34,27.34,and 4.30,respectively,all P<0.001).For the central compartment,lateral compartment,and overall compartment,ultrasound diagnosis showed higher sensitivity (χ 2=82.26,P<0.001;χ2=114.01,P<0.001;χ2=82.26,P<0.001) and accuracy (χ2=20.27,P<0.001;χ2=15.56,P<0.001;χ2=44.00,P<0.001) than CT,and had no significant differences from ultrasound combined with CT (all P>0.05).However,ultrasound diagnosis had lower specificity than CT (χ2=17.01,P<0.001;χ2=21.29,P<0.001) in the central compartment and lateral compartment.Receiver operating characteristic curve analysis showed that in the central compartment,lateral compartment,and overall compartment,ultrasound diagnosis had larger AUC than CT (Z=2.99,P=0.003;Z=3.86,P<0.001;Z=4.47,P<0.001) and had no significant difference from ultrasound combined with CT (Z=1.87,P=0.062;Z=1.68,P=0.093;Z=1.61,P=0.107). Conclusions Ultrasound and CT have their own advantages in the diagnosis of central and lateral CLNM.In general,ultrasound has better performance than CT in the diagnosis of CLNM.

Protective association of Klotho rs495392 gene polymorphism against hepatic steatosis in non-alcoholic fatty liver disease patients

Background/Aims@#Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic dysfunction. Among the multiple factors, genetic variation acts as important modifiers. Klotho, an enzyme encoded by the klotho (KL) gene in human, has been implicated in the pathogenesis of metabolic dysfunctions. However, the impact of variants in KL on NAFLD risk remains poorly understood. The aim of this study was to investigate the impact of KL rs495392 C>A polymorphism on the histological severity of NAFLD. @*Methods@#We evaluated the impact of the KL rs495392 polymorphism on liver histology in 531 Chinese with NAFLD and replicated that in the population-based Rotterdam Study cohort. The interactions between the rs495392, vitamin D, and patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 polymorphism were also analyzed. @*Results@#Carriage of the rs495392 A allele had a protective effect on steatosis severity (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.42–0.89; P=0.010) in Chinese patients. After adjustment for potential confounders, the A allele remained significant with a protective effect (OR, 0.66; 95% CI, 0.45–0.98; P=0.040). The effect on hepatic steatosis was confirmed in the Rotterdam Study cohort. Additional analysis showed the association between serum vitamin D levels and NAFLD specifically in rs495392 A allele carriers, but not in non-carriers. Moreover, we found that the rs495392 A allele attenuated the detrimental impact of PNPLA3 rs738409 G allele on the risk of severe hepatic steatosis. @*Conclusions@#The KL rs495392 polymorphism has a protective effect against hepatic steatosis in patients with NAFLD.

Application value of imaging examination in the diagnosis of Muller-Weiss disease / 中国骨伤

OBJECTIVE@#To analyze radiological characteristics of Muller-Weiss disease, evaluate the clinical value of the imaging examination in diagnosis of Muller-Weiss disease.@*METHODS@#The imaging data of 26 patients with Muller-Weiss disease were collected from September 2015 to August 2020, including 7 males and 19 females, aged 43 to 68 years old with an average of (52.7±4.6) years old. In the X-ray examination observed the shape and position of the navicular bone. The talar-first metatarsal angle(TFM) was measured on the weight-bearing anteroposterior radiograph. The arch angle and angle between mid-axis of talus and mid-axis of the first metatarsal(Meary angle) were measured on the weight-bearing lateral radiographs. The morphology, density, adjacent joint space and position of the navicular bone were evaluated by computed tomography(CT), and magnetic resonance imaging(MRI) was used to observe the shape, signal, cartilage and surrounding soft tissue changes of the navicular bone.@*RESULTS@#Among 26 patients, 21 cases were unilateral and 5 cases were bilateral;X-ray examination showed that the lateral part of navicular bone of foot was compressed and flattened, showing"comma like"or"drop like", navicular moved to the medial side, partial fragmentation of bone, peripheral articular hyperplasia, uneven density and narrowing of relationship gap. According to Meary angle and deformity degree of the affected foot on the lateral X-ray of the load-bearing foot, Maceira staging was performed. There were 0 cases in stageⅠ, 2 cases in stage Ⅱ, 11 cases in stage Ⅲ, 9 cases in stage Ⅳand 4 cases in stage Ⅴ. CT examination showed bone fragmentation, medial displacement of navicular bone and formation of the talocalcaneal joint. MRI examination showed the irregular shape and uneven signal of navicular bone, narrowing of joint space, talocalcaneal joint surface hyperplasia and cartilage destruction, tarsal joint effusion and swelling of surrounding soft tissue.@*CONCLUSION@#Muller-Weiss disease has specific imaging manifestation, and an accurate diagnosis can be made based on the patient's age, gender, and clinincal history. Preoperative imaging examination can stage the disease, help clinicians to formulate better surgical plans, and postoperative imaging examination can better evaluate the surgical effect.

Comparison of the long-term outcomes of focused ultrasound ablation surgery for uterine fibroids and myomectomy / 中华妇产科杂志

Objective:To compare the long-term outcomes after focused ultrasound ablation surgery (FUAS) versus myomectomy for uterine fibroids.Methods:A retrospective study was conducted on women who were treated by FUAS or myomectomy for uterine fibroids at First Medical Center of Chinese PLA General Hospital from January 2007 to January 2015. Regular follow-up was conducted to evaluate the symptoms relief, symptoms recurrence, the need for re-interventions and complications of the two groups.Results:The effective rates were 95.7% (730/763) and 95.5% (1 151/1 205) in women who were treated by FUAS and myomectomy, no statistical difference was seen between the two groups ( χ2 =0.027, P=0.869). The cumulative rates of symptoms recurrence at 1 year, 3 years, 5 years, 8 years and 10 years of follow-up in FUAS group were 1.8%, 6.8%, 11.9%, 15.2% and 15.9%, respectively; and the cumulative re-intervention rates were 0.7%, 4.1%, 6.8%, 9.9% and 11.0%, respectively. The cumulative rates of symptoms recurrence at 1 year, 3 years, 5 years, 8 years and 10 years of follow-up in myomectomy group were 1.8%, 5.9%, 10.6%, 14.2% and 14.9%, respectively; and the cumulative re-intervention rates were 0.9%, 4.5%, 7.8%, 10.3% and 11.4%, respectively. No statistical differences were seen between the two groups (all P>0.05). There were no significant differences in the effective rate, symptoms recurrence rate and re-intervention rate between the two groups in patients with intermural fibroids; but the effective rate of FUAS (95.9%, 235/245) was higher than that of myomectomy (89.1%, 115/129), the symptoms recurrence rate (11.9%, 28/235) was lower than that of myomectomy (27.8%, 32/115), and the re-intervention rate (7.7%, 18/235) was lower than that of myomectomy (17.4%, 20/115) in patients with submucosal fibroids, there were significant different (all P<0.05). The effective rate of FUAS (91.0%, 132/145) was lower than that of myomectomy (97.0%, 322/332), the symptoms recurrence rate (32.6%, 43/132) was higher than that of myomectomy (9.9%, 32/322), and the re-intervention rate (22.0%, 29/132) was higher than that of myomectomy group (6.2%, 20/132) in patients with subserosal fibroids, there were significant different (all P<0.01). The incidences of total [1.8% (14/763) vs 21.9% (264/1 205)], minor and moderate adverse events were lower in FUAS group than myomectomy group (all P<0.001). Conclusion:Satisfaction with long-term outcomes after FUAS treatment or myomectomy for uterine fibroids is comparable.

Expression profile and clinical significance of miRNA in children with autism spectrum disorder / 中国医师杂志

Objective:The purpose of this study was to analyze the expression profile of miRNAs in children with autism spectrum disorders (ASD), and to discuss the clinical significance of differentially expressed miRNAs.Methods:MiRNA microarray was used to analyze the expression of miRNA in peripheral blood of 3 pairs of ASD patients-healthy controls; 17 pairs of ASD patients-healthy controls were used to verify the differentially expressed miRNA; Receiver operating characteristic (ROC) curve was used to analyze the differential expression the value of miRNA in the diagnosis of ASD.Results:A total of 32 differentially expressed genes were screened by 3 pairs of miRNA microarray including 12 up-regulated miRNAs and 20 down-regulated miRNAs. miRNA verification of 20 differentially expressed miRNAs showed miR-15a-5p, miR-27a-3p , miR-142-3p and miR-142-5p were significantly down-regulated in children with ASD, with statistically significant difference (all P<0.05). ROC curve analysis showed that the area under the curve (AUC) of the above four miRNAs diagnosing ASD were all greater than 0.70, with sensitivities 94.12%, 100%, 100%, and 82.35%, respectively. Conclusions:The expression of miR-142-3p, miR-27a-3p/miR-15a-5p, and miR-142-5p is down-regulated in the peripheral blood of ASD patients, and has the potential as biomarkers for early screening of ASD.