Activation of the osteoblastic HIF-1α pathway partially alleviates the symptoms of STZ-induced type 1 diabetes mellitus via RegIIIγ.

The hypoxia-inducible factor-1α (HIF-1α) pathway coordinates skeletal bone homeostasis and endocrine functions. Activation of the HIF-1α pathway increases glucose uptake by osteoblasts, which reduces blood glucose levels. However, it is unclear whether activating the HIF-1α pathway in osteoblasts can help normalize glucose metabolism under diabetic conditions through its endocrine function. In addition to increasing bone mass and reducing blood glucose levels, activating the HIF-1α pathway by specifically knocking out Von Hippel‒Lindau (Vhl) in osteoblasts partially alleviated the symptoms of streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM), including increased glucose clearance in the diabetic state, protection of pancreatic ß cell from STZ-induced apoptosis, promotion of pancreatic ß cell proliferation, and stimulation of insulin secretion. Further screening of bone-derived factors revealed that islet regeneration-derived protein III gamma (RegIIIγ) is an osteoblast-derived hypoxia-sensing factor critical for protection against STZ-induced T1DM. In addition, we found that iminodiacetic acid deferoxamine (SF-DFO), a compound that mimics hypoxia and targets bone tissue, can alleviate symptoms of STZ-induced T1DM by activating the HIF-1α-RegIIIγ pathway in the skeleton. These data suggest that the osteoblastic HIF-1α-RegIIIγ pathway is a potential target for treating T1DM.

Prognostic implications of machine learning-derived echocardiographic phenotypes in community hypertensive patients.

BACKGROUND: Echocardiogram is commonly used to evaluate cardiac remodeling in hypertension (HTN). However, study on echocardiographic phenotypes and their prognostic implications in HTN is limited. OBJECTIVE: We aimed to evaluate the prognostic implications echocardiographic phenotypes in community hypertensive patients. METHOD: A total of 1881 community hypertensive patients without overt cardiovascular disease and severe renal disease (mean age 62.8 years, women 57.9%) were included. Using Two-Step cluster analysis with four conventional echocardiographic variables, two clusters with distinct echocardiographic phenotypes were identified. RESULT: The Cluster 1 (namely "mild-remodeling" HTN; n = 1492) had low prevalence of enlarged left atrium (LA; 0.9%) and left ventricular hypertrophy (LVH; 16.2%) and better LV diastolic function. They were younger and more likely to be men and had lower comorbid burden. The Cluster 2 (namely "severe-remodeling" HTN; n = 389) had higher prevalence of enlarged LA (26.0%) and LVH (83.0%) and worse LV diastolic function. They were older and more likely to be women and had higher comorbid burden. After a median follow-up of 4.2 years, compared to the Cluster 1, the Cluster 2 had higher incidence of cardiovascular (4.1% vs 1.7%; P = .006) and all-cause (9.8% vs 4.8%; P < .001) death, with adjusted hazard ratio of 2.80 (95% CI 1.39-5.62; P = .004) and 2.04 (95% CI 1.32-3.14; P < .001) respectively. CONCLUSION: These findings indicate that the conventional echocardiographic variables-based algorithm could help identify asymptomatic community hypertensive patients at risk for cardiovascular and all-cause death. Further studies are needed to develop and validate phenotype-specific prevention and intervention strategies in HTN.

A cross-sectional study of clinical emergency department nurses' occupational stress, job involvement and team resilience.

INTRODUCTION: The occupational stress of clinical nurses has drawn increasing attention. It has been proven that occupational stress is related to job involvement, and job involvement affects team resilience. However, research on the relationship between emergency nurses' occupational stress, job involvement and team resilience is lacking. AIM: To explore relationships between occupational stress, job involvement, and team resilience among a sample of emergency nurses and determined significant influencing factors of occupational stress in emergency departments. METHODS: In four hospitals in Shandong, China, 187 emergency room nurses participated in a study. The Utrecht Work Engagement Scale, the Chinese version of the Stressors Scale for Emergency Nurses, and a scale for evaluating the team resilience of medical professionals were used to collect data. RESULTS: The overall occupational stress score of nurses working in the emergency departments in Shandong province was 81.07 ± 25.80. The results of Single-factor analysis demonstrated that the scores indicating the occupational stress for emergency nurses differed significantly with respect to age, education level, marital status, children, professional title, work experience and work shift (P < 0.05). Additionally, there is a negative correlation between job involvement and team resilience and occupational stress. Multiple linear regression results showed that the job involvement, team resilience and work shift were statistically significant influencing factors of the level of occupational stress (change R2 = 17.5 %, F = 5.386, P < 0.001). CONCLUSIONS: Stronger team resilience and more active job involvement resulted in lower occupational stress levels experienced by emergency nurses.

Chinese version of the stressor scale for emergency nurse: A methodological study design.

AIM: The aim of this study was to modify and test the psychometric properties of the Chinese version of the stressor scale for emergency nurses. DESIGN: The methodological design was carried out in two phases: (a) form the Chinese version by Delphi method and (b) test the psychometric properties by cross-sectional survey. METHODS: The translated scale was administered to 420 nurses in Qingdao. Validity was assessed in terms of content validity, calibration correlation validity and construct validity using exploratory factor analysis and confirmatory factor analysis. Internal consistency was estimated using Cronbach α coefficients. RESULTS: The Chinese version of the SSEN retains 27 items, four common factors were extracted by exploratory factor analysis, and the factor cumulative variance contribution rate was 78.463%. The fitting indexes of the four-factor model of CFA were all in the acceptable range[χ2  = 711.30, df = 312, p < 0.001, χ2 /df = 2.280, CFI = 0.933, TLI = 0.924, IFI = 0.933, RMSEA = 0.079 (90% confidence interval = 0.071-0.086)].The item-level content validity index of the Chinese SSEN is 0.89 ~ 1.00; the scale-level content validity index is 0.98; the Cronbach α coefficient of the total table is 0.971 and the split-half reliability is 0.877. PATIENT OR PUBLIC CONTRIBUTION: The C-SSEN can be used to help nursing managers accurately formulate management measures to improve the stress coping ability of nurses in the ED, stabilize the nursing team and ensure nursing safety.

Establishment of a method for separating macrophage migrasomes / 细胞与分子免疫学杂志

Objective To establish an efficient method for isolating migrasomes from RAW264.7 macrophages and identifying these isolated migrasomes. Methods Scanning electron microscopy was used to observe the morphological characteristics of migrasomes produced by RAW264.7 cells. A 0.45 μm filter was employed for reverse filtration and elution to isolate the migrasomes. The morphological characteristics of the migrasomes were then observed using transmission electron microscopy. Western blot analysis was performed to determine the expression of characteristic markers of the migrasomes. The RNA carried by the migrasomes was analysed by using LabChip bioanalyzer. Results Scanning electron microscopy revealed that the migrasomes, with membranous structures, were attached to the tip or bifurcation of the retraction fiber formed in the tail of RAW264.7 cells. Transmission electron microscopy showed that the isolated migrasomes had a typical oval vesicle-like structure with wrinkled membrane surfaces. Western blot analysis confirmed the expression of the characteristic markers phosphatidylinositol glycan anchor biosynthesis class K (PIGK), epidermal growth factor domain-specific O-linked N-acetylglucosamine transferase (EOGT) and tetraspanin 4 (TSPAN4) in the migrasomes, while the EV (extracellular vesicle) markers tumor susceptibility gene 101 (TSG101) and Arabidopsis homolog of apoptosis-linked gene 2-interacting protein X (ALIX) were not detected. Furthermore, the isolated migrasomes were found to be rich in small RNA, which were approximately 25-200 nt in length. Conclusion A method for the extraction of well-structured and high quality migrasomes from macrophages is established.

Novel Effect of Hyaluronan and Proteoglycan Link Protein 1(HAPLN1) on Hair Follicle Cells Proliferation and Hair Growth

Hair loss is a common condition that can have a negative impact on an individual’s quality of life. The severe side effects and the low efficacy of current hair loss medications create unmet needs in the field of hair loss treatment. Hyaluronan and Proteoglycan Link Protein 1 (HAPLN1), one of the components of the extracellular matrix, has been shown to play a role in maintaining its integrity. HAPLN1 was examined for its ability to impact hair growth with less side effects than existing hair loss treatments. HAPLN1 was predominantly expressed in the anagen phase in three stages of the hair growth cycle in mice and promotes the proliferation of human hair matrix cells. Also, recombinant human HAPLN1 (rhHAPLN1) was shown to selectively increase the levels of transforming growth factor-β receptor II in human hair matrix cells. Furthermore, we observed concomitant activation of the ERK1/2 signaling pathway following treatment with rhHAPLN1. Our results indicate that rhHAPLN1 elicits its cell proliferation effect via the TGF-β2-induced ERK1/2 pathway. The prompt entering of the hair follicles into the anagen phase was observed in the rhHAPLN1-treated group, compared to the vehicle-treated group. Insights into the mechanism underlying such hair growth effects of HAPLN1 will provide a novel potential strategy for treating hair loss with much lower side effects than the current treatments.

A Novel Role of Hyaluronic Acid and Proteoglycan Link Protein 1(HAPLN1) in Delaying Vascular Endothelial Cell Senescence

Cardiovascular diseases (CVDs) are the most common cardiovascular system disorders. Cellular senescence is a key mechanism associated with dysfunction of aged vascular endothelium. Hyaluronic acid and proteoglycan link protein 1 (HAPLN1) has been known to non-covalently link hyaluronic acid (HA) and proteoglycans (PGs), and forms and stabilizes HAPLN1-containing aggregates as a major component of extracellular matrix. Our previous study showed that serum levels of HAPLN1 decrease with aging. Here, we found that the HAPLN1 gene expression was reduced in senescent human umbilical vein endothelial cells (HUVECs). Moreover, a recombinant human HAPLN1 (rhHAPLN1) decreased the activity of senescence-associated β-gal and inhibited the production of senescence-associated secretory phenotypes, including IL-1β, CCL2, and IL-6. rhHAPLN1 also downregulated IL-17A levels, which is known to play a key role in vascular endothelial senescence. In addition, rhHAPLN1 protected senescent HUVECs from oxidative stress by reducing cellular reactive oxygen species levels, thus promoting the function and survival of HUVECs and leading to cellular proliferation, migration, and angiogenesis. We also found that rhHAPLN1 not only increases the sirtuin 1 (SIRT1) levels, but also reduces the cellular senescence markers levels, such as p53, p21, and p16. Taken together, our data indicate that rhHAPLN1 delays or inhibits the endothelial senescence induced by various aging factors, such as replicative, IL-17A, and oxidative stress-induced senescence, thus suggesting that rhHAPLN1 may be a promising therapeutic for CVD and atherosclerosis.

Anti-vascular endothelial growth factor treatment in X-linked retinoschisis with vitreous hemorrhage / 中华眼底病杂志

Objective:To review the outcome of intravitreous anti-vascular endothelial growth factor (VEGF) treatment in patients with X-linked retinoschisis (XLRS) complicated with vitreous hemorrhage (VH).Methods:A retrospective clinical study. From March 1, 2016 to April 1, 2022, 18 patients (19 eyes) diagnosed with XLRS complicated with vitreous hemorrhage in Beijing Tongren Hospital, Capital Medical University of Eye Center were included. All the patients were male, with a median age of 7.05±3.8 years. Best corrected visual acuity (BCVA) and wide-angle fundus photography were performed in all the patients. BCVA was carried out using international standard visual acuity chart, and converted into logarithm of minimum resolution angle (logMAR) in statistics analysis. According to whether the patients received intravitreal injection of ranibizumab (IVR), the patients were divided into injection group and observation group, with 11 eyes in 10 cases and 8 eyes in 8 cases, respectively. In the injection group, 0.025 ml of 10 mg/ml ranibizumab (including 0.25 mg of ranibizumab) was injected into the vitreous cavity of the affected eye. Follow-up time after treatment was 24.82±20.77 months. The VH absorption time, visual acuity changes and complications were observed in the injection group after treatment. Paired sample t test was used to compare BCVA before and after VH and IVR treatment. Independent sample t test was used to compare the VH absorption time between the injection group and the observation group. Results:LogMAR BCVA before and after VH were 0.73±0.32 and 1.80±0.77, respectively. BCVA decreased significantly after VH ( t=-3.620, P=0.006). LogMAR BCVA after VH and IVR were 1.87±0.55 and 0.62±0.29, respectively. BCVA was significantly improved after IVR treatment ( t=6.684, P<0.001). BCVA records were available in 5 eyes before and after IVR, and the BCVA values after VH and IVR were 0.58±0.31 and 0.48±0.20, respectively, with no statistically significant difference ( t=1.000, P=0.374). BCVA increased in 1 eye and remained unchanged in 4 eyes after treatment. BCVA records were available in 5 eyes before VH and after VH absorption in the 8 eyes of the observation group. LogMAR BCVA before VH and after VH absorption were 0.88±0.28 and 0.90±0.26, respectively, with no significant difference ( t=-1.000, P=0.374). After VH absorption, BCVA remained unchanged in 4 eyes and decreased in 1 eye. The absorption time of VH in the injection group and the observation group were 1.80±1.06 and 7.25±5.04 months, respectively. The absorption time of VH was significantly shorter in the injection group than in the observation group, the difference was statistically significant ( t=-3.005, P=0.018). Multivariate linear regression analysis showed that IVR treatment was significantly correlated with VH absorption time ( B=-6.66, 95% confidence interval -10.93--2.39, t=-3.40, P=0.005). In the injection group, VH recurrence occurred in 1 eye after IVR treatment. Vitrectomy (PPV) was performed in one eye. In the 8 eyes of the observation group, VH recurrence occurred in 2 eyes, subsequent PPV in 1 eye. The rate of VH recurrence and PPV was lower in the injection group, however, the difference was not statistically significant( P=0.576, 1.000). In terms of complications, minor subconjunctival hemorrhage occurred in 2 eyes and minor corneal epithelial injury occurred in 1 eye in the injection group, and all recovered spontaneously within a short time. In the injection group, 9 eyes had wide-angle fundus photography before and after IVR treatment. There was no significant change in the range of peripheral retinoschisis after treatment. No obvious proliferative vitreoretinopathy, infectious endophthalmitis, retinal detachment, macular hole, complicated cataract, secondary glaucoma or other serious complications were found in all the treated eyes, and there were no systemic complications. Conclusion:Intravitreous anti-VEGF treatment may accelerate the absorption of vitreous hemorrhage in patients with XLRS. No impact is found regarding to the peripheral retinoschisis.

Distinguish mild cognitive impairment and normal cognitive change by β-amyloid PET imaging / 中华核医学与分子影像杂志

Objective:To explore the association of the impaired cognition and the deposition of β-amyloid (Aβ) in normal cognitive (NC) and mild cognitive impairment (MCI).Methods:From December 2018 to January 2021, 305 subjects (113 males, 192 females; age (64.0±7.7) years) who completed neuropsychological tests and MRI in Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University and 18F-florbetapir (AV45) PET imaging in Huashan Hospital, Fudan University were retrospectively analyzed. The subjects were divided into MCI group and NC group based on neuropsychological tests, and each group was further divided into Aβ-positive and Aβ-negative based on PET imaging results. Independent-sample t test, Mann-Whitney U test and χ2 test were used to analyze the data. Results:There were 118 subjects in MCI group and 187 subjects in NC group. The Aβ-positive rate in MCI group (37.3%, 44/118) was higher than that in NC group (26.2%, 49/187; χ2=4.19, P=0.041). The assessment performances of MCI group in general cognitive function, memory function, language function and executive function were inferior to those of NC group ( t values: from -10.63 to -6.31, z values: from -11.01 to -6.03, all P<0.001). The Auditory Verbal Learning Test-Long Delay Recall (AVLT-LDR) score of Aβ-positive subjects was lower than that of Aβ-negative subjects in MCI group (1.00(0.00, 3.00) and 3.00(1.00, 4.00); z=-2.49, P=0.013). The Montreal Cognitive Assessment Basic (MoCA-B) score of Aβ-positive subjects was lower than that of Aβ-negative subjects in NC group (25.29±2.67 and 26.36±2.42; t=-2.61, P=0.010). Conclusion:Compared to Aβ-negative subjects, MCI patients with Aβ-positive perform worse on memory tests, and NC subjects with Aβ-positive perform worse on general cognitive function.

Value of three-dimensional CT in the diagnosis of cricoarytenoid dislocation / 中华放射学杂志

Objective:To investigate the value of three-dimensional (3D) CT in diagnosing cricoarytenoid dislocation.Methods:From January 2021 to December 2021, 31 patients with unilateral cricoarytenoid dislocation who had been treated by reduction forceps at the Affiliated BenQ Hospital of Nanjing Medical University were collected retrospectively, and their voice recovered or improved significantly after therapy. The preoperative CT images were reconstructed by volume rendering (VR). The dislocated side (left and right), type of dislocation (total dislocation and subluxation), and dislocation direction (anterior, posterior, internal and external dislocation) of cricoarytenoid dislocation were observed. According to arytenoid articular surface of cricoid cartilage exposed completely or not (caused by arytenoid displacement), they were divided into complete dislocation and subluxation. According to the direction of arytenoid displacement and the part of arytenoid articular surface of cricoid cartilage exposed, they were divided into anterior, posterior, internal and external dislocation. According to the shape of the vocal cords on laryngoscope, anterior and posterior dislocation of each case was judged, and then compared with that of CT.Results:On VR images, there were 28 cases of cricoarytenoid subluxation (90.3%, 28/31) and 3 cases of complete dislocation (9.7%, 3/31). Left cricoarytenoid dislocation was 26 cases (83.9%, 26/31) and right cricoarytenoid dislocation was 5 cases (16.1%, 5/31). Posterior dislocation was 28 cases (90.3%, 28/31) and anterior dislocation was 3 cases (9.7%, 3/31). There were 23 cases of internal dislocation (74.2%, 23/31), 2 cases of external dislocation (6.4%, 2/31), and 6 cases without obvious internal and external dislocation (19.4%, 6/31). Three cases of complete dislocation were left posterior internal dislocation.There were 24 cases of left posterior dislocation (77.4%, 24/31), 4 cases of right posterior dislocation (12.9%, 4/31), 2 cases of left anterior dislocation (6.4%, 2/31) and 1 case of right anterior dislocation (3.2%, 1/31). On laryngoscope, there were 19 cases of posterior dislocation (61.3%, 19/31), 9 cases of anterior dislocation (29.0%, 9/31), 3 cases were difficult to assess (9.7%, 3/31) because of aryepiglottic fold covering. Sixteen cases (55.2%, 16/28) were consistent with 3D CT, and 12 cases (42.8%, 12/28) were inconsistent.Conclusion:The 3D CT is a reliable method to evaluate cricoarytenoid dislocation, which can show dislocated side, type and direction of cricoarytenoid dislocation clearly.

Effects of colpotomic approaches on prognosis and recurrence sites of stage Ⅰa2-Ⅱa2 cervical cancer after laparoscopic radical hysterectomy / 中华妇产科杂志

Objective:To investigate the factors affecting the prognosis of stage Ⅰa2-Ⅱa2 cervical cancer after laparoscopic radical hysterectomy (LRH), and to compare the prognosis and recurrence sites of patients with different colpotomy paths.Methods:The clinical data of 965 patients with stage Ⅰa2-Ⅱa2 cervical cancer who underwent LRH in the First Affiliated Hospital of Army Medical University from January 2015 to December 2018 were collected. The median age was 47.0 years of all patients with a median follow-up of 62 months (48-74 months). Cox regression was used to perform the univariate and multivariate analysis of the clinicopathological factors associated with the prognosis that included disease-free survival (DFS) and overall survival (OS). Patients were categorized into LRH through vaginal colpotomy (VC group, n=475) and LRH through intracorporeal colpotomy (IC group, n=490) according to the colpotomic approaches. The prognosis and recurrence sites of patients in each group were compared. Results:(1) During the follow-up period, 137 cases recurred (14.2%, 137/965) and 98 cases died (10.2%, 98/965). The 5-year DFS and OS were 85.8% and 89.9%, respectively. In univariate analysis, positive vaginal margin (PVM) was significantly affected the 5-year OS of patients with cervical cancer ( P=0.023), while clinical stage, maximum diameter of tumor, degree of pathological differentiation, lymph node metastasis (LNM), depth of cervical stromal invasion, parametrium involvement, and uterine corpus invasion (UCI) were significantly associated with 5-year DFS and OS in patients with cervical cancer (all P<0.05). In multivariate analysis, clinical stage ( HR=1.882, 95% CI: 1.305-2.716), LNM ( HR=2.178, 95% CI: 1.483-3.200) and UCI ( HR=3.650, 95% CI: 1.906-6.988) were independent risk factors of 5-year DFS (all P<0.001). Clinical stage ( HR=2.500, 95% CI: 1.580-3.956), LNM ( HR=2.053, 95% CI: 1.309-3.218), UCI ( HR=3.984, 95%C I: 1.917-8.280), PVM ( HR=3.235, 95% CI: 1.021-10.244) were independent risk factors of 5-year OS (all P<0.05). (2) Different colpotomy paths did not significantly affect the 5-year DFS and OS of patients with stage Ⅰa2-Ⅱa2 cervical cancer. The 5-year DFS in VC group and IC group were 85.9% and 85.6% ( P=0.794), and the 5-year OS were 90.8% and 89.3% ( P=0.966), respectively. Recurrence patterns consisted of intraperitoneal recurrence, pelvic recurrence, vaginal stump recurrence, and lymph node and distant metastasis. The intraperitoneal recurrence rate of VC group was significantly lower than that of IC group [0.6%(3/468) vs 2.3% (11/485), P=0.037], while the rates of pelvic recurrence, vaginal stump recurrence, lymph node and distant metastasis and overall recurrence were not significantly different between two groups (all P>0.05). Subgroup analysis of patients with different clinical stages, LNM and UCI showed that statistical differences of the intraperitoneal recurrence rates between two groups were only in patients without LNM (0.5% vs 2.3%, P=0.030) or without UCI (0.7% vs 2.3%, P=0.037). Conclusions:Clinical stage, LNM, PVM and UCI are independent risk factors for the prognosis of patients with stage Ⅰa2-Ⅱa2 cervical cancer. For patients without LNM or UCI, LRH through VC could reduce the intraperitoneal recurrence rate, while it is not enough to improve 5-year DFS and OS of patients. Low proportion of intraperitoneal recurrence, intra-operative tumor cells spillage to vagina stump and pelvic cavity might be the explanation.

Application of the fetal adrenal volume evaluated by three-dimensional ultrasound in fetuses with intrauterine growth restriction and its correlation with adverse perinatal outcomes / 中华超声影像学杂志

Objective:To evaluate the fetal adrenal gland volume (AGV) and corrected adrenal gland volume (cAGV) in intrauterine growth restriction (IUGR) fetuses and observe their associations with the adverse perinatal outcomes.Methods:From February 2021 to August 2022, 32 IUGR fetuses who underwent fetal ultrasound examination in the Second Xiangya Hospital of Central South University were prospectively selected as the IUGR group, and 32 normal fetuses matched for gestational age during the same period were selected as the control group. Three-dimensional ultrasound was used to obtain fetal adrenal volume images, and the virtual organ computer-aided analysis (VOCAL) was used to measure AGV, then the cAGV was calculated. The values of AGV and cAGV were appropriately compared between the IUGR and the control groups. The pregnancy outcomes were noted. Multiple logistic regression analysis was employed to evaluate the relationship between the cAGV and adverse perinatal outcomes in IUGR fetus, with maternal age and the CPR included as covariates to control for confounding factors.Results:A total of 32 fetuses with IUGR and 32 controls were involved in this prospective study. There was no significant difference in the AGV between these two groups ( P=0.417). The cAGV of the IUGR fetus was substantially larger than that of the normal fetus ( P=0.034). In the multivariate logistic regression analysis, after adjusting for maternal age and fetal CPR, the fetal cAGV was noticeably associated with the fetal distress (adjusted OR=0.005, 95% CI=0.000-0.587, P=0.029) and the total adverse perinatal outcomes (adjusted OR=0.014, 95% CI=0.000-0.475, P=0.018). Conclusions:The value of cAGV is increased in the IUGR fetuses and associated with adverse perinatal outcomes. The evaluation of fetal AGV could be beneficial to monitoring and managing IUGR fetuses.

Chinese version of the stressor scale for emergency nurse: assessment of reliability and validity / 中国实用护理杂志

Objective:To translate the Stressor Scale for Emergency Nurse (SSEN), and to test the reliability and validity of the Chinese version.Methods:According to the Brislin model to translate and back-translate the orginal English version, the Chinese version of the scale was determined after cross-cultural adaptation and pretesting. From October 2021 to January 2022, 401 emergency nurses in the Affiliated Hospital of Qingdao University were selected for a questionnaire survey to evaluate the reliability and validity of the translated Chinese scale.Results:The Chinese version of the SSEN retains 27 items, 4 common factors were extracted by exploratory factor analysis, and the factor cumulative variance contribution rate was 78.463%. Confirmatory factor analysis showed that χ2/ df=2.280, comparative fitness index=0.933, Tucker-Lewis index=0.924, incremental fit index=0.933, root mean square of approximate residual=0.079, all within the acceptable range. The item-level content validity index of the Chinese SSEN was 0.80-1.00; the scale-level content validity index was 0.97; it was positively correlated with the Maslach Burnout Inventory manual, and the correlation coefficient was 0.456 ( P<0.001); the Cronbach α coefficient of the total table was 0.971, the split-half reliability was 0.877, and the test-retest reliability was 0.958. Conclusions:The Chinese version of the SSEN has good reliability and validity, and it can be used to investgate the occupattional stressors for emergency nurses in the context of Chinese culture.

Effects of angiotensin-converting enzyme on reproduction of Culex pipiens pallens / 中国血吸虫病防治杂志

Objective To investigate the role of angiotensin-converting enzyme (ACE) in the reproduction of Culex pipiens pallens, so as to provide insights into selection of targets for controlling mosquito vector populations. Methods Cx. pipiens pallens was collected from Tangkou County, Shandong Province in 2009. Female and male mosquitoes were selected at 72 hours post-eclosion, and quantitative real-time reverse transcription PCR (qPCR) assay was used to detect the expression of ACE gene in the whole body and reproductive tissues of male mosquitoes and fertilized female mosquitoes before (0 h) and after blood meals (24, 48, 72 h), respectively. Then, 150 female and 150 male mosquitoes at 0 to 4 hours post-eclosion were selected and divided into the wild-type group (WT group), small interfering RNA-negative control group (siNC group) and small interfering RNA-ACE group (siACE group), of 50 mosquitoes in each group. Mosquitoes in the WT group were given no treatment, and mosquitoes in the siNC and siACE groups were given microinjection of siNC and siACE into the hemolymph at a dose of 0.3 μg per mosquito. The knockdown efficiency was checked using qPCR assay, and the reproductive phenotype of mosquitoes was observed. Results The relative ACE gene expression was higher in the whole body of male mosquitoes (5.467 ± 1.006) relative to females (1.199 ± 0.241) (t = 5.835, P = 0.004) at 72 h post-eclosion, and the highest ACE expression was seen in reproductive tissues of male mosquitoes (199.100 ± 24.429), which was 188.3 times higher than in remaining tissues (1.057 ± 0.340) (t = 6.602, P = 0.002). Blood meal induced high ACE expression in all body tissues of fertilized female mosquitoes, with peak expression at 24 h after blood meals (14.957 ± 2.815), which was 14.8 times higher than that before blood meals (1.009 ± 0.139) (P = 0.002). The transcriptional level of ACEs continued to increase in the ovaries of female mosquitoes after blood meals during the vitellogenesis phase, peaking at 48 h after blood meals (5.500 ± 0.734), which was 5.1 times higher than that before blood meals (1.072 ± 0.178) (P = 0.002). Small RNA interference targeting ACE resulted in a 57.2% reduction in ACE expression in female mosquitoes in the siACE group (0.430 ± 0.070) relative to the siNC group (1.002 ± 0.070) (P = 0.001), and a 41.1% reduction in male mosquitoes in the siACE group (0.588 ± 0.067) relative to the siNC group (1.008 ± 0.131) (P = 0.016). Knockdown of ACE expression resulted in a 48.0% decrease in the number of eggs laid by female mosquitoes in the siACE group [(94.000 ± 27.386) eggs] relative to the siNC group [(180.800 ± 27.386)] (P < 0.001), and a 45.0% decrease in the number of eggs laid by wild female mosquitoes mated with males in the siACE group [(104.500 ± 20.965) eggs] relative to the siNC group [(190.050 ± 10.698) eggs] (P < 0.001). Conclusions Reduced ACE expression may inhibit the fecundity of male and female mosquitoes, and ACE may be as a potential target for mosquito vector population suppression.

Outcome of COVID-19 Infection in Patients With Multiple Sclerosis Who Received Disease-Modifying Therapies: A Systematic Review and Meta-Analysis

Background@#and Purpose A systematic review and meta-analysis was performed of the outcome of Coronavirus disease 2019 (COVID-19) infection in patients with multiple sclerosis (MS) who received disease-modifying therapies (DMTs). @*Methods@#Relevant studies published before November 2022 in the PubMed, Cochrane Library, Chinese National Knowledge Infrastructure, and Web of Science databases were retrieved using the following search expression: (“multiple sclerosis” OR “MS”) AND (“DMT” OR “disease modifying therapies”) AND (“COVID-19”). Two authors independently screened the articles and extracted the data. Qualitative analyses and a meta-analysis constituted 22 of the 794 retrieved articles. Differences in the hospitalization and mortality rates were used as the main measures of efficacy, and the meta-analysis was performed using RevMan software. @*Results@#22 clinical trials were selected. The hospitalization rate was lower in the 3,216 patients who received DMTs than in the 774 patients who did not receive any treatment, with a moderate effect size of 0.43 (p<0.00001). The mortality rate was also lower among patients with MS treated using DMTs than in controls (odds ratio [OR]=0.19, 95% confidence interval [CI]=0.13–0.27, p<0.00001). The hospitalization rates for COVID-19 infection in patients with MS treated with anti-CD20 therapy also increased markedly (OR=3.32, 95% CI=2.63–4.20, p<0.00001). However, there was no significant difference between patients with MS who did and did not receive DMTs. @*Conclusions@#In summary, the application of DMTs was found to be valuable for patients with MS infected with COVID-19. However, more clinical studies are needed to determine the use of anti-CD20 drugs in patients with MS during the COVID-19 pandemic.

Desferrioxamine alleviates UHMWPE particle-induced osteoclastic osteolysis by inhibiting caspase-1-dependent pyroptosis in osteocytes.

BACKGROUND: Cell death and inflammation are the two important triggers of wear particle-induced osteolysis. Particles, including cobalt-chromium-molybdenum and tricalcium phosphate, have been reported to induce pyroptosis in macrophages and osteocytes. Although macrophage pyroptosis facilitates osteoclastic bone resorption and osteolysis, whether osteocyte pyroptosis is involved in osteoclastic osteolysis still needs further investigation. Desferrioxamine (DFO), an FDA-approved medication and a powerful iron chelator, has been proven to reduce ultrahigh-molecular-weight polyethylene (UHMWPE) particle-induced osteolysis. However, whether DFO can ameliorate UHMWPE particle-induced osteolysis by decreasing pyroptosis in osteocytes is unknown. RESULTS: A mouse calvarial osteolysis model and the mouse osteocyte cell line MLO-Y4 was used, and we found that pyroptosis in osteocytes was significantly induced by UHMWPE particles. Furthermore, our findings uncovered a role of caspase-1-dependent pyroptosis in osteocytes in facilitating osteoclastic osteolysis induced by UHMWPE particles. In addition, we found that DFO could alleviate UHMWPE particle-induced pyroptosis in osteocytes in vivo and in vitro. CONCLUSIONS: We uncovered a role of caspase-1-dependent pyroptosis in osteocytes in facilitating osteoclastic osteolysis induced by UHMWPE particles. Furthermore, we found that DFO alleviated UHMWPE particle-induced osteoclastic osteolysis partly by inhibiting pyroptosis in osteocytes. Schematic of DFO reducing UHMWPE particle-induced osteolysis by inhibiting osteocytic pyroptosis. Wear particles, such as polymers, generated from prosthetic implant materials activate canonical inflammasomes and promote the cleavage and activation of caspase-1. This is followed by caspase-1-dependent IL-ß maturation and GSDMD cleavage. The N-terminal fragment of GSDMD binds to phospholipids on the cell membrane and forms holes in the membrane, resulting in the release of mature IL-ß and inflammatory intracellular contents. This further facilitates osteoclastic differentiation of BMMs, resulting in excessive bone resorption and ultimately leading to prosthetic osteolysis. DFO reduces UHMWPE particle-induced osteolysis by inhibiting osteocytic pyroptosis.

SARS-CoV-2 S protein antagonizes type I interferon downstream signal pathway through interacting and attenuating phosphorylation of STAT1/STAT2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may keep patients in a clinically asymptomatic state by blocking cellular innate antiviral immunity, but the molecular mechanism remains unclear. Here, we screened the viral proteins of SARS-CoV-2 and found that the spike (S) protein inhibits the activation of interferon-stimulated genes (ISGs) and even reduces the expression of these genes to below background values. Mechanistically, the S protein interacted with STAT1, STAT2, and IRF9 and impedes the phosphorylation of STAT1/STAT2, thus preventing the formation of the interferon-stimulating gene factor 3 (ISGF3) complex and inhibiting the downstream production of Interferon-stimulated genes (ISGs). Remarkably, we also have found that the inhibitory mechanism of the S protein was conservative among SARS-CoV-2 variants and other human coronaviruses, including SARS-CoV, MERS-CoV, HCoV-229E, HCoV-NL63, and HCoV-HKU1. Truncation studies indicated that the most conserved S2 domain played a major inhibitory role. Altogether, our findings unveil a new mechanism by which SARS-CoV-2 S protein attenuated the hosts antiviral immune response and provide new insights into the pathogenic mechanism of coronavirus.

Impact of probiotics on the lung development of Bama minipig after premature birth / 中华儿科杂志

Objectives: To examine the impact of probiotics on the lung development of preterm birth of Bama pig. Methods: From April 2020 to October 2021, this animal experimental research was performed by setting up preterm (birth at gestation 104 d), full-term (birth at gestation 113 d), preterm with probiotics (birth at gestation 104 d treated with probiotics given at 3 d after birth), and full-term with probiotics (birth at gestation 113 d treated with probiotics given at 3 d after birth) groups and using the preterm Bama minipig model, the body weights were recorded and lung, ileum, and intestinal content samples were collected at birth, 4 days, 9 days, and 21 days after births of the piglets in preterm and full-term groups, the same samples were collected on 9 days after births of the piglets in preterm with probiotics and full-term with probiotics groups. The body weight and radial alveolar counts (RAC) were compared to evaluate the lung development of the piglets. The lengths of ileal villus were compared to evaluate the development of ileum. The composition structures of bacteria in ileum were analyzed by 16 S rRNA sequencing. The statistical analyses between different groups were performed by t test. Results: There were totally 30 piglets (16 female piglets and 14 male piglets) involving 12 piglets in preterm and full-term groups respectively and 3 piglets in preterm with probiotics and full-term with probiotics groups respectively. The body weights of the piglets in preterm group were lower than those in full-term group at 4, 9 and 21 d after birth ((507±27) vs. (694±56) g, (620±35) vs. (1 092±154) g, (1 660±210) vs. (2 960±418) g,t=2.96, 2.99, 2.78, all P<0.05). The alveolarization of the preterm piglets at 9 days after birth was significantly lower than that of the full-term piglets at the equivalent time point (4.00±0.29 vs. 6.11±0.35, t=4.64, P<0.01). The bacteria genus with the highest abundance in ileum were all different between the preterm and the full-term groups at 4, 9 and 21 d after birth (4 d Escherichia-Shigella (26.63%) and Enterococcus (30.48%) respectively;9 d Turicibacter (35.94%) and Lactobacillus (27.33%) respectively;21 d Escherichia-Shigella (28.02%) and Lactobacillus (46.29%) respectively). The heights of ileal villus of the preterm piglets at 9 d after birth were significantly lower than those of the full-term minipigs at the equivalent time point ((297±21) vs. (411±32) μm, t=3.01, P=0.007).There were both no differences in the body weight and alveolarization ((692±36) vs. (767±67) g, 5.44±0.34 vs. 5.89±0.26, t=0.74, 1.04, both P>0.05) between the piglets in preterm with probiotics group and those in full-term with probiotics group. Turicibacter was the dominant genus in the piglets of both preterm with probiotics and the full-term with probiotics groups. The heights of ileal villus of the piglets in preterm with probiotics group were significantly longer that those of the piglets in preterm group ((371±13) vs. (297±21) μm, t=3.04, P=0.006), and were both not significantly different from those of the piglets in full-term with probiotics group and full-term group ((371±13) vs. (338±12) and (411±32) μm, t=1.90, 1.15, both P>0.05). Conclusions: Premature birth could impact the lung alveolarization of piglets. The probiotics could improve the lung alveolarization of preterm minipigs by promoting the development of ileum.

Establishment and application of a nomogram model for prognostic risk prediction in patients with epithelial ovarian cancer / 中华妇产科杂志

Objective:To explore the prognostic factors of epithelial ovarian carcinoma (EOC), construct a nomogram model, and evaluate the prognosis of EOC patients.Methods:A retrospective analysis was performed on clinicopathological data of 208 cases of EOC patients who received initial treatment in the First Affiliated Hospital of Army Medical University from August 11, 2016 to July 11, 2018, including age, preoperative ascites, preoperative neoadjuvant chemotherapy, surgical method, pathological type, pathological differentiation degree, surgical pathology stage, preoperative and post-chemotherapy serum cancer antigen 125 (CA 125) level, human epididymal protein 4 (HE4) level, platelet count and platelet/lymphocyte number ratio (PLR). The univariate and multivariate Cox risk ratio models were used to analyze the related factors affecting progression free survival (PFS) in EOC patients, and the prediction nomogram of PFS in EOC patients was established to evaluate its efficacy in predicting PFS. Results:Univariate analysis showed that preoperative neoadjuvant chemotherapy, pathological type, pathological differentiation degree, surgical pathology stage, serum CA 125 and HE4 level before operation and after chemotherapy, platelet count and PLR before operation and after chemotherapy were significantly correlated with PFS in EOC patients (all P<0.05). Multivariate analysis showed that surgical pathology stage, preoperative PLR, serum CA 125 and HE4 level after chemotherapy were independent prognostic factors affecting PFS of EOC patients (all P<0.01). The index coefficient of the prediction model for the prognosis of EOC patients established by this method was 0.749 (95% CI: 0.699-0.798), which had good prediction ability, and could help clinicians to more accurately evaluate the prognosis of EOC patients. Conclusion:The nomogram model constructed based on surgical pathology stage, preoperative PLR, serum CA 125 and HE4 level after chemotherapy could effectively predict the PFS of EOC patients after initial treatment, could help clinicians to screen high-risk patients, provide individualized treatment, and improve the prognosis of EOC patients.

Sperm-specific protein ACTL7A as a biomarker for fertilization outcomes of assisted reproductive technology / 亚洲男科学杂志(英文版)

Obtaining high-quality embryos is one of the key factors to improve the clinical pregnancy rate of assisted reproductive technologies (ART). So far, the clinical evaluation of embryo quality depends on embryo morphology. However, the clinical pregnancy rate is still low. Therefore, new indicators are needed to further improve the evaluation of embryo quality. Several studies have shown that the decrease of sperm-specific protein actin-like 7A (ACTL7A) leaded to low fertilization rate, poor embryo development, and even infertility. The aim of this study was to study whether the different expression levels of ACTL7A on sperm can be used as a biomarker for predicting embryo quality. In this study, excluding the factors of severe female infertility, a total of 281 sperm samples were collected to compare the ACTL7A expression levels of sperms with high and low effective embryo rates and analyze the correlation between protein levels and in-vitro fertilization (IVF) laboratory outcomes. Our results indicated that the ACTL7A levels were significantly reduced in sperm samples presenting poor embryo quality. Furthermore, the protein levels showed a significant correlation with fertilization outcomes of ART. ACTL7A has the potential to be a biomarker for predicting success rate of fertilization and effective embryo and the possibility of embryo arrest. In conclusion, sperm-specific protein ACTL7A has a strong correlation with IVF laboratory outcomes and plays important roles in fertilization and embryo development.