Breast cancer cell-derived exosome-delivered microRNA-155 targets UBQLN1 in adipocytes and facilitates cancer cachexia-related fat loss.

Cachexia occurrence and development are associated with loss of white adipose tissues, which may be involved with cancer-derived exosomes. This study attempted to characterize the functional mechanisms of breast cancer (BC) cell-derived exosome-loaded microRNA (miR)-155 in cancer cachexia-related fat loss. Exosomes were incubated with preadipocytes and cellular lipid droplet accumulation was observed using Oil Red O staining. Western blotting evaluated the cellular levels of lipogenesis marker peroxisome proliferator activated receptor gamma (PPARγ) and adiponectin, C1Q and collagen domain containing (AdipoQ). Differentiated adipocytes were incubated with exosomes, and phosphate hormone sensitive lipase (P-HSL), adipose triglyceride lipase (ATGL) and glycerol were detected in adipocytes, in addition to uncoupling protein 1 (UCP1) and leptin levels. A mouse model of cancer cachexia was established where cancer exosomes were injected intravenously. The changes in body weight and tumor-free body weights were recorded and serum glycerol levels and lipid accumulation in adipose tissues were determined. Also, the relationship between miR-155 and UBQLN1 was predicted and verified. BC exosome treatment reduced PPARγ and AdipoQ protein levels, promoted the levels of P-HSL and ATGL proteins, facilitated glycerol release, increased UCP1 expression and lowered leptin expression in adipocytes. Exosomal miR-155 inhibited lipogenesis in preadipocytes and boosted the browning of white adipose tissues. miR-155 downregulation alleviated cancer exosome-induced browning of white adipose tissues and fat loss. Mechanistically, miR-155 targeted UBQLN1, and UBQLN1 upregulation reversed the impacts of cancer exosomes. miR-155 loaded by BC cell-derived exosomes significantly affects white adipose browning and inhibition of cancer-derived exosomes.

Predictors of Nicotine Replacement Therapy Adherence: Mixed-Methods Research With a Convergent Parallel Design.

BACKGROUND: Few studies have examined the effect of baseline attitudes toward nicotine replacement therapy (NRT) on its actual adherence in a smoking cessation intervention. PURPOSE: This study (i) examined the predictability of baseline variables (quantitative data) on NRT adherence and (ii) explored the congruence of participants' statements about NRT products (qualitative data) during counseling sessions with their baseline attitudes. METHODS: This is a mixed-methods research study using a convergent parallel design. Participants included 74 individuals in the treatment group who received behavioral counseling and combination NRT. A Poisson regression analysis was performed to identify baseline variables predicting NRT adherence. Thematic analysis was completed with a subset of participants (n = 38) who varied in NRT attitude scores and adherence. A joint display was created to integrate quantitative and qualitative data and discover convergence. RESULTS: Approximately 59% of the participants (41/74) used NRT continuously for ≥5 weeks. Having negative attitudes toward NRT and depressive symptoms predicted NRT adherence even after controlling for education and anxiety symptoms. Thematic analysis revealed that NRT adherence is a learning process that consists of the following three distinctive but interrelated phases: (i) information needs, (ii) comprehensive readiness, and (iii) experiential learning. Of the 38 participants, 34 (89.5%) showed convergence between baseline attitude scores and statements about NRT made during counseling sessions. CONCLUSIONS: Individuals who have negative attitudes toward NRT are less likely to use the products in a smoking cessation intervention. Counselors should assess attitudes toward NRT at baseline and address them proactively during counseling sessions.

Few research studies have explored how attitudes toward nicotine substitutes (nicotine patches, gum, and lozenges) affect people's adherence to those substitutes (using them consistently as directed). This study examined (i) whether age, gender, education, attitudes toward the substitutes, and depressive and anxiety symptoms would predict peoples' adherence to these nicotine substitutes during a study to help stop smoking and (ii) whether peoples' statements about their experiences with the substitutes would reveal any patterns. The study was conducted with 74 individuals who received behavioral counseling and combination nicotine substitutes. Having negative attitudes toward the substitutes and depressive symptoms predicted adherence. Age, gender, education, positive attitudes, and anxiety symptoms did not. Statements from a subset of participants (n = 38) revealed that adherence to the substitutes is a learning process that consists of the following three phases: (i) needing more information assuring the safety of the substitutes, (ii) being mentally and situationally ready, and (iii) learning while being involved in the process such as "trial and error." Individuals who have negative attitudes toward the substitutes are less likely to use them, and counselors should assess attitudes toward nicotine replacement therapy before suggesting their use and address these attitudes proactively during smoking cessation counseling sessions.

Disturbed white matter integrity on diffusion tensor imaging in young children with epilepsy.

AIM: To evaluate whether abnormalities in white matter (WM) integrity are present in young children with epilepsy. MATERIALS AND METHODS: Twelve children (3-6 years old) with epilepsy and six matched healthy controls were recruited for brain diffusion tensor imaging (DTI). Track-based spatial statistics (TBSS) was used to analyse and compare DTI indices of mean diffusivity (MD), fractional anisotropy (FA), axial and radial diffusivity (AD/RD) between patients and controls, and correlations between clinical variables and DTI parameters were analysed. RESULTS: Compared with controls, patients showed increased FA in the left superior corona radiata and increased AD in the bilateral superior corona radiata. In children with generalised epilepsy, FA was increased in the left external capsule, while AD was decreased in the body of the corpus callosum, the left external capsule and the left superior longitudinal fasciculus. In those with focal epilepsy, FA was increased in the genu and body of the corpus callosum, and RD was decreased in the genu of the corpus callosum and left external capsule. Compared with partial epilepsy, generalised epilepsy was associated with increased FA in the right anterior corona radiata and decreased RD in the right anterior corona radiata and the genu and body of the corpus callosum. No significant correlations were observed between clinical variables and DTI parameters. CONCLUSIONS: The results of this study indicate that the microstructure of the white matter is disturbed by epileptic discharges and a compensatory response occurs during early brain development.

Role of oedema and shrinkage patterns for prediction of response to neoadjuvant chemotherapy and survival outcomes in luminal breast cancer.

AIMS: To explore the independent and additional value of oedema and shrinkage patterns for predicting the disease-free survival (DFS) and neoadjuvant chemotherapy (NAC) response in luminal breast cancer (BC). MATERIALS AND METHODS: Patients with luminal BC who underwent NAC were enrolled in this study from 2017 to 2022. Traditional MRI features include BI-RADS-based MRI descriptors, tumor size, and ADC values, while emerging MRI features include oedema and shrinkage patterns, all of which were evaluated before, early, and after NAC. The changes in features during NAC were also evaluated. The value of features was evaluated through univariate, multivariate analyses. RESULTS: A total of 258 patients were enrolled in this study, of which 77 responded to NAC. Diffuse oedema, stable or increased oedema during early NAC were adverse predictors for treatment response, while a greater reduction in tumor size and increase in ADC value were favorable predictors (all P<0.05). Furthermore, 20 of 60 patients who were followed up experienced recurrence. Diffuse oedema, pre-pectoral or subcutaneous oedema, and non-concentric shrinkage patterns after NAC were risk factors for DFS, whereas a greater increase in ADC value was a protective factor. Incorporating oedema and shrinkage patterns into traditional MRI features improved the predictive performance for treatment response (AUC from 0.76-0.78 to 0.80-0.83) and DFS (C-index from 0.67-69 to 0.75-0.80). CONCLUSIONS: Oedema is an unfavorable predictor for treatment response and survival outcomes, while shrinkage patterns contribute more to the prognostic value, both of which could offer supplementary benefits for clinical outcomes in luminal BC.

Comparative investigation of transport and deposition of nebulized particles in nasal airways following various middle turbinectomy.

BACKGROUND: Topical intranasal medication is required following functional endoscopic sinus surgery (FESS). The optimal particle size of transnasal nebulization aimed at the sinonasal cavities is not conclusive. The current study aims to evaluate the effect of particle size and various surgery scope of middle turbinectomy (MT) on post-full FESS drug delivery to the sinonasal cavities. METHODS: Sinonasal reconstructions were performed from post-full FESS CT scans in 6 chronic rhinosinusitis with nasal polyps (CRSwNP) patients. Four additional models representing alternative surgery scopes of MT were established from each post-FESS reconstruction for simulation data comparison. Airflow and particle deposition of nebulized delivery were simulated via computational fluid dynamics (CFD) and validated through in vitro experiments. The optimal particle sizes reaching a deposition of at least 75% of the maximum in the targeted regions were identified. RESULTS: The drug deposition rate onto the targeted regions increased following MT, with the greatest deposition following posterior MT (P-MT). Droplets in the range of 18-26 λm reached a deposition of larger than 75% of the maximum onto the targeted regions. Drug delivery rate in the sinonasal cavities varied significantly among individuals and across different types of MT with varying surgical scopes. CONCLUSIONS: This study is the first to investigate the effect of various surgery scope on drug delivery by transnasal nebulization to the sinonasal cavities. The findings strongly affirm the vast potential of transnasal nebulization as an effective post-FESS treatment option. Moreover, it emphasizes that the drug delivery process via atomizers to the nasal cavity and paranasal sinuses is highly sensitive to the particle size.

Liquid nitrogen improves the decellularization effectiveness of whole-ovary.

BACKGROUND: Ovarian tissue cryopreservation for fertility preservation carries a risk of malignant cell re-seeding. Artificial ovary is a promising method to solve such a problem. However, ovary decellularization protocols are limited. Hence, further studies are necessary to get better ovarian decellularization techniques for the construction of artificial ovary scaffolds. OBJECTIVE: To establish an innovative decellularization technique for whole porcine ovaries by integrating liquid nitrogen with chemical agents to reduce the contact time between the scaffolds and chemical reagents. MATERIALS AND METHODS: Porcine ovaries were randomly assigned to three groups: novel decellularized group, conventional decellularized group and fresh group. The ovaries in the novel decellularized group underwent three cycles of freezing by liquid nitrogen and thawing at temperatures around 37 degree C before decellularization. The efficiency of the decellularization procedure was assessed through histological staining and DNA content analysis. The maintenance of ovarian decellularized extracellular matrix(ODECM) constituents was determined by analyzing the content of matrix proteins. Additionally, we evaluated the biocompatibility of the decellularized extracellular matrix(dECM) by observing the growth of granulosa cells on the ODECM scaffold in vitro. RESULTS: Hematoxylin and eosin staining, DAPI staining and DNA quantification techniques collectively confirm the success of the novel decellularization methods in removing cellular and nuclear components from ovarian tissue. Moreover, quantitative assessments of ODECM contents revealed that the novel decellularization technique preserved more collagen and glycosaminoglycan compared to the conventional decellularized group (P<0.05). Additionally, the novel decellularized scaffold exhibited a significantly higher number of granulosa cells than the conventional scaffold during in vitro co-culture (P<0.05). CONCLUSION: The novel decellularized method demonstrated high efficacy in eliminating DNA and cellular structures while effectively preserving the extracellular matrix. As a result, the novel decellularized method holds significant promise as a viable technique for ovarian decellularization in forthcoming studies. Doi.org/10.54680/fr24310110212.

[Efficacy evaluation of short-term personalized vestibular rehabilitation in the treatment of acute unilateral vestibulopathy].

Objective: To explore the efficacy and effective node of short-term personalized vestibular rehabilitation (ST-PVR) in treating acute unilateral vestibulopathy (AUVP). Methods: A randomized controlled trial was carried out. The AUVP patients who were admitted to the First Affiliated Hospital of Zhengzhou University from July 2022 to March 2023 were selected and randomized to the vestibular rehabilitation (VR) group and control group via computer-generated randomization. Standard care was the medical treatment with betahistine and prednisolone. Meanwhile, the VR group received ST-PVR. All the patients completed the baseline assessment and underwent follow-up assessments at 1 month and 3 months after the treatment. The assessments were consisted of spontaneous nystagmus (NYS), Romberg test (ROM), head thrust test (HTT), visual analogue scale (VAS) for vertigo, dizziness handicap inventory scale (DHI), activities-specific balance confidence scale (ABC), caloric test using video-electronystagmograph (VNG), and video-head impulse test (vHIT). The measurement data that did not conform to normal distribution were represented by M (Q1, Q3). Generalized estimating equation (GEE) was used to analyze the influence of the ST-PVR on the values of these clinical indicators and the VR grading score. The values of clinical indicators and the VR grading score were compared between the two groups at each follow-up point. Results: Seventy-one AUVP patients were included, with 35 cases in the VR group [14 males and 21 females, aged 51 (33, 55) years] and 36 cases in control group [17 males and 19 females, aged 46 (34, 59) years]. There were statistically significant differences in the impact of ST-PVR on the values of clinical indicators between the two groups (ABC: ß=10.89, P<0.001; VAS: ß=-1.64, P<0.001; DHI: ß=-8.70, P<0.001; NYS: ß=26.73, P<0.001; vHIT: ß=1.41, P=0.047; the VR grading score: ß=1.03, P=0.045). The assessments of the VR group in the positive rate of NYS [14.3% (5/35) vs 50.0% (18/36), P<0.001], ROM [48.6% (17/35) vs 55.6% (20/36), P<0.001], directional preponderance (DP) [34.3% (12/35) vs 75.0% (27/36), P<0.001] and DHI [26 (22, 32) vs 36 (30, 60), P=0.001] were significantly lower than that of the control group at 1 month after the treatment. The results showed a statistically significant difference in ABC [88 (80, 90) vs 76 (61, 88), P<0.001], VAS [2 (1, 3) vs 3 (2, 5), P<0.001] at 3-months after the treatment. The VR grading score of the VR group was improved significantly than those of the control group at 1 month after treatment [21 (17, 21) vs 16 (13, 20), P=0.001]. Conclusion: ST-PVR could improve the results of clinical indicators and VR grading score of the AUVP patients effectively after 1 month of the systematical treatment, and alleviate the symptoms and signs of dizziness in the acute phase as early as possible.

[The relationship between rapid eye movement electromyogram activity and sleep stability in rapid eye movement sleep behavior disorder].

Objective: To investigate the relationship between the types of electromyogram (EMG) activity and sleep stability during rapid eye movement (REM) in patients with rapid eye movement sleep behavior disorder(RBD). Methods: One hundred and three patients with RBD who met the inclusion and exclusion criteria at the Second Affiliated Hospital of Air Force Military Medical University from January 2017 to December 2019 were retrospectively analyzed. The general situation, clinical symptoms, sleep and emotion questionnaires and nocturnal PSG data were collected. According to the different proportions of tonic and phasic EMG activity, the group with a higher proportion of tonic EMG than phasic EMG was defined as the tonic dominant group, and the group with a higher proportion of phasic EMG than tonic was defined as the phasic dominant group. The sleep instability index was calculated according to the ratio of the number of transitions from sleep to wakefulness to the total sleep time of each sleep stage. Multiple linear regression was used to explore the relationship between REM EMG activity and sleep instability index. Results: A total of 35 idiopathic RBD (iRBD) patients were included, aged(54.5±18.2)years, with 17 males and 18 females. There were 27 RBD with Parkinson's disease (PD), with an average age of (59.4±7.9)years, including 17 males and 10 females. Additionally, there were 41 RBD patients with narcolepsy, aged (21.2±13.2)years, consisting of 22 males and 19 females. Both iRBD and RBD patients with PD had lower objective total sleep time, sleep latency, sleep efficiency, wake time after sleep onset and the percentage of N3 sleep compared to RBD with episodic sleep disorder (all P<0.05). N1-W index[M(Q1, Q3),10.6 (6.5, 16.9)/h vs 7.3 (4.7, 10.5)/h], N2-W index [4.0 (2.2, 5.6)/h vs 2.3 (1.5, 3.9)/h], NREM-W index [ (5.8±2.9)/h vs (4.5±3.2)/h] and REM-W index[ 3.9 (1.9, 7.3)/h vs 2.7 (1.0, 4.0)/h] in the phasic dominant group were higher than those in the tonic dominant group. After adjusting for confounding factors, the effect of phasic EMG dominant group on REM-W was higher than that in the tonic dominant group (ß=2.05, 95%CI: 0.09-3.26, P=0.012). Conclusion: In RBD patients, the phasic EMG activity has a significant impact on sleep stability, especially on REM sleep stability.

[Analysis of the effect of early subcutaneous specific immunotherapy on the levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism].

Objective: To investigate the effects of subcutaneous immunotherapy (SCIT) on patients' immune markers and metabolic levels in the early stage of allergen treatment, and to gain insight into the role of SCIT in regulating immune responses and metabolic levels, so as to provide reference data for the further discovery of potential biomarkers. Methods: A longitudinal study was used to include 40 subjects who underwent SCIT with dust mite allergens in the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University between November 2017 and February 2022, including 20 subjects each of single mite subcutaneous immunotherapy (SM-SCIT) and double mite subcutaneous immunotherapy (DM-SCIT). In this study, levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism were measured before and 12 months after treatment, while pulmonary function tests were performed. The therapeutic effects of the patients were followed up by visual analogue scale (VAS), asthma control test (ACT) and total medication scores (TMS). The results were statistically analyzed using t-test and Mann-Whitney U-test. Results: After 12 months of treatment with SCIT, both groups showed a significant decrease in total VAS score (SM-SCIT:Z=-2.298, P<0.05; DM-SCIT:Z=-3.411, P<0.001); total ACT score (SM-SCIT:Z=-2.054, P<0.05; DM-SCIT:Z=-2.014, P<0.05) and total medication scores (SM-SCIT:Z=-3.799, P<0.000 1; DM-SCIT:Z=-3.474, P<0.001) were significantly higher, in addition to significantly higher MMEF75/25 values in the DM-SCIT group (t=-2.253, P<0.05). There was no significant change in sIgE in the SM-SCIT group (P>0.05), and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 2, and p 21 fractions were significantly elevated (Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, and -3.285, respectively, all P<0.05); The sIgE of Der p 2, f 2, p 7 and p 23 fractions(Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, -3.285, all P<0.05) and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 1, f 2, p 10, p 21 and p 23 fractions (Z=-3.808, -3.845, -3.061, -2.688, -2.464, -3.211, -2.371, -2.091, -2.427, all P<0.05) of the DM-SCIT group were significantly elevated. Metabolomics analysis showed that arachidonic acid, docosahexaenoic acid, docosapentaenoic acid, eicosapentaenoic acid, 5, 9, 12-octadecatrienoic acid, 5(S)-hydroxylated eicosatetraenoic acid, and dihomo-gamma-linolenic acid were significantly elevated at the beginning of the treatment period after SM-SCIT treatment (Z of -2.191, -2.497, -1.988, -2.090, -2.19, -2.803, -2.073, all P<0.05); 5(S)-hydroxylated eicosatetraenoic acid showed elevated and alpha-linolenic acid, eicosadienoic acid, and eicosapentaenoic acid were significantly decreased in the DM-SCIT group after treatment (Z=-1.988, -2.090, -2.497, -1.988, respectively, all P<0.05). Correlation analysis showed that arachidonic acid was significantly negatively correlated with changes in dust mite-specific IgG4 (r=-0.499, P<0.05), and that alpha-linolenic acid, 5, 9, 12-octadecatrienoic acid, and eicosapentaenoic acid were positively correlated with the ΔsIgG4 of the dust mite der p 2 (r=0.451, 0.420, 0.474, respectively; all P<0.05). Conclusion: Significant changes in allergen-specific antibody levels and polyunsaturated fatty acid metabolism levels occur during SCIT, and the two may interact and influence each other.

[Clinicopathological and molecular genetic features of Crohn's disease].

Objective: To investigate the clinicopathological and molecular genetic characteristics of Crohn's disease (CD). Methods: A retrospective analysis was conducted on 52 CD patients who underwent surgical resection at the First Affiliated Hospital of Nanjing Medical University between January 2014 and June 2023. Clinical presentations and histopathological features were assessed. Whole-genome sequencing was performed on 17 of the samples, followed by sequencing and pathway enrichment analyses. Immunohistochemistry was used to assess the expression of frequently mutated genes. Results: Among the 52 patients, 34 were males and 18 were females, male-to-female ratio was 1.9∶1.0, with a median age of 45 years at surgery and 35 years at diagnosis. According to the Montreal classification, A3 (51.9%,27/52), B2 (61.5%, 32/52), and L3 (50.0%,26/52) subtypes were the most predominant. Abdominal pain and diarrhea were the common symptoms. Histopathological features seen in all 52 patients included transmural inflammation, disruption of cryptal architecture, lymphoplasmacytic infiltration, varying degrees of submucosal fibrosis and thickening, increased enteric nerve fibers and neuronal proliferation. Mucosal defects, fissure ulcers, abscesses, pseudopolyps, and adenomatous proliferation were also observed in 51 (98.1%), 38 (73.1%), 28 (53.8%), 45 (86.5%), and 28 (53.8%) cases, respectively. Thirty-one (59.6%) cases had non-caseating granulomas, and 3 (5.8%) cases had intestinal mucosal glandular epithelial dysplasia. Molecular analysis showed that 12/17 CD patients exhibited mutations in at least one mucin family gene (MUC2, MUC3A, MUC4, MUC6, MUC12, MUC17), and MUC4 was the most frequently mutated in 7/17 of cases. Immunohistochemical stains showed reduced MUC4 expression in epithelial cells, with increased MUC4 expression in the epithelial surface, particularly around areas of inflammatory cell aggregation; and minimal expression in the lower half of the epithelium. Conclusions: CD exhibits diverse clinical and pathological features, necessitating a comprehensive multidimensional analysis for diagnosis. Mutations and expression alterations in mucin family genes, particularly MUC4, may play crucial roles in the pathogenesis of CD.

Absolute and relative iodine concentrations in the spot sign and haematoma for prediction of haematoma expansion in spontaneous intracerebral haemorrhage.

AIM: To explore the predictive value of absolute and relative iodine concentrations in the spot sign (SS) and haematoma on gemstone spectral imaging (GSI) for haematoma expansion (HE). MATERIALS AND METHODS: Patients with spontaneous intracerebral haemorrhage (ICH) who underwent computed tomography (CT) angiography using GSI were divided into an SS-positive group and an SS-negative group. In the SS-positive group, absolute and relative iodine concentrations in the SS (aICIS and rICIS, respectively) were measured. In the SS-negative group, absolute and relative iodine concentrations in haematoma (aICIH and rICIH, respectively) were measured. The area under the receiver operating characteristic curve (AUC-ROC) was used to investigate the HE predictive performance of aICIS, rICIS, and their combination in the SS-positive group, as well as the HE predictive performance of aICIH, rICIH, and their combination in the SS-negative group. The risk variables for HE in the two groups were investigated separately using logistic regression. RESULTS: A total of 123 spontaneous ICH patients were enrolled. In the SS-positive group, the AUC of aICIS, rICIS, and their combination for predicting HE were 0.853, 0.893, and 0.922, respectively. rICIS was demonstrated to be a standalone predictor of HE via logistic regression. In the SS-negative group, aICIH, rICIH, and their combination had AUC-ROC values of 0.552, 0.783, and 0.851, respectively, to predict HE. According to multivariate analysis, rICIH was a reliable predictor of HE. CONCLUSION: Absolute and relative iodine concentrations in the SS and haematoma can predict HE.

Assessing the feasibility of SUVindex (a metric derived from FDG PET/CT) for the diagnosis of polymyalgia rheumatica.

AIM: To evaluate the feasibility of standard uptake value (SUV) index (ratio lesional maximum SUV [SUVmax] to liver mean SUV [SUVmean]) as a metabolic parameter for diagnosing polymyalgia rheumatica (PMR). MATERIALS AND METHODS: A retrospective group of patients with PMR and controls with symptoms similar to PMR but diagnosed with other diseases. Semiquantitative and qualitative analysis of 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) uptake at 18 sites was undertaken for all patients. The diagnostic value of positron-emission tomography/computed tomography (PET/CT) for PMR was assessed by R software using logistic regression and a generalised additive model (GAM). All images were examined independently by two nuclear medicine physicians with extensive work experience. RESULTS: The characteristic sites of PMR were the ischial tuberosity, interspinous bursa, periarticular hip, and symphysis pubis enthesis. The area under the curve (AUC) of the characteristic site SUV index was 0.930, and the best cut-off value was 1.685 with a sensitivity of 84.6% and a specificity of 92.6%. After adjusting for potential confounders, the probability of PMR diagnosis increased as the characteristic site SUV index increased and there was a nonlinear correlation between the two. When the characteristic site SUV index was ≥2.56, the probability of PMR gradually reached the threshold effect, which was as high as 90% or more. CONCLUSION: The characteristic site SUV index is an independent factor for diagnosing PMR, and PMR should be highly suspected when it is ≥ 1.685. Nonetheless, it is important to note that these findings are based on an initial retrospective single-centre study and require external validation and further prospective evaluation before being translated into clinical practice.

The incidence, prevalence, and survival analysis of pancreatic neuroendocrine tumors in the United States.

PURPOSE: The incidence of pancreatic neuroendocrine tumors (pNETs) was increasing. The main purpose of this study was to statistically analyze the incidence and prevalence of pNETs and the main risk factors for the prognosis. METHODS: Based on the Surveillance, Epidemiology, and End Results (SEER) database, with three registries integrated, this study comprehensively displayed the annual age adjust incidence of pNETs from 1975 to 2018, the estimated 20-year limited-duration prevalence, and conducted the univariate and multivariate survival analysis. RESULTS: The incidence of pNETs has increased to about 1.5 per 100,000 population, and the prevalence has reached about 0.008% with the aged, Grade 1 and nonfunctional tumors accounting for the majority. The average median overall survival (OS), 5-year survival rate, and median disease-free survival (DFS) of pNETs patients from 1975 to 2018 were 85 months, 57.55%, and 220 months, respectively. From 2000 to 2018, the median OS was 94 months, and the 5-year survival rate was 59.94%. In multivariate survival analysis, the greatest risk factor was Grade 3&4 with HR = 3.62 (3.10-4.28), followed by distant stage with HR = 2.77 (2.28-3.36), and aged over 80 years old with HR = 2.26 (1.33-3.83). Surgery was a protective prognostic factor with HR = 0.34 (0.29-0.40). CONCLUSION: The incidence and prevalence of pNETs were still increasing, but the trend was gradual and aging in recent years. The survival time of pNETs was longer but has not changed much in recent years. The degrees of malignancy, stage, and operation were the most important prognosis factors.

Description of Paravulvus zhongshanensis sp. nov. (Dorylaimida: Nygolaimidae) from Nanjing, China.

Paravulvus zhongshanensis sp. nov., isolated from soil in a location at Jiangsu Province, China, is described and illustrated based on morphological, morphometric and molecular characterizations. The new species is characterized by its body 1.17-1.53 mm long, lip region offset by marked constriction and 12.1-13.8 µm broad, mural tooth deltoid and 9.6-11.7 µm long, neck 278-360 µm long, pharyngeal expansion 164-208 µm long or occupying more than one-half (54-62%) of total neck length, uterus 32.5-35.3 µm long or 1.0-1.1 times the corresponding body diameter, V = 47.8-53.4, paravulvae absent, female tail subcylindrical conoid (30.5-39.5 µm, c = 36.0-45.5, c' = 1.7-2.2) with widely rounded end, and male unknown. The new species was compared with six known species of the genus including Paravulvus acuticaudatus, Paravulvus confusus, Paravulvus hartingii, Paravulvus iranicus, Paravulvus loofi and Paravulvus microdontus mainly by similarities in having conical tail and c' value larger than 1.3. The rRNA and mitochondrial cytochrome oxidase subunit 1 genes of the new species were obtained and were used for reconstructing the phylogenetic relationships of the new species.

[Nomogram analysis of risk factors for diabetic neuropathy in primary type 2 diabetic mellitus patients in Zhejiang Province].

Objective: To investigate the risk factors of diabetic nephropathy (DN) in primary type 2 diabetes mellitus (T2DM) patients and to quantitatively analyze the risk of DN by nomogram modeling. Methods: A total of 1 588 primary T2DM patients from 17 townships and streets in Zhejiang Province were enrolled from June 2018 to August 2018 in this cross-sectional study, with an average age of (56.8±10.1) years (50.06% male) and a mean disease duration of 9 years. The clinical data, biochemical test results, and fundus photographs of all T2DM patients were collected, and logistic regression analysis was used to screen the risk factors of DN. Then, a nomogram model was used to quantitatively analyze the risk of DN. Results: DN occurred in 27.71% (440/1 588 cases) primary type 2 diabetes patients. Hemoglobin A1c (HbA1c) (OR=1.159, 95%CI 1.039-1.292), systolic blood pressure (OR=1.041, 95%CI 1.031-1.051), serum creatinine (Scr) (OR=1.011, 95%CI 1.004-1.017), serum globulin (GLOB) (OR=1.072, 95%CI 1.039-1.105), diabetic retinopathy (DR) (OR=1.463, 95%CI 1.073-1.996), education level of more than junior high school (OR=2.018, 95%CI 1.466-2.777), and moderate-intensity exercise (OR=0.751, 95%CI 0.586-0.961) were influencing factors of DN. Nomogram model analysis showed that the total score of each factor of DN ranged from 64-138 points, and the corresponding risk rate ranged from 0.1-0.9. The nomogram model also predicted a C-index value of 0.753 (95%CI 0.726-0.781) and an area under the receiver operating characteristic curve of DN of 0.753. Internal verification of the C-index reached 0.738. The model displayed medium predictive power and could be applied in clinical practice. Conclusions: HbA1c, systolic blood pressure, Scr, GLOB, DR, and more than a junior high school education are independent risk factors of DN. Nomogram modeling can more intuitively evaluate the risk of DN in primary T2DM patients.

[Investigation on occupational burnout among medical staff of tuberculosis control in Beijing].

Objective: To understand the occupational burnout status of tuberculosis prevention and treatment medical staff in Beijing, and analyze the influencing factors of different degrees of occupational burnout. Methods: From April to May 2021, an anonymous questionnaire survey was conducted among the medical staff of tuberculosis prevention and control in Beijing and 16 districts under its jurisdiction. A total of 313 questionnaires were issued, 311 were recovered, and 311 were valid, with an effective recovery rate of 99.36%. The General Information Questionnaire and Maslach Burnout Inventory Generalized Scale (MBI-GS) were used to collect social demographic data and the occurrence of occupational burnout, analyze the occurrence degree of occupational burnout, and identify the influencing factors of the occurrence degree of occupational burnout by using the orderly multiple logistic regression model. Results: Among 311 tuberculosis prevention and control medical staff, the total detection rate of occupational burnout was 62.70% (195/311), and the detection rates of mild, moderate and severe occupational burnout were 22.19% (69/311), 38.59% (120/311) and 1.93% (6/311), respectively. Orderly multiple logistic regression analysis showed that medical staff in prevention and control positions (OR=1.616, 95% CI: 1.030-2.534, P=0.037) and not meeting expectations for title promotion (OR=2.969, 95%CI: 1.675-5.262, P<0.001), and not getting along well with colleagues (OR=2.177, 95%CI: 1.362-3.480, P=0.001) were the main factors affecting the occurrence and severity of occupational burnout among tuberculosis prevention and treatment medical staff. Conclusion: The main manifestations of tuberculosis prevention and control medical staff in Beijing are mild to moderate occupational burnout. It is suggested to pay attention to the occupational needs of different positions of tuberculosis prevention and control medical staff, cultivate professional achievement, carry out psychological counseling, and reduce the degree of occupational burnout.

Whole-genome and transcriptome analysis enhances precision cancer treatment options.

BACKGROUND: Recent advances are enabling delivery of precision genomic medicine to cancer clinics. While the majority of approaches profile panels of selected genes or hotspot regions, comprehensive data provided by whole-genome and transcriptome sequencing and analysis (WGTA) present an opportunity to align a much larger proportion of patients to therapies. PATIENTS AND METHODS: Samples from 570 patients with advanced or metastatic cancer of diverse types enrolled in the Personalized OncoGenomics (POG) program underwent WGTA. DNA-based data, including mutations, copy number and mutation signatures, were combined with RNA-based data, including gene expression and fusions, to generate comprehensive WGTA profiles. A multidisciplinary molecular tumour board used WGTA profiles to identify and prioritize clinically actionable alterations and inform therapy. Patient responses to WGTA-informed therapies were collected. RESULTS: Clinically actionable targets were identified for 83% of patients, of which 37% of patients received WGTA-informed treatments. RNA expression data were particularly informative, contributing to 67% of WGTA-informed treatments; 25% of treatments were informed by RNA expression alone. Of a total 248 WGTA-informed treatments, 46% resulted in clinical benefit. RNA expression data were comparable to DNA-based mutation and copy number data in aligning to clinically beneficial treatments. Genome signatures also guided therapeutics including platinum, poly-ADP ribose polymerase inhibitors and immunotherapies. Patients accessed WGTA-informed treatments through clinical trials (19%), off-label use (35%) and as standard therapies (46%) including those which would not otherwise have been the next choice of therapy, demonstrating the utility of genomic information to direct use of chemotherapies as well as targeted therapies. CONCLUSIONS: Integrating RNA expression and genome data illuminated treatment options that resulted in 46% of treated patients experiencing positive clinical benefit, supporting the use of comprehensive WGTA profiling in clinical cancer care.

The extracellular vesicular pseudogene LGMNP1 induces M2-like macrophage polarization by upregulating LGMN and serves as a novel promising predictive biomarker for ovarian endometriosis recurrence.

STUDY QUESTION: How does ectopic endometrial stromal cell (Ecto-ESC)-derived extracellular vesicular Legumain pseudogene 1 (EV-LGMNP1), a newly identified pseudogene of Legumain (LGMN), contribute to M2-phenotype macrophage polarization, and does it predict recurrence in patients with ovarian endometriosis (EMs)? SUMMARY ANSWER: EV-LGMNP1, which is abundant in Ecto-ESCs and serum from ovarian EMs, can direct macrophages towards an M2 phenotype by upregulating LGMN expression and is a promising biomarker for predicting ovarian EMs recurrence. WHAT IS KNOWN ALREADY: Extracellular vesicles (EVs) can mediate cell-to-cell crosstalk to promote disease progression via cargo molecule transport. Recently, LGMNP1, a newly identified pseudogene of LGMN, has been reported to promote cancer progression by upregulating LGMN. LGMN is a well-studied protein that can induce M2-like polarization. STUDY DESIGN, SIZE, DURATION: An in vitro study was conducted with Ecto-ESCs isolated from ectopic endometrial samples, collected from two patients with ovarian EMs (diagnosed by laparoscopy and histological analysis). A clinical retrospective cohort study of 52 ovarian EMs patients and 21 controls with available preoperative serum samples was carried out (2013-2017). The follow-up period ended either at the time of recurrence or on 31 December 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ecto-ESC-derived EVs (EV/Ecto-ESCs) were characterized by nanoparticle tracking analysis, transmission electron microscopy and western blotting. EV internalization by THP-1 cells, which are the most widely used primary human macrophages model, was detected by fluorescence labelling. After EV treatment, THP-1 cell polarization was detected by quantitative real-time PCR (qRT-PCR) and western blot analyses of CD86 (M1-related marker) and CD206 (M2-related marker). LGMNP1 mRNA expression level in EVs from both primary ectopic endometrioc stromal cells and serum was examined using qRT-PCR. Additionally, the expression of LGMN, the downstream target gene of LGMNP1, in THP-1 cells was evaluated using qRT-PCR and western blotting. Kaplan-Meier and multivariate Cox regression analyses were applied to evaluate the independent predictive factors of EMs recurrence-free survival. A novel nomogram model based on serum EV-LGMNP1 was then formulated to predict EMs recurrence. MAIN RESULTS AND THE ROLE OF CHANCE: In vitro assays demonstrated that EV/Ecto-ESCs drove macrophages towards an M2-like phenotype. Moreover, LGMNP1 contributed to EV/Ecto-ESC-induced M2 macrophage polarization by upregulating LGMN mRNA expression levels. Clinically, serum EV-LGMNP1 was more highly expressed in recurrent EMs patients than in controls and EMs patients without recurrence. Survival analysis and our novel nomogram reconfirmed that serum EV-LGMNP1 was a novel promising and meaningful non-invasive biomarker for predicting EMs recurrence. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: In vitro experiments were only performed on samples from two patients with ovarian endometriosis, and a larger sample size is needed. ESCs isolated from the eutopic endometrium of EMs and non-EMs patients should be studied in the future. Additionally, in vitro experiments should be performed using endometrial epithelium cells and further in vivo experiments, such as using mice endometriotic models to investigate whether EV/Ecto could induce M2 macrophage polarization, should be conducted. Moreover, multicentre, large-sample data are needed to validate our predictive nomogram model. WIDER IMPLICATIONS OF THE FINDINGS: Our study provides novel insights into the mechanism of M2 polarization involved in ovarian EMs progression mediated by an 'EV-shuttled pseudogene LGMNP1' mode. In addition, serum EV-LGMNP1 may serve as a novel non-invasive biomarker for predicting recurrence, providing a new therapeutic target for ovarian EMs. STUDY FUNDING/COMPETING INTEREST(S): This project was supported by funding from the National Natural Science Foundation of China (81971361), the Natural Science Foundation of Shanghai Science and Technology (19ZR1406900), the Shanghai 'Rising Stars of Medical Talent' Youth Development Program (AB83030002019004), the Clinical Research Plan of SHDC (SHDC2020CR4087), the Shanghai Municipal Health Commission (202040498), the Research and Innovation Project of the Shanghai Municipal Education Commission (2019-01-07-00-07-E00050) and the Clinical Research Plan of SHDC (SHDC2020CR1045B). There are no competing interests to declare.

Three novel structural variations at the major histocompatibility complex and IL12B predispose to psoriasis.

BACKGROUND: Structural variations (SVs; defined as DNA variants ≥ 50 base pairs) have been associated with various complex human diseases. However, research to screen the whole genome for SVs predisposing to psoriasis is lacking. OBJECTIVES: To investigate the association of SVs and psoriasis. METHODS: Using imputation, we performed a genome-wide screen of SVs on five independent cohorts with 45 386 participants from the Han Chinese population. Fine-mapping analysis, genetic interaction analysis and RNA expression analysis were conducted to explore the mechanism of SVs. RESULTS: In total, we obtained 4535 SVs and identified two novel deletions [esv3608550, odds ratio (OR) 2·73 (P < 2·00 × 10-308 ); esv3608542, OR 0·47 (P = 7·40 × 10-28 )] at 6q21·33 (major histocompatibility complex), one novel Alu element insertion [esv3607339; OR 1·22 (P = 1·18 × 10-35 )] at 5q33·3 (IL12B) and confirmed one previously reported deletion [esv3587563; OR 1·30 (P = 9·52 × 10-60 )] at 1q21·2 (late cornified envelope) for psoriasis. Fine-mapping analysis including single-nucleotide polymorphisms (SNPs) and small insertions/deletions revealed that esv3608550 and esv3608542 were independently associated with psoriasis, and a novel independent SNP [rs9378188; OR, 1·65 (P = 3·46 × 10-38 )] was identified at 6q21·33. By genetic interaction analysis and RNA expression analysis, we speculate that the association of two deletions at 6q21·33 with psoriasis might relate to their influence on the expression of HLA-C. CONCLUSIONS: We have constructed the most comprehensive SV map for psoriasis thus far and enriched the genetic architecture and pathogenesis of psoriasis, and highlight the non-negligible impact of SVs on complex diseases.

Association between cerebral blood flow changes and blood-brain barrier compromise in spontaneous intracerebral haemorrhage.

AIM: To quantitatively evaluate blood-brain barrier (BBB) permeability in the perihaematomal region of spontaneous intracerebral haemorrhage (ICH) and investigate the association between the alterations in cerebral blood flow and BBB permeability around the haematoma. MATERIALS AND METHODS: Spontaneous ICH patients underwent unenhanced computed tomography (CT) and CT perfusion (CTP) simultaneously. Haematoma volume was measured on CT. The values of cerebral haemodynamic parameters including cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP), and permeability-surface area product (PS) were measured in the perihaematomal region and the contralateral mirror region, and then relative values were calculated for statistical analysis. Linear regression was used to evaluate associations between BBB permeability and variables. RESULTS: A total of 87 ICH patients were included in this study. The focally elevated BBB permeability was observed in the perihaematomal region in ICH patients. Linear regression showed that reduced rCBF (ß = -0.379, p=0.001) and increased rCBV (ß = 0.412, p=0.000) correlated independently with increased relative PS (rPS) value in deep ICH, while only increased rCBV (ß = 0.423, p=0.071) correlated to increased rPS value in patients with lobar ICH. CONCLUSIONS: BBB permeability is focally elevated in the region around the haematoma. Cerebral haemodynamic alterations are associated with increased BBB permeability. Cerebral hypoperfusion may aggravate BBB compromise, and a compensatory increase in CBV may lead to reperfusion injury on BBB.