Interaction between handgrip strength and vitamin D deficiency on all-cause mortality in community-dwelling older adults: a prospective cohort study.

OBJECTIVE: Muscle strength decline and vitamin D deficiency are coexisting conditions associated with multiple adverse health outcomes. This prospective study aimed to investigate the multiplicative and additive interactions between handgrip strength (HS) and serum 25-hydroxyvitamin D [25(OH)D] on all-cause mortality in Chinese community-dwelling older adults. STUDY DESIGN: This is a population-based cohort study. METHODS: 2635 older adults (85.15 ± 12.01 years) were recruited from the Chinese Longitudinal Healthy Longevity Survey (2012-2018). Low HS was defined according to the Asian Working Group for Sarcopenia 2019 updated consensus (<28 kg for men and <18 kg for women). Serum 25(OH)D < 50 nmol/L were defined as vitamin D deficiency. Cox proportional hazard models were used to examine the association of HS and 25(OH)D with all-cause mortality. Socio-demographics, health status, and clinical characteristics were included as covariates. RESULTS: 1715 (65.09 %) and 1885 (71.54 %) participants had low HS and vitamin D deficiency, respectively. During a median follow-up of 3.52 years, 1107 older people died. After multivariable adjustment, both HS and 25(OH)D levels were inversely associated with all-cause mortality risk (Ps < 0.001). The hazard ratios (HRs) of low HS and vitamin D deficiency for all-cause mortality were 1.73 (95 % CI: 1.41-2.13) and 1.61 (95 % CI: 1.32-1.93), respectively. Although significant multiplicative interactions were not found, the association between low HS and all-cause mortality was attenuated in the higher 25(OH)D subgroup than in the lower 25(OH)D subgroup (stratified by 50 nmol/L). The multiple-adjusted HR of mortality for combined low HS and vitamin D deficiency was 2.18 (95 % CI: 1.73-2.56), which was higher than that for these two conditions alone. Significant additive interactions between low HS and vitamin D deficiency on mortality were observed (relative excess risk due to interaction: 0.71, 95 % CI: 0.37-1.05). CONCLUSIONS: Low HS and low 25(OH)D levels synergistically increased the risk of all-cause mortality. Our results added new insights to the priority of early detection for older adults with comorbid muscle strength decline and vitamin D deficiency.

Impact of economic growth on physical activity and sedentary behaviors: a Systematic Review.

OBJECTIVES: This study systematically reviewed scientific evidence regarding the impact of economic growth on physical activity (PA) and sedentary behaviors. METHODS: A keyword and reference search was conducted in PubMed, Web of Science, Cochrane Library, Scopus, and EBSCO from the inception of an electronic bibliographic database to November 2021. Studies that met all of the following criteria were included in the review: (1) study designs: observational studies; (2) study subjects: people of all ages; (3) exposure: macroeconomic growth; (4) outcomes: PA or sedentary behaviors/sitting time. RESULTS: 15 studies were identified. Eight among 12 studies found economic growth positively associated with at least one domain/measure of PA, whereas the remaining four found an inverse relationship. One of two studies examined the association of economic growth and physical inactivity found a positive relationship, while another found no significant relationship. Four studies examined the associations between economic growth and sedentary behaviors, and the results were inconclusive. The impact of economic growth on PA is through three main pathways-(a) building and maintaining parks and green spaces, (b) adoption of the modern workplace and high technology, and (c) motorized transportation. CONCLUSION: Building and maintaining parks and green spaces can effectively promote leisure time physical activity and active commute in developed countries, whereas promoting workplace and transportation-related PA could be prioritized in developing nations. Future research calls for longitudinal study design and further exploration of macro-environmental factors. Policymakers and stakeholders should be informed about the potential PA reduction resulting from economic growth and develop preventive strategies to alleviate the problem.

Independent and combined associations of upper and lower limb strength with all-cause mortality in community-based older adults: findings from the Chinese Longitudinal Healthy Longevity Survey.

OBJECTIVES: Life expectancy is increasing around the world, and it has been projected that China will have the largest elderly population globally by 2033. This study aimed to examine the association of upper limb strength (ULS) and lower limb strength (LLS) with all-cause mortality based on data from the Chinese Longitudinal Healthy Longevity Survey (2012-2018). STUDY DESIGN: This is a prospective cohort study. METHODS: Participants were 2442 older adults (aged 84.98 ± 11.94 years) recruited from eight regions with a high elderly population in China. Limb muscle strength was evaluated using handgrip strength and objective physical examinations. Cox proportional hazards regression was used to analyse the association of limb muscle strength with all-cause mortality. Demographic characteristics, health status and biological markers were included as confounders. RESULTS: Over a median follow-up period of 42.2 months, 993 participants died. After adjusting for all covariates, low ULS was associated with a higher mortality risk (hazard ratio [HR] = 1.51, 95% confidence interval [CI] = 1.25-1.84), and the association of low LLS with all-cause mortality was only significant for men (HR = 1.36, 95% CI = 1.04-1.79). Participants with combined low ULS and low LLS had the highest risk of mortality compared with participants with normal limb muscle strength (HR = 2.06, 95% CI = 1.61-2.63). The combined association of ULS and LLS with mortality was robust in subgroup and sensitivity analyses. CONCLUSION: Low ULS and low LLS were independently and synergistically associated with a higher all-cause mortality risk. Considering the high prevalence of limb muscle weakness among older adults in China, especially in those aged ≥80 years, limb strength could be considered as an easy-to-perform potential mortality predictor in community health care.

[Impact of the depth of remission by induction chemotherapy on the prognosis of limited stage small cell lung cancer].

Objective: To evaluate the effect of depth of remission of induction chemotherapy on the overall prognosis of limited stage small cell lung cancer (L-SCLC). Methods: The study was a retrospective, L-SCLC patients who contained complete imaging data and underwent consecutive standardized treatments at the Department of Thoracic Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University between January 2013 and June 2021 were included. To delineate the volume of tumor before and after induction chemotherapy and to calculate the depth of remission caused by the induced chemotherapy. The time receiver operating characteristic (timeROC) method was used to determine the optimal predictors for prognosis, multi-factor analysis using Cox risk proportional model. Results: A total of 104 patients were included in this study. The median PFS and OS of this cohort were 13.7 months and 20.9 months, respectively. It was observed by timeROC analysis that residual tumor volume after induction chemotherapy had the optimal predictive value of PFS at 1 year (AUC=0.86, 95% CI: 0.78~0.94) and OS at 2 years (AUC=0.76, 95% CI: 0.65~0.87). Multivariate analysis showed residual tumor volume after induction chemotherapy was the independent prognostic factor to PFS (HR=1.006, 95% CI: 1.003~1.009, P<0.01) and OS (HR=1.009, 95% CI: 1.005~1.012, P<0.001). For those whose residual tumor volume remitted to less than 10 cm(3) after induction chemotherapy, the favorable long-term outcomes could be achieved, regardless of their initial tumor load. Conclusion: The depth of remission of induction chemotherapy could be a promising prognostic predictor to the L-SCLC and provide the individualized treatment guidance.

Concrete damage analysis based on higher-order beam theories using fracture energy regularization.

This paper presents the numerical damage analysis of concrete structures using higher-order beam theories based on Carrera Unified Formulation (CUF). The concrete constitutive relation is modeled using continuum damage mechanics based on a modified Mazars concrete damage model, in which both the tensile and compressive softening behaviors are regularized with classical fracture energy methodology. An expression is proposed to estimate the characteristic length in higher-order beam theories, to prevent mesh dependency. Both softening constitutive laws and fracture energy calculations are obtained according to Model Code 2010. To assess the efficiency of the proposed model, three classical benchmark quasi-static experiments are taken for validation. From the comparison between numerical and experimental results, the proposed CUF model using continuum damage mechanics can present 3D accuracy with low computational costs and reduce the mesh dependency.

[Cross-sectional associations between reproductive lifespan duration and urinary albumin-creatinine ratio].

Objective: To investigate the association between reproductive lifespan duration (RLD) and urinary albumin-creatinine ratio (UACR) in a Chinese postmenopausal population. Methods: This cross-sectional study included 11 055 naturally postmenopausal women from seven regions of China from May to December 2011. RLD was divided into four groups. Propensity score matching was performed to reduce bias, and logistic regressions and stratifications were conducted to investigate the association between RLD and increased UACR (≥30 mg/g). Mediation effect analysis was performed to quantify the effect of RLD on cardiovascular disease (CVD) induced by elevated UACR. Results: There were 2 373 participants with a RLD of 18-31 years, 2 888 participants with a RLD of 32-34 years, 2 472 participants with a RLD of 35-36 years, and 3 322 participants with a RLD of 37-50 years. The shortest RLD (18-31 years) group was characterized with older age (P<0.001), a higher incidence of CVD (P=0.025), and the highest level of UACR (P<0.001). After adjusting for confounders, women with a longer RLD (37-50 years group) exhibited a lower risk of UACR elevation compared with those with the shortest RLD (18-31 years group) (OR=0.72, 95%CI 0.64-0.82, P<0.001). Every 1-year extension in RLD was linked to a 2% reduction in the risk of UACR elevation (OR=0.98, 95%CI 0.97-0.99, P<0.001). Stratified analysis revealed a more significant association between RLD and UACR in women who were a normal weight (P=0.003) or overweight (P=0.001), in those without CVD history (P=0.001), and in those with impaired estimated glomerular filtration rate (P=0.004). The mediation casual analysis showed that 3.0% of proteinuria inducing CVD events was mediated by RLD (P=0.048). Conclusion: A longer RLD (37-50 years) is associated with a lower UACR in Chinese postmenopausal women.

[The value of machine learning models based on biparametric MRI for diagnosis of prostate cancer and clinically significant prostate cancer].

Objective: To evaluate the value of machine learning (ML) models based on biparametric magnetic resonance imaging (bpMRI) for diagnosis of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). Methods: A total of 1 368 patients, aged from 30 to 92 (69.4±8.2) years, from 3 tertiary medical centers in Jiangsu Province were retrospectively collected from May 2015 to December 2020, including 412 cases of csPCa, 242 cases of clinically insignificant prostate cancer (ciPCa) and 714 cases of benign prostate lesions. The data of center 1 and center 2 were randomly divided into training cohort and internal testing cohort at a ratio of 7∶3 by random number sampling without replacement using Python Random package, and the data of center 3 were used as the independent external testing cohort. The training cohort includs 243 cases of csPCa, 135 cases of ciPCa and 384 cases of benign lesions, the internal testing cohort includs 104 cases of csPCa, 58 cases of ciPCa and 165 cases of benign lesions, and the external testing cohort includs 65 cases of csPCa, 49 cases of ciPCa and 165 cases of benign lesions. The radiomics features were extracted on T2-weighted imaging, diffusion-weighted imaging and apparent diffusion coefficient map, and optimal radiomics features were selected by using Pearson correlation coefficient method and analysis of variance. The ML models were built using two ML algorithms, including support vector machine and random forest (RF) and were further tested in the internal testing cohort and external testing cohort. Finally, the PI-RADS scores evaluated by the radiologists were adjusted by the ML models which had superior diagnostic performance, namely adjusted PI-RADS. The receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of the ML models and PI-RADS. DeLong test was used to compare the areas under curve (AUC) of models with those of PI-RADS. Results: For PCa diagnosis, in internal testing cohort, the AUC of ML model using RF algorithm and PI-RADS were 0.869 (95%CI: 0.830-0.908) and 0.874 (95%CI: 0.836-0.913), respectively, and the difference between the model and PI-RADS did not reach to the statistical significance (P=0.793). In the external testing cohort, the AUC of model and PI-RADS were 0.845 (95%CI: 0.794-0.897) and 0.915 (95%CI: 0.880-0.951), respectively, and the difference was statistically significant (P=0.01). For csPCa diagnosis, the AUC of ML model using RF algorithm and PI-RADS were 0.874 (95%CI: 0.834-0.914) and 0.892 (95%CI: 0.857-0.927), respectively, in internal testing cohort, and the difference between the model and PI-RADS was not statistically significant (P=0.341). In the external testing cohort, the AUC of model and PI-RADS were 0.876 (95%CI: 0.831-0.920) and 0.884 (95%CI: 0.841-0.926), respectively, and the difference between the model and PI-RADS was not statistically significant (P=0.704). When PI-RADS assessment was adjusted with the assistance of ML models, the specificities increased from 63.0% to 80.0% in the internal testing cohort and from 92.7% to 93.3% in the external test group in diagnosing PCa. In diagnosing csPCa, the specificities increased from 52.5% to 72.6% in the internal testing cohort and from 75.2% to 79.9% in the external testing cohort. Conclusions: The ML models based on bpMRI showed comparable diagnostic performance to PI-RADS assessed by senior radiologists and achieved good generalization ability in both diagnosing PCa and csPCa. The specificities of the PI-RADS were improved by ML models.

Differentially Expressed Circulating Long-Noncoding RNAS in Premature Infants with Respiratory Distress Syndrome.

Purpose: Recent studies have addressed the association between lung development and long-noncoding RNAs (lncRNAs). But few studies have investigated the role of lncRNAs in neonatal respiratory distress syndrome (RDS). Thus, this study aimed to compare the expression profile of circulating lncRNAs between RDS infants and controls. Methods: 10 RDS infants and 5 controls were enrolled. RDS patients were further divided into mild and severe RDS subgroups. Blood samples were collected for the lncRNA expression profile. Subsequently, differentially expressed lncRNAs were screened out. Bioinformatics analysis was applied to establish a co-expression network of differential lncRNAs and mRNAs, and predict the underlying biological functions. Results: A total of 135 differentially expressed lncRNAs were identified, including 108 upregulated and 27 downregulated lncRNAs (fold-change>2 and P<0.05) among the three groups (non-RDS, mild RDS and severe RDS groups). Of these lncRNAs, four were selected as showing higher fold changes and validated by qRT-PCR. ENST00000470527.1, ENST00000504497.1, ENST00000417781.5, and ENST00000440408.5 were increased not only in the plasma of total RDS patients but also in the severe RDS subgroup. Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses showed that differentially expressed lncRNAs may play important roles in RDS through regulating PI3KAkt, RAS, MAPK, and TGF-ß signaling pathways. Conclusion: The present results found that ENST00000470527.1, ENST00000504497.1, ENST00000417781.5, and ENST00000440408.5 may be invol ved in RDS. This could provide new insight into research of the potential pathophysiological mechanisms of preterm RDS.

[Clinical efficacy and prognostic risk factors of salvage liver transplantation, rehepatectomy, and local ablation in the treatment of postoperative recurrence of hepatocellular carcinoma].

Objective: To investigate and analyze the clinical efficacy of salvage liver transplantation (SLT), rehepatectomy (RH), local ablation (LA), and prognostic risk factors in patients with postoperative recurrence of hepatocellular carcinoma. Methods: Clinical data of 145 patients with recurrent liver cancer in the 900th Hospital of the Joint Logistics Support Force of the People's Liberation Army from January 2005 to June 2018 were retrospectively collected. SLT group, RH group, and LA group included 25, 44, and 76 cases, respectively. Follow-up and statistics were recorded on the overall survival rate, relapse-free survival rate, and complications of the three groups of patients at 1, 2, and 3 years after surgery. Univariate and multivariate COX analyses were used to analyze the prognostic risk factors in patients with recurrent HCC. Results: The overall survival rates of 1, 2, and 3 years following surgery in the SLT, RH, and LA groups were 100.0%, 84.0%, 72.0%, 95.5%, 77.3%, 65.9%, 90.8%, 76.3%, and 63.2%, respectively, when the recurrence of liver cancer met the Milan criteria. The overall survival rate did not differ statistically between SLT and RH (P = 0.303) or between RH and LA (P = 0.152). There were statistically significant differences in recurrence-free survival between SLT and RH or RH and LA (P = 0.046). There was no statistically significant difference in the incidence of complications between SLT and RH or RH and LA (P > 0.017). Age > 65 years was an independent risk factor affecting the overall survival rate in patients with recurrent HCC. Age > 65 years and recurrence time < 24 months were independent risk factors affecting the recurrence-free survival rate in patients with recurrent HCC. Conclusion: SLT is the best treatment option when the recurrence of HCC meets Milan's criteria. RH and LA are the appropriate treatment plans for recurrent HCC when the liver source is limited.

[Clinical features and prognostic analysis of transarterial chemoembolization combined with targeted immunotherapy in the treatment of patients with hepatitis B virus-related intermediate-and advanced-stage hepatocellular carcinoma with secondary cholestasis].

Objective: To study the clinical features and prognostic impact of transarterial chemoembolization (TACE), immune checkpoint inhibitors (ICIs), and tyrosine kinase inhibitors (TKIs) combination therapy regimens in the treatment of patients with hepatitis B virus-related intermediate-and advanced-stage hepatocellular carcinoma with secondary cholestasis. Methods: Patients with HBV-related intermediate-and advanced-stage hepatocellular carcinoma (HBV) who visited the Affiliated Hospital of Xuzhou Medical University between January 1, 2020, and December 31, 2022, were enrolled. TACE+TKIs +ICIs combination therapy was used to treat all patients. The occurrence and factors influencing cholestasis, as well as the impact on prognosis after combined therapy, were analyzed. The measurement data were compared using a t-test and a non-parametric rank sum test. The count data was compared using the χ(2) test. The survival rates were compared using a log-rank test between different groups. Results: A total of 106 cases with HBV-related intermediate-and advanced-stage hepatocellular carcinoma were enrolled. The probabilities of secondary cholestasis within 3 and 6 months, 1, 2, and 3 years after TACE+ICIs+TKIs combination therapy were 9.4%, 12.3%, 14.2%, 24.5%, and 24.5%, respectively. Patients with secondary cholestasis had persistent symptoms and rapid progression. During the treatment course, the median survival time was significantly longer in patients with hepatocellular carcinoma without secondary cholestasis than that of patients with cholestasis (26.9 months vs. 13.7 months, respectively, P < 0.05). Secondary cholestasis, baseline aspartate aminotransferase, and prothrombin activity levels were independent risk factors that affected the survival and prognosis of patients treated with combination therapy. There was no statistically significant difference in the occurrence of other adverse reactions between the two groups with secondary and non-secondary cholestasis during the treatment course (47.5% vs. 43.3%, χ(2)=0.058, P = 0.810). Conclusion: TACE+ICIs+TKIs therapy combination is relatively common in the treatment of patients with HBV-related intermediate-and advanced-stage hepatocellular carcinoma with secondary cholestasis. Moreover, accelerated disease progression is an independent risk factor affecting the survival and prognosis of patients.

Trabecular bone score and its association with Cobb angle kyphosis in older men: a cross-sectional study for the Osteoporotic Fractures in Men (MrOS) Study.

Hyperkyphosis (HK), or accentuated forward spinal curvature, commonly affects older people, although its causes are not completely understood. We tested whether a measure of bone quality, trabecular bone score (TBS), is associated with HK in 1997 older men, and determined that men with degraded TBS were more likely to have HK. INTRODUCTION: While vertebral fractures and low bone mineral density (BMD) contribute to kyphosis progression, it is unknown whether the trabecular bone score (TBS) may provide additional information on bone quality that could influence the degree of kyphosis. We hypothesized that degraded TBS would be associated with hyperkyphosis (HK) defined as a Cobb angle > 50°. METHODS: Using data from 1997 participants of the Osteoporotic Fractures in Men (MrOS) Study who had baseline TBS and Cobb angle kyphosis measured, we investigated whether men with degraded TBS were more likely to be hyperkyphotic, even after adjustment for BMD and prevalent vertebral fractures. RESULTS: Men were an average age of 74 ± 6 (mean ± SD) years with a mean kyphosis angle of 38.6 ± 11.5°, 295 (15%) were classified as hyperkyphotic, and 416 (21%) had degraded TBS. Compared with men with TBS > 1.2, men with degraded TBS were more likely to have HK (OR: 1.47, 95% CI: 1.06-2.06, p = 0.02) after adjusting for age, clinic, race, BMI, hip BMD, and prevalent vertebral fracture. If spine instead of hip BMD was included in the model, the odds ratio decreased to 1.35 (95% CI: 0.97-1.89, p = 0.08). CONCLUSIONS: Older men with degraded TBS are more likely to have HK not explained by underlying vertebral fractures.

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.

AnFiSA: An open-source computational platform for the analysis of sequencing data for rare genetic disease.

Despite genomic sequencing rapidly transforming from being a bench-side tool to a routine procedure in a hospital, there is a noticeable lack of genomic analysis software that supports both clinical and research workflows as well as crowdsourcing. Furthermore, most existing software packages are not forward-compatible in regards to supporting ever-changing diagnostic rules adopted by the genetics community. Regular updates of genomics databases pose challenges for reproducible and traceable automated genetic diagnostics tools. Lastly, most of the software tools score low on explainability amongst clinicians. We have created a fully open-source variant curation tool, AnFiSA, with the intention to invite and accept contributions from clinicians, researchers, and professional software developers. The design of AnFiSA addresses the aforementioned issues via the following architectural principles: using a multidimensional database management system (DBMS) for genomic data to address reproducibility, curated decision trees adaptable to changing clinical rules, and a crowdsourcing-friendly interface to address difficult-to-diagnose cases. We discuss how we have chosen our technology stack and describe the design and implementation of the software. Finally, we show in detail how selected workflows can be implemented using the current version of AnFiSA by a medical geneticist.

Predicting lung adenocarcinoma invasiveness by measurement of pure ground-glass nodule roundness by using multiplanar reformation: a retrospective analysis.

AIM: To explore the value of roundness measurement based on thin-section axial, coronal, and sagittal section computed tomography (CT) images for predicting pure ground-glass nodule (pGGN) invasiveness. MATERIALS AND METHODS: A total of 168 pGGNs in 155 patients (44 male, 111 females; mean age, 55.74 ± 10.57 years), and confirmed by surgery and histopathology, were analysed retrospectively and divided into pre-invasive (n=72) and invasive (n=96) groups. Photoshop (CS6) software was used to measure pGGN roundness based on conventional axial section, as well as coronal and sagittal sections generated by multiplanar reformation, from thin-section (1-mm-thick) CT lung images. RESULTS: pGGN roundness values, measured in axial, coronal, and sagittal thin-section CT sections from the pre-invasive group were 0.8 ± 0.049, 0.816 ± 0.05, and 0.818 ± 0.043, respectively, while those in the invasive group were 0.745 ± 0.077, 0.684 ± 0.106, and 0.678 ± 0.106; differences between the two groups were significant (all p<0.001). Binary logistic regression analysis showed that roundness values based on coronal and sagittal sections (p<0.001) were better than those from axial sections (p>0.05) in predicting pGGN invasiveness, with odds ratio (OR) values of 14.858 and 23.315, respectively. ROC analysis showed that evaluation of roundness measured in sagittal sections was better at predicting pGGN invasiveness than when coronal sections were used (AUC 0.870 versus 0.832). CONCLUSION: Roundness is useful for predicting pGGN invasiveness, with measurements from coronal and sagittal sections better than those from conventional axial sections, with sagittal section images having the best predictive value.

[Clinical characteristics of patients with obstructive sleep apnea hypopnea syndrome combined with alveolar hypoventilation].

Objective: To evaluate the clinical characteristics of patients with obstructive sleep apnea hypopnea syndrome (OSAHS) combined with alveolar hypoventilation. Methods: This retrospective study included patients who were diagnosed as OSAHS by polysomnography (PSG) and underwent daytime awake transcutaneous carbon dioxide (PtcCO2) monitoring from November 2019 to February 2021 at the Sleep Center of the Second Affiliated Hospital of Soochow University. A total of 177 patients were enrolled in the analysis, including 167 males and 10 females, aged (40±8) years old. Patients with daytime awake PtcCO2>45 mmHg (1 mmHg=0.133 kPa) were diagnosed as daytime alveolar hypoventilation, with which participants were divided into the daytime alveolar hypoventilation group and non-daytime alveolar hypoventilation group. Body mass index (BMI) cut-off value predicting daytime alveolar hypoventilation was calculated and the patients were divided into the high BMI group and low BMI group. The continuous nocturnal PtcCO2 data was available for a subset of 128 patients, and the patients were divided into two groups according the daytime alveolar hypoventilation or not. Across-group differences were compared, respectively. Results: Compared with the non-daytime alveolar hypoventilation group (n=125), the BMI [27.57 (26.55, 30.33) vs 26.60 (25.06, 28.09) kg/m2], Epworth sleepiness score(ESS) score [9.50 (6.25, 12.00) vs 7.00 (4.00, 10.75)], higher oxygen desaturation index (ODI) [38.00 (15.23, 64.93) vs 26.80 (11.30, 44.30) events/h] and percentage of total time with oxygen saturation level<90% (TS90%) [11.24% (1.88%, 32.44%) vs 4.35% (0.72%, 9.87%)] of the daytime alveolar hypoventilation group(n=52) were significantly higher (P<0.05), and lowest arterial oxygen saturation (LSaO2) [74.50% (60.25%, 82.00%) vs 79.00% (73.00%, 84.50%)], mean arterial oxygen saturation (MSaO2) [94.00% (91.00%, 95.00%) vs 95.00% (94.00%, 96.00%)] were significantly lower (P<0.05). The BMI cut-off value for predicting daytime alveolar hypoventilation was 27.04 kg/m2. Of the 177 enrolled patients, 90 were in the high BMI group and 87 were in low group. Compared with the low BMI group, the proportion of daytime sleepiness, the ESS score, the prevalence of hypertension, AHI and daytime awake PtcCO2 in the high BMI group were significantly higher (P<0.05). Among the subset of 128 patients with nocturnal PtcCO2 data available, the BMI, daytime PtcCO2 level, the nocturnal CO2 level and the prevalence of sleep related alveolar hypoventilation in the daytime alveolar hypoventilation group (n=40) were significantly higher than those in the non-daytime alveolar hypoventilation group (n=88) (P<0.05). Conclusions: The OSAHS patients with alveolar hypoventilation have higher BMI and more severe nocturnal hypoxia. OSAHS patients with BMI>27.04 kg/m2 are more likely to develop sleep related alveolar hypoventilation disorder.

[Two-dimensional equivalent mechanical modeling and finite element analysis of normal female pelvic floor system].

Objective: To construct the geometric model of the pelvic floor by a two-dimensional equivalent mechanics method, and to explore the effect of the shape and position of pelvic floor organs and tissues on the biomechanical properties of the pelvic floor under different abdominal pressure. Methods: A 28-year-old healthy and symmetrical married infertile female volunteer was included. The pelvic floor tissue was scanned in the supine position using a 3.0T magnetic resonance scanner (Philips Company, Holland). Based on the method of magnetic resonance imaging (MRI) two-dimensional parameter measurement and computer aided design, the geometric model and finite element model of the female pelvic floor were established, and the biomechanical characteristics of the pelvic floor support system under different abdominal pressure were analyzed. Results: In this study, four different working conditions of the pelvic floor force were simulated under 60, 99, 168, and 208 cmH2O (1 cmH2O=0.098 kPa) abdominal pressure loads. The trend was as follows: under the abdominal pressure load, the retrograde flexion of the uterus occurred, the cervical, the middle and upper vaginal segment and the levator anus muscle had the characteristic change of mechanical axial direction pointing to the sacrum and coccyx, and the deformation of the levator anus muscle in the horizontal direction was greater than that in the vertical direction. With the increase of the abdominal pressure, the maximum stress values of the pelvic floor whole system of healthy subjects under four different working conditions were 0.194 3, 0.389 6, 0.557 1, and 0.627 5 MPa, respectively, and the maximum displacement values were 10, 14, 21 and 25 mm, respectively. The maximum stress values of the cervical and vaginal middle and upper segment were 0.111 7, 0.161 8, 0.250 6, and 0.304 1 MPa, respectively, and the maximum displacement values were 3, 6, 9, and 11 mm, respectively. The maximum stress of the perineal body was 0.063 4, 0.119 6, 0.235 2, and 0.288 0 MPa, and the maximum displacement was 1, 2, 4, and 5 mm. The maximum stress values of the levator anus muscle were 0.194 3, 0.389 6, 0.557 1, and 0.627 5 MPa, and the maximum displacement values were 2, 4, 7, and 8 mm, respectively. The maximum stress and maximum displacement of pelvic organs increased with the increase of the abdominal pressure under different working conditions. The stress axial relationship of normal female pelvic floor was that the middle and upper segment of uterus and vagina mainly acted on the sacrococcyx and the levator anus muscle, and the lower vaginal segment acts on the perineal body. Conclusions: The two-dimensional equivalent mechanical modeling and finite element analysis of the female pelvic floor system can accurately reflect the biomechanical characteristics of the female pelvic floor, and the resultant stress direction of the pelvic organs points to the sacrum and coccyx. The sacrum and coccyx, levator anus and perineal body play important stress supporting roles in the pelvic floor system.

[An exploratory clinical study of the efficacy and safety of tumor-infiltrating lymphocytes in the treatment of metastatic osteosarcoma].

Objective: To explore the safety and efficacy of tumor-infiltrating lymphocytes (TILs) extracted from tumor tissue in patients with pulmonary metastasis of osteosarcoma, the TILs were amplified in vitro to reach clinical dosage and reinfused to the patients combined with high-dose interleukin 2 (IL-2). Methods: Twelve subjects with pathologically diagnosed osteosarcoma were enrolled from December 2019 to June 20, 2021 in Shanghai General Hospital. All subjects progressed with metastasis after standard chemotherapy and failed multiple lines of treatments. Fresh tumor tissue was obtained from the metastatic site and extracted and amplified by Good Manufacturing Practice (GMP) workshop to produce TILs to clinical treatment dosage (109-1011). High-dose IL-2 (100 000-200 000 U/kg) was administered immediately after autogenous TILs infusion to promote the activation, proliferation and antitumor cytolytic activity in vivo. Adverse events (AE) were graded according to Common Terminology Criteria for Adverse Events (CTCAE) standard and tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Results: One patient did not receive treatment due to failure in isolating TILs, total of 11 patients received a single re-infusion of autologous TILs. There were 10 males and 1 female with a median age of 19.9 years (12-33 years). Six of these patients received higher dose levels of 1.0×1010 TILs. The 11 patients were followed-up for 1 to 13 months and tolerated well. The most common adverse events reported were fever (10/11), constipation (3/11) and elevated gamma-glutamyl transferase (GGT) (3/11). The high incidence of fever was due to the IL-2 infusion. All patients experienced a transient drop in lymphocyte count and leukopenia leading to non-myeloid ablative lymphocyte clearance. The AE included grade 4 hematologic toxicity, including 8 cases of lymphocytopenia, 2 cases of neutropenia and 1 case of thrombocytopenia. No AE of neurotoxicity occurred. Of all the 11 patients, 9 patients got stable disease (SD) and 2 patients had progressive disease (PD). The disease control rate was 9/11. The median duration of SD was more than 4 months, and the maximum tumor volume decreased by close to 20%. Patient number 9 had sustained SD status for more than 6 months. Conclusions: TILs with in vitro expansion ability could be isolated from tumor tissues of advanced osteosarcoma patients. TILs amplified and reinfused in vitro have anti-osteosarcoma activity.

[Follow-up study of fetal cardiac birth defects after prenatal diagnosis and graded counseling].

Objective: To explore accurate prenatal diagnosis, full-coverage graded counseling and follow-up for the fetus with cardiac birth defects (CBD). Methods: CBD fetus diagnosed prenatal by echocardiography from January 2018 to December 2020 in Guangdong Provincial People's Hospital were enrolled. Fetal CBD was graded (Ⅰ-Ⅵ) according to prognosis and possible operation time after birth, and the classification criteria and common diseases included were proposed. After the prenatal grading counseling, the outcome of the fetus was followed-up. The induced labor rate, live birth rate, prenatal and postnatal ultrasound diagnosis coincidence rate and other indicators were calculated. The disease composition ratio, prognosis of fetus with different grades and the outcome of integrated treatment were analyzed. Results: The detection rate of fetal CBD was up to 16.2% (1 971/12 188), 30 cases of which were excluded. A total of 1 941 cases were included in this study, including 196 cases (10.1%) of gradeⅠ, 433 cases (22.3%) of gradeⅡ, 615 cases (31.7%) of grade Ⅲ, 261 cases (13.4%) of grade Ⅳ, 388 cases (20.0%) of gradeⅤ, 48 cases (2.5%) of grade Ⅵ. Grade Ⅱ and gradeⅢ (the operation time was within 1 year after birth) accounted for 54.0% (1 048/1 941). The distribution of some diseases in different grades had obvious proportion advantage, which was representative. Among 1 747 CBD fetus, 736 cases (induced labor rate 42.1%) chose to terminate pregnancy due to CBD. Of the 1 010 live births, 975 cases (96.5%) had the same prenatal and postnatal diagnosis, 3 cases were missed diagnosis and 32 cases were misdiagnosed. The diagnostic accuracy of live births with severe and complex congenital heart disease was 383 out of 389 (98.5%). A total of 258 cases have received surgery or intervention. The age at the time of surgery or intervention was different among grades（χ²=47.3，P<0.001）. With the improvement of prognosis from gradeⅠ to Ⅴ, the live birth rate increased and the induced labor rate decreased accordingly; the difference between grades was significant（χ²=623.6，P<0.001）. Conclusions: Prenatal diagnosis and graded counseling is important in the integrated model. Fetal CBD grading could refine post-natal treatment strategies, guide delivery decisions and become an evaluation standard.

[The clinical value of using a distant-image screen for reading and learning].

Objective: To investigate the effect and comfort of using a distant-image screen for reading and learning. Methods: It was a prospective cross-over study. Thirty-nine volunteers, including 13 males and 26 females, aged (26.4±4.5) years (20 to 37 years), were recruited from Beijing Tongren Hospital Affiliated to Capital Medical University in July 2021. The volunteers read the digital correction table printed on paper and displayed on a distant-image screen in a random order and rest in an interval of 2 hours. Reading speed, efficiency and accuracy of using the two devices were recorded, and the changes of logMAR vision, diopter, flicker fusion frequency and visual fatigue score after reading were calculated. Comparison of the quantitative data was performed using the paired t-test. Results: The speed, accuracy and efficiency were (41.2±11.6) digit groups/min, 80.7%±13.3% and (32.4±7.4) digit groups/min in reading on paper, (41.7±11.1) digit groups/min, 76.4%±12.6% and (31.1±6.4) digit groups/min in reading from screen, respectively. There was no significant difference in reading speed (t=-0.462, P=0.648) and reading efficiency (t=1.954, P=0.058), but there was significant difference in reading accuracy (t= 2.226, P=0.032). The logMAR visual acuity of right eye and left eye decreased by 0.014±0.032 and 0.013±0.050 after reading on paper, but increased by 0.007±0.033 and 0.007±0.036 after reading from screen, respectively. The difference was significant (right eye, t=2.592, P=0.013; left eye, t =2.154, P=0.038). The myopia degree of right eye and left eye increased by (0.07±0.29) D and (0.06±0.24) D after reading on paper, and increased by (0.01±0.29) D and (0.02±0.28) D after reading from screen, respectively. The flicker fusion frequency decreased by (0.1±1.0) Hz after reading on paper, but increased by (0.3±1.2) Hz after reading from screen. There was no significant difference (P>0.05). The subjective scale score of visual fatigue increased in both groups, with no statistically significant difference (t=1.165, P=0.251). Conclusion: The use of a distant-image screen for reading and learning does not affect the reading efficiency or increase the visual fatigue, and can avoid the decline of visual acuity caused by near viewing compared with using the printed matter.

[Impact of empagliflozin on peak oxygen uptake in HFmrEF patients: a randomized controlled trial].

Objective: To evaluate the impact of empagliflozin on peak oxygen uptake (VO2peak) in patients with heart failure with mildly reduced ejection fraction (HFmrEF). Methods: In this randomized controlled trial, consecutive HFmrEF patients admitted to the Department of Cardiology of China-Japan Friendship Hospital from September 2019 to October 2020 were screened, and randomly assigned to empagliflozin group (EG) or conventional group (CG) using a random number table. The enrolled patients were treated according to the guidelines, and patients in the empagliflozin group received additional empagliflozin (10 mg, once a day, orally) on top of the conventional treatment. The primary end points were VO2peak at 6 months after treatment, and the secondary end points included other parameters of cardiopulmonary exercise test (CPET), 6-minute walking distance, N-terminal B-type pro-natriuretic peptide (NT-proBNP) level, and Kansas City Cardiomyopathy Questionnaire (KCCQ) score. Results: A total of 112 patients were included (mean age 69 (57, 78) years, 84 male (75.0%)). There were 55 cases in CG group and 57 cases in EG group. There were no significant differences in baseline data including age, sex, body mass index, left ventricular ejection fraction, systolic blood pressure, heart rate, estimated glomerular filtration rate, glycosylated hemoglobin, hemoglobin, NT-proBNP, daily dose of tolasemi, combined medication, CPET parameters, the proportion of New York Heart Association heart function Ⅲ/Ⅳ, history of coronary heart disease, history of hypertension, history of diabetes (all P>0.05). At 6 months after treatment, VO2peak was significantly higher in EG group than in CG group(P=0.023). VE/VCO2 slope was significantly lower in EG group than in CG group(P=0.034). Oxygen uptake efficiency slope was significantly higher in EG group than in CG group(P=0.038). The level of NT-proBNP was significantly lower in EG group than in CG group(P=0.020). Six-minute walking distance was significantly higher in EG group than in CG group(P=0.037). KCCQ score was significantly higher in EG group than in CG group(P=0.048). Exercise oscillatory ventilation decreased in both groups (1 case in each group, P>0.05). Conclusion: Empagliflozin can significantly improve VO2peak in patients with HFmrEF.