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Electromagnetic pollution has become an increasingly important problem which has drawbacks to both the accurate operation of the electronic facilities and the safety of human beings. To alleviate and eliminate electromagnetic irradiation, it is inevitable to design microwave absorption materials with desirable absorption intensity and broad effective frequency bandwidth. The combination of carbon-based materials and magnetic materials is an adoptable strategy to perform remarkable microwave absorption performance, while the microstructure should not be ignored. Inspired by the electromagnetic response behaviors of the microstructure from the leafhopper, the hetero-microstructure with hollow void is constructed by adopting bimetal ZIF as the precursor, followed by an interfacial tailoring strategy through electrostatic assembling and calcinating process, which enhances the microwave absorption performance by integrating the merits between the components and the micro-structure. The minimum value of reflection loss achieved -76.40 dB at 7.50 GHz under filler loading of 20% with the thickness of 2.92 mm. Besides, the effective absorption bandwidth could be tailored from 3.55 to 18 GHz among different thicknesses as required. The bio-inspired strategy is validated as a promising method, exhibiting great potential in the designing of the next-generation microwave absorber.

Traditional surveillance of adverse infant outcomes following maternal medication exposures relies on pregnancy exposure registries, which are often underpowered. We characterize the statistical power of TreeScan, a data mining tool, to identify potential signals in the setting of perinatal medication exposures and infant outcomes.We used empirical data to inform background incidence of major congenital malformations and other birth conditions. Statistical power was calculated using two probability models compatible with TreeScan, Bernoulli and Poisson, while varying the sample size, magnitude of the risk increase, and incidence of a specified outcome. We also simulated larger referent to exposure matching ratios when using the Bernoulli model in the setting of fixed N:1 propensity score matching. Finally, we assessed the impact of outcome misclassification on power.The Poisson model demonstrated greater power to detect signals than the Bernoulli model across all scenarios and suggested a sample size of 4,000 exposed pregnancies is needed to detect a twofold increase in risk of a common outcome (approximately 8 per 1,000) with 85% power. Increasing the fixed matching ratio with the Bernoulli model did not reliably increase power. An outcome definition with high sensitivity is expected to have somewhat greater power to detect signals than an outcome definition with high positive predictive value.Use of the Poisson model with an outcome definition that prioritizes sensitivity may be optimal for signal detection. TreeScan is a viable method for surveillance of adverse infant outcomes following maternal medication use.

Yu Pu,1,* Xiuxiu Zhou,1,* Di Zhang,1,* Yu Guan,1,* Yi Xia,1 Wenting Tu,1 Yang Lu,2 Weidong Zhang,2 Chi-Cheng Fu,2 Qu Fang,2 Geertruida H de Bock,3 Shiyuan Liu,1 Li Fan1 1Department of Radiology, Changzheng Hospital, Naval Medical University, Shanghai, People’s Republic of China; 2Department of Scientific Research, Shanghai Aitrox Technology Corporation Limited, Shanghai, People’s Republic of China; 3Department of Epidemiology, University Medical Center Groningen, Groningen, the Netherlands*These authors contributed equally to this workCorrespondence: Shiyuan Liu; Li Fan, Department of Radiology, ChangZheng Hospital, Naval Medical University, No. 415 Fengyang Road, Shanghai, 200003, People’s Republic of China, Tel +86 21 81886012 ; Tel +86 21 81886012, Fax +86 21 63587668, Email cjr.liushiyuan@vip.163.com; fanli0930@163.comPurpose: To explore optimal threshold of FEV1% predicted value (FEV1%pre) for high-risk chronic obstructive pulmonary disease (COPD) using the parameter response mapping (PRM) based on machine learning classification model.Patients and Methods: A total of 561 consecutive non-COPD subjects who were screened for chest diseases in our hospital between August and October 2018 and who had complete questionnaire surveys, pulmonary function tests (PFT), and paired respiratory chest CT scans were enrolled retrospectively. The CT quantitative parameter for small airway remodeling was PRM, and 72 parameters were obtained at the levels of whole lung, left and right lung, and five lobes. To identify a more reasonable thresholds of FEV1% predicted value for distinguishing high-risk COPD patients from the normal, 80 thresholds from 50% to 129% were taken with a partition of 1% to establish a random forest classification model under each threshold, such that novel PFT-parameter-based high-risk criteria would be more consistent with the PRM-based machine learning classification model.Results: Machine learning-based PRM showed that consistency between PRM parameters and PFT was better able to distinguish high-risk COPD from the normal, with an AUC of 0.84 when the threshold was 72%. When the threshold was 80%, the AUC was 0.72 and when the threshold was 95%, the AUC was 0.64.Conclusion: Machine learning-based PRM is feasible for redefining high-risk COPD, and setting the optimal FEV1% predicted value lays the foundation for redefining high-risk COPD diagnosis.Keywords: chronic obstructive pulmonary disease, computed tomography, pulmonary function test, quantitative imaging, artificial intelligence

Circular RNAs (circRNAs) serve as critical regulatory factors in cancer development. Nonetheless, the potential regulatory mechanism of circRNA sorting nexin 27 (circ_SNX27) in hepatocellular carcinoma (HCC) is still unknown.The circ_SNX27, microRNA-637 (miR-637), and fibroblast growth factor receptor 1 (FGFR1) levels were quantified by quantitative real-time polymerase chain reaction and western blot analysis. Next, function experiments were conducted using in vitro assays and in vivo senograft study. The relationship between miR-637 with circ_SNX27 or FGFR1 was uncovered by dual-luciferase reporter and RNA pull-down assays.The circ_SNX27 and FGFR1 levels were up-regulated, but miR-637 content was reduced in HCC. Circ_SNX27 down-regulation inhibited HCC cell proliferation, motility, and invasion and promoted apoptosis in vitro, as well as weakened tumor growth in vivo. Circ_SNX27 served as a sponge of miR-637 to promote FGFR1 expression. MiR-637 reduction abolished the restrained effect of circ_SNX27 absence on HCC cell development. Moreover, miR-637 curbed HCC cell malignant phenotype by regulating FGFR1.Circ_SNX27 contributed to HCC development via miR-637/FGFR1 axis, offering a new idea for the treatment of HCC.

To observe the clinical and radiological effect of crenel lateral interbody fusion (CLIF) procedure in the management of lumbar spine adjacent segment degenerative (ASD).Thirty-seven patients with lumbar spine ASD who underwent the CLIF procedure between June 2018 and December 2019 were included in the study. There were 13 males and 24 females, with a mean age of 64.30 ± 5.92 years. The VAS score of the back (VAS_Back) and legs (VAS_Leg), Oswestry Disability Index (ODI) score, the height of the intervertebral space (HIS), the height of the intervertebral foramen (HIF), the cross-sectional area (CSA) of the vertebral canal, segmental lordosis (SL), and lumbar lordosis (LL) were recorded before the operation, 2 weeks after the operation, 3 months after the operation, and at the last follow-up respectively. Clinical and radiological outcomes before and after the surgery were compared, and correlation and regression analyses were performed.There were no vascular and nerve-related complications during the operation. The average follow-up time was 16.63 ± 4.24 months. The median of both VAS_Back and VAS_Leg was 7 before surgery and 1 at the last follow-up. Meanwhile, the average preoperative ODI score, HIS, HIF, CSA of the vertebral canal, LL, and SL was (67.48 ± 7.17) %, (4.80 ± 0.73) mm, (12.95 ± 2.07) mm, (59.52 ± 9.22) mmCrenel lateral interbody fusion is an effective procedure in the management of lumbar ASD. Not only was the postoperative swift recovery due to minimal invasion, but also adequate LL and SL were achievable.

Background: The ubiquitin-proteasome system (UPS) is critical in cellular protein degradation and widely involved in the regulations of cancer hallmarks. Targeting the UPS pathway has emerged as a promising novel treatment in hematological malignancies and solid tumors. Objective: This review mainly focuses on the preclinical results of proteasome inhibitors in solid tumors. Methods: We analyzed the published articles associated with the anticancer results of proteasome inhibitors alone or combination chemotherapy in solid tumors. Important data presented in abstract form were also discussed in this review. Results/Conclusion: Proteasome inhibitors, such as bortezomib and carfilzomib, are highly effective in treating solid tumors. The anticancer efficacy is not limited to affect the proteasomal inhibition- associated signaling pathways but also widely involves the signaling pathways related to cell cycle, apoptosis, and epithelial-mesenchymal transition (EMT). In addition, proteasome inhibitors overcome the conventional chemo-resistance of standard chemotherapeutics by inhibiting signaling pathways, such as NF-κB or PI3K/Akt. Combination chemotherapy of proteasome inhibitors and standard chemotherapeutics are widely investigated in multiple relapsed or chemo-resistant solid tumor types, such as breast cancer and pancreatic cancer. The proteasome inhibitors re-sensitize the standard chemotherapeutic regimens and induce synergistic anticancer effects. The development of novel proteasome inhibitors and delivery systems also improves the proteasome inhibitors’ anticancer efficacy in solid tumors. This review summarizes the current preclinical results of proteasome inhibitors in solid tumors and reveals the potential anticancer mechanisms.

We aimed to develop a risk prediction model for gestational diabetes mellitus (GDM) based on the common maternal demographics and routine clinical variables in Chinese population.Individual information was collected from December 2018 to October 2019 by a pretested questionnaire on demographics, medical and family history, and lifestyle factors. Multivariable logistic regression was performed to establish a predictive model for GDM by variables in pre- and early pregnancy. The consistency and discriminative validity of the model were evaluated by Hosmer-Lemeshow goodness-of-fit testing and ROC curve analysis. Internal validation was appraised by fivefold cross-validation. Clinical utility was assessed by decision curve analysis.Total 3263 pregnant women were included with 17.2% prevalence of GDM. The model equation was: LogitP = -11.432 + 0.065 × maternal age (years) + 0.061 × pre-pregnancy BMI (kg/mThe predictive model of GDM exhibited well acceptable predictive ability, discriminative performance, and clinical utilities. The project was registered in clinicaltrial.gov.com with identifier of NCT03922087.

Objective To investigate the relationship between different standing postures and surgical outcomes of K-Line (−) ossification of the posterior longitudinal ligament (OPLL) patients after laminoplasty with a titanium basket. Summary of Background Data There is a lack of data evaluating the relationship between the postoperative satisfaction of K-Line (−) patients and their standing postures. Methods OPLL patients enrolled in the study were divided into a K-Line (+) group (Group A) and a K-Line (− group (Group B) in natural and relaxed standing positions. We compared the postoperative outcomes after cervical laminoplasty with titanium basket surgery using the Japanese Orthopaedic Association score (JOA), recovery rate and the degree of improvement in the six JOA score items. The degree of satisfaction with the outcome was assessed at the 1-year follow-up using a 7-point numerical rating scale. Results A total of 34 K-Line (+) patients with OPLL (age 61.9 ± 2.9 years) in Group A and 40 K-Line (−)patients with OPLL (age 60.4 ± 3.5 years) in Group B in natural and relaxed standing positions were recruited. In Group A, the mean preoperative and postoperative JOA scores were 10.1 ± 1.4 and 13.1 ± 0.8 points, respectively, and in Group B, the mean preoperative and postoperative JOA scores were 9.7 ± 1.3 and 11.1 ± 0.9 points, respectively. A significant improvement in the JOA score was seen in both groups postoperatively, but the recovery rate of the patients’ JOA scores was significantly lower in Group B. In Group A, significant improvements were seen in all JOA score items, but in Group B, improvements were seen only in upper- and lower-extremity sensory functions. Conclusion Different standing postures are risk factors in the treatment of K-Line (−) patients, and therefore, natural and relaxed standing positions should be given more attention before devising the surgical plan.

To investigate the clinical characteristics, treatment, and prognosis of patients with metastatic head and neck adenoid cystic carcinoma (HNACC).The clinical data of metastatic HNACC from 1999 to 2020 at the National Cancer Center of China were retrospectively collected.One hundred seventy-four patients with metastatic HNACC were enrolled and median overall survival (OS) was 45.6 months. Univariate analysis indicated that smoking history, disease-free interval (DFI), number and sites of metastases, and systemic therapy were associated with OS. In the multivariate analysis, non-smokers, DFI ≥3 years, and lung metastasis were prognostic factors. Local therapy for localized disease could prolong survival in patients with both recurrent and metastatic disease.No smoking history, DFI ≥3 years, and lung metastasis were favorable prognostic factors. Local therapy for metastases could not provide survival benefits, but local therapy for localized disease may prolong survival. Whether initial systemic therapy could improve prognosis needs further exploration.

At present, the true sagittal alignment of the cervical spine is uncertain, resulting in no standard reference for subaxial cervical surgery. So, we aimed to explore the age difference of normal cervical sagittal alignment and to further investigate the mid-and long-term changes of sagittal alignment after subaxial cervical spine surgery.This was a retrospective study and 1223 asymptomatic volunteers and 79 patients undergoing subaxial cervical spine surgery were retrospectively reviewed in total. Asymptomatic volunteers and patients were divided into six subgroups: 20-29, 30-39, 40-49, 50-59, 60-69 and ≥70 groups. The age difference and trend with age of cervical sagittal parameters of asymptomatic volunteers were assessed by cervical lateral radiography and analyzed by ANOVA test, and the regression equation of C2-7 Cobb was established via multiple linear regression. Based on the C2-7 Cobb regression equations of different ages, the theoretical value, deviation value, loss value of the C2-7 Cobb, and JOA recovery rate of patients were calculated, and the correlation among the loss value, deviation value of the C2-7 Cobb, and JOA recovery rate of the 79 patients was evaluated by Pearson correlation analysis.For the asymptomatic volunteers, the C0-2 Cobb decreased gradually with increasing age. The C2-7 Cobb, C2-7 SVA, T1S, NT, and TIA increased gradually with increasing age. The CBVA fluctuated with increasing age. T1S demonstrated a moderate correlation with C2-7 Cobb (r = 0.60, p 0.01); C0-2 Cobb, C2-7 SVA, CBVA, and TIA demonstrated a fair correlation with C2-7 Cobb (r = -0.30, -0.33, 0.41, 0.40, p 0.01); age demonstrated a poor correlation with C2-7 Cobb (r = 0.19, p 0.01). The regression equations of C2-7 Cobb were established using C0-2 Cobb, C2-7 SVA, CBVA, and T1S. For the patients with subaxial cervical spine surgery, the loss of C2-7 Cobb was moderately correlated with the deviation of C2-7 Cobb (r = 0.33, p 0.01).The age difference of cervical sagittal alignment was obvious, and the C2-7 Cobb increased with age especially. The closer the postoperative C2-7 Cobb was to the theoretical value of corresponding age, the smaller the loss of correction angle was, and the better the mid- and long-term outcomes. The personalized sagittal reconstruction should be performed according to age difference for subaxial cervical spine surgery.

We investigated the safety and efficacy profile of intensity-modulated radiation therapy (IMRT) followed by gemcitabine, dexamethasone, cisplatin (GDP), plus chidamide in the first-line setting for intermediate- and high-risk early-stage extranodal natural killer/T-cell lymphoma, nasal type (ENKTCL).This was an open-label, randomized phase 2 trial performed at 2 centers in China. Patients were eligible if they were newly-diagnosed with intermediate- and high-risk early-stage ENKTCL with at least one risk factor based on a nomogram-revised risk index:60 years old, elevated serum lactate dehydrogenase, invasion of the primary tumor, stage II or Eastern Cooperative Oncology Group performance status1 or stage II disease. Patients were treated with IMRT followed by GDP, with or without chidamide, in the first-line setting. Two-year progression-free survival (PFS) comprised the primary endpoint. Toxicities, the 2-year overall survival (OS), and the response rate comprised the secondary endpoints.Eligible patients (N = 74) were enrolled between May 2015 and December 2019. Among them, 37 patients were treated with IMRT + GDP + chidamide (chidamide group), whereas 37 cases were treated with IMRT + GDP (control group). Follow-up comprised a median of 43.4 months (range, 1.0-74.6 months). The objective response rate was 86.5% in the chidamide group and 78.4% in the control group (P = .359) at the end of treatment completion. The 2 year OS and PFS rates were 89.2% and 75.2% in the chidamide group versus 83.8% (P = .388) and 70.2% (P = .821) in the control group. The main adverse events were hematological toxicities and mucositis, with similar rates in the 2 groups (P.05).The addition of chidamide to IMRT + GDP as first-line treatment achieved similar treatment outcomes and tolerable toxicities compared with IMRT + GDP in patients with intermediate- and high-risk early-stage ENKTCL.

Obesity is closely related to the occurrence of cardiovascular diseases, and an important reason for this is the induction of endothelial cell dysfunction. Mitochondria play an important role in maintaining the function of endothelial cells. In the present study, we examined the effects of the sodium-dependent glucose transporters 2 inhibitor dapagliflozin (DAPA) on the vascular endothelium in obese mice in vivo and on the structure and function of human umbilical vein endothelial cells (HUVECs) in vitro. The results revealed that DAPA rescued vascular endothelial damage in obese mice. Moreover, DAPA reversed the effects of palmitic acid (PA) on the reduction in angiogenesis and the increase in apoptosis in HUVECs. Furthermore, DAPA rescued the reduced mitochondrial membrane potential, mitochondrial viability, energy metabolism, mitochondrial biogenesis and the mitochondrial structural injury caused by PA. DAPA also activated the SIRT1/PGC-1α signaling pathway, while the SIRT1 inhibitor EX-527 abrogated the effects of DAPA on the mitochondria of HUVECs. In summary, our study suggests that DAPA improves endothelial cell mitochondrial function in obese mice by activating the SIRT1/PGC-1α pathway.

The study aimed to examine the association of obesity and chronic kidney disease (CKD) after nonalcoholic fatty liver disease (NAFLD) occurrence.The study enrolled 10,311 adult men with newly diagnosed NAFLD and without CKD in the Kailuan cohort (2006-2013). The Fine-Gray model was used to compare advanced CKD risk in NAFLD with different baseline or trajectories in obesity measures.During a median follow-up of 10 years, maintaining normal waist circumference or waist-hip ratio, or transition from obesity to nonobesity determined by BMI, decreased 31% (hazard ratio [HR] = 0.69; 95% CI: 0.51-0.93), 34% (HR = 0.66; 95% CI: 0.45-0.95), and 38% (HR = 0.62; 95% CI: 0.40-0.96) of the CKD hazard compared with the "constantly without obesity" subgroup, respectively. NAFLD patients with at least 10% weight loss (HR = 0.58; 95% CI: 0.34-0.97) and with 7.0% to 9.9% weight loss (HR = 0.53; 95% CI: 0.28-0.99) had a lower risk for CKD than those with weight change ±4.9%. Compared with the stable weight population, the lower risk of ≥7% weight loss was observed only in patients with elevated blood pressure (adjusted HR = 0.48; 95% CI: 0.28-0.81).Short-term weight loss of at least 7% could decrease CKD risk, especially among patients with obesity and elevated blood pressure. It is important to monitor waist circumference, waist-hip ratio, and weight for NAFLD management.

Polymeric carriers for RNA therapy offer potential advantages in terms of low immunogenicity, promoting modifiability and accelerating intracellular transport. However, balancing high transfection efficacy with low toxicity remains challenging with polymer-based vehicles; indeed, polyethyleneimine (PEI) remains the "gold standard" polymer for this purpose despite its significant toxicity limitations. Herein, we demonstrate the potential of polyvinylamine (PVAm), a commodity high-charge cationic polymer used in the papermaking industry and has similar structure with PEI, as an alternative carrier for RNA delivery. High levels of transfection of normal, tumor, and stem cells with a variety of RNA cargoes including small interfering RNA (siRNA), microRNA (miRNA), and recombinant RNA can be achieved in vitro under the proper complex conditions. While, both the anti-tumor effect achieved in a xenograft osteosarcoma model and lipid-lowering activity observed in a hyperlipidemia mice indicate the potential for highly effective in vivo activity. Of note, both the transfection efficiency and the cytotoxicity of PVAm compare more favorably with those of PEI, with PVAm offering the additional advantages of simpler purification and significantly lower cost. In addition, the mechanism for the difference in transfection efficiency between PVAm and PEI is explored by molecular docking as well as analyzing the process of association and dissociation between polymers (PVAm and PEI) and nucleic acids. Our research provides a novel, non-toxic, and cost-effective carrier candidate for next generation RNA therapy, and elucidates the potential mechanism of PVAm for its efficient delivery of RNA.

Steatorrhea, a sign of severe pancreatic exocrine insufficiency (PEI), is related to consequences caused by pancreatitis. This study aimed to identify predictors and to construct a nomogram for steatorrhea in idiopathic chronic pancreatitis (ICP).ICP patients admitted to our hospital from January 2000 to December 2013 were enrolled in this retrospective-prospective cohort study and randomly assigned to the training and validation cohorts. The cumulative rate of steatorrhea was calculated. A Cox proportional hazard regression model was used to identify predictors for steatorrhea and construct the nomogram. Internal and external validation of the nomogram was then performed.There were 1633 ICP patients enrolled, with a median follow-up duration of 9.8 years and 20.8% (339/1633) of patients developed steatorrhea following onset of ICP. Steatorrhea was observed in 93, 115, and 133 patients at 1, 3, and 5 years following diagnosis of CP, with a cumulative rate of 6.5% (95% confidence interval [CI] 5.1%-7.9%), 8.0% (95% CI 6.2%-9.8%), and 9.3% (95% CI 6.6%-12.0%), respectively. Male sex (hazard ratio [HR] 2.479, P 0.001), diabetes mellitus at/before diagnosis of ICP (HR 2.274, P = 0.003), and aged less than 18 years at onset of ICP (HR 0.095, P 0.001) were identified risk factors for steatorrhea. Initial manifestations were associated with development of steatorrhea. The nomogram was proven to have good concordance indexes.We identified predictors and developed a nomogram for predicting steatorrhea in ICP. It was recommended that high-risk populations be followed up closely, which might contribute to the early diagnosis and treatment of PEI.

Maternal overweight or obesity during early pregnancy can increase the subsequent risk of gestational diabetes mellitus (GDM). However, whether these associations are mediated by thyroid hormones and their effect sizes is still unknown. This study aimed to identify the mediating effects of thyroid parameters between prepregnancy body mass index (BMI) or maternal weight gain during early pregnancy on the subsequent risk of GDM.This prospective mother-infant cohort study was conducted from 2018 to 2019. A total of 2772 singleton pregnant women were included in the analysis. A questionnaire survey, anthropometric measures, and thyroid function testing were conducted during early pregnancy. Deiodinase activity was evaluated using the free-triiodothyronine-to-free-thyroxine ratio (FT3:FT4). The standard 75-g oral glucose tolerance test was performed during 24 to 28 weeks of gestation to diagnose GDM. A mediation analysis was performed using PROCESS 3.5 to examine the mediating effects of thyroid parameters between prepregnancy BMI or maternal weight gain during early pregnancy on the subsequent risk of GDM.The FT3:FT4 ratio was a significant mediator between prepregnancy BMI or maternal weight gain and GDM, accounting for 16.5% and 18.6% of total effects, respectively. FT3 also mediated the association of prepregnancy BMI with GDM, accounting for 3.3% of the total effects. Thyroid-stimulating hormone suppressed the effects of prepregnancy BMI and maternal weight gain on GDM risk, and the proportion of their total effects was 2.4% and 6.4%, respectively.Deiodinase activity, as indicated by the FT3:FT4 ratio, was the strongest mediator among thyroid parameters between prepregnancy BMI or maternal early weight gain and GDM.

Zhuang-E Shi,1 Meng-Yu Zhang,1 Jian-Yu Liu,1 Wen-Di Zhang,1 Dong-Mei Hu,1 Qing-Xiang Wang,1 Xiu-Li Ji,2 Yuan-Yuan Jiang,3 Yi-Qing Qu3 1Department of Pulmonary and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Shandong Key Laboratory of Infectious Respiratory Diseases, Jinan, People’s Republic of China; 2Department of Pulmonary Disease, Jinan Traditional Chinese Medicine Hospital, Jinan, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, Qilu Hospital of Shandong University, Shandong Key Laboratory of Infectious Respiratory Diseases, Jinan, People’s Republic of ChinaCorrespondence: Yi-Qing Qu, Department of pulmonary and Critical Care Medicine, Qilu Hospital of Shandong University, Shandong Key Laboratory of Infectious Respiratory Diseases, Jinan, People’s Republic of China, Tel +86 531 8216 9335, Fax +86 531 8296 7544, Email quyiqing@sdu.edu.cnPurpose: Chronic obstructive pulmonary disease (COPD) is a predominant cause of mortality worldwide. Autophagy, which depends on a lysosomal degradation pathway, plays an essential role in the occurrence of COPD. The aim of our study was to identify the potential function of autophagy and construct a BCL2-related competing endogenous RNA (ceRNA) network that induces autophagy in COPD.Methods: Blood sample data from GSE31568, GSE24709, and GSE61741 were collected from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs in COPD and controls were identified via GEO2R. Transcription factors were obtained from FunRich. DIANA, miRDB, miRTarBase, and TargetScan were used to predict target genes of miRNAs. Autophagy genes were collected from the Human Autophagy Database (HADb). The GSE151052 dataset was used to identify autophagy-related differentially expressed genes in tissues. Functional enrichment and protein–protein interaction (PPI) network analyses were conducted via Metascape and the STRING network. Spearman correlation analysis was used to analyze the relationship between autophagy-related differentially expressed genes and lung function. The BCL2-related ceRNA network was modeled by Cytoscape.Results: We obtained 41 differentially expressed miRNAs and 10 significantly different transcription factors. We identified 19 autophagy-related differentially expressed genes that were significantly different (P< 0.05) in tissue samples. The most significant enrichment in Metascape was an autophagy item, which further confirmed autophagy participation in the occurrence of COPD. PPI network analysis found four genes (BCL2, BECN1, MAPK8, and ITPR1), among which BCL2 was correlated with both FEV1/FVC and FEV1 prediction. Finally, the BCL2-related ceRNA network was constructed to clarify the interaction of RNAs and occurrence of autophagy, including 18 miRNAs and 65 lncRNAs.Conclusion: We identified 19 autophagy-related differentially expressed genes that participated in COPD; among them, BCL2 was correlated with lung function, and a BCL2-related ceRNA network was constructed, which further revealed the potential mechanism of autophagy involvement in COPD.Keywords: COPD, autophagy, bioinformatics, lung function, BCL2, ceRNA

In order to analyze the distribution characteristics of pharyngeal bacteria in patients with chronic pharyngitis (CP) by 16SrDNA-based detection technology, a prospective study is conducted to collect pharyngeal secretion samples from patients diagnosed with CP who are admitted to the Otorhinolaryngology Department of The Third People’s Hospital of Shenzhen from May 2021 to September 2021. Among them, 11 cases are chronic simple pharyngitis (CSP), 11 cases are chronic hypertrophic pharyngitis (CHP), and 8 cases are healthy subjects. All samples are detected by the 16SrDNA technique and analyzed by bioinformatics. 55724.64 ± 1772.80, 53697.73 ± 2252.19, and 55177.5 ± 1661.80 optimized sequences are obtained by 16SrDNA sequencing. The α diversity analysis of pharyngeal microflora showed that the abundance index SOBS of pharyngeal microflora is upregulated in patients with CHP compared with normal controls (NC), but the diversity index of pharyngeal bacteria in the three groups is not significantly changed, indicating that the abundance of pharyngeal bacteria in the CHP group is increased. The β diversity analysis of pharyngeal microflora showed that the three groups are similar in structure and composition, and there is no significant statistical difference. The structural difference analysis of pharyngeal flora combined with LEfSe difference analysis showed that at the phylum level, the relative abundance of Spirochaetes and Synergistetes in the CHP group is significantly higher than that in the CSP group. At the genus level, the relative abundance of opportunistic pathogens such as Selenomonas and Campylobacter increased significantly in the CSP group. The relative abundance of Escherichia, Mycoplasma, and Porphyromonas are significantly increased in the CHP group. The abundance of beneficial symbiotic bacteria decreased significantly in patients with CP. The pharyngitis of patients with CP is characterized by an increase in the abundance of pharyngitis, changes in the structure of pharyngitis, a decline in the symbiotic beneficial bacteria, and an increase in the content of opportunistic pathogens, which may be closely related to the onset and development of CP.

Early detection of hepatocellular carcinoma (HCC) remains a clinical challenge. Glypican 3 (GPC3) is a proteoglycan highly specific for HCC and is a potential diagnostic and therapeutic target for HCC. This work aims to develop GPC3-targeted immuno-positron emission tomography (immunoPET) imaging strategies and to assess the diagnostic values in preclinical HCC models.Flow cytometry was used to screen GPC3-positive HCC cell lines. The expression of GPC3 in HCCs was detected by immunohistochemistry on tissue microarray. A novel GPC3-specific single domain antibody (sdAb) was produced and labeled with gallium-68 (GPC3 was strongly expressed on HCC cell lines and patients with poorly differentiated HCC. [In the work, we successfully developed sdAb-derived GPC3-targeted immunoPET imaging strategies and characterized the superior diagnostic accuracies in preclinical HCC models. Furthermore, we synthesized a fusion protein ABDG2 with improved targeting and pharmacokinetic properties, serving as a promising candidate for developing radioimmunotherapy agents.

The aim of this study was to explore the association of lifelong smoking status with risk of major adverse cardiovascular events (MACE) accounting for weight change in a Chinese cohort.The cohort of the People's Republic of China-United States of America (PRC-USA) Collaborative Study of Cardiovascular and Cardiopulmonary Epidemiology was established in 1983 to 1984, resurveyed during 1987 to 1988 and 1993 to 1994, and followed up to 2005. A total of 5,849 participants who survived in 1993 to 1994 were classified into never smokers, long-term quitters, short-term quitters, short-term relapsers and new smokers, long-term relapsers and new smokers, and persistent smokers according to the information on lifelong smoking status collected in all three surveys. The associations of lifelong smoking status with MACE in the subsequent 10 years were explored with Cox proportional hazards models.During a median follow-up of 10.2 years, 694 participants had MACE. Compared with persistent smokers, the multivariable-adjusted hazard ratio of developing MACE was 0.83 (95% CI: 0.61-1.12) for short-term quitters, 0.75 (95% CI: 0.54-1.02) for long-term quitters, and 0.68 (95% CI: 0.54-0.85) for never smokers (pLifelong smoking status is significantly associated with risk of MACE. As time duration increased, health benefit to quitters would become close to that of never smokers, and harms to relapsers and new smokers would become close to that of persistent smokers.

There is growing evidence that air pollution plays a role in TB, but few studies have comprehensively included the six common air pollutants. Our objectives were to investigate the association between short-term exposure to six common air pollutants and the risk of tuberculosis outpatient visits in Fuyang, China, during the period 2015-2020. We combined the two models to explore the effects of exposure to six air pollutants on the risk of tuberculosis outpatient visits, including Poisson generalized linear regression model and distributed lag non-linear model (DLNM). We performed stratified analyses for season, gender and age. We used the lag-specific relative risks and cumulative relative risk obtained by increasing pollutant concentration by per 10 units to evaluate the connection between six air pollutants and TB, PM2.5 (RR=1.0018, 95%CI: 1.0004-1.0032, delay of 12 days) and (RR=1.0169,95%CI: 1.0007-1.0333, lag 0-16 days), SO2 were 0.9549 (95%CI: 0.9389-0.9712, lag 0 days) and 0.8212 (95%CI: 0.7351-0.9173, 0-20 days lag). Stratified analyses showed that seasonal differences had a greater impact on TB, and male more likely to develop TB than female, older people more likely to develop TB than younger people. Exposure to O3, CO, PM10, PM2.5, and NO2 increases the risk of TB outpatient visits, except SO2 reduces the risk. Male and elderly people should be protected. We need to pay more attention to the impact of seasonal effects on TB.

To compare the efficacy of different treatments for posterior semicircular canal benign paroxysmal positional vertigo (PC-BPPV) by using direct and indirect evidence from existing randomized data.Randomized case-control studies that compared the efficacy of various nonsurgical treatments in PC-BPPV patients at 1 week and 1 month of follow-up were comprehensively screened. Bayesian network meta-analysis was performed to evaluate direct and indirect treatment comparisons. We further conducted subgroup pairwise meta-analysis to explore the inconsistency between comparisons of the Epley versus a sham maneuver and the Epley versus the Semont maneuver.A total of 41 parallel, randomized controlled studies were included. The Epley with vestibular rehabilitation (EVR), Epley, Semont and Hybrid maneuvers were effective in eliminating nystagmus during a Dix-Hallpike test at 1 week of follow-up (odds ratios [ORs]: 11.41-23.8, 95% credible interval [CrI]: excluding null), among which EVR showed the best efficacy (the surface area under the cumulative ranking curves [SUCRA] = 77.5%). However, at 1 month of follow-up, only the Semont (rank first, SUCRA = 76.1%) and Epley maneuvers (rank second, SUCRA = 65.3%) were effective in eliminating nystagmus during a Dix-Hallpike test. In the pairwise subgroup meta-analysis, for patients younger than 55 years of age, the efficacy of the Epley maneuver was comparable to that of the Semont maneuver [rate ratio (RR): 0.99, 95% confidence interval (CI): 0.93-1.05]; for patients with a longer duration before treatment, the effect of the Epley maneuver was equivalent to that of a sham maneuver (RR: 1.07, 95% CI: 0.90-1.29).Among the 12 types of PC-BPPV treatments, the Epley, Semont, EVR, and Hybrid maneuvers were effective in eliminating nystagmus during a Dix-Hallpike test for PC-BPPV at 1 week of follow-up, whereas only the Epley and Semont maneuvers were effective at 1 month of follow-up. The duration before treatments and the age of patients might contribute to the efficacy of treatments.

Background Combining the multimodal imaging and synergistic treatment in one platform can enhance the therapeutic efficacy and diagnosis accuracy. Results In this contribution, innovative Mn-doped Prussian blue nanoparticles (MnPB NPs) were prepared via microemulsion method. MnPB NPs demonstrated excellent T1 and T2 weighted magnetic resonance imaging (MRI) enhancement in vitro and in vivo. The robust absorbance in the near infrared range of MnPB NPs provides high antitumor efficacy for photothermal therapy (PTT) and photoacoustics imaging property. Moreover, with the doping of Mn, MnPB NPs exhibited excellent Fenton reaction activity for chemodynamic therapy (CDT). The favorable trimodal imaging and Fenton reaction enhanced mild temperature photothermal therapy in vitro and in vivo were further confirmed that MnPB NPs have significant positive effectiveness for integration of diagnosis and treatment tumor. Conclusions Overall, this Mn doped Prussian blue nanoplatform with multimodal imaging and chemodynamic/mild temperature photothermal co-therapy provides a reliable tool for tumor treatment. Graphical Abstract

Anthropometric traits, measuring body size and shape, are highly heritable and significant clinical risk factors for cardiometabolic disorders. These traits have been extensively studied in genome-wide association studies (GWASs), with hundreds of genome-wide significant loci identified. We performed a whole-exome sequence analysis of the genetics of height, body mass index (BMI) and waist/hip ratio (WHR). We meta-analyzed single-variant and gene-based associations of whole-exome sequence variation with height, BMI, and WHR in up to 22,004 individuals, and we assessed replication of our findings in up to 16,418 individuals from 10 independent cohorts from Trans-Omics for Precision Medicine (TOPMed). We identified four trait associations with single-nucleotide variants (SNVs; two for height and two for BMI) and replicated the LECT2 gene association with height. Our expression quantitative trait locus (eQTL) analysis within previously reported GWAS loci implicated CEP63 and RFT1 as potential functional genes for known height loci. We further assessed enrichment of SNVs, which were monogenic or syndromic variants within loci associated with our three traits. This led to the significant enrichment results for height, whereas we observed no Bonferroni-corrected significance for all SNVs. With a sample size of ∼20,000 whole-exome sequences in our discovery dataset, our findings demonstrate the importance of genomic sequencing in genetic association studies, yet they also illustrate the challenges in identifying effects of rare genetic variants.

Objective Kashin–Beck disease (KBD) is an endemic osteoarthropathy, in which excessive apoptosis of chondrocytes occurs. O6-methylguanine-DNA methyltransferase (MGMT), a DNA damage repair gene, plays an important role in apoptosis, but the mechanism is unclear in KBD cartilage injury. This study was to investigate the expression and promoter methylation of MGMT in KBD patients and its role in DNA damage and apoptosis of chondrocytes. Methods MGMT mRNA and protein level were detected by quantitative real-time PCR and immunohistochemistry. Demethylation of MGMT was carried out using 5-Aza-2′-deoxycytidine, and the methylation level of MGMT promoter was measured by quantitative methylation specific PCR. Next, small hairpin RNA was used to knockdown the expression of MGMT. Cell viability, apoptosis and DNA damage were determined by MTT assay, flow cytometry, Hoechst 33342 staining and alkaline comet assay following T-2 toxin and selenium treatment. Results MGMT protein expression and mRNA levels were decreased (P = 0.02, P = 0.007) and promoter methylation was increased (P = 0.008) in KBD patients. Meanwhile, MGMT level was upregulated by 5-Aza-2′-deoxycytidine in chondrocytes (P = 0.0002). DNA damage and apoptosis rates were increased in MGMT-silenced chondrocytes (all P Conclusions MGMT might play a crucial part in the pathogenesis of KBD cartilage injury, which could provide a therapeutic target for KBD.

The ongoing Coronavirus disease 19 pandemic has likely changed the world in ways not seen in the past. Neutralizing antibody (NAb) assays play an important role in the management of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak. Using these tools, we can assess the presence and duration of antibody-mediated protection in naturally infected individuals, screen convalescent plasma preparations for donation, test the efficacy of immunotherapy, and analyze NAb titers and persistence after vaccination to predict vaccine-induced protective effects. This review briefly summarizes the various methods used for the detection of SARS-CoV-2 NAbs and compares their advantages and disadvantages to facilitate their development and clinical application.

This study introduces an experimental paradigm for a usability test of emerging technologies in a management information system (MIS). The usability test included both subjective and objective evaluations. For the subjective evaluation, a usability questionnaire and a NASA-TLX scale were adopted. For the objective evaluation, methods of Neuro-Information-Systems (NeuroIS) were used. From a NeuroIS perspective, this study used mobile fNIRS and eye tracking glasses for multimodal measurements, which solved the problem of ecological validity of cognitive neuroscience tools used in real-world behavior experiments. This study used Augmented Reality (AR) integrated into the Internet of Things (IoT) as an experimental object. Comparing the differences in the neuroimaging data, the physiological data, the usability questionnaire, and the NASA-TLX scale data between the two information-search modes (AR versus a website), information search with AR had a higher efficiency and a lower cognitive load compared with information search with a website during the process of consumption decision-making. The usability experiment results demonstrate that AR, as an emerging technology in retail, can effectively enhance consumer experiences and increase their purchase intention. The experimental paradigm, combining both subjective and objective evaluations in this study, could be applied to a usability test for emerging technologies, such as augmented reality, virtual reality, artificial intelligence, wearable technology, robotics, and big data. It provides a practical experimental solution for the user experience in human-computer-interactions with the adoption of emerging technologies.

Frizzled 7 (FZD7) is abnormally expressed and activated in a variety of cancers. In ovarian cancer, overexpression of FZD7 reduces the sensitivity of platinum-resistant ovarian cancer cells to ferroptosis, thereby allowing cancer cells to survive. However, whether FZD7 inhibits ferroptosis in ovarian cancer cells and its mechanisms are remain unclear. This study aims to explore the effects of FZD7 and its upstream regulator miR-1-3p on ferroptosis in ovarian cancer cells are evaluated to clarify the molecular mechanism for miR-1-3p and FZD7's involvement in ferroptosis in ovarian cancer cells.Human ovarian cancer cell lines HO8910 and SKOV3 were used as the research subjects. In the first part of the experiment, human ovarian cancer cells were transfected with blank plasmid and FZD7 overexpression plasmid, respectively; in the second and third parts, human ovarian cancer cells were transfected with miR-1-3p mimics negative control, miR-1-3p mimics, miR-1-3p inhibitors negative control, and miR-1-3p inhibitors, respectively; in the fourth part of the experiment, human ovarian cancer cells were transfected with miR-1-3p mimics and miR-1-3p mimics+FZD7 overexpression plasmid, respectively, and normal cultured cells were set as the control group. The human ovarian cancer cell ferroptosis model was established by incubating human ovarian cancer cells with different treatments with ferroptosis inducer Erastin or RSL3. Real-time RT-PCR was used to detect the mRNA expression levels of FZD7 and miR-1-3p; Western blotting was used to detect the protein expression levels of FZD7; CCK-8 assay was used to detect the cell viability; lipid peroxidation colorimetric assay kit was used to detect the level of intracellular MDA; and iron assay kit was used to detect the level of intracellular Fe2+. Dual-luciferase assay was used to detect the targeting relationship between miR-1-3p and FZD7.Overexpression of FZD7 increased the cell viability of human ovarian cancer cell lines HO8910 or SKOV3 (P0.05, P0.01, or P0.001) and decreased the intracellular MDA levels (P0.01) in Erastin-treated or RSL3-treated ovarian cancer cells. FZD7 was a direct target of miR-1-3p, which inhibited the expression of FZD7 (P0.01) by binding to the 3'-untranslated region (3'UTR) site of FZD7. MiR-1-3p mimics decreased the cell viability of human ovarian cancer cell lines HO8910 or SKOV3 (P0.05, P0.01, or P0.001) and increased the intracellular MDA levels (P0.01) in Erastin-treated or RSL3-treated ovarian cancer cells; while miR-1-3p inhibitors significantly increased the cell viability of human ovarian cancer cell lines HO8910 or SKOV3 (P0.05, P0.01, or P0.001) and decreased the intracellular MDA levels (P0.01) in Erastin-treated or RSL3-treated ovarian cancer cells. The effect of miR-1-3p mimics on enhancing the sensitivity of human ovarian cancer cells to Erastin-induced or RSL3-induced ferroptosis was abrogated by overexpression of FZD7(P0.05 or P0.01).MiR-1-3p enhances the sensitivity of ovarian cancer cells to ferroptosis by targeting FZD7.

In this report, the authors describe a case of the acute anterior disc displacement without reduction treated by manipulative reduction combined with the disc-condyle repositioning splint to improve the limited mouth opening and relieve the pain, including diagnostic images and treatment performed.

Many studies have shown that chitinase-3-like protein 1 (CHI3L1), also known as YKL-40, is associated with asthma. The purpose of this meta-analysis was to evaluate the role of serum YKL-40 in the diagnosis and differential diagnosis of asthma, severity grading, and determination of disease state. The PubMed, Ovid, and Cochrane databases were searched. A total of 17 articles involving 5696 subjects were included in this meta-analysis. The results showed that the level of YKL-40 was significantly higher in asthmatic patients than in the normal group regardless of age and residential location, and increased with severity and acute exacerbation (p

Background The aim of the present study was to establish a competing risk nomogram to predict parotid gland cancer-specific mortality (PGC-SM). Methods Seven thousand nine hundred and sixty-two patients extracted from SEER database were randomly categorized into training and validation sets. The competing risk model was used to identify factors associated with PGC-SM. The nomogram was evaluated via concordance indexes (C-indexes), calibration plots, and decision curve analysis (DCA). Results Male, elderly, white, widowed, larger tumor, no surgery, advanced tumor grade, lymph node (LN) metastasis, adenocarcinoma (ADC), and higher TNM stage were associated with higher incidence of PGC-SM. Calibration plots showed that the nomogram was well calibrated. C-indexes for nomogram were 0.84 (95% CI: 0.81-0.86) and 0.84 (95% CI: 0.82-0.86) in training and validation sets, respectively. DCA demonstrated the clinical usefulness of nomogram. Conclusions The competing risk nomogram shows high performance in predicting PGC-SM, which might enable clinicians formulate suitable treatment protocols for patients with parotid gland carcinoma (PGC).

BACKGROUND Chronic wounds are a worldwide health problem, with traditional imaging techniques failing in their accurate evaluation. Therefore, an effective imaging evaluation method is needed for the diagnosis and treatment or chronic wounds. This study is to investigate the application value of computed tomography (CT) and magnetic resonance imaging (MRI) sinography/fistulography in assessing the morphology and deep features of chronic wounds. METHODS We prospectively enrolled 43 chronic wounds patients who received both CT and MRI sinography/fistulography. The morphology and deep features of chronic wound on CT and MRI images were independently evaluated by 2 experienced radiologists. Kappa value and intraclass correlation coefficient (ICC) were calculated to evaluate the interobserver agreement and the consistency between CT and MRI sinography/fistulography in assessing the shape, number of branches, and involvement of body cavity and bones of chronic wounds. RESULTS There were substantial to almost perfect interobserver agreements for both CT and MRI sinography/fistulography in evaluating the morphology and deep features of chronic wounds. The consistency between CT and MRI was almost perfect for the 2 readers in evaluating the shape (reader 1, kappa value =1.000; reader 2, kappa value =0.932) and the number of branches [reader 1, ICC =0.951 (95% confidence interval: 0.909-0.973, P

From a mouse triple‐negative breast cancer cell line, 4T1, we previously established 4T1.3 clone with a high capacity to metastasize to bone after its orthotopic injection into mammary fat pad of immunocompetent mice. Subsequent analysis demonstrated that the interaction between cancer cells and fibroblasts in a bone cavity was crucial for bone metastasis focus formation arising from orthotopic injection of 4T1.3 cells. Here, we demonstrated that a member of the adhesion G‐protein–coupled receptor (ADGR) family, G‐protein–coupled receptor 56 (GPR56)/adhesion G‐protein–coupled receptor G1 (ADGRG1), was expressed selectively in 4T1.3 grown in a bone cavity but not under in vitro conditions. Moreover, fibroblasts present in bone metastasis sites expressed type III collagen, a ligand for GPR56/ADGRG1. Consistently, GPR56/ADGRG1 proteins were detected in tumor cells in bone metastasis foci of human breast cancer patients. Deletion of GPR56/ADGRG1 from 4T1.3 cells reduced markedly intraosseous tumor formation upon their intraosseous injection. Conversely, intraosseous injection of GPR56/ADGRG1‐transduced 4T1, TS/A (mouse breast cancer cell line), or MDA‐MB‐231 (human breast cancer cell line) exhibited enhanced intraosseous tumor formation. Furthermore, we proved that the cleavage at the extracellular region was indispensable for GPR56/ADGRG1‐induced increase in breast cancer cell growth upon its intraosseous injection. Finally, inducible suppression of Gpr56/Adgrg1 gene expression in 4T1.3 cells attenuated bone metastasis formation with few effects on primary tumor formation in the spontaneous breast cancer bone metastasis model. Altogether, GPR56/ADGRG1 can be a novel target molecule to develop a strategy to prevent and/or treat breast cancer metastasis to bone., GPR56/ADGRG1 expression conferred growth advantage on breast cancer cells in the bone cavity, thereby promoting bone metastasis formation.GPR56/ADGRG1 can be a novel target molecule to develop a strategy to treat breast cancer metastasis to bone.

Background Ovarian cancer(OC) is the gynecological tumor with the highest mortality rate, effective biomarkers are of great significance in improving its prognosis. In recent years, there have been many studies on alternative splicing (AS) events, and the role of AS events in tumor has become a focus of attention. Methods Data were downloaded from the TCGA database and Univariate Cox regression analysis was performed to determine AS events associated with OC prognosis.Eight prognostic models of OC were constructed in R package, and the accuracy of the models were evaluated by the time-dependent receiver operating characteristic (ROC) curves.Eight types of survival curves were drawn to evaluate the differences between the high and low risk groups.Independent prognostic factors of OC were analyzed by single factor independent analysis and multi-factor independent prognostic analysis.Again, Univariate Cox regression analysis was used to analyze the relationship between splicing factors(SF) and AS events, and Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis were performed on OS-related SFs to understand the pathways. Results Univariate Cox regression analysis showed that among the 15,278 genes, there were 31,286 overall survival (OS) related AS events, among which 1524 AS events were significantly correlated with OS. The area under the time-dependent receiver operating characteristic curve (AUC) of AT and ME were the largest and the RI was the smallest,which were 0.757 and 0.68 respectively. The constructed models have good value for the prognosis assessment of OC patients. Among the eight survival curves, AP was the most significant difference between the high and low risk groups, with a P value of 1.61e − 1.The results of single factor independent analysis and multi-factor independent prognostic analysis showed that risk score calculated by the model and age could be used as independent risk factors.According to univariate COX regression analysis,109 SFs were correlated with AS events and adjusted in two ways: positive and negative. Conclusions SFs and AS events can directly or indirectly affect the prognosis of OC patients. It is very important to find effective prognostic markers to improve the survival rate of OC.

Dandy-Walker syndrome (DWS) is a group of brain malformations which occasionally accompanied by psychotic symptoms. The co-occurrence of DWS and epilepsy in children is quite rare.We reported a 14-year-old male who presented with a 8-month history of inconsistent upper limb tremor and accidental seizure. The MRI showed the typical alterations of DWS: cystic dilatation of the fourth ventricle, vermian hypoplasia, enlarged posterior fossa. He received the ventriculoperitoneal shunting (VPS) placement for hydrocephalus and had a symptom-free period for 8 days. Then he experienced a recurrence of involuntary upper limb tremor and behavior disturbance after decreasing the pressure of cerebrospinal fluid (CSF) from 150 to 130 mm Hg. After being treated with Olanzapine 10 mg/d, Clonazepam 3 mg/qn and Valproate acid (VPA) 500 mg/bid for nearly a month, his mental status and psychotic symptoms fluctuated. A search of Pub Med showed little report of hydrocephalus and DWS comorbidity with seizure and psychosis. Here we presented the whole process of a rare disease from the very beginning with all his symptoms, examinations and treatments.VPS placement surgery at an earlier stage may be an effective way to avoid inevitable brain damage so as to improve the clinical outcomes for patients with DWS. Continued treatment with regard to DWS condition may include shunt placement, but it mainly focus on developmental concerns, with occupational and physical therapy along with ongoing supportive psychotherapy to improve the coping skills and quality of life.

Background Age has substantial influence on metabolic diseases patterns. Ethnic disparities of metabolic characteristics between Chinese and other populations also exist. Large-scale investigations of age-specific prevalence, subtypes and modifiable risk factors of metabolic disorders are essential to promote individualized strategies for the control and prevention of metabolic diseases in multi-ethnic populations. The study aims to address the age-specific prevalence, subtype characteristics and risk factor profiles of metabolic diseases among different races/ethnicities. Methods We analyzed data from the China Noncommunicable Disease Surveillance 2010 and the National Health and Nutrition Evaluation Survey (NHANES). We examined the prevalence and subtypes of hypertension, diabetes and hyperlipidemia across age groups in four ethnic populations. We also investigated the odds ratios (ORs) of metabolic diseases associated with 11 classical risk factors in the young and the elder Mainland Chinese. Results The sex and BMI standardized prevalence of hypertension in Chinese aged 18–40 years was 18.5% and was the highest among the four populations. The main pathophysiologic subtype of diabetes was characterized by insulin resistance, instead of β-cell dysfunction in Mainland Chinese, and this pattern was more evident in obese subjects. The major subtype of hyperlipidemia in Mainland Chinese was hypertriglyceridemia, while Non-Hispanic Whites and Blacks were more prone to high low-density lipoprotein cholesterol. For risk of hypertension, diabetes and hyperlipidemia, young Chinese adults were more prone to general and central obesity than older ones. The other factors showed similar effects on the young and the old. Conclusions The age-specific prevalence, subtypes and risk factors of metabolic diseases were substantially different in Chinese and other ethnic/racial populations.

Apparent mineralocorticoid excess is an autosomal recessive form of monogenic disease characterized by juvenile resistant low-renin hypertension, marked hypokalemic alkalosis, low aldosterone levels, and high ratios of cortisol to cortisone metabolites. It is caused by defects in the HSD11B2 gene, encoding the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which is primarily involved in the peripheral conversion of cortisol to cortisone. To date, over 50 deleterious HSD11B2 mutations have been identified worldwide. Multiple molecular mechanisms function in the lowering of 11β-HSD2 activity, including damaging protein stability, lowered affinity for the substrate and cofactor, and disrupting the dimer interface. Genetic polymorphism, environmental factors as well as epigenetic modifications may also offer an implicit explanation for the molecular pathogenesis of AME. A precise diagnosis depends on genetic testing, which allows for early and specific management to avoid the morbidity and mortality from target organ damage. In this review, we provide insights into the molecular genetics of classic and non-classic apparent mineralocorticoid excess and aim to offer a comprehensive overview of this monogenic disease.

To analyze the application characteristics of acupuncture and moxibustion in clinical treatment of Meniere's disease by using complex network technology, so as to provide evidence for selecting acupoints, needling and moxibustion methods and treatment ideas.Articles both in English and Chinese published from the inception of databases of CNKI, Wanfang VIP, Chinese biomedical literature database (SinoMed), PubMed, Embase, EBSCO (Academic Search Pre-mier), Web of Science and Ovid to April of 2021 were retrieved by using key words "acupuncture" or "moxibustion" or "acupuncture and moxibustion" and "Meniere disease" or "Meniere's syndrome" or "Ménières vertigo" or "otogenic vertigo" or "auditory vertigo", followed by screening the literature according to the inclusion and exclusion criteria and establishing a database of clinical li-terature about acupuncture treatment of Meniere's Disease with software Epidata 3.1. Then, the descriptive analysis was conducted first, followed by association rule analysis using SPSS Modeler 18.0, and complex network analysis using Gephi 0.9.2 software.A total of 232 articles were included, containing 152 acupoints [97 body acupoints as Baihui (GV20), Fengchi (GB20), Neiguan (PC6), etc., 28 otopoints as Ershenmen (MA-TF1), Shen (MA-SC), etc., 20 scalp points as Yunting Area, 7 extra-points as Sishencong (EX-HN1), Taiyang (EX-HN5), etc.] which were used to be a total frequency of 1 569. Descriptive analysis showed that the main meridians were the Governor Vessel, Stomach Meridian of Foot Yangming, Trienergizer Meridian of Hand Shaoyang, and Gallbladder Meridian of Foot Shaoyang. Acupuncture was the most commonly used therapy for Meniere's disease. The association analysis showed that the most relevant combination of acupoints was GV20 and GB20, GV20 and PC6, reflecting the principles of local acupoint selection and combination of local and distant acupoints. Finally, "K-core Analytic Hierarchy Process" and "Community Analysis" revealed that 3 core acupoint groups were most frequently used in clinical treatment of Meniere's disease, including 1) auricular acupoints, as MA-TF1, MA-SC, Neier(MA-L), Zhen(MA-AT) and Pizhixia(MA-AT1), 2) acupoints of the 14 meridians and extra-points, as Tinggong(SI19), Yifeng(TE17), GB20, 3) acupoints of the Shaoyang meri-dians of hand and foot, as Shuaigu (GB8), Tinghui (GB2), Zhongzhu (TE3), Ermen (TE21), etc.The principle of acupoint selection is mainly based on the combination of acupoints along the meridians and local areas, while paying attention to the coordination among the auricular points, scalp acupoints and extra-points, which may provide a reference for the clinical treatment and scientific research on acupuncture treatment of Meniere's disease.

Readmission due to chronic obstructive pulmonary disease (COPD) exacerbation contributes significantly to disease burden. Trend in readmission rate among COPD patients in China is not well characterized. We described the secular trend and identify risk factors of COPD-related 30-day readmission in Beijing during 2012–2017. In this retrospective cohort study, we used data from a citywide hospital discharge database in Beijing. We included patients ≥ 40 years with a primary diagnosis of COPD from 2012 to 2017. A total of 131 591 index admissions were identified. COPD-related 30-day readmission was defined as the initial admission with a primary diagnosis of COPD that occurs within 30 days from the discharge date of an index admission. Overall and annual 30-day readmission rates were calculated in the total population and subgroups defined by patient characteristics. We used multivariable logistic models to investigate risk factors for readmission and in-hospital mortality within 30 days. The overall 30-day COPD-related readmission rate was 15.8% (n = 20 808). The readmission rate increased from 11.5% in 2012 to 17.2% in 2017, with a multivariable-adjusted OR (95% CI) for annual change to be 1.08 (1.06–1.09) (P trend

Hepatocellular carcinoma (HCC) is a common malignancy with high mortality and poor prognosis due to a lack of predictive markers. However, research on small nuclear RNAs (snoRNAs) in HCC were very little. This study aimed to identify a potential diagnostic and prognostic snoRNA signature for HCC.HCC datasets from the cancer genome atlas (TCGA) and international cancer genome consortium (ICGC) cohorts were used. Differentially expressed snoRNA (DEs) were identified using the limma package. Based on the DEs, diagnostic and prognostic models were established by the least absolute shrinkage and selection operator (LASSO) regression and COX analysis, and Kaplan-Meier (K-M) survival analysis and receiver operating characteristic (ROC) curve analysis were conducted to evaluate the efficiency of signatures. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used to analyze the risk score and further explore the potential correlation between the risk groups and tumor immune status in TCGA. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to determine the functions of key snoRNAs.We constructed a 6-snoRNAs signature which could classify patients into high- or low-risk groups and found that patients in the high-risk group had a worse prognosis than those in the low-risk group and were significantly involved in p53 processes. Tumor immune status analysis revealed that CTLA4 and PDCD1 (PD1) were highly expressed in the high-risk group, which responded to PD1 inhibitor therapy. Additionally, a 25-snoRNAs diagnostic signature was constructed with an area under the curve (AUC) of 0.933 for distinguishing HCCs from normal controls. Finally, 3 key snoRNAs (SNORA11, SNORD124, and SNORD46) were identified with both diagnostic and prognostic efficacy, some of which were closely related to the spliceosome and Notch signaling pathways.Our study identified 6 snoRNAs that may serve as novel prognostic models and 3 key snoRNAs with both diagnostic and prognostic efficacy for HCC.

To compare therapeutic efficacy and safety of ultrasound (US)-guided selective nerve root block (SNRB) and fluoroscopy (FL)-guided transforaminal epidural steroid injection (TFESI) for cervical spine radiculopathy (CSR).156 patients with CSR randomly received US-guided SNRB verified by FL or FL-guided TFESI. We hypothesised that the accuracy rate of contrast dispersion into epidural or intervertebral foraminal space in the US group was not inferior to that in the FL group with a margin of clinical unimportance of -15%. Pain intensity assessed by Numeric Rating Scales (NRS) and functional disability estimated by neck disability index (NDI) were compared before treatment, at 1, 3 and 6 months after the intervention. Puncture time and complication frequencies were also reported.88.7% and 90.3% accuracy ratings were respectively achieved in the US and FL groups with a treatment difference of -1.6% (95%CI: -9.7%, 6.6%) revealing that the lower limit was above the non-inferiority margin. Both NRS and NDI scores illustrated improvements at 1, 3 and 6 months after intervention with no statistically significant differences between the two groups (allCompared with the FL group, the US group provided a non-inferior accuracy rate of epidural/foraminal contrast pattern. For the treatment of CSR, the US technique provided similar pain relief and functional improvements while facilitating distinguishing critical vessels adjacent to the foramen and requiring a shorter procedure duration without exposure to radiation. Therefore, it was an attractive alternative to the conventional FL method.Key messagesWe conducted a prospective, open-label, randomised and non-inferiority clinical trial to estimate a hypothesis that the precisely accurate delivery through ultrasound (US)-guided cervical selective nerve root block (SNRB) was non-inferior to that using FL-guided transforaminal epidural steroid injection. Additionally, US-guided SNRB was as effective as FL-guided TFESI in the treatment effect on pain relief and function improvements. Notably, the US technique might be an alternative to the conventional FL method due to the ability to prevent inadvertent vascular puncture (VP) and intravascular injection (IVI) with a shorter administration time and absence of radiation exposure.

Within the field of lipid nanoparticles (LNPs) for RNA delivery, the focus has been mainly placed on organ level delivery, which can mask cellular level effects consequential to therapeutic applications. Here, we studied a pair of LNPs with similar physical properties and discovered how the chemistry of the ionizable amino lipid can control the endogenous LNP identity, affecting cellular uptake in the liver and altering therapeutic outcomes in a model of liver cancer. Although most LNPs accumulate in the liver after intravenous administration (suggesting that liver delivery is straightforward), we observed an unexpected behavior when comparing two similar LNP formulations (5A2-SC8 and 3A5-SC14 LNPs) that resulted in distinct RNA delivery within the organ. Despite both LNPs possessing similar physical properties, ability to silence gene expression

The incidence of thyroid disease has gradually increased in recent years. Conventional ultrasound is one of the most critical thyroid imaging methods, but it still has certain limitations. The use of B-model ultrasound (BMUS) diagnosis of thyroid disease will be affected by a doctors' clinical experience. The ultrasound radiomics is based on ultrasound images to delineate the region of interest (ROI), and then extract features to quantify the disease information contained in the image, which helps to analyze the correlation between the image and the clinical pathology of the disease. By building a powerful model, it can be used to diagnose benign and malignant thyroid nodules, predict lymph node status in thyroid cancer, analyze molecular biological characteristics, and predict the survival of thyroid cancer patients. At present, the application of ultrasound radiomics in the thyroid is pervasive. These ultrasound radiomics studies have further promoted the progress of ultrasonic technology in the field of thyroid disease. Clinicians should be familiar with the workflow of ultrasound radiomics and understand the application of this technology to the thyroid. In this article, we first describe the workflow of ultrasound radiomics, followed by an overview of the application of ultrasound radiomics to the thyroid. Finally, some current limitations of the technology and areas for future improvement are discussed. This article aims to review the role of ultrasound radiomics and its application and limitations in the investigation of thyroid disease.

ObjectiveThe outbreak of COVID-19 in 2020 is reminiscent of the H7N9 outbreak in 2013, which poses a huge threat to human health. We aim to compare clinical features and survival factors in fatal cases of COVID-19 and H7N9.MethodsData on confirmed COVID-19 and H7N9 fatal cases identified in mainland China were analyzed to compare demographic characteristics and clinical severity. Survival curves were estimated by the Kaplan–Meier method and compared using log-rank tests and a restricted mean survival time model. A Cox regression model was used to identify survival factors in fatal cases of COVID-19 and H7N9.ResultsSimilar demographic characteristics were observed in fatal cases of COVID-19 and H7N9. The proportion of fatal cases of H7N9 receiving antibiotics, antiviral drugs, and oxygen treatment was higher than that of COVID-19. The potential protective factors for fatal COVID-19 cases were receiving antibiotics (HR: 0.37, 95% CI: 0.22–0.61), oxygen treatment (HR: 0.66, 95% CI: 0.44–0.99), and corticosteroids (HR: 0.46, 95% CI: 0.35–0.62). In contrast, antiviral drugs (HR: 0.21, 95% CI: 0.08–0.56) and corticosteroids (HR: 0.45, 95% CI: 0.29–0.69) were the protective factors for H7N9 fatal cases.ConclusionThe proportion of males, those having one or more underlying medical condition, and older age was high in COVID-19 and H7N9 fatal cases. Offering antibiotics, oxygen treatment, and corticosteroids to COVID-19 cases extended the survival time. Continued global surveillance remains an essential component of pandemic preparedness.

Tumor cells often exhibit metabolic reprogramming to maintain their rapid growth and proliferation. Glutaminase 1 (GLS1) has been viewed as a promising target in the glutamine metabolism pathway for the treatment of malignant tumors. Using structure-based drug design approaches, a novel series of GLS1 allosteric inhibitors were designed and synthesized. Compound 41a (LWG-301) with an alkane chain "tail" group had potent biochemical and cellular GLS1 activity, and improved metabolic stability. LWG-301 exhibited moderate antitumor effects in HCT116 xenograft model, with TGI of 38.9% in vivo. Mechanistically, LWG-301 could significantly block glutamine metabolism, resulting in changes in the corresponding amino acid levels in cells, induce a concentration-dependent increase in intracellular ROS levels, and induce apoptosis. Taken together, this paper provides more structural references and new design strategy for the development of GLS1 allosteric inhibitors.

This study was conducted to investigate the role of Tenascin-C (TNC) in paraquat (PQ)-induced lung injury in vivo and in vitro and explore its related mechanism during this process. Six- to eight-week-old male C57BL/6 mice were injected with 30 mg/kg PQ by intraperitoneal injection and sacrificed on 2 days, 7 days, 14 days, and 28 days after PQ administration. In vivo, we detected the expression of TNC at all time points of lung tissues in mice by reverse transcription-quantitative-polymerase chain reaction, western blotting, and immunohistochemistry. Expression of TLR4, NF-κB p65, TGF-β1, and α-SMA in lung tissues have also been tested. In vitro, siRNA was used to knock down TNC expression in A549 cells and TLR4, NF-κB p65, and TGF-β1 expressions were examined after PQ exposure. TNC expression increased in both lung tissues of mice model and A549 cells after PQ administration. In vivo, TNC mostly located at the extracellular matrix of thickened alveolar septum, especially at sites of injury, together with the increasing of TLR4, NF-κB p65, TGF-β1, and α-SMA. In vitro, PQ exposure also increased the expressions of TLR4, NF-κB p65, and TGF-β1 in A549 cells, but knocking down TNC gene expression obviously down-regulated the expressions of TLR4, NF-κB p65, NF-κB Pp65, and TGF-β1. The results of this study demonstrate, for the first time, that TNC participates in the development of lung injury induced by PQ poisoning. The role of TNC in this process is closely related to TLR4 and TGF-β signaling pathways.

Gastrointestinal (GI) cancers are among the most fatal diseases in the world. Numerous studies have demonstrated the relationship between autophagy and development of gastrointestinal cancers. However, whether autophagy-related genes can predict prognosis of GI cancers in individuals of Asian ancestry has not been defined. This study, evaluated the prognostic value of autophagy-related genes in gastrointestinal cancer. Expression profile of autophagy-related genes for 296 gastrointestinal cancer patients of Asian ancestry was downloaded from the TCGA database (TCGA-LIHC, TCGA-STAD, TCGA-ESCA, TCGA-PAAD, TCGA-COAD, TCGA-CHOL, and TCGA-READ). The prognostic value of the autophagy-related genes was evaluated using univariate Cox, LASSO, and multivariate Cox regression analyses. The risk score of the autophagy-related gene signature was calculated to assess its predictive prognostic value for GI cancers. Forty-seven differentially expressed autophagy-related genes, in Asian patients with gastrointestinal cancers, were identified. Of the 47 genes, 4 were associated with prognosis of GI cancer (SQSTM1, BIRC5, NRG3, and CXCR4). A prognostic model for GI cancer, based on the expression of the above 4 genes in the training set, showed that cancer patients were stratified into high-risk and low-risk groups ( P < 0.05 ). The utility of the model for overall survival (OS) of GI cancer patients was consistent across the entire set, training set, and test set (entire set: P = 4.568 × 10 − 4 ; train set: P = 5.718 × 10 − 3 ; test set: P = 3.516 × 10 − 2 ). The sensitivity and specificity of the ROC curve of the above prognostic model in predicting the 5-year prognosis of GI cancer was satisfactory (entire set: 0.728; train set: 0.727; test set: 0.733). Analysis of clinical samples validated the overexpression of the 4 genes (SQSTM1, BIRC5, NRG3, and CXCR4) in tumor tissues relative to paired normal tissues, consistent with bioinformatic findings. Expression of the 4 autophagy-related genes (SQSTM1, BIRC5, NRG3, and CXCR4) can accurately predict the prognosis of gastrointestinal tumors in Asian patients.

This study evaluated the differences in metabolites between cumulus cells (CCs) and mural granulosa cells (MGCs) from human preovulatory follicles to understand the mechanism of oocyte maturation involving CCs and MGCs. CCs and MGCs were collected from women who were undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment. The differences in morphology were determined by immunofluorescence. The metabolomics of CCs and MGCs was measured by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) followed by quantitative polymerase chain reaction (qPCR) and western blot analysis to further confirm the genes and proteins involved in oocyte maturation. CCs and MGCs were cultured for 48 h in vitro, and the medium was collected for detection of hormone levels. There were minor morphological differences between CCs and MGCs. LC-MS/MS analysis showed that there were differences in 101 metabolites between CCs and MGCs: 7 metabolites were upregulated in CCs, and 94 metabolites were upregulated in MGCs. The metabolites related to cholesterol transport and estradiol production were enriched in CCs, while metabolites related to antiapoptosis were enriched in MGCs. The expression of genes and proteins involved in cholesterol transport (ABCA1, LDLR, and SCARB1) and estradiol production (SULT2B1 and CYP19A1) was significantly higher in CCs, and the expression of genes and proteins involved in antiapoptosis (CRLS1, LPCAT3, and PLA2G4A) was significantly higher in MGCs. The level of estrogen in CCs was significantly higher than that in MGCs, while the progesterone level showed no significant differences. There are differences between the metabolomes of CCs and MGCs. These differences may be involved in the regulation of oocyte maturation.