Deubiquitinase UCHL1 promotes angiogenesis and blood-spinal cord barrier function recovery after spinal cord injury by stabilizing Sox17.

Improving the function of the blood-spinal cord barrier (BSCB) benefits the functional recovery of mice following spinal cord injury (SCI). The death of endothelial cells and disruption of the BSCB at the injury site contribute to secondary damage, and the ubiquitin-proteasome system is involved in regulating protein function. However, little is known about the regulation of deubiquitinated enzymes in endothelial cells and their effect on BSCB function after SCI. We observed that Sox17 is predominantly localized in endothelial cells and is significantly upregulated after SCI and in LPS-treated brain microvascular endothelial cells. In vitro Sox17 knockdown attenuated endothelial cell proliferation, migration, and tube formation, while in vivo Sox17 knockdown inhibited endothelial regeneration and barrier recovery, leading to poor functional recovery after SCI. Conversely, in vivo overexpression of Sox17 promoted angiogenesis and functional recovery after injury. Additionally, immunoprecipitation-mass spectrometry revealed the interaction between the deubiquitinase UCHL1 and Sox17, which stabilized Sox17 and influenced angiogenesis and BSCB repair following injury. By generating UCHL1 conditional knockout mice and conducting rescue experiments, we further validated that the deubiquitinase UCHL1 promotes angiogenesis and restoration of BSCB function after injury by stabilizing Sox17. Collectively, our findings present a novel therapeutic target for treating SCI by revealing a potential mechanism for endothelial cell regeneration and BSCB repair after SCI.

USP1/UAF1-Stabilized METTL3 Promotes Reactive Astrogliosis and Improves Functional Recovery after Spinal Cord Injury through m6A Modification of YAP1 mRNA.

RNA N6-methyladenosine (m6A) modification is involved in diverse biological processes. However, its role in spinal cord injury (SCI) is poorly understood. The m6A level increases in injured spinal cord, and METTL3, which is the core subunit of methyltransferase complex, is upregulated in reactive astrocytes and further stabilized by the USP1/UAF1 complex after SCI. The USP1/UAF1 complex specifically binds to and subsequently removes K48-linked ubiquitination of the METTL3 protein to maintain its stability after SCI. Moreover, conditional knockout of astrocytic METTL3 in both sexes of mice significantly suppressed reactive astrogliosis after SCI, thus resulting in widespread infiltration of inflammatory cells, aggravated neuronal loss, hampered axonal regeneration, and impaired functional recovery. Mechanistically, the YAP1 transcript was identified as a potential target of METTL3 in astrocytes. METTL3 could selectively methylate the 3'-UTR region of the YAP1 transcript, which subsequently maintains its stability in an IGF2BP2-dependent manner. In vivo, YAP1 overexpression by adeno-associated virus injection remarkably contributed to reactive astrogliosis and partly reversed the detrimental effects of METTL3 knockout on functional recovery after SCI. Furthermore, we found that the methyltransferase activity of METTL3 plays an essential role in reactive astrogliosis and motor repair, whereas METTL3 mutant without methyltransferase function failed to promote functional recovery after SCI. Our study reveals the previously unreported role of METTL3-mediated m6A modification in SCI and might provide a potential therapy for SCI.SIGNIFICANCE STATEMENT Spinal cord injury is a devastating trauma of the CNS involving motor and sensory impairments. However, epigenetic modification in spinal cord injury is still unclear. Here, we propose an m6A regulation effect of astrocytic METTL3 following spinal cord injury, and we further characterize its underlying mechanism, which might provide promising strategies for spinal cord injury treatment.

Assessing the utility of MRI-based vertebral bone quality (VBQ) for predicting lumbar pedicle screw loosening.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: The purpose of this study is to assess the potential of utilizing the MRI-based vertebral bone quality (VBQ) score as a predictive tool for pedicle screw loosening (PSL) in patients who have undergone pedicle screw fixation and to identify risk factors associated with VBQ scores. METHODS: One hundred and sixteen patients who had undergone pedicle screw fixation between December 2019 and January 2021 and had more than a year of follow-up were divided into two groups of PSL and non-PSL. The radiological and clinical parameters investigated were age, gender, body mass index, the VBQ score, length of fusion and the DXA T-score. RESULTS: Of the 116 patients included in the study, 22 patients developed pedicle screw loosening after surgery (18.97%). VBQ score of PSL group was higher than the non-PSL group (3.61 ± 0.63 vs. 2. 86 ± 0.43, p < 0.001). According to logistic regression, PSL was independently linked with a higher VBQ score (OR = 3.555, 95% confidence interval [1.620-7.802], p < 0.005). The AUC of predicting screw loosening was 0.774 (p < 0.001) for VBQ score, and the best threshold was 3.055 (sensitivity, 81.8%; specificity, 71.3%). High VBQ score was associated with age (r (114) = 0.29, p = 0.002), while it was not negatively correlated with T-scores of each part. CONCLUSION: VBQ score is an independent predictor of pedicle screw loosening, with higher scores indicating a greater risk. Our results showed that older patients and women had higher VBQ scores.

Diagnostic performance of metagenomic next-generation sequencing for Pneumocystis jirovecii pneumonia.

OBJECTIVE: Pneumocystis jirovecii pneumonia (PJP) can be a life-threatening opportunistic infection. We aimed to evaluate the diagnostic accuracy of metagenomic next-generation sequencing (mNGS) for PJP. METHODS: A comprehensive electronic literature search of Web of Knowledge, PubMed, Cochrane Library, CNKI and Wanfang data was performed. Bivariate analysis was conducted to calculate the pooled sensitivity, specificity, diagnostic odds ratio (DOR), the area under the summary receiver operator characteristic (SROC) curve and the Q-point value (Q*). RESULTS: The literature search resulted in 9 studies with a total of 1343 patients, including 418 cases diagnosed with PJP and 925 controls. The pooled sensitivity of mNGS for diagnosis of PJP was 0.974 [95% confidence interval (CI), 0.953-0.987]. The pooled specificity was 0.943 (95% CI, 0.926-0.957), the DOR was 431.58 (95% CI, 186.77-997.27), the area under the SROC curve was 0.987, and the Q* was 0.951. The I2 test indicated no heterogeneity between studies. The Deek funnel test suggested no potential publication bias. Subgroup analyses showed that the area under the SROC curve of mNGS for diagnosis of PJP in immunocompromised and non-HIV patients was 0.9852 and 0.979, respectively. CONCLUSIONS: Current evidence indicates that mNGS exhibits excellent accuracy for the diagnosis of PJP. The mNGS is a promising tool for assessment of PJP in both immunocompromised and non-HIV patients.

Pedigree investigation, clinical characteristics, and prognosis analysis of haematological disease patients with germline TET2 mutation.

BACKGROUND: Increasing germline gene mutations have been discovered in haematological malignancies with the development of next-generation sequencing (NGS), which is critical for proper clinical management and long-term follow-up of affected individuals. Tet methylcytosine dioxygenase 2 (TET2) is one of the most common mutations in haematological neoplasms. We aimed to compare the clinical characteristics of patients with germline and somatic TET2 mutations in haematological diseases and to analyse whether germline TET2 mutations have a family aggregation and tumour predisposition. METHODS: Out of 612 patients who underwent NGS of 34 recurrently mutated genes in haematological diseases, 100 haematological patients with TET2 mutations were selected for further study. Somatic mutations were detected by NGS in bone marrow/peripheral blood genomic DNA (gDNA). Germline TET2 mutations were validated in nail/hair gDNA by Sanger sequencing. Digital data were extracted from the haematology department of the West China Hospital of Sichuan University. TET2 mutation results were analysed by referencing online public databases (COSMIC and ClinVar). RESULTS: One hundred patients were studied, including 33 patients with germline and 67 patients with somatic TET2 mutations. For germline TET2 mutations, the variant allele frequency (VAF) was more stable (50.58% [40.5-55], P < 0.0001), and mutation sites recurrently occurred in three sites, unlike somatic TET2 mutations. Patients with germline TET2 mutations were younger (median age 48, 16-82 years) (P = 0.0058) and mainly suffered from myelodysplastic syndromes (MDS) (n = 13, 39.4%), while patients with somatic TET2 mutations were mainly affected by acute myeloid leukemia (AML) (n = 26, 38.8%) (P = 0.0004). Germline TET2 mutation affected the distribution of cell counts in the peripheral blood and bone marrow (P < 0.05); it was a poor prognostic factor for MDS patients via univariate analysis (HR = 5.3, 95% CI: 0.89-32.2, P = 0.0209) but not in multivariate analysis using the Cox regression model (P = 0.062). CONCLUSIONS: Germline TET2 mutation might have a family aggregation, and TET2 may be a predisposition gene for haematological malignancy under the other gene mutations as the second hit. Germline TET2 mutation may play a role in the proportion of blood and bone marrow cells and, most importantly, may be an adverse factor for MDS patients.

Rhubarb Alleviates Acute Lung Injury by Modulating Gut Microbiota Dysbiosis in Mice.

Intestinal microbiota disorders can aggravate pulmonary inflammation during acute lung injury (ALI). As a traditional Chinese herb, Rhubarb can regulated the gut microbiota. Therefore, this study was conducted to test the hypothesis that rhubarb alleviates gut microbiota dysbiosis and inflammation. Feces were collected from patients with ALI to detect the gut microbiota using 16S rDNA sequencing. Subsequently, a mouse model of ALI was established using lipopolysaccharide to investigate changes in the gut microbiota, the peripheral blood was attained for detecting the Th17/Treg cell ratio and the serum level of HDAC6 and HDAC9, and the effect of rhubarb treatment on the gut microbiota and Th17/Treg ratio were also evaluated. The results indicated that both the Firmicutes phylum decreased and the Bacteroidetes phylum increased were identified in patients with ALI, which induced the alternation of histone metabolites. The mice models also showed a similar imbalance in the Firmicutes/Bacteroidetes ratio at phylum of level. Rhubarb treatment alleviated the damaged lung tissue, accelerated Alistipes, Clostridium, and Lactobacillus proliferation at the level of genus, increased the level of HDAC6 in both the mice lung tissue and serum, and markedly reduced the Treg cells and increased the Th17 cells in the spleen tissue. The study suggested that both patients and mouse models with ALI presented gut microbiota dysbiosis, and lead to a Th17/Treg cell imbalance in ALI mouse. Rhubarb promoted Alistipes, Clostridium, and Lactobacillus proliferation, increased the HDAC6 concentration, restored the Th17/Treg cell balance, and protected against ALI.

Radiographic predictors for recurrence of lumbar symptoms after prioritized cervical surgery in patients with tandem spinal stenosis.

OBJECTIVES: The purpose of the current study was to explore radiographic predictors for recurrence of lumbar symptoms after prioritized cervical surgery in patients with tandem spinal stenosis (TSS). METHODS: The current retrospective cohort study included 74 patients with TSS, who underwent prioritized cervical surgery. Based on presence or absence of improvement in lower limb symptoms, patients were grouped into improved and non-improved groups. Medical records and radiological parameters including age, sex, body mass index, cervical and lumbar parameters were analyzed. In improved group, patients were divided into relapsed and non-relapsed groups based on recurrence in lower limb symptoms. RESULTS: Lumbar symptoms improved in 70.1% (n = 52) of patients. Comparison between the improved and non-improved group showed that there were no statistically significant differences in cervical parameters while comparisons between the relapsed and non-relapsed groups showed significant differences in redundant nerve roots (RNRs) (p = 0.029), narrow segment (p = 0.042) and lumbar stenosis index (LSI) (p = 0.003). In multivariate logistic regression analysis, LSI > 10 (p = 0.016) was independently associated with recurrence of lumbar symptoms. CONCLUSIONS: Finding of the current study indicated that LSI > 10 was associated with recurrence of lumbar symptoms in TSS patients following cervical surgery.

Small extracellular vesicles encapsulating CCL2 from activated astrocytes induce microglial activation and neuronal apoptosis after traumatic spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) is a severe traumatic disease which causes high disability and mortality rates. The molecular pathological features after spinal cord injury mainly involve the inflammatory response, microglial and neuronal apoptosis, abnormal proliferation of astrocytes, and the formation of glial scars. However, the microenvironmental changes after spinal cord injury are complex, and the interactions between glial cells and nerve cells remain unclear. Small extracellular vesicles (sEVs) may play a key role in cell communication by transporting RNA, proteins, and bioactive lipids between cells. Few studies have examined the intercellular communication of astrocytes through sEVs after SCI. The inflammatory signal released from astrocytes is known to initiate microglial activation, but its effects on neurons after SCI remain to be further clarified. METHODS: Electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting were applied to characterize sEVs. We examined microglial activation and neuronal apoptosis mediated by astrocyte activation in an experimental model of acute spinal cord injury and in cell culture in vitro. RESULTS: Our results indicated that astrocytes activated after spinal cord injury release CCL2, act on microglia and neuronal cells through the sEV pathway, and promote neuronal apoptosis and microglial activation after binding the CCR2. Subsequently, the activated microglia release IL-1ß, which acts on neuronal cells, thereby further aggravating their apoptosis. CONCLUSION: This study elucidates that astrocytes interact with microglia and neurons through the sEV pathway after SCI, enriching the mechanism of CCL2 in neuroinflammation and spinal neurodegeneration, and providing a new theoretical basis of CCL2 as a therapeutic target for SCI.

Comparison of monoclonal antibodies targeting CD38, SLAMF7 and PD-1/PD-L1 in combination with Bortezomib/Immunomodulators plus dexamethasone/prednisone for the treatment of multiple myeloma: an indirect-comparison Meta-analysis of randomised controlled trials.

BACKGROUND: Many clinical trials have assessed the effect and safety of monoclonal antibodies (MAbs) in combination with proteasome inhibitors or immunomodulators plus dexamethasone/prednisone for the treatment of multiple myeloma (MM). The treatment outcomes of comparing different MAbs in combination with the above-mentioned agents remained unclear. We performed the meta-analysis to indirectly compare the effect and safety of MAbs targeting CD38, SLAMF7, and PD-1/PD-L1 in combination with bortezomib/immunomodulators plus dexamethasone/prednisone for patients with MM. METHODS: We searched thoroughly in the databases for randomised controlled trials (RCTs) in which at least one of the three MAbs were included. We included eleven eligible RCTs with 5367 patients in the meta-analysis. Statistical analysis was carried out using StataMP14 and Indirect Treatment Comparisons software. RESULTS: We calculated hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and relative risk (RR) for overall response rate, complete response (CR) or better, very good partial response (VGPR) or better, VGPR, partial response, stable disease, and grade 3 or higher adverse events among the three groups. The HRs for PFS of the CD38 group vs SLAMF7 group, CD38 group vs PD-1/PD-L1 group, and SLAMF7 group vs PD-1/PD-L1 group were 0.662 (95%CI 0.543-0.806), 0.317 (95%CI 0.221-0.454), and 0.479 (95%CI 0.328-0.699), respectively. The HR for OS of the CD38 group vs SLAMF7 group was 0.812 (95%CI 0.584-1.127). The RR for CR or better in the CD38 group vs SLAMF7 group was 2.253 (95%CI 1.284-3.955). The RR for neutropenia of the CD38 group vs SLAMF7 group was 1.818 (95%CI 1.41-2.344). CONCLUSIONS: Treatment with the CD38 group had longer PFS and better treatment response than that with the SLAMF7 or PD-1/PD-L1 group. In addition, the SLAMF7 group prolonged PFS compared with the PD-1/PD-L1 group and was associated with a lower incidence of grade 3 or higher neutropenia than the CD38 and PD-1/PD-L1 group. In conclusion, MAbs targeting CD38 are the best, followed by those targeting SLAMF7; MAbs targeting PD-1/PD-L1 are the worst when in combination with bortezomib/immunomodulators plus dexamethasone/prednisone for the treatment of MM.

Extracellular vesicles derived from melatonin-preconditioned mesenchymal stem cells containing USP29 repair traumatic spinal cord injury by stabilizing NRF2.

Spinal cord injury (SCI) is a devastating trauma that leads to irreversible motor and sensory dysfunction and is, so far, without effective treatment. Recently, however, nano-sized extracellular vesicles derived from preconditioned mesenchymal stem cells (MSCs) have shown great promise in treating various diseases, including SCI. In this study, we investigated whether extracellular vesicles (MEVs) derived from MSCs pretreated with melatonin (MT), which is well recognized to be useful in treating diseases, including Alzheimer's disease, non-small cell lung cancer, acute ischemia-reperfusion liver injury, chronic kidney disease, and SCI, are better able to promote functional recovery in mice after SCI than extracellular vesicles derived from MSCs without preconditioning (EVs). MEVs were found to facilitate motor behavioral recovery more than EVs and to increase microglia/macrophages polarization from M1-like to M2-like in mice. Experiments in BV2 microglia and RAW264.7 macrophages confirmed that MEVs facilitate M2-like polarization and also showed that they reduce the production of reactive oxygen species (ROS) and regulate mitochondrial function. Proteomics analysis revealed that ubiquitin-specific protease 29 (USP29) was markedly increased in MEVs, and knockdown of USP29 in MEVs (shUSP29-MEVs) abolished MEVs-mediated benefits in vitro and in vivo. We then showed that USP29 interacts with, deubiquitinates and therefore stabilizes nuclear factor-like 2 (NRF2), thereby regulating microglia/macrophages polarization. In NRF2 knockout mice, MEVs failed to promote functional recovery and M2-like microglia/macrophages polarization. We also showed that MT reduced global N6-methyladenosine (m6 A) modification and levels of the m6 A "writer" methyltransferase-like 3 (METTL3). The stability of USP29 mRNA in MSCs was enhanced by treatment with MT, but inhibited by overexpression of METTL3. This study describes a very promising extracellular vesicle-based approach for treating SCI.

The prognostic impact of variant allele frequency (VAF) in TP53 mutant patients with MDS: A systematic review and meta-analysis.

Tumor protein p53 (TP53) is frequently expressed in patients with myelodysplastic syndromes (MDS). Studies have already reported the poor prognostic impact of TP53 gene mutations in MDS patients. However, parts of this subgroup of patients with low-risk MDS still have relatively better survival and longer remission times. Therefore, we performed a meta-analysis to evaluate the prognostic difference intra-gene of variant allele frequency (VAF). The primary endpoint was overall survival (OS), and event-free survival (EFS) was selected as the secondary endpoint. We extracted the hazard ratio (HR) and 95% confidence interval (CI) for OS and EFS from univariate and multivariate Cox proportional hazard models. A total of 4003 MDS patients and 1278 TP53-mutated patients from 13 cohorts of 11 studies up to February 24, 2020, were included in our meta-analysis. Pooled HRs suggested that a high mutant VAF had an adverse impact on OS (HR = 2.11, 95% CI: 1.48-3.01, P < .0001) but no impact on EFS (HR = 15.57, 95% CI: 0.75-324.44, P = .003) in MDS patients. Twenty percent is a proper threshold to set (HR = 2.02, 95% CI: 1.31-3.13, P = .001) and is a rough line between high clone burden and low clone burden, while 40% is an exact cutoff point (HR = 2.11, 95% CI: 1.26-3.55, P < .0001) to guide diagnosis and treatment. Beyond the traditional binary classification of gene mutation, we aimed to find a way to divide mutant molecular markers more specifically by VAF to provide clinical therapeutic values. Our meta-analysis indicates that a high VAF is an independent, adverse prognostic factor for OS in TP53 mutant MDS patients. Patients with mediate/low-frequency parts who could be treated like wide-type patients have relatively better survival and may choose allogeneic hematopoietic stem cell transplantation as conditions permitting. Further prospective studies are needed in the future, and a large subgroup analysis of the same cutoff point subgroups is needed to obtain a more reliable basis for the impact of other mutant gene VAFs on the prognosis of MDS.

Higher-Order Aberrations in Children and Adolescents of Southwest China.

SIGNIFICANCE: This study provides a descriptive characterization of higher-order optical aberrations for the eyes of a larger number of Chinese children and adolescents. PURPOSE: To determine the distribution of higher-order aberrations (HOAs) of Han Chinese young subjects with normal vision and their relationship to age. METHODS: Children and adolescents, aged from 3 to 17 years, with normal visual acuity were enrolled, and their wavefront aberrations for a 6-mm pupil were evaluated by the Zywave II aberrometer. Their correlations with age were analyzed, and the 95% statistical reference ranges were computed for each Zernike term. RESULTS: A total of 1634 eyes (287 for preschool-age children, 897 for school-age children, and 450 for adolescents) were analyzed. There was a significant correlation with age and the root mean square (RMS) of total HOAs (r = 0.256, P < .0001), third-order aberrations (r = 0.062, P = .029), fourth-order aberrations (r = 0.197, P < .0001), fifth-order aberrations (r = 0.067, P = .017), and trefoil-like aberrations (r = 0.100, P < .0001) in the myopic group. There were significant differences in RMS values (except coma-like aberrations, χ = 4.179, P = .124) as well as the Zernike coefficients among three different age groups. Therefore, the 95% statistical normal reference values were calculated separately for three age groups. CONCLUSIONS: The RMS value of total HOAs, coma-like, trefoil-like, third-order, fourth-order, and fifth-order aberrations are correlated with age, and the RMS values and Zernike coefficients of aberrations were different in different age stages of the subjects. This study described the distribution of HOAs in children and adolescents and established 95% statistical normal values of HOAs for different ages of children and adolescents by analyzing the HOAs in a large number of the Han Chinese clinical population.

Genome-wide Identification and analysis of the stress-resistance function of the TPS (Trehalose-6-Phosphate Synthase) gene family in cotton.

BACKGROUND: Trehalose (a-D-glucopyranosyl a-D-glucopyranoside) is a nonreducing disaccharide and is widely distributed in bacteria, fungi, algae, plants and invertebrates. In the study, the identification of trehalose-6-phosphate synthase (TPS) genes stress-related in cotton, and the genetic structure analysis and molecular evolution analysis of TPSs were conducted with bioinformatics methods, which could lay a foundation for further research of TPS functions in cotton. RESULTS: The genome information of Gossypium raimondii (group D), G. arboreum L. (group A), and G. hirsutum L. (group AD) was used in the study. Fifty-three TPSs were identified comprising 15 genes in group D, 14 in group A, and 24 in group AD. Bioinformatics methods were used to analyze the genetic structure and molecular evolution of TPSs. Real-time PCR analysis was performed to investigate the expression patterns of gene family members. All TPS family members in cotton can be divided into two subfamilies: Class I and Class II. The similarity of the TPS sequence is high within the same species and close within their family relatives. The genetic structures of two TPS subfamily members are different, with more introns and a more complicated gene structure in Class I. There is a TPS domain(Glyco transf_20) at the N-terminal in all TPS family members and a TPP domain(Trehalose_PPase) at the C-terminal in all except GrTPS6, GhTPS4, and GhTPS9. All Class II members contain a UDP-forming domain. The responses to environmental stresses showed that stresses could induce the expression of TPSs but the expression patterns vary with different stresses. CONCLUSIONS: The distribution of TPSs varies with different species but is relatively uniform on chromosomes. Genetic structure varies with different gene members, and expression levels vary with different stresses and exhibit tissue specificity. The upregulated genes in upland cotton TM-1 is significantly more than that in G. raimondii and G. arboreum L. Shixiya 1.

Involvement of CapG in proliferation and apoptosis of pulmonary arterial smooth muscle cells and in hypoxia-induced pulmonary hypertension rat model.

PURPOSE: Actin-binding protein capping protein gelsolin-like (CapG) was preferentially expressed in human pulmonary arterial smooth muscle cells (PASMCs) under hypoxia, and reduced CapG expression was accompanied by impaired migration ability in vitro. We intended to investigate the effects of CapG on rat PASMCs and hypoxia-induced pulmonary hypertension (HPH) rat model. MATERIALS AND METHODS: We investigated the effect of RNA interference-medicated down-regulation of CapG expression in rat PASMCs as well as in HPH rat model. The proliferation, apoptosis and cell cycle of PASMCs were evaluated. The HPH rat model was established by intratracheal instillation of lentiviral vector and subsequent hypoxia exposure for four weeks. Right ventricular systolic pressure, right ventricular hypertrophy and the percentage of medial wall thickness were measured to evaluate the development of HPH. RESULTS: Knock-down CapG in PASMCs resulted in decreased proliferation, increased apoptosis and induced cell cycle inhibition. Down-regulation of CapG expression locally could attenuate pulmonary hypertension, pulmonary vascular remodeling and right ventricular hypertrophy in HPH rat model. CONCLUSIONS: Our study indicated that CapG participated in the pathogenesis of pulmonary vascular remodeling in HPH rats, which was probably mediated by promoting the proliferation and inhibiting the apoptosis of PASMCs. We proposed CapG modulating protective effects of pulmonary hypertension.

Increased expression of endoplasmic reticulum protein 29 in lung adenocarcinoma is associated with chemosensitivity to gemcitabine.

Lung adenocarcinoma is the leading cause of cancer-related death worldwide. The aim of the present study was to investigate the potential function of endoplasmic reticulum protein 29 (ERp29) in lung adenocarcinoma. We examined the expression of ERp29 in 75 patients with lung adenocarcinoma by immunohistochemical analysis, as well as its association with clinicopathological features. We further tested the effects of inhibiting ERp29 on cell proliferation, migration ability, and chemosensitivity to gemcitabine in human lung adenocarcinoma cell lines. ERp29 was significantly overexpressed in lung adenocarcinoma when compared with matched nontumor tissues. However, we did not observe significant associations of ERp29 with any of the clinicopathologic characteristics, including sex, age, differentiation, tumor, node, and metastasis stage, T stage, and lymph node metastasis. Downregulation of ERp29 by small interfering RNA did not affect cell growth, but impaired cell migration of lung adenocarcinoma cells. Inhibition of ERp29 significantly enhanced the chemosensitivity of lung adenocarcinoma cells to gemcitabine. These results support a probable treatment combination of gemcitabine and inhibition of ERp29 overexpression for lung adenocarcinoma to promote the clinical curative effects.

Diagnostic Efficacy and Safety of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Intrathoracic Tuberculosis: A Meta-analysis.

OBJECTIVES: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive technique. A meta-analysis was performed to assess the efficacy and safety of EBUS-TBNA in intrathoracic tuberculosis (TB). METHODS: We searched PubMed, the Cochrane Library, and the Web of Science for suitable studies. The pooled sensitivity, specificity, likelihood ratios (LRs), and diagnostic odds ratio were calculated. A summary receiver operating characteristic (ROC) curve was constructed to calculate the area under the summary ROC curve and Qpoint value (Q*). RESULTS: A total of 8 studies with 809 patients were included. The pooled sensitivity and specificity of EBUS-TBNA for diagnosis of intrathoracic TB were 0.80 (95% confidence interval [CI] 0.74-0.85) and 1.00 (95% CI, 0.99-1.00), respectively. The positive LR was 38.25 (95% CI, 13.59-107.65); the negative LR was 0.24 (95% CI, 0.17-0.33); and the diagnostic odds ratio was 186.35 (95% CI, 63.57-546.28). The area under the summary ROC curve was 0.935, and the Q*was 0.871. The pooled sensitivity of EBUS-TBNA for diagnosis of intrathoracic tuberculous lymphadenopathy was 0.87 (95% CI, 0.80-0.95). Only 1 serious complication was reported. CONCLUSIONS: Endobronchial US-guided TBNA is an effective and safe diagnostic tool for intrathoracic TB, especially intrathoracic tuberculous lymphadenopathy.

Health impact of the 2008 cold spell on mortality in subtropical China: the climate and health impact national assessment study (CHINAs).

BACKGROUND: Many studies have investigated heat wave related mortality, but less attention has been given to the health effects of cold spells in the context of global warming. The 2008 cold spell in China provided a unique opportunity to estimate the effects of the 2008 cold spell on mortality in subtropical regions, spatial heterogeneity of the effects, stratification effect and added effects caused by sustained cold days. METHODS: Thirty-six study communities were selected from 15 provinces in subtropical China. Daily mortality and meteorological data were collected for each community from 2006 to 2010. A distributed lag linear non-linear model (DLNM) with a lag structure of up to 27 days was used to analyze the association between the 2008 cold spell and mortality. Multivariate meta-analyses were used to combine the cold effects across each community. RESULTS: The 2008 cold spell increased mortality by 43.8% (95% CI: 34.8% ~ 53.4%) compared to non-cold spell days with the highest effects in southern and central China. The effects were more pronounced for respiratory mortality (RESP) than for cardiovascular (CVD) or cerebrovascular mortality (CBD), for females more than for males, and for the elderly aged ≥75 years old more than for younger people. Overall, 148,279 excess deaths were attributable to the 2008 cold spell. The cold effect was mainly from extreme low temperatures rather than sustained cold days during this 2008 cold spell. CONCLUSIONS: The 2008 cold spell increased mortality in subtropical China, which was mainly attributable to the low temperature rather than the sustained duration of the cold spell. The cold effects were spatially heterogeneous and modified by individual-specific characteristics such as gender and age.