Bacteria and viruses and clinical outcomes of asthma-bronchiectasis overlap syndrome: A cohort study.

BACKGROUND: Despite the high prevalence of co-existing bronchiectasis and asthma (asthma-bronchiectasis overlap syndrome [ABOS]), little is known regarding the dominant pathogens and clinical correlates. OBJECTIVE: To investigate the bacteria and viruses which differentially dominate in ABOS (including its subtypes) compared with bronchiectasis alone, and determine their relevance with bronchiectasis severity and exacerbations. METHODS: This was a prospective observational cohort study conducted between March 2017 and August 2023. We included 81 patients with ABOS and 107 patients with bronchiectasis alone. At steady-state baseline, patients underwent comprehensive assessments and sputum collection for bacterial culture and viral detection (quantitative polymerase-chain-reaction). Patients were followed-up to record exacerbation and spirometry. RESULTS: Patients with ABOS had significantly higher symptom burden and exacerbation frequency than those with bronchiectasis alone. Despite similar pathogen spectrum, the rate of bacteria-virus co-detection increased less substantially at acute exacerbations (AE) onset than at steady-state compared with bronchiectasis alone. Pathogenic bacteria (particularly Pseudomonas aeruginosa) were detected fairly common (exceeding 50%) in ABOS and were associated with greater severity of bronchiectasis when stable and conferred greater exacerbation risks at follow-up. Viral but not bacterial compositions changed substantially at AE onset compared with clinical stability. Higher blood eosinophil count, moderate-to-severe bronchiectasis and non-atopy were associated with higher odds of bacterial, but not viral, detection (all p < 0.05). CONCLUSION: Detection of bacteria or virus is associated with bronchiectasis severity or clinical outcomes in ABOS. This highlights the importance of integrating sputum microbial assessment for ascertaining the dominant pathophysiology (atopy vs. infection) and longitudinal trajectory prediction in ABOS.

Sputum pathogen spectrum and clinical outcomes of upper respiratory tract infection in bronchiectasis exacerbation: a prospective cohort study.

Upper respiratory tract infection (URTI) is common in humans. We sought to profile sputum pathogen spectrum and impact of URTI on acute exacerbation of bronchiectasis (AE). Between March 2017 and December 2021, we prospectively collected sputum from adults with bronchiectasis. We stratified AEs into events related (URTI-AE) and unrelated to URTI (non-URTI-AE). We captured URTI without onset of AE (URTI-non-AE). We did bacterial culture and viral detection with polymerase chain reaction, and explored the pathogen spectrum and clinical impacts of URTI-AE via longitudinal follow-up. Finally, we collected 479 non-AE samples (113 collected at URTI-non-AE and 225 collected at clinically stable) and 170 AE samples (89 collected at URTI-AE and 81 collect at non-URTI-AE). The viral detection rate was significantly higher in URTI-AE (46.1%) than in non-URTI-AE (4.9%) and URTI-non-AE (11.5%) (both P < 0.01). Rhinovirus [odds ratio (OR): 5.00, 95% confidence interval (95%CI): 1.06-23.56, P = 0.03] detection was independently associated with URTI-AE compared with non-URTI-AE. URTI-AE tended to yield higher viral load and detection rate of rhinovirus, metapneumovirus and bacterial shifting compared with URTI-non-AE. URTI-AE was associated with higher initial viral loads (esp. rhinovirus, metapneumovirus), greater symptom burden (higher scores of three validated questionnaires) and prolonged recovery compared to those without. Having experienced URTI-AE predicted a greater risk of future URTI-AE (OR: 10.90, 95%CI: 3.60-33.05). In summary, URTI is associated with a distinct pathogen spectrum and aggravates bronchiectasis exacerbation, providing the scientific rationale for the prevention of URTI to hinder bronchiectasis progression.

Advances in holliday junction recognition protein (HJURP): Structure, molecular functions, and roles in cancer.

Oncogenes are increasingly recognized as important factors in the development and progression of cancer. Holliday Junction Recognition Protein (HJURP) is a highly specialized mitogenic protein that is a chaperone protein of histone H3. The HJURP gene is located on chromosome 2q37.1 and is involved in nucleosome composition in the mitotic region, forming a three-dimensional crystal structure with Centromere Protein A (CENP-A) and the histone 4 complex. HJURP is involved in the recruitment and assembly of centromere and kinetochore and plays a key role in stabilizing the chromosome structure of tumor cells, and its dysfunction may contribute to tumorigenesis. In the available studies HJURP is upregulated in a variety of cancer tissues and cancer cell lines and is involved in tumor proliferation, invasion, metastasis and immune response. In an in vivo model, overexpression of HJURP in most cancer cell lines promotes cell proliferation and invasiveness, reduces susceptibility to apoptosis, and promotes tumor growth. In addition, upregulation of HJURP was associated with poorer prognosis in a variety of cancers. These properties suggest that HJURP may be a possible target for the treatment of certain cancers. Various studies targeting HJURP as a prognostic and therapeutic target for cancer are gradually attracting interest and attention. This paper reviews the functional and molecular mechanisms of HJURP in a variety of tumor types with the aim of providing new targets for future cancer therapy.

Glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor regulate the interaction between astrocytes and Schwann cells at the trigeminal root entry zone.

The trigeminal root entry zone is the zone at which the myelination switches from peripheral Schwann cells to central oligodendrocytes. Its special anatomical and physiological structure renders it susceptible to nerve injury. The etiology of most primary trigeminal neuralgia is closely related to microvascular compression of the trigeminal root entry zone. This study aimed to develop an efficient in vitro model mimicking the glial environment of trigeminal root entry zone as a tool to investigate the effects of glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor on the structural and functional integrity of trigeminal root entry zone and modulation of cellular interactions. Primary astrocytes and Schwann cells isolated from trigeminal root entry zone of postnatal rats were inoculated into a two-well silicon culture insert to mimic the trigeminal root entry zone microenvironment and treated with glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor. In monoculture, glial cell line-derived neurotrophic factor promoted the migration of Schwann cells, but it did not have effects on the migration of astrocytes. In the co-culture system, glial cell line-derived neurotrophic factor promoted the bidirectional migration of astrocytes and Schwann cells. Brain-derived neurotrophic factor markedly promoted the activation and migration of astrocytes. However, in the co-culture system, brain-derived neurotrophic factor inhibited the migration of astrocytes and Schwann cells to a certain degree. These findings suggest that glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor are involved in the regulation of the astrocyte-Schwann cell interaction in the co-culture system derived from the trigeminal root entry zone. This system can be used as a cell model to study the mechanism of glial dysregulation associated with trigeminal nerve injury and possible therapeutic interventions.

Motile Ciliary Disorders of the Nasal Epithelium in Adults With Bronchiectasis.

BACKGROUND: Motile ciliary disorder (MCD) has been implicated in chronic inflammatory airway diseases such as asthma and COPD. RESEARCH QUESTION: What are the characteristics of MCD of the nasal epithelium and its association with disease severity and inflammatory endotypes in adults with bronchiectasis? STUDY DESIGN AND METHODS: In this observational study, we recruited 167 patients with bronchiectasis and 39 healthy control participants who underwent brushing of the nasal epithelium. A subgroup of patients underwent bronchoscopy for bronchial epithelium sampling (n = 13), elective surgery for bronchial epithelium biopsy (n = 18), and blood sampling for next-generation sequencing (n = 37). We characterized systemic and airway inflammatory endotypes in bronchiectasis. We conducted immunofluorescence assays to profile ultrastructural (dynein axonemal heavy chain 5 [DNAH5], dynein intermediate chain 1 [DNAI1], radial spoke head protein 9 [RSPH9]) and ciliogenesis marker expression (Ezrin). RESULTS: MCD was present in 89.8% of patients with bronchiectasis, 67.6% showed secondary MCD, and 16.2% showed primary plus secondary MCD. Compared with healthy control participants, patients with bronchiectasis yielded abnormal staining patterns of DNAH5, DNAI1, and RSPH9 (but not Ezrin) that were more prominent in moderate to severe bronchiectasis. MCD pattern scores largely were consistent between upper and lower airways and between large-to-medium and small airways in bronchiectasis. Coexisting nasal diseases and asthma did not confound nasal ciliary ultrastructural marker expression significantly. The propensity of MCD was unaffected by the airway or systemic inflammatory endotypes. MCD, particularly an ultrastructural abnormality, was notable in patients with mild bronchiectasis who showed blood or sputum eosinophilia. INTERPRETATION: Nasal ciliary markers profiling provides complimentary information to clinical endotyping of bronchiectasis.

Influence of group B streptococcus and vaginal cleanliness on the vaginal microbiome of pregnant women.

BACKGROUND: The vaginal microbiome plays a critical role in the health of pregnant women and their newborns. Group B Streptococcus (GBS) and vaginal cleanliness significantly affect the vaginal microecosystem and are closely associated with vaginal diseases. AIM: To explore the effects of GBS status and vaginal cleanliness on vaginal microecosystems. METHODS: We collected 160 vaginal swabs from pregnant women and divided them into the following four groups based on GBS status and vaginal cleanliness: GBS-positive + vaginal cleanliness I-II degree, GBS-negative + vaginal cleanliness I-II degree, GBS-positive + vaginal cleanliness III-IV degree, and GBS-negative + vaginal cleanliness III-IV degree. Samples were subjected to 16S rRNA gene amplicon sequencing. RESULTS: Alpha diversity analysis showed that the Shannon index did not significantly differ between the four groups. We identified significant variation in taxa abundance between the GBS-positive and GBS-negative groups and between the vaginal cleanliness I-II degree and III-IV degree groups. Principal coordinate analysis and non-metric multidimensional scaling analysis further confirmed the microbial diversity of the four groups. Moreover, the linear discriminant analysis demonstrated that Lactobacillus jensenii and Actinobacteria were strongly associated with GBS-positive status, and Lactobacillus iners, Lactobacillaceae, Lactobacillus, Lactobacillales, Bacilli and Firmicutes were closely correlated with GBS-negative status. CONCLUSION: GBS status and vaginal cleanliness significantly affect vaginal microbiome differences in pregnant women. Our findings provide instructional information for clinical antibiotic treatment in pregnant women with different GBS statuses and vaginal cleanliness degrees.

SnoN residue (1-366) attenuates hypertrophic scars through resistance to transforming growth factor-ß1-induced degradation.

Hypertrophic scars (HSs) are characterized by fibroblast hyperproliferation and excessive matrix deposition. During wound healing, transforming growth factor (TGF)-ß1/Smad signaling acts as a key regulator. As a transcriptional corepressor of TGF-ß1/Smads, SnoN is expressed at low levels in many fibrotic diseases due to TGF-ß1/Smad-induced degradation. SnoN residue (1-366; SR) is resistant to TGF-ß1-induced degradation. However, the expression and role of SR in HSs are unknown. Here, we inhibited TGF-ß1/Smad signaling via overexpression of SR to block fibroblast transdifferentiation, proliferation, and collagen deposition during HS formation. Our results showed that SnoN was downregulated in HS fibroblasts (HSFs) owing to TGF-ß1/Smad-induced degradation. Overexpression of SR in normal human dermal fibroblasts (NHDFs) and HSFs successfully blocked phosphorylation of Smad2 and Smad3, thereby inhibiting NHDF transdifferentiation and HSF proliferation and reducing type I collagen (ColI) and type III collagen (ColIII) production and secretion. In addition, we applied overexpressed full-length SnoN (SF) and SR to wound granulation tissue in a rabbit model of HSs. SR reduced wound scarring, improved collagen deposition and arrangement of scar tissue, and decreased mRNA and protein expression of ColI, ColIII, and α-smooth muscle actin (α-SMA) more effectively than SF in vivo. These results suggest that SR could be a promising therapy for the prevention of HS.

High-density genetic map construction and QTL mapping of first flower node in pepper (Capsicum annuum L.).

BACKGROUND: First flower node (FFN) is an important trait for evaluating fruit earliness in pepper (Capsicum annuum L.). The trait is controlled by quantitative trait loci (QTL); however, studies have been limited on QTL mapping and genes contributing to the trait. RESULTS: In this study, we developed a high density genetic map using specific-locus amplified fragment sequencing (SLAF-seq), a high-throughput strategy for de novo single nucleotide polymorphism discovery, based on 146 recombinant inbred lines (RILs) derived from an intraspecific cross between PM702 and FS871. The map contained 9328 SLAF markers on 12 linkage groups (LGs), and spanned a total genetic distance of 2009.69 centimorgan (cM) with an average distance of 0.22 cM. The sequencing depth for the map was 72.39-fold in the male parent, 57.04-fold in the female parent, and 15.65-fold in offspring. Using the genetic map, two major QTLs, named Ffn2.1 and Ffn2.2, identified on LG02 were strongly associated with FFN, with a phenotypic variance explanation of 28.62 and 19.56%, respectively. On the basis of the current annotation of C. annuum cv. Criollo de Morelos (CM334), 59 candidate genes were found within the Ffn2.1 and Ffn2.2 region, but only 3 of 59 genes were differentially expressed according to the RNA-seq results. Eventually we identified one gene associated with the FFN based on the function through GO, KEGG, and Swiss-prot analysis. CONCLUSIONS: Our research showed that the construction of high-density genetic map using SLAF-seq is a valuable tool for fine QTL mapping. The map we constructed is by far the most saturated complete genetic map of pepper, and using it we conducted fine QTL mapping for the important trait, FFN. QTLs and candidate genes obtained in this study lay a good foundation for the further research on FFN-related genes and other genetic applications in pepper.

[Clinical observation of rapid massage at Shuidao (ST 28) to prevent postpartum urinary retention].

OBJECTIVE: To explore the clinical effect of rapid massage at Shuidao (ST 28) to prevent puerpera from postpartum urinary retention. METHODS: A total of 200 puerpera giving birth through vagina were enrolled and divided into an observation group and a control group according to the random number table method, 100 cases in each group. In the observation group, rapid massage at Shuidao (ST 28) was applied. In the control group,there was no intervention and urinated naturally. The traditional Chinese medicine syndrome scale was used to evaluate poor sense of urination, and record puerpera with or without postpartum urinary retention, the poor sense of first urination, the first time of urination, the amount of first urination and postpartum hemorrhage. RESULTS: The poor sense of first urination in the observation group was significantly lower than that in the control (P<0.001), the first time of urination in the observation group was significantly earlier than that in the control group (P<0.001), the amount of first urination in the observation group was significantly more than that in the control group (P<0.001), the observation group was superior to the control group to prevent postpartum urinary retention (P<0.05). CONCLUSION: Rapid massage at Shuidao (ST 28) can reduce the poor sense of first urination, significantly advance the time of spontaneous urination, significantly increase the amount of first urination and effectively prevent postpartum urinary retention.

Dachengqi Decoction Attenuates Intestinal Vascular Endothelial Injury in Severe Acute Pancreatitis in Vitro and in Vivo.

BACKGROUND/AIMS: Dachengqi decoction (DCQD) is a well-known traditional Chinese herbal drug with strong anti-inflammatory effects. Angiopoietin-1 (Ang-1) plays a vital role in maintaining the stability and integrity of the vascular wall and prevents vascular leakage due to inflammatory mediators. Our previous work found that DCQD protects against pancreatic injury in rats with severe acute pancreatitis (SAP). This study aims to investigate the effects of DCQD on intestinal endothelial damage in both damaged human umbilical vein endothelial cells (HUVECs) and SAP rats. METHODS: HUVECs were randomly divided into four groups: control group, TNF-α group, TNF-α plus Ang-1 group (Ang-1 group), and TNF-α plus DCQD group (DCQD group). Cells were incubated for 6 h, 12 h, and 24 h, before collection. The treatment concentration of DCQD was decided based on a Cell Counting Kit-8 (CCK-8) assay. The monolayer permeability of the HUVECs was assessed by measuring the transendothelial electrical resistance (TEER). Apoptosis was analyzed by flow cytometry. mRNA and protein expression of aquaporin 1 (AQP-1), matrix metalloproteinase 9 (MMP9), and junctional adhesion molecule-C (JAM-C) was evaluated by RT-PCR, immunocytofluorescence, and western blot. Forty male Sprague-Dawley rats were randomized into a control group, SAP group, SAP plus Ang-1 group (Ang-1 group), and SAP plus DCQD group (DCQD group). SAP was induced by intraperitoneal injection of cerulein and lipopolysaccharide (LPS), while the control group received 0.9% saline solution. Evans blue was injected through the penile vein and the rats were then sacrificed 12 h after modeling. Levels of serum amylase, TNF-α, IL-1ß, IL-2, and IL-6 were determined by using ELISA. Intestinal tissue was analysed by histology, and capillary permeability in the tissues was evaluated by Evans blue extravasation assay. Protein and mRNA expression of AQP-1, MMP9, and JAM-C were assessed by immunohistofluorescence, western blot, and RT-PCR. RESULTS: DCQD reduced the permeability of HUVEC induced by TNF-α in vitro. Furthermore, DCQD altered the mRNA and protein levels of JAM-C, MMP9, and AQP-1 in HUVECs after TNF-α induction. SAP intestinal injury induced by cerulein combined with lipopolysaccharides was concomitant with increased expression of JAM-C and MMP9, and reduced expression of AQP-1 in intestinal tissue. Pretreatment with DCQD attenuated SAP intestinal injury and lowered the levels of serum amylase, TNF-α, IL-1ß, IL-2, and IL-6 effectively. Our study demonstrated that DCQD decreased the expression of JAM-C and MMP9 and increased the expression of AQP-1 both in vitro and in vivo. CONCLUSION: DCQD can reduce capillary endothelial damage in acute pancreatitis-associated intestinal injury and the mechanism may be associated with the regulation of endothelial barrier function-associated proteins AQP-1, MMP9, and JAM-C.

Susceptibility-Weighted Imaging of the Anatomic Variation of Thalamostriate Vein and Its Tributaries.

BACKGROUND AND PURPOSE: Thalamostriate vein (TSV) is an important tributary of the internal cerebral vein, which mainly drains the basal ganglia and deep medulla. The purpose of this study was to explore the anatomic variation and quality of TSV and its smaller tributaries using susceptibility-weighted imaging (SWI). METHODS: We acquired SWI images in 40 volunteers on a 3.0T MR system using an 8-channel high-resolution phased array coil. The frequencies of the TSV and its tributaries were evaluated. We classified TSV into types I (forming a venous angle) and II (forming a false venous angle). We classified anterior caudate vein (ACV)into types 1 (1 trunk) and 2 (2 trunks) as well as into types A (joiningTSV), B (joining anterior septal vein), and C (joining the angle of both veins). RESULTS: The TSV drains the areas of caudate nucleus, internal capsule,lentiform nucleus, external capsule, claustrum, extreme capsule and the white matter of the frontoparietal lobes,except thalamus. The frequencies of the TSV, ACV and transverse caudate vein (ACV) were 92.5%, 87.5% and 63.8%, respectively. We found TSV types I and II in 79.7%, and 20.3% with significantly different constitution ratios (P< 0.05). The most common types of ACV were type 1 (90.0%) and type A (64.3%). CONCLUSION: The complex three-dimensional (3D) venous architecture of TSV and its small tributaries manifests great variation, with significant and practical implications for neurosurgery.

Susceptibility-weighted imaging of the venous networks around the brain stem.

INTRODUCTION: The venous network of the brainstem is complex and significant. Susceptibility-weighted imaging (SWI) is a practical technique which is sensitive to veins, especially tiny veins. Our purpose of this study was to evaluate the visualization of the venous network of brainstem by using SWI at 3.0 T. METHODS: The occurrence rate of each superficial veins of brainstem was evaluated by using SWI on a 3 T MR imaging system in 60 volunteers. The diameter of the lateral mesencephalic vein and peduncular vein were measured by SWI using the reconstructed mIP images in the sagittal view. And the outflow of the veins of brainstem were studied and described according to the reconstructed images. RESULTS: The median anterior pontomesencephalic vein, median anterior medullary vein, peduncular vein, right vein of the pontomesencephalic sulcus, and right lateral anterior pontomesencephalic vein were detected in all the subjects (100%). The outer diameter of peduncular vein was 1.38 ± 0.26 mm (range 0.8-1.8 mm). The lateral mesencephalic vein was found in 75% of the subjects and the mean outer diameter was 0.81 ± 0.2 mm (range 0.5-1.2 mm). The inner veins of mesencephalon were found by using SWI. CONCLUSION: The venous networks around the brain stem can be visualized by SWI clearly. This result can not only provide data for anatomical study, but also may be available for the surgical planning in the infratentorial region.