Elastic interactions compete with persistent cell motility to drive durotaxis.

Many animal cells that crawl on extracellular substrates exhibit durotaxis, i.e., directed migration toward stiffer substrate regions. This has implications in several biological processes including tissue development and tumor progression. Here, we introduce a phenomenological model for single-cell durotaxis that incorporates both elastic deformation-mediated cell-substrate interactions and the stochasticity of cell migration. Our model is motivated by a key observation in an early demonstration of durotaxis: a single, contractile cell at a sharp interface between a softer and a stiffer region of an elastic substrate reorients and migrates toward the stiffer region. We model migrating cells as self-propelling, persistently motile agents that exert contractile traction forces on their elastic substrate. The resulting substrate deformations induce elastic interactions with mechanical boundaries, captured by an elastic potential. The dynamics is determined by two crucial parameters: the strength of the cellular traction-induced boundary elastic interaction (A), and the persistence of cell motility (Pe). Elastic forces and torques resulting from the potential orient cells perpendicular (parallel) to the boundary and accumulate (deplete) them at the clamped (free) boundary. Thus, a clamped boundary induces an attractive potential that drives durotaxis, while a free boundary induces a repulsive potential that prevents antidurotaxis. By quantifying the steady-state position and orientation probability densities, we show how the extent of accumulation (depletion) depends on the strength of the elastic potential and motility. We compare and contrast crawling cells with biological microswimmers and other synthetic active particles, where accumulation at confining boundaries is well known. We define metrics quantifying boundary accumulation and durotaxis, and present a phase diagram that identifies three possible regimes: durotaxis, and adurotaxis with and without motility-induced accumulation at the boundary. Overall, our model predicts how durotaxis depends on cell contractility and motility, successfully explains some previous observations, and provides testable predictions to guide future experiments.

Diverse functions of Tribbles homolog 3 in cancers and its potential as a therapeutic target.

Currently, cancer is the second leading cause of death worldwide, and potential targeted drugs and molecular pathways for cancer development and progression have been a hot research topic worldwide. In recent years, the importance of the kinase superfamily in diseases has been well demonstrated by studies on various molecular mechanisms of kinases and the successful application of their inhibitors in diseases. Pseudokinases are members of the kinase superfamily, which have been increasingly documented to play a crucial role in cancers year after year. As a member of pseudokinases, tribbles homolog 3 (TRIB3) also exerts diverse functions in different cancers through different interacting proteins and molecular pathways, especially in tumor immunity, stemness, drug resistance, metabolism, and autophagy. In addition, peptide drugs targeting TRIB3 have high specificity in preclinical studies, which shows great promise for TRIB3 application in diseases including cancers. In this review, we dissect diverse functions played by TRIB3 in different cancers, describing the underlying mechanisms in detail. Notably, inhibitors and agonists currently available for TRIB3 are discussed, indicating the potential for TRIB3 as a therapeutic target.

[Clinical phenotype and genetic analysis of a patient with a heterozygous 6p25.3 deletion and partial trisomy 15q].

OBJECTIVE: To investigate the clinical phenotype and genetic characteristics of a patient with a heterozygous 6p25.3 deletion and partial trisomy 15q. METHODS: A patient who had presented at the Genetics and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University on May 14, 2021 was selected as the study subject. Clinical data of the patient was collected, and G-banded chromosomal karyotyping and copy number variation sequencing (CNV-seq) were carried out. RESULTS: The patient's main clinical features have included complete uterine septum, vaginal septum, atrophy of left eyeball, abnormal fingers and toes, and mental retardation. The karyotype of the patient was 46,XX,der(6)t(6;15)(p25.3;q26.1). CNV-seq result has indicated a 1.20 Mb heterozygous deletion in the 6p25.3 region and a 10.20 Mb duplication in the 15q26.1q26.3 region. The deletion segment has included the FOXQ1 gene, which may be related with the abnormal development of the left eye. The duplication segment has a 96.16% overlap with the region associated with 15q26 overgrowth syndrome (including the IGF1R gene), which may be related to the patient' s abnormal development of the Müllerian duct, abnormal fingers and toes, and mental developmental delay. CONCLUSION: The heterozygous deletion of the 6p25.3 region and duplication of the 15q26.1q26.3 region probably underlay the abnormal clinical phenotype in this patient.

[Effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on proteomics and autophagy in mice with type 2 diabetes mellitus induced by high-fat diet coupled with streptozotocin].

To compare the pancreatic proteomics and autophagy between Rehmanniae Radix-and Rehmanniae Radix Praeparata-treated mice with type 2 diabetes mellitus(T2DM). The T2DM mouse model was established by high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days). The mice were then randomly assigned into a control group, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) catalpol groups, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) 5-hydroxymethyl furfuraldehyde(5-HMF) groups, and a metformin(250 mg·kg~(-1)) group. In addition, a normal group was also set and each group included 8 mice. The pancreas was collected after four weeks of administration and proteomics tools were employed to study the effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on protein expression in the pancreas of T2DM mice. The expression levels of proteins involved in autophagy, inflammation, and oxidative stress response in the pancreatic tissues of T2DM mice were determined by western blotting, immunohistochemical assay, and transmission electron microscopy. The results showed that the differential proteins between the model group and Rehmanniae Radix/Rehmanniae Radix Prae-parata group were enriched in 7 KEGG pathways, such as autophagy-animal, which indicated that the 7 pathways may be associated with T2DM. Compared with the control group, drug administration significantly up-regulated the expression levels of beclin1 and phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR and down-regulated those of the inflammation indicators, Toll-like receptor-4(TLR4) and Nod-like receptor protein 3(NLRP3), in the pancreas of T2DM mice, and Rehmanniae Radix showed better performance. In addition, the expression levels of inducible nitric oxide synthase(iNOS), nuclear factor erythroid 2-related factor 2(Nrf2), and heine oxygenase-1(HO-1) in the pancreas of T2DM mice were down-regulated after drug administration, and Rehmanniae Radix Praeparata demonstrated better performance. The results indicate that both Rehmanniae Radix and Rehmanniae Radix Praeparata can alleviate the inflammatory symptoms, reduce oxidative stress response, and increase the autophagy level in the pancreas of T2DM mice, while they exert the effect on different autophagy pathways.

Variational methods and deep Ritz method for active elastic solids.

Variational methods have been widely used in soft matter physics for both static and dynamic problems. These methods are mostly based on two variational principles: the variational principle of minimum free energy (MFEVP) and Onsager's variational principle (OVP). Our interests lie in the applications of these variational methods to active matter physics. In our former work [H. Wang, T. Qian and X. Xu, Soft Matter, 2021, 17, 3634-3653], we have explored the applications of OVP-based variational methods for the modeling of active matter dynamics. In the present work, we explore variational (or energy) methods that are based on MFEVP for static problems in active elastic solids. We show that MFEVP can be used not only to derive equilibrium equations, but also to develop approximate solution methods, such as the Ritz method, for active solid statics. Moreover, the power of the Ritz-type method can be further enhanced using deep learning methods if we use deep neural networks to construct the trial functions of the variational problems. We then apply these variational methods and the deep Ritz method to study the spontaneous bending and contraction of a thin active circular plate that is induced by internal asymmetric active contraction. The circular plate is found to be bent towards its contracting side. The study of such a simple toy system gives implications for understanding the morphogenesis of solid-like confluent cell monolayers. In addition, we introduce a so-called activogravity length to characterize the importance of gravitational forces relative to internal active contraction in driving the bending of the active plate. When the lateral plate dimension is larger than the activogravity length (about 100 micron), gravitational forces become important. Such gravitaxis behaviors at multicellular scales may play significant roles in the morphogenesis and in the up-down symmetry broken during tissue development.

Onsager's variational principle in active soft matter.

Onsagers variational principle (OVP) was originally proposed by Lars Onsager in 1931 [L. Onsager, Phys. Rev., 1931, 37, 405]. This fundamental principle provides a very powerful tool for formulating thermodynamically consistent models. It can also be employed to find approximate solutions, especially in the study of soft matter dynamics. In this work, OVP is extended and applied to the dynamic modeling of active soft matter such as suspensions of bacteria and aggregates of animal cells. We first extend the general formulation of OVP to active matter dynamics where active forces are included as external non-conservative forces. We then use OVP to analyze the directional motion of individual active units: a molecular motor walking on a stiff biofilament and a toy two-sphere microswimmer. Next we use OVP to formulate a diffuse-interface model for an active polar droplet on a solid substrate. In addition to the generalized hydrodynamic equations for active polar fluids in the bulk region, we have also derived thermodynamically consistent boundary conditions. Finally, we consider the dynamics of a thin active polar droplet under the lubrication approximation. We use OVP to derive a generalized thin film equation and then employ OVP as an approximation tool to find the spreading laws for the thin active polar droplet. By incorporating the activity of biological systems into OVP, we develop a general approach to construct thermodynamically consistent models for better understanding the emergent behaviors of individual animal cells and cell aggregates or tissues.

Caregivers' perceptions, challenges and service needs related to tackling childhood overweight and obesity: a qualitative study in three districts of Shanghai, China.

BACKGROUND: Childhood overweight and obesity (OWO) has become a major public concern worldwide including in Shanghai, one of the most developed areas of China. Understanding perceptions and challenges of tackling childhood OWO among caregivers of children is critical to provide services in need. METHODS: A qualitative descriptive study including in-depth interviews with seven parents and six focus group discussions with a total of 32 parents or grandparents of children zero to 6 years of age. Participants lived in three districts of Shanghai and indexed children included both those with OWO or non-OWO children. Data were analyzed using qualitative thematic analysis. RESULTS: Caregivers tended to underestimate children's weight status, and to regard chubby children as a sign of good parental care. Some caregivers even suggested that there were positive effects of childhood overweight. Caregivers identified a number of challenges to prevention of OWO in children, including difficulties in controlling dietary intake or increasing children's physical activities; discordant views between parents and grandparents, and barriers to accessing professional guidance. Caregivers desired more detailed advice regarding children's nutrition intake and physical activity, and preferred online approaches. CONCLUSIONS: Misconceptions regarding childhood overweight were found in caregivers of children in Shanghai. Professional guidance on childhood weight control for caregivers is desired via digital applications such as mobile phone applications and social media.

Protein mass spectrometry reveals lycorine exerting anti-multiple-myeloma effect by acting on VDAC2 and causing mitochondrial abnormalities.

OBJECTIVE: Two-dimensional electrophoresis (2-DE) and MALDI-TOF/TOF mass spectrometry were performed to compare the proteomic alterations of lycorine-treated and control cells to further investigate the anti-multiple myeloma (MM) mechanisms of lycorine. RESULTS: Mass spectrometry results showed that after lycorine treatment of MM cells, 42% of the differentially expressed proteins had subcellular localization, mainly, on mitochondria. Voltage-dependent anion-selective channel protein 2 (VDAC2), the most abundant protein in the outer mitochondrial membrane, was up-regulated after treatment with lycorine and was subsequently verified by western blot analysis. Further studies on mitochondria found that lycorine was able to increase abnormal mitochondria and increase mitochondrial membrane potential. CONCLUSIONS: Lycorine can achieve the effect of resisting multiple myeloma by acting on VDAC2 and causing mitochondrial abnormalities.

Lycorine targets multiple myeloma stem cell-like cells by inhibition of Wnt/ß-catenin pathway.

Multiple myeloma (MM) is characterised by the proliferation and accumulation of malignant plasma cells in the bone marrow. Despite the progress in treatment over the last few years, MM remains incurable and the majority of patients relapse. MM stem-like cells (MMSCs) have been considered as the main reason for drug resistance and eventual relapse. Currently, therapeutic agents are not enough to eradicate MMSCs, and finding effective strategies to eradicate MMSCs may improve the outcome of patients. Here we showed that lycorine, a natural compound from the Amaryllidaceae species, effectively inhibits the proliferation of myeloma cells from cell lines or patients, mainly through decreasing ALDH1+ cells. Mechanistically, lycorine decreases the MMSC population through inhibition of the Wnt/ß-catenin pathway by reducing the ß-catenin protein level. Moreover, lycorine could overcome the increasing proportion of ALDH1+ cells caused by bortezomib (BTZ) treatment, and a combination BTZ and lycorine have a synergistic effect on anti-myeloma cells. Furthermore, we found a similar reduction of MMSC characteristics by lycorine in BTZ-resistant MM cells and primary CD138+ plasma cells. Collectively, our findings indicate lycorine as a promising agent to target MMSCs to overcome the drug resistance of BTZ, and that, alone or in combination with BTZ, lycorine is a potential therapeutic strategy for MM treatments.

The Wee1 kinase inhibitor MK1775 suppresses cell growth, attenuates stemness and synergises with bortezomib in multiple myeloma.

Multiple myeloma stem-like cells (MMSCs) are responsible for initiation and relapse, though novel treatment paradigms that effectively eradicate MMSCs are yet to be developed. Selective inhibition of the cell cycle regulatory kinase Wee1 by MK1775 is being explored as a potential anti-cancer therapeutic. We report that higher expression of Wee1 is correlated with poor survival in multiple myeloma (MM). The MM models and patient-derived CD138+ plasma cells are particularly sensitive to the growth-inhibitory effects of the Wee1 inhibitor MK1775. MK1775 induces Mus81-Eme1 endonuclease-mediated DNA damage in S-phase cell cycle that results in a blockade of replication and then apoptosis. Furthermore, MK1775 strongly suppresses the features of stemness in vitro, in vivo and in primary CD138+ cells by decreasing ALDH1+ cell fraction and the expression of ALDH1. In addition, co-treatment of MK1775 with bortezomib is synergistic in vitro and in vivo. Bortezomib, although it enhances ALDH1+ cells, when combined with MK1775 abrogates this stimulatory effect on stemness. Considering MM as an invariably incurable malignancy due to the presence of heterogenic myeloma stem-like cells, our study presents inhibition of Wee1 as a promising targeted therapy for MM and provides a compelling rationale to further investigate the activity of MK1775 against myeloma in clinical settings.

Continuum elastic models for force transmission in biopolymer gels.

We review continuum elastic models for the transmission of both external forces and internal active cellular forces in biopolymer gels, and relate them to recent experiments. Rather than being exhaustive, we focus on continuum elastic models for small affine deformations and intend to provide a systematic continuum method and some analytical perspectives on the study of force transmission in biopolymer gels. We start from a very brief review of the nonlinear mechanics of individual biopolymers and a summary of constitutive models for the nonlinear elasticity of biopolymer gels. We next show that the simple 3-chain model can give predictions that fit well the shear experiments of some biopolymer gels, including the effects of strain-stiffening and negative normal stress. We then review continuum models for the transmission of internal active forces that are induced by a spherically contracting cell embedded in a three-dimensional biopolymer gel. Various scaling regimes for the decay of cell-induced displacements are identified for linear isotropic and anisotropic materials, and for biopolymer gels with nonlinear compressive-softening and strain-stiffening elasticity, respectively. After that, we present (using an energetic approach) the generic and unified continuum theory proposed in [D. Ben-Yaakov et al., Soft Matter, 2015, 11, 1412] about how the transmission of forces in the biogel matrix can mediate long-range interactions between cells with mechanical homeostasis. We show the predictions of the theory in a special hexagonal multicellular array, and relate them to recent experiments. Finally, we conclude this paper with comments on the limitations and outlook of continuum modeling, and highlight the need for complementary theoretical approaches, such as discrete network simulations, to force transmission in biopolymer gels and phenomenological active gel theories for multicellular systems.

LncRNA-ANRIL inhibits cell senescence of vascular smooth muscle cells by regulating miR-181a/Sirt1.

BACKGROUND: Cardiovascular disease is one of the major threats to human life and health, and vascular aging is an important cause of its occurrence. Antisense non-coding RNA in the INK4 locus (ANRIL) is a kind of long non-coding RNA (lncRNA) that plays important roles in cell senescence. However, the role and mechanism of ANRIL in senescence of vascular smooth muscle cells (VSMCs) are unclear. METHODS: Cell viability and cell cycle were evaluated using an MTT assay and flow cytometry analysis, respectively. Senescence-associated (SA)-ß-galactosidase (gal) staining was used to determine cell senescence. Dual luciferase reporter assays were conducted to confirm the binding of ANRIL and miR-181a, as well as miR-181a and Sirt1. The expression of ANRIL, miR-181a, and Sirt1 was determined using qRT-PCR and protein levels of SA-ß-gal and p53-p21 pathway-related proteins were evaluated by Western blotting. RESULTS: ANRIL and Sirt1 were down-regulated, whereas miR-181a was up-regulated in aging VSMCs. In young and aging VSMCs, over-expression of ANRIL could down-regulate miR-181a and up-regulate Sirt1. MTT and SA-ß-gal staining assays showed that over-expression of ANRIL and inhibition of miR-181a promoted cell viability and inhibited VSMC senescence. The dual-luciferase reporter assay determined that miR-181a directly targets ANRIL and the 3'-UTR of Sirt1. Furthermore, over-expression of ANRIL inhibited cell cycle arrest and the p53-p21 pathway. CONCLUSION: ANRIL promotes cell viability and inhibits senescence in VSMCs, possibly by regulating miR-181a/Sirt1, and alleviating cell cycle arrest by inhibiting the p53-p21 pathway. This study provides novel insights for the role of ANRIL in the development of cell senescence.

The Clinical Significance of miR-34a in Pancreatic Ductal Carcinoma and Associated Molecular and Cellular Mechanisms.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) exhibits poor prognosis and resistance to chemotherapy. This study was to identify the biomarkers associated with the progression, poor prognosis and chemoresistance of PDAC. METHODS: miR-34a and miR-150 levels in the plasma and tissues from PDAC patients were measured by real-time PCR. Xenograft PDAC tumor models were established in mice by inoculation of CD133+ stem cells isolated from PDAC tumors. Protein expression was measured by Western blot. RESULTS: The plasma miR-34a and miR-150 levels were significantly lower in PDAC patients than in patients with benign pancreatic lesions and in healthy subjects. The miR-34a and miR-150 levels in the tumor tissues were significantly lower than in pancreatic tissues with benign lesions. The protein levels of CD133, Notch1, Notch2 and Notch4 receptors in PDAC tumor tissues were significantly higher than in pancreatic tissues with benign lesions. miR-34a injection significantly inhibited the tumor growth of PDAC tumors and sensitized the anticancer effects of 5-fluorouracil (5-FU). miR-34a significantly inhibited Notch1, Notch2 and Notch4 expression in xenograft tumor tissues in vivo and BxPC-3 cells in vitro. miR-34a and miR-150 significantly induced apoptosis and inhibited proliferation, invasion and migration in BxPC-3 cells. miR-34a, but not miR-150, significantly sensitized the anticancer effect of 5-FU in BxPC-3 cells in vitro. CONCLUSION: A loss of expression of miR-34a, but not of miR-150, is associated with disease progression and poor prognosis in PDAC patients, and may be involved in the chemoresistance of PDAC cells.

miR-30a-5p targets ITGA6 to inhibit oral squamous cell carcinoma progression.

OBJECTIVE: Nowadays, many studies focus on the relationship between microRNAs (miRs) and the development of oral squamous cell carcinoma (OSCC). Here, we broaden the understanding of miR-30a-5p in OSCC. METHODS: In silico analysis was implemented to screen differentially expressed genes in OSCC and the related upstream regulatory miR. OSCC SCC9 cells were manipulated with lentivirus-mediated miR-30a-5p mimic, oe-ITGA6 or sh-ITGA6 and LY294002 (the PI3K/AKT pathway inhibitor) for studying their roles in cell biological processes. Tumors were xenografted in nude mouse for in vivo mechanism verification. RESULTS: In silico analysis results depicted that ITGA6 was highly expressed in OSCC, and that miR-30a-5p was the upstream regulatory miR of ITGA6. miR-30a-5p was downregulated and ITGA6 was highly expressed in OSCC tissues and cells. miR-30a-5p targeted and downregulated ITGA6. ITGA6 promoted epithelial-mesenchymal transition, migration and invasion in OSCC cells by activating PI3K/AKT pathway. miR-30a-5p could suppress the in vivo growth and metastasis of OSCC by inhibiting the ITGA6/PI3K/AKT axis. CONCLUSION: Taken together, miR-30a-5p prevents OSCC progression by inhibiting PI3K/AKT pathway through inhibition of ITGA6 expression.

Overexpressed FAM111B degrades GSDMA to promote esophageal cancer tumorigenesis and cisplatin resistance.

BACKGROUND: Chemotherapeutic agents such as cisplatin are commonly used in patients with clinically unresectable or recurrent esophageal cancer (ESCA). However, patients often develop resistance to cisplatin, which in turn leads to a poor prognosis. Studies have shown that FAM111B may be involved in the development of tumors as an oncogene or tumor suppressor gene. However, the pathological role and corresponding mechanism of FAM111B in ESCA are still unclear. METHODS: The GEPIA web tool, ENCORI Pan-Cancer Analysis Platform and UALCAN-TCGA database were used to study the expression of FAM111B in ESCA. CCK-8, angiogenesis, Transwell and xenograft assays were applied to explore the biological function of FAM111B in ESCA. Western blot, RT-qPCR, and RNA-seq analyses were applied to study the FAM111B/GSDMA axis in the progression of ESCA cells. CCK-8 and xenograft assays were used to study the role of the FAM111B/GSDMA axis in determining the sensitivity of ESCA to cisplatin. RESULTS: Our results demonstrated that FAM111B is highly expressed in ESCA tissues compared to normal tissues. We showed that FAM111B promotes the progression of ESCC cells by binding to GSDMA and that the trypsin protease domain is essential for the activity of FAM111B. Furthermore, we showed that the FAM111B/GSDMA axis regulates cisplatin sensitivity in ESCA. CONCLUSIONS: Overall, we identified a novel FAM111B/GSDMA axis regulating ESCA tumorigenesis and chemosensitivity, at least in ESCC cells.

Integrated bioinformatics analysis of nucleotide metabolism based molecular subtyping and biomarkers in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD), a predominant subtype of non-small cell lung cancers, continues to challenge treatment outcomes due to its heterogeneity and complex tumor microenvironment (TME). Dysregulation in nucleotide metabolism has been identified as a significant factor in tumorigenesis, suggesting its potential as a therapeutic target. Methods: This study analyzed LUAD samples from The Cancer Genome Atlas (TCGA) using Non-negative Matrix Factorization (NMF) clustering, Weighted Correlation Network Analysis (WGCNA), and various machine learning techniques. We investigated the role of nucleotide metabolism in relation to clinical features and immune microenvironment through large-scale data analysis and single-cell sequencing. Using in vivo and in vitro experiments such as RT-qPCR, Western Blot, immunohistochemistry, and subcutaneous tumor formation in mice, we further validated the functions of key nucleotide metabolism genes in cell lines and animals. Results: Nucleotide metabolism genes classified LUAD patients into two distinct subtypes with significant prognostic differences. The 'C1' subtype associated with active nucleotide metabolism pathways showed poorer prognosis and a more aggressive tumor phenotype. Furthermore, a nucleotide metabolism-related score (NMRS) calculated from the expression of 28 key genes effectively differentiated between patient outcomes and predicted associations with oncogenic pathways and immune responses. By integrating various immune infiltration algorithms, we delineated the associations between nucleotide metabolism signature genes and the tumor microenvironment, and characterized their distribution differences at the cellular level by analyzing single-cell sequencing dataset related to immunochemotherapy. Finally, we demonstrated the differential expression of the key nucleotide metabolism gene AUNIP acts as an oncogene to promote LUAD cell proliferation and is associated with tumor immune infiltration. Conclusion: The study underscores the pivotal role of nucleotide metabolism in LUAD progression and prognosis, highlighting the NMRS as a valuable biomarker for clinical outcomes and therapeutic responses. Specifically, AUNIP functions as a critical oncogene, offering a promising target for novel treatment strategies in LUAD.

The Effects of Budesonide Inhalation Treatment on the Expression Levels of Serum IL-6, TGF-ß1, and IgE and Pulmonary Function in Patients with Cough Variant Asthma and an Evaluation of Treatment Efficacy.

Objective: To retrospectively study the effects of budesonide inhalation combined with conventional symptomatic treatment on serum inflammatory factor expression levels and pulmonary function in patients with cough variant asthma (CVA) and to evaluate treatment efficacy. Methods: This retrospective cohort study included 200 patients diagnosed with CVA at the Second Hospital of Jiaxing between January 2022 and June 2023 and given conventional symptomatic treatment plus budesonide inhalation were included in this study. Patients were divided into a no remission group, a partial remission group and a complete remission group based on treatment effect. The expression levels of serum inflammatory factors, cough symptom scores, and small airway function indicators in the three groups of patients at different time points were compared. Results: In the three groups of CVA patients, after receiving budesonide inhalation combined with conventional symptomatic treatment, the expression levels of serum IL-5, IL-6, IL-8, TNF-α, TGF-ß1, and IgE and number of eosinophils significantly decreased (P <0.05). There were statistically significant differences in the IL-6 and TGF-ß1 levels among the three groups of CVA patients at T1, T2 and T3. There were statistically significant differences in IgE levels, number of eosinophils, cough symptom scores, and small airway function indicators between T2 and T3 (P<0.05). The receiver operating characteristic (ROC) curve prediction analysis revealed significant differences in the expression of IL-6 and TGF-ß1 at T1, T2, and T3. Conclusion: Budesonide inhalation combined with conventional symptomatic treatment can significantly reduce the levels of serum inflammatory factors in patients with CVA to reduce inflammation and the allergic response, thereby reducing the cough symptom score, improving pulmonary function, and improving therapeutic efficacy. In addition, IL-6 and TGF-ß1 can be used as early predictors of budesonide inhalation efficacy.

Type B3 thymoma complicated with Chlamydia psittaci pneumonia with rare features: A case report.

The case of a patient with type B3 thymomacomorbid with Chlamydia psittaci (C. psittaci) pneumonia exhibiting rare features is presented in the current report. The patient was admitted at the Second Affiliated Hospital of Jiaxing University (Jiaxing, China) with a history of direct contact with poultry. Clinical manifestations included fever, shivers, cough, fatigue and poor appetite. Chest computed tomography (CT) indicated right lung pneumonia, while metagenomics next-generation sequencing using bronchoalveolar lavage fluid confirmed infection with C. psittaci. Additionally, positron emission tomography-CT suggested the presence of thymoma. After surgery and treatment with doxycycline and imipenem cilastatin, the patient was discharged showing signs of improvement.

Detection of PD­L1 expression and epithelial­mesenchymal transition of circulating tumor cells in non­small cell lung cancer.

The present study aimed to assess the roles of peripheral circulating tumor cell (CTC) count, CTC subtypes and programmed death ligand 1 (PD-L1) expression in the clinical staging and prognosis of patients with non-small cell lung cancer (NSCLC). A total of 100 patients with NSCLC with available tumor tissues were enrolled in the present study, and 7.5 ml peripheral blood was collected. Patients were divided into PD-L1-positive and PD-L1-negative groups according to PD-L1 immunohistochemical staining. Peripheral blood samples from both groups were analyzed to determine the CTC count, epithelial-type CTCs (E-CTCs), mesenchymal-type CTCs (M-CTCs) and PD-L1 expression. Clinical data were collected, and patients were followed up for a maximum of 36 months, with patient death as the endpoint event. Patients with PD-L1-positive tumors had a worse prognosis compared with those with PD-L1-negative tumors (P=0.045). The PD-L1-positive group exhibited significantly higher numbers of CTCs and M-CTCs compared with the PD-L1-negative group (P≤0.05). However, the number of E-CTCs did not differ significantly between the two groups (P>0.05). PD-L1-positive patients with higher CTC and M-CTC counts had relatively poorer prognoses (P≤0.05), while the number of E-CTCs had no significant effect on prognosis (P>0.05). Compared with the early-stage NSCLC group, the late-stage NSCLC group exhibited a significant increase in the CTC count (P≤0.05), while E-CTC and M-CTC counts did not significantly differ between the two groups (P>0.05). The PD-L1-positive group exhibited a significant increase in the number of PD-L1+ CTCs and PD-L1+ M-CTCs compared with the PD-L1-negative group (P≤0.05), while PD-L1+ E-CTC counts did not differ significantly between the two groups (P>0.05). The PD-L1-positive patients with a higher number of PD-L1+ CTCs and PD-L1+ M-CTCs had relatively poorer prognoses (P≤0.05), while the PD-L1+ E-CTC count had no significant effect on prognosis (P>0.05). Compared with the early-stage NSCLC group, the late-stage NSCLC group exhibited a significant increase in the number of PD-L1+ CTCs and PD-L1+ M-CTCs (P≤0.05), while PD-L1+ E-CTC counts did not significantly differ between the two groups (P>0.05). Based on univariate and multivariate analyses, the number of PD-L1+ M-CTCs was identified as an independent prognostic factor for NSCLC. In conclusion, the presence of CTCs in peripheral blood, particularly PD-L1+ M-CTC subtype, indicated poorer clinical staging and prognosis in patients with NSCLC. These findings suggested that CTCs, specifically the PD-L1+ M-CTC subtype, could serve as a monitoring indicator for the clinical staging and prognosis of patients with NSCLC.

Asia's Growing Contribution to Obesity Surgery Research: A 40-year Bibliometric Analysis.

Bariatric metabolic surgery's global research interest is growing, particularly in Asia due to its high obesity rates. This study focuses on Asia, especially China, analyzing 3904 publications (1221 from China) from 1980 to 2022. Research output accelerated until the COVID-19 pandemic, driven by economic growth and rising obesity rates. China led contributions from 2010, but Western Asia led when adjusted for population. An intra-regional research collaboration network emerged, driven by geographic proximity and similar economic environments. Keyword analysis highlighted emerging topics like "laparoscopic sleeve gastrectomy" and "non-alcoholic fatty liver disease," indicating a shift in focus. The study recommends disseminating research in top-tier journals to enhance visibility and impact.