[Evaluation of the effect of MTF-S on the removal of impacted mandibular wisdom teeth with complete or partial crown impaction].

PURPOSE: To evaluation the effect of modified triangular flap-secondary healing (MTF-S) on the treatment of mandibular impacted wisdom teeth with full or partial bone impaction. METHODS: A total of 207 patients with mandibular impacted wisdom teeth were selected in Shaoxing Stomatological Hospital from June 2022 to June 2023. Among them, 86 patients had completely impacted wisdom teeth (group A), and 121 patients had partially impacted wisdom teeth (group B). All patients had bilateral impacted wisdom teeth. One of the wisdom teeth was removed first and was sutured with triangular flap-primary healing (TF-P). The other wisdom tooth was removed two weeks later and was sutured with MTF-S. Patients in groups A and B were divided into two subgroups based on suture methods, with TF-P used for group A1 and B1, and MTF-S used for groups A2 and B2. Perioperative indicators, including surgical time, root loss rate, and completeness of extraction sockets were recorded; Postoperative complications of four groups, including pain, swelling, and limited mouth opening were compared. SPSS 22.0 software package was used for statistical analysis. RESULTS: The surgical time of group A1, A2, B1 and B2 was (17.69±3.28), (18.22±3.06), (12.37±3.72) and (12.64±4.13) minutes, respectively. The surgical time of group A1 and A2 was significantly longer than that of group B1 and B2 (P＜0.05). Seven days after surgery, the VAS scores of group A1, A2, B1 and B2 were (1.17±0.34), (0.93±0.29), (0.48±0.15) and (0.76±0.21), respectively. The VAS scores of group B1 and B2 were lower than those of group A1 and A2, and group A2 was lower than group A1 and B2 was higher than group B1 group(P＜0.05). On the 1st day, 3rd day, and 7th day after surgery, the swelling degree in group A1 was greater than that in group B1, and the swelling degree in group B1 was greater than that in group A2 and B2(P＜0.05); while the limitation of mouth opening mouth in group A2 and B2 was lower than that in group A1 and B1, and the limitation of opening mouth in group B2 was lower than that in group A2(P＜0.05). CONCLUSIONS: Compared with partially impacted wisdom teeth, the extraction of completely impacted wisdom teeth has a longer surgical time. For completely impacted wisdom teeth, MTF-S is beneficial for reducing postoperative pain, swelling and mouth opening limitations. For partially impacted wisdom teeth, MTF-S is beneficial for reducing postoperative swelling and mouth opening limitations, but the effect is not significant in reducing patient pain.

Prognostic and immunotherapeutic potential of regulatory T cell-associated signature in ovarian cancer.

Tumour-induced immunosuppressive microenvironments facilitate oncogenesis, with regulatory T cells (Tregs) serving as a crucial component. The significance of Treg-associated genes within the context of ovarian cancer (OC) remains elucidated insufficiently. Utilizing single-cell RNA sequencing (scRNA-Seq) for the identification of Treg-specific biomarkers, this investigation employed single-sample gene set enrichment analysis (ssGSEA) for the derivation of a Treg signature score. Weighted gene co-expression network analysis (WGCNA) facilitated the identification of Treg-correlated genes. Machine learning algorithms were employed to determine an optimal prognostic model, subsequently exploring disparities across risk strata in terms of survival outcomes, immunological infiltration, pathway activation and responsiveness to immunotherapy. Through WGCNA, a cohort of 365 Treg-associated genes was discerned, with 70 implicated in the prognostication of OC. A Tregs-associated signature (TAS), synthesized from random survival forest (RSF) and Least Absolute Shrinkage and Selection Operator (LASSO) algorithms, exhibited robust predictive validity across both internal and external cohorts. Low TAS OC patients demonstrated superior survival outcomes, augmented by increased immunological cell infiltration, upregulated immune checkpoint expression, distinct pathway enrichment and differential response to immunotherapeutic interventions. The devised TAS proficiently prognosticates patient outcomes and delineates the immunological milieu within OC, offering a strategic instrument for the clinical stratification and selection of patients.

Cytokine profile in first-episode drug-naïve major depressive disorder patients with or without anxiety.

OBJECTIVE: It is known that cytokines play a role in both depression and anxiety. This study aimed to compare the levels of multiple cytokines in patients with first-episode drug-naive major depressive disorder (MDD) with or without anxiety and analyze the correlation between the level of depression or anxiety and the serum cytokine levels. METHODS: The study involved 55 patients with first-episode drug-naive MDD. To assess anxiety symptoms, the 14-item HAMA was used. MDD patients were divided into two groups: 23 MDD patients without anxiety and 32 MDD patients with anxiety. The measurement of 37 cytokines was conducted. Serum cytokine levels between patients with MDD without anxiety and anxiety were compared. In multiple linear regression models, the relationship between the group and abnormal cytokines was explored. The receiver operating characteristic (ROC) curve analysis was performed to estimate diagnostic performance of serum cytokines in discriminating MDD patients with anxiety from MDD patients without anxiety. A correlation was evaluated between the scores of HAMD or HAMA and the serum cytokine levels. RESULTS: In MDD patients with anxiety, IL-17 C and CCL17 levels were significantly lower than in MDD patients without anxiety (all P < 0.05). Multiple measurements were corrected with Benjamini-Hochberger corrections, but none of these differences persisted (all P > 0.05). The results of multiple linear regression models revealed that after controlling for other independent variables, group was not a significant independent predictor of serum IL-17 C or CCL17 (all P > 0.05). The AUC values of IL-17 C and CCL17 were 0.643 and 0.637, respectively, in discriminating MDD patients with anxiety from MDD patients without anxiety. The results of partial correlation analyses showed the scores of HAMD were negatively correlated with the IL-17 C (r = -0.314, P = 0.021) levels with sex as a covariate. CONCLUSIONS: The findings suggest that there is a potential absence of disparity in the levels of circulating cytokines among individuals diagnosed with first-episode drug-naïve MDD, regardless of the presence or absence of comorbid anxiety.

Serum indoleamine 2, 3-dioxygenase and tryptophan-2, 3-dioxygenase: potential biomarkers for the diagnosis of major depressive disorder.

OBJECTIVE: The objective of this study was to observe the changes in the levels of indoleamine 2, 3-dioxygenase (IDO) and tryptophan-2, 3-dioxygenase (TDO) in patients with major depressive disorder (MDD) and investigate their potential role as novel biomarkers for diagnosing MDD. METHODS: A total of 55 MDD patients and 55 healthy controls (HC) were enrolled in the study. The severity of MDD was assessed using the 24-item Hamilton Depression Rating Scale (HAMD-24) before and after treatment. The serum concentrations of IDO and TDO were measured at baseline and after treatment. The correlations between the serum levels of IDO and TDO and HAMD-24 scores were evaluated using Pearson's correlation test. Receiver operating characteristic (ROC) curve analysis was used to evaluate the area under the curve (AUC) of serum levels of IDO and TDO for discriminating MDD patients from HC. RESULTS: The serum IDO and TDO concentrations were significantly higher in patients with MDD at baseline than in healthy controls, and decreased significantly after 2 weeks or 1 month of treatment. The levels of IDO and TDO were significantly positively correlated with HAMD-24 scores. Furthermore, the AUC values for IDO and TDO were 0.999 and 0.966, respectively. CONCLUSION: The study suggests that serum IDO and TDO may serve as novel biomarkers for diagnosing MDD. These findings may lead to a better understanding of the pathogenesis of MDD and the development of new therapeutic targets.

REG3A promotes proliferation and DDP resistance of ovarian cancer cells by activating the PI3K/Akt signaling pathway.

This study explored the effect of Regenerating Islet-Derived 3-Alpha (REG3A) on ovarian cancer (OC) progression. REG3A expression was scrutinized in clinical tissues of 97 OC cases by quantitative real-time polymerase chain reaction (qRT-PCR). REG3A expression in OC cells and cisplatin (DDP) resistance OC cells was regulated by transfection. LY294002 (10 µM, inhibitor of the PI3K/Akt signaling pathway) was used to treat OC cells and DDP resistance OC cells. Cell counting kit-8 and methyl-thiazolyl-tetrazolium assays were applied for proliferation and DDP resistance detection. Flow cytometry was utilized for cell cycle and apoptosis analysis. The effect of REG3A on the OC cell in vivo growth was researched by establishing xenograft tumor model via using nude mice using nude mice. The expression of genes in clinical samples, cells and xenograft tumor tissues was investigated by qRT-PCR, Western blot and immunohistochemistry. As a result, REG3A was over-expressed in OC patients and cells, associating with dismal prognosis of patients. REG3A knockdown repressed proliferation, DDP resistance, induced cell cycle arrest and apoptosis of OC cells, and reduced the expression MDR-1, Cyclin D1, Cleaved caspase 3 proteins and the PI3K/Akt signaling pathway activity in OC cells. LY294002 treatment abrogated the promotion effect of REG3A on OC cell proliferation, apoptosis inhibition and DDP resistance. REG3A knockdown suppressed the in vivo growth of OC cells. Thus, REG3A promoted proliferation and DDP resistance of OC cells by activating the PI3K/Akt signaling pathway. REG3A might be a promising target for the clinical treatment of OC.

[Research progress on the biological effects of HIF-1α on follicle development and ovulation].

Hypoxia inducible factor-1α (HIF-1α), as a hypoxia inducible factor, affects women's reproductive function by regulating the development and excretion of follicles. HIF-1α induces glycolysis and autophagy in the granule cells by promoting oocyte development, regulating the secretion of related angiogenic factors, and improving follicle maturity. In addition, HIF-1α promotes the process of luteinization of follicular vesicles, maintains luteal function, and finally completes physiological luteal atrophy through cumulative oxidative stress. Dysfunction of HIF-1α will cause a series of pathological consequences, such as angiogenesis defect, energy metabolism abnormality, excessive oxidative stress and dysregulated autophagy and apoptosis, resulting in ovulation problem and infertility. This article summarizes the previous studies on the regulation of follicle development and excretion and maintenance of luteal function and structural atrophy by HIF-1α. We also describe the effective intervention mechanism of related drugs or bioactive ingredients on follicular dysplasia and ovulation disorders through HIF-1α, in order to provide a systematic and in-depth insights for solving ovulation disorder infertility.

Integrated BATF transcriptional network regulates suppressive intratumoral regulatory T cells.

Human regulatory T cells (Tregs) are crucial regulators of tissue repair, autoimmune diseases, and cancer. However, it is challenging to inhibit the suppressive function of Tregs for cancer therapy without affecting immune homeostasis. Identifying pathways that may distinguish tumor-restricted Tregs is important, yet the transcriptional programs that control intratumoral Treg gene expression, and that are distinct from Tregs in healthy tissues, remain largely unknown. We profiled single-cell transcriptomes of CD4+ T cells in tumors and peripheral blood from patients with head and neck squamous cell carcinomas (HNSCC) and those in nontumor tonsil tissues and peripheral blood from healthy donors. We identified a subpopulation of activated Tregs expressing multiple tumor necrosis factor receptor (TNFR) genes (TNFR+ Tregs) that is highly enriched in the tumor microenvironment (TME) compared with nontumor tissue and the periphery. TNFR+ Tregs are associated with worse prognosis in HNSCC and across multiple solid tumor types. Mechanistically, the transcription factor BATF is a central component of a gene regulatory network that governs key aspects of TNFR+ Tregs. CRISPR-Cas9-mediated BATF knockout in human activated Tregs in conjunction with bulk RNA sequencing, immunophenotyping, and in vitro functional assays corroborated the central role of BATF in limiting excessive activation and promoting the survival of human activated Tregs. Last, we identified a suite of surface molecules reflective of the BATF-driven transcriptional network on intratumoral Tregs in patients with HNSCC. These findings uncover a primary transcriptional regulator of highly suppressive intratumoral Tregs, highlighting potential opportunities for therapeutic intervention in cancer without affecting immune homeostasis.

Central sleep apnea treated by a constant low-dose CO2 supplied by a novel device.

CO2 inhalation has been previously reported as a treatment for central sleep apnea both when associated with heart failure or where the cause is unknown. Here, we evaluated a novel CO2 supply system using a novel open mask capable of comfortably delivering a constantly inspired fraction of CO2 ([Formula: see text]) during sleep. We recruited 18 patients with central sleep apnea (13 patients with cardiac disease, and 5 patients idiopathic) diagnosed by diaphragm electromyogram (EMG) recordings made during overnight full polysomnography (PSG) (night 1). In each case, the optimal [Formula: see text] was determined by an overnight manual titration with PSG (night 2). Titration commenced at 1% CO2 and increased by 0.2% increments until central sleep apnea (CSA) disappeared. Patients were then treated on the third night (night 3) with the lowest therapeutically effective concentration of CO2 derived from night 2. Comparing night 1 and night 3, both apnea-hypopnea index (AHI; 31 ± 14 vs. 6 ± 3 events/h, P < 0.01) and arousal index (22 ± 8 vs. 15 ± 8 events/h, P < 0.01) were significantly improved during CO2 treatment. Sleep efficiency improved from 71 ± 18 to 80 ± 11%, P < 0.05, and sleep latency was shorter (23 ± 18 vs. 10 ± 10 min, P < 0.01). Heart rate was not different between night 1 and night 3. Our data confirm the feasibility of our CO2 delivery system and indicate that individually titrated CO2 supplementation with a novel device including a special open mask can reduce sleep disordered breathing severity and improve sleep quality. Randomized controlled studies should now be undertaken to assess therapeutic benefit for patients with CSA.NEW & NOTEWORTHY A novel device using a special mask was developed and proved that CO2 therapy using the device could eliminate central sleep apnea (CSA) events and improve sleep quality including reducing arousal index in patients with heart failure. The device would become a useful clinical treatment for heart failure patients with CSA.

[Effects of moxibustion at "Tianshu"（ST25） and "Shangjuxu" （ST37） on colonic metabolites and inflammatory factors in rats with Crohn's disease].

OBJECTIVE: To observe the effects of moxibustion at "Tianshu"（ST25） and "Shangjuxu"（ST37） on the colonic metabolites and inflammatory factors in rats with Crohn's disease（CD）, so as to explore the mechanisms of moxibustion in protecting colon of CD rats based on metabolomics. METHODS: Twelve rats were first randomly selected from 36 male SD rats as a normal group（NG）. The CD model was induced by 2, 4, 6 trinitrobenzene sulfonic acid（TNBS） enema on the rest 24 rats. After successful modeling, rats were randomly divided into model（TNBS） and moxibustion（TNBS+MOX） groups（n=10 rats/group）. Moxibustion was applied at bilateral ST25 and ST37 for 30 min, once daily for 7 consecutive days in the TNBS+MOX group, while rats in the NG and TNBS groups did not receive any interventions. Body weight of rats was recorded and disease activity index（DAI） was assessed during the experiment. After interventions, HE staining was performed to observe pathological damage of colon. Serum levels of inflammatory factors were measured by ELISA. NMR hydrogen spectroscopy was used to detect colonic metabolites of each group, and orthogonal partial least squares discriminant analysis（OPLS-DA） was used to screen differential colonic metabolites between groups, followed by pathway analysis using MetaboAnalyst 5.0 platform. RESULTS: After modeling, compared with the NG group, the body weight of the rats in the TNBS group was significantly decreased（P<0.05）, the DAI score was increased （P<0.05）, the colon had obvious inflammatory damage and the pathological injury index was increased（P<0.05）, and levels of serum tumor necrosis factor-α（TNF-α）, interleukin（IL）-1ß and interferon-γ（IFN-γ） were significantly increased（P<0.05）. After moxibustion intervention, compared with the TNBS group, the body weight was significantly increased（P<0.05）, while the levels of serum TNF-α, IL-1ß, IFN-γ, and DAI score of the rats in the TNBS+MOX group were significantly decreased（P<0.05）, with alleviated colonic inflammatory injury detected by HE staining. Compared with the NG group, the relative expressions of colonic hypoxanthine, betaine, creatine, inositol, taurine, uracil, and methanol of the TNBS group were decreased（P<0.05）, while the relative expressions of histidine, leucine, proline, lysine, isoleucine, phenylalanine, tyrosine, propionic acid, and valine were increased（P<0.05） in the TNBS group, among which, relative expressions of hypoxanthine, leucine, lysine, isoleucine, betaine, tyrosine, and taurine were reversed in the TNBS+MOX group relevant to the TNBS group, mainly involving phenylalanine, tyrosine and tryptophan biosynthesis, and taurine and subtaurine metabolism pathway. CONCLUSION: The mechanism of moxibustion at ST25 and ST37 for CD may be related to improving colon metabolic disorder state by regulating multiple metabolic metabolites and metabolic pathways, and reducing the level of inflammatory factors, so as to maintain intestinal immune homeostasis.

Peripheral Complement Factor-Based Biomarkers for Patients with First-Episode Schizophrenia.

Objective: Schizophrenia (SCZ) is a severe, protracted neurological disorder that causes disruptive conduct in millions of individuals globally. Discovery of potential biomarkers in clinical settings would lead to the development of efficient diagnostic techniques and an awareness of the disease's pathogenesis and prognosis. The aim of the present study was to discover and identify serum complement factor-based biomarkers in discriminating patients with first-episode SCZ from healthy controls. Methods: Eighty-nine patients with first-episode SCZ and 89 healthy controls were included in this study. Psychiatric symptom severity of patients with SCZ was measured with the Brief Psychiatric Rating Scale-18 Item Version (BPRS) and the Scales for the Assessment of Negative/Positive Symptoms (SANS/SAPS). A total of 5 complement factors including complement component 1 (C1), C2, C3, C4, and 50% hemolytic complement (CH50) were measured using commercially available enzyme-linked immunosorbent assay (ELISA) kits. The levels of serum complement factors in the SCZ and control groups were compared, and the receiver operating characteristic (ROC) curve method was used to assess the diagnostic values of various complement factors for separating SCZ patients from healthy controls. Pearson's correlation test was used to assess the relationships between serum complement factor concentrations and the psychiatric symptom severity. Results: There was an increase in serum levels of C1, C2, C3, C4, and CH50 among patients with SCZ. Moreover, based on ROC curve analysis, the AUC value of a combined panel of C1, C2, C3, C4, and CH50 was 0.857 when used to discriminate patients with SCZ from healthy controls. Furthermore, serum C2, C3, and CH50 levels were positively correlated to the scores of SANS, SAPS, and BPRS in patients with SCZ, respectively. Conclusion: These results suggested that circulating complement factors including C1, C2, C3, C4, and CH50 may have potential in discovering biomarkers for diagnosing first-episode SCZ.

Effects of microbial diversity loss on the stability of CO2 production and N2O emission in agricultural soils.

The relationship between biodiversity and ecosystem stability is a hot topic in ecology. However, current studies focus mainly on aboveground system with plants, little attention has been paid to belowground system with soils. In this study, we constructed three soil suspensions with varying microbial diversity (100, 10-2, 10-6) by the dilution method and inoculated separately into agricultural Mollisols and Oxisols to examine the stability (indicated by resistance and resilience) of soil CO2 production and N2O emission to copper pollution and heat stress. Results showed that the stability of CO2 production in Mollisols was not influenced by microbial diversity loss, while the resistance and resilience of N2O emission in Mollisols were significantly decreased at the 10-6 diversity. In the Oxisols, the resistance and resilience of N2O emission to copper pollution and heat stress started to decrease even at the 10-2 diversity, and the stability of CO2 production decreased at the 10-6 diversity. These results suggested that both soil types and the identity of soil functions influenced the relationship between microbial diversity and the stability of function. It was concluded that soils with ample nutrients and resistant microbial communities tend to have higher functional stability, and that the fundamental soil functions (e.g., CO2 production) are more resistant and resilient than the specific soil functions (e.g., N2O emission) in response to environmental stress.

Treatment of obstructive sleep apnea with a simple CPAP device.

PURPOSE: CPAP is the "gold standard" treatment for obstructive sleep apnea (OSA). Current CPAP models have developed additional functions including automatic CPAP and pressure relief. However, CPAP adherence has not improved over the last three decades. Many patients in low-income countries cannot afford these CPAP devices. A novel simple CPAP device with a fixed pressure without pressure controller was developed. METHODS: Manual CPAP pressure titration was performed in 127 patients with OSA. Six patients with a titration pressure higher than 11 cmH2O and 14 patients who could not tolerate CPAP were excluded, leaving 107 participating in the following 2 studies. In study one, 54 of 107 patients were treated by both conventional fixed CPAP and simple CPAP in random order. In the second study, another 53 patients were treated by both autoCPAP in automatic function and simple CPAP in random order. Simple CPAP was fixed at 10 cmH2O, 8 cmH2O, and 6 cmH2O for patients whose titration pressure was between 9-10, 7-8, and ≤ 6 cmH2O, respectively. Conventional fixed CPAP device was set exactly the same as manual titration pressure. RESULTS: All patients whose manual titration pressure ≤ 10 cmH2O were effectively treated by simple CPAP (AHI 40.7 ± 2.3 events/h before vs 2.5 ± 0.3 events/h after, p < 0.001). Patients expressed similar preferences for simple CPAP, autoCPAP, and conventional fixed CPAP (p > 0.05). CONCLUSIONS: We conclude that a novel simple CPAP is an alternative treatment for most patients with OSA, which may widen access to CPAP therapy in the developing countries because of its low cost.

Serum cytokines-based biomarkers in the diagnosis and monitoring of therapeutic response in patients with major depressive disorder.

BACKGROUND: Several lines of evidence have suggested that cytokines are implicated in the pathophysiology of depression and antidepressant treatment outcome. However, the results are not always congruent and partly contradictory. We therefore examined the serum levels of multiple cytokines in patients with major depressive disorder (MDD), with the aim to identify serum cytokines-based biomarkers for MDD diagnosis and antidepressant response. METHODS: Fifty-nine patients with MDD and 61 healthy controls were included. The baseline levels of serum cytokines between MDD group and control group were compared, and the discriminative ability of different cytokines in predicting MDD patients from healthy controls was investigated using the receiver operating characteristic (ROC) curve method. The baseline levels of serum cytokines between antidepressant nonresponders and responders were compared, and the discriminative ability of different cytokines in predicting nonresponders from responders was evaluated using the ROC curve method. RESULTS: Compared to controls, 15 of the 37 serum cytokines were increased, while 8 cytokines were decreased in MDD patients (all P < 0.05). The results of ROC curve showed that the Area Under Curve (AUC) values of 15 cytokines including IL-2, IL-5, IL-6, IL-8, IL-12, IL-13, IL-16, CCL3, CCL4, CCL17, CXCL10, TNF-α, TNF-ß, VEGF-C, and FGF basic were greater than 0.7 in discriminating MDD patients from healthy control. Moreover, after 4-week treatment, levels of the 2 cytokines (IL-12 and TSLP) elevated at baseline significantly down-regulated, and levels of the 6 cytokines (IL-5, IL-16, CCL17, CXCL10, TNF-ß, and PIGF) decreased at baseline significantly up-regulated (all P < 0.05). Furthermore, a positive relationship was found between TNF-α levels and Hamilton Depression Rating Scale-24 (HAMD-24) scores in patients with MDD at baseline (r = 0.302, P = 0.019). Additionally, compared to responders, nonresponders exhibited decreased levels of IL-1α, IL-5, IL-13, IL-15, VEGF, and ICAM-1 (all P < 0.05). The ROC curve analysis demonstrated that a combined panel of IL-1α, IL-5, and ICAM-1 achieved a high accuracy in discriminating antidepressant nonresponders from responders (AUC = 0.850, sensitivity = 83.3%, specificity = 81.8%). CONCLUSIONS: These results suggested that alterations in peripheral cytokines levels hold significant promise as biomarkers for MDD diagnosis and antidepressant response.

Circ-sh3rf3/GATA-4/miR-29a regulatory axis in fibroblast-myofibroblast differentiation and myocardial fibrosis.

The transdifferentiation from cardiac fibroblasts to myofibroblasts is an important event in the initiation of cardiac fibrosis. However, the underlying mechanism is not fully understood. Circ-sh3rf3 (circular RNA SH3 domain containing Ring Finger 3) is a novel circular RNA which was induced in hypertrophied ventricles by isoproterenol hydrochloride, and our work has established that it is a potential regulator in cardiac hypertrophy, but whether circ-sh3rf3 plays a role in cardiac fibrosis remains unclear, especially in the conversion of cardiac fibroblasts into myofibroblasts. Here, we found that circ-sh3rf3 was down-regulated in isoproterenol-treated rat cardiac fibroblasts and cardiomyocytes as well as during fibroblast differentiation into myofibroblasts. We further confirmed that circ-sh3rf3 could interact with GATA-4 proteins and reduce the expression of GATA-4, which in turn abolishes GATA-4 repression of miR-29a expression and thus up-regulates miR-29a expression, thereby inhibiting fibroblast-myofibroblast differentiation and myocardial fibrosis. Our work has established a novel Circ-sh3rf3/GATA-4/miR-29a regulatory cascade in fibroblast-myofibroblast differentiation and myocardial fibrosis, which provides a new therapeutic target for myocardial fibrosis.

Comprehensive bioinformatics analysis and molecular validation of lncRNAs-mediated ceRNAs network in schizophrenia.

AIMS: The present study aimed to investigate how Schizophrenia (SCZ)-specific long non-coding RNAs (lncRNAs) served as competing endogenous RNAs (ceRNAs) to modulate the biological functions and pathways involved in the pathogenesis of SCZ. MAIN METHODS: Microarray dataset (GSE54913) was obtained from Gene Expression Omnibus (GEO) database. Differently expressed (DE) lncRNAs and mRNAs were identified by "limma" package. The binding miRNAs of lncRNAs and target mRNAs of shared miRNAs were predicted by miRcode, miRDB, miRTarbase and targetscan databases. Following the ceRNAs theory, interaction network was established and visualized with the cytoscape. Functional enrichment analysis uncovered the concentrated functions and signaling pathways that may be associated with SCZ progression. Protein-protein interaction (PPI) analysis was utilized to determine hub genes. Quantitative real-time PCR (qRT-PCR) and receiver operating characteristic curve (ROC) were performed to evaluate the expression and diagnostic value of ceRNAs members, respectively. KEY FINDINGS: DElncRNAs and DEmRNAs were initially screened from GSE54913 to construct the SCZ-related ceRNAs network with 42 nodes and 53 edges. Functional enrichment analysis revealed that ceRNAs members appeared to be highly correlated with transcription factor activation, cell replication and tumor-related pathways. Once validated, a significant ceRNAs subnetwork was proposed as being implicated in the pathogenesis of SCZ. ROC analysis indicated that SCZ-related ceRNAs members may be sensitive diagnostic biomarkers for SCZ. SIGNIFICANCE: The significant SCZ-related ceRNAs subnetworks (lncRNA-C2orf48A/hsa-miR-20b-5p,-17-5p/KIF23, FOXJ2) may represent promising predictive and diagnostic biomarkers and provide novel insights into the mechanism by which lncRNAs act as microRNA sponges and contribute to the pathogenesis of SCZ.

Role of aryl hydrocarbon receptor in down-regulation of Clara cell secretory protein expression during endotoxin-induced lung injury in rats / 中华麻醉学杂志

Objective:To evaluate the role of aryl hydrocarbon receptor (AhR) in the down-regulation of Clara cell secretory protein (CCSP) expression during endotoxin-induced lung injury in rats.Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 8 weeks, weighing 200-250 g, were divided into 4 groups ( n=6 each) using a random number table method: normal control group (group C), acute lung injury (ALI) group, ALI+ AhR antagonist group, and ALI+ vehicle group. Lipopolysaccharide(LPS) 1 mg/kg was intratracheally instilled to develop the model of lung injury, while the equal volume of normal saline was given instead in group C. At 2 h before LPS injection, AhR antagonist 6, 2′, 4′-trimethoxyflavone solution 5 mg/kg (diluted to 1 ml in dimethyl sulfoxide solution) was intraperitoneally injected in ALI+ AhR antagonist group, while dimethyl sulfoxide solution 1 ml was given in ALI+ vehicle group. The rats were sacrificed under anesthesia at 48 h after LPS administration. The left lung was lavaged and the broncho-alveolar lavage fluid (BALF) was collected for determination of the concentrations of CCSP by enzyme-linked immunosorbent assay, and the expression of CCSP in the bronchial epithelium in right lung tissues was determined by immunohistochemistry. Results:Compared with group C, the expression of CCSP in the bronchial epithelium was significantly down-regulated, and the concentrations of CCSP in BALF were decreased in the other three groups ( P<0.05 or 0.01). Compared with ALI group and ALI+ vehicle group, the histopathological injury was significantly reduced, the expression of CCSP in the bronchial epithelium was up-regulated, and the concentrations of CCSP in BALF were increased in ALI+ AhR antagonist group ( P<0.01). Conclusions:AhR partially mediates the down-regulation of CCSP expression during endotoxin-induced lung injury in rats.

Analysis of changes in plasma endothelin-1 concentrations in patients with acute respiratory distress syndrome / 中华麻醉学杂志

Objective:To analyze the changes in plasma endothelin-1 (ET-1) concentrations in the patients with acute respiratory distress syndrome (ARDS).Methods:Fourteen patients with ARDS induced by trauma, 8 males and 6 females, aged 19-80 yr, were studied. The severity of ARDS was graded according to the Berlin definition of ARDS after admission to intensive care unit (ICU). Venous blood samples were obtained on 1st, 3rd and 5th days after admission to ICU, the plasma ET-1 concentrations were measured by radioimmunoassay, the pulmonary vascular permeability index (PVPI) was determined by PiCCO technique, and multiple organ dysfunction (MOD) score and lung injury score (LIS) were assessed. Spearman correlation of plasma ET-1 concentrations with MOD score, LIS and PVPI was analyzed.Results:MOD score, LIS, PVPI and plasma ET-1 concentrations were significantly decreased in mild ARDS patients ( n=5) as compared with moderate ARDS patients ( n=9, P<0.05). The plasma ET-1 concentration was positively correlated with MOD score, LIS and PVPI ( r=0.69, 0.76, 0.62, P<0.001). Conclusions:Plasma ET-1 concentrations can reflect the pulmonary vascular permeability and even the severity of the disease in the early stage of ARDS, so it is necessary to carry out dynamic monitoring in the patients.

Application of multiplex PCR capillary electrophoresis and analysis of distribution characteristics of HPV infection subtypes / 中华预防医学杂志

Objective: To analyze the characteristics of human papillomavirus (HPV) infection and the distribution of HPV subtypes in Shijiazhuang, Hebei Province, and to explore the application evaluation of multiple PCR capillary electrophoresis fragment analysis for HPV typing test. Methods: A population-based cross-sectional study was conducted among 434 women (age range 17 to 74 years old, 260 patients and 174 physical examinations) included from May to August 2022 in Hebei General Hospital. HPV typing was detected by multiple PCR-capillary electrophoresis fragment analysis. Using the multiple fluorescence quantitative PCR kit as a reference, Chi-square test was used to analyze the diagnostic effect of multiple PCR-capillary electrophoresis fragment analysis, and the consistency was analyzed by Kappa value. Results: The total HPV infection rate was 45.85%(199/434), including 35.48% (154/434) of high-risk HPV (HR-HPV), 3.92% (17/434) of low-risk HPV (LR-HPV), 6.45% (28/434) of HR-HPV and LR-HPV mixed infection, 27.88% (121/434) of single type HPV and 17.97% (78/434) of multi type HPV. HPV52 (9.68%, 42/434), HPV16 (6.91%, 30/434), and HPV58 (6.91%, 30/434) are common HPV subtypes. The positive rate of physical examination was 45.40% (79/174), which was slightly lower than that of patients 46.15% (120/260), there was no significant difference (χ2=0.024,P>0.05). The highest infection rate in the 17-30 age group was 54.76% (46/84), and there was no statistical difference among the age groups(χ2=4.123,P>0.05). The sensitivity and specificity of multiplex PCR capillary electrophoresis fragment analysis were 92.96% and 94.04%, respectively, and Kappa value was 0.870, with the multiplex fluorescent quantitative PCR as the reference. Conclusion: HPV infection may appear younger, and the positive rate of HR-HPV infection is the highest, with HPV52, 16, 58 as the main infection subtypes. The detection results of multiplex PCR capillary electrophoresis fragment analysis method are highly consistent with those of multiplex fluorescent quantitative PCR method, which is suitable for HPV DNA typing.

Peripheral blood cytokines as potential diagnostic biomarkers of suicidal ideation in patients with first-episode drug-naïve major depressive disorder.

Objective: Major Depressive Disorder (MDD) is a leading cause of disability, with a high risk of suicidal ideation (SI). Few studies have evaluated the potential of multiple cytokines as biomarkers for SI in patients with MDD. In the present study, we examined the serum levels of multiple cytokines in patients with first-episode drug-naïve MDD, with the aim to discover and identify serum cytokines-based biomarkers for identification of SI in MDD. Methods: A total of 55 patients with first-episode drug-naïve MDD were enrolled and divided into two groups: 26 MDD patients without SI and 29 MDD patients with SI. Beck Scale for Suicide Ideation was used to estimate SI. A total of 37 cytokines were measured using Multiplex Luminex Assays. The levels of serum cytokines between MDD patients without SI and MDD patients with SI were compared and diagnostic values of different cytokines were evaluated using the receiver operating characteristic (ROC) curve method for discriminating MDD patients with SI from MDD patients without SI. The relationship between the group and the abnormal cytokines were investigated in multiple linear regression models, with adjustments for age, gender, BMI, smoking, and Hamilton Depression Rating Scale-24 (HAMD-24) scores. Results: The levels of CCL26 and VEGF in MDD patients with SI were significantly lower than those in MDD patients without SI (all P < 0.05). On the contrary, the levels of IL-17C, CXCL10, and TNF-ß in MDD patients with SI were significantly higher than those in MDD patients without SI (all P < 0.05). Moreover, the results of multiple linear regression revealed that group was a significant independent predictor of serum IL-17C, CCL-26, VEGF, and TNF-ß levels (all P < 0.05). In terms of CXC10, group was also likely to be a significant independent predictor (ß = 0.257, P = 0.063). Furthermore, the AUC values of IL-17C and TNF-ß were 0.728 and 0.732, respectively. Additionally, a combined panel of IL-17C and TNF-ß achieved a high accuracy in discriminating MDD patients with SI from MDD patients without SI (AUC = 0.848, sensitivity = 75.9%, specificity = 72.7%). Conclusions: These results suggested that circulating IL-17C and TNF-ß may hold promise in the discovery of biomarkers for identification of SI in MDD.

Comparison of serum cytokines levels in normal-weight and overweight patients with first-episode drug-naïve major depressive disorder.

Objective: Abnormal levels of blood cytokines have been demonstrated to be associated with both excess weight and major depressive disorder (MDD). However, few studies have addressed the direct effect of body mass index (BMI) on basal serum cytokines in individuals with first-episode drug-naïve MDD. Methods: A total of 49 patients with first-episode drug-naïve MDD were categorized into normal weight (18.5 ≤ BMI < 25 kg/m2) and overweight (25 ≤ BMI < 30 kg/m2) groups according to WHO-criteria. The severity of depressive symptoms was assessed using the 24-items Hamilton Depression Scale (HAMD-24). A total of 37 cytokines were measured using Multiplex Luminex Assays. The scores of HAMD-24 and the levels of serum cytokines between normal weight group and overweight group were compared. Multiple linear regression analysis was performed to evaluate the association between abnormal serum cytokines levels and group after adjusting for HAMD-24 scores. The correlation between BMI and the scores of HAMD-24 and the levels of serum cytokines was evaluated using Pearson correlation analysis. Results: The scores of HAMD-24 in overweight group were significantly higher than normal weight group (t = -2.930, P = 0.005). Moreover, the levels of IL-1α, IL-1RA, IL-3, CXCL10, TNF-α, and ICAM-1 in overweight patients with MDD were significantly higher than those in normal-weight patients with MDD (all P < 0.05). Furthermore, after adjustment for HAMD-24 scores, there was a significant correlation between abnormal serum cytokines levels (IL-1α, IL-1RA, IL-3, CXCL10, TNF-α, and ICAM-1) and group (all P < 0.05). Additionally, BMI was positively correlated to the serum levels of IL-1α (r = 0.428, P = 0.002), IL-3 (r = 0.529, P < 0.001), IL-6 (r = 0.285, P = 0.050), IL-10 (r = 0.423, P = 0.003), IL-12 (r = 0.367, P = 0.010), IL-15 (r = 0.300, P = 0.036), CXCL10 (r = 0.316, P = 0.030), TNF-α (r = 0.338, P = 0.021), and ICAM-1 (r = 0.440, P = 0.002) in MDD patients. Conclusions: These results provide direct evidence, probably for the first time, that overweight may be associated with several serum cytokines in patients with first-episode drug-naïve MDD. The underlying mechanisms are unclear and require further investigation.