CACNA1C, as a type of voltage-dependent calcium ion transmembrane channel, played regulatory roles in the development and progress of multiple tumors. This study was aimed to analyze the roles of ...CACNA1C in ovarian cancer (OC) of overall survival (OS) and to explore its relationships with immunity.
Single gene mRNA sequencing data and corresponding clinical information were obtained from The Cancer Genome Atlas Database (TCGA) and the International Cancer Genome Consortium (ICGC) datasets. Gene set enrichment analysis (GSEA) was used to identify CACNA1C-related signal pathways. Univariate and multivariate Cox regression analyses were applied to evaluate independent prognostic factors. Besides, associations between CACNA1C and immunity were also explored.
CACNA1C had a lower expression in OC tumor tissues than in normal tissues (P < 0.001), with significant OS (P = 0.013) and a low diagnostic efficiency. We further validated the expression levels of CACNA1C in OC by means of the ICGC dataset (P = 0.01), qRT-PCR results (P < 0.001) and the HPA database. Univariate and multivariate Cox hazard regression analyses indicated that CACNA1C could be an independent risk factor of OS for OC patients (both P < 0.001). Five significant CACNA1C-related signaling pathways were identified by means of GSEA. As for genetic alteration analysis, altered CACNA1C groups were significantly associated with OS (P = 0.0169), progression-free survival (P = 0.0404), disease-free survival (P = 0.0417) and disease-specific survival (P = 9.280e-3), compared with unaltered groups in OC. Besides, CACNA1C was dramatically associated with microsatellite instability (MSI) and immunity.
Our results shed light on that CACNA1C could be a prognostic predictor of OS in OC and it was closely related to immunity.
Background:
Due to the absence of direct comparisons of different therapeutic drugs in preventing opioid-induced cough (OIC) during the induction of general anesthesia, clinicians often faced ...difficulties in choosing the optimal drug for these patients. Hence, this network meta-analysis was conducted to solve this problem.
Methods:
Online databases, including Pubmed, Embase, Web of Science, Cochrane, and Google Scholar, were searched comprehensively to identify eligible randomized controlled trials (RCTs), up to March 15th, 2021. Within a Bayesian framework, network meta-analysis was performed by the “gemtc” version 0.8.2 package of R-3.4.0 software, and a pooled risk ratio (RR) associated with 95% credible interval (CrI) was calculated.
Results:
A total of 20 RCTs were finally enrolled, and the overall heterogeneity for this study was low to moderate. Traditional pair-wise meta-analysis results indicated that all of the five drugs, namely, lidocaine, ketamine, dezocine, butorphanol, and dexmedetomidine could prevent OIC for four clinical outcomes, compared with the placebo (all
p-values
< 0.05). Moreover, dezocine had the best effect, compared with that of the other drugs (all
p-values
< 0.05). Network meta-analysis results suggested that the top three rank probabilities for four clinical outcomes from best to worst were dezocine, butorphanol, and ketamine based on individual/cumulative rank plots and surface under the cumulative ranking curve (SUCRA) probabilities. The node-splitting method indicated the consistency of the direct and indirect evidence.
Conclusions:
Our results indicated that all of these five drugs could prevent OIC compared with the placebo. Moreover, the top three rank probabilities for four clinical outcomes from best to worst were dezocine, butorphanol, and ketamine. Our results were anticipated to provide references for guiding clinical research, and further high-quality RCTs were required to verify our findings.
Systematic Review Registration:
https://www.crd.york.ac.uk/prospero/
, identifier CRD42021243358.
Background
We aimed to assess the clinical behavior of gynecologic large-cell neuroendocrine carcinoma (LCNEC)
via
a retrospective analysis of data from 469 patients.
Methods
Patients diagnosed with ...gynecologic LCNEC from 1988 to 2015 were identified using the Surveillance, Epidemiology, and End Results database. Univariate and multivariate Cox hazard regression analyses were performed to assess independent predictors of overall survival (OS) and cancer-specific survival (CSS). OS and CSS were also evaluated using the Kaplan–Meier method, and the effects of different treatment regimens on prognosis were compared according to disease stage.
Results
Cervical, ovarian, and endometrial LCNEC were observed in 169, 219, and 79 patients, respectively. The 5-year OS rates for patients with cervical, ovarian, and endometrial LCNEC were 35.98%, 17.84%, and 23.21%, respectively, and the median duration of overall survival was 26, 11, and 11 months in each group. The 5-year CSS rates for the three groups were 45.23%, 19.23%, and 31.39%, respectively, and the median duration of CSS was 41, 12, and 11 months in each group. Multivariate analysis revealed that American Joint Committee on Cancer stage, lymph node metastasis, and chemotherapy were independent prognostic factors for OS and CSS in patients with cervical LCNEC. Lymph node metastasis, surgery, and chemotherapy were independent prognostic factors for OS and CSS in the ovarian group and for OS in the endometrial group. Lymph node metastasis and surgery were also independent prognostic factors for CSS in the endometrial group.
Conclusion
Surgery alone may help to improve overall survival and CSS in patients with early-stage cervical LCNEC. In contrast, surgery+chemotherapy and surgery+radiotherapy may help to improve survival in those with early-stage ovarian and endometrial LCNEC, respectively. Regardless of subtype, comprehensive treatment involving surgery, CTX, and RT should be considered to improve prognosis in patients with advanced-stage gynecologic LCNEC.
Long-term continuous monoculture cropping of tobacco leads to high incidence of tobacco bacterial wilt (TBW) caused by Ralstonia solanacearum, which threatening world tobacco production and causing ...great economy loss. In this study, a safe and effective way to control TBW by microbial degradation of phenolic allelochemicals (PAs) was explored. Eleven kinds of PAs were identified from continuous tobacco cropping soil. These PAs exhibited various effects on the growth, chemotaxis and biofilm formation of R. solanacearum. Then we isolated eight strains of Bacillus, one strain of Brucella, one strain of Enterobacter and one strain of Stenotrophomonas capable of degrading these PAs. The results of degradation assay showed that these isolated strains could degrade PAs both in culture solutions and soil. Besides, the incidence of TBW caused by R. solanacearum and deteriorated by PAs were significantly decreased by treating with these degrading strains. Furthermore, six out of eleven isolated strains were combined to degrade all the identified PAs and ultimately sharply reduced the incidence of TBW by 61.44% in pot experiment. In addition, the combined degrading bacteria could promote the plant growth and defense response. This study will provide a promising strategy for TBW control in tobacco production.
Tumors are highly heterogeneous, and within their parenchyma, a small population of tumor-stem cells possessing differentiation potential, high oncogenicity, and self-renewal capabilities exists. ...These cells are pivotal in mediating tumor development, chemotherapy resistance, and recurrence. Ovarian cancer shares characteristics with tumor stem cells, making it imperative to investigate molecular markers associated with these cells.
Stem cell-related genes were collected, and molecular subtypes were established based on gene expression profiles from The Cancer Genome Atlas using the R package tool "ConsensusClusterPlus." Multi-gene prognostic markers were identified using LASSO regression analysis. Gene set enrichment analysis was employed to gain insights into the potential molecular mechanisms of these identified markers. The robustness of these prognostic markers was analyzed across different cohorts, and their clinical independence was determined through multivariate Cox analysis. A nomogram was constructed to assess the model's clinical applicability. Immunohistochemistry was performed to validate the expression of hub genes.
Utilizing 49 tumor stem cell-related genes associated with prognosis, 362 ovarian cancer samples were divided into two distinct clusters, revealing significant prognostic disparities. A seven-gene signature (GALP, CACNA1C, COL16A1, PENK, C4BPA, PSMA2, and CXCL9), identified through LASSO regression, exhibited stability and robustness across various platforms. Multivariate Cox regression analysis confirmed the signature's independence in predicting survival in patients with ovarian cancer. Furthermore, a nomogram combining the gene signature demonstrated strong predictive abilities. Immunohistochemistry results indicated significantly elevated GALP, CACNA1C, COL16A1, PENK, C4BPA, PSMA2, and CXCL9 expression in cancer tissues.
The seven-gene signature holds promise as a valuable tool for decision-making and prognosis prediction in patients with ovarian cancer.
Purpose
Intrauterine adhesion (IUAs) in women is a debatable topic and there is no clear consensus in its management and treatment strategies. Previous treatment measures have limitations which ...necessitates to consider effective measures for prevention of recurrence of IUAs. Hence, the aim of this study to explore the efficacy and safety of intrauterine infusion of autologous platelet gel (APG) and medical chitosan in preventing recurrence of IUAs in females after transcervical resection of adhesion (TCRA).
Methods
A prospective, randomized controlled trial was conducted among 80 patients presented with moderate to severe IUAs. Patients were randomized into two groups, APG group (
n
= 40) and medical chitosan group (
n
= 40). All patients were injected with either APG or medical chitosan after TCRA.
Results
The postoperative recurrence rate of adhesions in APG group was significantly lower than those in medical chitosan group (21% vs 49%). The median AFS score during the second-look hysteroscopy was significantly lower in APG group than in medical chitosan group (
P
= 0.008). The median AFS score reduction after TCRA surgery was significantly higher in APG group than in medical chitosan group (median, 95% CI 7.000, 6.0 to 8.3 vs. 6.000, 5.0 to 7.0,
P
= 0.004). Subgroup analysis of platelet concentration (1000 as cut-off value) into high- and low-dose subgroups reported no significant correlation existed between APG and baseline characteristics, recurrence rate and postoperative AFS reduction score except for previous intrauterine operation (
P
< 0.05).
Conclusion
Thus, after TCRA, intrauterine injections of APG provides better efficacy and safety compared with intrauterine injections of medical chitosan in preventing recurrence of intrauterine adhesions.
Ovarian tumors/cancers are threatening women's health worldwide, which demands high-performance detection methods and accurate strategies to effectively detect, diagnose and treat them. Here, we ...report a nanographene oxide particle-functionalized microfluidic fluorescence biosensor to simultaneously detect four biomarkers, CA125, HE4, CEA and APF, for ovarian tumor/cancer diagnosis. The developed biosensor exhibits good selectivity and a large biomarker detection range with a limit of detection of 0.01 U/mL for CA125 and ~1 pg/mL for HE4, CEA and APF. The current results indicate that (1) the proposed biosensor is a promising tool for the simultaneous detection of multiple biomarkers in ovarian tumors/cancer and (2) CA125 and HE4 are strong indicators, AFP may be helpful, and CEA is a weak biomarker for ovarian tumor/cancer diagnosis. The proposed biosensor would be a potential tool, and an analytical approach for the simultaneous detection of multiple biomarkers will provide a new strategy for the early screening, diagnosis and treatment of ovarian tumors/cancers, as well as other cancers.
•A Chinese family with Lynch syndrome was introduced.•Two novel germline mutations at MLH1 and PMS2 were found in this family.•3D structure maps of the two mutant proteins were made and were compared ...with the wild type 3D structure maps.
In recent years, since the need for anesthetic interventions in pregnant women, newborns, and older patients has been increasing, the anesthesia-induced cognitive impairment has received widespread ...attention and highlighted the urgent requirement for preventive and therapeutic measures with low risk of side effects. Environmental enrichment (EE), a novel and easy-to-implement rehabilitation treatment strategy, exerts its protective potential on the cognitive abilities of developing and aging brains after anesthetic exposure. This review summarizes the improvement of cognition by EE described in recent studies and explores the molecular mechanisms by which EE exerts neuroprotective effects. The literature indicates that the intervention mode, timing, and duration of EE are vital to its effect.
•EE exerts its protective potential in anesthesia-induced neurocognitive disorders.•EE exerts its protective potential through different molecular mechanisms.•The intervention mode, timing, and duration of EE are very important to its effect.
Stress diarrhea is a major challenge for weaned piglets and restricts pig production efficiency and incurs massive economic losses. A traditional Chinese medicine prescription (QJC) composed of
...Astragalus propinquus
Schischkin (HQ),
Zingiber officinale
Roscoe (SJ), and
Plantago asiatica
L. (CQC) has been developed by our laboratory and shows marked anti-stress diarrhea effect. However, the active compounds, potential targets, and mechanism of this effect remain unclear and warrant further investigation. In our study, we verified the bioactive compounds of QJC and relevant mechanisms underlying the anti-stress diarrhea effect through network pharmacology and
in vivo
experimental studies. After establishing a successful stress-induced diarrhea model, histomorphology of intestinal mucosa was studied, and Quantitative real-time PCR (RT-qPCR) probe was used for the phosphoinositide 3-kinase (PI3K)–Akt signaling pathway to verify the therapeutic effect of QJC on diarrhea. First, using the network pharmacology approach, we identified 35 active components and 130 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in QJC. From among these, we speculated that quercetin, luteolin, kaempferol, scutellarein, and stigmasterol were the main bioactive compounds and assumed that the anti-diarrhea effect of QJC was related to the PI3K–Akt signaling pathway. The RT-qPCR indicated that QJC and its bioactive components increased the expression levels of
PI3K
and
Akt
, inhibited the expression of
phosphatase and tensin homolog
(
PTEN
), and activated the PI3K–Akt signaling pathway to relieve stress-induced diarrhea. Furthermore, we found that QJC alleviated the pathological condition of small intestine tissue and improved the integrity of the intestinal barrier. Taken together, our study showed that the traditional Chinese medicine QJC, quercetin, luteolin, kaempferol, scutellarein, and stigmasterol alleviated the pathological condition of small intestine tissue and relieved stress-induced diarrhea by increasing the expression levels of
PI3K
and
Akt
and inhibiting the expression levels of
PTEN
.
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