Abstract
In order to promote the development of water conservancy and improve the quality of water conservancy project, this paper expounds the causes of leakage in water conservancy project ...construction through theoretical analysis, and expounds two basic construction methods of seepage prevention and plugging in water conservancy project, and puts forward guarantee measures for seepage prevention and plugging construction in water conservancy project, for reference of relevant personnel.
Thriving at work is a relatively new concept in the field of organizational behavior, and many scholars have emphasized the importance of its outcomes in the last decade or so, but we still know ...little about the possible dark side of thriving at work. In this study, based on the conservation of resources theory, we studied the effect of thriving at work on work-family conflict, the mediating effects of workaholism, and the moderating effects of work-family separation preference and trust climate. By analyzing 372 samples, we found that thriving at work was significantly and positively related to work-family conflict; workaholism partially mediated the relationship between thriving at work and work-family conflict; work-family separation preference negatively moderated the relationship between thriving at work and workaholism. The moderating role of the trust climate was not verified. This paper explores the internal mechanisms by which thriving at work negatively affects the family sphere and helps individuals avoid falling into the dark side of thriving at work.
Abstract Purpose A possible carcinogenic role of human papillomavirus (HPV) has been investigated in esophageal squamous cell carcinoma (ESCC) for nearly 30 years with mixed results. We performed a ...meta-analysis to assess the prevalence of “high-risk” HPV, HPV-16/18, in this disease. We also evaluated the association between infection with HPV-16/18 and ESCC risk by meta-analysis of case–control studies. Methods Eligible studies published up to September 30, 2012 were retrieved via both computer searches of MEDLINE and EMBASE and manual review of references. A random-effects model was used to calculate summary prevalence and odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Results A total of 5755 cases of ESCC from 68 studies were included in this meta-analysis. Overall, 11.67% (95% CI, 7.74%–16.21%) of ESCC cases harbored HPV-16 and 1.82% (95% CI, 0.90%–2.95%) harbored HPV-18. In addition, meta-analysis of 10 case–control studies showed a significant increase in ESCC risk with HPV-16 infection (summary ORs = 3.55; 95% CIs, 2.05%–6.14%). However, this increased risk in ESCC was not made for HPV-18 infection (summary ORs = 1.25; 95% CIs, 0.46%–3.43%). Conclusions This meta-analysis indicated that HPV-16 and -18 can be detected in ESCC. HPV-16, but not HPV-18, is significantly associated with the risk of ESCC. However, it is early to conclude that both types of HPV are involved in esophageal carcinogenesis.
Dysfunction of microRNAs (miRNAs) is a major cause of aberrant expression of inflammatory cytokines and contributes to macrophage polarization. Proinflammatory M1 macrophages promote T helper (Th) 1 ...responses and show tumoricidal activity, whereas M2 macrophages display regulatory functions in tissue repair and remodeling and promote Th2 immune responses. Previous studies have shown that miRNA let-7 is associated with cellular differentiation and that the expression of let-7b-5p is significantly augmented in M2 macrophages. However, the mechanism by which let-7b-5p regulates macrophage differentiation in prostate cancer (PCa) remains largely unknown.
Human macrophages were induced by blood monocytes from healthy male donors, and M1 macrophages were polarized by stimulating them overnight with 100 ng/ml of lipopolysaccharides and 100 ng/ml of IFN-γ. Conditioned medium from PC-3 cells was used to induce prostatic macrophages (M-CMs) in vitro, and we then transfected let-7b-5p mimics or inhibitors into M1 and M-CMs for 72 h. The expression of cluster of differentiation 206 (CD206) in each group was detected with the High-Throughput Connotation of Imaging System. We used quantitative real-time polymerase chain reaction (qRT-PCR) to examine the expression of the inflammatory cytokines IL-10, IL-12, IL-13, TNF-alpha, and let-7b in macrophages. SOCS1 protein levels were evaluated by ELISA, and the phosphorylation difference in STAT family member proteins was analyzed using CST signal-pathway chip. Phagocytosis by macrophages and the effect of macrophages on the proliferation of prostate cancer PC-3 cells were evaluated with phagocytosis assay or the Cell Counting Kit-8 (CCK-8) and colony formation assay. The relationship between SOCS1 and let-7b-5p was confirmed with a dual-luciferase reporter.
The expression of cluster of differentiation 206 (CD206, a M2-like macrophage surface molecule) was significantly increased in M1 macrophages treated with let-7b-5p mimics, while CD206 expression was decreased in M-CMs treated with let-7b-5p inhibitors. Overexpression or knockdown of let-7b-5p significantly affected the expression of inflammatory factors in macrophages-including interleukin 10 (IL-10), IL-12, IL-13, and tumor necrosis factor alpha. Let-7b-5p downregulated the expression of suppressor of cytokine signaling 1 (SOCS1) and increased the phosphorylation of signal transducer and activator of transcription 1 (STAT1), STAT3, and STAT5a proteins in M-CMs and M1 macrophages with let-7b-5p mimics relative to the other groups. In addition, with the elevated expression of let-7b-5p, the phagocytosis by macrophages showed a commensurate and significant decrease. As a result, M-CMs treated with let-7b-5p inhibitors reduced the proliferation of PC-3 PCa cells.
Collectively, these data indicated that let-7b-5p may regulate M2 polarization through the SOCS1/STAT pathway and that reversal of M2 differentiation by let-7b-5p inhibitors enhanced macrophage phagocytosis, ultimately inhibiting the proliferation of PCa cells.
The proposed trial is to examine the feasibility of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-guided cytoreduction plus apalutamide and ...androgen deprivation therapy (ADT) for newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) at oligometastatic state.
CHAMPION (NCT05717582) is an open-label, single-arm, phase II trial, planning to enroll newly diagnosed mHSPC cases with oligometastases (≤ 10 distant metastatic sites in conventional imaging). Patients will receive 6 cycles of apalutamide plus ADT. Patients with oligometastatic disease at PSMA PET/CT after 3 treatment cycles will receive cytoreductive radical prostatectomy. PSMA PET/CT-guided metastasis-directed external radiation therapy will be determined by the investigators. Apalutamide plus ADT will be continued for 2 weeks postoperatively. The primary endpoint is the proportion of patients with undetectable prostate-specific antigen (PSA), no disease progression, and no symptom deterioration after 6 cycles of apalutamide plus ADT. Secondary endpoints include the percentage of patients with PSA ≤ 0.2 ng/mL and oligometastases by the end of 3 treatment cycles, PSA response rate, and safety. Fleming's two-stage group sequential design will be adopted in the study, where the null hypothesis is that the rate of patients with an undetectable PSA is ≤ 40% after 6 cycles of treatment, while the alternate hypothesis is an undetectable PSA of > 60%; with one-sided α = 0.05, power = 0.80, and an assumed dropout rate of 10%, the required number of patients for an effective analysis is 47. Enrolment in the study commenced in May 2023.
The multi-modal therapy based on treatment response may improve the prognosis of newly diagnosed mHSPC patients with oligometastases.
The study is registered with Clinical Trials.Gov (NCT05717582). Registered on 8th February 2023.
The success of the PROfound, IPATential150, and TheraP trials promoted the transition from sequential treatment to therapeutic targets (TTs)‐guided precision treatment in metastatic ...castration‐resistant prostate cancer (mCRPC). The objective of this study was to evaluate the prevalence and prognostic value of TTs from these three trials. All included Chinese mCRPC patients underwent circulating tumor DNA (ctDNA) sequencing, PTEN status assessment, and dual‐tracer 68Ga‐prostate‐specific membrane antigen (PSMA) and 18F‐fluorodexyglucose (FDG) positron emission tomography/computed tomography (PET/CT). Previous treatment with cabazitaxel, Lu‐PSMA or olaparib was unallowed. Patients with known significant sarcomatoid or spindle cell or neuroendocrine small cell components were also excluded. TTs were defined as positive as follows: (a) high PSMA and no PSMA−/FDG+ disease on dual‐tracer PET/CT scans; (b) defects in homologous recombination repair (HRR) genes in ctDNA; and (c) loss of PTEN immunohistochemistry staining in tumor tissue. The prevalence and prognostic value on progression‐free survival (PFS) of TTs were evaluated. A total of 106 consecutive mCRPC patients were included. The prevalence of positive PET/CT, HRR defect, and PTEN loss was 30%, 29% and 16%, respectively. Sixty‐three patients had at least one TT. Metastatic volume (odds ratio = 5.0; P = 0.017) was the only independent factor of positive TT in multivariate analysis. Seventy‐four patients received abiraterone after TT screening. Patients with positive PET/CT (P = 0.011) and HRR defect (P = 0.002) had a significantly shorter PFS after receiving abiraterone than patients with negative TTs. However, PTEN status was unrelated to PFS, which may be due to a less number of patients with PTEN loss (P = 0.952). Overall, patients with any positive TTs had a significantly shorter PFS after abiraterone than patients with negative TTs (P = 0.009). Nearly 60% of Chinese patients with mCRPC who had a poor prognosis on abiraterone were candidates for precision treatments based on the specific criteria of TTs.
Results of the PROfound, IPATential150 and TheraP trials were evaluated to determine the frequency of mCRPC patients who had therapeutic targets. All included mCRPC patients underwent ctDNA sequencing, PTEN status assessment and dual‐tracer (68Ga‐PSMA and 18F‐FDG) PET/CT. Nearly 60% of patients had positive therapeutic targets. In addition, patients with positive therapeutic targets had a shorter progression‐free survival under abiraterone treatment.
The lack of a well-established animal model limits the clarification of the detailed mechanisms of the pathogenesis of systemic sclerosis with pulmonary hypertension (SSc-PH) and the development of ...effective treatments for it.
In this study, New Zealand rabbits were injected with monocrotaline (MCT), bleomycin (BLM), and MCT plus BLM, respectively. Three and six weeks after the first injection, the mean pulmonary artery pressure (mPAP) was measured. Skin and lung samples were isolated and the histological changes were analyzed by hematoxylin and eosin staining or Masson's trichrome staining.
All groups of rabbits showed an increased mean mPAP compared with the saline-injected rabbits. The high mPAP persisted until week six only in the MCT and MCT + BLM groups. Furthermore, persistent high Fulton's indices were found in the MCT and MCT + BLM groups, indicating that these treatments successfully induced right ventricular hypertrophy. The rabbits in the MCT + BLM group developed severe lung inflammation, as evidenced by a high level of neutrophil infiltration in the pulmonary interstitium. Importantly, pathological changes of the skin in the MCT + BLM group were observed, and further damage to the skin was caused by additional exposure to MCT plus BLM. Meanwhile, an excessive production of cytokines, including tumor necrosis factor alpha (TNF-α), and transforming growth factor beta 1 (TGF-β1), were detected in the MCT + BLM group.
These data indicate that SSc-PH induced by co-injection with MCT plus BLM shows persistent fibrosis and progressive PH, constituting a potential study model for SSc-PH.
PSMA-negative but FDG-positive (PSMA-/FDG+) lesion in dual-tracer (
Ga-PSMA and
F-FDG) positron emission tomography/computed tomography (PET/CT) is associated with an unfavorable response to ...Lutetium-177 (
Lu)-PSMA-617. This study sought to develop both radiomics and clinical models for the precise prediction of the presence of PSMA-/FDG+ lesions in patients with castration-resistant prostate cancer (CPRC).
A cohort of 298 patients who underwent dual-tracer PET/CT with a less than 5-day interval was included. The evaluation of the prognostic performance of the radiomics model drew upon the survival data derived from 40 patients with CRPC treated with
Lu-PSMA-617 in an external cohort. Two endpoints were evaluated: (a) prostate-specific antigen (PSA) response rate, defined as a reduction exceeding 50% from baseline and (b) overall survival (OS), measured from the initiation of
Lu-PSMA-617 to death from any cause.
PSMA-/FDG+ lesions were identified in 56 (18.8%) CRPC patients. Both radiomics (area under the curve AUC, 0.83) and clinical models (AUC, 0.78) demonstrated robust performance in PSMA-/FDG+ lesion prediction. Decision curve analysis revealed that the radiomics model yielded a net benefit over the 'screen all' strategy at a threshold probability of ⩾4%. At a 5% probability threshold, the radiomics model facilitated a 21% reduction in
F-FDG PET/CT scans while only missing 2% of PSMA-/FDG+ cases. Patients with a low estimated score exhibited significantly prolonged OS (hazard ratio = 0.49,
= 0.029) and a higher PSA response rate (75%
35%,
= 0.011) compared to those with a high estimated score.
This study successfully developed two models with accurate estimations of the risk associated with PSMA-/FDG+ lesions in CRPC patients. These models held potential utility in aiding the selection of candidates for
Lu-PSMA-617 treatment and guiding
Ga-PSMA PET/CT-directed radiotherapy.
Abstract
In order to better develop the cause of water conservancy project, improve the quality of water conservancy project construction, and bring more benefits to the public, this paper expounds ...the current situation of water conservancy project informatization construction in China through theoretical analysis, discusses the feasibility of big data in water conservancy project informatization construction, and points out the specific application of big data technology, so as to achieve the purpose of water conservancy project informatization construction.
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