Search

Simple Summary: Bladder cancer occurs mainly in older people and is expensive to manage. Swedish Herbal Rhodiola-5 (SHR-5), a standardized Rhodiola Rosea extract from the Swedish Herbal Institute (the SHI, Gothenburg, Sweden), has been in clinical studies for managing mild to moderate depression and physical and mental fatigue. Previous studies have shown that SHR-5 extended the life span of the fruit fly through a mechanism that was not associated with dietary restriction. In this study, we examined whether drinking SHR-5 can delay tumor development in a superficial bladder cancer mouse model. Drinking SHR-5 daily markedly improved the survival rate of the bladder tumor-bearing mice, by an absolute 61.7%, and reduced urinary tract obstruction and tumor burden. SHR-5 drinking reshaped the tumor metabolism via the inhibition of the mTOR leading to a decreased tumor cell proliferation. Background: SHR-5 has been used as an "adaptogen" for enhancing physical and mental performance and for fighting stress in the healthy population. The purpose of this study is to determine the chemopreventive efficacy of SHR-5 for superficial bladder cancer and to investigate the underlying mechanisms of action. Methods: UPII-mutant Ha-ras bladder-cancer-transgenic mice, that developed low-grade and noninvasive papillary transitional urothelial cell carcinoma, were fed with 1.25 and 6.25 mg/mL SHR-5 in drinking water for 6 months. The survival of the mice, obstructive uropathy, tumor burden and morphology, and proliferation were evaluated by pathological, molecular, metabolic, and statistical analyses. Results: Approximately 95% or more of the male UPII-mutant Ha-ras mice that drank SHR-5 daily survived over 6 months of age, while only 33.3% of those mice that drank normal water survived over 6 months of age (p < 0.0001); SHR-5 drinking exposure also reduced tumor-bearing bladder weight and urinary tract obstruction and inhibited mTOR signaling in neoplastic tissues. Global metabolic analysis revealed that SHR-5 resulted in increased phenolic metabolites and decreased CoA, a critical metabolic cofactor for lipid metabolism. Conclusions: Our findings highlight the potential of SHR-5 as an anti-aging agent for bladder cancer prevention through reshaping tumor metabolism via the inhibition of the mTOR signaling. Global metabolomics profiling provides a unique and efficient tool for studying the mechanisms of complex herb extracts' action. [ABSTRACT FROM AUTHOR]

Background: Compound epidermal growth factor receptor (EGFR) mutations are less responsive to tyrosine kinase inhibitors (TKIs) than single EGFR mutations in non-small cell lung cancer (NSCLC). However, the detailed clinical characteristics and prognosis of various compound EGFR mutations remain to be elucidated. Methods: We retrospectively studied the next-generation sequencing (NGS) data of treatment-naïve tumors from 1025 NSCLC patients with compound EGFR mutations, which were sub-categorized into different combinations of common mutations (19-Del and EGFR exon 21 p.L858R), rare mutations, and variants of uncertain significance (VUSs). Prognosis and drug resistance to first-line TKIs were analyzed in 174 and 95 patients, respectively. Results: Compound EGFR mutations were enriched with EGFR exon 21 p.L858R and rare mutations, but not 19-Del (P < 0.001). The common + rare and rare + rare subtypes had fewer concurrent mutations in the PI3K pathway (P = 0.032), while the rare + rare and common + VUSs subtypes showed increased association with smoking- and temozolomide-related mutational signatures, respectively (P < 0.001). The rare mutation-dominant subtypes (rare + VUSs and rare + rare) had the worst clinical outcomes to first-line TKIs (P < 0.001), which was further confirmed using an external cohort (P = 0.0066). VUSs in the rare + VUSs subtype selectively reside in the EGFR kinase domain (P < 0.001), implying these tumors might select additional mutations to disrupt the regulation/function of the kinase domain. Conclusions: Different subtypes of compound EGFR mutations displayed distinct clinical features and genetic architectures, and rare mutation-dominant compound EGFR mutations were associated with enriched kinase domain-resided VUSs and poor clinical outcomes. Our findings help better understand the oncogenesis of compound EGFR mutations and forecast prognostic outcomes of personalized treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: The use of diverse omics platforms and small sample sizes in current studies of cancer chemoresistance limits consensus regarding the molecular mechanisms underlying chemoresistance and the applicability of those study findings. We built transcriptome data for chemotherapy-resistant breast cancer samples for two cohorts and conducted pathway and subpathway analyses that revealed the activation of several molecular pathways associated with chemoresistance in Cushing's syndrome, human papillomavirus infection, proteoglycans in cancer, fluid shear stress, and focal adhesion that have not been reported in the resistance of breast cancer to chemotherapy. However, analysis of a subset of triple-negative breast cancer samples revealed activation of the identical chemoresistance pathways. Chemoresistance has been a major challenge in the treatment of patients with breast cancer. The diverse omics platforms and small sample sizes reported in the current studies of chemoresistance in breast cancer limit the consensus regarding the underlying molecular mechanisms of chemoresistance and the applicability of these study findings. Therefore, we built two transcriptome datasets for patients with chemotherapy-resistant breast cancers—one comprising paired transcriptome samples from 40 patients before and after chemotherapy and the second including unpaired samples from 690 patients before and 45 patients after chemotherapy. Subsequent conventional pathway analysis and new subpathway analysis using these cohorts uncovered 56 overlapping upregulated genes (false discovery rate [FDR], 0.018) and 36 downregulated genes (FDR, 0.016). Pathway analysis revealed the activation of several pathways in the chemotherapy-resistant tumors, including those of drug metabolism, MAPK, ErbB, calcium, cGMP-PKG, sphingolipid, and PI3K-Akt, as well as those activated by Cushing's syndrome, human papillomavirus (HPV) infection, and proteoglycans in cancers, and subpathway analysis identified the activation of several more, including fluid shear stress, Wnt, FoxO, ECM-receptor interaction, RAS signaling, Rap1, mTOR focal adhesion, and cellular senescence (FDR < 0.20). Among these pathways, those associated with Cushing's syndrome, HPV infection, proteoglycans in cancer, fluid shear stress, and focal adhesion have not yet been reported in breast cancer chemoresistance. Pathway and subpathway analysis of a subset of triple-negative breast cancers from the two cohorts revealed activation of the identical chemoresistance pathways. [ABSTRACT FROM AUTHOR]

Objective. To explore the efficacy of risperidone orally disintegrating tablets combined with oxazepam in the treatment of schizophrenia. Methods. From May 2019 to May 2021, 60 patients with schizophrenia treated in our hospital were recruited and assigned into an observation group (risperidone orally disintegrating tablets combined with oxazepam treatment) and a control group (alprazolam combined with chlorpromazine treatment) according to the random number table method. The positive and negative symptom score (PANSS), quality of life score (QOL-75), ability of daily living score (ADL), clinical efficacy, incidence of adverse reactions, and disease recurrence were compared between the two groups before and after treatment. Results. The PANSS scores were similar in the two groups before treatment (P > 0.05). The two groups presented a declining trend in PANSS score after treatment, whereas a remarkable lower score in the observation group was observed (P < 0.05). The QOL scores of the two groups of patients before treatment was not significantly different (P > 0.05). Both groups witnessed improvements one month and three months after treatment, with considerable improvements being obtained in the observation group (all P < 0.05). The two groups did not differ in ADL scores before treatment (P > 0.05). At 1 month and 3 months after treatment, the ADL scores of the two groups were improved, with a higher score in the observation group (P < 0.05). The observation group had a markedly higher total effective rate as compared to the control group (X2 = 5.455, P = 0.020). Adverse reaction occurred in both groups, with milder results in the observation group. The recurrence rate of the two groups was not statistically different one month after treatment (P > 0.05), while two and three months after treatment, they were lower than those of the control group (all P < 0.05). Conclusion. Risperidone orally disintegrating tablets combined with oxazepam shows potential in the treatment of schizophrenia by relieving patients' mental symptoms, improving quality of life and activities of daily living, and minimizing the incidence of adverse reactions. [ABSTRACT FROM AUTHOR]

To analyze the effect of sandplay (SP) therapy on the mental health level of college students. 500 college students were openly recruited, using the University Student Mental Health Questionnaire (UPI) to screen out 76 students in the UPI category. 34 college students were randomly selected and divided into two groups, 17 in the control group and 17 in the SP therapy group (experimental group); the control group received no treatment, and the experimental group was treated with SP therapy, to analyze the differences between groups before and after the intervention of SCL-90 and self-made group self-reflection questionnaire. (1) With a detection rate of 15.2 percent, 76 of the 500 college students solicited openly were identified as UPI students; (2) except for the terror factor, there were significant differences in other aspects and overall scores for the experimental group following SP therapy intervention, and the scores reduced. There were no significant differences in the total scores and scores of all factors in the control group (P > 0.05). The overall score, somatization, interpersonal connection, depression, paranoia, and psychosis were all significantly different between the experimental and control groups in the independent sample t -test (P < 0.05). [ABSTRACT FROM AUTHOR]

Good patient–provider communication and high level of trust can decrease patients' risk perception and promote their acceptability of medical risks.The extent to which communication can be effective may be distinguished by different levels of trust. The present study examined the effect of patient–provider communication and treatment outcome on patients' risk awareness, and explored the moderating effect of trust. This research adopted a paper‐based scenario experiment with a 2 (communication: good vs. poor) × 2 (treatment outcome: good vs. poor) between‐subjects design. Three hundred sixteen college students were enrolled. They were randomly assigned to four groups and instructed to read more information about the two independent variables. Finally, all participants finished the manipulation check (eight items), affect‐ and cognition‐based trust scales (10 items), and risk awareness scales (eight items) by questionnaire. The results showed the positive interaction effects between communication and treatment outcome on patients' acceptance of uncertainties. Affect‐ and cognition‐based trust had similar moderating mechanisms on the interaction effect of communication and treatment outcome on uncertainty acceptability, and different moderating mechanisms on patient risk perception. In clinical work, we should develop the strategy to improve patien–provider communication and trust to improve patients' acceptability of uncertainty. [ABSTRACT FROM AUTHOR]

Objective: To investigate the safety and efficacy of intensive statin in the acute phase of ischemic stroke after intravenous thrombolysis therapy. Methods: A total of 310 stroke patients treated with rt-PA were randomly scheduled into the intensive statin group (rosuvastatin 20 mg daily × 14 days) and the control group (rosuvastatin 5 mg daily × 14 days). The primary clinical endpoint was excellent functional outcome (mRS ≤ 1) at 3 months, and the primary safety endpoint was symptomatic intracranial hemorrhage (sICH) in 90 days. Results: The intensive statin users did not achieve a favorable outcome in excellent functional outcome (mRS ≤ 1) at 3 months compared with controls (70.3% vs. 66.5%, p = 0.464). Intensive statin also not significantly improved the overall distribution of scores on the modified Rankin scale, as compared with controls (p = 0.82 by the Cochran–Mantel–Haenszel test). The incidence of primary safety endpoint events (sICH) in 90 days did not significantly differ between the intensive statin group and control group (0.6% vs. 1.3%, p > 0.999). Conclusion: The INSPIRE study indicated that intensive statin therapy may not improve clinical outcomes compared with the low dose of statin therapy in AIS patients undergoing intravenous thrombolysis, and the two groups had similar safety profile. Clinical trial registration: URL: http://www.chictr.org. Unique identifier: ChiCTR-IPR-16008642 [ABSTRACT FROM AUTHOR]

• The recurrence of leukemia is largely due to the presence of residual cells. • To predict their prognosis, Minimal Residual Disease is needed to monitor patients' response to therapy. • This is the first meta-analysis which systematically investigates the prognostic value of Minimal Residual Disease for patients with Mantle Cell Lymphoma. • To complement the understanding of Mantle Cell Lymphoma and demonstrate its strong association with clinical outcomes in Mantle Cell Lymphoma patients, we conducted this meta-analysis. Some studies have elucidated that Minimal residual disease (MRD) in patient with Mantle Cell Lymphoma (MCL) was a significant prognostic factor, with potential value in assessing overall survival (OS) and progression-free survival (PFS). However, most studies were widely varied in included population, sample sources and MRD detection time points. Some studies even have conflicting results. In view of this, a meta-analysis was performed to evaluate association of MRD levels with clinical outcomes in patients with MCL. We identified 7 included articles, which were published in recent 20 years. Then, we extracted or calculated hazard ratios (HRs) and their 95 % confidence intervals (CIs). Our results reveal that patients with MRD negativity have improved OS (HR = 0.63; 95 % CI: 0.50−0.79) and PFS (HR = 0.40, 95 % CI: 0.21−0.76), comparing with patients with MRD positivity. There are also consistent results in subgroups based on sample sources and MRD detection time points. Our study also demonstrates that MRD level is a strong prognostic factor of clinical outcomes. Thus, MRD is expected to be an effective clinical indicator for assessing prognosis and guide treatment decisions in MCL patients. [ABSTRACT FROM AUTHOR]