Serine/threonine kinase 36 induced epithelial-mesenchymal transition promotes docetaxel resistance in prostate cancer.

To investigate the role and potential mechanism of serine/threonine kinase 36 (STK36) in docetaxel resistance-prostate cancer (PCa). The expression of STK36 in PCa and the correlation with clinicopathological characteristics of PCa patients were analyzed using the data from different databases and tissue microarrays. To investigate the role of STK36 on cell proliferation, invasion, and migration, STK36 was overexpressed and silenced in DU-145 and PC-3 cell lines. Cell counting kit-8 (CCK8) was used to test cell proliferation. Cell invasion and migration were detected by cell wound scratch assay and trans well, respectively. The expression profile of STK36, E-Cadherin, and Vimentin was analyzed by Western blot. Cell apoptosis was detected by the TUNEL assay. STK36 expression was upregulated in PCa tissue compared with adjacent benign PCa tissue; it was higher in patients with advanced stages compared with lower stages and was significantly correlated with decreased overall survival. Up-regulation of STK36 significantly promoted the proliferation, invasion, and migration of DU-145 and PC-3 cells and compensated for the suppression caused by docetaxel treatment in vitro. A striking apoptosis inhibition could be observed when dealing with docetaxel, although the apoptosis of DU-145 and PC-3 cells was not affected by the STK36 exclusive overexpression. Besides, E-Cadherin expression was restrained while the expression levels of vimentin were all enhanced. The knockdown of STK36 reversed the above process. STK36 up-regulation could accelerate the biological behavior and docetaxel resistance of PCa by epithelial-mesenchymal transition (EMT) activation. STK36 may be potentially used as a target in PCa resolvent with docetaxel.

Disease-Related Factors Associated with Acupuncture Response in Patients with Chronic Tension-Type Headache: A Secondary Analysis of A Randomized Controlled Trial.

OBJECTIVE: To explore the demographic and disease-related factors associated with acupuncture response in patients with chronic tension-type headache (CTTH). METHODS: Using data from a randomized clinical trial (218 cases) consisting of 4 weeks of baseline assessment, 8 weeks of treatment, and 24 weeks of follow-up, participants were regrouped into responders (at least a 50% reduction in monthly headache days at week 16 compared with baseline) and non-responders. Twenty-three demographic and disease-related factors associated with acupuncture response in 183 participants were analyzed by multivariable logistic regression. RESULTS: One hundred and nineteen (65.0%) participants were classified as responders. Four factors were significantly independently associated with acupuncture response, including treatment assignment, headache intensity at baseline, and 2 domains [general health (GH) and social functioning (SF)] from the 36-Item Short Form Health Survey quality of life questionnaire. Treatment assignment was associated with non-response: participants receiving true acupuncture were 3-time more likely to achieve a CTTH response than those receiving superficial acupuncture [odds ratio (OR) 0.322, 95% confidence interval (CI) 0.162 to 0.625, P=0.001]. Compared with patients with mild-intensity headache, patients with moderate-intensity headache were twice as likely to respond to acupuncture (OR 2.001, 95% CI 1.020 to 4.011, P=0.046). The likelihood of non-response increased by 4.5% with each unit increase in the GH grade (OR 0.955, 95% CI 0.917 to 0.993, P=0.024) while decreased by 3.8% with each unit increase in the SF grade (OR 1.038, 95% CI 1.009 to 1.069, P=0.011). CONCLUSIONS: Greater headache intensity, lower GH score, and higher SF score were associated with better acupuncture responses in CTTH patients. These 3 factors require independent validation as predictors of acupuncture effectiveness in CTTH.

Efficacy of Acupuncture for Chronic Spontaneous Urticaria : A Randomized Controlled Trial.

BACKGROUND: The effectiveness of acupuncture for patients with chronic spontaneous urticaria (CSU), reported in a few small-scale studies, is not convincing. OBJECTIVE: To investigate whether acupuncture leads to better effects on CSU than sham acupuncture or waitlist control. DESIGN: A multicenter, randomized, sham-controlled trial. (Chinese Clinical Trial Registry: ChiCTR1900022994). SETTING: Three teaching hospitals in China from 27 May 2019 to 30 July 2022. PARTICIPANTS: 330 participants diagnosed with CSU. INTERVENTION: Participants were randomly assigned in a 1:1:1 ratio to receive acupuncture, sham acupuncture, or waitlist control over an 8-week study period (4 weeks for treatment and another 4 weeks for follow-up). MEASUREMENTS: The primary outcome was the mean change from baseline in the Weekly Urticaria Activity Score (UAS7) at week 4. Secondary outcomes included itch severity scores, self-rated improvement, and Dermatology Life Quality Index scores. RESULTS: The mean change in UAS7 (range, 0 to 42) for acupuncture from baseline (mean score, 23.5 [95% CI, 21.8 to 25.2]) to week 4 (mean score, 15.3 [CI, 13.6 to 16.9]) was -8.2 (CI, -9.9 to -6.6). The mean changes in UAS7 for sham acupuncture and waitlist control from baseline (mean scores, 21.9 [CI, 20.2 to 23.6] and 22.1 [CI, 20.4 to 23.8], respectively) to week 4 (mean scores, 17.8 [CI, 16.1 to 19.5] and 20.0 [CI, 18.3 to 21.6], respectively) were -4.1 (CI, -5.8 to -2.4) and -2.2 (CI, -3.8 to -0.5), respectively. The mean differences between acupuncture and sham acupuncture and waitlist control were -4.1 (CI, -6.5 to -1.8) and -6.1 (CI, -8.4 to -3.7), respectively, which did not meet the threshold for minimal clinically important difference. Fifteen participants (13.6%) in the acupuncture group and none in the other groups reported adverse events. Adverse events were mild or transient. LIMITATION: Lack of complete blinding, self-reported outcomes, limited generalizability because antihistamine use was disallowed, and short follow-up period. CONCLUSION: Compared with sham acupuncture and waitlist control, acupuncture produced a greater improvement in UAS7, although the difference from control was not clinically significant. Increased adverse events were mild or transient. PRIMARY FUNDING SOURCE: The National Key R&D Program of China and the Science and Technology Department of Sichuan Province.

Applying OHSA to Detect Road Accident Blackspots.

With increasing numbers of crashes and injuries, understanding traffic accident spatial patterns and identifying blackspots is critical to improve overall road safety. This study aims at detecting blackspots using optimized hot spot analysis (OHSA). Traffic accidents were classified by their participants and severity to explore the relationship between blackspots and different types of accidents. Based on the outputs of incremental spatial autocorrelation, OHSA was then implemented on different types of accidents. Finally, the performance of OHSA in evaluating the road safety level of the proposed RBT index are examined using a binary correlation analysis (i.e., R2 = 0.89). The results show that: (1) The optimal scale distance varies from 0.6 km to 2.8 km and is influenced by the distance of the travel mode. (2) Central cities, with 54.6% of the total accidents, experiences more rigorous challenges regarding traffic safety than satellite cities. (3) There are many types of black spots in vulnerable communities, but in some specific areas, there are only black spots of non-motor vehicle accidents. Considering the practical significance of the above results, policy makers and traffic engineers are expected to give higher attention to central cities and vulnerable communities or prioritize the implementation of relevant optimization measures.

Grim-19 plays a key role in mitochondrial steroidogenic acute regulatory protein stability and ligand-binding properties in Leydig cells.

Grim-19 (gene associated with retinoid-IFN-induced mortality 19), the essential component of complex I of mitochondrial respiratory chain, functions as a noncanonical tumor suppressor by controlling apoptosis and energy metabolism. However, additional biological actions of Grim-19 have been recently suggested in male reproduction. We investigated here the expression and functional role of Grim-19 in murine testis. Testicular Grim-19 expression was detected from mouse puberty and increased progressively thereafter, and GRIM-19 protein was observed to be expressed exclusively in interstitial Leydig cells (LCs), with a prominent mitochondrial localization. In vivo lentiviral vector-mediated knockdown of Grim-19 resulted in a significant decrease in testosterone production and triggered aberrant oxidative stress in testis, thus impairing male fertility by inducing germ cell apoptosis and oligozoospermia. The control of testicular steroidogenesis by GRIM-19 was validated using the in vivo knockdown model with isolated primary LCs and in vitro experiments with MA-10 mouse Leydig tumor cells. Mechanistically, we suggest that the negative regulation exerted by GRIM-19 deficiency-induced oxidative stress on steroidogenesis may be the result of two phenomena: a direct effect through inhibition of phosphorylation of steroidogenic acute regulatory protein (StAR) and subsequent impediment to StAR localization in mitochondria and an indirect pathway that is to facilitate the inhibiting role exerted by the extracellular matrix on the steroidogenic capacity of LCs via promotion of integrin activation. Altogether, our observations suggest that Grim-19 plays a potent role in testicular steroidogenesis and that its alterations may contribute to testosterone deficiency-related disorders linked to metabolic stress and male infertility.

Acupuncture and Related Therapies for Chronic Urticaria: A Critical Overview of Systematic Reviews.

Background: Chronic urticaria (CU) can severely impair the quality of life. Acupuncture and related therapies have been widely used in the treatment of CU in China. This study aimed to summarize and critically evaluate the methodological and reporting quality of relevant systematic reviews (SRs) and present objective and comprehensive evidence on the effectiveness and safety of acupuncture and related therapies for CU. Methods: Eight electronic databases were searched from inception to October 2021 for SRs examining acupuncture and related therapies for CU, and gray literature was manually searched. Two authors independently identified SRs and extracted data. The methodological and reporting quality of these SRs were assessed by the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) tool and preferred reporting items for SRs and meta-analyses (PRISMA, 2020), respectively. In addition, the risk of bias in systematic reviews (ROBIS) was used to evaluate the risk of bias. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework was applied to evaluate the quality of evidence for outcome measures. Results: In total, 23 SRs, including a total of 11 outcome indicators, were published before October 2021. The AMSTAR-2 results showed that the methodological quality of all SRs was critically low; items 2, 3, 7, 9, 10, and 16 were found to have particularly low quality. For PRISMA, the reporting quality of the included SRs was unsatisfactory, and major reporting flaws were observed in the search strategy, synthesis method, certainly assessment, reporting biases, registrations, and financial support of the included SRs. For ROBIS, 22 SRs (95.65%) had a high risk of bias. Among the 55 outcomes assessed using the GRADE framework, there were 3 (5.45%) outcomes with moderate-quality evidence, 6 (10.91%) outcomes with low-quality evidence, and 46 (83.64%) outcomes with very low-quality evidence. We found the moderate quality of evidence indicating that the total effective rate and curing rate of the acupuncture group were higher than those of the western medicine group, and the recurrence rate was lower than that of the western medicine group. Conclusions: Acupuncture and related therapies for the treatment of CU are supported by low-quality evidence-based medicine. However, considering the poor quality of these SRs, we suggest that studies with more rigorous designs, larger sample sizes, and higher methodological and reporting quality are necessary to provide stronger evidence. Registration. The protocol for this study has been registered (PROSPERO registration number: CRD42021259131).

Cupping therapy for patients with chronic urticaria: A systematic review and meta-analysis.

BACKGROUND: Chronic urticaria (CU) is a common skin disease, which has a negative effect on quality of life. Current treatments do not fully control the symptoms of urticaria for many CU patients, thus effective and safe treatments for CU are still needed. OBJECTIVE: This review aims to evaluate the effectiveness and safety of cupping therapy in patients with CU. SEARCH STRATEGY: The search strategy looked for the presence of related keywords, such as "chronic urticaria" and "cupping therapy," in the title and abstract of research articles indexed in major databases. Randomized controlled trials (RCTs) were selected after querying nine electronic databases from their inception to May 2019 with the above search terms. INCLUSION CRITERIA: RCTs were included if they recruited patients with CU who were intervened with dry or wet cupping. Publications could be written in Chinese or English. DATA EXTRACTION AND ANALYSIS: Data were extracted, and the studies were assessed for the quality of their methodological design and risk of bias. Meta-analyses of the RCT data were conducted to assess the total effective rate of the treatment as the primary outcome. Skin disease quality of life index score, recurrence rate, and adverse events were assessed as secondary outcomes. Subgroup analyses were conducted based on different interventions. RESULTS: Thirteen comparisons from 12 RCTs involving 842 participants were included. There were no significant differences between wet cupping and medications in total effective rate (n = 372; risk ratio [RR] = 1.10, 95% confidence interval [CI] 0.97 to 1.25; P = 0.14) or recurrence rate (n = 240; RR = 0.56, 95% CI 0.23 to 1.36; P = 0.20). Cupping therapy, in combination with antihistamine treatment was more efficacious than antihistamines alone, with a greater total effective rate (n = 342; RR = 1.18, 95% CI 1.01 to 1.39; P = 0.03) and lower recurrence rate (n = 342; RR = 0.52, 95% CI 0.32 to 0.84; P = 0.007). Cupping therapy combined with acupuncture was more effective than acupuncture alone (n = 156; RR = 1.25, 95% CI 1.07 to 1.46; P = 0.006). No serious adverse events were reported. CONCLUSION: Wet cupping may be as effective as treatment with antihistamines. When cupping therapy is used as an adjuvant therapy to antihistamines or acupuncture, it may enhance the efficacy. Results drawn from these studies should be interpreted with caution and applied with care to clinical practice, because of the poor quality among the studies that were reviewed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42019137451.

The GSTT1 null genotype contributes to increased risk of prostate cancer in Asians: a meta-analysis.

BACKGROUND: Many studies have investigated the association between glutathione S-transferase T 1 (GSTT1) null genotype and risk of prostate cancer, but the impact of GSTT1 null genotype in Asians is still unclear owing to inconsistencies across results. Thie present meta-analysis aimed to quantify the strength of the association between GSTT1 null genotype and risk of prostate cancer. METHODS: We searched the PubMed, Embase and Wangfang databases for studies of associations between the GSTT1 null genotype and risk of prostate cancer in Asians and estimated summary odds ratio (OR) with their 95% confidence interval (95% CI). RESULTS: A total of 11 case-control studies with 3,118 subjects were included in this meta-analysis, which showed the GSTT1 null genotype to be significantly associated with increased risk of prostate cancer in Asians (random-effects OR = 1.49, 95% CI 1.15-1.92, P = 0.002), also after adjustment for heterogeneity (fixed-effects OR = 1.45, 95% CI 1.23-1.70, P< 0.001). No evidence of publication bias was observed. CONCLUSIONS: This meta-analysis of available data suggested the GSTT1 null genotype does contribute to increased risk of prostate cancer in Asians.