Progression-directed therapy in patients with oligoprogressive castration-resistant prostate cancer.

PURPOSE: Oligoprogressive lesions are observed in a subset of patients who progress to castration-resistant prostate cancer (CRPC), while other lesions remain controlled by systemic therapy. This study evaluates the impact of progression-directed therapy (PDT) on these oligoprogressive lesions. MATERIALS AND METHODS: This retrospective study included 40 patients diagnosed with oligoprogressive CRPC. PDT was performed for treating all progressive sites using radiotherapy. Fifteen patients received PDT using radiotherapy for all progressive sites (PDT group) while 25 had additional first-line systemic treatments (non-PDT group). In PDT group, 7 patients underwent PDT and unchanged systemic therapy (PDT-A group) and 8 patients underwent PDT with additional new line of systemic therapy on CRPC (PDT-B group). The Kaplan-Meier method was used to assess treatment outcomes. RESULTS: The prostate specific antigen (PSA) nadir was significantly lower in PDT group compare to non-PDT group (p=0.007). A 50% PSA decline and complete PSA decline were observed in 13 patients (86.7%) and 10 patients (66.7%) of PDT group and in 18 patients (72.0%) and 11 patients (44.0%) of non-PDT group, respectively. The PSA-progression free survival of PDT-B group was significantly longer than non-PDT group. The median time to failure of first-line systemic therapy on CRPC was 30.2 months in patients in PDT group and 14.9 months in non-PDT group (p=0.014). PDT-B group showed a significantly longer time to progression than non-PDT group (p=0.025). Minimal PDT-related adverse events were observed. CONCLUSIONS: PDT can delay progression of disease and enhance treatment efficacy with acceptable tolerability in oligoprogressive CRPC.

Expired Platelet Concentrate Up-Cycling: Growth Factor-Rich Bioproduct Preparation for FBS Substitute.

Due to the short storage period, large quantities of platelet concentrate (PC) are expiring. The expired PC cannot be injected into a blood vessel, but the activity of bioactive molecules, especially growth factors, is still preserved. In this paper, we organized a process to obtain a growth factor-rich bioproduct for use as a supplement in human cell culture by optimizing freezing, thawing, and sterilization conditions. Each unit of PC displayed visual differences, diverse biochemical values, and growth factor concentrations. To minimize lot-to-lot variation, we pooled a minimum of 10 PC units. The concentrations of growth factors were maximized through five freeze-thaw cycles for 12 h at -80 °C for freezing and for 5 min at 36 °C for thawing. We used a cell strainer with 40 µm pores, followed by a 0.45 µm filter and a 0.22 µm filter sequentially to sterilize the bioproduct with minimizing loss. The obtained growth factors remained stable for 4-6 h at room temperature (23 °C), 24 h at 4 °C, and 12 months at -80 °C. Cellular responses to the growth factor-rich bioproduct were tested with primary human renal proximal tubule epithelial cells. The cells exhibited a significantly increased growth rate, compared to the fetal bovine serum (FBS)-treated control group. The cells maintained their characteristic cuboidal shape, and stem cells and renal progenitor cells also preserved their genetic characteristics during culture. Therefore, the growth factor-rich bioproduct isolated from expired PC through our process can be used as a medium supplement to replace FBS in human cell culture for clinical application.

Histology and morphometry of the skin of purple spaghetti-eel Moringua raitaborua (Anguilliformes, Moringuidae).

The purple spaghetti-eel Moringua raitaborua lives on the sandy or muddy bottoms of estuaries, which are subject to rapid and wide changes in salinity, pH, and osmoregulatory and hypoxic conditions due to the influx of organic materials from sources of freshwater. The species has adapted to hypoxic environments by developing a thicker epidermis with stratified polygonal cells, club cells, two types of mucous cells (goblet and, oval cells), stratified cuboidal cells and dermis with abundant blood capillaries. Among them, histological modification of thinner dorsal, lateral, and ventral body skin to include abundant capillaries and well-developed dermal vascularization may provide cutaneous respiration, permitting survival in brackish waters with low levels of oxygen and variable environmental parameters.

Prostate Cancer Progression Relies on the Mitotic Kinase Citron Kinase.

Prostate cancer remains the second leading cause of cancer death in men in Western cultures. A deeper understanding of the mechanisms by which prostate cancer cells divide to support tumor growth could help devise strategies to overcome treatment resistance and improve survival. Here, we identified that the mitotic AGC family protein kinase citron kinase (CIT) is a pivotal regulator of prostate cancer growth that mediates prostate cancer cell interphase progression. Increased CIT expression correlated with prostate cancer growth induction and aggressive prostate cancer progression, and CIT was overexpressed in prostate cancer compared with benign prostate tissue. CIT overexpression was controlled by an E2F2-Skp2-p27 signaling axis and conferred resistance to androgen-targeted treatment strategies. The effects of CIT relied entirely on its kinase activity. Conversely, CIT silencing inhibited the growth of cell lines and xenografts representing different stages of prostate cancer progression and treatment resistance but did not affect benign epithelial prostate cells or nonprostatic normal cells, indicating a potential therapeutic window for CIT inhibition. CIT kinase activity was identified as druggable and was potently inhibited by the multikinase inhibitor OTS-167, which decreased the proliferation of treatment-resistant prostate cancer cells and patient-derived organoids. Isolation of the in vivo CIT substrates identified proteins involved in diverse cellular functions ranging from proliferation to alternative splicing events that are enriched in treatment-resistant prostate cancer. These findings provide insights into the regulation of aggressive prostate cancer cell behavior by CIT and identify CIT as a functionally diverse and druggable driver of prostate cancer progression. SIGNIFICANCE: The poorly characterized protein kinase citron kinase is a therapeutic target in prostate cancer that drives tumor growth by regulating diverse substrates, which control several hallmarks of aggressive prostate cancer progression. See related commentary by Mishra et al., p. 4008.

Corrigendum: Correction of the Figure. Trends of stratified prostate cancer risk in a single Korean province from 2003 to 2021: A multicenter study conducted using regional training hospital data.

This corrects the article on p. 140 in vol. 64, PMID: 36882172.

Protaetia Brevitarsis-Derived Protein Hydrolysate Reduces Obesity-Related Colitis Induced by High-Fat Diet in Mice through Anti-Inflammatory Pathways.

Ulcerative colitis is an inflammatory bowel disease characterized by inflammation in the mucosal and submucosal layers of the colon. Obesity is closely related to the occurrence and progression of colitis. The most plausible mechanism linking obesity and colitis is an excessive adipogenesis-related inflammatory response, which causes mucosal dysfunction. Obesity and colitis are linked by several etiologic mechanisms, including excessive adipogenesis, lipotoxicity, pro-inflammatory adipokines/cytokines, macrophage polarization, oxidative stress, endoplasmic reticulum (ER) stress, and gut microbiota. These low-grade enteric inflammations cause mucosal layer damage, especially goblet cell dysfunction through mucin 2 (MUC2) misfolding, ultimately leading to colitis. Inhibiting the inflammatory response can be the most effective approach for treating obesity-related colitis. We focused on the anti-inflammatory effects of polyphenols in Protaectia brevitas larvae. The P. brevitas was prepared as a low molecular protein hydrolysate (PHPB) to increase the concentration of anti-inflammatory molecules. In the current study, we investigated the anti-inflammatory effect of PHPB in an obesity-induced colitis mouse model. Compared with the high-fat diet (HFD) group, the group treated with PHPB exhibited reduced body/organ/fat weight, appetite/food intake inhibition, hypolipidemic effect on ectopic fat, and anti-adipogenic mechanism through the AMPK signaling pathway. Furthermore, we observed attenuated expression of PPARγ and C/EBPα, inhibition of pro-inflammatory molecules, stimulation of anti-inflammatory molecules, probiotic-like effect against obesogenic gut microbiota, inhibition of macrophage polarization into M1, suppression of oxidative/ER stress, and reduction of Muc2 protein misfolding in colon. These diverse anti-inflammatory responses caused histological and functional recovery of goblet cells, eventually improving colitis. Therefore, our findings suggest that the protein hydrolysate of Protaetia brevitarsis can improve obesity-related colitis through its anti-inflammatory activities.

Diagnosis and Management of an Intramyometrial Ectopic Pregnancy Within a Septate Uterus.

BACKGROUND: An intramyometrial pregnancy is a rare form of ectopic pregnancy, making up an estimated 1% of all ectopic pregnancies. Previously described management options have included surgical excision in the emergency setting. CASE: A 32-year-old woman, gravida 4 para 0, at 6 0/7 weeks of gestation by last menstrual period, was noted to have a gestational sac implanted entirely within the uterine myometrium. Ultrasonography and magnetic resonance imaging confirmed the presence of an intramyometrial ectopic pregnancy within a septate uterus. The patient's abnormal pregnancy was successfully treated with multidose methotrexate. CONCLUSION: Intramyometrial pregnancy is a rare entity that should be considered when it is suggested by ultrasonography or if an intrauterine pregnancy is surgically inaccessible from the endometrial cavity. In a stable patient, multidose systemic methotrexate may be a feasible management strategy.

Influence of Vitamin D Deficiency on the Expression of Genes and Proteins in Patients With Medium Rotator Cuff Tears.

BACKGROUND: Whether vitamin D deficiency is related to rotator cuff muscle and tendon physiology is controversial. PURPOSE: To assess the relationship between vitamin D deficiency and various gene expression patterns in patients with rotator cuff tears. STUDY DESIGN: Controlled laboratory study. METHODS: During arthroscopic surgery, samples from the supraspinatus muscle, deltoid muscle, and supraspinatus tendon were acquired from 12 patients with vitamin D deficiency (serum 25-hydroxyvitamin D concentration <20 ng/dL) and 12 patients with sufficient vitamin D levels (control group, serum 25-hydroxyvitamin D concentration ≥30 ng/dL) who were matched for age, sex, and tear size. Alterations in the expression of genes and proteins associated with myogenesis, muscle atrophy, adipogenesis, inflammation, and apoptosis, as well as in vitamin D receptor expression, were assessed using quantitative reverse transcription polymerase chain reaction, Western blotting, and immunohistochemistry and were compared between the 2 groups. RESULTS: Vitamin D receptor gene expression in the deltoid muscle was significantly lower in the vitamin D deficiency group than in the control group (P = .043). Additionally, in the deltoid muscle, myoDgene expression levels were lower and atrogin levels were higher in the vitamin D deficiency group than in the control group (P = .034 and P = .011, respectively). However, in the supraspinatus muscle, no differences were observed between groups in the expression of myogenesis- or atrophy-related genes (all P > .05). The expression of inflammation-related genes (interleukin (IL)-1ß and IL-6) was significantly higher in the vitamin D deficiency group, in both the deltoid and supraspinatus muscles (all P < .05). The supraspinatus tendon tissue did not show any significant differences in any gene expression evaluated (all P > .05). A correlation between gene and protein expression was observed for atrogin and IL-1ß in the deltoid muscle (P = .019 and P = .037, respectively) and for IL-6 in the supraspinatus muscle (P = .044). CONCLUSION: Vitamin D deficiency was not associated with the expression of myogenesis-related or muscle atrophy-related genes in the supraspinatus muscle of patients with rotator cuff tears, unlike in the deltoid muscle; rather, vitamin D deficiency was associated with increased proinflammatory cytokine expression. CLINICAL RELEVANCE: In patients with rotator cuff tears, vitamin D deficiency was observed to be associated with increased levels of proinflammatory cytokines in the rotator cuff muscles, without significant changes in gene expression related to myogenesis or muscle atrophy.

Nutrition and Theriogenology: A Glimpse Into Nutrition and Nutritional Supplementation During Gestation, Lactation, Weaning and Breeding Dogs and Cats.

Feeding during normal reproduction is often not thought of until there is a problem with conception or gestational losses. Energy demands of lactation and early puppy/kitten are of concern, particularly in large and giant breed dogs where mineral balance is crucial to normal development. There is a paucity of information around optimizing feeding during conception and gestation with many myths around ingredients which will be explored in this article along with supplements that may be able to support spermatogenesis and conception which primarily comes from the human literature and may have validity in times of difficult conception.

Current treatment patterns within 1 year after prostate cancer diagnosis in Korean patients over 75 years old: a retrospective multicenter study.

Background: We aimed to evaluate the current status of first-line treatment options for prostate cancer in patients aged ≥75 years in Korea. Materials and methods: The study included 873 patients diagnosed with biopsy-proven prostate cancer at 5 institutions in Korea from January 2009 to December 2018. Inclusion criteria were aged ≥75 years at diagnosis, prostate biopsy with ≥12 cores, and follow-up period ≥1 year. Clinical data were retrospectively collected from electronic medical records. Results: Primary treatment for prostate cancer in patients aged ≥75 years included androgen deprivation therapy (ADT) (n = 614), radical prostatectomy (RP) (n = 114), and radiation therapy (n = 62). Among patients with RP, nine patients received ADT before RP. The RP group was younger with better Eastern Cooperative Oncology Group Performance Status (ECOG PS), lower initial prostate-specific antigen (PSA), Gleason score (GS), max percent positive cores, less positive cores, and less advanced clinical Tumor Node Metastasis (TNM) stage compared with the ADT group. Multivariate analysis showed that age, ECOG PS, and PSA were independent prognostic factors for RP. When the ADT group was classified by therapeutic regimens, the most common therapeutic regimen was maximal androgen blockade (MAB) (n = 571), and leuprolide + bicalutamide (n = 330) was the most common MAB regimen. Multivariate analysis for secondary treatment showed that age, ECOG PS, GS, and clinical N1 or M1 stage were independent predictive factors. Enzalutamide was the most preferred treatment for tertiary treatment. Conclusion: In patients with prostate cancer aged ≥75 years, the most common treatment option was MAB, and the leuprolide + bicalutamide was the most common MAB regimen. Age, ECOG PS, and PSA are the useful indicators of surgical treatment, which increased during the study period. Younger patients with high GS and advanced clinical stage were more likely to undergo secondary treatment.

Trends of stratified prostate cancer risk in a single Korean province from 2003 to 2021: A multicenter study conducted using regional training hospital data.

PURPOSE: To identify changes in prostate cancer (PCa) risk-stratification during the last two decades in Korea, where the social perception of PCa was limited due to a relatively low incidence but has recently been triggered by the rapidly increasing incidence of benign prostate hyperplasia. MATERIALS AND METHODS: Retrospective data of patients who had received a diagnosis of PCa in a single Korean province (Daegu-Gyeongsangbuk) at all seven training hospitals in the years 2003, 2007, 2011, 2015, 2019, and 2021 were subjected to analysis. Changes in PCa risk-stratification were investigated with respect to serum prostate-specific antigen (PSA), Gleason score (GS), and clinical stage. RESULTS: Of the 3,393 study subjects that received a diagnosis of PCa, 64.1% had high-risk disease, 23.0% intermediate, and 12.9% low-risk disease. The proportion diagnosed with high-risk disease was 54.8% in 2003, 30.6% in 2019, but then increased to 35.1% in 2021. The proportion of patients with high PSA (>20 ng/mL) steadily decreased from 59.4% in 2003 to 29.6% in 2021, whereas the proportion with a high GS (>8) increased from 32.8% in 2011 to 34.0% in 2021, and the proportion with advanced stage disease (over cT2c) increased from 26.5% in 2011 to 37.1% in 2021. CONCLUSIONS: In this retrospective study, conducted in a single Korean province, high-risk PCa accounted for the largest proportion of newly registered Korean PCa patients during the last two decades and increased in the early 2020s. This outcome supports the adoption of nationwide PSA screening, regardless of current Western guidelines.

Clinical characteristics of surgically managed patients with asymptomatic renal stones: Comparison of patients with symptomatic renal stones.

PURPOSE: This study aimed to compare the characteristics of asymptomatic and symptomatic nephrolithiasis in patients who underwent surgical treatment for kidney stones. MATERIALS AND METHODS: Between 2015 and 2019, 245 patients who underwent percutaneous nephrolithotomy or retrograde intrarenal surgery for kidney stones were included. The patients were divided into asymptomatic (n=124) and symptomatic (n=121) groups. All patients underwent blood and urine tests, preoperative non-contrast computed tomography, and postoperative stone composition analysis. We retrospectively analyzed and compared the characteristics of the patients and stones, operation time, stone-free rate, and postoperative complications between the two groups. RESULTS: In the asymptomatic group, mean body mass index (BMI) was significantly higher (25.7±3.8 kg/m² vs. 24.3±2.8 kg/m², p=0.002) and urine pH was significantly lower (5.6±0.9 vs. 5.9±0.9, p=0.013). The ratio of calcium oxalate dihydrate stones was significantly higher in the symptomatic group (5.3% vs. 15.5%, p=0.023). No significant differences were observed in stone characteristics, postoperative outcomes, or complications. In the multivariate logistic regression analysis for predicting variables for asymptomatic renal stones, BMI (odds ratio [OR], 1.144; 95% confidence interval [CI], 1.038-1.260; p=0.007), and urine pH (OR, 0.608; 95% CI, 0.407-0.910; p=0.016) were independent predictive variables for asymptomatic renal stones. CONCLUSIONS: This study demonstrated that thorough medical check-ups are needed for the early detection of renal stones in individuals with a high BMI or low urine pH.

Design of Eu(TTA)3phen-incorporated SiO2-coated transition metal oxide nanoparticles for efficient luminescence and magnetic performance.

The development of multifunctional nanoparticles (NPs) combining individual properties, such as magnetic, luminescence, and optical properties, has attracted significant research interest. In this study, europium (Eu)-incorporating iron oxide nanoparticles (IONPs) with Eu(TTA)3phen (ET-SIOPs) were successfully designed and shown to have luminescence and magnetic properties. The proposed synthetic method has three steps: (1) IONP synthesis, (2) SiO2 layer coating (1st coating), and (3) Eu-SiO2 layer coating (2nd coating). The morphology of the ET-SIOPs was well preserved after the 2nd coating was conducted. According to the photoluminescence (PL) spectra in the range of 500 to 700 nm, the Eu-incorporating SIOPs with Eu(TTA)3phen (ET-SIOPs) exhibited the highest emission intensity compared to the Eu-incorporating SIOPs synthesized with other Eu precursors. Furthermore, the ET-SIOPs exhibited long-term luminescence stability of 6 months. In addition, this method of double-layer coating can be applied to other materials synthesized with different compositions and shapes, such as MnO and SiO2 NPs. The findings of this study will not only provide new insights for the synthesis of luminescent-magnetic NPs with long-term luminescence stability and paramagnetic properties, but can also be applied for the design of various multifunctional NPs.

The Efficacy and Safety of a Human Perirenal Adipose Tissue-Derived Stromal Vascular Fraction in an Interstitial Cystitis Rat Model.

BACKGROUND: Interstitial cystitis (IC) is a chronic and intractable disease that can severely deteriorate patients' quality of life. Recently, stem cell therapy has been introduced as a promising alternative treatment for IC in animal models. We aimed to verify the efficacy and safety of the human perirenal adipose tissue-derived stromal vascular fraction (SVF) in an IC rat model. METHODS: From eight-week-old female rats, an IC rat model was established by subcutaneous injection of 200 µg of uroplakin3A. The SVF was injected into the bladder submucosal layer of IC rats, and pain scale analysis, awakening cytometry, and histological and gene analyses of the bladder were performed. For the in vivo safety analysis, genomic DNA purification and histological analysis were also performed to check tumorigenicity and thrombus formation. RESULTS: The mean pain scores in the SVF 20 µl group were significantly lower on days 7 and 14 than those in the control group, and bladder intercontraction intervals were significantly improved in the SVF groups in a dose-dependent manner. Regeneration of the bladder epithelium, basement membrane, and lamina propria was observed in the SVF group. In the SVF groups, however, bladder fibrosis and the expression of inflammatory markers were not significantly improved compared to those in the control group. CONCLUSION: This study demonstrated that a perirenal adipose tissue-derived SVF is a promising alternative for the management of IC in terms of improving bladder pain and overactivity.

Graph approaches for analysis of brain connectivity during dexmedetomidine sedation.

Sedation is commonly used to relieve fear and anxiety during procedures. Dexmedetomidine (DEX), approved by the US Food and Drug Administration in 1999 for short-term sedation, is a selective alpha2-adrenoreceptor agonist. The use of DEX is increasing due to minimal respiratory depression and easy and quick awakening from sedation. Its sedative mechanisms are suggested to be related to changes in the interaction between brain regions. In this study, we used graph theory to investigate whether the altered network connection is associated with sedation. Electroencephalogram (EEG) recordings of 32 channels were acquired during awake and DEX-induced sedation for 20 participants. We extracted EEG epochs from the awake and the DEX sedation state. Using the graph theory, we compared the changes in the network connection parameters with the awake state. We observed that the slopes in 1/f dynamics, which indicate overall brain network characteristics, were greater during DEX-induced sedation compared to the awake state, suggesting a transition towards a random network behavior. In addition, network connections from the perspective of information processing were significantly disturbed in the alpha frequency band, unlike other frequency bands augmenting network connections. The alpha frequency band plays a prominent role in the function and interaction of cognitive activities. These results collectively indicate that changes in the brain network critical to cognition during DEX administration may also be related to the mechanism of sedation.

Comparison of the efficacy of the early LI-SWT plus daily tadalafil with daily tadalafil only as penile rehabilitation for postprostatectomy erectile dysfunction.

This study compares the efficacy of the early low-intensity shock wave therapy (LI-SWT) plus daily tadalafil with daily tadalafil only therapy as penile rehabilitation for postprostatectomy erectile dysfunction in patients with prostate cancer who underwent bilateral interfascial nerve-sparing radical prostatectomy (robotic or open). From April 2019 to March 2021, 165 patients were enrolled, and 80 of them successfully completed this prospective study. Daily tadalafil were administered to all the patients. LI-SWT consisted of a total of six sessions. Each session was performed on days 4, 5, 6, and 7, and on the second and fourth weeks after surgery. Each LI-SWT session consisted of 300 shocks at an energy density of 0.09 mJ/mm2 and a frequency of 120 shocks per minute that were delivered at each of the five treatment points for 15 min. Thirty-nine patients were treated with tadalafil-only (group A) while 41 were treated with tadalafil and LI-SWT simultaneously (group B). At postoperative 6 months, the proportion of patients with erection hardness scores (EHS) ≥ 3 (4/39 vs. 12/41) was significantly higher in group B (p = 0.034), and LI-SWT was the only independent factor for predicting EHS ≥ 3 (OR, 3.621; 95% CI, 1.054-12.437; p = 0.041). There were no serious side effects related to early LI-SWT. Early LI-SWT plus daily tadalafil therapy as penile rehabilitation for postprostatectomy erectile dysfunction is thought to be more efficacious than tadalafil only. Further large-scaled randomized controlled trials will be needed to validate these findings.

Perirenal adipose tissues as a human elastin source, and optimize the extraction process.

Elastin is very rarely repaired extracellular matrix (ECM) in physiological condition. The commercial human elastin for exogenous medical treatment is very expensive, and has a potential for disease transmission. Animal-origin elastin is relatively low price, but has concerns for xenogeneic immune responses. Considering cost and safety, we focused on the perirenal adipose tissue, donated from healthy young people via donor nephrectomy. Until now, all of the perirenal adipose tissues are discarded as a medical waste after kidney transplantation. In the present study, we applied perirenal adipose tissues as the source of human elastin, and optimized the extraction process to get high purified and quantified elastin. Through pre-processing step, the delipidated and decellularized ECM was prepared. Next, with four different elastin extraction process (acidic solvents, neutral salt, organic solvents or hot alkali method), elastin was extracted, and the concentration of amino acid between each product was compared, and bright-field/electron microscopy, Fourier transform infrared (FT-IR) spectroscopy and cytotoxicity analysis were also performed. As controls, bovine neck ligament-derived and human skin-derived elastin were used. Among the elastin extraction methods, the hot alkali insoluble product showed (1) relatively high positive area of Verhoeff's and low Masson's trichrome stain, (2) 64.24% purity, 159.29 mg/g quantity, and ∼6.37% yield in amino acid analysis, (3) ß-sheet second structure, and (4) thin fiber composed mesh-like sheet structure in SEM image. These values were higher than those of the commercial human skin elastin. When comparing hydrolyzed forms, α-elastin from hot alkali insoluble product showed enhanced cell proliferation and maintained cell properties compared to the κ-elastin. Therefore, we confirmed that the perirenal adipose tissue is an ideal source of human elastin with safety assurance, and the hot alkali process combined with pre-process seems to be the optimal method for elastin extraction with high purity and quantity.

Anti-Metastatic Effect of Pyruvate Dehydrogenase Kinase 4 Inhibition in Bladder Cancer via the ERK, SRC, and JNK Pathways.

Bladder cancer is a common global cancer with a high percentage of metastases and high mortality rate. Thus, it is necessary to identify new biomarkers that can be helpful in diagnosis. Pyruvate dehydrogenase kinase 4 (PDK4) belongs to the PDK family and plays an important role in glucose utilization in living organisms. In the present study, we evaluated the role of PDK4 in bladder cancer and its related protein changes. First, we observed elevated PDK4 expression in high-grade bladder cancers. To screen for changes in PDK4-related proteins in bladder cancer, we performed a comparative proteomic analysis using PDK4 knockdown cells. In bladder cancer cell lines, PDK4 silencing resulted in a lower rate of cell migration and invasion. In addition, a PDK4 knockdown xenograft model showed reduced bladder cancer growth in nude mice. Based on our results, PDK4 plays a critical role in the metastasis and growth of bladder cancer cells through changes in ERK, SRC, and JNK.

Scalp acupuncture for stroke: A protocol for an overview of systematic reviews and meta-analysis.

BACKGROUND: Scalp acupuncture (SA) is a new acupuncture method that connects head acupoints and aculines, and many systematic reviews (SRs) have been published on its use against neuropsychiatric diseases. However, no overview of SRs on the effectiveness of SA in stroke recovery has been conducted. Therefore, our overview aims to evaluate the methodological bias and reliability of the conclusions of SRs regarding SA for stroke recovery and help clinical decision-makers translate this research into clinical policy and practice. METHODS: We will consider SRs and meta-analyses of randomized controlled trials to evaluate the effects of SA on stroke recovery. Two reviewers will identify relevant studies, extract data information, and assess the methodological quality using the Assessment of Multiple Systematic Reviews-2 tool. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses report checklist will also be included in the study to assess the quality of the reports. We will use evaluations of the Grading of Recommendations Assessment, Development and Evaluation of the authors of the included SRs. The Risk of Bias in Systematic Review tool will be used to assess the risk of bias of SRs. The screening of SRs, eligibility evaluation, data extraction, methodological quality, and quality of evidence will be conducted by independent reviewers in pairs. The outcomes of interest include the Modified Edinburgh-Scandinavian Stroke Scale, Ability of Daily Living, Functional Independence Measure, Barthel index, Fugl-Meyer assessment, clinical effective rate, and adverse events. Data will be extracted using predefined forms designed to summarize the important characteristics of each review. The evidence will be a descriptive synthesis of the type and content of the intervention and the results reported. RESULTS: The results will be published in a peer-reviewed journal. CONCLUSIONS: We expect to organize evidence from multiple SRs on the effectiveness of SA for stroke recovery and synthesize the findings in an accessible and useful documentation.