The STRAT-PARK cohort: A personalized initiative to stratify Parkinson's disease.

The STRAT-PARK initiative aims to provide a platform for stratifying Parkinson's disease (PD) into biological subtypes, using a bottom-up, multidisciplinary biomarker-based and data-driven approach. PD is a heterogeneous entity, exhibiting high interindividual clinicopathological variability. This diversity suggests that PD may encompass multiple distinct biological entities, each driven by different molecular mechanisms. Molecular stratification and identification of disease subtypes is therefore a key priority for understanding and treating PD. STRAT-PARK is a multi-center longitudinal cohort aiming to recruit a total of 2000 individuals with PD and neurologically healthy controls from Norway and Canada, for the purpose of identifying molecular disease subtypes. Clinical assessment is performed annually, whereas biosampling, imaging, and digital and neurophysiological phenotyping occur every second year. The unique feature of STRAT-PARK is the diversity of collected biological material, including muscle biopsies and platelets, tissues particularly useful for mitochondrial biomarker research. Recruitment rate is ∼150 participants per year. By March 2023, 252 participants were included, comprising 204 cases and 48 controls. STRAT-PARK is a powerful stratification initiative anticipated to become a global research resource, contributing to personalized care in PD.

Case report: Ectopic corpus cavernosum presented as bladder tumor in a 3-year-old boy.

Background: Ectopic tissue is rarely found in the bladder for adults. Currently, there have been reports of ectopic prostate and colon tissue in the bladder. These ectopic tissues are manifested as a bladder mass and cause lower urinary tract symptoms. However, the ectopic corpus cavernosum in the bladder has never been reported, and its clinical characteristics and treatment have not been explored yet. Case summary: A 3-year-old boy was admitted to the hospital due to 1 month of urinary frequency. The physical examination was unremarkable. Urine analysis from other hospitals showed an elevated urine white blood cell count of 17.9/ul. In addition, ultrasound indicated a possible bladder mass. CT and MRI showed a well-margined lesion (1.9×1.9 cm) in the bladder trigone. Through preoperative imaging, we diagnosed a bladder tumor (inclined towards benign). The transurethral resection of the bladder tumor was performed. Unfortunately, the surgery was unsuccessful due to the difficulty in removing the excised tissue through the urethra. Subsequently, bladder incision and tumor resection were performed. The tumor was successfully removed. Surprisingly, the postoperative pathology showed that the tumor tissue was corpus cavernosum. The pathological diagnosis was ectopic corpus cavernosum in the bladder. No complications were found after the operation, and no recurrence was observed during follow-up. Conclusion: The ectopic corpus cavernosum in the bladder has never been reported for children, which is presented as a benign tumor with rapid proliferation and large size. Surgery is recommended. However, the transurethral resection of bladder tumors is difficult to perform due to narrow urethra and limited surgical instruments. Bladder incision and tumor resection may be preferred.

The performance of ultrasound and upper gastrointestinal study in diagnosing malrotation in children, with or without volvulus.

BACKGROUND: Rapid diagnosis is crucial for pediatric patients with midgut volvulus and malrotation to prevent serious complications. While the upper gastrointestinal study (UGIS) is the traditional method, the use of ultrasound (US) is gaining prominence. OBJECTIVES: To assess the diagnostic sensitivity and specificity of US compared to UGIS for malrotation and midgut volvulus. METHODS: A cross-sectional study was performed on 68 pediatric patients who underwent US and/or UGIS before surgery for suspected midgut volvulus or malrotation in Kuala Lumpur (PPUKM and HTA), referencing surgical outcomes as the gold standard. RESULTS: US demonstrated a higher specificity (100%) than UGIS (83%) for diagnosing malrotation, with a slightly lower sensitivity (97% vs. 100%). For midgut volvulus, US surpassed UGIS in sensitivity (92.9% vs. 66.7%) while maintaining comparable specificity. The SMA/SMV criteria showed better sensitivity (91.1%) than the D3 assessment (78.9%) on US, though both had high specificity. CONCLUSION: US is equivalent to UGIS for identifying malrotation and is more sensitive for detecting midgut volvulus, supporting its use as a primary diagnostic tool. The study advocates for combined US and UGIS when either yields inconclusive results, optimizing diagnostic precision for these conditions.

OTX1 regulates tumorigenesis and metastasis in glioma.

The most prevalent kind of primary brain tumors, gliomas, have a dismal prognosis. Recent advances in the tumor-promoting ability of OTX1 have drawn increasing attention. The overexpression of OTX1 has been reported to be associated with tumor-promoting effects in several malignancies, but its expression in gliomas is unknown. The oncogene OTX1 is increased in gliomas and is linked to a poor prognosis, as we show here. The degree of OTX1 positive expression is doubtlessly concomitant with the grade of glioma. We observed that OTX1 was up-regulated in gliomas, influenced the epithelial-mesenchymal transition (EMT), encouraged glioma cell growth and proliferation, and was linked to a poor clinical outcome for patients. At present, the prognosis of glioma is still not optimistic, and further research is needed to find a new target for treatment. According to our research, OTX1 is anticipated to emerge as a novel biological target for determining glioma prognosis and treatment.

Acupoint application therapy alleviates pain by regulating immune function through inhibiting TLR4/MyD88/NF-κB p65 signaling in a primary dysmenorrhea rat model. / 穴位贴敷通过TLR4/MyD88/NF-κBé€šè·¯è°ƒèŠ‚åŽŸå‘æ€§ç—›ç»å¤§é¼ çš„å ç–«åŠŸèƒ½.

OBJECTIVES: To investigate the effects of graphene-based warm uterus acupoint paste on uterine Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear transcription factor-kappa B p65 (NF-κB p65) signaling pathway and Th1/Th2 immune balance in primary dysmenorrhea ( PD ) model rats, so as to reveal its immunological mechanisms of relieving dysmenorrhea. METHODS: Thirty SD female rats were randomly divided into 3 groups：normal group, model group and acupoint paste group, with 10 rats in each group. PD rat model was established by subcutaneous injection of estradiol benzoate for 10 consecutive days. At the same time of modeling, graphene-based warm uterus acupoint paste was applied to the acupoints of "Guanyuan" (CV4), bilateral "Zigong" (EX-CA1) and "Sanyinjiao" (SP6) of rats in the acupoint paste group. The application was continuously applied once daily for 10 d, 5 h each time. On the 11th day, oxytocin was injected intraperitoneally to observe the writhing latency, writhing times within 30 min and writhing score of rats in each group. The spleen and thymus indexes were calculated. The pathological changes of spleen and thymus tissue were observed after HE staining. The contents of serum immunoglobulin (Ig) A, IgG, tumor necrosis factor-α (TNF-α), interleukin (IL)-2, interferon-γ (IFN-γ), IL-4 and IL-10 were detected by ELISA . The protein and mRNA expression levels of TLR4, MyD88 and NF-κB p65 in rat uterine tissue were detected by Western blot and real-time quantitative PCR, respectively. RESULTS: Compared with the normal group, the writhing times and writhing scores within 30 min of rats in the model group were significantly increased(P<0.001), and the rats showed writhing reaction (P<0.01). The spleen index and thymus index were significantly decreased(P<0.01, P<0.05). The spleen and thymus had obvious pathological changes. The contents of IgA, IgG, TNF-α, IL-2 and IFN-γ in serum were significantly increased, while the contents of serum IL-4 and IL-10 were significantly decreased(P<0.001, P<0.01). The expression levels of TLR4, MyD88, NF-κB p65 protein and corresponding mRNA in uterine tissue were significantly increased(P<0.001). Following intervention, compared with the model group, the writhing latency time of rats in the acupoint paste group was prolonged, and the writhing times and writhing scores within 30 min were significantly decreased (P<0.001). The spleen index and thymus index were significantly increased(P<0.01, P<0.05). The pathological changes of spleen and thymus were improved. The contents of serum IgA, IgG, TNF-α, IL-2 and IFN-γ were significantly decreased, while the contents of IL-4 and IL-10 were significantly increased(P<0.001, P<0.05, P<0.01). The expression of TLR4, MyD88, NF-κB p65 protein and the corresponding mRNA levels in uterine tissue were decreased(P<0.001, P<0.01). CONCLUSIONS: Graphene-based warm uterus acupoint paste can regulate the immune balance of Th1/ Th2 by regulating TLR4/ MyD88/ NF-κB p65 signaling pathway, repair the pathological damage of immune tissue, improve immune function, and effectively relieve the pain symptoms of PD rats.

A Feasibility Study on a Telemedicine Hybrid Protocol for Preoperative Anesthetic Assessment.

Background Over the past decade, telemedicine has experienced significant growth due to technological advancement, and the coronavirus disease 2019 (COVID-19) pandemic further accelerated its adoption. However, the field of anesthesiology has been slow in integrating and embracing telemedicine compared to other medical specialties. Methods We conducted an observational pilot feasibility study at a tertiary hospital in Singapore to assess the viability of a telemedicine hybrid protocol for preoperative anesthetic assessment. The study included patients aged 21 to 65 years, classified as American Society of Anesthesiology (ASA) physical status class 1 or 2, with a body mass index (BMI) below 35 kg/m2, who were capable of managing video conferencing. The patients selected were scheduled for low-risk surgeries. The primary objective was to evaluate the medical and technical feasibility of our telemedicine hybrid protocol, while the secondary objectives included assessing patient satisfaction and obtaining feedback from relevant stakeholders. Results From November 2021 to April 2022, a total of 116 patients were recruited, with 96 patients completing the study. No technical difficulties, surgical case cancellations, or incidents of unanticipated difficult airways were reported. The majority of survey respondents (88%) expressed satisfaction with the video consultation and indicated a preference for it over physical consultations for future preoperative anesthesia evaluations. Conclusion Based on our findings, a telemedicine hybrid protocol for preoperative anesthetic assessment demonstrated both technical and medical feasibility while yielding high patient satisfaction. Future research could focus on expanding the protocol to encompass more complex surgeries and include patients with higher ASA status.

TRIM21 promotes tumor progression and cancer stemness in cervical squamous cell carcinoma.

BACKGROUND: The ubiquitin ligase family member triplex motif protein 21 (TRIM21), which is involved in the proliferation, metastasis, and selective death of tumor cells, is crucial in the ubiquitination of a number of tumor marker proteins. As research progresses, more studies demonstrate that TRIM21 expression levels can be used to predict cancer prognosis. However, it is unclear how exactly TRIM21 contributes to cervical squamous carcinoma. METHODS: Immunohistochemistry, Western Blot, and q-PCR were utilized to determine the expression level of TRIM21 in 113 patients with CESC removed by stage I surgery at Xijing Hospital from 2018 to 2023 using paraffin-embedded tumor tissues and 12 pairs of fresh tumor tissues and their paracancerous tissues. Log-rank analysis using SPSS 23.0 was performed for prognosis and survival analysis using univariate/multifactorial analysis. CCK-8, wound-healing and Scratch assay verified that TRIM21 promoted cell proliferation, migration and invasion. The effect of overexpression and knockdown of TRIM21 on tumor stemness was examined using sphere-forming assay and Western Blot. Finally, we constructed a xenograft model to observe the effect of TRIM21 on tumorigenesis in Si Ha cell lines in vivo. RESULTS: TRIM21 expression is greater in CESC tissues than in paracancerous tissues, according to immunohistochemical data. Similarly, at the protein and mRNA levels, we verified this conclusion using Western-Blotting and q-PCR. Prognostic and OS analysis showed that TRIM21 expression levels are associated with individual prognostic factors. CCK-8, Wound healing, Transwell, and Sphere-forming tests all demonstrated that TRIM21 overexpression enhances Ca Ski cell proliferation, migration, invasion, and stemness. TRIM21 knockdown in Si Ha inhibited tumor cell proliferation, migration, invasion, and stemness. The experimental results of xenograft models demonstrated that TRIM21 knockdown in Si Ha cells inhibited tumor development. CONCLUSION: TRIM21 is a poor predictor of prognosis for cervical squamous cell carcinoma and might open up new avenues for investigation into therapeutic targets.

Case report: Rudimentary uterine horn with ovarian endometriosis manifested as pelvic ectopic kidney.

Background: Unicornuate uterus is a congenital uterine malformation. Unicornuate uterus with rudimentary horn, ovarian endometriosis, and congenital renal agenesis are rare combinations that can be easily misdiagnosed due to the lack of typical clinical manifestations. Case summary: A 19-year-old woman with pelvic pain was admitted to the hospital after a month. Physical examination was unremarkable. B-ultrasound and CT scan both indicated pelvic ectopic kidney. In addition, renal scintigraphy revealed normal perfusion and function of the right kidney, but the perfusion and function of the left kidney were not visible. A left pelvic ectopic kidney was diagnosed by preoperative images. A laparoscopic left pelvic ectopic nephrectomy was performed after adequate surgical preparation. However, the postoperative pathological diagnosis revealed a rudimentary uterine horn with ovarian endometriosis and congenital renal agenesis. Fortunately, she got recovered and was discharged from the hospital after 5 days following the operation. Moreover, she received regular follow-ups at the gynecology clinic. To date, no right adnexal or uterine abnormalities have been detected on ultrasound during the follow-up visits. Conclusion: Rudimentary uterine horn with ovarian endometriosis and congenital renal agenesis are rare and are easily Misdiagnosed due to the lack of typical clinical manifestations. A gynecological examination is recommended for patients who may have this disease.

Single-Nanoparticle-Based Nanomachining for Fabrication of a Uniform Nanochannel Sensor.

The structure of nanomaterials and nanodevices determines their functionality and applications. A single uniform nanochannel with a high aspect ratio is an attractive structure due to its unique rigid structures, easy preparation, and diverse pore structures and it holds significant promising importance in fields such as nanopore sensing and nanomanufacturing. Although the metal-nanoparticle-assistant silicon etching technique can produce uniform nanochannels, however, the fabrication of single through nanochannels remains a challenge thus far. A simple and versatile strategy is developed that allows for the retention of individual gold nanoparticle on a substrate, enabling single-nanoparticle nanomachining. This method involves three steps: the formation of a carbon protective layer on individual nanoparticles via electron-beam irradiation, selective removal of unprotected nanoparticles using a corrosive agent, and subsequent elimination of the carbon layer. This enables the fabrication of a single submillimeter-long uniform through nanochannel in the silicon wafer, which can be employed for nanopore sensing and shape-based nanoparticle distinguishing. The developed method can also facilitate single-nanoparticle studies and nanomachining for a broad application in materials science, electronics, micro/nano-optics, and catalysis.

UCHL1 acts as a prognostic factor and promotes cancer stemness in cervical squamous cell carcinoma.

BACKGROUND: The incidence and death rate of cervical cancer rank fourth among female malignant tumors worldwide. A growing number of researches are devoted to exploring more effective treatment methods and cancer stem cells (CSCs) are thought to be a potential therapeutic target in cervical cancer. In our study, we focused on the expression and function of UCHL1 in cervical squamous cell carcinoma (CESC). METHODS: We detected and the expression of UCHL1 in 134 CESC patients through immunohistochemistry and further confirm UCHL1 was a prognostic factor by univariate and multivariate analysis. Then, according to TCGA database for CESC, we found that UCHL1 expression correlated with the markers associated with CSCs (CD133, ABCG2 and SOX2). Therefore, we used western blot and spheroid formation assays to future evaluate the function of UCHL1 on cancer stemness in C-33A and SiHa cell lines. At the same time, we detected the cell proliferation, migration and invasion change by CCK-8 assay, scratch assay and transwell assay, when UCHL1 was knockdown or overexpressed. Finally, xenograft models were used to examine the effect of UCHL1 in vivo. RESULTS: We found the expression of UCHL1 in mRNA and protein was higher in tumor than in paired normal tissue and was a prognostic factor in CESC. The UCHL1 high expression group showed a shorter survival in the overall survival. According to TCGA database, the expression of UCHL1 was correlated with CD133, ABCG2 and SOX2. The results of sphere-forming ability and CSCs related markers expression were showed UCHL1 promoted cancer stemness in CESC. Similarly, CCK-8 assay, scratch assay and transwell assay were applied to demonstrate that overexpression of UCHL1 promoted the proliferation, migration and invasion in SiHa, but when UCHL1 was knockdown in C-33A, the function of UCHL1 displayed the opposite result. Finally, knockdown UCHL1 inhibited CESC tumor propagation in xenograft models. CONCLUSION: Our results suggest that UCHL1 is a prognostic factor and correlated with cancer stemness, proliferation, migration and invasion of CESC, which may provide a novel therapeutic strategy for CESC treatment.

BTG2 suppresses the growth and metastasis of cervical squamous cell carcinoma.

BACKGROUND: Cervical cancer is the fourth most common malignancy in women, of which cervical squamous cell carcinoma (CESC) is the main pathological type of cervical cancer. B-cell translocation gene 2 (BTG2) protein has been recognized as a tumor suppressor in several cancer types. However, BTG2 expression and molecular function in CESC are unknown. METHODS: In this study, we first assessed the expression of BTG2 in tumor tissue specimens from CESC patients using immunohistochemical staining and real-time quantitative PCR, and explored the relationship between BTG2 expression status and clinical manifestations. Next, we constructed BTG2 knockdown and overexpression CESC cell lines to observe the effects of BTG2 on CESC proliferation and metastasis at the cellular level. Finally, we employed a nude mouse xenograft tumor model in an in vivo experiment to observe the effect of BTG2 on tumorigenesis in vivo. RESULTS: The results showed that the expression of BTG2 protein was lower in CESC tissues than in normal tissues, and high BTG2 expression was associated with better survival in CESC patients versus CESC patients. The results of cellular assays confirm that overexpression of BTG2 inhibits the proliferation, migration and metastasis of CESC cells. Nude mouse xenograft tumor model showed that overexpression of BTG2 inhibited tumor growth in vivo, and conversely knockdown of BTG2 promoted tumor growth. CONCLUSION: In summary, our data suggest that BTG2 acts as a tumor suppressor in CESC and inhibits the growth and metastasis of CESC. BTG2 may serve as a potential prognostic marker in CESC and is expected to provide a therapeutic strategy for patients with CESC.

USP18 regulates the malignant phenotypes of glioblastoma stem cells.

Glioblastoma (GBM) is the most malignant primary brain tumor. The 5-year survival rate of the patients is poor, and they are prone to relapse and the treatment is limited. Therefore, the search for biological targets is one of the key measures for the treatment and prognosis of GBM. Ubiquitin-specific peptidase 18 (USP18) plays a regulatory role in tumorigenesis. In this study, we found that USP18 was up-regulated in GBM, promoted the growth and proliferation of glioblastoma stem cells (GSCs), affected the epithelial-mesenchymal transition (EMT), and was associated with poor clinical prognosis of patients. Finally, our findings reveal a critical role for USP18 in GBM malignancy, targeting USP18 may open new avenues for GBM treatment.

Ferroptosis in cancer stem cells.

Ferroptosis is an iron-dependent form of RCD correlates with the accumulation of markers of lipid peroxidation. Bulks of studies focusing on revealing ferroptosis and its regulators involved in oncogenic pathways. Connection between iron metabolism and abnormal iron metabolism in CSCs synergistically making ferroptosis a target process of great potential in combating with CSCs to improve therapeutic effectiveness and reverse resistance. Ferroptosis inducers could specifically induce CSCs death in tumors, predisposing ferroptosis to a target in killing CSCs to overcome cancer resistances. By ferroptosis induction and other cell death pathways in CSCs, cancer therapeutic outcome would be improved.

Ischemic Stroke and Savings in Time to Achieve Functional Recovery: Experience from NeuroAiD.

Despite recent progress with revascularisation interventions after acute ischemic stroke, many patients remain disabled after stroke. Using data from a multi-centre, randomised, double-blind, placebo-controlled trial of a neuro-repair treatment (NeuroAiD/MLC601) with a long-term follow-up, we analysed the savings in time to functional recovery, measured by a modified Rankin Scale (mRS) score of 0 or 1, in patients receiving a 3-month oral course of MLC601. Analysis of time to recovery was assessed by a log-rank test and hazard ratios (HRs) adjusted for prognosis factors. A total of 548 patients with baseline NIHSS scores 8-14, mRS scores ≥ 2 at day 10 post-stroke, and at least one mRS assessment on or after month 1 were included in the analysis (placebo = 261; MLC601 = 287). Time to functional recovery was significantly shortened for patients receiving MLC601 versus patients receiving placebo (log-rank test: p = 0.039). This result was confirmed by Cox regression adjusting for the main baseline prognostic factors (HR: 1.30 [0.99, 1.70]; p = 0.059) and was more pronounced in patients with additional poor prognosis factors. The Kaplan-Meier plot showed that approximately 40% cumulative incidence of functional recovery was achieved within 6 months after stroke onset in the MLC601 group versus 24 months in the placebo group. The main findings are that MLC601 reduced the time to achieve functional recovery, and a 40% functional recovery rate was achieved 18 months earlier compared to placebo.

Light-Driven Conversion of Silicon Nitride Nanopore to Nanonet for Single-Protein Trapping Analysis.

The single-molecule technique for investigation of an unlabeled protein in solution is very attractive but with great challenges. Nanopore sensing as a label-free tool can be used for collecting the structural information of individual proteins, but currently offers only limited capabilities due to the fast translocation of the target. Here, a reliable and facile method is developed to convert the silicon nitride nanopore to a stable nanonet platform for single-entity sensing by electrophoretic or electroosmotic trapping. A nanonet is fabricated based on a material reorganization process caused by electron-beam and light-irradiation treatment. Using protein molecules as a model, it is revealed that the solid-state nanonet can produce collision and trapping flipping signals of the protein, which provides more structural information than traditional nanopore sensing. More importantly, thanks to the excellent stability of the solid-state silicon nitride nanonet, it is demonstrated that the ultraviolet-light-irradiation-induced structural-change process of an individual protein can be captured. The developed nanonet supplies a robust platform for single-entity studies but is not limited to proteins.

MUC1 promotes cancer stemness and predicts poor prognosis in osteosarcoma.

Osteosarcoma (OS) is one of the most common primary bone malignancy. Combining chemotherapy and surgical treatment significantly improved clinical outcomes for osteosarcoma patients. Osteosarcoma stem cells (OSCs) are often more malignant than differentiated cancer cells and are a key determinant of responses to chemotherapy and radiation therapy, therefore, the removal of OSCs could be an effective therapeutic strategy. Myxoprotein 1 (MUC1) is aberrantly overexpressed in many human cancers and it promotes cancer stemness through activation of pluripotency networks. In this study, we observed elevated MUC1 in osteosarcoma and a depressed prognosis in patients with high MUC1 expression profiles. Our observations also revealed that MUC1 promoted OS stemness and tumor metastasis both in vivo and in vitro. These data led us to hypothesize that MUC1 may be a therapeutic target for patients with OS.

ZIC5 promotes aggressiveness and cancer stemness in cervical squamous cell carcinoma.

BACKGROUND: Cervical cancer is one of the major malignancies causing morbidity and mortality in women in developing countries. ZIC5 has been found to be associated with a variety of cancers, yet the expression and molecular function of ZIC5 in cervical squamous cell carcinoma (CESC) is unknown. METHODS: We examined the expression of ZIC5 in tumors and normal tissues of CESC patients using immunohistochemistry, immunoblotting and fluorescent quantitative PCR, and used statistical methods to explore its relationship with clinical manifestations. Next, we constructed ZIC5 knockdown and overexpression CESC cell lines to observe the effect of ZIC5 on the proliferation and metastasis of CESC cells. Finally, we applied a nude mouse xenograft tumor model to observe the effect of ZIC5 on tumorigenesis in vivo. RESULTS: Our results showed that the expression of ZIC5 was higher in cancer tissues than in normal tissues. Prognostic analysis showed that ZIC5 expression level was an independent prognostic factor in CESC patients, and the results of Transwell, CCK-8 and wound healing assays confirmed that overexpression of ZIC5 could promote the proliferation and migration of CESC cells. A nude mouse xenograft tumor model showed that knockdown of ZIC5 inhibited tumor growth in vivo. Database, immunoblotting assay and in vitro sphere-forming assay confirmed that ZIC5 could promote the stemness of CESC cells. CONCLUSION: ZIC5 is a factor that indicates a poor prognosis of CESC patients and promotes stemness in CESC cells. ZIC5 may be a potential biomarker and therapeutic target for CESC patients.