Vasculature injury occurs rarely in traumatic brain injury but increases lifetime risk of ischemic or hemorrhage stroke. The diverse and nonspecific clinical manifestations make the diagnosis and treatment of these injuries highly challenging. With advancements in device design, endovascular treatments have become widely adopted, playing an increasingly vital role in the management of vascular diseases. The purpose of this review is to introduce and summarize endovascular treatments of traumatic cerebrovascular injury and other related pathological states after traumatic brain injury. Given the innovations of neuroendovascular devices and improvements in the techniques over the past decade, this review will outline several recent advancements in endovascular treatment strategies for cerebrovascular pathologies. Popularizing more treatment options to clinicians will benefit in dealing with a variety of clinical scenarios and reduce the overall morbidity of traumatic cerebrovascular injury.
Humans ; Endovascular Procedures/methods* ; Brain Injuries, Traumatic/complications* ; Cerebrovascular Trauma/therapy*

OBJECTIVES: Bladder cancer is a common malignancy with high incidence and poor prognosis. N⁶-methyladenosine (m⁶A) modification is widely involved in diverse physiological processes, among which the m⁶A recognition protein YTH N⁶-methyladenosine RNA binding protein F2 (YTHDF2) plays a crucial role in bladder cancer progression. This study aims to elucidate the molecular mechanism by which O-linked N-acetylglucosamine (O-GlcNAc) modification of YTHDF2 regulates its downstream target, period circadian regulator 1 (PER1), thereby promoting bladder cancer cell proliferation. METHODS: Expression of YTHDF2 in bladder cancer was predicted using The Cancer Genome Atlas (TCGA). Twenty paired bladder cancer and adjacent normal tissues were collected at the clinical level. Normal bladder epithelial cells (SV-HUC-1) and bladder cancer cell lines (T24, 5637, EJ-1, SW780, BIU-87) were examined by quantitative real-time PCR (RT-qPCR), Western blotting, and immunohistochemistry for expression of YTHDF2, PER1, and proliferation-related proteins [proliferating cell nuclear antigen (PCNA), minichromosome maintenance complex component 2 (MCM2), Cyclin D1]. YTHDF2 was silenced in 5637 and SW780 cells, and cell proliferation was assessed by Cell Counting Kit-8 (CCK-8), colony formation, and EdU assays. Bioinformatics was used to predict glycosylation sites of YTHDF2, and immunoprecipitation (IP) was performed to detect O-GlcNAc modification levels of YTHDF2 in tissues and cells. Bladder cancer cells were treated with DMSO, OSMI-1 (O-GlcNAc inhibitor), or Thiamet G (O-GlcNAc activator), followed by cycloheximide (CHX), to assess YTHDF2 ubiquitination by IP. YTHDF2 knockdown and Thiamet G treatment were further used to evaluate PER1 mRNA stability, PER1 m⁶A modification, and cell proliferation. TCGA was used to predict PER1 expression in tissues; SRAMP predicted potential PER1 m⁶A sites. Methylated RNA immunoprecipitation (MeRIP) assays measured PER1 m⁶A modification. Finally, the effects of knocking down YTHDF2 and PER1 on 5637 and SW780 cell proliferation were assessed. RESULTS: YTHDF2 expression was significantly upregulated in bladder cancer tissues compared with adjacent tissues (mRNA: 2.5-fold; protein: 2-fold), which O-GlcNAc modification levels increased 3.5-fold (P<0.001). YTHDF2 was upregulated in bladder cancer cell lines, and its knockdown suppressed cell viability (P<0.001), downregulated PCNA, MCM2, and CyclinD1 (all P<0.05), reduced colony numbers 3-fold (P<0.01), and inhibited proliferation. YTHDF2 exhibited elevated O-GlcNAc modification in cancer cells. OSMI-1 reduced YTHDF2 protein stability (P<0.01) and enhanced ubiquitination, while Thiamet G exerted opposite effects (P<0.001). Thiamet G reversed the proliferation-suppressive effects of YTHDF2 knockdown, promoting cell proliferation (P<0.01) and upregulating PCNA, MCM2, and CyclinD1 (all P<0.05). Mechanistically, YTHDF2 targeted PER1 via m⁶A recognition, promoting PER1 mRNA degradation. Rescue experiments showed that PER1 knockdown reversed the inhibitory effect of YTHDF2 knockdown on cell proliferation, upregulated PCNA, MCM2, and Cyclin D1 (all P<0.05), and promoted bladder cancer cell proliferation (P<0.001). CONCLUSIONS O-GlcNAc modification YTHDF2 promotes bladder cancer development by downregulating the tumor suppressor gene PER1 through m⁶A-mediated post-transcriptional regulation.
Humans ; Urinary Bladder Neoplasms/metabolism* ; RNA-Binding Proteins/genetics* ; Cell Proliferation ; Cell Line, Tumor ; Disease Progression ; Acetylglucosamine/metabolism* ; Adenosine/metabolism* ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor

Colorectal cancer (CRC) is one of the most common malignant tumors recorded worldwide. This condition has high morbidity and mortality and seriously endangers people's health. Traditional diagnostic models fail to meet people's current needs for real-time monitoring of tumors. Compared with traditional detection methods, ctDNA detection is not only noninvasive but can also attain real-time detection of comprehensive genomic information of tumors. The advancement of detection technology has gradually highlighted the potential of ctDNA detection in the clinical treatment of CRC. This article reviews the advancements on the clinical application of ctDNA in early screening, minimal residual disease detection, and guidance on individualized treatment of CRC patients.

Objective:This study compiled a comprehensive overview of the academic misconduct cases handled by the National Natural Science Foundation of China (NSFC) over the past decade, and took it as a representative to analyze the current situation of China′s academic research integrity to propose further enhancement suggestions.Methods:We collected data on academic misconduct cases notified by the NSFC between 2013 and 2022, and conducted a statistical analysis to gain insights into the time of occurrence, the way of discovery, the distribution of disciplines, the types of misconduct, and the handling measures of the NSFC.Results:Between 2013 to 2022, the Funding Committee notified 273 decisions regarding misconduct cases, indicating a general upward trend over time. Among the 158 cases with a labeled discovery pathway, the most common way was funding paper retraction by scientific journals, followed by reporting, and then review by the Funding Committee. The majority of individuals involved were from universities (44.81%) and hospitals affiliated with universities (45.45%). The top three most frequent types of misconduct were plagiarism, manipulation of reviews, and falsification. The Fund Committee's handling measures primarily involved in restrictions on applying for national funds within 2~7 years, notifications and criticisms, project withdrawals, and fund recoveries.Conclusions:Over the past ten years, the number of investigations of academic misconduct by the Fund Committee has been increasing, and the way of discovery has shifted from reporting and retraction by research journals to self-investigation by the Fund Committee. Biomedicine is a key field where misconduct occurs, and universities are the primary institutions where such cases are detected. Common causes of academic misconduct include plagiarism, manipulated peer review, and falsification. The foundation typically imposes punishments that restrict funding applications and issues public criticisms. To strengthen the academic integrity system, it is essential to establish and implement an early warning mechanism for academic integrity, reform the scientific research evaluation system, and establish an academic integrity management platform.

Objective To investigate the consistency between mismatch repair proyeins expressions detected by immunohistochemistry(IHC)and microsatellite instability(MSI)identified by next-generation sequencing(NGS),and evaluate the correlation of these results with the clinical characteristics of Chinese colorectal cancer(CRC).Methods Using IHC and NGS to identify mismatch repair(MMR)and MSI status in CRC,and assessing the consistency between these different detection methods.Results The concordance rate of MSI status detected by IHC and NGS was 98.36%,indicating good agreement(Kappa=0.856).Certain pathogenic or likely pathogenic germline variants were present in the pMMR/MSI-H subtype.The co-deficiency of MLH1 and PMS2 was most common in the dMMR/MSS subtype.Patients with inconsistent typing were more likely to have early-onset right-sided colon cancer(P<0.01)and the tumor with relatively poor differentiation.Conclusions The consistency of MSI status detected by IHC and NGS is very high,98%or more.To avoid the misdiagnosis of MSI status affecting clinical decision-making for treatment plans,it is imperative to ensure the accuracy of MSI analysis,particularly in poorly differentiated early-stage right-sided colon cancers.

Objective:To investigate the clinical efficacy of liver transplantation for intra-hepatic cholangiocarcinoma.Methods:The retrospective cohort study was conducted. The clinico-pathological data of 22 patients with intrahepatic cholangiocarcinoma who underwent liver trans-plantation in the 5 medical centers, including First Hospital of Jilin University, et al, from September 2005 to December 2021 were collected. There were 18 males and 4 females, aged 57(range, 38?71)years. Observing indicators: (1) clinicopathological characteristics of patients with intrahepatic cholangiocarcinoma; (2) follow-up; (3) prognosis. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages. The Kaplan-Meier method was used to draw survival curves. The Log-Rank test was used for survival analysis. Results:(1) Clinicopathological characteristics of patients with intrahepatic cholangio-carcinoma. Of the 22 patients, 20 cases were diagnosed as intrahepatic cholangiocarcinoma before liver transplantation, 7 cases had viral hepatitis type B, 1 case had primary sclerosing cholangitis, 7 cases had tumor treatment before liver transplantation, 7 cases, 6 cases and 9 cases were classified as grade A, grade B and grade C of the Child-Pugh classification, 16 cases had preoperative CA19-9 >40 U/mL, 14 cases had single tumor, 11 cases with tumor located at right lobe of liver, 6 cases with tumor located at both left and right lobe of liver, 5 cases with tumor located at left lobe of liver, 9 cases with tumor vascular invasion. All 22 patients were diagnosed as moderate-poor differentiated tumor. There were 9 cases with liver cirrhosis, 4 cases with tumor lymph node metastasis, 10 cases with tumor burden within Milan criteria. The tumor diameter of 22 patients was 4.5(range, 1.5?8.0)cm. (2) Follow-up. All 22 patients were followed up for 15(range, 3?207)months. Of the 22 patients, 9 cases had tumor recurrence and 8 cases died. (3) Prognosis. The 1-year overall survival rate and 1-year disease-free survival rate of the 22 patients was 72.73% and 68.18%, respectively. Results of subgroup analysis showed there were significant differences in overall survival and disease-free survival between the 10 patients with tumor burden within Milan criteria and the 12 patients with tumor burden beyond Milan criteria who underwent liver transplantation ( hazard ratio=0.13, 0.26, 95% confidence interval as 0.03?0.53, 0.08?0.82, P<0.05). Results of further analysis of the 12 patients with tumor burden beyond Milan criteria showed there were significant differences in overall survival and disease-free survival between the 5 patients with preoperative tumor down-staging treatment and the 7 patients without preoperative tumor down-staging treatment ( hazard ratio=0.18, 0.14, 95% confidence interval as 0.04?0.76, 0.04?0.58, P<0.05). Conclusions:Intrahepatic cholangiocarcinoma patients with tumor burden within Milan criteria have a better prognosis than patients with tumor burden beyond Milan criteria after liver transplantation. For patients with tumor burden beyond Milan criteria, active tumor down-staging treatment before liver transplantation can improve the prognosis.

In recent years, the biopharmaceutical industry has developed rapidly, creating urgent demand for high-quality, innovative, and application-oriented talents. In the context of "first-class undergraduate education", it is of great significance to reform and explore biopharmaceutics blended learning to foster professional talents who can adapt to the industrial development. The blended teaching of biopharmaceutics course in Hubei University was based on small private online course (SPOC) and ChaoXing platform, aiming to meet the first-class "AIC (advanced, innovation, challenge)". The course strengthened the three phases of teaching: before, during, and after class, and innovated teaching methods actively to achieve curriculum goals, and integrated typical cases organically. In addition, the course improved the discriminative power of assessment by strengthening the formative performance evaluation. Moreover, the course provided guidance for students to improve the learning efficiency through investigating the students' learning behavior and employing the marginal utility curve to analyze the characteristics of group activities. Furthermore, the course also offered students personalized learning guidance based on their career planning. The reform of biopharmaceutics blended teaching has achieved significant outcomes, such as improving students' satisfaction, students' innovation and entrepreneurship ability, and curriculum construction level, thus may serve as a reference for the teaching reform and research of the related courses.
Humans ; Biopharmaceutics ; Curriculum ; Learning ; Students

Objective:Based on experience of robotic gastrointestinal surgery at the Department of General Surgery, Clinical Medicine Center of Gansu Provincial Hospital, this study explored the principles and methods of trocar layout for robotic "3+2" mode gastrointestinal surgery, suitable for beginners.Methods:From Apr 2017 to Oct 2022, the robotic gastrointestinal surgery team of Gansu Provincial Hospital completed 998 cases of robotic "3+2" mode gastrointestinal surgery, including 600 cases of gastric cancer, 100 cases of rectal cancer, 98 cases of descending colon and sigmoid colon cancer, 20 cases of transverse colon cancer, and 180 cases of right colon cancer. Through the continuous optimization and improvement of the problems encountered during the operation, combined with the operator's experience, and taking into account various aspects, we developed the robotic "3+2" mode trocar layout for gastrointestinal surgery.Results:Four principles of trocar layout were developed, namely, the principle of lens placement around the navel, the principle of symmetry in the main operation, the principle of 8-10cm distance between trocar holes, and the principle of symmetry in the auxiliary hole lens. Three trocar layout methods and principles applicable to robotic gastric surgery, and four applicable to robotic colorectal surgery were developed.Conclusion:The trocar layout method of robotic "3+2" mode gastrointestinal surgery is established based on a large number of robotic gastrointestinal surgery experiences. This method is simple and easy to learn, with strong repeatability and operability.

The uPA-uPAR system is highly expressed in various tumor tissues. This system can promote the degradation of extracellular matrix proteins, as well as combine with vitronectin and integrin to transmit intracellular signal transduction. Subsequently, it mediates the occurrence and development of tumors. In recent years, a series of therapeutic programs that target this system has achieved notable results in tumor treatment, and some of them have been under the clinical trial stage, thus providing new ideas for tumor targeted therapy. Therefore, this paper intends to provide a review of research progress on the gene therapy, drug therapy, and immunotherapy targeting uPA-uPAR system.

Objective To study the process of single stent and double-stent thrombectomy at the Y-shaped bifurcation of the ideal internal carotid artery by finite element simulation, analyze the stent-thrombus-vessel interaction during the thrombectomy process based on the simulation results, and provide guidance for improving the effect of stent thrombectomy at the bifurcation. Methods The CAD software was used to build the model and the finite element analysis software was used to simulate the process of single stent and double-stent thrombectomy. Results Thrombectomy was unsuccessful in single stent model and successful in double-stent model, and the maximum stress of thrombus during embolus retrieval was twice that of single stent, the maximum strain was 1.12 times that of single stent, and the maximum contact pressure on the surface of vessel was approximately twice that of single stent. Conclusions Double Solitaire stents can effectively prevent thrombus displacement at the bifurcation and successfully retrieve the thrombus, but there is a risk of fracture due to the high stress level in the middle section of the thrombus. The contact pressure of the vessel on the anterior artery side is higher during thrombectomy, and the risk of vessel damage is greater. Therefore, it is necessary to optimize the design of the stent-retriever to improve its flexibility.