RNA-binding proteins (RBPs) are ubiquitous components within cells, fulfilling essential functions in a myriad of biological processes. These proteins interact with RNA molecules to regulate gene expression at various levels, including transcription, splicing, transport, localization, translation, and degradation. Understanding the intricate network of RBP-RNA interactions is crucial for deciphering the complex regulatory mechanisms that govern cellular function and organismal development. Ultravidet (UV) cross-linking and immunoprecipitation (CLIP) stands out as a powerful approach designed to map the precise locations where RBPs bind to RNA. By using UV light to create covalent bonds between proteins and RNA, followed by immunoprecipitation to isolate the protein-RNA complexes, researchers can identify the direct targets of specific RBPs. The advent of high-throughput sequencing technologies has revolutionized CLIP, enabling the identification of not only the types but also the exact sequences of RNA bound by RBPs on a genome-wide scale. The evolution of CLIP has led to the development of specialized variants, each with unique features that address specific challenges and expand the scope of what can be studied. High-throughput sequencing CLIP (HITS-CLIP) was one of the first advancements, significantly increasing the throughput and resolution of RNA-protein interaction mapping. Photoactivatable-ribonucleoside-enhanced CLIP (PAR-CLIP) introduced the use of photoactivatable ribonucleosides to enhance cross-linking efficiency and specificity, reducing background noise and improving the detection of low-abundance RNA-protein interactions. Individual-nucleotide resolution CLIP (iCLIP) further refined the technique, achieving unprecedented precision by resolving individual nucleotides involved in RBP binding, which is particularly valuable for studying the fine details of RNA structure and function. Despite the remarkable progress, there remains room for improvement in CLIP technology. Researchers continue to seek methods to increase sensitivity, reduce technical variability, and improve the reproducibility of results. Advances in sample preparation, data analysis algorithms, and computational tools are critical for addressing these challenges. Moreover, the application of CLIP to more diverse biological systems, including non-model organisms and clinical samples, requires the development of tailored protocols and the optimization of existing ones. Looking forward, the field of RNA biology is poised to benefit greatly from ongoing innovations in CLIP technology. The exploration of non-canonical RNA-protein interactions, such as those involving long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), promises to reveal new layers of cellular regulation and may lead to the discovery of novel therapeutic targets. Furthermore, integrating CLIP data with other omics approaches, such as proteomics and metabolomics, will provide a more comprehensive understanding of the dynamic interplay between RNA and its binding partners within the cell. In conclusion, the continuous refinement and expansion of CLIP techniques have not only deepened our knowledge of RNA biology but have also opened up new avenues for investigating the molecular underpinnings of health and disease. As the technology matures, it is expected to play an increasingly pivotal role in both basic and applied research, contributing to the advancement of medical science and biotechnology.

[This corrects the article DOI: 10.1016/j.apsb.2021.08.008.].

Objective To investigate the association between the serum creatinine/cystatin C ratio(SCr/Cys C)as a Sarcopenia index(SI)and the incidence of in-hospital adverse events in patients with acute myocardial infarction(AMI)undergoing emergency percutaneous coronary intervention(PCI).Additionally,we evaluate the predictive efficacy of the SI in predicting major adverse cardiovascular events(MACEs)during hospitalization.Methods A total of 306 patients with AMI who underwent emergency PCI in the 904th Hospital of PLA Joint Logistics Support Force from January 2020 to March 2023 were consecutively included in this retrospective analysis.Patients were divided into two groups based on the occurrence of MACEs during hospitalization:MACEs group(n=43)and non-MACEs group(n=263).Clinical characteristics and pre-PCI laboratory test results were collected.Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for MACEs.The predictive performance of SI was assessed using receiver operating characteristic(ROC)curve analysis.Results The incidence of in-hospital MACEs in AMI patients was 14.1%.The results of the independent samples t-test showed that the SI level in MACEs group was significantly lower than that in non-MACEs group,with a statistically significant difference(P<0.001).The results of the multivariate logistic regression analysis suggested that new-onset atrial fibrillation,Killip class 2-4,SI,and TG were independent risk factors for in-hospital adverse events after emergency PCI.The ROC curve results showed that the predictive value of SI(AUC=0.741,95%CI 0.666-0.816)using the SCr/Cys C ratio was superior to that of single Cys C(AUC=0.658,95%CI 0.570-0.746)for predicting post-PCI MACEs,with a statistically significant difference(P<0.05),and the optimal cutoff value for SI was 78.14.After stratifying SI based on the cutoff value,the results of the independent samples t-test showed that compared to the higher SI group,the lower SI group had a higher occurrence of specific adverse events such as heart failure(P<0.001),malignant arrhythmias(P=0.009),and strokes(P=0.003),with statistically significant differences.Conclusions The results highlight SI as an independent risk factor for MACEs during hospitalization after emergency PCI in AMI patients.Furthermore,SI has proven to be an effective prognostic index for patient outcomes.

Objective Discuss the safety and effectiveness of flow diverter device and traditional stent inthetreatment of unruptured ophthalmic segment aneurysms.Methods A retrospective analysis from January 2017 to January 2023 was performed on the clinical data of 70 cases of unruptured aneurysms in the Department of Neurosurgery of Southern Theater General Hospital treated with stent-assisted embolization.According to the type of implanted stents,theywere divided into flow diverter device group(n = 21)and traditional stent group(n = 49),and the postoperative clinical effects and complications of the two groups were compared.Results The two groups of patients followed 3 to 24 months,with an average of(14.4±1.82)months.The results of periopera-tive and follow-up showed that the inclusion rate was higher in the flow diverter device group and the traditional stent group(93.3%vs.87.9%),with no significant difference(P>0.05),and the incidence of perioperative and short-term complications was lower(0 vs.6.1%)in the flow diverter device group than in the traditional stent group,and there currencies rate in the flow diverter device group was lower than that in the traditional stent group(0 vs.6.1%),but the difference was not significant(P>0.05).Conclusion Flow diverter devices and traditional stents in the treatment of unruptured ophthalmic segment aneurysmsare feasible,safe and effective.Preliminary results suggest that the incidence of short-term complications and retreatment is lower after treatment with flow diverter devices,and the operation time is short,but further studies are needed to validate long-term complica-tions in patients.

OBJECTIVE To establish a ultra-high-performance liquid chromatography-mass spectrum/mass spectrum(UPLC-MS/MS) method for the determination of anlotinib in human plasma and assessment of clinical application. METHODS Zanubrutinib was used as internal standard and the extraction process was performed through protein precipitation method using acetonitrile, followed by separation on an Ultimate XB-C18(100 mm×2.1 mm, 3.0 μm) column using acetonitrile and 10 mmol·L−1 ammonium acetate-0.1% formic acid step-elution gradient. The flow rate was 0.6 mL·min−1 and injection volume was 5 μL. The mass analysis was performed by positive ion electrospray ionization in multiple-reaction monitoring mode, and the mass spectrometer was set at m/z 408.1→339.1 for anlotinib and m/z 472.2→290.1 for internal standard, respectively. The specificity, standard curve and lower limit of quantification, precision and recovery, matrix effect and stability of the method and clinical application were investigated. RESULTS The method was validated over the concentration range of 1.0−100.0 ng·mL−1, with R2=0.998 4. The precision RSD was<9%, the recovery and matrix effect were 104.81%−107.32% and 102.54%−105.26%, respectively, and this method had good stability and was not affected by matrix effect. The method had been used for determined 52 advanced non-small cell lung cancer patients treated with anlotinib. The trough plasma concentration (Ctrough) was measured on day 43 after initiation of anlotinib treatment. Anlotinib Ctrough were higher than lower limit of quantitation (1.0 ng·mL−1) from 52 patients. The plasma concentration of anlotinib Ctrough was (11.38±4.29)ng·mL−1 with 37.66% coefficients of variation, which were shown large inter-patient variability. CONCLUSION This method is high sensitivity, specificity and accurate, and suitable for determination of anlotinib in human plasma.

Objective:To investigate the application value of a multi-dimensional digital moni-toring platform for perioperative period in gastric cancer patients.Methods:The retrospective cohort study was conducted. The clinical data of 50 patients who underwent laparoscopic radical gastrec-tomy in The Affiliated Hospital of Nanjing University of Chinese Medicine from July 2022 to January 2024 were collected. There were 35 males and 15 females, aged (64±12)years. All patients followed the concept of enhanced recovery after surgery, and the multi-dimensional digital monitoring platform based on wearable monitoring equipment was used to implement perioperative management measures. Observation indicators: (1) results of heart rate variability (HRV) monitoring; (2) results of blood glucose and blood oxygen monitoring; (3) results of exercise and sleep monitoring; (4) results of body composition monitoring. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(IQR). Repeated measurement data were analyzed using the repeated ANOVA. Measurement data with skewed distri-bution were transformed to normal distribution by SPSS transformation function before testing. For comparison between pre- and postoperation, paired sample t test was used for measurement data with normal distribution, and nonparametric Wilcoxon signed rank sum test was used for measure-ment data with skewed distribution. Results:(1) Results of HRV monitoring. From preoperation to the third day after surgery, the standard deviation normal to normal heart beat of 50 patients was changed from(103±26)ms to(101±36)ms, the mean of the standard deviations of normal to normal heart beat calculated per 5 min segment was changed from (45±16)ms to(33±12)ms, the number of pairs of adjacent NN intervals differing by more than 50 ms in the entire recording was changed from 6.02%(4.96%) to 5.79%(4.20%), the low frequency power was changed from 376.78(468.96)ms 2 to 742.79(525.20)ms 2, the high frequency power was changed from 273.61(273.58)ms 2 to 397.48(164.87)ms 2, the ratio of low frequency power to high frequency power was changed from 1.6±0.5 to 1.6±0.6, showing significant differences in above indicators before and after operation ( F=34.43, 26.15, 24.58, 5.51, 6.11, 6.02, P<0.05). (2) Results of blood glucose and blood oxygen monitoring. From preoperation to the third day after surgery, the blood glucose of 50 patients was changed from 6.75(2.05)mmol/L to 6.90(2.63)mmol/L, showng a significant difference before and after operation ( F=45.84, P<0.05). The blood oxygen was changed from 97.00%(5.00%) to 97.50%(3.00%), showing no significant difference before and after operation ( F=2.25, P>0.05). (3) Results of exercise and sleep monitoring. From preoperation to the third day after surgery, the number of steps fo 50 pati-ents was changed from 3 043(1 224) to 1 473(767), sleep duration was changed from(8.2±1.1)hours to(7.3±0.8)hours, sleep score was changed from 80±10 to 78±5,showing significant differences in above indicators before and after operation ( F=716.46, 29.02, 47.32, P<0.05).(4) Results of body composition monitoring. The body weight of 50 patients was changed from (63±8)kg to(61±8)kg before and after operation, body fat rate was changed from 24%±8% to 22%±9%, muscle mass was changed from 43 (12)kg to 41(17)kg, body mass index was changed from (23.0±2.6)kg/m 2 to(22.1±2.5)kg/m 2, showing significant differences in above indicators before and after operation ( t=8.19, 3.00, Z=-2.78, t=7.34, P<0.05), while there was no significant difference in basal metabolic indicators from (1 390±134)kcal to (1 379±139)kcal before and after operation ( t=1.02, P>0.05). Conclusion:The multi-dimensional digital monitoring platform for preoperative period can accurately monitor the perioperative stress level and evaluate the postoperative recovery of gastric cancer patients, which can present the visual results.

Humans ; Consensus ; Pancreatic Neoplasms/therapy* ; Neuroendocrine Tumors/therapy*

OBJECTIVE: To investigate the effects of two types of temperature rinses on body temperature, inflammatory cytokine levels, and bleeding volume in percutaneous endoscopic lumbar discectomy. METHODS: Eighty patients underwent percutaneous endoscopic lumbar discectomy from January 2018 to December 2020 were selected and divided into experimental group (40 cases) and control group(40 cases). In experimental group, there were 19 males and 21 females, aged (38.8±9.8) years old;7patients on L_4,5 and 33 patients on L₅S₁;Body msss index(BMI) was (27.8±7.2) kg·m^-2. In contral group, there were 18 males and 22 females, aged (41.5±10.9) years old, 5 patients on L_4,5 and 35 patients on L₅S₁;BMI was (26.4±6.2) kg·m^-2. The patients in the control group were received normal saline rinse at room temperature, and the patients in the experimental group were received normal saline rinse heated to 37 ℃. Body temperature, chills, nausea, vomiting, and other adverse reactions were recorded. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) in two groups were recorded before and 2 hours after operation. Visual analogue scale (VAS) was used to evaluate the degree of lumbar pain in two groups before and 2 hours after surgery. Fibrinolytic-coagulation indexes with preoperative and 2 hours after surgery, including the D-dimer (DD), fibrinogen degradation products (FDP), activated partial thrombin time (APTT) and prothrombin time (PT) were recorder. Operation time and blood loss in two groups were recorded. RESULTS: The body temperature of both groups showed a downward trend, while the body temperature of the control group was lower than that of the experimental group. The levels of TNF-α, IL-6 and IL-10 in two groups were increased 2 hours after surgery compared with those before surgery(P<0.05), while the levels in experimental group were lower than those in control group(P<0.05). Postoperative VAS in experimental group 2.19±1.13 was significantly lower than that in the control group 3.38±1.35(P<0.05). The levels of DD and FDP at 2 hours after surgery in both groups were higher than those before surgery (P<0.05), while the levels of DD and FDP in the experimental group were higher than those in the control group (P<0.05). There was no significant difference in APTT and PT levels between two groups after operation (P>0.05). The blood loss in the experimental group of (45.2±14.1) ml was lower than that in the control group of (59.52±15.6) ml. The operation time of experimental group (46.7±13.8) min was less than that of control group (58.3±15.2) min(P<0.05). CONCLUSION Body temperature rinse can reduce the incidence of adverse reactions, alleviate local inflammatory reactions, reduce intraoperative blood loss and shorten the operation time.
Female ; Male ; Humans ; Adult ; Middle Aged ; Diskectomy, Percutaneous ; Interleukin-10 ; Body Temperature ; Interleukin-6 ; Saline Solution ; Tumor Necrosis Factor-alpha ; Intervertebral Disc Displacement/surgery* ; Lumbar Vertebrae/surgery* ; Diskectomy

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

This study aims to characterize the cell atlas of the epididymis derived from a 46,XY disorders of sex development (DSD) patient with a novel heterozygous mutation of the nuclear receptor subfamily 5 group A member 1 (NR5A1) gene. Next-generation sequencing found a heterozygous c.124C>G mutation in NR5A1 that resulted in a p.Q42E missense mutation in the conserved DNA-binding domain of NR5A1. The patient demonstrated feminization of external genitalia and Tanner stage 1 breast development. The surgical procedure revealed a morphologically normal epididymis and vas deferens but a dysplastic testis. Microfluidic-based single-cell RNA sequencing (scRNA-seq) analysis found that the fibroblast cells were significantly increased (approximately 46.5%), whereas the number of main epididymal epithelial cells (approximately 9.2%), such as principal cells and basal cells, was dramatically decreased. Bioinformatics analysis of cell-cell communications and gene regulatory networks at the single-cell level inferred that epididymal epithelial cell loss and fibroblast occupation are associated with the epithelial-to-mesenchymal transition (EMT) process. The present study provides a cell atlas of the epididymis of a patient with 46,XY DSD and serves as an important resource for understanding the pathophysiology of DSD.
Male ; Humans ; Epididymis ; Disorder of Sex Development, 46,XY/genetics* ; Disorders of Sex Development ; Mutation ; Mutation, Missense ; Steroidogenic Factor 1/genetics*