OBJECTIVES: To explore the value of serum cystatin C (CysC) levels in evaluating renal prognosis in IgA nephropathy (IgAN) patients. METHODS: We retrospectively collected the clinical data of IgAN patients diagnosed by renal biopsy at Guangdong Provincial People's Hospital from January, 2014 to December, 2018. Based on baseline serum CysC levels, the patients were divided into high serum CysC (>1.03 mg/L) group and normal serum CysC (≤1.03 mg/L) group. The composite endpoint for poor renal prognosis was defined as ≥50% decline in estimated glomerular filtration rate (eGFR) and/or progression to end-stage renal disease (ESRD). Lasso regression, multivariate Cox regression and Kaplan-Meier survival analysis were used to identify the risk factors and compare renal survival rates between the two groups. Smooth curves fitting and threshold effect analysis were used to explore the relationship between serum CysC levels and the outcomes. A nomogram model was constructed and its predictive performance was evaluated using concordance index, calibration curve, receiver operating characteristic (ROC) curve and the area under curve (AUC). RESULTS: A total of 356 IgAN patients were enrolled, who were followed up for 4.65±0.93 years. The composite endpoint occurred in 74 patients. High serum CysC was identified as an independent risk factor for poor renal prognosis in IgAN (HR=2.142, 95% CI 1.222 to 3.755), and the patients with high serum CysC levels had a lower renal survival rate (Log-rank χ²=47.970, P<0.001). In patients with serum CysC below 2.12 mg/L, a higher CysC level was associated with an increased risk of poor renal prognosis (β=3.487, 95% CI: 2.561-4.413, P<0.001), while above this level, the increase of the risk was not significant (β=0.676, 95% CI: -0.642-1.995, P=0.315). The nomogram model based on serum CysC and 3 other independent risk factors demonstrated good internal validity with a concordance index of 0.873 (95% CI: 0.839-0.907) and an AUC of 0.909 (95% CI: 0.873-0.945). CONCLUSIONS Serum CysC levels are associated with renal prognosis in IgAN patients, and high serum CysC an independent risk factor for poor renal prognosis.
Humans ; Glomerulonephritis, IGA/diagnosis* ; Cystatin C/blood* ; Prognosis ; Risk Factors ; Retrospective Studies ; Glomerular Filtration Rate ; Kidney Failure, Chronic ; Male ; Female ; Adult ; Nomograms ; Middle Aged

Objective:To compare the efficacy and safety of postauricular injection (PI) and intratympanic injection (II) of glucocorticoids (GC) in the initial treatment of sudden sensorineural hearing loss (SHL).Methods:Electronic databases retrieval (PubMed, Web of Science, CNKI, VIP, WANFANG) was performed to identify all randomized controlled trials about PI and II of GC in the initial treatment of SHL between 2015 and 2024. Meta-analysis was performed on the studies met the inclusion criteria by RevMan5.4.Results:A total of 971 articles were retrieved, and 23 Chinese articles were included after screening. Meta-analysis found that the total effective rate of PI was significantly higher than that of II ( OR=1.37, 95% CI:1.15-1.65, P=0.000 6), with higher recovery of the hearing threshold (SMD=1.24, 95% CI:0.01-2.46, P=0.05) and a lower incidence of adverse reactions and complications ( OR=0.20, 95% CI:0.15-0.28, P<0.000 01). Conclusions:Compared with II, PI has a better efficacy and safety. Nonetheless, whatever topical administration of GC that can be regarded as the first choice of initial therapeutic schedules to SHL requires further studied.

BACKGROUND:As a common disease in middle-aged and elderly,osteoarthritis is difficult to cure,and the pathogenesis is not clear.Long non-coding RNA participates in the pathogenesis of osteoarthritis through many ways,such as regulating translation,promoting or inhibiting mRNA,and adsorbing miRNAs. OBJECTIVE:To review the types of common long non-coding RNA in osteoarthritis,and the influence of multiple long non-coding RNAs on the pathological factors related to osteoarthritis,to analyze the future application of long non-coding RNAs in osteoarthritis. METHODS:Literature retrieval was conducted in CNKI,WanFang Data,VIP database,PubMed,Web of Science and Sciencedirect databases,using the search terms of"osteoarthritis,degenerative joint disease,degenerative arthritis,OA,LncRNA,long non-coding RNA,long noncoding RNA,long intergenic non-coding RNA"in Chinese and English.All relevant literature published from 1976 and May 2024 was retrieved.After literature screening,induction,analysis and summary,93 articles were finally included for review. RESULTS AND CONCLUSION:This review collected 25 long non-coding RNAs that are well studied with osteoarthritis.Long non-coding RNAs,as a molecular sponge for miRNA,are competing endogenous RNAs to competitively adsorb miRNAs and then affect downstream targets.Long non-coding RNAs can regulate physiopathological processes such as chondrocyte apoptosis and proliferation,cartilage extracellular matrix degradation,and inflammatory responses.Long non-coding RNAs are expected to become a biomarker and potential therapeutic target for the clinical diagnosis and therapeutic prognosis of osteoarthritis,and it may become a new strategy for the clinical treatment of osteoarthritis in the future.

Objective:To compare the efficacy and safety of postauricular injection (PI) and intratympanic injection (II) of glucocorticoids (GC) in the initial treatment of sudden sensorineural hearing loss (SHL).Methods:Electronic databases retrieval (PubMed, Web of Science, CNKI, VIP, WANFANG) was performed to identify all randomized controlled trials about PI and II of GC in the initial treatment of SHL between 2015 and 2024. Meta-analysis was performed on the studies met the inclusion criteria by RevMan5.4.Results:A total of 971 articles were retrieved, and 23 Chinese articles were included after screening. Meta-analysis found that the total effective rate of PI was significantly higher than that of II ( OR=1.37, 95% CI:1.15-1.65, P=0.000 6), with higher recovery of the hearing threshold (SMD=1.24, 95% CI:0.01-2.46, P=0.05) and a lower incidence of adverse reactions and complications ( OR=0.20, 95% CI:0.15-0.28, P<0.000 01). Conclusions:Compared with II, PI has a better efficacy and safety. Nonetheless, whatever topical administration of GC that can be regarded as the first choice of initial therapeutic schedules to SHL requires further studied.

OBJECTIVE: A prospective randomized controlled study was conducted to investigate the early postoperative analgesic effectiveness of using liposomal bupivacaine (LB) for local infiltration anesthesia (LIA) in unicompartmental knee arthroplasty (UKA). METHODS: Between January 2024 and July 2024, a total of 80 patients with knee osteoarthritis (KOA) who met the selection criteria were enrolled in the study. Patients were randomly assigned to either the LB group or the "cocktail" group in a 1∶1 ratio using a random number table, with 40 patients in each group. Baseline characteristics, including gender, age, body mass index, operated side, Kellgren-Lawrence grade, and preoperative American Society of Anesthesiologists (ASA) classification, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and knee joint range of motion, showed no significant difference between the two groups ( P>0.05). Both groups received LIA and comprehensive pain management. The surgical duration, incision length, pain-related indicators [resting and activity visual analogue scale (VAS) scores, total dosage of oral morphine, WOMAC scores], knee joint range of motion, first ambulation time after operation, length of hospital stay, and postoperative adverse events. RESULTS: There was no significant difference between the two groups in surgical duration, incision length, first ambulation time after operation, length of hospital stay, total dosage of oral morphine, and pre-discharge satisfaction with surgery and WOMAC scores ( P>0.05). At 4, 12, and 24 hours after operation, the resting and activity VAS scores in the "cocktail" group were lower than those in the LB group; at 60 and 72 hours postoperatively, the resting VAS scores in the LB group were lower than those in the "cocktail" group, with the activity VAS scores also being lower at 60 hours; all showing significant differences ( P<0.05). There was no significant difference in the above indicators between the two groups at other time points ( P>0.05). On the second postoperative day, the sleep scores of the LB group were significantly higher than those of the "cocktail" group ( P<0.05), while there was no significant difference in sleep scores on the day of surgery and the first postoperative day ( P>0.05). Additionally, the incidence of complications showed no significant difference between the two groups ( P>0.05). CONCLUSION The use of LB for LIA in UKA can provide prolonged postoperative pain relief; however, it does not demonstrate a significant advantage over the "cocktail" method in terms of short-term analgesic effects or reducing opioid consumption and early functional recovery after UKA. Nevertheless, LB may help reduce postoperative sleep disturbances, making it a recommended option for UKA patients with cardiovascular diseases and insomnia or other mental health issues.
Aged ; Female ; Humans ; Male ; Middle Aged ; Anesthesia, Local/methods* ; Anesthetics, Local/administration & dosage* ; Arthroplasty, Replacement, Knee/methods* ; Bupivacaine/administration & dosage* ; Liposomes ; Osteoarthritis, Knee/surgery* ; Pain Measurement ; Pain, Postoperative/prevention & control* ; Prospective Studies ; Treatment Outcome

The orphan nuclear receptor Nur77 is emerging as an attractive target for cancer therapy, and activating Nur77's non-genotypic anticancer function has demonstrated strong therapeutic potential. However, few Nur77 site B ligands have been identified as excellent anticancer compounds. There are no co-crystal structures of effective anticancer agents at Nur77 site B, which greatly limits the development of novel Nur77 site B ligands. Moreover, the lack of pharmaceutical ligands restricts Nur77's therapeutic proof of concept. Herein, we developed a first-in-class Nur77 site B ligand (NB1) that significantly inhibited cancer cells by mediating the Nur77/Bcl-2-related apoptotic effect at mitochondria. The X-ray crystallography suggests that NB1 is bound to the Nur77 site B with a distinct binding mode. Importantly, NB1 showed favorable pharmacokinetic profiles and safety, as evidenced by its good oral bioavailability in rats and lack of mortality, bodyweight loss, and pathological damage at the 512.0 mg/kg dose in mice. Furthermore, oral administration of NB1 demonstrated remarkable in vivo anticancer efficacy in an MDA-MB-231 xenograft model. Together, our work discovers NB1 as a new generation Nur77 ligand that activates the Nur77/Bcl-2 apoptotic pathway with a safe and effective cancer therapeutic potency.

Purpose/Significance To use multimodal data analysis method to mine medical Q&A data in online healthcare platforms and predict whether patients will adopt online doctors'responses.Method/Process First,numerical,categorical,textual,and visual data related to doctor-patient Q&A are obtained from online healthcare platforms,and three datasets of acute disease,chronic disease and mixed disease are constructed according to disease types.Then,normalization,one-hot encoding,Med-BERT,and convolutional neural network are used respectively to process numerical,categorical,textual,and visual data.Finally,a gradient boosting decision tree is used to predict whether patients will adopt online doctors'responses.Result/Conclusion Doctors'profile pictures can improve the prediction effect of online doctor response adoption,and multimodal data mining can effectively predict the response adoption.

Brain-computer interfaces (BCIs) have become one of the cutting-edge technologies in the world, and have been mainly applicated in medicine. In this article, we sorted out the development history and important scenarios of BCIs in medical application, analyzed the research progress, technology development, clinical transformation and product market through qualitative and quantitative analysis, and looked forward to the future trends. The results showed that the research hotspots included the processing and interpretation of electroencephalogram (EEG) signals, the development and application of machine learning algorithms, and the detection and treatment of neurological diseases. The technological key points included hardware development such as new electrodes, software development such as algorithms for EEG signal processing, and various medical applications such as rehabilitation and training in stroke patients. Currently, several invasive and non-invasive BCIs are in research. The R&D level of BCIs in China and the United State is leading the world, and have approved a number of non-invasive BCIs. In the future, BCIs will be applied to a wider range of medical fields. Related products will develop shift from a single mode to a combined mode. EEG signal acquisition devices will be miniaturized and wireless. The information flow and interaction between brain and machine will give birth to brain-machine fusion intelligence. Last but not least, the safety and ethical issues of BCIs will be taken seriously, and the relevant regulations and standards will be further improved.
Humans ; Brain-Computer Interfaces ; Medicine ; Algorithms ; Artificial Intelligence ; Brain

In contrast to traditional representational perspectives in which the motor cortex is involved in motor control via neuronal preference for kinetics and kinematics, a dynamical system perspective emerging in the last decade views the motor cortex as a dynamical machine that generates motor commands by autonomous temporal evolution. In this review, we first look back at the history of the representational and dynamical perspectives and discuss their explanatory power and controversy from both empirical and computational points of view. Here, we aim to reconcile the above perspectives, and evaluate their theoretical impact, future direction, and potential applications in brain-machine interfaces.
Biomechanical Phenomena ; Brain-Computer Interfaces ; Motor Cortex/physiology* ; Neurons/physiology*