ObjectiveTo evaluate the effects of Tongnaoyin on the blood-brain barrier status and neurological impairment in acute ischemic stroke （AIS） patients with the syndrome of phlegm-stasis blocking collaterals by dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI）. MethodsA total of 63 patients diagnosed with AIS in the Jiangsu Province Hospital of Chinese Medicine from October 2022 to December 2023 were enrolled in this study. According to random number table method，the patients were assigned into a control group （32 cases） and an observation group （31 cases）. The control group received conventional Western medical treatment，and the observation group took 200 mL Tongnaoyin after meals，twice a day from day 2 of admission on the basis of the treatment in the control group. After 7 days of treatment，the patients were examined by DCE-MRI. The baseline data for two groups of patients before treatment were compared. The National Institute of Health Stroke Scale （NIHSS） score and modified Rankin Scale （mRS） score were recorded before treatment and after 90 days of treatment for both groups. The rKtrans，rKep，and rVe values were obtained from the region of interest （ROI） of the infarct zone/mirror area and compared between the two groups. ResultsThere was no significant difference in the NIHSS or mRS score between the two groups before treatment. After 90 days of treatment，the NIHSS and mRS scores declined in both groups，and the observation group had lower scores than the control group （P<0.05）. After treatment，the rKtrans and rVe in the observation group were lower than those in the control group （P<0.01）. ConclusionCompared with conventional Western medical treatment alone，conventional Western medical treatment combined with Tongnaoyin accelerates the repair of the blood-brain barrier in AIS patients，thereby ameliorating neurological impairment after AIS to improve the prognosis.

Biliary atresia （BA） is characterized by progressive inflammation and fibrous obstruction of bile ducts， ultimately leading to cholestatic liver cirrhosis. Kasai surgery is the standard procedure for the treatment of BA， and early diagnosis is a key influencing factor for the prognosis of BA. Indocyanine green （ICG） is a near-infrared photosensitive dye that is efficiently and selectively absorbed by hepatocytes after intravenous injection， and it enters the intestine via bile and is excreted with the feces in the free form， with a favorable safety profile. In addition， ICG can emit fluorescence under near-infrared light， which can be captured by camera instruments and converted into visual images， and ICG fluorescence imaging technology can reflect the intraoperative situation in real time and significantly improve the success rate of the surgical procedure. This article reviews the advances in the application of ICG in early preoperative diagnosis， intraoperative imaging， and postoperative liver function assessment in recent years.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

BACKGROUND: Fibrosis of the connective tissue in the vaginal wall predominates in pelvic organ prolapse (POP), which is characterized by excessive fibroblast-to-myofibroblast differentiation and abnormal deposition of the extracellular matrix (ECM). Our study aimed to investigate the effect of ECM stiffness on vaginal fibroblasts and to explore the role of methyltransferase 3 (METTL3) in the development of POP. METHODS: Polyacrylamide hydrogels were applied to create an ECM microenvironment with variable stiffness to evaluate the effects of ECM stiffness on the proliferation, differentiation, and expression of ECM components in vaginal fibroblasts. METTL3 small interfering RNA and an overexpression vector were transfected into vaginal fibroblasts to evaluate the effects of METTL3 silencing and overexpression on matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal modulation of the ECM. Both procedures were detected by 5-ethynyl-2'-deoxyuridine (EdU) staining, Western blotting (WB), quantitative real-time polymerase chain reaction (RT-qPCR), and immunofluorescence (IF). RESULTS: Vaginal fibroblasts from POP patients exhibited increased proliferation ability, increased expression of α-smooth muscle actin (α-SMA), decreased expression of collagen I/III, and significantly decreased expression of tissue inhibitors of matrix metalloproteinases (TIMPs) in the stiff matrix ( P <0.05). Compared with those from non-POP patients, vaginal wall tissues from POP patients demonstrated a significant increase in METTL3 content ( P <0.05). However, silencing METTL3 expression in vaginal fibroblasts with high ECM stiffness resulted in decreased proliferation ability, decreased α-SMA expression, an increased ratio of collagen I/III, and increased TIMP1 and TIMP2 expression. Conversely, METTL3 overexpression significantly promoted the process of increased proliferation ability, increased α-SMA expression, decreased ratio of collagen I/III and decreased TIMP1 and TIMP2 expression in the soft matrix ( P <0.05). CONCLUSIONS Elevated ECM stiffness can promote excessive proliferation, differentiation, and abnormal ECM modulation, and the expression of METTL3 plays an important role in alleviating or aggravating matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal ECM modulation.
Humans ; Female ; Extracellular Matrix/metabolism* ; Cell Differentiation/genetics* ; Methyltransferases/metabolism* ; Pelvic Organ Prolapse/pathology* ; Fibroblasts/metabolism* ; Myofibroblasts/metabolism* ; Vagina/metabolism* ; Cell Proliferation/physiology* ; Cells, Cultured ; Middle Aged

In recent years, hybrid brain-computer interfaces (BCIs) have gained significant attention due to their demonstrated advantages in increasing the number of targets and enhancing robustness of the systems. However, Existing studies usually construct BCI systems using intense auditory stimulation and strong central visual stimulation, which lead to poor user experience and indicate a need for improving system comfort. Studies have proved that the use of peripheral visual stimulation and lower intensity of auditory stimulation can effectively boost the user's comfort. Therefore, this study used high-frequency peripheral visual stimulation and 40-dB weak auditory stimulation to elicit steady-state visual evoked potential (SSVEP) and auditory steady-state response (ASSR) signals, building a high-comfort hybrid BCI based on weak audio-visual evoked responses. This system coded 40 targets via 20 high-frequency visual stimulation frequencies and two auditory stimulation frequencies, improving the coding efficiency of BCI systems. Results showed that the hybrid system's averaged classification accuracy was (78.00 ± 12.18) %, and the information transfer rate (ITR) could reached 27.47 bits/min. This study offers new ideas for the design of hybrid BCI paradigm based on imperceptible stimulation.
Brain-Computer Interfaces ; Humans ; Evoked Potentials, Visual/physiology* ; Acoustic Stimulation ; Photic Stimulation ; Electroencephalography ; Evoked Potentials, Auditory/physiology* ; Adult

OBJECTIVE: To investigate the analgesic effect of locally injecting a "cocktail" analgesia containing a high-dose compound betamethasone during revision hip arthroplasty, and also to study the usage of opioid drugs. METHODS: A retrospective analysis was conducted on the clinical data of 180 patients who underwent revision hip arthroplasty due to aseptic loosening of the hip prosthesis between January 2015 and December 2021. Among them, 95 patients received intraoperative injection of "cocktail" analgesia containing high-dose compound betamethasone (group A), and 85 patients received intraoperative injection of traditional "cocktail" analgesia (group B). There was no significant difference in baseline data such as gender, age, body mass index, presence or absence of diabetes mellitus between the two groups ( P>0.05). The hospital stay, use of opioid drugs within 72 hours, and the incidence of adverse reactions within 72 hours after operation [including nausea and vomiting, insomnia, deep venous thrombosis (DVT), infection, etc.] were recorded and compared between the two groups. The pain relief of patients was evaluated using the static and dynamic visual analogue scale (VAS) scores at 12, 24, 48, and 72 hours after operation. The incidence of complications (including prosthesis re-loosening, hip joint dislocation, hip joint stiffness, limping, chronic pain, etc.) at 2 years after operation was recorded, and the Harris Hip Score (HHS) was used to evaluate the function at 2 years after operation. RESULTS: In group A, the utilization rate of opioid drugs within 72 hours after operation was significantly lower than that in group B ( P<0.05). However, there was no significant difference between the two groups in terms of hospital stay, as well as the incidence of adverse reactions such as nausea and vomiting, insomnia, DVT, and infection within 72 hours after operation ( P>0.05). The VAS scores of both groups decreased with time, and the differences between different time points were significant ( P<0.05). The static and dynamic VAS scores of group A were significantly lower than those of group B at 12, 24, and 48 hours after operation ( P<0.05), but there was no significant difference in static and dynamic VAS scores between the two groups at 72 hours after operation ( P>0.05). All patients in both groups were followed up 2-8 years, with an average of 5.73 years. At 2 years after operation, no significant difference was found between the two groups in the incidence of complications and HHS score ( P>0.05). CONCLUSION "Cocktail" analgesia containing a high-dose compound betamethasone for early analgesia after revision hip arthroplasty can effectively reduce postoperative pain and the use of opioid drugs, but will not increase the incidence of infection and DVT after operation.
Humans ; Arthroplasty, Replacement, Hip/adverse effects* ; Betamethasone/therapeutic use* ; Retrospective Studies ; Male ; Female ; Analgesics, Opioid/administration & dosage* ; Pain, Postoperative/prevention & control* ; Middle Aged ; Reoperation ; Aged ; Analgesia/methods* ; Adult ; Pain Measurement ; Pain Management/methods* ; Prosthesis Failure ; Hip Prosthesis

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

ObjectiveTo investigate the changes in cerebral blood perfusion in patients with acute cerebral infarction after taking Tongnaoyin， a traditional Chinese medicine， based on head and neck computed tomography （CT） angiography （CTA） combined with brain CT perfusion imaging （CTP）. MethodA total of 240 patients with cerebral infarction of phlegm and blood stasis syndrome treated in Jiangsu Province Hospital of Traditional Chinese Medicine from March 2018 to September 2023 were randomly divided into a control group （99 cases） and a Tongnaoyin group （141 cases）. Based on the guidelines， the control group was treated with conventional treatment such as anti-aggregation， anticoagulation， lipid-lowering and plaque stabilization， brain protection， and supportive treatment. The Tongnaoyin group was treated with Tongnaoyin of 200 mL in warm conditions in the morning and evening on the basis of the control group. Both groups underwent CTA combined with CTP within 24 hours after admission， and they were reexamined by CTA and CTP in the sixth month after admission. The degree of intracranial artery stenosis was determined according to the North American Symptomatic Carotid Endarterectomy Trial （NASCET） method. The relative cerebral blood volume （rCBV）， relative cerebral blood flow （rCBF）， mean transit time （MTT）， and time to peak （TTP） of the lesion area before and after treatment were compared. The adverse outcomes of the two groups within six months after discharge were compared. ResultCompared with the group before treatment， the degree of vascular stenosis in the Tongnaoyin group was significantly reduced， and the difference was statistically significant （Z=105.369，P<0.05）. Compared with the control group after treatment， the improvement rate of vascular stenosis in the Tongnaoyin group was higher （χ²=84.179，P<0.01）， and the curative effect was better.After treatment， the rCBV and rCBF of patients in the Tongnaoyin group were significantly increased， and the difference was statistically significant （P<0.01）. MTT and TTP showed a trend of shortening， but the difference was not statistically significant. There was no statistically significant difference in rCBV， rCBF， MTT， and TTP in the control group. Compared with those in the control group after treatment， the rCBV and rCBF in the Tongnaoyin group were significantly increased， while MTT and TTP were significantly reduced （P<0.01）. After six months of discharge， the risk of poor prognosis in the Tongnaoyin group was significantly reduced compared with the control group （P<0.05）. ConclusionTongnaoyin has a good effect on improving cerebral blood perfusion in patients with acute cerebral infarction. It can be used as an effective supplement for the conventional treatment of ischemic stroke to improve clinical efficacy.

Objective:To investigate the expression of long non-coding RNA(lncRNA) ZFP36-AS1 in bladder cancer and the effect of ZFP36-AS1/miR-221 axis on the proliferation and immune escape of bladder cancer cells.Methods:The expression difference of ZFP36-AS1 in bladder cancer tissues was analyzed by cBioPortal database. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to analyze the expression difference of ZFP36-AS1 in bladder cancer cell lines (J82, RT-4, MGH-U3, 5637). MGH-U3 cells were randomly divided into negative control (NC) group and ZFP36-AS1 group, which were transfected with pcDNA3.1-NC plasmid and pcDNA3.1-ZFP36-AS1 plasmid, respectively. Colony formation assay and flow cytometry were used to analyze the proliferation activity and cell cycle of MGH-U3 cells, respectively. T lymphocytes were co-cultured with MGH-U3 cells in each group, and the levels of interleukin-10 (IL-10), γ-interferon (IFN-γ), and interleukin-4 (IL-4) in the supernatants of each group were detected by enzyme-linked immunosorbent assay (ELISA). The dual-luciferase reporter gene assay verified the targeting relationship between ZFP36-AS1 and miR-221. The effect of ZFP36-AS1 on the expression of miR-221 in MGH-U3 cells was detected by RT-qPCR. Western blotting was used to detect the effect of ZFP36-AS1/miR-221 axis on the protein expression of CDK3, Cyclin C, CDK5, Cyclin D1 and Cyclin D3 in MGH-U3 cells.Results:Compared with normal bladder tissue, ZFP36-AS1 was abnormally low-expressed in bladder cancer tissue ( P<0.01). Compared with SV-HUC-1 cells, ZFP36-AS1 was abnormally low-expressed in bladder cancer cell lines (J82, RT-4, MGH-U3, 5637) ( P<0.01), and the expression was lowest in MGH-U3 cells ( P<0.01). The number of MGH-U3 cell colonies formed in the NC group and the ZFP36-AS1 group were (220.80±34.65) and (77.84±19.11), respectively, and the number of MGH-U3 cell colonies formed in the ZFP36-AS1 group was significantly down-regulated, the difference was statistically significant ( P<0.01). The proportions of G 0/G 1 phase cells in NC group and ZFP36-AS1 group were (48.04±2.89)% and (72.89±3.46)%, respectively, and the proportion of S phase cells were (35.38±2.98)% and (20.62±2.56)%, respectively. The proportion of G 2/M stage cells was (16.59±1.46)% and (6.48±1.50)%, respectively. The proportion of cells in G 0/G 1 phase were up-regulated in ZFP36-AS1 group ( P<0.01), and the proportion of cells in S phase and G 2/M phase were both down-regulated ( P<0.01). Compared with the NC group, the levels of IL-4 and IFN-γ in the ZFP36-AS1 group were significantly up-regulated ( P<0.01), and the level of IL-10 was significantly down-regulated ( P<0.01). ZFP36-AS1 can target miR-221 ( P<0.01). The relative expression of miR-221 in the NC group and the ZFP36-AS1 group was 6.84±1.35 and 1.00±0.21, respectively. Compared with the NC group, overexpression of ZFP36-AS1 could significantly inhibit the expression of miR-221 ( P<0.01). Compared with the NC group, the expressions of CDK3, Cyclin C, CDK5, Cyclin D1, and Cyclin D3 in the ZFP36-AS1 group were significantly decreased. Conclusion:ZFP36-AS1 is abnormally low-expressed in bladder cancer, and it reduces the proliferation activity of bladder cancer cells and inhibits their immune escape by inhibiting the expression of miR-221.

Demyelination of the central nervous system often occurs in neurodegenerative diseases， such as multiple sclerosis （MS）. The myelin sheath， a layer of myelin membrane wrapping the axon， plays a role in the rapid conduction and metabolic coupling of impulses for neurons. The exposure of the axon will lead to axonal degeneratio， and further neuronal degeneration， which is the main cause of dysfunction and even disability in patients with demyelinating neurodegenerative diseases. In addition to the demyelination of mature myelin sheath， remyelination disorder is also one of the major reasons leading to the development of the diseases. The myelin sheath is composed of oligodendrocytes （OLs） derived from oligodendrocyte progenitor cells （OPCs） which are differentiated from neural stem cells （NSCs）. The process of myelin regeneration， i.e.， remyelination， is the differentiation of NSCs into OLs. Recent studies have shown that this process is regulated by a variety of genes. MicroRNAs， as important regulators of neurodegenerative diseases， form a complex regulatory network in the process of myelin regeneration. This review summarizes the main molecular pathways of myelin regeneration and microRNAs involved in this process and classifies the mechanisms and targets. This review is expected to provide a theoretical reference for the future research on the treatment of demyelinating diseases by targeting the regulation of microRNAs.