The role of KDM4A-mediated histone methylation on temozolomide resistance in glioma cells through the HUWE1/ROCK2 axis.

Temozolomide (TMZ) resistance presents a significant challenge in the treatment of gliomas. Although lysine demethylase 4A (KDM4A) has been implicated in various cancer-related processes, its role in TMZ resistance remains unclear. This study aims to elucidate the contribution of KDM4A to TMZ resistance in glioma cells and its potential implications for glioma prognosis. We assessed the expression of KDM4A in glioma cells (T98G and U251MG) using qRT-PCR and Western blot assays. To explore the role of KDM4A in TMZ resistance, we transfected siRNA targeting KDM4A into drug-resistant glioma cells. Cell viability was assessed using the CCK-8 assay and the TMZ IC50 value was determined. ChIP assays were conducted to investigate KDM4A, H3K9me3, and H3K36me3 enrichment on the promoters of ROCK2 and HUWE1. Co-immunoprecipitation confirmed the interaction between HUWE1 and ROCK2, and we examined the levels of ROCK2 ubiquitination following MG132 treatment. Notably, T98G cells exhibited greater resistance to TMZ than U251MG cells, and KDM4A displayed high expression in T98G cells. Inhibiting KDM4A resulted in decreased cell viability and a reduction in the TMZ IC50 value. Mechanistically, KDM4A promoted ROCK2 transcription by modulating H3K9me3 levels. Moreover, disruption of the interaction between HUWE1 and ROCK2 led to reduced ROCK2 ubiquitination. Inhibition of HUWE1 or overexpression of ROCK2 counteracted the sensitization effect of si-KDM4A on TMZ responsiveness in T98G cells. Our findings highlight KDM4A's role in enhancing TMZ resistance in glioma cells by modulating ROCK2 and HUWE1 transcription and expression through H3K9me3 and H3K36me3 removal.

Central and peripheral analgesic active components of triterpenoid saponins from Stauntonia chinensis and their action mechanism.

Triterpenoid saponins from Stauntonia chinensis have been proven to be a potential candidate for inflammatory pain relief. Our pharmacological studies confirmed that the analgesic role of triterpenoid saponins from S. chinensis occurred via a particular increase in the inhibitory synaptic response in the cortex at resting state and the modulation of the capsaicin receptor. However, its analgesic active components and whether its analgesic mechanism are limited to this are not clear. In order to further determine its active components and analgesic mechanism, we used the patch clamp technique to screen the chemical components that can increase inhibitory synaptic response and antagonize transient receptor potential vanilloid 1, and then used in vivo animal experiments to evaluate the analgesic effect of the selected chemical components. Finally, we used the patch clamp technique and molecular biology technology to study the analgesic mechanism of the selected chemical components. The results showed that triterpenoid saponins from S. chinensis could enhance the inhibitory synaptic effect and antagonize the transient receptor potential vanilloid 1 through different chemical components, and produce central and peripheral analgesic effects. The above results fully reflect that "traditional Chinese medicine has multi-component, multi-target, and multi-channel synergistic regulation".

Nomogram for Prediction of Postoperative Delirium after Deep Brain Stimulation of Subthalamic Nucleus in Parkinson's Disease under General Anesthesia.

Introduction: Postoperative delirium can increase cognitive impairment and mortality in patients with Parkinson's disease. The purpose of this study was to develop and internally validate a clinical prediction model of delirium after deep brain stimulation of the subthalamic nucleus in Parkinson's disease under general anesthesia. Methods: We conducted a retrospective observational cohort study on the data of 240 patients with Parkinson's disease who underwent deep brain stimulation of the subthalamic nucleus under general anesthesia. Demographic characteristics, clinical evaluation, imaging data, laboratory data, and surgical anesthesia information were collected. Multivariate logistic regression was used to develop the prediction model for postoperative delirium. Results: A total of 159 patients were included in the cohort, of which 38 (23.90%) had postoperative delirium. Smoking (OR 4.51, 95% CI 1.56-13.02, p < 0.01) was the most important risk factor; other independent predictors were orthostatic hypotension (OR 3.42, 95% CI 0.90-13.06, p=0.07), inhibitors of type-B monoamine oxidase (OR 3.07, 95% CI 1.17-8.04, p=0.02), preoperative MRI with silent brain ischemia or infarction (OR 2.36, 95% CI 0.90-6.14, p=0.08), Hamilton anxiety scale score (OR 2.12, 95% CI 1.28-3.50, p < 0.01), and apolipoprotein E level in plasma (OR 1.48, 95% CI 0.95-2.29, p=0.08). The area under the receiver operating characteristic curve (AUC) was 0.76 (95% CI 0.66-0.86). A nomogram was established and showed good calibration and clinical predictive capacity. After bootstrap for internal verification, the AUC was 0.74 (95% CI 0.66-0.83). Conclusion: This study provides evidence for the independent inducing factors of delirium after deep brain stimulation of the subthalamic nucleus in Parkinson's disease under general anesthesia. By predicting the development of delirium, our model may identify high-risk groups that can benefit from early or preventive intervention.

Triallyl Isocyanurate as an Efficient Electrolyte Additive for Layered Oxide Cathode Material-Based Lithium-Ion Batteries with Improved Stability under High-Voltage.

In this study, a new electrolyte additive 1,3,5-tri-2-propenyl-1,3,5-triazine-2,4,6-(1H, 3H, 5H)-trione (TAIC) for lithium-ion batteries is reported. The additive is introduced as a novel electrolyte additive to enhance electrochemical performances of layered lithium nickel cobalt manganese oxide (NCM) and lithium cobalt oxide (LiCoO2) cathodes, especially under a higher working voltage. Encouragingly, we found protective films would be formed on the cathode surface by the electrochemical oxidation, and the stability of the cathode material-electrolyte interface was greatly promoted. By adding 0.5 wt.% of TAIC into the electrolyte, the battery exhibited outstanding performances. The thickness swelling decreased to about 6% after storage at 85 °C for 24 h, while the capacity retention of cycle-life performances under high temperature of 45 °C after the 600th cycle increased 10% in comparison with the batteries without TAIC. Due to its specific function, the additive can be used in high energy density and high voltage lithium-ion battery systems.

Optimized Propofol Anesthesia Increases Power of Subthalamic Neuronal Activity in Patients with Parkinson's Disease Undergoing Deep Brain Stimulation.

INTRODUCTION: Propofol is a general anesthetic option for deep brain stimulation (DBS) of the subthalamic nucleus (STN) of patients with Parkinson's disease (PD). However, its effects on STN activity and neuropsychological outcomes are controversial. The optimal propofol anesthesia for asleep DBS is unknown. This study investigated the safety and effectiveness of an optimized propofol anesthesia regimen in asleep DBS. METHODS: This retrospective study enrolled 68 PD patients undergoing bilateral STN-DBS surgery. All patients received local scalp anesthesia, with (asleep group, n = 35) or without (awake group, n = 33) propofol-remifentanil general anesthesia by target-controlled infusion under electroencephalogram monitoring. The primary outcome was subthalamic neuronal spiking characterization during microelectrode recording. The secondary outcomes were clinical outcomes including motor, cognition, mind, sleep, and quality of life at 6 months. RESULTS: Significantly increased delta and theta power were obtained under propofol anesthesia (awake vs. asleep group, mean ± standard deviation; delta: 31.97 ± 9.87 vs. 39.77 ± 10.56, p < 0.01; theta: 21.09 ± 5.55 vs. 24.82 ± 6.63, p = 0.01). After excluding the influence of confounding factors of age and preoperative motor scores, there was a statistically significant influence on the delta, theta, and alpha power of STN neuronal activity under different anesthesia regimens (delta: ß = 2.64, p < 0.01; theta: ß = 2.11, p < 0.01; alpha: ß = 1.42, p = 0.01). There were no differences in modified burst index, firing rate, tract numbers of microelectrode recording, and other clinical outcomes between the two groups. CONCLUSION: Optimized propofol anesthesia enhanced the delta, theta, and alpha power in STN compared with the awake technique and likely contributed to target recognition under propofol anesthesia. These results demonstrate that propofol is suitable, but needs to be optimized, for asleep STN-DBS. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identification number: ChiCTR2100045942. Registered 29 April 2021-Retrospectively registered.

Improving the Stability of High-Voltage Lithium Cobalt Oxide with a Multifunctional Electrolyte Additive: Interfacial Analyses.

In recent years, various attempts have been made to meet the increasing demand for high energy density of lithium-ion batteries (LIBs). The increase in voltage can improve the capacity and the voltage platform performance of the electrode materials. However, as the charging voltage increases, the stabilization of the interface between the cathode material and the electrolyte will decrease, causing side reactions on both sides during the charge-discharge cycling, which seriously affects the high-temperature storage and the cycle performance of LIBs. In this study, a sulfate additive, dihydro-1,3,2-dioxathiolo[1,3,2]dioxathiole 2,2,5,5-tetraoxide (DDDT), was used as an efficient multifunctional electrolyte additive for high-voltage lithium cobalt oxide (LiCoO2). Nanoscale protective layers were formed on the surfaces of both the cathode and the anode electrodes by the electrochemical redox reactions, which greatly decreased the side reactions and improved the voltage stability of the electrodes. By adding 2% (wt.%) DDDT into the electrolyte, LiCoO2 exhibited improved Li-storage performance at the relatively high temperature of 60 °C, controlled swelling behavior (less than 10% for 7 days), and excellent cycling performance (capacity retention rate of 76.4% at elevated temperature even after 150 cycles).

Genomic profiling of lower-grade gliomas uncovers cohesive disease groups: implications for diagnosis and treatment.

Lower-grade gliomas (including low- and intermediate-grade gliomas, World Health Organization grades II and III) are diffusely infiltrative neoplasms that arise most often in the cerebral hemispheres of adults and have traditionally been classified based on their presumed histogenesis as astrocytomas, oligodendrogliomas, or oligoastrocytomas. Although the histopathologic classification of lower-grade glioma has been the accepted standard for nearly a century, it suffers from high intra- and inter-observer variability and does not adequately predict clinical outcomes. Based on integrated analysis of multiplatform genomic data from The Cancer Genome Atlas, lower-grade gliomas have been found to segregate into three cohesive, clinically relevant molecular classes. Molecular classes were closely aligned with the status of isocitrate dehydrogenase (IDH) mutations, tumor protein 53 mutations and the co-deletion of chromosome arms 1p and 19q, but were not closely aligned with histologic classes. These findings emphasize the potential for improved definition of clinically relevant disease subsets using integrated molecular approaches and highlight the importance of biomarkers for brain tumor classification.

A Clinical Multicenter Randomized Controlled Study on JianpiQinghua Decoction in Treating Stage 3 Chronic Kidney Disease with A Syndrome Type of Dampness-heat due to Spleen Deficiency.

Objective To evaluate the clinical effectiveness of JianpiQinghua decoction in treating stage 3 chronic kidney disease (CKD3) with syndrome type of dampness-heat due to spleen deficiency. Methods A multicenter, randomized, controlled, prospective, double-blind, and double-simulation study was undertaken. A total of 270 CKD3 patients with syndrome type of dampness-heat due to spleen deficiency from the outpatient departments of six general hospitals were randomly divided into telmisartan+analog traditional Chinese medicine (TA) group, traditional Chinese medicine+analog telmisartan (TCMA) group, and telmisartan+traditional Chinese medicine (TTCM) group, in which the corresponding treatment was applied in addition to basic treatment. Six months later, changes in the traditional Chinese medicine (TCM) clinical symptom scores and renal functions before and after treatment were compared among these three groups. Results Of these 270 CKD3 patients who had been enrolled in this study, 30 cases lost to follow-up. The baseline data were comparable among these three groups. After treatment, the TCM clinical symptom scores of both syndrome of spleen-qi deficiency and dampness-heat in TA group were significantly higher than those in TCMA group and TTCM group (P<0.001). With the treatment time prolonged, the TCM clinical symptom scores showed similar descending trends in TCMA group and TTCM group but were different from that in TA group. After treatment, abnormal creatinine rate decreased (P=0.003), and these three treatments and their interactions with each visit had no effect on serum urea nitrogen value (P=0.270, P=0.520); with prolonged treatment, the estimated glomerular filtration rates in three groups tended to be relatively stable after the first rise. The liver function and abnormal serum potassium rate were not statistically significant before and after treatment (P>0.05). Conclusions JianpiQinghua decoction can improve clinical symptoms of TCM in CKD3 patients with syndrome type of dampness-heat due to spleen deficiency and thus improve the quality of life and prognosis. The clinical efficacy of JianpiQinghua decoction alone or combined with telmisartan is superior to telmisartan monotherapy.

[Risk Factors for Post-surgery Recurrence of Multiple Pulmonary Cystic Echinococcosis].

Clinical information of patients with multiple pulmonary cystic echinococcosis who received surgery in the Department of Thoracic Surgery of the Hospital from January 2005 to October 2014 was collected. Multivariate logistic regression analysis was used to analyze the predisposing factors for post-surgery recurrence of multiple pulmonary cystic echinococcosis. Among the 73 cases of multiple pulmonary cystic echinococcosis, 40 were males and 33 were females, with a male-to-female ratio of 1.21 : 1. The average age of patients was 37.6 years. All the patients reported a living history in pastoral areas or contacts with dogs. Thirty-eight patients were administered with albendazole tablets or liposomal albendazole for 3 to 12 months after surgery. Recurrence occurred in 6 cases, with a rate of 8.2%. Multivariate logistic regression analysis revealed the preoperative rupture of hydatid cyst to be the risk factor for post-surgery recurrence. The administration of anti-hydatid drugs after surgery plays a protective role against recurrence, and may reduce the risk of recurrence.

[A prospective randomized control clinical trial about clopidogrel combined with warfarin versus clopidogrel alone in the prevention of restenosis after femoral-popliteal artery angioplasty].

OBJECTIVE: Using two antithrombotic treatment (clopidogrel vs. clopidogrel combined warfarin) strategies after femoral-popliteal artery angioplasty prospectively, to evaluate which strategy is more effective for the restenosis prevention. METHODS: Totally 50 patients referred for endovascular treatment (including the percutaneous transluminal angioplasty (PTA) and stent implantation) of the superficial femoral artery and popliteal artery from January 2008 to May 2009 were randomly divided into clopidogrel group (group A, 25 cases, 30 limbs) and clopidogrel plus warfarin group (group B, 25 cases, 33 limbs) before operation. Clinical outcomes and restenosis rate of the target lesions were evaluated at 3, 6 and 12 months after operation. RESULTS: Totally 88 patients were screened for participation in the study, 56 patients were included after the follow-up of 12 months. At 3 months, the rates of restenosis were 16.7% in group A and 18.2% in group B (χ² = 0.025, P = 0.874). At 6 months, the accumulated restenosis rates were 36.7% in group A and 36.4% in group B (χ² = 0.001, P = 0.98). At 12 months, the accumulated restenosis rates were 53.3% in group A and 42.4% in group B (χ² = 0.75, P = 0.387). Analysis for the critical limb ischemia sub-group showed that follow-up of 12 months, the accumulated restenosis rate was 8/10 in group A and 6/12 in group B (χ² = 1.023, P = 0.312). CONCLUSION: The clopidogrel alone treatment for PTA or PTA plus stent implantation of femoral popliteal artery has no statistically significant difference in comparison with the clopidogrel combined warfarin treatment in terms of the cumulative vascular restenosis rate at 3, 6, 12 months postoperatively.

Effects of dietary lysine levels on apparent nutrient digestibility and cationic amino acid transporter mRNA abundance in the small intestine of finishing pigs, Sus scrofa.

One hundred and twenty pigs were used to evaluate the effects of different dietary lysine levels on the growth performance, apparent nutrient digestibility, and abundance of cationic amino acid transporter messenger RNA (mRNA) in the small intestine of finishing pigs. Pigs received a low lysine diet (LL, 0.60% lysine), moderate lysine diet (ML, 0.80% lysine) or a high lysine diet (HL, 1.00% lysine) for 28 days. A digestion test was carried out during the third week. Although the apparent nutrient digestibility in pigs fed experimental diets were different (P < 0.05) and the highest when pigs were fed ML diet, diets did not change the growth performance. In the duodenum, mRNA abundance of PepT-1, as detected by real-time RT-PCR, was reduced in the LL diet (P < 0.05). A greater abundance of b(0,+) AT and PepT-1 mRNA was associated with the ML diet (P < 0.05) in the jejunum and ileum, respectively. In the ileum, the HL diet had a lower abundance of CAT-1 mRNA compared with other diets. These results showed that the finishing pigs would gain better nutrient digestibility when the dietary lysine content was 0.80%, and dietary lysine levels influenced the expression of cationic amino acid transporter mRNA in the small intestine of finishing pigs.

[Application of serum proteomic patterns for the detection of esophageal carcinoma in Kazakh in Xinjiang].

OBJECTIVE: To detect the serum protein profiles of Kazakh's esophageal carcinoma (EC) patients in Xinjiang by SELDI-TOF-MS (surface enhanced laser desorption & ionization time-of-flight mass spectrometry) and build up a diagnostic model of Kazakh's EC in Xinjiang. METHODS: The serum samples from 41 Kazakh's EC patients and 20 Kazakh's healthy controls were collected and analyzed on weak cation exchange and hydrophobic surface protein chip by SELDI-TOF-MS technology. The differentially expressed markers of esophageal carcinoma were detected. RESULTS: The values of M/Zs were significantly different between Kazakh's EC patients and controls (P < 0.05). Among these, 6 proteins peaks were up-regulated (5495.2265, 15 964.6951, 16 152.0872, 4488.4818, 8164.7652, 4979.4223) and 4 down-regulated (6900.3285, 13 790.9241, 8790.8130, 8714.7915) in the Kazakh's EC group. According to cross validation, the model of Kazakh's EC made up of 7 proteins (M/Z 6900.3285, 13 790.9241, 8790.8130, 15 964.6951, 16 152.0872, 4488.4818, 4979.4223) was established. The sensitivity and specificity of this model were 100% (41/41) and 100% (20/20) respectively. CONCLUSION: The model with 7 proteins markers has a higher sensitivity and specificity for Kazakh's EC patients in Xinjiang. It may provide a new serum diagnostic tool for Kazakh's EC patients in Xinjiang.

[The clinical analysis of 93 children with pulmonary echinococcus].

OBJECTIVE: To approach the clinical characteristics and surgical treatment of children with pulmonary echinococcus. METHODS: Retrospective analysis of child patients with pulmonary echinococcus from January 1980 to December 2008 was carried out, associated with clinical manifestations, diagnosis and treatment, operation methods (complete removal of endocyst and cystectomy with needle aspiration), prognosis and recurrence. There were 93 patients (54 male and 39 female) aged from 2 to 14 years. There were 82 cases lived in the echinococcosis pulmonary endemic areas, accounting for 88.1% (82/93), and 79 cases of patients had obvious contact with dogs or sheep, accounting for 84.9% (79/93). There were 68 cases with simple pulmonary echinococcus accounted for 73.1% (68/93), 25 cases suffered from complexity pulmonary hydatid, accounting for 26.9% (25/93). RESULTS: All patients were cured or improved after surgery except one dead. Six cases got postoperative pulmonary infection, 3 cases had wound infection, 1 case suffered from bile-pleura fistula. There were 76 patients (81.7%) followed up for 1 to 10 years after surgery. Five cases had recurrence, the recurrence rate was 5.4% (5/93). CONCLUSIONS: The clinical symptoms of pulmonary echinococcus in children is not typical, misdiagnosis and missed diagnosis take place easily. Complete removal of endocyst has low postoperative complications and lower relapse rate.

Research progress in cancer stem cells and their drug resistance.

Traditional theories suggest that tumor growth occurs when all tumor cells work together and result in proliferation, so treatment has been mainly directed against the majority of the cells in tumor tissue, which often relapse, metastasize, and lead to treatment failure. As cancer stem cells have been successfully isolated from different tumor tissues, in-depth study of their function in relation to traditional cancer treatment faces enormous challenges. At the same time, a new theoretical basis has been provided for the in-depth study of tumorigenesis and the evaluation of prognosis of cancer therapy. Also, new ideas have been introduced for cancer therapy. Therefore, radical treatment of cancer can be achieved through killing cancer stem cells. This article reviews the research progress on cancer stem cells and their drug resistance.

[Application of cerebral protection to carotid endarterectomy at perioperation, intraoperation, and postoperation].

OBJECTIVE: To evaluate the significance of cerebral protection applied at carotid endarterectomy (CEA) at perioperation, intraoperation, and postoperation. METHODS: Thirty patients underwent CEA with application of cerebral protection at perioperation, intraoperation, and postoperation in our hospital from January 2002 to August 2005. Perioperative carotid Doppler ultrasound and computed tomography angiography (CTA) were applied in 29 patients and carotid angiography applied in only one patient. The key methods of intraoperative cerebral protection included general anaesthesia, selective shunting, monitoring of transcranial Doppler, and careful manipulation. The methods of postoperative cerebral protection included leaving tracheal cannula and brain ice-bag, maintaining normal blood pressure, and applying dehydrant under guidance by monitoring of transcranial Doppler. RESULTS: Among all the 30 patients, shunts were used in 10 patients (33%), and angioplasty by patch was applied in 17 patients (57%). No cranial nerve-associated complications or death was documented. CONCLUSION: Application of cerebral protection at CEA at perioperation, intraoperation, and postoperation can effectively prevent the occurance of cranial nerve-associated complications.

[The effect of examination of enzymes in serum to diagnosis of acute mesenteric ischemia in rabbit].

OBJECTIVE: To study the change regulation of enzymes in serum for the diagnosis and treatment of acute mesenteric ischemia by earlier period. METHODS: Thirty-six of rabbits were divided into three groups included from artery, vein and artery with vein by interrupted in mesenteric vessels respectively and there was twelve rabbits in every groups. It was observed that ALT, AST, ALP, gamma-GT, CK, CK-MB, LDH in serum at mesenteric vessels pre-interrupted and post-interrupted 1, 3, 6, 9 h respectively and the bowel color variety was observed at the same time too. RESULTS: After 3 h from post-occluded of mesenteric vessels, among the three groups there was bowel infarction and ALT, AST, ALP, gamma-GT, LDH in serum all to obviously go up. CONCLUSION: It is beneficial to diagnosis of acute mesenteric ischemia at earlier by the examination of enzymes in serum.