Objective： To investigate the relationship between the lipid metabolism-related gene sterol carrier protein 2(SCP2) and prostate cancer (PCa) from a multi-omics perspective using single-cell transcriptomes combined with Mendelian randomization. Methods： Single-cell transcriptome data of benign and malignant prostate tissues were obtained from GSE120716, GSE157703 and GSE141445 datasets, respectively. Integration, quality control and annotation were performed on the data to categorize the epithelial cells into high and low SCP2 expression groups, followed by further differential and trajectory analyses. Single nucleotide polymorphism (SNP) data for SCP2 expression quantitative trait loci (eQTL) were subsequently downloaded from Genotype-Tissue Expression (GTEx) and investigated from the PCa Society Cancer-Related Genomic Alteration Panel for the Investigation of Cancer-Related Alterations (PRACTICAL) to obtain PCa outcome data for Mendelian randomization analysis to validate the causal relationship between SCP2 and PCa. Results： High SCP2-expressing epithelial cells had higher energy metabolism and proliferation capacity with low immunotherapy response and metastatic tendency. Trajectory analysis showed that epithelial cells with high SCP2 expression may have a higher degree of malignancy, and SCP2 may be a key marker gene for differentiation of malignant epithelial cells in the prostate. Further Mendelian randomization results showed a significant causal relationship between SCP2 and PCa development (OR=1.045, 95% CI: 1.010 －1.083, P=0.011). Conclusion： By combining single-cell transcriptome and Mendelian randomization, the role of the lipid metabolism-related gene SCP2 in PCa development has been confirmed, and new targets and therapeutic directions for PCa treatment have been provided.
Humans ; Prostatic Neoplasms/genetics* ; Male ; Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Single-Cell Analysis ; Sequence Analysis, RNA ; Carrier Proteins/genetics* ; Transcriptome ; Lipid Metabolism

Objective:To evaluate the accuracy and safety profile of a novel cuboid orientation-guided frontal horn ventriculostomy technique in patients with large hemispheric infarction (LHI).Methods:It was conducted a retrospective cohort study of 48 consecutive LHI patients who underwent the innovative ventriculostomy procedure between time period. Primary outcomes included procedural accuracy (success rates, catheter positioning) and safety indicators (complication rates).Results:All the punctured ventricles were small or of normal size. The success rate of puncture was 100%, the success rate of one-time puncture was 87% (42/48), and the average number of puncture was 1.13 times per case. The ratio of well-positioned tube heads was 87.5% (42/48). The actual angle of the inward deviation of the puncture ranged from -2o to 5o, with an average of 0o±0.3o. The depth of puncture was 7.0-8.0 cm ( 7.3±0.3) cm. The incidence of bleeding around the puncture path was 1.3% (2/48 ) and no massive bleeding occurred. At the 6-month follow-up, one case (2.94%) among the 34 survivors had epilepsy.Conclusions:The cuboid orientation-guided frontal horn ventriculostomy technique demonstrates exceptional procedural accuracy and an excellent safety profile in LHI patients, with high first-pass success rates (87.5%) and minimal complications (4.2% minor hemorrhage). These findings support its clinical adoption for this patient population.

Objective:To investigate the expression characteristics of the SLFN11 gene in pancreatic cancer and its relationship with cis-diamminedichloroplatinum(DDP)resistance.Methods:This study analyzed multiple publicly available datasets, including GSE207611, GSE186205, GSE73978, GSE217845, and GSE238163 from the gene expression omnibus(GEO)datasets.These datasets comprise gene expression data and single-cell sequencing data from pancreatic cancer cell lines and patients, which were utilized to examine the expression characteristics of the SLFN11 gene and its association with cisplatin resistance.Receiver operating characteristic (ROC) curves were generated, and the area under the curve (AUC) value along with the confidence interval ( CI) were calculated.Additionally, Kaplan-Meier survival analysis and single-cell RNA sequencing(scRNA-seq)data analysis were conducted. Results:The differential expression of the SLFN11 gene between tumor and adjacent normal tissues was statistically significant( P<0.05). The AUC value for SLFN11 in diagnosing pancreatic cancer was 0.761.SLFN11, along with its associated genes PTN and SLC15A3, collectively influenced the survival of pancreatic cancer patients.Results from single-cell sequencing demonstrated high expression of SLFN11 in mesenchymal stem cells. Conclusions:The SLFN11 gene demonstrates significant diagnostic and prognostic value in pancreatic cancer and may play a role in the mechanism of cisplatin resistance.

Diabetic nephropathy(DN)is a serious complication of diabetes mellitus and a leading cause of end-stage renal diseases.In DN patients,key pathological mechanisms include proteinuria,glomerulo-sclerosis,and fibrosis,largely driven by poor glycemic control and oxidative stress caused by prolonged hyperglycemia.This stress damages renal podocytes and triggers inflammatory mesenchymal infiltration of renal tubular cells,exacerbating the progression of proteinuria and fibrosis.Human umbilical cord-de-rived mesenchymal stem cells(hUC-MSCs)offer promising potential for treating DN due to their strong anti-oxidative properties.In this study,we developed a DN mouse model and treated the mouse via tail vein injections of hUC-MSCs(1×106 cells/mouse).The results indicated that hUC-MSCs significantly lowered fasting blood glucose levels(22.5±3.0 vs 14.7±1.1,P＜0.01)and improved glucose toler-ance,as shown by intraperitoneal glucose tolerance test(IPGTT)results(P＜0.05).Additionally,the renal function improved in hUC-MSCs-treated mice,with marked reductions in oxidative stress markers,including blood urea nitrogen(BUN),urinary creatinine(Ucr),urinary protein(PRO),superoxide dismutase(SOD),and malondialdehyde(MDA)(P＜0.05).Histological analyses through hematoxy-lin-eosin(H&E),Periodic Acid-Schiff(PAS),and Sirius red staining demonstrated alleviation of glo-merular mesangial hyperplasia,glomerular hypertrophy,and tubular inflammation.Furthermore,hUC-MSCs treatment downregulated the expression of oxidative stress-related proteins,such as NADPH oxi-dase 4(NOX4)and thioredoxin-interacting protein(TXNIP),and reduced reactive oxygen species(ROS)production(P＜0.05).Meanwhile,human renal cortical proximal tubule epithelial cells(HK-2 cells)were selected for validation in vitro experiments using high glucose treatment followed by super-natants of hUC-MSCs(MSC-CM),and Western blotting showed that the expression of both NOX4 and TXNIP was inhibited(P＜0.05)and ROS expression was reduced.In conclusion,hUC-MSC treatment effectively lowered blood glucose levels and improved renal function in DN mice,likely through the sup-pression of NOX4 expression and TXNIP-mediated oxidative stress.

Diabetic nephropathy(DN)is a serious complication of diabetes mellitus and a leading cause of end-stage renal diseases.In DN patients,key pathological mechanisms include proteinuria,glomerulo-sclerosis,and fibrosis,largely driven by poor glycemic control and oxidative stress caused by prolonged hyperglycemia.This stress damages renal podocytes and triggers inflammatory mesenchymal infiltration of renal tubular cells,exacerbating the progression of proteinuria and fibrosis.Human umbilical cord-de-rived mesenchymal stem cells(hUC-MSCs)offer promising potential for treating DN due to their strong anti-oxidative properties.In this study,we developed a DN mouse model and treated the mouse via tail vein injections of hUC-MSCs(1×106 cells/mouse).The results indicated that hUC-MSCs significantly lowered fasting blood glucose levels(22.5±3.0 vs 14.7±1.1,P＜0.01)and improved glucose toler-ance,as shown by intraperitoneal glucose tolerance test(IPGTT)results(P＜0.05).Additionally,the renal function improved in hUC-MSCs-treated mice,with marked reductions in oxidative stress markers,including blood urea nitrogen(BUN),urinary creatinine(Ucr),urinary protein(PRO),superoxide dismutase(SOD),and malondialdehyde(MDA)(P＜0.05).Histological analyses through hematoxy-lin-eosin(H&E),Periodic Acid-Schiff(PAS),and Sirius red staining demonstrated alleviation of glo-merular mesangial hyperplasia,glomerular hypertrophy,and tubular inflammation.Furthermore,hUC-MSCs treatment downregulated the expression of oxidative stress-related proteins,such as NADPH oxi-dase 4(NOX4)and thioredoxin-interacting protein(TXNIP),and reduced reactive oxygen species(ROS)production(P＜0.05).Meanwhile,human renal cortical proximal tubule epithelial cells(HK-2 cells)were selected for validation in vitro experiments using high glucose treatment followed by super-natants of hUC-MSCs(MSC-CM),and Western blotting showed that the expression of both NOX4 and TXNIP was inhibited(P＜0.05)and ROS expression was reduced.In conclusion,hUC-MSC treatment effectively lowered blood glucose levels and improved renal function in DN mice,likely through the sup-pression of NOX4 expression and TXNIP-mediated oxidative stress.

Objective:To investigate the expression characteristics of the SLFN11 gene in pancreatic cancer and its relationship with cis-diamminedichloroplatinum(DDP)resistance.Methods:This study analyzed multiple publicly available datasets, including GSE207611, GSE186205, GSE73978, GSE217845, and GSE238163 from the gene expression omnibus(GEO)datasets.These datasets comprise gene expression data and single-cell sequencing data from pancreatic cancer cell lines and patients, which were utilized to examine the expression characteristics of the SLFN11 gene and its association with cisplatin resistance.Receiver operating characteristic (ROC) curves were generated, and the area under the curve (AUC) value along with the confidence interval ( CI) were calculated.Additionally, Kaplan-Meier survival analysis and single-cell RNA sequencing(scRNA-seq)data analysis were conducted. Results:The differential expression of the SLFN11 gene between tumor and adjacent normal tissues was statistically significant( P<0.05). The AUC value for SLFN11 in diagnosing pancreatic cancer was 0.761.SLFN11, along with its associated genes PTN and SLC15A3, collectively influenced the survival of pancreatic cancer patients.Results from single-cell sequencing demonstrated high expression of SLFN11 in mesenchymal stem cells. Conclusions:The SLFN11 gene demonstrates significant diagnostic and prognostic value in pancreatic cancer and may play a role in the mechanism of cisplatin resistance.

Objective:To explore the effect and safety of stereotactic aspiration of necrotic brain tissue for the patients≥61 years with malignant middle cerebral artery infarction (MMI).Methods:A total of 102 MMI patients aged≥61 years were enrolled retrospectively. All patients were subject to conservative medical treatment alone or in addition to stereotactic aspiration of necrotic brain tissue 24-72 hours after symptom onset. Perioperative outcomes and 6-month follow-up outcomes were observed and evaluated.Results:Baseline data characteristics were well balanced between the conservative treat group and aspiration group, except for the prevalence of hypertension. The incidence of early cerebral herniation (9.1% vs. 48.3%, χ2=17.843, P<0.001) and death (13.6% vs. 60.3%, χ2=22.707, P<0.001)in the aspiration group was significantly lower than that in the conservative group, and there was no significant difference in the incidence of cerebral hemorrhage ( P=0.726) and intracranial infection ( P=0.186) between the groups. At 6-month follow-up, compared with the conservative treatment group, the aspiration group had a higher proportion of favorable outcome (mRS 0-3) (38.6% vs. 3.4%, χ2 =20.438, P<0.001) and survival without severe disability (mRS 0-4) (68.2% vs. 22.4%, χ2=21.492, P<0.001). Comparison of clinical characteristics of favorable outcome (mRS 0-3) group and unfavorable (mRS 4-6) group showed that the proportion of patients treated with aspiration was significantly higher than that treated with medical therapy alone (89.5% vs. 10.5%, P<0.001). Multivariate logisitic regression used to adjust the confound factors such as atrial fibrillation, diabetes and smoking, the GCS and the NIHSS score of 24 hours after onset, etc, revealed that the treatment with aspiration was an independent association factor for the ratio of 6-month favorable outcome for the elderly patients with MMI ( OR=126.704, 95% CI: 7.236-2218.610, P<0.001). Conclusions:The stereotactic aspiration of necrotic brain tissue are effective and safe for the elderly patients with MMI.

Epilepsy is a common neurological disease,has the characteristics of recurrent attacks and long-term treatment,thus bringing great pressure to patients and their families.Therefore,it is particularly important to do a good job of disability assessment.In recent years,with the development of the discipline,academic organizations such as the International League Against Epilepsy(ILAE)and China Association Against Epilepsy(CAAE)have successively updated the definition and diagnostic criteria of epilepsy and seizures.However,some items of epilepsy in the current Criteria for Disability Rating of Military Personnel(Trial)issued by People's Liberation Army(PLA)in 2011 can no longer meet the latest guidelines at home and abroad.Therefore,we suggest that the items related to epilepsy in the Criteria for Disability Rating of Military Personnel(Trial)should be revised to ensure that the disability evaluation being completed fairly and successfully.

Evaluating toxicity and decoding the underlying mechanisms of active compounds are crucial for drug development.In this study,we present an innovative,integrated approach that combines air flow-assisted desorption electrospray ionization mass spectrometry imaging(AFADESI-MSI),time-of-flight secondary ion mass spectrometry(ToF-SIMS),and spatial metabolomics to comprehensively investi-gate the nephrotoxicity and underlying mechanisms of nitidine chloride(NC),a promising anti-tumor drug candidate.Our quantitive AFADESI-MSI analysis unveiled the region specific of accumulation of NC in the kidney,particularly within the inner cortex(IC)region,following single and repeated dose of NC.High spatial resolution ToF-SIMS analysis further allowed us to precisely map the localization of NC within the renal tubule.Employing spatial metabolomics based on AFADESI-MSI,we identified over 70 discriminating endogenous metabolites associated with chronic NC exposure.These findings suggest the renal tubule as the primary target of NC toxicity and implicate renal transporters(organic cation transporters,multidrug and toxin extrusion,and organic cation transporter 2(OCT2)),metabolic en-zymes(protein arginine N-methyltransferase(PRMT)and nitric oxide synthase),mitochondria,oxidative stress,and inflammation in NC-induced nephrotoxicity.This study offers novel insights into NC-induced renal damage,representing a crucial step towards devising strategies to mitigate renal damage caused by this compound.

It has gradually become a consensus in the industry that the traditional Chinese medicine gypsum should be decocted first, but the understanding of decocting method is not completely unified in the works of doctors since ancient times, and there are occasional disputes about whether it is necessary to decocting first. In this study, the phase determination, physical and chemical characterization, qualitative and quantitative analysis of inorganic and organic components of the decoctions of herbal pairs and the whole prescription Maxingshigan decoction with gypsum as the center, and the pre-decoctions and co-decoctions of them were carried out to explore the scientific connotation of the pre-decoctions of gypsum. Results show that decoction phases were different between the co-decoctions and pre-decoctions of licorice-gypsum (Gancao-Shigao, GC-SG), ephedra-gypsum (Mahuang-Shigao, MH-SG) and almond-gypsum (Xingren-Shigao, XR-SG). The results of the micromorphology, particle size and zeta potential of herbal pairs and prescription (Quanfang, QF) showed that the supramolecular particles in pre-decoctions were smaller, more uniform and more stable than the co-decoctions. The results of organic components analysis showed that different cooking methods did not change the organic composition and content. ICP-OES results showed that the content of inorganic components in pre-decoctions was higher than in co-decoctions for the same boiling time of gypsum. The IR results showed that the pre-decoctions had stronger chemical functional group effect than the co-decoctions. To sum up, compared with the co-decoction, the pre-decoction of gypsum has different phase state and chemical composition interaction, and the difference of inorganic composition is an important material basis affecting the change of phase state compared with the co-decoction. It indicates that the material basis of traditional Chinese medicine decoction is indeed different whether gypsum is decocted first or not, which can provide a basis for the clinical application of decocted gypsum.