OBJECTIVE To explore comprehensive management and potential issues associated with long-term prescriptions medications of psychiatry， in order to provide a reference for the comprehensive management of long-term prescriptions of psychiatry in psychiatric hospitals and other medical institutions’ pharmacies. METHODS Starting from the applicable principles for long-term prescriptions of psychiatry， this study introduced the standardized assessment and precautions before issuing long-term prescriptions， the formulation and adjustment of the drug list， as well as the rational management of the long-term prescriptions. It also analyzed potential issues that may arise in the comprehensive management of long-term prescription medications and proposed corresponding countermeasures and suggestions. RESULTS & CONCLUSIONS Prior to initiating long-term prescriptions， a standardized assessment should be conducted on patients from the aspects of their psychiatric condition and long-term potential risk factors， pharmacological treatment plans and other non-pharmacological therapies， physical illnesses. Additionally， healthcare providers should fulfill their obligation to inform patients or their family members. The comprehensive management of long-term prescription medications should be jointly established and improved by multiple departments， and the formulation of drug catalogs should avoid including drugs with potential social harm or medication risks while complying with policy requirements. Furthermore， measures such as adding special identifiers to long-term prescriptions， providing patients with reminders about （No.YGLX202537） prescription expiration， or offering online consultations can also effectively enhance the rationality of medication use under long-term prescriptions. Currently， the implementation of long-term prescriptions in psychiatry remains challenged by inconsistencies in prescription duration， incomplete coverage of diagnostic categories， poor patient adherence， and the risk of deviation in clinical assessments. In this regard， measures such as collaborating with multiple departments to strengthen long-term prescription information management， providing matching pharmaceutical services， ensuring the quality and rationality of long-term prescription implementation， and using modern methods to screen high-risk patients can be taken to improve patient medication compliance and safety.

Integrated metabolomic and lipidomic profiling,utilizing liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS),has emerged as a pivotal strategy for biomarker discovery.However,the inherent polarity disparity between metabolites and lipids complicates simultaneous analysis.To address this,a dual-stationary phase polarity-extended liquid chromatography(PELC)system was developed,which surpassed conventional one-dimensional LC(1D-LC)by enabling comprehensive coverage of both polar and non-polar compounds within a single injection.This system enhanced chromatographic resolution,peak capacity,and throughput while minimizing analytical variability.Extracellular vesicles(EVs),lipid bilayer-enclosed nanoparticles ubiquitously present in biofluids,had gained prominence as reservoirs of cancer biomarkers due to their cargo stability and pathophysiological relevance.Herein,the application of PELC-HRMS for concurrent metabolome-lipidome profiling in EVs was pioneered.A total of 193 metabolites were identified using this technique coupled with MS-DIAL software and Human Metabolome Database.Subsequently,this technique was employed to explore potential biomarkers for prostate cancer(PCa).Multivariate analysis identified 17 differentially abundant metabolites in PCa,implicating dysregulated pathways including purine metabolism,starch and sucrose metabolism,galactose metabolism,cysteine and methionine metabolism,and biosynthesis of unsaturated fatty acids.Notably,creatine(AUC=0.92)and DG 42:5(AUC=0.80)demonstrated robust diagnostic efficacy,attributable to their broad polarity ranges and EV-specific enrichment.This study established PELC as a high-fidelity platform for multi-omics integration in complex biospecimens,advancing mechanistic insights into metabolic rewiring and disease pathophysiology.

Aim To screen and study the expression of long non-coding RNA (IncRNA) in rats with middle cerebral artery occlusion (MCAO) with MCAO treated with Tao Hong Si Wu decoction (THSWD) and determine the possible molecular mechanism of THSWD in treating MCAO rats. Methods Three cerebral hemisphere tissue were obtained from the control group, MCAO group and MCAO + THSWD group. RNA sequencing technology was used to identify IncRNA gene expression in the three groups. THSWD-regulated IncRNA genes were identified, and then a THSWD-regu-lated IncRNA-mRNA network was constructed. MCODE plug-in units were used to identify the modules of IncRNA-mRNA networks. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) were used to analyze the enriched biological functions and signaling pathways. Cis- and trans-regulatory genes for THSWD-regulated IncRNAs were identified. Reverse transcription real-time quantitative pol-ymerase chain reaction (RT-qPCR) was used to verify IncRNAs. Molecular docking was used to identify IncRNA-mRNA network targets and pathway-associated proteins. Results In MCAO rats, THSWD regulated a total of 302 IncRNAs. Bioinformatics analysis suggested that some core IncRNAs might play an important role in the treatment of MCAO rats with THSWD, and we further found that THSWD might also treat MCAO rats through multiple pathways such as IncRNA-mRNA network and network-enriched complement and coagulation cascades. The results of molecular docking showed that the active compounds gallic acid and a-mygdalin of THSWD had a certain binding ability to protein targets. Conclusions THSWD can protect the brain injury of MCAO rats through IncRNA, which may provide new insights for the treatment of ischemic stroke with THSWD.

In the past few decades,supercritical fluid chromatography(SFC)as a supplement to liquid chromatography(LC)separation technology has attracted people's interest,especially in the combination of SFC and mass spectrometry(MS),which has shown important application prospects in metabolomics,lipidomics,and other fields.Compared to the interface of LC-MS,the interface of SFC-MS presents some unique challenges that require special solutions to be designed.This article categorizes and summarizes the existing interfaces used for SFC-MS,focuses on the impact of different interface designs on detection performance,provides the applicable characteristics of different types of interfaces,and finally briefly introduces the application progress of SFC-MS in different fields.

A boy,aged 7 months,presented with severe global developmental delay(GDD),refractory epilepsy,hypotonia,nystagmus,ocular hypertelorism,a broad nasal bridge,everted upper lip,a high palatal arch,and cryptorchidism.Genetic testing revealed a de novo heterozygous missense mutation of c.364G>A(p.E122K)in the EEF1A2 gene,and finally the boy was diagnosed with autosomal dominant developmental and epileptic encephalopathy 33 caused by the EEF1A2 gene mutation.This case report suggests that for children with unexplained infancy-onset severe to profound GDD/intellectual disability and refractory epilepsy,genetic testing for EEF1A2 gene mutations should be considered.This is particularly important for those exhibiting hypotonia,nonverbal communication,and craniofacial deformities,to facilitate a confirmed diagnosis.

Aim To screen and study the effects of Tao Hong Si Wu decoction(THSWD)-mediated treat-ment on circular RNA(circRNA)expression profiles in rats with middle cerebral artery occlusion(MCAO),and investigate the possible roles and molecular mecha-nisms of THSWD.Methods Next-generation RNA sequencing was conducted to identify circRNA expres-sion profiles in MCAO rats after treatment with THSWD and compared with the MCAO model group and control group.Bioinformatics analysis was performed to predict the potential target microRNAs and mRNAs.Gene On-tology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses for the potential target mRNAs were applied to explore the potential roles of differentially expressed circRNAs.RT-qPCR was performed to verify circRNAs with significant differences in expression.Results We identified 87 significantly differentially expressed circRNAs between the MCAO group versus the control group,and 86 sig-nificantly differentially expressed circRNAs between the MCAO group versus the THSWD group.respective-ly.Among them,17 circRNAs induced by the MCAO model were reversed via treatment with THSWD.To demonstrate the roles of mRNAs targeted by DECs,the GO and KEGG databases were used.Further analysis revealed that five circRNAs may play important roles in the development of MCAO.Conclusions The com-prehensive expression profile of circRNAs in rats with middle cerebral artery occlusion after THSWD treat-ment is determined for the first time,suggesting that the therapeutic effect of THSWD on MCAO may be a-chieved by regulating the expression of circRNAs.

AIM To prepare cucurbitacin B nanosuspensions,and to investigate their in vivo pharmacokinetics.METHODS The nanosuspensions were prepared by high-pressure homogenization method.With stabilizer type,stabilizer-drug ratio and homogeneous frequency as influencing factors,particle size and PDI as evaluation indices,the formulation was optimized by single factor test,after which the solubility and stability were determined,and crystalline form analysis was performed.Eighteen rats were randomly assigned into three groups and given intragastric administration of the 0.5%CMC-Na suspensions of cucurbitacin B,physical mixture and cucurbitacin B nanosuspensions(10 mg/kg),respectively,after which blood collection was made at 0.5,1,2,3,4,8,10,12 h,UPLC-MS/MS was adopted in the plasma concentration determination of cucurbitacin B,and main pharmacokinetic parameters were calculated.RESULTS The optimal formulation was hydroxypropyl cellulose+sodium dodecyl sulfate(1 ∶ 1)as stabilizer,3 ∶ 1 for stabilizer-drug ratio,80 MPa for homogeneous pressure,and 12 times for homogeneous frequency,the average particle size,PDI and Zeta potential were 200 nm,0.140 and-32 mV,respectively.The nanosuspensions demonstrated obviously higher solubility than that of raw medicine and physical mixture,along with good stability within 6 months.Cucurbitacin B existed in the nanosuspensions in an amorphous state.Compared with raw medicine and physical mixture,the nanosuspensions displayed shortened tmax(P<0.01),prolonged t1/2(P<0.05,P<0.01),and increased Cmax,AUC0-t,AUC0-∞(P<0.01),whose relative bioavailability was enhanced to 4.32 times as compared with that of raw medicine.CONCLUSION Nanosuspensions can improve the dissolution rate and oral bioavailability of cucurbitacin B.

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.
Male ; Humans ; Prostate-Specific Antigen ; Treatment Outcome ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies

Purpose: In non-metastatic prostate cancer (nmPCa) setting, it is important to early identify the patients at risk of biochemical recurrence (BCR) for immediate postoperative intervention. Our study aimed to evaluate the potential clinical utility of circulating tumor DNA (ctDNA) for predicting disease recurrence. Materials and Methods: This real-world observational study evaluated 161 cases of nmPCa undergoing next-generation sequencing at our institution. A total of 139 ctDNA samples and 31 biopsied tumor tissue underwent genomic profiling. The study endpoint was BCR after radical prostatectomy. Relationships between the ctDNA status and the biochemical progression-free survival (bPFS) were analyzed by log-rank test and multivariate Cox regression. Results: Of 161 enrolled patients, 19 (11.8%) harbored deleterious alterations in NCOR2, followed by BRCA2 (3.7%), ATR (2.5%), and CDK12 (2.5%). Of available pre-operative blood samples (n=139), ctDNA was detectable in 91 (65.5%). Until last follow-up, 56 of 68 patients (85.3%) with detectable ctDNA had achieved BCR, whereas only eight of 39 patients (20.5%) with undetectable ctDNA had achieved BCR. Patients who had undetectable ctDNA experienced significantly longer bPFS compared with those who had detectable ctDNA (not available vs. 8.2 months; hazard ratio, 0.14; p < 0.01). Pre-operative ctDNA status was a significant prognostic factor of disease recurrence. Conclusion Pre-operative ctDNA detection could identify patients at high risk of recurrence and has the potential to inform immediate postoperative interventions, but these approaches remain to be validated in prospective studies. ctDNA studies can provide insights into accurate monitoring and precise treatment rather than simply following routine clinical care.

Objective Coronary arteriography(CAG)and percutaneous coronary intervention(PCI)are the most effective methods for the treatment of coronary atherosclerotic heart disease(CAD),but radial artery vascular variation,especially the presence of 360° tortuous(annular tortuous)radial artery seriously affects the success rate of trans-radial artery approach(TRA)interventional operation.This article provides a preliminary exploration of CAG and PCI through the annular tortuous radial artery.Methods We retrospectively analyzed 15 patients with annular tortuous right radial artery who successfully completed CAG or PCI by annular tortuous radial artery,and summarized the procedures performed through the annular tortuous radial artery.Results We found that the annular tortuous radial artery could be passed through by the catheter with the assistance of percutaneous transluminal coronary angioplasty(PTCA)guide wire or combined with a diameter of 2.0 mm balloon(6-8 atm dilatation state),and then the PTCA wire and the balloon can be replaced with a coronary angiography guide wire after the catheter passed through annular tortuous radial artery,and finally the annular tortuous radial artery could be straightened by fixing the coronary angiography guide wire and rotating and pulling the catheter.Finally,the catheter could be advanced to the coronary orifice and subsequent CAG or PCI could be performed while the annular tortuous radial artery was kept straightening.Both the left and right coronary arteries could perform coronary intervention using this technique,and there were no complications such as forearm hematoma or vascular rupture after this operation.Conclusions It is possible to successfully complete the coronary interventional therapy through annular tortuous radial artery by using the technique with the help of PTCA wire combined with balloon.