Chronic pain is a complex condition shaped by long-standing alterations in both physiological and psychological processes. Rather than representing a simple continuation of acute nociceptive signaling, chronic pain is increasingly understood as the outcome of progressive dysregulation within distributed neural systems that govern sensation, affect, motivation, and cognitive control. Neuroimaging and electrophysiological studies indicate that this state is accompanied by extensive plastic changes in deep brain structures and large-scale networks. Beyond well-described central sensitization processes, chronic pain is characterized by disrupted oscillatory rhythms and altered connectivity within large-scale brain networks, including thalamo-cortical circuits and prefrontal-limbic-reward networks. These findings support a conceptual shift from viewing chronic pain as a focal, lesion-driven phenomenon toward recognizing it as a disorder of distributed network pathology. Pharmacological treatments remain central to clinical practice, yet their long-term efficacy is often limited and frequently accompanied by substantial side effects. The ongoing concerns about opioid-related risks and the inadequate therapeutic response in a subset of patients highlight the need for safe, non-pharmacological approaches that can address not only pain but also comorbid disturbances in mood, sleep, and social functioning. Neuromodulation provides a promising path toward mechanism-based and non-pharmacological management of chronic pain by employing physical or chemical stimulation to alter the excitability and synchrony of specific neural populations within central, peripheral, and autonomic systems. While invasive deep brain stimulation demonstrates that targeting deep brain structures can be effective, its clinical application is restricted by surgical risks and cost, highlighting the importance of non-invasive techniques capable of reaching deep targets. Current non-invasive approaches, such as transcranial electric stimulation, are constrained by limited penetration depth and insufficient spatial precision. These limitations hinder reliable engagement of deep regions implicated in pain, including the thalamus and nucleus accumbens, and tend to produce broad, non-specific modulation of cross-network oscillatory activity. Temporal interference (TI) stimulation has emerged as a means of overcoming these obstacles. By delivering interacting high-frequency currents that generate a low-frequency envelope within the head, TI enables focal stimulation of deep targets while minimizing superficial current delivery. Recent multiscale modeling and animal studies indicate that TI exploits the nonlinear rectification properties of neuronal membranes in response to high-frequency carriers, as well as their phase-locked responses to low-frequency envelopes, to generate “peak-focused” electric fields in deep regions under relatively low superficial current loads. Moreover, TI appears to exhibit potential advantages in terms of cell-type selectivity and rhythm-specific engagement, including differential responses across neuronal subtypes and distinct coupling to θ-, β-, and γ-band oscillations. These features suggest a promising avenue for correcting abnormal rhythms and network dynamics that contribute to chronic pain. This review summarizes current knowledge of the neural mechanisms underlying chronic pain and recent advances in TI research. It examines functional disturbances across key pain-related regions and networks, outlines the principles and technical characteristics of TI, and discusses potential deep-brain targets and stimulation strategies relevant to chronic pain. Evidence to date indicates that TI, with its non-invasiveness, tolerability, and capacity for precise deep brain modulation, holds great promise for the management of treatment-resistant chronic pain and may evolve into a new generation of precise and efficient non-pharmacological analgesic strategies.

Chronic pain is a complex condition shaped by long-standing alterations in both physiological and psychological processes. Rather than representing a simple continuation of acute nociceptive signaling, chronic pain is increasingly understood as the outcome of progressive dysregulation within distributed neural systems that govern sensation, affect, motivation, and cognitive control. Neuroimaging and electrophysiological studies indicate that this state is accompanied by extensive plastic changes in deep brain structures and large-scale networks. Beyond well-described central sensitization processes, chronic pain is characterized by disrupted oscillatory rhythms and altered connectivity within large-scale brain networks, including thalamo-cortical circuits and prefrontal-limbic-reward networks. These findings support a conceptual shift from viewing chronic pain as a focal, lesion-driven phenomenon toward recognizing it as a disorder of distributed network pathology. Pharmacological treatments remain central to clinical practice, yet their long-term efficacy is often limited and frequently accompanied by substantial side effects. The ongoing concerns about opioid-related risks and the inadequate therapeutic response in a subset of patients highlight the need for safe, non-pharmacological approaches that can address not only pain but also comorbid disturbances in mood, sleep, and social functioning. Neuromodulation provides a promising path toward mechanism-based and non-pharmacological management of chronic pain by employing physical or chemical stimulation to alter the excitability and synchrony of specific neural populations within central, peripheral, and autonomic systems. While invasive deep brain stimulation demonstrates that targeting deep brain structures can be effective, its clinical application is restricted by surgical risks and cost, highlighting the importance of non-invasive techniques capable of reaching deep targets. Current non-invasive approaches, such as transcranial electric stimulation, are constrained by limited penetration depth and insufficient spatial precision. These limitations hinder reliable engagement of deep regions implicated in pain, including the thalamus and nucleus accumbens, and tend to produce broad, non-specific modulation of cross-network oscillatory activity. Temporal interference (TI) stimulation has emerged as a means of overcoming these obstacles. By delivering interacting high-frequency currents that generate a low-frequency envelope within the head, TI enables focal stimulation of deep targets while minimizing superficial current delivery. Recent multiscale modeling and animal studies indicate that TI exploits the nonlinear rectification properties of neuronal membranes in response to high-frequency carriers, as well as their phase-locked responses to low-frequency envelopes, to generate “peak-focused” electric fields in deep regions under relatively low superficial current loads. Moreover, TI appears to exhibit potential advantages in terms of cell-type selectivity and rhythm-specific engagement, including differential responses across neuronal subtypes and distinct coupling to θ-, β-, and γ-band oscillations. These features suggest a promising avenue for correcting abnormal rhythms and network dynamics that contribute to chronic pain. This review summarizes current knowledge of the neural mechanisms underlying chronic pain and recent advances in TI research. It examines functional disturbances across key pain-related regions and networks, outlines the principles and technical characteristics of TI, and discusses potential deep-brain targets and stimulation strategies relevant to chronic pain. Evidence to date indicates that TI, with its non-invasiveness, tolerability, and capacity for precise deep brain modulation, holds great promise for the management of treatment-resistant chronic pain and may evolve into a new generation of precise and efficient non-pharmacological analgesic strategies.

ObjectiveThe exacerbating trend of global population aging poses profound socioeconomic and public health challenges, making the comprehensive elucidation of biological aging mechanisms and the discovery of effective anti-aging interventions an urgent priority in the life sciences. Based on our previous serum metabolomics findings that dimethylglycine, an intermediate metabolite of amino acid metabolism naturally present in the human body, was significantly enriched in the serum of longevity families, this study aimed to systematically investigate the anti-aging effects of dimethylglycine both in living organisms and in controlled laboratory environments, and to preliminarily elucidate its underlying molecular mechanisms. While existing literature indicates that dimethylglycine possesses antioxidant and immunomodulatory properties, its direct anti-aging efficacy and the specific molecular pathways through which it operates remain largely unexplored. MethodsTo comprehensively evaluate the anti-aging properties of dimethylglycine, we utilized replicative senescent human embryonic lung fibroblasts, specifically the WI-38 cell line, as an experimental model in a controlled laboratory environment. Cell viability and safety were thoroughly assessed using Cell Counting Kit-8 and lactate dehydrogenase release assays across various concentrations of dimethylglycine. The impact of dimethylglycine on cellular senescence phenotypes, oxidative stress, and proliferative capacity was evaluated via senescence-associated beta-galactosidase staining, reactive oxygen species fluorescence detection, and 5-ethynyl-2'-deoxyuridine incorporation assays. Furthermore, the molecular alterations of senescence-associated secretory phenotype factors and core senescence signaling pathways were quantified using quantitative reverse transcription polymerase chain reaction for the messenger RNA levels of interleukin-6, interleukin-8, p21, and matrix metalloproteinase-1, and enzyme-linked immunosorbent assay for the measurement of p16 and p21 protein expression levels. For the living organism model, the wild-type nematode Caenorhabditis elegans was used to evaluate systemic physiological effects. We conducted a comprehensive lifespan analysis at 20°C, heat stress resistance survival assays at 35℃, senescence-associated beta-galactosidase staining, lipofuscin accumulation tracking, intracellular reactive oxygen species measurement, and Oil Red O staining to ascertain systemic lipid accumulation. Additionally, network pharmacology bioinformatics tools, including PharmMapper and STRING databases, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were utilized to predict target pathways, alongside highly detailed molecular docking simulations utilizing SwissDock and Protein-Ligand Interaction Profiler to examine interactions with the cytochrome P450 family 2 subfamily C member 9 protein. ResultsThe experimental outcomes robustly demonstrate the potent anti-aging capabilities of dimethylglycine. At the cellular level, toxicity analyses firmly confirmed that dimethylglycine is highly safe; continuous treatment with 50 mol/L and 70 mol/L of dimethylglycine for 5 d did not induce any cellular membrane damage or cytotoxicity, but rather actively promoted cellular proliferation. Utilizing the optimal standardized concentration of 50 mol/L, dimethylglycine treatment significantly ameliorated senescent phenotypic markers in human embryonic lung fibroblasts, which was evidenced by a drastic and highly significant reduction in the senescence-associated beta-galactosidase positive cell percentage (P<0.000 1) and intracellular reactive oxygen species levels (P<0.000 1), alongside a marked increase in the 5-ethynyl-2'-deoxyuridine-positive proliferation rate (P=0.003 5). On a molecular expression scale, dimethylglycine significantly downregulated the messenger RNA expression of multiple core senescence-associated secretory phenotype inflammatory factors, including interleukin-6, interleukin-8, p21, and matrix metalloproteinase-1. Concurrently, it effectively suppressed the protein expression of critical cell cycle arrest markers, diminishing p16 protein levels by 57.3% (P=0.000 4) and p21 protein levels by 27.2% (P=0.000 7). In the nematode Caenorhabditis elegans animal model, dimethylglycine significantly extended the mean lifespan from 20.402 d to an impressive 23.066 d (P<0.000 1) and notably enhanced overall survival rates under severe heat stress environmental conditions (P=0.017). Furthermore, systemic dimethylglycine intervention significantly mitigated age-related physiological decline by decreasing bodily lipofuscin accumulation (P<0.000 1), significantly reducing senescence-associated beta-galactosidase activity, lowering systemic reactive oxygen species fluorescence (P=0.008), and effectively alleviating overall fat accumulation (P<0.000 1). Mechanistically, extensive network pharmacology and Kyoto Encyclopedia of Genes and Genomes analyses strongly revealed that the potential targets of dimethylglycine are significantly enriched in fundamental drug metabolism and oxidative stress response pathways. Precision molecular docking simulations conclusively demonstrated that dimethylglycine forms highly stable structural interactions with the cytochrome P450 family 2 subfamily C member 9 protein, specifically highlighting the definitive formation of 5 stable hydrogen bonds involving serine 365, leucine 366, and serine 429 residues, as well as two critical salt bridge formations with arginine 97 and histidine 368 residues. It is additionally predicted to interact favorably with glutathione S-transferase family proteins. ConclusionDimethylglycine exhibits a profoundly significant and multifaceted anti-aging activity at both the cellular and entire living animal levels. By powerfully alleviating oxidative stress, heavily suppressing the core p16 and p21-dependent cellular senescence signaling pathways, and substantially mitigating the detrimental senescence-associated secretory phenotype, dimethylglycine effectively delays fundamental cellular senescence processes and drastically extends whole-organism lifespan. The biological mechanisms driving these robust protective effects are highly likely closely associated with its direct stable interactions with crucial metabolic and detoxifying enzyme systems, such as cytochrome P450 family 2 subfamily C member 9 and glutathione S-transferase family proteins, thereby systemically improving metabolic dysregulation and restoring critical redox homeostasis. This comprehensive study provides highly solid experimental evidence supporting dimethylglycine as a highly potent and safe potential anti-aging intervention agent, while simultaneously offering a clear molecular mechanistic explanation for the previously documented high abundance of dimethylglycine observed within exceptionally long-lived human populations.

OBJECTIVE To investigate the effects and mechanism of the Yishen paidu formula on renal fibrosis in rats with chronic renal failure （CRF） through the reactive oxygen species （ROS）/thioredoxin-interacting protein （TXNIP）/NOD-like receptor thermal protein domain associated protein 3 （NLRP3） pathway. METHODS Rats were randomly divided into control group， model group， Yishen paidu formula low-dose （Yishen paidu formula-L） group， Yishen paidu formula high-dose （Yishen paidu formula- H） group， Yishen paidu formula-H+pcDNA-NC group， and Yishen paidu formula-H+ pcDNA-TXNIP group， with 10 rats in each group. Except for control group， all other rats were fed a diet containing 0.5% adenine to establish a CRF model； the rats were then administered corresponding drugs or normal saline intragastrically or via tail vein， once daily， for 8 consecutive weeks. After the last administration， the levels of serum creatinine （Scr）， blood urea nitrogen （BUN）， ROS， superoxide dismutase （SOD）， malondialdehyde （MDA）， tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-1β were measured in each group. Pathological changes in renal tissue were observed， and the protein expression levels of Collagen Ⅲ， α-smooth muscle actin （α-SMA）， transforming growth factor-β1 （TGF-β1）， TXNIP and NLRP3 in renal tissue were detected. RESULTS Compared with model group， the renal histopathological damage and fibrosis of rats in Yishen paidu formula-L group and Yishen paidu formula-H group were significantly alleviated. The levels of Scr， BUN， ROS， MDA， TNF- α， IL-6 and IL-1β， and the protein expressions of Collagen Ⅲ， α-SMA， TGF-β1， TXNIP and NLRP3 were significantly decreased， while SOD levels were significantly increased （P＜0.05）. Moreover， the changes were more pronounced in the Yishen paidu formula-H group （P＜0.05）. Compared with Yishen paidu formula-H+pcDNA-NC group， above indexes of rats in Yishen paidu formula-H+pcDNA-TXNIP group were reversed significantly （P＜0.05）. CONCLUSIONS Yishen paidu formula can inhibit renal fibrosis in CRF rats by suppressing the ROS/TXNIP/NLRP3 pathway.

Objective To analyze the characteristics of viral hepatitis mortality and life loss among residents in Pudong New Area from 2003 to 2023, and to provide a basis for related prevention and control work. Methods Viral hepatitis mortality data were obtained from the Pudong New Area mortality monitoring system. The crude mortality rate (CMR), standardized mortality rate (SMR), potential years of life lost (PYLL), average years of life lost (AYLL), and standardized potential years of life lost (SPYLL) were calculated to analyze viral hepatitis deaths. The average annual change (AAPC) and annual percentage change (APC) of the mortality rate were calculated by Joinpoint regression analysis to analyze the trend of mortality. Results The CMR and SMR of viral hepatitis among residents in Pudong New Area from 2003 to 2023 were 3.89/100000 and 1.98/100000, respectively. Both CMR and SMR of viral hepatitis showed a decreasing trend over time (CMR:APC=-5.476, t=-13.581, P<0.001; SMR:APC=- 7.624, t= -21.253, P<0.001). The CMR for males was 4.75/100000 and the SMR for males was 2.65/100000; the CMR for females was 3.04/100000 and the SMR for females was 1.32/100000, with a higher mortality rate for males than for females（Z_CME=12.094，P<0.001; Z_SMR=-14.718，P<0.001). Deaths were concentrated in the age groups of 45-64 years old and 65 years old and above, accounting for 91.62% of the total deaths. The PYLL of deaths due to viral hepatitis among residents in Pudong New Area from 2003 to 2023 was 26912 person-years, with a PYLLR of 0.45% and an AYLL of 8.88 years per person. Conclusion The mortality rate of viral hepatitis among the residents of Pudong New Area in 2003-2023 shows a decreasing trend over time. The mortality rate of males is higher than that of females, and the deaths of middle-aged and elderly people account for a large proportion of the total deaths. Chronic hepatitis B is the main cause of death.

OBJECTIVE To establish the high-performance liquid chromatography （HPLC） fingerprint of Sagina japonica ， and to establish a quantitative analysis of multi-components by single-marker （QAMS） method for simultaneous determination of six componen ts in S. japonica ， aiming to provide references for the quality control of this medicinal herb. METHODS HPLC method was used to establish the fingerprints of 12 batches （No. S1-S12） of S . japonica according to Similarity Evaluation System of Chromatographic Fingerprint of Traditional Chinese Medicine . The similarity evaluation and identification of common peaks were conducted， followed by cluster analysis （CA） and principal component analysis （PCA） for 12 batches of samples. Using vicenin-2 as internal reference， the contents of p-hydroxy cinnamic acid， apigenin-6-C-arabinoside-8-C-glucoside， isoorientin， vitexin and 20-hydroxyecdysone were determined by QAMS method. The results were then compared with those obtained by the external standard method. RESULTS The similarities of HPLC fingerprints for 12 batches of S . japonica ranged from 0.828-0.998. A total of 17 common peaks were calibrated， and 6 common peaks were identified. Specifically， peak 5 was identified as vicenin-2， peak 7 as p-hydroxycinnamic acid， peak 10 as apigenin-6-C-arabinoside-8-C-glucoside， peak 11 as isoorientin， peak 13 as vitexin， and peak 15 as 20-hydroxyecdysone. The results of CA showed that S1-S5， S7 and S9-S11 were clustered into one category， S6 was clustered into one category， and S8 and S12 were clustered into one category. The results of PCA revealed that the accumulative contribution rate of the four main components was 89.430%. The content ranges measured by QAMS method for p-hydroxy cinnamic acid， apigenin-6-C-arabinoside-8-C-glucoside， isoorientin， vitexin and 20-hydroxyecdysone were 0.017 4-0.269 4， 0.568 8-4.240 3， 0.503 2-5.040 3， 0.024 0-0.132 0 and 2.551 3-4.881 1 mg/g， respectively. There was no significant difference in the contents of components measured between QAMS method and the external standard method （ P ＞0.05）. CONCLUSIONS The established HPLC fingerprint and QAMS method can be used for quality evaluation and quality control of S . japonica.

Background Di(2-ethylhexyl) phthalate (DEHP) is the most prevalent environmental endocrine disruptor among phthalate acid esters (PAEs) worldwide. Previous studies have indicated that exposure to DEHP may disrupt glucose metabolism. Objective To investigate the impact of DEHP on glucose homeostasis in rats, focusing on oxidative stress-induced impairment of autophagy in islet β cells. Methods Forty male SD rats were randomly assigned to four groups, receiving DEHP doses of 0, 187, 375, and 750 mg·kg⁻¹ for 12 weeks. Oral glucose tolerance (OGTT) and insulin tolerance tests (ITT) were conducted 24 h after the final exposure. Pancreatic microstructural alterations were assessed using hematoxylin and eosin (HE) staining and transmission electron microscopy (TEM). Commercial ELISA kits were employed to quantify the levels of insulin, adenosine triphosphate (ATP), and adenosine monophosphate (AMP) in rat serum, as well as the protein expression level of activated caspase-3 in pancreatic tissue. Additionally, commercial microplate kits were utilized to measure the concentration of reduced glutathione (GSH) in serum, the activity of superoxide dismutase (SOD) using water-soluble tetrazolium salt-1, the content of malondialdehyde (MDA) by thiobarbituric acid method, and the level of reactive oxygen species (ROS) in pancreatic tissue by chemical fluorescence method. Reverse transcription polymerase chain reaction (RT-PCR) was used to measure sequestosome1 (SQSTM1/p62), Beclin1, microtubule-associated protein 1 light chain 3 (LC3), and cysteinyl aspartate specific proteinase-8 (Caspase-8) mRNA levels. Western blot analysis was applied to detect the protein relative expression levels of p62, Beclin-1, LC3-I, LC3 II, AMPK, p-AMPK, mTOR, p-mTOR, ULK1, and Caspase-8. Results Compared to the 0 mg·kg⁻¹ DEHP group, the 750 mg·kg⁻¹ DEHP group exhibited a significant increase in fasting blood glucose levels at 2, 4, 6, and 12 weeks (P<0.05). The OGTT showed that, following high-glucose gavage, the 187 mg·kg⁻¹ DEHP group had elevated blood glucose at 30 min (P<0.05), the 375 mg·kg⁻¹ DEHP group showed increased glucose levels at 15, 30, and 180 min (P<0.05), and the 750 mg·kg⁻¹ DEHP group exhibited elevated levels at 15, 30, 60, and 180 min (P<0.05). The 375 and 750 mg·kg⁻¹ DEHP groups demonstrated significantly increased OGTT area under the curve (AUC) values (P<0.05). In contrast, ITT results indicated no significant differences in blood glucose levels or AUC among the DEHP exposure groups at all time points (P>0.05). Compared to the 0 mg·kg⁻¹ DEHP group, the 750 mg·kg⁻¹ DEHP group exhibited significantly higher HOMA-IR levels and markedly lower HOMA-ISI values (P<0.05). HE and TEM showed that in each DEHP exposure group, the number of islet cells decreased, the islet area reduced, and chromatin condensation occurred. The endocrine granules in the cytoplasm of islet β cells decreased, and there were varying degrees of widening of the nuclear membrane gap, flattening and expansion of the Golgi complex, and expansion of the endoplasmic reticulum. Ribosome separation was observed, and autophagosomes were visible. In the 375 and 750 mg·kg⁻¹ DEHP groups, the mitochondria were deformed to varying degrees, and some cristae structures disappeared, presenting vacuolization. Moreover, the chromatin condensation in the nuclei was more severe in the 750 mg·kg⁻¹ DEHP group. The serum SOD activity was significantly elevated in the 750 mg·kg⁻¹ DEHP group (P<0.05). Both the 375 mg·kg⁻¹ and 750 mg·kg⁻¹ DEHP groups exhibited a significant increase in the relative ROS content in pancreatic tissue (P<0.05). In DEHP-treated groups, the MDA content increased (P<0.05), while the GSH content decreased (P<0.05). Additionally, in the 750 mg·kg⁻¹ DEHP group, the AMP/ATP ratio in serum was significantly raised (P<0.05), and the expression of cleaved Caspase-3 protein in pancreatic tissue was also significantly increased (P<0.05). The relative mRNA levels of p62, Beclin-1, LC3, and Caspase-8 in the pancreatic tissue of rats exposed to DEHP were significantly elevated (P<0.05). The relative expression levels of p-AMPK/AMPK, p-ULK1/ULK1, and Beclin-1 proteins in the DEHP-treated groups were significantly increased (P<0.05). In the 375 mg·kg⁻¹ and 750 mg·kg⁻¹ DEHP treatment groups, the relative expression levels of p62, LC3 II/LC1, and Caspase-8 proteins were significantly increased (P<0.05), while the relative expression level of p-mTOR/mTOR was significantly decreased (P<0.05). Conclusion DEHP can disrupt glucose homeostasis by inducing oxidative stress, which subsequently activates autophagy via the ROS/AMPK/ULK1 pathway, impairing autophagic flux and promoting apoptosis of islet β cells, ultimately decreasing their function and number.

Compared to traditional suturing, lung stapling using automatic staplers offers advantages such as smaller trauma, faster wound healing, ease of operation, and lower complication rates, making it widely used in clinical practice. However, there are significant differences in bronchial tissue thickness at different anatomical locations, and the market is flooded with various types of staplers. Currently, there is a lack of recommended stapling schemes for bronchial staplers at different anatomical locations. This article reviews the development and application of automatic staplers and summarizes some types of staplers that are currently used in clinical practice, with the aim of promoting the formation of individualized stapler selection protocols for minimally invasive thoracic surgery based on the Chinese population.

OBJECTIVE To evaluate the efficacy and safety of guideline-directed medical therapy （GDMT） combined with vericiguat in treating heart failure with reduced ejection fraction （HFrEF）. METHODS A retrospective study was conducted on 346 patients with HFrEF who received standardized diagnosis and treatment at the First People’s Hospital of Changzhou from January 2023 to May 2024. They were divided into standard treatment group （n＝215） and vericiguat group （n＝131）. Patients in the standard treatment group received GDMT， while patients in the vericiguat group received GDMT combined with vericiguat. Propensity score matching （PSM） was used to balance confounding factors between two groups， and the effectiveness （including outcome and prognostic indicators） and safety （occurrence of adverse events） of both groups were evaluated. Kaplan-Meier survival curves for primary and secondary outcome events were drawn， and the influential factors of primary outcome events were screened through univariate and multivariate Cox regression analysis. RESULTS After PSM， there were 100 patients in the standard treatment group and 100 patients in the vericiguat group， and there was no statistically significant differences in baseline data between two groups （P＞0.05）. During a 1-year follow-up， there were statistically significant differences in the cumulative incidence of major outcome events between the standard treatment group and the vericiguat group， cumulative incidence of hospitalization events due to heart failure， changes in N-terminal pro-B-type natriuretic peptide levels before and after treatment between the standard treatment group and the vericiguat group （P＜0.05）. There was no statistically significant difference in the incidence of adverse events between the two groups （P＞0.05）. Multivariate Cox regression analysis results showed that left ventricular ejection fraction ≤35% was a risk factor for the occurrence of major outcome events within 1 year [hazard ratio （HR）＝ 2.090， 95% confidence interval （CI）： 1.175-3.718， P＝0.012]， while the use of vericiguat was a protective factor for the occurrence of major outcome events within 1 year （HR＝0.505， 95%CI： 0.284-0.899， P＝0.020）. CONCLUSIONS Compared with GDMT， GDMT combined with vericiguat can improve the clinical symptoms and prognosis of HFrEF patients， and has good safety.

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.