ObjectiveTo investigate the anti-Alzheimer's disease （AD） effect of Dipsacus asper（DA） in the Caenorhabditis elegans model， and decipher the underlying mechanism via the peroxisome proliferator-activated receptor α （PPARα）/transcription factor EB （TFEB） pathway. MethodsFirst， transgenic AD C. elegans individuals were assigned into the blank control， model， positive control （WY14643， 20 µmol·L^-1）， and low-， medium-， and high-dose （100， 200， and 400 mg·L^-1， respectively） DA groups. The amyloid β-42 （Aβ₄₂） formation in the muscle cells， the paralysis time， and the deposition of amyloid β-protein （Aβ） in the head were detected. The lysosomal autophagy in the BV2 cell model was examined by Rluc-LC3wt/G120A. The expression levels of lysosomal autophagy-related proteins LC3Ⅱ， LC3I， LAMP2， and TFEB were detected by Western blot. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of autophagy-related genes beclin1 and Atg5 and lysosome-related genes LAMP2 and CLN2 downstream of PPARα/TFEB. A reporter gene assay was used to detect the transcriptional activities of PPARα and TFEB. Immunofluorescence was used to detect the fluorescence intensity of PPARα， and the active components of the ethanol extract of DA were identified by UPLC-MS. RCSB PDB， Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and Autodock were used to analyze the binding between the active components and PPARα-ligand-binding domain （LBD）. ResultsCompared with the model group， the positive control group and 200 and 400 mg·L^-1 DA groups showed prolonged paralysis time （P<0.05）， and all the treatment groups showed decreased Aβ deposition in the head （P<0.01）. DA within the concentration range of 50-500 mg·L^-1 did not affect the viability of BV2 cells. In addition， DA enhanced the autophagy flux （P<0.05）， up-regulated the mRNA levels of beclin1， Atg5， LAMP2， and CLN2 （P<0.05， P<0.01）， promoted the nuclear translocation of TFEB （P<0.05）， increased LAMP2 expression and autophagy flux （P<0.05， P<0.01）， and enhanced the transcriptional activities of PPARα and TFEB （P<0.01）. The positive control group and 200 and 400 mg·L^-1 DA groups showed enhanced fluorescence intensity of PPARα in the BV2 nucleus （P<0.01）. UPLC-MS detected nine known compounds of DA， from which 8 active components of DA were screened out. The docking results suggested that a variety of components in DA could bind to PPARα-LBD and form stable hydrogen bonds. ConclusionDA may reduce the pathological changes in AD by regulating the PPARα-TFEB pathway.

Background Existing studies have confirmed that fine particulate matter (PM_2.5)is one of the important factors inducing pulmonary fibrosis. Pulmonary fibrosis is the terminal stage of a major category of lung diseases characterized by the destruction of tissue structure, and eventually leading lung ventilation and ventilation dysfunction. No effective pulmonary fibrosis treatment is available yet. Objective To investigate the protective effect of salidroside on pulmonary fibrosis induced by the exposure of PM_2.5 and its molecular mechanism. Methods Seventy 7-week-old male C57BL/6 mice were randomly divided into four groups: control group (intratracheal instillation of normal saline + saline by gavage, n=25), Sal group (intratracheal instillation of normal saline + Sal 60 mg·kg⁻¹ by gavage, n=10), PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ + saline by gavage, n=10), and Sal + PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ +Sal 60 mg·kg⁻¹ by gavage, n=10). The mice were administered by gavage once daily, intratracheal instillation once every 3 d, and every 3 d constituted an experimental cycle. At the end of the 26-30th cycles, 3 mice in the control group and 3 mice in the PM_2.5 group were randomly sacrificed, and the lung tissues were collected for Masson staining to verify whether the pulmonary fibrosis model was successfully established. After 30 cycles, the model was successfully constructed. After 1 week of continuous observation, the mice were sacrificed, and the blood and lung tissues of the mice were collected to make lung tissue sections. Assay kits were correspondingly employed to detect oxidative stress indicators such as serum malondialdehyde (MDA) and superoxide dismutase (SOD). Western blotting was used to detect the expression of fibrosis-related proteins (Collagen-III, α-SMA), mitochondrial dynamics-related proteins (MFN1, Drp1), and mitophagy-related proteins (PINK1, Parkin, and LC3). Results Compared with the control group, the weight gain rate of the PM_2.5 group was slowed down (P<0.05), which was alleviated by the Sal intervention (P<0.05). The lung coefficient increased after the PM_2.5 exposure (P<0.05), which was alleviated by Sal intervention. Compared with the control group, the PM_2.5 group showed severe alveolar structure damage, inflammatory cell infiltration, and blue collagen deposition, and significantly increased the lung injury score, collagen volume fraction (CVF), Szapiel score, and Ashcroft score (P<0.05), as well as serum oxidative stress levels (P<0.05). The protein expression levels of Collagen-III, α-SMA, Drp1, PINK1, Parkin, and LC3 II/I were increased (P<0.05), and the expression of MFN1 was decreased (P<0.05). Compared with the PM_2.5 group, the Sal intervention alleviated lung injury, reduced inflammatory cell infiltration and collagen deposition, showing decreased lung injury score, CVF, Szapiel score, and Ashcroft score (P<0.05), and decreased serum oxidative stress levels (P<0.05); the protein expression levels of Collagen-III, α-SMA, PINK1, Parkin, and LC3 II/I were decreased (P<0.05), the expression level of Drp1 was decreased, and the expression level of MFN1 was increased. Conclusion In the process of pulmonary fibrosis induced by PM_2.5 exposure in mice, Sal may affect mitochondrial autophagy through PINK1/Parkin pathway and play a protective role. The specific mechanism needs to be further verified.

Objective To explore the application status and development trend of machine learning in the field of pharmacovigilance worldwide,and to provide reference for the research on the application of machine learning in the field of pharmacovigilance.Methods Relevant literature was searched in the Web of Science with the key words of"machine learning"and"pharmacovigilance"from the inception to March 1,2023.R language and other software were used to quantitatively analyze the literature data in this field.The clustering,co-occurrence and emergence visual analysis were carried out on the characteristics of annual published papers,institutions,countries,keywords and other aspects.Results A total of 904 literature were included.The number of literature published showed a fluctuating upward trend since 1994.There was cross-regional,cross-regional and cross-agency cooperation among the cooperative network institutions.The top 5 countries in the number of publications were the United States,China,Japan,South Korea and India,China and the United States had relatively close cooperation in this field.Signal detection,social media and electronic health records were high-frequency keywords in this field.Clustering and association rule analysis showed that this field focused on three aspects signal recognition,unstructured text mining and analysis,and processing and analysis of electronic medical information.At present,machine learning has made significant progress in signal recognition,social media information mining,and unstructured text processing of electronic medical information,which broaden the data sources of pharmacovigilance,improve the real-time monitoring ability of adverse drug reactions,bringing innovation impetus to the field of pharmacovigilance.Conclusion The rapid development of big data and artificial intelligence technologies has led to an increasing integration of machine learning into the field of pharmacovigilance,which promotes technical exchanges and cooperation and cross-disciplinary integration.It is necessary to optimize each machine learning algorithm to improve its accuracy and stability in pharmacovigilance,strengthen the protection measures of data privacy and security to ensure the safety of patient information.Integrating expertise in the fields of science,medicine,and data statistics with a view to promoting technological progress in the field of pharmacovigilance.

In humans, the liver is a central metabolic organ with a complex and unique histological microenvironment. Hepatocellular carcinoma (HCC), which is a highly aggressive disease with a poor prognosis, accounts for most cases of primary liver cancer. As an emerging hallmark of cancers, metabolic reprogramming acts as a runaway mechanism that disrupts homeostasis of the affected organs, including the liver. Specifically, rewiring of the liver metabolic microenvironment, including lipid metabolism, is driven by HCC cells, propelling the phenotypes of HCC cells, including dissemination, invasion, and even metastasis in return. The resulting formation of this vicious loop facilitates various malignant behaviors of HCC further. However, few articles have comprehensively summarized lipid reprogramming in HCC metastasis. Here, we have reviewed the general situation of the liver microenvironment and the physiological lipid metabolism in the liver, and highlighted the effects of different aspects of lipid metabolism on HCC metastasis to explore the underlying mechanisms. In addition, we have recapitulated promising therapeutic strategies targeting lipid metabolism and the effects of lipid metabolic reprogramming on the efficacy of HCC systematical therapy, aiming to offer new perspectives for targeted therapy.

Objective:To explore the behavioral intention of nurses for pain management after abdominal surgery based on the planned behavior theory.Methods:According to the framework of planned behavior theory, an interview outline was developed. Using the purposive sampling method, a total of 11 General Surgical Department nurses from the First Affiliated Hospital of Wenzhou Medical University from July to November 2022 were selected as the interview subjects for semi-structured interviews to understand their behavioral intentions regarding postoperative pain management in abdominal surgery. Colaizzi 7-step analysis was used to analyze the original data. Two researchers repeatedly compared, verified, analyzed and summarized the interview data. When different opinions were generated, the group members discussed and decided together to ultimately determine the code and theme.Results:Based on the three dimensions of behavioral attitude, subjective norms and perceived behavioral control in the theoretical framework of planned behavior, three themes and seven sub-themes were extracted, such as behavioral attitude (positive attitude, negative attitude), pressure sources (group pressure, leadership pressure, patient and family pressure), subjective perception and behavior (imprisonment of comfort zone, insufficient support from external resources) .Conclusions:Most nurses hold a positive attitude towards pain management behavior after abdominal surgery, and the behavioral intention of postoperative pain management is affected by colleagues, leaders, patients and their families. At the same time, there are also obstacles such as insufficient personal ability and insufficient support from external resources.

Objective:To describe disability rates of dementia in community residents aged 65 years and over in China,and explore related risk factors of disability.Methods:This study conducted an in-depth data analysis of the China Mental Health Survey.World Health Organization Disability Assessment Schedule 2.0(WHODAS 2.0)was used to assess dementia disability,Community Screening Interview for Dementia(CSID)and Geriatric Mental Status Examination(GMS)were used for dementia screening and diagnosing.Univariate analysis was used to calcu-late the weighted disability rates of dementia in population and in patients,and their population distribution.Multiple linear regression and logistic regression were used to analyze the risk factors of the occurrence of dementia disability and its severity.Results:The weighted disability rate of dementia was 2.1％in population,and 38.6％in pa-tients.The disability rates of comorbid dementia in population and in patients were higher than those of patients with only dementia.Female,older age,lower education level,lower economic status,and lower cognitive test scores in CSID had higher disability rates of dementia in population.Female and urban resident had higher disability rates of dementia in patients.Multiple linear regression showed economic status(β=0.11),gender(β=0.11),age(β=0.10),and treatment in the last 12 months(β=-0.20)were statistically associated with WHODAS 2.0 scores.Multiple logistic regression showed female(OR=2.81)and treatment in the last 12 months(OR=2.38)were statistically associated with disability.Conclusions:Persons with low economic status,female and elderly peo-ple are the high-risk groups for dementia disability.It should be paid attention to prevent dementia and its conse-quential disabilities.

Objective:To explore the cerebral cortical mechanism of intravesical electrical stimulation (IVES) on neurogenic underactive bladder (UAB).Methods:A prospective study was conducted on healthy subjects (HS) recruited in our center and patients with neurogenic UAB treated with IVES from March 2022 to June 2023 were included. HS inclusion criteria: females aged 18-60 years; the 72-hour voiding diary was normal; the urine volume was 200-400 ml, and the free urine flow rate > 20 ml/s. HS exclusion criteria: urinary and neurological related disorders; major diseases of all systems of the body; cognitive dysfunction. Inclusion criteria for UAB patients: females aged 18-60 years; neurogenic UAB due to incomplete spinal cord injury (grade D or E) with a duration of > 3 months; previous routine use of intermittent catheterization, or indication of intermittent catheterization (residual urine accounts for > 40% of functional bladder capacity). Exclusion criteria for UAB patients: decreased bladder compliance on urodynamic examination; symptomatic urinary tract infection; concomitant hydronephrosis, vesicoureteral reflux or renal insufficiency (serum creatinine greater than 1.5 times of the normal upper limit); bladder tumors; neurological related diseases; pregnant or trying to conceive; a pacemaker or defibrillator has been implanted in the body. At baseline, the 24-hour voiding diary, residual urine, voiding efficiency, first sensation of bladder filling volume and American Urological Association Symptom Index Quality of Life scores(AUA-SI-QOL)were recorded, and the resting state-functional near-infrared spectroscopy scans of the prefrontal cortex was completed in the bladder emptying state and the strong desire to void stage. The UAB group was re-evaluated after completing 20 IVES treatments. Improvement in residual urine > 50% was defined as success of IVES treatment. The differences in functional connectivity in the prefrontal lobe between the successful UAB group before and after IVES and between the successful UAB group and the HS group were compared.Results:A total of 16 HS and 18 UAB patients were included. Eleven UAB patients were successfully treated by IVES, and 7 UAB patients were failed. Compared with pre-treatment, the post-treatment residual urine volume [90.0(50.0, 120.0) ml vs. 210.0(110.0, 300.0) ml], 24-h intermittent catheterization [3.0(2.0, 4.0) times vs. 4.0(3.0, 4.0) times], first sensation of bladder filling volume [275.0(245.0, 280.0) ml vs. 295.0 (290.0, 315.0) ml] and AUA-SI-QOL score [2.0 (2.0, 3.0) vs. 4.0 (4.0, 4.0)] of the successful UAB group were significantly lower ( P<0.05), and the voiding efficiency [75.0% (69.0%, 85.0%) vs. 42.0% (35.0%, 77.0%)] was significantly higher ( P< 0.05). Before IVES, the successful UAB group compared with the HS group, internal prefrontal functional connectivity was significantly attenuated in the bladder emptying state involving 5 brain regions: bilateral dorsolateral prefrontal cortex (DLPFC), bilateral frontopolar area, and left pars triangularis. And in the strong desire to void stage significantly attenuated involving 4 brain regions: bilateral DLPFC and bilateral frontopolar area. In the successful UAB group after IVES compared with the HS group, internal prefrontal functional connectivity was significantly attenuated in the bladder emptying state involving 2 brain regions: left pars triangularis and left DLPFC. And in the strong desire to void stage involving 4 brain regions: left DLPFC, right frontopolar area, the left pars opercularis Broca's area, and the left pars triangularis. After IVES in the successful UAB group compared with pretreatment, prefrontal internal functional connectivity was significantly enhanced in the bladder emptying state involving 4 brain regions: bilateral DLPFC and bilateral frontopolar area, and in the strong desire to void stage involving 4 brain regions: bilateral DLPFC, bilateral frontopolar area. Conclusions:Significant enhancement of functional connectivity within the prefrontal lobes (bilateral DLPFC and bilateral frontopolar area) may be the cortical mechanism of IVES for neurogenic UAB.

Objective:To investigate the efficacy and safety of a wearable percutaneous tibial nerve stimulator (TTNS) for tibial neuromodulation (TNM) in the treatment of overactive bladder (OAB).Methods:This research utilizes a single-center, prospective, open clinical trial design. Patients with OAB who were treated at the urology outpatient department of Beijing Bo’ai Hospital from July 2023 to June 2024 were enrolled. All patients met the diagnostic criteria for OAB. All patients received a transcutaneous tibial nerve regulation stimulation therapy, with a frequency of 20 Hz and a pulse width of 0.2 ms. The treatment lasted for 30 minutes each session, twice daily, for a duration of 12 weeks. Follow up evaluations were conducted at weeks 4, 8, and 12 after treatment, including a 72-hour voiding diary, Overactive Bladder Symptom Score (OABSS), patient perception of bladder condition scale (PPBC-S) score, American Urological Association Symptom Index (AUA-SI) score, American Urological Association Symptom Index Quality of Life Score (AUA-SI-QOL) score, vital signs, and adverse events.Results:This study included 68 patients, with 28 males and 40 females. Their mean age was (49.6±9.0) years old, the body mass index was(23.2 ± 2.5) kg/m 2. The duration of the disease was(42.0±14.4)months. After 12 weeks of intervention, patient's daily urination frequency decreased from (18.5 ± 3.9) times to (10.3 ± 4.5) times, nocturia frequency decreased from (6.5±2.2) times to (3.9±2.0) times, daily urine leakage decreased from (796.5±140.0) ml to (534.8±135.8)ml, OABSS decreased from (12.6±2.8) to (9.8±3.8), PPBC-S decreased from (5.5±0.6) to (3.8±1.2), AUA-SI decreased from (25.5±2.2) to (16.6±3.6), and AUA-SI-QOL decreased from (5.5±0.5) to (3.7±1.1). The differences in the above indicators before and after treatment were statistically significant ( P<0.05). During the treatment process, there were no serious adverse events related to the equipment, and no neurological related adverse events such as numbness or tingling occurred. Conclusions:The application of wearable percutaneous tibial nerve stimulators in TNM can effectively alleviate OAB symptoms like frequent urination and urgency, with minimal adverse reactions, offering a new treatment option for OAB patients.

Objective To deeply analyze the problems of public hospitals in medical service satisfaction,construct a more applicable and explanatory service satisfaction evaluation model,and provide reference for the improvement path of patients'medical service satisfaction.Methods Based on the ESCI model,this paper puts forward a research hypothesis,compiles the"Medical Service Satisfaction Evaluation Scale of Public Hospitals in S City",selects S public hospitals as the research object,and evaluates medical service satisfaction from the perspective of patients.Results At present,the main problems affecting the improvement of patients'satisfaction with medical service management in public hospitals in S city are as follows:it is urgent to improve the diagnosis and treatment technology in terms of hardware quality and optimize the environmental hygiene of public hos-pitals,and it is an urgent task to shorten the waiting time for medical treatment in software quality.The score of medical service satisfaction evaluation of S public hospitals was 3.76,and the satisfaction of patients in S public hospitals with their medical serv-ices was at a moderately low level.Conclusion In view of the above problems,it is recommended to strengthen the construction of key specialties,strengthen the construction of talent team,optimize the medical process,open digital linkage services,and strengthen service management,so as to promote the improvement of patients'satisfaction with medical services.

Objective:To investigate the clinical efficacy and safety of ferric derisomaltose injection versus iron sucrose injection in the treatment of iron deficiency anemia (IDA) .Methods:A total of 120 patients with iron deficiency anemia admitted from June 2021 to March 2023 were given intravenous iron supplementation with ferric derisomaltose to assess the efficacy and safety of hemoglobin (HGB) elevation before and after treatment. Simultaneously, the clinical effects of iron supplementation with iron sucrose were compared to those of inpatient patients during the same period.Results:Baseline values were comparable in both groups. Within 12 weeks of treatment, the elevated HGB level in the ferric derisomaltose group was higher than that of the iron sucrose group, with a statistical difference at all time points, and the proportion of HGB increased over 20 g/L in the patients treated for 4 weeks was higher (98.7%, 75.9% ). During the treatment with ferric derisomaltose and iron sucrose, the proportion of mild adverse reactions in the ferric derisomaltose group was slightly lower than that of the iron sucrose group, and neither group experienced any serious adverse reactions. The patients responded well to the infusion treatment, with no reports of pain or pigmentation at the injection site.Conclusion:The treatment of IDA patients with ferric derisomaltose has a satisfactory curative effect, with the advantages of rapidity, accuracy, and safety. Therefore, it is worthy of widespread clinical use.