OBJECTIVE To ensure the safety of patients’ drug use and control the risk of medical insurance expenditure by upgrading the pre-prescription review system to conduct pre-review on prescriptions from internet hospitals and external prescriptions， as well as to review the payment methods of drugs （including in-hospital and external drug dispensing）. METHODS The data interfaces of prescriptions from internet hospitals and external prescriptions were integrated to achieve real-time rational drug use intervention. Additionally， an intelligent review project for payment method was added to precisely intervene in the medical insurance payment methods of drugs. The effect of the system upgrade was evaluated by comparing the qualification rates of prescriptions from internet hospitals and external prescriptions and the suspected amounts of drug violations from January to April 2025 （before the system upgrade） and May to August 2025 （after the system upgrade）. RESULTS After the upgrade of the pre-prescription review system， the qualification rates of prescriptions from internet hospitals and external prescriptions increased by 3.5% [95% confidence interval （CI）＝0.3%-6.7%， P ＝0.037 ] ； the suspected amounts of drug violations decreased to 52.9% of the pre-upgrade level （95%CI＝31.6%-88.5%， P ＝0.026）， and the average monthly sequential decrease was 29.5% （95%CI＝12.2%-43.4%， P ＝0.012）. Moreover， the addition of the intelligent review project for payment methods promoted the management of off-label drug use in our hospital. After the upgrade， a total of 79 filling valid applications for off-label drug use were received and archived. CONCLUSIONS The upgrade of the pre-prescription review system effectively improves the review qualification rates of prescriptions from internet hospitals and external prescriptions and the accuracy of medical insurance payment for drugs， and strengthens the supervision of off-label drug use， achieving dual guarantees of clinical rationality and medical insurance compliance.

ObjectiveTo investigate the intervention effects of modified Linggui Zhugan Tang （LGZGT） on patients with obstructive sleep apnea-hypopnea syndrome （OSAHS） of the spleen deficiency and dampness obstruction with blood stasis type， reveal its possible mechanisms， and provide a theoretical basis for the clinical treatment of OSAHS with traditional Chinese medicine （TCM）. MethodsEighty OSAHS patients with spleen deficiency and dampness obstruction with blood stasis were randomly assigned to a control group and an observation group （1∶1） using a random number table， with 40 patients in each group. The control group received standard basic treatment combined with oral Doxofylline tablets， while the observation group received standard basic treatment combined with modified LGZGT. Serum levels of macrophage migration inhibitory factor （MIF）， microRNA-223 （miR-223）， and interleukin-18 （IL-18） were measured by enzyme-linked immunosorbent assay （ELISA）， and the mRNA expression levels of MIF， miR-223， and IL-18 were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. After two months of treatment， the total clinical efficacy， apnea-hypopnea index （AHI）， lowest nocturnal oxygen saturation （LSpO₂）， body mass index （BMI）， TCM syndrome scores， and expression levels of MIF， miR-223， and IL-18 before and after treatment were compared between the two groups. Correlations between MIF， miR-223， IL-18 and AHI and LSpO₂ were also analyzed. ResultsCompared with the control group， the observation group showed a significantly higher total clinical effective rate （P<0.01， Z=-3.49）. Within the control group， no significant changes were observed in AHI， LSpO₂， BMI， TCM syndrome scores， or MIF， miR-223， IL-18 levels and their mRNAs after treatment. In the observation group， AHI， BMI， TCM syndrome scores， and MIF and IL-18 levels and their mRNAs decreased significantly， while LSpO₂ increased significantly （P<0.01）. After treatment， compared with the control group， the observation group exhibited significantly lower AHI， BMI， TCM syndrome scores， and MIF and IL-18 levels and their mRNAs， and significantly higher LSpO₂ （P<0.01）. Correlation analysis showed that MIF and IL-18 were positively correlated with AHI （P<0.01） and negatively correlated with LSpO₂ （P<0.01）， whereas miR-223 was negatively correlated with AHI （P<0.01） and positively correlated with LSpO₂ （P<0.01）. ConclusionModified LGZGT may improve OSAHS of the spleen deficiency and dampness obstruction with blood stasis type by reducing airway inflammatory factors， alleviating airway inflammation， relieving airway edema and stenosis， and improving airway obstruction.

OBJECTIVE To develop a pharmacist-led intervention model for reducing drug-related medical insurance claim denial risks， so as to provide practical references for healthcare institutions in fulfilling their primary responsibility for medical insurance fund supervision. METHODS A risk matrix method was employed by the pharmacists to assess the risks associated with drug‑related medical insurance claim rejections in our hospital during 2024. Intervention measures were developed targeting high‑risk factors (including inappropriate indications for medical insurance coverage, exceeding the covered treatment course, and inappropriateness of gender and age) from three dimensions, namely organizational structure, technical prevention and control, and closed‑loop management. Changes in drug‑related claim rejection data were compared between 2024 (pre‑intervention) and 2025 (post‑intervention), and the interception effect of the pre‑prescription review system was evaluated after the intervention. RESULTS After the intervention, the total amount of drug‑related medical insurance claim rejections in our hospital was reduced by 57.24% compared with that before the intervention, and the number of rejected items decreased from 10 108 to 2 892. Specifically, the number of rejected items due to inappropriate indications, exceeded treatment course, inappropriate gender, and inappropriate age was reduced by 70.94%, 74.26%, 83.86%, and 96.70%, respectively. Throughout the year following the intervention, a total of 5.605 yuan million in outpatient prescription drug amounts and 4.683 million yuan in inpatient medication order amounts that did not meet the insurance‑limited payment requirements were intercepted by the pre‑prescription review system. The proportion of drug‑related claim rejection amount to the total medical service claim rejection amount of our hospital decreased to 19.7%. CONCLUSIONS The pharmacist-led multi-department collaborative， technical prevention and control， and dynamic optimization integrated full-process intervention model is highly operable and has significant practical effects. It has important promotion value in reducing drug-related medical insurance claim denial risks.

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc), primarily manifesting as motor dysfunctions such as resting tremor, muscle rigidity, and bradykinesia. According to the classical model of basal ganglia motor control, approximately half of the medium spiny neurons (MSNs) in the striatum are D1-MSNs, which constitute the direct pathway. These neurons express D₁-dopamine receptor (D₁R) and substance P, and they mainly participate in the selection, initiation, and execution of movements. The other half are D2-MSNs, which constitute the indirect pathway. These neurons express D₂-dopamine receptor (D₂R) and adenosine 2A receptors and are involved in inhibiting unnecessary movements or terminating ongoing movements, thereby adjusting movement sequences to perform more precise motor behaviors. The direct pathway in the striatum modulates the activity of motor cortex neurons by exciting D1-MSNs through neurotransmitters such as glutamate (Glu), allowing the motor cortex to send signals more freely to the motor system, thus facilitating the generation and execution of specific motor behaviors. Studies using D1-Cre and D2-Cre mice with neurons labeled for D₁R and D₂R have shown that both types of neurons are involved in the execution of movements, with D1-MSNs participating in movement initiation and D2-MSNs in inhibiting actions unrelated to the target movement. These findings suggest that the structural and functional plasticity of D1-MSNs and D2-MSNs in the basal ganglia circuitry enables motor learning and behavioral regulation. Additionally, when SNpc DA neurons begin to degenerate, D1-MSNs are initially affected but do not immediately cause motor impairments. In contrast, when D2-MSNs undergo pathological changes, they are first activated by upstream projecting neurons, leading to the inhibition of most motor behaviors and resulting in motor dysfunction. Therefore, it is hypothesized that motor impairments such as bradykinesia and initiation difficulties are more closely related to the functional activity of D2-MSNs. The extracellular signal-regulated kinase (Erk)/mitogen-activated protein kinase (MAPK) signaling pathway has been identified as a critical modulator in the pathophysiology of PD. Recent findings indicate that Erk/MAPK signaling pathway can mediate DA and Glu signaling in the central nervous system, maintaining normal functional activity of striatal MSNs and influencing the transmission of motor control signals. Within this complex regulatory network, the Erk/MAPK signaling pathway plays a key role in transmitting motor information to downstream neurons, regulating normal movements, avoiding unnecessary movements, and finely tuning motor behaviors. Our laboratory’s previous research found that 4 weeks of aerobic exercise intervention improved motor dysfunction in PD mice by inhibiting the Erk1/2 signaling upstream of striatal MSNs, primarily involving the Erk1/2 signaling in D2-MSNs rather than D1-MSNs. This review summarizes the neurobiological mechanisms of Erk/MAPK signaling pathway in D2-MSNs for the prevention and treatment of motor dysfunction in PD. By exploring the role of this signaling pathway in regulating motor abnormalities and preventing motor dysfunction in the central nervous system of PD, this review provides new theoretical perspectives for related mechanistic research and therapeutic strategies.

Geniposidic acid(GA), a natural iridoid, exists in the roots, stems, leaves, flowers, bark, fruits, and seeds of medicinal plants of Rubiaceae, Eucommiaceae, and Plantaginaceae. Modern pharmacological studies have revealed that GA has multiple pharmacological activities, including organ-protective, anti-inflammatory, antioxidative, anti-osteoporosis, anti-neurodegenerative, and anti-cardiovascular effects. GA can enhance cell/organism defenses by upregulating key anti-inflammatory and antioxidant cytokines, while downregulating key node proteins in pro-inflammatory signaling pathways such as AhR and TLR4/MyD88, thereby exerting pharmacological effects such as organ protection. Pharmacokinetic investigations have suggested that after oral administration, GA can be distributed in multiple organs(kidney, liver, heart, spleen, lung, etc.). In addition, the pharmacokinetic behavior of GA could be significantly altered under disease conditions, as demonstrated by a marked increase in systematic exposure. This article comprehensively summarizes the reported pharmacological activities and mechanisms and systematically analyzes the pharmacokinetic characteristics and key parameters of GA, with the aim of providing a theoretical basis and scientific reference for the precise clinical application of GA-related Chinese patent medicines, as well as for the investigation and development of innovative drugs based on GA.
Humans ; Drugs, Chinese Herbal/chemistry* ; Animals ; Iridoid Glucosides/chemistry* ; Plants, Medicinal/chemistry* ; Anti-Inflammatory Agents/pharmacology*

OBJECTIVES: To develop and validate a preoperative clinical-radiomics model for predicting overall survival (OS) and disease-free survival (DFS) in patients with extrahepatic cholangiocarcinoma (eCCA) undergoing radical resection. METHODS: In this retrospective study, consecutive patients with pathologically-confirmed eCCA who underwent radical resection at our institution from 2015 to 2022 were included. The patients were divided into a training cohort and a validation cohort according to the chronological order of their CT examinations. Least absolute shrinkage and selection operator (LASSO)-Cox regression was employed to select predictive radiomic features and clinical variables. The selected features and variables were incorporated into a Cox regression model. Model performance for 1-year OS and DFS prediction was assessed using calibration curves, area under receiver operating characteristic curve (AUC), and concordance index (C-index). RESULTS: This study included 123 patients (mean age 64.0 ± 8.4 years, 85 males/38 females), with 86 in the training cohort and 37 in the validation cohort. The OS-predicting model included four clinical variables and four radiomic features. It achieved a training cohort AUC of 0.858 (C-index = 0.800) and a validation cohort AUC of 0.649 (C-index = 0.605). The DFS-predicting model included four clinical variables and four other radiomic features. It achieved a training cohort AUC of 0.830 (C-index = 0.760) and a validation cohort AUC of 0.717 (C-index = 0.616). CONCLUSIONS The preoperative clinical-radiomics models show promise as a tool for predicting 1-year OS and DFS in eCCA patients after radical surgery.
Humans ; Male ; Female ; Retrospective Studies ; Middle Aged ; Cholangiocarcinoma/mortality* ; Prognosis ; Bile Duct Neoplasms/mortality* ; Tomography, X-Ray Computed/methods* ; Aged ; Radiomics

Recent studies have shown that shorter periods of ejaculatory abstinence may enhance certain sperm parameters, but the molecular mechanisms underlying these improvements are still unclear. This study explored whether reduced abstinence periods could improve semen quality, particularly for use in assisted reproductive technologies (ART). We analyzed semen samples from men with normal sperm counts ( n = 101) and those with low sperm motility or concentration ( n = 53) after 3-7 days of abstinence and then after 1-3 h of abstinence, obtained from the Reproductive & Genetic Hospital of CITIC-Xiangya (Changsha, China). Physiological and biochemical sperm parameters were evaluated, and the dynamics of transfer RNA (tRNA)-derived fragments (tRFs) were analyzed using deep RNA sequencing in five consecutive samples from men with normal sperm counts. Our results revealed significant improvement in sperm motility and a decrease in the DNA fragmentation index after the 1- to 3-h abstinence period. Additionally, we identified 245 differentially expressed tRFs, and the mitogen-activated protein kinase (MAPK) signaling pathway was the most enriched. Further investigations showed significant changes in tRF-Lys-TTT and its target gene mitogen-activated protein kinase kinase 2 ( MAP2K2 ), which indicates a role of tRFs in improving sperm function. These findings provide new insights into how shorter abstinence periods influence sperm quality and suggest that tRFs may serve as biomarkers for male fertility. This research highlights the potential for optimizing ART protocols and improving reproductive outcomes through molecular approaches that target sperm function.
Male ; Humans ; Spermatozoa/metabolism* ; RNA, Transfer/genetics* ; Sperm Motility/genetics* ; Adult ; Semen Analysis ; Sexual Abstinence/physiology* ; Sperm Count ; DNA Fragmentation

Objective To explore the effectiveness and safety of transurethral thermal steam ablation for the treatment of benign prostatic hyperplasia(BPH)patients with high-grade and high-risk.Methods Clinical data of elderly BPH pa-tients with high-risk treated with transurethral water vapour thermal from February 2022 to January 2025 were retrospectively ana-lyzed.The operation time,intraoperative bleeding,the number of injections during surgery,postoperative indwelling urinary catheter time,and surgical complications were recorded.And the differences in the International Prostate Symptom Score(IPSS),Quality of Life Score(QOL),Maximum Urinary Flow Rate(Qmax),and Residual Volume of Urine(PVR)before and after 3 and 6 months of the operation were recorded respectively.Results All 30 cases were successfully completed with an operation time of(10.167±2.984)min,intraoperative bleeding of(1.600±1.133)mL,the number of injections during surgery(6.600±1.793).No case of transfusion occurred.And the mean postoperative indwelling urinary catheter time was(8.467±3.246)d.After 3 and 6 months of postoperative follow-up,the Qmax increased from the preoperative(3.463±2.503)mL/s to(10.177±1.625)mL/s and(11.747±1.888)mL/s.PVR decreased from preoperative(209.623±191.960)mL to(40.433±23.713)mL and(30.300±20.223)mL.IPSS score decreased from preoperative(29.533±4.216)to(15.067±3.183)and(12.100±3.546).And QOL score decreased from preoperative(5.033±0.718)to(2.600±0.814)and(2.367±0.850).There were significant differences in observational indexes before and after the operation(P＜0.05).There was no case of postoperative urinary incontinence or secondary bleeding.Conclusion Transurethral water vapour thermal therapy is safe and effective for the treatment of elderly BPH patients with high-risk.

Objective:To investigate the potential value of cerebral glucose metabolism characteristics in anti-leucine-rich glioma-inactivated protein 1 (LGI1) antibody-related encephalitic patients during acute phase as the clinical indicator of disease outcomes.Methods:From October 2019 to December 2023, 28 patients (18 males, 10 females; age (56.6±11.9) year) with anti-LGI1 antibody-related encephalitis diagnosed at Huashan Hospital, Fudan University were prospectively enrolled. All patients received baseline brain 18F-FDG PET imaging and were divided into different subgroups according to the prognosis (good prognosis and poor prognosis groups) and recurrence (recurrence and non-recurrence groups) after follow-up. The difference of Montreal Cognitive Assessment (MoCA) score between the two groups was compared by Mann-Whitney U test. Statistical parametric mapping (SPM) analysis was used to analyze the PET images of different groups by independent-sample t test, and the characteristics of cerebral glucose metabolism of patients with different outcomes were obtained. Results:MoCA scores between the recurrence group ( n=6) and the non-recurrence group ( n=22; 14.0(9.8, 20.5) vs 22.0(18.0, 24.0); Z=2.17, P=0.030), and between the poor prognosis group ( n=13) and the good prognosis group ( n=15; 14.0(10.0, 22.0) vs 22.0(19.8, 25.3); Z=2.47, P=0.013) were significantly different. Compared with the good prognosis group, the cerebral glucose metabolism in the poor prognosis group was decreased in the bilateral frontal lobe, lateral temporal lobe, inferior parietal lobule and cingulate gyrus, but increased in the brainstem, bilateral lentiform nucleus and bilateral paracentral lobule/postcentral gyrus (all t=1.71, all P<0.05). Compared with the non-recurrence group, the metabolism of bilateral medial frontal gyrus, anterior cingulate gyrus, bilateral insula, superior temporal gyrus and thalamus decreased in the recurrence group, while the metabolism of bilateral precentral gyrus, inferior frontal gyrus and bilateral lentiform nucleus increased (all t=1.71, all P<0.05). Conclusion:18F-FDG PET imaging reveals the differences in brain metabolism of anti-LGI1 antibody-related encephalitic patients at baseline with different outcomes (prognosis, recurrence or not), which can provide a new perspective for the clinical evaluation of the disease at baseline.

Background With the rapid development of the food delivery industry, take-away deliverymen become an essential component of urban logistics. However, high labor intensity, unstable income, and extended working hours place them at considerable risk of occupational burnout. Available studies have paid insufficient attention to the mental health of this population, and effective predictive or preventive approaches remain limited. Objective To understand the status of occupational burnout among take-away deliverymen, identify influencing factors based on restricted cubic spline analysis, and develop a predictive model to provide a theoretical basis for improving their mental health. Methods A cross-sectional survey was conducted among full-time take-away deliverymen registered to the "Ele.me" and "Meituan" platforms in Hangzhou between September 1 and November 30, 2024, using both online and offline approaches. A questionnaire covered sociodemographic, household, and occupational information, and the Maslach Burnout Inventory–General Survey were used in this survey. Univariate analyses and logistic regression were used to identify factors associated with burnout and to construct a predictive model. Model performance was evaluated using receiver operating characteristic (ROC) curve and calibration curve. Furthermore, restricted cubic spline was used to further explore the relationship between age, working hours, and occupational burnout. Results Among the 1192 participants, 735 (61.66%) experienced occupational burnout. The logistic regression model indicated that older age (OR=1.021, P=0.010), educational attainment of college level or above compared to junior high school or below, (OR=2.837, P<0.001), and longer daily working hours (OR=1.081, P=0.001) were positively associated with occupational burnout. In contrast, work experience of 3−5 years (OR=0.666, P=0.016) and more than 5 years (OR=0.382, P<0.001) compared to those with <3 years, as well as providing three social insurances (OR=0.655, P=0.006) or five social insurances (OR=0.478, P<0.001) compared to those without any social insurances coverage, were negatively associated with occupational burnout. The predictive model based on these variables achieved an area under the curve (AUC) of 0.783 (95% CI: 0.756~0.809), and good agreement between calibration curves. The restricted cubic spline analysis revealed that the risk of occupational burnout was highest among delivery workers aged 33−46 years. Those with daily working hours between 3.5 and 8.1 h had a lower risk, while the risk significantly increased when working hours exceeded 8.1 h per day. Conclusion The prevalence of reporting occupational burnout among take-away deliverymen in Hangzhou is high. The developed predictive model provides valuable insights for the prevention and control of burnout in this population. Measures such as optimizing social security systems, rational work schedule allocation, and enhancing psychological support may help reduce occupational burnout among take-away deliverymen.