BACKGROUND: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke. METHODS: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes. RESULTS: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P  <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P  <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P  <0.01). CONCLUSIONS: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes. REGISTRATION ClinicalTrials.gov , NCT03222024.
Humans ; Male ; Female ; Prospective Studies ; Ischemic Stroke/mortality* ; Aged ; Middle Aged ; Aged, 80 and over ; Stroke ; Brain Ischemia

OBJECTIVE: To investigate the influence of different scanning conditions on the image quality of medical electron accelerator cone-beam computed tomography (CBCT) and provide a reference for the selection of scanning conditions for different body parts. Methods Set different scanning conditions, the Catphan 503 phantom was scanned using CBCT parameters to analyze the influence of spatial resolution, noise, uniformity, spatial geometric accuracy, and low-contrast resolution on the image quality of CBCT. RESULTS: For the head, chest, and abdomen, with the increase in scanning parameter values, the noise value decreased by 47.4%, 26.1%, and 51.3% respectively, and the uniformity values decreased by 30.2%, 26.6%, and 47.9% respectively. The low-contrast resolution values decreased by 50.6%, 34.2%, and 12.0%. The influence of different scanning conditions on spatial geometric accuracy and spatial resolution is not significant. CONCLUSION Different scanning parameters have a certain influence on the image quality of medical electron accelerator CBCT. Lower scanning parameters can be selected based on individual patients to reduce the additional radiation dose, providing a reference for the safe application of CBCT image guidance in radiotherapy.
Cone-Beam Computed Tomography/instrumentation* ; Phantoms, Imaging ; Particle Accelerators

Vein graft (VG) failure (VGF) is associated with VG intimal hyperplasia, which is characterized by abnormal accumulation of vascular smooth muscle cells (VSMCs). Most neointimal VSMCs are derived from pre-existing VSMCs via a process of VSMC phenotypic transition, also known as dedifferentiation. There is increasing evidence to suggest that ginger or its bioactive ingredients may block VSMC dedifferentiation, exerting vasoprotective functions; however, the precise mechanisms have not been fully characterized. Therefore, we investigated the effect of ginger on VSMC phenotypic transition in VG remodeling after transplantation. Ginger significantly inhibited neointimal hyperplasia and promoted lumen (L) opening in a 3-month VG, which was primarily achieved by reducing ferroptotic stress. Ferroptotic stress is a pro-ferroptotic state. Contractile VSMCs did not die but instead gained a proliferative capacity and switched to the secretory type, forming neointima (NI) after vein transplantation. Ginger and its two main vasoprotective ingredients (6-gingerol and 6-shogaol) inhibit VSMC dedifferentiation by reducing ferroptotic stress. Network pharmacology analysis revealed that 6-gingerol inhibits ferroptotic stress by targeting P53, while 6-shogaol inhibits ferroptotic stress by targeting 5-lipoxygenase (Alox5), both promoting ferroptosis. Furthermore, both ingredients co-target peroxisome proliferator-activated receptor gamma (PPARγ), decreasing PPARγ-mediated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (Nox1) expression. Nox1 promotes intracellular reactive oxygen species (ROS) production and directly induces VSMC dedifferentiation. In addition, Nox1 is a ferroptosis-promoting gene that encourages ferroptotic stress production, indirectly leading to VSMC dedifferentiation. Ginger, a natural multi-targeted ferroptotic stress inhibitor, finely and effectively prevents VSMC phenotypic transition and protects against venous injury remodeling.

Alzheimer's disease(AD)is a neurodegenerative disease with highly heterogeneous pathological and clinical manifesta-tions,and it is the most common cause of dementia.This heterogeneity poses challenges for diagnosis,treatment,and evaluating novel pharmacological efficacy.This review summarizes the latest progress in the major clinical subtypes of AD based on clinical manifesta-tions,genetic,and pathological features.Early-onset and late-onset AD clinical subtypes may share the same symptoms but differ in etiology,age of onset,mode of presentation,disease progression,and associated comorbidities.Typical and atypical AD differ signifi-cantly in clinical manifestations,pathological features,and diagnostic criteria.Research on AD subtypes based on imaging and omics data has also made considerable progress.This review also outlines the molecular pathological heterogeneity of AD.A deep understand-ing of these heterogeneities is crucial for diagnosis,the formulation of pharmacological treatment strategies,and clinical management.

【Objective】 To explore the safety of transrectal ultrasound-guided transperineal injection of sodium hyaluronate to expand the Dirichlet gap in laparoscopic radical prostatectomy. 【Methods】 A total of 14 healthy male purebred beagle dogs were selected and randomly divided into 2 groups, with 7 in either group.The control group was treated with conventional laparoscopic radical prostatectomy, while the experimental group was treated with laparoscopic radical prostatectomy after 2.5 mL sodium hyaluronate was injected into the Dirichlet gap under the guidance of transrectal ultrasound.The total operation time, prostate separation time, intraoperative blood loss and rectal status of the 2 groups were observed. 【Results】 After the injection of sodium hyaluronate into the Dirichlet gap between the prostate and the rectum, no rectal tissue was found in the prostate, and no obvious damage was found in the posterior rectum in either groups.The postoperative hemoglobin (HGB) was [(118.70±2.56) g/L vs.(122.10±2.19) g/L, P=0.02]; the total operation time was [(141.40±9.80) min vs.(119.10±9.16) min, P<0.05]; the prostate separation time was [(24.99±1.75) min vs.(16.64±2.34) min, P<0.05]; the amount of bleeding was [(47.43±4.32) mL vs.(34.86±5.18) mL, P<0.05] in the control group and experimental group. 【Conclusion】 Laparoscopic radical prostatectomy performed after 2.5 mL of sodium hyaluronate injection into the Dirichlet gap under the guidance of transrectal ultrasound can shorten the total operation time, the separation and resection time of the prostate, and reduce the amount of bleeding, which can improve and reduce the incidence of rectal injury, and prove the feasibility of this approach for prostatic cancer.

BackgroundCompared with absenteeism， health-related productivity loss has a long-lasting negative effect， and poses a greater harm and loss. The health-related productivity loss is mediated by self-efficacy， and perceived social support has been shown to have an impact on health-related productivity loss， whereas the interaction mechanism among the three remains unclear. ObjectiveTo investigate the status of perceived social support， occupational coping self-efficacy and health-related productivity loss among ICU nurses， and to test the mediation role of perceived social support in the relationship between occupational coping self-efficacy and health-related productivity loss. MethodsFrom September to November， 2021， purposive sampling technique was adopted to select 468 ICU nurses in 8 tertiary hospitals in Sichuan Province. Subjects were assessed using self-made general information questionnaire， Perceived Social Support Scale （PSSS）， Occupational Coping Self Efficacy Scale for Nurses （OCSE-N） and Stanford Presenteeism Scale-6 （SPS-6）. Pearson correlation analysis was used to examine the correlation among variables. Amos 24.0 was utilized to test the mediation role of perceived social support in the relationship between occupational coping self-efficacy and health-related productivity loss. ResultsA total of 415 ICU nurses completed the valid questionnaire survey. ICU nurses scored （63.13±11.62） on PSSS， （22.24±6.15） on OCSE-N， and （16.83±4.24） on SPS-6. Health-related productivity loss was detected in 279 ICU nurses （67.23%）. Correlation analysis denoted that PSSS total score was positively correlated with OCSE-N total score （r=0.348， P<0.05）， and negatively correlated with SPS-6 total score （r=-0.274， P<0.05）. OCSE-N total score was negatively correlated with SPS-6 total score （r=-0.421， P<0.05）. The direct effect value of occupational coping self-efficacy on health-related productivity loss was -0.401， and perceived social support showed a mediation role in the relationship between occupational coping self-efficacy and health-related productivity loss （the indirect effect value was -0.052， accounting for 11.48% of the total effect）. ConclusionThe occupational coping self-efficacy of ICU nurses may affect the health-related productivity loss through the action path of perceived social support.［Funded by Scientific Research Project of Sichuan Provincial Health Commission （number， 19PJ042）］

OBJECTIVE To provide reference for perfecting prescription circulation service and related platforms construction and improving online medical service level. METHODS A questionnaire was designed after literature review and consulting expert opinions. Patients who had received prescription circulation service in the prescription circulation platform of a Grade-A third-class hospital in Sichuan Province from November 22， 2019 to May 2022 were randomly selected， and the knowledge， attitude and practice of prescription circulation service were investigated by questionnaires， which were sent through telephone contact and short message. RESULTS A total of 285 patients were investigated， and the number of effective responses was 200. Most of the surveyed patients in prescription circulation service for 1-5 times in the past year （129 cases， 64.50%）； 77.0% of the patients had a “general understanding” or “no understanding” of prescription circulation services， and the main prescription circulation services they received were online consultation service （169 cases， 84.50%） and drug delivery service （106 cases， 53.00%）. The average waiting time and expected waiting time were 1-5 min. The services with the largest number of demand （145 cases， 72.50%） and the highest demand （3.585 points） were drug delivery services. Most of the respondents’ willingness to pay was “general willingness” （83 cases， 41.50%）， and most of the patients were willing to pay less than or equal to 5 yuan per time （92 cases， 46.00%）. Totally 73.0% of the surveyed patients were “satisfied” or “relatively satisfied” with the prescription transfer service. The results of univariate analysis showed that the main factors influencing patients’ satisfaction with prescription circulation service were service awareness， service waiting time， patients’ demand satisfaction and patients’ willingness to pay. CONCLUSIONS The surveyed patients are generally satisfied with prescription circulation service， and the service content with high satisfaction is drug distribution service， and patients are willing to pay a lower price for prescription circulation service. It is suggested that relevant departments should strengthen the publicity of prescription circulation service， improve the content of prescription circulation service and reduce the payment price of prescription circulation service， so as to improve the operation efficiency of Chinese medical system while facilitating patients.

OBJECTIVE To provide reference for the access to medical insurance for rare diseases in China based on the existing access pathway and framework by analyzing the access policy of medical insurance for rare diseases in the United Kingdom （UK）. METHODS After collecting relevant guidelines and policy documents related to drug use for rare diseases in the UK， content analysis method was used to analyze the evaluation mechanism of drug use for rare diseases， reimbursement decision- making standards， stakeholder participation， coping strategies for dealing with uncertainties and risks， and policy implementation effects， and extract the key points of medical insurance access for drug use for rare diseases in the UK， to provide some suggestions for the establishment of medical insurance access system for rare diseases in China. RESULTS & CONCLUSIONS From the perspective of access， the UK had adopted a separate approach and clear criteria to assess and reimburse drugs for rare diseases. From the perspective of evaluation mechanism， multi-stakeholders such as doctors， patients and applicants participated in the decision-making process in the UK. The UK addressed uncertainty and risk by gathering better clinical evidence and using the patient access programme. After the implementation of the policy related to drug use for rare diseases， the UK had achieved remarkable results in terms of funding for drug use for rare diseases， the reimbursement rate of drug application， and the number of funded patients. It is suggested that in the process of establishing and improving the evaluation and reimbursement system for rare diseases drugs in China， the availability of rare diseases drugs should be improved by establishing a separate access assessment path for rare diseases drugs and involving more stakeholders.

Objective     To explore the association between the preoperative systemic immune-inflammation index (SII) and prognosis in non-small cell lung cancer (NSCLC) patients. Methods     A comprehensive literature survey was performed on PubMed, Web of Science, EMbase, The Cochrane Library, Wanfang, and CNKI databases to search the related studies from inception to December 2021. The hazard ratio (HR) and 95% confidence interval (CI) were combined to evaluate the correlation of the preoperative SII with overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) in NSCLC patients. Results     A total of 11 studies involving 9 180 patients were eventually included. The combined analysis showed that high SII levels were significantly associated with worse OS (HR=1.61, 95%CI 1.36-1.90, P<0.001), DFS (HR=1.50, 95%CI 1.34-1.68, P<0.001), and RFS (HR=1.17, 95%CI 1.04-1.33, P<0.001). Subgroup analyses also further verified the above results. Conclusion     Preoperative SII is a powerful prognostic biomarker for predicting outcome in patients with operable NSCLC and contribute to prognosis evaluation and treatment strategy formulation. However, more well-designed and prospective studies are warranted to verify our findings.