ObjectiveTo investigate the material basis of the pathogenesis of cerebral ischemic injury with blood stasis and toxin syndrome and to explore the protective effects of Huayu Jiedu prescription （HYJDP） on neutrophil extracellular trap-related cell death （NETosis） in cerebral ischemic injury following acute cerebral infarction. MethodsSeventy-two Sprague-Dawley （SD） rats were randomly divided into six groups （n=12 per group）： sham operation （Sham） group， blood stasis and toxin model （Model） group， low-， medium-， and high-dose HYJDP groups （HYJDP-L， HYJDP-M， and HYJDP-H； 9， 18， and 36 g·kg^-1， respectively）， and butylphthalide （NBP） group （0.06 g·kg^-1）. Except for the Sham group， rats in all other groups were subjected to carrageenan/dry yeast combined with a modified intraluminal filament method to establish a focal cerebral ischemia model of the middle cerebral artery with blood stasis and toxin syndrome. Neurological function was evaluated at 24 h after modeling using the Zea-Longa neurological deficit score. Cerebral infarction rate was assessed by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Pathological morphology of brain tissue was observed using hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was used to determine serum levels of interleukin-8 （IL-8）， myeloperoxidase-DNA complexes （MPO-DNA）， and citrullinated histone H3 （CitH3）. Protein expression of phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， protein kinase B （p-Akt）， mammalian target of rapamycin （p-mTOR）， sequestosome 1 （p62）， and CitH3 in brain tissue was detected by Western blot. Immunofluorescence （IF） was used to detect the expression of neutrophil-specific marker Ly6G， CitH3， and neuron-specific nuclear protein （NeuN） in brain tissue. ResultsCompared with the Sham group， neurological deficit scores and cerebral infarction rates in the model group were significantly increased （P<0.01 for both）. HE staining showed varying degrees of neuronal degeneration and necrosis， characterized by blurred neuronal structures， nuclear pyknosis and fragmentation， cytoplasmic dissolution into a vacuolated reticular pattern， and mild glial cell proliferation. ELISA results showed that serum levels of IL-8， MPO-DNA， and CitH3 were significantly increased （P<0.01）. Western blot analysis demonstrated decreased expression of p-PI3K， p-Akt， p-mTOR， and p62， while CitH3 expression was significantly increased （P<0.01）. IF results showed an increased number of NETs⁺ cells and a significant decrease in NeuN⁺ cells （P<0.01）. Compared with the Model group， neurological deficit scores in the HYJDP-H group were significantly decreased （P<0.05）， and cerebral infarction rates in the HYJDP-H and NBP groups were significantly reduced （P<0.01）. HE staining showed that brain tissue damage was markedly alleviated in the HYJDP-H group. ELISA results showed that levels of IL-8， MPO-DNA， and CitH3 were significantly decreased in the HYJDP-M， HYJDP-H， and NBP groups （P<0.01）. Western blot analysis showed that expression of p-PI3K， p-Akt， p-mTOR， and p62 was significantly increased in the HYJDP-H and NBP groups， while CitH3 expression was significantly reduced in all drug intervention groups （P<0.01）. IF results showed that the number of NETs⁺ cells was significantly decreased and the number of NeuN⁺ cells was significantly increased in all drug intervention groups （P<0.01）. ConclusionNETs may be the material basis of the pathogenesis of cerebral ischemic injury characterized by blood stasis and toxin. HYJDP can regulate the PI3K/Akt/mTOR signaling pathway， reduce the release of pro-inflammatory mediators and NETosis-related products， alleviate cerebral ischemic injury caused by autophagy-dependent NETosis， and thereby exert a neuroprotective effect.

Diabetic retinopathy(DR), the most common microvascular complication of diabetes, has become a leading cause of visual impairment and blindness across all age groups. The early diagnosis and severity assessment of DR rely on the precise evaluation of retinal microvascular alterations. The periarterial capillary-free zone(paCFZ), a physiological avascular region surrounding retinal arteries, has recently been recognized as an important biomarker reflecting the status of retinal microcirculation. Advances in optical coherence tomography angiography(OCTA)have enabled noninvasive, high-resolution quantification of the paCFZ, offering a novel approach for the early detection and stratification of DR. This review systematically summarizes the definition and developmental mechanism of the paCFZ, as well as its morphological characteristics across different stages of DR, with a particular focus on the advantages of OCTA in visualizing and quantifying the paCFZ. We further discuss the differential manifestations of the paCFZ in nonproliferative DR and proliferative DR, and its associations with retinal ischemia and oxygenation status. In addition, the potential clinical value of paCFZ in evaluating responses to anti-vascular endothelial growth factor(VEGF)therapy and predicting disease progression is summarized. Finally, the challenges in clinical translation and future research directions are addressed, aiming to provide theoretical support and new perspectives for early screening, risk stratification, and personalized management of DR.

AIM:To assess the longitudinal changes in ocular biometric parameters after intravitreal ranibizumab(IVR)injection for the treatment of retinopathy of prematurity(ROP)in premature infants during the first year of life.METHODS:A longitudinal observational and comparative study was conducted on premature infants diagnosed with type 1 ROP, with a one-year follow-up. In treatment group, patients were administered with ranibizumab injection. The control group was set up without any intervention. All the patients were examined by A-scan ultrasound biometry at 0(40 gestational wk), 3, 6, and 12 mo of corrected gestational age(GA). Anterior chamber depth(ACD), lens thickness(LT), vitreous chamber depth(VCD), and axial length(AL)were measured. Anterior segment(AST)was calculated by summing up the ACD and LT.RESULTS:A total of 60 premature infants(60 eyes)were enrolled in this study, with a mean postmenstrual age of 36.80±2.86 wk, including 30 cases(30 eyes)in the treatment group and 30 cases(30 eyes)in the control group. The mean birth weight was 1157.50±232.12 and 1327.00±432.92 g, and the mean GA was 28.46±1.70 and 30.25±2.12 wk in treatment and control groups, respectively. No significant differences were found in all parameters at baseline(P>0.05). However, after correcting GA by 3, 6, and 12 mo, ACD was significantly greater than that of the control group at the 3rd, 6th, and 12th mo. LT was significantly thinner in the treatment group at the 3rd and 6thmo, but no statistically significant difference was observed between the two groups by the 12th mo. Throughout the follow-up period, AST, VCD, and AL were no significant differences in two groups(all P>0.05).CONCLUSION:Ranibizumab administered for the treatment of ROP only affected on ACD and LT. No significant effects are observed on AST, VCD, and AL during the first year of life.

Objective:To analyze the clinical data of seven patients with a clinical diagnosis of likely sporadic Creutzfeldt-Jakob disease (sCJD) in order to improve the understanding and diagnosis of sporadic Creutzfeldt-Jakob disease.Methods:The clinical data of 7 sCJD patients admitted to the Department of Neurology of Our Hospital from 2021 to 2023 were retrospectively analyzed.Results:All seven patients had a subacute onset of disease, and the main clinical features included rapidly progressive dementia (RPD), cerebellar symptoms, pyramidal signs, myoclonus and akinetic mutism. Magnetic resonance diffusion-weighted imaging (DWI) reveals widespread asymmetrical lace-like high signal distributed along the cortex and a basal curved ball-and-stick sign. Electroencephalography (EEG) shows diffuse spiking and spiking slow waves, and periodic triphasic waves in advanced stages of the disease. Cerebrospinal fluid 14-3-3 protein testing was performed in 6 of the 7 patients, and 4 were positive. Four patients died within six months of onset of illness.Conclusions:The disease is prevalent in middle-aged and elderly patients, with a non-significant male-to-female ratio, and is dominated by the presence of Rapidly Progressive Dementia (RPD), especially the presence of cortical high signals in the DWI sequences and diffuse sharp and slow wave issuance in the electroencephalograph (EEG), which need to be alerted to the occurrence of Creutzfeldt-Jakob Disease. Dynamic review of MRI, EEG, cerebrospinal fluid 14-3-3 protein, prion protein gene (PRNP) sequence analysis and cerebrospinal fluid prion real-time vibration-induced protein amplification (RT-QuIC) monitoring whenever possible to avoid misdiagnosis, under-diagnosis, and under-recognition.

Objective To systematically evaluate influence factors hospitalization infections in multiple myeloma(MM)patients after chemotherapy.Methods Computer searches were conducted on relevant literature in CNKI,China Biology Medicine disc,VIP,Wanfang Data Knowledge Service Platform,PubMed,Web of Science,Embase,Cochrane Library and CINAHL from the database inception until December 16,2024.Two researchers independently screened and assessed the quality of the literature,obtained the necessary information,and a Meta-analysis of risk factors was conducted by using RevMan 5.4 software.Results 19 articles were included in total.Meta-analysis results showed that high body mass index,length of stay,smoking history,Eastern Cooperative Oncology Group(ECOG)score,granulocyte deficiency,neutropenia,Durie-Salmon stage,international staging system(ISS)stage and combined with diabetes,renal insufficiency,anemia,hypoalbuminemia were the risk factors for hospitalization infections in patients with MM after chemotherapy(P＜0.05).Conclusion This study provides a reference for intervening in the risk factors of hospitalization infections in MM patients after chemotherapy.Medical staff should prevent infections early based on relevant factors,identify high-risk populations,and maximize the protection of patient health outcomes and good prognosis.

In recent years, information systems have become an important tool for hospitals to enhance the quality of medical services. The consistent transmission of test results is crucial for the safety of clinical diagnosis and treatment. In 2019, Zhejiang Hospital initiated a practice for consistency verification of test results based on information transmission. This practice clarified data sources, intermediate storage points, and data destinations by sorting out the flow of test result information; established a collaborative mode led by the department of clinical laboratory, involving personnel from the information center, software engineers, and clinical medical staff; refined the verification content and its elements to make the verification more comprehensive; conducted risk assessments and advanced verification processes to control the occurrence of risks from the source of data. By conducting this verification, the hospital actively identified and evaluated potential risks and existing problems, and took targeted improvement measures to ensure the consistency and accuracy of the transmission of test results. As of 2024, the practice covered all information systems involved in the transmission of test result information in the hospital, incorporated 711 test items, with the verification content increasing from 4 to 11 items, achieving significant outcomes and providing references for other hospitals to improve the consistency verification of test results.

Alzheimer's disease(AD)is a common degenerative disease of the central nervous system that gradually worsens,characterized by memory loss and cognitive decline,and the condition worsens over time.The pathogenesis of AD is currently unclear,but known evidence suggests that a combination of genetic,environmental,and lifestyle factors can lead to the occurrence and development of AD.Recent studies have shown that hypoxia may be an important risk factor for inducing AD.Under low oxygen conditions,abnormal accumulation of β-amyloid(Aβ)and Tau proteins in the brain can accelerate the progression of AD.In addi-tion,hypoxia can promote the release of inflammatory mediators,intensify the inflammatory response in the brain,and damage nerve cells.Further hypoxia may also affect the blood flow and nutrient supply to the brain,thereby damaging the vascular health of the brain and accelerating the process of neurodegeneration.This arti-cle focuses on the molecular mechanisms related to hypoxia in AD,aiming to further deepen people's under-standing of the relationship between hypoxia and AD,and contribute to the development of new disease treat-ment strategies.

OBJECTIVE: To analyze the efficacy and safety of decitabine-based myeloablative preconditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML). METHODS: The clinical characteristics and efficacy of 115 AML patients who underwent allo-HSCT at the First Medical Center of Chinese PLA General Hospital from August 2018 to August 2022 were retrospectively analyzed, including 37 patients treated with decitabine conditioning regimen (decitabine group) and 78 patients without decitabine conditioning regimen (non-decitabine group). The cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), non-relapse mortality (NRM) and graft versus host disease (GVHD) were analyzed. RESULTS: For the patients in first complete remission (CR1) state before allo-HSCT, the 1-year relapse rates of decitabine group(22 cases) and non-decitabine group(69 cases) were 9.1% and 29.6%, respectively, the difference was statistically significant(P =0.042). The 1-year cumulative incidence of acute graft-versus-host disease (aGVHD) in decitabine group and non-decitabine group was 62.2% and 70.5%, respectively, and the 1-year cumulative incidence of chronic inhibitor-versus-host disease (cGVHD) was 18.9% and 14.1%, respectively, there were no significant differences in the incidence of aGVHD and cGVHD between the two groups (P >0.05). Of the 115 patients, there were no significantly differences in the 1-year CIR(21.7% vs 28.8%, P =0.866), NRM(10.9% vs 3.9%, P =0.203), OS(75.2% vs 83.8%, P =0.131) and LFS(74.6% vs 69.1%, P =0.912) between the decitabine group(37 cases) and the non-decitabine group(78 cases). CONCLUSION Decitabine-based conditioning regimen could reduce the relapse rate of AML CR1 patients with good safety.
Humans ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation/methods* ; Decitabine/therapeutic use* ; Transplantation Conditioning/methods* ; Retrospective Studies ; Graft vs Host Disease ; Transplantation, Homologous ; Male ; Female ; Adult ; Middle Aged ; Adolescent ; Young Adult

OBJECTIVE: To investigate possible associations between physical function assessment scales, such as Short Physical Performance Battery (SPPB) and Berg Balance Scale (BBS), with all-cause mortality in acute decompensated heart failure (ADHF) patients. METHODS: A total of 108 ADHF patients were analyzed from October 2020 to October 2022, and followed up to May 2023. The association between baseline clinical characteristics and all-cause mortality was analyzed by univariate Cox regression analysis, while for SPPB and BBS, univariate Cox regression analysis was followed by receiver operating characteristic curves, in which the area under the curve represented their predictive accuracy for all-cause mortality. Incremental predictive values for both physical function assessments were measured by calculating net reclassification index and integrated discrimination improvement scores. Optimal cut-off value for BBS was then identified using restricted cubic spline plots, and survival differences below and above that cut-off were compared using Kaplan-Meier survival curves and the log-rank test. The clinical utility of BBS was measured using decision curve analysis. RESULTS: For baseline characteristics, age, female, blood urea nitrogen, as well as statins, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or angiotensin receptor-neprilysin inhibitors, were predictive for all-cause mortality for ADHF patients. With respect to SPPB and BBS, higher scores were associated with lower all-cause mortality rates for both assessments; similar area under the curves were measured for both (0.774 for SPPB and 0.776 for BBS). Furthermore, BBS ≤ 36.5 was associated with significantly higher mortality, which was still applicable even adjusting for confounding factors; BBS was also found to have great clinical utility under decision curve analysis. CONCLUSIONS BBS or SPPB could be used as tools to assess physical function in ageing ADHF patients, as well as prognosticate on all-cause mortality. Moreover, prioritizing the improvement of balance capabilities of ADHF patients in cardiac rehabilitation regimens could aid in lowering mortality risk.

OBJECTIVE: To investigate the mechanism of electroacupuncture (EA) in treating diabetic gastroparesis (DGP) by inhibiting the activation of Nod-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome and pyroptosis mediated via NLRP3/cysteinyl aspartate specific proteinase-1 (caspase-1)/gasdermin D (GSDMD) signaling pathway. METHODS: Forty Sprague-Dawley rats were randomly divided into 4 groups including the control, DGP model, EA, and MCC950 groups. The DGP model was established by a one-time high-dose intraperitoneal injection of 2% streptozotocin and a high-glucose and high-fat diet for 8 weeks. EA intervention was conducted at Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6) with sparse-dense wave for 15 min, and was administered for 3 courses of 5 days. After intervention, the blood glucose, urine glucose, gastric emptying, and intestinal propulsive rate were observed. Besides, HE staining was used to observe histopathological changes in gastric antrum tissues, and TUNEL staining was utilized to detect DNA damage. Protein expression levels of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), pro-caspase-1, caspase-1 and GSDMD were measured by Western blot. Immunofluorescence staining was employed to assess the activity of GSDMD-N. Lactate dehydrogenase (LDH) levels were detected by using a biochemical kit. RESULTS: DGP rats showed persistent hyperglycemia and a significant decrease in gastrointestinal motility (P<0.05 or P<0.01), accompanied by pathological damage in their gastric antrum tissues. Cellular DNA was obviously damaged, and the expressions of NLRP3, ASC, pro-caspase-1, caspase-1 and GSDMD proteins were significantly elevated, along with enhanced fluorescence signals of GSDMD-N and increased LDH release (P<0.01). EA mitigated hyperglycemia, improved gastrointestinal motility in DGP rats and alleviated their pathological injury (P<0.05). Furthermore, EA reduced cellular DNA damage, lowered the protein levels of NLRP3, ASC, pro-caspase-1, caspase-1 and GSDMD, suppressed GSDMD-N activity, and decreased LDH release (P<0.05 or P<0.01), demonstrating effects comparable to MCC950. CONCLUSION EA promotes gastrointestinal motility and repairs the pathological damage in DGP rats, and its mechanism may be related to the inhibition of NLRP3 inflammasome and pyroptosis mediated by NLRP3/caspase-1/GSDMD pathway.
Animals ; Electroacupuncture ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Pyroptosis ; Rats, Sprague-Dawley ; Caspase 1/metabolism* ; Gastroparesis/physiopathology* ; Signal Transduction ; Male ; Diabetes Mellitus, Experimental/physiopathology* ; Phosphate-Binding Proteins/metabolism* ; Gastrointestinal Motility ; Rats ; Intracellular Signaling Peptides and Proteins/metabolism* ; Diabetes Complications/physiopathology* ; Gasdermins