1.TGF-β1-engineered Biomimetic Platelet Nanoparticles for Targeted Therapy of Ischemic Stroke
Li-Qi CHEN ; Tian-Fang KANG ; Guo-Jun HUANG ; Ting YIN ; Ai-Qing MA ; Lin-Tao CAI ; Hong PAN
Progress in Biochemistry and Biophysics 2026;53(3):697-710
ObjectivePost-ischemic acute inflammation and the subsequent persistent dysregulation of the immune microenvironment represent major pathological drivers that aggravate neuronal injury and severely restrict functional recovery following ischemic stroke. Although current reperfusion therapies partially restore blood flow, they fail to effectively modulate the secondary inflammatory cascade and oxidative stress, which remain critical barriers to neurological restoration. To address this challenge, this study aimed to engineer and systematically evaluate a biomimetic nanosystem composed of transforming growth factor-β1 (TGF-β1)-loaded platelet membrane-camouflaged lipid nanoparticles (PLP). This nanosystem was designed to achieve dual lesion-targeted delivery and immune microenvironment remodeling. By verifying its spatiotemporal accumulation, anti-inflammatory activity, and neuroprotective efficacy, we sought to establish an integrated therapeutic strategy that simultaneously enables lesion targeting, immune regulation, and functional recovery after ischemic injury. MethodsThe physicochemical properties of PLP, including hydrodynamic particle size, zeta potential, structural stability, and morphology, were characterized using dynamic light scattering, zeta potential analysis, and transmission electron microscopy. The preservation of platelet membrane-derived adhesion and immunoregulatory proteins was confirmed by SDS-PAGE through comparative analysis of protein band profiles between PLP and native platelet membranes. The in vitro biological activities of PLP were evaluated using two complementary cellular models. LPS-induced M1-polarized RAW264.7 macrophages were employed to assess inflammatory modulation, while oxygen glucose deprivation/reperfusion (OGD/R)-induced BV2 microglial cells and SH-SY5Y neuronal cells were utilized to investigate neuroinflammatory regulation and neuronal protection. For in vivo validation, a transient middle cerebral artery occlusion (tMCAO) mouse model was established to mimic ischemia-reperfusion injury. The spatiotemporal biodistribution and lesion-targeting capability of the PLP were monitored through live fluorescence imaging. Therapeutic efficacy was comprehensively evaluated by triphenyltetrazolium chloride (TTC) staining, glial fibrillary acidic protein (GFAP) immunofluorescence analysis, body weight monitoring, and neurological severity score (NSS) assessment. ResultsPLP nanoparticles displayed a uniform spherical morphology, nanoscale particle size distribution, and stable negative surface charge, indicating favorable colloidal stability and circulation potential. SDS-PAGE results confirmed the effective retention of key platelet membrane proteins associated with endothelial adhesion, immune evasion, and inflammatory regulation, demonstrating the successful biomimetic construction. Optimal therapeutic concentrations were determined in OGD/R-induced BV2 cells, where PLP exhibited excellent cytocompatibility and anti-inflammatory activity.In vitro experiments demonstrated that PLP significantly inhibited the polarization of RAW264.7 macrophages toward the pro-inflammatory M1 phenotype and markedly reduced neuronal apoptosis under ischemia-reperfusion conditions. In vivo fluorescence imaging revealed that PLP rapidly accumulated in the ischemic brain hemisphere and maintained prolonged retention for up to 7 d, suggesting enhanced lesion-specific targeting and sustained drug release. Compared with control group, PLP treatment significantly reduced cerebral infarct volume, attenuated reactive astrogliosis, improved weight recovery, and accelerated neurological functional restoration, as reflected by significantly improved NSS scores. ConclusionThis study establishes a multifunctional biomimetic nanoplatform that integrates platelet membrane-mediated active targeting with the anti-inflammatory, antioxidative, and neuroprotective properties of TGF-β1. The PLP system enables rapid lesion homing and long-term retention while synergistically regulating the post-stroke inflammatory microenvironment by suppressing pro-inflammatory immune activation, reducing neuronal apoptosis, and limiting excessive astrocyte reactivity. Importantly, this study proposes a conceptually therapeutic paradigm that combines targeted delivery with immune microenvironment remodeling to achieve comprehensive neurovascular protection. These findings provide strong experimental evidence supporting the translational potential of biomimetic nanotherapeutics as next-generation precision interventions for ischemic stroke.
2.A preliminary study on Toxoplasma gondii interfering with copper metabolism pathways in mouse kidney
Jun YANG ; Chuanming REN ; Min LIU ; Kunting WANG ; He CHEN ; Yihong CAI
Acta Universitatis Medicinalis Anhui 2026;61(1):127-132
ObjectiveTo investigate the effect of Toxoplasma gondii infection on copper metabolism in the kidneys of mice. MethodsA total of 80 7-8-week-old C57BL/6 female mice were randomly divided into four groups of 20 mice in each group after one week of adaptation, including Control group, Cu group, TgCtwh6 group and Cu+TgCtwh6 group. Mice that were not infected and fed with normal diet and water were used as the Control group; Mice fed with 1 g/kg of copper chloride processing diet and 0.1% copper chloride water for 60 consecutive days were used as Cu group; Mice infected with 25-30 TgCtwh6 cysts (one of the predominant genotype Chinese 1 in China) fed with normal diet and water were used as the TgCtwh6 group; mice infected with 25-30 TgCtwh6 cysts and fed with a processed diet containing 1 g/kg of copper chloride and water with 0.1% copper chloride for 60 consecutive days were used as the Cu+TgCtwh6 group. ICP-MS was used to determine the changes in copper content in kidney tissues. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of mouse kidney tissue. The number of apoptotic cells was observed by PI staining. Western blot was used to detect the protein expression levels of glutathione peroxidase 4 (GPX4) and superoxide dismutase (SOD1, SOD2). RT-qPCR was used to detect the mRNA expression of cuproptosis-related genes. ResultsPathological manifestations such as inflammatory cell infiltration in the Cu group and TgCtwh6 group were seen under the microscope, and the inflammatory infiltrating cells of the renal interstitial were reduced in the Cu+TgCtwh6 group, and the pathological manifestations
3.Survival Analysis of 478 Hospitalized Patients with Prostate Cancer
Jun XU ; Haizhen CHEN ; Lingling LU ; Bo CAI ; Hong XU ; Yuexia GAO ; Jianguo CHEN
China Cancer 2025;34(6):477-483
[Purpose]To analyze the survival rate of prostate cancer patients hospitalized in Nan-tong Tumor Hospital from 2007 to 2017.[Methods]A total of 478 prostate cancer patients were admitted in Nantong Tumor Hospital from 2007 to 2017 and 476 cases(99.58%)were followed up till December 31,2020.The survival rate of patients was analyzed with Kaplan-Meier method;Soft-ware SPSS 25.0 and the Log-rank test were employed for statistical analysis.[Results]The aver-age age of prostate cancer patients at admission was(71.74±8.02)years old,and 79.08%were aged 60~79 years.The median survival time was 43 months,and the observed 1-,3-,5-and 10-year survival rates were 77.20%,56.07%,43.01%and 24.53%,respectively.The 5-year survival rates for the age groups of 35~59,60~79 and ≥80 years old were 31.73%,46.64%and 29.65%,respectively(P<0.05).The 5-year survival rates for patients with stage Ⅰ~Ⅱ,stage Ⅲ,stage IV,and unknown stage were 88.10%,71.66%,33.35%and 37.55%,respectively(P<0.001).The 5-year survival rates for the periods 2007-2012 and 2013-2017 were 32.85%and 47.79%,re-spectively(P<0.05).Furthermore survival rates differed significantly across different regions within the jurisdiction(P<0.05).[Conclusion]Over the past decade,the survival rate of hospital-based prostate cancer patients has significantly improved.Early-stage cases can achieve better survival rates,but the survival rate of elderly patients remains a challenge.Efforts should be made to reduce the proportion of patients with unknown staging Comprehensive measures for prostate cancer prevention and control should be strengthened to reduce incidence,improve prognosis and enhance quality of life of patients.
4.Development, reliability, and validity of a treatment-related quality of life scale for Chinese patients with multiple myeloma
Chunyan SUN ; Zhen CAI ; Bing CHEN ; Lijuan CHEN ; Wenming CHEN ; Kaiyang DING ; Juan DU ; Rong FU ; Chengcheng FU ; Da GAO ; Guangxun GAO ; Yanjuan HE ; Jian HOU ; Ming JIANG ; Fei LI ; Jian LI ; Juan LI ; Zhenyu LI ; Aijun LIAO ; Jing LIU ; Jun LUO ; Jianmin LUO ; Yanping MA ; Jianqing MI ; Ting NIU ; Hongling PENG ; Yongping SONG ; Luqun WANG ; Rong ZHAN ; Xi ZHANG ; Yu HU
Chinese Journal of Hematology 2025;46(8):713-721
Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.
5.Determination of median effective dose of remimazolam for preoperative sedation in pediatric patients
Mei-Chao WU ; Fang-Fang YANG ; Chen-Xu DAI ; Xing-Jun MA ; Ning CAI
Medical Journal of Chinese People's Liberation Army 2025;50(2):141-145
Objective To determine the median effective dose(ED50)of remimazolam for preoperative sedation in pediatric patients aged 1-6 years using the modified Dixon sequential method.Methods This is a prospective clinical study.Pediatric patients scheduled for elective short surgery(surgery time≤1 h)under general anesthesia from January to July 2023 were selected.Inclusion criteria were age 1-6 years,an ASA physical status Ⅰ-Ⅱ and the preoperative parent separation anxiety scale(PSAS)score≥3 points.Remimazolam was administered intravenously preoperatively,and its sedative effect was assessed.The modified Dixon sequential method was used to determine the ED50 of remimazolam,with the initial dose set at 0.10 mg/kg and the dose increment set at 0.02 mg/kg.Sedation was considered successful(positive,included in positive group)if the child with sedation score≥2 points,preoperative PSAS score<3 points,and the mask acceptance score of 4 points during anesthesia induction.If any criterion was not met,sedation was considered failure(negative,included in negative group),and the next patient's dosage was increased by 0.02 mg/kg based on the previous patient's dosage.The test was completed after 7 consecutive positive and negative turning points appeared alternately.Probabilistic unit regression analysis was used to determine the ED50,ED95 and the corresponding 95%confidence interval(CI)of remimazolam for preoperative sedation.Postoperative recovery time and adverse events such as airway spasm,respiratory depression,hypotension,nausea and vomiting during anesthesia were recorded.Results A total of 23 pediatric patients were included,with 13 in positive group and 10 in negative group.There were no statistically significant differences in mean arterial pressure,pulse oxygen saturation or heart rate before and after sedation(P>0.05).Compared with negative group,positive group showed a significant reduction in preoperative parent separation anxiety and an increase in mask acceptance during anesthesia(P<0.05).There was no significant difference in sedation score and anesthesia awakening time between two groups(P>0.05).The ED50 of remimazolam for preoperative sedation in pediatric patients aged 1-6 years was 0.051 mg/kg(95%CI 0.033-0.065 mg/kg),and the ED95 was 0.077 mg/kg(95%CI 0.064-0.161 mg/kg).No adverse events such as airway spasm,respiratory depression,hypotension,nausea and vomiting occurred during anesthesia in any of pediatric patients.Conclusion The ED50 of intravenous administration of remimazolam for preoperative sedation in pediatric patients aged 1-6 years is 0.051 mg/kg(95%CI 0.033-0.065 mg/kg).
6.Comparison of the hemodynamic effects of remimazolam tosylate and etomidate for anesthetic induction in elderly frail patients
Xiao-Yu TAO ; Shuang-Shuang GUAN ; Chen-Xu DAI ; Qiu-Feng WANG ; Hui-Hui LI ; Xing-Jun MA ; Ning CAI
Medical Journal of Chinese People's Liberation Army 2025;50(8):958-963
Objective To compare the hemodynamic effects of anesthesia induction with remimazolam tosylate and etomidate in elderly frail patients.Methods This study was a single-center,prospective,randomized,single-blind trial.From January to April 2024,96 elderly frail patients undergoing elective surgery in Fuyang People's Hospital were recruited.After excluding 6 cases(3 refused to participate,1 had tracheal intubation time>30 s,and 2 had missing data),90 patients were finally included.They were randomly divided into remimazolam tosylate group(intravenous injection of 0.2 mg/kg remimazolam tosylate for anesthesia induction,n=45)and etomidate group(intravenous injection of 0.3 mg/kg etomidate for anesthesia induction,n=45)by the random number table method.The area under the curve for mean arterial pressure(MAP)below or above baseline values(AUCMAP-and AUCMAP+),the heart rate(HR)below or above baseline values by 10%(AUCHR-and AUCHR+)within 10 minutes of anesthesia induction,the time to loss of consciousness,the time from the start of anesthesia induction to a bispectral index(BIS)<60,the incidence of drug-related adverse reactions,the incidence of cardiovascular adverse events,and the usage of vasoactive drug administrations were compared between the two groups.Results Compared with the etomidate group,the AUCMAP-(145.10±35.75 vs.178.52±39.78)and AUCHR-[43.20(26.58,56.35)vs.54.99(43.01,65.85)]in remimazolam tosylate group were significantly reduced(P<0.001,P=0.001).The time to loss of consciousness and the time from the start of anesthesia induction to BIS<60 were prolonged(P<0.001).The incidence of drug-related adverse reactions was significantly decreased(P<0.05),and the number of norepinephrine administrations was significantly reduced(P<0.05)in remimazolam tosylate group.However,there were no statistically significant differences in AUCMAP+,AUCHR+,the incidence of cardiovascular adverse events,and the usages of atropine,urapidil,and esmolol between the two groups(P>0.05).Conclusion The use of remimazolam tosylate during anesthesia induction in elderly frail patients can provide more stable hemodynamic parameters and results in fewer adverse reactions than etomidate.
7.Ultrasonic characteristics of hip joints in preterm infants with different gestational ages
Min CHEN ; Ruyi CAI ; Jing WANG ; Lei XIA ; Xia CHI ; Jun QIAN
Journal of Clinical Medicine in Practice 2025;29(9):70-74
Objective To analyze the results of ultrasonic examinations of hip joints in preterm infants,clarify the developmental characteristics of hip joints across different gestational ages.Meth-ods A total of 881 preterm infants who attended the Child Healthcare Outpatient Clinic of Nanjing Maternity and Child Health Care Hospital between January 2023 and April 2024 were enrolled.The first ultrasonic examination of the hip joints was performed at a corrected gestational age of 4 to 6 weeks.The Graf classification method was employed to categorize the ultrasonic findings.Differences in hip joint development among preterm infants of varying gestational ages were compared,and rele-vant influencing factors were statistically analyzed.Results A total of 1,762 hip joints were exam-ined,with 30 cases of abnormal hip joints detected,yielding an abnormality detection rate of 3.4%(30/881).Among these,26 hips were classified as type Ⅱa and 8 as type Ⅱb.Statistically signifi-cant differences were observed in the detection of left-sided abnormal hip joints between preterm in-fants of other gestational age groups and late preterm infants(P<0.05).A statistically significant difference was found in the classification of right-sided hip joints between preterm infants of different genders(P<0.05),while no significant difference was observed for left-sided hip joints(P>0.05).Statistically significant differences were noted in the detection rates of bilateral abnormal hip joints among preterm infants with varying birth weights(P<0.05).Advanced maternal age was found to influence the development of left-sided hip joints inpreterm infants,whereas factors such as assisted reproductive technology,breech presentation,and nulliparity had no significant impacts on abnormal hip joint development in preterm infants.Conclusion Ultrasonic technology demonstrates signifi-cant advantages in screening for developmental dysplasia of the hip(DDH)in preterm infants.Dif-ferent gestational ages exert a notable influence on the development of left-sided hip joints in preterm infants.Female preterm infants exhibit a higher risk of right-sided hip joint abnormalities compared to the left side.Breech presentation,assisted reproductive technology,and nulliparity are not risk factors for DDH in preterm infants.However,higher birth weight in preterm infants and advanced maternal age are associated with abnormal hip joint development.Clinical attention should focus on high-risk factors,and enhanced dynamic ultrasonic monitoring of hip joints in preterm infants is war-ranted to facilitate early intervention and treatment.
8.Natural human leukocyte antigen antibodies and corresponding clinical response strategies
Junchao CAI ; Duqiang ZONG ; Lan ZHU ; Chenhong ZHAO ; Shengnan ZHANG ; Lei ZHANG ; Jun HE ; Hongxia DAI ; Gang CHEN
Chinese Journal of Organ Transplantation 2025;46(5):344-350
Natural human leukocyte antigen (HLA) antibodies refer to preformed antibodies present in the body that are not induced by prior exposure to allogeneic HLA antigens. In healthy individuals without a sensitization history, the detection rate of natural HLA antibodies is approximately 20%-29% when using screening assays with low sensitivity, and can reach up to 63% when more sensitive HLA-specific detection methods are employed. It is therefore inferred that natural HLA antibodies may also be present in transplant candidates with a similar prevalence. This review comprehensively discusses the potential mechanisms of natural HLA antibody generation, the characteristics of the recognized epitopes, detection techniques, clinical relevance in transplantation, their potential to confound therapeutic decisions, and approaches to distinguish and mitigate their impact. The goal is to raise clinician awareness of the objective existence of natural HLA antibodies, provide guidance on evaluating their association with allograft rejection, and inform appropriate clinical management strategies when encountering natural HLA antibody-positive transplant candidates.
9.Assay for detection of toxigenic Clostridioides difficile with combined microfluidic chip and immunochromatography technology
Hong-rui CHENG ; Xiao-jun SONG ; Yu CHEN ; Meng ZHANG ; Meng-ting CAI ; Kun ZHU ; Yu-lei TAI ; Shi-bo YING ; Da-zhi JIN
Chinese Journal of Zoonoses 2025;41(2):142-149
An assay was established for detection of toxigenic Clostridioides difficile by combining microfluidic chip analysis with immunochromatography,and its performance was evaluated and compared with those of the Xpert C.difficile/Epi and VIDAS CD AB tests.Primer pairs were designed according to the tcdB and tpi genes in C.difficile.The specificity,limit of detection,reproducibility,and stability were evaluated.A total of 215 stool samples from patients with diarrhea were collected and tested in parallel with the Xpert C.difficile/Epi,VIDAS CDAB,and our assay.C.difficile was isolated from samples,and the tcdB gene was identified when discrepant results were obtained from the three above assays.Our assay showed no cross-reaction with other diarrhea-associated pathogens.Its reproducibility was 100%in testing of two standard plasmids containing tcdB and tpi genes at two concentrations(105 and 102 copies/μL).Two standard plasmids were detected after the PCR and immunochromatography reagents had been stored for 3,6,9,and 12 months,and all the results were posi-tive.The limit of detection was 10 copies/μL for toxigenic C.difficile.Testing of 33 samples positive for C.difficile with our assay(33/215,15.3%)yielded findings statistically coherent with those of the Xpert C.difficile/Epi test(kappa value=0.965).The sensitivity,specificity,positive predictive value,and negative predictive value of our assay,with respect to Xpert C.difficile/Epi as the standard,were 94.3%,100.0%,100.0%,and 98.9%;these values were significantly higher than those of VIDAS CDAB(60.0%,98.9%,91.3%,and 92.7%)(Kappa=0.714,OR=157.50,95%CI:62.03-847.28,P=0.013).In conclusion,our newly developed assay is specific,stable,and reproducible,and may be used for rapid and accu-rate detection of toxigenic C.difficile.The assay could be used for C.difficile infection screening in outpatient and emergen-cy,community medical service center,and epidemiological settings.
10.Deep learning model based on fundus images for detection of coronary artery disease with mild cognitive impairment
Yi YE ; Wei FENG ; Yao-dong DING ; Qing CHEN ; Yang ZHANG ; Li LIN ; Tong MA ; Bin WANG ; Xian-gang CHANG ; Zong-yuan GE ; Xiao-yi WANG ; Long-jun CAI ; Yong ZENG
Chinese Journal of Interventional Cardiology 2025;33(6):303-311
Objective To develop a deep learning model based on fundus retinal images to improve the detection rate of mild cognitive impairment(MCI)in patients with coronary heart disease,achieve early intervention and improve prognosis.Methods The study was a single-center cross-sectional study that retrospectively included patients diagnosed with coronary heart disease(CHD)by coronary angiography(≥50% stenosis of at least one coronary vessel)from Beijing Anzhen Hospital between November 2021 and December 2022.The whole data set was randomly divided into the training set and the testing set according to the ratio of 8∶2 for model development.After that,the patient data of the same center from January 2023 to April 2023 were included in the time verification method to verify the model.The diagnostic criteria for MCI were MMSE<27 or MoCA<26.Four kinds of convolutional neural network(CNN)architectures were used to train fundus images,and a comprehensive vision model of MCI detection was established through model integration.The area under the curve(AUC),sensitivity and specificity of the receiver operating curve(ROC)were used to evaluate the performance of the AI model.Results We collected 5 880 eligible fundus images from 3 368 CHD patients.Based on the results of the MMSE scale,the algorithm was labeled,including 2 898 males and 527 MCI patients.The AUC of the deep learning model in the test group is 0.733(95%CI 0.688-0.778),and the sensitivity of the algorithm in the test group is 0.577(95%CI 0.528-0.625)by using the operating point with the maximum sum of sensitivity and specificity.With a specificity of 0.758(95%CI 0.714-0.802),corresponding to a validated AUC of 0.710(95%CI 0.601-0.818).Based on the results of the MoCA scale,the algorithm labels 2 437 males and 1 626 MCI patients.The AUC of the deep learning model in the test group was 0.702(95%CI 0.671-0.733).The operating point with the maximum sum of sensitivity and specificity was selected,and the sensitivity of the algorithm was 0.749(95%CI 0.719-0.778)and the specificity was 0.561(95%CI 0.527-0.595),corresponding to the AUC value of the verification group was 0.674(95%CI 0.622-0.726).Conclusions The deep learning algorithm model based on fundus images has good diagnostic performance,and may be used as a new non-invasive,convenient and rapid screening method for MCI in CHD population.

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