Chimeric antigen receptor T (CAR-T) cells have reshaped the treatment landscape of hematological malignancies, offering a potentially curative option for patients. Despite these major milestones in the field of immuno-oncology, growing experience with CAR-T cells has also highlighted several limitations of this strategy. The production process of CAR-T cells is complex, time-consuming, and costly, thus leading to poor drug accessibility. The potential carcinogenic risk of viral transfection systems remains a matter of controversy. Treatment-related side effects, such as cytokine release syndrome, can be life-threatening. And the biggest challenge is the inadequate efficacy related to poor infiltration and retention of CAR-T cells in tumor tissues and impaired T cell activation caused by the immunosuppressive tumor microenvironment (TME). Innovative strategies are urgently needed to address these problems, and nanomedicine offers good solutions to these challenges. In this review, we provide a comprehensive summary of recent advancements in the application of nanomaterials to enhance CAR-T cell therapy. We examine the role of innovative nanoparticle-based delivery systems in the production of CAR-T cells, with a particular focus on polymeric delivery systems and lipid nanoparticles (LNPs). Furthermore, we explore various strategies for delivering immune stimulators, which significantly enhance the efficacy of CAR-T cells by modulating T cell viability and functionality or by reprogramming the immunosuppressive TME. In addition, we discuss several novel therapeutic approaches aimed at mitigating the adverse effects associated with CAR-T therapies. Finally, we offer an integrated perspective on the future challenges and opportunities facing CAR-T therapies.
Humans ; Nanomedicine/methods* ; Receptors, Chimeric Antigen/metabolism* ; Immunotherapy, Adoptive/methods* ; T-Lymphocytes/immunology* ; Nanoparticles/chemistry* ; Animals

Objective To explore the effect of Roy's adaptive model nursing on the rehabilitation in patients with multiple myeloma.Methods Eighty patients with multiple myeloma who were treated in Huaibei Miners General Hospital from October 2018 to October 2021 were selected by convenient sampling.They were divided into two groups by random number table method,with 40 patients in each group.Routine nursing was applied in the control group,and Roy's adaptive model nursing was given to the study group.The nutritional status,psychological resilience and lifestyle improvement were compared between the two groups.Results Before nursing,there was no significant difference in the nutritional indicators,Connor-Davidson Resilience Scale(CD-RISC)score,or Health-Promoting Lifestyle Scale(HPLP Ⅱ)score between the two groups(P>0.05).After nursing,body mass index(BMI),triceps skinfold thickness(TSF),albumin(ALB)and prealbumin(PA),the scores of toughness,strength and optimism in CD-RISC,and the scores of interpersonal relationship,nutrition management,health responsibility,exercise management,stress management and mental growth in HPLP Ⅱ were increased in both groups(P<0.05),and these indexes in the study group were significantly higher than those in the control group(P<0.05).Conclusion Roy's adaptive model nursing can improve nutritional status,enhance psychological resilience and promote healthy lifestyle of patients with multiple myeloma.

Objective To explore the risk factors of cardiomyopathy in patients with diabetes and their correlations with the levels of serum fork head box protein O1(FOXO1),growth differentiation factor 11(GDF11),and matrix metalloproteinase-3(MMP3).Methods 200 patients with diabetes complicated with cardiomyopathy and 200 patients with simple diabetes admitted to the People's Hospital of Xinjiang Uygur Autonomous Region from September 2023 to April 2025 were selected to detect serum FOXO1,GDF11 and MMP3 levels,analyze their correlation with cardiac function parameters,screen risk factors through multifactor logistic regression,construct a nomogram model and a receiver operating characteristic(ROC)curve,and evaluate the diagnostic value.Results The duration of diabetes cardiomyopathy group≥10 years,the expression rate of reactive oxygen species(ROS)≥90%,the insulin resistance index and the levels of FOXO1 and MMP3 were significantly higher than those in the simple diabetes group(P<0.05),and the level of GDF11 was lower than that in the simple diabetes group(P<0.05).FOXO1 and MMP3 were positively correlated with E/e'and negatively correlated with LVEF and E/A;GDF11 was negatively correlated with E/e'and positively correlated with LVEF and E/A(P<0.05).The nomogram model showed that the weights of the influencing factors were GDF11,FOXO1,insulin resistance index,MMP3,ROS expression rate,and the course of diabetes.The model calibration was good(χ2=7.336,P=0.719).The combined diagnostic AUC of FOXO1,GDF11,and MMP3 was 0.950,which was better than that of a single indicator(P<0.05).Conclusion GDF11,FOXO1,Insulin resistance index,MMP3,ROS expression rate and the course of diabetes are risk factors for diabetes cardiomyopathy,and the combination of the three is of high diagnostic value.

ObjectiveTo analyze the epidemiological and clinical characteristics of pertussis in Baoshan District, Shanghai from 2017 to 2024, so as to provide an evidence-based reference for optimizing prevention and control strategies. MethodsData on pertussis cases were collected from the China Disease Prevention and Control Information System, Shanghai Integrated Management and Immunization Service Information System, and follow-up epidemiological investigations. Descriptive epidemiological analyses were performed to analyze the epidemiological characteristics, clinical manifestations, and vaccine effectiveness. Joinpoint regression analyses were used to examine the temporal trends in incidence rates, and a Poisson model was constructed for spatiotemporal scan analyses. ResultsA total of 1 634 pertussis cases were reported in Baoshan District from 2017 to 2024, with a male-to-female ratio of 1.08∶1. More cases were observed in males than in females, with the age ranged from 20 days to 81 years. Among them, 59.92% were in the 6‒<11 years age group, and 63.34% were students. Low-level sporadic incidence persisted during 2017‒2023, followed by a sharp increase in 2024 (71.37/100 000). Starting in January 2024, the incidence rate showed an upward trend, peaking in May before declining. The majority of cases occurred between April and June. The trend in reported pertussis incidence rates in Baoshan District from 2017 to 2023 showed no statistically significant change (APC=10.039%, t=2.586, P=0.150). Incidence rate rose from January 2024, peaked in May (APC=133.641%, t=3.841, P=0.006), then declined significantly (APC=-47.816%, t=2.586, P<0.001). The 12 subdistricts of Baoshan District were divided into low, medium, and high population density areas, with an average annual reported incidence rate of 6.09/100 000, 8.19/100 000 and 11.96/100 000, respectively. The reported incidence rate increased with an increase in population density. Spatiotemporal scan analyses showed that cases clustered in the southwest and northeast of Baoshan District. Epidemiological follow-up investigations of 1 520 cases revealed that the main clinical symptoms were cough (97.63%) and sputum production (41.58%), and 98.13% of the cases were confirmed by positive nucleic-acid test results. Among the 1 475 cases with immunization records, 83.53% had completed the four-dose pertussis vaccine before onset. The complication incidence rates, from high to low, were in the 0-dose vaccination group, 1‒3-dose vaccination group and 4-dose vaccination group. The duration of cough, from long to short, was observed in the the 0-dose vaccination group, 1‒3-dose vaccination group and 4-dose vaccination group, correspondingly. ConclusionIt is recommended to improve the pertussis surveillance system in medical institutions and establish an active monitoring network, prioritizing deployment in school settings and areas with high population density. Enhancing diphtheria-tetanus-pertussis (DTP) vaccination coverage among 6-year-old children and further optimizing the pertussis immunization strategies are essential to prevent and reduce the risk of pertussis among school-aged children.

BACKGROUND:Croton cream can activate ERK pathways and have anti-apoptotic effects on neuronal cells.It is not clear whether it synergistically exerts anti-apoptotic effects by inhibiting the activation of JNK and p38 pathways. OBJECTIVE:To explore the effects and mechanisms of croton cream on neuronal damage and apoptosis in the ischemic cortex of rats with cerebral ischemia-reperfusion injury. METHODS:(1)Ninety Sprague-Dawley rats were randomly divided into sham operation group,model group,croton cream low-dose group,croton cream medium-dose group,croton cream high-dose group and nimodipine group,with 15 rats in each group.Except for the sham operation group,animal models of middle cerebral artery occlusion were prepared in rats by the thread method.Rats in the three croton cream groups were given 20,40,and 60 mg/kg croton cream,respectively.Rats in the sham operation and model groups were given the same amount of normal saline,once a day,for 7 consecutive days.The optimal concentration of croton cream,namely the high dose of croton cream,was selected based on neurological deficit score,TTC staining,brain tissue water content,hematoxylin-eosin staining and Nissl staining.(2)Another 120 Sprague-Dawley rats were randomly divided into sham operation group,model group,croton cream group,JNK inhibitor group,croton cream+JNK inhibitor group,p38 MAPK inhibitor group,croton cream+p38 MAPK inhibitor group,and nimodipine group,with 15 rats in each group.Animal models of middle cerebral artery occlusion were prepared using the thread method in all the groups except in the sham operation group.Thirty minutes before modeling,10 μL of SP600125(JNK inhibitor)and 10 μL of SB203580(p38 MAPK inhibitor)were injected into the lateral ventricle of the rats,respectively.Rats in croton cream groups were intragastrically given 60 mg/kg croton cream.Seven days later,the JNK/p38 MAPK signaling pathway,apoptosis-related proteins and cell apoptosis were detected by western blot,TUNEL staining and flow cytometry,respectively. RESULTS AND CONCLUSION:(1)Compared with the sham operation group,neurological deficit score,cerebral water content,cerebral infarction volume and apoptosis rate were significantly increased in the model group(P<0.05),where nerve cells showed scattered distribution.Compared with the model group,neurological deficit score,water content of brain tissue and cerebral infarction volume were significantly decreased in the croton cream medium-dose group,high-dose group and nimodipine group(P<0.05),and the pathological morphology of nerve cells was significantly improved.(2)Compared with the JNK inhibitor group,p-JNK/JNK,p-p38/p38 and Bax expressions in rat brain tissue and the apoptotic rate were significantly decreased in the croton cream+inhibitor groups(P<0.05),while the expression of and Bcl-2 was significantly increased(P<0.05).To conclude,croton cream may inhibit the activation of JNK/p38 MAPK signaling pathway and reduce neuronal apoptosis to achieve neuroprotective effects in rats with cerebral ischemia-reperfusion injury.

Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of～260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.

Objective To explore the risk factors of 1-year readmission in patients after percutaneous coronary intervention(PCI)treated with Bayaspirin combined with Clopidogrel and to construct a risk prediction model.Methods The clinical data of patients with myocardial infarction(MI)who underwent primary PCI in the Department of Cardiovascular Medicine of Lishui People's Hospital from January 2020 to June 2023 were retrospectively analyzed.The patients were divided into the readmission group(RG)and the non-readmission group(NRG)according to whether they were readmitted due to myocardial reinfarction or complications of MI within 1 year.Univariate analysis was used to explore the differential variables between the RG and NRG groups.Multivariate Logistic regression(Stepwise)was used to explore the risk factors of 1-year readmission in patients after PCI and the"optimal model".The"optimal model"was visualized using R software and transformed into a nomogram risk prediction model.The predictive ability of the Nomogram risk prediction model was evaluated using the receiver operating characteristic(ROC)curve.The calibration of the Nomogram risk prediction model was evaluated using the calibration curve(resampling,Bootstrap n=1 000).The net benefit of the nomogram risk prediction model was evaluated using the decision curve.Results A total of 100 patients were included in the study and the readmission rate within 1 year was 34.00％.Age(≥63 years old),diabetes,the number of diseased vessels(≥2),monocyte-high-density lipoprotein ratio(≥0.36),and prognosis nutrition(＜39.39)were independent risk factors for readmission in patients with MI after PCI(all P＜0.05).ROC analysis showed that the readmission risk prediction model had a good predictive efficiency for readmission in patients with MI after PCI,with an area under ROC curve of 0.903(95％CI:0.836-0.970).The calibration curve showed that the"predicted readmission probability"was approximately consistent with the"actual readmission probability";the decision curve showed that the net benefit of the readmission risk prediction model nomogram was higher than that of the"all"clinical net benefit.Conclusion The readmission prediction model of patients with MI after PCI constructed in this study can accurately identify high-risk groups of readmission and may be beneficial for the standardized management of patients after PCI in clinical practice,improve the long-term prognosis of patients.

OBJECTIVE To explore the neuroprotective effect and possible mechanism of celastrol （Cel） and its derivatives （Cel-1， Cel-2） in terms of neuroinflammation and oxidative damage. METHODS Neuroinflammation model of microglial BV2 cells was induced by 1 μg/mL lipopolysaccharide （LPS）； oxidative damage model of human neuroblastoma SH-SY5Y cells was induced by 200 μmol/L hydrogen peroxide （H2O2）. The toxicity of different concentrations of Cel， Cel-1 and Cel-2 （0.625-20 μmol/L） to the two types of cells was investigated. The levels of nitric oxide （NO）， tumor necrosis factor α （TNF-α）， interleukin 1β （IL-1β）， and IL-6 in BV2 cells induced by LPS at safe concentrations （0.039-0.625 μmol/L） were all detected. The survival rate of SH-SY5Y cells induced by H2O2 was also determined. The expression levels of phosphoinositide 3-kinase （PI3K）， p-PI3K， protein kinase B （Akt）， p-Akt， cystatinase 3 （caspase-3）， B-cell lymphoma 2 （Bcl-2） and Bcl-2-related X protein （Bax） in SH- SY5Y cells induced by H2O2 at 0.156， 0.313， 0.625 μmol/L of active compound 2 were all detected. RESULTS In the concentration gradient range between 0.039 and 0.625 μmol/L， the results of neuroinflammation model experiments showed that Cel， Cel-1 and Cel-2 could reduce the contents of NO， TNF-α， IL-1β， and IL-6 in culture medium of BV2 cells （P＜0.05 or P＜ 0.01）； their IC50 values for neuroinflammation were （0.25±0.04）， （0.61±0.14） and （0.11±0.02） μmol/L respectively. Meanwhile， all of them could reverse the phenomenon of decreased cell survival rate after H2O2 treatment in the oxidative damage experiments at a certain concentration （P＜ 0.05 or P＜0.01）， with neuroprotective EC50 values of （0.43± XJC2023009） 0.08）， （0.45±0.04） and （0.28±0.03） μmol/L， respectively.Induced by H2O2， the phosphorylation of PI3K and Akt protein， protein expressions of Bcl-2 and Bcl-2/Bax ratio were all increased significantly （P＜0.05 or P＜0.01）， while the protein expressions of caspase-3 and Bax were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Cel， Cel-1， and Cel-2 all have significant neuroprotective activities at certain concentrations， and Cel-2 shows the most significant protective effect. The mechanism of action of Cel-2 may be related to regulating the PI3K/Akt and caspase-3/Bcl-2/Bax signaling pathways， reducing the inflammatory response， oxidative stress damage and inhibiting neuronal apoptosis.

ObjectiveTo investigate the effect of Rehmanniae Radix Praeparata on neurological function injury in ischemic stroke rats and explore its mechanism. MethodMale SD rats were randomized into sham operation， model， low- and high -dose （3.5 g·kg^-1 and 7 g·kg^-1） Rehmannia Radix Praeparata， and nimodipine （0.01 g·kg^-1） groups. The rat model of middle cerebral artery occlusion （MCAO） was established with the modified suture occlusion method. Zea-Longa 5-point scoring was employed to evaluate the neurological function of rats. The cerebral infarction volume was detected by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Hematoxylin-eosin staining and Nissl staining were employed to observe the morphology and damage of the brain tissue. Meanwhile， the serum levels of lactate dehydrogenase （LDH）， oxidative stress-related indicators superoxide dismutase （SOD）， glutathione peroxidase 4 （GPX4）， and malondialdehyde （MDA）， and the iron （Fe） content in the brain tissue were determined. To explore the mechanism of Rehmanniae Radix Preparata in mitigating the neurological damage in ischemic stroke rats， Western blotting was employed to determine the expression levels of proteins in the ischemic brain tissue. The autophagy-associated proteins included autophagy effector （beclin-1）， microtubule-associated protein light chain 3 （LC3B）， and ubiquitin-binding protein p62 （p62）. The ferroptosis-associated proteins included transferrin （TF）， transferrin receptor 1 （TFR1）， ferritin heavy chain 1 （FTH1）， and ferropotin （FPN1）. The neurological function injury-associated proteins included brain-derived neurotrophic factor （BDNF） and tyrosine kinase receptor B （TrkB）. ResultCompared with the sham operation group， the model group showed increased neurological function score， cerebral infarction volume， and appearance of nuclear pyknosis and vacuole of cells in the cerebral cortex. In addition， the model group presented elevated levels of LDH， MDA， and Fe （P<0.01） and lowered levels of SOD and GPX4 （P<0.01）. Compared with the model group， Rehmanniae Radix Praeparata decreased the content of LDH， MDA， and Fe （P<0.05， P<0.01） and elevated the levels of SOD and GPX4 （P<0.05， P<0.01）. Compared with the sham operation group， the modeling promoted the expression of beclin-1，LC3B Ⅱ/Ⅰ， TF， and TFR1 and inhibited the expression of p62， FTH1， FPN1， BDNF， and TrkB （P<0.01）. The expression levels of these proteins were recovered after the treatment with Rehmanniae Radix Praeparata. ConclusionRehmanniae Radix Praeparata may inhibit ferroptosis and improve the neurological function in ischemic stroke rats by down-regulating the autophagy level in the brain tissue.

Objective:To summarize the best evidence for spasticity management in spinal cord injury patients, so as to provide references for clinical practice.Methods:PubMed, Embase, CLINICAL, BMJ Best Clinical Practice website, JBI Evidence-based Health Care Center database, National Institute for Health and Clinical Excellence, Ontario Guidelines Network, US National Guidelines Network, Scottish Interhospital Guidelines Network, UpToDate, Cochrane Library, CNKI, Wanfang Database, Medlive, China Biology Medicine disc and professional association websites were syatematically searched for clinical decisions, guidelines, evidence summary, systematic reviews and expert consensus or opinions on spasm management. The quality of the included studies was evaluated and the evidence content was extracted. The search period was from the establishment of the databases to February 28, 2023.Results:A total of 15 articles were included, including 2 clinical decision-making articles, 1 guideline, 3 expert consensus or opinions articles and 9 systematic evaluations. A total of 18 pieces of evidence were summarized from 4 aspects, such as regular evaluation, intervention measures, intervention principles, and effectiveness evaluation of patients with spinal cord injury.Conclusions:This study summarizes the best evidence for spasticity management in patients with spinal cord injury and provides an evidence-based basis for clinical work. It is recommended that when applying the evidence, an individualized spasticity treatment plan should be developed according to the needs of the patient and the actual clinical situation.