Tumors are the second leading cause of death worldwide. Exosomes are a type of extracellular vesicle secreted from multivesicular bodies, with particle sizes ranging from 40 to 160 nm. They regulate the tumor microenvironment, proliferation, and progression by transporting proteins, nucleic acids, and other biomolecules. Compared with other drug delivery systems, exosomes derived from different cells possess unique cellular tropism, enabling them to selectively target specific tissues and organs. This homing ability allows them to cross biological barriers that are otherwise difficult for conventional drug delivery systems to penetrate. Due to their biocompatibility and unique biological properties, exosomes can serve as drug delivery systems capable of loading various anti-tumor drugs. They can traverse biological barriers, evade immune responses, and specifically target tumor tissues, making them ideal carriers for anti-tumor therapeutics. This article systematically summarizes the methods for exosome isolation, including ultracentrifugation, ultrafiltration, size-exclusion chromatography (SEC), immunoaffinity capture, and microfluidics. However, these methods have certain limitations. A combination of multiple isolation techniques can improve isolation efficiency. For instance, combining ultrafiltration with SEC can achieve both high purity and high yield while reducing processing time. Exosome drug loading methods can be classified into post-loading and pre-loading approaches. Pre-loading is further categorized into active and passive loading. Active loading methods, including electroporation, sonication, extrusion, and freeze-thaw cycles, involve physical or chemical disruption of the exosome membrane to facilitate drug encapsulation. Passive loading relies on drug concentration gradients or hydrophobic interactions between drugs and exosomes for encapsulation. Pre-loading strategies also include genetic engineering and co-incubation methods. Additionally, we review approaches to enhance the targeting, retention, and permeability of exosomes. Genetic engineering and chemical modifications can improve their tumor-targeting capabilities. Magnetic fields can also be employed to promote the accumulation of exosomes at tumor sites. Retention time can be prolonged by inhibiting monocyte-mediated clearance or by combining exosomes with hydrogels. Engineered exosomes can also reshape the tumor microenvironment to enhance permeability. This review further discusses the current applications of exosomes in delivering various anti-tumor drugs. Specifically, exosomes can encapsulate chemotherapeutic agents such as paclitaxel to reduce side effects and increase drug concentration within tumor tissues. For instance, exosomes loaded with doxorubicin can mitigate cardiotoxicity and minimize adverse effects on healthy tissues. Furthermore, exosomes can encapsulate proteins to enhance protein stability and bioavailability or carry immunogenic cell death inducers for tumor vaccines. In addition to these applications, exosomes can deliver nucleic acids such as siRNA and miRNA to regulate gene expression, inhibit tumor proliferation, and suppress invasion. Beyond their therapeutic applications, exosomes also serve as tumor biomarkers for early cancer diagnosis. The detection of exosomal miRNA can improve the sensitivity and specificity of diagnosing prostate and pancreatic cancers. Despite their promising potential as drug delivery systems, challenges remain in the standardization and large-scale production of exosomes. This article explores the future development of engineered exosomes for targeted tumor therapy. Plant-derived exosomes hold potential due to their superior biocompatibility, lower toxicity, and abundant availability. Furthermore, the integration of exosomes with artificial intelligence may offer novel applications in diagnostics, therapeutics, and personalized medicine.

Calcified lesions increase the difficulty of interventional therapy for coronary heart disease,and increase the risk of perioperative and long-term complications.Pretreatment of calcified lesions is very important.Coronary lithotripsy(IVL)is used more and more in calcified lesions,and many clinical trials have proved its effectiveness and safety.Stent underexpansion is an important risk factor for stent thrombosis and restenosis,which increases the incidence of complications.At present,there is no effective coping strategy or clear consensus or guidelines for the treatment of stent underexpansion caused by calcified lesions.There are few reports about the treatment of stent under expansion by IVL,and most of them are case reports and small sample studies.In this paper,two cases of stent under expansion were reported.After stent implantation,stent under expansion was found,and IVL was used to treat the cases,which achieved good results.This paper reports 2 cases of stent under expansion to explore the efficacy and safety of IVL in the treatment of such lesions.

Objective:To explore the influence of environment temperature on the incidence of testicular torsion.Methods:We collected the clinical data on 172 cases of testicular torsion diagnosed in the Second Hospital of Hebei Medical University from De-cember 2013 to December 2020.According to the local environment temperature on the day of onset,we divided the patients into groups A(below 0℃),B(0-10℃),C(10-20℃)and D(above 20℃),and compared the incidence rates of testicular torsion among the four groups,followed by correlation analysis.Results:The incidence rate of testicular torsion was 12.8％(n=22)in group A,35.5％(n=61)in B,34.9％(n=60)in C and 16.9％(n=29)in D,the highest at 0-10℃ in group B,with sta-tistically significant difference among the four groups(x2=29.07,P＜0.001).Spearman correlation analysis indicated that the inci-dence of testicular torsion was negatively correlated with the environment temperature(r=-0.261,P＜0.01),with no statistically significant difference among different seasons(x2=5.349,P＞0.05),but higher in autumn and winter than in the other two sea-sons.Conclusion:The incidence of testicular torsion is negatively correlated with the environment temperature,elevated when the temperature decreases,but has no statistically significant difference among different seasons,though relatively higher in autumn and winter.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To investigate the prevalence of tension-type headache(TTH)in children and adolescents aged 0-19 years globally in 1990-2021,and to provide a basis for the prevention and treatment of TTH.Methods Based on the Global Burden of Disease Study data,the age-standardized prevalence distribution of TTH and its changing trend were analyzed among the children and adolescents aged 0-19 years,with different sexes,age groups,sociodemographic index(SDI)regions and countries/territories.Results The age-standardized prevalence rate(ASPR)of TTH in children and adolescents aged 0-19 globally in 2021 was 17 339.89/100 000,which was increased by 1.73%since 1990.The ASPR in females was slightly higher than that in males(1990:17 707.65/100 000 vs 16 403.78/100 000;2021:17 946.29/100 000 vs 16 763.09/100 000).The ASPR in adolescence was significantly higher than that in school-aged and preschool periods(1990:27 672.04/100 000 vs 10 134.16/100 000;2021:28 239.04/100 000 vs 10 059.39/100 000).Regions with high SDI exhibited a higher ASPR than the other regions,with significant differences in prevalence rates across different countries.From 1990 to 2021,there was a slight increase in global ASPR,with an average annual percentage change(AAPC)of 0.06%.Females experienced a smaller increase than males based on AAPC(0.04%vs 0.07%).There was reduction in ASPR in preschool and school-aged groups,with an AAPC of-0.02%,while there was a significant increase in ASPR in adolescence,with an AAPC of 0.07%.ASPR decreased in regions with low-middle and low levels of SDI,with an AAPC of-0.02%and-0.04%,respectively,while it increased in regions with middle SDI,with an AAPC of 0.24%.Conclusions There is a consistent increase in the ASPR of TTH in children and adolescents aged 0-19 years globally,with significant differences across sexes,age groups,SDI regions and countries/territories.

Objective To preliminarily investigate the anti-tumor effects of phytosphingosine(PHS)and the involvement of inducing apoptosis of leukemia cells.Methods Cellular model of leukemia was established in leukemia cell lines K562 and SUP-B15.CCK-8 assay and EdU assay were used to measure the viability and DNA synthesis of K562 and SUP-B15 cells.RNA-seq was carried out to verify the differentially expressed genes(DEGs)after PHS treatment.Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were applied to analyze the involved functions and signaling pathways.Comparative Toxicogenomics Database(CTD)and Discovery Studio software were employed to predict the underlying targets of PHS and molecular docking.Cell apoptosis was detected by flow cytometry,mitochondrial membrane potential was evaluated by JC-1 probe,and protein expression of key molecules was validated by Western blotting.Results PHS inhibited the proliferation of K562 and SUP-B15 cells in a time-and dose-dependent manner.The half-maximal inhibitory concentration(IC50)of K562 cells was 17.67 and 12.52 pmol/L for 24 and 48 h,respectively,and the IC50 value of SUP-B15 cells was 17.58 and 14.86 μmol/L for 24 and 48 h,respectively.PHS treatment at a dose of 20 μmol/L for 48 h resulted in significant inhibition of DNA synthesis.GO enrichment analysis of the K562 cells showed that PHS might be involved in positive regulation of apoptotic process,plasma membrane and its integral components,and protein kinase binding and activity.Reverse predictive analysis showed that BCL-2 protein was the most likely target of PHS.PHS significantly increased the apoptotic rate of leukemia cells(P＜0.05)in a dose-dependent manner,reduced the mitochondrial membrane potential,and down-regulated BCL-2 level(P＜0.05)and up-regulated the levels of Cleaved caspase-3 and Cleaved caspase-9(P＜0.05).Conclusion PHS may inhibit the proliferation of leukemia cells by inducing mitochondria-dependent apoptosis,possibly through PHS and BCL-2 interaction.

Objective To observe the effect of ultrasound-guided iliopsoas plane block(IPB)on the quality of postoperative recovery in patients undergoing hip arthroplasty.Methods Sixty patients who underwent hip arthroplasty were selected,37 males and 23 females,aged 40-79 years,BMI 18-30 kg/m2,ASA physical status Ⅰ-Ⅲ.The patients were divided into two groups by random number table method:the iliopsoas plane block group(group IPB)and the femoral nerve block(FNB)group(group FNB),30 pa-tients in each group.Before anesthesia induction,IPB was performed with 0.5%ropivacaine 10 ml and lat-eral femoral cutaneous nerve block was performed with 0.5%ropivacaine 5 ml in group IPB.And FNB was performed with 0.5%ropivacaine 10 ml and lateral femoral cutaneous nerve block was performed with 0.5%ropivacaine 5 ml in group FNB.The dosages of propofol,remifentanil,and cis-atracurium during operation were recorded.The quality of recovery-15(QoR-15)scale was evaluated preoperatively and postoperatively 1 day,2 and 3 days.The max VAS(VASmax)pain score and manual muscle test(MMT)score of quadri-ceps muscle were recorded 12,24,and 48 hours after surgery.The time of getting out of bed for the first time,opioid dosage,and patient satisfaction were recorded.The incidence of nerve injury,vascular injury,puncture site infection,and local anesthetic poisoning were recorded.The postoperative complications of diz-ziness,nausea and vomiting,deep vein thromboses,and elirium were also recorded.Results There was no significant difference in the dosage of propofol,remifentanil,and cis-atracurium between the two groups.Compared with group FNB,the QoR-15 scale score in group IPB was significantly higher 1 day,2 and 3 days after operation(P＜0.05).Compared with group FNB,the MMT scores of quadriceps muscle was sig-nificantly higher in group IPB 12 and 24 hours after surgery(P＜0.05),and the first time of getting out of bed was shortened in group IPB(P＜0.05).However,there were no significant differences in the VASmax pain score,MMT score of quadriceps muscle 48 hours after surgery,opioid dosage,and patient satisfaction between the two groups.No nerve block related complications were found in both groups.There were no sig-nificant differences in postoperative complications between the two groups.Conclusion The iliopsoas plane block can improve the quality of postoperative recovery and accelerate the recovery of patients with hip re-placement,and the effect is better than that of femoral nerve block.

ObjectiveSodium hyaluronate (HA) was used as the research object to modify it with phenolic acid in order to obtain the molecular structure with better antioxidant activity or even new activity. MethodsIn this study, 5 kinds of phenolic acid-sodium hyaluronate was prepared by free radical-mediated grafting method, and the grafts with the highest grafting degree were selected to optimize the synthesis conditions. Then, grafts structure and physicochemical properties were analyzed. The grafts were characterized by IR, UV, ¹H NMR, FESEM and TGA spectra. The in vitro antioxidant capacity of grafts was determined by the scavenging ability of DPPH·, ABTS⁺· and O^2-·. ResultsAmong 5 kinds of phenolic acid-sodium hyaluronate, the grafting rate of ferulic acid-sodium hyaluronate copolymer (FA-HA) was highest , which was chosen as experimental sample in the following tests. Firstly, the reaction conditions were investigated and the highest grafting rate was (16.59±0.31) mg/g at the optimal preparation conditions. Then, FA-HA structure and physicochemical properties were analyzed. Data from UV, IR, ¹H NMR analyses, TGA showed that FA were successfully grafted to HA. Compared with HA, the results of gel permeation chrematography (GPC) showed that the molecular mass distribution ofFA-HA copolymer decreased from 34.4 to 31.5 ku, but the uniformity of molecular distribution was improved. FESEM results showed that the structure of copolymer exhibited a closely connected lamellar structure with a relatively smooth surface. TGA results showed that thermal stability of FA-HA had a little decline. The antioxidant performance in vitro results showed that, during 0.25-10 g/L, FA-HA can eliminate (83.76±4.86)% DPPH·, (76.95±5.06)% ABTS⁺· and (83.08±2.51)% O^2-· respectively at 10 g/L. which were higher than that of native HA and FA. ConclusionFA and HA were successfully grafted together by free radical grafting, and the grafted FA-HA had better antioxidant activity in vitro, which provided a theoretical basis for further research and development of phenolic acid-HA grafts.

ObjectiveTo observe the efficacy and safety of Uyghur medicine Yangxin Dawayimixike Honey Paste （养心达瓦依米西克蜜膏， YDMHP） in the treatment of stable angina pectoris （SAP） of qi stagnation and blood stasis syndrome. MethodsA randomized ， double-blind， positive-controlled，multi-center clinical trial was conducted， in which 370 patients with SAP of qi stagnation and blood stasis syndrome were randomly divided into treatment group（279 cases）and control group（91cases）at a ratio of 3∶1. The treatment group was orally administered with YDMHP， 3 g each time， and placebo of Xuefu Zhuyu Capsule （血府逐瘀胶囊）， 2.4 g each time， while the control group was treated with Xuefu Zhuyu Capsule， 2.4 g each time， and placebo of YDMHP， 3 g each time， both twice a day for a course of 12 weeks. The primary outcome was the effect of angina pectoris symptom. The secondary outcomes include single angina symptom scores such as number of attacks， duration of attacks， pain intensity and usae of nitroglycerin scores， the total angina symptom score before and after the treatment， the usage of nitroglycerin， the exercise duration in treadmill exercise test （TET） and the Duck treadmill score among patients，the scores of Seattle Angina Questionnaire （SAQ） on five dimensions including physical limitations， anginal stability， anginal frequency， treatment satisfaction， and disease perception， and efficacy of TCM syndrome and of each single TCM symptom after treatment. The safety were evaluated by examine blood routine， urine routine， liver and kidney function， fasting blood sugar， electrocardiogram， adverse events. ResultsThe total effective rate of angina symptom in the treatment group was 71.69% （200/279）， significantly higher than 51.64% （47/91） in the control group （P＜0.01）. The curative and markedly effective rate of TCM syndrome in the treatment group was 53.05% （148/279）， which was significantly higher than 25.27% （23/91） in the control group （P＜0.01）. After treatment， scores of the number as well as duration of angina attacks and pain severity， the total score of angina symptoms， and the usage of nitroglycerin significantly decreased in both groups， and more changes were seen in the treatment group than in the control group； the scores of physical limitations， anginal stability， anginal frequency， treatment satisfaction， and disease perception in both groups significantly increased， and more improvement were shown in the experimental group regarding the anginal stability， anginal frequency and treatment satisfaction （P＜0.05 or P＜0.01）. The effects of chest pain， chest tightness， palpitation， shortness of breath and fatigue in experimental group were significantly higher than those in control group （P＜0.05 or P＜0.01）. There was no significant difference in the exercise duration of treadmill test and Duke score among patients between the two groups either before or after treatment （P＞0.05）. Adverse events occurred in 66 cases （23.66%） of the experimental group and 16 cases （17.58%） of the control group， with no statistical significance between the two groups （P＞0.05）. ConclusionThe Uyghur medicine YDMHP can effectively improve symptoms of angina pectoris， reduce the number， duration， and intensity of attacks， decrease the dosage of nitrogly-cerin and improve the individual TCM symptoms and has good safety in the treatment of SAP patients of qi stagnation and blood stasis.

Objective To observe the clinical effects of cognitive behavioral therapy (CBT) combined with pulmonary rehabilitation on the treatment of patients with pneumoconiosis. Methods A total of 108 patients with pneumoconiosis were selected as the research subject using convenient sampling method. They were randomly divided into control group and CBT group, with 54 cases in each group. Patients in the control group were treated with conventional symptomatic treatment and pulmonary rehabilitation treatment for 12 weeks. While patients in the CBT group were treated with CBT treatment in addition to treatments of the control group. The therapeutic effect was analyzed. Results Before treatment, there was no statistical difference on score of Montreal Cognitive Assessment (MoCA), percentage of forced expiratory volume in one second to the predicted value (FEV₁%), forced expiratory volume in one second to force vital capacity ratio (FEV₁/FVC%), score of the Modified Medical Research Council Dyspnea Scale (mMRC), six minute walk distance (6MWD), Hospital Anxiety and Depression Scale (HADS) subscale scores of anxiety (HADS-A) and depression (HADS-D), and scores of Chronic Obstructive Pulmonary Disease Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), and serum levels of leptin, interleukin-6 (IL-6) and C-reactive protein (CRP) between the two groups (all P>0.05). After treatment, the score of MoCA, FEV₁%, FEV₁/FVC% and 6MWD increased (all P<0.05), while the scores of mMRC, HDS-A, HDS-D, CAT and SGRQ decreased (all P<0.05), and the levels of serum leptin, IL-6 and CRP decreased (all P<0.05) in the CBT group compared with the control group. Conclusion The combined treatment of CBT and pulmonary rehabilitation can better improve the cognitive ability, respiratory function, motor function, negative emotion and quality of life, and alleviate inflammatory response in patients with pneumoconiosis. It is of certain clinical application value.