BACKGROUND:As a common method of cancer treatment,chemotherapy has a certain therapeutic effect in the early stage.However,as the frequency of chemotherapy increases,the resistance of tumor cells to drugs gradually increases,that is,chemotherapy resistance.At present,the main mechanisms of chemotherapy resistance include the failure of chemotherapy drugs to reach the tumor site,the loss of drug activity leading to a decrease in drug efficacy,and tumor cells evading drug attack by reshaping their metabolic functions,gene phenotypes,and microenvironment.However,the specific mechanism remains to be discussed in depth. OBJECTIVE:To summarize the mechanisms by which exosomal miRNA is involved in drug resistance in different tumors,and to propose potential targets. METHODS:The PubMed database was searched using the English search terms"hematological malignancies,liver cancer,lung cancer,breast cancer,melanoma,colorectal cancer,drug resistance,exosomal miRNAs."The search time range was from January 2013 to August 2023.Preliminary screening was carried out by reading the titles and abstracts,and the exclusion criteria were for literature with poor relevance to the research content or repetitive content.Finally,60 articles were included for review. RESULTS AND CONCLUSION:(1)Exosomal miRNA enters the intercellular matrix and circulation,and participates in the formation and development of different tumor biological processes,including tumor microenvironment remodeling,angiogenesis,and drug resistance,by exerting local paracrine or distal effects.(2)Exosomal miRNA can penetrate the cell membrane into the cytoplasm of another cell,activate or inhibit the signaling pathway in the recipient cell by delivering miRNA,and maintain cell survival,proliferation,and metastasis during chemotherapy,thus leading to drug resistance.(3)Many exosomal miRNAs related to chemotherapy resistance have been identified and studied as common tumor treatment targets.(4)Although exosomal miRNA holds great promise as potential biomarkers and therapeutic targets,there are still some research deficiencies that need to be addressed:Firstly,there is a lack of standardized protocols for exosome isolation and characterization,resulting in differences in the methods used in different studies;secondly,although the presence and abundance of miRNAs in exosomes have been widely studied,their functional roles and mechanisms are not completely clear.Elucidating the specific targets and pathways regulated by exosomal can provide valuable insights into their biological significance and potential therapeutic applications.Addressing these research gaps will contribute to a more comprehensive understanding of exosomal miRNAs and their potential applications in various fields,including diagnosis,therapy,and personalized medicine.

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

Objective To investigate the impact of intravenous inject esketamine before operation on postoperative fatigue syndrome(POFS)in patients undergoing laparoscopic radical surgery for colorectal cancer.Methods Sixty-two patients,41 males and 21 females,aged 34-64 years,BMI 18-25 kg/m2,ASA physical statusⅠ orⅡ,scheduled for laparoscopic radical surgery for colorectal cancer under general anesthesia,were randomly assigned into two groups:the esketamine group(group E)and the control group(group C),31 patients in each group.Group E received a single intravenous injection of esketamine 0.25 mg/kg 5 minutes before surgery,while group C received sodium chloride 5 ml.The intravenous analgesia program was identical between the two groups.The jugular venous blood samples were taken for determination of serum concentrations of tumor necrosis factor-α(TNF-α)and superoxide dismutase(SOD)10 minutes before anesthesia,at the end of operation,and 12 and 24 hours after operation.Identity-consequence fatigue scale(ICFS-10)score were performed 1 day before surgery,3,5,and 7 days after op-eration,respectively,and the occurrence of POFS(ICFS-10 score＞24 points)were recorded.The time of extubation and the occurrence of adverse reactions such as coughing,delirium and restlessness during awak-ening,the complications of systems postoperatively,and the postoperative hospitalization time were recorded.Results Compared with group C,the concentration of serum TNF-α were significantly decreased while the concentration of serum SOD were significantly increased at the end of operation,12 and 24 hours after operation(P＜0.05),ICFS-10 score 3,5,and 7 days after operation,and the incidence of POFS 7 days after operation were significantly decreased(P＜0.05).There were no significant differences in extu-bation time,coughing,delirium and restlessnes,the complications postoperatively,and postoperative hospi-talization time between the two groups.Conclusion A single intravenous injection of esketamine can reduce the incidence of POFS in patients undergoing laparoscopic radical surgery for colorectal cancer,and no postoperative adverse reactions increased.

Objective:The transjugular or transfemoral approach is used as a common method for hepatic venous pressure gradient (HVPG) measurement in current practice. This study aims to confirm the safety and effectiveness of measuring HVPG via the forearm venous approach.Methods:Prospective recruitment was conducted for patients with cirrhosis who underwent HVPG measurement via the forearm venous approach at six hospitals in China and Japan from September 2020 to December 2020. Patients' clinical baseline information and HVPG measurement data were collected. The right median cubital vein or basilic vein approach for all enrolled patients was selected. The HVPG standard process was used to measure pressure. Research data were analyzed using SPSS 22.0 statistical software. Quantitative data were used to represent medians (interquartile ranges), while qualitative data were used to represent frequency and rates. The correlation between two sets of data was analyzed using Pearson correlation analysis.Results:A total of 43 cases were enrolled in this study. Of these, 41 (95.3%) successfully underwent HVPG measurement via the forearm venous approach. None of the patients had any serious complications. The median operation time for HVPG detection via forearm vein was 18.0 minutes (12.3~38.8 minutes). This study confirmed that HVPG was positively closely related to Child-Pugh score ( r = 0.47, P = 0.002), albumin-bilirubin score ( r = 0.37, P = 0.001), Lok index ( r = 0.36, P = 0.02), liver stiffness ( r = 0.58, P = 0.01), and spleen stiffness ( r = 0.77, P = 0.01), while negatively correlated with albumin ( r = -0.42, P = 0.006). Conclusion:The results of this multi-centre retrospective study suggest that HVPG measurement via the forearm venous approach is safe and feasible.

[Objective]To explore the effects of electricity on sperm quality,sex hormone levels,and related proteins in TGF-β 1/smads signaling in testicular tissue.[Methods]Forty male SD rats were randomly divided into blank group,model group,electroacupuncture group,and positive drug group.Adenine gavage method was used to establish the model,in the electroacupuncture group,rats received electroacupuncture treatment at the acupoints Zhongji,Guanyuan,Zusanli,and Sanyinjiao once daily for 30 minutes;in the positive drug group,rats were administered L-carnitine oral solution via gavage at a dosage of 10 mL/kg,both intervention groups underwent continuous treatment for 28 days.After treatment,the changes of sperm number,sperm motility rate,follicle-stimulating hormone(FSH),luteizing hormone(LH)and serum sex hormone testosterone(T)were detected by HE staining,and the expression of TGF-β-1/smads signaling pathway in testicular tissue was examined by Western Blot.[Results]Compared to the blank group,the model group showed a significant decrease in sperm count and sperm motility rate(P<0.05),both the electroacupuncture group and the positive drug group exhibited significant increases compared to the model group(P<0.05).Compared to the blank group,the model group had a significant decrease in serum testosterone(T)levels(P<0.05),and significant increases in serum FSH and LH levels(P<0.05);in comparison to the model group,the electroacupuncture group and the positive drug group showed significant increases in serum T levels(P<0.05),and significant decreases in serum FSH and LH levels(P<0.05).The HE staining results showed typical pathological features of AR in the testicular tissue of model group rats,with varying degrees of improvement observed in electroacupuncture and positive drug group rats.Western Blot analysis revealed that in the model group,the protein levels of TGF-β,p-smad2,and p-smad3 in the TGF-β1/smads pathway in testicular tissue were significantly increased(P<0.05);in comparison to the model group,the electroacupuncture group and the positive drug group showed significant decreases in the protein levels of TGF-β,p-smad2,and p-smad3(P<0.05).[Conclusion]Acupuncture can improve the sperm number and sperm motility rate,regulate sex hormone level and improve the spermatogenic environment,and affect the spermatogenesis process via TGF-β 1/smads signaling pathway.

Stroke has the highest morbidity and mortality in the adults of China, with heavy burden to the society and family. In recent years, the third generation of thrombolytic drug tenecteplase has made breakthrough in many fields of acute ischemic stroke reperfusion, and has been recommended by domestic and foreign guidelines for intravenous thrombolysis or intravenous thrombolysis bridging to mechanical thrombectomy for acute ischemic stroke. Results of several large clinical trials of tenecteplase have been published in the European Stroke Organization Conference in 2024, which provides more evidence-based medical evidences for tenecteplase in acute ischemic stroke reperfusion. This article reviews the latest research on tenecteplase in acute ischemic stroke reperfusion, and looks forward to the future direction of this field, in order to provide some references for clinicians and further related clinical study using tenecteplase.

BACKGROUND: More than 75 million procedures with intravascular iodine-based contrast media (ICM) are performed worldwide every year, and some patients undergoing these procedures do not have normal thyroid function. The long-term effects of ICM in patients with mild thyroid dysfunction (TD) are unclear. METHODS: This prospective cohort study was conducted in China. Patients with stable angina pectoris with total triiodothyronine (TT3) reduction, normal thyroid-stimulating hormone, and reverse triiodothyronine (rT3) were enrolled and divided into high-dose (≥100 mL ICM) and low-dose groups (<100 mL ICM). We dynamically investigated the trends in thyroid function, rT3, and thyroid antibodies one year after ICM exposure. RESULTS: A total of 154 patients completed 6 months of follow-up and 149 completed 1 year of follow-up. Thyroglobulin antibody (TGAB) levels were elevated in 41 (26.6%) patients before ICM exposure, 11 (7.1%) of whom also had elevated thyroid peroxidase antibody levels. Transient subclinical TD occurred 6 months after ICM exposure; 75.5% (34/45) of post-operative TD occurred in the high-dose group. One patient developed severe hypothyroidism with myxedema, requiring drug intervention 1 year after ICM exposure. The level of rT3 showed no statistically significant changes during post-operative follow-up ( P  = 0.848). The TGAB level decreased at 6th month ( P  < 0.001), but increased at 1 year after ICM exposure ( P  = 0.002). CONCLUSIONS Patients with T3 reduction are at a risk of transient subclinical TD and hypothyroidism after a single large dose of ICM. Follow-up of this population at 9-12 months after ICM exposure is warranted.
Humans ; Contrast Media/adverse effects* ; Prospective Studies ; Hypothyroidism ; Triiodothyronine ; Iodine/adverse effects* ; Thyrotropin ; Thyroxine

Objective:To explore the application effect of immersive experiential teaching strategies in the teaching of clinical anesthesiology for undergraduates.Methods:Undergraduates majoring in 5-year clinical medicine in Air Force Medical University from January 2022 to May 2022 were enrolled as the research objects. Students were randomly divided into the immersive teaching group and the traditional teaching group, with 35 students in each. Students in the immersive teaching group underwent immersive experiential teaching strategies and the traditional teaching group received lecture-based teaching strategies. After classes, all students in these two groups took the same theoretical and operational examination, and conducted a teaching satisfaction survey and a comprehensive ability evaluation. The results were analyzed by t-test and Chi-square test using SPSS 22.0 software. Results:Students in the immersive teaching group were more satisfied with teaching (88.32±7.28 vs.70.15±7.11) ( P=0.001), and had higher scores of theorical examination (86.34±7.42 vs. 77.31±5.32) ( P=0.020) and operational examination (92.23±5.33 vs. 81.21±4.98) ( P=0.022) than those in the traditional teaching group. In addition, the scores of communication ability ( P=0.026), response ability ( P<0.001) adaptability ( P=0.007), and critical thinking ( P<0.001) in the immersive teaching group were higher than those in the traditional teaching group. Conclusion:The immersive experiential teaching strategies can effectively improve the theoretical and practical operational ability of undergraduates after completing courses of clinical anesthesiology, and can effectively stimulate the enthusiasm of students. It is worthy to be popularized in subsequent teaching abilities.

Objective:In order to investigate the genetic diversity of mitochondrial cytochrome b (Cytb) gene of Taenia asiatica ( T. asiatica) in Dali Bai Autonomous Prefecture (Dali Prefecture), Yunnan Province. Methods:From May 2019 to August 2021, a total of 131 samples of Taenia were collected from patients admitted to the Dali Prefecture Institute of Schistosomiasis Control, involving five locations (i.e., five groups), including Dali City (58 samples), Weishan Yi and Hui Autonomous County (Weishan County, 14 samples), Midu County (18 samples), Yangbi Yi Autonomous County (Yangbi County, 24 samples) and Eryuan County (17 samples). Primers were designed based on mitochondrial Cytb gene sequence, and part of the Cytb gene sequence was amplified by PCR, then sequenced and homology comparisons were performed. MEGA 7.0 and DNASP 5.10.01 were used to analyze the measured sequence, and data such as base composition, genetic distance, genetic diversity parameters, genetic differentiation index and gene flow were obtained. Results:The amplified fragments of Cytb gene in 131 samples of Taenia were 235 bp. After homology comparisons, they were all T. asiatica. The average contents of A, T, G and C bases were 23.8%, 42.3%, 24.0% and 9.9%, respectively. Of the 131 samples of T. asiatica, 12 haplotypes were defined. The haplotype diversity and nucleic acid diversity were 0.295 9 and 0.006 0, respectively. The ranges of genetic differentiation index and gene flow among the five groups were-0.053 00 to 0.050 40 and 4.710 31 to 162.087 66, respectively. The genetic distance between the five groups ranged from 0.003 5 to 0.009 0, of which the genetic distance between Midu County and Weishan County was the largest, and the genetic distance between Dali City and Yangbi County was the smallest. Conclusions:The mitochondrial Cytb gene of T. asiatica in Dali Prefecture has rich genetic diversity. There is frequent gene exchange among the five groups, and no significant genetic differentiation has been formed.

Objective:To explore the method and effect of blepharoplasty of upper eyelid combined with orbicularis oculi myocutaneous flap in repair of the canthus defect after excision of xanthelasma.Methods:According to the relaxation of the upper eyelid skin and the width of the xanthoma to be removed, the double eyelid line and the peeling line were designed individually, and the myocutaneous flap was removed to repair the inner canthus defect. After resection of the xanthelasma, the orbicularis oculi myocutaneous flap was transferred retrogradely to repair the defect, and then the upper eyelid plasty was performed.Results:During the follow-up of 3-12 months after operation, 13 cases (24 eyes) of the transferred flaps in the inner canthus survived well, the incision scars were hidden, and the double eyelids on both sides were naturally symmetrical.Conclusions:The method of upper eyelid plasty combined with the reverse transfer of orbicularis oculi myocutaneous flap provides more options for the treatment of defects after resection of xanthoma of the inner canthus. The flap survives well, improves the shape of the upper eyelid while completely removing the focus, and avoids complications such as postoperative deformation and obvious scars.