Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

Objective:To investigate the role and underlying mechanisms of neurotrophin-3 (NT-3) in promoting neurological functional recovery following spinal cord injury (SCI) in rats.Methods:In vivo: Fifteen 8-week-old SPF-grade Sprague-Dawley rats were randomly assigned (via a random number method) to three groups ( n=5 per group): sham-operated (Sham) group, SCI group, and SCI+NT-3 group. A spinal cord compression model was established using a clip method. NT-3 (20 μg/kg) was continuously infused into the subarachnoid space via a microinfusion pump for 7 days. The Basso-Beattie-Bresnahan (BBB) scale was used to assess locomotor function post-SCI, with scores below 21 indicating successful model establishment. Western blotting was performed to analyze the expression levels of NT-3, microtubule-associated protein 1 light chain 3B (LC3B), oligodendrocyte transcription factor 1 (Olig1), and myelin basic protein (MBP) at 1, 3, 5, and 7 days post-injury. In vitro: Oligodendrocytes were isolated from neonatal rat brain tissues, cultured (5×10 4/cm 2), and divided into four groups: oxygen-glucose deprivation (OGD) group, OGD+NT-3 group, OGD+NT-3+ubiquitination inhibitor (UCHL1) group, and OGD+NT-3+ubiquitination agonist (MG132) group. Western blotting was conducted to detect the expression levels of TrkC, Ub-TrkC, and LC3B in each experimental group. Immunofluorescence staining was utilized to observe LC3B aggregation in oligodendrocytes. Morphological alterations in cells were examined through microscopy. Statistical analysis was performed using one-way ANOVA, followed by pairwise comparisons using the least significant difference method. Results:Compared with the SCI group, the SCI+NT-3 group exhibited significant improvement in BBB scores, reduced autophagy levels, increased Olig1 and MBP expression, and elevated TRAF6 ubiquitin ligase expression (all P<0.05). At 5 h post-OGD, immunofluorescence revealed reduced LC3B aggregation and near-normal oligodendrocyte morphology in the OGD+NT-3 group. Compared to the OGD, OGD+NT-3, and OGD+NT-3+UCHL1 groups, the OGD+NT-3+MG132 group demonstrated increased Ub-TrkC expression and markedly reduced autophagy levels at 5-7 h (all P<0.05). The OGD+NT-3+UCHL1 group exhibited lower Ub-TrkC expression and elevated autophagy levels compared to the OGD+NT-3 group (all P<0.05). Conclusion:NT-3 inhibits oligodendrocyte autophagy through TrkC receptor ubiquitination, thereby maintaining oligodendrocyte survival and promoting neurological recovery after SCI in rats.

Objective To investigate the role and mechanism of neurotrophin-3(NT-3)in promoting neurological recovery after sep-sis-associated encephalopathy(SAE).Methods Twenty-four Sprague-Dawley(SD)rats were randomly divided into the Sham,SAE,and+NT-3 groups(n=8).Neurological deficits were evaluated using a behavioral scoring system.Western blotting was performed to assess the expression levels of NT-3,S100β,caspase-1,and microtubule-associated protein 1 light chain 3B(LC3B)in brain tissues.Immuno-histochemistry(IHC)was performed to assess interleukin-1 β(IL-1β)expression level.For cellular experiments,groups included normal,lipopolysaccharide(LPS),LPS+NT-3,LPS+NT-3+3-MA(autophagy inhibitor),and LPS+NT-3+compound C(AMPK inhibitor).Western blotting was used to analyze LC3B,NLRP3,ASC,AMPK,phosphorylated AMPK(p-AMPK),mTOR,and phosphorylated mTOR(p-mTOR)expression levels.Caspase-1 expression in cells was evaluated using immunofluorescence(IF).Results NT-3 expression in septic rat brain tissues increased progressively from d1 to d2(P＜0.05).Compared with the SAE group,the SAE+NT-3 group exhibited elevated neurological scores.The expression levels of IL-1β,S100β,and caspase-1 decreased from d1 to d2,while the aurtophagy level increased from d1 to d2(all P＜0.05).In cellular models,the LPS+NT-3 group showed decreased caspase-1 expression and increased autophagy activity compared to that in the LPS group from 1 h to 3 h(P＜0.05).Compared to the LPS+NT-3 group,the LPS+NT-3+3-MA group exhibited elevated NLRP3,ASC,and caspase-1-positive cells(P＜0.05),whereas the LPS+NT-3+Compound C group exhibited reduced p-AMPK,increased p-mTOR,and attenuated autophagy(P＜0.05).Conclusion NT-3 activates autophagy through the AMPK/mTOR signaling pathway during the early phase of SAE,thereby eliminating pyroptosis-associated proteins NLRP3 and ASC to promote neurolog-ical recovery.

Objective To investigate the role and mechanism of neurotrophin-3(NT-3)in promoting neurological recovery after sep-sis-associated encephalopathy(SAE).Methods Twenty-four Sprague-Dawley(SD)rats were randomly divided into the Sham,SAE,and+NT-3 groups(n=8).Neurological deficits were evaluated using a behavioral scoring system.Western blotting was performed to assess the expression levels of NT-3,S100β,caspase-1,and microtubule-associated protein 1 light chain 3B(LC3B)in brain tissues.Immuno-histochemistry(IHC)was performed to assess interleukin-1 β(IL-1β)expression level.For cellular experiments,groups included normal,lipopolysaccharide(LPS),LPS+NT-3,LPS+NT-3+3-MA(autophagy inhibitor),and LPS+NT-3+compound C(AMPK inhibitor).Western blotting was used to analyze LC3B,NLRP3,ASC,AMPK,phosphorylated AMPK(p-AMPK),mTOR,and phosphorylated mTOR(p-mTOR)expression levels.Caspase-1 expression in cells was evaluated using immunofluorescence(IF).Results NT-3 expression in septic rat brain tissues increased progressively from d1 to d2(P＜0.05).Compared with the SAE group,the SAE+NT-3 group exhibited elevated neurological scores.The expression levels of IL-1β,S100β,and caspase-1 decreased from d1 to d2,while the aurtophagy level increased from d1 to d2(all P＜0.05).In cellular models,the LPS+NT-3 group showed decreased caspase-1 expression and increased autophagy activity compared to that in the LPS group from 1 h to 3 h(P＜0.05).Compared to the LPS+NT-3 group,the LPS+NT-3+3-MA group exhibited elevated NLRP3,ASC,and caspase-1-positive cells(P＜0.05),whereas the LPS+NT-3+Compound C group exhibited reduced p-AMPK,increased p-mTOR,and attenuated autophagy(P＜0.05).Conclusion NT-3 activates autophagy through the AMPK/mTOR signaling pathway during the early phase of SAE,thereby eliminating pyroptosis-associated proteins NLRP3 and ASC to promote neurolog-ical recovery.

Objective:To overview the systematic reviews of prevention and management measures of medication errors, so as to provide evidence support for clinical decision-making for medical staff.Methods:Cochrane Library, Australia Joanna Briggs Institute Evidence-based Healthcare Center database, CINAHL, PubMed, Embase, CNKI, SinoMed, Wanfang database and VIP database were searched by computer to search for systematic reviews of prevention and management measures of medication errors, and the search period was from establishment of the databases to June 30, 2023. Two researchers with systematic evidence-based training applied A Measure Tool to Assess Systematic Reviews 2 (AMSTAR 2) to evaluate the literature quality, and Grades of Recommendations Assessment, Development and Evaluation (GRADE) was used to evaluate the quality of outcome indicators.Results:Finally, a total of 19 systematic reviews were included. The overall quality evaluation using AMSTAR 2 was relatively low, with one article rated as high-quality, one article rated as low-quality and 17 articles rated as extremely low-quality. According to the evidence quality evaluation results of GRADE system for 55 outcome indicators of 19 systematic reviews, 3 pieces of evidence were medium, 27 pieces of evidence were low and 25 pieces of evidence were extremely low, indicating an overall low quality of evidence.Conclusions:The related researches on prevention and management of medication errors have been carried out extensively, and the computer system is one of the effective measures to reduce medication errors. The effectiveness of measures such as administration process modification, doctor/nurse education and training, double check, pharmacist intervention, automated dispensing cabinet/ automated pump and drug display is still unclear and needs to be further confirmed by large sample size and high-quality studies.

Objective:To investigate the clinical efficacy of da Vinci Xi surgical system assisted laparoscopic exocytosis for hepatic echinococcosis.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 7 patients who underwent da Vinci Xi surgical system assisted laparoscopic exocytosis for hepatic echinococcosis in Xinjiang Uiger Municipal People′s Hospital from October 2019 to July 2021 were collected. There were 3 males and 4 females, aged (43±12)years. Observation indicators: (1) surgical situations; (2) complications; (3) follow-up. Mea-surement data with normal distribution were represented as Mean±SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Surgical situations. All 7 patients underwent da Vinci Xi surgical system assisted laparoscopic exocytosis for hepatic echinococcosis successfully, without conversion to laparotomy and laparoscopic surgery. None of the 7 patients underwent intraoperative blood transfusion and the operation time, volume of intraoperative blood loss, time to postoperative first and flatus, time to postoperative initial liquid food intake, time to postoperative abdominal drainage tube removal, time to postoperative urethral catheter removal, duration of postoperative hospital stay of 7 patients was (225±45)minutes, 100(range, 50-200)mL, (1.9±0.7)days, (4.2±1.2)days, (7±4)days, (2.9±0.8)days, (7±4)days, respectively. (2) Complications. None of the 7 patients had postoperative complications such as bile leakage, abdominal hemorrhage, incision infection, hydatid cavity infection, secondary operation, intestinal obstruction, pulmonary infection and deep venous thrombosis of lower limbs. (3) Follow-up. All 7 patients were followed up for 7 (range, 3-12) months. None of the 7 patients had recurrence of hepatic echinococcosis or peritoneal implantation and incision implantation, and all patients survived during follow-up.Conclusion:da Vinci Xi surgical system assisted laparoscopic exocytosis for hepatic echinococcosis is safe and feasible.

Objective To investigate the effects of lncRNA SBF2-AS1 on the proliferation and invasion of hepatoma cells by regulating the miR-372-3p/CDK6 pathway. Methods Bel7402 and SK-hep1 cells were selected as research objects. The expression levels of SBF2-AS1, miR-372-3p, and CDK6 were up- or down-regulated according to different experimental stages, while the expression levels of miR-372-3p and CDK6 in cells were detected by real-time fluorescence quantitative PCR and Western blot. Dual luciferase reporter assay verified the targeting relationships between SBF2-AS1 and miR-372-3p as well as miR-372-3p and CDK6, respectively. CCK-8, colony formation assay, Transwell, cell cycle assay, and flow cytometry were used to analyze cell proliferation, colony formation, migration/invasion ability, cell cycle activity, and apoptosis. Results SBF2-AS1 was highly expressed in hepatocellular carcinoma cells (P<0.05). SBF2-AS1 knockdown resulted in decreased proliferation and invasion of Bel7402 and SK-hep1 cells (P<0.05). After miR-372-3p knockdown, the proliferation capacity and invasion number of Bel7402 cells were significantly increased. However, the above results were reversed after SBF2-AS1 knockdown (P<0.05). In addition, miR-372-3p targeted CDK6 and inhibited its expression, although over-expressing SFB2-AS1 could reverse the above results (P<0.05). Over-expressing CDK6 could reverse the inhibition of over-expressing miR-372-3p on the proliferation and invasion of Bel7402 cells. Conclusion LncRNA SBF2-AS1 can positively regulate the expression of CDK6 through miR-372-3p. It can also influence the distribution of cell cycle and affect the proliferation and invasion abilities of hepatocellular carcinoma cells.

OBJECTIVE To analyze the current status and research hot spots of traditional Chinese medicine （TCM）in the prevention and treatment of myocardial ischemia -reperfusion injury （MIRI），and to provide reference for developing relevant studies. METHODS A bibliometric analysis was performed with the literature on TCM treatments for MIRI included in the Web of Science as the data source . RESULTS A total of 972 literatures were included in this study . The research on TCM for prevention and treatment of MIRI in recent 10 years showed an increasing trend year by year ，and the literature published in 2021 were cited most frequently ；most research scholars focused in China ；Peking Union Medical College ，Chinese Academy of Medical Sciences had the most papers in this field ，and a lot of collaboration with other institutions ，which had a large influence in the field ；Sun Guibo and Sun Xiaobo were high -yielding authors in the field ，but the global authorship was not very close and had not formed cooperative teams of some scale ；Molecular Medicine Reports was perhaps the most popular journal in the field . Co-citation analysis found that the research direction in this field was mostly focused on exploring the pathogenesis of MIRI and finding intervention targets . Key words analysis revealed that TCM regulated apoptosis ， pyroptosis， mitochondrial dysfunction ， miRNA and other pathways to improve MIRI research was a hot spot in the field ，and more studies had focused on the Nrf 2 pathway，NF-κB pathway ，NLRP3 inflammasomepathway， TNF pathway ， SIRT3 pathway， JNK pathway ，PI3K/Akt pathway and AMPK pathway . CONCLUSIONS Much attention has been paid to the prevention and treatment of MIRI by TCM in the past 10 years，and the current hot spots in this field are mostly focused on the studies about the intervention mechanism of TCM ’s active ingredients and Chinese patent medicines on MIRI . Moreover，the research about TCM in the treatment of MIRI is mostly focused on the field of basic experiments at present ，and it is recommended that many large -scale，high-quality， multicenter，randomized controlled clinical studies should be carried out in the future ，to provide high -grade evidence -based evidence for the application of TCM in clinic .

Objective:To synthesize Gd labeled probe targeting transporter protein(TSPO) 2-(8-amino-2-(4-chlorophenyl)imidazo[1, 2-a]pyridine-3-yl)- N, N-dipropylacetamide (CB86)-diethylene triamine pentaacetic acid (DTPA), and investigate its MRI effect in rheumatoid arthritis (RA) model. Methods:CB86-DTPA was prepared by coupling a bifunctional chelating agent, and then chelated with Gd to obtain MRI targeted contrast agent CB86-DTPA-Gd. The cytotoxicity, MR relaxation rate and in vitro stability of CB86-DTPA-Gd were determined. RA model was established with Freund′s adjuvant and the biodistribution study and MRI was performed. The RA lesion and its surrounding normal tissue were used as regions of interest (ROI) to calculate the signal to noise ratio (SNR). Independent-sample t test was used to analyze the data. Results:CB86-DTPA-Gd had excellent biosafety and a good MR relaxation rate ( r1=11.05 mmol·L -1·s -1). The survival rate of RAW264.7 cells and 4T1 cells was still more than 90% at the maximum concentration (20 μmol/L) of Gd 3+. CB86-DTPA-Gd also exhibited good stability in human serum and phosphate buffer saline solution (PBS; pH=7.4). The in vivo biodistribution showed that CB86-DTPA-Gd had better inflammatory targeting efficiency, and the uptake of Gd in the inflamed site of the ankle joint was still (2.33±0.29) percent dose rate per gram of tissue (%ID/g) at 120 min after injection. MicroMRI showed that the inflammation of the right ankle joint displayed significant enhancement after the injection of CB86-DTPA-Gd and Gd-DTPA. The SNR of CB86-DTPA-Gd group was up to 23.21±1.44, and the maximum intensification time was 90 min after injection, and can be significantly inhibited by CB86-DTPA at all time points ( t values: 6.083-12.451, all P<0.05), while the Gd-DTPA group had a strengthening time of 30 min after injection with the SNR of 16.12±1.24. Conclusion:CB86-DTPA-Gd shows good macrophage targeting and good uptake in arthritic reaction sites, and is expected to be a novel MRI molecular probe for peripheral inflammation imaging.

ObjectiveTo investigate the expression and clinical significance of serum exosomal microRNA(miRNA)-221-3p in hepatocellular carcinoma (HCC). MethodsA total of 66 patients who underwent surgery in Nanjing Drum Tower Hospital, Nanjing University Medical School, from February 2010 to December 2014 and were diagnosed with HCC were enrolled as HCC group, and 25 individuals who underwent physical examination in our hospital during the same period of time were enrolled as control group. The exosome extraction kit was used to isolate the exosomes in serum; Western blotting was used to measure the expression of exosome markers; a transmission electron microscope was used to observe the morphology of serum exosomes; quantitative real-time PCR was used to measure the expression of serum exosomal miRNA-221-3p. The Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier method and the log-rank test were used to analyze the association of the expression of serum exosomal miRNA-221-3p with prognosis, and the Cox proportional hazards regression model was used to analyze the influencing factors for prognosis. ResultsSerum exosomes were small membranous vesicles with a diameter of about 40-100 nm, and HSP70, Alix, and CD63 were expressed in the exosomes. The HCC group had significantly higher expression of serum exosomal miRNA-221-3p than the control group (U=354.00, P＜0.001). In the patients with HCC, the high expression of serum exosomal miRNA-221-3p was associated with tumor size (χ2=6.016, P=0.014), capsular invasion (χ2=7.580, P=0.006), and TNM stage (χ2=6.340, P=0012). In addition, the HCC patients with high expression of serum exosomal miRNA-221-3p had a significantly lower overall survival rate than those with low expression (χ2=17.105, P＜0.001). The multivariate analysis showed that the expression of serum exosomal miRNA-221-3p (hazard ratio ［HR］=2.434, 95% confidence interval ［CI］: 1.178-5.027, P=0.016) and tumor stage (HR=2.653, 95% CI: 1.222-5.760, P=0.014) were independent risk factors for the prognosis of patients with HCC. ConclusionThere is a significant increase in the expression of serum exosomal miRNA-221-3p in HCC patients, which provides a reference for the diagnosis and prognostic evaluation of HCC.