Recently, significant progress has been made in the field of endovascular repair of complex aortic disease involving the major branches (aortic arch disease and complex abdominal aortic aneurysms). Open surgery was considered the “gold standard” for the treatment of these complicated aortic diseases, but was challenged by the huge surgical trauma and high risk of post-operative complications. However, the rapid development of branched and fenestrated endografts has provided an alternative safe and effective minimally invasive treatment for patients who cannot tolerate open surgery. Preliminary evidence has also shown that branched and fenestrated endografts have achieved significant technical success rates and clinical outcomes and have gradually become an important direction of innovation and development for endovascular repair of complex aortic disease. Nevertheless, both branched and fenestrated endografts are currently in the early stages of experience and a series of high-quality research studies are needed in the future to further compare them with open surgery and within different endovascular techniques.

Recently, significant progress has been made in the field of endovascular repair of complex aortic disease involving the major branches (aortic arch disease and complex abdominal aortic aneurysms). Open surgery was considered the “gold standard” for the treatment of these complicated aortic diseases, but was challenged by the huge surgical trauma and high risk of post-operative complications. However, the rapid development of branched and fenestrated endografts has provided an alternative safe and effective minimally invasive treatment for patients who cannot tolerate open surgery. Preliminary evidence has also shown that branched and fenestrated endografts have achieved significant technical success rates and clinical outcomes and have gradually become an important direction of innovation and development for endovascular repair of complex aortic disease. Nevertheless, both branched and fenestrated endografts are currently in the early stages of experience and a series of high-quality research studies are needed in the future to further compare them with open surgery and within different endovascular techniques.

Objective:To evaluate the role of the CC chemokine ligand 2/CC chemokine receptor 2 (CCL2/CCR2) signaling pathway in electroacupuncture (EA)-induced reduction of spinal cord injury (SCI) in rats.Methods:Sixty clean-grade healthy adult female Sprague-Dawley rats, weighing 210-250 g, were divided into 5 groups ( n=12 each) using a random number table method: sham operation group (group S), group SCI, SCI+ Anti-CCL2 group (group SCI+ A), SCI+ EA group (group SCI+ EA), and spinal cord injury+ EA+ rCCL2 group (group SCI+ EA+ R). The SCI model was established using the Allen method in anesthetized animals. Group S only underwent spinous process and laminectomy without damaging the spinal cord. In SCI+ A group, CCL2 neutralizing antibody 50 μg/kg was intrathecally injected at 0, 3 and 6 days after successful development of the SCI model. On the 7th day after the successful development of the SCI model, Jiaji, Dazhui and Mingmen acupoints were stimulated with a depth of 2 mm, voltage of 12-15 mV and frequency of 2 Hz for 30 min once a day for 7 consecutive days in SCI+ EA group. In SCI+ EA+ R group, recombinant rat CCL2 2.5 μg/kg was intrathecally injected at the site of injury at 0, 3 and 6 days after successful development of the SCI model, and the remaining treatments were similar to those in SCI+ EA group. At 1 day before developing the model, 0, 3, 7, 14, 21 and 28 days after developing the model, the mechanical paw withdraw threshold (MWT) and thermal paw withdrawal latency (TWL) were measured, and the motor function was assessed by BBB score. The rats were sacrificed after the final behavioral testing, and their spinal cord tissues were obtained for determination of the expression of CCL2 and CCR2 protein and mRNA (by Western blot or quantitative real-time polymerase chain reaction), the expression of GFAP (by immunofluorescence), contents of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 (by enzyme-linked immunosorbent assay) and for examination of the pathological changes (using HE staining). Results:Compared with S group, the MWT and BBB scores were significantly decreased and the TWL was shortened at each time point after developing the model, the expression of CCL2 and CCR2 protein and mRNA and GFAP was up-regulated, and the contents of TNF-α, IL-1β and IL-6 were increased in SCI group ( P<0.05). Compared with SCI group, the MWT and BBB scores were significantly increased, and the TWL was prolonged at 7 days after developing the model in SCI+ A group, the MWT and BBB scores were significantly increased, and the TWL was prolonged at 14 days after developing the model in SCI+ EA group, and the expression of CCL2 and CCR2 protein and mRNA and GFAP was significantly down-regulated, and the contents of TNF-α, IL-1β and IL-6 were decreased in SCI+ A and SCI+ EA groups ( P<0.05). Compared with SCI+ EA group, the MWT and BBB scores were significantly decreased at 14 days after developing the model, the TWL was shortened, the expression of CCL2 and CCR2 protein and mRNA and GFAP was up-regulated, and the contents of TNF-α, IL-1β and IL-6 were increased in SCI+ EA+ R group ( P<0.05). Compared with SCI+ A and SCI+ EA groups, the histopathological injury were significantly attenuated in SCI group, and the histopathological injury was aggravated in SCI+ EA+ R group. Conclusions:The CCL2/CCR2 signaling pathway is involved in the process by which EA reduces SCI, and the mechanism is related to the inhibition of astrocyte activation, thereby reducing the inflammatory response.

Objective To study whether electroacupuncture(EA)attenuates traumatic brain injury(TBI)by down-regulating glutamate carboxypeptidase Ⅱ(GCPII)gene expression in rats.Methods Rats were divided into Sham group(n=10),TBI group(n=11),TBI+EA group(n=11),TBI+EA+GCPII-NC group(n=11)and TBI+EA+GCPII-OE group(n=11).Sham group rats underwent sham surgery,while other groups rats underwent TBI modeling using an electronic brain injury instrument.The rats in Sham group and TBI group were fed normally,and the rats in other groups were treated with electroacupuncture for 14 days.On the basis of electroacupuncture treatment,rats in TBI+EA+GCPII-NC group and TBI+EA+GCPII-OE group were injected with GCPII-NC and GCPII-OE,respectively.After treatment,the cognitive function of rats was evaluated by neurological function score and Morris water labyrinth task.HE and TUNEL staining were performed on brain tissue.The water content,glutamate(Glu)content,calcium(Ca2+)concentration,superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-Px)and malondialdehyde(MDA)in brain tissue of rats in each group were measured.The mRNA or protein expression of GCPII,Bax,Bcl2 and cleaved caspase-3 in brain tissue were detected by qRT-PCR or Western blot.Results Compared with Sham group,the expression of mRNA and protein of GCPII in TBI group increased,the neurological function score and escape latency increased,the number of crossing the platform decreased,the water content increased,the cortex showed obvious damage,the content of Glu increased,the concentration of calcium increased,the levels of SOD,CAT and GSH-Px decreased,the level of MDA increased,the positive rate of TUNEL increased,the expression of Bax and cleaved caspase-3 protein increased,and the expression of Bcl2 protein decreased significantly(P<0.05).Compared with TBI group,the expression level of mRNA and protein of GCPII in TBI+EA group decreased,the neurological function score and escape latency decreased,the number of crossing platform increased,the water content decreased,the morphology of cortex improved obviously,the content of Glu decreased,the concentration of calcium decreased,the level of SOD,CAT and GSH-Px increased,the level of MDA decreased,the positive rate of TUNEL decreased,the expression level of Bax and cleaved caspase-3 protein decreased,and the expression level of Bcl2 protein increased significantly(P<0.05).Compared with TBI+EA group and TBI+EA+GCPII-NC group,the expression level of mRNA and protein of GCPII in TBI+EA+GCPII-OE group increased,neurological function score and escape latency increased,the number of crossing platform decreased,water content increased,cortical injury aggravated,Glu content increased,calcium concentration increased,SOD,CAT and GSH-Px levels decreased,MDA level increased,TUNEL positive rate increased,Bax and cleaved caspase-3 protein expression increased,and the expression of Bcl2 protein decreased significantly(P<0.05).Conclusion By down-regulating the expression of GCPII gene,electroacupuncture reduced the content of glutamate in the brain tissue of TBI rats,thereby inhibiting calcium overload,oxidative stress and neuronal apoptosis in the brain tissue,and thereby improving cognitive function and alleviating brain injury.

OBJECTIVE To understand the drug resistance,serotypes,virulence-associated genes and epidemiologi-cal characteristics of group B Streptococcus(GBS)isolated from puerpera in this area so as to provide bases for prevention of mother-to-infant infections.METHODS Totally 67 strains of GBS were isolated from obstetrics out-patient department of The First Affiliated Hospital of Nanchang University from Jan.2023 to Dec.2023.The spe-cies of the strains were identified by VITEK MS,the drug susceptibility testing was carried out by disc diffu-sion method.Multilocus sequencing types,capsular types,virulence genes and drug resistance genes were analyzed by means of whole genome sequencing technique.RESULTS The 67 strains of GBS were sensitive to penicillin,vancomycin,ceftriaxone and linezolid;the drug resistance rates to erythromycin and clindamycin were 76.12％and 55.22％,respectively.All strains fell into 7 serotypes,with serotype V predominant;21 sequence types were in-volved,with ST529 most prevalent;8 clonal complexes(CCs)were involved,with CC12 most common.Totally 17 types of drug resistance genes were identified,and the carrying rate of macrolide resistance gene ErmB was highest.Among all the virulence genes except for the adhesion genes fbsA and fbsB,the carrying rates of 18 genes involving in invasion,adhesion,and immune evasion-associated virulence genes were more than 86.57％;67.16％of the strains co-expressed both PI-1 and PI-2a pilus islands.CONCLUSIONS The drug resistance rate of the GBS strains isolated from the puerpera is high,and the strains carry multiple drug resistance genes and viru-lence genes and present with molecular clonal diversity.The serotype V/ST529 is the predominant clone,for which the prevention and control should be strengthened.

Objective:To prepare ((2-(2-chlorophenyl)-3-(4-((2- 18F-fluoroethyl)oxy)phenyl)-5, 6, 7, 8-tetrahydrooxepino[3, 2-c]pyrazol-8-yl)amino)methanoic acid methyl ester ( 18F-JR-1001) and evaluate its binding affinity to the cannabinoid type 1 receptor (CB1R). Methods:18F-JR-1001 was synthesized using an integrated automated synthesis module, and its radiochemical yield (RCY) and molar activity were determined. Cell-specific uptake, lipid-water partition coefficient (log P), competitive binding assays, and in vitro stability tests were performed. Rimonabant-fed rat models (blocking group) with pre-occupied CB1R were established. Radioautography and microPET/CT imaging were conducted on both the blocking group and normal Sprague-Dawley (SD) rats to evaluate the brain uptake of 18F-JR-1001 and its blood-brain barrier (BBB) penetration capability. Results:The RCY of the synthetic 18F-JR-1001 after decay correction was (32.5±9.2)% ( n=10), with the molar activity of (194.6±67.3)GBq/μmol. Cell experiments demonstrated that 18F-JR-1001 exhibited specificity for CB1R, with log P of 3.40±0.11 ( n=3) and half-maximal inhibitory concentration of 0.975nmol/L. Within 3h at 37℃, the radiochemical purity of 18F-JR-1001 in physiological saline and blood remained above 92%, with no significant radioactive by-product peaks observed. Radioautography showed that the whole brain uptake of 18F-JR-1001 in the blocking group was 65.6% of that in normal SD rats. MicroPET/CT imaging showed that the mean whole brain uptake of 18F-JR-1001 in the blocking group was 0.4706, which was lower than that in normal SD rats (1.0561). Additionally, continuous scanning for 60min demonstrated that 18F-JR-1001 exhibited good BBB penetration capability. Conclusion:The synthesized 18F-JR-1001 meets the requirements of production and application, and is proved the potential as a CB1R-targeted tracer in the in vitro experiments, microPET/CT imaging and radioautography.

This study retrospectively analyzed 12 patients with transfusion-dependent, non-severe aplastic anemia (TD-NSAA) refractory to cyclosporine A (CsA) , who were treated with lusutrombopag monotherapy. These patients either had a variety of chronic comorbidities or medication-related risks, or they were unresponsive to or intolerant of other thrombopoietin receptor agonists (TPO-RA) . The median treatment duration with lusutrombopag was 4 months (range: 3-11 months) , while the median follow-up period was 8 months (range: 6-11 months) . The overall response (OR) rates at months 3, 6, and the end of follow-up were 50.0%, 58.3%, and 50.0%, respectively, with a median time to OR of 2 months (range: 1-4 months) . Complete response (CR) rates were 8.3%, 16.7%, and 16.7% at the same time points, with a median time to CR of 4 months (range: 2-5 months) . Adverse events were all Grade 1, with an incidence rate of 25.0%. During follow-up, one patient experienced a loss of OR after discontinuing treatment, with a relapse rate of 14.3%; no clonal evolution or mortality was observed. These findings suggest that lusutrombopag is both effective and well-tolerated in CsA-refractory TD-NSAA patients and represents a promising therapeutic option for those with poor treatment tolerability.

Objectives:To investigate the impact of the Micra AV leadless pacemaker on cardiac function.Methods:A total of 76 patients who received the implantation of Micra AV leadless pacemaker due to sick sinus syndrome or atrioventricular block at Ruijin Hospital,Shanghai Jiao Tong University School of Medicine from September 2022 to April 2023 were included in this study.Among them,26 patients(34.2%)had sick sinus syndrome,and 50 patients(65.8%)had atrioventricular block.The patients were followed up for 1 year postoperatively.Cardiac function was evaluated by echocardiography,and the parameters of the pacemaker were collected through the outpatient clinic programming system.Results:After a follow-up of 120(87,181)days,compared with the preoperative state,the left ventricular ejection fraction(LVEF)decreased postoperatively([66.6±5.6]%vs.[63.8±5.2]%,P<0.001),and the cardiac output increased[(4.3±1.2)L/min vs.(5.3±1.5)L/min,P<0.001].There were no statistically significant differences in various cardiac function indexes of patients with sick sinus syndrome between the postoperative and preoperative states(all P>0.05).Compared with the preoperative state,in patients with atrioventricular block,the LVEF decreased postoperatively([67.0±5.1]%vs.[63.4±4.4]%,P<0.001),the cardiac output increased([4.2±1.1]L/min vs.[5.2±1.2]L/min,P<0.001),and the left ventricular end-diastolic diameter decreased[(49.9±5.4)mm vs.(48.6±5.0)mm,P=0.044].Firth's logistic regression analysis indicated that the preoperative LVEF(for every 1%increase,OR=1.56,95%CI:1.12-2.17,P=0.001),stroke volume(for every 1 ml increase,OR=1.15,95%CI:1.04-1.28,P=0.001),body mass index(for every 1 kg/m2 increase,OR=1.49,95%CI:1.02-2.17,P=0.020),and hypertension(OR=12.71,95%CI:1.11-145.13,P=0.039)were independent risk factors for the decrease in LVEF after surgery in patients with atrioventricular block.After the implantation of the MciraTM AV leadless pacemaker,the overall atrioventricular synchrony rate was 81.2%(68.8%,89.0%).The atrioventricular synchrony rates of patients with sick sinus syndrome and those with atrioventricular block were 70.6%(59.5%,83.4%)and 82.4%(74.2%,89.3%)respectively(P<0.05).Firth's logistic regression analysis indicated that sick sinus syndrome(OR=0.26,95%CI:0.07-0.89,P=0.029)and preoperative LVEF(for every 1%increase,OR=1.18,95%CI:1.03-1.35,P=0.015)were independent predictive factors for the atrioventricular synchrony rate>80%.Conclusions:There are differences in the impacts of the Micra AV leadless pacemaker on the LVEF and atrioventricular synchrony rate between patients with sick sinus syndrome and those with atrioventricular block.The preoperative LVEF,stroke volume,body mass index,and hypertension have independent predictive effects on the decrease in postoperative LVEF in patients with atrioventricular block.Sick sinus syndrome and preoperative LVEF are independent predictive factors for the atrioventricular synchrony rate>80%after surgery.

Recently,diffusion models have emerged as a promising paradigm for molecular design and optimization.However,most diffusion-based molecular generative models focus on modeling 2D graphs or 3D geom-etries,with limited research on molecular sequence diffusion models.The International Union of Pure and Applied Chemistry(IUPAC)names are more akin to chemical natural language than the simplified molecular input line entry system(SMILES)for organic compounds.In this work,we apply an IUPAC-guided conditional diffusion model to facilitate molecular editing from chemical natural language to chemical language(SMILES)and explore whether the pre-trained generative performance of diffusion models can be transferred to chemical natural language.We propose DiffIUPAC,a controllable molecular editing diffusion model that converts IUPAC names to SMILES strings.Evaluation results demonstrate that our model out-performs existing methods and successfully captures the semantic rules of both chemical languages.Chemical space and scaffold analysis show that the model can generate similar compounds with diverse scaffolds within the specified constraints.Additionally,to illustrate the model's applicability in drug design,we conducted case studies in functional group editing,analogue design and linker design.

OBJECTIVE: The objective of this study was to analyse fungal composition and exploit application potential in the Bantou (BT) agarwood-forming trunk of Aquilaria sinensis. METHODS: BT agarwood is a naturally formed agarwood that was collected after cutting. Total genomic DNA of the fungi in BT agarwood was extracted by the hexadecyltrimethy ammonium bromide (CTAB) method, followed by PCR amplification and library construction. The effective tags were obtained by the HiSeq2500 platform, and the data were subjected to bioinformatics and statistical analyses. RESULTS: A total of 7 850 040 effective tags were obtained, Ascomycota was the most abundant fungus at the phylum level, with a relative abundance of 56.36%-61.44%, followed by Basidiomycota, with a relative abundance of 10.49%-20.39%. Dothideomycetes, Agaricomycetes and Sordariomycetes were dominant at the class level, accounting for 26.21%-33.88%, 8.40%-17.66%, and 18.41%-24.11%, respectively. Lignosphaeria, Phaeoacremonium and Hermatomyces were dominant at the genus level, with relative abundances of 6.25%-7.64%, 1.95%-9.05% and 1.5%-5.4%, respectively. Diversity and richness analysis showed that the fungal composition in the agarwood formation sites (agarwood layer, upper agarwood layer and lower agarwood layer) were significantly lower than those in the decomposing layer and the healthy layer. That is, the fungal diversity and richness were significantly reduced during agarwood formation by the action of open wounds. The fungal community structure in the decomposing layer and agarwood formation sites obviously differed from that in the healthy layer. The number of Aspergillus taxa in agarwood formation sites decreased significantly (healthy layer is 0.5%, decomposing layer is 0.022%, upper agarwood layer is 0.012%, agarwood layer is 0.01%, and lower agarwood layer is 0.013%), indicating that agarwood may contain potential substances to inhibit the growth of Aspergillus. CONCLUSION Agarwood from agarwood formation sites contains potential substances that inhibit Aspergillus, which provides valuable information for the control of the genus of Aspergillus.