Objective:To evaluate the safety and efficacy of 225Ac-prostate specific membrane antigen (PSMA) in the treatment of metastatic castration-resistant prostate cancer (mCRPC). Methods:Eleven patients (age (70.0±8.8) years) with mCRPC who were treated with 225Ac-PSMA-617 between July 2021 and October 2023 in the Affiliated Hospital of Southwest Medical University were retrospectively analyzed. In order to assess efficacy, the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria were used to evaluate the changes in prostate specific antigen (PSA) level after the treatment. 68Ga-PSMA-11 PET/CT imaging was performed at the baseline and after the treatment, and molecular imaging response was assessed using the modified PET response criteria in solid tumors (PERCIST) 1.0. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Toxicity was assessed by common terminology criteria for adverse events version 5.0 (CTCAE 5.0). The paired t test or Wilcoxon signed rank test was used to compare the parameters before and after treatment. Results:Post-treatment PSA levels were significantly lower than pre-treatment in 9 of 11 patients (17.83(4.74, 41.25) vs 124.33(77.85, 784.22) μg/L; z=-2.67, P=0.008), and 6 of them decreasing by more than 50% and 2 patients experienced progressive disease (PD) with PSA levels rising by more than 25%. Post-treatment 68Ga-PSMA-11 PET/CT showed that 7 patients achieved partial response (PR), 2 patients achieved stable disease (SD), and 2 patients were with PD. The OS was 12.0(10.0, 18.0) months and PFS was 8.0(6.0, 11.0) months in 11 patients. There were no statistically significant differences after therapy in WBC counts, Hb, PLT, creatinine, glomerular filtration rate, alanine aminotransferase, aspartate aminotransferase, total bilirubin ( z values: from -1.07 to 0.00, t values: from -0.77 to 1.76, all P>0.05). No grade Ⅲ/Ⅳ nephrotoxicity or salivary gland toxicity was observed. Conclusion:225Ac-PSMA-617 is a promising novel therapeutic option for mCRPC with favorable safety and tolerability.

Objective To observe the effects of brain-computer interface-controlled pedal training system on bal-ance function and serum interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)levels in ischemic stroke pa-tients.Methods Forty patients with ischemic stroke who were hospitalized from September 2022 to September 2023 were selected as observation subjects.The patients were equally divided into stroke control group and stroke experimental group according to the random number table method.At the same time,20 healthy subjects with similar gender and age were recruited as the healthy control group to collect relevant plantar pressure data.Patients in the stroke control group received conventional rehabilitation training including the upper and lower extremity active and passive motor training system,and the stroke experimental group replaced the upper and lower extremity active and passive motor training system in the stroke control group with the brain-computer interface-controlled pedal training system for rehabilitation treatment,and other things remained unchanged.Bilateral plantar pressure symmetry index(SI)and center of body pressure(COP)swing area were collected from both groups of stroke patients with eyes open and closed using the plantar pressure assessment system before and after 4 weeks of treatment.Fugl-meyer low-er extremity motor function score(FMA-LE)and berg balance scale(BBS)were used to evaluate the two groups of stroke patients.Serum IL-6 and TNF-α levels were also compared between the two groups before and after treat-ment.Results ① The SI value and COP swing area in the eyes open and closed state improved in both groups of stroke patients after treatment compared with that before admission,and the results of the stroke experimental group were better than those of the stroke control group(P＜0.05),but there was still a gap with the healthy control group(P＜0.05).②The BBS and FMA-LE scores of stroke patients in both groups were higher after treatment than before treatment,and the scores of the stroke experimental group were greater than those of the stroke control group,with statistically significant differences(all P＜0.05).③Serum IL-6 and TNF-α levels decreased in both groups of stroke patients after treatment compared with before,and the degree of decrease in serum IL-6 and TNF-αlevels in the stroke experimental group was greater than that in the stroke control group,and the difference was sta-tistically significant(P＜0.001,P＜0.05).Conclusion Brain-computer interface-controlled pedal training sys-tem has a facilitating effect on the recovery of balance function in hemiplegic patients with ischemic stroke,and its mechanism may be related to the reduction of serum IL-6 and TNF-α levels.

Objective To observe the susceptibility test result in vitro of the combination of two drugs to carbapenem-resistant Enter-obacteriaceae(CRE)for screening the effective anti-infective therapy.Methods A total of 60 CRE strains which were isolated from the specimens from the clinic of Qingdao Eighth People's Hospital from January 2023 to December 2023.Carbapenem enzyme type was detected by colloidal gold immunochromatography.The minimal inhibitory concentration(MIC)was determined by micro broth dilution method.Ceftazidime/avibactam(CZA)combined with aztreonam(ATM),COL combined with tigecycline(TGC),meropenem(MEM),cefoperazone/sulbactam(SCF),amikacin(AK)and levofloxacin(LEV),TGC combined with MEM,SCF and AK,MEM combined with SCF and ertapenem(ETP)were performed by the checkerboard dilution method respectively.Fractional inhibitory con-centration(FIC)index was used to determine the combined effects.Results Carbapenem enzyme was detected in all the 60 CRE strains,including 49 Klebsiella pneumoniae carbapenemases(KPC)-type,10 New Delhi metallo-β-lactamase(NDM)-type and 1 Imi-penem enzyme(IMP)-type.The MICs of CZA to 49 KPC-producing strains were ≤8 mg/L,showing all sensitive,and to 11 NDM-and IMP-producing strains were＞128 mg/L,showing all resistant.The synergy rate of CZA was 100％after combining with ATM.MEM combined with SCF had the highest synergy rate of 63.4％,and the sum of synergistic rate and addition rate was 96.7％.The syn-ergistic rate and additive rate of TGC combined with AK were the lowest,which was 31.7％.Among KPC and NDM enzyme types strains,the sum of synergy rate and addition rate of MEM combined with SCF were the highest,which were 100.0％and 80.0％respec-tively.The sum of synergy rate and addition rate of COL combined with LEV were the lowest,which were 32.6％and 30.0％.None of the 11 combination regimens showed antagonistic effect.The MICrange,MIC50 and MIC90 of combination regimens for CRE strains were decreased to some extent compared with those of each single drug.Conclusion CZA alone or in combination with ATM were effective for CRE strains.The MEM combined with SCF had the highest synergy rate and addition rate,which could provide reference for clinical experience medication.

Abstract Allergic diseases can occur in all systems of the body, covering the whole life cycle, from children to adults and to old age, can be lifelong onset and even fatal in severe cases. Children account for the largest proportion of the victims of allergic disease, Children s allergies start from scratch, ranging from mild to severe, from less to more, from single to multiple systems and systemic performance, so the prevention and treatment of allergic diseases in children is of great importance, which can not only prevent high risk allergic conditions from developing into allergic diseases, but also further block the process of allergy. At present, there is no consensus on the management system of allergic children in kindergartens and primary schools. The "Consensus on Allergy Management and Prevention in Kindergartens and Primary Schools", which includes the organizational structure, system construction and management of allergic children, provides evidence informed recommendations for the long term comprehensive management of allergic children in kindergartens and primary schools, and provides a basis for the establishment of the prevention system for allergic children.

Phytoremediation plays an important role in the treatment of heavy metal pollution in soil. In order to elucidate the mechanism of salicylic acid (SA) on copper absorption, seedlings from Xuzhou (with strong Cu-tolerance) and Weifang Helianthus tuberosus cultivars (with weak Cu-tolerance) were selected for pot culture experiments. 1 mmol/L SA was sprayed upon 300 mg/kg soil copper stress, and the photosynthesis, leaf antioxidant system, several essential mineral nutrients and the changes of root upon copper stress were analyzed to explore the mechanism of copper resistance. The results showed that Pn, Tr, Gs and Ci upon copper stress decreased significantly compared to the control group. Meanwhile, chlorophyll a, chlorophyll b and carotenoid decreased with significant increase in initial fluorescence (F₀), maximum photochemical quantum yield of PSⅡ (Fv/Fm), electron transfer rate (ETR) and photochemical quenching coefficient (qP) content all decreased. The ascorbic acid (AsA) content was decreased, the glutathione (GSH) value was increased, the superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) activity in the leaves were decreased, and the peroxidase (POD) activity was significantly increased. SA increased the Cu content in the ground and root system, and weakened the nutrient uptake capacity of K, Ca, Mg, and Zn in the root stem and leaves. Spray of exogenous SA can maintain the opening of leaf stomata, improve the adverse effect of copper on photosynthetic pigment and PSⅡ reaction center. Mediating the SOD and APX activity started the AsA-GSH cycle process, effectively regulated the antioxidant enzyme system in chrysanthemum taro, significantly reduced the copper content of all parts of the plant, and improved the ion exchange capacity in the body. External SA increased the content of the negative electric group on the root by changing the proportion of components in the root, promoted the absorption of mineral nutrient elements and the accumulation of osmoregulatory substances, strengthened the fixation effect of the root on metal copper, and avoided its massive accumulation in the H. tuberosus body, so as to alleviate the inhibitory effect of copper on plant growth. The study revealed the physiological regulation of SA upon copper stress, and provided a theoretical basis for planting H. tuberosus to repair soil copper pollution.
Antioxidants ; Copper ; Helianthus/metabolism* ; Salicylic Acid/pharmacology* ; Chlorophyll A/pharmacology* ; Spectroscopy, Fourier Transform Infrared ; Chlorophyll/pharmacology* ; Ascorbic Acid ; Superoxide Dismutase/metabolism* ; Photosynthesis ; Glutathione ; Plant Leaves ; Stress, Physiological ; Seedlings

Objective:To conduct a Meta-analysis on the application effect of information management on safe in-hospital transfer of patients in China.Methods:Using computers to search for randomized controlled trials and quasi experimental studies on the effect of information management on safe in-hospital transfer of patients in China from China National Knowledge Infrastructure, VIP, Wanfang Database, China Biomedical Mediline disc, PubMed, Embase, Web of Science, CINAHL and Cochrane Library. The search period was from establishment of databases to May 17, 2022. Literature screening, quality evaluation and data extraction were conducted independently by two trained researchers. Stata 15.1 software was used for Meta-analysis.Results:A total of 14 articles were included, involving a total of 130 670 patients. The results of Meta-analysis showed that the incidence of adverse event in in-hospital transfer of patients in the information management group was shorter than that in the control group ( OR=0.24, 95% CI: 0.17-0.35, P<0.01), duration of in-hospital tranfer was longer than that in the control group ( WMD=-5.76, 95% CI: -8.30-3.22, P<0.01), and patients' satisfaction ( OR=1.11, 95% CI: 1.05-1.17, P<0.01) and satisfaction of medical personnel responsible for transfer ( OR=1.37, 95% CI: 1.13-1.66, P<0.01) were higher than those of the control group. Conclusions:Information management can effectively control the incidence of adverse events in in-hospital transfer of patients in China, shorten the time required for hospital transfers and improve the satisfaction of patients and medical staff in hospital transfers.

OBJECTIVES: Patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) confront multiple difficulties during the disease adaptation process. Based on the comprehensive task-based adaptation model, this study aims to explore the process and experience of adapting to living with HIV among HIV/AIDS patients and to provide evidence for promoting the adaptation of this population. METHODS: With the design of the phenomenon study, we purposefully recruited 43 HIV/AIDS patients and conducted semi-structural interviews. The qualitative data was analyzed by Van Manen method. RESULTS: There were 1 307 significant quotes and 6 themes with 14 sub-themes. "The shadow comes along with the sunshine" was proposed to describe the process of adapting to life with HIV. Another 5 themes emerged to represent the tasks as follows: the direction of the mental anchor, the management of physical tasks, social network and support, the occupational dilemma and benefits, and the consideration of the future. CONCLUSIONS The adapting process possesses both common and personalized characteristics. Future intervention development should address the integrality and interaction of the adaptation tasks, contributing to the positive adaptation outcomes of HIV/AIDS patients.
Humans ; Acquired Immunodeficiency Syndrome ; HIV ; Patients ; Physical Examination

This research aims to investigate the encapsulation and controlled release effect of the newly developed self-assembling peptide R-LIFE-1 on exosomes. The gelling ability and morphological structure of the chiral self-assembling peptide (CSAP) hydrogel were examined using advanced imaging techniques, including atomic force microscopy, transmission electron microscopy, and cryo-scanning electron microscopy. The biocompatibility of the CSAP hydrogel was assessed through optical microscopy and fluorescent staining. Exosomes were isolated via ultrafiltration, and their quality was evaluated using Western blot analysis, nanoparticle tracking analysis, and transmission electron microscopy. The controlled release effect of the CSAP hydrogel on exosomes was quantitatively analyzed using laser confocal microscopy and a BCA assay kit. The results revealed that the self-assembling peptide R-LIFE-1 exhibited spontaneous assembly in the presence of various ions, leading to the formation of nanofibers. These nanofibers were cross-linked, giving rise to a robust nanofiber network structure, which further underwent cross-linking to generate a laminated membrane structure. The nanofibers possessed a large surface area, allowing them to encapsulate a substantial number of water molecules, thereby forming a hydrogel material with high water content. This hydrogel served as a stable spatial scaffold and loading matrix for the three-dimensional culture of cells, as well as the encapsulation and controlled release of exosomes. Importantly, R-LIFE-1 demonstrated excellent biocompatibility, preserving the growth of cells and the biological activity of exosomes. It rapidly formed a three-dimensional network scaffold, enabling the stable loading of cells and exosomes, while exhibiting favorable biocompatibility and reduced cytotoxicity. In conclusion, the findings of this study support the notion that R-LIFE-1 holds significant promise as an ideal tissue engineering material for tissue repair applications.
Exosomes ; Delayed-Action Preparations ; Hydrogels ; Microscopy, Electron, Scanning ; Peptides

Objective:To investigate the difference in the peri-coronary fat attenuation index (FAI) between using coronary calcium score (CCS) images and coronary CT angiography (CCTA) images, and to explore the feasibility and befitting threshold of FAI measured on CCS images.Methods:The clinical and imaging data of patients who underwent CCTA examination from August 2019 to August 2020 were retrospectively analyzed in the First Affiliated Hospital of Soochow University. According to the inclusion and exclusion criteria, there were 122 cases in non-calcified plaque group (144 coronary arteries) and 97 cases in none-plaque group (186 coronary arteries). The coronary arteries were delineated both on CCS and CCTA images with Perivascular Fat Analysis Tool; the regions of interest of peri-coronary adipose tissue were generated automatically after setting the threshold of fat tissue. Then the FAI value was calculated. The thresholds were set in four levels (-190--30, -185--25, -180--20 and -175--15 HU) for CCS images and one level (-190--30 HU) for CCTA images. The intra-class correlation coefficient (ICC) was used to evaluate the consistency of the measurements of FAI values on CCS and CCTA images between the two physicians. Paired t test was used to compare the differences of FAI values between CCS and CCTA images, and Pearson correlation coefficient was used to evaluate the correlation between CCS-FAI and CCTA-FAI. Results:(1) FAI values measured on CCS and CCTA images by 2 physicians showed good consistency; (2) At the threshold of -185--25 HU, there was no significant difference in FAI values between the CCS and CCTA images for non-calcified plaque group [(-84.15±5.99)HU vs. (-83.83±5.98)HU, t=0.79, P=0.429], as well as for the none-plaque group [(-83.41±5.75)HU vs.(-83.84±6.25)HU, t=-1.08, P=0.280]; (3) There were significant differences on FAI values between the CCS images and CCTA images at the threshold of -190--30、-180--20 and -175--15 HU (all P<0.05); (4) There were moderate correlations on FAI values between the CCS images and CCTA images under different thresholds both in non-calcified plaque group and none-plaque group. Conclusion:It is feasible to measure FAI on CCS images, and the befitting threshold is -185--25 HU.

SIRT6 belongs to the conserved NAD⁺-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD⁺. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC₅₀ of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.