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.

Advancements in artificial intelligence (AI) and emerging technologies are rapidly expanding the exploration of chemical space, facilitating innovative drug discovery. However, the transformation of novel compounds into safe and effective drugs remains a lengthy, high-risk, and costly process. Comprehensive early-stage evaluation is essential for reducing costs and improving the success rate of drug development. Despite this need, no comprehensive tool currently supports systematic evaluation and efficient screening. Here, we present druglikeFilter, a deep learning-based framework designed to assess drug-likeness across four critical dimensions: 1) physicochemical rule evaluated by systematic determination, 2) toxicity alert investigated from multiple perspectives, 3) binding affinity measured by dual-path analysis, and 4) compound synthesizability assessed by retro-route prediction. By enabling automated, multidimensional filtering of compound libraries, druglikeFilter not only streamlines the drug development process but also plays a crucial role in advancing research efforts towards viable drug candidates, which can be freely accessed at https://idrblab.org/drugfilter/.

OBJECTIVE: To investigate the effects of the combined Yiqi Huoxue Jiedu formula (YHJF) on intestinal microbiota in elderly patients with pulmonary-derived sepsis and identify potential microbial targets. METHODS: A prospective randomized double-blind controlled trial was conducted. Elderly patients with pulmonary infection-induced sepsis admitted to the emergency department of Guangdong Provincial Hospital of Traditional Chinese Medicine (TCM), intensive care unit (ICU) of Fangcun Hospital, and ICU of Daxuecheng Hospital, from November 2020 to October 2021 were enrolled and randomized into two groups. Both groups received conventional Western medicine treatment. The observation group additionally received YHJF (composed of 15 g of Panax ginseng, 9 g of Panax notoginseng, and 3 g of Rheum palmatum, dissolved in 50 mL warm water) orally or via nasogastric tube twice daily for 7 days; while the control group received a placebo. Clinical data and fresh fecal samples were collected before treatment and on days 5-7 of treatment. Intestinal microbiota diversity and structure were analyzed via 16S rDNA sequencing and bioinformatics [α diversity, β diversity, and linear discriminant analysis effect size (LEfSe)]. RESULTS: Fifty-five patients were included (29 in the control group, 26 in the observation group). There were no significantly differences in gender, age, comorbidities, and baseline sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation II (APACHE II), acute gastrointestinal injury (AGI) classification score, and gastrointestinal failure (GIF) score between the two groups. Compared to the control group, the observation group showed significantly lower serum procalcitonin, APACHE II score, and greater reduction in GIF score by day 7. Thirty fecal samples were collected pre-treatment (baseline group), 29 post-treatment from the control group, and 26 from the observation group. Gut microbiota α diversity analysis revealed that Simpson index in the observation group and control group were significantly decreased compared to the baseline group [0.75 (0.53, 0.91), 0.81 (0.32, 0.91) vs. 0.88 (0.87, 0.89), both P < 0.05], but there was no significantly difference between the observation group and the control group. There were no significantly differences in Chao1, Ace, and Shannon indices among three groups. β diversity analysis indicated that distinct microbiota structures among three groups (R² = 0.096, P = 0.026). Species difference analysis showed that, at the phylum level, Firmicutes (53.69%), Actinobacteria (16.23%), Proteobacteria (15.39%), and Bacteroidetes (9.57%) dominated, with no significant intergroup differences. At the genus level, 38 taxa showed significant differences. Compared to the control group, the observation group exhibited increased Erysipelatoclostridium (P = 0.014) and Faecalibacterium (P = 0.013), and decreased Bacteroides (P = 0.009), Bilophila (P = 0.005), Eggerthella (P = 0.002), and Collinsella (P = 0.043). LEfSe analysis highlighted Lactobacillus salivarius, Erysipelatoclostridium, Collinsella, Cloacibacillus, and Bacteroides as key discriminators. CONCLUSION YHJF combined with conventional therapy alters intestinal microbiota structure in patients with elderly pulmonary-derived sepsis, with Bacteroides, Erysipelatoclostridium, and Collinsella identified as potential microbial targets.
Humans ; Gastrointestinal Microbiome/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Double-Blind Method ; Sepsis/drug therapy* ; Aged ; Prospective Studies ; RNA, Ribosomal, 16S/genetics* ; Male ; Female ; Panax notoginseng ; Rheum

Occupational pneumoconiosis remains the most common occupational disease in China, with occupational mineral dust exposure being its primary causative factor. Although national standards for online monitoring and early warning systems of coal mine dust concentrations have been established, national occupational health standards for rapid and online monitoring of dust concentration and particle size distribution in other industries are still limited. Among dust concentration sensor technologies, the light scattering method is the preferred choice for online dust monitoring owing to its wide measurement range and low cost. The beta-ray absorption method is mature but highly sensitive to humidity. The electrostatic induction method offers high sensitivity, simple structure, and low maintenance costs but exhibits high errors in low-concentration dust monitoring. The tapered element oscillating microbalance method is highly sensitive but costly. Multi-sensor data fusion technology can improve monitoring reliability, however, mature domestic products are not yet available. For monitoring dust particle size distribution, sieving and sedimentation methods are cumbersome. The aerodynamic method shows broad prospects in the online monitoring of respirable dust but has obvious measurement errors for larger dust particles. The use of optical measurement method is limited by dust morphology and is not suitable for monitoring coal dust particle size distribution. The electrical mobility method is primarily applicable to submicron dust. Future research should focus on promoting the application of monitoring technology for respirable dust particle size distribution in online monitoring of industrial dust. By integrating Internet of Things, data mining, and artificial intelligence technologies, along with multi-sensor data fusion and numerical simulation, dust concentration prediction models can be established to achieve accurate dust concentration monitoring and early warning of exceedances. The advancements of technologies will provide scientific support for the assessment of industrial dust hazards and the prevention and control of occupational pneumoconiosis.

Objective To explore the application value of simultaneous multi-slice(SMS)technique in diffusion tensor imaging(DTI)for evaluating brain glioma.Methods Thirty-four brain glioma patients were prospectively enrolled,and brain conventional DTI and SMS-DTI were acquired.The subjective scores of image quality,signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were compared between SMS-DTI and conventional DTI,so were the numbers of whole brain fiber bundles,tumor relative fractional anisotropy(rFA)and relative mean diffusivity(rMD)obtained based on SMS-DTI and conventional DTI.Results Among 34 patients,there were 23 cases of high-grade glioma and 11 cases of low-grade glioma.No significant difference of subjective scores of image quality,tumor edge clarity nor magnetic susceptibility artifacts was found between SMS-DTI and conventional DTI(all P＞0.05).SNR and CNR on SMS-DTI were both lower than those on conventional DTI(both P＜0.05).No significant difference of the numbers of whole brain fiber bundles,rFA nor rMD of gliomas with different pathological grades was detected based on SMS-DTI compared with those on conventional DTI(all P＞0.05).Conclusion SMS applicated in DTI for evaluating brain gliomas was able to shorten acquisition time under the condition of ensuring image quality and quantitative analysis accuracy.

Objectives:To investigate the association of trajectories of atherogenic index of plasma(AIP)with the risk of atherosclerotic cardiovascular disease(ASCVD). Methods:A total of 51 831 employees and retirees who participated in Kailuan Group health examination for three consecutive times from 2006 to 2010 were included in this study.AIP was calculated using the log(triglycerides[TG]/high-density lipoprotein-cholesterol[HDL-C])formula.AIP trajectory models were fitted by the SAS Proc Traj program,and according to AIP trajectory,the subjects were divided into low stability group(n=11 114),low to moderate stability group(n=21 647),medium to high stability group(n=13 659),and high stability group(n=5 411).Kaplan-Meier method was used to calculate the cumulative incidence of ASCVD in different groups and compared by log-rank test.Cox proportional risk regression model was used to analyze the effects of different AIP trajectories on ASCVD risk. Results:Finally,51 831 patients were included in the analysis.During a mean follow-up of(10.19±2.22)years,5 142(9.92%)subjects developed ASCVD,4 013(7.74%)subjects died.Cox regression analysis after adjusting for confounding factors showed:compared with the low stability group,the risk of ASCVD increased by 13%(HR=1.13,95%CI:1.04-1.23,P=0.003)and 20%(HR=1.20,95%CI:1.10-1.31,P＜0.001)and 41%(HR=1.41,95%CI:1.27-1.57,P＜0.001)in the low to moderate stability group,moderate to high stability group and high stability group,respectively,and the risk increased gradually(Ptrend＜0.001).Stratified analysis showed that the risk of ASCVD in people aged＜65 years and low-density lipoprotein cholesterol(LDL-C)＜3.4 mmol/L with long-term high levels of AIP was higher than that in people aged≥65 years and LDL-C≥3.4 mmol/L(both Pinteraction＜0.01). Conclusions:In Kailuan Study cohort,those with long-term high levels of AIP had a higher risk of ASCVD,and the risk gradually increased.In addition,we found that the risk of ASCVD in people with long-term high levels of AIP was higher in＜65 years old than in≥65 years old,and the risk of ASCVD in people with LDL-C＜3.4 mmol/L was higher than that in people with LDL-C≥3.4 mmol/L.

Objective:To explore the curative effect and prognostic assessment value of percutaneous kyphoplasty(PKP)in treating osteoporosis-caused spinal vertebral compression fractures by using imaging parameters of pelvic sagittal X-ray.Methods:A total of 198 patients with osteoporosis-caused spinal vertebral compression fractures who received treatment from January 2022 to January 2023 were selected,and they were divided into effective group(171 cases)and ineffective group(27 cases)according to the treatment effect.All patients underwent PKP treatment,and the parameters of preoperative measurements included sagittal vertical axis(SVA)of cervical vertebra 7(C7),the thoracic vertebra 1 pelvic angle(T1PA),thoracic kyphosis(TK),lumbar lordosis(LL)and sacral slope(SS).The clinically curative effect and prognosis between two groups were compared.Results:After PKP treatment,49 cases of 198 patients were cured,and 69 cases appeared significant effect,and 53 cases were effective,and 27 cases were ineffective.The SVA,LL and SS levels of effective group were significantly lower than those of ineffective group,and the differences of them were statistically significant(t=6.485,3.250,2.325,P<0.05),and the T1PA and TK of the effective group were significantly higher than those of the ineffective group(t=2.387,3.245,P<0.05),respectively.In 198 patients,39 cases occurred postoperative complications(20 cases occurred bone cement leakage,and 15 cases occurred recurrent adjacent vertebral fracture,and 2 cases occurred pulmonary embolism,and 2 cases occurred others),and 159 cases did not occurred complications.The SVA,LL and SS levels in patients without complications were significantly lower than those in patients with complications(t=10.304,5.669,0.844,P<0.05),and the T1PA and TK of patients without complications were significantly higher than those of patients with complications,and the differences were significant(t=3.494,5.550,P<0.05),respectively.The results of receiver operating characteristic(ROC)curve analysis showed that SVA,T1PA,TK,LL and SS had a certain value in assessing the curative effect and prognosis of PKP in treating osteoporosis-caused spinal vertebral compression fractures.Conclusion:Preoperative detection of imaging parameters of pelvic sagittal X-ray can assess the curative effect and prognosis of osteoporosis-caused spinal vertebral compression fractures,which can provide a certain reference for clinical treatment.

This research provides an overview of the perioperative nursing care for a patient with a massive renal cell carcinoma and Mayo Stage Ⅲ tumor thrombus who underwent a robot-assisted nephrectomy complicated by sig-nificant intraoperative bleeding and CO2 embolism.Key nursing considerations included multidisciplinary preoperative discussions,developing stepwise intraoperative emergency plans,establishing an integrated nursing workstation,and the optimization of patient monitoring.During the surgery,nursing efforts were focused on supporting the robot-as-sisted procedure,closely monitoring the patient's condition,preventing intraoperative complications,initiating emergency plans as needed,actively managing major bleeding and CO2 embolism,and implementing structured positioning to minimize the risk of falls during the procedure.Postoperatively,the focus was on preventing secondary thrombus formation,managing active bleeding,and monitoring for liver and kidney ischemia-reperfusion injury.Through multi-disciplinary interventions and meticulous nursing care,the patient was discharged after a 13-day postoperative recovery.

Objective:To evaluate the safety and efficacy of the domestic robotic surgical system for general surgery.Methods:A prospective single-center, single-arm exploratory study was conducted at Gansu Provincial People's Hospital from Jun 2022 to Oct 2023, enrolling 54 patients undergoing general surgery using domestically produced Toumai? Endoscopic Surgical Robotic System. The primary study endpoint was surgical success rate, and the secondary study endpoints were intraoperative bleeding, operative time, complications, system performance, hospitalization days.Results:In this study, robotic surgery was successfully completed in 52 patients, and in 2 patients undergoing thyroid operation it was converted to open surgery due to bleeding, with a success rate of 96%, no organ injury or death during surgery, and no system failure. The types of surgery included cholecystectomy, radical gastric cancer resection, radical colorectal cancer resection, inguinal hernia repair, partial hepatectomy, total thyroidectomy and choledocho-jejunal anastomosis.Conclusion:The study provides preliminary evidence of the safety and efficacy of the Toumai? Endoscopic Surgical Robotic System for the treatment of general surgical diseases.

Objective:To investigate the impact of non-high-density lipoprotein cholesterol (non-HDL-C) level on major adverse cardiovascular and cerebrovascular events (MACCE) and all-cause mortality in the Kailuan Study cohort undergoing revascularization.Methods:This is a prospective cohort study, with participants from the Kailuan Study cohort who participated in physical examinations from 2006 to 2020 and received revascularization therapy for the first time. According to the level of non-HDL-C, the study subjects were divided into 3 groups:<2.6 mmol/L group, 2.6-<3.4 mmol/L group, and≥3.4 mmol/L group. Annual follow-up was performed, and the endpoint events were MACCE and all-cause mortality. Cox proportional regression model was implemented to estimate the impact on MACCE and all-cause mortality associated with the different non-HDL-C groups. The partial distributed risk model was used to analyze the impact of different non-HDL-C levels on MACCE event subtypes, and death was regarded as a competitive event. The restricted cubic spline regression model was used to explore the dose-response relationship between non-HDL-C level and all-cause mortality, MACCE and its subtypes.Results:A total of 2 252 subjects were enrolled in the study, including 2 019 males (89.65%), aged (62.8±8.3) years, the follow-up time was 5.72 (3.18, 8.46) years. There were 384 cases(17.05%) of MACCE and 157 cases(6.97%) of all-cause mortality. Compared with patients with non-HDL-C≥3.4 mmol/L, patients with non-HDL-C<2.6 mmol/L were associated with a 38% reduced risk of MACCE after revascularization [ HR=0.62(95% CI: 0.48-0.80)]. Every 1 mmol/L decrease in non-HDL-C was associated with a 20% reduction in the risk of MACCE [ HR=0.80(95% CI: 0.73-0.88)]. The results of restricted cubic spline also showed that non-HDL-C levels after revascularization therapy were positively correlated with MACCE events (overall association P<0.001, non-linear association P=0.808). For all-cause mortality, compared to the non-HDL-C≥3.4 mmol/L group, the HR for all-cause mortality after revascularization in non-HDL-C<2.6 mmol/L group was 0.67(95% CI: 0.46-1.01). Every 1 mmol/L decrease in non-HDL-C was associated with a 15% reduction in the risk of all-cause mortality [ HR=0.85(95% CI: 0.73-0.99)]. The restricted cubic spline results showed a linear association between non-HDL-C levels after revascularization therapy and the risk of all-cause mortality (overall association P=0.039, non-linear association P=0.174). Conclusion:The decrease in non-HDL-C levels after revascularization were significantly associated with a reduced risk of MACCE and all-cause mortality.