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.

Myocardial fibrosis （MF） is a common pathological manifestation of various heart diseases. Due to the non-renewable nature of myocardial cells， the occurrence of MF represents irreversible damage to the myocardium. Previous studies have suggested that fibroblast-mediated collagen deposition is the main mechanism of MF. Recent studies have found that there is an immune regulation mechanism in the heart itself， and macrophage activation/polarization plays an important role in MF. With the deepening of traditional Chinese medicine research， scholars have found that traditional Chinese medicine can interfere with MF by regulating the renin-angiotensin-aldosterone system （RAAS） system and the inflammatory process， repairing the extracellular matrix， managing oxidative stress， and maintaining the balance of autophagy. This process is closely related to the activation and M1/M2 polarization of macrophages. Throughout the MF process， macrophage activation is beneficial， but excessive activation will be harmful. In the early stage of MF， appropriate M1 macrophage polarization is conducive to activating immunity and removing harmful substances. In the middle and late stages of MF， appropriate M2 macrophage polarization is conducive to remodeling the damaged myocardium. If macrophage activation is excessive/insufficient， or the balance of M1/M2 macrophage polarization is broken， the effect changes from improvement to destruction. Traditional Chinese medicines that regulate the activation/polarization of macrophages have the effects of replenishing Qi and nourishing Yin， as well as regulating Qi and activating blood， but there are also some heat-clearing， dampness-drying， and detoxification products. Therefore， the occurrence of MF may be caused by Qi and Yin deficiency， damp heat accumulation， and Qi stagnation and blood stasis. By summarizing the biological processes involved in macrophage activation/polarization in MF， this paper expounded on the research progress of traditional Chinese medicine in regulating macrophage activation and M1/M2 polarization from different angles to improve MF， so as to provide a reference for the treatment of MF with traditional Chinese medicine.

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.

In recent years, with the in-depth study of PD-1 and PD-L1 and the development of immunotherapy, the first problem is how to screen the beneficiaries. Recent clinical studies have shown that the expression level of PD-L1 in circulating tumor cells (CTC) can be used as a potential biomarker to play a guiding role in immunotherapy of malignant tumors. This article reviews the latest clinical research progress on the expression of PD-L1 in circulating tumor cells in various solid tumors.

OBJECTIVE：To eva luate the risk of abno rmal female reproductive system haemorrhage induced by novel oral anticoagulants （NOACs）. METHODS ：The abnormal female reproductive system haemorrhage reports induced by 4 kinds of NOACs as “dabigatran etexilate ”，“rivaroxaban”，“apixaban”and“edoxaban”were used as the first suspected dugs to collected from FDA adverse event reporting system （FAERS）database during Jan. 1st，2004-May 31st，2019. The report odd ratio （ROR） method was used to detect the signal of abnormal female reproductive system haemorrhage induced by NOACs. RESULTS ：A total of 2 658 adverse events related to abnormal female reproductive system haemorrhage were collected from FAERS database ， involving 330 reports of dabigatran etexilate ，2 049 reports of rivaroxaban ，267 reports of apixaban ，and 12 reports of edoxaban. The abnormal female reproductive system haemorrhage caused by dabigatran etexilate ，apixaban and edoxaban mainly occurred in patients aged 75 and older ，accounting for 37.27％，36.70％ and 58.33％ respectively；that of rivaroxaban mainly occurred in patients with 45-64 years old ，accounting for 33.04％. The incidence of severe adverse events （SAE）induced by dabigatran etexilate，rivaroxaban，apixaban and edoxaban were 96.36％，84.53％，47.19％ and 58.33％，respectively. All of patients in the included reports were mainly hospitalized and hospitalization stay wa s prolonged ，accounting for 64.78％，90.01％，86.51％ and 71.43％ ，respectively. A total of 12 suspected signals were detected，involving cervix uteri ，fallopian tube ，ovary，pelvis cavity，uterus，vagina，urinary tract ，etc. Among them ，there were 11 positive signals of rivaroxaban ，and the bleeding events were concentrated in vaginal hematoma [ROR ＝12.07， 药。95％CI（8.51，17.12）]，postmenopausal hemorrhage [ROR ＝ 9.89，95％CI（8.31，11.77）]，pelvic hematoma [ROR ＝7.68，95％CI（5.66，10.43）]. There were 4，4 and 2 suspicious signals for dabigatran etexilate ，apixaban and edoxaban. The main bleeding events of both apixaban [ ROR＝5.18，95％CI（1.81，5.85）] and edoxaban [ROR ＝48.19，95％CI（6.76，343.77）] were vaginal hematoma ；dabigatran etexilate-induced pelvic hematoma [ROR ＝ 12.56，95％CI（8.92，17.70）] had the strongest signal ，followed by urinary tract bleeding [ROR ＝5.41，95％CI（3.34，8.76）] and pelvic hemorrhage [ ROR＝2.53，95％CI（1.88，3.40）]. CONCLUSIONS ：Totally 4 kinds of NOACs can cause abnormal female reproductive system haemorrhage ，and the incidence of SAE is high ，of requiring hospitalization or prolonging hospitalization time. The risk of haemorrhage in rivaroxaban is the highest ，usually manifesting as vaginal hematoma ，postmenopausal hemorrhage and pelvic hematoma. Dabigatran etexilate mainly induce pelvic hematoma ，while apixaban and edoxaban are mainly cause vaginal hematoma.

Objective: To explore the safety, feasibility and advantages of Da Vinci robot "3+ 2" mode in radical gastrectomy. Methods: Clinical data of 30 patients received radical gastrectomy at our department under the "3+ 2" mode of Da Vinci robot from Jan. 2018 to Oct. 2018 were retrospectively analyzed. 30 patients who received classical robot mode in the same period were randomly selected as control group. Results: Compared with the control group, the observation group had a shorter operative time (174±16)min vs.(197±19)min, t=-3.275, P<0.01) , a lower operation costs[(22 794±3 660)yuan vs.(29 307±3 220)yuan, t=-3.316, P<0.01; and inhospital costs (70 910±6 399)yuan vs.(78 180±6 636)yuan), t=-7.316, P<0.01]. Conclusion The "3+ 2" mode of Da Vinci robot in radical gastrectomy is beneficial to enhance the exposure of the surgical field, improve the cooperation of assistants, reduce the costs of surgery, shorten the operative time and the learning curves. In addition, it has similar clinical efficacy to radical gastrectomy under the classical robot mode.

OBJECTIVE:To excavate and evaluate the security alert signals of linezolid after marketing,and to provide refer-ence for rational drug use in clinic. METHODS:The reporting odds ratio(ROR)method was used to excavate the security alert signals from the adverse drug events(ADE)data in the OpenFDA platform of FDA during second quarter of 2004-2016. The low-er limit of 95%CI >1 was regarded as suggestive of ADE alert signal. RESULTS:A total of 6828534 reports were extracted, among which there were 7224 reports mainly induced by linezolid. Top 10 ADE reports were thrombocytopenia,drug interac-tion,thrombocytopenia,nausea,anaemia,serotonin syndrome,diarrhoea,pyrexia,drug ineffective,vomiting. After the detec-tion of top 200 ADE reports by ROR method,120 signals related to 18 system organ class(SOC)were identified. Top 5 ADE sig-nals in turn by SOC were medical examination,nervous system disorders,blood and lymphatic system disorders,metabolism and nutrition disorders,cardiac disorders. The high risk signals with clinical reference value included 42 cases of optic neuropathy (ROR=56.33),350 cases of serotonin syndrome(ROR=52.86),162 cases of lactic acidosis(ROR=18.30),31 cases of endo-carditis (ROR=15.38),566 cases of thrombocytopenia (ROR=14.29),122 cases of bone marrow failure (ROR=14.20),261 cases of panhematopenia (ROR=11.92),86 cases of disseminated intravascular coagulation (ROR=10.91),58 cases of toxic epidermal necrolysis(ROR=9.06),etc. As for ADE reports,male was slightly higher than female,and the patients in age group of ≥45 reported evidently more compared to younger age group. CONCLUSIONS:By detecting and evaluating alert signals of li-nezolid through OpenFDA platform,we could effectively lay the foundation for further research of pharmacovigilance.

Objective To explore the distribution characteristics of plasma renin concentration in patients with hypertension and the possibly methodological problems.Methods The subjects including 361 patients with hypertension[male: 184 cases, average age: (45.16±13.74)years old;female: 177 cases, average age: (51.04±12.68) years old]and 187 apparent healthy individuals[male: 92 cases, average age: (46.74±13.17)years old;female: 95 cases, average age: (47.33±13.18) years old]were recruited from Departments of Healthy Check-up and outpatients for hypertension in Tangshan Gongren Hospital. The plasma renin concentration was detected by chemiluminescence-Immunoassay.Results The plasma renin concentration shows log-transformed normal distribution both in healthy group and hypertension group. The range of plasma renin concentration in hypertension group is from 0.05 to 574.07 pg/ml, while that in apparent healthy group is from 3.24 to 120.40 pg/ml. The plasma renin concentration in both groups is higher in male than female (Hypertension t=2.19,P=0.029;Healthy people t=2.85,P=0.005). The average concentration of plasma renin in hypertension group is slightly higher, and the width of density distribution is larger in comparison with healthy group although there is no significant difference between them. However, the percentage of plasma renin abnormality was 26.59% (96/361) in hypertension group with 13.85%(50/361)of low renin subtype and 12.74%(46/361)of high renin subtype ConclusionsThe plasma renin concentration measured by Chemiluminescence-Immunoassay can be used as an effective tool for hypertension screening.

Objective To explore the factors influencing serum trough concentration of vancomycin in pediatric patients with severe gram-positive cocci pneumonia. Methods The general information, the biochemical test results, and plasma concentration of vancomycin were collected from 93 pediatric patients with severe gram-positive cocci pneumonia. The relative factors influencing trough concentration of vancomycin were analyzed retrospectively. Results With the dosage of 40-60 mg/(kg·d), serum trough concentration of vancomycin were between 10-20 mg/L in 26 patients, <10 mg/L in 54 cases, ≥20 mg/L in 13 cases. The ALT, AST, GFR, and γ-GT were significantly different among three groups (P<0.05); the 10-20 mg/L group had the highest levels of AST and γ-GT, the ≥20 mg/L group had the highest level of ALT and the lowest level of GFR. Multiple linear regression analysis showed that GFR was negatively linearly correlated with the serum trough concentration of vancomycin (R2=0.039, P<0.05). The median serum trough concentration of vancomycin in pediatric patients with GFR≥90, 60–90, 30–60 mL/(min·1.73m2) were 8.66, 18.21, 8.45 mg/L respectively, and the difference is statistically significant (P<0.05). Conclusions The serum trough concentration of vancomycin is negatively linearly correlated with GFR in pediatric patients with severe gram-positive cocci pneumonia. The patients with impaired renal function are easier to reach the target serum trough concentration of vancomycin. Clinical use of vancomycin should follow the low doses in the range the guideline recommended, and the serum trough concentration should be closely monitored.

OBJECTIVE:To investigate the general regularity and characteristics of propylthiouracil (PTU)-associated small vasculitis (ASV),and to provide reference for rational drug use in the clinic. METHODS:ADR/ADE case reports of PTU-ASV published during 1990-2016 were retrieved. The data of 118 ADR cases were analyzed statistically. RESULTS:The incidence of PTU-ASV was higher in female and was highest in 18-59 age group. Drug dose of 87 patients were within 600 mg/d,and the inci-dence of PTU-ASV was the highest within 1-5 years after medication. Main clinical manifestations were renal and lung function in-jury. After drug withdrawal,59 patients received hormone therapy,and 30 patients received hormone combined immunosuppressive agent. Finally,115 patients were recovered and 3 patients died. CONCLUSIONS:In older to reduce or avoid the occurrence of ADR,it is necessary to regularly check antineutrophil cytoplasmic antibody related indexes and evaluate the symptoms of ADR.