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Tumor vaccine is a promising strategy for cancer immunotherapy by introducing tumor antigens into the body to activate specific anti-tumor immune responses. Along with the technological breakthroughs in genetic engineering and delivery systems, messenger ribonucleic acid (mRNA) technology has achieved unprecedented development and application over the last few years, especially the emergency use authorizations of two mRNA vaccines during the COVID-19 pandemic, which has saved countless lives and makes the world witness the powerful efficacy of mRNA technology in vaccines. However, unlike infectious disease vaccines, which mainly induce humoral immunity, tumor vaccines also need to activate potent cellular immunity to control tumor growth, which creates a higher demand for mRNA delivery to the lymphatic organs and antigen-presenting cells (APCs). Here we review the existing bottlenecks of mRNA tumor vaccines and advanced nano-based strategies to overcome those challenges, as well as future considerations of mRNA tumor vaccines and their delivery systems.

Diagnosis and treatment of negative pressure hydrocephalus: analysis of 5 cases and literature review / 中国综合临床

Objective:To investigate the clinical manifestations, pathogenesis,diagnosis and treatment of negative pressure hydrocephalus (NPH).Methods:A retrospective analysis was performed on the 5 patients with NPH admitted to the Department of Neurosurgery, Tianjin Huanhu Hospital from January 2019 to December 2021. All of the patients underwent lumbar puncture and ventricular puncture to test the pressure. Three patients underwent endoscopic third ventriculostomy (ETV), the outcome of the patients was observed.Results:The pressure of subarachnoid was not equal to intraventricular, and the pressure of intraventricular was negative. Cisternography showed cerebrospinal fluid circulation obstruction in all 5 cases. The symptoms of 1 patient were improved after external negative pressure drainage, 3 patients were improved after further ETV and 1 patient had pulmonary infection without further surgical treatment.Conclusion:With the obstruction of cerebrospinal fluid circulation, the pressure of lateral ventricle and subarachnoid is different, when the pressure of brain or subarachnoid drop, the ventricular expansion under the effect of pressure gradient, intraventricular pressure drop even for the negative pressure. CT cisternography provides strong evidence for the diagnosis of this disease. External ventricular drainage with negative pressure and ETV are effective treatment methods.

Application of metagenomic next-generation sequencing in the detection of pathogenic bacteria in brain abscesses / 中国综合临床

Objective:To analyze the application value of metagenomic next-generation sequencing (mNGS) in the detection of pathogenic bacteria in brain abscesses.Methods:The data of patients with brain abscess in Tianjin Huanhu Hospital from January 2019 to December 2021 were retrospectively analyzed. All patients underwent stereotaxic abscess puncture and drainage. According to the different methods of pathogen detection, they were divided into bacterial culture group (bacterial culture only) and mNGS group (bacterial culture with mNGS). The clinical symptoms, abscess site, bacterial culture and mNGS results, antibiotic application protocol and prognosis of the patients were analyzed. The bacterial detection results of the two groups were analyzed, and the antibiotic application and prognosis were compared. χ 2 test, exact probability method and Mann Whitney test were used to compare the difference between the two groups. Results:A total of 43 patients with brain abscess were enrolled, including 21 cases in bacterial culture group and 22 cases in mNGS group. The positive rate of bacteria culture group was 42.9% (9/21), the positive rate of bacteria culture group was 45.5% (10/22), and the positive rate of mNGS detection was 100% (22/22). Only 3 cases in the bacterial culture group could have a clear bacterial source, while 17 cases in the mNGS group could have a clear bacterial source according to the bacterial results, showing a significant statistical difference between the two groups (χ 2=19.69, P<0.001). The return time of bacterial culture was 7.0 (4.0,7.0) days, and the average return time of mNGS was 1.5 (1.5,1.5) days, the difference of bacterial return time between the two groups was statistically significant ( Z=0.00, P<0.001). The cost of antibiotic use in bacterial culture group was 24.00 (5.60,31.00) thousands yuan, and the cost of antibiotic use in mNGS group was 12.00 (2.10, 20.00) thousands yuan, and there was significant statistical difference between them ( Z=5.22, P=0.026). Conclusions:MNGS can quickly and accurately identify the types and sources of brain abscess pathogens, guide the clinical application of antibiotics more targeted, reduce the cost of antibiotic use, and is an effective method for the detection of brain abscess pathogenic bacteria.

Advances in using adaptive laboratory evolution technology for engineering of photosynthetic cyanobacteria / 生物工程学报

Cyanobacteria are the only prokaryotes capable of oxygenic photosynthesis, which have potential to serve as "autotrophic cell factories". However, the synthesis of biofuels and chemicals using cyanobacteria as chassis are suffered from poor stress tolerance and low yield, resulting in low economic feasibility for industrial production. Thus, it's urgent to construct new cyanobacterial chassis by means of synthetic biology. In recent years, adaptive laboratory evolution (ALE) has made great achievements in chassis engineering, including optimizing growth rate, increasing tolerance, enhancing substrate utilization and increasing product yield. ALE has also made some progress in improving the tolerance of cyanobacteria to high light intensity, heavy metal ions, high concentrations of salt and organic solvents. However, the engineering efficiency of ALE strategy in cyanobacteria is generally low, and the molecular mechanisms underpinning the tolerance to various stresses have not been fully elucidated. To this end, this review summarizes the ALE-associated technical strategies and their applications in cyanobacteria chassis engineering, following by discussing how to construct larger ALE mutation library, increase mutation frequency of strains and shorten evolution time. Moreover, exploration of the construction principles and strategies for constructing multi-stress tolerant cyanobacteria, and efficient analysis the mutant libraries of evolved strains as well as construction of strains with high yield and strong robustness are discussed, with the aim to facilitate the engineering of cyanobacteria chassis and the application of engineered cyanobacteria in the future.

Characteristics of whole blood donors from 26 blood stations before and after the outbreak of COVID-19:a multicenter study / 中国输血杂志

【Objective】 To analyze the basic characteristics of whole blood donors from blood stations before and after the outbreak of COVID-19. 【Methods】 After excluding invalid data, data related to the basic characteristics of whole blood donors collected from 26 blood stations in China during 2018 to 2021 were statistically analyzed, including the trend of total whole blood donors, the number of repeated blood donors, the frequency of blood donation, the average age of donors and the recruitment of first-time blood donors. 【Results】 Affected by the epidemic, 8 out of 14 indicators were with large variations, accounting for 57%. The overall growth rate of total whole blood donors during the epidemic was higher than before the epidemic (P<0.05).The number of repeated blood donors has shown an increased trend, with a higher number during the epidemic than before (P<0.05). The frequency of blood donation was lower during the epidemic than before(P<0.05).Average ages of blood donors and female blood donors fluctuated widely during the epidemic, both higher than those before the epidemic(P<0.05).The donation rate of first-time blood donors <25 years old and ≥25 years old varied widely and irregularly during the epidemic (both P<0.05). The percentage of first-time blood donors fluctuated irregularly during the epidemic, with overall percentage lower than that before the epidemic(P<0.05). 【Conclusion】 Whole blood donors from 26 blood stations increased after the outbreak of COVID-19, and some indicators in certain areas showed significant fluctuations during the epidemic.

ACT001 exerts anti-inflammatory and antioxidative activity to alleviate sepsis-induced acute lung injury through STAT1/CIITA/MHC- II pathway / 中国药理学通报

Aim This study aimed to assess the therapeutic potential of ACT001, a micheliolide derivative, in the treatment of acute lung injury ( ALI) induced by sepsis and investigate its pharmacological mechanisms. Methods At the animal level, an ALI model was established in mice through intraperitoneal injection of li-popolysaccharide (LPS). Subsequently, ACT001 was administered to the ALI-afflicted mice. The therapeutic effects of ACT001 were assessed by evaluating factors such as individual survival rate, lung inflammation, and pulmonary edema. At the cellular level, RAW264. 7 cells were stimulated with LPS to explore the pharmacological mechanism of ACT001. The study examined inflammatory response and oxidative stress levels, and proteomics analysis was conducted to investigate the underlying molecular mechanisms. Results At the animal level, ACT001 can improve the survival of mice with ALI, reduce lung inflammation, and reduce the levels of inflammatory cytokines in serum. At the cellular level, ACT001 promotes the polarization of RAW264. 7 cells toward an anti-inflammatory pheno-type by inhibiting MHC-II related pathways, inhibiting the production of NO and related inflammatory cytokines while increasing SOD content and scavenging ROS. Conclusions ACT001 exhibited the potential to alleviate ALI via its anti-inflammatory and antioxidative activity, mainly by inhibiting the STAT1/ CIITA/ MHC-II pathway. ACT001 holds promise as a novel therapeutic candidate for the treatment of ALI induced by sepsis.

Analyzing the influencing factors of work-related musculoskeletal disorders in neck, shoulder and lower back of live-electric line workers / 中国职业医学

{L-End}Objective To investigate the prevalence and influencing factors of work-related musculoskeletal disorders (WMSDs) of live-electric line workers in the power supply enterprises. {L-End}Methods A total of 1 479 live-electric frontline workers in the power supply bureaus under China Southern Power Grid Co., LTD in Guangxi Zhuang Autonomous Region, Guangdong Province and Yunnan Province were selected as the research subjects using the cluster sampling method. The revised Chinese version of the Musculoskeletal Disorders Questionnaire was used to investigate the prevalence of WMSDs and their influencing factors in the past year. {L-End}Results The prevalence of WMSDs was 61.4%. The prevalence of WMSDs in nine body sites ranged from 11.3% to 45.1%, with the highest prevalence being on three sites of neck, shoulder and lower back with a prevalence of 45.1%, 36.0% and 30.8%, respectively. The results of multivariate logistic regression analysis showed that the influencing factors of WMSDs in the neck, shoulder, and lower back were different, but all related to individual factors, poor ergonomics factors, and unreasonable work organization factors. The influencing factors simultaneously affecting these three sites included length of service, educational level, working in a sitting posture for a long time, working in uncomfortable postures, adequate rest time, starting to work after rest, deciding when to start and finish by oneself, and shortage of staff in the department or group. The factors affecting both neck and shoulder WMSDs were gender and back bending slightly for a long time. The factors affecting both neck and lower back were age and back bending significantly for a long time. {L-End}Conclusion The prevalence of WMSDs in the live-electric line workers in power supply enterprises is high, mainly occurring in the neck, shoulders, and lower back. The influencing factors are individual factors, poor ergonomics factors, and unreasonable work organization.

Immunogenicity of mucosal COVID-19 vaccine candidates based on the highly attenuated vesicular stomatitis virus vector (VSVMT) in golden syrian hamster

COVID-19 is caused by coronavirus SARS-CoV-2. Current systemic vaccines generally provide limited protection against viral replication and shedding within the airway. Recombinant VSV (rVSV) is an effective vector which inducing potent and comprehensive immunities. Currently, there are two clinical trials investigating COVID-19 vaccines based on VSV vectors. These vaccines were developed with spike protein of WA1 which administrated intramuscularly. Although intranasal route is ideal for activating mucosal immunity with VSV vector, safety is of concern. Thus, a highly attenuated rVSV with three amino acids mutations in matrix protein (VSVMT) was developed to construct safe mucosal vaccines against multiple SARS-CoV-2 variants of concern. It demonstrated that spike protein mutant lacking 21 amino acids in its cytoplasmic domain could rescue rVSV efficiently. VSVMT indicated improved safeness compared with wild-type VSV as the vector encoding SARS-CoV-2 spike protein. With a single-dosed intranasal inoculation of rVSVΔGMT-SΔ21, potent SARS-CoV-2 specific neutralization antibodies could be stimulated in animals, particularly in term of mucosal and cellular immunity. Strikingly, the chimeric VSV encoding SΔ21 of Delta-variant can induce more potent immune responses compared with those encoding SΔ21 of Omicron- or WA1-strain. VSVMT is a promising platform to develop a mucosal vaccine for countering COVID-19.

Research progress and considerations on non-clinical studies of the drugs administered through the ocular vitreous body / 药学学报

In recent years, with the development of ophthalmic therapeutic drugs, the vitreous body, as a channel for the treatment of ophthalmic diseases, especially fundus diseases, has opened up a new therapeutic approach for various choroidal neovascular diseases, macular edema, uveitis and other diseases associated with fundus diseases, which is represented by wet age-related macular degeneration (wAMD). The drugs administered through the vitreous body mainly include ocular anti-vascular endothelial growth factor (VEGF) injections, microplasmin and hormones. For this kind of ophthalmic products, there are no clear technical guidelines and norms for non-clinical research at home and abroad. This article combines review practices and cases of marketed products to sort out the research progress and considerations on non-clinical studies of ophthalmic drugs dosing through the ocular vitreous body, in order to provide references for the research and evaluation of such drugs.

ROS-removing nano-medicine for navigating inflammatory microenvironment to enhance anti-epileptic therapy

As a neurological disorder in the brain, epilepsy is not only associated with abnormal synchronized discharging of neurons, but also inseparable from non-neuronal elements in the altered microenvironment. Anti-epileptic drugs (AEDs) merely focusing on neuronal circuits frequently turn out deficient, which is necessitating comprehensive strategies of medications to cover over-exciting neurons, activated glial cells, oxidative stress and chronic inflammation synchronously. Therefore, we would report the design of a polymeric micelle drug delivery system that was functioned with brain targeting and cerebral microenvironment modulation. In brief, reactive oxygen species (ROS)-sensitive phenylboronic ester was conjugated with poly-ethylene glycol (PEG) to form amphiphilic copolymers. Additionally, dehydroascorbic acid (DHAA), an analogue of glucose, was applied to target glucose transporter 1 (GLUT1) and facilitate micelle penetration across the blood‒brain barrier (BBB). A classic hydrophobic AED, lamotrigine (LTG), was encapsulated in the micelles via self-assembly. When administrated and transferred across the BBB, ROS-scavenging polymers were expected to integrate anti-oxidation, anti-inflammation and neuro-electric modulation into one strategy. Moreover, micelles would alter LTG distribution in vivo with improved efficacy. Overall, the combined anti-epileptic therapy might provide effective opinions on how to maximize neuroprotection during early epileptogenesis.

A neutrophil-biomimic platform for eradicating metastatic breast cancer stem-like cells by redox microenvironment modulation and hypoxia-triggered differentiation therapy

Metastasis accounts for 90% of breast cancer deaths, where the lethality could be attributed to the poor drug accumulation at the metastatic loci. The tolerance to chemotherapy induced by breast cancer stem cells (BCSCs) and their particular redox microenvironment further aggravate the therapeutic dilemma. To be specific, therapy-resistant BCSCs can differentiate into heterogeneous tumor cells constantly, and simultaneously dynamic maintenance of redox homeostasis promote tumor cells to retro-differentiate into stem-like state in response to cytotoxic chemotherapy. Herein, we develop a specifically-designed biomimic platform employing neutrophil membrane as shell to inherit a neutrophil-like tumor-targeting capability, and anchored chemotherapeutic and BCSCs-differentiating reagents with nitroimidazole (NI) to yield two hypoxia-responsive prodrugs, which could be encapsulated into a polymeric nitroimidazole core. The platform can actively target the lung metastasis sites of triple negative breast cancer (TNBC), and release the escorted drugs upon being triggered by the hypoxia microenvironment. During the responsiveness, the differentiating agent could promote transferring BCSCs into non-BCSCs, and simultaneously the nitroimidazole moieties conjugated on the polymer and prodrugs could modulate the tumor microenvironment by depleting nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) and amplifying intracellular oxidative stress to prevent tumor cells retro-differentiation into BCSCs. In combination, the BCSCs differentiation and tumor microenvironment modulation synergistically could enhance the chemotherapeutic cytotoxicity, and remarkably suppress tumor growth and lung metastasis. Hopefully, this work can provide a new insight in to comprehensively treat TNBC and lung metastasis using a versatile platform.

Robot-assisted PVP for the treatment of osteoporotic fractures of the upper thoracic vertebra / 中国骨伤

OBJECTIVE@#To investigate the clinical effect of "Tianji" orthopedic robot-assisted percutaneous vertebro plasty(PVP) surgery in the treatment of upper thoracic osteoporotic fracture.@*METHODS@#A retrospective analysis was performed on 32 patients with upper thoracic osteoporotic fracture who underwent PVP surgery in Shenzhen Hospital of Traditional Chinese Medicine from August 2016 to June 2022. There were 8 males and 24 females, ranging in age from 58 to 90 years old, with a mean of (67.75±12.27) years old. Fifteen patients were treated with robot-assisted PVP surgery (robot group), including 3 males and 12 females, with an average age of (68.5±10.3) years. Fracture location:1 case of T2 fracture, 1 case of T3 fracture, 3 cases of T4 fracture, 3 cases of T5 fracture, and 7 cases of T6 fracture. The follow-up period ranged from 1.0 to 3.0 months, with a mean of (1.6±0.7) months. Seventeen patients underwent routine PVP surgery (conventional group), including 5 males and 12 females, with an average age of (66.8±11.6) years old. Fracture location:1 case of T1 fracture, 5 cases of T4 fracture, 2 cases of T5 fracture and 9 cases of T6 fracture. The follow-up period ranged from 0.5 to 4.0 months, with a mean of (1.5±0.6) months. Preoperative and postoperative visual analogue scale(VAS) and Oswestry disability index(ODI) scores were compared between the two groups, and the number of punctures, perspective times, operation time, intraoperative blood loss, bone cement distribution, bone cement leakage, and intraoperative radiation dose were compared between the two groups.@*RESULTS@#Number of punctures times, perspective times, operation time, intraoperative blood loss, bone cement distribution, bone cement leakage and intraoperative radiation dose in the robot group were all significantly better than those in the conventional group(P<0.05). VAS of 2.03±0.05 and ODI of (22.16±4.03) % in the robot group were significantly better than those of the robot group before surgery, which were (8.67±0.25) score and (79.40±7.72)%(t=100.869, P<0.001;t=25.456, P<0.001). VAS of 2.17±0.13 and ODI of (23.88±6.15)% in the conventional group were significantly better than those before surgery, which were (8.73±0.18) score and (80.01±7.59)%(t=121.816, P<0.001;t=23.691, P<0.001). There was no significant difference in VAS and ODI between the two groups after operation (t=-3.917, P=0.476;t=-0.922, P=0.364).@*CONCLUSION@#Robot-assisted PVP in the treatment of upper thoracic osteoporotic fractures can further improve surgical safety, reduce bone cement leakage, and achieve satisfactory clinical efficacy.

Effect of Juanbi Qianggu Formula on biological behaviors of fibroblast-like synoviocytes in rheumatoid arthritis by regulating FGFR1 signaling pathway based on network pharmacology and cell function experiments / 中国中药杂志

This study aimed to explore the molecular mechanism of Juanbi Qianggu Formula(JBQGF), an empirical formula formulated by the prestigious doctor in traditional Chinese medicine, in the treatment of rheumatoid arthritis based on network pharmacology and cell function experiments. The main active components and targets of JBQGF were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and Encyclopedia of Traditional Chinese Medicine(ETCM), and the core targets underwent functional enrichment analysis and signaling pathway analysis. Cytoscape 3.6.0 was used to construct a visualized "active component-target-signaling pathway" network of JBQGF. After screening, nine potential pathways of JBQGF were obtained, mainly including G protein-coupled receptor signaling pathway and tyrosine kinase receptor signaling pathway. As previously indicated, the fibroblast growth factor receptor 1(FGFR1) signaling pathway was highly activated in active fibroblast-like synoviocytes(FLS) in rheumatoid arthritis, and cell and animal experiments demonstrated that inhibition of the FGFR1 signaling pathway could significantly reduce joint inflammation and joint destruction in collagen-induced arthritis(CIA) rats. In terms of the tyrosine kinase receptor signal transduction pathway, the analysis of its target genes revealed that FGFR1 might be a potential target of JBQGF for rheumatoid arthritis treatment. The biological effect of JBQGF by inhibiting FGFR1 phosphorylation was preliminarily verified by Western blot, Transwell invasion assay, and pannus erosion assay, thereby inhibiting matrix metalloproteinase 2(MMP2) and receptor activator of nuclear factor-κB ligand(RANKL) and suppressing the invasion of fibroblasts in rheumatoid arthritis and erosive effect of pannus bone. This study provides ideas for searching potential targets of rheumatoid arthritis treatment and TCM drugs through network pharmacology.

Entinostat, a class I selective histone deacetylase inhibitor, plus exemestane for Chinese patients with hormone receptor-positive advanced breast cancer: A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

Study on the efficacy and safety of combination of sufficient argon plasma coagulation cauterization and clipping in the treatment of colonic diverticular bleeding / 中华消化杂志

Objective:To evaluate the efficacy and safety of combination of sufficient argon plasma coagulation(APC) cauterization and clipping in the treatment of colonic diverticular bleeding.Methods:From June 2018 to April 2022, the clinical data of patients were retrospectively analyzed, who visited Department of Gastroenterology of Air Force Medical Center due to overt gastrointestinal bleeding, and were confirmed or suspected to have colonic diverticular bleeding and received combination of sufficient APC cauterization and clipping treatment. The deadline for follow-up was September 30, 2022. During the follow-up after endoscopic treatment, the re-bleeding rate, hemoglobin level difference between the last follow-up and before treatment, wound healing under colonoscopy as well as the intraoperative and postoperative complications of patients were statistically analyzed. Descriptive analysis was used for statistical analysis.Results:A total of 15 patients were enrolled, including 13 males and 2 females, aged (60.8±14.8) years old. The course of the disease was 1 day to 13 years. A total of 145 colonic diverticula of 15 patients were treated under endoscopy. The median follow-up time was 14.5 months (5.3 to 49.5 months) months. Among the 15 patients, 12 patients received endoscopic therapy once and no bleeding occurred till the end of follow-up. Three patients suspected with diverticular bleeding received a second endoscopic treatment because of bleeding at the 12 days, 3 months and 8 months after the first treatment, respectively.No rebleeding occurred after the second endoscopic therapy till the end of follow-up. The re-bleeding rate of the first treatment was 3/15 and the re-bleeding rate of re-treatment was 0. At the end of follow-up, the hemoglobin concentration increased (35.9±26.3) g/L compared with that before the treatment. Two patients had perforation during operation and were closed with multiple titanium clips. There was no abdominal pain or other symptoms after operation. And the patients were discharged 3 and 4 days after treatment, respectively. Two patients suffered short-term postoperative wound bleeding and successful hemostasis was achieved after endoscopic treatment. One patient developed postoperative infection and the symptoms disappeared after anti-infection treatment.Conclusions:Combination of sufficient APC cauterization and titanium clipping is safe and effective in the treatment of colonic diverticular bleeding. For patients with dominant diverticular hemorrhage, or patients with recurrent gastrointestinal bleeding, if other etiology are excluded and colonic diverticular bleeding is highly suspected, the combination of sufficient APC cauterization and titanium clipping under endoscopy is feasible.

Preparation and targeting evaluation of reductant-sensitive oxaliplatin-loaded Fe3O4 nanoparticles / 药学学报

The non-specific accumulation and release of drugs are the main factors affecting the therapeutic effect as well as causing toxic side effects of chemotherapeutic drugs. Nowadays, the application of nanotechnology and responsive drug release is an important strategy to improve the tumor-specific accumulation of drugs and reduce their side effects. In this study, an α-enolase targeted peptide (ETP)-modified polyethylene glycol poly-lysine block copolymer loaded with oxaliplatin prodrug was synthesized first, and then, polymer-coating Fe3O4 nanoparticles were prepared by phase transfer dialysis method to improve the blood circulation stability and tumor targeting of oxaliplatin. At the same time, the physicochemical properties, reductant-responsive drug release, cellular uptake, tumor targeting and other biological functions of ETP modified oxaliplatin-loaded Fe3O4 nanoparticles were studied in vitro and in vivo. First, the results of reductant-triggered drug release study showed that the drug-loaded nanoparticles could achieve rapid release of more than 80% of the prototype oxaliplatin within 3 h under the reduction conditions simulating the tumor cytoplasmic microenvironment. Secondly, the results of flow cytometry showed that the modification of ETP could increase the ratio of cellular uptake of drug-loaded nanoparticles in tumor cells, and the way that drug-loaded nanoparticles endocytosed by tumor cells were mainly through the energy-dependent and receptor protein and fossin-mediated endocytosis pathway. The animal procedures were approved by the Institutional Animal Care and Use Committee of School of Pharmacy of Fudan University. Moreover, the results of pharmacokinetic experiment showed that the area under the curve (AUC0-∞) of oxaliplatin could be significantly increased by nano-formulation which was about 5 times than that of free oxaliplatin. Besides, the pharmacokinetic results also showed that the drug-loaded Fe3O4 nanoparticles constructed by covalent linkage and chelation had good overall stability in vivo. Finally, the in vivo imaging results showed that ETP modification could increase tumor accumulation of drug-loaded nanoparticles, which would be conducive to the efficacy of oxaliplatin in tumor lesions. In summary, the oxaliplatin-loaded Fe3O4 nanoparticles with the capability of reductant-responsive drug release have good drug release characteristics, blood circulation stability and tumor targeting ability, and have the potential to improve the anti-tumor therapeutic effect of oxaliplatin.

Value of urinary C-terminal agrin fragment in monitoring the progression of early kidney injury in type 2 diabetic patients / 中华检验医学杂志

Objective:This study aimed to explore the feasibility and clinical value of monitoring the progression of early kidney injury in type 2 diabetic patients by assessment of the urinary C-terminal agrin fragment (uCAF) with enzymatic chemiluminescence immunoassay.Methods:A total of 251 patients with type 2 diabetes, who attended the Second Affiliated Hospital of Wenzhou Medical University from October 2018 to March 2020, were included in this retrospective analysis. One hundred and fifty-six participants undergoing health check-up at the Second Affiliated Hospital of Zhejiang University School of Medicine in February 2021 served as controls. Basic clinical information, glycosylated hemoglobin type A 1c and serum creatinine values were recorded, and urine specimens were collected for urinary creatinine, urinary α 1 microglobulin(uα 1M), urinary immunoglobulin G (uIgG), urinary albumin, urinary N-Acetyl-B-D-glycosaminidase (uNAG) and uCAF measurements. Based on the estimated glomerular filtration rate (eGFR), 251 patients were classified into G1~G5 stage groups with 116, 22, 28, 55 and 30 patients in each group. One hundred and sixty-six patients with early diabetic kidney disease (stage G1-G3) were divided into subgroups A1 (79), A2 (48) and A3 (39) according to the urinary albumin/creatinine ratio (UACR), the uα1M levels were divided into uα1M subgroup 1 (83 cases), uα1M subgroup 2 (42 cases), and uα1M subgroup 3 (41 cases), and uIgG subgroup 1 (83 cases), uIgG subgroup 2 (42 cases), and uIgG subgroup 3 (41 cases) according to uIgG levels. The Spearman method was used to analyze the correlation between uCAF levels and eGFR, UACR, uα1M and uIgG levels. Results:(1) The linear range of the uCAF detected by enzymatic chemiluminescence immunoassay was 3.97-2 000.00 ng/ml, with a detection limit of 2.28 ng/ml, intra-batch coefficients of variation of 1.15% and 1.57%, inter-batch coefficients of variation of 1.63% and 5.78%, and a biological reference interval of <95.35 μg/g Cr. (2) The uCAF level and positive rate (UACR≥30 mg/g) increased with the decrease of eGFR from G1-G3, uCAF level was negatively correlated with eGFR value ( r=-0.543, P<0.000 1), and the positive rate increased from 24.14% (28/116) to 85.71% (24/28) from G1-G3. The uCAF level and positivity rate decreased with the decrease of eGFR from G4 to G5. uCAF level was positively correlated with eGFR value ( r=0.495, P<0.001), and the positivity rate decreased from 30.91% (17/55) to 23.33% (7/30) from G4 to G5. (3) In patients with early diabetic kidney disease, uCAF levels and positivity rates increased gradually with the increase of UACR. uCAF levels were positively correlated with UACR values ( r=0.602, P<0.001), and the uCAF positivity rate reached 21.52% (17/79) in the A1 subgroup. (4) uCAF level was positively correlated with uα1M and uIgG levels in patients with early diabetic kidney disease ( r=0.757, 0.596, both P<0.001). Conclusion:Analytical performance of enzyme chemiluminescence immunoassay for the detection of CAF is satisfactory and could be used a biomarker for monitoring damage and progression of early diabetic kidney disease in patients with type 2 diabetes.

Analysis of application value on acute kidney injury biomarkers / 中华检验医学杂志

Acute kidney injury is a common and severe clinical event, the morbidity and mortality of acute kidney injury are increasing steadily, which is related with heavy burden to the country and social economy. Early diagnosis and intervention could significantly reduce the occurrence and progression of acute kidney injury. Therefore, it is of particular importance to find sensitive, specific, and economic biomarkers for acute kidney injury. In recent years, efforts have been made on exploring proteins in blood and urine as biomarkers of acute kidney injury. Present review summarizes progress in this field based on results of recent basic and clinical research.

Clinical value of endoscopic stricturotomy under balloon-assisted enteroscopy in the treatment of benign jejuno-ileal stenosis / 中华消化杂志

Objective:To evaluate the efficacy and safety of endoscopic stricturotomy (EST) under balloon-assisted enteroscopy (BAE) in treatment of benign jejuno-ileal stenosis.Methods:From December 2015 to August 2021, at the Air Force Medical Center, 41 patients who were diagnosed with benign jejuno-ileal stenosis underwent BAE deep small bowel EST and/or surgery due to ineffective or ineffective drug treatment were retrospectively analyzed. Twenty-one patients were treated with EST (EST group) and 20 patients were treated with surgery (surgery group). The etiology and follow-up time were analyzed, the general conditions (male proportion and age), the immediate technical success rate (the percentage of the stenosis that the enteroscope could pass through after EST in the total number of treated stenoses), the incidence of complications (including perforation, bleeding, etc.), the symptom remission rates at 3-month, 6-month, and 1-year after treatment (the percentage of patients with complete or partial remission in the total number of patients), cumulative symptom-free survival rate (no obstruction-related symptoms after EST or surgery till the last follow-up) and cumulative surgery-free survival rate of two groups were compared. Chi-square test, independent t-test, Fisher′s exact probability method and Kaplan-Meier analysis were used for statistical analysis. Results:The main etiology of stricture of EST group and surgery group was Crohn′s disease (71.4%, 15/21 and 60.0%, 12/20, respectively), and the median follow-up time was 12 months (6 to 46 months) and 45 months (14 to 73 months), respectively. There were no significant differences in male proportion, age, immediate technical success rate and incidence of complication between EST group and surgery group (57.1%, 12/21 vs. 65.0%, 13/20; (45.2±17.4) years old vs. (43.1±20.3) years old; 95.3%, 41/43 vs. 100.0%, 30/30; 26.9%, 7/26 vs. 10.0%, 2/20, all P>0.05). In the EST group, 9.5% (2/21) of the patients received surgery because of perforation during EST, 76.2% (16/21) of the patients did not need surgery after EST, and the median symptom-free survival time of patients without symptoms in EST group was 13.3 months. There was no significant difference in the symptom remission rate at 3-month after treatment between EST group and the surgery group (17/19 vs. 100.0%, 20/20, P>0.05). The symptom remission rate at 6-month and 1-year of EST group were lower than those of the surgery group (15/19 vs. 100.0%, 20/20; 8/11 vs. 100.0%, 20/20), and the differences were statistically significant (both were Fisher′s exact probability method, P=0.047 and 0.037). The cumulative symptom-free survival rates at 3-month, 6-month and 1-year of EST group and surgery group were 66.0% vs. 90.0%, 61.0% vs. 85.0% and 54.0% vs. 80.0%, respectively.The results of Kaplan-Meier analysis indicated that there was no significant difference in the symptom-free survival curve between two groups ( P>0.05). The 3-month, 6-month and 1-year cumulative surgery-free survival rates after treatment in EST group were 90.0%, 81.0% and 73.0%, respectively. The 3-month, 6-month and 1-year cumulative surgery-free survival rates after treatment in surgery group were all 100.0%. Conclusion:EST under BAE is technically feasible, and safe in the treatment of benign jejuno-ileal stenosis, and can effectively relieve clinical obstruction symptoms and avoid or delay surgery in the short term.

Comparison of the detection rates of colorectal cancer liver metastasis using different MRI sequences and enhanced CT / 中华肝胆外科杂志

Objective:To study the detection rates of using different MRI sequences and enhanced CT in colorectal cancer liver metastasis (CRLM).Methods:The imaging data of CRLM patients who were treated at Peking University Third Hospital from March 2018 to September 2021 were retrospectively analyzed. Sixty-six CRLM lesions with a maximum diameter ≤10 mm were selected. Different MRI sequences such as T 1 weighted imaging (T 1WI), T 2 weighted imaging (T 2WI), diffusion weighted imaging (DWI), dynamic enhanced phase of MRI (MR-Dyn), gadolinium-etoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA), enhanced hepatobiliary phase of MRI (HBP) and CT enhancement phase (CT-Dyn) were reviewed independently to determine whether the target lesions were detected. The pathological results were used as the gold standard. Paired chi-square test was used to compare the detection rate of CRLM in each group. Results:Among the 66 liver metastases, 15, 31, 55, 21, 56 and 20 were detected by T 1WI, T 2WI, DWI, MR-Dyn, HBP and CT-Dyn, respectively. Their detection rates were 22.7%, 47.0%, 83.3%, 31.8%, 84.8% and 30.3%, respectively. The detection rates of HBP and DWI were higher than those of T 2WI, MR-Dyn, CT-Dyn and T 1WI, respectively (all P<0.05). The detection rate of T 2WI was higher than that of MR-Dyn, CT-Dyn and T 1WI (all P<0.05). The detection efficiencies of non-contrast MRI and Gd-EOB-DTPA enhanced MRI for CRLM were highly consistent ( Kappa=0.745). Conclusions:The detection rates of HBP, DWI and T 2WI for CRLM were high. Non-contrast MRI could replace Gd-EOB-DTPA enhanced MRI for detection of large CRLM.