GPS2 promotes erythroid differentiation in K562 erythroleukemia cells primarily via NCOR1.

G protein pathway suppressor 2 (GPS2) has been shown to play a pivotal role in human and mouse definitive erythropoiesis in an EKLF-dependent manner. However, whether GPS2 affects human primitive erythropoiesis is still unknown. This study demonstrated that GPS2 positively regulates erythroid differentiation in K562 cells, which have a primitive erythroid phenotype. Overexpression of GPS2 promoted hemin-induced hemoglobin synthesis in K562 cells as assessed by the increased percentage of benzidine-positive cells and the deeper red coloration of the cell pellets. In contrast, knockdown of GPS2 inhibited hemin-induced erythroid differentiation of K562 cells. GPS2 overexpression also enhanced erythroid differentiation of K562 cells induced by cytosine arabinoside (Ara-C). GPS2 induced hemoglobin synthesis by increasing the expression of globin and ALAS2 genes, either under steady state or upon hemin treatment. Promotion of erythroid differentiation of K562 cells by GPS2 mainly relies on NCOR1, as knockdown of NCOR1 or lack of the NCOR1-binding domain of GPS2 potently diminished the promotive effect. Thus, our study revealed a previously unknown role of GPS2 in regulating human primitive erythropoiesis in K562 cells.

BRISC is required for optimal activation of NF-κB in Kupffer cells induced by LPS and contributes to acute liver injury.

BRISC (BRCC3 isopeptidase complex) is a deubiquitinating enzyme that has been linked with inflammatory processes, but its role in liver diseases and the underlying mechanism are unknown. Here, we investigated the pathophysiological role of BRISC in acute liver failure using a mice model induced by D-galactosamine (D-GalN) plus lipopolysaccharide (LPS). We found that the expression of BRISC components was dramatically increased in kupffer cells (KCs) upon LPS treatment in vitro or by the injection of LPS in D-GalN-sensitized mice. D-GalN plus LPS-induced liver damage and mortality in global BRISC-null mice were markedly attenuated, which was accompanied by impaired hepatocyte death and hepatic inflammation response. Constantly, treatment with thiolutin, a potent BRISC inhibitor, remarkably alleviated D-GalN/LPS-induced liver injury in mice. By using bone marrow-reconstituted chimeric mice and cell-specific BRISC-deficient mice, we demonstrated that KCs are the key effector cells responsible for protection against D-GalN/LPS-induced liver injury in BRISC-deficient mice. Mechanistically, we found that hepatic and circulating levels of TNF-α, IL-6, MCP-1, and IL-1ß, as well as TNF-α- and MCP-1-producing KCs, in BRISC-deleted mice were dramatically decreased as early as 1 h after D-GalN/LPS challenge, which occurred prior to the elevation of the liver injury markers. Moreover, LPS-induced proinflammatory cytokines production in KCs was significantly diminished by BRISC deficiency in vitro, which was accompanied by potently attenuated NF-κB activation. Restoration of NF-κB activation by two small molecular activators of NF-κB p65 effectively reversed the suppression of cytokines production in ABRO1-deficient KCs by LPS. In conclusion, BRISC is required for optimal activation of NF-κB-mediated proinflammatory cytokines production in LPS-treated KCs and contributes to acute liver injury. This study opens the possibility to develop new strategies for the inhibition of KCs-driven inflammation in liver diseases.

VPS37C facilitates erythroid differentiation by promoting EKLF stability.

The process of erythroid differentiation is orchestrated at the molecular level by a complex network of transcription factors. Erythroid Krüppel-like factor (EKLF/KLF1) is a master erythroid gene regulator that directly regulates most aspects of terminal erythroid differentiation. However, the underlying regulatory mechanisms of EKLF protein stability are still largely unknown. In this study, we identified Vacuolar protein sorting 37 C (VPS37C), a core subunit of the Endosomal sorting complex required for transport-I (ESCRT-I) complex, as an essential regulator of EKLF stability. Our study showed that VPS37C interacts with EKLF and prevents K48-linked polyubiquitination of EKLF and proteasome-mediated EKLF degradation, thus enhancing EKLF protein stability and transcriptional activity. VPS37C overexpression in murine erythroleukemia (MEL) cells promotes hexamethylene bisacetamide (HMBA)-induced erythroid differentiation manifested by up-regulating erythroid-specific EKLF target genes and increasing benzidine-positive cells. In contrast, VPS37C knockdown inhibits HMBA-induced MEL cell erythroid differentiation. Particularly, the restoration of EKLF expression in VPS37C-knockdown MEL cells reverses erythroid-specific gene expression and hemoglobin production. Collectively, our study demonstrated VPS37C is a novel regulator of EKLF ubiquitination and degradation, which plays a positive role in erythroid differentiation of MEL cells by enhancing EKLF protein stability.

Mechanical Behavior of Radial Support of a Novel Balloon Expandable Tapered Stent / 医用生物力学

Objective To explore influences of the taper and connecting rib form on supporting performance of the stent, and provide an important scientific basis for structural design and clinical selection of the tapered stent. Methods A nonlinear finite element model for radial support performance of a novel balloon-expandable tapered stent was constructed, and the radial stiffness (RS) and stress distributions of the stent at different tapers (0°, 0.565°and 1.13°) and with different structural forms of stent linker (V-shape, I-shape, C-shape, S-shape, M-shape) were analyzed by plane compression. The relationship between structural design of the vascular stent and its radial support performance was studied. Results The RS of 0°stent, 0.565°stent, 1.13° stent was 2.51, 1.61, 0.85 N/mm, respectively. The RS of 0.565°stent and 1.13° stent was 35.86% and 66.14% lower than that of 0°stent (round straight stent), respectively. Except that the RS of C-shape linker stent was 1.48 N/mm, the RS of I, M, S and V-shape linker stents was not significantly different, which was 2.51, 2.61, 2.41, 2.52 N/mm, respectively, indicating that radial compression resistance of these four linker stents was almost the same. Conclusions Compared with traditional round straight stents, the RS of tapered stents will decrease, and the RS of stents will gradually decrease with the the taper increasing. Among all stent types in this study, except C-shape linker stents, the RS of other linker shapes has little effect on the RS of stents. The radial support performance of the stent can be improved by reducing the taper of the tapered stent, without changing the form of stent connecting ribs.

Clinical outcomes of reverse shoulder arthroplasty for the treatment of failed fixation of proximal humeral fracrtures in the elderly patients / 中国骨伤

OBJECTIVE@#To evaluate the clinical outcomes of reverse total shoulder arthroplasty as a revision procedure for the failed fixation of proximal humeral fractures in the elderly patients.@*METHODS@#A retrospective analysis was performed on 8 patients with failed internal fixation of proximal humeral fractures from May 2014 to March 2020, including 3 males and 5 females, aged from 65 to 75 years old. All 8 patients underwent reverse total shoulder arthroplasty, and the mean time between initial fixation and reverse total shoulder arthroplasty ranged from 8 to 16 months. Range of motion(ROM), University of California at Los Angeles(UCLA) shoulder score, visual analogue scale (VAS), self-rating anxiety scale(SAS), and Constant-Murley score of shoulder function were assessed pre-operatively and at the last follow-up. Complications relating to the surgery were recorded.@*RESULTS@#All 8 patients successfully followed up. The mean follow-up after reverse total shoulder arhroplasty ranged from 16 to 28 months. The range of motion (forward flexion, external rotation, abduction and internal rotation) of the affected shoulder was significantly improved after surgery, and the post-operative VAS, SAS and UCLA scores were also significantly improved. For the Constant-Murley score of shoulder joint function, the total scores and the subscores of pain, daily activities, range of motion and strength test at the last follow-up were all significantly improved. Scapular glenoid notch was observed in patient, which was evaluated as grade 1 on imaging. All the other patients did not develop specific or non-specific complications.@*CONCLUSION@#Reverse total shoulder arhroplasty is an appropriate treatment as a revision surgery for failed fixation of proximal humeral fractures. It has shown satisfactory clinical outcomes, accelerating the rehabilitation of shoulder function and improving the quality of life.

Awareness of HPV and HPV vaccine and willingness to be vaccinated among parents of children aged 9-14 / 公共卫生与预防医学

Objective To investigate the HPV vaccination status of children aged 9-14 years, parents’ vaccine-related cognition, willingness to vaccinate children and their influencing factors. Methods From January to April 2021, the convenience sampling method was used to collect data based on the online platform and the Department of Pediatrics and Adolescent Gynecology of the Children's Hospital of Zhejiang University School of Medicine. The data were analyzed by descriptive analysis, Chi-square test, and logistic regression. Results A total of 864 questionnaires were collected, and 846 valid questionnaires were obtained after screening, with an effective rate of 97.9%. 13.57% of mothers and 3.09% of girls were vaccinated, and the vaccine awareness rate was 68.43%. 87.22% of parents were willing to bring their children for vaccination. Risk perception (OR=4.79, 95% CI: 2.22-10.35), willingness to vaccinate themselves (OR =29.01, 95% CI: 12.62-66.69), awareness of sex education (OR =3.73, 95% CI: 1.08-12.83) and whether the vaccines were free (P<0.001) were related to whether parents were willing to vaccinate their children. Conclusion Parents of children aged 9-14 have high awareness of HPV and HPV vaccine and are willing to vaccinate their children with HPV vaccine , but the vaccination rate in children is low. Disease perception, willingness to vaccinate, awareness of sex education, and whether vaccines are free are all the factors influencing parents' willingness to vaccinate children.

Candidate biomarkers in brown adipose tissue for post-mortem diagnosis of fatal hypothermia.

Post-mortem diagnosis of fatal hypothermia (FHT) is challenging in forensic practice because traditional morphological and biochemical methods lack specificity. Recent studies have reported that brown adipose tissue (BAT) is activated during cold-induced non-shivering thermogenesis in mammals, but BAT has not been used to diagnose FHT. The aim of this study was to identify novel biomarkers in BAT for FHT based on morphological changes and differential protein expression. Two FHT animal models were created by exposing mice to 4 or -20 °C at 50% humidity. Morphologically, the unilocular lipid droplet content was significantly increased in BAT of FHT model mice compared with that of control mice. Proteomics analysis revealed a total of 283 and 266 differentially expressed proteins (DEPs) between the 4 or -20 °C FHT subgroups and control group, respectively. In addition, 140 proteins were shared between the FHT subgroups. GO and KEGG analyses revealed that the shared DEPs were mainly enriched in pathways associated with metabolism, oxidative phosphorylation, and thermogenesis. Further screening (|log2FC| > 1.6, q-value (FDR) < 0.05) identified GMFB, KDM1A, DDX6, RAB1B, SHMT-1, CLPTM1, and LMF1 as candidate biomarkers of FHT. Subsequent validation experiments were performed in FHT model mice using classic immunohistochemistry and western blotting. RAB1B and GMFB expression was further verified in BAT specimens from human cases of FHT. The results demonstrate that BAT can be used as a target organ for FHT diagnosis employing RAB1B and GMFB as biological markers, thus providing a new strategy for the post-mortem diagnosis of FHT in forensic practice.

Bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin lymphoma: a multicenter, open-label, single-arm, phase 3 study / 中华医学杂志(英文版)

BACKGROUND@#Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment.@*METHODS@#This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR.@*RESULTS@#A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities.@*CONCLUSION@#Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients.@*CLINICAL TRIAL REGISTRATION@#ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621.

Clinical oberservation on rotator cuff suture threader and strapping suture in meniscus tear under arthroscopy / 中国骨伤

OBJECTIVE@#To explore clinical effect of arthroscopic meniscus tear strapping suture by rotator cuff suture threader.@*METHODS@#Forty patients with meniscus tear injury admitted from July 2015 to May 2019, including 27 males and 13 females, aged from 20 to 55 years old with an average of (36.0±1.4) years old. Menisci laceration was sutured with rotator cuff suture thread under arthroscopy. Postoperative complication was observed, Lysholm knee joint score before and after operation at 12 months were used to evaluate clinical effects, visual analogue scale (VAS) and range of knee flexion and extension were applied to evaluate recovery of pain and function.@*RESULTS@#All patients were followed up from 12 to 15 months with an average of (12.6±0.7) months.No complication such as joint effusion, suture failure occurred. Two patients occurred mild pain after activity without clinical physical abnormality, and 1 patient manifested moderate pain with joint space tenderness, the other rest without abnormal. Lysholm knee joint score was increased from (49.55±1.21) preoperatively to (98.95±0.42) at 12 months after operation, VAS score decreased from (5.18±0.78)preoperatively to (1.03±0.77) at 12 months after operation, and range of knee joint flexion and extension activity increased from (50.63±9.20)°preoperatively to (130.38±4.99)°after operation, and there were statistical differences in Lysholm knee joint score, VAS and range of knee joint flexion and extension activity (@*CONCLUSION@#Arthroscopic strapping suture by rotator cuff suture threading device applies to most meniscus injuries, including medial meniscus posterior horn tears, lateral meniscus body tears and lateral meniscus posterior horn tears. This technique meets the need of full-internal meniscus suture without specialmeniscus suture, and has advantages of convenient operation, less complications and good postoperative function.

A novel approach for the forensic diagnosis of drowning by microbiological analysis with next-generation sequencing and unweighted UniFrac-based PCoA.

The diagnosis of drowning is one of the major challenges in forensic practice, especially when the corpse is in a state of decomposition. Novel indicators of drowning are desired in the field of forensic medicine. In the past decade, aquatic bacteria have attracted great attention from forensic experts because they can easily enter the blood circulation with drowning medium, and some of them can proliferate in the corpse. Recently, the advent of next-generation sequencing (NGS) has created new opportunities to efficiently analyze whole microbial communities and has catalyzed the development of forensic microbiology. We presumed that NGS could be a potential method for diagnosing drowning. In the present study, we verified this hypothesis by fundamental experiments in drowned and postmortem-submersed rat models. Our study revealed that detecting the bacterial communities with NGS and processing the data in a transparent way with unweighted UniFrac-based principal coordinates analysis (PCoA) could clearly discriminate the skin, lung, blood, and liver specimens of the drowning group and postmortem submersion group. Furthermore, the acquired information could be used to identify new cases. Taken together, these results suggest that we could build a microbial database of drowned and postmortem-submersed victims by NGS and subsequently use a bioinformatic method to diagnose drowning in future forensic practice.

Method development and validation of LC-MS/MS-based assay for the simultaneous quantitation of trastuzumab and pertuzumab in cynomolgus monkey serum and its application in pharmacokinetic study.

We present a simple and robust LC-MS/MS assay for the simultaneous quantitation of an antibody cocktail of trastuzumab and pertuzumab in monkey serum. The LC-MS/MS method saved costs, decreased the analysis time, and reduced quantitative times relative to the traditional ligand-binding assays. The serum samples were digested with trypsin at 50°C for 60 min after methanol precipitation, ammonium bicarbonate denaturation, dithiothreitol reduction, and iodoacetamide alkylation. The tryptic peptides were chromatographically separated using a C18 column (2.1 × 50 mm, 2.6 µm) with mobile phases of 0.1% formic acid in water and acetonitrile. The other monoclonal antibody, infliximab, was used as internal standards to minimize the variability during sample processing and detection. A unique peptide for each monoclonal antibody was simultaneously quantified using LC-MS/MS in the multiple reaction monitoring mode. Calibration curves were linear from 2.0 to 400 µg/mL. The intra- and inter-assay precision (%CV) was within 8.9 and 7.4% (except 10.4 and 15.1% for lower limit of quantitation), respectively, and the accuracy (%Dev) was within ±13.1%. The other validation parameters were evaluated, and all results met the acceptance criteria of the international guiding principles. Finally, the method was successfully applied to a pharmacokinetics study after a single-dose intravenous drip administration to cynomolgus monkeys.

Analysis of Pulmonary Microbial Diversity in Patients with Advanced Lung Cancer Based on High-throughput Sequencing Technology / 中国肺癌杂志

BACKGROUND@#The pulmonary microbiome is closely related to the occurrence of pulmonary diseases. The morbidity and mortality of lung cancer are relatively high in the world. It has been confirmed that lung microecology changes in lung cancer patients compared with healthy individuals. Furthermore, the abundance of some bacterial species shows obvious changes, suggesting their potential use as a microbial marker for the detection of lung cancer. The composition of the pulmonary microbiome in patients with different histological types of lung cancer has not been determined. We aim to study the correlation and difference of microbiome between different histological types of lung cancer.@*METHODS@#Illumina HiSeq high-throughput sequencing technology was used to sequenced the 16S rDNA V3-V4 region of bacterial in sputum samples of patients with advanced lung cancer.@*RESULTS@#It was found that Streptococcus, Neisseria and Prevotella were the main bacteria of lung cancer patients. Advantage bacterium group differ between different histological types of lung cancer. Adenocarcinoma (AD) group was dominated by Streptococcus and Neisseria, followed by Veillonella. Small cell lung cancer (SCLC) group was dominated by Neisseria, followed by Streptococcus. Squamous carcinoma (SCC) group was dominated by Streptococcus, followed by Veillonella. Combined small cell lung cancer (C-SCLC) group was dominated by Streptococcus, followed by Prevotella.@*CONCLUSIONS@#The pulmonary bacterial microbiome of lung cancer of different histological types is different. This experiment enrichs the pulmonary bacterial microbiome data of lung cancer and fills the gap of pulmonary microbiome of small cell lung cancer.

Clinical significance of multidisciplinary team collaboration for the treatment of hip fractures in the elderly / 中华老年医学杂志

Objective To investigate the clinical value of multidisciplinary team collaboration (MDT)for the treatment of hip fractures in elderly patients.Methods A total of 157 elderly patients with hip fractures meeting inclusion and exclusion criteria were admitted into our department from 1st September 2015 to 31st December 2017.The patients were randomly divided into the traditional treatment group and the MDT group.The differences in treatment time,cost,postoperative outcomes and postoperative Harris hip function score were compared between the two groups.Results The preoperative length of stay,total hospitalization time and the time of antibiotic use after operation were shorter in the MDT treatment group than in the traditional treatment group (all P ＜0.05).Total costs of treatment and costs for bed,laboratory examinations,and nursing were lower in the MDT treatment group than in the traditional treatment group(all P＜0.05).The off-bed activity time after operation was earlier in the MDT treatment group with femoral neck fractures [(5.36 ± 1.56)d vs.(10.07±2.26)d,P =0.002]than in the traditional treatment group with intertrochanteric fracture patients [(30.26 ± 3.01) d vs.(42.28 ± 3.52) d,P =0.017].Harris hip function score was higher in the MDT treatment group than in the traditional treatment group at 3 and 6 months after surgery (P ＜ 0.05).Conclusions As compared with the traditional treatment mode,MDT treatment mode can shorten the preoperative stay in bed,the length of hospital stay after surgery and the off-bed activity time after operation,reduce hospitalization costs and postoperative complications,and can promote the recovery of hip joint function in elderly hip fracture patients.

Analysis of correlation between plasma trough level and response of generic imatinib in the treatment of Chinese patients with chronic myeloid leukemia / 中华血液学杂志

Objective: To analyze the correlation between plasma trough level of generic imatinib and its metabolism and clinical outcomes in Chinese patients with chronic myeloid leukemia in chronic phase (CML-CP) . Methods: The 21 patients with CML-CP who enrolled in a clinical trial YMTN 1.0 from Oct 11(th), 2012 to May 8(th), 2013 and received generic imatinib were as study subjects. The correlation between steady plasma trough levels of imatinib and its metabolism with clinical response, age, weight and body surface area (BSA) were evaluated. Results: ①The mean steady plasma trough level of generic imatinib and its metabolism was (1 185.07±417.91) μg/L and (251.53±76.50) μg/L, respectively. ②Age, weight and BSA has no significant effects on plasma trough level of generic imatinib and its metabolism (P>0.05) . ③Patients with steady plasma trough level of generic imatinib more than 1 000 μg/L are possible to have higher major molecular response (MMR) /complete molecular response (CMR) rate than those below 1 000 μg/L (42% vs 0, P<0.05) . Conclusion: Plasma trough levels of generic imatinib varied in CML patients. The steady plasma trough levels of generic imatinib is maybe related to molecular response in CML patients.

Relationship between the Degeneration and Regeneration of Neuromuscular Junction and Wound Age during the Repair of Mouse Skeletal Muscle Contusion / 法医学杂志

Objective To investigate the morphological changes in the degeneration and regeneration of neuromuscular junctions （NMJ） during the repair of mouse skeletal muscle contusion and discuss the correlation between the degeneration and regeneration of NMJ and wound age. Methods A total of 50 healthy adult male mice were randomly divided into 10 groups, including 9 experimental groups and 1 control group. Immunofluorescent staining was applied, and neurofilament was marked with neurofilament protein-H （NF-H）, presynaptic membrane was marked with synaptophysin （Syn）, presynaptic membrane was marked with acetylcholine receptor （AChR）. Morphological changes of NMJ regeneration at different time points after mouse skeletal muscle contusion were detected. Results The neurofilament and presynaptic membrane of NMJ at the junction of contusion zones began to degrade after contusion, and completed degradation at about 3 d post-injury. Then they gradually regenerated, roughly completing the regeneration at about 21 d and basically reaching the control group level. The ratio of presynaptic membrane quantity to presynaptic membrane quantity showed a trend of decreasing then rising and finally reaching the control level. Conclusion During the repair of mouse skeletal muscle contusion, the morphological changes and wound age of the NMJ at the junction of contusion zones have a close correlation, which is expected to be one of the biological indicators for forensic skeletal muscle wound age estimation.

Expression of Nrf2 in Different Cells after Human Cerebral Cortex Contusion / 法医学杂志

Objective To observe the expression changes of nuclear factor-erythroid derived 2-related factors （Nrf2） in different cells at different time points after human cerebral cortex contusion, and to discuss its application in brain wound age estimation. Methods Thirty-six human brain tissues were selected, of which 6 were for control and 30 were cortical contusion at different time points post-injury, which were divided into 0-1 h, 3-6 h, 1-3 d, 5-7 d, and 10-14 d post-injury groups, with 6 cases in each group. Based on paraffin embedded sections, HE staining was used to observe the morphological changes post-injury, and double immunofluorescence staining was used to detect the expression of Nrf2 in neurons, astrocytes, and microglia. The number of positive cells was counted and statistical analysis was made. Results The number of neurons decreased 1-3 d post-injury. The expression of Nrf2 cells in neurons increased after injury, and the rate of positive cells peaked at 1-3 d post-injury. Glial cells were activated 1-3 d post-injury, and the activation peaked at 5-7 d post-injury. The cerebromalacia began to form at 10-14 d post-injury. Glial fibrillary acidic protein （GFAP） positive cells in mice increased gradually after injury and peaked at 5-7 d post-injury, while the proportion of Nrf2 in GFAP positive cells was relatively stable. After injury, ionized calcium-binding adapter molecule 1 （IBA1） positive cells increased and activated gradually. The expression proportion of Nrf2 in IBA1 positive cells increased gradually, reached its peak at 5-7 d post-injury, and then decreased. Conclusion The expression of Nrf2 in different cells involves in the biological function of different cells post-injury, and the dynamic expression of single cells has a time-dependent pattern. This may provide a new reference index for the wound age estimation of brain contusion in human.

Relationship between Expression Changes of CB2R and Wound Age of Brain Contusion in Mice / 法医学杂志

Objective To investigate the expression of cannabinoid type 2 receptor （CB2R） at different time points after brain contusion and its relationship with wound age of mice. Methods A mouse brain contusion model was established with PCI3000 Precision Cortical Impactor. Expression changes of CB2R around the injured area were detected with immunohistochemical staining, immunofluorescent staining and Western blotting at different time points. Results Immunohistochemical staining results showed that only a few cells in the cerebral cortex of the sham operated group had CB2R positive expression. The ratio of CB2R positive cells gradually increased after injury and reached the peak twice at 12 h and 7 d post-injury, followed by a decrease to the normal level 28 d post-injury. The results of Western blotting were consistent with the immunohistochemical staining results. Immunofluorescent staining demonstrated that the changes of the ratio of CB2R positive cells in neurons, CB2R positive cells in monocytes and CB2R positive cells in astrocytes to the total cell number showed a single peak pattern, which peaked at 12 h, 1 d and 7 d post-injury, respectively. Conclusion The expression of CB2R after brain contusion in neurons, monocytes and astrocytes in mice suggests that it is likely to be involved in the regulation of the biological functions of those cells. The changes in CB2R are time-dependent, which suggests its potential applicability as a biological indicator for wound age estimation of brain contusion in forensic practice.

Aptamer-drug conjugate: targeted delivery of doxorubicin in a HER3 aptamer-functionalized liposomal delivery system reduces cardiotoxicity.

INTRODUCTION: The toxic side effects of doxorubicin (DOX) have limited its use in chemotherapy. Neither liposomal DOX nor pegylated liposomal DOX are able to completely resolve this issue. This is a proof-of-concept study testing aptamer-drug conjugate (ApDC) targeted delivery systems for chemotherapeutic drugs. METHODS: Aptamer library targeting human epidermal growth factor receptor 3 (HER3) was screened and affinity was determined by enzyme-linked immunosorbent assay. Specificity was tested in MCF-7HER3-high, BT474HER3-high, and 293THER3-negative cells using flow cytometry and confocal microscopy. We further developed a HER3 aptamer-functionalized liposome encapsulating DOX and the efficiency of this ApDC was detected by cellular uptake analysis and cell viability assay. In MCF-7 tumor-bearing mice, tumor targeting evaluation, efficacy, toxicity and preliminary pharmocokinetic study was performed. RESULTS: The candidate #13 aptamer had highest affinity (Kd =98±9.7 nM) and specificity. ApDC effectively reduces the half maximal inhibitory concentration of DOX compared with lipsome-DOX and free DOX. In vivo imaging and preliminary distribution studies showed that actively targeted nanoparticles, such as Apt-Lip-DOX molecules, could facilitate the delivery of DOX into tumors in MCF-7-bearing mice. This targeted chemotherapy caused greater tumor suppression than other groups and alleviated side effects such as weight loss, low survival rate, and organ (heart and liver) injury demonstrated by H&E staining. CONCLUSION: The results indicate that targeted chemotherapy using the aptamer-drug conjugate format could provide better tolerability and efficacy compared with non-targeted delivery in relatively low-dose toxic drugs.

Effects of the Aerobic Exercise on the AGE-RAGE Axis and NF-κB Pathway in T2DM Rats / 昆明医科大学学报

Objective The aim of this study was to evaluate the effects of aerobic exercise on AGE-RAGE axis and nuclear factor kappa B pathway in type 2 diabete rats and to discuss the rehabilitation function of aerobic exercise in type 2 diabetes mellitus (T2DM) . Methods After the 8-week-old male Wistar rats were fed with a high sugar and high fat for 4 weeks, type 2 diabetes rats were induced by streptozotocin way. 30 type 2 diabetes rats were allocated at random into 3 groups:type 2 diabetes mellitus (T2DM), low- and moderate- intensity exercise groups (T2DML, T2DMM) . Exercise group performed exercise protocol respectively. The AGEs, RAGE and NF-κB levels of the blood,muscle and heart were detected by ELISA method respectively. Results Compared with T2DM group, the NF-κB level of the blood, muscle and heart were decreased in T2DML group significantly (P<0.05);the AGEs, RAGE and NF-κB level of the blood, muscle and heart were decreased in T2DMM group significantly ( <0.05) . Compared with T2DML group, the NF-κB level of the blood, muscle and heart were decreased in T2DMM group significantly ( <0.05) . Conclusion Moderate intensity aerobic exercise inhibits AGE-RAGE axis and NF-κB pathway, which may decrease oxidative stress and inflammation, and so reduce tissue injure for the prevention and treatment of complications of the T2DM.

Application of drilling columnar autogenous iliac bone graft and clinical analysis of postoperative complications in the donor bone region / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the clinical effect of drilling columnar autogenous iliac bone graft and analyze the effect of bone grafting on postoperative complications in donor site.</p><p><b>METHODS</b>From March 2014 to October 2016, 68 patients with autogenous iliac bone graft were retrospectively analyzed, and divided into drilling group and osteotomy group, 34 patients in each group. In drilling group, there were 24 males and 10 females with an average age of (40.06±5.60) years old ranging from 23 to 53 years old;in osteotomy group, there were 26 males and 18 females with an average age of (39.32±6.44) ranging from 22 to 56 years old. The operative time of bone extraction, blood loss in donor area, healing time of donor site and postoperative donor site complications were observed and compared between the two groups. VAS score was used to evaluate the pain of donor site in different periods after operation.</p><p><b>RESULTS</b>All patients were followed up for 12 to 24 months, with an average of 16.9 months in drilling group and 17.1 months in osteotomy groups. The bone healing structure was displayed in the recipient area in two groups, the effect of autogenous iliac bone grafting was good. There was no significant difference in operative time between two groups (>0.05). There was significant difference between two groups in the amount of donor site bleeding and the time of donor site wound healing(<0.05). Postoperative complications(iliac depression and numbness) were significantly different between two groups (<0.05). There was no significant difference in VAS score between two groups at 2 weeks after operation(>0.05). VAS scores of drilling group at 6 months and 1 year after operation were lower than those of osteotomy group (1.85±0.61 vs 2.97±0.67, 0.000; 1.15±0.56 vs 2.41±0.61, 0.000).</p><p><b>CONCLUSIONS</b>When bone graft is no need to have large pieces of special shape or more cortical bone iliac, it is simple to operate and less complications postoperative by drilling type columnar autogenous iliac bone graft. What's more, it has the obvious advantages of promote healing, improve patient quality of life compared with traditional osteotomy.</p>