Synthesis and antibacterial activity evaluation of octapeptin derivatives / 药学学报

Octapeptin has strong antibacterial activity against Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii, while it also has activity against some Gram-positive bacteria. This study used natural octapeptin A3 and B3 as lead compounds for structural modification. Twenty-one peptide derivatives (including A3 and B3) containing eight amino acid residues were prepared by solid-phase synthesis, and evaluated for antibacterial activity and renal cytotoxicity. Among them, three compounds 6, 7 and 17 exhibited broad-spectrum antibacterial activity and significantly enhanced the activity for Gram-positive bacteria while maintaining the activity of Gram-negative bacteria. Several compounds improved the activity for Pseudomonas aeruginosa. Compound 7 was active against all test strains and had relatively low renal cytotoxicity. The results provide a basis for the further development of novel polypeptide antibiotics.

AZD1775 and anti-PD-1 antibody synergistically sensitize hepatoma to radiotherapy / 中华医学杂志(英文版)

BACKGROUND@#Radiation (IR)-induced DNA damage triggers cell cycle arrest and has a suppressive effect on the tumor microenvironment (TME). Wee1, a cell cycle regulator, can eliminate G2/M arrest by phosphorylating cyclin-dependent kinase 1 (CDK1). Meanwhile, programed death-1/programed death ligand-1 (PD-1/PDL-1) blockade is closely related to TME. This study aims to investigate the effects and mechanisms of Wee1 inhibitor AZD1775 and anti-PD-1 antibody (anti-PD-1 Ab) on radiosensitization of hepatoma.@*METHODS@#The anti-tumor activity of AZD1775 and IR was determined by 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide (MTT) assay on human and mouse hepatoma cells HepG2, Hepa1-6, and H22. The anti-hepatoma mechanism of AZD1775 and IR revealed by flow cytometry and Western blot in vitro . A hepatoma subcutaneous xenograft mice model was constructed on Balb/c mice, which were divided into control group, IR group, AZD1775 group, IR + AZD1775 group, IR + anti-PD-1 Ab group, and the IR + AZD1775 + anti-PD-1 Ab group. Cytotoxic CD8 + T cells in TME were analyzed by flow cytometry.@*RESULTS@#Combining IR with AZD1775 synergistically reduced the viability of hepatoma cells in vitro . AZD1775 exhibited antitumor effects by decreasing CDK1 phosphorylation to reverse the IR-induced G2/M arrest and increasing IR-induced DNA damage. AZD1775 treatment also reduced the proportion of PD-1 + /CD8 + T cells in the spleen of hepatoma subcutaneous xenograft mice. Further studies revealed that AZD1775 and anti-PD-1 Ab could enhance the radiosensitivity of hepatoma by enhancing the levels of interferon γ (IFNγ) + or Ki67 + CD8 T cells and decreasing the levels of CD8 + Tregs cells in the tumor and spleen of the hepatoma mice model, indicating that the improvement of TME was manifested by increasing the cytotoxic factor IFNγ expression, enhancing CD8 + T cells proliferation, and weakening CD8 + T cells depletion.@*CONCLUSIONS@#This work suggests that AZD1775 and anti-PD-1 Ab synergistically sensitize hepatoma to radiotherapy by enhancing IR-induced DNA damage and improving cytotoxic CD8 + T cells in TME.

Effects of higher femoral tunnels on clinical outcomes, MRI, and second-look findings in double-bundle anterior cruciate ligament reconstruction with a minimal 5-year follow-up / 中华医学杂志(英文版)

BACKGROUND@#To perform anatomical anterior cruciate ligament reconstruction (ACLR), tunnels should be placed relatively higher in the femoral anterior cruciate ligament (ACL) footprint based on the findings of direct and indirect femoral insertion. But the clinical results of higher femoral tunnels (HFT) in double-bundle ACLR (DB-ACLR) remain unclear. The purpose was to investigate the clinical results of HFT and lower femoral tunnels (LFT) in DB-ACLR.@*METHODS@#From September 2014 to February 2016, 83 patients who underwent DB-ACLR and met the inclusion and exclusion criteria were divided into HFT-ACLR (group 1, n = 37) and LFT-ACLR (group 2, n = 46) according to the position of femoral tunnels. Preoperatively and at the final follow-up, clinical scores were evaluated with International Knee Documentation Committee (IKDC), Tegner activity, and Lysholm score. The stability of the knee was evaluated with KT-2000, Lachman test, and pivot-shift test. Cartilage degeneration grades of the International Cartilage Repair Society (ICRS) were evaluated on magnetic resonance imaging (MRI). Graft tension, continuity, and synovialization were evaluated by second-look arthroscopy. Return-to-sports was assessed at the final follow-up.@*RESULTS@#Significantly better improvement were found for KT-2000, Lachman test, and pivot-shift test postoperatively in group 1 ( P >0.05). Posterolateral bundles (PL) showed significantly better results in second-look arthroscopy regarding graft tension, continuity, and synovialization ( P <0.05), but not in anteromedial bundles in group 1. At the final follow-up, cartilage worsening was observed in groups 1 and 2, but it did not reach a stastistically significant difference ( P >0.05). No statistically significant differences were found in IKDC subjective score, Tegner activity, and Lysholm score between the two groups. Higher return-to-sports rate was found in group 1 with 86.8% (32/37) vs. 65.2% (30/46) in group 2 ( P = 0.027).@*CONCLUSION@#The HFT-ACLR group showed better stability results, better PL, and higher return-to-sports rate compared to the LFT-ACLR group.

SRF-rearranged cellular perivascular myoid tumor: a clinicopathological analysis of two cases / 中华病理学杂志

Objective: To investigate the clinicopathological features, immunophenotype, diagnosis and differential diagnosis of SRF-rearranged cellular perivascular myoid tumor. Methods: Two cases of SRF-rearranged cellular perivascular myoid tumor diagnosed in the Department of Pathology, Fudan University Shanghai Cancer Center from October 2021 to March 2022 were collected. Immunohistochemical staining, fluorescence in-situ hybridization (FISH) and next-generation sequencing (NGS) were performed, and the literature was reviewed. Results: Case 1, a 3-month-old boy presented with a painless tumor of the scalp, measuring about 2 cm in diameter. Case 2, a 3-year-old girl complained with a painless tumor of the knee, measuring approximately 1.5 cm in diameter. Microscopically, the tumor had a clear boundary and showed multinodular growth. The tumor was mainly composed of spindle cells arranged in long intersecting fascicles associated with thin, slit-like or branching ectatic vessels, focally forming hemangiopericytoma-like appearance. The tumor cells were abundant, but there was no obvious atypia. Mitotic figures (3-4/10 HPF) were noted. H-caldesmon and SMA were positive in both cases. Case 1 showed diffuse and strong positivity for Desmin, and focally for CKpan. Ki-67 proliferation index was 20% and 30%, respectively. FISH displayed NCOA2 gene translocation in case 1 and the RELA gene translocation in case 2. NGS detected the SRF-NCOA2 gene fusion in case 1 and the SRF-RELA gene fusion in case 2. Both patients underwent local excisions. During the follow-up of 5-14 months, case 1 had no local recurrence, while case 2 developed local recurrence 1 year post operatively. Conclusions: SRF-rearranged cellular perivascular myoid tumor is a novel variant of perivascular cell tumor, which tends to occur in children and adolescents. The tumor forms a broad morphologic spectrum ranging from a pericytic pattern to a myoid pattern, and include hybrid tumors with a mixture of pericytic and myoid patterns. Due to its diffuse hypercellularity and increased mitotic figures and smooth muscle-like immunophenotype, the tumor is easy to be misdiagnosed as myogenic sarcomas. The tumor usually pursues a benign clinical course and rare cases may locally recur.

Effect of oral fish oil on wound healing in patients with diabetic foot ulcers:a randomized,double-blind,placebo-controlled study / 重庆医学

Objective To investigate the effect of oral fish oil on wound healing and related indexes in patients with diabetic foot ulcer(DFU).Methods A randomized,double-blind,placebo-controlled design was used to recruit 68 patients with DFU aged 18-80 years old in the hospital,and the baseline clinical data of the patients were collected.The patients were randomly divided into experimental group(32 cases,fish oil soft capsule,3 g/d)and control group(33 cases,corn oil soft capsule,3 g/d)by random number generated by Ex-cel,and the intervention lasted for 12 weeks.The primary endpoints included the proportion of complete wound healing and healing area≥50%.The secondary endpoints included wound area,healing time,inflamma-tion index,glucose metabolism index,nutrition related index and wound reinfection.Additionally,the influen-cing factors of wound healing were analyzed.Results After intervention,the proportion of complete wound healing and healing area≥50%in the experimental group was significantly higher than that in the control group(P=0.007,0.039).In the subjects with complete wound healing,the mean healing time in the experi-mental group was shorter than that in the control group,but the difference was not statistically significant(P=0.132).The reduction area of wound area in the experimental group was significantly larger than that in the control group(P=0.045).The decrease of interleukin(IL)-6 and IL-8 in the experimental group was significantly higher than that in the control group(P<0.05).There was no significant difference in the reduc-tion of C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),neutrophil-to-lymphocyte ratio(NLR),glycated hemoglobin A1c(HbA1c)and platelet-to-lymphocyte ratio(PLR)between the two groups(P>0.05).The improvement of prealbumin(PA)in the experimental group was higher than that in the control group,but the difference was not statistically significant(P>0.05).Multivariate logistic regression analysis showed that oral fish oil intervention(OR=6.771,95%CI:1.787-25.652),HbA1c(OR=4.149,95%CI:1.026-16.770)and ulcer type(OR=4.319,95%CI:1.026-18.173)were the influencing factors of wound healing(P<0.05).Conclusion Oral fish oil promotes wound healing in patients with DFU,which may be re-lated to improving the level of chronic inflammation in the body.

Activation of A1 reactive astrocytes in the medullary dorsal horn of rats participates in the chronification of trigeminal neuralgia / 中南大学学报(医学版)

Objective:The activation of astrocytes is an important process in the formation of chronic pain.This study aims to observe the activation of A1 reactive astrocytes in the medullary dorsal horn in the rat model of trigeminal neuralgia,and to explore the mechanism of central sensitization caused by A1 reactive astrocyte. Methods:The adult male rats were randomly divided into a sham group and a chronic constriction injury of infraorbital nerve(ION-CCI)group.The facial mechanical pain threshold and thermal withdrawal latency were measured before the operation and on the 1st,3rd,7th,10th,and 14th day after the operation.After pain behavior observation,the expression of glial fibrillary acidic protein(GFAP)in the medullary dorsal horn was observed by immunohistochemistry and immunofluorescence colocalization of GFAP,complement 3(C3)/S100A10,and 4',6-diamidino-2-phenylindole(DAPI)was analyzed.Primary astrocytes were cultured and randomly divided into a naive group and a DHK group.The DHK group was treated with 1 mmol/L of astrocyte activation inhibitor dihydrokainic acid(DHK).Fura-2/AM was used to stain the astrocytes and the calcium wave of the 2 groups under the stimulation of high potassium was recorded and compared.The expression of C3 was detected by Western blotting. Results:The facial mechanical pain threshold and thermal withdrawal latency of the ION-CCI group were significantly lower than those of the sham group(both P<0.05).There were a large number of GFAP positive astrocytes in the medullary dorsal horn of the ION-CCI group.The fluorescence intensity of GFAP in the ION-CCI group was higher than that in the sham group(P<0.05).GFAP and C3/S100A10 were co-expressed in astrocytes.Compared with the sham group,the fluorescence intensity of C3 and the protein expression of C3 in the ION-CCI group were increased(both P<0.05).The expression of C3 in ION-CCI group was significantly increased(P<0.05).Compared with the naive group,the C3 protein expression was significantly decreased in the DHK group(P<0.05).The intensity of calcium fluorescence was increased after high potassium stimulation in both groups.Furthermore,the peak and increase amplitude of calcium fluorescence in the naive group were much higher than those in the DHK group(both P<0.05). Conclusion:A1 reactive astrocytes in the medullary dorsal horn of trigeminal neuralgia model rats are increased significantly,which may participate in central sensitization of trigeminal neuralgia by impacting astrocyte calcium wave.

Micromorphological characteristics of the pedicle of the lower cervical vertebra / 中国组织工程研究

BACKGROUND:The lower cervical vertebral pedicle is the main stress site of the posterior column of the spine,which is of great significance for the maintenance of the stability of the human center of gravity and the reduction of shock.At present,there are few reports on the characteristics of the internal bone trabeculae,and the characteristics of the joint site of the vertebral pedicle with the articular process and the vertebral body.It is urgent to understand the fine anatomical structure of the vertebral pedicle and the relationship and function of each part. OBJECTIVE:To observe the microanatomical morphology of the vertebral pedicle by Micro-CT scanning of cervical vertebra specimens,and to measure and analyze the microstructure and morphometric parameters of the bone trabecula in the cervical pedicle under normal conditions to evaluate the safety performance of the cervical spine. METHODS:Micro-CT scanning was performed on 31 sets of cervical vertebrae C3-C7.By checking and reconstructing the areas of interest in the bone trabecular within the vertebral pedicle,the morphological characteristics and distribution direction of the bone trabecular within the cervical pedicle were observed,and the bone microstructure parameters were detected,and the differences in the bone microstructure of the C3-C7 vertebral pedicle were analyzed and compared. RESULTS AND CONCLUSION:(1)The Micro-CT images showed that the honeycomb bone trabeculae of the pedicle of the lower cervical spine presented a complex network of microstructures.The trabeculae near the cortical bone were lamellar and relatively compact,extending forward toward the vertebral body and backward toward the articular process lamina.Abatoid bone trabeculae extended into the medullary cavity and transformed into a network structure,and then into rod-shaped bone trabeculae.The rod-shaped bone trabeculae were sparsely distributed in the medullary cavity.(2)Statistical results of morphological parameters of bone trabeculae showed that bone volume fraction values in C4 and C5 were higher than that in C7(P＜0.05).The bone surface/bone volume value in C7 was higher than that in C3,C4 and C6(P＜0.05).The bone surface density of bone trabeculae in C7 was higher than that in C3,C4,C5 and C6(P＜0.05).Trabecular thickness in C7 was higher than that in C3,C4 and C5(P＜0.05).Bone surface/bone volume and bone surface density of the left pedicle bone trabecular were greater than those on the right side(P＜0.05).(3)The microstructural changes of C3-C7 were summarized,in which the load capacity and stress of the C7 pedicle were poor,and the risk of injury was high in this area.

Cerium and cerium-based materials in dental applications / 中国组织工程研究

BACKGROUND:Cerium(Ce)is the most abundant element among lanthanides,which is mostly in the form of ceria.The reversible transformation between Ce3+and Ce4+ ions contributes to the high redox activity of cerium.Because of its antibacterial,anti-inflammatory,osteogenic,angiogenic and anti-tumor properties,cerium has been widely used in stomatology. OBJECTIVE:To summarize the antibacterial,anti-inflammatory,osteogenic,angiogenic and anti-tumor mechanism of cerium,and to review the research status and application prospects of cerium and cerium-based materials in the modification of oral materials and the diagnosis and treatment of oral diseases in recent years. METHODS:The articles published from database inception to 2023 were retrieved from Web of Science,PubMed,CNKI and WanFang databases with the search terms"cerium,ceria,prosthodontics,prosthesis,restorative dentistry,denture,dental implant,caries,endodontics,pulpitis,periodontitis,periodontal diseases,oral cancer"in English and"cerium,ceria,prosthodontics,implant,dental caries,dental pulp,periodontitis,periodontal disease,oral cancer"in Chinese.By analyzing and reading literature for screening,according to the inclusion and exclusion criteria,73 articles were finally included in this review. RESULTS AND CONCLUSION:(1)Cerium exerts an antibacterial effect through direct contact with bacteria,oxidative stress and destroying bacterial biofilm,and exerts an anti-inflammatory function based on mimetic enzyme activity.The osteogenic and angiogenic activities of cerium involve a series of signaling pathways including ERK and Wnt signaling pathways.(2)Antibacterial,anti-inflammatory,osteogenic,and angiogenic activities allow cerium significant potential in the treatment of oral infectious diseases and regeneration of oral soft and hard tissues.However,there is still a certain gap in the application of cerium's anti-tumor properties in the oral field.(3)Due to excellent mechanical properties and a low light-transmitting property,ceria-stabilized zirconia as a dental ceramic material can be used for core ceramics,the frameworks of dental prostheses and dental implants.(4)Benefited from its biological properties,cerium-based materials have the ability to promote osseointegration and soft tissue integration,inhibit demineralization and cariogenic bacteria,facilitate regeneration of the dentin-pulp complex,lessen inflammatory response and enhance periodontal tissue regeneration.There are wide applications of cerium in surface modifications of implants and treatments of caries,pulpitis,periodontitis and oral cancers.(5)Cerium shows certain toxicity under conditions of high concentration and long-term administration.To further expand clinical applications of cerium in dentistry,biosafety and optimization of cerium-based materials need to be further explored in the future.

Clinical significance of digital measurement of occipital condyle and foramen magnum in children / 中国组织工程研究

BACKGROUND:Due to the young age of children,the occipital condyle and foramen magnum are not fully developed,and they are prone to various diseases and injuries in the occipitocervical junction,which requires surgical treatment in severe cases.However,anatomical parameters for the development of the occipital condyle and foramen magnum in children are lacking. OBJECTIVE:To measure the morphological structure of the occipital condyle and foramen magnum by three-dimensional reconstruction technique,and to provide important anatomical parameters for occipitocervical junction lesions,related surgical procedures and forensic identification. METHODS:Imaging data of 389 cases of primitive children and adolescents involved in skull base undergoing spiral CT scanning(247 males and 142 females)aged 1-18 years were collected and divided into 1-3-year-old group,4-6-year-old group,7-9-year-old group,10-12-year-old group,13-15-year-old group,and 16-18-year-old group according to their age.Mimics 16.0 software was used to reconstruct the skull base and measure the length and width of the foramen magnum.A formula was used to calculate the area and index of the foramen magnum.We measured the length,width and height of the occipital condyle,the angle between the long axis and the sagittal axis of the occipital condyle(O-S angle),the included angle between the midpoint of the front and back edges of the foramen magnum and the connection between the back edge of occipital condyle and the intersection point of the foramen magnum(F-O angle),and the included angle between the midpoint of the front and back edges of the foramen magnum and the midpoint of the back wall of the sublingual neural tube(F-H angle).Gender,side and age differences were analyzed among the indicators. RESULTS AND CONCLUSION:(1)In foramen magnum measurement,there was no significant difference between sexes in the index of the foramen magnum(P>0.05),but there were significant differences in length,width and area of the foramen magnum(P<0.05).(2)The O-S angle,F-O angle and F-H angle of the occipitral condyle were not significantly different between genders(P>0.05),but length,width and height of the occipital condyle were significantly different between genders(P<0.05).(3)There were no significant differences in the length of the occipital condyle among different groups(P>0.05),but there were significant differences in the width and height of the occipital condyle,O-S angle,F-O angle and F-H angle among different groups(P<0.05).(4)Length,width and area of the foramen magnum,length,width and height of the occipital condyle showed a wavy increasing trend with the increase of age,while O-S,F-O and F-H angles showed a wavy decreasing trend with the increase of age,while the index of the foramen magnum showed no significant change.(5)In conclusion,there are gender and lateral differences in the morphological indexes of the foramen magnum and the occipital condyle in children.These differences can provide an important reference for clinical surgical approach selection and forensic examination.

Differential Study on Intestinal Flora between Knee Osteoarthritis with Dampness-heat Obstruction Syndrome and Cold-dampness Blockage Syndrome Based on 16S rDNA Sequencing Technology / 中国中医药信息杂志

Objective To compare the differences in the composition and diversity of intestinal flora between knee osteoarthritis(KOA)patients with dampness-heat obstruction syndrome,cold-dampness blockage syndrome and healthy people;To explore the characteristics of intestinal flora of KOA patients with the above two TCM syndrome types.Methods According to the inclusion and exclusion criteria,dampness-heat obstruction syndrome group,cold-dampness blockage syndrome group,and healthy control group were screened,with 10 cases for each group,and then their fecal samples were collected.16S rDNA sequencing technology was used to compare the differences of intestinal flora among groups by Alpha and Beta diversity analysis.Results There was no significant difference in species richness of intestinal flora among the three groups,but there was statistical significance in species diversity between cold-dampness blockage syndrome group and dampness-heat obstruction syndrome group,and healthy control group(P<0.05).There were statistical significance among the three groups in intestinal flora composition(P= 0.001).At the phylum level,Bacteroidota and Firmicutes were significantly dominant,and at genus level,the abundance of Prevotella in dampness-heat obstruction syndrome group and cold-dampness blockage syndrome group increased.The abundance of Enterobacteriaceae,Lachnospira and Klebsiella was relatively large in dampness-heat obstruction syndrome group.The abundance of Prevotella and Pseudomonas in cold-dampness blockage syndrome group was large.Conclusion There are differences in the intestinal flora structure between KOA patients with dampness-heat obstruction syndrome and cold-dampness blockage syndrome.

Modified and traditional iliolumbar pedicle screw-rod system for the fixation of vertically unstable posterior pelvic ring dislocation: a biomechanical comparative study / 中华创伤杂志

Objective:To compare the biomechanical properties of the modified and traditional iliolumbar pedicle screw-rod system for the fixation of vertically unstable posterior pelvic ring dislocation.Methods:The CT images of the lumbar spine, pelvis, and femur from a 31-year-old healthy male volunteer were used to establish models of posterior pelvic ring dislocation and unilateral and bilateral fixation models of modified and traditional iliolumbar pedicle screw-rod systems with the three-dimensional virtual software using the finite element method. By restraining the distal ends of the femurs of both sides and applying a vertical load of 500 N to the L 1 vertebral body, the maximum stress of the intact pelvis model and the stiffness of the posterior pelvic ring dislocation model were evaluated to validate the reliability of the models. After the validation of the models, a follower load of 400 N was applied in the direction of the L 1 vertebral curve to simulate the upper body weight; the maximum vertical displacement, the maximum posterior displacement, the maximum right displacement, and the overall maximum displacement of the sacrum of the modified and traditional iliolumbar pedicle screw-rod system models were compared. Additionally, stress distributions of the implant and the pelvis were also compared. Results:(1) The maximum stress of the intact pelvis model was 22.0 MPa, with the stiffness of the posterior pelvic ring dislocation model as 180.03 N/mm. (2) In terms of the maximum vertical displacement of the sacrum, the bilateral modified iliolumbar pedicle screw-rod system was similar to the bilateral traditional iliolumbar pedicle screw-rod system. However, the maximum posterior displacement, the maximum right displacement, and the overall maximum displacement of the sacrum in the bilateral modified iliolumbar pedicle screw-rod system were 0.57 mm, 0.19 mm and 0.68 mm respectively, which were markedly smaller than those of the bilateral traditional iliolumbar pedicle screw-rod system (1.38 mm, 0.26 mm and 1.41 mm respectively). (3) The maximum vertical displacement, the maximum posterior displacement, the maximum right displacement, and the overall maximum displacement of the sacrum in the unilateral modified iliolumbar pedicle screw-rod system were 0.70 mm, 0.73 mm, 0.17 mm and 0.88 mm respectively, which were markedly smaller than those of the unilateral traditional iliolumbar pedicle screw-rod system (1.17 mm, 2.21 mm, 0.31 mm and 2.29 mm respectively). (4) The stress of the implant was concentrated on the connecting rod between the iliac pedicle screw-rod and the lumbar pedicle screw-rod in the modified iliolumbar pedicle screw-rod system, but it was mainly concentrated on the connecting rod at the upper edge of the iliac screw in the traditional iliolumbar pedicle screw-rod system. The maximum stress of the implant was 340.84 MPa in the bilateral modified iliolumbar pedicle screw-rod system, which was 30.4% less than that in the bilateral traditional iliolumbar pedicle screw-rod system (489.77 MPa), and was 351.23 MPa in the unilateral modified iliolumbar pedicle screw-rod system, which was 15.5% less than that in the unilateral traditional iliolumbar pedicle screw-rod system (415.82 MPa). (5) In both modified and traditional iliolumbar pedicle screw-rod systems, the stress of the pelvis was concentrated on the contact area between the iliac screw and the cortical bone. The maximum stress of the pelvis was 19.21 MPa in the bilateral modified iliolumbar pedicle screw-rod system, which was 78.1% less than that in the bilateral traditional iliolumbar pedicle screw-rod system (87.59 MPa), and was 39.91 MPa in the unilateral modified iliolumbar pedicle screw-rod system, which was 70.4% less than that in the unilateral traditional iliolumbar pedicle screw-rod system (134.98 MPa).Conclusion:Compared with the traditional iliolumbar pedicle screw-rod system, the modified iliolumbar pedicle screw-rod system can effectively reduce the displacements of all directions in vertically unstable posterior pelvic ring dislocation and significantly reduce the stress of the implant and the pelvis, thus having good biomechanical stability.

Ultra-high dose rate FLASH irradiation reduces radiation-induced intestinal injury in mice / 中华放射肿瘤学杂志

Objective:To investigate whether ultra-high dose rate (FLASH) irradiation can reduce radiation-induced intestinal injuries of mice compared to conventional dose rate (CONV) irradiation.Methods:Both FLASH and CONV irradiation were delivered with electron beam, with dose rates of 750 Gy/s and 0.5G y/s, respectively. A total of 105 mice were randomly divided into groups using a simple randomization method. Twenty-one mice were selected for weight observation, 7 mice in each group. After 9 Gy FLASH and CONV irradiation on the abdomen, the weight changes of mice were measured every other day, and compared among three groups. Twenty-four mice were selected for pathological examination including 5 mice in the control group. Three-and-a-half-day days after 12 Gy FLASH ( n=10) and CONV irradiation ( n=9) on the abdomen, the intestines of the mice were taken. Pathological sections were stained with hematoxylin-eosin (HE) to compare the number and percentage of regenerated crypts of the small intestine between two groups. After 12 Gy FLASH ( n=10) and CONV irradiation ( n=10) on the abdomen, the survival of 20 mice was observed. After FLASH using 4.5 Gy×2 times ( n=10) and CONV irradiation at 9 Gy×1 time ( n=10) on the abdomen, the weight changes were observed. After FLASH using 6 Gy×2 times ( n=10) and CONV irradiation at 12 Gy×1 time ( n=10) on the abdomen, the survival of mice was observed. The time interval between two irradiation was 1 min. EBT3 film was employed to monitor the actual exposure dose of the mice. The variables conforming to normal distribution were expressed by Mean±SD. Inter group comparison was performed by independent t-test. The survival of mice among different groups was compared by log-rank test. Results:After 9 Gy of abdominal irradiation, the mean weight of mice in the FLASH group was significantly higher than that in the CONV group. The weight of mice in the FLASH and CONV groups was (19.8±0.8) g and (18.0±1.8)g ( P=0.036) at 7 days after irradiation, (22.0±1.0)g and (21.2±0.5)g ( P=0.075) at 15 days after irradiation, and (24.2±1.4)g and (22.0±1.2)g ( P=0.012) at 25 days after irradiation, respectively. After 12 Gy irradiation, the mean survival of mice in FLASH and CONV groups was 4 days and 4.7 days ( P=0.029). After 12 Gy total abdominal irradiation, the mean number of intestinal regenerative crypts in the FLASH and CONV groups was 2.9/mm and 1.2/mm ( P=0.041), and the percentage of intestinal regenerative crypts was 34.1% and 14.1%, respectively. The survival of mice irradiated by FLASH using 6 Gy×2 times was longer compared with that of mice after CONV irradiation at 12 Gy×1 time. The weight of mice after 4.5 Gy×2 times irradiation was higher than that of mice after CONV irradiation at 9 Gy×1 time. Conclusion:Weight, survival and the number of intestinal regenerative crypts in the FLASH group are higher than those in the CONV group after irradiation, indicating that radiation-induced intestinal injury caused by FLASH irradiation is slighter than that of CONV irradiation.

Clinical effects of Jingu Xiaotong Powder combined with platelet-rich plasma on patients with knee osteoarthritis / 中成药

AIM To investigate the clinical effects of Jingu Xiaotong Powder combined with platelet-rich plasma on patients with knee osteoarthritis.METHODS Ninety-six patients were randomly assigned into control group(48 cases)for 8-week administration of platelet-rich plasma,and observation group(48 cases)for 8-week administration of both Jingu Xiaotong Powder and platelet-rich plasma.The changes in clinical effects,IL-17,SDF-1,TLR4,GSH-Px,NO,ox-LDL,WOMAC scores,TCM syndrome score,AIM2-SF score were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P<0.05).After the treatment,the two groups displayed decreased IL-17,SDF-1,TLR4,NO,ox-LDL,WOMAC scores,TCM syndrome score(P<0.05),and increased GSH-Px,AIM2-SF score(P<0.05),especially for the observation group(P<0.05).CONCLUSION For the patients with knee osteoarthritis,Jingu Xiaotong Powder combined with platelet-rich plasma can reduce IL-17,SDF-1,TLR4 levels,inhibit body inflammation,improve oxidative stress indices,alleviate pain,and enhance clinical efficacy and life quality.

A case of rhino-orbito-cerebral mucormycosis complicated with bilateral anterior circulation cerebral infarction / 中华神经科杂志

Rhino-orbito-cerebral mucormycosis (ROCM) is an acute, rapidly progressive, and lethal opportunistic fungal disease. Due to the atypical clinical manifestations, the disease is easily misdiagnosed in the early stage. The patients with ROCM associated cerebrovascular complications generally have a high mortality rate. This article reports a 47-year-old female patient with diabetic ketoacidosis and COVID-19 admitted to Central Hospital Affiliated to Shandong First Medical University. The results of radiological examinations and cerebrospinal fluid metagenomic next-generation sequencing confirmed as Rhizopus oryzae associated ROCM. In spite of receiving amphotericin B colloidal dispersion and isavuconazole treatments, the patient died of ROCM complicated with severe cerebral infarctions and pulmonary infection. The purpose of this case report is to summarize the clinical characteristics of ROCM with cerebrovascular ischemic events and the rare condition of bilateral anterior circulation involvements, and introduce recent diagnostic and therapeutic approaches for this disease.

Interpretation and Elaboration for the ARRIVE Guidelines 2.0—Animal Research: Reporting In Vivo Experiments (V) / 实验动物与比较医学

Improving the reproducibility of biomedical research results is a major challenge. Transparent and accurate reporting of the research process enables readers to evaluate the reliability of the research results and further explore the experiment by repeating it or building upon its findings. The ARRIVE 2.0 guidelines, released in 2019 by the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), provide a checklist that is applicable to any in vivo animal research report. These guidelines aim to improve the standardization of experimental design, implementation, and reporting, as well as enhance the reliability, repeatability, and clinical translation of animal experimental results. The use of the ARRIVE 2.0 guidelines not only enriches the details of animal experimental research reports, ensuring that information on animal experimental results is fully evaluated and utilized, but also enables readers to understand the content expressed by the author accurately and clearly, promoting the transparency and completeness of the fundamental research review process. At present, the ARRIVE 2.0 guidelines have been widely adopted by international biomedical journals. This article is based on the best practices following the ARRIVE 2.0 guidelines in international journals, and it interprets, explains, and elaborates in Chinese the fifth part of the comprehensive version of the ARRIVE 2.0 guidelines published in PLoS Biology in 2020 (the original text can be found at https://arriveguidelines.org). This section includes the items 6-11 of Recommended 11 section, covering "Animal Care and Monitoring", "Interpretation/Scientific Implications", "Generalisability/Translation", "Protocol Registration", "Data Access" and "Declaration of Interests". Its aim is to promote a comprehensive understanding and use of the ARRIVE 2.0 guidelines among domestic researchers, to enhance the standardization of experimental animal research and reporting, and to promote high-quality development of experimental animal sciences and comparative medicine research in China.

Diagnosis and treatment of 11 cases of liver injury due to percutaneous nephrolithotripsy / 现代泌尿外科杂志

【Objective】 To explore the diagnosis and management of liver injury caused by percutaneous nephrolithotripsy (PCNL), so as to provide reference for the diagnoise and treatment of similar patients. 【Methods】 The clinical data of 926 patients who underwent PCNL during Oct.2017 and Oct.2022 were searched, and the data of those complicated with liver injury were analyzed. 【Results】 A total of 11 cases were collected, including 6 males and 5 females, average age (55.00±13.25)years.All injuries were confirmed with CT.The average decrease of hemoglobin after operation was (14.00±11.97)g/L.One patient needed blood transfusion due to pyonephrosis and multiple operations, and all patients were cured and discharged after delaying the removal of nephrostomy tube [an average of (6.73±1.27)days] . 【Conclusion】 In the absence of obvious signs of peritonitis and hemodynamic stability, conservative treatment of liver injury caused by PCNL is safe and effective.

Quantitative analysis of vessel density in the optic disc and macular of patients with idiopathic optic neuritis / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To assess the changes of vessel density in the optic disc and macular of the affected eye and the uninvolved contralateral eye in patients with idiopathic optic neuritis(ON)and to provide clinical guidance for the treatment and follow-up of idiopathic ON.METHODS: A total of 16 patients with first-episode monocular idiopathic ON ≤3 mo diagnosed between December 2019 and December 2021 were included in this cross-sectional study. The eye of patients was divided into 16 eyes in the affected eye group and 16 eyes in the uninvolved contralateral eye group, and 20 healthy age-matched eyes(n=20)served as controls. Optical coherence tomography angiography(OCTA)was performed in all eyes at 4.5 mm×4.5 mm region of the optical disc and 6 mm×6 mm region of the macular, and blood flow indicators were collected and compared. RESULTS: Compared with the control group and the uninvolved contralateral eye group, the density of all vessels and capillary were reduced in the whole area of optic disc, and all subdivisions of the peripapillary region in the ON group(all P&#x003C;0.05). Compared with the uninvolved contralateral eye group, the density of superficial capillary plexus(SCP)was significantly lower in the whole area of macular and perifovea region, and its all subdivisions of the ON eye, as well as in the superior-hemi and superior subdivision of the parafovea region(all P&#x003C;0.05). Compared with the control group, the density of SCP in the inferior-hemi, nasal, and inferior perifovea region was significantly reduced in the ON affected eye group(all P&#x003C;0.05). Compared with the control group, the whole area of macular and its subdivisions in the uninvolved contralateral eye group showed an increase in the density of SCP(P&#x003C;0.05)and an increase in the density of SCP in the parafovea region(P&#x003C;0.05), but no significant change in the inferior-hemi and nasal subdivisions; the increase in the density of SCP in the perifovea region was only significant in the superior-hemi and superior subdivisions(P&#x003C;0.05).CONCLUSION: Patients with ON in the duration of ≤3 mo may showed a decreased vessel density in all peripapillary subdivisions, and a decreased density of SCP in some subdivisions of the perifovea region, accompanied by an increased density of SCP in some subdivisions of the macular region of the contralateral eyes.

Intervention effect of HSP60 on learning and memory impairment induced by combined exposure to lead and hypertension in mice / 中国职业医学

ObjectiveTo investigate the intervention effect of heat shock protein 60 (HSP60) on learning and memory impairment induced by combined exposure to lead and hypertension in mice, and the relative mechanism of triggering receptor expressed on myeloid cells 2 (TREM2). Methods Specific pathogen-free C57BL/6J male mice were randomly divided into control group, hypertension group, lead-exposed group and lead-exposed + hypertension group, or into control group, heat shock protein 60 (HSP60) control group, lead-exposed + hypertension group and HSP60 intervention group, with 10 mice in each group. Mice of hypertension group and lead-exposed + hypertension group were intraperitoneally injected with angiotensin Ⅱ at a dose of 0.5 mg/(kg·d) for seven consecutive days to induce hypertension model. Mice of the lead-exposed group, lead-exposed + hypertension group, and HSP60 intervention group were given lead acetate drinking water with a mass concentration of 250.0 mg/L, while mice in the control group, hypertension group, and HSP60 control group were given purified water for 12 weeks. Mice of the HSP60 control group and HSP60 intervention group were intraperitoneally injected with a solution of HSP60 at a dose of 4 mg/kg body weight, every other day for a total of three times at the 12th week. The learning and memory ability of mice was detected using the Morris water maze test. The enzyme-linked immunosorbent assay was used to detect the levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in the hippocampal tissues of the mice. The relative expression of ionized calcium binding adaptor molecule-1 (IBA1) and TREM2 protein in the hippocampus of mice was detected using Western blot. Results i) The number of platform crossings of the mice in the hypertension group and the lead-exposed group was lower than that in the control group (both P<0.05). The escape latency of the mice on the third day was longer and the number of platform crossings was lower in the lead-exposed + hypertension group compared with the control group, hypertension group and lead-exposed group (all P<0.05). The levels of IL-1β, IL-6, and TNF-α in the hippocampus of the other three groups increased compared with the control group (all P<0.05). The relative expression of IBA1 protein in the hippocampus of lead-exposed group and lead-exposed + hypertension group increased (all P<0.05), while the relative protein expression of TREM2 decreased compared with the control group (all P<0.05). The levels of IL-1β, IL-6, TNF-α, and the relative protein expression of IBA1 protein in the hippocampus of the lead-exposed+hypertension group were higher (all P<0.05), and relative expression of TREM2 protein was lower (P<0.05) than those in the hypertension group. The level of TNF-α and the relative expression of IBA1 protein in the hippocampus of lead-exposed+hypertension group were higher than those in lead-exposed group (all P<0.05). ii) The escape latency of mice in the lead-exposed + hypertension group was longer than that in the control group (P<0.05), and the number of platform crossings was fewer than that in the control group (P<0.05). The escape latency of mice in the HSP60 intervention group was shortened (P<0.05), the number of platform crossings increased (P<0.05), and the levels of IL-1β, IL-6, TNF-α and relative expression of IBA1 protein decreased in the hippocampus (all P<0.05), while the relative expression of TREM2 protein increased (P<0.05) compared with the lead-exposed+hypertension group. Conclusion Combined exposure of lead and hypertension has a synergistic effect on learning and memory impairment in mice. The mechanism may be related to the inhibition of TREM2 expression by lead in the hippocampus of hypertensive mice and aggravating the neuroinflammatory response. Intervention with TREM2 receptor agonist HSP60 can alleviate learning and memory impairment in mice exposed to lead and hypertension by up-regulating TREM2 expression in the hippocampus.

An Enhancer LncRNA Regulates NFE2 Expression and Proliferation in Human Leukemic K562 Cells / 生物化学与生物物理进展

ObjectiveTranscription factor NFE2 was observed abnormal expression in myeloproliferative neoplasm (MPN) patients. However, how NFE2 is transcriptionally regulated remains ambiguous. This study aims to explore the elements and molecular mechanisms involved in the transcriptional regulation of NFE2. MethodsActive enhancers were predicted by public NGS data and conformed experimentally via dual luciferase reporter assay. After that, PRO-seq and GRO-seq data was used to detect enhancer RNAs transcribed from these enhancers. RACE was utilized to clone the full length enhancer RNA (eRNA) transcripts, and RT-qPCR was used to measure their expression in different leukemia cell lines as well as the transcript levels during induced differentiation. Finally, to investigate the molecular function of the eRNA, overexpression and knockdown of the eRNA via lentivirus system was performed in K562 cells. ResultsWe identified three enhancers regulating NFE2 transcription, which located at -3.6k, -6.2k and +6.3k from NFE2 transcription start site (TSS) respectively. At the -3.6k enhancer, we cloned an eRNA transcript and characterized that as a lncRNA which was expressed and located in the nucleus in three types of leukemia cell lines. When this lncRNA was overexpressed, expression of NFE2 was upregulated and decreases of K562 cell proliferation and migration ability were observed. While knocking down of this lncRNA, the level of NFE2 decreases correspondingly and the proliferation ability of K562 cells increases accordingly. ConclusionWe identified an enhancer lncRNA that regulates NFE2 transcription positively and suppresses K562 cell proliferation.

Final Fate of Cancer Cells After Nuclear Genetic Material Damage / 肿瘤防治研究

Cancer cells refer to a group of malignant cells with strong division and proliferation abilities. Cancer cells rely on the unstable plunder of human nutrition to sustain the large amount of energy that they need for their own division and proliferation. The division and proliferation of cancer cells are linked to the synthesis and replication of genetic material in the nucleus. Blockage or destruction of the synthesis of genetic material in cancer cells is one of the mechanisms underlying the action of most antitumor drugs. As the key material that dominates cell division, proliferation, and death, nuclear genetic material which mainly refers to the deoxyribonucleic acid located on the chromatin in the nucleus, plays a decisive role in the final fate of cells. The final fate of cancer cells after the damage of the genetic material is worthy of investigation and analysis. In this paper, we discuss and analyze the fate of cancer cells after genetic material damage from the aspect of cellular cycle arrest, apoptosis, autophagy, and senescence to provide ideas for the mechanism research on antitumor drugs.