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Objective@#: To investigate the efficacy and safety of the posterior endoscopic cervical foraminotomy (PECF) using ultrasonic osteotome for the treatment of cervical osseous foraminal stenosis，focusing on introduction of the advantages of ultrasonic osteotome in partial pediculectomy and ventral osteophyte resection in PECF. @*Methods@#: Nineteen patients with cervical osseous foraminal stenosis who underwent PECF using ultrasonic osteotome in our institution between April 2018 and April 2021 were enrolled in this study. All the patients were followed up more than 12 months. The patients’ medical data, as well as pre- and postoperative radiologic findings were thoroughly investigated. The visual analogue score (VAS), Japanese Orthopaedic Association (JOA) score, cervical dysfunction index (Neck disability index, NDI), and modified MacNab criteria were used to assess the surgical efficacy. @*Results@#: All the patients were successfully treated with PECF using ultrasonic osteotome. The pre- and postoperative VAS, NDI, and JOA scores were significantly improved (p<0.05). According to the modified MacNab criteria, 17 patients were assessed as “excellent”, two patients were assessed as “good” at the last follow-up. There was no dura tear, nerve root damage, incision infection, neck deformity, or other complications. @*Conclusion@#: Adequate nerve root decompression can be accomplished successfully with the help of ultrasonic osteotome in PECF, which has the advantage of reducing the probability of damage to the nerve root and dura mater, in addition to the original merits of endoscopic surgery.
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Since the application of biomedical nanotechnology in the field of drug delivery breathes new life into the research and development of high-end innovative agents, a substantial number of novel nano-drug delivery systems (nano-DDSs) have been successively developed and applied in the clinical practice. Among them, small molecule pure drug and prodrug-based nanoassemblies have grasped great attention, owing to the facile fabrication, ultrahigh drug loading and feasible industrial production. Herein, we provide an overview on the latest updates of small-molecule nanoassemblies. Firstly, the self-assembled prodrug-based nano-DDSs are introduced, including nanoassemblies formed by amphiphilic monomeric prodrugs, hydrophobic monomeric prodrugs and dimer monomeric prodrugs. Then, the recent advances on nanoassemblies of small molecule pure chemical drugs and biological drugs are presented. Furthermore, carrier-free small-molecule hybrid nanoassemblies of pure drugs and/or prodrugs are summarized and analyzed. Finally, the rational design, application prospects and clinical challenges of small-molecule self-assembled nano-DDSs are discussed and highlighted. This review aims to provide scientific reference for constructing the next generation of nanomedicines.
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Objective:To investigate the risk factors and missed diagnosis of intraductal carcinoma of prostate (IDC-P) in patients with metastatic prostate cancer.Methods:The preoperative PSA, prostate MRI, bone scans and lung CT of all patients who underwent prostate biopsy in Department of Urology, Xiangya Hospital, Central South University from January 2018 to July 2020 were reviewed. A total of 261 patients with high suspicion of metastatic prostate cancer were screened for inclusion. Two full-time senior pathologists of urogenital tumors in Xiangya Hospital independently reviewed their pathological sections and detected IDC-P according to the 2016 WHO tumor classification. Diagnostic criteria are defined as malignant epithelial cells filling large acini and prostatic ducts, with preservation of basal cells and solid or dense cribriform pattern/loose cribriform or micropapillary pattern with either marked nuclear atypia or non-focal comedonecrosis.Results:The detection rate of IDC-P was 29.12%(76/261), while the actual reporting rate was only 9.96%(26/261). The results of subgroup analysis including age, PSA level, Gleason score as well as different metastatic sites showed that detection rate of IDC-P was 33.69% in the PSA≥50 ng/ml subgroup, much higher than 17.57% in the PSA <50 ng/ml subgroup ( P=0.0039); And it was 32.33% in the Gleason score ≥ 8 subgroup, much higher than 3.45% in the Gleason score < 8 subgroup ( P<0.01). It was not significantly different in different age subgroups as well as different metastatic site subgroups. These data suggest that PSA ≥ 50 ng/ml as well as Gleason score ≥ 8 may be risk factors of IDC-P.157 samples were stained by immunohistochemistry. The detection rates of IDC-P were 84.21% (16/19) in P63 (+ ) samples, 36.00% (9/25) in ERG (+ ) samples. There were 3 samples with both P63 (+ ) and ERG (+ ), all of which had IDC-P. Conclusions:There is misdiagnosis of IDC-P on prostate needle biopsy in patients with metastatic prostate cancer currently. PSA ≥ 50 ng/ml and Gleason score ≥ 8 are risk factors of IDC-P. Thus, attention should be paid to the possibility of IDC-P in such patients. When the diagnosis is difficult, immunohistochemical staining for ERG and P63 is helpful in IDC-P determination.
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At present, cancer is still one of the most serious threats to human health. Despite the wide application of multiple cancer therapies in clinical practice, the therapeutic effects of most cancers are still far from satisfactory. In recent years, the discovery of regulated cell death may be a good first step on the road to treat cancer. Ferroptosis is triggered by lipid peroxidation of unsaturated fatty acids in cell membrane catalyzed by iron ion. It has been widely concerned as an emerging target for cancer therapy. With the booming of biomedical nanotechnology, ferroptosis as an emerging therapeutic target has attracted extensive attention. Here, we review the advance on the intersection of ferroptosis and biomedical nanotechnology. First, the research background of ferroptosis and nano-preparation as well as the feasibility of ferroptosis-based nano-drug delivery systems (nano-DDS) for cancer treatment are presented and analyzed. Then, the strategies for inducing ferroptosis based on nano-DDS are summarized, mainly including: the promotion of Fenton reaction, the inhibition of glutathione peroxidase 4 (GPX-4) and the restriction of the cysteine-glutamate exchange transporter (system Xc-). Furthermore, the combination therapy strategies based on biomedical nanotechnology induced ferroptosis are also discussed. Finally, we shine the spotlight on the prospects and challenges of ferroptosis-based nanotherapeutics in clinical application.
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Pure drug-assembled nanomedicines (PDANs) are currently under intensive investigation as promising nanoplatforms for cancer therapy. However, poor colloidal stability and less tumor-homing ability remain critical unresolved problems that impede their clinical translation. Herein, we report a core-matched nanoassembly of pyropheophorbide a (PPa) for photodynamic therapy (PDT). Pure PPa molecules are found to self-assemble into nanoparticles (NPs), and an amphiphilic PEG polymer (PPa-PEG
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With the development of molecular biology research, targeted therapy has become the fourth effective method for the treatment of malignant tumors after surgery, radiotherapy, and chemotherapy. Unlike the traditional chemotherapeutic drugs, molecular targeted drugs possess the advantages of high specificity, definite curative effects, and less adverse effects. CLDN18.2 protein is a transmembrane protein that is highly selective and stably overexpressed during the development of various malignant tumors, especially gastrointestinal tumors, and metastases. A specific antibody against this protein, claudiximab (zolbetuximab/IMAB362), has achieved great success in recent clinical trials. Thus, CLDN18.2 protein is expected to be a safe and effective molecular target for targeted therapy in some malignancies.
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Objective To investigate the clinical efficacy of open reduction and internal fixation with K-wires for old Gartland Ⅲ supracondylar fracture in children.Methods A retrospective case series study was conducted on 49 children with old Gartland Ⅲ supracondylar humeral fracture admitted from June 2012 to January 2017.There were 35 boys and 14 girls,with average age of 6.1 years (range,3.4-11.5 years).The duration from initial trauma to operation ranged from 22 days to 60 days (mean,29.8 days).There were five cases of radial nerve injury,one case of median nerve injury,and one case of Volkmann ischemic contracture.All patients were surgically treated with open reduction and internal fixation with K-wires + plaster external fixation.Six patients with nerve injury underwent neurological exploration and release.Nerve partial fracture was seen in one patient during operation,and nerve repair was performed.The fracture healing and complications were observed.At the final follow up,Flynn's criteria was applied to evaluate the elbow joint function.The humerus length and transverse diameter of humeral condyle between the healthy limb and the suffered one were compared to evaluate the humerus growth.Results All patients were followed up for 6-24 months,with an average of 12.5 months.All fractures were healed,with no fracture redisplacement or bone nonunion occurred.The neurological symptoms of six patients with nerve injury disappeared after two months.One patient had superficial skin infection at the incision and recovered after treatment.Six patients (12％) developed cubitus varus deformity after operation.At the final follow-up,the clinical and radiographic outcomes were assessed via Flynn's criteria,and the results were excellent in 37 patients,good in five,fair in one,and poor in six patients,with an excellent and good rate of 86％.There were no significant differences in the humerus length [(189.3 ± 27.8) mm vs.(190.6 ± 28.8) mm] and transverse diameter of humeral condylar [(29.5 ± 3.5) mm vs.(29.7 ± 3.6) mm] (P ＞ 0.05) between the healthy limb and the suffered one,respectively.Conclusion For old Gartland type Ⅲ supracondylar humeral fracture in children,open reduction and internal fixation with K-wires + plaster external fixation can attain satisfactory function recovery of elbow joint and reduce the incidence of cubitus varus deformity,without negative influence on children's humerus growth or development.
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Coronary atherosclerotic heart disease (CHD) remains the leading cause of morbidity and mortality in the world, with elevated low density lipoprotein-cholesterol (LDL-C) levels as a major risk factor. Lower levels of LDL-C can effectively reduce the risk of CHD. To date, lipid-lowering medicines such as statins are effective in lowering LDL-C, but a proportion of patients do not achieve lipid reduction target with statins or are intolerant to statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a new class of agents reducing LDL-C which gain more and more concerns. Through inhibitory effect on PCSK9 and increasing low-density lipoprotein receptors recycling, they can significantly reduce serum LDL-C levels. PCSK9 inhibitors are currently in phase Ⅲ of clinical trials, and the results showed that they had good lipid-lowering effects and tolerability. This review provided an overview of the latest advances and challenges about PCSK9 inhibitors.
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Coronary atherosclerotic heart disease (CHD) remains the leading cause of morbidity and mortality in the world, with elevated low density lipoprotein-cholesterol (LDL-C) levels as a major risk factor. Lower levels of LDL-C can effectively reduce the risk of CHD. To date, lipid-lowering medicines such as statins are effective in lowering LDL-C, but a proportion of patients do not achieve lipid reduction target with statins or are intolerant to statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a new class of agents reducing LDL-C which gain more and more concerns. Through inhibitory effect on PCSK9 and increasing low-density lipoprotein receptors recycling, they can significantly reduce serum LDL-C levels. PCSK9 inhibitors are currently in phase III of clinical trials, and the results showed that they had good lipid-lowering effects and tolerability. This review provided an overview of the latest advances and challenges about PCSK9 inhibitors.
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Chemotherapy resist is the problem for clinic,and some researches find that chemotherapy with anthracycline and oxaliplatin not only induces the tumor cell apoptosis,but also the celt immunogenic cell death (ICD) by inducing the tumor cell apoptosis and releasing three kinds of signals:exposure of calreticulin on the cell surface to stimulate the dendritic cell (DC) to engulf,and the secretion of adenosine triphosphate to recruit DC to enter into tumor bed,and the release of the high mobility group B1 to promote DC to steadily bind with dying tumor cell to induce specific T cell antitumor immune response.It is with great meaning to promote the chemotherapy protocol by studying the ICD induced by chemotherapy.
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Objective To study the preliminary effect of sartorius iliac flap in repair of acetabulum defect for developmental dysplasia of the hip (DDH) in elder children.Methods We retrospectively studied 17 elder children with acetabulum defect in DDH at the age＞6 years old who received acetabular repair with sartorius bone flap in this hospital from 2014 to 2016.All patients with acetabulum defect in DDH were treated with open reduction in general anesthesia.Three-dimensional osteotomy under the femur rotor was conducted to correct the femoral anteversion and neck-shaft angle.According to the height of femoral head dislocation lines,femur tuberosity was shorten and fixied with steel plates,joint capsule was reconstructed,The iliac sartorius musculocutaneous flap was took to the upper edge of the acetabular to repair the acetabular defect.The lower extremities were treated with plaster for 6 to 8 weeks after surgery.The hip joint function was trained and the function was evaluated with Mckay's criteria.The hip joint morphological evaluation was performed with reference to Severin's X-ray standard.Results Seventeen patients were followed up for 6 to 29 months.Postoperative reduction of the femoral head was good,the head mortar inclusive was satisfactory;there were no wound infection and femoral head necrosis.According to Mckay's criteria,2 patients got excellent,13 good,and 2 fair,with the fineness ratio at 88.2％;According to Severin's critera:11 patients excellent.Conclusion The overturned sartorius iliac flap can repair acetabulum defect,promote bone healing,and effectively improve acetabulum to cover head of femur.
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Aim To evaluate the potency of anti-D. acutus venom IgY neutralizing the main activities of D. acutus venom.Methods After mixing the different a-mounts of IgY with snake venom and incubating togeth-er,the main activities of snake venom were assayed by biochemical methods.Results The in vitro assays in-dicated that anti-D.acutus venom IgY obviously neu-tralized the activities of PLA2 ,5′-nucleotidase,hyalu-ronidase,metalloprotease and serine proteinase (fi-brinogenase)in D.acutus venom.Mouse experiments showed that the ED50 value of IgY for mouse was 1 131.09 μg.Conclusion Anti-D.acutus venom IgY antibodies have good effects in neutralizing D.acutus venom without the toxicities themselves.
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Objective To investigate the application of sandwich teaching method based on CBL principle in clinical teaching of pediatric surgery combined with network database. Methods A total of 147 undergraduate students in clinical medicine were selected and randomly divided into experimental group (84 persons) and control group (63 persons). The experiment group used sandwich teaching based on CBL principle + bedside demonstration + network resource library, while the control group adopted tradi-tional teaching + bedside teaching. The teaching effect was evaluated through theoretical and practical ex-aminations and quantitative feedback questionnaires. The t-test of independent samples was performed in two groups, and the scores of the questionnaires were matched by paired t-test. Results The scores of net-work test, case discussion, summary and written test in the experimental group were better than those in the control group [(37.56 ±1.32) vs. (35.10 ±1.25); (27.61 ±0.94) vs. (24.71 ±1.51); (27.02 ±1.11) vs. (26.29±1.30); (88.28±1.97) vs. (83.60±4.58)], the difference was statistically significant. The question-naire survey showed that the students in the experimental group were better than the control group in the learning efficiency, team cooperation, independent thinking, theory connection, and so on. Conclusions The sandwich teaching method based on CBL principle, combined with the network database, is better than the traditional method in the clinical teaching of pediatric surgery, and can promote the theoretical and overall teaching effect, which is worth popularizing.
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In order to develop potent antidiabetic agents that have inhibitory effect to α-glucosidase, twelve β-acetamido ketone derivatives such as N-{[(substituted-4-oxo-thiochroman-3-yl)phenyl]-methyl}acetamide are designed and synthesized through one-pot Dakin-West reaction. Their chemical structures are confirmed by 1H NMR, 13C NMR, IR and HR-MS. In vitro α-glucosidase inhibition assays of compounds 4a-4l were carried out using glucose oxidase method. The result indicated that most of them possess inhibitory activity in vitro. Compound 4k showed the most potent inhibitory activity with 87.3% inhibition of α-glucosidase at the concentration of 5.39 mmol·L-1. The structure-activity relationship of these β-acetamido ketone derivatives was discussed preliminarily. Moreover, the molecular docking method was used to study the interaction mode of compound 4k and α-glucosidase. Our results will be helpful for designing of α-glucosidase inhibitors in the future.
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Objective To compare the clinical effect of tensile band wire fixation and plate fixation for treating children with olecroanon fracture.Methods Sixty-three children with olecroanon fracture at Children's Hospital of Chongqing Medical University from January 2006 to January 2014 were selected.In those cases of fracture by means of open reduction,41 cases were treated with tensile band wire,and 22 cases were treated with internal fixation with anatomical plate.Operation time,bleeding during operation,recovery time postoperatively,postoperative complications and joint function recovery were analyzed by using independent sample t-test and chi-square test.Results In the group of tensile band wire,there was no case of Kirschner wire loosening and displacement fracture.In group of steel plate,there were 2 cases of myositis ossificans.In the 2 groups,there was no case of bone nonunion.The average operation time:plate fixation group was (65.3 ± 8.4) min and tension band wire group was (58.4 ± 12.6) min,and there was a significant difference between the both groups (t =7.419,P ＜ 0.05);blood loss:plate fixation group was (5.3 ±0.8) mL and tension band wire group was (4.7-± 1.2) mL,and there was a significant difference between the both groups (t =2.595,P ＜ 0.05);fracture healing time:plate fixation group was (74.1 ± 8.4) d and tension band wire group was (61.7 ±9.3) d,and there was a significant difference between the both groups (t =10.636,P ＜0.05).With Broberg-Morrey to evaluate two groups'quality rate of function recovery,there was no significant difference in statistics with 85.3％ (35/41 cases) in tensile band wire group and 81.8％ (17/22 cases) in steel plate group(x2 =0.651,P ＞ 0.05).Conclusions Olecranon fracture in children using tension band wire fixation may be a better way,more suitable for promotion and implementation at basic hospital.
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In order to develop potent antidiabetic agents that have inhibitory effect to a-glucosidase, twelve β-acetamido ketone derivatives such as N-{[(substituted-4-oxo-thiochroman-3-yl)phenyl]-methyl}acetamide are designed and synthesized through one-pot Dakin-West reaction. Their chemical structures are confirmed by 1H NMR, 13C NMR, IR and HR-MS. In vitro α-glucosidase inhibition assays of compounds 4a-41 were carried out using glucose oxidase method. The result indicated that most of them possess inhibitory activity in vitro. Compound 4k showed the most potent inhibitory activity with 87.3% inhibition of α-glucosidase at the concentration of 5.39 mmol x L(-1). The structure-activity relationship of these β-acetamido ketone derivatives was discussed preliminarily. Moreover, the molecular docking method was used to study the interaction mode of compound 4k and α-glucosidase. Our results will be helpful for designing of α-glucosidase inhibitors in the future.
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Acetamides , Glycoside Hydrolase Inhibitors , Pharmacology , Hypoglycemic Agents , Pharmacology , Molecular Docking Simulation , Structure-Activity Relationship , alpha-Glucosidases , MetabolismABSTRACT
To explore in vitro release rules of isoniazid [INH] when Isoniazid Super paramagnetic Iron Oxide Microspheres [ISPIOM] are subject to no external magnetic field, applied mechanical magnetic field and scillating magnetic field. ISPIOM was prepared by using the spray drying method; Isoniazid contented in the microspheres was determined, the drug loading capacity and encapsulation efficiency were calculated. Release of isoniazid in the microspheres was determined respectively under the effect of no external magnetic field, applied mechanical magnetic field and oscillating magnetic field, to explore the release rules. In solution with pH=7.4 PBS, microspheres featured 8-hour sustained release under the effect of magnetic field, the released rate of the microspheres is accelerated. In solution with pH=3 PBS, microspheres release faster and could realize the fastest completion of release in 2 hours under the effect of oscillating magnetic field. To join the external magnetic field in different point time to can't affect the release, under pH=3 of medium, ISPIOM release faster; under the effect of magnetic field, the released rate of the microspheres is accelerated, and the longer effect of magnetic field, the faster release. Oscillating magnetic field can make ISPIOM within a certain period of time, get ideal release curve, so as to achieve good control release effect
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The purpose of this study is to investigate the effect of superparamagnetic chitosan FGF-2 gelatin microspheres (SPCFGM) on the proliferation and differentiation of mouse mesenchymal stem cells. The superparamagnetic iron oxide chitosan nanoparticles (SPIOCNs) were synthesized by means of chemical co-precipitation, combined with FGF-2. Then The SPCFGM and superparamagnetic chitosan gelatin microspheres (SPCGM) were prepared by means of crosslinking-emulsion. The properties of SPCFGM and SPIONs were measured by laser diffraction particle size analyser and transmisson electron microscopy. The SPCFGM were measured for drug loading capacity, encapsulation efficiency and release pharmaceutical properties in vitro. The C3H10 cells were grouped according to the different ingredients being added to the culture medium: SPCFGM group, SPCGM group and DMEM as control group. Cell apoptosis was analyzed by DAPI staining. The protein expression level of FGF-2 was determined by Western blot. The proliferation activity and cell cycle phase of C3H10 were examined by CCK8 and flow cytometry. The results demonstrated that both of the SPIOCNs and SPCFGM were exhibited structure of spherical crystallization with a diameter of (25 ± 9) nm and (140 ± 12) μm, respectively. There were no apoptosis cells in the three group cells. Both the protein expression level of FGF-2 and cell proliferation activity increased significantly in the SPCFGM group cells (P < 0.05). The SPCFGM is successfully constructed and it can controlled-release FGF-2, remained the biological activity of FGF-2, which can promote proliferation activity of C3H10 cells, and are non-toxic to the cell.
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Animals , Mice , Cell Differentiation , Cell Line , Cell Proliferation , Chitosan , Fibroblast Growth Factor 2 , Pharmacology , Gelatin , Magnetite Nanoparticles , Mesenchymal Stem Cells , Microspheres , PlasmidsABSTRACT
Objective To compare the effect of titanium elastic nailing (TEN) and plating in treatment of both radius and ulna fractures in children older than 10 years.Methods This retrospective analysis comprised 38 children (50 sides) of both radius and ulna fractures treated with TEN (30sides) or plate (20 sides) between 2009 and 2014.Parameters compared between the two fixation methods were operation time,ratio of open/close reduction,time to internal fixation removal,incidence of postoperative complications,and bone union time.Anderson score was used to evaluate the treatment results.Results Operation time [(94.3 ± 39.5) min vs (120.5 ± 45.4) min],time to internal fixation removal [(210.8 ± 84.1) d vs (264.4 ± 88.9) d],and ratio of open/close reduction (20/10 vs 20/0)varied significantly between TEN and plating groups (P ＜ 0.05 or 0.01).Whereas,no statistically significant differences were noted in regard to complication rate,bone union time,and effect evaluation.Conclusion For fracture of the radius and ulna in children older than 10 years,TEN should be used for closed type without obvious displacement,but plate fixation is associated with lower incidence of fracture malunion and better outcome in treatment of open type with obvious displacement.
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BACKGROUND:Using degradable materials for bone tissue engineering to treat bone defects is the best choice at present. How to ensure adequate vascularization in materials in order to meet the need of blood supply and an exchange of nutrients for seed cells in the process of bone regeneration is becoming a critical problem reversed from basic research to clinical application. OBJECTIVE:To review the biodegradable materials for bone tissue engineering and the ways to promote vascularization in materials. METHODS:A computer-based search of PubMed and PMC databases was performed by the first author for the literature about biodegradable materials for bone tissue engineering and their vascularization published from 1993 to 2013. The key words were“degradable materials, bone tissue engineering, angiogenesis, vasculogenesis, osteogenesis”in English. RESULTS AND CONCLUSION:The commonly used biodegradable materials for bone tissue engineering include synthetic polymer materials, magnesium al oy, bioactive glass ceramics, calcium phosphate ceramics and composites. We can promote the vascularization of tissue-engineered bone by the fol owing aspects:scaffold fabrication, growth factors, the application of endothelial progenitor cells, cells co-culture and microsurgical techniques. Although the research on the vascularization of tissue-engineered bone has made a great progress, there is stil a lot of shortcomings. We believe that, with the development of mechanism of angiogenesis, the vascularized tissue-engineered bone wil have a promising prospect because of improving the structure and properties of materials, promoting the ability of release-control ed growth factors and their synergies, optimizing the selection and mixed culture of seed cells and improving the microsurgical techniques.