BACKGROUND:Cartilage defects are one of the major clinical challenges faced by orthopedic surgeons.Tissue engineering is an interdisciplinary approach that combines knowledge of engineering and cell biology to provide new ideas and approaches for the repair of cartilage defects. OBJECTIVE:To prepare a multi-component composite scaffold based on silk fibroin,gelatin,and chitosan to screen for a three-dimensional porous scaffold suitable for cartilage regeneration by evaluating its physicochemical properties and biological performance. METHODS:Four groups of porous scaffolds were prepared by vacuum freeze-drying method using silk fibroin,gelatin and chitosan as the base materials,namely chitosan/gelatin scaffold,silk fibroin/chitosan scaffold,silk fibroin/gelatin scaffold and silk fibroin/chitosan/gelatin scaffold.The suitable cartilage scaffolds were screened by scanning electron microscopy,X-ray diffractometer,porosity,water absorption and swelling rate,biodegradation rate and mechanical property detection.Then cartilage scaffolds were co-cultured with chondrocytes isolated and extracted from patients with osteoarthritis.The feasibility of porous scaffolds for cartilage injury repair was evaluated in vitro by cell adhesion rate assay,cell live-dead staining and cell activity proliferation assay. RESULTS AND CONCLUSION:(1)All four groups of scaffolds had porous structures.The comprehensive physical performance test results showed that the silk fibroin/gelatin/chitosan scaffold was more in line with the requirements of cartilage defect repair.This scaffold had a pore size of(176.00±53.68)μm,the porosity of(80.15±2.57)%,and water absorption and swelling rate of(3 712±358)%.After immersion in PBS containing lysozyme for 28 days in vitro,the biodegradation rate was(46.87±3.25)%,and it had good mechanical properties.(2)Chondrocytes could adhere well on the silk fibroin/gelatin/chitosan scaffold,and the cell adhesion rate increased with time.CCK8 and live/dead cell double staining results showed that silk fibroin/gelatin/chitosan scaffold had good biocompatibility and low cytotoxicity.(3)The results showed that silk fibroin/gelatin/chitosan scaffold had a highly hydrated 3D structure,suitable pore size and porosity,good biodegradability and superior mechanical properties,which can provide a good reticular skeleton and microenvironment for nutrient transport and chondrocyte attachment and proliferation.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Objective:To explore the risk factors of septic acute kidney injury (sAKI) in patients with sepsis, construct a predictive model for sAKI, verify the predictive value of the model, and develop a dynamic nomogram to help clinical doctors identify patients with high-risk sAKI earlier and more easily.Methods:A cross-sectional study was conducted. A total of 245 patients with sepsis admitted to intensive care unit (ICU) of the Affiliated Hospital of Jining Medical University from May 2013 to November 2023 were enrolled as the research subjects. The patients were divided into sAKI group and non-sAKI group based on whether they suffered from sAKI during ICU hospitalization. The differences of the demographic, clinical and laboratory indicators of patients between the two groups were compared. Logistic ordinal regression analysis was performed to analyze the imbalanced variables between the two groups, and to construct a sAKI predictive model. The predictive value of the sAKI predictive model was evaluated through 5-fold cross validation, calibration curve, and decision curve analysis (DCA), and to develop an online dynamic nomogram for the predictive model.Results:A total of 245 patients were enrolled in the final analysis. 110 (44.9%) patients developed sAKI during ICU hospitalization and 135 (55.1%) patients did not develop sAKI. Compared with the non-sAKI group, the patients in the sAKI group had higher ratios of female, hypertension, invasive mechanical ventilation (IMV), renal replacement therapy (RRT), vasopressin usage, and neutrophil count (NEU), aspartate aminotransferase (AST), blood urea nitrogen (BUN), serum creatinine (SCr), uric acid (UA), Na +, K +, procalcitonin (PCT), acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, and sequential organ failure assessment (SOFA) score. Multivariate Logistic ordinal regression analysis showed that female [odd ratio ( OR) = 2.208, 95% confidence interval (95% CI) was 1.073-4.323, P = 0.020], hypertension ( OR = 2.422, 95% CI was 1.255-5.073, P = 0.012), vasopressin usage ( OR = 2.888, 95% CI was 1.380-6.679, P = 0.002), and SCr ( OR = 1.015, 95% CI was 1.009-1.024, P < 0.001) were independent risk factors for sAKI in septic patients, and a sAKI predictive model was constructed: ln[ P/(1+ P)] = -4.665+0.792×female+0.885×hypertension+1.060×vasopressin usage+0.015×SCr. The 5-fold cross validation showed that the average area under the receiver operator characteristic curve (AUC) was 0.860, indicating the sAKI predictive model had a good performance. The calibration curve analysis showed that the calibration degree of the sAKI predictive model was good. DCA showed that the net profit of the sAKI predictive model was relatively high. A static nomogram and an online dynamic nomogram were constructed for the sAKI predictive model. Compared with the static nomogram, the dynamic nomogram allowed for manual selection of corresponding patient characteristics and viewing the corresponding sAKI risk directly. Conclusions:Female, hypertension, vasopressin usage, and SCr are the main risk factors for sAKI in patients with sepsis. The sAKI predictive model constructed based on these factors can help clinical doctors identifying high-risk patients as early as possible, and intervene in a timely manner to provide preventive effects. Compared with the common static nomogram, online dynamic nomogram can make predictive models clearer, more intuitive, and easier.

Objective To investigate the biocompatibility of new gadolinium-doped hydroxyapatite(Gd-HA)composite scaffolds and to explore their feasibility as cell culture materials and bone tissue engineering scaffolds.Methods The Gd-HA composite scaffolds were chemically synthesized and placed under the electron microscope for observation.The experiment was divided into three groups,the HA group,the Gd-HA group,and the control group.Rabbit adipose-derived mesenchymal stem cells(ADSCs)were isolated,cultured and characterized,and the Gd-HA composite scaffold extract was added to the ADSCs in vitro culture system.Cell survival and cytotoxicity were assessed by live-dead cell staining,cell proliferation ability within the scaffolds was assessed by CCK-8 assay,and the scaffolds were assessed by alizarin red staining for cell osteogenic differentiation.The toxic reactions of the scaffold materials were observed by skin irritation test,systemic acute toxicity test and muscle tissue and liver and kidney pathology at the site of intramuscular implantation of the scaffolds.Results The Gd-HA composite scaffold showed irregular void structure under electron microscope.Cell morphology observation showed that ADSCs grew adherently to the wall and were long shuttle-shaped.The positivity rate of CD29 was 96.94％,CD44 was 97.90％,CD45 was 0.10％,and CD34 was 0.46％,which was obtained using flow cytometry.Live-dead cell staining showed that the amount of live cells in the Gd-HA group was significantly better than that in the hydroxyapatite(HA)group after 5 days of co-culture.CCK-8 assay showed no significant difference in cell proliferation within 0-3 days.After 3 days,the Gd-HA group was significantly better than the HA group and the control group(P＜0.05).Calcium nodule deposition after alizarin red staining was significantly better in the Gd-HA group than in the HA and control groups,showing a deeper red color.No skin irritation was observed in gross and skin tissue HE observations after the contact of the extract with the skin.The general condition of the experimental groups was good after the infusion of the extract into the abdominal cavity,and the body mass tended to increase steadily(P＞0.05).HE staining showed that inflammatory reaction at the interface between the material and muscle tissue of the stent intramuscular implantation site in Gd-HA group was significantly higher than that of the control group,and the inflammatory cell infiltration was gradually reduced with the prolongation of implantation time.At the 8th weeks the morphology of the tissue around the material was close to normal muscle tissue,and no pathological changes were observed in the HE staining of liver and kidney at the 12th week.Conclusion Gd-HA composite scaffolds exhibit good biocompatibility and facilitate cell proliferation and osteogenic differentiation,and they are expected to serve as good carriers for stem cell transplantation in tissue engineering.

Objective To explore the effectiveness and safety of percutaneous coronary artery shock wave balloon angioplasty(IVL)under the guidance of intravascular ultrasound(IVUS)for the treatment of severe calcification lesions in the left main artery(LM).Methods A total of 26 patients with severe LM(mouth,body,bifurcation)calcification admitted to Jiangnan University Affiliated Hospital from October 2022 to April 2024 were included,with an average age of 72.0(61.8,75.4)years.Under the guidance of IVUS,IVL was used for pre-treatment of calcified lesions,followed by percutaneous coronary intervention(PCI)with stent/drug balloon implantation.All patients were evaluated using IVUS before and after the use of IVL and after PCI.And compare the IVUS intracavity related data before and after treatment[plaque burden(PB)、minimum lumen area(MLA)、minimum lumen diameter(MLD)]and calcification fracture number,minimum stent area(MSA),stent expansion coefficient(expansion,EXP),etc.Results There were 26 patients(2 with opening lesions,7 with body lesions,and 17 with bifurcation lesions at the end of the main trunk),including 7 with stable angina pectoris(SAP),10 with unstable angina(UA),4 with acute ST-segment elevation myocardial infarction(STEMI),and 5 with non ST-segment elevation myocardial infarction(NSTEMI).The PB at the most severe site of calcification decreased by 79.50(76.00,83.75)％compared to 80.00(76.00,83.75)％after IVL(P=0.001),MLA increased by 3.39(3.14,3.68)mm2 compared to 3.38(3.14,3.67)mm2 after IVL(P=0.039),MLD increased by 3.21(3.07,3.30)mm compared to 3.20(3.07,3.30)mm after IVL(P=0.024),and there was 100％calcification rupture(1/2 cases,2/9 cases,≥3/15 cases).The stent/drug ball was successfully implanted 100％,with EXP of(89.15±4.42)％and an MSA of 7.20(6.46,7.45)mm2.No adverse events such as death,angina or recurrent myocardial infarction occurred during the 3 months follow-up after surgery.Conclusions After evaluation by IVUS and pre-treatment with IVL,PCI was successfully completed for severe calcification lesions in LM,and IVL can be used as an option for the treatment of severe calcification in LM.

The distal tibial epiphyseal fractures is a common type of fracture in adolescents.The distal tibia is adjacent to the ankle joint,where the epiphysis is fragile and easily damaged when the fracture occurs,resulting in ischemic necrosis of the epiphysis and impaired bone growth,and the degree of damage and treatment effect directly influence the shape and function of the ankle joint,seriously affect the prognosis and quality of life of adolescents.Therefore,anatomical reduction should be achieved after injury as much as possible to achieve stable fixation.For stable fractures of the distal tibial epiphysis(such as Salter-Harris type Ⅰ or Ⅱ fractures),the conservative treatment can be used;whereas for unstable fractures,especially Salter-Harris type Ⅲ and Ⅳ fractures with a high risk of displacement,surgical treatment is preferred.However,due to the physiological characteristics of the epiphysis of adolescents,the distal tibia grow and develop differently,the individualized treatment plans should be developed according to the situation of adolescents.3D printing technology combined with imaging technologies including CT and MRI can print complex shapes of geometric structures to meet individual needs,and play an important role in the surgical treatment of distal tibial epiphyseal fractures,especially Salter-Harris type Ⅲ and Ⅳ fractures,which can contribute to formulating individualized surgical plans,improving the success rate of surgery,reducing the incidence of long-term complications,and greatly improving the prognosis of adolescents.Based on the literature reports in the past decade,this paper reviews the research progress of the application of 3D printing technology in the diagnosis and treatment of distal tibial epiphyseal fractures in adolescents.

OBJECTIVE: To investigate the causes of soft tissue complications in patients with dorsal displacement distal radius fractures (DRF) after volar locking plate surgery. METHODS: From July 2016 to May 2021, 112 patients with dorsal displacement DRF were treated with volar locking plate surgery, including 45 males and 67 females. The average age was (46.24±10.08) years old, ranging from 18 to 85 years old. According to whether there were soft tissue complications after operation, they were divided into complication group (40 cases) and non complication group (72 cases). Compared with preoperation, the radial metacarpal inclination and ulnar deflection angle, wrist flexion activity and dorsal extension activity, and grip strength of patients after operation were significantly improved (P<0.05). Compared with the non complication group, the proportion of patients in the complication group whose age was>60 years, body mass index (BMI) more than 30 kg·m^-2, smoking, diabetes, fracture type C, open fracture and operation time more than 90 min was higher (P<0.05). The age, BMI, smoking, diabetes, fracture AO classification, fracture type and operation time were analyzed by multifactor Logistic regression to determine the independent risk factors affecting the occurrence of postoperative soft tissue complications of patients, establish a nomogram prediction model, and evaluate the model. RESULTS: At the latest follow-up, the excellent and good rate of wrist joint function recovery was 83.93% (94/112), and the excellent and good rate of fracture reduction was 84.82% (95/112). Multivariate Logistic regression analysis showed that age more than 60 years old, diabetes, fracture type C, open fracture and operation time more than 90 min were independent risk factors for postoperative soft tissue complications (P<0.05). The receiver operating characteristic (ROC), calibration curve and clinical decision curve of the nomogram prediction model showed discrimination, accuracy and validity were good. CONCLUSION Age more than 60 years, diabetes mellitus, fracture type C, open fracture, and operation time more than 90 min are all independent risk factors for soft tissue complications after DRF volar plate fixation. In clinical treatment, perioperative soft tissue management should be done in such patients to prevent complications.
Female ; Male ; Humans ; Adult ; Middle Aged ; Adolescent ; Young Adult ; Aged ; Aged, 80 and over ; Wrist Fractures ; Fractures, Open ; Risk Factors ; Wrist Joint/surgery* ; Metacarpal Bones

Objective:To analyze the mechanism of Jindan Tablets, Xiaoyan Lidan Tablets and ursodeoxycholic acid in the treatment of gallstone and cholecystitis based on network pharmacology; To conduct a comparative analysis.Methods:The chemical components of Jindan Tablets, Xiaoyan Lidan Tablets and ursodeoxycholic acid and their drug targets were collected from Traditional Chinese Medicine Database and Analysis Platform (TCMSP). DAVID 6.8 database was used to search for the associated diseases of the drug targets. The disease targets of gallstone and cholecystitis were collected from GeneCards and other databases. The protein-protein interactions network was established based on the intersecting targets of three drugs and two diseases. KEGG enrichment analysis was performed based on the DAVID 6.8 database. Cytoscape 3.7.1 software was used to construct a complex network and topology analysis of component- target- disease between three drugs and diseases.Results:222 chemical components and 3 133 drug targets were collected for Jindan Tablets. 104 chemical components and 1 425 action targets were collected for Xiaoyan Lidan Tablets. 1 chemical component and 119 action targets were collected for ursodeoxycholic acid. The three drugs were associated with 31 diseases. 1 382 disease targets for gallstones and cholecystitis were collected. There were 237, 163 and 33 targets for gallstones and cholecystitis in the three drugs, of which 17 were shared by the three drugs and 20 were shared by Jindan Tablets and Xiaoyan Lidan Tablets. Based on the DAVID database, 113, 74 and 10 significant KEGG enrichment pathways were obtained for the three drugs respectively.Conclusions:The three drugs shared many targets and pathways in the treatment of gallstones and cholecystitis, which all had the function of regulating metabolism and inhibiting inflammatory response, while participating in apoptosis, oxidative stress and cancer pathology process. However, they had their own special effects, with Jindan Tablets favoring involving in the cancer process and inhibition of inflammation, and promoting angiogenesis. Xiaoyan Lidan Tablets and ursodeoxycholic acid focused on regulating cholesterol metabolism, and Xiaoyan Lidan Tablets also regulated steroid metabolism and inhibit inflammation, while ursodeoxycholic acid regulated bile acid metabolism.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

OBJECTIVE: Campylobacter jejuni NCTC11168 is commonly used as a standard strain for flagellar biosynthesis research. In this report, two distinguished phenotypic isolates (CJ1Z, flhA mutant strain, lawn; CJ2S, flhA complemented strain, normal colony) appeared during laboratory passages for NCTC11168. METHODS: Phenotypic assessments, including motility plates, transmission electron microscopy, biofilm formation assay, autoagglutination assay, and genome re-sequencing for these two isolates (CJ1Z, flhA mutant strain; CJ2S, flhA complemented strain) were carried out in this study. RESULTS: Transmission electron microscopy revealed that the flagellum was lost in CJ1Z. Phenotypic assessments and genome sequencing of the two isolates were performed in this study. The capacity for biofilm formation, colony auto-agglutination, and isolate motility was reduced in the mutant CJ1Z. Comparative genomic analysis indicated a unique native nucleotide insertion in flhA (nt, 2154) that caused the I719Y and I720Y mutations and early truncation in flhA. CONCLUSION FlhA has been found to influence the expression of flagella in C. jejuni. To the best of our knowledge, this is the first study to describe the function of the C-terminal of this protein.
Campylobacter jejuni/genetics* ; Bacterial Proteins/metabolism* ; Mutation ; Biological Variation, Population