BACKGROUND:Most of the silver coating materials prepared using active screen plasma technology in the past do not involve the nanotechnology field.The formed silver coating is in a"thin film"form,which is coated on the surface of the substrate,and the distribution of silver particles on the surface is uneven.Its long-term antibacterial ability is challenged. OBJECTIVE:To prepare nano silver coatings capable of being"buried"within stainless steel(SS)substrates using active screen plasma surface modification(ASPSM)and to observe antibacterial activity. METHODS:The nano-silver coating was prepared by ASPSM technique on stainless steel substrate.Three groups of coating samples were prepared by adjusting the bombardment time(1,2,and 4 hours),which were denoted as 1 h-Ag-ASPSM@SS,2 h-Ag-ASPSM@SS and 4 h-Ag-ASPSM@SS,respectively.The antibacterial activity of the coatings was analyzed by antibacterial ring test and Gram staining.The antibiotic coating samples of gentamicin combined with vancomycin were prepared by using stainless steel as substrate and were recorded as ACNs.Stainless steel,2 h-Ag-ASPSM@SS,and ACNs were inserted into Staphylococcus aureus or Pseudomonas aeruginosa suspension,respectively.The long-acting(84 days)antibacterial activity of the samples was analyzed by coating plate method.Bone marrow mesenchymal stem cells were co-cultured with stainless steel,2 h-Ag-ASPSM@SS,and ACNs,respectively.CCK-8 assay,dead/alive staining,and lactate dehydrogenase activity of cell supernatant were detected.Stainless steel,2 h-Ag-ASPSM@SS,and ACNs were taken after continuous exposure to Staphylococcus aureus suspension for 12 weeks.The amount of residual viable bacteria on the surface of the material was evaluated by spread plate method.Vancomycin drug sensitive disk method was used to evaluate the resistance of residual live bacteria on the surface of materials. RESULTS AND CONCLUSION:(1)With increasing bombardment time,the diameter of nano silver on the sample surface and the silver content in the coating gradually increased.Among them,the 2 h-Ag-ASPSM@SS exhibited the highest surface silver content while forming uniformly spherical nanoparticles.(2)Antibacterial ring test and Gram staining results demonstrated that compared with 1 h-Ag-ASPSM@SS and 4 h-Ag-ASPSM@SS,the 2 h-Ag-ASPSM@SS exhibited better inhibitory effect on Staphylococcus aureus and pseudomonas aeruginosa.After co-culturing with bacteria for 42 and 84 days,the number of viable bacteria on the spread plate method was significantly lower in the 2 h-Ag-ASPSM@SS group compared to the stainless steel and ACNs groups.After co-culturing with Staphylococcus aureus for 84 days and Pseudomonas aeruginosa for 42 days,the number of viable bacteria on the surface of the eluate from the ACNs group was higher than that of the stainless steel group.(3)CCK-8 assay,live/dead staining and lactate dehydrogenase activity of cell supernatant displayed that 2 h-Ag-ASPSM@SS did not have obvious cytotoxicity.ACNs showed obvious cytotoxicity.(4)After co-culture with Staphylococcus aureus for 12 weeks,the residual viable bacteria on the surface of 2 h-Ag-ASPSM@SS group was less than that of stainless steel group,and the residual viable bacteria on the surface of the ACNs group was more than that of stainless steel group.Compared with the stainless steel group,the sensitivity to vancomycin was significantly decreased in the ACNs group(P＜0.001),and there was no significant change in sensitivity to vancomycin in 2 h-Ag-ASPSM@SS group(P＞0.05).(5)The above results indicate that the silver nanoparticle coated stainless steel greatly improves the deposition efficiency of silver nanoparticles on the stainless steel surface and has long-lasting antibacterial properties and good cell compatibility.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

In the field of biomedicine,two-dimensional(2D)cell lines and animal models have played an im-portant role in the study of cell pathways and drug targets.However,due to species differences between humans and other animals,and the lack of hierarchy,cellular diversity,and cell-cell or cell-matrix interactions,2D cell lines could not ful-ly reflect what cells actually look like in the human body.Organoids are three-dimensional(3D)in vitro culture models de-rived from autologous tissue stem cells,which make up for the defects of 2D culture and can simulate the structure and function of real human organs to a certain extent,providing new ideas for disease diagnosis and treatment.Among them,lung organoids(LO)are a typical case studying the development process of human lung and the generation principle of lung diseases.Relevant studies have provided help for the treatment of pulmonary fibrosis,lung cancer,lung injury and other diseases.This paper aims to summarize and analyze the research progress of lung organoids in recent years,and fur-ther summarize the application of LO in the diagnosis and treatment of lung diseases.

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

Objective:To study the clinical characteristics and risk factors for hypertriglyceridemia-induced severe acute pancreatitis (HTG-SAP) complicated by acute kidney injury.Methods:The clinical data of HTG-SAP patients admitted to the Department of Critical Care Medicine of the Second Affiliated Hospital of Anhui Medical University from January 2014 to July 2022 were retrospectively collected, and divided into an AKI group and a non-AKI group according to whether AKI occurred. The general condition, laboratory data and clinical characteristics of the two groups were compared. Factors with statistically significant differences were screened for logistic regression analysis and a predictive model was constructed. We plotted the receiver operating characteristic curve and used the area under the curve (AUC) to evaluate the predictive ability of each predictor for HTG-SAP complicated with AKI.Results:A total of 91 patients were included, including 37 (40.7%) with AKI and 54 (59.3%) without AKI. The proportions of extrapancreatic infection, sepsis and multiple organ dysfunction syndrome, requiring mechanical ventilation, continuous renal replacement therapy (CRRT), retroperitoneal puncture, and surgical intervention were higher in the AKI group than in the non-AKI group (all P<0.05). The length of ICU stay, total length of hospitalization, and mortality rate in the AKI group were higher than those in the non-AKI group (all P<0.05). Multivariate logistic regression analysis showed that acute physiology and chronic health status scoreⅡ (APACHEⅡ) ( OR=2.069, 95% CI: 1.286-3.417, P=0.003), abdominal pressure ( OR=1.469, 95% CI: 1.108-1.958, P=0.007), and lactic acid ( OR=3.156, 95% CI: 1.013-9.831, P=0.047) were independent risk factors for AKI in HTG-SAP patients. The AUCs of the APACHEⅡ score, abdominal pressure, lactic acid level and combined prediction model were 0.951, 0.918, 0.837 and 0.986, respectively. Conclusions:Patients with HTG-SAP complicated with AKI were more likely to have complications related to extrapancreatic infection, sepsis and multiple organ dysfunction, and the proportion of mechanical ventilation, CRRT, retroperitoneal puncture and surgical intervention required during hospitalization was greater, the lengths of ICU stay and total hospital stay were longer, and the mortality rate was higher. APACHEⅡ score, abdominal pressure and lactic acid were independent risk factors for HTG-SAP concurrent AKI, and the prediction model established based on these three factors had higher value in predicting HGT-SAP concurrent AKI

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:To study the clinical effect of different application times of antibiotics in patients with hypertriglyceridemic severe acute pancreatitis(HTG-SAP).Methods:The clinical data of 92 patients with HTG-SAP who were treated at the Department of Critical Care Medicine of the Second Affiliated Hospital of Anhui Medical University from January 2016 to February 2022 were analyzed retrospectively. There were 65 males and 27 females, aged (40.82±10.55) years old. These patients were divided into three groups based on the time of prophylactic use of antibiotics: the early prevention group (used within 72 h after admission, n=39), the delayed prevention group (used after 72 h after admission, n=30) and the nonprevention group ( n=23). The clinical data such as the general data, length of stay and all cause mortality rate of the three groups of patients were analyzed. Results:Compared with patients in the nonprevention group, the incidence rate of pancreatic/peripancreatic infection [10.0%(3/30) vs. 39.1%(9/23)] and the incidence rate of bloodstream infection [6.7%(2/30) vs. 34.8%(8/23)] in the delayed prevention group were significantly decreased (pancreas/peripancreatic infection: χ 2=6.31, P=0.012; bloodstream infection: χ 2=6.72, P=0.010). The infection rate of multiple/pan resistant bacteria in the early prevention group [23.1%(9/39)] was significantly higher than the nonprevention group [4.3%(1/23)] (χ 2=4.49, P=0.034). There were no significant differences in the all cause mortality rate, length of stay, duration of intensive care, hospitalization cost, incidence of intestinal fistula and retroperitoneal hemorrhage, and the proportion of patients requiring surgery among the 3 groups (all P>0.05). Conclusions:Pophylactic use of antibiotics within 72 h of hospital admission significantly reduced the incidence of pancreatic/peripancreatic infection and bloodstream infection in patients with HTG-SAP. There were no significant differences in the final prognosis among these patients with HTG-SAP treated with antibiotics at different times.

Background: Antimicrobial peptides (AMPs) have been identified as promising compounds for consideration as novel antimicrobial agents. Objectives: This study analyzed the efficacy of cecropin B against Haemophilus parasuis isolates through scanning electron microscopy (SEM) and atomic force microscopy (AFM) experiments. Results: Cecropin B exhibited broad inhibition activity against 15 standard Haemophilus parasuis (HPS) strains and 5 of the clinical isolates had minimum inhibition concentrations (MICs) ranging from 2 to 16 μg/mL. Microelectrophoresis and hexadecane adsorption assays indicated that the more hydrophobic and the higher the isoelectric point (IEP) of the strain, the more sensitive it was to cecropin B. Through SEM, multiple blisters of various shapes and dents on the cell surface were observed. Protrusions and leakage were detected by AFM. Conclusions Based on the results, cecropin B could inhibit HPS via a pore-forming mechanism by interacting with the cytoplasmic membrane of bacteria. Moreover, as cecropin B concentration increased, the bacteria membrane was more seriously damaged. Thus, cecropin B could be developed as an effective anti-HPS agent for use in clinical applications.

Background: Antimicrobial peptides (AMPs) have been identified as promising compounds for consideration as novel antimicrobial agents. Objectives: This study analyzed the efficacy of cecropin B against Haemophilus parasuis isolates through scanning electron microscopy (SEM) and atomic force microscopy (AFM) experiments. Results: Cecropin B exhibited broad inhibition activity against 15 standard Haemophilus parasuis (HPS) strains and 5 of the clinical isolates had minimum inhibition concentrations (MICs) ranging from 2 to 16 μg/mL. Microelectrophoresis and hexadecane adsorption assays indicated that the more hydrophobic and the higher the isoelectric point (IEP) of the strain, the more sensitive it was to cecropin B. Through SEM, multiple blisters of various shapes and dents on the cell surface were observed. Protrusions and leakage were detected by AFM. Conclusions Based on the results, cecropin B could inhibit HPS via a pore-forming mechanism by interacting with the cytoplasmic membrane of bacteria. Moreover, as cecropin B concentration increased, the bacteria membrane was more seriously damaged. Thus, cecropin B could be developed as an effective anti-HPS agent for use in clinical applications.

Objective:To compare the short-term clinical effect of arthroscopic and open reduction and internal fixation with Herbert screws in treatment of Mason type II radial head fractures.Methods:A retrospective case-control study was conducted to analyze the clinical data of 38 patients with unilateral radial head fractures (Mason type II) admitted to Shanghai Zhongye Hospital from January 2017 to December 2018, including 22 males and 16 females, aged from 20 to 65 years [(37.4±12.6)years]. Twenty patients were treated by arthroscopic reduction and internal fixation with Herbert screw (Group A), and eighteen by open reduction and internal fixation with Herbert screw (Group B). The operation time and fracture healing time were recorded. The visual analogue scale (VAS), elbow flexion and extension range, forearm rotation range and Mayo elbow function score were compared between the two groups before and at 1, 3, 6, and 12 months after operation. The results of Mayo elbow performance score (MEPS) and upper limb function assessment using the disabilites of the arm, shoulder, and hand (DASH) score were compared between the two groups. Complications including screw breakage or fracture displacement were also evaluated.Results:All patients were followed up for 12-14 months [(12.3±2.3)months]. There was no significant difference in operation time between the two groups ( P>0.05). The fracture healing time was (8.9±0.6)weeks in Group A and (8.7±0.6)weeks in Group B ( P>0.05). There was no significant difference in VAS between the two groups before operation ( P>0.05). The VAS was (4.8±0.5)points at 1 month after operation in Group A, lower than (6.0±0.7)points in Group B ( P<0.05). There was no significant difference in VAS between Group A and Group B at 3, 6, and 12 months after operation ( P>0.05). There was no significant difference in elbow flexion and extension range between the two groups before operation ( P>0.05). The elbow flexion and extension range in Group A was (110.4±3.8)° and (137.1±4.0)° at 1, 3 months after operation, which was significant greater than (90.6±4.7)° and (125.1±3.5)° in Group B ( P<0.05). There was no significant difference in elbow flexion and extension range between the two groups at 6 and 12 months after operation ( P>0.05). There was no significant difference in the range of forearm rotation between the two groups before operation ( P>0.05). The range of forearm rotation in Group A was (107.1±2.8)° and (138.1±2.9)° at 1, 3 months after operation, significantly greater than (95.5±3.9)°, (121.5±3.0)° in Group B ( P<0.05). There was no significant difference in forearm rotation range between the two groups at 6 and 12 months after surgery ( P>0.05). There was no significant difference in MEPS between the two groups before operation ( P>0.05). The MEPS in Group A was (50.4±3.8)points at 1 month after operation, higher than (40.6±4.7)points in Group B ( P<0.05). There was no significant difference in MEPS between the two groups at 3, 6, and 12 months after operation ( P>0.05). There was no significant difference in DASH score between the two groups before operation ( P>0.05). The DASH score was (57.1±2.8)points at 1 month after surgery in Group A, higher than (42.5±3.9)points in Group B ( P<0.05). The DASH score was not significantly different between the two groups at 3, 6, and 12 months after operation ( P>0.05). There was no screw loosening or fracture after operation, and one patient in each group had fracture displacement ( P>0.05). Conclusion:For Mason type II radial head fractures, arthroscopic Herbert screw fixation has the advantages of less trauma, less pain and faster functional recovery of the affected limb compared with open reduction and Herbert screw fixation.