An All-Suture Anchor Offers Equivalent Clinical Performance to an Established Solid Suture Anchor in the Arthroscopic Repair of Rotator Cuff Tears: A Prospective, Randomized, Multicenter Trial With 12-Month Follow-Up.

PURPOSE: To evaluate the safety and efficacy of a next-generation, all-suture anchor in patients undergoing arthroscopic repair of rotator cuff tears, compared with that of an established solid suture anchor. METHODS: Between April 2019 and January 2021, a prospective, comparative, randomized controlled noninferiority study conducted on people with Chinese ethnicity at 3 tertiary hospitals enrolled patients (18-75 years) requiring arthroscopic treatment for rotator cuff tears. Patients were randomized into 2 cohorts receiving either all-suture anchor or solid suture anchor and followed for 12 months. The primary outcome was the Constant-Murley score at the 12-month follow-up. Magnetic resonance imaging assessments determined the rate of retear of rotator cuff repair (defined as Sugaya classification 4 and 5). Safety evaluation was performed at all follow-up points to determine the adverse events (AEs). RESULTS: In total, 120 patients with rotator cuff tears (mean age, 58.3 years; 62.5% female; 60 receiving all-suture anchor) underwent treatment. Five patients were lost to follow-up. Both cohorts showed significant improvement in Constant-Murley scores between baseline and 6 months (P < .001) and between 6 and 12 months (P < .001). There were no significant differences in Constant-Murley scores between the 2 cohorts at 12 months (P = .122) after operation. The retear rate at 12 months was 5.7% and 1.9% in the all-suture and solid suture anchor cohorts, respectively (P = .618). There were 2 cases of intraoperative anchor pullout, both of which were successfully resolved. No cases of postoperative reoperation or other anchor-related AEs were reported. CONCLUSIONS: The all-suture anchor offered equivalent clinical performance to an established solid suture anchor at the 12-month follow-up in patients undergoing arthroscopic repair of rotator cuff tears. The retear rate was not statistically significantly different between the 2 cohorts. LEVEL OF EVIDENCE: Level I, randomized controlled trial.

All-Arthroscopic Glenoid Bone Augmentation Using Iliac Crest Autograft Procedure for Recurrent Anterior Shoulder Instability: Button Fixation Is a Feasible and Satisfactory Alternative to Screw Fixation.

PURPOSE: To investigate the efficacy of all-arthroscopic glenoid bone augmentation surgery using the iliac crest autograft procedure. Furthermore, we sought to compare the clinical and radiographic outcomes of using screw versus button fixation, in patients with recurrent anterior shoulder instability. METHODS: Between 2015 and 2019, 134 shoulders with persistent instability were surgically treated with an arthroscopically placed autologous iliac crest bone graft transfer procedure. Preoperative and postoperative clinical follow-up data were evaluated using the range of motion, and the Walch-Duplay, American Shoulder and Elbow Society, and Rowe scores. Radiologic assessment on 3-dimensional computed tomography scans was performed preoperatively, immediately after surgery, as well as postoperatively, at 3 months, 6 months, 1 year, and at the final follow-up stage. Graft positions, healing, and resorption were evaluated from postoperative images. RESULTS: This study included 102 patients who underwent arthroscopic iliac crest bone grafting procedure with 2 screws fixation (n = 37; group 1) and 2 button fixation (n = 65; group 2). The mean follow-up period was 37 months. There were no significant differences between groups in terms of clinical scores, shoulder motion range, graft healing, or graft positions on computed tomography scans (P>.05). In group 1, 1 patient showed mechanical irritation and persistent pain around the screw insertion site, being treated through the arthroscopic removal of the screws. The average postoperative bony resorption percentages were 20.3% and 11.2% at 6 months, and 32.4% and 19.3% at 12 months, in group 1 and group 2, respectively. A statistically significant difference was detected between the two groups (P<.05). CONCLUSIONS: In the arthroscopic iliac crest bone grafting procedure for the treatment of chronic osseous anterior shoulder instability, excellent functional results were obtained after both button fixation and screw fixation techniques. In addition, less graft resorption and no hardware-related complications were detected with suture button fixation technique. LEVEL OF EVIDENCE: Level III, retrospective comparative therapeutic trial.

Screening and verification of antiviral compounds against HSV-1 using a method based on a plaque inhibition assay.

BACKGROUND: Herpes simplex virus type 1 (HSV-1) infection is a common viral disease that mainly causes oral lesions, but can also cause genital lesions in some instances. Current treatments with nucleoside analogs are limited by the emergence of drug resistance. Therefore, novel anti-HSV-1 drugs are urgently needed. METHODS: In this study, we screened a library of 2080 compounds for anti-HSV-1 activity using a plaque formation assay. We selected 11 potential inhibitors of HSV-1 and further evaluated their antiviral effects by plaque reduction assay and real-time polymerase chain reaction (qPCR). RESULTS: Five compounds, namely ginsenoside Rd, brassinolide, rosamultin, 3'-hydroxy puerarin, and clinafloxacin HCl, showed potent anti-HSV-1 activity and completely suppressed plaque formation at a concentration of 10 µM. Among them, clinafloxacin HCl, a fluoroquinolone antibiotic, exhibited a high selectivity index for HSV-1. CONCLUSIONS: Our findings suggest that these five compounds have potential antiviral properties against HSV-1 and may have different mechanisms of action. Further studies are warranted to elucidate the antiviral mechanisms of these compounds and to explore their therapeutic potential for HSV-1 infection.

Seroprevalence of neutralizing antibodies to human mastadenovirus serotypes 3 and 7 in healthy children from guangdong province.

Severe adenovirus pneumonia is becoming more common in children infected with human mastadenovirus (HAdV)-3 and HAdV-7 than in those infected with other types of adenoviruses. Recently, there has been a trend toward an increasing prevalence of pneumonia caused by HAdV-7, an important viral pathogen in Pediatric Intensive Care Unit infections. Children infected with HAdV-7 have more serious symptoms of acute respiratory infections and other complications than those infected with HAdV-3. No specific anti-adenovirus drugs or vaccines are available for treatment or prevention. Therefore, we investigated the seroprevalence and titer levels of neutralizing antibodies (NAbs) against HAdV-3 and HAdV-7 in healthy children in Guangdong Province. We found that the seropositivity rates and antibody titers for HAdV-3 NAb were higher than those for HAdV-7 NAb. In children between 6 and 12 months of age, the seropositivity rates and titers were significantly low against HAdV-3 and HAdV-7. The HAdV-7-positive rate was significantly higher in the HAdV-3-positive samples than in the HAdV-3-negative samples. The HAdV-7 NAbs carried by the 0-6-month age group were dominated by low titers. These results reveal a low level of herd immunity against HAdV-3 and HAdV-7 in children, clarifying the importance of monitoring these two highly virulent adenoviruses, developing prophylactic vaccines, and predicting potential outbreaks.

Serum 25-Hydroxy Vitamin D Levels in Children with Acute Respiratory Infections Caused by Respiratory Virus or Atypical Pathogen Infection.

We aimed to clarify the involvement of vitamin D status in virus or atypical pathogens infection in children with acute respiratory infections (ARIs). In this retrospective study, 295 patients with ARIs were attacked by a respiratory virus or a single atypical pathogen; 17 patients with ARIs induced by two pathogens, and 636 healthy children were included. Serum 25(OH)D levels of all children were measured. Oropharyngeal samples of the patients for viruses or atypical pathogens were studied by polymerase chain reaction (PCR) or reverse transcription-polymerase chain reaction (RT-PCR). In our studies, 58.98% of the 295 single-infected subjects and 76.47% of the 17 co-infected subjects had 25(OH)D levels below the recommended 50.0 nmol/L; the mean 25(OH)D levels were 48.48 ± 19.91 nmol/L and 44.12 ± 12.78 nmol/L. Low serum 25(OH)D levels were remarkable in patients with one of seven viruses or atypical pathogens infected. These results were significantly different from those in the healthy group. There were no significant differences in 25(OH)D levels between single infection and co-infection groups. There were no differences in severity among means of 25(OH)D levels. Female or >6-year-old children patients with low serum 25(OH)D levels were more vulnerable to pathogenic respiratory pathogens. However, serum 25(OH)D levels may be related to the recovery of ARIs. These findings provide additional evidence for the development of strategies to prevent ARIs in children.

Remodeling process and clinical outcomes following all-arthroscopic modified Eden-Hybinette procedure using iliac crest autograft and 1-tunnel double Endobutton fixation system.

BACKGROUND: Arthroscopically modified Eden-Hybinette procedures for glenohumeral stabilization have been used for a long time. With the advancement of arthroscopic techniques and the development of sophisticated instruments, a double Endobutton fixation system has been used clinically to secure bone graft to the glenoid rim placed through a specifically designed guide. The purpose of this report was to evaluate clinical outcomes and serial glenoid remodeling process following all-arthroscopic anatomical glenoid reconstruction using autologous iliac crest bone grafting technique through 1-tunnel fixation. METHODS: Forty-six patients with recurrent anterior dislocations and significant glenoid defects greater than 20% underwent arthroscopic surgery with a modified Eden-Hybinette technique. Instead of firm fixation, autologous iliac bone graft was fixed to the glenoid by double Endobutton fixation system through 1-tunnel placed in the glenoid surface. Follow-up examinations were performed at 3, 6, 12, and 24 months. The patients were followed up for a minimum of two years using the Rowe score, the Constant score, the Subjective Shoulder Value, and the Walch-Duplay score; patient satisfaction with the procedure outcome was also rated. Graft positions, healing, and absorption were evaluated postoperatively with computed tomography imaging. RESULTS: At a mean follow-up of 28 months, all patients were satisfied and had a stable shoulder. The Constant score improved from 82.9 to 88.9 points (P ＜ .001), the Rowe score, improved from 25.3 to 89.1 points (P < .001), the Subjective Shoulder Value improved from 31% to 87% (P < .001), and the Walch-Duplay score improved from 52.5 to 85.7 points (P ＜ .001). One donor-site fracture occurred during the follow-up period. All grafts were well-positioned and achieved optimal bone healing with zero excessive absorption. The preoperative glenoid surface (72.6% ± 4.5%) increased significantly immediately after surgery to 116.5% ± 9.6% (P ＜ .001). After a physiological remodeling process, the glenoid surface remained significantly increased at the last follow-up (99.2% ± 7.1%) (P ＜ .001). The glenoid surface area appeared to decrease serially when compared between the first 6 months and 12 months postoperatively, while there was no significant interval change between 12 and 24 months postoperatively. CONCLUSION: Patient outcomes were satisfactory following the all-arthroscopic modified Eden-Hybinette procedure using an autologous iliac crest grafting technique through one-tunnel fixation system with double Endobutton. Graft absorption mostly occurred on the edge and outside the ''best-fit'' circle of the glenoid. Glenoid remodeling occurred within the first year after all-arthroscopic glenoid reconstruction with an auto iliac bone graft.

Human adenovirus (HAdV) infection in children with acute respiratory tract infections in Guangzhou, China, 2010-2021: a molecular epidemiology study.

BACKGROUND: Human adenovirus (HAdV) infection can cause a variety of diseases. It is a major pathogen of pediatric acute respiratory tract infections (ARIs) and can be life-threatening in younger children. We described the epidemiology and subtypes shifting of HAdV among children with ARI in Guangzhou, China. METHODS: We conducted a retrospective study of 161,079 children diagnosed with acute respiratory illness at the Guangzhou Women and Children's Medical Center between 2010 and 2021. HAdV specimens were detected by real-time PCR and the hexon gene was used for phylogenetic analysis. RESULTS: Before the COVID-19 outbreak in Guangzhou, the annual frequency of adenovirus infection detected during this period ranged from 3.92% to 13.58%, with an epidemic peak every four to five years. HAdV demonstrated a clear seasonal distribution, with the lowest positivity in March and peaking during summer (July or August) every year. A significant increase in HAdV cases was recorded for 2018 and 2019, which coincided with a shift in the dominant HAdV subtype from HAdV-3 to HAdV-7. The latter was associated with a more severe disease compared to HAdV-3. The average mortality proportion for children infected with HAdV from 2016 to 2019 was 0.38% but increased to 20% in severe cases. After COVID-19 emerged, HAdV cases dropped to 2.68%, suggesting that non-pharmaceutical interventions probably reduced the transmission of HAdV in the community. CONCLUSION: Our study provides the foundation for the understanding of the epidemiology of HAdV and its associated risks in children in Southern China.

Diagnostic accuracy of calprotectin in periprosthetic joint infection: a diagnostic meta-analysis.

BACKGROUND: Periprosthetic joint infection (PJI) is considered to be one of the most challenging complications of joint replacement, which remains unpredictable. As a simple and emerging biomarker, calprotectin (CLP) has been considered to be useful in ruling out PJI in recent years. The purpose of this study was to investigate the accuracy and sensitivity of CLP in the diagnosis of PJI. METHODS: We searched and screened the publications from PubMed, Web of Science, EMBASE, and Cochrane Library from database establishment to June 2021. Subsequently, Stata version 16.0 software was used to combine the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), operating characteristic curve, and area under the curve (AUC). Heterogeneity across articles was evaluated by the I2 statistics. Finally, sources of heterogeneity were detected by subgroup analysis based on study design, detection method, sample size, and cutoff values. RESULTS: A total of 7 studies were included in our study, comprising 525 patients. The pooled sensitivity, specificity, PLR, and NLR of CLP for PJI diagnosis were 0.94(95% CI 0.87-0.98), 0.93(95% CI 0.87-0.96), 13.65(95% CI 6.89-27.08), and 0.06(95% CI 0.02-0.15), respectively, while the DOR and AUC were 222.33(95% CI 52.52-941.11) and 0.98 (95% CI 0.96-0.99), respectively. CONCLUSION: Synovial CLP is a reliable biomarker and can be used as a diagnostic criterion for PJI in the future. However, the uncertainty resulting from the poor study numbers and sample sizes limit our ability to definitely draw conclusions on the basis of our study.

Arthroscopic Autologous Iliac Crest Bone Grafting for Reconstruction of the Glenoid: A Nonrigid Fixation Technique.

Massive glenoid bone loss in recurrent anterior instability of the shoulder represents a surgical challenge. Some clinical trials have been published assessing the role of arthroscopic iliac crest bone grafting techniques for the management of recurrent anterior instability with glenoid bone loss. However, bone graft fixation is still controversial. We developed a method for anatomic reconstruction of anterior glenoid bone defects using autologous iliac crest graft. This technique is based on the assumption that anatomic restoration of glenoid depth and width is essential to restore stability to the shoulder.

Curcumin induced G2/M cycle arrest in SK-N-SH neuroblastoma cells through the ROS-mediated p53 signaling pathway.

Neuroblastoma (NB) is a solid tumor in the nervous system and has a high mortality rate in children. Curcumin has well-characterized anticancer properties, while there is no effective method in clinical treatment. MTT assays revealed that curcumin dramatically inhibited the proliferation of SK-N-SH cells. Compared with the control group, curcumin markedly restrained the migration of SK-N-SH cells. Curcumin induced SK-N-SH cell apoptosis by G2/M cycle arrest and activated caspase-3 activity. Furthermore, curcumin promoted the overproduction of intracellular ROS and apoptosis induced by activating p53 and Bcl-2 signal pathways. This finding demonstrated the application of curcumin is an effective strategy for the therapeutics of NB.

The inhibition of enterovirus 71 induced apoptosis by Durvillaea antarctica through P53 and STAT1 signaling pathway.

The infection of enterovirus 71 (EV71) resulted in hand, foot, and mouth disease and may lead to severe nervous system damage and even fatalities. There are no effective drugs to treat the EV71 virus and it is crucial to find novel drugs against it. Polysaccharide isolated from Durvillaea antarctica green algae has an antiviral effect. In this study, D. antarctica polysaccharide (DAPP) inhibited the infection of EV71 was demonstrated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), reverse transcription polymerase chain reaction, flow cytometry, and western blot. MTT assay showed that DAPP had no toxicity on Vero cells at the concentration 250 µg/ml. Furthermore, DAPP significantly reduced the RNA level of EV71 in a dose-dependent manner. Moreover, DAPP inhibited the Vero cells apoptosis induced by EV71 via the P53 signaling pathway. Meanwhile, the expression of signal transducer and activator of transcription 1 and mammalian target of rapamycin were increased and the proinflammatory cytokines were significantly inhibited by DAPP. Taken together, these results suggested that DAPP could be a potential pharmaceutical against the infection of EV71 virus.

Seroprevalence of Neutralizing Antibodies against Six Human Adenovirus Types Indicates the Low Level of Herd Immunity in Young Children from Guangzhou, China.

Human adenoviruses (HAdVs) commonly cause many diseases such as respiratory diseases, gastroenteritis, cystitis worldwide. HAdV-3, -7, -4 and emergent HAdV-55 and HAdV-14 are the most important types causing severe respiratory diseases. There is no effective drug available for clinical treatment, and no vaccine available for the general population. Therefore, it is important to investigate the seroprevalence against HAdV for developing novel vaccines and vectors. In this study, we investigated the seroprevalence and titer levels of neutralizing antibodies (NAb) against HAdV-3, -4, -7, -14, -55, and -11 in total 278 healthy populations between 0 months and 49 years of age (228 children and 50 adults) from Guangzhou. In children under the age of 18 years, the seropositive rates were significantly increased against HAdV-3 at 12.07%, 33.96%, and 64.29% and against HAdV-7 at 0%, 18.87%, and 19.05% in age groups of 1-2, 3-5, and 6-17 years, respectively. The seroprevalence was very low (0% ~ 8.1%) for all other four types. In adults aged between 18 and 49 years, HAdV-3, -4, and -7 (> 50.00%) were the most common types, followed by HAdV-14 (38.00%), -55 (34.00%), and -11 (24.00%). Adults tended to have high NAb titers against HAdV-4 and -55. HAdV-55-seropositive donors tended to be HAdV-11- and HAdV-14-seropositive. These results indicated the low level of herd immunity against all six HAdV types in young children, and HAdV-14, -55, -11 in adults from Guangzhou City. Our findings demonstrate the importance of monitoring HAdV types and developing vaccines against HAdV for children and adults.

Epidemiological features of traumatic spinal cord injury in Guangdong Province, China.

Study design: A retrospective hospital-based study.Objective: To describe the epidemiological profile of traumatic spinal cord injury (TSCI) in Guangdong Province.Setting: Two hospitals within Guangdong Province, China.Methods: Medical records of patients diagnosed with TSCI admitted to Foshan Hospital of Traditional Chinese Medicine and Zhujiang Hospital of South Medical University from 1 January 2011 to 31 December 2015 were retrospectively reviewed. Epidemiological characteristics, such as age, sex, occupation, etiology, neurological level of injury, American Spinal Injury Association Impairment Scale at admission, death and cause of death during the acute hospitalization and concomitant injuries.Results: During the study period, 482 cases were identified. Male-to-female ratio was 3.4:1, with a mean age of 41.5 ± 12.6 years old. The leading cause was falls (49.3%), followed by motor vehicle collisions (MVCs) (34.8%). The most common injury site was the cervical spinal cord, especially C4-C6, accounting for 39.8%.Conclusion: The number of TSCI patients in Guangdong Province is large and is exhibiting a rising trend. The leading causes were falls and MVCs. The low-falls (height < 1 m) group has expanded over this period. With China entering an ageing society, more appropriate preventative measures should be implemented for fall-related injuries among the elderly.

Tumor-targeted delivery of siRNA to silence Sox2 gene expression enhances therapeutic response in hepatocellular carcinoma.

RNA interference (RNAi) is one of the most promising methods for the treatment of malignant tumors. However, developing an efficient biocompatible delivery vector for small interfering RNA (siRNA) remains a challenging issue. This study aimed to prepare a non-viral tumor-targeted carrier, named RGDfC-modified functionalized selenium nanoparticles (RGDfC-SeNPs). RGDfC-SeNPs were used to selectively deliver siSox2 to HepG2 liver cancer cells and tissues for the treatment of hepatocellular carcinoma (HCC). In the current study, RGDfC-SeNPs were successfully synthesized and characterized. It was shown that RGDfC-SeNPs could effectively load siSox2 to prepare an antitumor prodrug RGDfC-Se@siSox2. RGDfC-Se@siSox2 exhibited selective uptake in HepG2 liver cancer cells and LO2 normal liver cells, indicating RGDfC-SeNPs could effectively deliver siSox2 to HepG2 liver cancer cells. RGDfC-Se@siSox2 entered HepG2 cells via clathrin-mediated endocytosis by firstly encircling the cytoplasm and then releasing siSox2 in the lysosomes. RGDfC-Se@siSox2 could effectively silence Sox2 and inhibit the proliferation, migration and invasion of HepG2 cells. RGDfC-Se@siSox2 induced HepG2 cells apoptosis most likely via overproduction of reactive oxygen species and disruption of the mitochondrial membrane potentials. Most importantly, RGDfC-Se@siSox2 significantly inhibited the tumor growth in HepG2 tumor-bearing mice without obvious toxic side effects. These studies indicated that RGDfC-SeNPs may be an ideal gene carrier for delivering siSox2 to HepG2 cells and that RGDfC-Se@siSox2 may be a novel and highly specific gene-targeted prodrug therapy for HCC.

Development and Biocompatibility Analysis of NBD Peptide Sustained- Release Microsphere Scaffold Nanoparticle SP-Sr-CaS/NBD.

BACKGROUND: In clinical treatment, it is difficult to carry out effective bone tissue transplantation and anti-inflammatory treatment at the same time due to bone defects and osteomyelitis where the tissue is contaminated or infected. As a downstream target of TNF-α, NF-κB has an inhibition effect on the proliferation and differentiation of cells surrounding the lesion. As a negative effect, it leads to a reduction in bone growth and development. METHODS: In this study, the small molecule NBD polypeptide and bone conduction matrix Sr-CaS are microspheres, formed to prepare Sr-CaS, NBD drug-loaded sustained-release microspheres in order to achieve a Sr-CaS/NBD peptide drug-loaded sustained release microsphere scaffold material (SP-Sr-CaS/NBD). We prepared the microspheres and optimized the production process to obtain particles with stable morphological properties and sustained release properties. RESULT: In vitro experiments demonstrated that SP-Sr-CaS/NBD could reduce TNF-α-induced cell growth inhibition, caspase-3 activity and NF-κB transcriptional activation as the function of continuous NBD peptide dosing regimen. CONCLUSION: Also, the introduction of the Sr-CaS matrix potentiates microspheres to promote cell proliferation and provides a basis to become a promising 3D bone scaffold material in the future.

Silencing of MEF2D by siRNA Loaded Selenium Nanoparticles for Ovarian Cancer Therapy.

BACKGROUND: Delivery of therapeutic small interfering RNA (siRNA) via functionalized nanoparticles holds great promise for cancer therapy. However, developing a safe and efficient delivery carrier of siRNA is a challenging issue. METHODS: RGDfC peptide was used to modify the surface of selenium nanoparticles (SeNPs) to synthesize a biocompatible siRNA delivery vehicle (R-SeNPs), and MEF2D-siRNA was loaded onto R-SeNPs to prepare a functionalized selenium nanoparticle R-Se@MEF2D-siRNA. The chemical properties of R-SeNPs were characterized, and the anticancer efficacy as well as related mechanisms of R-Se@MEF2D-siRNA were further explored. RESULTS: R-Se@MEF2D-siRNA was significantly taken up by SKOV3 cells and could enter SKOV3 cells mainly in the clathrin-associated endocytosis way. The result of in vitro siRNA release demonstrated that R-Se@MEF2D-siRNA could release MEF2D-siRNA quicker in a microenvironment simulating a lysosomal environment in tumor cells compared to a normal physiological environment. The results of qRT-PCR assay proved that R-Se@MEF2D-siRNA could effectively silence the expression of the MEF2D gene in SKOV3 cells. R-Se@MEF2D-siRNA remarkably suppressed the proliferation of SKOV3 cells and further triggered its apoptosis. In addition, R-Se@MEF2D-siRNA had the capability to disrupt mitochondrial membrane potential (MMP) in SKOV3 cells and resulted in the overproduction of reactive oxygen species (ROS), indicating that mitochondrial dysfunction and ROS generation played an important role in the apoptosis of SKOV3 cells induced by R-Se@MEF2D-siRNA. In vivo, R-Se@MEF2D-siRNA also exhibited excellent antitumor activity mainly through decreasing tumor cells proliferation and triggering their apoptosis in tumor-bearing nude mice. CONCLUSION: R-Se@MEF2D-siRNA provides an alternative strategy for ovarian cancer treatment in the clinic.

The Inhibition of H1N1 Influenza Virus-Induced Apoptosis by Surface Decoration of Selenium Nanoparticles with ß-Thujaplicin through Reactive Oxygen Species-Mediated AKT and p53 Signaling Pathways.

ß-Thujaplicin possess a variety of biological activities. The use of modified biological nanoparticles (NPs) to develop novel anti-influenza drugs has increased in recent years. Selenium nanoparticles (SeNPs) with antiviral activity have attracted increasing attention for biomedical intervention. Functionalized SeNPs by ß-thujaplicin (Se@TP) surface modified with superior antiviral activity were synthesized in this study. Compared to a virus group (43%), when treated with Se@TP (88%), the cell survival rate of MDCK cells was 45% higher. Se@TP could inhibit H1N1 from infecting Madin-Darby canine kidney (MDCK) cells and block chromatin condensation and DNA fragmentation. Se@TP obviously prevented MDCK cells from generating reactive oxygen species. Furthermore, Se@TP prevents lung injury in H1N1-infected mice through eosin staining and hematoxylin in vivo. Mechanistic investigation revealed that Se@TP inhibited H1N1 influenza virus from infecting MDCK cells through induction of apoptosis via suppressing AKT and p53 signaling pathways through immunohistochemical assay. Our results suggest that ß-thujaplicin-modified SeNPs as carriers are an efficient way to achieve an antiviral pharmaceutical candidate for H1N1 influenza.

Outcome of bone-patellar tendon-bone vs hamstring tendon autograft for anterior cruciate ligament reconstruction: A meta-analysis of randomized controlled trials with a 5-year minimum follow-up.

BACKGROUND: Many systematic reviews have compared the short-term outcomes of anterior cruciate ligment (ACL)reconstruction with hamstring and patellar tendon autograft,but few differences have been observed. The purpose of this meta-analysis was to compare the medium-term outcome of bone-patellar tendon-bone and hamstring tendon autograft for anterior cruciate ligament reconstruction in terms of clinical function, knee stability, postoperativecomplications, and osteoarthritis changes. METHODS: This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The PubMed, Embase, and the Cochrane Library databases were searched from inception to November 2, 2019. This meta-analysis included only randomized controlled trials that compared BPTB and HT autografts for ACL reconstruction with a 5-year minimum follow-up. The Cochrane Collaboration's risk-of-bias tool was used to estimate the risk-of-bias for all included studies. RevMan 5.3 software was used to performed statistical analysis of the outcomes. RESULTS: Fifteen RCTs, involving 1298 patients (610 patients in the BPTB group and 688 patients in the HT group) were included. In terms of clinical function, no significant difference was found in the objective International Knee Documentation Committee score (OR = 0.94, 95%CI: 0.64-1.37, P = .75), Lysholm knee score (MD = -2.26, 95%CI: -4.56 to 0.05, P = .06), return to preinjury activity level (OR = 1.01, 95%CI: 0.67-1.52, P = .96), and Tegner activity level (OR = 0.03, 95%CI: -0.36 to 0.41, P = .89). There was no statistically significant difference in the Lachman test (OR = 0.86, 95%CI: 0.5-1.32, P = .50), pivot-shift test (OR = 0.68, 95%CI: 0.44-1.06, P = .09), and side-to-side difference (MD = -0.32, 95%CI: -0.81 to 0.16, P = .19). As for postoperative complications and OA changes, there were no statistically significant difference in flexion loss (OR = 1.09, 95%CI: 0.47-2.54, P = .85) and OA changes (OR = 0.76, 95%CI: 0.52-1.10, P = .15), but we found significant differences in favor of the HT group in the domains of kneeling pain (OR = 1.67, 95%CI: 1.04-2.69, P = .03), anterior knee pain (OR = 2.90, 95%CI: 1.46-5.77, P = .002), and extension loss (OR = 1.75, 95%CI: 1.12-2.75, P = .01). There was a significant difference in favor of the BPTB group in the domain of graft failure (OR = 0.59, 95%CI: 0.38-0.91, P = .02). CONCLUSIONS: Based on the results above, HT autograft is comparable with the BPTB autograft in terms of clinical function, postoperative knee stability, and OA changes, with a medium-term follow-up. The HT autograft for ACL reconstruction carries a lower risk of complications, such as anterior knee pain, kneeling pain, and extension loss, but an increased incidence of graft failure. Patients should be informed of the differences when deciding on graft choice with their physician.

Inhibition of Enterovirus 71 by Selenium Nanoparticles Loaded with siRNA through Bax Signaling Pathways.

Enterovirus 71 (EV71) is the principal pathogen leading to severe cases of hand, foot, and mouth disease (HFMD). Specific drugs for EV71 are not discovered currently. Small interfering RNA (siRNA) provides a promising antiviral treatment pathway, but it is difficult to cross cell membranes and is easy to degrade. Nanoparticles are promising for their carrying capacity currently. In this study, the siRNA targeting EV71 VP1 gene was loaded with selenium nanoparticles (SeNPs) and surface decorated with polyethylenimine (PEI) (Se@PEI@siRNA). Se@PEI@siRNA showed a remarkable interference efficiency in the nerve cell line SK-N-SH and prevented the cells to be infected. The mechanism study revealed that Se@PEI@siRNA could lighten the extent of SK-N-SH cells for staying in the sub-G1 phase. Activation of Bax apoptosis signaling was restrained either. Taken together, this study demonstrated that Se@PEI@siRNA is a promising drug against EV71 virus.

A novel method to diagnose the infection of enterovirus A71 in children by detecting IgA from saliva.

Enterovirus A71 (EV-A71) is one of the main pathogens causing hand, foot, and mouth disease, and often causes diseases of the central nervous system. Early diagnosis is important to prevent EV-A71 outbreaks. The detection of serum immunoglobulin M (IgM) is widely used for the early diagnosis of EV-A71 in clinics, especially in rural areas. However, this technique requires the extraction of blood from children who have thin blood vessels and who might fear the use of needles. Therefore, difficulties in the detection process are often encountered. This study developed a noninvasive method to detect EV-A71-specific immunoglobulin A (IgA) in saliva for the diagnosis of EV-A71 infection. The sensitivity and specificity of IgA detection did not differ significantly compared with IgM detection. IgA antibodies were present in saliva for a relatively shorter period than IgM antibodies were present in serum. The sensitivity of IgA detection was higher than that of IgM detection for secondary EV-A71 infections. These results suggest that the detection of EV-A71-specific IgA in the saliva allows the effective early diagnosis of EV-A71 and may be suitable for detecting EV-A71 infections in children.