Radiologic, clinical, and functional evaluation of children with displaced T-condylar fractures treated by closed reduction and percutaneous fixation using the Mayo Elbow Performance Score.

PURPOSE: T-condylar (T-C) fractures of the distal humerus are rare in children. There is no accepted treatment for such an injury, and there is a lack of reports evaluating the outcome of T-C fractures treated by closed reduction and percutaneous fixation. The aim of this study was to evaluate the feasibility of closed reduction and percutaneous K-wire and screw (CRPKS) fixation in patients with type II and III T-C fractures according to the Toniolo-Wilkins classification modified by Canavese et al. (TWC classification). METHODS: The clinical data of 12 consecutive patients (8 males, 4 females) who were younger than 14 years of age and who had a T-C fracture that was managed by CRPKS were retrospectively evaluated. Fractures were classified according to the TWC classification. The baseline information of the patients, carrying angle (CA) and Mayo Elbow Performance Score (MEPS) were used to evaluate clinical and functional outcomes; related complications were recorded. Statistical analysis was performed. RESULTS: The mean age at the time of injury was 11.6 ± 1.8 years (range, 8-14). The time from injury to surgical treatment was 1.5 ± 1.0 days (range, 0-3), and the mean follow-up duration was 33.7 ± 12.3 months (range, 18-61). Surgery lasted 45.7 ± 7.6 min on average (range, 35-58). All fractures healed in 4.9 ± 1.0 weeks on average (range, 4-7). At the last follow-up visit, the CA was 12.6° ± 5.8° on the injured side and 13.8° ± 1.8° on the uninjured side (p=0.432). The MEPS was 100 (95, 100) on the injured side and 100 (100, 100) on the uninjured side (p=0.194). Three complications were recorded. CONCLUSION: Good functional and radiological outcomes can be expected in pediatric patients with type II and III T-C fractures treated by CRPKS. The technique is relatively simple to perform and has a lower rate of complications.

Outcomes in children with delayed surgical treatment of medial humeral condyle fractures.

PURPOSE: Medial humeral condyle (MHC) fractures are easily overlooked in young patients. This can lead to delayed or incorrect diagnosis, resulting in delayed treatment, which is often associated with complications such as nonunion, osteonecrosis, fishtail deformity, and cubitus varus. The purpose of this study is to evaluate the clinical and radiographic outcomes in a cohort of paediatric patients who underwent delayed surgery for an untreated MHC fracture. METHODS: From January 2017 to December 2022, we conducted a retrospective study of paediatric patients who underwent delayed treatment for a MHC fracture. In all cases, the initial diagnosis was incorrect and surgery was performed at least one week after injury. Patients were divided into two groups based on the time between trauma and surgery: Group 1 consisted of individuals who underwent early delayed treatment within seven to 30 days of injury, while Group 2 consisted of those who underwent late delayed treatment more than one month after injury. Elbow function was assessed using the Mayo Elbow Performance Score (MEPS) and range of motion (ROM). The related literature was also reviewed (1970-2023). RESULTS: We enrolled 12 patients (7 boys, 5 girls); the average age at the time of surgery was 7.7 years (range, 2-14 years). Six patients underwent early delayed treatment (Group 1) while another six underwent late delayed treatment (Group 2). The mean time from injury to surgery was 17.7 days (range, 7-30 days) and 33.3 months (range, 70 days-9 years) in Groups 1 and 2, respectively. Open reduction and internal fixation were performed via a medial approach in 11 patients, while one patient underwent closing wedge osteotomy and internal fixation to correct cubitus varus deformity. The mean duration of follow-up was 39.4 months (range, 8-60 months). The average MEPS score was 98.3 in Group 1 (range, 95-100) and 94.2 in Group 2 (range, 85-100; P = 0.21). The following postoperative complications were recorded: heterotopic ossification (n = 2), fishtail deformity (n = 1), MHC necrosis (n = 1), and reduction of elbow ROM (n = 1); one complication occurred in Group 1 and five occurred in Group 2 (P = 0.18). We reviewed nine related studies (n = 14 patients). CONCLUSIONS: Diagnosis of MHC fractures can be challenging in paediatric patients, especially in younger individuals with incompletely ossified trochlea. Patients requiring surgery for delayed MHC fractures with an unossified trochlea should undergo ORIF to prevent progressive varus deformity. On the other hand, in patients with cubitus varus and an already ossified trochlea, distal humeral osteotomy should be considered instead of ORIF. This will minimize the potential negative impact on joint mobility.

Distraction osteogenesis at the proximal third of the ulna for the treatment of Masada type I/IIb deformities in children with hereditary multiple exostoses: a retrospective review of twenty cases.

BACKGROUND: Ulna distraction by monolateral external fixator (MEFix) is a good option for the treatment of Masada type I and IIb deformities in children with hereditary multiple exostoses (HMEs). However, there is no consensus regarding where to perform ulnar osteotomy. Our hypothesis is that osteotomy at the proximal third of the ulna and progressive distraction with MEFix can simultaneously correct elbow and wrist deformities in patients with HME. METHODS: We retrospectively reviewed patients with HME who underwent ulna distraction osteogenesis from June 2014 to March 2019. The carrying angle (CA), radial articular angle (RAA), ulnar variance (UV), radial variance (RV) and range of motion (ROM) of the affected forearm and elbow were clinically assessed before lengthening and at the last follow-up visit. The total ulna lengthening distance (LD) and radiographic outcome were also recorded. RESULTS: Nineteen patients (20 forearms) with HME aged 9.1 ± 2.4 years at the time of surgery were retrospectively reviewed. The mean follow-up period was 26.1 ± 5.6 months. There were 11 patients (12 forearms) with Masada type I deformities and eight patients (8 forearms) with Masada type IIb deformities. Patients with type IIb deformity had higher RV, lower CA values, less elbow flexion and forearm pronosupination than those with type I deformity (p < 0.05); RV was an independent risk factor for radial head dislocation, with the cut off at RV > 15.5 mm. The mean LDs in patients with type I and type IIb deformities were 33.6 ± 6.6 mm and 41.4 ± 5.4 mm, respectively. The mean CA, UV, RV, forearm pronation and ulna deviation at the wrist improved significantly following surgery in all patients. In particular, five of eight patients (62.5%) with type IIb deformities had concentric reduction of the radiocapitellar joint, while no radial head subluxation was detected in patients with type I deformities at the last follow-up. Three complications were recorded: two pin-track infections and one delayed union. CONCLUSIONS: Distraction osteogenesis at the proximal third of the ulna provides satisfactory clinical and radiological outcomes in patients with Masada type I and IIb deformities. Early treatment of Masada type I deformities is indicated before progression to more complex type IIb deformities.

Is Femoral Neck System a Valid Alternative for the Treatment of Displaced Femoral Neck Fractures in Adolescents? A Comparative Study of Femoral Neck System versus Cannulated Compression Screw.

Background and Objectives: The femoral neck system (FNS) is a new minimally invasive internal fixation system for femoral neck fractures (FNFs), but its use has not been reported in adolescents. The aim of this study was to compare the clinical and radiographic outcomes of displaced FNF in adolescents treated with FNS or a cannulated compression screw (CCS). Materials and Methods: A retrospective study of 58 consecutive patients with displaced FNF treated surgically was performed; overall, 28 patients underwent FNS and 30 CCS fixation. Sex, age at injury, type of fracture, associated lesions, duration of surgery, radiation exposure, and blood loss were collected from the hospital database. The clinical and radiographic results, as well as complications, were recorded and compared. Results: The patients were followed up for 16.4 ± 3.1 months on average after index surgery (range, 12 to 24). Consolidation time among patients treated with FNS was significantly lower than those managed by CCS (p = 0.000). The functional scores of patients treated with FNS were significantly higher than those managed by CCS (p = 0.030). Unplanned hardware removal in patients treated with FNS was significantly lower than in those managed by CCS (p = 0.024). Conclusions: FNS has a lower complication rate and better functional outcome than CCS. It may be a good alternative to treat femoral neck fractures in adolescents.

New role of sertraline against Toxoplasma gondii-induced depression-like behaviours in mice.

Toxoplasma gondii (T. gondii) is a neurotropic protozoan parasite, which can cause mental and behavioural disorders. The present study aimed to elucidate the effects and underlying molecular mechanisms of sertraline (SERT) on T. gondii-induced depression-like behaviours. In the present study, a mouse model and a microglial cell line (BV2 cells) model were established by infecting with the T. gondii RH strain. In in vivo and in vitro experiments, the underlying molecular mechanisms of SERT in inhibiting depression-like behaviours and cellular perturbations caused by T. gondii infection were investigated in the mouse brain and BV2 cells. The administration of SERT significantly ameliorated depression-like behaviours in T. gondii-infected mice. Furthermore, SERT inhibited T. gondii proliferation. Treatment with SERT significantly inhibited the activation of microglia and decreased levels of pro-inflammatory cytokines such as tumour necrosis factor-alpha, and interferon-gamma, by down-regulating tumour necrosis factor receptor 1/nuclear factor-kappa B signalling pathway, thereby ameliorating the depression-like behaviours induced by T. gondii infection. Our study provides insight into the underlying molecular mechanisms of the newly discovered role of SERT against T. gondii-induced depression-like behaviours.

Species Diversity and Toxigenic Potential of Fusarium incarnatum-equiseti Species Complex Isolates from Rice and Soybean in China.

Fusarium incarnatum-equiseti species complex (FIESC) strains are generally considered moderately virulent to many agricultural crops and produce a variety of mycotoxins, which represent a serious threat to food safety and public health. The occurrence of the FIESC strain in agricultural crops has been reported in various climatic regions, but detailed information on the species composition and toxigenic ability is rare in China. In this study, phylogenetic analyses were performed with combined sequences of EF-1a and RPB2 of 186 Fusarium isolates obtained from rice (Oryza sativa) and soybean (Glycine max). Twelve species were identified and 156 of the isolates were resolved within the Incarnatum clade of the FIESC species. Host influenced the population composition: rice isolates belonged to 12 species, among which FIESC 16, 18, and 24 strains were predominant; whereas five species were found among soybean isolates and FIESC 1, 16, and 18 strains dominated. Forty-three isolates were arbitrarily selected and analyzed for their Tri gene sequences and mycotoxigenic potential. Phylogenetic results based on the combined Tri5, Tri7, and Tri13 sequences were coincident with those from housekeeping markers. Type-A and -B trichothecenes were the main metabolites. Diacetoxyscirpenol was detected in all strains at varying concentrations. Nivalenol, 4-acetyl nivalenol, 3-acetyl deoxynivalenol, and neosolaniol were produced in members of the FIESC 1, 3, 7, 8, 15, 16, 17, and 18 strains. Our findings contribute valuable phylogenetic and toxigenic information necessary for the risk evaluation of mycotoxins in agricultural products.

Total Synthesis of (-)-Daphnezomines A and B.

Daphnezomines A and B are structurally unusual Daphniphyllum alkaloids that contain a unique aza-adamantane core skeleton. Herein, a modular approach to these alkaloids is presented that exploits a diverse array of reaction strategies. Commencing from a chiral pool terpene-(S)-carvone, the azabicyclo[3.3.1]nonane backbone, which occurs widely in Daphniphyllum alkaloids, was easily accessed through a Sharpless allylic amination and a palladium-catalyzed oxidative cyclization. A protecting group enabled a stereoselective B-alkyl Suzuki-Miyaura coupling sequence and an Fe-mediated hydrogen atom transfer (HAT)-based radical cyclization were then applied to construct C6 and C8 stereocenters. A final epimer locking strategy enabled the assembly of the highly congested aza-adamantane core, thereby achieving the first total synthesis of (-)-daphnezomines A and B in 14 steps.

Fusarium fujikuroi Species Complex Associated With Rice, Maize, and Soybean From Jiangsu Province, China: Phylogenetic, Pathogenic, and Toxigenic Analysis.

Species belonging to the Fusarium fujikuroi species complex (FFSC) are of vital importance and are a major concern for food quantity and quality worldwide, as they not only cause serious diseases in crops but also produce various mycotoxins. To characterize the population structure and evaluate the risk of poisonous secondary metabolites, a total of 237 candidate strains were isolated from rice, maize, and soybean samples in Jiangsu Province, China. Species identification of the individual strain was accomplished by sequencing the translation elongation factor 1α gene (TEF-1α) and the fumonisin (FB) synthetic gene (FUM1). The distribution of Fusarium species among the different crops was observed. The maize seeds were dominated by F. proliferatum (teleomorph, Gibberella intermedia) and F. verticillioides (teleomorph, G. moniliformis), whereas F. fujikuroi (teleomorph, G. fujikuroi) was the most frequently isolated species from rice and soybean samples. In addition, phylogenetic analyses of these strains were performed, and the results suggested clear groups showing no obvious relationship with the origin source. FFSC species pathogenicity and toxigenicity were studied. All of the species reduced the rice seed germination rate, with no significant differences. F. fujikuroi showed two distinct patterns of influencing the length of rice seedlings, which were correlated with FBs and gibberellic acid synthesis. FBs were mainly produced by F. verticillioides and F. proliferatum. F. proliferatum and F. fujikuroi also produced moniliformin and beauvericin. The toxigenicity of F. andiyazi (teleomorph, G. andiyazi) was extremely low. Further analysis indicated that the sequence variations in TEF-1α and the differences in the expression levels of the toxin synthesis genes were associated with the diversity of secondary metabolites in F. fujikuroi strains. These findings provide insight into the population-level characterization of the FFSC and might be helpful in the development of strategies for the management of diseases and mycotoxins.

Children with open tibial fractures show significantly lower infection rates than adults: clinical comparative study.

PURPOSE: The purpose of this study is to investigate and compare the surgical site infection (SSI) rates of children and adults after open tibia fracture at a single medical centre. METHODS: A retrospective study was performed on patients who sustained open tibia fractures and who received treatment at our hospital from 2012 to 2016. Data on age, gender, fracture site, Gustilo-Anderson grade, treatment management, and culture results from the infection site were recorded. RESULTS: Overall, 37 children with a mean age of 7.19 ± 2.28 years and 89 adults with a mean age of 40.38 ± 13.53 years were enrolled. The rate of SSIs was 13.5% (6/37) in children, which was significantly lower than the 21.3% (19/89) rate in adults (p < 0.001). The mean number of days to discharge was 12.86 ± 10.25 in children, which was significantly lower than the mean of 28.67 ± 16.92 days in adults (p < 0.001). Furthermore, the average waiting time for soft tissue recovery before definitive surgery was 1.41 ± 1.79 and 8.42 ± 4.38 days in children and in adults, respectively, and the difference was significant (p < 0.001). Early infection occurred more frequently in adults (5/19) than in children (0/6). Staphylococcus aureus was the most commonly found pathogen in both groups. CONCLUSION: The SSI rate of paediatric patients after open tibia fracture fixation is significantly lower than that of adults, and the prognosis of the former is superior. The results indicate a superior ability of soft tissue recovery and infection resistance after open tibia fracture fixation among children.

Predicting Label Distribution From Tie-Allowed Multi-Label Ranking.

Label distribution offers more information about label polysemy than logical label. There are presently two approaches to obtaining label distributions: LDL (label distribution learning) and LE (label enhancement). In LDL, experts must annotate training instances with label distributions, and a predictive function is trained on this training set to obtain label distributions. In LE, experts must annotate instances with logical labels, and label distributions are recovered from them. However, LDL is limited by expensive annotations, and LE has no performance guarantee. Therefore, we investigate how to predict label distribution from TMLR (tie-allowed multi-label ranking) which is a compromise on annotation cost but has good performance guarantees. On the one hand, we theoretically dissect the relationship between TMLR and label distribution. We define EAE (expected approximation error) to quantify the quality of an annotation, provide EAE bounds for TMLR, and derive the optimal range of label distributions corresponding to a given TMLR annotation. On the other hand, we propose a framework for predicting label distribution from TMLR via conditional Dirichlet mixtures. This framework blends the procedures of recovering and learning label distributions end-to-end and allows us to effortlessly encode our knowledge by a semi-adaptive scoring function. Extensive experiments validate our proposal.

Adaptive Weighted Ranking-Oriented Label Distribution Learning.

Label distribution learning (LDL) is a novel machine-learning paradigm generalized from multilabel learning (MLL). LDL attaches a label distribution to each instance, giving the description degree of different labels. In many real-world applications, key labels, that is, labels with relatively higher description degrees, are preferable to be better predicted. Unfortunately, existing LDL metrics measure the distance or similarity between label distributions from a global perspective, failing to give sufficient attention to key labels. Therefore, we design a novel LDL metric, the description-degree percentile average (DPA), which simultaneously integrates both the exact ranking value and the description degree of each label. The DPA can enhance accuracy in predicting key labels. Furthermore, noting the shape characteristics of the label distributions, we minimize the variance distance between the predicted and the ground-truth label distributions, to better maintain the distinguishability of labels. Finally, we propose an adaptive weighted ranking-oriented LDL algorithm, which is more suitable for realistic LDL problems that require higher accuracy in predicting key labels. We conduct extensive comparison experiments on various types of LDL datasets. Experimental results on both traditional and newly introduced metrics demonstrate the effectiveness of our proposal.

Does the management of osteofibrous dysplasia of the tibia and fibula in children should be tailored to the extent and location of the lesion? A case control study investigating different surgical options.

BACKGROUND: Osteofibrous dysplasia (OFD) is a rare non neoplastic, self-limited intracortical fibro-osseous lesion that most commonly affects the diaphysis of the tibia and fibula of children, the best treatment is still debated. Therefore we performed a retrospective study in children mostly under 10 years old with OFD aiming to determine whether early surgery is necessary and which is the best treatment. HYPOTHESIS: Symptomatic OFD lesions should be treated proactively, and appropriate treatment can achieve favorable outcome. METHODS: We retrospectively reviewed 23 patients with OFD of the tibia (n=22) and fibula. Management varied according to the severity of symptoms (deformity, pain or pathological fracture) and the extent of the lesion. Cases were divided into four groups (Gr.): Gr. 1: observation (n=4); Gr. 2: curettage and allograft (n=6); Gr. 3: curettage, allograft and elastic stable intramedullary nailing (ESIN) fixation (n=9); Gr. 4: extra-periosteal resection and bone transport (n=5). One patient received two different treatments successively (23 patients and 24 cases). All patients had regular clinical and radiographic follow-up to assess bone consolidation and complications. RESULTS: In Gr. 1, four asymptomatic patients underwent observation after open biopsy. Gr. 4 had the lowest local recurrence rate: 0 cases (0%) vs. 4 (66.7%; Gr. 2) vs. 1 (11.1%; Gr. 3) (p=0.002), incidence of deformity: 0 case (0%) vs. 0 (0%; Gr. 2) vs. 3 (50%; Gr. 3) (p=0.023), and pathological fracture: 0 case (0%) vs. 0 (0%; Gr. 2) vs. 1 (16.7%; Gr. 3) (p=0.006), although the consolidation time was longer: 6.8 vs. 2 (Gr. 2) vs. 2.7 months (Gr. 3) (p=0.017) and the rate of complication was higher than those of Gr. 2 and Gr. 3 (p<0.05). Gr. 3 had a lower local recurrence rate: 1 case (11.1%) vs. 4 cases (66.7%) (p=0.002), incidence of deformity: 0 case (0%) vs. 3 cases (50%) (p=0.023), and pathological fracture: 0 case vs. 1 case (16.7%) (p=0.006) than Gr. 2. DISCUSSION: Open biopsy is an important step in the management of patients with imaging suggestive of OFD in order to rule out Adamantinoma and other bone tumors or infection. Observation should be reserved for asymptomatic patients, while surgical treatment is indicated in patients with persistent pain, pathological fracture or significant deformity of the tibia. ESIN is a valid option to preserve the anatomical axis of the tibia in symptomatic patients with lesions of limited size; large circumferential lesions or recurrence can be managed by extra-periosteal resection and bone transport, although the complication rate can be relatively high. LEVEL OF EVIDENCE: III; case control study.

Diagnosis and treatment of "medial to lateral diagonal injury of the elbow" in children: Concomitant medial epicondylar and radial neck fractures.

Purpose: The simultaneous and ipsilateral occurrence of medial epicondylar and radial neck fractures is rare. This study evaluated the clinical and radiological outcomes of medial to lateral diagonal injury of the elbow (MELAINE). Methods: Six males and 6 females were diagnosed with MELAINE (left: 10, 83.3%; right: 2, 16.7%). Medial epicondylar and radial neck fractures were classified according to Papavasiliou's classification (seven type II, two type III, three type IV) and Judet's classification (three type I, four type II and five type III), respectively. All patients underwent surgery. The carrying angle, range of motion, and Kim et al. Elbow Performance Score were used to evaluate clinical and functional outcomes; related complications were recorded. Results: Mean age at injury and mean follow-up were 11.1 ± 2.5 (range, 6-14) and 40 ± 25.6 months (range, 13-90), respectively. All fractures consolidated in 6.3 ± 1.2 weeks on average (4-9). Outcomes were good (n = 1; 8.3%) to excellent (n = 11; 91.7%). The carrying angle of the injured and uninjured side was 15.5°± 2.6° and 14.7°± 2°, respectively (p = 0.218). The range of motion of elbow flexion-extension and forearm pronation-supination of the injured side was 144.2°± 10.4°, 4.6°± 5.4°, 76.7°± 9.1°, 80.4°± 9.2°, respectively, with no significant differences from the healthy side (p > 0.05). The Elbow Performance Score of the injured and uninjured side was 96.3 ± 5.3 and 98.8 ± 2.3, respectively (p = 0.139). No cases of infection, cubitus valgus, stiffness, or instability were recorded. Conclusion: Although uncommon, MELAINE should not be neglected. Surgery aims to stabilize the elbow and avoid valgus deformity. If diagnosed and treated, clinical and radiological results are excellent in most cases.

Risk of Urinary Tract Infection in Patients with Type 2 Diabetes Mellitus Treated with Dapagliflozin: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND OBJECTIVE: To investigate whether dapagliflozin (as a selective inhibitor of sodium-glucose cotransporter 2), increases the risk of urinary tract infection (UTI) in the treatment of type 2 diabetes mellitus (T2DM) remains an ongoing issue. We performed a systematic review and meta-analysis of randomized clinical trials (RCTs) to estimate the short-term and long-term risks of UTI in patients with T2DM who received dapagliflozin at different doses. METHODS: The PubMed, EMBASE, and the Cochrane Library and ClinicalTrials.gov website were searched up to December 31, 2022. Only RCTs involving adult T2DM patients with a trial duration of at least 12 weeks were included. The data were summarized using random- or fixed-effects models based on overall heterogeneity. A subgroup analysis was also performed. The review protocol was previously registered in the PROSPERO database (CRD42022299899). RESULTS: In total, 42 RCTs involving 35,938 patients were assessed for eligibility. The results showed that dapagliflozin imposed a higher risk of UTI compared to placebo and other active treatments, with a heterogeneity of 11% (odds ratio [OR] 1.17, 95% CI 1.04-1.31, p = 0.006). In the subgroup analysis, dapagliflozin 10 mg/day with a treatment period of > 24 weeks was associated with a significantly higher UTI risk than placebo or other active treatments (OR 1.27, 95% CI 1.13-1.43, p < 0.0001). The ORs for dapagliflozin as monotherapy and combination therapy in the control group were 1.05 (95% CI 0.88-1.25, p = 0.571) and 1.27 (95% CI 1.09-1.48, p = 0.008), respectively. CONCLUSIONS: High-dose, long-term treatment, and add-on therapy of dapagliflozin call for careful consideration of the risk of UTI in T2DM patients.

Coixol ameliorates Toxoplasma gondii infection-induced lung injury by interfering with T. gondii HSP70/TLR4/NF-κB signaling pathway.

Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite that causes pulmonary toxoplasmosis, although its pathogenesis is incompletely understood. There is no cure for toxoplasmosis. Coixol, a plant polyphenol extracted from coix seeds, has a variety of biological activities. However, the effects of coixol on T. gondii infection have not been clarified. In this study, we infected a mouse macrophage cell line (RAW 264.7) and BALB/c mice with the T. gondii RH strain to establish infection models in vitro and in vivo, respectively, to explore protective effects and potential mechanisms of coixol on lung injury caused by T. gondii infection. Anti-T. gondii effects and underlying anti-inflammatory mechanisms of coixol were investigated by real-time quantitative PCR, molecular docking, localized surface plasmon resonance, co-immunoprecipitation, enzyme-linked immunosorbent assay, western blotting, and immunofluorescence microscopy. The results show that coixol inhibits T. gondii loads and T. gondii-derived heat shock protein 70 (T.g.HSP70) expression. Moreover, coixol reduced inflammatory cell recruitment and infiltration, and ameliorated pathological lung injury induced by T. gondii infection. Coixol can directly bind T.g.HSP70 or Toll-like receptor 4 (TLR4) to disrupt their interaction. Coixol prevented overexpression of inducible nitric oxide synthase, tumor necrosis factor-α, and high mobility group box 1 by inhibiting activation of the TLR4/nuclear factor (NF)-κB signaling pathway, consistent with effects of the TLR4 inhibitor CLI-095. These results indicate that coixol improves T. gondii infection-induced lung injury by interfering with T.g.HSP70-mediated TLR4/NF-κB signaling. Altogether, these findings suggest that coixol is a promising effective lead compound for the treatment of toxoplasmosis.

Elastic Stable Intramedullary Nailing and Temporary External Fixation for the Treatment of Unstable Femoral Shaft Fractures in Children Aged 5-11 Years Old: A Retrospective Study of 28 Cases.

Purpose: Unstable femoral shaft fractures (UFSFs) in children aged 5-11 years remain challenging due to their intrinsic instability. The aim of this study was to evaluate the clinical and radiographic outcomes of UFSF in children aged 5 to 11 years managed by the combined use of ESIN and temporary EF. Methods: Children with UFSF (long oblique and comminuted) treated by ESIN and temporary EF were retrospectively reviewed. Sex, age at injury, side involved, type of fracture, presence or absence of associated lesions or neurovascular complications, type of treatment, time from trauma to surgery, duration of surgery, radiation exposure and length of postoperative immobilization were collected from the medical charts. Radiological and functional outcomes were evaluated according to Beaty's and Flynn's criteria, respectively. Results: A total of 28 consecutive patients with closed or open (Gustilo type I or II) UFSF were reviewed (18 boys and 10 girls). The mean age at injury was 8.7 ± 1.6 years (range, 5-11); the average weight was 38.1 ± 7.6 kg (range, 26-55). The mean hospital stay was 3.7 ± 1.4 days (range, 2-7), and the mean time to EF and ESIN removal was 6.5 ± 1.1 weeks (range, 4-8) and 9.4 ± 1.6 months (range, 6-12), respectively. Twenty-seven out of 28 patients had excellent radiographic outcomes according to Beaty's criteria, and 24/28 had excellent functional outcomes according to Flynn's criteria. Overall, 4 complications (14.3%) were recorded. No statistically significant correlation was found between complication rates and sex, age, weight or fracture characteristics (P < 0.05). Conclusions: The combined use of ESIN and temporary EF provides good clinical and radiological outcomes in children with UFSF aged between 5 and 11 years, with a reduced complication rate.

Protective effect of ginsenoside Rh2 against Toxoplasma gondii infection-induced neuronal injury through binding TgCDPK1 and NLRP3 to inhibit microglial NLRP3 inflammasome signaling pathway.

BACKGROUND: Toxoplasma gondii (T. gondii) is a neurotropic obligate intracellular parasite that can activate microglial and promote neuronal apoptosis, leading to central nervous system diseases. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome signaling complex plays a key role in inducing neuroinflammation. Our previous studies have found that ginsenoside Rh2 (GRh2) inhibits T. gondii infection-induced microglial activation and neuroinflammation by downregulating the Toll-like receptor 4/nuclear factor-kappa B signaling pathway. However, whether GRh2 reduces T. gondii infection-induced neuronal injury through actions on microglial NLRP3 inflammasome signaling has not yet been clarified. METHODS: In this study, we employed T. gondii RH strain to establish in vitro and in vivo infection models in BV2 microglia cell line and BALB/c mice. Molecular docking, localized surface plasmon resonance assay, quantitative competitive-PCR, ELISA, western blotting, flow cytometric analysis, and immunofluorescence were performed. RESULTS: Our results showed that GRh2 alleviated neuropathological damage and neuronal apoptosis in cortical tissue of T. gondii-infected mice. GRh2 and CY-09 (an inhibitor of NLRP3) exhibited potent anti-T. gondii effects through binding T. gondii calcium-dependent protein kinase 1 (TgCDPK1). GRh2 decreased Iba-1 (a specific microglial marker) and NLRP3 inflammasome signaling pathway-related protein expression by binding NLRP3. Co-culture of microglia/primary cortical neurons revealed that T. gondii-induced microglial activation caused neuronal apoptosis, but GRh2 reduced this effect, consistent with the effects of CY-09. CONCLUSION: Taken together, our results show that GRh2 has a protective effect against T. gondii infection-induced neuronal injury by binding TgCDPK1 and NLRP3 to inhibit NLRP3 inflammasome signaling pathway in microglia.

Ginsenoside Rh2 reduces depression in offspring of mice with maternal toxoplasma infection during pregnancy by inhibiting microglial activation via the HMGB1/TLR4/NF-κB signaling pathway.

BACKGROUND: Maternal Toxoplasma gondii (T. gondii) infection during pregnancy has been associated with various mental illnesses in the offspring. Ginsenoside Rh2 (GRh2) is a major bioactive compound obtained from ginseng that has an anti-T. gondii effect and attenuates microglial activation through toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. GRh2 also alleviated tumor-associated or lipopolysaccharide-induced depression. However, the effects and potential mechanisms of GRh2 on depression-like behavior in mouse offspring caused by maternal T. gondii infection during pregnancy have not been investigated. METHODS: We examined GRh2 effects on the depression-like behavior in mouse offspring, caused by maternal T. gondii infection during pregnancy, by measuring depression-like behaviors and assaying parameters at the neuronal and molecular level. RESULTS: We showed that GRh2 significantly improved behavioral measures: sucrose consumption, forced swim time and tail suspended immobility time of their offspring. These corresponded with increased tissue concentrations of 5-hydroxytryptamine and dopamine, and attenuated indoleamine 2,3-dioxygenase or enhanced tyrosine hydroxylase expression in the prefrontal cortex. GRh2 ameliorated neuronal damage in the prefrontal cortex. Molecular docking results revealed that GRh2 binds strongly to both TLR4 and high mobility group box 1 (HMGB1). CONCLUSION: This study demonstrated that GRh2 ameliorated the depression-like behavior in mouse offspring of maternal T. gondii infection during pregnancy by attenuating the excessive activation of microglia and neuroinflammation through the HMGB1/TLR4/NF-κB signaling pathway. It suggests that GRh2 could be considered a potential therapy in preventing and treating psychiatric disorders in the offspring mice of mothers with prenatal exposure to T. gondii infection.

Role and Mechanism of Epithelial-Mesenchymal Transition Mediated by Inflammatory Stress-Induced TGF-ß1 in Promoting Arteriovenous Fistula Stenosis.

Objective: To explore the role and mechanism of epithelial-mesenchymal transition (EMT) mediated by inflammatory stress-induced TGF-ß1 in promoting arteriovenous fistula stenosis. Methods: The inflammatory cells HK-2 were cultured by adding TGF-ß1. The optimal stimulation time was determined after TGF-ß1 was added. HK-2 cells were divided into two groups, DMEM/F12 medium was added to one group (the control group), and the other group was treated with TGF-ß1 (10 ng/ml) in serum-free DMEM/F12 medium to stimulate cell differentiation to mesenchymal. Results: TGF-ß1 was stably expressed after being transfected into EMT. The expression of TGF-ß1 in the experimental group was higher than that in the control group (P < 0.05) 7 days after transfection. Western blot showed that TGF-ß1 protein expression was higher in the experimental group 7 days after transfection, and no TGF-ß1 protein expression was detected in the control group. The smooth muscle cells showed α-SMA expression in the control group, but no cells with expression of SMA and CD31/vWF were found at the same time; α-SMA expression was shown in smooth muscle cells and proliferative myofibroblasts, but no cells with expressions of SMA and CD31/vWF were found at the same time. The observation group showed that the expression of α-SMA was detected in smooth muscle cells and proliferative myofibroblasts, CD31/vWF was also expressed in endothelial cells, and α-SMA and vWF were also observed in endothelial cells, but no CD31 expression was found. Conclusion: The inflammatory stress-induced TGF-ß1 could act on epithelial-mesenchymal transition and promote the degree of arteriovenous fistula stenosis.