Pneumococcal Meningitis Induces Hearing Loss and Cochlear Ossification Modulated by Chemokine Receptors CX3CR1 and CCR2.

PURPOSE: Pneumococcal meningitis is a major cause of hearing loss and permanent neurological impairment despite widely available antimicrobial therapies to control infection. Methods to improve hearing outcomes for those who survive bacterial meningitis remains elusive. We used a mouse model of pneumococcal meningitis to evaluate the impact of mononuclear phagocytes on hearing outcomes and cochlear ossification by altering the expression of CX3CR1 and CCR2 in these infected mice. METHODS: We induced pneumococcal meningitis in approximately 500 C57Bl6 adult mice using live Streptococcus pneumoniae (serotype 3, 1 × 105 colony forming units (cfu) in 10 µl) injected directly into the cisterna magna of anesthetized mice and treated these mice with ceftriaxone daily until recovered. We evaluated hearing thresholds over time, characterized the cochlear inflammatory response, and quantified the amount of new bone formation during meningitis recovery. We used microcomputed tomography (microCT) scans to quantify cochlear volume loss caused by neo-ossification. We also performed perilymph sampling in live mice to assess the integrity of the blood-perilymph barrier during various time intervals after meningitis. We then evaluated the effect of CX3CR1 or CCR2 deletion in meningitis symptoms, hearing loss, macrophage/monocyte recruitment, neo-ossification, and blood labyrinth barrier function. RESULTS: Sixty percent of mice with pneumococcal meningitis developed hearing loss. Cochlear fibrosis could be detected within 4 days of infection, and neo-ossification by 14 days. Loss of spiral ganglion neurons was common, and inner ear anatomy was distorted by scarring caused by new soft tissue and bone deposited within the scalae. The blood-perilymph barrier was disrupted at 3 days post infection (DPI) and was restored by seven DPI. Both CCR2 and CX3CR1 monocytes and macrophages were present in the cochlea in large numbers after infection. Neither chemokine receptor was necessary for the induction of hearing loss, cochlear fibrosis, ossification, or disruption of the blood-perilymph barrier. CCR2 knockout (KO) mice suffered the most severe hearing loss. CX3CR1 KO mice demonstrated an intermediate phenotype with greater susceptibility to hearing loss compared to control mice. Elimination of CX3CR1 mononuclear phagocytes during the first 2 weeks after meningitis in CX3CR1-DTR transgenic mice did not protect mice from any of the systemic or hearing sequelae of pneumococcal meningitis. CONCLUSIONS: Pneumococcal meningitis can have devastating effects on cochlear structure and function, although not all mice experienced hearing loss or cochlear damage. Meningitis can result in rapid progression of hearing loss with fibrosis starting at four DPI and ossification within 2 weeks of infection detectable by light microscopy. The inflammatory response to bacterial meningitis is robust and can affect all three scalae. Our results suggest that CCR2 may assist in controlling infection and maintaining cochlear patency, as CCR2 knockout mice experienced more severe disease, more rapid hearing loss, and more advanced cochlear ossification after pneumococcal meningitis. CX3CR1 also may play an important role in the maintenance of cochlear patency.

A randomized double-blind clinical trial: Comparison of oclacitinib with a traditional Chinese herbal medicine product (Dihuang Guiqin capsule) in the treatment of canine atopic dermatitis.

Canine atopic dermatitis (cAD) is a common chronic inflammatory skin disease, which seriously affects the quality of life for both dogs and their owners. Currently, the common therapeutic drugs in the clinic have disadvantages such as obvious adverse effects and high prices. Traditional Chinese herbal medicine (TCHM) has great potential for the treatment of cAD. The aim of this study is to compare the effects of different doses of the TCHM product (Dihuang Guiqin capsule) and oclacitinib in the treatment of cAD through a randomized, double-blind trial. Sixty dogs diagnosed with AD were randomly and evenly divided into four groups (n = 15). The TCHM treatment group consisted of three subgroups that received three different oral doses (20, 40, and 60 mg/kg BW), while the control group received 0.5 mg/kg BW of oclacitinib. Each group was administered twice daily for 14 consecutive days. The results showed that both TCHM and oclacitinib significantly improved cAD-induced itching (evaluated by pVAS) and skin lesions (evaluated by CADESI-04), while interleukin 31 (IL-31) concentrations decreased significantly (P < 0.05) and serum biochemical indicators returned to normal. In particular, The therapeutic effects of TCHM medium- and high-dose groups were similar to those of oclacitinib (P > 0.05). The preliminary recommended dose of Dihuang Guiqin capsule for the treatment of cAD has been determined to be 40-60 mg/kg BW twice daily for 14 consecutive days, which can be reduced to once daily as appropriate. Dihuang Guiqin capsule was safe and well tolerated, which may be a new option for the treatment of cAD.

The Upregulation of Leucine-Rich Repeat Containing 1 Expression Activates Hepatic Stellate Cells and Promotes Liver Fibrosis by Stabilizing Phosphorylated Smad2/3.

Liver fibrosis poses a significant global health risk due to its association with hepatocellular carcinoma (HCC) and the lack of effective treatments. Thus, the need to discover additional novel therapeutic targets to attenuate liver diseases is urgent. Leucine-rich repeat containing 1 (LRRC1) reportedly promotes HCC development. Previously, we found that LRRC1 was significantly upregulated in rat fibrotic liver according to the transcriptome sequencing data. Herein, in the current work, we aimed to explore the role of LRRC1 in liver fibrosis and the underlying mechanisms involved. LRRC1 expression was positively correlated with liver fibrosis severity and significantly elevated in both human and murine fibrotic liver tissues. LRRC1 knockdown or overexpression inhibited or enhanced the proliferation, migration, and expression of fibrogenic genes in the human hepatic stellate cell line LX-2. More importantly, LRRC1 inhibition in vivo significantly alleviated CCl4-induced liver fibrosis by reducing collagen accumulation and hepatic stellate cells' (HSCs) activation in mice. Mechanistically, LRRC1 promoted HSC activation and liver fibrogenesis by preventing the ubiquitin-mediated degradation of phosphorylated mothers against decapentaplegic homolog (Smad) 2/3 (p-Smad2/3), thereby activating the TGF-ß1/Smad pathway. Collectively, these results clarify a novel role for LRRC1 as a regulator of liver fibrosis and indicate that LRRC1 is a promising target for antifibrotic therapies.

Event-Related EEG Desynchronization Reveals Enhanced Motor Imagery From the Third Person Perspective by Manipulating Sense of Body Ownership With Virtual Reality for Stroke Patients.

Virtual reality (VR)-based rehabilitation training holds great potential for post-stroke motor recovery. Existing VR-based motor imagery (MI) paradigms mostly focus on the first-person perspective, and the benefit of the third-person perspective (3PP) remains to be further exploited. The 3PP is advantageous for movements involving the back or those with a large range because of its field coverage. Some movements are easier to imagine from the 3PP. However, the 3PP training efficiency may be unsatisfactory, which may be attributed to the difficulty encountered when generating a strong sense of ownership (SOO). In this work, we attempt to enhance a visual-guided 3PP MI in stroke patients by eliciting the SOO over a virtual avatar with VR. We propose to achieve this by inducing the so-called out-of-body experience (OBE), which is a full-body illusion (FBI) that people misperceive a 3PP virtual body as his/her own (i.e., generating the SOO to the virtual body). Electroencephalography signals of 13 stroke patients are recorded while MI of the affected upper limb is being performed. The proposed paradigm is evaluated by comparing event-related desynchronization (ERD) with a control paradigm without FBI induction. The results show that the proposed paradigm leads to a significantly larger ERD during MI, indicating a bilateral activation pattern consistent with that in previous studies. In conclusion, 3PP MI can be enhanced in stroke patients by eliciting the SOO through induction of the "OBE" FBI. This study offers more possibilities for virtual rehabilitation in stroke patients and can further facilitate VR application in rehabilitation.

Quantification and Characterization of Fine Plastic Particles as Considerable Components in Atmospheric Fine Particles.

The negative effects of air pollution, especially fine particulate matter (PM2.5, particles with an aerodynamic diameter of ≤2.5 µm), on human health, climate, and ecosystems are causing significant concern. Nevertheless, little is known about the contributions of emerging pollutants such as plastic particles to PM2.5 due to the lack of continuous measurements and characterization methods for atmospheric plastic particles. Here, we investigated the levels of fine plastic particles (FPPs) in PM2.5 collected in urban Shanghai at a 2 h resolution by using a novel versatile aerosol concentration enrichment system that concentrates ambient aerosols up to 10-fold. The FPPs were analyzed offline using the combination of spectroscopic and microscopic techniques that distinguished FPPs from other carbon-containing particles. The average FPP concentrations of 5.6 µg/m3 were observed, and the ratio of FPPs to PM2.5 was 13.2% in this study. The FPP sources were closely related to anthropogenic activities, which pose a potential threat to ecosystems and human health. Given the dramatic increase in plastic production over the past 70 years, this study calls for better quantification and control of FPP pollution in the atmosphere.

The Effects of Immersion and Visuo-Tactile Stimulation on Motor Imagery in Stroke Patients are Related to the Sense of Ownership.

Visual guided motor imagery (MI) is commonly used in stroke rehabilitation, eliciting event-related desynchronization (ERD) in EEG. Previous studies found that immersion level and visuo-tactile stimulation could modulate ERD during visual guided MI, and both of two factors could also improve sense of ownership (SOO) over target limb (or body). Additionally, the relationship was also reported between the performance of MI and SOO. This study aims to investigate whether immersion and visuo-tactile stimulation affect visual guided MI through the SOO over virtual body in stroke patients. Nineteen stroke patients were recruited. The experiment included two phases (i.e., SOO induction and visual guided MI with SOO) that was manipulated across four conditions in a within-subject design: 2×2 , i.e., immersion (VR, 2D monitor display) × multisensory stimulation (visuo-tactile stimulation, observation without tactile stimulation). Results found peaks ERD amplitude during MI were significantly higher in stronger SOO conditions than weaker SOO conditions. Interestingly, the ERD during visual guided MI under the condition of vision only in VR and visuo-tactile stimulation in 2D monitor are similar, which indicates that SOO may be an important factor behind this phenomenon (due to the similar SOO between these two conditions). A moderate correlation was also found between SOO scores and peaks ERD amplitude during MI. This study discussed the possible factor underlying the effects of immersion and multisensory stimulation on visual guided MI in post-stroke patients, identifying the effect of SOO in this process, and could be referred in future studies for coming up with better MI paradigms for stroke rehabilitation.

Discovery of the first ataxia telangiectasia and Rad3-related (ATR) degraders for cancer treatment.

The first examples of ataxia telangiectasia and Rad3-related (ATR) PROTACs were designed and synthesized. Among them, the most potent degrader, ZS-7, demonstrated selective and effective ATR degradation in ATM-deficient LoVo cells, with a DC50 value of 0.53 µM. Proteasome-mediated ATR degradation by ZS-7 lasted approximately 12 h after washout in the LoVo cell lines. Notably, ZS-7 demonstrated reasonable PK profiles and, as a single agent or in combination with cisplatin, showed improved antitumor activity and safety profiles compared with the parent inhibitor AZD6738 in a xenograft mouse model of LoVo human colorectal cancer cells upon intraperitoneal (i.p.) administration.

Research progress on the catalytic and thermal decomposition of ammonium dinitramide (ADN).

Ammonium dinitramide (NH4N(NO3)2, ADN) is regarded as a promising oxidizer due to its low signature and high specific impulse. Generally, ADN undergoes exothermic decomposition above 140 °C accompanied by the byproduct of ammonium nitrate (AN). The inevitable endothermic decomposition of AN decreases the overall heat release, and so there is a need to develop efficient catalysts to guide ADN decomposition along desired pathways with a lower decomposition temperature and higher heat release. A suitable catalyst should be able to withstand the harsh conditions in a thruster to achieve a stable thrust force, which poses a huge obstacle for manufacturing a stable and active catalyst. This review gives a comprehensive summary of the thermal and catalytic decomposition pathways of ADN for the first time, which is expected to deepen the understanding of its reaction mechanism and provide useful guidance for designing prospective catalysts toward efficient ADN decomposition.

Synthesis of novel fluorescence probes and their application in the enantioselective recognition of arginine.

Arginine (Arg) plays a crucial and multifaceted role in various biological processes, encompassing cell division, wound healing, immune system modulation, and plant signaling. This study introduced a pair of novel chiral fluorescent probes, (R)-5 and (S)-5, constructed upon the BINOL framework, which exhibited enantiomeric selectivity and sensitivity to d-Arg/l-Arg in fluorescence experiments. These probes offered a simple, rapid, low-cost, and highly selective method for detecting Arg enantiomers, thereby providing a highly sensitive approach for their qualitative and quantitative analysis. The enantioselective fluorescence enhancement ratios {ef = [(I1 - I0)/(I2 - I0) = ΔI1/ΔI2]} of (R)-5 and (S)-5 to Arg were 1694 and 5163, respectively. Moreover, the probes demonstrated the capability to detect the concentration of d-Arg and l-Arg with a limit of detection of 4.84 × 10-7 M and 3.35 × 10-7 M, respectively, as well as determine the enantiomeric excess. These probes exhibited high chemical selectivity and enantioselectivity, enabling the identification of different configurations of Arg, quantification of Arg concentrations, and determination of the enantiomeric composition of Arg. This study provides valuable insights for the development of sensitive and selective chiral molecular detection methods, significantly advancing our comprehension of the relationship between Arg concentration and probe fluorescence response.

Matrix metalloproteinase-9 inhibition prevents aquaporin-4 depolarization-mediated glymphatic dysfunction in Parkinson's disease.

INTRODUCTION: The glymphatic system offers a perivascular pathway for the clearance of pathological proteins and metabolites to optimize neurological functions. Glymphatic dysfunction plays a pathogenic role in Parkinson's disease (PD); however, the molecular mechanism of glymphatic dysfunction in PD remains elusive. OBJECTIVE: To explore whether matrix metalloproteinase-9 (MMP-9)-mediated ß-dystroglycan (ß-DG) cleavage is involved in the regulation of aquaporin-4 (AQP4) polarity-mediated glymphatic system in PD. METHODS: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD and A53T mice were used in this study. The glymphatic function was evaluated using ex vivo imaging. TGN-020, an AQP4 antagonist, was administered to investigate the role of AQP4 in glymphatic dysfunction in PD. GM6001, an MMP-9 antagonist, was administered to investigate the role of the MMP-9/ß-DG pathway in regulating AQP4. The expression and distribution of AQP4, MMP-9, and ß-DG were assessed using western blotting, immunofluorescence, and co-immunoprecipitation. The ultrastructure of basement membrane (BM)-astrocyte endfeet was detected using transmission electron microscopy. Rotarod and open-field tests were performed to evaluate motor behavior. RESULTS: Perivascular influx and efflux of cerebral spinal fluid tracers were reduced in MPTP-induced PD mice with impaired AQP4 polarization. AQP4 inhibition aggravated reactive astrogliosis, glymphatic drainage restriction, and dopaminergic neuronal loss in MPTP-induced PD mice. MMP-9 and cleaved ß-DG were upregulated in both MPTP-induced PD and A53T mice, with reduced polarized localization of ß-DG and AQP4 to astrocyte endfeet. MMP-9 inhibition restored BM-astrocyte endfeet-AQP4 integrity and attenuated MPTP-induced metabolic perturbations and dopaminergic neuronal loss. CONCLUSION: AQP4 depolarization contributes to glymphatic dysfunction and aggravates PD pathologies, and MMP-9-mediated ß-DG cleavage regulates glymphatic function through AQP4 polarization in PD, which may provide novel insights into the pathogenesis of PD.

Global research trends of Mycoplasma pneumoniae pneumonia in children: a bibliometric analysis.

Background: Mycoplasma pneumoniae pneumonia (MPP), attributable to Mycoplasma pneumoniae (MP), represents a predominant form of community-acquired pneumonia in pediatric populations, thereby posing a significant threat to pediatric health. Given the burgeoning volume of research literature associated with pediatric MPP in recent years, it becomes imperative to undertake a bibliometric analysis aimed at delineating the current research landscape and emerging trends, thereby furnishing a framework for subsequent investigations. Methods: A comprehensive literature search targeting pediatric MPP was conducted in the Web of Science Core Collection. After the removal of duplicate entries through Endnote software, the remaining articles were subject to scientometric analysis via Citespace software, VOSviewer software and R language, focusing on variables such as publication volume, contributing nations, institutions and authors, references and keywords. Results: A total of 1,729 articles pertinent to pediatric MPP were included in the analysis. China and the United States emerged as the nations with the highest publication output. Italian scholar Susanna Esposito and Japanese scholar Kazunobu Ouchi were the most influential authors in the domain of pediatric MPP. Highly-cited articles primarily focused on the epidemiological investigation of pediatric MPP, the clinical characteristics and treatment of macrolide-resistant MPP, and biomarkers for refractory Mycoplasma pneumoniae pneumonia (RMPP). From the corpus of 1,729 articles, 636 keywords were extracted and categorized into ten clusters: Cluster #0 centered on molecular-level typing of macrolide-resistant strains; Cluster #1 focused on lower respiratory tract co-infections; Clusters #2 and #6 emphasized other respiratory ailments caused by MP; Cluster #3 involved biomarkers and treatment of RMPP; Clusters #4 and #9 pertained to extrapulmonary complications of MPP, Clusters #5 and #7 addressed etiological diagnosis of MPP, and Cluster #8 explored pathogenic mechanisms. Conclusions: The past few years have witnessed extensive attention directed towards pediatric MPP. Research in pediatric MPP principally revolves around diagnostic techniques for MP, macrolide resistance, complications of MPP, treatment and diagnosis of RMPP, and elucidation of pathogenic mechanisms. The present study provides pediatric clinicians and researchers with the research status and focal points in this field, thereby guiding the orientation of future research endeavors.

The effect of dopamine replacement therapy on cortical structure in Parkinson's disease.

AIMS: To explore the cortical structural reorganization in Parkinson's disease (PD) patients under chronic dopamine replacement therapy (DRT) in cross-sectional and longitudinal data and determine whether these changes were associated with clinical alterations. METHODS: A total of 61 DRT-treated, 60 untreated PD patients, and 61 normal controls (NC) were retrospectively included. Structural MRI scans and neuropsychological tests were conducted. Cortical thickness and volume were extracted based on FreeSurfer and were analyzed using general linear model to find statistically significant differences among three groups. Correlation analyses were performed among significant cortical areas, medication treatment (duration and dosage), and neuropsychological tests. Longitudinal cortical structural changes of patients who initiated DRT were analyzed using linear mixed-effect model. RESULTS: Significant cortical atrophy was primarily observed in the prefrontal cortex in treated patients, including the cortical thickness of right pars opercularis and the volume of bilateral superior frontal cortex (SFC), left rostral anterior cingulate cortex (rACC), right lateral orbital frontal cortex, right pars orbitalis, and right rostral middle frontal cortex. A negative correlation was detected between the left SFC volume and levodopa equivalent dose (LED) (r = -0.316, p = 0.016), as well as the left rACC volume and medication duration (r = -0.329, p = 0.013). In the patient group, the left SFC volume was positively associated with digit span forward score (r = 0.335, p = 0.017). The left SFC volume reduction was longitudinally correlated with increased LED (standardized coefficient = -0.077, p = 0.001). CONCLUSION: This finding provided insights into the influence of DRT on cortical structure and highlighted the importance of drug dose titration in DRT.

Dynamic Cross-Linked Polyethylene Networks with High Energy Storage and Electrical Damage Self-Healability.

Dielectric polymers that exhibit high energy density Ue, low dielectric loss, and thermal resistance are ideal materials for next-generation electrical equipment. The most widely utilized approach to improving Ue involves augmenting the polarization through increasing the dielectric constant εr or the breakdown strength Eb. However, as a conflicting parameter, the dielectric loss also increases inevitably at the same time. In addition, due to the long-term work under a strong electric field or high potential, dielectric materials often produce electrical damage (electrical tree), which is one of the main factors affecting the reliability and service life of electrical equipment. To address these problems, we herein develop dynamic cross-linked polyethylene materials (PE-MA-Epo) by polyethylene-graft-maleic anhydride (PE-MA) and polar epoxy monomers, which showed high εr (>7), low dielectric loss (<0.02), high Ue (5.16 J/cm3 at 425 MV/m), and outstanding discharge efficiency (97%). The performances of the materials are adequate to rival biaxially oriented polypropylene (BOPP) films. Moreover, the excellent self-healing capability of PE-MA-Epo enables the total recovery of εr and tan δ after electrical tree healing. After two cycles of electrical breakdown healing, Eb remained at 80%, which improves the durability and reliability of dielectric polymers. Therefore, PE-MA-Epo shows great potential for applications in advanced electronic power devices.

Predicting sepsis onset in ICU using machine learning models: a systematic review and meta-analysis.

BACKGROUND: Sepsis is a life-threatening condition caused by an abnormal response of the body to infection and imposes a significant health and economic burden worldwide due to its high mortality rate. Early recognition of sepsis is crucial for effective treatment. This study aimed to systematically evaluate the performance of various machine learning models in predicting the onset of sepsis. METHODS: We conducted a comprehensive search of the Cochrane Library, PubMed, Embase, and Web of Science databases, covering studies from database inception to November 14, 2022. We used the PROBAST tool to assess the risk of bias. We calculated the predictive performance for sepsis onset using the C-index and accuracy. We followed the PRISMA guidelines for this study. RESULTS: We included 23 eligible studies with a total of 4,314,145 patients and 26 different machine learning models. The most frequently used models in the studies were random forest (n = 9), extreme gradient boost (n = 7), and logistic regression (n = 6) models. The random forest (test set n = 9, acc = 0.911) and extreme gradient boost (test set n = 7, acc = 0.957) models were the most accurate based on our analysis of the predictive performance. In terms of the C-index outcome, the random forest (n = 6, acc = 0.79) and extreme gradient boost (n = 7, acc = 0.83) models showed the highest performance. CONCLUSION: Machine learning has proven to be an effective tool for predicting sepsis at an early stage. However, to obtain more accurate results, additional machine learning methods are needed. In our research, we discovered that the XGBoost and random forest models exhibited the best predictive performance and were most frequently utilized for predicting the onset of sepsis. TRIAL REGISTRATION: CRD42022384015.

The third-person perspective full-body illusion induced by visual-tactile stimulation in virtual reality for stroke patients.

This paper attempts to induce the third-person perspective full body illusion (3PP-FBI) with virtual reality (VR) in stroke patients. Nineteen individuals with stroke were recruited. The 3PP-FBI induction method, which was well-established in healthy individuals, using synchronous visual-tactile stimulation on one body part was used. Questionnaire scores and proprioceptive drift values were collected under different conditions for characterizing the induced 3PP-FBI. Results showed that synchronous visual-tactile stimulation of a single body part (back or upper limb) was sufficient to elicit 3PP-FBI in stroke patients, forming a sense of ownership (SOO) over the entire virtual body. Moreover, the intensity of 3PP-FBI was stronger when the back was stimulated, compared to stimulating the impaired upper limb. This study demonstrated the viability of visual-guided rehabilitation training while having a SOO to a virtual body from the third-person perspective, in anticipation of achieving better rehabilitation outcome for movements beyond the first-person perspective.

Does the timing of surgery affect outcomes in young and middle-aged patients undergoing surgical stabilization of rib fractures? Feedback was based on real data from physicians, patients, and family caregivers.

BACKGROUND: There is a general clinical consensus that early surgical stabilization of rib fractures (SSRF, ≤ 48-72 h after admission) can benefit patients, and this is only regarding the surgeon's opinions. This study assessed the true outcomes of young and middle-aged patients at different surgical timings. METHODS: This retrospective cohort study was conducted among patients aged 30-55 years who were hospitalized with a diagnosis of isolated rib fractures and underwent SSRF between July 2017 and September 2021. The patients were divided into early (≤ 3 days), mid- (4-7 days) and late (8-14 days) groups, according to the interval (days) between surgery and injury date. The impact of different surgical timings on clinical outcomes, patients, and families was assessed by comparing SSRF-related data during hospitalization and follow-up studies of clinicians, patients themselves, and family caregivers 1-2 months after surgery. RESULTS: In this study, 155 complete patient data were finally included, including 52, 64, and 39 patients in the early, mid, and late groups, respectively. Length of operation, preoperative closed chest drainage rate, length of hospital stay, intensive care unit length of stay, duration of invasive mechanical ventilation in the early group were lower than those in the intermediate and late groups. Additionally, hemothorax and excess pleural fluid incidence after SSRF was lower in the early group than in the intermediate and late groups. Postoperative follow-up results showed that patients in the early group had higher SF-12 physical component summary scores and shorter duration of absence from work. Family caregivers had lower Zarit Burden Interview scores than those in the mid- and late groups. CONCLUSION: From the experience of our institution's SSRF, early surgery is safe and offers additional potential benefits for young and middle-aged patients and families with isolated rib fractures.

Network pharmacology and molecular docking to explore Polygoni Cuspidati Rhizoma et Radix treatment for acute lung injury.

BACKGROUND: Polygoni Cuspidati Rhizoma et Radix (PCRR), a well-known traditional Chinese medicine (TCM), inhibits inflammation associated with various human diseases. However, the anti-inflammatory effects of PCRR in acute lung injury (ALI) and the underlying mechanisms of action remain unclear. AIM: To determine the ingredients related to PCRR for treatment of ALI using multiple databases to obtain potential targets for fishing. METHODS: Recognized and candidate active compounds for PCRR were obtained from Traditional Chinese Medicine Systems Pharmacology, STITCH, and PubMed databases. Target ALI databases were built using the Therapeutic Target, DrugBank, DisGeNET, Online Mendelian Inheritance in Man, and Genetic Association databases. Network pharmacology includes network construction, target prediction, topological feature analysis, and enrichment analysis. Bioinformatics resources from the Database for Annotation, Visualization and Integrated Discovery were utilized for gene ontology biological process and Kyoto Encyclopedia of Genes and Genomes network pathway enrichment analysis, and molecular docking techniques were adopted to verify the combination of major active ingredients and core targets. RESULTS: Thirteen bioactive compounds corresponding to the 433 PCRR targets were identified. In addition, 128 genes were closely associated with ALI, 60 of which overlapped with PCRR targets and were considered therapeutically relevant. Functional enrichment analysis suggested that PCRR exerted its pharmacological effects in ALI by modulating multiple pathways, including the cell cycle, cell apoptosis, drug metabolism, inflammation, and immune modulation. Molecular docking results revealed a strong associative relationship between the active ingredient and core target. CONCLUSION: PCRR alleviates ALI symptoms via molecular mechanisms predicted by network pharmacology. This study proposes a strategy to elucidate the mechanisms of TCM at the network pharmacology level.

Assessment of surgical management for locked fracture-dislocations of the proximal humerus in patients of different ages.

Background: Locked fracture-dislocation of the proximal humerus (LFDPH) is a very severe complex injury; neither arthroplasty nor internal plating are fully satisfactory. This study aimed to evaluate different surgical treatments for LFDPH to determine the optimal option for patients of different ages. Methods: From October 2012 to August 2020, patients who underwent open reduction and internal fixation (ORIF) or shoulder hemiarthroplasty (HSA) for LFDPH were retrospectively reviewed. At follow-up, radiologic evaluation was performed to evaluate bony union, joint congruence, screw cut-out, avascular necrosis of the humeral head, implant failure, impingement, heterotopic ossification, and tubercular displacement or resorption. Clinical evaluation comprised the Disability of the Arm, Shoulder, and Hand (DASH) questionnaire and Constant-Murley and visual analog scale (VAS) scores. Additionally, intraoperative and postoperative complications were assessed. Results: Seventy patients (47 women and 23 men) with final evaluation results qualified for inclusion. Patients were divided into three groups: group A: patients aged under 60 years who underwent ORIF; group B: patients aged ≥60 years who underwent ORIF; and group C: patients who underwent HSA. At a mean follow-up of 42.6 ± 26.2 months, function indicators, namely shoulder flexion, and Constant-Murley and DASH scores, in group A were significantly better than those in groups B and C. Function indicators in group B were slightly but not significantly better compared with group C. Regarding operative time and VAS scores, there were no significant differences between the three groups. Complications occurred in 25%, 30.6%, and 10% of the patients in groups A, B, and C, respectively. Conclusions: ORIF and HSA for LFDPH provided acceptable but not excellent results. For patients aged <60 years, ORIF might be optimal, whereas, for patients aged ≥60 years, both ORIF and HSA provided similar results. However, ORIF was associated with a higher rate of complications.

Long Non-Coding RNA LPP-AS2 Plays an Anti-Tumor Role in Thyroid Carcinoma by Regulating the miR-132-3p/OLFM1 Axis.

The cancer-promoting function of the long non-coding RNA (lncRNA) LPP-AS2 has been documented in different cancers. Nonetheless, its role in thyroid carcinoma (THCA) remains unestablished. Reverse transcription quantitative polymerase chain reaction and Western blotting were conducted to estimate the expressions of lncRNA LPP-AS2, miR-132-3p, and OLFM1. The THCA cells' functions were assessed through CCK8 assays, Transwell invasion assays, scratch wound-healing migration assays, and quantification of caspase-3 activity. The in vivo assays were also implemented to assess tumor growth. Luciferase reporter and RNA immuno-precipitation assay (RIPA) experiments were executed to elucidate the interactions of miR-132-3p with lncRNA LPP-AS2 and OLFM1. THCA tissues and cells exhibited poor lncRNA LPP-AS2 and OLFM1 expressions and a robust expression of miR-132-3p. Overexpressing lncRNA LPP-AS2 constrained THCA cell proliferation, migration, and invasion and improved caspase-3 activity. The anti-tumor function of lncRNA LPP-AS2 was also validated in vivo. miR-132-3p had an interplay with lncRNA LPP-AS2 and OLFM1. Functionally, overexpressing miR-132-3p promoted the malignant THCA cell phenotypes. However, that tumor promotion was abolished by the additional overexpression of lncRNA LPP-AS2. The in vitro experiments also demonstrated that the repressive effect of OLFM1 overexpression on THCA cell malignant action could be offset by the miR-132-3p mimic. lncRNA LPP-AS2 impedes THCA progression via the miR-132-3p/OLFM1 axis. Our findings contribute a potential strategy in interfering with THCA progression.