This review aimed to provide a comprehensive analysis of the etiology, epidemiology, pathology, and conventional treatment of heterotopic ossification (HO), especially emerging potential therapies. HO is the process of ectopic bone formation at non-skeletal sites. HO can be subdivided into two major forms, acquired and hereditary, with acquired HO predominating. Hereditary HO is a rare and life-threatening genetic disorder, but both acquired and hereditary form can cause severe complications, such as peripheral nerve entrapment, pressure ulcers, and disability if joint ankylosis develops, which heavily contributes to a reduced quality of life. Modalities have been proposed to treat HO, but none have emerged as the gold standard. Surgical excision remains the only effective modality; however, the optimal timing is controversial and may cause HO recurrence. Recently, potential therapeutic strategies have emerged that focus on the signaling pathways involved in HO, and small molecule inhibitors have been shown to be promising. Moreover, additional specific targets, such as small interfering RNAs (siRNAs) and non-coding RNAs, could be used to effectively block HO or develop combinatorial therapies for HO.
Humans ; Ossification, Heterotopic/genetics*

Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC_{50, SMS2} = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t _{1/2, cornea} = 1.11 h; t _{1/2, meibomian glands} = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Objective To investigate dynamic shifts in the oral microbiota and their association with the progression and aggravation of radiotherapy-induced oral mucositis(RIOM)in patients with head and neck malignancies undergoing radiotherapy.Methods Based on 16S rRNA gene sequencing,dynamic changes of oral microbiota in patients was analyzed.Results Firmicutes,Bacteroidetes,and Actinobacteria consistently constituted the predominant bacteria in the oral cavity.While there were no significant changes in the abso-lute abundance of microbiota,there were notable alterations in their relative richness and evenness.Analyses including CCA/RDA and Kruskal-Wallis indicated a significant increase in the proportions of Streptococcus and Lactobacillus genera in the later stages post-radio-therapy,showing statistically meaningful differences.Conclusion RIOM is associated with dysbiosis of oral microbiota.Microbial dys-biosis may aggravate the severity of RIOM.Streptococcus and Lactobacillus could be closely related to the progression of RIOM,pending further validation through animal experiments.

Objective To explore the clinical and imaging features of phosphaturic mesenchymal tumor(PMT).Methods The clinical presentations,laboratory examinations,and imaging manifestations of seven patients with PMT diagnosed by surgery and pathology were analyzed retrospectively.Results Among the 7 patients,four patients had clinical presentations of long-term fatigue and bone pain.All patients showed preoperative blood phosphorus reduction in varying degrees.X-ray examination showed systemic osteomalacia and osteoporosis,accompanied by multiple pathological fractures.On CT,the primary tumor appeared as a soft tissue density mass or a ground glass high-density nodule with irregular calcification and local bone destruction.MRI showed long T1,long T2 signal intensity,and irregular low signal foci were scattered in the T2WI fat-suppressed sequence.The enhanced scans showed moderate to significant inhomogeneous enhancement.One patient who underwent 18F-FDG PET/CT and two patients who underwent 18F-ALF-NOTA-Octreotide(18F-OC)PET/CT examinations showed varying degrees of radioactive concentration in the lesions.Conclusion The clinical presentations and laboratory examinations of patients with PMT have certain characteristics.Systemic osteomalacia with pseudofracture line,calcification matrix within the tumor,and significant inhomogeneous enhancement of the lesion are the key imaging features for diagnosing PMT.18F-OC PET/CT examination plays a crucial role in the systemic localization diagnosis of tumors.

Objective To rescue a recombinant oncolytic influenza virus chimeric with IL-21 and evaluate its inhibitory effects and safety against hepatocell ular carcinoma(HCC)both in vitro and in vivo,and to explore the mechanism by which this virus enhances antitumor effects when combined with anti-programmed cell death protein 1(anti-PD-1)antibody.Methods The IL-21 gene fragment was inserted into the nonstructural protein(NS)sequence of the influenza virus PR8 using reverse genetics(RG)technology to rescue the recombinant oncolytic influenza virus rOV-IL-21-NS.The virus titer and virulence were determined using the 50％tissue culture infectious dose(TCID50)and hemagglutination assays.The successful insertion of the exogenous gene into the NS sequence was verified using RT-qPCR,gel electrophoresis,and sequencing analysis.Viral morphology and size were observed with transmission electron microscopy.The impact of the virus on the viability of hepatocellular carcinoma cells was assessed with CCK-8 assay.A subcutaneous tumor model of HCC was established in 45 female C57BL/6 mice(8 weeks old,weighing 16～20 g),and then the mice were randomly assigned into PBS,PR8,anti-PD-1,rOV-IL-21-NS,and the rOV-IL-21-NS+anti-PD-1 treatment groups,with 9 mice in each group,to evaluate the anti-tumor effects of monotherapy versus combination therapy.Flow cytometry was conducted to assess the regulatory effects of monotherapy and combination therapy on the tumor immune microenvironment.Results RG technology successfully rescued the recombinant oncolytic influenza virus rOV-IL-21-NS.Sequencing confirmed the successful insertion of IL-21 into the target sequence,and the obtained virus could be stably propagated,with its sixth passage reaching a hemagglutination titer of 211,and a viral titer of 6 Log10(TCID50/mL).Oncolytic virus rOV-IL-21-NS,at a multiplicity of infection(MOI)of 3,selectively reduced the viability of HCC cells without significantly affecting normal liver cells.Compared to the control group,the combination of rOV-IL-21-NS and anti-PD-1 antibodies significantly inhibited tumor growth(P＜0.001)and increased the proportions of CD4+T and CD8+T cells in the spleen tissue of the mouse model of subcutaneous HCC tumor(P＜0.001).Conclusion The recombinant oncolytic influenza virus rOV-IL-21-NS chimeric with IL-21 can effectively and safely exert targeted killing to HCC cells,enhance T cell activation by synergizing with anti-PD-1 antibodies,and improve the immune microenvironment.

OBJECTIVE: To analyze the predictors of successful weaning off extracorporeal membrane oxygenation (ECMO) after extracorporeal cardiopulmonary resuscitation (ECPR). METHODS: The clinical data of 56 patients with cardiac arrest who underwent ECPR in Hunan Provincial People's Hospital (the First Affiliated Hospital of Hunan Normal University) from July 2018 to September 2022 were retrospectively analyzed. According to whether ECMO was successfully weaning off, patients were divided into the successful weaning off group and the failed weaning off group. The basic data, duration of conventional cardiopulmonary resuscitation (CCPR, the time from cardiopulmonary resuscitation to ECMO), duration of ECMO, pulse pressure loss, complications, and the use of distal perfusion tube and intra-aortic balloon pump (IABP) were compared between the two groups. Univariate and multivariate Logistic regression analyses were performed to identify the risk factors for weaning failure of ECMO. RESULTS: Twenty-three patients (41.07%) were successfully weaned from ECMO. Compared with the successful weaning off group, patients in the failed weaning off group were older (years old: 46.7±15.6 vs. 37.8±16.8, P < 0.05), higher incidence of pulse pressure loss and ECMO complications [81.8% (27/33) vs. 21.7% (5/23), 84.8% (28/33) vs. 39.1% (9/23), both P < 0.01], and longer CCPR time (minutes: 72.3±19.5 vs. 54.4±24.6, P < 0.01), shorter duration of ECMO support (hours: 87.3±81.1 vs. 147.7±50.8, P < 0.01), and worse improvement in arterial blood pH and lactic acid (Lac) levels after ECPR support [pH: 7.1±0.1 vs. 7.3±0.1, Lac (mmol/L): 12.6±2.4 vs. 8.9±2.1, both P < 0.01]. There were no significant differences in the utilization rate of distal perfusion tube and IABP between the two groups. Univariate Logistic regression analysis showed that the factors affecting the weaning off ECMO of ECPR patients were pulse pressure loss, ECMO complications, arterial blood pH and Lac after installation [pulse pressure loss: odds ratio (OR) = 3.37, 95% confidence interval (95%CI) was 1.39-8.17, P = 0.007; ECMO complications: OR = 2.88, 95%CI was 1.11-7.45, P = 0.030; pH after installation: OR = 0.01, 95%CI was 0.00-0.16, P = 0.002; Lac after installation: OR = 1.21, 95%CI was 1.06-1.37, P = 0.003]. After adjusting for the effects of age, gender, ECMO complications, arterial blood pH and Lac after installation, and CCPR time, showed that pulse pressure loss was an independent predictor of weaning failure in ECPR patients (OR = 1.27, 95%CI was 1.01-1.61, P = 0.049). CONCLUSIONS Early loss of pulse pressure after ECPR is an independent predictor of failed weaning off ECMO in ECPR patients. Strengthening hemodynamic monitoring and management after ECPR is very important for the successful weaning off ECMO in ECPR.
Humans ; Extracorporeal Membrane Oxygenation ; Blood Pressure ; Retrospective Studies ; Perfusion ; Cardiopulmonary Resuscitation

Objective:To elucidate the recent therapeutic efficacy of the intelligent fracture reduction robotic system in managing pelvic fractures.Methods:A retrospective evaluation of 49 pelvic fracture patients treated using the intelligent fracture reduction robotic system at Beijing Jishuitan Hospital's trauma orthopedics department between March 2021 and December 2022 was conducted. The cohort included 30 males and 19 females, with a mean age of 51.51±18.71 years (20-92 years range). Fractures were classified according to the Tile system: B1 type in 2 cases, B2 in 7, B3 in 3, C1 in 30, and C2 in 3. The median interval between injury and surgery was 6 days, with a range of 2-22 days. The robotic system assisted in pelvic fracture reduction and stabilization surgeries. Preoperative and postoperative evaluations involved pelvic CT scans, anteroposterior, inlet, and outlet radiographic images. Fracture displacement and reduction outcomes were assessed via X-ray imagery. Data captured included intraoperative blood loss, duration of surgery, fracture stabilization techniques, and postoperative monitoring period. The Majeed scoring system gauged functional outcomes.Results:Of the patients, 48 underwent minimally invasive interventions with robotic assistance, while one case necessitated open reduction and internal fixation due to an unsuccessful reduction. The duration between injury and operation ranged from 2 to 22 days. Average surgical time stood at 206.5±7.1 minutes (105-440 min range), and median intraoperative blood loss was 100ml (10-600 ml range). Using the Matta reduction criteria, 30 postoperative cases exhibited excellent and 9 good outcomes for posterior pelvic ring displacement, translating to a 93% (38/41) positive rate. For anterior pelvic ring shifts, 45 showed excellent and 3 good outcomes, culminating in a 100% (48/48) success rate. Follow-up for the 48 cases lasted 11.0 months (3-23 months range), with the Majeed functional score averaging 81.9±17.0 points (42-100 point range). 27 cases scored excellent, and 11 good, yielding a combined positive outcome rate of 79.2% (38/48).Conclusion:Employing the intelligent fracture reduction robotic system in pelvic fracture treatments facilitates minimally invasive interventions and yields favorable short-term clinical results.

Objective:To evaluate the efficacy of high-flow nasal cannula (HFNC) oxygen therapy in optimizing painless transesophageal echocardiography in elderly patients.Methods:Sixty American Society of Anesthesiologists Physical Status classification Ⅱ patients, regardless of gender, aged 60-75 yr, with body mass index of 18.5-23.9 kg/m 2, were randomized into 2 groups ( n=30 each) by a random number table method: group HFNC and conventional ventilation group (group C). Pure oxygen 10 L/min was inhaled for 3 min preoxygenation using the HFNC device in group HFNC. Group C inhaled pure oxygen at 6 L/min for 3 min preoxygenation via a nasal cannula. Sufentanil 0.1 μg/kg and remazolam 0.25-0.30 mg/kg were intravenously injected in turn. Group HFNC was connected to a high-flow humidification oxygen therapy device and inhaled pure oxygen at 60 L/min (37℃, FiO 2 100%). The flow rate of pure oxygen was maintained at 6 L/min (FiO 2 100 %) in group C. The patients were placed in left lateral decubitus position, esophageal ultrasound was performed after the eyelash reflex disappeared, and remazolam 0.1 mg/kg was intravenously injected intermittently when bucking and body movement were induced by operation stimulation. The occurrence of hypoxia-related adverse events, mandibular intervention and ventilation-related adverse events was observed during examination. The operation time, time of emergence from anesthesia and consumption of remazolam were recorded. Results:Compared with group C, the incidence of severe hypoxia and rate of mandibular intervention were significantly decreased (7%/0 and 53%/17%, P<0.05), the lowest intraoperative SpO 2 was increased ( P<0.05), and no significant change was found in the operation time, time of emergence from anesthesia and consumption of remazolam in group HFNC ( P>0.05). No ventilation-related adverse events occurred in both groups. Conclusions:HFNC can markedly optimize the ventilation management of elderly patients undergoing painless transesophageal echocardiography.