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.

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.

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 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

Mortality review is an important way to identify deficiencies and gaps in the healthcare system and can effectively improve the quality and safety of healthcare delivery.It analyzes and summarizes the relevant domes-tic and international literature and review the current development,methods and characteristics of different applica-tion areas of death case review at home and abroad,with a view to guiding healthcare departments or institutions to establish a scientific and standardized mortality review system.

Objective To collect the data of hospitalized death cases in a provincial grade A tertiary general hospital,analysis the characteristics,changing trends,rescue conditions and related influencing factors of inpatient death cases,and provide a reference for the hospital's death case management and improvement of medical quality.Methods The gender,age,inpatient department,length of hospitalization,cause of death,rescue measures,sequential organ failure assessment(SOFA)score,and the date of death cases in a grade A tertiary general hospital from January 1,2012,to December 31,2022,were collected from the hospital medical record database.The characteristics of death cases were then statistically summarized through data aggregation.Spearman's rank correlation coefficient was used to analyze the relationship between the two research variables,while multivariate Logistic regression analysis was employed to explore the relevant factors affecting the implementation of rescue measures when death events occur in hospitalized patients,and draw the receiver operator characteristic curve(ROC curve)to analyze the relevant factors affecting the implementation of cardiopulmonary resuscitation in the event of death in hospitalized patients.Results ① The in-hospital mortality rate of inpatients in this hospital in the past 10 years was 0.26％,the mortality rate of males was significantly higher than that of females[0.32％(1 959/607 170)vs.0.19％(1 021/549 802),χ2 = 210.615,P<0.01],the mortality rate of hospitalized patients increased with age(r = 0.860,P = 0.037),and elderly patients>65 years old were the main group of hospital deaths;②The top 5 main causes of death among patients in this hospital were tumors,circulatory system diseases,respiratory system diseases,digestive system diseases and the symptoms,signs,clinical and laboratory abnormal findings,and those who died due to these 5 types of diseases accounted for 82.05％(2 445/2 980)of the total number of deaths;③Before the death event,the electrocardiogram(ECG)monitoring rate of inpatients in this hospital was 77.99％,the epinephrine usage rate was 83.46％,the endotracheal intubation rate was 57.55％,the cardiopulmonary resuscitation implementation rate was 44.93％,and the defibrillation rate was 12.85％.The epinephrine usage rate[86.17％(1 688/1 959)vs.78.26％(799/1 021)],the endotracheal intubation rate[59.37％(1 163/1 959)vs.54.06％(552/1 021)]and the cardiopulmonary resuscitation implementation rate[46.30％(907/1 959)vs.42.31％(432/1 021)]of male patients was significantly higher than that of female patients(all P<0.05);the cardiopulmonary resuscitation implementation rate for patients who died over 65 years old was significantly lower than those in other age groups[43.25％(734/1 697)vs.47.16％(605/1 283),P<0.05],before the death of inpatients in the surgical department,the ECG monitoring rate[68.63％(641/934)vs.82.26％(1 679/2 041)],the epinephrine usage rate[75.48％(705/934)vs.87.21％(1 780/2 041)]and the cardiopulmonary resuscitation implementation rate[31.16％(291/934)vs.51.34％(1 048/2 041)]were significantly lower than those in other department(all P<0.05).Patients who died from tumors had the lowest implementation rate of rescue measures when the death event occurred.Except for tumor patients,the ECG monitoring rate[68.33％(233/341)vs.93.07％(1 356/1 457)],the epinephrine usage rate[86.22％(294/341)vs.95.47％(1 391/1 457)],the endotracheal intubation rate[60.12％(205/341)vs.71.31％(1 039/1 457)],the cardiopulmonary resuscitation rate[40.18％(137/341)vs.55.66％(811/1 457)]and the defibrillation rate[7.92％(27/341)vs.19.42％(283/1 457)]of patients who died due to digestive system diseases were significantly lower than those who died due to circulatory diseases,respiratory diseases,and symptoms,signs,clinical and laboratory abnormalities(all P<0.05);④Multivariate Logistic regression analysis showed that urban household registration and SOFA score≥14 points before death were independent factors influencing the likelihood of cardiopulmonary resuscitation being performed in patients with severe death[odds ratio(OR)and 95％confidence interval(95％ CI)were 6.731(1.891-23.958)and 10.023(3.169-31.704),P values are 0.003 and<0.001 respectively];⑤ROC curve analysis shows that urban household registration,SOFA score≥14 points before death and their combination had a certain predictive value for cardiopulmonary resuscitation in hospitalized patients with digestive diseases(all P<0.05),and the combined value was higher,the area under ROC curve(AUC)= 0.840,95％ CI was 0.742-0.934.sensitivity was 82.76％,specificity was 75.51％,positive predictive value was 78.18％,and negative predictive value was 73.91％.Conclusions Hospitals should specifically strengthen the medical quality management of inpatient death cases,enhance the early warning system for high-risk patients,and consistently standardize the rescue measures and procedures for inpatients.Additionally,hospitals should prioritize the care of elderly and male patients with circulatory and respiratory-related critical illnesses,they should also strive to improve their ability to identify and treat critically ill surgical patients,as well as enhance their expertise in managing severe digestive system diseases.

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.