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*

BACKGROUND: Neoadjuvant therapeutic strategies play a pivotal role in the comprehensive treatment of non-small cell lung cancer (NSCLC). However, lung squamous cell carcinoma (SCC) generally exhibits a more favorable response to neoadjuvant therapy compared with lung adenocarcinoma (ADC). The aim of this study is to elucidate how baseline cancer-associated fibroblasts (CAFs) and tumor-associated endothelial cells (TAECs) influence the differential therapeutic outcomes of neoadjuvant treatment in SCC versus ADC. METHODS: We retrospectively collected pretreatment biopsy samples from 104 patients with stage II-III NSCLC who underwent neoadjuvant chemotherapy (NAC) or neoadjuvant chemoimmunotherapy (NAIC) at Shandong Cancer Hospital between January 1, 2018 and December 31, 2023. Tissue microarrays were constructed using an automated arrayer, and multiplex immunofluorescence staining (α-SMA/CD31/CK/DAPI) was performed to identify CAFs (α-SMA+/CK-) and TAECs (CD31+/CK-). Quantitative analyses included CAFs and TAECs densities, the nearest neighbor distance (NND) between CAFs and TAECs, and their spatial proximity (30 μm). Differences in major pathological response (MPR) between groups, defined as residual viable tumor cells ≤10% in resected specimens after neoadjuvant therapy, were assessed using the χ² test. The Mann-Whitney U test was applied to analyze intergroup differences in quantitative indicators, and receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive performance of immune-related markers for MPR in the NAIC cohort. RESULTS: Among the 104 NSCLC patients who received neoadjuvant therapy, 35 underwent NAIC and 69 received NAC. Overall, patients with SCC were more likely to achieve MPR compared with those with ADC (50.0% vs 22.4%, P=0.006). This trend persisted in the NAIC subgroup (72.7% vs 30.8%, P=0.038), whereas no significant difference in MPR rates was observed between SCC and ADC in the NAC subgroup. At baseline, prior to NAIC or NAC, programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) expression, CAFs and TAECs densities, CAFs-TAECs NND, and CAFs-TAECs proximity (30 μm) showed no significant differences between SCC and ADC. In patients with SCC receiving NAIC, baseline PD-L1/PD-1 expression, CAFs density, and TAECs density showed not significant differences between MPR and NMPR groups. However, the CAFs-TAECs distance was significantly greater in the MPR group (NND: 31.2 vs 24.7 μm, P=0.038), and the number of TAECs within 30 μm of CAFs was significantly lower (proximity: 1.1 vs 3.6, P=0.038). Univariate Cox regression analysis indicated that low TAECs density was associated with MPR following NAIC (OR=36.00, 95%CI: 2.68-1486.88, P=0.019). Furthermore, ROC analysis demonstrated that baseline CAFs-TAECs NND and proximity (30 μm) exhibited strong predictive performance for MPR in SCC patients treated with NAIC, with an area under the curve (AUC) of 0.893, sensitivity of 0.857, and specificity of 1.000. CONCLUSIONS CAFs are more spatially distant from TAECs and more prone to MPR after NAIC in SCC, which may be related to the reduced interaction of CAFs with TAECs and reduced tumor-associated angiogenesis.
Humans ; Lung Neoplasms/therapy* ; Neoadjuvant Therapy ; Male ; Female ; Middle Aged ; Retrospective Studies ; Endothelial Cells/drug effects* ; Aged ; Cancer-Associated Fibroblasts/drug effects* ; Immunotherapy ; Carcinoma, Squamous Cell/drug therapy* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Adult

OBJECTIVES: Endometrial tuberculosis, which commonly affects women of reproductive age, is a significant cause of intrauterine adhesions (IUA), potentially leading to hypomenorrhea, amenorrhea, and infertility. Hysteroscopic adhesiolysis is the primary treatment for IUA; however, studies specifically addressing its efficacy in tuberculosis-induced IUA remain scarce. This study aims to evaluate the therapeutic outcomes of hysteroscopic adhesiolysis for IUA caused by endometrial tuberculosis. METHODS: This retrospective cohort study included patients diagnosed with tuberculosis-induced IUA who underwent hysteroscopic adhesiolysis at the Third Xiangya Hospital of Central South University between May 2014 and October 2022. Clinical data including age, medical history, adhesion severity, surgical treatment, and reproductive outcomes were analyzed. RESULTS: Among 39 patients identified, 2 were lost to follow-up. A total of 37 patients were included, with a follow-up duration ranging from 6 months to 9 years. Hypomenorrhea was reported in 24 (64.9%) patients, secondary amenorrhea in 10 (27.0%) patients, and normal menstruation in 3 (8.1%) patients. Most patients presented with primary infertility (59.5%), and only 2 (5.4%) had secondary infertility. The median American Fertility Society (AFS) score at initial assessment was 10 (range, 8-12); 8 (21.6%) patients had moderate IUA, and 29 (78.4%) had severe IUA. A total of 86 surgical procedures were performed across 37 patients, with 27 patients undergoing 2 or more surgeries. Postoperatively, 25 (67.6%) patients achieved normalization of the uterine cavity, while 12 (32.4%) still had a reduced cavity. Only 7 (18.9%) patients had a grossly normal endometrium at the final surgery, all of whom had moderate adhesions at the initial procedure. Menstrual flow returned to normal in 12 (32.4%) patients, while 25 (67.6%) continued to experience hypomenorrhea. Of 29 patients who attempted in vitro fertilization and embryo transfer (IVF-ET), only 6 (20.7%) conceived. Among these, 4 (13.8%) delivered at term via cesarean section; one case was complicated by postpartum hemorrhage due to uterine atony and another by placental adhesion. CONCLUSIONS Endometrial tuberculosis can lead to severe IUA. Hysteroscopic adhesiolysis facilitates cavity restoration and improvement of menstrual conditions, but the overall reproductive outcomes remain suboptimal.
Humans ; Female ; Hysteroscopy/methods* ; Tissue Adhesions/etiology* ; Retrospective Studies ; Adult ; Uterine Diseases/etiology* ; Infertility, Female/surgery* ; Treatment Outcome ; Tuberculosis, Female Genital/surgery* ; Fertility ; Pregnancy

Toxoplasma gondii is a single-celled parasite that infects nearly all warm-blooded animals, including humans (Montoya and Liesenfeld, 2004). It occurs worldwide and can persist for a lifetime in mammals. Humans get infected by eating undercooked meat of animals containing the tissue cysts of this parasite. In immune-competent individuals, T. gondii infection usually does not cause significant clinical symptoms, whereas in pregnant or immunocompromised individuals, T. gondii infection (toxoplasmosis) can cause more serious problems like abortion and even death (Dunn et al., 1999; Wang et al., 2017). A combination of pyrimethamine and sulfadiazine is usually used to treat toxoplasmosis, although it is generally inefficient and causes side effects (Alday and Doggett, 2017). Worse still, there is a lack of vaccines to prevent T. gondii infection in humans or animals.
Toxoplasma/enzymology* ; Animals ; Humans ; Toxoplasmosis ; Mitochondria/enzymology* ; Protozoan Proteins/metabolism*

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.

OBJECTIVE: To investigate the frequency and related factors of ineffective triggering (IT) and double triggering (DT) in patients with acute brain injury undergoing invasive mechanical ventilation. METHODS: A retrospective cohort study was conducted using data from a single-center observational trial. Patients with acute brain injury [traumatic brain injury, stroke, and post-craniotomy for brain tumors] undergoing mechanical ventilation in the intensive care unit (ICU) of Beijing Tiantan Hospital, Capital Medical University between June 2017 and July 2019 were retrospectively analyzed. Demographic and clinical data were collected. Respiratory parameters and waveforms during the first 3 days of mechanical ventilation were recorded, with 15-minute waveform segments collected 4 times daily. Airway occlusion pressure (P_0.1) was measured via end-expiratory hold at the end of each recording. IT and DT were identified based on airway pressure, flow, and esophageal pressure waveforms, and the ineffective triggering index (ITI) and DT incidence were calculated. Multivariate Logistic regression was used to identify factors associated with IT and DT. RESULTS: A total of 94 patients with acute brain injury were ultimately enrolled, including 19 cases of traumatic brain injury (20.2%), 39 cases of stroke (41.5%), and 36 cases of post-craniotomy for brain tumor (38.3%). Supratentorial injury was observed in 49 patients (52.1%), while infratentorial injury was identified in 45 patients (47.9%). A total of 94 patients with 1 018 datasets were analyzed; 684 (67.2%) datasets were on pressure support ventilation (PSV), and 334 (32.8%) were on mandatory ventilation. IT was detected in 810 (79.6%) datasets, with a median incidence of 2.1% (0.3%, 12.0%). Datasets demonstrating IT were characterized by lower P_0.1, higher tidal volume (VT), reduced respiratory rate (RR), and decreased minute ventilation (MV) compared to those without IT. The proportion of datasets exhibiting IT was higher during PSV than in mandatory ventilation [83.8% (573/684) vs. 71.0% (237/334), P < 0.05], while, the prevalence of ITI ≥ 10% was lower [23.8% (163/684) vs. 33.5% (112/334), P < 0.05]. DT was detected in 305 datasets (30%), with a median incidence of 0.6% (0.4%, 1.3%). Datasets exhibiting DT were characterized by higher VT, reduced RR, and lower pressure support levels. The incidence of DT was lower in PSV compared to mandatory ventilation modes [0% (0%, 0.3%) vs. 0% (0%, 0.5%), P < 0.05]. The post-craniotomy for brain tumors group exhibited higher ITI, lower RR, reduced MV, and a greater proportion of infratentorial lesions, compared to the TBI group. The infratentorial lesion group demonstrated higher ITI and incidence of DT compared to the supratentorial lesion group [ITI: 3.1% (0.7%, 17.8%) vs. 1.5% (0%, 8.3%), incidence of DT: 0% (0%, 0.5%) vs. 0% (0%, 0%), both P < 0.05]. After adjusting for confounding factors through multivariate logistic regression analysis, infratentorial lesion [odds ratio (OR) = 2.029, 95% confidence interval (95%CI) was 1.465-2.811, P < 0.001], lower P_0.1 (OR = 0.714, 95%CI was 0.616-0.827, P < 0.001), and mandatory ventilation (OR = 1.613, 95%CI was 1.164-2.236, P = 0.004) were independently associated with IT. Additionally, infratentorial lesion (OR = 1.618, 95%CI was 1.213-2.157, P = 0.001), large tidal volume (OR = 1.222, 95%CI was 1.137-1.314, P < 0.001), lower pressure support levels (OR = 0.876, 95%CI was 0.829-0.925, P < 0.001), and mandatory ventilation (OR = 2.750, 95%CI was 1.983-3.814, P < 0.001) were independently associated with DT. CONCLUSION IT and DT were common in patients with acute brain injury. Infratentorial lesions and mandatory ventilation were independently associated with both IT and DT.
Humans ; Respiration, Artificial/methods* ; Retrospective Studies ; Brain Injuries/therapy* ; Intensive Care Units ; Male ; Female ; Middle Aged ; Brain Injuries, Traumatic/therapy* ; Logistic Models ; Aged ; Adult

Geriatric oral health care encounters significant challenges with the increase in the proportion of older individuals. Age-related changes in the dentition, muscles, and joints result in a decline in objective masticatory function, subjective restoration requirements, and acceptability among the elderly population, with individual variations influenced by systemic health. Considering functional requirements, the adaptability of stomatognathic and systemic health conditions, health economics and other factors, the authors believe that it should not be limited to the conventional "one-to-one" strategy for replacing missing teeth in geriatric prosthodontics. There is an urgent need for a precise and adaptable restoration strategy that is more suitable for older individuals. The proposal of a new concept of functional tooth loss updates the minimal restoration standards for elderly patients and establishes the theory of age-friendly functional restoration. Based on the restoration strategy of functional tooth loss, this paper proposes a new concept termed "age-friendly functional restoration of the stomatognathic system", which integrates treatment considerations including endodontics, periodontology, mucosa, muscles, temporomandibular joint, and systemic health. Efforts should be made in four areas as follows. Firstly, the "assessment of accessible function" should be enhanced by considering the interrelationship between stomatognathic and systemic health. Secondly, the "evaluation of appropriate function" is supposed to be optimised in view of subjective needs and objective evaluation of the stomatognathic system. Moreover, the "formulation of treatment plans" needs to be accomplished with the aid of assistive technologies, such as artificial intelligence, to accurately exert appropriate functional restoration. Lastly, the "management and maintenance of health" is likely to be strengthened through follow-ups, propaganda and education, and preventive healthcare, so as to improve quality of life and ultimately achieve healthy ageing among older individuals.
Humans ; Tooth Loss/therapy* ; Aged ; Stomatognathic System ; Oral Health ; Dental Care for Aged ; Dental Restoration, Permanent/methods*

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:The clinical data of prenatal stillbirth were analyzed in order to increase the understand-ing of the causes of stillbirth.Methods:Prenatal stillbirth cases that terminated pregnancy in Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University from January 2018 to December 2022 were col-lected,and the distribution characteristics of clinical data and the stillbirth causes were analyzed.The causes of death were classified according to the standards developed by the Stillbirth Collaborative Research Network(SCRN)in the United States,and they were divided into clear cause-of-death group and unknown cause-of-death group.The different characteristics of the two groups were compared and analyzed.Results:There were 210 ca-ses of prenatal stillbirth during the study period,and 104 cases met the inclusion criteria.Among them,33 cases(31.7%)had autopsy results,39 cases(37.5%)had genetic results,and 75 cases(72.1%)had placental pathol-ogy.According to the classification of SCRN standard,55 cases(52.9%)were probably related to the cause of death,33 cases(31.7%)were classified as possible,13 cases(12.5%)were probably unrelated,and 3 cases(2.9%)could not be attributed to the cause of death,that is,84.6%(88 cases)in the clear cause of death group and 15.4%(16 cases)in the unknown cause of death group.The rate of placental pathological examination in the clear cause of death group was significantly higher than that in the unknown cause of death group(78.4%).In the classification of causes of death,placental pathological changes accounted for the largest proportion,account-ing for 26.9%(28 cases),followed by pregnancy complications accounting for 25.0%(26 cases),and 15.4%of the cases were still unexplained.Conclusions:Placental pathology is of great significance for clarifying the cause of stillbirth.It is feasible to use SCRN to classify the etiology of stillbirth.Pathological placental conditions account for a relatively high proportion in the classification of stillbirth causes.It is recommended that each case of stillbirth placenta should undergo pathological examination.

Objective:The clinical data of prenatal stillbirth were analyzed in order to increase the understand-ing of the causes of stillbirth.Methods:Prenatal stillbirth cases that terminated pregnancy in Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University from January 2018 to December 2022 were col-lected,and the distribution characteristics of clinical data and the stillbirth causes were analyzed.The causes of death were classified according to the standards developed by the Stillbirth Collaborative Research Network(SCRN)in the United States,and they were divided into clear cause-of-death group and unknown cause-of-death group.The different characteristics of the two groups were compared and analyzed.Results:There were 210 ca-ses of prenatal stillbirth during the study period,and 104 cases met the inclusion criteria.Among them,33 cases(31.7%)had autopsy results,39 cases(37.5%)had genetic results,and 75 cases(72.1%)had placental pathol-ogy.According to the classification of SCRN standard,55 cases(52.9%)were probably related to the cause of death,33 cases(31.7%)were classified as possible,13 cases(12.5%)were probably unrelated,and 3 cases(2.9%)could not be attributed to the cause of death,that is,84.6%(88 cases)in the clear cause of death group and 15.4%(16 cases)in the unknown cause of death group.The rate of placental pathological examination in the clear cause of death group was significantly higher than that in the unknown cause of death group(78.4%).In the classification of causes of death,placental pathological changes accounted for the largest proportion,account-ing for 26.9%(28 cases),followed by pregnancy complications accounting for 25.0%(26 cases),and 15.4%of the cases were still unexplained.Conclusions:Placental pathology is of great significance for clarifying the cause of stillbirth.It is feasible to use SCRN to classify the etiology of stillbirth.Pathological placental conditions account for a relatively high proportion in the classification of stillbirth causes.It is recommended that each case of stillbirth placenta should undergo pathological examination.