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*

Objective:To evaluate the accuracy of 3D ultrasound calibration in image guided radiotherapy for prostate cancer by taking cone beam CT calibration as the gold standard, and to analyze the risk factors of accuracy.Methods:From December 2018 to December 2021, 51 patients with prostate cancer from the Department of Radiation Oncology, First Affiliated Hospital of Hebei North University were selected as the study subjects. They received cone beam CT calibration based on bone and 3D ultrasound calibration based on soft tissue before fraction volumetric modulated arc therapy treatment three times a week. Taking cone beam CT calibration data as the gold standard, the Bland-Altman method was used to analyze the consistency of 3D ultrasound calibration data with the former. Taking 3 mm as the allowable threshold of accuracy, the calibration accuracy of 3D ultrasound relative to cone beam CT was evaluated. Logistic regression was used to analyze the risk factors affecting the accuracy of 3D ultrasound calibration.Results:A total of 765 pairs of cone beam CT and 3D ultrasound calibration data were obtained from 51 patients in left-right, superior-inferior and anterior-posterior directions. The calibration data of 3D ultrasound and cone beam CT were (1.39±0.11) and (1.13±0.07) mm in the left-right direction, (1.98±0.20) and (1.61±0.12) mm in the superior-inferior direction, (2.68±0.48) and (1.78±0.27) mm in the anterior-posterior direction, respectively, with statistically significant differences ( t=-6.42, P<0.001; t=-7.07, P<0.001; t=-7.34, P<0.001). The analysis results of Bland-Altman showed that the consistency of calibration data of the two methods were acceptable in three directions. The number of pairs of 3D ultrasound relative to cone beam CT calibration data difference <3 mm in the three directions were 676 (88.37%) on the left-right direction, 604 (78.95%) on the superior-inferior direction, and 577 (75.42%) on the anterior-posterior direction. The factors with statistically significant differences in the left-right direction included age ( χ2=18.27, P<0.001), prostate volume ( χ2=14.55, P<0.001), Charlson comorbidity index (CCI) ( χ2=8.01, P=0.005) and field range ( χ2=11.30, P<0.001). Age ( OR=2.02, 95% CI: 1.90-3.39, P=0.010) and the field range ( OR=1.45, 95% CI: 1.18-2.55, P=0.020) were the independent risk factors affecting the accuracy of 3D ultrasound calibration in the left-right direction. The factors with statistically significant differences in the superior-inferior direction included age ( χ2=80.68, P<0.001), body mass index ( χ2=35.89, P<0.001) and field range ( χ2=40.39, P<0.001). Age ( OR=1.49, 95% CI: 1.15-2.09, P=0.021) and the field range ( OR=1.10, 95% CI: 1.01-1.90, P=0.034) were the independent risk factors affecting the accuracy of 3D ultrasound calibration in the superior-inferior direction. The factors with statistically significant differences in the anterior-posterior direction included age ( χ2=46.07, P<0.001), CCI ( χ2=47.97, P<0.001) and field range ( χ2=11.86, P=0.001). Age ( OR=1.91, 95% CI: 1.22-3.45, P=0.015) and the field range ( OR=2.89, 95% CI: 1.45-3.90, P=0.001) were the independent risk factors affecting the accuracy of 3D ultrasound calibration in the anterior-posterior direction. Conclusion:The consistency and accuracy of the calibration results of 3D ultrasound relative to cone beam CT are acceptable. It is necessary to consider the patient's age and field range to reduce the impact on accuracy before conducting 3D ultrasound calibration.

Background::Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.Methods::We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.Results::The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 ( ERAP1) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1. The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes. Conclusion::The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1. Trial Registration::No. NCT00454519 (https://clinicaltrials.gov/)

Objective:To summarize the clinical characteristics and first aid measures of children with drowning，and to provide scientific basis for the treatment and prevention of drowning in children.Methods:The clinical data of drowning children admitted to the Children's Medical Center of the First Affiliated Hospital of Hunan Normal University（Hunan Provincial People's Hospital）from January 2011 to December 2021 were retrospectively summarized. Baseline characteristics，prehospital emergency care and prognosis of the included children were analyzed.According to the time span, drowning children were divided into two stages, the first stage (2011-2016) and the second stage (2017-2021). According to cerebral performance category assessment scale,drowning children with cardiac arrest were divided into two groups: a group with good neurological prognosis and a group with poor neurological prognosis. The baseline characteristics,pre-hospital emergency care, and prognosis of drowning children during different periods and with different prognosis were analyzed.Results:A total of 53 children were enrolled during the study period，with 24 cases in the first phase（2011-2016）and 29 cases in the second phase（2017-2021）.Boys accounted for 73.6%（39/53）of the cases, the age ranged from 1 month and 24 days to 14 years old，with 1-4 years old being the most common，accounting for 58.5%（31/53）, and the season in which drowning occurred was more common in the summer（39.6%, 21/53）.Six cases (11.3%) had significant neurological sequelae, and the mortality rate was 3.8%（2/53）.There was a decrease in the proportion of drowning with water control in the second stage compared to the first stage（37.5% vs. 13.79%, P=0.046）.Thirty-two（60.4%）children experienced on-site cardiopulmonary resuscitation(CPR) after drowning，with 24 cases in the group with good neurological prognosis and 8 cases in the group with poor neurological prognosis.Children in the poor neurological prognosis group required CPR for a long duration [10.00（1.50, 25.00）min]，had lower body temperature，Glasgow Coma Score，pH and higher blood glucose levels on admission（all P < 0.05）. Conclusion:Drowning is most common in preschool children，common in boys，and drowning prevention measures for young children deserve focused attention. Children found to be in cardiac arrest at the time of drowning have a long duration of drowning and CPR，which predicts a poor neurological prognosis，and timely and effective on-site CPR is the key to reducing the drowning rate.

With the continuous advancement of modern research on tongue diagnosis in traditional Chinese medicine,tongue diagnostic equipment plays an undeniable role in promoting the objectification of tongue diagnosis.Traditional Chinese medicine tongue diagnosis is only the subjective judgment of clinical doctors on tongue color,coating,etc.,while digital tongue diagnostic equipment and digital image processing technology can visually display tongue color,coating,etc.through digital representation,obtain the color distribution of the tongue body,saturation,brightness,and other parameter values of tongue color,objectively reflecting physiological and pathological changes in the body.The article briefly introduces the main working principles,technical parameters,image segmentation processing methods,and tongue image analysis techniques of digital tongue diagnostic equipment.It focuses on summarizing the research status of digital tongue diagnostic equipment in promoting the objectification of traditional Chinese medicine tongue diagnosis in some common diseases,and looks forward to the future application and development of digital tongue diagnostic equipment.

Objective:To evaluate the efficacy and safety of dupilumab in the treatment of prurigo nodularis (PN) in the real world.Methods:PN patients who were subcutaneously injected with dupilumab for over 12 weeks were collected from the China Type Ⅱ Inflammatory Skin Disease Clinical Research and Standardized Diagnosis and Treatment Project Database from June 2021 to October 2022. Their clinical data were retrospectively analyzed, which included demographic data, and changes in pruritus numeric rating scale (NRS), investigator global assessment for PN-Stage (IGA PN-S), dermatology life quality index (DLQI) and hospital anxiety and depression scale (HADS) scores before and after treatment. Differences in scores before and after treatment, as well as in efficacy between patients with and without a history of atopic diseases, were analyzed using Wilcoxon signed-rank test, paired t-test or chi-square test. Results:A total of 66 PN patients were collected, including 42 males and 24 females, and they were aged 8 to 89 (44.12 ± 24.17) years. Thirty-six patients had a history of atopic diseases, and 27 had a family history of atopic diseases. After 12-week treatment with dupilumab, the pruritus NRS, IGA PN-S and DLQI scores in the 66 patients significantly decreased from the baseline scores (7.00 [5.00, 8.00], 3.00 [3.00, 4.00], 12.00 [7.75, 20.25], respectively) to 3.00 [2.00, 4.25], 2.00 [2.00, 3.00], 5.00 [1.75, 8.25], respectively (all P < 0.001). Among the 66 patients, 39 continued the regular treatment with dupilumab after 12 weeks and were followed up to 16 weeks; their pruritus NRS and IGA PN-S scores at week 16 further decreased compared with those at week 12 (both P < 0.05). There were no significant differences in the proportion of patients showing an improvement of ≥ 4 points in the NRS score or the proportion of patients achieving IGA 0/1 at week 12 between the patients with history of atopic diseases and those without (both P > 0.05). Before treatment, 32 PN patients were accompanied by mild to severe anxiety and/or depression; after 12-week treatment, the HADS-A scores in the 28 patients with anxiety (HADS-A scores > 7 points) and the HADS-D scores in the 20 patients with depression (HADS-D scores > 7 points) significantly decreased compared with their baseline scores (both P < 0.001) ; 18 (56.52%) patients achieved remission in anxiety and depression (both HADS-A and HADS-D scores < 7 points). Among the 66 PN patients, there were 13 minor patients, including 7 males and 6 females, and they were aged 8 to 17 (13.77 ± 3.09) years; after 12-week treatment, their pruritus NRS, IGA PN-S, and DLQI scores significantly decreased compared with the corresponding baseline scores (all P < 0.05) ; 8 minor patients continued dupilumab treatment for 16 weeks, with a further decrease in the IGA PN-S score compared with that at week 12 ( P < 0.05), but without significant differences between the pruritus NRS and DLQI scores at week 16 and those at week 12 (both P > 0.05). Adverse reactions were observed in 7 adult patients, including eye pruritus, local injection reactions, and systemic erythema accompanied by pruritus on the day of injection. No adverse reactions were reported in minor patients. Conclusion:In the real world, dupilumab could markedly alleviate pruritus, skin lesions, anxiety and depression symptoms in PN, improve the quality of life, and exhibited a good safety profile.

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 effect of Compacept on different types of diabetic macular edema(DME)classified by optical coherence tomography(OCT).Methods Clinical data of 89 DME patients who were admitted to Leshan People's Hospital from September 2021 to September 2022 were collected.There were 32 patients with diffuse macular edema(DRT group),31 patients with cystic macular edema(CME group),and 26 patients with serous retinal detachment(SRD group).All patients were treated with intravitreal injection of Compaercept.The best corrected visual acuity(BCVA),central foveal thickness(CFT),and ellipsoid band integrity were compared among groups after treatment.The correlation between the logarithm of the minimum angle of resolution(logMAR)BCVA grade and ellipsoid band integrity was analyzed.Results LogMAR BCVA and CFT were significantly decreased in all patients at 1,3 and 6 months after treatment;logMAR BCVA in the DRT group was lower than that in the CME group and SRD group at 1,3 and 6 months after treatment,while CFT in the SRD group was higher than that in the DRT group and CME group(all P<0.05).The number of eyes with improved vision was as follows:DRT group>CME group>SRD group,and the average frequency of injection was as follows:DRT group

Objective:To investigate any anti-aging effect of repeated transcranial magnetic stimulation (rTMS) and explore the relationship between the effect and relief of clinical symptoms in patients with Parkinson′s disease (PD).Methods:A total of 108 PD patients were randomly divided into an rTMS group and a control group, each of 54, while another 54 healthy counterparts were selected to form a normal group. In addition to anti-PD drug therapy, the rTMS group was given daily rTMS treatment, 5 days a week for 4 weeks, while the control group received sham rTMS treatment, with no treatment of the normal group. Before the treatment and after 4 weeks of treatment as well as and 1 month after the ending of the treatment, the subjects′ clinical exercise symptoms were evaluated using the Unified Parkinson′s Disease Rating Scale (UPDRS), a timed exercise test and the 10m re-entry exercise test. Non-exercise symptoms were assessed using the Hamilton Depression Scale (HAMD), the Hamilton Anxiety Scale (HAMA) and the Mini-mental State Examination (MMSE). Fasting venous blood samples were analyzed to quantify the serum levels of tumor necrosis factor (TNF), interleukin-6 (IL-6), interleukin-1β (IL-1β) and matrix metalloproteinase-3 (MMP-3).Results:Four weeks and 1 month after the treatment, the average UPDRS scores, exercise test times and 10m re-entry exercise test results of the rTMS group were significantly better than those before treatment and significantly better than those of the control group at the same time point. The rTMS group′s average HAMA, HAMD and MMSE scores, as well as its average P300 latency and amplitude were also significantly better than those of the control group at the same time point and significantly better than those before treatment. After 4 weeks, the average MMP-3 content in the rTMS group was significantly lower than the control group′s average, and after a month the average levels of TNF, IL-6, IL-1β and MMP-3 of the rTMS group were all significantly different from those before treatment and those of the control group. The TNF, IL-6, IL-1β and MMP-3 levels were all positively correlated with the average UPDRS total score.Conclusion:High-frequency rTMS therapy can change the phenotypes related to cell senescence, and thus has good therapeutic effect on motor and non-motor symptoms of PD.

The Coronavirus disease 2019 (COVID-19) has spread globally. Although mixed liver impairment has been reported in COVID-19 patients, the association of liver injury caused by specific subtype especially chronic hepatitis B (CHB) with COVID-19 has not been elucidated. In this multi-center, retrospective, and observational cohort study, 109 CHB and 327 non-CHB patients with COVID-19 were propensity score matched at an approximate ratio of 3:1 on the basis of age, sex, and comorbidities. Demographic characteristics, laboratory examinations, disease severity, and clinical outcomes were compared. Furthermore, univariable and multivariable logistic and Cox regression models were used to explore the risk factors for disease severity and mortality, respectively. A higher proportion of CHB patients (30 of 109 (27.52%)) developed into severe status than non-CHB patients (17 of 327 (5.20%)). In addition to previously reported liver impairment markers, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin, we identified several novel risk factors including elevated lactate dehydrogenase (⩾ 245 U/L, hazard ratio (HR) = 8.639, 95% confidence interval (CI) = 2.528-29.523; P < 0.001) and coagulation-related biomarker D-dimer (⩾ 0.5 µg/mL, HR = 4.321, 95% CI = 1.443-12.939; P = 0.009) and decreased albumin (< 35 g/L, HR = 0.131, 95% CI = 0.048-0.361; P < 0.001) and albumin/globulin ratio (< 1.5, HR = 0.123, 95% CI = 0.017-0.918; P = 0.041). In conclusion, COVID-19 patients with CHB were more likely to develop into severe illness and die. The risk factors that we identified may be helpful for early clinical surveillance of critical progression.
COVID-19 ; Cohort Studies ; Hepatitis B, Chronic/epidemiology* ; Humans ; Retrospective Studies ; Risk Factors