[Establishment and validation of a prediction model for early-stage epithelial ovarian cancer based on LASSO regression].

Objective: To establish and validate a prediction model for early-stage epithelial ovarian cancer based on least absolute shrinkage and selection operator (LASSO) regression. Methods: A total of 509 cases ovarian mass patients who underwent surgical treatment in Tianjin Medical General Hospital from January 2018 to March 2023 were retrospectively analyzed. The patients were randomly divided into modeling group [n=356, M(Q1,Q3) for age were 43 (31, 61) years] and internal validation group [n=153, age 42 (31, 60) years] by 7∶3 ratio. In addition, 86 patients [age 44 (33, 61) years] who underwent surgical treatment for ovarian mass in Tianjin Medical University General Hospital from April to November 2023 were collected as external validation group. The variables were screened by LASSO regression. The nomogram model was established and plotted by multivariate logistic regression. Internal and external validation were then conducted. The model performance and clinical applicability were evaluated using receiver operating characteristic (ROC) curve, calibration curve and decision curve. Results: Five variables including age (OR=1.040,95%CI:1.000-1.050,P=0.002), carbohydrate antigen 125 (CA125) (OR=1.001, 95%CI: 1.000-1.010, P=0.017), human epididymis protein 4 (HE4) (OR=1.020, 95%CI: 1.000-1.030, P=0.002), carbohydrate antigen 199 (CA199) (OR=1.001, 95%CI:1.000-1.020, P=0.023) and lactate dehydrogenase (LDH) (OR=1.020, 95%CI: 1.010-1.022, P=0.001) were screened as risk factors for early-stage epithelial ovarian cancer. The nomogram model was constructed based on these above five risk factors to predict early-stage epithelial ovarian cancer. ROC curves showed the area under curve (AUC) were 0.915(95%CI:0.910-0.932)for modeling group, 0.891(95%CI:0.874-0.905) for internal validation group, and 0.924(95%CI:0.907-0.942) for external verification. The calibration curves and clinical decision curves showed the model exhibited good consistency and clinical practicability. Conclusions: The nomogram model built includes age, CA125, HE4, CA199, and LDH. It can effectively predict early-stage epithelial ovarian cancer and has strong clinical practicability.

[Remodeling of tumor stroma combined with photothermal therapy in the treatment of triple-negative breast cancer].

Objective: Polyethylene glycol-modified gold nanostar particles (GNS-PEG) were constructed to investigate whether the degradation of extracellular matrix in triple-negative breast cancer could improve the tumor delivery of GNS-PEG and enhance the efficacy of photothermal therapy. Methods: GNS-PEG were constructed and characterized for physicochemical properties as well as photothermal properties. At the cellular level, the cytotoxicity of halofuginone (HF) and the effect of photothermal therapy were detected. Mouse model of triple negative breast cancer was established by subcutaneous inoculation of 4T1 cells in BALB/c nude mice. Five injections of HF were given via tail vein (HF group), and tumor sections were stained with Masson stain and immunohistochemical staining for transforming growth factor ß1 (TGFß1), α-smooth muscle actin (α-SMA) and CD31 to observe the effect of tumor stromal degradation. Five injections of HF via tail vein followed by GNS-PEG (HF+ GNS-PEG group) were applied to determine the content of gold in tumor tissues by inductively coupled plasma mass spectrometry. The tumor sites of the mice in the GNS-PEG and HF+ GNS-PEG groups were irradiated with NIR laser and the temperature changes were recorded with an IR camera. The tumour growth and weight changes of mice in each group were observed. Ki-67 immunohistochemical staining, TdT-mediated dUTP nick-end labeling and HE staining were performed on tumor tissue sections from each group to observe tumor proliferation, apoptosis and necrosis. HE staining was performed on heart, liver, spleen, lung and kidney tissues from each group to observe the morphological changes of cells. Results: GNS-PEG nanoparticles showed a multi-branched structure with a particle size of 73.5±1.4 nm. The absorption peak of GNS was 810 nm, which is in the near infrared region. The photothermal conversion rate of GNS-PEG was up to 79.3%, and the photothermal effect could be controlled by the laser energy. HF has a concentration-dependent cytotoxicity, with a cell survival rate being as low as (22.8±2.6)% at HF concentration of up to 1 000 nmol/L. The photothermal effect of GNS-PEG was significant in killing tumor cells, with a cell survival rate of (32.7±5.2)% at the concentration of 25 pmol/L. The collagen area fraction, TGFß1 integrated optical density and α-SMA integrated optical density in the tumor tissues of mice in the HF group were (2.1±0.2)%, 3.1±0.4 and 5.2±1.9, respectively, which were lower than those of the control group (all P<0.01), and the vessel diameter was 8.6±2.9 µm, which was higher than that of the control group (P<0.05). In the HF+ GNS-PEG group, the concentration of gold in tissues was 52.4 µg/g, higher than that in the GNS-PEG group (15.9 µg/g, P<0.05). After laser irradiation, the temperature of the tumor site in the HF+ GNS-PEG group was significantly higher than that in the GNS-PEG group. At the 4th minute, the temperatures of the tumor site in the GNS-PEG and HF+ GNS-PEG groups were 51.5 ℃ and 57.7 ℃ respectively; the tumor volume in the HF+ GNS-PEG group was effectively suppressed. The body weights of the mice in each group did not change significantly during the monitoring period. No significant abnormalities were observed in the main organs of the mice in the GNS-PEG group, but some hepatocytes in the HF and HF+ GNS-PEG groups showed edema and degeneration. Conclusion: The remodeling of extracellular matrix in triple-negative breast cancer could significantly improve the intratumoral delivery of GNS-PEG and thus achieve better photothermal therapy effect.

[Efficacy of different regimens and prognostic factors in patients with first relapsed multiple myeloma treated after front-line bortezomib, cyclophosphamide, and dexamethasone].

Objective: To analyze the efficacy of second-line regimens and prognostic factors in patients with first-relapsed multiple myeloma (MM) treated with bortezomib, cyclophosphamide, and dexamethasone (BCD). Methods: A retrospective cohort study. Clinical data were collected in first-relapsed MM patients after BCD treatment from three tertiary hospitals in north China from July 2009 to October 2022. Patients were classified according to the second-line regimen into the immunotherapy group, single novel agent group [either proteasome inhibitor (PI) or immunomodulatory drug (IMiD)], combination treatment group (both PI+IMiD), and traditional treatment group. Responses to second-line regimens and survival data were analyzed. The Kaplan-Meier method was used for survival analysis and the Cox proportional risk model was used for univariate and multivariate analyses. Results: A total of 217 patients were enrolled including 8.8% (19/217) in the immunotherapy group, 48.4% (105/217) in the PI/IMiD group, 29.9% (65/217) in the PI+IMiD group, and 12.9% (28/217) in the traditional treatment group. The median age was 62 years (range 31-83 years) and 56.2% (122/217) were males. The overall response rates (ORRs) in the four groups were 94.7% (18/19) vs. 56.2% (59/105) vs. 73.8% (48/65) vs. 32.1% (9/28) (χ2=24.55; P<0.001), respectively. The progression-free survival (PFS) of the second-line regimens (2ndPFS) was 17.7 vs. 9.0 vs. 9.2 vs. 4.6 months (χ2=22.74; P<0.001), respectively, among which patients in the PI/IMiD and PI+IMiD groups had comparable 2ndPFS (χ2=1.76; P=0.923). Patients with high-risk cytogenetic abnormalities (HRCAs) achieved the longest 2ndPFS of 22.0 months in the immunotherapy group (χ2=15.03; P=0.002). Multivariate analysis suggested that immunotherapy (HR=0.11, 95%CI 0.05-0.27), achievement of efficacy of partial response or better (HR=0.47, 95%CI 0.34-0.66), and non-aggressive relapse (HR=0.25, 95%CI 0.17-0.37) were independent prognostic factors of 2ndPFS. Conclusion: In this real-world study, immunotherapy was associated with a more favorable efficacy and PFS for first-relapsed MM patients after BCD treatment, with similar outcomes in patients with HRCAs.

[Analysis of changes in reporting and diagnosis of pulmonary tuberculosis among children in Liangshan Yi Autonomous Prefecture, Sichuan Province from 2019 to 2021].

Objective: To compare the characteristics of children's pulmonary tuberculosis (PTB) cases reported from 2019 to 2021 before and during the implementation of the Action Plan to Stop Tuberculosis. Methods: Based on the reported incidence data and population data of child pulmonary tuberculosis (PTB) notified to the Chinese Center for Disease Control and Prevention (CDC) Tuberculosis Information Management System (TBIMS) from 2019 to 2021, the population information and clinically relevant information in different years were compared. Results: From 2019 to 2021, the reported cases of PTB in children were 363, 664 and 655, respectively. The number of reported cases increased significantly. The median age of the cases in children increased from 10.4 years in 2019 to 11.7 years in 2021 (P=0.005) over a three-year period. The etiological positive rate increased significantly from 11.6% (42/363) in 2019 to 32.2% (211/655) in 2021 (P<0.001). The positive rate of molecular testing increased most significantly, which became the main means of etiological detection and accounted for 16.7% (7/42), 62.0% (57/92) and 75.4% (159/211) of the children with positive etiological results, respectively. The resistance rates of isoniazid and rifampicin were analyzed in children with PTB who underwent drug sensitivity tests. The results showed that the resistance rates of isoniazid and/or rifampicin were 2/9, 3.9% (2/51) and 6.7% (11/163), respectively, with an average of 6.7% (15/223) over three years. The median patients' delay was 27 (12, 49) days in 2019. It was reduced to 19 (10, 37) days in 2020 and 15 (7, 34) days in 2021, both significantly lower than 2019 (P=0.009 and 0.000 2, respectively). Conclusion: From 2019 to 2021, the reported numbers of children with PTB and children with positive etiological results increase significantly in Liangshan Prefecture, while the diagnosis delay of patients significantly reduces.

[Animal study on left bundle branch current of injury and anatomic location of leads in His-purkinje conduction system pacing].

Objective: Explore the relationship between tip of the left bundle branch pacing lead and anatomic location of left bundle branch as well as the mechanism of left bundle branch current of injury. To clarify the clinical value of left bundle branch current of injury during operation. Methods: The pacing leads were implanted in the hearts of two living swines. Intraoperative electrophysiological study confirmed that the left bundle branch or only the deep left ventricular septum was captured at low output. Immediately after operation, the gross specimen of swine hearts was stained with iodine to observe the gross distribution of His-purkinje conduction system on the left ventricular endocardium and its relationship with the leads. Subsequently, the swine hearts were fixed with formalin solution, and the pacing leads were removed after the positions were marked. The swine hearts were then sectioned and stained with Masson and Goldner trichrome, and the relationship between the anatomic location of the conduction system and the tip of the lead was observed under a light microscope. Results: After iodine staining of the specimen, the His-purkinje conduction system was observed with the naked eye in a net-like distribution, and the lead tip was screwed deeply and fixed in the left bundle branch area of the left ventricular subendocardium in the ventricular septum. Masson and Goldner trichrome staining showed that left bundle branch pacing lead directly passed through the left bundle branch when there was left bundle branch potential with left bundle branch current of injury, while it was not directly contact the left bundle branch when there was left bundle branch potential without left bundle branch current of injury. Conclusion: The left bundle branch current of injury observed on intracardiac electrocardiogram during His-purkinje conduction system pacing suggests that the pacing lead directly contacted the conduction bundle or its branches, therefore, the captured threshold was relatively low. Left bundle branch current of injury can be used as an important anatomic and electrophysiological evidence of left bundle branch capture.

The Rat Genome Database (RGD) facilitates genomic and phenotypic data integration across multiple species for biomedical research.

Model organism research is essential for discovering the mechanisms of human diseases by defining biologically meaningful gene to disease relationships. The Rat Genome Database (RGD, ( https://rgd.mcw.edu )) is a cross-species knowledgebase and the premier online resource for rat genetic and physiologic data. This rich resource is enhanced by the inclusion and integration of comparative data for human and mouse, as well as other human disease models including chinchilla, dog, bonobo, pig, 13-lined ground squirrel, green monkey, and naked mole-rat. Functional information has been added to records via the assignment of annotations based on sequence similarity to human, rat, and mouse genes. RGD has also imported well-supported cross-species data from external resources. To enable use of these data, RGD has developed a robust infrastructure of standardized ontologies, data formats, and disease- and species-centric portals, complemented with a suite of innovative tools for discovery and analysis. Using examples of single-gene and polygenic human diseases, we illustrate how data from multiple species can help to identify or confirm a gene as involved in a disease and to identify model organisms that can be studied to understand the pathophysiology of a gene or pathway. The ultimate aim of this report is to demonstrate the utility of RGD not only as the core resource for the rat research community but also as a source of bioinformatic tools to support a wider audience, empowering the search for appropriate models for human afflictions.

Using transvaginal ultrasonography and MRI to evaluate ovarian volume and follicle count of infertile women: a comparative study.

AIM: To compare two-dimensional (2D) transvaginal ultrasonography (TVUS) and 2D/three-dimensional (3D) magnetic resonance imaging (MRI) in estimating ovarian volume and follicle count. MATERIALS AND METHODS: The ovarian volume (OV) and follicle count (FC) of 84 women with infertility were evaluated by 2D TVUS and 2D/3D MRI. Bland-Altman analysis was used for comparison. RESULTS: The OV from 3D MRI was 0.50 ml (95% confidence interval [CI], 0.25-0.74, p<0.001) smaller than that by 2D TVUS. OV from 2D MRI was 2.65 ml (95% CI, 2.36-2.95, p<0.001) and 3.15 ml (95% CI, 2.77-3.53, p<0.001) smaller than that from 3D MRI and 2D TVUS, respectively. The FC1-9 mm and total follicle count (tFC) estimated by 2D TVUS were 7.81 (95% CI, 6.96-8.66, p<0.001) and 7.82 (95% CI, 6.97-8.67) smaller than those from 2D MRI, respectively. Further analysis showed that 2D TVUS detected lower FC1-3 mm but higher FC4-6 mm than 2D MRI. No significant difference was shown in the results of FC7-9 mm and FC ≥ 10 mm. CONCLUSION: In women with infertility, 2D MRI underestimated OV as compared with 2D TVUS. OV from 3D MRI was lower but very close to that from 2D TVUS. For patients unsuitable for TVUS, 3D MRI is recommended for OV evaluation. 2D TVUS underestimated FC1-9 mm and tFC compared with 2D MRI. In fertility counselling and research, 2D MRI is a useful alternative to TVUS when an accurate FC is needed.

Vitamin D inadequacy combined with high BMI affects paraspinal muscle atrophy and pain intensity in postmenopausal women.

OBJECTIVE: This study was performed to assess the effects of vitamin D deficiency/insufficiency combined with a high body mass index (BMI) on paraspinal muscle (PSM) atrophy and pain intensity in postmenopausal women with lower back pain (LBP). METHODS: In total, 365 postmenopausal women were analyzed in the study. We divided the women into four groups according to BMI and vitamin D status. Outcome measurements included PSM atrophy, fatty infiltration (FI) and severity of LBP. Binary logistic regression was used to analyze the odds ratio (OR), and the interaction between the BMI and vitamin D status was tested. RESULTS: Compared with the control group, the high BMI with vitamin D deficiency/insufficiency group had a significantly increased risk of FI > grade 2 (OR = 10.69, p < 0.001), hand grip strength of <16 kg (OR = 8.96, p < 0.001), Short Physical Performance Battery score of ≤8 (OR = 3.69, p < 0.001) and visual analog scale (VAS) score of >3 (OR = 4.76, p < 0.001). A significant positive additive interaction was found between the BMI and vitamin D status on PSM atrophy. CONCLUSION: Vitamin D deficiency/insufficiency combined with a high BMI was associated with PSM atrophy and LBP intensity in postmenopausal women. The interaction analysis showed a positive additive interaction between BMI and vitamin D status.

[Study on the reliability and validity of the Chinese Criteria of Health Scale for the elderly people].

Objective: To evaluate the reliability and validity of the Chinese Criteria of Health Scale for the elderly people. Methods: A cross-sectional study was performed among older adults of Meiyuan Community in Haidian District, Beijing and Nanwangkong Village in Qingzhou City,Shandong Province during July 2021. Using a cluster sampling method, totally 667 elderly people were investigated by face-to-face interview, using the scale which was formulated after two rounds of the Delphi method and pilot study. The overall scale includes physical health, mental health and social health subscales, including 9, 52 and 15 items, respectively. Four weeks after the survey, 56 elderly people were randomly selected and repeated the survey with the same method. The test-retest reliability, split-half reliability and internal consistency reliability of the scale were evaluated, and the validity was evaluated at the same time, including construct validity and content validity. Results: A total of 710 questionnaires were distributed and 667 valid questionnaires were obtained, with a total effective rate of 93.94%. The score of the overall scale was 79.79±16.22, the scores of the physical health, mental health, social health sub-scores were 41.64±9.76, 26.82±3.92 and 11.34±5.19, respectively. The scale had excellent reliability. In the test-retest reliability, the intraclass correlation coefficient (ICC) of the overall scale and each subscale were 0.766-0.861, and the weighted Kappa values were 0.762-0.817. The Spearman-Brown coefficient of the overall scale and each subscale in the split-half reliability were 0.722-0.855 (all P<0.001). The Cronbach's α coefficients of the overall scale of internal consistency reliability and each subscale were 0.748-0.899, and the Cronbach's α coefficients of each dimension were from 0.709 to 0.963(all P<0.001). At the same time, the scale had good construct validity and content validity. The correlation coefficients between the score of each dimension and its sub-scale were larger, from 0.641 to 0.873 (all P<0.05). The cumulative variance contribution rates of the scale and three subscales were all more than 50% of the approved standard. A total of 11 common factors were extracted, and all the load values of each item on the corresponding factors were ≥0.04. Conclusion: The Chinese Criteria of Health Scale for the elderly people has good validity and excellent reliability. It can be used as a basis for the scientific division of the health status of the elderly, the formulation of relevant policies by the government and the provision of appropriate health services for the elderly.

Chemosensory proteins participate in insecticide susceptibility in Rhopalosiphum padi, a serious pest on wheat crops.

Rhopalosiphum padi is a worldwide agricultural pest. Chemosensory proteins (CSPs) are considered to be a type of transporters which can bind chemicals from external environments. Previous research showed that the expression of some insect CSPs were significantly increased after exposure to insecticides, and CSPs were involved in insecticide resistance or susceptibility. However, the role of CSPs in the susceptibility and response of R. padi to insecticides is still unknown. In this study, we identified eight CSP (RpCSP) from R. padi by genome-wide investigation. Seven RpCSP genes had two exons, while RpCSP7 had three exons. qPCR analyses showed that the mRNA levels of the eight RpCSP genes were significantly affected by imidacloprid and beta-cypermethrin in different post-treatment periods. Molecular docking predicted that there were hydrogen bonding sites which played key roles in binding of RpCSP4, RpCSP5, RpCSP6, RpCSP7 and RpCSP10 with imidacloprid and beta-cypermethrin. Knockdown of RpCSP4, RpCSP5, RpCSP6 and RpCSP10 by RNA interference significantly increased the aphid mortality under two sublethal concentrations of imidacloprid. Mortalities under two sublethal concentrations of beta-cypermethrin conditions were significantly higher after injection of R. padi with dsCSP4 and dsCSP6. The results indicate that some RpCSP genes are involved in the insecticide susceptibility of R. padi.

Characterization of ecdysteroid biosynthesis in the pond wolf spider, Pardosa pseudoannulata.

Ecdysteroids, as the key growth hormones, regulate moulting, metamorphosis and reproduction in arthropods. Ecdysteroid biosynthesis is catalysed by a series of cytochrome P450 monooxygenases (CYP450s) encoded by Halloween genes, including spook (spo), phantom (phm), disembodied (dib), shadow (sad) and shade (shd). The ecdysteroid biosynthesis in insects is clear with 20-hydroxyecdysone (20E) as the main ecdysteroid. However, the information on the major ecdysteroids in arachnids is limited. In this study, Halloween genes spo, dib, sad and shd, but not phm, were identified in the pond wolf spider, Pardosa pseudoannulata. Phylogenetic analysis grouped arachnid and insect Halloween gene products into two CYP450 clades, the CYP2 clan (spo and phm) and the mitochondrial clan (dib, sad, and shd). In P. pseudoannulata, the temporal expression profile of the four Halloween genes in concurrence with spiderling moulting with steady increase in the course of the 2nd instar followed by a rapid dropdown once moulting was completed. Spatially, the four Halloween genes were highly expressed in spiderling abdomen and in the ovaries of female adults. In parallel, ponasterone A (PA), but not 20E, was detected by LC-MS/MS analysis in P. pseudoannulata, and it was demonstrated as a functional ecdysteroid in the spider by accelerating of moulting with PA addition. The present study revealed the different ecdysteroid biosynthesis pathways in spiders and insects.

[Analysis of the efficacy and prognostic factors of 1 637 esophageal cancer patients treated with intensity-modulated radiotherapy].

Objective: To summarize survival outcomes and prognostic factors in esophageal cancer (EC) patients treated with intensity-modulated radiotherapy (IMRT). Methods: A retrospective analysis was performed on the clinical and follow-up data of 1 637 patients with EC who were admitted to our hospital from January 2005 to December 2017 and met the inclusion criteria.The 5-year overall survival (OS), progression-free survival (PFS) and pattern of recurrence were analyzed. The Kaplan-Meier method was used to calculate survival rates, Log-rank test for univariate analysis and Cox method for multivariate analysis were used to detect survival difference. Results: 1-year, 3-year and 5-year OS and PFS of the entire group were 65.9% and 45.8%, 34.2% and 25.0%, 27.0% and 18.5%, respectively. Median OS and PFS were 19.4 months (95% CI=18.0-20.7 months) and 10.4 months (95% CI=9.3-11.3 months), respectively. Univariate analysis showed that the sex, KPS, tumor location, T stage, N stage, M stage, TNM stage, radiation dose and treatment modality were prognostic factors for 5-year OS and PFS of EC patients (P<0.05). Multivariate analysis indicated that the sex, KPS, TNM stage, radiation dose and treatment modality were independent prognostic factors for 5-year OS and PFS (P<0.05). Conclusions: EC patients treated with IMRT can obtain a promising survival. The sex, KPS, TNM stage, radiation dose and treatment modality are independent prognostic factors for prognosis.

[Characteristics of magnetic resonance imaging and clinical etiology of ovarian infertility].

Objective: To analyze the characteristics of magnetic resonance imaging (MRI) and clinical etiology of ovarian infertility. Methods: The data of infertile women who underwent 3.0T MRI and magnetic resonance hysterosalpingography (MR-HSG) examination in the Affiliated Hospital of Nanjing University of Chinese Medicine from September 2017 to March 2020 were collected. The ovarian factors of infertility, as well as the abnormalities of bilateral fallopian tubes and uterus, were evaluated. Etiologies assessed by MRI were finally confirmed by hysteroscopy, laparoscopy, surgery, or a comprehensive clinical diagnosis. Results: Among 1 351 patients, 1 296 cases were eligible and included for further analysis. Evaluated by MRI and MR-HSG, 494(38.12%) cases had ovarian abnormalities, including 239(48.38%) cases of ovarian endometriosiss, 116(23.48%) cases of polycystic ovary syndrome (PCOS), 37(7.49%) cases of diminished ovarian reserve (DOR), 33(6.68%) cases of ovarian mass, 28(5.67%) cases of ovarian injury, and 41(8.30%) cases who had at least two kinds of ovarian diseases. Unilateral and bilateral ovarian abnormalities accounted for 52.02% (257/494) and 47.98%(237/494), respectively.In total, 453 of 494(91.7%) patients had only one kind of ovarian disease. Among the 494 patients, 103(20.85%) cases had abnormal ovary with normal uterus and fallopian tubes, and the other 391(79.15%) cases had abnormalities not only in ovary, but in fallopian tube and/or uterus. Conclusion: Infertility-related ovarian diseases have certain characteristics of MRI findings. 3.0T MRI is useful for comprehensive analysis of etiology in ovarian infertility. Combined with MR-HSG, it provides one-stop assessments of the pelvic factors in female infertility.

[Mutation analysis and prenatal diagnosis of MYO7A gene in a case of Usher syndrome type 1].

Objective: To analyze the clinical characteristics and identify the causative gene of a case with congenital deafness. Methods: Detailed medical history and clinical examination of a 4-year-old male child with congenital deafness were conducted in the First Affiliated Hospital of Army Military Medical University in June 2016. He was diagnosed with sensorineural deafness. The venous blood of the child and his parents was drawn, and genomic DNA was extracted. Proband's DNA was performed with targeted capture of high-throughput sequencing, then Sanger sequencing was used to verify the suspected mutation and segregation in this pedigree. According to the genetic diagnosis of the proband's deafness, ophthalmic examinations were performed. Genetic prenatal diagnosis was performed when the proband's mother was pregnant again. Results: The patient was detected with p.Trp1466Ter/p.Tyr2042Ter compound heterozygous mutations of MYO7A gene with targeted high-throughput sequencing. The mutation of p.Trp1466Ter was a reported mutation, while p.Tyr2042Ter has not been reported. In addition to congenital deafness, retinitis pigmentosa was also found by ophthalmologic examination, and the patient was clinically diagnosed with Usher syndrome type 1. Amniocentesis and fetal DNA sequencing were performed on the repregnancy fetus of this family at 18 weeks of gestation. The heterozygous mutation of MYO7A gene p.Tyr2042Ter was found, and the other allele was the wild type, indicating that the child will not exhibit clinical manifestations of Usher syndrome type 1. Indeed, the second child passed neonatal hearing screening. Conclusions: The clinical features and genetic variants were delineated in this family with Usher syndrome type 1. The results of the current study have enriched the phenotype and genotype data of the disease and provided a basis for genetic counseling.

Skin Ultrastructure and the Changes of HIF-2α, H-FABP Expression in the Myocardium of Electric Shock Death Rats.

ABSTRACT: Objective To observe the skin ultrastructure change of electric shock death rats and to test the expression changes of hypoxia-inducible factor-2α （HIF-2α） and heart type-fatty acid-binding protein （H-FABP） of myocardial cells, in order to provide basis for forensic identification of electric shock death. Methods The electric shock model of rats was established. The 72 rats were randomly divided into control group, electric shock death group and postmortem electric shock group. Each group was divided into three subgroups, immediate （0 min）, 30 min and 60 min after death. The skin changes of rats were observed by HE staining, the changes of skin ultrastructure were observed by scanning electron microscopy, and the expression of HIF-2α and H-FABP in rats myocardium was tested by immunohistochemical staining. Results The skin in the electric shock death group and postmortem electric shock group had no significant difference through the naked eye or by HE staining. Under the scanning electron microscope, a large number of cellular debris, cells with unclear boundaries, withered cracks, circular or elliptical holes scattered on the cell surface and irregular edges were observed. A large number of spherical foreign body particles were observed. Compared with the control group, the expression of HIF-2α in all electric shock death subgroups increased, reaching the peak immediately after death. In the postmortem electric shock group, HIF-2α expression only increased immediately after death, but was lower than that of electric shock death group （P<0.05）. Compared with the control group, the expression of H-FABP in all subgroups of electric shock death group and postmortem electric shock group significantly decreased. The expression of H-FABP in all subgroups of electric shock death group was lower than that of the postmortem electric shock group （P<0.05）. Conclusion Electric shock can increase HIF-2α expression and decrease H-FABP expression in the myocardium, which may be of forensic significance for the determination of electric shock death and identification of antemortem and postmortem electric shock.

The efficacy and safety of topical rapamycin-calcitriol for facial angiofibromas in patients with tuberous sclerosis complex: a prospective, double-blind, randomized clinical trial.

BACKGROUND: The efficacy of topical rapamycin is well documented for tuberous sclerosis complex (TSC)-related facial angiofibromas (FAs). Calcitriol has been shown to lessen skin fibrosis and may be therapeutically beneficial to FAs. OBJECTIVES: To evaluate whether topical rapamycin-calcitriol combination is an effective and safe treatment for TSC-related FAs. METHODS: Fifty-two patients with TSC with FAs were enrolled in this prospective study including three 12-week periods. In period 1, either topical rapamycin 0·1% or calcitriol 0·0003% single-agent therapy vs. their combination was applied in a double-blind, left-right-randomized, split-face comparison. The primary outcome was the reduction of modified Facial Angiofibroma Severity Index (mFASI) at week 12. In period 2, the patients were reassigned to use on both cheeks the ointment that resulted in the better primary outcome in period 1. The treatment was discontinued in period 3 (week 25-36) and a follow-up mFASI was scored to evaluate the degree of recurrence. RESULTS: The mean changes in mFASI at week 12 compared with baseline were -0·92, -0·44 and -1·09 for rapamycin (P ≤ 0·001), calcitriol (P = 0·039) and rapamycin-calcitriol combination (P ≤ 0·001), respectively. Although rapamycin-calcitriol combination and rapamycin had similar statistically significant decreases of mFASI at week 12, rapamycin-calcitriol combination resulted in faster improvement in erythema, greater reduction of papule elevation and longer durability after discontinuing treatment than rapamycin alone. The treatments were well tolerated. CONCLUSIONS: This randomized clinical trial demonstrates that topical rapamycin-calcitriol combination therapy is an effective and safe regimen for TSC-related FAs. What is already known about this topic? Facial angiofibromas (FAs) cause substantial psychological distress in individuals with tuberous sclerosis complex (TSC), but invasive procedural treatments are not applicable to all patients. Topical rapamycin has been demonstrated as an effective and safe treatment regimen for TSC-related FAs. What does this study add? Compared with baseline (day 0), both topical rapamycin 0·1% and rapamycin 0·1%-calcitriol 0·0003% combination ointment achieved statistically significant reductions in modified Facial Angiofibroma Severity Index at week 12. Compared with rapamycin alone, extended use of the rapamycin-calcitriol combination regimen until week 24 showed more effectiveness in decreasing papule elevation and could maintain a longer therapeutic effect after treatment discontinuation. Linked Comment: Lee. Br J Dermatol 2020; 183:604-606.

[Nutritional knowledge, attitudes and dietary behaviors of teachers and students in a medical college in Beijing and their influencing factors].

OBJECTIVE: To investigate nutritional knowledge, attitudes and dietary behaviors of teachers and students in a medical college in Beijing and their influencine factors, and to provide evidence for nutrition education and promotion. METHODS: The subjects of this study were teachers, as well as first-year and second-year graduate students, and first-year to third-year undergraduate students. The teachers and students were respectively sampled by stratified cluster sampling with equal proportion. t-test or ANOVA was used to compare the means between the groups, and multiple linear regression was used to analyze the influencing factors of knowledge, attitude and practice (KAP) score. RESULTS: The average score of nutrition knowledge was 5.7±1.5. The knowledge rate of nutrition was 57.3%. The average score of nutritional attitudes was 8.3±3.0. The mean nutritional behavior score was 5.1±2.0. The average nutritional KAP score was 19.1±4.6, with the teachers 19.9±5.2 higher than the students 18.9±4.5; the female 19.5±4.5 higher than the male 18.4±4.5; All the differences were statistically significant (P < 0.05). The scores of nutritional attitudes, nutritional behavior and total KAP scores of doctoral students were significantly higher than those of the undergraduate and postgraduate students (P < 0.01). CONCLUSION: The nutrition attitudes of teachers and students is relatively correct, the nutrition knowledge needs to be further strengthened, and there are some unreasonable aspects in the nutrition behaviors. Gender, identity and degree are the main influencing factors of the nutrition score of knowledge, attitudes and behaviors. It is necessary to carry out nutritional education in schools to improve the nutrition knowledge of teachers and students, correct bad eating habits, and promote the construction of healthy China action.

[Application of computer-assisted design for anterolateral thigh flap in oral and maxillofacial reconstruction].

OBJECTIVE: To investigate the feasibility and accuracy of using digital technology to design anterolateral thigh flap (ALTF) in oral and maxillofacial defect reconstruction. METHODS: Ten cases underwent oral and maxillofacial defects reconstruction with ALTFs in Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology from June 2019 to Oct. 2019 were enrolled. There were 7 males and 3 females with the mean age of 47.1 years. Preoperative high frequency color Doppler ultrasound examination was performed to detect the perforators of ALTF. CT data of the thigh was imported in DICOM (digital imaging and communications in medicine) format to the Proplan CMF 3.0 software (Materalise, Belgium), then virtual harvest of ALTF was performed according to the points of perforators detected by high frequency color Doppler ultrasound and the virtual flap volume was calculated by Proplan CMF 3.0 software. ALTF was harvested followed by preoperative virtual design, and the actual flap volume of ALTF was measured by the draining method during the surgery. Finally, the accuracy rate of using high frequency color Doppler ultrasound to detect perforators of ALTFs was calculated, and the differences between the virtual flap volume measured by Propaln CMF 3.0 software and the actual volume of ALTF by the draining method were compared using paired samples T test. RESULTS: Fifteen perforators in the flaps area of 10 patients who underwent oral and maxillofacial defects reconstruction with ALTFs were detected by high frequency color Doppler ultrasound, and 16 perforators were identified during the surgery, with the accuracy rate of 87.5%. The flaps size ranged from 5 cm×7 cm to 8 cm×15 cm, all the 10 flaps survived. The donor sites were primarily closed without skin graft, and no surgery complication was found on the donor site. The mean flap volume measured by Propaln CMF 3.0 software was 71.4 cm³ (range: 36.1-188.4 cm³), and the mean volume measured by the draining method was 70.7 cm³ (range: 38.3-172.5 cm³). There was no significant difference between the virtual flap volume measured by Propaln CMF 3.0 software and the actual volume measured by draining method (t=0.318; P=0.758). CONCLUSION: Preoperative virtual design of ALTF has good feasibility and accuracy and can be used to guide the harvest of ALTF during operation.

[Clinical efficacy of short-term halo-pelvic traction combined with surgery in the treatment of severe spinal deformities].

OBJECTIVE: To evaluate the clinical efficacy of short-term halo-pelvic traction (HPT) combined with surgery in the treatment of severe spinal deformities. METHODS: In the study, 24 patients diagnosed as severe spinal deformity accepted the treatment of one-stage short-term HPT and two-stage surgery from January 2015 to May 2018 in our orthopedics department. 24 cases (9 males and 15 females) were retrospectively reviewed. The average age of the cohort was (28.8±10.0) years (12－48 years). The height, scoliosis angle, kyphosis angle, the height difference of shoulders, the height difference of crista iliaca, C7PL-CSVL and the perpendicular distance of S1 and the convex point of the patients were assessed at pre-traction, post-traction and post-surgery. The paired t test was used to analyze the difference among pre-traction, post-traction and post-surgery. RESULTS: The average traction time of 24 cases was (2.5±1.1) weeks (1－5 weeks). The height of pre-traction and post-traction were (141.7±11.2) cm (116-167 cm) and (154.1±9.5) cm (136－176 cm) respectively, showing significant difference (P < 0.05), and the increased height was (12.4±4.6) cm (4－20 cm). The average scoliosis angle before traction was 104.9°±35.0°(25°ï¼158°), and it was significantly decreased in post-traction[64.8°±21.0°(19°ï¼92°)] and post-surgery[39.3°±17.0° (10°-70°)] (P < 0.05). The traction's coronal correction rate was 37.2%±10.9% (11.9%－51.2%) and the total coronal correction rate was 61.9%±12.6%(26.9%-79.0%). The average kyphosis angle before traction was 106.9°±29.2°(54°ï¼163°), and it was significantly decreased in post-traction [63.1°±17.1°(32°ï¼92°)] and post-surgery [39.0°±16.8°(10°ï¼68°)](P < 0.05). The traction's sagittal correction rate was 40.0%±10.7%(16.7%－55.5%) and the total sagittal correction rate was 64.3%±10.7%(49.0%－87.5%). The average C7PL-CSVL before traction was (3.2±2.8) cm, and it was significantly decreased in post-traction [(2.5±2.5) cm] (P < 0.05). The perpendicular distance of S1 and the convex point before traction was (10.5±4.8) cm, and it was significantly decreased in post-traction[(8.4±3.5) cm] (P < 0.05). CONCLUSION: The one-stage short-term HPT combined with two-stage surgery is a safe and effective procedure for severe spinal deformities. The clinical efficacy is satisfactory and the complication is relatively less.

[Occurrence pattern of musculoskeletal disorders and its influencing factors among manufacturing workers].

OBJECTIVE: To explore the occurrence pattern and its influencing factors of multi-site work-related musculoskeletal disorders (WMSDs) of the main affected body sites among manufacturing workers. METHODS: Musculoskeletal disorders questionnaire was adopted to investigate the prevalence of WMSDs and the influencing factors among workers from four manufacturing factories in China. The case of WMSDs was defined as the one who had symptoms such as pain, numbness, discomfort, or limitation of activities in one or more of the nine body sites, including neck, shoulder, elbow, wrist/hand, upper back, lower back, hip/thigh, knee and ankle/foot during the last year, which lasted for more than 24 hours and did not completely relieve after rest. Besides, trauma, disability, other acute injuries or sequelae were excluded. The correlation of WMSDs between different body sites was estimated by the prevalence ratio (PR) calculated by log-binominal model. The influencing factors of multi-site WMSDs of the main affected body sites were analyzed by multinomial logistic regression model. RESULTS: The overall prevalence rate of WMSDs was 79.7% among the manufacturing workers. The main affected body sites were lower back, neck, shoulder and upper back, of which the prevalence rates were 62.3%, 55.7%, 45.6%, and 38.7%, respectively. The PR values of WMSDs among these sites were relatively high. The prevalence of multi-site WMSDs involving these four sites at the same time was 25.2%, and that of three to four sites was 41.4%. Multinomial Logistic regression analysis suggested that influencing factors of multi-site WMSDs in 3-4 sites of neck, shoulder, upper back and lower back involved several aspects. Among these factors, females (OR=2.86, 95%CI 2.38-3.33) and individuals with job tenure of 15-19 years (OR=1.87, 95%CI 1.49-2.34) might have higher risk of disease. Biomechanical factors, such as often bending neck forward or holding neck in a forward position for long periods (OR=2.15, 95%CI 1.86-2.48), often twisting neck or holding neck in a twisted position for long periods (OR=1.64, 95%CI 1.40-1.92) and often twisting trunk heavily (OR=1.40, 95%CI 1.20-1.64) might be risk factors. In the aspect of work organization, doing the same work every day (OR=1.73, 95%CI 1.44-2.08), shortage of workers (OR=1.50, 95%CI 1.31-1.71) and often working overtime (OR=1.38, 95%CI 1.20-1.60) might increase the risk of disease. Factors, such as often standing for long periods at work (OR=0.77, 95%CI 0.65-0.91) and feeling breaks sufficient (OR=0.51, 95%CI 0.44-0.59) were suggested to be protective factors with OR<1. CONCLUSION: The pre-valence rates of WMSDs in neck, shoulder, upper back, and lower back were high among manufacturing workers in this study. The correlation of WMSDs of these four sites was close in this study, and the comorbidity rate of 3-4 sites of these sites was relatively high, suggesting that there might be a multi-site occurrence pattern of WMSDs in "neck-shoulder-upper back-lower back" among manufacturing workers. The main influencing factors of this pattern included individual factors, biomechanical factors and work organization factors.