Gender associations between phthalate exposure and biomarkers of oxidative stress: A prospective cohort study.

Previous epidemiologic research has shown that phthalate exposure in pregnant women is related to adverse birth outcomes in a sex-specific manner. However, the biological mechanism of phthalate exposure that causes these birth outcomes remains poorly defined. In this research, we investigated the association between phthalate exposure and placental oxidative stress in a large population-based cohort study, aiming to initially explore the relationship between phthalate exposure and gene expression in placental oxidative stress in a sex-specific manner. Quantitative PCR was performed to measure the expression of placental inflammatory mRNAs (HO-1, HIF1α, and GRP78) in 2469 placentae. The multiple linear regression models were used to investigate the associations between mRNA and urinary phthalate monoesters. Phthalate metabolites monomethyl phthalate (MMP) and mono-n-butyl phthalate (MBP) were positively correlated with higher HIF1α expression in placentae of male fetuses (p < .05). Mono-benzyl phthalate (MBzP) increased the expression of HO-1, HIF1α, and GRP78 in placentae of male fetuses, and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) up-regulated the expression of HIF1α and GRP78. Additionally, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) was negatively correlated with HO-1, HIF1α, and GRP78 in placentae of female fetuses. Maternal phthalate exposure was associated with oxidative stress variations in placental tissues. The associations were closer in the placentas of male fetuses than in that of female ones. The placenta oxidative stress is worth further investigation as a potential mediator of maternal exposure-induced disease risk in children.

TGF-ß1/SMAD3-driven GLI2 isoform expression contributes to aggressive phenotypes of hepatocellular carcinoma.

Hedgehog signaling is activated in response to liver injury, and modulates organogenesis. However, the role of non-canonical hedgehog activation via TGF-ß1/SMAD3 in hepatic carcinogenesis is poorly understood. TGF-ß1/SMAD3-mediated non-canonical activation was found in approximately half of GLI2-positive hepatocellular carcinoma (HCC), and two new GLI2 isoforms with transactivating activity were identified. Phospho-SMAD3 interacted with active GLI2 isoforms to transactivate downstream genes in modulation of stemness, epithelial-mesenchymal transition, chemo-resistance and metastasis in poorly-differentiated hepatoma cells. Non-canonical activation of hedgehog signaling was confirmed in a transgenic HBV-associated HCC mouse model. Inhibition of TGF-ß/SMAD3 signaling reduced lung metastasis in a mouse in situ hepatic xenograft model. In another cohort of 55 HCC patients, subjects with high GLI2 expression had a shorter disease-free survival than those with low expression. Moreover, co-positivity of GLI2 with SMAD3 was observed in 87.5% of relapsed HCC patients with high GLI2 expression, indicating an increased risk of post-resection recurrence of HCC. The findings underscore that suppressing the non-canonical hedgehog signaling pathway may confer a potential strategy in the treatment of HCC.

Bisphenol A and its analogue bisphenol S exposure reduce estradiol synthesis via the ROS-mediated PERK/ATF4 signaling pathway.

As a kind of endocrine-disrupting chemicals, BPA may affect the human placenta. Due to consumer unease about BPA, many manufacturers are using alternatives to BPA, such as BPS. However, some reports suggest that BPS may produce similar results to BPA. To understand how BPA/BPS leads to reduced synthesis of placental estradiol (E2), we conducted studies using a human choriocarcinoma cell (JEG-3) model for research. In this study. Elisa assay revealed that both BPA/BPS exposures decreased E2 synthesis in JEG-3 cells. The results of RT-PCR showed that both BPA and BPS could reduce the mRNA expression of CYP19A1, a key enzyme for E2 synthesis in JEG-3 cells. In addition, Western blot assay showed that BPA/BPS-induced ER-stress PERK/eIF2α/ATF4 signaling protein expression was increased. The expression of ROS in cells after exposure to BPA/BPS was detected using the 2,7-dichlorodihydrofluorescein diacetate (DCF-DA) method. The results of this experiment showed that BPA/BPS significantly induced an inhibition of ROS in JEG-3 cells. The present study concluded that, firstly, BPS exposure induced almost the same effect as BPA in reducing E2 synthesis in JEG-3 cells. Second, BPA/BPS exposure may reduce E2 synthesis in JEG-3 cells by increasing ROS levels and thus activating endoplasmic reticulum stress.

Effects of blood flow restriction training on bone turnover markers, microstructure, and biomechanics in rats.

Objective: The present study aimed to investigate the effects of blood flow restriction training on muscle strength, bone tissue structure material, and biomechanical properties in rats applying various exercise interventions and to analyze the process by identifying the bone turnover markers, it provides a theoretical basis for the application of BFRT in clinical rehabilitation. Methods: A total of 24, 3-month-old male SD (Sprague Dawley) rats were randomly divided into pressurized control group (CON, n=6), low-intensity training group (LIRT, n=6), high-intensity training group (HIRT, n=6), and blood flow restriction training group (LIBFR, n=6) for 8-week ladder-climbing exercises. The pressured control group were given only ischemia treatments and did not undertake any burden. The low-intensity training group was allowed to climb the ladder with 30% of the maximum voluntary carrying capacity (MVCC). The rats in the high-intensity training group were allowed to climb the ladder with 70% MVCC. The blood flow restriction training group climbed the ladder with 30% MVCC while imposing blood flow restriction. Before sampling, the final MVCC was measured using a ladder-climbing protocol with progressively increasing weight loading. The serum, muscle, and bone were removed for sampling. The concentrations of the bone turnover markers PINP, BGP, and CTX in the serum were measured using ELISA. The bone mineral density and microstructure of femur bones were measured using micro-CT. Three-point bending and torsion tests were performed by a universal testing machine to measure the material mechanics and structural mechanics indexes of the femur bone. Results: The results of maximum strength test showed that the MVCC in LIRT, HIRT, and LIBFR groups was significantly greater than in the CON group, while the MVCC in the HIRT group was significantly higher than that in the LIRT group (P<0.05). According to the results of the bone turnover marker test, the concentrations of bone formation indexes PINP (amino-terminal extension peptide of type I procollagen) and BGP (bone gla protein) were significantly lower in the CON group than in the HIRT group (P<0.01), while those were significantly higher in the LIRT group compared to the HIRT group (P<0.01). In terms of bone resorption indexes, significant differences were identified only between the HIRT and other groups (P<0.05). The micro-CT examination revealed that the HIRT group had significantly greater bone density index values than the CON and LIRT groups (P<0.05). The results of three-point bending and torsion test by the universal material testing machine showed that the elastic modulus and maximum load indexes of the HIRT group were significantly smaller than those of the LIBFR group (P<0.05). The fracture load indexes in the HIRT group were significantly smaller than in the LIBFR group (P<0.05). Conclusion: 1. LIRT, HIRT, LIBFR, and CON all have significant differences, and this training helps to improve maximum strength, with HIRT being the most effective. 2. Blood flow restriction training can improve the expression of bone turnover markers, such as PINP and BGP, which promote bone tissue formation. 3. Blood flow restriction training can improve muscle strength and increase the positive development of bone turnover markers, thereby improving bone biomechanical properties such as bone elastic modulus and maximum load.

Application of integrated problem-based learning combined with lecture-based classroom teaching in undergraduate medical education: An effective teaching model in a Medical School in China.

The problem-based learning (PBL) is increasingly used in undergraduate education. However, the application of integrated PBL to medical undergraduate education has not been well assessed. An observational study was designed to compare integrated PBL combined with lecture-based classroom (LBC) with traditional LBC teaching in 2 semesters of a Medical School in China. This study was conducted from March 2021 to July 2022. A total of 118 undergraduates majoring in clinical medicine were randomly allocated in 2 groups, 1 group receiving the integrated PBL + LBC teaching (experimental group, n = 60) and another group receiving LBC teaching (control group, n = 58). The experimental group attended the integrated PBL courses for the basic and clinical medicine conducted in the 6th and 8th semesters, respectively, as well as taking the LBC courses. The experimental group was required to preview the course materials before class, make presentations in class and take online feedback questionnaires after class, while the control group was required to preview the textbooks and listen to the traditional LBC courses. The students' scores of these 2 groups were compared, and feedback questionnaires were performed to evaluate the effectiveness of the experimental group over the control group. Results showed that the experimental group scored significantly higher than the control group in Clinical Skills (95% confidence interval [CI] 4.19-5.89), Internal Medicine I (95% CI: 1.85-9.93), Internal Medicine II (95% CI: 8.07-15.90), Introduction to Surgery (95% CI: 5.08-10.25), Surgery (General Surgery) (95% CI: 7.82-12.72), Surgery (Specialty) (95% CI: 6.47-9.97), and Clinical Medical Level Test (95% CI: 1.60-5.15) (all P < .01). In the feedback questionnaires of integrated PBL, up to 80% and 90% of students were satisfied with the teaching methods and lecturers, respectively. More than 80% of students agreed that the integrated PBL improved their abilities to learn independently, understand knowledge, and to raise, analyze and solve problems. In terms of stress in and out of class, a small number of students, <36.7%, felt stressed. The integrated PBL combined with LBC is an effective teaching approach, which may provide new ideas for teaching research and reform on undergraduate medical education in clinical medicine specialty and other medical majors.

Development and validation of a mutation-annotated prognostic score for intrahepatic cholangiocarcinoma after resection: a retrospective cohort study.

BACKGROUND: The value of existing prognostic models for intrahepatic cholangiocarcinoma is limited. The inclusion of prognostic gene mutations would enhance the predictive efficacy. METHODS: In the screening cohorts, univariable Cox regression analysis was applied to investigate the effect of individual mutant genes on overall survival (OS). In the training set, multivariable analysis was performed to evaluate the independent prognostic roles of the clinicopathological and mutational parameters, and a prognostic model was constructed. Internal and external validations were conducted to evaluate the performance of this model. RESULTS: Among the recurrent mutations, only TP53 and KRASG12 were significantly associated with OS across all three screening cohorts. In the training cohort, TP53 and KRASG12 mutations in combination with seven other clinical parameters (tumor size, tumor number, vascular invasion, lymph node metastasis, adjacent invasion, CA19-9, and CEA), were independent prognostic factors for OS. A mutation-annotated prognostic score (MAPS) was established based on the nine prognosticators. The C-indices of MAPS (0.782 and 0.731 in the internal and external validation cohorts, respectively) were statistically higher than those of other existing models ( P <0.05). Furthermore, the MAPS model also demonstrated significant value in predicting the possible benefits of upfront surgery and adjuvant therapy. CONCLUSIONS: The MAPS model demonstrated good performance in predicting the OS of intrahepatic cholangiocarcinoma patients. It may also help predict the possible benefits of upfront surgery and adjuvant therapy.

The development and application of pediatric complicated appendicitis prediction model.

BACKGROUND: Acute appendicitis in children refers to the acute inflammation of the appendix, which accounts for 20% ∼ 30% of cases of acute abdomen in pediatric surgery. OBJECTIVE: This study aimed to establish a decision tree model of complicated appendicitis in children using appendiceal ultrasound combined with an inflammatory index and evaluated its clinical efficacy in pediatric patients. METHODS: A total of 395 children admitted to the Emergency Department of the Shanghai Children's Hospital from January 2018 to December 2021 and diagnosed with appendicitis by postoperative pathology were retrospectively analyzed. According to the postoperative pathology, the children were divided into a complicated and non-complicated appendicitis group, respectively. Routine laboratory inflammatory indicators, including white blood cell count, N(%), neutrophil (Neu) count, Neu/lymphocyte ratio (NLR), C-reactive protein (CRP), and procalcitonin were collected from the two groups. Collecting data on ultrasound examination of the appendix includes whether the appendix diameter is thickened, whether the echogenicity of the mesenteric rim surrounding the appendix is enhanced, whether there is rich blood supply in the appendix, and whether there are fecaliths in the appendix lumen. The risk factors for complicated appendicitis were screened out by univariate and multivariate logistic regression analyses, the binary logistic regression prediction and decision tree models were established, respectively, and the receiver operating characteristic (ROC) curve was used to verify the accuracy of the two prediction models. RESULTS: Binary logistic regression analysis showed that CRP, NLR, the presence of an appendicolith, and peripheral retina echo enhancement were independent risk factors for complicated appendicitis in children (P< 0.05). The decision tree model had an overall accuracy of 79%, an area under the ROC curve (AUC) of 0.809 (95% confidence interval [CI] 0.780-0.865), and sensitivity and specificity of 71.3% and 77.7%, respectively. The logistic regression model had an overall accuracy of 74.9%, an AUC value of 0.823 (95% CI, 0.765-0.853), a sensitivity value of 80.3%, and a specificity of 71.8%. CONCLUSION: This predictive model, based on ultrasound of the appendix combined with inflammatory markers, provides a useful method to assist pediatric emergency physicians in diagnosing childhood appendicitis. The decision tree model reflected the interaction of various indexes, and the model was simple, intuitive, and effective.

Incidence and predictors of abdominal pain after transarterial chemoembolization of hepatocellular carcinoma: a single-center retrospective study.

PURPOSE: To assess the incidence and predictive factors of abdominal pain following transarterial hepatic chemoembolization (TACE) in patients with hepatocellular carcinoma. METHODS: In this single-center retrospective cohort study, abdominal pain was defined as a score of 4 or more within 72 h after TACE and requiring additional drug intervention. Patient, tumor characteristics, and technical factors associated with severe pain were identified using the decision tree and binary logistic regression model. RESULTS: Of 220 patients who were included in the study, 126 (57.3%) had abdominal pain after 206 of 420 TACE procedures (49.0%). A predictive model built based on the logistic regression identified the drug-eluting bead TACE (DEB-TACE) (odds ratio [OR] = 3.340; 95% confidence interval [CI] 2.169-5.141), the number of tumors (OR = 2.235; 95% CI 1.060-4.713), embolization of both hepatic lobes (OR = 2.310; 95% CI 1.109-4.813), and concomitant extrahepatic artery embolism (OR = 2.654; 95% CI 1.227-5.739) as the independent predictors of severe abdominal pain. Similarly, the decision tree confirmed the DEB-TACE as the strongest predictor of subsequent performance, followed by the history of hepatectomy and the embolization in the right or both lobes. The area under the receiver operating characteristic curve (AUC) of the classification prediction effect of the two models was 0.706 for the logistic regression and 0.676 for the decision tree. Internal validation results show that the accuracy of logistic regression model prediction was 71.4%. CONCLUSION: The model suggests that DEB-TACE and multiple treatment sites are predictors of abdominal pain after TACE in patients with hepatocellular carcinoma. It may help improve nursing management practices.

Preoperative simulated surgery on 3D model assists osteotomy feasibility verification and surgical guidance for patients with cubitus valgus/varus deformity: a retrospective observational study.

BACKGROUND: As the common delayed complication of supracondylar fractures in children, cubitus valgus/varus deformity might lead to pain and loss of motion of the elbow. The current corrective treatment might not be accurate enough and even contribute to postoperative deformity. This study retrospectively analyzed the clinical value of preoperative simulated surgery on 3D model-assisted osteotomy feasibility verification and surgical guidance for cubitus valgus/varus deformity. METHODS: Seventeen patients were selected from October 2016 to November 2019. Deformities were analyzed from imaging data and 3D models and corrected after the simulated operations. The radiographic evaluation comprised osseous union, carrying angle, and anteversion angle of the distal humerus. The clinical evaluation was performed according to the Hospital for Special Surgery (HSS) scoring system. RESULTS: All patients underwent the operation successfully and had no postoperative deformity. The carrying angle was significantly improved postoperatively (P < 0.001). The anteversion angle of the distal humerus did not change significantly (P > 0.05). The HSS score rose after surgery (P < 0.001). The function of the elbow joint was excellent in seven cases and good in ten cases. CONCLUSION: Simulated surgery on 3D model plays an important role in osteotomy plan and surgical guidance, contributing to good surgical efficacy.

[Finite element analysis of different reconstruction methods of coracoclavicular ligament for acromioclavicular joint dislocation].

OBJECTIVE: This study aims to examine the biomechanical effects of different reconstruction methods, including single-bundle, double-bundle anatomical reconstruction, and double-bundle truly anatomical reconstruction of the coracoclavicular ligament on the acromioclavicular joint using finite element analysis, to provide a theoretical basis for the clinical application of truly anatomical coracoclavicular ligament reconstruction. METHODS: One volunteer, aged 27 years old, with a height of 178 cm and a weight of 75 kg, was selected for CT scanning of the shoulder joint. Three-dimensional finite element models of single-bundle reconstruction, double-bundle anatomical reconstruction, and double-bundle truly anatomical reconstruction of coracoclavicular ligament were established by using Mimics17.0, Geomagic studio 2012, UG NX 10.0, HyperMesh 14.0 and ABAQUS 6.14 software. The maximum displacement of the middle point of the distal clavicle in the main loading direction and the maximum equivalent stress of the reconstruction device under different loading conditions were recorded and compared. RESULTS: The maximum forward displacement and the maximum backward displacement of the middle point of the distal clavicle in the double-bundle truly anatomic reconstruction were the lowest, which were 7.76 mm and 7.27 mm respectively. When an upward load was applied, the maximum displacement of the distal clavicle midpoint in the double-beam anatomic reconstruction was the lowest, which was 5.12 mm. Applying three different loads forward, backward, and upward, the maximum equivalent stress of the reconstruction devices in the double-beam reconstruction was lower than that in the single-beam reconstruction. The maximum equivalent stress of the trapezoid ligament reconstruction device in the double-bundle truly anatomical reconstruction was lower than that in the double-bundle anatomical reconstruction, which was 73.29 MPa, but the maximum equivalent stress of the conoid ligament reconstruction device was higher than that of the double-bundle anatomical reconstruction. CONCLUSION: The truly anatomical reconstruction of coracoclavicular ligament can improve the horizontal stability of acromioclavicular joint and reduce the stress of the trapezoid ligament reconstruction device. It can be a good method for the treatment of acromioclavicular joint dislocation.

Nanocrystalline Alumina-Zirconia-Based Eutectic Ceramics Fabricated with High-Energy Beams: Principle, Solidification Techniques, Microstructure and Mechanical Properties.

Nanocrystalline alumina-zirconia-based eutectic ceramics fabricated with high-energy beams and composed of ultrafine, three-dimensionally entangled, single-crystal domains are a special category of eutectic oxides that exhibit exceptionally high-temperature mechanical properties, such as strength and toughness as well as creep resistance. This paper aims to provide a comprehensive review on the basic principles, advanced solidification processes, microstructure and mechanical properties of alumina-zirconia-based eutectic ceramics, with particular attention to the status of the art on a nanocrystalline scale. Some basic principles of coupled eutectic growth are first introduced based on previously reported models, followed by concise introduction of solidification techniques and the control strategy of solidification behavior from the processing variables. Then, the microstructural formation of nanoeutectic structure is elucidated with regard to different hierarchical scales, and mechanical properties such as hardness, flexural and tensile strength, fracture toughness and wear resistance are discussed in detail for a comparative study. Nanocrystalline alumina-zirconia-based eutectic ceramics with unique microstructural and compositional characteristics have been produced with high-energy beam-based processes, and in many cases, promising improvements in mechanical performance have been reported as contrasting with conventional eutectic ceramics.

The association between pregnancy-related anxiety and behavioral development in 18-month-old children: The mediating effects of parenting styles and breastfeeding methods.

BACKGROUND: Pregnancy-related anxiety (PRA) is a distinct type of anxiety from general anxiety, affects many pregnant women, and is correlated with poor behavioral development in children. However, the mediation paths were unclear. METHODS: A total of 2032 mother-infant pairs from the Ma'anshan Birth Cohort were included in the current study. Maternal PRA was assessed in the second and third trimesters. Children's behavioral development was evaluated at the age of 18 months. In addition, information on parenting styles and breastfeeding methods was obtained at postpartum. Multivariate regression and structural equation modeling were used to examine the associations between maternal PRA and children's behavioral development. RESULTS: Significant intercorrelations were found between maternal PRA, the potential mediators (parenting styles and breastfeeding methods), and 18-month-old children's ASQ scores. Parenting styles played an intermediary role in the relationship between maternal PRA and children's behavioral development (ß = 0.030, 95 % confidence interval: 0.017-0.051), and the mediating effect accounted for 29.1 % of the total effect. However, breastfeeding methods did not mediate the link between PRA and children's behavior. LIMITATIONS: Depression and postpartum anxiety were not controlled for in our analysis, which left us unable to estimate the independent impact of PRA on children's behavior. CONCLUSIONS: Parenting rather than breastfeeding is the mediating factor of behavioral problems in children caused by PRA.

The effect of phthalates exposure during pregnancy on asthma in infants aged 0 to 36 months: a birth cohort study.

This cohort study sought to investigate the effects of phthalates exposure during pregnancy on offspring asthma and its association with placental stress and inflammatory factor mRNA expression levels. A total of 3474 pregnant women from the China Ma'anshan birth cohort participated in this study. Seven phthalate metabolites were detected in urine samples during pregnancy by solid phase extraction-high-performance liquid chromatography tandem mass spectrometry. Placenta stress and inflammation mRNA expression were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). Early pregnancy may be the critical period when phthalates exposure increases the risk of asthma in infants and young children, and there is a certain gender difference in the risk of asthma in infants and young children. Moreover, through the placenta stress and inflammatory factor associated with infant asthma found anti-inflammatory factor of interleukin-10 (IL-10) mRNA expression will reduce the risk of 36-month-old male infant asthma. The expression of interleukin-4(IL-4) and macrophage (M2) biomarker cluster of differentiation 206(CD206) mRNA reduced the risk of asthma in 18-month-old female infants. Placental stress and inflammatory response were analyzed using mediating effects. Tumor necrosis factor-α (TNFα) showed a complete mediating effect between mono-benzyl phthalate (MBzP) exposure in early pregnancy and asthma in 12-month-old males, and IL-10 also showed a complete mediating effect between mono-n-butyl phthalate (MBP) exposure in early and late pregnancy and asthma in 36-month-old males. In summary, exposure to phthalates during pregnancy may contribute to the development of asthma in infants, which may be associated with placental stress and inflammation.

Time-course changes of intraosseous environment and shear resistance mechanical properties of jawbone in SD rats with fluorosis / 环境与职业医学

Background At present, a large number of reports focus on the bones of limbs and trunk, while there are few studies on the effect of fluorosis on jawbone which is the inevitable structural basis for the development and treatment of oral diseases. Objective To preliminarily investigate the effect of fluoride exposure on the mechanical properties of jawbone by observing the changes in the intraosseous environment and the maximum load against shearing force (LSFmax) of the jawbone in rats with chronic fluoride treatment. Methods Screening experiment: 48 SD male rats were randomly divided into a control group and three fluoride exposure groups (50, 150, and 250 mg·L−1 fluoride concentration), 12 rats in each group. The fluoride exposure groups were molded by feeding different concentrations of sodium fluoride solution, and the control group drank tap water from Guizhou area. Each group was further divided into 4 subgroups with 3 animals each according to observation time points after 0, 2, 4, and 6 months. The LSFmax of the jawbone was measured with an electronic universal ergometer, the expression of type I collagen (Col1) was shown by Sirius red staining, and the expression of runt-related transcription factor 2 (Runx2) was determined semi-quantitatively by immunohistochemistry at selected time points. Formal experiment: 12 male SD rats were randomly divided into a fluoride exposure group and a control group. The fluoride exposure group were fed with 150 mg·L−1 sodium fluoride solution, and the control group drank tap water from Guizhou. After feeding with fluoride for 5 months, the ergometer was used to measure the LSFmax of the jawbone. Osteoclasts were counted after tartrate resistant acid phosphatase (TRAP) staining. Col1, Runx2, bone morphogenetic protein 2 (BMP-2), alkaline phosphatase (ALP), and cathepsin K (Cath K) were detected semi-quantitatively by immunohistochemistry expression and Sirius red staining. Micro computed tomography (Micro CT) was used to observe the trabecular bone microstructure. Results Screening experiment: The LSFmax of the control group and the 50 mg·L−1 fluoride exposure group reached the peak value at the 2nd month, and the LSFmax of the 50 mg·L−1 fluoride exposure group reached the valley value at the 4th month. The LSFmax of the 150 mg·L−1 fluoride exposure group at the 4th month was higher than that at the 6th month (P<0.05). There was no significant difference in the LSFmax at each time point in the 250 mg·L−1 fluoride exposure group. At the same time point, there was no statistically significant difference in LSFmax among the groups. The Col1 levels of the 50 mg·L−1, 150 mg·L−1, and 250 mg·L−1 fluoride exposure groups were higher than the time point 0 from the 2nd month (P＜0.05). The Runx2 showed no statistically significant difference by concentration or time. Formal experiment: After feeding with 150 mg·L−1 fluoride for 5 months, the LSFmax of the fluoride exposure group was greater than that of the control group (P<0.05). The expressions of Col1, Runx2, BMP2, ALP, and Cath K in the fluorosis exposure group were higher than those in the control group (P<0.05). There were no statistically significant differences in osteoclast count or indicators of bone trabecular microstructure. Conclusion Chronic fluoride exposure may increase the shear strength of jaw bone.

Progresses and analysis in fibrinolytic drugs induced hemorrhage / 药学学报

At present, most clinical thrombolytic drugs are plasminogen activators, which are highly dependent on the plasminogen level of the patient. Therefore, the efficacy of those drugs is restricted. Unlike the conventional thrombolytic plasminogen activator drugs, fibrinolytic drugs have direct fibrinolytic activity. Thus, fibrinolytic drugs can directly dissolve the thrombus, and its thromlysis efficacy is not restricted by the patients' plasminogen. This is a new type of thrombolytic drug with higher thrombolytic efficiency and safety, and has become one of the research hotspots at present. Although more and more agents that can be used as fibrinolytic drugs have been discovered, only a few of them can successfully be applied in clinical practice. The mainly underlying reason is the risk of bleeding. In this paper, based on the latest research progress of fibrinolytic drugs, the bleeding mechanisms and coping strategies of fibrinolytic drugs were systematically reviewed, five types of bleeding mechanisms of fibrinolytic drugs were summarized, and three types of coping strategies were proposed. We hope our work can provide theoretical basis for the development of safer and more efficient fibrinolytic drugs.

Prevalence and influencing factors of thyroid nodules in children aged 8-10 years old in Suzhou / 公共卫生与预防医学

Objective To investigate the prevalence and influencing factors of thyroid nodules in children aged 8-10 years in Suzhou , and to provide a scientific basis for the rational prevention and treatment of iodine deficiency disorders (IDD). Methods PPS sampling method was used in this study. Questionnaire survey, physical examination and thyroid B-ultrasound examination were conducted on students aged 8-10 years. Salt samples and urine samples were collected for laboratory detection of the salt iodine and urinary iodine. Univariate and multivariate logistic regression models were used to analyze the risk factors related to thyroid nodules. Results A total of 2 048 children aged 8-10 years were included in the present survey, and the prevalence of thyroid nodules was 23.34% (478/2 048). The prevalence of nodules in boys was 20.98% (218/1 039), and the prevalence of nodules in girls was 25.77% (260/1 009). Multivariate analysis showed that gender (OR=1.338, P=0.006), height (OR=1.993, P=0.001), frequency of iodine-rich food intake (OR=0.862, P=0.048) and nutritional supplements (OR=1.469, P=0.008) were correlated with the prevalence of thyroid nodules. Conclusion The prevalence rate of thyroid nodules in children aged 8-10 years old in Suzhou is 23.34%. Female gender, higher height, regular intake of iodine-rich foods and dietary supplements are statistically associated with the prevalence of thyroid nodules, which may be risk factors for the prevalence of thyroid nodules , but further research is needed to confirm.

Kaufman Oculocerebrofacial syndrome in a newborn: a case report and literature review / 中国新生儿科杂志

Objective:To study the clinical features, treatment, and prognostic features of Kaufman Oculocerebrofacial syndrome.Methods:The clinical characteristics of a newborn with Kaufman Oculocerebrofacial syndrome admitted to the neonatal unit of Guiyang Maternal and Child Health Care Hospital was reported. Using "Kaufman Oculocerebrofacial syndrome", "Blepharophimosis-ptosis-intellectual disability syndrome" and "UBE3B gene" as keywords, databases including CNKI, VIP database, Wanfang database, Chinese medical journals full-text database, PubMed, Web of Science database and Embase database were searched from the date of establishment to June 2022. The clinical characteristics, treatment and prognosis of Kaufman Oculocerebrofacial syndrome from published literature were summarized.Results:The proband was a boy presenting with small lid fissure, wide eye spacing and feeding difficulties. Whole exome sequencing revealed compound heterozygous mutation in the UBE3B gene, c.1445_1448dupTCAC inherited from his father and c.1703dupA inherited from his mother, both variants had not been reported in the domestic and foreign literature thus far. A total of 34 newborn cases were summarized from 11 case reports, including this report. The main clinical manifestations were developmental delay (35/35), peculiar facial features (35/35), narrow eye slits (35/35), feeding difficulties (33/35), ear abnormalities (33/35), hypotonia (32/35), mouth abnormalities (31/35), breathing difficulties (26/35), small jaws (25/35) and low birth weight (16/35).There is no effective treatment available, and a total of 4 cases followed up to over 16 years old have been reported, all of which have severe mental retardation, language deficiency, along with other serious neurological diseases.Conclusions:when children exhibit symptoms such as narrow eye fissures, feeding difficulties, hypotonia, developmental delays, and peculiar facial features in the neonatal period, whole exome sequence can be used to aid diagnosis and evaluate for Kaufman Oculocerebrofacial syndrome. Families with children of Kaufman Oculocerebrofacial syndrome may undergo prenatal diagnosis based on genetic findings.

Yangyin Huayu Jiedu Preseription Regulates Autophagy and Apoptosis of Colon Cancer Cells in Hypoxic Environment Through PI3K/Akt Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of different oxygen concentration on the proliferation and autophagy of colon cancer cells and to explore the effect of Yangyin Huayu Jiedu Preseription （YHJP） on autophagy and apoptosis of colon cancer cells under hypoxia based on phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway. MethodHCT-116 cells were divided into normoxia group， 1% O2 group， and 5% O2 group. Cell viability was detected by cell proliferation assay （MTS）， and autophagy was observed based on monodansylcadaverine （MDC） staining. HCT-116 cells were treated with YHJP in 5% O2 microenvironment. The cells were divided into normal group， blank serum group， and low-， medium-， high-dose YHJP groups （5%， 15%， 25% serum containing YHJP）. Cell inhibition rate in each group was calculated by MTS， and changes in the rate of autophagy were detected based on MDC staining. Annexin V-fluorescein isothiocyanate （FITC）/propidium iodide （PI） was employed to detect the apoptosis rate of each group. Western blotting was applied to measure the expression of autophagy proteins microtubule-associated protein 1 light chain 3 （LC3Ⅱ/Ⅰ）， yeast Atg6 homolog （Beclin-1）， ubiquitin-binding scaffold protein p62 （p62）， apoptosis-related proteins B-cell lymphoma-2 （Bcl-2）， Bcl-2/adenovirus E1B interacting protein 3 （BNIP-3）， and Bcl-2 associated X protein （Bax）， cleaved cysteine-aspartic acid protease-3 （Caspase-3）， hypoxia-inducible factor-1α （HIF-1α） and pathway proteins PI3K， phosphorylated （p）-PI3K， Akt， and p-Akt. ResultCell survival rates of the 1% O2 and 5% O2 groups were increased compared with that in the normoxia group， particularly the 5% O2 group （P<0.01）. The fluorescence intensity for autophagy in 1% O2 and 5% O2 groups was significantly increased compared with that in the normoxia group， especially the 5% O2 group. In the presence of 5% O2， compared with the blank serum group， medium-dose and high-dose YHJP groups showed high cell inhibition rate， low autophagy rate， high apoptosis rate （P<0.01）， and low expression of Beclin-1 protein （P<0.05）. Compared with low-dose YHJP group， high-dose YHJP group demonstrated low expression of Beclin-1 protein （P<0.05）. Compared with the blank serum group， the three YHJP groups had low expression of LC3Ⅱ/Ⅰ protein （P<0.05， P<0.01）. Compared with the blank serum group， medium-dose and high-dose YHJP groups showed high expression of p62 protein （P<0.01）. Compared with low-dose YHJP group， high-dose YHJP group showed high expression of p62 protein （P<0.05）. Compared with the blank serum group， high-dose YHJP increased the expression of BNIP-3 and Bax and decreased the expression of Bcl-2 （P<0.01）. The expression of Bax protein in the high-dose YHJP group was increased compared with that in the low-dose YHJP group （P<0.05）. The expression of HIF-1α in the medium-dose and high-dose YHJP groups was decreased （P<0.01） and the expression of p-PI3K/PI3K and p-Akt/Akt in the high-dose YHJP group was increased （P<0.05， P<0.01） compared with that in the blank serum group. The expression of p-Akt/Akt was higher in the high-dose YHJP group than in the medium-dose YHJP （P<0.05）. ConclusionHypoxic microenvironment can significantly promote autophagy and proliferation of colon cancer cells. YHJP can significantly inhibit autophagy and proliferation and promote apoptosis of colon cancer cells in 5% O2 environment by up-regulating the PI3K/Akt signaling pathway.

Finite element analysis of different reconstruction methods of coracoclavicular ligament for acromioclavicular joint dislocation / 中国骨伤

OBJECTIVE@#This study aims to examine the biomechanical effects of different reconstruction methods, including single-bundle, double-bundle anatomical reconstruction, and double-bundle truly anatomical reconstruction of the coracoclavicular ligament on the acromioclavicular joint using finite element analysis, to provide a theoretical basis for the clinical application of truly anatomical coracoclavicular ligament reconstruction.@*METHODS@#One volunteer, aged 27 years old, with a height of 178 cm and a weight of 75 kg, was selected for CT scanning of the shoulder joint. Three-dimensional finite element models of single-bundle reconstruction, double-bundle anatomical reconstruction, and double-bundle truly anatomical reconstruction of coracoclavicular ligament were established by using Mimics17.0, Geomagic studio 2012, UG NX 10.0, HyperMesh 14.0 and ABAQUS 6.14 software. The maximum displacement of the middle point of the distal clavicle in the main loading direction and the maximum equivalent stress of the reconstruction device under different loading conditions were recorded and compared.@*RESULTS@#The maximum forward displacement and the maximum backward displacement of the middle point of the distal clavicle in the double-bundle truly anatomic reconstruction were the lowest, which were 7.76 mm and 7.27 mm respectively. When an upward load was applied, the maximum displacement of the distal clavicle midpoint in the double-beam anatomic reconstruction was the lowest, which was 5.12 mm. Applying three different loads forward, backward, and upward, the maximum equivalent stress of the reconstruction devices in the double-beam reconstruction was lower than that in the single-beam reconstruction. The maximum equivalent stress of the trapezoid ligament reconstruction device in the double-bundle truly anatomical reconstruction was lower than that in the double-bundle anatomical reconstruction, which was 73.29 MPa, but the maximum equivalent stress of the conoid ligament reconstruction device was higher than that of the double-bundle anatomical reconstruction.@*CONCLUSION@#The truly anatomical reconstruction of coracoclavicular ligament can improve the horizontal stability of acromioclavicular joint and reduce the stress of the trapezoid ligament reconstruction device. It can be a good method for the treatment of acromioclavicular joint dislocation.