Isolated non-immune mediated second-degree atrioventricular block in fetus: natural history and predictive factors for spontaneous recovery.

OBJECTIVES: To uncover the clinical course of fetal isolated non-immune mediated second-degree AVB and determine the factors associated with the spontaneous recovery for fetal non-immune second-degree atrioventricular block (AVB). METHODS: A total of 20 fetuses with isolated, non-immune mediated second-degree AVB were prospectively recruited between 2014 and 2022. These fetuses were divided into the spontaneous recovery group (n=12) and the non-spontaneous recovery group (n=8). Maternal and fetal basic characteristics, intrauterine and postnatal outcomes were compared between groups. RESULTS: Twelve fetuses restored 1:1 atrioventricular conduction in utero and did not recur during the postnatal follow-up period. The residual eight fetuses maintained as second-degree AVB and six of them were aborted due to parental request in utero. Of the two live children with second-degree AVB, one of them progressed to complete AVB at the latest follow up at the age of 34 months, but without any symptoms, heart enlargement or dysfunction. The residual one progressed to complete AVB and was finally diagnosed with type 2 long-QT syndrome. Fetuses in the spontaneous recovery group presented with earlier gestational age at diagnosis (20.0[17.0-26.0] vs. 24.5[18.0-35.0] weeks, p=0.004) and higher atrial rate (147[130-160] vs 138.00[125.00-149.00] bpm, p=0.006) in comparison with the non-spontaneous recovery group. A cut-off value of 22.5 weeks of gestational age and 144 bpm of atrial rate at diagnosis could predict the failure of spontaneous recovery, with sensitivities of 87.5%, 75%, and specificities of 92.0%, 87.5%, respectively. CONCLUSIONS: The outcome of fetal non-immune second-degree AVB was favorable. Earlier gestational age at diagnosis and higher atrial rate were related to spontaneous reversion for isolated non-immune-mediated second-degree AVB. However, prenatal gene test should be performed for those with persistent AVB to exclude the heritable disorders including LQTS. These findings may provide important references for clinical management and prenatal counseling. This article is protected by copyright. All rights reserved.

[Research status of potential therapeutic targets for thyroid-associated ophthalmopathy].

Thyroid-associated ophthalmopathy (TAO) is an autoimmune eye disease that affects visual function and appearance, involving pathological remodeling processes of orbital tissue such as inflammatory reaction, oxidative stress, lipogenesis, and fibrosis. Current clinical first-line treatment options cannot be effective for all patients. This article summarizes the research on potential therapeutic targets of TAO at home and abroad in recent years, including receptor protein targets, immune cell targets, fat suppression targets, anti-fibrosis targets, transcription factor targets, and metabolic regulatory enzyme targets. Both non-natural compounds and natural compounds are introduced, with a view to providing clinical researchers with reference and ideas in the treatment of TAO and promoting the clinical application of new therapeutic drugs.

Immunogenicity of the mRNA-1273 and ChAdOx1 nCoV-19 vaccines in Asian patients with autoimmune rheumatic diseases under biologic and/or conventional immunosuppressant treatments.

OBJECTIVE: Nucleic acid-based vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection are effective in the general population. However, it is unknown whether this is true in Asian patients with autoimmune rheumatic diseases (ARDs) who have received various combinations of disease-modifying anti-rheumatic drugs (DMARDs). METHOD: We designed a large prospective observational study recruiting 228 patients with ARDs in a tertiary rheumatology centre in Taiwan. Altogether, 142 received biological or targeted synthetic DMARDs and 86 received only conventional synthetic (cs) DMARDs. Serum levels of immunoglobulin G antibody against SARS-CoV-2 spike proteins were measured 2-6 weeks after COVID-19 vaccination with mRNA-1273 (Moderna®) or ChAdOx1 nCoV-19 (Oxford/AstraZeneca®). The immunomodulatory therapies were not modified before or after vaccination. RESULTS: Overall, 194 patients (85.09%) exhibited antibodies (758.33 ± 808.43 ng/mL) but 34 patients did not (103.24 ± 41.08 ng/mL). Patients with systemic lupus erythematosus or rheumatoid arthritis had significantly lower humoral responses to COVID-19 vaccination than those with other ARDs (p < 0.05). There was no significant difference in immunogenicity among patients on different csDMARD treatments. Compared to patients treated with only csDMARDs, those on rituximab or abatacept therapy had significantly lower immune response to the vaccination (p = 0.008 and p = 0.035, respectively). Patients who were treated with anti-tumour necrosis factor-α or interleukin-6 inhibitor exhibited higher titres of vaccination antibodies than those treated with direct lymphocyte inhibitors. CONCLUSIONS: mRNA-1273 and ChAdOx1 nCoV-19 vaccines were immunogenic in the majority of ARD patients. Rituximab and abatacept were associated with significantly diminished COVID-19 vaccination immunogenicity.

A spectral CT-based nomogram for predicting the response to induction chemotherapy in nasopharyngeal carcinoma.

AIM: To establish a spectral computed tomography (CT)-based nomogram for predicting the response to induction chemotherapy (ICT) in nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Fifty-four patients with NPC who underwent spectral CT examination before ICT were enrolled prospectively. Patients were assigned to response and non-response groups according to response evaluation. The predictive indicators were spectral CT parameters of venous phase, including iodine concentration (IC), normalised IC (NIC), slope of the spectral attenuation curve in Hounsfield units (λHU), effective atomic number (Eff-Z), and water concentration. Multivariate logistic regression was used to construct a predictive model. The receiver operating characteristic (ROC) and calibration curves were used to evaluate the robustness of model, while the bootstrap method was used for internal validation. The Hosmer-Lemeshow test was used to test the goodness of fit of the discriminant model. RESULTS: Multivariate logistic regression analysis showed that NIC, λHU, and Eff-Z were the potential predictors, and the three indicators were further used to establish a predictive model. The nomogram was evaluated to have good predictive performance, the area under the ROC curve was 0.909 (95% confidence interval [CI]: 0.799-0.970), and the model was well calibrated (χ2 = 8.149, p=0.419). CONCLUSIONS: The spectral CT nomogram has potential clinical value in predicting response to ICT in NPC and may help guide individualised treatment decisions.

A multimodality intervention to improve musculoskeletal health, function, metabolism, and well-being in spinal cord injury: study protocol for the FIT-SCI randomized controlled trial.

BACKGROUND: A spinal cord injury (SCI) is a devastating, life-changing event that has profoundly deleterious effects on an individual's health and well-being. Dysregulation of neuromuscular, cardiometabolic, and endocrine organ systems following an SCI contribute to excess morbidity, mortality and a poor quality of life. As no effective treatments currently exist for SCI, the development of novel strategies to improve the functional and health status of individuals living with SCI are much needed. To address this knowledge gap, the current study will determine whether a Home-Based Multimodality Functional Recovery and Metabolic Health Enhancement Program that consists of functional electrical stimulation of the lower extremity during leg cycling (FES-LC) plus arm ergometry (AE) administered using behavioral motivational strategies, and testosterone therapy, is more efficacious than FES-LC plus AE and placebo in improving aerobic capacity, musculoskeletal health, function, metabolism, and wellbeing in SCI. METHODS: This single-site, randomized, placebo-controlled, parallel group trial will enroll 88 community-dwelling men and women, 19 to 70 years of age, with cervical and thoracic level of SCI, ASIA Impairment Scale grade: A, B, C, or D, 6 months or later after an SCI. Participants randomized to the multimodality intervention will undergo 16 weeks of home-based FES-LC and AE training plus testosterone undecanoate. Testosterone undecanoate injections will be administered by study staff in clinic or by a visiting nurse in the participant's home. The control group will receive 16 weeks of home-based FES-LC and AE exercise plus placebo injections. The primary outcome of this trial is peak aerobic capacity, measured during an incremental exercise testing protocol. Secondary outcomes include whole body and regional lean and adipose tissue mass; muscle strength and power; insulin sensitivity, lipids, and inflammatory markers; SCI functional index and wellbeing (mood, anxiety, pain, life satisfaction and depressive symptoms); and safety. DISCUSSION: We anticipate that a multimodality intervention that simultaneously addresses multiple physiological impairments in SCI will result in increased aerobic capacity and greater improvements in other musculoskeletal, metabolic, functional and patient-reported outcomes compared to the control intervention. The findings of this study will have important implications for improving the care of people living with an SCI. TRIAL REGISTRATION: ClinicalTrials.gov :  ( NCT03576001 ). Prospectively registered: July 3, 2018.

[Efficacy of one-stage total spondylectomy and circumferential reconstruction for axial tumors through a combined anterior retropharyngeal-posterior approach].

Objective: To elucidate the safety and efficacy of one-stage total spondylectomy and circumferential reconstruction through a combined anterior retropharyngeal-posterior approach for axial tumors. Methods: A total of 20 patients with axial tumor who received total spondylectomy through a combined anterior retropharyngeal-posterior approach in Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology from February 2006 to December 2018 were retrospectively analyzed. Anterior reconstruction was performed with a special-shaped titanium mesh or three-dimensional printed (3DP) implants. The degree of local pain and neurological function was assessed by the visual analogue scale (VAS) and Frankel classification systems, respectively. Status of internal fixation and local recurrence was analyzed by radiological examination during follow-up. Results: Among the 20 patients, 12 were male and 8 were female with a mean age of (59.1±11.0) years (31 to 72 years). The mean operation time was (605.0±60.1) minutes (430 to 700 minutes) with a mean intraoperative blood loss of (1 250±347) ml (800 to 2 400 ml). The mean postoperative hospital stay was (13.2±2.8) days (8 to 20 days), and mean follow-up duration was (37.2±14.2) months(14 to 66 months). Anterior reconstructions were performed with a special-shaped titanium mesh in 14 patients and with 3DP implants in another 6 patients. Posterior occipital-cervical fixation was performed in 5 patients, while cervical fixation only in another 15 patients. The mean VAS score of pain at the last follow-up decreased significantly when compared with that before operation (1.6±0.6 vs 7.1±1.1, P<0.001). Nine patients with neurological deficits indicated significant improvement by at least 1 level at the last follow-up; among them, 2 cases of Frankel B improved to Frankel C and D, respectively; 3 cases of Frankel C all improved to Frankel D, and 4 cases of Frankel D improved to Frankel E. The perioperative complications included: 2 cases of vertebral artery injury, 2 cases of dysphagia, 3 cases of hoarseness and cough, 2 cases of cerebrospinal fluid leakage, and 1 case of greater occipital neuralgia. At the last follow-up, 5 patients died and 3 patients relapsed. Only 1 case suffered fixation failure due to local recurrence at the last follow up. Conclusions: One-stage total spondylectomy and circumferential reconstruction through a combined anterior retropharyngeal-posterior approach is safe and effective for axial tumors with favorable clinical outcomes and minor complications. Circumferential reconstruction with special-shaped titanium mesh or 3DP implant and posterior fixation can effectively reconstruct mechanical stability.

[Study of clinical characteristics in patients with gp210 antibody-positive primary biliary cholangitis].

Objective: To analyze the clinical characteristics and prognostic value of liver function in a large samples of patients with anti-glycoprotein 210 (gp210 antibody) positive primary biliary cholangitis (PBC). Methods: A retrospective study was performed on 931 PBC cases in Beijing You'an Hospital affiliated to Capital Medical University from 2010 to 2019. According to the detection of gp210 antibody, 318 cases were divided into gp210 antibody positive group (positive group) and 613 cases were divided into gp210 antibody negative group (negative group). The differences in demographic, medical history, clinical indicators, B-ultrasound and pathological indicators as well as the histopathological basis were compared between the two groups. SPSS 16.0 software was used for statistical analysis. Measurement data were analyzed by t-test or rank sum test, and enumeration data by χ2 test. Multivariate analysis was used for logistic test, and and survival analysis was used for prognosis. Results: The positive and the negative groups were compared. The ratio of male to female was significantly higher in positive than negative group (1:5.35 vs. 1:9.73, P＜0.05), and the difference was statistically significant. The proportion of hormone use in history of past diagnosed and treated was higher in positive than negative group (12.9% vs. 3.47%, P＜0.05), and the difference was statistically significant. The detection of biochemical indexes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), alkaline phosphatase (ALP), glutamyl transpeptidase (GGT) were higher in positive than the negative group (51.1 U/L vs. 41.1 U/L, 62.6 U/L vs. 49.6 U/L, 24.1 µmol/L vs. 17.9 µmol/L, 228.3 U/L vs. 169.6 U/L, 203.9 U/L vs. 147.6 U/L), (P＜0.05), and the differences were statistically significant. Antinuclear antibody (ANA)-positive rate, high titer ratio and immunoglobulin G (IgG) levels were higher in positive than negative group (95.2% vs. 81.6%, 69.7% vs. 48.8%, 17.2 g/L vs. 16.2 g/L), (P＜0.05), and the differences were statistically significant. The incidence of liver failure was higher in positive than negative group (P＜0.05). CK7 and inflammation score were higher in positive group than negative group in liver histopathological observations (0.83±0.53 vs. 0.28±0.47; 1.06±0.39 vs. 0.54±0.65), (P＜0.05), and the differences were statistically significant. Conclusion: The illness condition of patients with gp210 antibody positive PBC is more severe than patients with gp210 antibody negative PBC, and the incidence of liver failure is significantly increased. Cholangiocytes may be the histopathological basis of the clinical characteristics of gp210 antibody positive PBC patients.

[Expert consensus on measurement and clinical application of serum HBV RNA in patients with chronic HBV infection].

Since the discovery of circulating hepatitis B virus (HBV) RNA in the peripheral blood of patients with chronic hepatitis B in 1996, a growing number of studies have focused on clarifying the biological characteristics and clinical application value of serum HBV RNA. This consensus mainly summarizes the research progress of serum HBV RNA existing profiles, quantitative detection methods, and current clinical applications. In order to better apply this indicator for the clinical management of patients with chronic HBV infection, recommendations on quantitative detection target regions, detection results, and clinical applications are put forward.

Gut microbiome is more stable in males than in females during the development of colorectal cancer.

AIMS: Gut microbial alterations have great potential to predict the development of colorectal cancer (CRC); however, how gut microbes respond to the development of CRC in males and females at the community level is unknown. We aim to investigate the differences of gut microbiota between the male and female. METHODS AND RESULTS: We reanalysed the dataset in a published project from a sex perspective at the community level by characterizing the gut microbiome in patients (including males and females) from three clinical groups representative of the stages of CRC development: healthy, adenoma, and carcinoma. The results indicated that the microbial α-diversity showed no significant difference in the male gut but had decreased significantly in the female gut with the development of CRC. In males, a significant difference in the microbial ß-diversity was only observed between the healthy and carcinoma subgroups. However, significant community deviations were detected with the development of CRC in females. The microbial community assembly processes changed from deterministic to stochastic in males, whereas they became increasingly deterministic in females with the development of CRC. Moreover microbial co-occurrence associations tended to be more complicated in males; rare species were enriched in the co-occurrence network of the male gut, whereas key species loss was observed in the co-occurrence network of the female gut. CONCLUSIONS: The microbial communities in the male gut were more stable than those in the female gut, and microbial community assembly in the gut was sex dependent with the development of CRC. Our study suggests that sexual dimorphism needs to be considered to better predict the risk of CRC based on microbial shifts. SIGNIFICANCE AND IMPACT OF THE STUDY: To the best of our knowledge, this is the first report showing how gut microbes respond to the development of CRC in males and females at the community scale.

CircTP53 promotes the proliferation of thyroid cancer via targeting miR-1233-3p/MDM2 axis.

BACKGROUND: Follicular cells give rise to thyroid cancer. Worldwide thyroid cancer incidence continues to rise in recent decades but the mortality rate remains at a stable level. The discovery of novel molecular mechanisms in the pathogenesis of thyroid cancer will promote new diagnostic or therapeutic strategies. Circular RNA (circRNA) is a type of noncoding RNA which is characterized by the covalently closed loop and non-protein coding capacity. The abnormal expression of circRNAs is an important part during the pathogenesis and development of thyroid cancer. CircTP53 is a novel circRNA, and we aimed to investigate its function in the pathogenesis of thyroid cancer and to further demonstrate the underlying molecular mechanism. METHODS: The levels of circTP53, miR-1233-3p, and other relative mRNA were analyzed by qRT-PCR. Protein levels were shown by Western blot. RNA-pulldown assay and luciferase assay were employed to examine the interaction between circTP53 and miR-1233-3p. Cell proliferation was analyzed by the MTT assay. RESULTS: CircTP53 was a circRNA highly expressed in thyroid cancer tissues. CircTP53 promoted cell proliferation and cell viability of TPC-1 cells. Knockdown of circTP53 inhibited the expression of Mouse double minute 2 (MDM2) and increased the protein level of p53. CircTP53 acted as a target of miR-1233-3p to increase MDM2 expression. p53 expression in thyroid cancer tissue exhibited a negative correlation with circTP53 expression. CONCLUSION: In thyroid cancer, overexpressed circTP53 decreased the protein level of p53 via targeting miR-1233-3p/MDM2 axis and promoted cancer cell proliferation.

[Navigation-guided nasal endoscopy for removal of the cavernous hemangioma of the orbital apex through the sphenoid approach].

Objective: To explore the feasibility of navigation-guided nasal endoscopy for removal of the cavernous hemangioma of the orbital apex through the sphenoid approach. Methods: Retrospective case series study. From May 2012 to December 2019, 12 patients (12 eyes) with imaging findings of cavernous hemangioma in the orbital apex were collected at the Eye Hospital Affiliated to Nanchang University, including 3 males and 9 females aged 32 to 59 years. All patients underwent navigation-guided sinusoscopy through the sphenoid approach to remove the cavernous hemangioma of the orbital apex (video attached). Changes of visual function and complications after operation were analyzed. Results: In 3 patients without visual impairment, the postoperative visual function was still normal. Among the remaining 9 patients with preoperative visual impairment, visual function was fully recovered in 3 patients after operation, was improved in 2 patients, and had no change in 4 patients. There were no complications in 3 of the 12 patients, and 9 patients had transient, mildly limited intraocular rotation with diplopia after operation, which all returned to normal within 1 month. Conclusion: Navigation-guided sinus endoscopy through the sphenoid approach is effective and feasible in the removal of the cavernous hemangioma of the orbital apex. (Chin J Ophthalmol, 2021, 57: 837-843).

Association of FLAIR vascular hyperintensity and acute MCA stroke outcome changes with the severity of leukoaraiosis.

PURPOSE: The clinical significance of FLAIR vascular hyperintensity (FVH), a marker of collateral circulation in ischaemic stroke, remains controversial. We hypothesised that the association between FVH and outcomes varies with the severity of leukoaraiosis (LA), another marker of collaterals, and that their combined significance may vary with time. METHODS: We included 459 consecutive patients with middle cerebral artery (MCA) stroke. Proximal and distal FVHs were distinguished based on location. LA was divided into two grades, according to Fazekas scores of 0-2 and 3-6. Symptom-to-MRI time was divided into two categories: ≤ 14 days and ≥ 15 days. RESULTS: We found no difference in FVH proportion according to LA grade. Multivariate analysis revealed that LA and FVH status were independently associated with unfavourable outcomes (modified Rankin scale ≥ 2) in patients with symptom-to-MRI times ≤ 14 days (P = 0.008), but not in those with symptom-to-MRI times ≥15 days (P = 0.61). In the group with symptom-to-MRI times ≤14 days, patients with LA 3-6 and FVH(+) (OR, 3.044; 95% CI, 1.116-8.305) were more likely to have unfavourable clinical outcomes compared with patients with LA 0-2 and FVH(+) but not compared with those with LA 0-2 and FVH(-) or LA 3-6 and FVH(-). In addition, FVH location did not influence the relationship between FVH and outcomes. CONCLUSIONS: The association between FVH and outcomes was influenced by the degree of LA in the acute but not in the subacute and chronic stages of MCA infarction. FVH predicts clinical outcomes independently only in those with more extensive LA.

Hypoxia-responsive miR-346 promotes proliferation, migration, and invasion of renal cell carcinoma cells via targeting NDRG2.

Renal cell carcinoma (RCC) is the most common malignant tumor of the kidney. In this study, we investigated the role of miR-346 in RCC cells under hypoxia. OS-RC-2 and 786-O cells were cultured in 1% O2 or normal oxygen. Cell proliferation, migration, and invasion abilities were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, transwell migration, and invasion assays, respectively. Quantitative real-time PCR (qRT-PCR) was performed to detect the expression of miR-346 and N-myc downstream-regulated gene 2 (NDRG2). Then bioinformatics analysis, dual-luciferase reporter assay, and RNA immunoprecipitation were carried out to determine the relationship between miR-346 and NDRG2. The protein expression of NDRG2 was detected by western blot assay. Hypoxia promoted cell proliferation, migration, and invasion in OS-RC-2 and 786-O cells. Meanwhile, we found that miR-346 was upregulated in RCC cells under hypoxia as relative to normoxia. miR-346 deletion could decrease the viability, migration, and invasion abilities of RCC cells under hypoxia. Besides, our data demonstrated that NDRG2 was a target gene of miR-346. The expression of NDRG2 in OS-RC-2 and 786-O cells was lower under hypoxia than under normal oxygen conditions. Moreover, NDRG2 overexpression could inhibit cell proliferation, migration, and invasion in RCC cells under hypoxia. And NDRG2 silencing reversed the inhibitory effects of the miR-346 inhibitor on the viability, migration, and invasion abilities of RCC cells in hypoxia conditions. miR-346 promoted the viability, migration, and invasion of RCC cells under hypoxia by targeting NDRG2.

[Ergonomic risk factors of carpal tunnel syndrome in workers of an automobile factory].

Objective: To investigate the occurrence of pain symptoms and risk factors of carpal tunnel syndrome (CTS) in automobile manufacturing workers and provide theoretical basis for the prevention of CTS. Methods: From Nov.5th to Nov.19th, 2017, 446 workers in an automobile factory whose work age was above one year participate in questionnaires by cluster sampling. Chi square test and multifactor logistics regression analysis were used to analyze the factors related to the occurrence of CTS pain symptoms in workers. Results: The incidence of CTS pain among workers in this automobile factory was 20.8%. Working in the same position for a long time (OR=2.137, 95% CI:1.183-3.862) and unable to work reasonably because of uncomfortable posture (OR =2.067, 95% CI: 1.075-3.974) were identified as the risk factors of CTS pain symptoms by multifactor logistics regression analysis. Working age (OR=0.537, 95%CI:0.311-0.926) and work break (OR= 0.489, 95% CI: 0.282-0.849) were identified as the benefit factors of CTS pain symptoms. Conclusion: The incidence of CTS pain in automobile manufacturing workers is related to the posture in the process of labor . Effective ergonomic interventions should be carried out to prevent the occurrence of CTS pain in automobile manufacturing workers.

Incidence and risk factors of osteomyelitis in adult and pediatric systemic lupus erythematosus: a nationwide, population-based cohort study.

OBJECTIVE: The objective of this paper is to investigate the incidence rate, risk factors and outcome of osteomyelitis among patients with systemic lupus erythematosus (SLE). MATERIALS AND METHODS: We conducted a cohort study using data for patients enrolled in the Taiwan National Health Insurance Database from 2000 to 2012. Patients with SLE and age- and sex-matched controls without SLE were enrolled. Primary endpoint was the first occurrence of osteomyelitis. Risks of osteomyelitis in SLE patients were analyzed with Cox proportional hazards regression models, including age, sex, comorbidities and medications. RESULTS: Among 24,705 SLE patients (88.4% women, mean age 35.8 years) with a median follow-up of 9.1 years, 386 patients had osteomyelitis. The incidence rate ratio (IRR) of osteomyelitis in the SLE group vs the control group was 8.52 (95% confidence interval (CI) 7.24-10.05). The SLE group had higher incidence rates of osteomyelitis than the control group, especially in pediatric subgroups (IRR 41.1 95% CI 18.57-107.35). Compared to controls, SLE patients experienced osteomyelitis at a younger age (42.3 vs 58.1 years) but did not have an increased risk of mortality (hazard ratio 0.7; 95% CI 0.21-2.38). Age >60 years, male gender, malignancy within five years, prior bone fracture and higher daily prednisolone dose (>7.5 mg) cumulatively for >180 days increased risk for osteomyelitis. CONCLUSIONS: SLE patients have a higher IRR of osteomyelitis than controls. Pediatric and elder SLE patients, patients with a history of bone fracture, malignancy within five years and higher-dose glucocorticoid use have a higher risk of osteomyelitis and should be carefully monitored.

Genistein attenuates pathological cardiac hypertrophy in vivo and in vitro.

BACKGROUND: We investigated the effects and underlying mechanisms of genistein on pathological cardiac hypertrophy in vivo and in vitro. MATERIALS AND METHODS: A cardiac hypertrophy model was developed by aortic banding (AB). C57/BL6 mice were randomly assigned to sham + vehicle (CON), sham + genistein (GEN), AB + vehicle (AB), and AB + genistein groups. Genistein (40 mg/kg/day) was administered by gavage for 7 weeks. After assessing the echocardiographic and hemodynamic parameters, mouse hearts were harvested for histopathological and molecular biological analysis. In the in vitro experiments, neonatal rat cardiomyocytes (NRCM) were prepared to test whether genistein could prevent cardiomyocyte hypertrophy induced by phenylephrine (PE). RESULTS: Compared with the CON or GEN group, mice in the AB group exhibited a markedly increased cross-sectional area of cardiomyocytes, collagen volume fraction, and up-regulated expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), beta-myosin heavy chain (ß-MHC) promoter, connective tissue growth factor (CTGF), collagen Iα, collagen III, fibronectin, transforming growth factor (TGF)-ß1, and vimentin mRNA, as well as down-regulated expression of SERCA2α and α­MHC mRNA. Genistein significantly attenuated the expression of these abnormal hypertrophic and fibrotic markers. This anti-hypertrophic effect might be associated with the inhibition of MAPK (ERK1/2, P38, and JNK1/2) and AKT/GSK-3ß signaling. However, in the in vitro experiment, genistein only inhibited hyperphosphorylation of JNK1/2 in the early stage of prohypertrophic stimulation. Genistein could not attenuate PE-induced cardiomyocyte hypertrophy even after pretreatment with sp61005 (a selective inhibitor of JNK1/2). CONCLUSION: Genistein attenuated pressure overload-induced cardiac hypertrophy in vivo and PE induced NRCM hypertrophy in vitro. The underlying mechanisms of genistein activity may be associated with blocking the JNK1/2 signaling pathways.

[Efficacy and safety of tocilizumab in patients with Takayasu arteritis].

Objective: To assess the efficacy and safety of tocilizumab and cyclophosphamide in patients with Takayasu arteritis (TA). Methods: Twenty-seven TA patients treated with tocilizumab (TCZ group) and 22 treated with cyclophosphamide (CTX group) were enrolled and retrospectively analyzed. The duration of treatment was 6 months. Disease activity and side effects were compared between the two groups. Results: After treatment, the median C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and disease activity scores in TCZ group were significantly lower than those in CTX group respectively [ESR 3 mm/1h vs. 8 mm/1h; CRP 0.13 mg/L vs. 1.09 mg/L; National Institutes of Health (NIH) score 0(0,1) vs. 0(1,1); the Indian Takayasu clinical activity score (ITAS 2010) 0(0,2) vs. 2(0,3.5), and the Indian Takayasu activity score with the acute phase response (ITAS-A) 0(0,2) vs. 2.5(0,3.5); all P<0.05]. The daily prednisone doses before treatment and after treatment in TCZ group were significantly lower than those in CTX group [(20.1±15.9) mg/d vs. (39.3±16.7) mg/d;(5.1±4.2)mg/d vs. (12.1±4.6) mg/d,both P<0.05)].The incidence of drug-related side effects in TCZ group was significantly lower than that in CTX group, which was 22.2% vs. 54.5% (P<0.05). Conclusion: Compared with CTX treatment, TCZ treatment for TA with less prednisone has better efficacy and safety.

Comparative clinical study on seldom segment with multiple segment intramedullary primary spinal cord tumors.

OBJECTIVE: Several clinical studies were performed on multi-segment intramedullary primary spinal cord tumors. However, no clinical study focused on the relationship between different vertebral segments intramedullary tumors involvement and neurological functions, as well as prognosis of the patients. This prospective study was performed to compare clinical analysis on neurological functions and prognosis of the patients with intramedullary spinal cord primary tumors. METHODS: A prospective cohort study was performed in a single medical center, Neurosurgical Department, Peking University Third Hospital. Between Jan. 1, 2010 and Dec. 30, 2015, 135 patients underwent microsurgery for intramedullary primary spinal cord tumors. The intramedullary tumor length occupying 3 or more vertebral body levels was considered as multiple segments intramedullary primary spinal cord tumor, and occupying one or two vertebral body levels considered as seldom segments. Preoperative and postoperative functions were assessed using IJOA (improved Japanese orthopaedic association) scoring system, and analyzed using the appropriate statistical tests. RESULTS: Among the 135 patients, 52 cases had seldom segments intramedullary primary spinal cord tumors, and 83 cases had multiple segments. In the seldom group, 32 (62%) patients presented with normal urine and stool function, 8 (15%) patients with severe dysfunction, 7 (14%) with slight dysfunction, and 5 (9%) with incontinence, and 30 (58%) patients demonstrated various degrees of limbs weakness. The preoperative IJOA scores of the patients were 16.9±2.4. The postoperative IJOA scores at the end of 3 months were 16.6±2.3. The current IJOA scores until the end of the follow-up were 17.5±4.4. In the multiple group, 37 (45%) patients presented with normal urine and stool functions, 26 (31%) patients with slight dysfunction, 11 (13%) with severe dysfunction, and 9 (11%) with incontinence, and 62 (75%) patients demonstrated various degrees of limbs weakness. The preoperative IJOA scores of the patients were 15.6±3.4. The postoperative IJOA scores at the end of 3 months were 15.5±3.8. The current IJOA scores until the end of the follow-up were 16.9±5.8. The difference of presenting urine and stool dysfunction (Z=-1.35, P=0.18) was not statistically significant between the different patient groups. However, the difference of presenting limbs weakness (Z=-2.06, P=0.04) was statistically significant between the two groups. Most patients with multiple segment intramedullary tumors suffered from various limbs weakness. The difference of the preoperative IJOA score (P=0.02) and the postoperative early IJOA score (P=0.004) of the patients was statistically significant between the seldom and multiple segments groups. Preoperative and early postoperative neurological function of the patients was better with seldom segments tumor than with multiple segments tumor. Most patients with multi-segment intramedullary tumors experienced various limbs weakness. However, the difference of long-term neurological function (P=0.12) between the seldom and multiple segments groups was not statistically significant. The neurological function of the patients with multiple segments intramedullary tumor was remarkably improved after physical therapy. CONCLUSION: Perioperative neurological function of the patients with seldom segments primary tumor was superior to that of the patients with multiple segments primary tumor, especially for limb strength. The neurological function of the patients with multiple segments intramedullary primary tumor was remarkably improved after physical therapy during long-term follow-up.

[Re-recognition of occult hepatitis B virus infection].

Hepatitis B virus (HBV) infection remains to be a serious public health problem in China. There used to be a high prevalence of HBV infection in China, which resulted in a large number of HBV susceptible and post-infected population. Single anti-HBc positive usually indicates post HBV infection and its prevalence is particularly high among people over 40 years old, some of whom may be occult hepatitis B virus infection (OBI). The clinical diagnosis of OBI is difficult and easily missed. Since OBI may cause chronic liver disease progression and even lead to cirrhosis and hepatocellular carcinoma eventually, and more importantly, patients with OBI may leed to HBV reactivation when the immune function decreases or immunosuppressive therapy is performed, the accurate identify of OBI is of particular importance. Moreover, OBI is the potential source of HBV infection, which may transmit through blood transfusion, organ transplantation and mother-to-child transmission. In view of this situation, we reviewed the mechanism, prevalence and definition of OBI, and proposed a determination system for replication-competent HBV DNA based on our understanding of the updated OBI definition. It is expected to be beneficial for OBI diagnosis, treatment and management.

[Advances in the research and application of orbital blowout fracture repair material].

Orbital blowout fractures can easily lead to defects of the orbital wall. In order to restore the continuity of the bone wall and avoid a series of clinical symptoms caused by orbital contents herniation or incarceration, the site of the defect should be reconstructed. The effect of reconstruction depends on the choice of surgical plan and repair material. The typical materials for bone wall defect repair include bone sheet, high density porous polyethylene, titanium mesh, absorbable polymer, bioactive ceramics and tissue engineering bone. This paper reviews the research findings and application of material for repairing of orbital blowout fracture. (Chin J Ophthalmol, 2019, 55: 876-880).