[Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation in the treatment of secondary acute myeloid leukemia].

Objective: To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with secondary acute myeloid leukemia (sAML) . Methods: In this multicenter, retrospective clinical study, adult patients aged ≥18 years who underwent allo-HSCT for sAML at four centers of the Zhejiang Hematopoietic Stem Cell Transplantation Collaborative Group from January 2014 to November 2022 were included, and the efficacy and prognostic factors of allo-HSCT were analyzed. Results: A total of 95 patients were enrolled; 66 (69.5%) had myelodysplastic syndrome-acute myeloid leukemia (MDS-AML) , 4 (4.2%) had MDS/MPN-AML, and 25 (26.3%) had therapy-related AML (tAML) . The 3-year CIR, LFS, and overall survival (OS) rates were 18.6% (95% CI 10.2%-27.0%) , 70.6% (95% CI 60.8%-80.4%) , and 73.3% (95% CI 63.9%-82.7%) , respectively. The 3-year CIRs of the M-AML group (including MDS-AML and MDS/MPN-AML) and the tAML group were 20.0% and 16.4%, respectively (P=0.430) . The 3-year LFSs were 68.3% and 75.4%, respectively (P=0.176) . The 3-year OS rates were 69.7% and 75.4%, respectively (P=0.233) . The 3-year CIRs of the groups with and without TP53 mutations were 60.0% and 13.7%, respectively (P=0.003) ; the 3-year LFSs were 20.0% and 76.5%, respectively (P=0.002) ; and the 3-year OS rates were 40.0% and 77.6%, respectively (P=0.002) . According to European LeukmiaNet 2022 (ELN2022) risk stratification, the 3-year CIRs of patients in the low-, intermediate-, and high-risk groups were 8.3%, 17.8%, and 22.6%, respectively (P=0.639) . The three-year LFSs were 91.7%, 69.5%, and 65.6%, respectively (P=0.268) . The 3-year OS rates were 91.7%, 71.4%, and 70.1%, respectively (P=0.314) . Multivariate analysis revealed that advanced disease at allo-HSCT and TP53 mutations were independent risk factors for CIR, LFS, and OS. Conclusion: There was no significant difference in the prognosis of patients who underwent allo-HSCT among the MDS-AML, MDS/MPN-AML, and tAML groups. Advanced disease at transplantation and TP53 mutations were poor prognostic factors. ELN2022 risk stratification had limited value for predicting the prognosis of patients with sAML following allo-HSCT.

Serum fibroblast growth factor-2 levels complement vital biomarkers for diagnosing heart failure.

BACKGROUND: Early diagnosis of atrial fibrillation is important as it is crucial for improving patient outcomes. Fibroblast growth factor-2 (FGF2) may serve as a diagnostic biomarker for heart failure due to its ability to promote cardiac fibrosis and hypertrophy; however, the relationship between FGF2 concentration and heart failure is unclear. Therefore, this study aimed to explore whether FGF2 could aid in distinguishing patients with heart failure from healthy controls and those with dyspnea without heart failure. Additionally, to evaluate the possible correlation between serum FGF2 levels and its diagnostic parameters in patients with heart failure. METHODS: Plasma FGF2 concentration was measured in 114 patients with a complaint of dyspnea (enrolled in the study between January 2022 and August 2022). Based on heart failure diagnosis, the patients were assigned to three groups, as follows: heart failure (n = 80), non-heart-failure dyspnea (n = 34), and healthy controls (n = 36), following physical examination. Possible correlations between serum FGF2 levels and other prognostic parameters in patients with heart failure were analyzed. RESULTS: Serum FGF2 levels were higher in patients with heart failure (125.60 [88.95, 183.40] pg/mL) than in those with non-heart-failure dyspnea (65.30 [28.85, 78.95] pg/mL) and healthy controls (78.90 [60.80, 87.20] pg/mL) (p < 0.001). Receiver operating characteristic curve analysis identified FGF2 concentration as a significant predictor in heart failure diagnosis, with an area under the curve of 0.8693 (p < 0.0001). Importantly, in the heart failure group, serum FGF2 concentrations correlated with key prognostic parameters for heart failure, such as reduced left ventricular ejection fraction and elevated serum levels of N-terminal pro-B-type natriuretic peptide. CONCLUSIONS: Elevated serum FGF2 level is strongly associated with an increased risk of heart failure and could serve as a useful biomarker to complement vital diagnostic parameters for heart failure.

[Mediating effect of unhealthy lifestyle and depressive symptom on association between life course factors and ageing health].

Objective: To explore the mediating effect of unhealthy lifestyle and depressive symptom on the associations between life course factors and aging health. Methods: The study included 6 217 participants (aged ≥45 years) from the China Health and Retirement Longitudinal Study (CHARLS). We used principal component analysis (PCA) and hierarchical clustering analysis (HCA) to divide participants into six subgroups based on 70 life course factors. Five key life course factors were identified based on correlation analysis and their contribution to aging health. Physiological dysregulation (PD) was calculated by using eight biomarkers in the 2015 CHARLS biomarker dataset. Linear regression, logistic regression, and mediation models were used to explore the complex associations of life course subgroups, key factors, unhealthy lifestyle, depression symptom with PD. Results: Life course subgroups were significantly associated with PD after adjusting chronological age and gender (ß: 0.08-0.17, all P<0.05). Life-course subgroups and key factors, including adverse experiences in adulthood and lower education level, were significantly associated with unhealthy lifestyle (ß: 0.04-0.52, all P<0.05). Life-course subgroups and key factors, including childhood trauma, parental health in childhood, adverse experiences in adulthood, and lower education level, were significantly associated with depression symptom (OR: 1.16-4.76, all P<0.05). Mediation analysis showed that unhealthy lifestyle had partial mediating effect on the association of life course subgroups and key factors, including adverse experiences in adulthood, and lower education levels, with PD (3.1%-3.6%). Depression symptom had partial mediating effect on the association of life course subgroups and key factors, including childhood trauma, adverse experience in adulthood, and lower education level, with PD (6.0%-16.2%). Conclusions: Unhealthy lifestyle and depression symptom has partial mediating effect on the impact of life course factors on aging health. It is important to pay attention to these two modifiable factors while targeting childhood trauma and adverse experience in adulthood.

Intraosseous schwannoma of the mandible: new case series, literature update, and proposal of a classification.

Intraosseous schwannoma of the mandible is rare, with diagnostic and therapeutic challenges. The aims of this study were to report new cases of intraosseous schwannoma of the mandible and to propose a clinical classification, providing suggestions for treatment methods. The cases of 13 patients treated at the authors' hospital and 86 cases reported previously in the literature were reviewed. The most common clinical feature was facial swelling (60/93). The rate of cortical thinning or expansion was 44.8% (43/96); widening of the inferior alveolar nerve canal on radiographs was observed in 15 patients.

Effects of personalized oral exercises on swallowing function among patients with oral cancer after free flap transplantation: a cluster randomized controlled trial.

Dysphagia is a common complication in patients with oral cancer who have undergone free flap transplantation. The aim of this cluster randomized controlled trial was to evaluate the effect of personalized oral exercises on swallowing function in this group of patients. Eligible patients were randomly assigned to the intervention (n = 34) or control (n = 34) group. Intervention group patients received personalized oral exercises starting on day 6 after surgery. Swallowing function was evaluated on days 6 and 15, and at 1 month postoperative using the Mann Assessment of Swallowing Ability-Oral Cancer tool (MASA-OC). On day 15 and at 1 month after surgery, the total MASA-OC score (P = 0.003, P < 0.001) and the mouth opening (P = 0.001, P < 0.001) and lip seal (both P < 0.001) item scores showed a significantly greater improvement in the intervention group than in the control group. Moreover, the changes in salivation (P < 0.001) and tongue movement (P = 0.025) scores at 1 month after surgery were significantly greater in the intervention group than in the control group. There was no significant difference between the groups in the change in tongue strength scores on day 15 or at 1 month postoperative (P = 0.476, P = 0.223). Personalized oral exercises can improve swallowing function in patients with oral cancer after free flap transplantation.

[Circular RNA hsa_circ_0006834 is a potential prognostic biomarker for hepatocellular carcinoma].

OBJECTIVE: To explore the differentially expressed circular RNAs (circRNAs) in hepatocellular carcinoma (HCC) and their association with clinical features and prognosis of HCC patients. METHODS: RNA sequencing was performed on 56 pairs of HCC and adjacent tissues to identify the differentially expressed circRNAs in HCC, whose expressions were validated by RT-qPCR in another 15 pairs of HCC and adjacent tissues. The correlation of the selected circRNAs with the clinical features and prognosis of the patients was analyzed using Chi-square test, Cox proportional hazards regression model and Kaplan-Meier analysis. The predictive value of the identified circRNA for recurrence-free survival and overall survival of HCC patients was assessed using ROC curves. RESULTS: We identified 17 significantly up-regulated and 45 down-regulated circRNAs in HCC tissues using RNA sequencing (P < 0.05). Among these circRNAs, hsa_circ_0006834 was found to be significantly down-regulated in HCC tissues, and its expression level was negatively correlated with vascular invasion and Barcelona Clinic Liver Cancer (BCLC) stage and positively with recurrence-free survival and overall survival of the patients (P < 0.05). As an independent prognostic factor for HCC, hsa_circ_0006834 had an AUC of 0.750 and 0.7601 for predicting 2-year recurrence-free survival and overall survival of HCC patients, respectively. CONCLUSION: hsa_circ_0006834 is a new potential biomarker for evaluating the prognosis of HCC patients.

[Comparison of risk factors for hemorrhagic stroke and ischemic stroke, a prospective long-term follow-up cohort study].

Objective: To analyze and compare the risk factors for hemorrhagic stroke and ischemic stroke and understand the exposure levels in population. Methods: A cohort study of risk factors of stroke was conducted in a rural community in Fengxian District of Shanghai in 2003, and the common risk factors of stroke were investigated at baseline survey, the cerebrovascular hemodynamics indexes were detected, the cerebrovascular function score was calculated according to the unified integral rule, and the incidence of stroke was observed in follow up. The risk factors for hemorrhagic stroke and ischemic stroke were analyzed by cohort study. The risk factors for two subtypes of stroke were compared. Result: A total of 10 565 participants were included in the study, with a mean follow-up period of (11.15±2.26) years, and 103 hemorrhagic stroke cases and 268 ischemic stroke cases were observed during follow-up period. The independent risk factors of hemorrhagic stroke included decreased cerebrovascular function score [hazard ratio (HR)=1.56, 95%CI: 1.23-1.98], history of alcohol consumption (HR=2.46, 95%CI: 1.39-4.34), hypertension (HR=1.75, 95%CI: 1.00-3.07) and older age (HR=1.07, 95%CI: 1.04-1.10). The independent risk factors of ischemic stroke included decreased cerebrovascular function score (HR=1.43, 95%CI: 1.25-1.65), smoking history (HR=1.52, 95%CI: 1.13-2.05), hypertension (HR=1.51, 95%CI: 1.10-2.07), family history of stroke (HR=1.89, 95%CI: 1.13-3.15), left ventricular hypertrophy (HR=1.74, 95%CI: 1.07-2.81) and older age (HR=1.07, 95%CI: 1.05-1.08). Conclusions: Decreased cerebrovascular function score, hypertension, and older age were common independent risk factors of both types of stroke, alcohol consumption history was an independent risk factor of hemorrhagic stroke, and smoking history, and family history of stroke and left ventricular hypertrophy were independent risk factors of ischemic stroke.

[Application of methylene blue near-infrared fluorescence imaging for oral sentinel lymph node mapping in rats].

OBJECTIVE: To explore the concentration range and penetration depth of methylene blue near-infrared fluorescence imaging, and to clarify the role of methylene blue in oral lymphatic drainage and sentinel lymph node localization, so as to lay a foundation for the potential research and application of sentinel lymph node in oral cancer. METHODS: 10% (mass fraction) methylene blue injection was diluted into 29 different concentrations with 0.9% (mass fraction) normal saline, and the concentration range of methylene blue near-infrared fluorescence imaging was determined by near-infrared fluorescence imager. The maximum penetration depth of methylene blue near-infrared fluorescence was determined by covering pigskin with different thicknesses (1, 2, 3, 4 and 5 mm) in methylene blue solution. 0.2 mL methylene blue solution was injected into the submucosal 0.5 cm at the lateral margin of tongue on one side of the rats. The near-infrared fluorescence imager was used for continuously monitoring for 3 hours. The first near-infrared fluorescence hotspot was identified as sentinel lymph node and labeled by percutaneous observation. The rats were then sacrificed and dissected in the head and neck. Near-infrared fluorescence imaging was performed again to observe whether the fluorescent tissue was consistent with the labeled fluorescent hotspot in vitro, and the presence of lymphoid tissue was confirmed by pathological examination after resection. RESULTS: Except that no fluorescence signals were detected in the blank control groups, the fluorescence intensity of methylene blue increased first and then decreased with its solution concentration decreased. When the concentration of methylene blue was diluted to the picomole level, the fluorescence signal could still be detected. The maximum penetration depth of methylene blue fluorescence was 4 mm. Methylene blue near-infrared fluorescence could be localized in oral lymphatic drainage and sentinel lymph node. The fluorescence was sustained for more than 3 hours after methylene blue injection. Methylene blue solution concentrations of 3.34 mmol/L, 6.68 mmol/L, 13.37 mmol/L and 26.74 mmol/L were selected in the rats to map sentinel lymph node by near-infrared fluorescence. CONCLUSION: Methylene blue near-infrared fluorescence has a certain penetrating ability and can transcuta-neously map the sentinel lymph node and their associated lymphatic vessels in rats, which is expected to be further applied in the study of sentinel lymph node in oral cancer.

[Application value of whole exon sequencing and immune related indicators in the precision treatment of oral squamous cell carcinoma].

OBJECTIVE: To explore the significance and feasibility of whole exon sequencing and immune related indexes in personalized precision treatment of oral squamous cell carcinoma (OSCC). METHODS: We retrospectively screened the patients who underwent surgery for oral cancer in Peking University Hospital of Stomatology and underwent genetic and immune biomarkers tests between January 2021 and June 2022. Combined with the clinicopathological characteristics of patients, potential targeted drugs and immunotherapy drugs were screened to evaluate the possibility of gene testing benefiting OSCC. The main evaluation indicators included the number of gene mutations, combined positive score (CPS), tumor mutation burden (TMB), microsatellite sequence status and human leukocyte antigen B (HLA-B) locus. Excel was used for statistical analysis. RESULTS: A total of 10 patients were enrolled and 9 were included in this study, including 6 males and 3 females, with an average age of (55.44±9.59) years. The tumor location was buccal (5 cases), tongue (3 cases) and gingival (1 case). The results of genetic testing showed that 3 (33.3%) patients had no gene mutations in the tumor tissue, 5 (55.6%) patients had unique TP53 gene mutations, and 1 (11.1%) patient had TP53 and CHEK1 mutations. However, no drugs were available for targeted therapy of the mutated genes. The genetic tumor gene testing results showed that no genetic tumor gene was found in all the patients, suggesting that OSCC had a low possibi-lity of hereditary tumor. In terms of immune efficacy related markers, CPS test results showed that 8 patients had CPS≥1. TMB detection results showed that the median value of TMB value was 0.72 mutations/Mb, and the range was 0 to 4.32 mutations/Mb. The negative and positive control results of microsatellite sequence status were consistent, indicating that all the tumor tissues detected were microsatellite stability. The results of HLA-B detection showed that only one patient had B62 gene mutation, suggesting that the B44 and B62 related genotypes of HLA-B in OSCC tissue samples were low. CONCLUSION: The present results do not support the wide application and promotion of genetic testing and immune related indexes in OSCC.

[Category of facial symmetry perception after maxillary reconstruction using anterolateral thigh flap].

OBJECTIVE: To preliminarily establish a category of facial symmetry perception after maxillary reconstruction using anterolateral thigh flap (ALTF) by the methods of stereophotogrammetry and subjective assessment. METHODS: The patients underwent maxillectomy due to neoplasms invasion, and all the maxillary defects were reconstructed using ALTF.Three-dimensional (3D) photographs were captured from the patients with a stereophotogrammatrical camera set-up.In the Geomagic software, the mirror image was created by reflecting along an arbitrary plane outside of the face.After the registration, the postoperative side on the original 3D photograph was segmented into 6 areas.The 3D change of the facial soft-tissue was measured using surface-based color map.Twenty laypeople took part in the study as observers, and they were asked to rate the 3D photographs using 5 point Likert-type scale according to their own aesthetic standard.The soft tissue asymmetry was graded according to the score.The collected data were subjected to statistical analysis using the SPSS 24.0 software. RESULTS: In the study, 44 subjects were recruited (21 males and 23 females, age range from 19 to 79 years).The soft-tissue symmetry was graded into three levels according to the subjective scores.The grade Ⅰ was basically symmetrical.The grade Ⅱ was slightly asymmetrical.The grade Ⅲ was obviously asymmetrical.Statistically significant differences were found in the suborbital (P < 0.05) and zygomatic (P < 0.05) areas when comparing all grades of soft-tissue asymmetry, and in the buccal (P < 0.05) and superiolabial (P < 0.05) areas when comparing grades Ⅰ and Ⅲ.The extent of maxillary defect had significant impact on the symmetry of the midface soft-tissue after maxillary reconstruction. CONCLUSION: Varying extent maxillectomy would result in varying degrees of asymmetry, and cause different grades of symmetry perception even if they had been reconstructed using ALTF.The higher the grade, the worse the symmetry of facial soft-tissue.Suborbital and zygomatic areas were important aesthetic units that affected the facial symmetry perception, followed by buccal and superiolabial areas.The clinicians should pay attention to the soft-tissue support in these areas when reconstructing the maxillary defect, especially large defect with orbital floor involved.

Invited review: Good practices in genome-wide association studies to identify candidate sequence variants in dairy cattle.

Genotype data from dairy cattle selection programs have greatly facilitated GWAS to identify variants related to economic traits. Results can enhance the accuracy of genomic prediction, analyze more complex models that go beyond additive effects, elucidate the genetic architecture of a trait, and finally, decipher the underlying biology of traits. The entire process, comprising data generation, quality control, statistical analyses, interpretation of association results, and linking results to biology should be designed and executed to minimize the generation of false-positive and false-negative associations and misleading links to biological processes. This review aims to provide general guidelines for data analysis that address data quality control, association tests, adjustment for population stratification, and significance evaluation to improve the reliability of conclusions. We also provide guidance on post-GWAS strategy and the interpretation of results. These guidelines are tailored to dairy cattle, which are characterized by long-range linkage disequilibrium, large half-sib families, and routinely collected phenotypes, requiring different approaches than those applied in human GWAS. We discuss common limitations and challenges that have been overlooked in the analysis and interpretation of GWAS to identify candidate sequence variants in dairy cattle.

[Clinical and genetic characteristics of children with dopa-responsive dystonia caused by tyrosine hydroxylase gene variations].

Objective: To explore the clinical and genetic characteristics of children with dopa-responsive dystonia (DRD) caused by tyrosine hydroxylase (TH) gene variations. Methods: Clinical data of 9 children with DRD caused by TH gene variations diagnosed in the Department of Children Rehabilitation, the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2022 were retrospectively collected and analyzed, including the general conditions, clinical manifestations, laboratory tests, gene variations and follow-up data. Results: Of the 9 children with DRD caused by TH gene variations, 3 were males and 6 were females. The age at diagnosis was 12.0 (8.0, 15.0) months. The initial symptoms of the 8 severe patients were motor delay or degression. Clinical symptoms of the severe patients included motor delay (8 cases), truncal hypotonia (8 cases), limb muscle hypotonia (7 cases), hypokinesia (6 cases), decreased facial expression (4 cases), tremor (3 cases), limb dystonia (3 cases), diurnal fluctuation (2 cases), ptosis (2 cases), limb muscle hypertonia (1 case) and drooling (1 case). The initial symptom of the very severe patient was motor delay. Clinical symptoms of the very severe patient included motor delay, truncal hypotonia, oculogyric crises, status dystonicus, hypokinesia, decreased facial expression, and decreased sleep. Eleven TH gene variants were found, including 5 missense variants, 3 splice site variants, 2 nonsense variants, and 1 insertion variant, as well as 2 novel variants (c.941C>A (p.T314K), c.316_317insCGT (p.F106delinsSF)). Nine patients were followed up for 40 (29, 43) months, and no one was lost to follow-up. Seven of the 8 severe patients were treated by levodopa and benserazide hydrochloride tablets and 1 severe patient was treated by levodopa tablets. All the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets. Although the weight of the patients increased and the drug dosage was not increased, the curative effect remained stable and there was no obvious adverse reaction. One severe patient developed dyskinesia in the early stage of treatment with levodopa and benserazide hydrochloride tablets and it disappeared after oral administration of benzhexol hydrochloride tablets. Until the last follow-up, motor development of 7 severe patients returned to normal and 1 severe patient still had motor delay due to receiving levodopa and benserazide hydrochloride tablets for only 2 months. The very severe patient was extremely sensitive to levodopa and benserazide hydrochloride tablets and no improvement was observed in this patient. Conclusions: Most of the DRD caused by TH gene variations are severe form. The clinical manifestations are varied and easily misdiagnosed. Patients of the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets, and it takes a long time before full effects of treatment become established. Long-term effect is stable without increasing the drug dosage, and no obvious side effect is observed.

[Bioinformatics analysis in metagenomic next-generation sequencing of pathogenic microorganisms: current status and challenges].

The clinical application of metagenomic next-generation sequencing (mNGS) in the diagnosis of unknown pathogenic infections and critical infections has become increasingly valuable. Due to the huge volume of mNGS data and the complexity of clinical diagnosis and treatment, mNGS has difficulties in data analysis and interpretation in practical application. Therefore, in the process of clinical practice, it is crucial to grasp the key points of bioinformatics analysis and establish a standardized bioinformatics analysis process, which is an important step in the transformation of mNGS from laboratory to clinic. At present, bioinformatics analysis of mNGS has made great progress, but with the high requirements of clinical standardization of bioinformatics analysis and the development of computer technology, bioinformatics analysis of mNGS is also facing new challenges. This article mainly elaborates on quality control, and identification and visualization of pathogenic bacteria.

Bone resorption after maxillary reconstruction with the vascularized free iliac flap.

The aim of this study was to evaluate the resorption of the iliac bone after maxillary reconstruction with a vascularized free iliac flap. Twenty-seven patients with maxillary defects who underwent maxillary reconstruction with the vascularized free iliac flap between January 2017 and January 2021 were included. Computed tomography (CT) images taken at 1 week, approximately 6 months, and 1 year after the surgery were used for evaluation. The total iliac bone thickness and height, cortical bone thickness, and cancellous bone density were measured in the CT images. Compared with 1 week after the surgery, the total thickness and height of the iliac bone were reduced significantly 1 year after the surgery, and the cortical bone thickness and cancellous bone density were reduced significantly at 6 months and 1 year after the surgery. Compared with 6 months after the surgery, cancellous bone density was reduced significantly 1 year after the surgery. In conclusion, during the first year after maxillary reconstruction with a vascularized free iliac flap, there was significant resorption of iliac bone, including the total iliac bone thickness and height, the cortical bone thickness, and the cancellous bone density.

Accurate occlusion-driven maxillary reconstruction with deep circumflex iliac artery flap using computer-assisted techniques and intraoral anastomosis: a case series.

The aim of this study was to evaluate the feasibility and accuracy of occlusion-driven maxillary reconstruction with the deep circumflex iliac artery (DCIA) flap, using computer-assisted design and manufacturing (CAD/CAM) technology and intraoral anastomosis. The data of 11 patients who underwent occlusion-driven maxillary reconstruction with this method between December 2018 and December 2020 in the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology were reviewed retrospectively. Postoperative complications and functional and aesthetic outcomes were recorded. The accuracy of the postoperative restoration was assessed using Geomagic Control 2014. Reconstruction was successful in nine patients; all were satisfied with their aesthetic and functional outcomes. One patient underwent extraoral anastomosis after failure of intraoral anastomosis. In another patient, the DCIA flap had to be removed after the operation because of flap failure. Among the 10 patients with DCIA flap success, colour map analysis showed a mean deviation of 0.40 ± 0.08 mm between the preoperative and postoperative craniomaxillary models. Thus, occlusion-driven maxillary reconstruction with the DCIA flap, using CAD/CAM technology and intraoral anastomosis, appears to be a feasible and accurate method for the repair of maxillary defects.

[Changes of myocardial calcium currents in rats with myocardial injury induced by running exercise during acute hypoxia].

OBJECTIVE: To investigate the changes in myocardial calcium currents in rats subjected to forced running exercise during acute hypoxia and their association with myocardial injury. METHODS: Forty SD rats were randomized into quiescent group and running group either in normal oxygen (NQ and NR groups, respectively) or in acute hypoxia (HQ and HR groups, respectively). Hypoxia was induced by keeping the rats in a hypobaric oxygen chamber (PaO2=61.6kpa) for 4 h a day; the rats in the two running groups were forced to run on running wheels for 4 h each day. Rat ventricular myocytes was isolated by enzymatic digestion for recording action potentials and currents using patch clamp technique, and confocal Ca2+ imaging was used to monitor intracellular Ca2+ levels. The expressions of Cav1.2 channel and the cardiac ryanodine receptor (RyR2) were determined using Western blotting. RESULTS: Compared with those in NQ group, the rats in HR group showed significantly decreased SOD activity (P < 0.01), increased h-FABP, hs-CRP and IMA levels (P < 0.05 or 0.01), obvious myocardial pathology, and prolonged APD50 and APD90 (P < 0.05). Of the different stress conditions, forced running in acute hypoxia resulted in the most prominent increase of the densities of ICa, L currents, causing also a significant left shift of the steady state activation curve and a significant right shift of the steady state inactivation curve. Compared with those in NQ group, the rats in NR, HQ and HR groups all exhibited higher rates of spontaneous calcium wave events in the cardiac myocytes, increased frequency of calcium sparks with lowered amplitude, enhanced calcium release amplitude in the ventricular myocytes, and delayed calcium ion reabsorption; in particular, these changes were the most conspicuous in HR group (P < 0.05 or 0.01). There was also a significant increase in the protein levels of Cav1.2 channel and RyR2 receptor in HR group (P < 0.05 or 0.01). CONCLUSIONS: The mechanism of myocardial injury in rats subjected to forced running in acute hypoxia may involve the increase of oxidative stress and calcium current and intracellular calcium overload.

[Naringenin inhibits thoracic aortic aneurysm formation in mice with Marfan syndrome].

OBJECTIVE: To identify whether naringenin plays a protective role during thoracic aneurysm formation in Marfan syndrome. METHODS: To validate the effect of naringenin, Fbn1C1039G/+ mice, the mouse model of Marfan syndrome, were fed with naringenin, and the disease progress was evaluated. The molecular mechanism of naringenin was further investigated via in vitro studies, such as bioluminescence resonance energy transfer (BRET), atomic force microscope and radioligand receptor binding assay. RESULTS: Six-week-old Fbn1C1039G/+ mice were fed with naringenin for 20 weeks. Compared with the control group, naringenin significantly suppressed the aortic expansion [Fbn1C1039G/+ vs. Fbn1C1039G/++naringenin: (2.49±0.47) mm, n=18 vs. (1.87±0.19) mm, n=22, P < 0.05], the degradation of elastin, and the expression and activity of matrix metalloproteinase 2 (MMP2) and MMP9 in the ascending aorta of Fbn1C1039G/+ mice. Besides, treatment with naringenin for 6 weeks also attenuated the disease progress among the 20-week-old Fbn1C1039G/+ mice with established thoracic aortic aneurysms [Fbn1C1039G/+ vs. Fbn1C1039G/++naringenin: (2.24±0.23) mm, n=8 vs. (1.90±0.17) mm, n=8, P < 0.05]. To understand the underlying molecular mechanisms, we examined the effects of naringenin on angiotensin Ⅱ type 1 receptor (AT1) signaling and transforming growth factor-ß (TGF-ß) signaling respectively, which were the dominant signaling pathways contributing to aortopathy in Marfan syndrome as previously reported. The results showed that naringenin decreased angiotensin Ⅱ (Ang Ⅱ)-induced phosphorylation of protein kinase C (PKC) and extracellular regulating kinase 1/2 (ERK1/2) in HEK293A cell overexpressing AT1 receptor. Moreover, naringenin inhibited Ang Ⅱ-induced calcium mobilization and uclear factor of activated T-cells (NFAT) signaling. The internalization of AT1 receptor and its binding to ß-arrestin-2 with Ang Ⅱ induction were also suppressed by naringenin. As evidenced by atomic force microscope and radioligand receptor binding assay, naringenin inhibited Ang Ⅱ binding to AT1 receptor. In terms of TGF-ß signaling, we found that feeding the mice with naringenin decreased the phosphorylation of Smad2 and ERK1/2 as well as the expression of TGF-ß downstream genes. Besides, the serum level of TGF-ß was also decreased by naringenin in the Fbn1C1039G/+ mice. Furthermore, we detected the effect of naringenin on platelet, a rich source of TGF-ß, both in vivo and in vitro. And we found that naringenin markedly decreased the TGF-ß level by inhibiting the activation of platelet. CONCLUSION: Our study showed that naringenin has a protective effect on thoracic aortic aneurysm formation in Marfan syndrome by suppressing both AT1 and TGF-ß signaling.

[Preliminary analysis of the promotion effect of laparoscopic standardized surgical treatment for gastric cancer in regional medical centers in Shanghai].

Objective: To explore the promotion effect of laparoscopic standardized surgery for gastric cancer observational in some regional medical centers in Shanghai. Methods: A retrospective cohort study was carried out. Eleven regional medical centers in Shanghai received the promotion program of laparoscopic standardized surgery for gastric cancer, which was led by Ruijin Hospital, Shanghai Jiaotong University School of Medicine (Shanghai Minimally Invasive Surgery Center) from January to December 2020. Clinicopathological data of gastric cancer patients treated at these 11 regional medical centers before and after the promotion program were collected. Inclusion criteria were as follows: patients undergoing laparoscopic distal gastrectomy or total gastrectomy; gastric cancer confirmed by pathology; without distant metastasis or peritoneal metastasis. Patients who did not undergo laparoscopic D2 radical resection, or received neoadjuvant chemotherapy before surgery, or without complete clinical data were excluded. Patients undergoing laparoscopic surgery from January to December 2019 were included in the pre-promotion group (46 cases). Patients undergoing laparoscopic surgery from January to December 2021 were included in the post-promotion group (102 cases). In addition, patients undergoing laparoscopic surgery at Ruijin Hospital from January 2021 to December were included in the control group (138 cases). The baseline data, perioperative measurements postoperative complications, and pathological results of the three groups were analyzed and compared. Results: There were no significant differences in baseline characteristics among the three groups (all P>0.05). Compared with the pre-promotion group, the operation time in post-promotion group was significantly shorter [(207.3±36.0) minutes vs. (254.2±47.1) minutes, t=7.038,P<0.001], and the number of harvested lymph node was significantly more (24.4±12.2 vs. 18.9±5.5, t=2.900, P=0.004). However, there were no significant differences in the extent of resection, time to fluid intake, and postoperative hospital stay between the two groups (all P>0.05). Compared with the control group, the operation time [(207.3±36.0) minutes vs (172.6±26.0) minutes, t=8.281, P<0.001], time to fluid intake [(6.3±3.2) days than (5.5±3.0) days, t=2.029, P=0.044], and the postoperative hospital stay [(14.3±5.6) days vs. (10.1±4.8) days, t=6.036, P<0.001] in the post- promotion group were still longer. Total gastrectomy was less common in the post-promotion group compared with the control group [18 cases (17.6%) vs. 41 cases (29.7%), χ2=7.380, P=0.007]. However, there was no significant difference in the number of harvested lymph node between the two groups (P>0.05). The morbidity of postoperative complication in the post-promotion group (9.8%, 10/102) was significantly lower than that in the pre-promotion group (23.9%, 11/46) (χ2=5.183, P=0.023), while above morbidity was not significantly different between the post-promotion group and the control group [9.8% vs. 6.5% (9/138), χ2=0.867, P=0.352]. Conclusion: After the promotion of laparoscopic standardized surgery for gastric cancer in regional medical centers, the standardization degree of surgery has been improved, and the morbidity of postoperative complication decreases. Laparoscopic standardized surgery for gastric cancer can be promoted to more regional medical centers.

Global prevalence, risk factors, and reporting practice of needlestick and sharps injuries among dental students: a systematic review and meta-analysis.

BACKGROUND: Dental students are vulnerable to needlestick injuries (NSIs) due to their inadequate training. However, the global prevalence of NSI among dental students is unknown. AIM: To determine the pooled prevalence among dental students, epidemiological profile, and risk factors for NSI. METHODS: A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The review protocol was registered at the International Prospective Register of Systematic Reviews (CRD 42022312778). Eligible studies were identified from PubMed, Scopus, Web of Science, Embase, OVID, and EBSCO databases. A meta-analysis with a random effects model was performed to estimate the pooled prevalence, and meta-regression was conducted to explore heterogeneity among studies. FINDINGS: A total of 25 studies from 15 countries met the inclusion criteria. The estimated pooled prevalence of NSI among dental students was 44% (95% confidence interval: 38-51%). Local anaesthesia, tooth cleaning or scaling, and waste disposal were associated with highest risk for NSI. Most studies observed under-reporting of NSI. Dental students had inadequate knowledge regarding post-exposure management. CONCLUSION: Dental students had a high prevalence and low reporting rate of NSI exposure. Inadequate knowledge might increase the probability of NSI exposure.