Objective To evaluate expression of HDAC2 in peripheral blood mononuclear cells(PBMCs)from glucocorticoid-resistant versus glucocorticoid-sensitive patients with sudden sensorineural hearing loss and identi-ty the relationship between the level of HDAC2 and glucocorticoid insensitivity.Methods PBMCs were collected from10 patients with deviation of nasal septum (control group)and 20 sudden sensorineural hearing loss patients be-fore and after intratympanic methylprednisolone for 10 days.We divided the SSNHL patients into 2 groups (GC sensitive group and GC insensitive group)according to their hearing recovery.Real time PCR and HDAC2 Assay Kit were used to detect the expression level of HDAC2 mRNA and HDAC2 activity in PBMCs.The data were analyzed with SPSS 17.0 software.ResuIts Before intratympanic methylprednisolone,the level of HDAC2 activity were sig-nificantly depressed in SSNHL patients,while the HDAC2 mRNA expressing much higher than the control group. The expression level of HDAC2 mRNA increased significantly after intratympanic methylprednisolone.The HDAC2 activity in GC sensitive group increased significantly.ConcIusion Knockdown of HDAC2 expression induces corti-costeroid in-sensitivity.Glucocorticoids can increase the expression of HDAC2 mRNA.HDAC2 activity can be down-regulated by post-translational modifications.

Objective To investigate the clinical and pathological characteristics of IgA nephropathy (IgAN) with macrohematuria (MH).Method 1512 consecutive patients with biopsyproven IgAN diagnosed from January 2006 to December 2011 were enrolled,and divided into MH group and control group respectively,according to whether there existed episodes of MH before renal biopsy.The clinical and pathological characteristics were compared between two groups.Patients in MH group were then divided into three groups according to the interval from the last episode of MH to renal biopsy to clarify the concomitant clinicopathological changes associated with occurrence of MH.Results The rate of MH in history was 22.1％.MH group patients had significantly lower serum creatinine,slighter proteinuria,lower prevalence of hypertension and heavier microhematuria than control group (all P ＜ 0.001).The prebiopsy durations were similar in two groups (P=0.627).In MH group,chronic pathological indicators,including global/segmental sclerosis,tubule atrophy/interstitial fibrosis were all slighter (all P＜ 0.001),whereas activity indicators,including necrosis lesions,crescents and mesangial proliferation were all more severe compared with control group (all P ＜ 0.05).Those who underwent renal biopsy within 30 days of the last episode of MH had more severe proteinuria and microhematuria,higher prevalence of necrosis lesions,more severe crescents formation,and endothelial proliferation (all P ＜ 0.05).Conclusions IgAN patients with MH in history have relatively milder clinical and chronic pathological manifestations,however more active pathological changes especially in those who suffer episode of MH recently.

Long-term medical education program requires that the medical students should ac-quire both professional knowledge and scientific research ability. These students,with heavy task and course,have difficulty in performing the scientific research systematically. It is very important to develop the early scientific research training. Department of pathology in Central South University,took early sci-entific research activities in various forms,such as literature searching,reviews writing,research design-ing,experiment performing,lecture communicating and clinical practicing after combining the discipline characteristic and arranging the overall process. Satisfactory effects were achieved with efforts.

Objective:To clarify the influence and influence paths of stigma on the time of the healthcare-seeking decision in caregivers of elderly patients with dementia, and to provide a theoretical basis for the construction of corresponding humanistic care strategies.Methods:A total of 176 caregivers of elderly patients with dementia who visited the Affiliated Hospital of Xuzhou Medical University and Xuzhou Oriental People ′s Hospital from February 2021 to February 2022 were selected as the study subjects. The General Information Questionnaire, self-designed Scale of Stigma for Caregivers of Senile dementia patients, Multidimensional Scale of Perceived Social Support, self-designed Elderly Dementia Caregivers′ Perceived Barriers Scale for Healthcare-seeking Decision, and self-designed Scale of the Intention to Seek Healthcare for caregivers of senile dementia patients were used in the survey. AMOS 20.0 was used to establish a structural equation model for path analysis. Results:The higher the stigma of caregivers, the longer the time of the healthcare-seeking decision ( β=0.05, P<0.05). Social support, perceived barriers to the healthcare-seeking decision, and the intention to seek healthcare were the mediating variables of caregivers ′ stigma affecting the time of the healthcare-seeking decision, with a total effect of -0.04, 0.14, and 0.36, respectively, and all P<0.05. Conclusions:The stigma in caregivers of senile dementia patients is an important factor affecting the time of the healthcare-seeking decision. By improving mediating factors including social support, perceived barriers to the healthcare-seeking decision, and the intention to seek healthcare, the implementations of targeted humanistic care strategies are expected to help shorten the time of the healthcare-seeking decision.

Objective To explore the clinicopathological features and renal outcomes of primary IgA nephropathy (IgAN) patients with chronic tonsillitis.Methods Patients with biopsyproven primary IgAN admitted to The First Affiliated Hospital,Sun Yat-sen University from January 2006 to December 2011 were enrolled.The clinicopathological features and renal outcomes of patients with and without chronic tonsillitis were retrospectively compared.The primary outcome was progression to end stage renal diseases and/or doubling of serum creatinine.Results A total of 981 primary IgAN patients were enrolled and 98 patients (9.99％) had a history of chronic tonsillitis.Compared with patients without chronic tonsillitis,IgAN patients with chronic tonsillitis exhibited significantly higher prevalence of acute episodes of tonsillitis as a predisposition (P ＜ 0.001),higher serum IgA levels (P=0.012),and higher prevalence of macrohematuria (P=0.006).No significant difference in renal pathological features was observed in patients with and without chronic tonsillitis.Moreover,the renal outcomes were similar as regards IgAN patients with and without chronic tonsillitis.Conclusion IgAN patients with chronic tonsillitis had higher prevalence of acute episodes of tonsillitis and macrohematuria as well as higher serum IgA levels.However,IgAN patients with and without chronic tonsillitis showed no significant difference in renal pathological features and renal outcomes.

OBJECTIVESWe identified the long QT syndrome (LQTS) patients, and detected the potential risk of LQTS in family members by using genetic testing and electrophysiological analysis, which helped provide clinical evaluation and appropriate treatment.

METHODSDetailed clinical characteristics and familiar history were obtained from the whole family members of an idiopathic pediatric LQTS patient. Two hundred healthy subjects with the same ethnic background were recruited as controls. The entire coding sequences of three candidate genes including KCNQ1, KCNH2 and SCN5A were screened for mutations in the proband. The function of the mutation was then explored by whole-cell patch clamp techniques, and the genetic testing and risk assessment of the family members were performed.

RESULTSThe proband was clinically preliminary diagnosed as LQTS by 12-lead electrocardiogram. On the third day of metoprolol intake (25 mg, bid), she died suddenly at lunch. One heterozygous missense mutation (SCN5A-V411M) was identified in this proband, but the mutation was absent in 200 healthy subjects. The electrophysiological analysis indicated that SCN5A-V411M significantly increased the peak current density ((230.8 ± 27.6)pA/pF vs. (101.2 ± 10.9)pA/pF, n=10, P<0.01) and the late sodium current ((156.6 ± 13.6)pA/pF vs. (95.9 ± 7.9)pA/pF, n=12, P<0.01) of sodium channel compared to wide type. The enhanced sodium channel activation with a negative shift in the peak I-V relationship was significantly higher by -50 mV than wide type (85.0%± 7.4% vs. 41.5% ± 2.6%, P<0.01), while the steady-state inactivation curves remained unchanged. Additionally, mother and grandmother of the proband were the silent mutation carriers with no symptoms, who needed the appropriate clinical assessment and follow-up. The proband's twin sister and aunt died of sudden infant death syndrome.

CONCLUSIONSWe firstly reported a heterozygote missense mutation (SCN5A-V411M) in this Chinese family. V411M induced "gain of function" of sodium channel and formed the basis of type-3 LQTS. Genetic testing could help to increase the diagnostic accuracy, and facilitate clinical assessment and appropriate therapy to prevent sudden cardiac death of individuals with SCN5A-V411M mutation.

Distant metastasis is one of the main obstacles to cancer treatment.Overexpression of S1PR1 in malignant tumors enhances cell invasion and migration activity,mediates EMT and induces lymphangiogenesis and angiogenesis via activation of its downstream signaling pathways,eventually results in the occurrence of tumor metastasis.S1PR1 is also closely related to generation of acquired radiotherapy resistance.This article discusses the roles of S1PR1 in tumor metastasis and radiotherapy resistance.

Objective: To explore the clinical and molecular genetic features of a Chinese patient with catecholaminergic polymorphic ventricular tachycardia (CPVT). Methods: Clinical data including resting electrocardiography, echocardiography and treadmill exercise testing of a patient with CPVT admitted to our department in March 2013 were analyzed, and the peripheral venous blood samples of the patient and his family members and 400 ethnicity-matched healthy controls were obtained. All exons and exon-intron boundaries of the six CPVT-related genes including RYR2, CASQ2, TRDN, CALM1, KCNJ2 and ANKB were sequenced to detect the variants related to CPVT. The relationship between the genotypes and phenotypes was analyzed to direct the target therapy. Results: Recurrent syncope induced either by exercise or extreme frightened fear was observed in this patient. There was no positive family history of syncope or sudden death. The resting electrocardiography and echocardiography of the patient were normal, while the exercise testing revealed bidirectional and polymorphic ventricular tachycardia. A cardiac ryanodine receptor gene mutation (R2401H) was identified in this patient, while this mutation was absent in his parents and sister and 400 controls. No variant was detected in the remaining five candidate genes. Treatment with high dose of metoprolol succinate (118.75 mg/d) was effective and patient was free of syncopal attack during the 2 years follow-up. Conclusion This is the first report on RyR2-R2401H mutation in Chinese patient with CPVT, and high dose of metoptolol is the effective therapy option for CPVT related to RyR2 mutation.

Objective: To investigate the mechanism of resveratrol promoting fibronectin type Ⅲ domain-containing 5 (FNDC5) degradation in skeletal muscle of male obese mice． Methods: Six-week-old male C57BL /6 mice were randomly divided into three groups : standard control diet ( SCD) ，high-fat diet ( HFD) and high-fat diet treated with resveratrol (HFD + RES) ．HFD + RES group was intervened with resveratrol via gavage ［400 mg / kg · d) ］ while fed HFD for 20 weeks．The body mass，serum TG，TC，LDL-C and HDL-C levels were detected．The pathological changes in skeletal muscle were detected by HE staining．The expression of FNDC5，SIRT1，SIRT2，LC3， p62，Beclin-1，ATG5，ATG7 was assessed by immunohistochemistry，RT-PCR and Western blot respectively. Results: The body mass ，serum TG ，TC and LDL-C levels increased significantly ，meanwhile HDL-C levels decreased in HFD group．Lipid deposition between skeletal muscle fibers were obvious in HFD group．The immuno- histochemistry results showed that protein expression levels of SIRT1，SIRT2 and LC3 obviously decreased，while the protein levels of FNDC5 and p62 obviously increased．The expression levels of FNDC5 significantly increased， while the gene expression levels of SIRT1，SIRT2，LC3，Atg7 and Beclin-1 obviously decreased．All these responses were attenuated by treatment with RES． Conclusion RES has obvious effects of lipid-lowering and promoting FNDC5 degradation in skeletal muscle tissues，which may be related with SIRT1 and SIRT2-induced autophagy， thus resulting in degradation of FNDC5 .