[Phase â ¡ clinical trial of PD-1 inhibitor combined with chemotherapy for locally advanced resectable oral squamous cell carcinoma].

Objective: To explore the effectiveness and safety of programmed death 1(PD-1) inhibitory combined with chemotherapy as a neoadjuvant therapy for locally advanced resectable oral squamous cell carcinoma. Methods: This study was a randomized controlled phase Ⅱ trial. Patients recruited from Tianjin Medical University Cancer Institute and Hospital from July 2021 to February 2023 were randomly divided into two groups in a 1∶1 ratio: the experimental group (Toripalimab combined with albumin paclitaxel and cisplatin) and the control group (albumin paclitaxel and cisplatin); patients in both groups underwent three cycles of neoadjuvant therapy. After completion of neoadjuvant therapy, patients were evaluated and subsequent surgical treatment was performed. According to the completion of treatment, the analysis was conducted on both the full analysis set and the protocol set. The effectiveness and safety of treatments were evaluated. SPSS 20.0 software was used for statistical analysis. Results: A total of 41 cases with oral cancer were enrolled, including 26 males and 15 females, aged between 34 and 74 years old. There were 23 cases in the experimental group and 18 cases in the control group. A total of 23 cases completed neoadjuvant therapy and surgery according to the protocol. Experimental group and control group showed respectively the complete response rates of 1/19 and 0/17, the partial response rates of 13/19 and 8/17, the stage-down rates of 4/19 and 3/17, the pathologic complete response rate of 8/14 and 2/9, with no statistically significant differences in individual rates between two groups (P>0.05). The major pathological response rate of 13/14 in experimental group was higher than that of 2/9 in control group (P<0.05). The incidence of grade 3-4 adverse reactions related to treatment was low in both groups (4/23 vs. 3/18, χ2=0.13, P=0.72), and the most common serious adverse reactions in the experimental group were granulocyte deficiency and electrolyte disorder. There were no adverse reactions that affected subsequent surgical treatment or caused death, and the safety and tolerability were good. The median follow-up time was 15 months, and the one-year disease-free survival rate of the experimental group was higher than that of control group (92.86% vs. 77.78%, χ2=0.62, P=0.42), with a relative decrease of 87% in the risk of disease progression or death (P=0.029). For patients with programmed death-ligand 1(PD-L1) protein expression combined positive score≥20, the experimental group showed higher major pathological response rate than control group (5/5 vs. 0/4, P=0.03). Conclusion: The neoadjuvant therapy of immunotherapy combined with chemotherapy can improve the pathological remission of oral squamous cell carcinoma and the long-term survival benefits and the prognosis of patients.

[Clinical features and long-term outcomes after laparoscopic surgery in patients co-existing with ovarian endometrioma and deep infiltrating endometriosis].

Objective: To investigate the clinical features and long-term prognosis of patients co-existing with ovarian endometrioma (OMA) and deep infiltrating endometriosis (DIE). Methods: Totally 358 OMA patients were retrospectively analyzed, who had a minimum of 8 years follow-up after laparoscopic cystectomy, which was performed by one professional endometriosis surgery team at Peking Union Medical College Hospital from January 2009 to April 2013. All women were divided into DIE group and non-DIE group, and analysis was performed in preoperative characteristics, surgical findings and postoperative outcomes during follow-up. Results: A total of 358 OMA patients were included, of which 190 patients (53.1%, 190/358) were in the DIE group, while other 168 patients (46.9%, 168/358) in the non-DIE group. The average ages between the two groups were (33.7±5.4), (32.5±5.3) years (P=0.047), the average parity was (0.4±0.6) times vs (0.3±0.5) times (P=0.079). There were significant differences in the proportions of moderate to severe dysmenorrhea [67.4% (128/190) vs 56.5% (95/168)], chronic pelvic pain [24.2% (46/190) vs 7.7% (13/168)], and the increase in CA125 [79.9% (139/190) vs 65.2% (101/168)] between the two groups (all P<0.05). The average operation time in the DIE and non-DIE groups was (75±21) vs (39±36) minutes (P<0.01). There was a significant difference in adenomyosis presence between the two groups [41.6% (79/190) vs 22.0% (37/168); P=0.001]. All patients were followed up for at least 8 years. At the end of the follow-up, though the DIE group was with higher total rate of disease relapse, yet no significant difference was found between the two groups in statistical comparison [21.6% (41/190) vs 16.1% (27/168); P=0.185]. A total of 41 cases in the DIE group recurred, the recurrence rate of pain was 15.8% (30/190), and the recurrence rate of cyst was 8.4% (16/190); 27 cases had recurrence after operation in the non-DIE group, the recurrence rate of pain was 8.9% (15/168), and the recurrence rate of cyst was 10.7% (18/168). There were no significant differences in the pain recurrence rate (P=0.067) and cyst recurrence rate (P=0.460) between the two groups. As for the successfully pregnant patients, live birth rates were 100.0% (65/65) vs 94.4% (68/72) between DIE group and non-DIE groups (P=0.120). Conclusions: Compared with the non-DIE group, OMA patients with concurrent DIE might have severe pain symptoms, higher probability of abnormal CA125 levels and more severe pelvic adhesions. Although there are no significant differences in the total recurrence rate and the recurrence rate of various types between the two groups, the proportion of pain recurrence in the DIE group is higher than that in the non-DIE group. In terms of fertility outcomes, patients in the DIE group are with lower likelihood of pregnancy after surgery during the long-time follow-up. DIE has no significant influence on the fertility outcome.

[Repair of skin and soft tissue defects in shoulder and elbow with rotator scapular artery perforator flap, lateral thoracic perforator flap, or medial brachial artery perforator flap].

From January 2014 to June 2018, 12 patients with skin and soft tissue defects in shoulder and elbow were admitted to General Hospital of Ningxia Medical University with skin and soft tissue defect size of 6 cm×5 cm to 11 cm×8 cm, including 9 males and 3 females aged 15-56 years. Wounds of 5 patients were repaired with rotator scapular artery perforator flap (flap area of 8 cm×7 cm to 12 cm×6 cm), and the donor flap area was sutured directly. Wounds of 3 patients were repaired with lateral thoracic perforator flap (flap area of 8 cm×7 cm to 13 cm×9 cm). The donor flap area of two patients was sutured directly, the majority of the donor flap area of one patient was sutured directly, and a small part was covered by split-thickness skin graft from ipsilateral thigh. Wounds of 4 patients were repaired with medial brachial artery perforator flap (flap area of 6 cm×5 cm to 12 cm×10 cm). The donor flap area of two patients was sutured directly, and two patients were covered with split-thickness skin graft from left chest wall. The flaps of 11 patients survived after surgery. Blood flow disorder at the distal end of the flap was observed in one patient. After treatment, the distal end of the flap presented 3 cm×2 cm necrosis, and the skin graft survived after second skin grafting and debridement. During the follow-up of 6 to 24 months post surgery, all patients had good texture of flap, with light scar hyperplasia in the donor flap area, and good recovery of elbow and shoulder joint function. The rotator scapular artery perforator flap, lateral thoracic perforator flap, and medial brachial artery perforator flap with the advantages being of relatively simple operation, high survival rate, and good surgical outcome, are good choices for repairing the skin and soft tissue defects in shoulder and elbow.

Upregulation of lncRNA DANCR functions as an oncogenic role in non-small lung cancer by regulating miR-214-5p/CIZ1 axis.

OBJECTIVE: Lung cancer has an unfavorable prognosis due to the lack of efficient diagnostic and therapeutic strategies. Therefore, this study sought to figure out the effect of long non-coding RNA (lncRNA) DANCR on lung cancer progression. PATIENTS AND METHODS: LncRNA DANCR and miR-214-5p expressions in non-small cell lung cancer (NSCLC) were detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). Function assays, including Cell Counting Kit-8 (CCK-8) and flow cytometric analysis were conducted to clarify the role of DANCR and miR-214-5p in the progression of NSCLC. Western blot, Dual-Luciferase reporter assay, and RNA immunoprecipitation assay (RIP) were performed to elucidate the underlying mechanism. RESULTS: LncRNA DANCR was upregulated in NSCLC. The knockdown of lncRNA DANCR inhibited cell proliferation and accelerated cell apoptosis in NSCLC. LncRNA DANCR interacted with miR-214-5p. MiR-214-5p over-expression partially reversed the regulatory effects of DANCR on proliferation and apoptosis in NSCLC. In addition, CIZ1 was the downstream gene binding miR-214-5p. LncRNA DANCR could regulate the miR-214-5p/CIZ1 axis. CONCLUSIONS: Downregulation of lncRNA DANCR inhibited cell proliferation and induced cell apoptosis in NSCLC by regulating the miR-214-5p/CIZ1 axis. LncRNA DANCR may act as an oncogene and promote the progression of NSCLC.

Supracondylar humeral fractures in children: American Academy of Orthopaedic Surgeons appropriate use criteria versus actual management in a teaching hospital.

PURPOSE: The objective of this study was to explore whether there were any differences between the theoretical recommendations for children's supracondylar humeral fractures (CSHF) according to the American Academy of Orthopaedic Surgeons (AAOS) guidelines and the treatments they actually received in our institution. METHODS: We retrospectively reviewed the medical charts and radiographs of all CSHFs at our hospital between January 2015 and December 2018. In all, 301 children meeting our inclusion criteria were identified and evaluated using the AAOS-Appropriate Use Criteria (AUC) application for supracondylar humerus fractures. Actual treatment was then compared with the treatment recommended by the AUC. RESULTS: Actual operative management was undertaken in 0/58 (0%) Gartland type I fractures, 61/108 (56.5%) type II fractures and 98/135 (72.6%) type III fractures. Actual nonoperative management was undertaken in 58/58 (100%) Gartland type I fractures, 47/108 (43.5%) type II fractures and 37/135 (27.4%) type III fractures. Surgeon decisions for nonoperative treatment were in agreement with the AUC recommendations 100% of the time, whereas surgeon decisions for surgery matched the AUC recommendations 65.4% of the time. Predictors of actual operative management were age (p =0.003), fracture classification (p =0.000), associated orthopaedic injury requiring surgery (p =0.025) and anterior humeral line (AHL) not intersecting the capitellum (p =0.008). CONCLUSION: We found low agreement between actual treatments and the AUC-recommended 'appropriate' treatments. The AUC favoured operative intervention more frequently largely on the basis of fracture classification while we emphasized age, fracture classification, associated orthopaedic injury requiring surgery and alignment of the AHL with the capitellum in our operative decision-making process. LEVEL OF EVIDENCE: Therapeutic Level II.

Chondrosarcoma in a paediatric population: a study of 247 cases.

PURPOSE: The aims of present study are to clarify the follow questions: 1) what constitutes paediatric chondrosarcoma?; 2) what are the effects of the demographic and tumour characteristics on survival in patients with paediatric chondrosarcoma?; 3) which prognostic factors of paediatric chondrosarcoma differ from those of the adult population, which have been reported previously? METHODS: Paediatric patients who were diagnosed with chondrosarcoma were searched for using the case listing session protocol of the National Cancer Institute's Surveillance, Epidemiology, and End Results 18 databases (1973 to 2014). The extracted demographic information includes: age, race, gender, year of diagnosis, tumour sites, tumour histological subtype, grade, stage and treatment. RESULTS: A total of 247 paediatric chondrosarcoma patients were extracted and included in our present study. We find that the paediatric patients have significantly better survival rates than the adult patients. The year of diagnosis, tumour sites, tumour histological subtype, grade, stage and surgery received are independent prognostic factors for the survival rate of paediatric chondrosarcoma patients, but race, gender and age are not. CONCLUSION: The paediatric chondrosarcoma patients have better survival rates than the adults. Paediatric patients with a diagnosis at an early age, tumour site at the vertebral column and pelvis/sacrococcyx, myxoid variants, high grade, distant stage and who did not have surgery have a poorer prognosis than patients with a diagnosis at a later age, tumour site at limbs, head and base, chondrosarcoma not otherwise specified, lower grade, localized stage and who received surgery. LEVEL OF EVIDENCE: II -Prognostic Study.

Polymorphisms in the androgen receptor CAG repeat sequence are related to tumour stage but not to ERG or androgen receptor expression in Malaysian men with prostate cancer.

INTRODUCTION: Polymorphic expression of a CAG repeat sequence in the androgen receptor (AR) gene may influence the activity of the AR and the occurrence of prostate cancer and the TMPRSS2-ERG fusion event. Furthermore, this polymorphism may be responsible for the ethnic variation observed in prostate cancer occurrence and expression of the ERG oncogene. We investigate the expression of AR and ERG in the biopsies of Malaysian men with prostate cancer and in the same patients relate this to the length of the CAG repeat sequence in their AR gene. MATERIALS AND METHODS: From a PSA screening initiative, 161 men were shown to have elevated PSA levels in their blood and underwent prostatic tissue biopsy. DNA was extracted from the blood, and exon 1 of the AR gene amplified by PCR and sequenced. The number of CAG repeat sequences were counted and compared to the immunohistochemical expression of ERG and AR in the matched tumour biopsies. RESULTS: Of men with elevated PSA, 89 were diagnosed with prostate cancer, and 72 with benign prostatic hyperplasia (BPH). There was no significant difference in the length of the CAG repeat in men with prostate cancer and BPH. The CAG repeat length was not associated with; age, PSA or tumour grade, though a longer CAG repeat was associated with tumour stage. ERG and AR were expressed in 36% and 86% of the cancers, respectively. There was no significant association between CAG repeat length and ERG or AR expression. However, there was a significant inverse relationship between ERG and AR expression. In addition, a significantly great proportion of Indian men had ERG positive tumours, compared to men of Malay or Chinese descent. CONCLUSIONS: CAG repeat length is not associated with prostate cancer or expression of ERG or AR. However, ERG appears to be more common in the prostate cancers of Malaysian Indian men than in the prostate cancers of other Malaysian ethnicities and its expression in this study was inversely related to AR expression.

[Current status of national free antiretroviral therapy in interprovincial migrating people living with HIV/AIDS and influencing factors, China, 2011-2015].

Objective: To understand the current status of national free antiretroviral therapy in interprovincial migrating people living with HIV/AIDS (PLWHA) and influencing factors in China. Methods: Descriptive and trend test analyses were performed to evaluate the historical characteristics and trends of main descriptive indicators on national free antiretroviral therapy for the interprovincial migrating PLWHA by using the data collected from National Comprehensive HIV/AIDS Information System from 2011 to 2015. Logistic regression model was used to explore the main factors that influencing the coverage of national free antiretroviral therapy among the interprovincial migrating PLWHA in China. Results: The proportion of interprovincial migrating PLWHA gradually increased in last 5 years from 7.1% (17 784/250 645) in 2011 to 10.3% (54 596/528 226) in 2015 (Z=51.38, P<0.000 1) in China. The coverage rate of free antiretroviral therapy in interprovincial migrating PLWHA increased from 37.3% (6 641/17 784) in 2011 to 71.0% (38 783/54 596) in 2015, showing a significant rising tendency (Z=96.23, P<0.000 1), but it was slightly lower than that in non-interprovincial migrating PLWHA in 2015 (71.5%, 338 654/473 630). Multivariate logistic regression analysis showed that the PLWHA who were females, aged ≥50 years, of Han ethnic group, married or had spouse, had the educational level of high school or above, infected through homosexual intercourse, with CD(4)(+)T cells counts ≤500 cells/µl at the first visit, identified to be infected with HIV in medical setting, living in urban areas et al, were more likely to receive free antiretroviral therapy. Conclusions: The coverage rate of free antiretroviral therapy varied among the interprovincial migrating PLWHA with different characteristics. It is still necessary to take effective measures to further increase the coverage of free antiretroviral therapy in interprovincial migrating PLWHA and to include the free antiretroviral therapy in interprovincial migrating PLWHA into standardized management system as soon as possible.

[Effects of arnebia root oil on wound healing of rats with full-thickness skin defect and the related mechanism].

Objective: To observe the effects of arnebia root oil on wound healing of rats with full-thickness skin defect, and to explore the related mechanism. Methods: Eighty SD rats were divided into arnebia root oil group and control group according to the random number table, with 40 rats in each group, then full-thickness skin wounds with area of 3 cm×3 cm were inflicted on the back of each rat. Wounds of rats in arnebia root oil group and control group were treated with sterile medical gauze and bandage package infiltrated with arnebia root oil gauze or Vaseline gauze, respectively, with dressing change of once every two days. On post injury day (PID) 3, 7, 14, and 21, 10 rats in each group were sacrificed respectively for general observation and calculation of wound healing rate. The tissue samples of unhealed wound were collected for observation of histomorphological change with HE staining, observation of expressions of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) with immunohistochemical staining, and determination of mRNA expressions of VEGF and bFGF with real time fluorescent quantitive reverse transcription polymerase chain reaction. Data were processed with analysis of variance of factorial design, t test, and Bonferroni correction. Results: (1) On PID 3, there were a few secretions in wounds of rats in the two groups. On PID 7, there were fewer secretions and more granulation tissue in wounds of rats in arnebia root oil group, while there were more secretions and less granulation tissue in wounds of rats in control group. On PID 14, most of the wounds of rats in arnebia root oil group were healed and there was much red granulation tissue in unhealed wounds, while part of wounds of rats in control group was healed and there were a few secretions and less granulation tissue in unhealed wounds. On PID 21, wounds of rats in arnebia root oil group were basically healed, while there were still some unhealed wounds of rats in control group. (2) On PID 3 and 7, the wound healing rates of rats in arnebia root oil group were (39±5)% and (46±4)% respectively, which were close to (34±3)% and (44±4)% of rats in control group (with t values respectively 0.807 and 0.481, P values above 0.05). On PID 14 and 21, the wound healing rates of rats in arnebia root oil group were (76±4)% and (90±3)% respectively, which were significantly higher than (60±6)% and (73±5)% of rats in control group (with t values respectively 2.308 and 3.072, P<0.05 or P<0.01). (3) On PID 3, 7, and 14, granulation tissue, fibroblasts, and nascent capillaries in unhealed wound tissue of rats in the two groups both gradually increased, and more ranulation tissue, fibroblasts, and nascent capillaries were seen in unhealed wound tissue of rats in arnebia root oil group. On PID 21, granulation tissue, fibroblasts, and nascent capillaries in unhealed wound tissue of rats in the two groups both gradually decreased. (4) On PID 3, 7, and 14, the numbers of VEGF positive cells and bFGF positive cells in unhealed wound tissue of rats in the two groups both gradually increased; there were more VEGF positive cells and bFGF positive cells in unhealed wound tissue of rats in arnebia root oil group than those in control group. On PID 21, positive expressions of VEGF and bFGF both decreased in unhealed wound tissue of rats in the two groups. (5) On PID 3, 7, and 14, mRNA expressions of VEGF in unhealed wound tissue of rats in arnebia root oil group were higher than those of control group (with t values from 2.967 to 4.173, P values below 0.01). On PID 21, mRNA expression of VEGF in unhealed wound tissue of rats in arnebia root oil group was lower than that of control group (t=-4.786, P<0.001). From PID 3 to 21, mRNA expressions of bFGF in unhealed wound tissue of rats in arnebia root oil group were higher than those of control group (with t values from 2.326 to 4.702, P<0.05 or P<0.01). Conclusions: Arnebia root oil can promote wound healing of rats with full-thickness skin defect, which may relate to increasing expressions of VEGF and bFGF.

[Fine needle aspiration cytology of thyroid nodules: a cytopathologic study of 2 043 cases].

OBJECTIVE: To evaluate the clinical value of thyroid fine needle aspiration cytology(FNAC) and the Bethesda system for reporting thyroid cytopathology(TBSRTC). METHODS: FNAC was performed for 2 043 cases and cytopathological data were retrospectively analyzed. Cytopathological diagnoses according to TBSRTC were classified as non-diagnostic, benign, atypia of undetermined significance/follicular lesion of undetermined significance(AUS/FLUS), follicular neoplasm/suspicious for follicular neoplasm(FN/SFN), suspicious for malignancy(SM) and malignancy. The results of 234 FNAC samples in which surgery was performed were compared with the histological diagnoses. RESULTS: Of the 2 043 FNAC samples, 15.7%(320/2 043)were non-diagnostic, 51.2%(1 047/2 043)were benign, 16.6%(339/2 043) were AUS/FLUS, 2.3%(46/2 043)were FN/SFN, 8.6%(176/2 043)were SM and 5.6%(115/2 043)were malignant. In 234 cases, there was follow-up histology. Rates of malignancy were as follows: non-diagnostic, 18.2%(2/11); benign(2.2%, 1/45); AUS/FLUS(25.6%, 10/29); FN/SFN(12.1%, 10/39); SM(91.8%, 56/61); malignant(100.0%, 45/45). The sensitivity, specificity, false positive rate, false negative rate and overall accuracy of FNAC in the diagnosis of thyroid nodules was 87.1%(101/116), 95.3%(102/107), 4.7%(5/107), 12.9%(15/116), 91.0%(203/223). CONCLUSIONS: FNAC is a reliable diagnostic method for evaluation of thyroid disease. TBSRTC is a accurate and effective reporting system for cytopathological diagnoses, so it is worthy of being widely popularized in clinical application.

Microinjection of salusin-beta into the nucleus tractus solitarii inhibits cardiovascular function by suppressing presympathetic neurons in rostral ventrolateral medulla in rats.

Salusin-beta is newly identified bioactive peptide of 20 amino acids, which is widely distributed in hematopoietic system, endocrine system, and the central nervous system (CNS). Although salusin-beta extensively expressed in the CNS, the central cardiovascular functions of salusin-beta are unclear. Our main objective was to determine the cardiovascular effect of microinjection of salusin-beta into the nucleus tractus solitarii (NTS) in anesthetized rats. Bilateral or unilateral microinjection of salusin-beta (0.94-94 microg/rat) into the NTS dose-dependently decreased blood pressure and heart rate. Bilateral NTS microinjection of salusin-beta (9.4 microg/rat) did not alter baroreflex sensitivity. Prior application of the glutamate receptor antagonist kynurenic acid (0.19 microg/rat, n=9) into the NTS did not alter the salusin-beta (9.4 microg/rat) induced hypotension and bradycardia. However, pretreatment with the GABA receptor agonist muscimol (0.5 ng/rat) within the rostral ventrolateral medulla (RVLM) completely abolished the hypotension (-14+/-5 vs. -3+/-5 mm Hg, P<0.05) and bradycardia (-22+/-6 vs. -6+/-5 bpm, P<0.05) evoked by intra-NTS salusin-beta (9.4 microg/rat). In addition, we found that vagotomy didn't influence the actions of salusin-beta (9.4 microg/rat) in the NTS. In conclusion, our present study shows that microinjection of salusin-beta into the NTS significantly produces hypotension and bradycardia, presumably by suppressing the activities of presympathetic neurons in the RVLM.

Involvement of two distinct signalling pathways in IGF-1-mediated central control of hypotensive effects in normotensive and hypertensive rats.

AIMS: Insulin-like growth factor-1 (IGF-1) is abundantly expressed in the nucleus tractus solitarii (NTS). In a previous study, we revealed that the induction of nitric oxide (NO) production in the NTS reduces blood pressure (BP). It is well known that both acute administration and chronic administration of IGF-I reduce BP. The aim of this study was to evaluate the short-term hypotensive effect of IGF-1 in the NTS and to delineate the underlying molecular mechanisms of IGF-1 in the NTS of normotensive WKY rats and spontaneously hypertensive rats (SHRs). METHOD: Microinjections of the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and the MAP kinase-ERK kinase (MEK) inhibitor PD98059 into the NTS in WKY rats and SHRs were used to study the involvement of IGF-1-induced depressor effects. RESULT: An IGF-1 (7.7 pmol) injection into the NTS resulted in a significant decrease in BP and HR in WKY rats and SHRs. Immunoblotting and immunohistochemical analysis showed that the microinjection of LY294002 (0.6 pmol) or PD98059 (3.0 pmol) into the NTS attenuated the IGF-1-induced depressor effects and Akt or ERK phosphorylation in WKY rats. An attenuation effect of LY294002, but not PD98059, was found in the SHRs. However, the mRNA and protein expression levels of the IGF-1R showed no significant differences in the NTS of the WKY rats and the SHRs. CONCLUSION: These results suggest that distinct Akt and ERK signalling pathways mediated the IGF-1 control of the central depressor effects in WKY rats and SHRs. ERK signalling defects may be associated with the development of hypertension.

AR3 messenger ribonucleic acid expression and its functional implication in human primary testicular failure.

AR3, a major one of androgen receptor (AR) splice variants, has been shown to play a pivotal role in concert with AR signalling in prostate cancer. The present study was undertaken to characterise the expression pattern of AR3 in normal and impaired spermatogenesis. Expression of AR3 mRNA showed significantly lower level in testicular tissues with impaired spermatogenesis when compared to normal tissues. This aberrant expression profile of AR3 in human pathological testes was further confirmed by immunoblotting analysis. Moreover, in situ hybridisation studies revealed that the transcripts of the gene were dominantly localised in the pachytene spermatocytes and round spermatids, suggesting a potential involvement of this transcriptional regulator in the auto-/paracrine regulation of meiotic and post-meiotic differentiation. This hypothesis was strengthened by the observation that AR3 mRNA expression was positively correlated to average seminiferous tubule score and was negatively correlated to serum FSH level. To the best of our knowledge, such a distinct expression profile of AR3 has not been reported previously in human testis. Overall, our data are suggestive of a novel site of action of AR3 during human spermatogenesis and should shed light on the complicated circuit composed of AR and its splice variants.

Genetic variants on 17q21 are associated with asthma in a Han Chinese population.

A genome-wide study has shown an association between SNPs located on 17q21 and asthma. Such associations have been identified in several populations, but little is known about the Han Chinese population. We conducted a case-control study in a Han Chinese population to investigate the relationship between SNPs located on 17q21 and asthma; 241 asthmatic patients and 212 healthy controls were recruited from the outpatient clinics of the Nanfang Hospital, Guangdong Province, southern China. We genotyped six SNPs (rs8067378, rs8069176, rs2305480, rs4795400, rs12603332, and rs11650680) located on 17q21 with the Sequenom MassARRAY iPLEX platform. For two of these six loci (rs2305480 and rs8067378), there was evidence of association with asthma, and there was a weak association of asthma with rs8069176. We confirm that genetic variants on 17q21 are associated with asthma in the Han Chinese population.

Malignant phyllodes tumor of the prostate.

This is a report of a 70-year-old man with malignant phyllodes tumor of prostate. The retropubic prostatectomy was done. The stroma of the tumor was cellular and composed of elongated cells with spindle shaped nuclei and fragmented bizarre giant cells. After recovery from surgery, prophylatic radiotherapy was given over 2 months. A case report of a patient treated at our medical center and a review of the literature was done.

Modulation of I(Kr) inactivation by mutation N588K in KCNH2: a link to arrhythmogenesis in short QT syndrome.

OBJECTIVE: Short QT syndrome (SQTS) is characterized by ventricular arrhythmias and sudden death. One form of SQTS is caused by mutation N588K in human ether-a-go-go-related gene (HERG). In this study we sought to determine the potential role of N588K in arrhythmias. METHODS: We measured the characteristics of HERG current generated by wild-type (WT) KCNH2 and the N588K mutant channel expressed in mammalian TSA201 cells. RESULTS: Whole-cell patch-clamp recordings of WT HERG currents showed the usual rapid onset of inactivation (rectification) at potentials more positive than +10 mV. In contrast, N588K currents rectified at potentials over +80 mV. Over the physiological range of potentials, N588K currents do not inactivate. During an action potential clamp, WT currents displayed a "hump" like waveform with slow activation kinetics and a rapid increase during phase 3 repolarization. In contrast, N588K currents were proportional to the amplitude of the action potential and displayed a dome-like configuration and a much larger current during the initial phases in the ventricle. Purkinje cell action potentials display a more negative phase 2 repolarization than the ventricle and elicited much smaller WT and N588K currents of similar amplitudes. CONCLUSIONS: Physiologically the N588K mutation abolishes rectification of HERG currents and specifically increases I(Kr) in the ventricle with minimal effects on the Purkinje fiber action potential duration. Such preferential prolongation may explain the separation of the T and U waves observed in the ECG of SQTS patients and lead to re-excitation of the ventricle endocardium.

Humoral immune responses of the grouper Epinephelus akaara against the microsporidium Glugea epinephelusis.

The humoral immune responses of grouper Epinephelus akaara to a natural infection with Glugea epinephelusis was studied by ELISA utilizing intact mature spores as the coated antigen. Results showed that a specific humoral immune response was elicited, but the intensity of infection (in terms of the number of cysts) was not related to the antibody level in naturally infected hosts. The differences in the antigenicity of intact mature spores and soluble spore proteins derived from cracked mature spores were also analyzed. Results suggested that similar antigen epitopes existed between the 2 groups. Additionally, antigen component patterns and the distribution of antigen with immunogenicity were investigated by using the western blot and the immunofluorescent antibody technique (IFAT). The new parasitic microsporidium has specific polypeptide patterns comparable to the reported fish microsporidians. The main antigenic substances are concentrated on the surface of spores, and are mostly located on the anterior and posterior end of the spore bodies. Most surface components of the G. epinephelusis spores are soluble. The potential role of the surface components in initiating infection was also discussed.

Contribution of neuronal sodium channels to the cardiac fast sodium current INa is greater in dog heart Purkinje fibers than in ventricles.

OBJECTIVE: To determine the presence and the potential contribution of neuronal sodium channels to dog cardiac function. METHODS: We used a combination of electrophysiological (patch clamp), RT-PCR, biochemical and immunohistochemical techniques to identify and localize neuronal Na(+) channels in dog heart and determine their potential contribution to the fast sodium current. RESULTS: In all cardiac tissues investigated, Na(v)1.1, Na(v)1.2 and Na(v)1.3 transcripts were detected. In immunoblots, we found Na(v)1.1 and Na(v)1.2 proteins in the ventricle (V) and in Purkinje fibers (PF). Na(v)1.3 immunoblots suggested strong proteolytic activity against this isoform in the heart. Na(v)1.6 was not found in any of the tissues tested. Confocal immunofluorescence on cardiac myocytes showed that Na(v)1.1 was predominantly localized at the intercalated disks in V and PF and around the nucleus (V). Na(v)1.2 was only present at the Z lines (V). Consistent with the immunoblot data, an intense but diffuse intracellular staining was observed for Na(v)1.3. Na(v)1.6 fluorescence staining was faint and diffuse. Surprisingly, immunoblots indicated the presence of two Na(v)beta 2 variants: a 42-kDa protein that co-localized with Na(v)1.2 at the Z lines in V and a 34-kDa protein that co-localized with Na(v)1.1 at the intercalated disks in PF. In agreement with the biochemical data, electrophysiological results suggest that neuronal sodium channels generate 10+/-5% and 22+/-5% of the peak sodium current in dog ventricle and Purkinje fibers, respectively. CONCLUSIONS: Our results suggest that neuronal NaChs are more abundant in Purkinje fibers than in ventricles, and this suggests a role for them in cardiac conduction.