Effects of Liver-Regulating Herb Compounds on Varicocele-Associated Testicular Dysfunction Through Restoring Hormones and Spermatocytes Apoptosis.

PURPOSE: Varicocele is considered one of the causes of male infertility. Though varicocelectomy is supposed to improve semen parameters in adult infertile men, some patients with varicocele were still infertile after varicocelectomy. Previous studies showed Traditional Chinese Medicine, Liver-regulating herb compounds (LRHC) could improve the semen quality and increase fertility rates of infertile patients with varicocele. This study aimed to throw light on the mechanism of LRHC on varicocele-associated infertility. MATERIALS AND METHODS: Rats with varicocele-induced were treated with LRHC at dosage of 1mL/100g by intragastric administration for 90 days. The effects of LRHC on hormones and spermatocytes apoptosis were examined using ELISA assay, Western blotting, and flow cytometry. RESULTS: Rats induced with varicocele showed a higher level of follicle stimulating hormone (FSH) in serum, which was brought back to normal level by LRHC. After treatment with LRHC, both testicular tissue in vivo and Sertoli cell TM4 cells in vitro showed elevated expressions of FSHR. Cell viabilities of TM4 cells and spermatocyte GC-2 cells were improved by LRHC treatment under normoxia and hypoxia conditions. Moreover, LRHC protected GC-2 cells from apoptosis induced by hypoxia. The expression of Bax reduced, while that of Bcl-2 increased after treatment with LRHC. CONCLUSION: This study revealed that LRHC had protective effects on spermatogenic disturbance caused by varicocele through regulating hormones and reducing spermatogenic cell apoptosis under hpoxia conditions.

Fecal Microbiota Transplantation May Represent a Good Approach for Patients with Focal Segmental Glomerulosclerosis: A Brief Report.

This is the first report of fecal microbiota transplantation (FMT) in patients with chronic kidney disease. The patient was subjected to focal segmental glomerulosclerosis (FSGS), with onset in April 2021. The main manifestation featured abnormal renal function and no proteinuria at the level of nephrotic syndrome. In May 2021, she showed biopsy-proven FSGS and was treated with glucocorticoid. However, after glucocorticoid reduction, the patient's serum creatinine increased again, so she adjusted the dosage and continued use until now. In April 2022, the patient was prescribed the FMT capsules. After FMT, the renal function remained stable, urinary protein decreased, reaching the clinical standard of complete remission, and there was no recurrence after glucocorticoid reduction. Furthermore, the patient showed significantly decreased hyperlipidemia, triglyceride (TG) and cholesterol (CHO) after FMT. During FMT, the level of cytokines fluctuated slightly, but returned to the pre-transplantation level after three months. From this, we conclude that FMT is a potential adjuvant therapy for FSGS, and patients can benefit from improving renal function and dyslipidemia.

Symptomatic Complete Discoid Medial Meniscus Completely Coalesced with the Anterior Cruciate Ligament: A Case Report and Literature Review.

BACKGROUND: Complete discoid medial meniscus is an extremely rare abnormality of the knee joint whose meniscus has a discoid shape rather than a normal semilunar one. Several medial meniscus anomalies including anomalous insertion have been reported in the literature. This report presents a rare case of symptomatic complete discoid medial meniscus whose anterolateral (apical) portion was completely coalesced with the ACL. MRI, radiographic, and arthroscopic findings in the medial compartment are to be submitted. CASE PRESENTATION: A 29-year-old male presented with intermittent pain and swelling of the right knee for 2 years. Based on radiographic, MRI, and physical examination findings, he was diagnosed with discoid medial meniscus tears. Arthroscopic saucerization was performed for the torn discoid medial meniscus of the right knee. Arthroscopic examination revealed a complete discoid medial meniscus and the anterolateral (apical) portion of which was completely coalesced with the ACL. Careful Probing of the meniscal surface revealed there was a longitudinal tear extending from the tibial spine to the midportion of the meniscus. Arthroscopic saucerization of the discoid meniscus was performed after closely cutting the meniscus around the ACL. The patient reported no symptoms, and he had returned to his daily and sports activities, including football, basketball, and jogging, at the 12-month follow-up. CONCLUSION: Complete discoid medial meniscus is an extremely rare abnormality, and this case presents the third complete discoid medial meniscus whose anterolateral (apical) portion was completely coalesced with the ACL. The current case we present strongly supports the hypothesis that ACL and meniscus were differentiated from the same mesenchyme.

Effects of HIF-1α on Spermatogenesis of Varicocele Rats by Regulating VEGF/PI3K/Akt Signaling Pathway.

Hypoxia-inducible factor-1α (HIF-1α) participates in the regulation of spermatogenic function in rats with varicocele (VC), and the PI3K/Akt pathway plays an important role in it. In the present research, we applied the CRISPR/Cas9 gene editing technique to silence the HIF-1α gene of VC rat testis, to explore the effect of HIF-1α on apoptosis of spermatogenic cells in VC rats through the PI3K/Akt pathway. Sprague Dawley rats were randomly assigned to four groups, including the normal rat group (group N), VC model group (group V), VC + HIF-1α-lentivirus group (group H), and VC + luciferase-lentivirus group (group L). Apoptosis of spermatogenic cells in rat testis was tested by TUNEL Kit. The morphologic changes of seminiferous tubules were viewed by a light microscope. Expressions of VEGF, Akt, p-Akt, p70S6K, and p-p70S6K were detected by means of Western blot, immunofluorescence, or immunohistochemistry methods. One-way ANOVA was applied to analyze the diverseness between groups. Compared with group N, the distribution of germ cells was disordered, apoptosis of spermatogenic cells increased significantly, and the expression of VEGF, p-Akt, and p-p70S6K was also increased in group V. Compared with group V, the damage of seminiferous epithelium in group H was improved, and the arrangement of the seminiferous epithelium was almost orderly. Apoptosis of spermatogenic cells decreased significantly, and the expression of VEGF, p-Akt, and p-p70S6K protein was decreased (P < 0.05). There was no significant difference between group N and group H (P > 0.05).In conclusion, HIF-1α is regulated by hypoxia in rats with varicocele to regulate its downstream gene VEGF which regulates spermatogenesis, and the PI3K/Akt signaling pathway plays a regulatory role in this process.

Effects of liver-regulating herb compounds on testicular morphological and ultrastructural changes in varicocele rats through SCF/C-KIT pathway.

Liver-regulating herb compound (LRHC) has good effects on improving sperm quality and male fertility of varicocele (VC) patients. But the mechanism of LRHC on VC is still not clear. This study explored the effects of LRHC on histomorphological and ultrastructural changes and expression of stem cell factor (SCF) and C-KIT of VC rat testis. Twenty-four male rats were divided into three groups with eight rats in each group as sham, varicocele and LRHC groups. Testis specimens were collected for light microscopy and transmission electron microscopy respectively. The expression of SCF/C-KIT was detected with Western blot. Results showed that seminiferous tubules in VC rats were damaged and cell numbers were decreased. Ultrastructural alterations were observed, such as increased thickness of lamina propria, vacuolation in Sertoli cells, spermatocytes and spermatids, and abnormal head and mitochondria in spermatozoa. While in LRHC-treated rats, the architectures of seminiferous tubules were as organised and compact as that of sham animals, and ultrastructure of Sertoli, Leydig and germ cells developed well. LRHC ameliorated histological appearance and ultrastructure by VC. In addition, the abnormal expression of SCF and C-KIT were observed in testicular tissues from rats with VC, which were brought back to normal level by LRHC.

Elevated Expression of NOTCH1 Associates with Lymph Node Metastasis of Gastric Cancer and Knock-Down of NOTCH1 Attenuates Tumor Cell Progression.

BACKGROUND Gastric cancer is the third leading cause of cancer-related death, while its molecular mechanism has not been fully clarified. This study aims to explore the role of Notch signaling in the pathogenesis of gastric cancer. MATERIAL AND METHODS A total of 64 patients with gastric cancer were enrolled. The expressions of NOTCH1 in tumor tissues and adjacent non-tumor tissues were detected by immunohistochemistry staining. The correlation between NOTCH1 expression and clinicopathological features of patients was analyzed. NOTCH1 was knocked down in gastric cancer cells. The effects of NOTCH1 blockade on cell proliferation, migration and cell cycle distribution were analyzed. The expressions of ERK1/2 and phospho-ERK1/2 (p-ERK1/2) were detected using western blotting. RESULTS Gastric cancer tissues expressed higher level of NOTCH1 than adjacent non-tumor tissues (P<0.05). The high level of NOTCH1 was found to be correlated with gender (male) and lymph node metastasis. However, the expression level of NOTCH1 did not affect the overall survival of patients with gastric cancer. NOTCH1 knock-down repressed the migration and proliferation of gastric cancer cells. Moreover, the cell cycle was arrested at G0/G1 phase by NOTCH1 blockade. The expressions of ERK1/2 and p-ERK1/2 decreased with NOTCH1 knock-down. Further inhibition of ERK1/2 signaling by a MEK1/2 inhibitor U0126 reduced the proliferation of AGS cells, which aggravated the inhibition effect of NOTCH1 knock-down on cell proliferation. CONCLUSIONS NOTCH1 may play an oncogenic role in gastric cancer. Inhibition of NOTCH1 can efficiently attenuate gastric cancer cell progression, probably in part through cross-talking with ERK1/2 signaling pathway.

Effect of silencing HIF-1α gene on testicle spermatogenesis function in varicocele rats.

This study uses the CRISPR/Cas9 gene editing technique to silence the expression of hypoxia-inducible factor-1α (HIF-1α) gene and investigate its effect on testicle spermatogenesis function in varicocele (VC) rats. Sprague Dawley rats were divided into four groups; the control, VC model, VC+HIF-1α-lentivirus and VC+Luciferase-lentivirus group. The sperm count and survival rate were analyzed using computer-aided sperm analysis. The morphological changes of seminiferous tubules were observed by a microscope. Expressions of HIF-1α, Bax, cleaved caspase-3 and Bcl-2 were detected via Western blot, immunofluorescence and real-time polymerase chain reaction methods. One-way ANOVA was used to analyze the differences between groups. The sperm count and survival rate were significantly lower (p < 0.05) and the seminiferous epithelium was more disordered in the VC group than that in the control group. The expression of Bax and cleaved caspase-3 were increased and Bcl-2 was reduced in the VC group than the control group. Compared with the VC group, sperm count and survival rate noticeably increased (p < 0.05), seminiferous epithelium was inordered arrangement and fewer spermatogenic cells were injured in the VC+HIF-1α-lentivirus group. Expression of Bax and cleaved caspase-3 were decreased significantly in the VC+HIF-1α-lentivirus group compared with the VC group and VC+Luciferase-lentivirus group (p < 0.05), whereas the expression of Bcl-2 was increased (p < 0.05). No significant difference was observed between the control group and the VC+HIF-1α-lentivirus group (p > 0.05). Results show that the apoptosis of spermatogenic cells was decreased and the testicle spermatogenesis function was significantly improved after silencing HIF-1α gene in testis of VC rats. HIF-1α may play a crucial role during spermatogenesis in VC inducing male infertility.

Graft choice for anatomic anterior cruciate ligament reconstruction: The comparison between thin autograft and thick hybrid graft. An observational study.

Great controversy over the graft choice has been lasted now. This study compared the second-look evaluation and clinical outcomes of anatomic anterior cruciate ligament reconstruction (ACL-R) using a thin autograft versus a thick hybrid graft.Seventy-six patients with complete follow-up data were categorized into the autograft group (N = 34) and hybrid group (N = 42). The Lysholm score, Tegner activity level, International Knee Documentation Committee (IKDC) Knee Evaluation Form, and KT-1000 test were performed before and at follow-up. Results were compared, and further comparisons were made for grafts thicker than 8.5 mm.The hybrid graft was thicker than the autograft (9.10 ±â€Š0.52 vs 8.57 ±â€Š0.48 mm, P < .001). The KT-1000 test, subjective evaluation, and activity level scores increased significantly between pre- and postoperation for all patients (P < .001). No significant differences were, however, found between the 2 groups. Only grafts thicker than 8.5 mm were selected from the autograft (N = 14) and hybrid (N = 34) groups, the Lysholm, IKDC, and KT-1000 test scores were significantly superior for the autograft than the hybrid graft (P = .021, P = .005, and P = .024, respectively).For anatomic ACL-R, a pure autograft is superior to a hybrid graft of the same diameter. The purity of the autograft was more important than the size, and augmenting allografts may be unnecessary.

The adaptive change of patellofemoral joint after arthroscopic discoid lateral meniscus plasty: An observational study.

The purpose of this study was to investigate the patellofemoral joint adaptive changes after discoid lateral meniscus (DLM) plasty.Forty-one patients with unilateral complete type DLM tears were included in this study. Demographic variables, including gender, age, body mass index (BMI), injury to operation interval, type of injury, and follow-up time, were recorded. The evolution of physical examination, imaging index, and functional score were analyzed by Chi-squared test, Wilcoxon signed ranks test, and Friedman test. Mann-Whitney test was used to analyze the difference at different time points between group PFI > 1.6 and PFI < 1.6.After the patients received arthroscopic DLM plasty, the positive rate of Patella grinding test increased from 19.5% to 29.3%, and it showed significant increased at last follow-up time point (48.8%) (P = .005). Mechanical axis deviation (MAD) significant decreased from -0.7 ±â€Š2.1 mm to -9.4 ±â€Š3.2 mm (P < .001). Lateral patellofemoral angle (LPFA) and lateral shift distance (LSD), respectively, decreased from 11.9 ±â€Š5.8° and 1.0 ±â€Š4.0 mm to 7.2 ±â€Š4.5° and -0.5 ±â€Š3.3 mm (P < .001). Patellofemoral index (PFI) increased from 1.7 ±â€Š0.3 to 1.9 ±â€Š0.4 (P < .001). Kujala score and Lysholm score, respectively, increased from 65.9 ±â€Š10.0 and 85.2 ±â€Š6.4 mm to 61.8 ±â€Š10.2 and 89.5 ±â€Š5.0 (P < .001). Only LSD in group > 1.6 were significant lower than those in group < 1.6 (>1.6: -1.5 ±â€Š2.8, -1.6 ±â€Š2.7, -1.5 ±â€Š2.6; <1.6: 0.8 ±â€Š3.4, 0.4 ±â€Š3.6, 0.6 ±â€Š2.8. P = .010,.038,.011) at the 3 postoperative follow-up time points.After arthroscopic plasty for complete type DLM which decreased the thickness and width of the residual meniscus, in turn causing the varus deformity significantly decreased or a valgus inclination developed. Moreover, the consequent changes of patellofemoral joint caused a certain amount of patellar tilt and patellar dislocation, might aggravated the symptomatic anterolateral knee pain or the lateral patellar compression syndrome.

An anatomical-like triangular-vector ligament reconstruction for the medial collateral ligament and the posterior oblique ligament injury with single femoral tunnel: a retrospective study.

BACKGROUND: The purpose of this study was to evaluate the clinical outcomes of anatomical-like triangular-vector ligament reconstruction (TLR) in treating the combined injury of medial collateral ligament (MCL) and posterior oblique ligament (POL). METHODS: During July 2013 to May 2014, 26 patients who received anatomical-like TLR were included into this study. All patients received clinical physical examination, imaging examination, and knee joint function score both preoperative and follow-up. The stability of the medial structure of the knee joint was examined by physical examination and imaging evaluation, including excessive knee medial opening (EKMO) and tibial external rotation angle (TERA). The function of the knee was evaluated by the subjective questionnaire, including Lysholm, Tegner, and IKDC score. SPSS software was used for statistics analysis. RESULTS: The mean follow-up time exceeds 24 months. Two patients occurred with serious heterotopic ossification, and one patient received revision because of screw breakage. EKMO over the contralateral state at 0° decreased from 9.76 ± 2.76 mm to 2.79 ± 1.02 mm with statistical significance (P < .001) and 10.32 ± 2.75 mm decreased to 3.13 ± 0.85 mm at 30° (P < .001). Meanwhile, TERA significantly decreased from 53.38 ± 6.71° to 27.15 ± 4.92° (P < .001). The postoperative Lysholm, Tegner, and IKDC score were superior to preoperative with statistical significance (P < .001). CONCLUSIONS: Anatomical-like TLR can reconstruct the graft to cover the insertions which can regain anatomic form and function with a cramped space. Not only the valgus stability and rotational stability can be restored obviously at follow-up but also the usage of implantation can be reduced, decreasing the incidence rate of allergy and saving costs.

Protective effect of lutein on ARPE-19 cells upon H2O2-induced G2/M arrest.

Oxidative damage is a key factor for the pathogenesis of age­related macular degeneration (AMD), therefore, anti-oxidative stress is a valuable method for the prevention or treatment of AMD. The aim of the present study was to reveal the protective mechanism of lutein on retinal pigment epithelium (RPE) cells subjected to oxidative stress. Acute retinal pigment epithelial 19 (ARPE­19) cells were exposed to oxidative stress induced by H2O2 following lutein pretreatment. The activities of caspases, level of intracellular reactive oxygen species (ROS) and cell cycle were analyzed using flow cytometry. The expression levels of cell cycle regulatory proteins and inflammation­associated genes were detected using western blot and reverse transcription­polymerase chain reaction analyses, respectively. The data showed that oxidative stress reduced cell viability, and increased total apoptosis and ROS generation, however, lutein prevented cells from oxidative stress­induced damage. In addition, oxidative damage triggered G2/M phase arrest of the ARPE­19 cells, which was reversed by lutein in a concentration­dependent manner, through the activation of cyclin­dependent kinase 1 and cell division cycle 25C, and degradation of cyclin B1. These results demonstrated that lutein may be an effective antioxidant, which can be applied in the prevention of AMD, or other age-related diseases associated with oxidative damage.

Increased Level of c-kit in Semen of Infertile Patients with Varicocele.

PURPOSE: Varicocele is the most common risk factor for male infertility, however, not all males with varicocele experience infertility. In fact, most patients with varicocele have normal spermatogenesis. The molecular mechanism of varicocele-associated infertility is yet to be completely understood. The aim of this study is to assess the association of a number of fertility regulatory factors on varicocele associated infertility and to throw light on the mechanism of varicocele-associated infertility. MATERIALS AND METHODS: Semen from 30 infertile patients with varicocele and 30 fertile men with varicocele were collected. The concentrations of the following factors in seminal plasma were determined by ELISA: follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), androgen binding protein (ABP), transferrin (Trf), inhibin B (INHB) and stem cell factor (SCF). The expression level of c-kit in seminal precipitate of patients with varicocele was detected by real-time PCR. RESULTS: The concentrations of sexual hormones, FSH, LH and T, had no differences between infertile patients with varicocele and fertile men with varicocele (P > 0.05). Factors secreted by Sertoli cells, ABP, Trf, INHB andSCF, showed no significant differences between the two groups (P > 0.05). Interestingly, the expression of c-kit was significant higher in infertile patients with varicocele than that in fertile men with varicocele (P < 0.01). CONCLUSION: Neither the sexual hormones nor the Sertoli cells was responsible for the infertility induced by varicocele.The aberrant expression of c-kit in infertile patients with varicocele may provide new insight into the mechanism of varicocele-associated infertility.

Reduced Glutamate Release in Adult BTBR Mouse Model of Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a developmental disorder characterized by impairments in social and communication abilities, as well as by restricted and repetitive behaviors. The BTBR T + Itpr3 tf (BTBR) mice have emerged as a well characterized and widely used mouse model of a range of ASD-like phenotype, showing deficiencies in social behaviors and unusual ultrasonic vocalizations as well as increased repetitive self-grooming. However, the inherited neurobiological changes that lead to ASD-like behaviors in these mice are incompletely known and still under active investigation. The aim of this study was to further evaluate the structure and neurotransmitter release of the glutamatergic synapse in BTBR mice. C57BL/6J (B6) mice were used as a control strain because of their high level of sociability. The important results showed that the evoked glutamate release in the cerebral cortex of BTBR mice was significantly lower than in B6 mice. And the level of vesicle docking-related protein Syntaxin-1A was reduced in BTBR mice. However, no significant changes were observed in the number of glutamatergic synapse, level of synaptic proteins, density of dendritic spine and postsynaptic density between BTBR mice and B6 mice. Overall, our results suggest that abnormal vesicular glutamate activity may underlie the ASD relevant pathology in the BTBR mice.

Inhibition of IL-6 trans-signaling in the brain increases sociability in the BTBR mouse model of autism.

Autism is a severe neurodevelopmental disorder with a large population prevalence, characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests. The BTBR T(+)Itpr3(tf) (BTBR) mice have emerged as strong candidates to serve as models of a range of autism-relevant behaviors. Increasing evidences suggest that interleukin (IL)-6, one of the most important neuroimmune factors, was involved in the pathophysiology of autism. It is of great importance to further investigate whether therapeutic interventions in autism can be achieved through the manipulation of IL-6. Our previous studies showed that IL-6 elevation in the brain could mediate autistic-like behaviors, possibly through the imbalances of neural circuitry and impairments of synaptic plasticity. In this study, we evaluate whether inhibiting IL-6 signaling in the brain is sufficient to modulate the autism-like behaviors on the BTBR mice. The results showed that chronic infusion of an analog of the endogenous IL-6 trans-signaling blocker sgp130Fc protein increased the sociability in BTBR mice. Furthermore, no change was observed in the number of excitatory synapse, level of synaptic proteins, density of dentitic spine and postsynaptic density in BTBR cortices after inhibiting IL-6 trans-signaling. However, inhibition of IL-6 trans-signaling increased the evoked glutamate release in synaptoneurosomes from the cerebral cortex of BTBR mice. Our findings suggest that inhibition of excessive production of IL-6 may have selective therapeutic efficacy in treating abnormal social behaviors in autism.

Abnormal glutamate release in aged BTBR mouse model of autism.

Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests. Most of the available research on autism is focused on children and young adults and little is known about the pathological alternation of autism in older adults. In order to investigate the neurobiological alternation of autism in old age stage, we compared the morphology and synaptic function of excitatory synapses between the BTBR mice with low level sociability and B6 mice with high level sociability. The results revealed that the number of excitatory synapse colocalized with pre- and post-synaptic marker was not different between aged BTBR and B6 mice. The aged BTBR mice had a normal structure of dendritic spine and the expression of Shank3 protein in the brain as well as that in B6 mice. The baseline and KCl-evoked glutamate release from the cortical synaptoneurosome in aged BTBR mice was lower than that in aged B6 mice. Overall, the data indicate that there is a link between disturbances of the glutamate transmission and autism. These findings provide new evidences for the hypothesis of excitation/inhibition imbalance in autism. Further work is required to determine the cause of this putative abnormality.

Identification and characterization of novel alternative splice variants of human SAMD11.

Sterile alpha motif domain-containing 11 (SAMD11) is evolutionarily conserved from zebrafish to human. Mouse Samd11 is predominantly expressed in developing retinal photoreceptors and the adult pineal gland, and its transcription is directly regulated by the cone-rod homeodomain protein Crx. However, there has been little research on human SAMD11. To investigate the function of human SAMD11, we first cloned its coding sequence (CDS) and identified up to 45 novel alternative splice variants (ASVs). Mouse Samd11 ASVs were also identified by aligning the mouse Samd11 expressed sequence tags (ESTs) with the annotated sequence. However, the range of expression and transcriptional regulation of SAMD11 differs between human and mouse. Human SAMD11 was found to be widely expressed in many cell lines and ocular tissues and its transcription was not regulated by CRX, OTX2 or NR2E3 proteins. Furthermore, functional analysis indicated that human SAMD11 could promote cell proliferation slightly. In conclusion, this study elucidated the basic characteristics of human SAMD11 and revealed that, although the occurrence of alternative splicing of SAMD11 was conserved, the function of SAMD11 may vary in different species.

Blockage of Notch signaling inhibits the migration and proliferation of retinal pigment epithelial cells.

The Notch signaling is an evolutionarily conserved cell-cell communication pathway that plays critical roles in the proliferation, survival, apoptosis, and fate determination of mammalian cells. Retinal pigment epithelial (RPE) cells are responsible for supporting the function of the neural retina and maintaining vision. This study investigated the function of Notch signaling in RPE cells. We found that the members of the Notch signaling pathway components were differentially expressed in RPE cells. Furthermore, blockage of Notch signaling inhibited the migration and proliferation of RPE cells and reduced the expression levels of certain Notch signaling target genes, including HES1, MYC, HEY2, and SOX9. Our data reveal a critical role of Notch signaling in RPE cells, suggesting that targeting Notch signaling may provide a novel approach for the treatment of ophthalmic diseases related to RPE cells.

Abnormal expression of seven myogenesis-related genes in extraocular muscles of patients with concomitant strabismus.

Hyperplasia or hypoplasia of muscles gradually leads to strabismus. Myogenesis-related genes are involved in extraocular muscle development, including myogenic differentiation 1 (MYOD1), myogenin (MYOG), retinoblastoma 1 (RB1), cyclin-dependent kinase inhibitor 1A (P21), cyclin­dependent kinase inhibitor 1C (P57), insulin-like growth factor 1 (IGF1) and muscle creatine kinase (MCK). This study evaluated the expression of the above seven myogenesis-related genes by real-time quantitative RT-PCR in 18 resected extrocular muscles of patients with concomitant strabismus and 12 normal control muscle samples from one presumably healthy male 6 h after sudden mortality. We found that although there was a great divergence among the expression levels of 6 myogenesis-related regulatory factors, the relative expression patterns were similar in all the normal muscles, including the synergistic, antagonistic and yoke muscles. However, their expression levels in the 18 diseased extraocular muscles were abnormal; the expression levels of all the genes, with the exception of P57, were reduced in most of the diseased muscle tissues. These results imply that the abnormal expression of these myogenesis-related genes may contribute to concomitant strabismus.

Overexpression of Six1 leads to retardation of myogenic differentiation in C2C12 myoblasts.

The Six1 homeoprotein belongs to the Six (sine oculis) transcription factor family, the members of which are known to act as master regulators of development. Six1 is essential for promoting myogenesis during mammalian somitogenesis. Previous studies have shown that Six1 participates in later steps of myogenic differentiation by enhancing early activation of myogenin via binding to the Mef3 site of the myogenin promoter. In the present study, however, we show that overexpression of Six1 via retroviral infection suppresses the expression of myogenin and myosin in C2C12 myoblasts, consequently retarding myogenic differentiation without affecting cell proliferation or expression of Mef2 and Mef3. These findings further demonstrate the functional role of Six1 in myogenesis.

[Habituation of seasickness in adult during a long voyage].

OBJECTIVE: To observe the habituation of seasickness in non marine subjects during a long voyage. METHODS: A crew of 106 staffs of the Hospital Ship Ark Peace was included in this study. There were 59 male and 47 female with an age ranged from 23 to 53 years (mean 37.2 years). They all took part in the Mission Harmony 2011 for medical service in four countries around the Caribbean Sea. Questionnaires and visual analogue scales (VAS) were used to investigate the prevalence and degree of the seasickness in different periods. RESULTS: The prevalence of seasickness was 72.64% in the initial period of voyage. The prevalence and degree of seasickness in female and in staff with motion sickness history were higher and more severe than that in male and in staff without motion sickness history(P < 0.05). After two weeks, the prevalence and degree of seasickness decreased, which meant habituation of seasickness occurred. With the voyage going longer, the prevalence and degree of seasickness were further decreased, but the severe sea condition make the prevalence and degree of seasickness worse. The rate of habituation of seasickness was 62.33%, and the habituation rate of seasickness in male (76.92%) was higher than that in female (47.37%) (χ(2) = 7.161, P = 0.007). CONCLUSIONS: The habituation of the seasickness occurred after two weeks in a long voyage. Male are easier to get habituation of seasickness than female. The severe sea condition influences the prevalence and degree of seasickness.