Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by recurrent abdominal pain or discomfort associated with abnormal bowel habits. Diarrhea-predominant IBS (IBS-D) is a major subtype of IBS, the predominant manifestations of which are abdominal pain and diarrhea. The pathogenesis of IBS-D remained unknown until recently. The effects of psychosocial stress, central hypervigilance, neuroendocrine abnormality, disturbed gastrointestinal motility, mucosal immune activation, intestinal barrier dysfunction, visceral hypersensitivity (VH), altered gut flora, and genetic susceptibility may be involved in its development. Recently, increased attention has been placed on the neural-immune-endocrine network mechanism in IBS-D, especially the role of various neuroendocrine mediators. As a member of the neurotrophin family, nerve growth factor (NGF) has diverse biological effects, and participates in the pathogenesis of many diseases. Basic studies have demonstrated that NGF is associated with inflammatory- and stress-related VH, as well as stress-related intestinal barrier dysfunction. The aim of this study is to summarize recent literature and discuss the role of NGF in the pathophysiology of IBS-D, especially in VH and intestinal barrier dysfunction, as well as its potential as a therapeutic target in IBS-D.

DNA mismatch repair (MMR) is one of the biological pathways, which plays a critical role in DNA homeostasis, primarily by repairing base-pair mismatches and insertion/deletion loops that occur during DNA replication. MMR also takes part in other metabolic pathways and regulates cell cycle arrest. Defects in MMR are associated with genomic instability, predisposition to certain types of cancers and resistance to certain therapeutic drugs. Moreover, genetic and epigenetic alterations in the MMR system demonstrate a significant relationship with human fertility and related treatments, which helps us to understand the etiology and susceptibility of human infertility. Alterations in the MMR system may also influence the health of offspring conceived by assisted reproductive technology in humans. However, further studies are needed to explore the specific mechanisms by which the MMR system may affect human infertility. This review addresses the physiological mechanisms of the MMR system and associations between alterations of the MMR system and human fertility and related treatments, and potential effects on the next generation.

Objective: To investigate male reproductive parameters via changes of potential testicular protein markers in restraint-stress rats. Methods: Male Sprague-Dawley rats were divided into two groups (non-immobilized control and restraint-immobilized/stress groups, n=8 each group). The stress animals were immobilized (12 h/d) by a restraint cage for 7 consecutive days. All reproductive parameters, morphology and histology were observed and compared between groups. In addition, the expression of steroidogenic acute regulatory (StAR) and phosphotyrosine proteins (previously localized in Sertoli and late spermatid cells) in testicular lysate was assayed by immuno-Western blotting. Results: Testosterone level, sperm concentration and sperm head normality of stress rats were significantly decreased while the corticosterone level was increased as compared with the control (P<0.05). Histologically, stress rats showed low sperm mass in epididymal lumen and some atrophy of seminiferous tubules. Although the expression of testicular StAR protein was not significantly different between groups, changed patterns of the 131, 95, and 75 kDa testicular phosphorylated proteins were observed in the stress group compared with the control group. The intensity of a testicular 95-kDa phosphorylated protein was significantly decreased in stress rats. Conclusions: This study has demonstrated the alteration of testicular phosphorylated protein patterns, associated with adverse male reproductive parameters in stress rats. It could be an explanation of some infertility in stress males.

Objective: To construct a recombinant adenovirus vector-carrying human growth and differentiation factor-5 (GDF-5) gene, investigate the biological effects of adenovirus-mediated GDF-5 (Ad-GDF-5) on extracellular matrix (ECM) expression in human degenerative disc nucleus pulposus (NP) cells, and explore a candidate gene therapy method for intervertebral disc degeneration (IDD). Methods: Human NP cells of a degenerative disc were isolated, cultured, and infected with Ad-GDF-5 using the AdEasy-1 adenovirus vector system. On Days 3, 7, 14, and 21, the contents of the sulfated glycosaminoglycan (sGAG), deoxyribonucleic acid (DNA) and hydroxyproline (Hyp), synthesis of proteoglycan and collagen II, gene expression of collagen II and aggrecan, and NP cell proliferation were assessed. Results: The adenovirus was an effective vehicle for gene delivery with prolonged expression of GDF-5. Biochemical analysis revealed increased sGAG and Hyp contents in human NP cells infected by Ad-GDF-5 whereas there was no conspicuous change in basal medium (BM) or Ad-green fluorescent protein (GFP) groups. Only cells in the Ad-GDF-5 group promoted the production of ECM, as demonstrated by the secretion of proteoglycan and up-regulation of collagen II and aggrecan at both protein and mRNA levels. The NP cell proliferation was significantly promoted. Conclusions: The data suggest that Ad-GDF-5 gene therapy is a potential treatment for IDD, which restores the functions of degenerative intervertebral disc through enhancing the ECM production of human NP cells.

Objective: Statins’ therapy in osteoporosis can aggravate muscle damage. This study was designed to assess which agent, L-carnitine or coenzyme Q10, could enhance the anti-osteoporotic effect of atorvastatin while antagonizing myopathy in ovariectomized rats. Methods: Forty-eight female Sprague Dawley rats were used; forty rats were ovariectomized while eight were sham-operated. Eight weeks post-ovariectomy, rats were divided into ovariectomized-untreated group and four ovariectomized-treated groups (n=8) which received by gavage (mg/(kg∙d), for 8 weeks) 17β-estradiol (0.1), atorvastatin (50), atorvastatin (50)+L-carnitine (100), or atorvastatin (50)+coenzyme Q10 (20). At the end of therapy, bone mineral density (BMD), bone mineral content (BMC), and serum levels of bone metabolic markers (BMMs) and creatine kinase (CK) were measured. Femurs were used for studying the breaking strength and histopathological changes. Results: Treatment with atorvastatin+L-carnitine restored BMD, BMC, and bone strength to near normal levels. Estrogen therapy restored BMD and BMC to near normal levels, but failed to increase bone strength. Although atorvastatin and atorvastatin+coenzyme Q10 improved BMD, BMC, and bone strength, they failed to restore levels to normal. All treatments decreased BMMs and improved histopathological changes maximally with atorvastatin+L-carnitine which restored levels to near normal. Atorvastatin aggravated the ovariectomy-induced increase in CK level while estrogen, atorvastatin+L-carnitine, and atorvastatin+coenzyme Q10 decreased its level mainly with atorvastatin+L-carnitine which restored the level to near normal. Conclusions: Co-administration of L-carnitine, but not coenzyme Q10, enhances the anti-osteoporotic effect of atorvastatin while antagonizing myopathy in ovariectomized rats. This could be valuable in treatment of osteoporotic patients. However, further confirmatory studies are needed.

There is a paucity of data regarding trends in the incidence of heart disease in China during recent years. Using a large echocardiography database in our center, we analyzed trends in the prevalence of several common heart diseases from Dec. 2003. This study retrospectively analyzed the echocardiographic database in our Department from 2003 to 2012. A total of 385 682 cases were included in the study. The prevalence of rheumatic heart disease decreased over the 10-year period, from 4.04% in 2003 to 3.06% in 2012 (P<0.01). Infective endocarditis also decreased, from a mean prevalence of 0.37% in July 2003 to 0.27% in Dec. 2008 (P<0.001). The prevalence of hypertrophic cardiomyopathy, which includes 20% apical hypertrophic cardiomyopathy and 20% hypertrophic obstructive cardiomyopathy, was about 1.8%. The prevalence of the three most common adult congenital heart diseases (CHDs) decreased by about 10% from July 2003 to Dec. 2008 (all P<0.001). The prevalence of moderate pulmonary arterial hypertension (PAH) or left ventricular systolic dysfunction (LVSD) decreased during the 10-year period (P<0.001), but there was no change in the prevalence of severe PAH or LVSD (P>0.05). The present study indirectly demonstrates that the prevalence of several common heart diseases in China has declined in recent years.

Objective: The subclavian vein (SCV) is usually used to inject the indicator of cold saline for a transpulmonary thermodilution (TPTD) measurement. The SCV catheter being misplaced into the internal jugular (IJV) vein is a common occurrence. The present study explores the influence of a misplaced SCV catheter on TPTD variables. Methods: Thirteen severe acute pancreatitis (SAP) patients with malposition of the SCV catheter were enrolled in this study. TPTD variables including cardiac index (CI), global end-diastolic volume index (GEDVI), intrathoracic blood volume index (ITBVI), and extravascular lung water index (EVLWI) were obtained after injection of cold saline via the misplaced SCV catheter. Then, the misplaced SCV catheter was removed and IJV access was constructed for a further set of TPTD variables. Comparisons were made between the TPTD results measured through the IJV and misplaced SCV accesses. Results: A total of 104 measurements were made from TPTD curves after injection of cold saline via the IJV and misplaced SCV accesses. Bland-Altman analysis demonstrated an overestimation of +111.40 ml/m² (limits of agreement: 6.13 and 216.70 ml/m²) for GEDVI and ITBVI after a misplaced SCV injection. There were no significant influences on CI and EVLWI. The biases of +0.17 L/(min·m²) for CI and +0.17 ml/kg for EVLWI were revealed by Bland-Altman analysis. Conclusions: The malposition of an SCV catheter does influence the accuracy of TPTD variables, especially GEDVI and ITBVI. The position of the SCV catheter should be confirmed by chest X-ray in order to make good use of the TPTD measurements.

Percutaneous transluminal renal artery stenting (PTRAS) has been proved to have no more benefit than medication alone in treating atherosclerotic renal artery stenosis (ARAS). Whether PTRAS could improve left ventricular hypertrophy (LVH) and reduce adverse events when based on percutaneous coronary intervention (PCI) for patients with coronary artery disease (CAD) and ARAS is still unclear. A retrospective study was conducted, which explored the effect of concomitant PCI and PTRAS versus PCI alone for patients with CAD and ARAS complicated by heart failure with preserved ejection fraction (HFpEF). A total of 228 patients meeting inclusion criteria were divided into two groups: (1) the HFpEF-I group, with PCI and PTRAS; (2) the HFpEF-II group, with PCI alone. Both groups had a two-year follow-up. The left ventricular mass index (LVMI) and other clinical characteristics were compared between groups. During the follow-up period, a substantial decrease in systolic blood pressure (SBP) was observed in the HFpEF-I group, but not in the HFpEF-II group. There was marked decrease in LVMI in both groups, but the HFpEF-I group showed a greater decrease than the HFpEF-II group. Regression analysis demonstrated that PTRAS was significantly associated with LVMI reduction and fewer adverse events after adjusting for other factors. In HFpEF patients with both CAD and ARAS, concomitant PCI and PTRAS can improve LVH and decrease the incidence of adverse events more than PCI alone. This study highlights the beneficial effect of ARAS revascularization, as a new and more aggressive revascularization strategy for such high-risk patients.

The homozygous loss of the survival motor neuron 1 (SMN1) gene is the primary cause of spinal muscular atrophy (SMA), a neuromuscular degenerative disease. A genetically similar gene, SMN2, which is not functionally equivalent in all SMA patients, modifies the clinical SMA phenotypes. We analyzed the methylation levels of 4 CpG islands (CGIs) in SMN2 in 35 Chinese children with SMA by MassARRAY. We found that three CpG units located in CGI 1 (nucleotides (nt) −871, −735) and CGI 4 (nt +999) are significantly hypomethylated in SMA type III compared with type I or II children after receiving Bonferroni correction. In addition to the differentially methylated CpG unit of nt −871, the methylation level of the nt −290/−288/−285 unit was negatively correlated with the expression of SMN2 full-length transcripts (SMN2-fl). In addition, the methylation level at nt +938 was inversely proportional to the ratio of SMN2-fl and lacking exon 7 transcripts (SMN2-(7, fl/(7), and was not associated with the SMN2 transcript levels. Thus, we can conclude that SMN2 methylation may regulate the SMA disease phenotype by modulating its transcription.