Function and dysfunction of plasma cells in intestine.

As the main player in humoral immunity, antibodies play indispensable roles in the body's immune system. Plasma cells (PCs), as antibody factories, are important contributors to humoral immunity. PCs, recognized by their unique marker CD138, are always discovered in the medullary cords of spleen and lymph nodes and in bone marrow and mucosal lymphoid tissue. This article will review the origin and differentiation of PCs, characteristics of short- and long-lived PCs, and the secretion of antibodies, such as IgA, IgM, and IgG. PCs play a crucial role in the maintenance of intestinal homeostasis using immunomodulation though complex mechanisms. Clearly, PCs play functional roles in maintaining intestinal health, but more details are needed to fully understand all the other effects of intestinal PCs.

Functional macrophages and gastrointestinal disorders.

Macrophages (MΦ) differentiate from blood monocytes and participate in innate and adaptive immunity. Because of their abilities to recognize pathogens and activate bactericidal activities, MΦ are always discovered at the site of immune defense. MΦ in the intestine are unique, such that in the healthy intestine, they possess complex mechanisms to protect the gut from inflammation. In these complex mechanisms, they produce anti-inflammatory cytokines, such as interleukin-10 and transforming growth factor-ß, and inhibit the inflammatory pathways mediated by Toll-like receptors. It has been demonstrated that resident MΦ play a crucial role in maintaining intestinal homeostasis, and they can be recognized by their unique markers. Nonetheless, in the inflamed intestine, the function of MΦ will change because of environmental variation, which may be one of the mechanisms of inflammatory bowel disease (IBD). We provide further explanation about these mechanisms in our review. In addition, we review recent discoveries that MΦ may be involved in the development of gastrointestinal tumors. We will highlight the possible therapeutic targets for the management of IBD and gastrointestinal tumors, and we also discuss why more details are needed to fully understand all other effects of intestinal MΦ.

Evaluation of the simplified therapeutic intervention scoring system: Chinese version.

OBJECTIVE: To prepare the Simplified Therapeutic Intervention Scoring System (TISS-28) to measure nursing workload in Intensive Care Units in Guangdong Province of China. METHODS: A non-experimental descriptive study was conducted in the intensive care units in the Province. TISS-28, TISS-76, Acute Physiology and Chronic Health Evaluation (APACHE II) were all measured. RESULTS: There were significant positive correlations between TISS-28 and APACHE II (n=91, r=0.432, p<0.001), TISS-76 scores (n=83, r=0.764, p<0.001). A significant difference was found between the mean TISS-28 score in the first day of the intensive care stay and the last day (30.76±6.86 vs 24.67±5.48, p<0.001). A significant intra-class correlation was found between TISS-28 scores collected by the researcher and research associates (ICC=0.959, p<0.001). CONCLUSION: The reliability and validity of TISS-28 were shown in Chinese intensive care units. It is a practical tool for estimating the nursing workload and providing opportunities to compare the data between intensive care units in different facilities. The TISS-28 Chinese version is recommended to guide the allocation of nursing manpower in Chinese intensive care units.

The distinguishing cellular features of pulmonary artery smooth muscle cells from chronic thromboembolic pulmonary hypertension patients.

In chronic thromboembolic pulmonary hypertension (CTEPH), central thrombi are the most likely disease initiators, and progressive pulmonary vascular remodeling, which is characterized by marked proliferation of pulmonary artery smooth muscle cells (PASMCs), may also contribute to the long-term progression of CTEPH. This study was designed to investigate the cellular characteristics of PASMCs isolated from the organized thrombotic tissues of CTEPH. In the present study, analysis of PASMCs isolated from five CTEPH patients and three control subjects showed that cells from CTEPH patients had certain characteristics that distinguished them from control cells, including inferior or no cell-cell contact inhibition growth, increased sensitivity to hypoxia-induced proliferation, resistance to serum starvation-induced apoptosis, and mitochondrial metabolism disorder. These differences in the PASMCs in endarterectomized tissue of CTEPH patients may prove useful in understanding the pathobiology of CTEPH.

Inhibition of SOC/Ca2+/NFAT pathway is involved in the anti-proliferative effect of sildenafil on pulmonary artery smooth muscle cells.

BACKGROUND: Sildenafil, a potent phosphodiesterase type 5 (PDE5) inhibitor, has been proposed as a treatment for pulmonary arterial hypertension (PAH). The mechanism of its anti-proliferative effect on pulmonary artery smooth muscle cells (PASMC) is unclear. Nuclear translocation of nuclear factor of activated T-cells (NFAT) is thought to be involved in PASMC proliferation and PAH. Increase in cytosolic free [Ca2+] ([Ca2+]i) is a prerequisite for NFAT nuclear translocation. Elevated [Ca2+]i in PASMC of PAH patients has been demonstrated through up-regulation of store-operated Ca2+ channels (SOC) which is encoded by the transient receptor potential (TRP) channel protein. Thus we investigated if: 1) up-regulation of TRPC1 channel expression which induces enhancement of SOC-mediated Ca2+ influx and increase in [Ca2+]i is involved in hypoxia-induced PASMC proliferation; 2) hypoxia-induced promotion of [Ca2+]i leads to nuclear translocation of NFAT and regulates PASMC proliferation and TRPC1 expression; 3) the anti-proliferative effect of sildenafil is mediated by inhibition of this SOC/Ca2+/NFAT pathway. METHODS: Human PASMC were cultured under hypoxia (3% O2) with or without sildenafil treatment for 72 h. Cell number and cell viability were determined with a hemocytometer and MTT assay respectively. [Ca2+]i was measured with a dynamic digital Ca2+ imaging system by loading PASMC with fura 2-AM. TRPC1 mRNA and protein level were detected by RT-PCR and Western blotting respectively. Nuclear translocation of NFAT was determined by immunofluoresence microscopy. RESULTS: Hypoxia induced PASMC proliferation with increases in basal [Ca2+]i and Ca2+ entry via SOC (SOCE). These were accompanied by up-regulation of TRPC1 gene and protein expression in PASMC. NFAT nuclear translocation was significantly enhanced by hypoxia, which was dependent on SOCE and sensitive to SOC inhibitor SKF96365 (SKF), as well as cGMP analogue, 8-brom-cGMP. Hypoxia-induced PASMC proliferation and TRPC1 up-regulation were inhibited by SKF and NFAT blocker (VIVIT and Cyclosporin A). Sildenafil treatment ameliorated hypoxia-induced PASMC proliferation and attenuated hypoxia-induced enhancement of basal [Ca2+]i, SOCE, up-regulation of TRPC1 expression, and NFAT nuclear translocation. CONCLUSION: The SOC/Ca2+/NFAT pathway is, at least in part, a downstream mediator for the anti-proliferative effect of sildenafil, and may have therapeutic potential for PAH treatment.

Functional expression of transient receptor potential vanilloid-related channels in chronically hypoxic human pulmonary arterial smooth muscle cells.

Transient receptor potential vanilloid (TRPV) channels are nonselective cation channels pertinent to diverse physiological functions. Multiple TRPV channel subtypes have been identified in different tissues and cloned. The aim of this study was to investigate the role of TRPV channels in hypoxia-induced proliferation of human pulmonary artery smooth muscle cells (PASMCs) and its possible signal pathway. Reverse transcriptase-polymerase chain reaction, real-time polymerase chain reaction, and Western blot analysis were used to detect the expression of TRPV in human PASMCs. Cell number was determined with a hemocytometer. Cytosolic Ca2+ concentration ([Ca2+]cyt) was measured with a dynamic digital Ca2+ imaging system. The mRNA of TRPV1-4 was detected in human PASMCs and chronic hypoxia up-regulated expression levels of the TRPV1 gene and protein. The ability to proliferate, the resting [Ca2+]cyt, and cyclopiazonic acid-induced capacitative Ca2+ entry in human PASMCs were enhanced significantly by chronic hypoxia compared with the control, and these effects were inhibited in a dose-dependent manner by capsazepine, a TRPV1 channel inhibitor. These results suggest that TRPV1 may be a critical pathway or mediator in chronic hypoxia-induced proliferation of human PASMCs.

[Comparison of retaining or removing negative vertical coma in wavefront guided LASIK for myopia and astigmatism].

OBJECTIVE: To investigate the efficacy and safety of wavefront guided (WG) LASIK for the myopia and astigmatism. METHODS: This study is a randomized control trial. 42 cases (78 eyes) were collected in the study through the routine examinations and wavefront analysis, which were divided into two groups (A and B). The value of Z (3, -1) being less than -0.15 microm was evaluated as Group A (24 cases, 45 eyes); The value of Z (3, -1) being more than +0.15 microm was as Group B (18 cases, 33 eyes). Both A and B were also divided into two subgroups (test and control). WG-LASIK was performed in tested groups, and classic LASIK was performed in control group. Visual quality, wavefront examination, and CSF were analyzed after surgery 3-6 months compared with that of preoperation. RESULTS: In the earlier period of post-operation time, diopters of the two groups were both slightly overcorrected, and then began to decrease slightly later and the diopters of both tested and control groups were corrected perfectly. RMSh of tested group increased higher than that of control group when Z (3, -1) was negative and the CSF in control group was better than that in test group after WG-LASIK in Group A. RMSh of tested group increased lower than that of control group when Z (3, -1) was positive and the CSF in tested group was better than that in control group after WG-LASIK in Group B. CONCLUSIONS: These results suggest that retaining negative vertical coma and removing positive vertical coma were beneficial to the visual function after the WG-LASIK, which could save the corneal tissue reasonably in order to improve visual quality effectively.