[Exploration of clinical pathway-oriented optimal management diagnosis and treatment model for rare diseases].

This study takes Cushing's syndrome, a rare disease, as a model, and adopts the path of "Plan, Do, Check, Action" (PDCA) to explore new methods to optimize the clinical path, can improve the quality and efficiency of diagnosis and treatment of rare diseases. After sorting out the problems existing in the previous diagnosis and treatment mode, our team optimizes the path in various ways and establishes a standard operation procedure (SOP) for the new path. In the evaluation of the optimized mode, 55 patients with Cushing's syndrome were admitted to the Department of Endocrinology, Peking Union Medical College Hospital, including 19 males and 36 females, aged (41.8±14.4) years (6-68 years). The pathway group (28 cases) and the control group (27 cases) were divided according to whether they were included in the new path management at the time of admission, and the effect of path optimization was assessed in terms of time, efficacy, safety and cost. The results showed that compared with the control group, the pathway group had a shorter time of hospitalization in the Department of Endocrinology and critical tests, such as blood cortisol rhythm, low-dose dexamethasone inhibition test, and bilateral inferior petrosal sinus sampling (all P<0.05). There was no significant differences in the decrease of total cortisol after operation, the incidence of postoperative complications, and hospitalization expenses (all P>0.05). The optimized path improves the medical efficiency while ensuring medical quality, safety and no increase in cost. This study proposes PDCA path optimization for complex diseases and establishes SOP process, which provides experience in management optimization for the patient-centered and clinical path-oriented diagnosis and treatment mode of rare diseases.

[Effect of inherent depression on chronic visceral hypersensitivity induced by colon acetate stimulation in neonatal rats].

OBJECTIVE: To explore the effect of inherent depression on chronic visceral hypersensitivity. The differences of visceral sensitivity, colitis, and brain activation between Fawn-Hooded (FH/Wjd) and Sprague-Dawley(SD) rats were identified after neonatal colon acetate stimulation. METHODS: The specific pathogen free Fawn-Hooded (FH/Wjd) and Sprague-Dawley(SD) rats were used to establish irritable bowel syndrome (IBS) model. The visceral sensitivity was measured by colorectal distension (CRD). The expression of 5-hydroxytryptamine (5-HT), mast cell (MC), indoleamine 2,3-dioxygenase (IDO) in colon and IDO in specific cerebral regions were detected through immunohistochemistry. RESULTS: Abdominal withdrawal reflex (AWR) scores showed that visceral sensitivity of acetate-enema groups was significantly higher than that of saline-enema groups (FH/Wjd:2.44 ± 0.04 vs.1.96 ± 0.07, P < 0.05; SD: 1.75 ± 0.13 vs.1.32 ± 0.05, P < 0.05). Furthermore, FH/Wjd rats of IBS group scored significantly higher than SD rats of IBS group (2.44 ± 0.04 vs.1.75 ± 0.13, P < 0.05). The MC amounts of both SD and FH/Wjd IBS group rats were significantly more than those of their control groups (FH/Wjd:43.24 ± 1.72 vs. 24.92 ± 1.38, P < 0.01. SD: 23.80 ± 1.28 vs. 14.24 ± 0.92, P < 0.01). Besides, the MC amounts of control and IBS group of FH/Wjd rats were significantly more than that of SD IBS group rats (P < 0.01). The IDO and 5-HT positive cells in colonic mucosa of IBS group of both SD and FH/Wjd rats were significantly more than those of their control groups, respectively(P < 0.01). The IDO, 5-HT positive cells in colonic mucosa of both control and IBS group of FH/Wjd rats were significantly more than those of both control and IBS group of SD rats (control:IDO,24.64 ± 2.22 vs. 15.52 ± 1.39;5-HT,21.32 ± 1.26 vs. 12.72 ± 1.12. IBS: IDO,44.92 ± 2.31 vs. 20.85 ± 1.72; 5-HT, 31.84 ± 1.57 vs. 19.65 ± 1.09.P <0.01). The expression of IDO in prelimbic cortex (PrL) areas of FH/Wjd IBS rats was significantly higher than that of IBS group of SD rats (49.60 ± 4.31 vs. 35.60 ± 2.42, P <0.01), and the expression of IDO in rostral anterior cingulate cortex (rACC) areas of FH/Wjd IBS rats was significantly more than that of FH/Wjd control rats (45.44 ± 1.16 vs. 34.08 ± 2.76, P <0.01). CONCLUSION: Inherent depressive FH/Wjd rats were more sensitive to neonatal colon acetate stimulation, presenting as visceral hypersensitivity which maybe associated with increased MC amounts and over-expression of 5-HT and IDO in colon, suggesting that depression disorder may aggravate functional disturbance of gastrointestinal tract by regulating the response to inflammatory stimulation.

Cytosolic phospholipase A2 participates with TNF-alpha in the induction of apoptosis of human macrophages infected with Mycobacterium tuberculosis H37Ra.

Macrophage (MPhi) apoptosis, an important innate microbial defense mechanism induced by Mycobacterium tuberculosis (Mtb) H37Ra, depends on the induction of TNF-alpha synthesis. When protein synthesis is blocked, both infection with Mtb and addition of TNF-alpha are required to induce caspase 9 activation, caspase 3 activation and apoptosis. In this study, we show that the second protein synthesis-independent signal involves activation of group IV cytosolic phospholipase A2 (cPLA2). Apoptosis of Mtb-infected MPhi and concomitant arachidonic acid release are abrogated by group IV cPLA2 inhibitors (methyl arachidonyl fluorophosphate and methyl trifluoromethyl ketone), but not by inhibitors of group VI Ca2+-independent (iPLA2; bromoenol lactone) or of secretory low molecular mass PLA2. In MPhi homogenates, the predominant PLA2 activity showed the same inhibitor sensitivity pattern and preferred arachidonic acid over palmitic acid in substrates, also indicating the presence of one or more group IV cPLA2 enzymes. In concordance with these findings, MPhi lysates contained transcripts and protein for group IV cPLA2-alpha and cPLA2-gamma. Importantly, group IV cPLA2 inhibitors significantly reduced MPhi antimycobacterial activity and addition of arachidonic acid, the major product of group IV cPLA2, to infected MPhi treated with cPLA2 inhibitors completely restored the antimycobacterial activity. Importantly, addition of arachidonic acid alone to infected MPhi significantly reduced the mycobacterial burden. These findings indicate that Mtb induces MPhi apoptosis by independent signaling through at least two pathways, TNF-alpha and cPLA2, which are both also critical for antimycobacterial defense of the MPhi.

Expression and changes of HSP70 in the rat forebrain subjected to gamma knife (100Gy) irradiation targeted on the caudate putamen and survived for different times.

Forebrain heat shock protein 70 (HSP70) immunohistochemical reactivity was investigated in rats subjected to gamma knife irradiation focusing on the right caudate putamen nucleus. The forebrain sections of all experimental animals were processed with anti-HSP70 antiserum and then by avidin-biotin peroxidase complex immunohistochemistry after gamma ray irradiation with a dose of 100Gy and they each survived for different times (from 30 min to 30 days). Some neurons, glial cells, and endothelial cells were HSP70-like immunoreactivity (HSP70-LI) positive. HSP70-LI was mainly distributed in the target area of irradiation, as well as in non-target regions, e.g. the cortex, hippocampus, and hypothalamus, etc. The expression and change of HSP70-LI from 3 h to 30 days after irradiation followed the following rules: (1) Within 3 to 24 h, the dilated vessels with HSP70-LI endothelial cells were found at first, and a few lightly stained HSP70-LI neurons and glias were observed in the target and non-target regions; (2) In 3-7 days, darkly stained HSP70-LI neurons and glias were apparently increased and formed an expression peak. From 14 to 30 days, HSP70-LI cells were distinctly decreased and became weakly stained or negative. These results suggested that although the irradiation target of the gamma knife was localized, the response to irradiation occurred extensively.

TCM treatment with the modified wendan tang in 40 cases of melancholia.

Melancholia is a syndrome caused by emotional stress and stagnation of qi, involving the liver, affecting the heart and spleen, and leading to disharmony of qi of the zang-fu organs. Because of the complicated condition, it is not easy to determine the therapeutic principles. In this series of 40 cases, the modified Wen Dan Tang (Decoction for Clearing Away Gallbladder-Heat) was used for the treatment. Of them, 19 cases were cured, 16 improved, and 5 failed, with total effective rate of 87.5%.