BACKGROUNDH syndrome (OMIM 612391) is a recently described autosomal recessive genodermatosis characterized by indurated hyperpigmented and hypertrichotic skin, as well as other systemic manifestations. Most of the cases occurred in the Middle East areas or nearby countries such as Spain or India. The syndrome is caused by mutations in solute carrier family 29, member 3 (SLC29A3), the gene encoding equilibrative nucleoside transporter 3. The aim of this study was to identify pathogenic SLC29A3 mutations in a Chinese patient clinically diagnosed with H syndrome.

METHODSPeripheral blood samples were collected from the patient and his parents. Genomic DNA was isolated by the standard method. All six SLC29A3 exons and their flanking intronic sequences were polymerase chain reaction (PCR)-amplified and the PCR products were subjected to direct sequencing.

RESULTSThe patient, an 18-year-old man born to a nonconsanguineous Chinese couple, had more extensive cutaneous lesions, involving both buttocks and knee. In his genomic DNA, we identified a novel homozygous insertion-deletion, c. 1269_1270delinsA, in SLC29A3. Both of his parents were carriers of the mutation.

CONCLUSIONSWe have identified a pathogenic mutation in a Chinese patient with H syndrome.

Abnormalities, Multiple ; diagnosis ; genetics ; Adolescent ; Asian Continental Ancestry Group ; Genetic Predisposition to Disease ; Humans ; Male ; Mutation ; Nucleoside Transport Proteins ; genetics ; Skin Abnormalities ; diagnosis ; genetics

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly desmoplastic tumor with poor prognosis even after curative resection. We investigated the associations between the composition of the ICC stroma and immune cell infiltration and aimed to develop a stromal-immune signature to predict prognosis in surgically treated ICC. Patients and methods: We recruited 359 ICC patients and performed immunohistochemistry to detect α-smooth muscle actin (α-SMA), CD3, CD4, CD8, Foxp3, CD68, and CD66b. Aniline was used to stain collagen deposition. Survival analyses were performed to detect prognostic values of these markers. Recursive partitioning for a discrete-time survival tree was applied to define a stromal-immune signature with distinct prognostic value. We delineated an integrated stromal-immune signature based on immune cell subpopulations and stromal composition to distinguish subgroups with different recurrence-free survival (RFS) and overall survival (OS) time. Results: We defined four major patterns of ICC stroma composition according to the distributions of α-SMA and collagen: dormant (α-SMAlow/collagenhigh), fibrogenic (α-SMAhigh/collagenhigh), inert (α-SMAlow/collagenlow), and fibrolytic (α-SMAhigh/collagenlow). The stroma types were characterized by distinct patterns of infiltration by immune cells. We divided patients into six classes. Class I, characterized by high CD8 expression and dormant stroma, displayed the longest RFS and OS, whereas Class VI, characterized by low CD8 expression and high CD66b expression, displayed the shortest RFS and OS. The integrated stromal-immune signature was consolidated in a validation cohort. Conclusion We developed and validated a stromal-immune signature to predict prognosis in surgically treated ICC. These findings provide new insights into the stromal-immune response to ICC.

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly desmoplastic tumor with poor prognosis even after curative resection. We investigated the associations between the composition of the ICC stroma and immune cell infiltration and aimed to develop a stromal-immune signature to predict prognosis in surgically treated ICC. Patients and methods: We recruited 359 ICC patients and performed immunohistochemistry to detect α-smooth muscle actin (α-SMA), CD3, CD4, CD8, Foxp3, CD68, and CD66b. Aniline was used to stain collagen deposition. Survival analyses were performed to detect prognostic values of these markers. Recursive partitioning for a discrete-time survival tree was applied to define a stromal-immune signature with distinct prognostic value. We delineated an integrated stromal-immune signature based on immune cell subpopulations and stromal composition to distinguish subgroups with different recurrence-free survival (RFS) and overall survival (OS) time. Results: We defined four major patterns of ICC stroma composition according to the distributions of α-SMA and collagen: dormant (α-SMAlow/collagenhigh), fibrogenic (α-SMAhigh/collagenhigh), inert (α-SMAlow/collagenlow), and fibrolytic (α-SMAhigh/collagenlow). The stroma types were characterized by distinct patterns of infiltration by immune cells. We divided patients into six classes. Class I, characterized by high CD8 expression and dormant stroma, displayed the longest RFS and OS, whereas Class VI, characterized by low CD8 expression and high CD66b expression, displayed the shortest RFS and OS. The integrated stromal-immune signature was consolidated in a validation cohort. Conclusion We developed and validated a stromal-immune signature to predict prognosis in surgically treated ICC. These findings provide new insights into the stromal-immune response to ICC.

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly desmoplastic tumor with poor prognosis even after curative resection. We investigated the associations between the composition of the ICC stroma and immune cell infiltration and aimed to develop a stromal-immune signature to predict prognosis in surgically treated ICC. Patients and methods: We recruited 359 ICC patients and performed immunohistochemistry to detect α-smooth muscle actin (α-SMA), CD3, CD4, CD8, Foxp3, CD68, and CD66b. Aniline was used to stain collagen deposition. Survival analyses were performed to detect prognostic values of these markers. Recursive partitioning for a discrete-time survival tree was applied to define a stromal-immune signature with distinct prognostic value. We delineated an integrated stromal-immune signature based on immune cell subpopulations and stromal composition to distinguish subgroups with different recurrence-free survival (RFS) and overall survival (OS) time. Results: We defined four major patterns of ICC stroma composition according to the distributions of α-SMA and collagen: dormant (α-SMAlow/collagenhigh), fibrogenic (α-SMAhigh/collagenhigh), inert (α-SMAlow/collagenlow), and fibrolytic (α-SMAhigh/collagenlow). The stroma types were characterized by distinct patterns of infiltration by immune cells. We divided patients into six classes. Class I, characterized by high CD8 expression and dormant stroma, displayed the longest RFS and OS, whereas Class VI, characterized by low CD8 expression and high CD66b expression, displayed the shortest RFS and OS. The integrated stromal-immune signature was consolidated in a validation cohort. Conclusion We developed and validated a stromal-immune signature to predict prognosis in surgically treated ICC. These findings provide new insights into the stromal-immune response to ICC.

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly desmoplastic tumor with poor prognosis even after curative resection. We investigated the associations between the composition of the ICC stroma and immune cell infiltration and aimed to develop a stromal-immune signature to predict prognosis in surgically treated ICC. Patients and methods: We recruited 359 ICC patients and performed immunohistochemistry to detect α-smooth muscle actin (α-SMA), CD3, CD4, CD8, Foxp3, CD68, and CD66b. Aniline was used to stain collagen deposition. Survival analyses were performed to detect prognostic values of these markers. Recursive partitioning for a discrete-time survival tree was applied to define a stromal-immune signature with distinct prognostic value. We delineated an integrated stromal-immune signature based on immune cell subpopulations and stromal composition to distinguish subgroups with different recurrence-free survival (RFS) and overall survival (OS) time. Results: We defined four major patterns of ICC stroma composition according to the distributions of α-SMA and collagen: dormant (α-SMAlow/collagenhigh), fibrogenic (α-SMAhigh/collagenhigh), inert (α-SMAlow/collagenlow), and fibrolytic (α-SMAhigh/collagenlow). The stroma types were characterized by distinct patterns of infiltration by immune cells. We divided patients into six classes. Class I, characterized by high CD8 expression and dormant stroma, displayed the longest RFS and OS, whereas Class VI, characterized by low CD8 expression and high CD66b expression, displayed the shortest RFS and OS. The integrated stromal-immune signature was consolidated in a validation cohort. Conclusion We developed and validated a stromal-immune signature to predict prognosis in surgically treated ICC. These findings provide new insights into the stromal-immune response to ICC.

OBJECTIVETo compared outcomes of robotic mitral valve repair with those of standard sternotomy, and right anterolateral thoracotomy.

METHODFrom August 2010 to July 2011, 70 patients with degenerative mitral valve disease and posterior leaflet prolapsed scheduled for elective isolated mitral valve repair were prospectively nonrandomized to undergo mitral valve operation by standard sternotomy (n = 30), right anterolateral thoracotomy (n = 30), or a robotic approach (n = 10). There were 49 male and 21 female patients, aging from 16 to 70 years with a mean of 53.4 years. Outcomes of the three groups were compared.

RESULTSMitral valve repair was achieved in all patients except 1 patient in the standard group. There were no in-hospital deaths. The median operation time [(300 ± 41) min, (184 ± 20) min and (169 ± 22) min, F = 112.5, P < 0.01], cardiopulmonary bypass time [(139 ± 26) min, (82 ± 20) min and (69 ± 23) min, F = 36.8, P < 0.01], aortic cross-clamping time [(93 ± 23) min, (47 ± 10) min and (38 ± 8) min, F = 75.0, P < 0.01] were longer for robotic than standard sternotomy and right anterolateral thoracotomy. The robotic group had shortest time of mechanical ventilation time [(4.9 ± 2.1) h, (5.3 ± 4.5) h and (14.1 ± 10.2) h, F = 13.2, P < 0.01], ICU time [(15.1 ± 2.1) h, (16.4 ± 5.4) h and (28.7 ± 16.1) h, F = 11.6, P < 0.01], postoperative hospital stay time [(4.6 ± 1.0) d, (5.7 ± 1.7) d and (8.8 ± 5.1) d, F = 8.0, P < 0.01] with the lowest of drainage [(192 ± 200) ml, (215 ± 163) ml and (405 ± 239) ml, F = 7.1, P < 0.01] and ratio of the patients needed blood transfusion (0, 20.0% and 66.7%, χ(2) = 22.7, P < 0.01). Patients were followed up 6 to 17 months, with 100% completed. No patients died during follow-ups, and no moderate or more mitral regurgitation was observed. The robotic group had the shortest time of return to normal activities compared with the other two groups [(2.4 ± 0.7) weeks, (4.2 ± 1.2) weeks and (8.2 ± 1.8) weeks, F = 83.0, P < 0.01].

CONCLUSIONThis study shows mitral valve repair via the right anterolateral thoracotomy and a robotic approach is safe and feasible, with good cosmetic results and rapid postoperative recovery, and is worthy of clinical selective application.

Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Mitral Valve ; surgery ; Mitral Valve Prolapse ; surgery ; Prospective Studies ; Robotics ; Thoracic Surgical Procedures ; methods ; Treatment Outcome ; Young Adult

Objective To investigate the significance of the expression of phosphatidic acid phosphatase type 2 domain containing 1A(PPAPDC1A) in human colorectal cancer cell lines.Methods The high metastatic potential cells LOVO,SW620 and low metastatic potential cells SW480,RKO,HCT116 and DLD-1 were cultured,the expression of PPAPDC1A mRNA and protein in different colorectal cancer cells in logarithmic growth period was detected by real-time quantitative polymerase chain reaction and Western blot.Results There were significant differences in the expressions of PPAPDC1A mRNA and protein among the six human colorectal cancer cells (F =41.213,344.1 16;P ＜ 0.05).The expression of PPAPDC1 A mRNA and protein in highly metastatic potential cells LOVO and SW620 was significantly higher than that in DLD-1,HCT116,RKO and SW480 cells (P ＜0.05).The expression of PPAPDC1A protein in LOVO cells with high metastatic potential was significantly higher than that in SW620 cells(P ＜ 0.05).The expression of PPAPDC1A protein in DLD-1 cells was significantly higher than that in HCT116,RKO and SW480 cells (P ＜0.05).The expression of PPAPDC1 A protein in HCT116 cells with low metastatic potential was significantly higher than that in RKO and SW480 cells (P ＜ 0.05).The expression of PPAPDC1 A protein in RKO cells was significantly higher than that in SW480 cells (P ＜ 0.05).There was no significant difference in the expression of PPAPDC1A mRNA between LOVO and SW620 cells (P ＜ 0.05).There was no significant difference in the expression of PPAPDC1A mRNA between SW480,RKO,HCT116 and DLD-1 cells (P＜ 0.05).Conclusion PPAPDC1A expresses differentially in colorectal cancer cell lines,which may be involved in the invasion and metastasis of colorectal cancer.

Aim To investigate the neuroprotective effect of prophylactic administration of salidroside (Sal) on MCAO rats. Methods A total of 52 SD adult male rats were randomly divided into sham operation group (Sham), model group (MCAO) and salidroside pre-administration group (MCAO + Sal). The dose of Sal was 50 mg·kg

The active ingredients of Ficus hirta and Hypericum perforatum were collected from Traditional Chinese Medicine Database and Analysis Platform(TCMSP) and related papers. The potential targets of these two medicinal herbs were searched from HERB database, and those associated with microvascular angina were screened out from GeneCards, Online Mendelian Inheritance in Man(OMIM), Therapeutic Target Database(TTD), and HERB. Cytoscape was used to construct a protein-protein interaction(PPI) network of the common targets shared by the two herbs and microvascular angina based on the data of String platform. Metascape was employed to identify the involved biological processes and pathways enriched with the common targets. Cytoscape was used to draw the "active ingredient-target-pathway" network. AutoDock Vina was used to dock the core ingredients with the key targets. A total of 19 potential active ingredients and 71 potential targets were identified to be associated with microvascular angina. Bioinformatics analysis showed that phosphatidylinositol-3-kinase/protein kinase B(PI3 K-AKT), interleukin-17(IL17), hypoxia-inducible factor 1(HIF-1) and other signaling pathways were related to the treatment of microvascular angina by F. hirta and H. perforatum. Molecular docking results showed that β-sitosterol, luteolin and other ingredients had strong affinity with multiple targets including mitogen-associated protein kinase 1(MAPK1), epidermal growth factor receptor(EGFR) and so on. These findings indicated that F. hirta and H. perforatum may regulate PI3 K-AKT, IL17, HIF-1 and other signaling pathways by acting on multiple targets to alleviate oxidative stress, inhibit inflammatory response, regulate angiogenesis, and improve vascular endothelium and other functions. This study provides reference for in vitro and in vivo studies of the treatment of microvascular angina.
Drugs, Chinese Herbal/pharmacology* ; Ficus ; Humans ; Hypericum ; Medicine, Chinese Traditional ; Microvascular Angina ; Molecular Docking Simulation ; Network Pharmacology

Aim To investigate the neuroprotective effect and mechanism of salidroside (Sal) on rats with permanent middle cerebral artery occlusion model (pMCAO) by regulating the PI3 K/AKT signaling pathway. Methods A total of 80 healthy adult SPF male SD rats were randomly divided into sham operation group (sham group), model group (pMCAO group), drug administration group (pMCAO + Sal group) and inhibitor group (pMCAO + Sal + YL group). After the pMCAO model rats were prepared by the line bolt method, salidroside (50 mg · kg