Background::Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD.Methods::Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. Results::Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. Conclusions::Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.

With the improvement of sanitation, the infection rate of hookworm is greatly reduced and the severe infected case is rarely reported. Combined morphological and molecular biological examinations, a severe hookworm infection patient was diagnosed in Department of Laboratorial Examination, Quanzhou First Affiliated Hospital of Fujian Medical University. The morphological methods such as direct fecal smear microscopy, saturated brine flotation and hookworm larvae culture methods were used to identify the eggs and larvae from stool samples of the patient. There were a large number of hookworm eggs in patient's stool samples, and the average count was 60 840 per gram by modified Kato method, which belonged to severe hookworm infection. Meanwhile, to distinguish the hookworm species, the semi-nested RT-PCR assay was employed to detect hookworm internal transcribed spacer series from eggs in patient's stool samples, and the result showed that the hookworm species was confirmed to be Necator americanus.
Ancylostomatoidea/genetics* ; Animals ; Feces ; Hookworm Infections/diagnosis* ; Humans ; Necator americanus/genetics* ; Polymerase Chain Reaction

Congenital heart disease (CHD) is the most common birth defect worldwide. Long non-coding RNAs (lncRNAs) have been implicated in many diseases. However, their involvement in CHD is not well understood. This study aimed to investigate the role of dysregulated lncRNAs in CHD. We used Gene Expression Omnibus data mining, bioinformatics analysis, and analysis of clinical tissue samples and observed that the novel lncRNA SAP30-2:1 with unknown function was significantly downregulated in damaged cardiac tissues from patients with CHD. Knockdown of lncRNA SAP30-2:1 inhibited the proliferation of human embryonic kidney and AC16 cells and decreased the expression of heart and neural crest derivatives expressed 2 (HAND2). Moreover, lncRNA SAP30-2:1 was associated with HAND2 by RNA immunoprecipitation. Overall, these results suggest that lncRNA SAP30-2:1 may be involved in heart development through affecting cell proliferation via targeting HAND2 and may thus represent a novel therapeutic target for CHD.
Basic Helix-Loop-Helix Transcription Factors ; Cell Proliferation ; Heart Defects, Congenital/genetics* ; Histone Deacetylases ; Humans ; RNA, Long Noncoding/genetics* ; Transcription Factors

Objective To investigate the therapeutic effect and mechanism of non-mitogenic acid fibroblast growth factor 1( NMFGF1) on diabetic cardiomyopathy ( DCM) by using PEG-modified nano-liposomes combined with ultrasound-targeted microbubble destruction technique ( UTMD ) . Methods The NMFGF1 loaded PEG-modified nano-liposomes were prepared by a water-in-water emulsion method and their quality inspections were also investigated. Type 1 diabetes animal model was induced by intraperitoneal injection of streptozotocin ( 70 mg/kg) in male SD rats. The diabetic rats were raised twelve weeks after the diabetes model was established and DCM rats were selected by ultrasonic heart function examination. After two weeks of intervention, all rats were kept for another two weeks and then underwent transthoracic echocardiography examination. The rats were sacrificed and myocardial tissue was obtained to quantify myocardial collagen fraction ( CVF ) and cardiac myocyte apoptotic index by Sirius red staining and TUNEL staining. Results NMFGF1-loaded PEG-nano-liposomes showed a good morphology and 90.3％± 1.4％ NMFGF1 encapsulation efficiency. Compared with DCM group, NMFGF1group, and NMFGF1-PEG-nano-liposomes group, NMFGF1-loaded PEG-nano-liposome plus UTMD group showed increased left ventricular end diastolic diameter (LVIDd) [(7.36±0.42) vs (5.75±0.24), (6.64±0.27), (6.72±0.24)mm, all P<0.05]and leftventricularfractionshortening(LVFS) [(50±3) vs (33±2), (44±5), (43±3)mm, all P<0.05], and decreased left ventricular posterior wall thickness (LVPW) [(1.65±0.07) vs (1.89±0.08), (1.73±0.11), (1.73 ±0.07) mm, all P<0.05], with decreased CVF and apoptotic index(all P<0.05). Conclusion PEG-nano-liposomes combining with UTMD technique has a greater translational potential in the delivery of NMFGF1 for the treatment of DCM by attenuating oxidative stress-induced injury and may provide a promising strategy for treating diabetes cardiomyopathy.

Objective To investigate the advanced preventive effect of acid fibroblast growth factor (aFGF) on diabetic cardiomyopathy(DCM) by using heparin-modified nano-liposomes combined with ultrasoundtargeted microbubble destruction technique (UTMD).Methods aFGF-loaded nano-liposomes (aFGF-lips) were prepared by lyophilization technique.Type Ⅰ diabetes model was induced by intraperitoneal injection of streptozotocin (STZ,70 mg/kg) in male SD rats.Before and twelve weeks after intervention,all rats underwent the transthoracic echocardiography.The segmental mean peak systolic radial velocity (Vs),systolic circumferential strain (Sc),and systolic circumferential strain rate (SRc) were measured.The expression of aFGF in DCM rats was detected by western blot.The rats were sacrificed and myocardial tissue were stained with masson staining and Tunel staining to quantify myocardial collagen fraction(CVF) and cardiac myocyte apoptosis index(AI).Results aFGF-lips showed good morphology and aFGF encapsulation efficiency (89.4±1.2)％ with high stability.From the animal experiments,the echocardiographic indexes including Vs,Sc and SRc had significantly improvements over DM group (P＜0.05) and all other treatment group (P＜0.05).The Masson's trichrome staining demonstrated that CVF was significantly higher in DM group than in the control group and was significantly lower in the aFGF-loaded nano-liposome+UTMD group than other groups(all P＜0.05).The TUNEL results showed that AI was significantly higher in DM group than in the control group and was significantly lower in aFGF-loaded nano-liposome +UTMD group than other groups (all P＜0.05).Conclusion aFGF nano-liposome combining with UTMD technique can improve the functions and pathologies of the hearts in type 1 diabetes mellitus model,which might provide a novel technique for aFGF in DCM prevention.

Objective Evaluation of efficacy and safety of combination of Yinxin Damo injection and low molecular heparin for deep venous thrombosis (DVT) in orthopedics operation.Methods Randomized controlled trials of combination of Yinxin Damo injection and low molecular heparin intervention study of DVT in orthopedics operation were searched from the Cochrane Library,clinicaltrials,gov,PubMed,EMBASE,CNKI,Wanfang database,VIP database,and Chinese biomedical database (CBM).According to the Cochrane Handbook 5.1,Meta analysis was performed by Revman 5.3 software.Results A total of 4 studies included 358 patients.The results of Meta-analysis showed that,compared with control group,incidence of DVT was significantly reduced (P =0.01),value of D-D significantly decreased (P ＜0.000 01) and value of PT increased (P =0.04),and increased value of APTT (P =0.07) in combined group.Heterogeneous sources of PT and APTT were analyzed,and the results after excluding literature 7,as compared with the control group,APTT and PT were significantly increased in combined group (P ＜ 0.000 1).Conclusion Based on the current clinical evidence,combination of Yinxin Damo injection and low molecular heparin treatment for DVT of orthopedics operation patients is effective and safe,but there is certain heterogeneity between the studies,therefore it is necessary to design a randomized controlled trial of high quality,large scale and multicenter to research.

Objective: The therapeutic effect of acid fibroblast growth factor 1(FGF1) on rats with diabetic cardiomyopathy (DCM) was evaluated by using nano-liposomes combined with ultrasound-targeted microbubble destruction technique (UTMD). Methods: The FGF1-loaded nano-liposomes were prepared by water-in-water emulsion method combined with lyophilization technique.TypeⅠdiabetes model was induced by intraperitoneal injection of streptozotocin (STZ, 70 mg/kg) in 60 male SD rats.Sixteen weeks later, diabetic rats were randomly divided into: placebo group (saline treatment), FGF1 group, FGF1-loaded nano-liposomes group, and FGF1-loaded nano-liposomes plus UTMD group (n=15 each). After two weeks of intervention followed by 2 weeks intervention stop, all rats underwent cardiac catheterization, and the left ventricular end-systolic pressure (LVESP), left ventricular end-diastolic pressure (LVEDP) and the maximal increase/decrease rate of left ventricular pressure (LV±dp/dtmax) were measured.Then, the rats were sacrificed and myocardial tissue were obtained for Masson trichrome staining, TUNEL apoptotic staining and CD31 immunohistochemistry staining to quantify myocardial collagen fraction (CVF), cardiac myocyte apoptotic index and myocardial microvascular density (MVD). Results: (1)Scanning electron microscope results revealed good morphology and FGF1 encapsulation efficiency (84.3±2.8)% with high stability and dispensability of FGF1 loaded nano-liposomes.(2)The hemodynamic evaluation showed that LVESP, LV + dp/dt_max and LV -dp/dt_max were all significantly higher, while LVEDP was significantly lower in the FGF1-loaded nano-liposome+ UTMD group than in DCM group, FGF1 solution group, and FGF1 nano-liposome group(all P<0.05). (3)The Masson trichrome staining demonstrated that CVF was significantly higher in all DCM groups than in control group and was significantly lower in the FGF1-loaded nano-liposome+ UTMD group than in DCM group, FGF1 solution group, and FGF1 nano-liposome group (all P<0.05). (4)The CD31 immunohistochemical staining results showed that MVD was significantly lower in all DCM groups than in control group and was significantly higher in the FGF1-loaded nano-liposome+ UTMD group than in DCM group, FGF1 solution group, and FGF1 nano-liposome group (all P<0.05). (5)The TUNEL results showed that apoptotic index was significantly higher in all DCM groups than in control group and was significantly lower in the FGF1-loaded nano-liposome + UTMD group than in DCM group, FGF1 solution group, and FGF1 nano-liposome group (all P<0.05). Conclusion FGF1 nano-liposomes combining with UTMD technique can significantly improve cardiac functions and attenuate myocardial CVF and apoptosis and enhance myocardial MVD in DCM rats.

AIM:To investigate the influence of Jiedu hugan granule on the inflammatory factor and tight junction protein of small intestine in rats with immunological liver injury.METHODS:Fifty SD rats were randomly divided into control group,model group,low,middle and high experimental group of Jiedu hugan granule (2.7,5.4,and 10.8 g/kg).All the groups excepted the control group received intraperitoneal injections of 0.5 mL pig serum for each to establish immunological liver injury model.The experimental group was irrigated ltime/d,continuous dosing for 14 d.The liver tissue and small intestinal tissue pathological changes were observed by HE staining,the serum alanine aminotransferase (ALT),aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were detected,and the expression of liver tissue TNF-α and small intestine tissue occludin-5 were detected by immunohistochemical method.RESULTS:The model group liver tissue showed accumulation of fat cells,liver cells enlargement,disorganized liver and associated with inflammatory cells infiltration;the experimental group liver cell morphological ruled,hepatic cords in alignment and inflammatory cells infiltration significantly decrease.The model group small intestinal mucosa villi showed atrophy,fall off of epithelial cell,edema,large number of inflammatory cells infiltration;the experimental group showed closelyknitted small intestinal mucosa villi,relieve edema,and no obvious infiltration of inflammatory cells.The levels of ALT,AST,LDH and TNF-α in experimental group were statistically lower than the model group,and the levels were statistically reduce with the dose of jiedu hugan granule increased.The levels of occludin-5 in experimental group were statistically highter than those of the model group,and the levels of occludin-5 were statistically increase with the dose of Jiedu hugan granule increased,the differences were statistically significant (P ＜ 0.05).CONCLUSION:Jiedu hugan granule can improve the organizational structure of liver and small intestine,protect the damage of liver,reduce inflammation,and maintain small intestine mucosal barrier function.

OBJECTIVETo investigate the clinical effect of steroids on reducing postoperative edema in rhinoplasty.

METHODSCochrane, Medline data, Pubmed date, were searched and updated on October 2013. Randomized controlled trials(RCTS) studies were included to assess the efficacy of steroids on decreasing postoperative edema after rhinoplasty. The methodological quality of the included studies was evaluated, and date analyses were performed using the Cochrane Collaboration's software RevMan 5.2.

RESULTSA total of 4 RCTS involved 172 patients with rhinoplasty, including 87 patients in the experimental group( steroid) and 85 paitents in control group (placebo). Meta analysis results showed the edema in experimental group was significantly less than that in the control group on postoperative day 1 and 3 (P < 0.01), while the difference was not significant on postoperative day 7 (P = 0.19).

CONCLUSIONSPerioperative application of steroid in rhinoplasty can significantly reduce periorbital edema in the first postoperative day. The edema can completely be relieved after application of steroid for 3 days. It is a safe and effective way to reduce the postoperative edema.

Objective To explore the clinical efficacy of early surgery combined with electron linac therapy on keloid.Methods The keloid patients with stable phase were selected;complete resection of keloid and relaxation suture were performed;after the surgery within 24 hours 6 MeV with Varian 2300CD radiotherapy was given,each measuring 4 Gy,total dose of 20 Gy.Results 860 cases of patients were colected for a period of 3 months to 36 months of regular follow-up,which recovered in 802 cases (cure rate was 93.26％),effective results were observed in 41 cases (effective rate of 4.77％),including 17 cases of recurrence (recurrence rate 1.98％),the total efficiency (cure plus effective) was 98.02％.Conclusions More accurately immediate radiotherapy after surgery can effectively reduce the recurrence rate,which is a safe and effective method in the treatment of keloids.