PARP [poly(ADP-ribose)polymerase] represents a novel potential target in cancer therapy. It is involved in a DNA repair process by catalyzing the transfer of ADP-ribose units from NAD to a number of its substrate proteins. In this work, a series of novel azaindole derivatives was designed and synthesized. Moreover, 16 target molecules were screened and 8 compounds displayed inhibitory activity against PARP-1. It has been demonstrated that these azaindoles bearing cycloamine substituents at 2-position were active to both PARP-1 and PARP-2.

Objective To study the clinic imaging features and the clinic applications of the contrastenhanced ultrasound(CEUS) in the diagnosis of gallbladder carcinoma.Methods The characteristics of CEUS were reviewed in 24 patients with gallbladder carcinoma proven pathologically. Results After injection of SonoVue, all gallbladder carcinoma of 24 cases showed enhancement and these lesions looked clearer than those in conventional ultrasound.The analysis of time-intensity curve indicated the upslope of curve was steep in the lesions,which was flat in normal liver parenchyma around.In 10 cases of thick wall of gallbladder carcinoma, quick and obvious enhancement was seen in 9 cases, 1 case showed poor enhancement during scanning,but thick and tortile blood vessels could be seen in the thickening wall.Quick and uneven enhancement was been seen in both 8 cases of soft-tissue mass and 6 cases of nodules within gallbladder.Five cases of gallbladder carcinoma with liver metastasis revealed more liver metastasis depend on CEUS.Conclusions CEUS plays an important role in diagnosis and improving the diagnostic accuracy for gallbladder carcinoma.

Objective To investigate the potential association between SEPS1 variants and Hashimoto's thyroiditis (HT)in the Chinese Han population and evaulate the effects of SEPS1 haplotypes on the susceptibility to immunity-mediated diseases.Methods We analyzed 7 SNPs with minor allele frequency (MAF)≥0.05 in a cohort of 1013 HT patients and 2998 healthy controls from genetically independent Han Chinese individuals.Single SNP,haplotype and gender-specific associations were performed. Results We found that rs28665122 was significantly associated with HT,and SNP was associated with HT in females.Further haplotypic analysis indicated that a haplotype block (rs2009895-rs28665122)spanning the promoter of SEPS1 gene was highly associated with HT. Additionally,the haplotype CA in the block had an almost 1.5-fold increase in these cases,which remained significantly associated with HT in females.Conclusion SEPS1 plays a role in the pathogenesis and etiology of HT.

Aim To observe the infarct size, apoptosis of the neurocytes,the expressions of Bcl-2 and Bax pro-teins after focal cerebral ischemia-reperfusion injury (CIRI) in the brain tissue of rats and the protective effects of rofecoxib.Methods The model of local CIRI was induced by reversible middle cerebral artery occlusion (MCAO) with inserting a thread through internal carotid artery,2 h occlusion followed by 24 h reperfusion.Rofecoxib was administrated (ig) at the reperfusion initiation. Using TTC staining technique to measure the infarct size of brain,TUNEL technique to examine apoptosis of the neurocytes,immunohistochemical method to examine the expression level of Bcl-2 and Bax proteins in brain tissue.Results After focal CIRI,the infarct focus of brain was showed,both apoptosis rate of the neurocytes and Bax protein expression were significantly increased and the ratio of Bcl-2 to Bax was significantly reduced.With the use of both 1.12 and 2.24 mg?kg -1 doses of rofecoxib,the brain infarct size was dramatically reduced. With the use of 2.24 mg?kg -1 dose of rofecoxib,both apoptosis rate of the neurocytes and Bax protein expression were significantly decreased,both Bcl-2 protein expression and the ratio of Bcl-2 to Bax were significantly higher than that in the group Model.Conclusion The highly selective COX-2 inhibitor rofecoxib may increase Bcl-2 protein expression and decrease Bax protein expression then increase the ratio of Bcl-2 to Bax and so reduce the neurocytes apoptosis in brain tissue thus significantly improve the brain injury after CIRI.

Objective:To investigate the efficacy and safety of fecal microbiota transplantation (FMT) in the treatment of irritable bowel syndrome (IBS), and to explore the effects of FMT on the gut microbiota of IBS patients.Methods:From September 2016 to August 2017, at Guangzhou First People′s Hospital, 28 hospitalized IBS patients who underwent FMT treatment were enrolled. Before FMT, four and 12 weeks after FMT, all the IBS patients completed the irritable bowel syndrome quality of life scale (IBS-QOL), irritable bowel syndrome severity scoring system (IBS-SSS) and gastrointestinal symptom rating scale (GSRS). 16S rDNA sequencing was performed before FMT and four weeks after FMT. The effects of FMT on gut microbiota diversity and microbiota structure of IBS patients were analyzed respectively from the level of phylum, family and genus, and linear discriminant analysis effect size (LEfSe) was further used to screen the different bacteria. Paired t test and paired rank sum test were used for statistical analysis. Results:Twelve weeks after FMT, the scores of the six dimensions of IBS-QOL including dysthymia, behavioral disorder, auto imagery, health concerns, eating avoidance, and relationship expansion were all lower than those before FMT (43.750, 22.656 to 56.250 vs. 48.438, 32.031 to 60.938; 37.500, 18.750 to 56.250 vs. 46.429, 21.429 to 62.500; 31.250, 14.063 to 42.188 vs. 31.250, 18.750 to 50.000; 41.667, 27.083 to 56.250 vs. 50.000, 41.667 to 66.667; 54.167, 43.750 to 72.917 vs. 66.667, 58.333 to 83.333; 8.333, 0.000 to 33.333 vs. 16.667, 8.333 to 33.333, respectively), and the differences were statistically significant ( Z=-2.157, -3.429, -2.274, -3.197, -3.042 and -2.329, all P<0.05). Twelve weeks after FMT, the scores of the two dimensions of IBS-QOL including behavioral disorder and relationship expansion were both lower than those of four weeks after FMT (37.500, 18.750 to 56.250 vs. 39.286, 19.643 to 62.500 and 8.333, 0.000 to 33.333 vs. 16.670, 2.083 to 41.667, respectively), and the differences were statistically significant ( Z=-1.998 and -2.110, both P<0.05). Four and 12 weeks after FMT, the scores of IBS-SSS and GSRS were both lower than those before FMT ((190.32±106.51), (201.43±102.48) vs. (245.93±86.10) and 5.50, 4.00 to 9.00 and 5.50, 4.00 to 8.75 vs. 7.00, 6.00 to 9.75), and the differences were statistically significant ( t=4.402 and 3.848, Z=-3.081 and -3.609; all P<0.01). No serious adverse reactions occurred in the patients after FMT. At the phylum level, after FMT the abundance of Verrucomicrobia in the feces of IBS patients was richer than that before FMT (6.74% vs. 0.37%); at the family level, after FMT the abundance of Verrucomicrobiaceae in the feces of IBS patients was richer than that before FMT (6.74% vs. 0.37%); at the genus level, after FMT the abundance of Akkermansia was richer than that before FMT (6.74% vs. 0.37%); and the differences were statistically significant (all Z=-2.589, all P=0.010). The results of LEfSe method indicated that four weeks after FMT the abundance of Akkermansia in the gut microbiota of IBS patients was richer than that before FMT (6.74% vs. 0.37%), and the difference was statistically significant (linear discriminant analysis value=4.5, P=0.049). Conclusions:FMT is safe and effective in the treatment of IBS. The mechanism may be through upregulating the diversity of gut microbiota and changing the structure of gut microbiota of IBS patients.

Objective To explore the diagnostic value of tumor necrosis factor-alpha (TNF-α) , interleukin-6 (IL-6) and neuron enolase (NSE) in the cerebrospinal fluid of children with central nervous sys-tem infection (CNSI).Methods 54 cases of CNSI hospitalized children ,admitted in the hospital from October 2015 to January 2017 ,were enrolled in the study and divided into viral meningitis group (30 cases) and suppu-rative meningitis group (24 cases).Another 20 cases who underwent cerebrospinal fluid examination and other related examinations were enrolled in the study as the control group.The levels of three biomarkers TNF-α , IL-6 and NSE in cerebrospinal fluid of three groups were detected by enzyme linked immunosorbent assay (ELISA).Results The levels of TNF-α ,IL-6 and NSE in purulent meningitis group were the hightest ,and the levels of these three factors in viral meningitis group were highter than the control group ,and the differ-ence was statistically significant in three groups (P＜0.05).But there were a lot of data overlaps.There was no significant difference in the levels of TNF-α ,IL-6 and NSE between the brain group and the control group (P＞0.05).Conclusion The detection of TNF-α ,IL-6 and NSE in cerebrospinal fluid has a certain clinical val-ue for the diagnosis of CNSI ,but it needs to be further verified by a large sample clinical trial.

The clinical data of a child with anaplastic lymphoma kinase positive histiocytosis (ALK+ H) diagnosed in April 2020 by Kunming Children′s Hospital were retrospectively analyzed.The male child was 4 months and 29 days old and had multiple nodules throughout the body since 1 week after birth.Skin sarcoidosis examination showed non-Langerhans cell histiocytosis, and immunohistochemistry showed ALK (+ ), CD1a (-), and CD 163(+ ). Therefore, this patient was diagnosed as ALK+ H, which was very rare in clinical practice.Previously reported cases mainly showed soft tissue nodules or thrombocytopenia with anemia.In addition to multiple nodules throughout the body, this patient also had elevated platelets, neutropenia, and abnormal liver function, which was different from previous reports.Hence, this case could be used as a supplement to the disease database.

Objective To evaluate the effect of preoperative pulmonary artery pressure on perioperative prognosis of the recipients with end-stage heart failure undergoing heart transplantation. Methods Clinical data of 105 recipients receiving heart transplantation were retrospectively analyzed. The mean pulmonary artery pressure (mPAP) was used as the diagnostic criterion. The optimal cut-off value of mPAP for predicting perioperative prognosis of heart transplant recipients was determined. According to the optimal cut-off value of mPAP, all recipients were divided into the low mPAP group (n=66) and high mPAP group (n=39). Intraoperative indexes (cardiopulmonary bypass time, aortic occlusion time, assisted circulation time and cold ischemia time of donor heart) and postoperative indexes [intra-aortic balloon pump (IABP) support rate, IABP support time, extracorporeal membrane oxygenation (ECMO) support rate, ECMO support time, mechanical ventilation time, length of ICU stay, incidence of moderate and severe tricuspid regurgitation and perioperative mortality rate] were compared between the low and high mPAP groups. The prognosis of the two groups was compared. Results The optimal cut-off value of mPAP in predicting clinical prognosis of heart transplant recipients was 30.5 mmHg. In the high mPAP group, the ECMO support rate and perioperative mortality rate were higher than those in the low mPAP group (both P < 0.05). No significant differences were observed in the cardiopulmonary bypass time, aortic occlusion time, assisted circulation time, cold ischemia time of donor heart, IABP support rate, IABP support time, ECMO support time, mechanical ventilation time, length of ICU stay and incidence of moderate and severe tricuspid regurgitation between two groups (all P > 0.05). No significant differences were noted in the 1-, 2-, 3- and 4- survival rates between two groups (all P > 0.05). Conclusions Preoperative mPAP in patients with end-stage heart failure is intimately correlated with perioperative prognosis of heart transplant recipients. The optimal cut-off value of mPAP in predicting perioperative prognosis of heart transplant recipients is 30.5 mmHg. In the high mPAP group, perioperative ECMO support rate and perioperative mortality rate are high, which do not affect the medium and long-term prognosis of the recipients undergoing heart transplantation.

Objective:To explore the clinical features and diagnostic methods of primary ciliary dyskinesia (PCD).Methods:A case of PCD diagnosed by Kunming Children's Hospital was analyzed retrospectively (including general information, clinical characteristics, auxiliary examination results), and the literature was reviewed.Results:The patient, an 8-year-old female, went to hospital for repeated cough and suffered from pneumonia and sinusitis repeatedly in the past. The electron microscope of cilia biopsy showed that the number of cilia was reduced. The mutation of c.7615T>C (p.W2539R) in DNA H5 gene located in chr5-13,809,290 was detected by gene test, so the patient was diagnosed as PCD.The mutation site was a new mutation site.Conclusion:PCD is a rare disease in children. Electron microscopy and genetic examination are helpful to the diagnosis of PCD. Children with recurrent respiratory tract infection and wet cough should be alert to the possibility of PCD.

Objective:To explore the clinical outcomes of recipients with refractory heart failure requiring an insertion of mechanical circulation support(MCS)device prior to heart transplantation(HT).Methods:From March 2017 to December 2021, retrospective review is performed for clinical data of 7 recipients with refractory heart failure requiring a bridging placement of MCS.There are 2 males and 5 females with an average age of(39.0±16.3)years(7~56 years)and an average weight of(57.6±19.9)kg(7~56 kg).The primary diseases of recipients are dilated cardiomyopathy(4 cases)severe viral myocarditis(2 cases)and ischemic cardiomyopathy(1 case).All of them develope acute decompensation of congestive heart failure.Before implanting MCS, two or more inotropic drugs are offered at maximal doses ages or IABP device, 6 cases required cardio-pulmonary resuscitation treatment and another patient for Heartcon assistance.All the patients bridge to heart transplatation.Results:Adjuvant therapy of MCS was offered for(20.0±11.5)d(7~34 d).Emergency HT is performed.Two post-HT deaths occurr due to multiple organ failure(1 case)and severe infection(1 case).The remainders recover smoothly during a follow-up period of(6~24 months).Conclusions:MCS device is recommended as a bridging too for HT recipients with refractory heart failure.It is imperative to improve clinical outcomes with MCS support before an onset of multiple organ dysfunction.Despite a perioperative mortality, long-term prognosis is generally satisfactory.