OBJECTIVE: To evaluate the efficacy and safety of Cidan Capsule combined with adjuvant transarterial chemoembolization (TACE) in patients with a high risk of early recurrence after curative resection of hepatocellular carcinoma (HCC). METHODS: A multicenter, randomized controlled trial was conducted in patients with high-risk recurrence factors after curative resection of HCC from 9 medical centers between July 2014 and July 2018. Totally 249 patients were randomly assigned to TACE with or without Cidan Capsule administration groups by stratified block in a 1:1 ratio. Postoperative adjuvant TACE was given 4-5 weeks after hepatic resection in both groups. Additionally, 125 patients in the TACE plus Cidan group were administrated Cidan Capsule (0.27 g/capsule, 5 capsules every time, 4 times a day) for 6 months with a 24-month follow-up. Primary endpoints included disease-free survival (DFS) and tumor recurrence rate (TRR). Secondary endpoint was overall survival (OS). Any drug-related adverse events (AEs) were observed and recorded. RESULTS: As the data cutoff in July 9th, 2018, the median DFS was not reached in the TACE plus Cidan group and 234.0 days in the TACE group (hazard ratio, 0.420, 95% confidence interval, 0.290-0.608; P<0.01). The 1- and 2-year TRR in the TACE plus Cidan and TACE groups were 31.5%, 37.1%, and 60.8%, 63.4%, respectively (P<0.01). Median OS was not reached in both groups. The 1- and 2-year OS rates in TACE plus Cidan and TACE groups were 98.4%, 98.4%, and 89.5%, 87.9%, respectively (P<0.05). The most common grade 3-4 AEs included fatigue, abdominal pain, lumbar pain, and nausea. One serious AE was reported in 1 patient in the TACE plus Cidan group, the death was due to retroperitoneal mass hemorrhage and hemorrhagic shock, and was not related to study drug. CONCLUSIONS Cidan Capsule in combination with TACE can reduce the incidence of early recurrence in HCC patients at high-risk of recurrence after radical hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment. (Registration No. NCT02253511).

Objective:To investigate the effects of myeloid differentiation protein-2 (MD-2) on paclitaxel resistance cells in triple negative breast cancer (TNBC) through EGFR signaling pathway.Methods:Immunohistochemical method was used to detect the expression of MD-2 in cancer tissue and adjacent tissue of TNBC patients, and the relationship between MD-2 expression and clinicopathological parameters of patients was analyzed. The TNBC paclitaxel-resistant cell line was constructed and MD-2 expression in cells was interfered. Cell invasion was detected by Transwell, and cell apoptosis was detected by flow cytometry. The signaling pathways regulated by MD-2 were screened by transcriptome sequencing and verified by Western blot.Results:The expression of MD-2 was significantly enhanced in cancer tissues relative to adjacent tissues. High expression of MD-2 was closely related to clinical stage, tumor size, tumor recurrence and metastasis ( χ2=4.50, P=0.032; χ2=2.55, P=0.011; χ2=4.40, P=0.036). In cell experiments, compared with normal breast cells, the expression of MD-2 in TNBC cell lines was significantly enhanced. Compared with sh-NC group (100±11.52) (6.81±0.57), knockdown of MD-2 could inhibit the invasion (61.44±6.78) ( t=4.99, P=0.008) but promote apoptosis (15.19±1.06) ( t=12.06, P<0.001) of paclitaxel resistant TNBC cells. Transcriptome sequencing and Western blot results showed that MD-2 mainly affects the biological behavior of TNBC cells by regulating the EGFR signaling pathway. Conclusions:MD-2 promoted TNBC cell invasion and paclitaxel resistance, which may be achieved by affecting the EGFR signaling pathway. MD-2 is expected to become an effective target in TNBC treatment.

Objective To investigate the effects of Sacubitril/Valsartan on amino terminal probrain natriuretic peptide (NT-proBNP),high sensitivity C-reactive protein (hs-CRP),soluble suppression of tumorigenicity 2(sST2)levels and on left ventricular(LV)structure in NYHA Ⅳ heart failure with reduced ejection fraction(HFrEF) patients.Methods A total of 67 HFrEF patients with NYHA Ⅳ were randomly divided into the control group (n =30)receiving conventional medical treatment,and the observation group(n=32)receiving Sacubitril/Valsartan instead of ACEI(or ARB if ACEI induced cough) in conventional medical treatment.NT-proBNP levels were determined by fluorescer-enhanced chemiluminescence.hs CRP levels were detected by latecx enhanced immunoturbidimetric assay.sST2 levels were determined by enzyme-linked immunosorbent assay (ELISA).The modified Simpson method was used to detect left ventricular end-diastolic diameter (LVEDD),LV posterior wall(LVPW)and LV ejection fraction(LVEF).Two groups of patients were treated and followed-up for 6 months.Results Clinical efficacy was better in the observation group than in the control group(effective rate,20 cases or 61.3％ vs.8 cases or 26.7％,P＜0.05).As compared with the control group,the observation group of patients had an increased LVEF[(46.7±9.2) ％ vs.(41.8±8.0)％,P＜0.05]and a decreased LVEDD[(52.6±6.7)mm vs.(58.8±7.5)mm,P＜0.05].After vs.before treatment,NT-proBNP,hs-CRP and sST2 levels were decreased in both control and observation groups [(1 427 ± 219) μg/L vs.(2 615 ± 273)μg/L,(1.14 ± 1.02) mg/L vs.(1.55±1.38)mg/L,(0.30±0.12)μg/L vs.(0.41±0.10)μg/L,all P＜0.05],and the decrements were much more in the observation group than in the control group (P＜0.05).The annual accumulated frequence and duration of hospitalization were less in the observation group than in the control group[(0.8±0.6)times vs.(1.8±1.0) times,(10.2±5.8)d vs.(16.5±7.2)d,P＜0.05].The maintenance dose of tolasemide was lower in the observation group than in the control group [(15.2±8.4)mg vs.(20.6±10.8)mg,P＜0.05].Conclusions Sacubitril/valsartan therapy is safe and effective and it can reduce hs-CRP and sST2 levels and improve the ventricular remodeling in HFrEF patients of HYHA Ⅳ.

Objective: To observe the effect of edaravone combining ulinastatin on brain protection in patients of type A aortic dissection (AAD) after total arch replacement. Methods: A total of 60 AAD patients with total arch replacement in our hospital from 2014-09 to 2016-01 were prospectively studied. Based on peri-operative application of edaravone and ulinastatin, the patients were divided into 2 groups: EU group: 1) the patients received ulinastatin 300000 U/8h and edaravone 0.5mg/Kg/12h from administration to 3 days post-operation, 2) during cardiopulmonary bypass, the patients received ulinastatin 300000 U/2h and edaravone 0.5mg/Kg; Control group, the patients had no such treatment.n=30 in each group. The following items were observed:①operative condition;②blood levels of speciifc brain injury markers as S-100 and neuron speciifc enolase (NSE) at different time points: beginning of surgery (T0), opening aorta clamp (T1), right after cardiopulmonary bypass (T2), entering ICU (T3), 24h post-operation (T4) and 3 days post-operation (T5); ③post-operative condition. Results:①Durations of operation, cardiopulmonary bypass, cardiac arrest and bilateral antegrade selective cerebral perfusion (BACP), the frequency of BACP and UACP (unilateral antegrade selective cerebral perfusion), the lowest rectal temperature and blood levels of S-100, NSE at T0 were similar between 2 groups.②Compared with Control group, EU group had decreased S-100 and NSE from T1 to T5,P<0.05.③The in-hospital and ventilation time, frequency of PND and TND, the patients with CSS score≥16 before discharge and the in-hospital death rate were similar between 2 groups,P>0.05. Conclusion: Edaravone combining ulinastatin had brain protective effect in AAD patients after total arch replacement;it may reduce blood speciifc brain injury markers while the clinical signiifcance should be further investigated.

Objective To summarize and analyze the clinical features,diagnosis,surgical approaches and treatment outcomes of patients with primary nasal sinus osteoma.Methods A retrospective review of 48 cases with primary nasal sinus osteoma treated from January 2007 to December 2013 was performed.All patients underwent preoperative CT scan and postoperative histopathologic examination.The surgical approaches included lateral rhinotomy in 14 cases,nasal endoscopic resection in 12 cases,coronal surgical incision craniotomy in 13 cases,combined craniofacial approach in 4 cases,and Caldwell-Luc approach in 5 cases.Results The postoperative pathological diagnosis consisted of 3 variants,including 20 for compact type and 15 for cancellous type,and 13 for mixed type.Six cases were lost to follow-up and 42 cases were followed up for 6-60 months,5 cases recurred.The post-operative complications included sinus mucous cyst in 4 cases,cerebrospinal fluid leak in 3 cases.Conclusions Nasal sinus osteoma are common.CT or MRI is helpful to evaluate the osteoma size,location and possible sources,and to make operation scheme.Surgery is the first choice for sinus osteoma.Lateral rhinotomy and nasal endoscopic resection can be applied to most sinus osteoma.The prognosis of sinus osteoma is good,with fewer recurrence.

OBJECTIVETo assess the effect of normothermic arch-first technique without extracorporeal circulation in total aortic arch replacement for management of acute Stanford type A dissection.

METHODSThe surgical data were reviewed for 23 patients (age range 32-58 years) with Stanford type A dissection undergoing total aortic arch replacement with the arch-first technique in our department between January, 2006 and November, 2011. During the surgery, a 4-branched prosthetic graft was connected with the inflow tube and femoral artery using the Y-type tube. The 3 aortic branches were disconnected and anastomosed to the respective branches of the graft, with continuous perfusion of the brain by femoral arterial return. After clamping of the ascending aorta, the graft was connected to the remaining arch before the common stem of the graft was anastomosed with the aortic root.

RESULTSThe operations were successfully completed in all the 23 cases with a mean total bypass time of 187∓60 min (117-254 min), mean ascending aorta clamping time of 35∓8 min, and mean nasopharyngeal temperature of 22∓2 celsius;. Death occurred in one case (4.3%) after the operation, and 2 (8.7%) patients experienced temporary neurological dysfunctions. The postoperative consciousness recovery time was 6-8 h in these cases. The shortest postoperative mechanical ventilation time was 18 h, and 11 (48%) patients were weaned from mechanical ventilation within 48 h postoperatively. The ICU stay ranged from 3 to 7 days in these cases.

CONCLUSIONNormothermic arch-first technique without extracorporeal circulation can provide better brain protection and reduced the incidence of postoperative complications by shortening the time of circulation bypass and aortic clamping.

Adult ; Aneurysm, Dissecting ; surgery ; Aorta ; surgery ; Aorta, Thoracic ; surgery ; Aortic Aneurysm, Thoracic ; surgery ; Cardiovascular Surgical Procedures ; methods ; Extracorporeal Circulation ; Female ; Humans ; Hypothermia, Induced ; Male ; Middle Aged ; Stents ; Treatment Outcome

Objective To study the clinical diagnosis and treatment of malignant gastrointestinal stromal tumor. Methods To retrospectively analyze the clinical data of 28 cases with malignant gastrointestinal stromal tumors underweat surgical treatment . Results The malignant gastrointestinal stromal tumor in adults were more than 50 years old,71.4%(20/28) ,and common clinical symptoms were gastrointestinal bleeding,anemia,and pain. The lesion site: 19 cases of gastric bowel, 8 cases of small intestine, 1 case of colon, radical excision in 22 cases, local excision palliative resection in 5 cases, three cases were multi-visceral resection. Conclusion Malignant gastrointestinal stromal tumor could be diagnosed by the means of endoscopic imaging and clear,and preoperative diagnosis was difficult. Surgical resection was the pathology diagnosis and treatment of primary method,if necessary,to ensure multi-visceral resection of the tumor to prevent recurrence of thoroughness, had important significance.

To investigate the immunological activities of the recombinant human phosphatase D2 (rhPLD2) in vitro and in vivo, especially its ability to reduce inflammatory reactions, the cDNA fragment encoding rhPLD2 was cloned into prokaryotic expression vector pET30a by RT-PCR and the recombinant protein rhPLD2 expressed in E.coli was purified from the inclusion bodies, while the anti inflammatory activity of rhPLD2 was determined by the amount of eosinophils in bronchoalveolar fluid(BALF) and blood and the expression of IL-5 and MMP-9 in lung tissues of guinea pig model of chronic asthma. It was found that the rhPLD2 recombinant protein was obtained from human Daudi cells by cloning to E.coli, which contained no membrane-binding site and signal peptide. The cDNA sequence encoded 631 amino acid residues (GenBank Accession Number: AY178289). The purity of the rhPLD2 approached up to 76% with a bioactivity of 50.9745 units/L (0.9212 g/L). In addition, the anti inflammatory effect of rhPLD2 protein could be demonstrated in the guinea pig model of chronic asthma after treatment with rhPLD2 protein, such as down regulation in the expression of the inflammatory cytokine IL-5. It is concluded that the anti-inflammator activity of the recombinant human truncated PLD2 protein produced from the E.coli plasmid can be demonstrated both in vitro and in vivo.

OBJECTIVE To study whether immunosuppressant(IS,cyclophosphamide,CPA) have the function of prevention and treatment of congenitalautoimmune sensorineural hearing loss or not.METHODS The female guinea pigs were immunized by crude conspecific inner ear antigens(CIEAgs),and took orally IS or not at the same time during gestation.Then the pregnant guinea pig's and their offspring's hearing function were measured and inner ear histopathologic changes were observed.Some of offspring borne by the female guinea pigs which immunized with CIEAgs and not treated with IS showed hearing loss and were treated by IS,and their hearing functions were measured and inner ear histopathologic changes were observed with same techniques.RESULTS After immunizing with CIEAgs,some of female guinea pigs which immunized with CIEAgs and not treated with IS showed different degrees of hearing loss(the thresholds of acoustic nerve compound active potential and cochlear microphonic potentials elevated) and immune inflammations in inner ear tissues.All females guinea pigs in experimental group which immunized with CIEAgs and treated with IS at same time,and their offspring have no any hearing loss and inner ear histopathologic changes.After IS therapy,the hearing function improved(mainly at the low-frequency region) in some offspring guinea pigs,which borne by the female guinea pigs which immunized with CIEAgs and not treated with IS.CONCLUSION IS could effectively prevent offspring's congenital sensorineural hearing loss induced by their mother's special antibodies against inner ear tissues antigens.IS showed effective result for treatment of congenitalautoimmune sensorineural hearing loss,but the curative effect was limited.

Objective To rapidly detect and identify pathogenic fungi of some deep fungal infections by PCR.Methods The suspensions of22pathogenic fungi(23strains)were amplified by PCR with fungal universal primers ITS86and ITS4which were labeled by FAM.The precise length of amplified fragments was determined by ABI PRISM TM 377Sequencer and Genescan analysis software,then compared with that of am-plicons of corresponding fungal DNA which were previously extracted.Results(1)Amplification of17pathogenic fungi with ITS4,ITS86resulted in a unique fragment length(except for A.nidulans and A.niger,C.albicans and C.stellatoidea,F.pedrosoi and E.dermatitidis).(2)No significant difference of the length of am-plicons was found between the fungal suspension and control organisms,based on the results of Genescan analysis.(3)The whole process took only6h to complete the detection.Conclusion The combination of fun-gal suspension PCR with ITS fungal universal primers and Genescan analysis might provide an accurate,spe-cific,sensitive,and rapid approach to detect and identify22pathogenic fungi causing deep fungal infections,and hold promise to be applied for the diagnosis of deep fungal infection.