Objective:To analyze the efficacy and safety of Daratumumab for the treatment of primary AL light chain systemic amyloidosis.Methods:Twenty one patients who were diagnosed as primary AL light chain systemic amyloidosis and treated with Daratumumab from 7 centers were retrospectively analyzed. Daratumumab was administrated as first line therapy in seven patients and 14 patients with relapsed settings. Hematological response, safety and survival were analyzed.Results:All 7 patients achieved very good partial response (VGPR) or better with first-line application of daratumumab. Three patients died, and the other four achieved organ remission. Among 14 relapsed patients, 2 patients had a difference of free light chain (dFLC) less than 20 mg/L before treatment, and 9 with a dFLC of more than 50 mg/L. All patients reached partial response (PR) or better, including 4 patients with complete response (CR), 3 with VGPR and 2 with PR. The response rate was 100% in 3 patients with dFLC 20-50 mg/L at baseline. The organ remission rate was 50% in patients with heart involvement and 58.3% in patients with kidney impairment. The overall median follow-up period was 5.3 months, and 11 months in surviving patients. One patient died of severe infection and disseminated intravascular coagulation (DIC) with stable amyloidosis. One patient switched to other regimens because dFLC elevated but did not fulfill progressive disease after 2 year application. As to safety, no grade 3/4 infusion reaction developed, and grade 1 infusion reaction occurred in 3 cases during the first infusion. Lymphocytopenia was seen in 75% patients including grade 3 or more in 30% patients.Conclusion:Daratumumab is effective to eliminate serum free light chain in both newly diagnosed and relapsed patients with systemic amyloidosis.

Disorders of sex development (DSD) are a group of rare complex clinical syndromes with multiple etiologies. Distinguishing the various causes of DSD is quite difficult in clinical practice, even for senior general physicians because of the similar and atypical clinical manifestations of these conditions. In addition, DSD are difficult to diagnose because most primary doctors receive insufficient training for DSD. Delayed diagnoses and misdiagnoses are common for patients with DSD and lead to poor treatment and prognoses. On the basis of the principles and algorithms of dynamic uncertain causality graph (DUCG), a diagnosis model for DSD was jointly constructed by experts on DSD and engineers of artificial intelligence. "Chaining" inference algorithm and weighted logic operation mechanism were applied to guarantee the accuracy and efficiency of diagnostic reasoning under incomplete situations and uncertain information. Verification was performed using 153 selected clinical cases involving nine common DSD-related diseases and three causes other than DSD as the differential diagnosis. The model had an accuracy of 94.1%, which was significantly higher than that of interns and third-year residents. In conclusion, the DUCG model has broad application prospects as a computer-aided diagnostic tool for DSD-related diseases.

Objective:To investigate the cost-effectiveness of Helicobacter pylori ( H. pylori) antimicrobial susceptibility testing-guided therapy versus an effective empiric modified bismuth quadruple therapy for first-line H. pylori treatment. Methods:This cost-effectiveness analysis was based on the data from a multicenter prospective randomized controlled clinical trial (NCT02935010), which included 382 patients with H. pylori infection. Among them, 286 cases were in the antimicrobial susceptibility testing group, which were diagnosed by biopsy under endoscopy. And according to the results of antimicrobial susceptibility testing of H. pylori, patients were treated with triple or quadruple therapy of eradicating H. pylori for 14 days. A total of 96 patients were in empirical therapy group, which were diagnosed by biopsy under endoscopy (96 cases, endoscopy empirical group), who were treated with 14-day empiric bismuth quadruple therapy. At the same time, based on the patients of empirical group, a simulated 13C-urea breath test (UBT) empirical group (UBT empirical group) was set up (96 cases, H. pylori infection was first diagnosed by 13C-UBT examination) and in the cost accounting the expenses related to endoscopy, biopsy and drug sensitivity test were removed and the expense of 13C-UBT was added. The information of patients of endoscopy empirical group was kept. Taking the eradication rate of H. pylori as an effectiveness indicator, the cost, cost-effective ratio (CER), incremental cost-effective ratio (ICER) among antimicrobial susceptibility testing group, endoscopy empirical group and UBT empirical group were compared by intention-to-treat (ITT) analysis and per-protocol (PP) analysis. Sensitivity analysis was conducted based on the results of ITT analysis to evaluate the reliability of the research results. Results:The results of ITT analysis indicated that the cost of antimicrobial susceptibility testing group, endoscopy empirical group and UBT empirical group were (1 747.41±149.30), 1 032.71 and 657.71 Yuan, respectively. The cost of antimicrobial susceptibility testing group was (714.70±149.30) and (1 089.70±149.30) Yuan higher than that of the endoscopy empirical therapy group and UBT empirical therapy group, respectively. The CER of antimicrobial susceptibility testing group, endoscopy empirical group and UBT empirical group were (19.08±1.49), 12.09 and 7.70 Yuan/%, respectively. ICER of antimicrobial susceptibility testing group was (115.27±1.49) and (175.76±1.49) Yuan /% in comparison with the endoscopy empirical group and the UBT empirical therapy group. Compared with that of empirical group, the ICER of antimicrobial susceptibility testing group was more likely to be affected by H. pylori eradication rate and the cost of antimicrobial susceptibility testing. When the H. pylori eradication rate decreased in the empirical group, the ICER of the antimicrobial susceptibility testing group also decreased; when the H. pylori eradication rate increased in antimicrobial susceptibility testing group, the ICER decreased, and vice versa. When the cost of antimicrobial susceptibility test was upregulated or downregulated by 20%, for every 1% increase in the eradication rate of H. pylori in comparison with that of the endoscopy empirical group, the cost of the antimicrobial susceptibility testing group increased by 99.15 and 131.40 Yuan; in comparison with that of the UBT empirical group, the cost of the antimicrobial susceptibility testing group increased by 159.63 and 191.89 Yuan. Conclusions:For patients diagnosed with H. pylori infection by 13C-UBT and without indications for endoscopy examination, the empirical quadruple therapy is the first choice. For patients intended to do endoscopy to confirm H. pylori infection, with additional affordability of 115.27 Yuan for every 1% increase in the eradication rate of H. pylori, antimicrobial susceptibility testing can be conducted and personalized. H. pylori eradication therapy can be carried out based on the results of antimicrobial susceptibility test. Reduced cost of the antimicrobial susceptibility test will be more conductive to the promotion of personalized treatment after antimicrobial susceptibility test.

Objective : To observe the changes of soft tissue in patients with Angle class Ⅱ division Ⅰ malocclusion during mixed dentition treated with MRC functional appliance. Methods : Twenty patients with Class Ⅱ division Ⅰ malocclusion of Angle were treated with functional MRC. The facial features before and after treatment were measured by software and the results were analyzed statistically. Results: The patients′soft tissue profiles were improved significantly before and after treatment, The OE-Prn-Pos angle, OE-N′-B′ angle, OE-N′-Pos angle, OE-Prn-N′angle, Cm-Sn-UL angle, and N′-Sn-Pos angle increased significantly (P < 0.05). The OE-Sn-UL angle, and Sn-N′-B′ angle decreased significantly (P < 0.05); the distance between the lateral soft tissue line and the middle Sn-H line, UL-E line and LL-E line were significantly different (P < 0.05). The distances were all reduced, and the difference was statistically significant (P < 0.05). Conclusion The application of an MRC functional appliance can improve the relationship among nasolabial soft tissue, upper and lower lip soft tissue, and chin-lip soft tissue, thus improving the protrusion profile of patients.

Objective To explore the mechanisms of ligament of Marshall (LOM) initiat and sustain atrial fibrillation (AF).Methods The electrophysiologic properties of canine LOM were investigated using multipolar catheter mapping(normal canines,n =4,group A;AF canines,n =5,group B).The programmed stimulation were performed in the LOM,PV-left atrium(LA)junction and LA,respectively.Activations maps of LOM were analyzed from episodes of spontaneous onset of AF and initiation of induced AF by a single extrastimulus.The effectives refractory period of each part was compared and statistically analyzed among three parts in each group and between the two groups.LOM were cutted with surgical incision technology.The inducing rate of AF and the mapping rate of double potential and fragmented electrocardiogram were compared and statistically analyzed pro and post isolation of LOM.Results The incidence of abnormal potential of LOM in the two groups was significantly different(P ＜0.01),re-entry cycle(group A 25％ vs.B group 80％),tachycardia(group A 25％ vs.B 100％),double potential(group A 25％ vs.group B 80％),fragmentation potential(group A 25％ vs.group 80％).There was a significant difference in the rate of LOM tachycardia induction before and after LOM intervention in group B (P ＜ 0.05,before 100％ vs.after 20％).Conclusion There are two possible mechanisms of LOM involved in the occurrence and maintenance of AF:one is that LOM induces AF through spontaneous excitation,the other is that LOM participates in the reentry of left atrium and pulmonary vein in the form of bypass to induce and maintain AF.

Objective To investigate the correlation between the elastographic characteristics of liver and postoperative function of liver allografts.Methods Forty-eight cases of liver transplantation from The First Affiliated Hospital of Sun Yat-sen University were analyzed,Shear wave elastography (SWE) was performed before operation or at one week or one month post-operation.Liver function was evaluated by measuring alanine aminotransferase (ALT),aspartate transaminase (AST),total bilirubin (TBIL),γ-glutamine transferase (GGT),albumin (ALB),alkaline phosphatase (ALP),prothrombin time (PT),activated partial thromboplastin time (APTT),and international normalized ratio (INR).Early allograft dysfunction (EAD) was also analyzed with reference to SWE among liver transplant recipients.Results SWE at one week after transplantation was significantly correlated with TBIL (r=0.525 6,P<0.01),APTT (r=0.668 3,P<0.000 1),PT (r=0.593 7,P=0.000 1),INR (r=0.609 6,P<0.000 1) and prealbumin (r=-0.464 1,P<0.01).However,no significant correlation was observed between pre-operative SWE and parameters of post-operative liver function.SWE in EAD patients was higher than that of patients without EAD (17.60±1.09 kPa vs.13.38±0.99 kPa,P<0.01).The optimal cut-off value of SWE at one week post-operation was 14.85 kPa.Conclusion Postoperative SWE is significantly correlated with postoperative liver function tests and EAD,suggesting SWE is a potential test for evaluating the quality of liver allografts.

Objective Ischemia reperfusion injury (IRI) is a major limiting factor of graft survival in organ transplantation.We've established a novel procedure called ischemia-free liver transplantation (IFLT) in big animal study.In this report,we aimed to investigate the feasibility and early outcomes of IFLT.Methods We have performed 3 cases of IFLT during July 23,2017 to August 9,2017.We analyzed the surgical methods,normothermic perfusion parameters,blood gas analysis,liver function tests and complications early after liver transplantation.Pathologic studies and immunohistochemical staining of donor liver biopsies were conducted before procurement,at the end of machine perfusion,as well as after re-vascularization for evaluating IRI.Results The surgical procedures of all 3 patients were successful,without stoppage of blood supply for the liver grafts throughout organ procurement,ex vivo preservation and implantation.During normothermic perfusion,the pH value was stable within the normal range and the lactate levels dropped quickly to lower than detected (＜0.3 mmol/L) within 1.5-3 h.The livers continued to produce bile with the volume of 2-6 mL/h.Hematoxylin and eosin (HE) staining evaluation and TdT-mediated dUTP nick end labeling (TUNEL) assay of biopsies taken from liver tissues before procurement,at the end of machine perfusion and after re-vascularization,showed few necrostic and apoptotic hepatocytes in the liver biopsies.The immunohistochemical staining of IL-1β and vWF suggested no inflammatory cytokine release and sinusoidal endothelial cell activation.The three patients recovered smoothly without rejection,vascular and biliary complications.Conclusion IFLT is a feasible and effective procedure,which is able to overcome the major limitations of conventional procedure.The novel IFLT will become one of the mainstream transplant procedures in the future.

OBJECTIVE:To investigate clinical efficacy and safety of Kang'ai injection adjuvant chemotherapy for advanced lung cancer. METHODS:A total of 146 patients with advanced lung cancer during May 2013-Apr. 2014 were divided into observa-tion group and control group according to odd-even admission number,with 73 cases in each group. Control group was given GP (gemcitabine+cisplatin)chemotherapy. Observation group was additionally given Kang'ai injection 60 mL added into normal saline 250 mL,qd,ivgtt,for consecutive 14 d each chemotherapy cycle,on the basis of control group. Both groups were given tropise-tron 5 mg for preventing gastrointestinal reaction during chemotherapy. A treatment course lasted for 3 weeks,and both groups were treated for 3 courses. Clinical efficacies of 2 groups were compared;the levels of serum inflammatory factors (hs-CRP, TNF-α,IFN-γ,IL-10),immune function indexes(CD3+,CD4+,CD8+,CD4+/CD8+)and tumor markers(SCC-Ag,CEA,CA50, CA72-4) were compared before and after treatment. The occurrence of ADR were recorded in 2 groups. RESULTS:The response rate and disease control rate of observation group were 39.73％ and 84.93％,which were significantly higher than 23.29％ and 71.23％ of control group,with statistical significance(P<0.05). Before treatment,there was no statistical significance in the lev-els of serum inflammatory factors,immune function indexes or tumor markers between 2 groups (P>0.05). After treatment,the levels of hs-CRP,TNF-αand IFN-γin 2 groups were significantly lower than before treatment,while the level of IL-10 was signifi-cantly higher than before treatment;above indexes of observation group were significantly better than control group,with statistical significance(P<0.05). The levels of CD4+ and CD4+/CD8+ in control group were decreased significantly and lower than observa-tion group,with statistical significance(P<0.05). Serum levels of SCC-Ag,CEA,CA50 and CA72-4 in 2 groups were decreased significantly,and observation group was significantly lower than control group,with statistical significance(P<0.05). The inci-dence of thrombocytopenia,neutropenia,abnormal liver function,nausea and vomiting,anemia in observation group were signifi-cantly lower than control group,with statistical significance(P<0.05). CONCLUSIONS:Kang'ai injection adjuvant chemothera-py can effectively relieve inflammation symptoms of patients with advanced lung cancer,reduce toxic reactions,enhance immune function, and improve short-term therapeutic efficacy with good safety.

Although the efficacy of nucleos(t)ide analogue (NA) has been confirmed for treatment of chronic hepatitis B,long-term therapy has been recommended due to the high frequency of off-therapy viral DNA rebound and disease relapse.In this review,the RNA virion-like particles of hepatitis B virus (HBV) are integrated into the life cycle of HBV replication,and the potential significance of serum HBV RNA is systematically described.The production of HBV RNA virion-like particles should not be blocked by NA;in this regard,serum HBV RNA is found to be a suitable surrogate marker for the activity of intrahepatic covalently closed circular DNA (cccDNA),particularly among patients receiving NA therapy.Therefore,the concept of virological response is redefined as persistent loss of serum HBV DNA and HBV RNA.In contrast to hepatitis B surface antigen (HBsAg) that can originate from either the cccDNA or the integrated HBV DNA fragment,serum HBV RNA,with pregenomic RNA origination,can only be transcribed from cccDNA.Therefore,the loss of serum HBV RNA would likely be a promising predicator for safe drug discontinuation.The clinical status of consistent loss of serum HBV RNA accompanied with low serum HBsAg levels might be implicated as a "para-functional cure," a status nearly close to the functional cure of chronic hepatitis B,to distinguish the "functional cure" characterized as serum HBsAg loss with or without anti-HBs seroconversion.

Objective To investigate the long-term effect and radiation side reaction of different boost methods in patients with local remnants of locally advanced nasopharyngeal carcinoma after curative radiotherapy Methods Based on the retrospective analysis , 102 patients with local remnants of locally advanced nasopharyngeal carcinoma, after curative radiotherapy, were enrolled from February 2009 to May 2011. Forty-nine patients received gamma knife boost and 53 patients received 3-dimensional conformal radiotherapy (3D-CRT). The long-term effect and radiation side reaction were compared between the two groups. Results The 1-year, 3-year, and 5-year relapse-free survival rate (RFS) in the gamma knife boost group and the 3D-CRT group was 97.8%, 90.0%, 80.8%, and 94.3%,76.1%,72.9%, respectively (P < 0.05). No significant differences of the overall survival and metastasis-free survival rate wer found in two groups , as well as the long-term radioactive reaction. Conclusion The gamma knife boost is better than 3D-CRT with respect to local control rate , but the long-term radiation side reactions were similar between the methods.