Objective:To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province.Methods:This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized.Results:Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion:Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.

Objective:To summarize the distributional characteristics of postoperative occurrence of multi-drug resistant organism (MDRO) infections and their risk factors in simultaneous pancreas-kidney transplantation (SPK) recipients and examine the impact of MDRO infections on the survival of SPK recipients.Method:From January 2016 to December 2022, the relevant clinical data were retrospectively reviewed for 218 SPK recipients. The source of donor-recipient specimens and the composition percentage of MDRO pathogens were examined. According to whether or not MDRO infection occurred post-transplantation, they were assigned into two groups of MDRO (98 cases) and non-MDRO (120 cases). The clinical data of two groups of donors and recipients were analyzed. And the risk factors for an onset of MDRO infection were examined by binary Logistic regression. The survival rate of two recipient groups was compared by Kaplan-Meier method.Result:A total of 98/218 recipients (45%) developed MDRO infections. And 46 (46.9%) of sputum and 34 (34.7%) of urine were cultured positively and 49 (50%) pathogens expressed extended spectrum beta-lactamase. There were pneumonia (46 cases, 46.9%), urinary tract infections (34 cases, 34.7%), abdominal infections (16 cases, 16.3%) and bloodstream infections (2 cases, 2.0%). Univariate regression analysis revealed that length of renal failure ( P=0.037), length of hospitalization ( P<0.001), length of antibiotic use ( P<0.001), novel antibiotics ( P=0.014), albumin ( P<0.001) and leukocyte count ( P<0.001) were risk factors for an onset of MDRO infections. The results of multifactorial regression indicated that low albumin ( OR=0.855, 95% CI: 0.790~0.925, P<0.001) and leukopenia ( OR=0.656, 95% CI: 0.550~0.783, P<0.001) were independent risk factors for an onset of MDRO infections. The survival rates of recipients in MDRO group at Year 1/3 post-operation were 92.9% (91/98) and 89.8% (88/98). And the survival rate of recipients in non-MDRO group was 96.7% (116/120) at Year 1/3 post-operation. Inter-group difference was not statistically significant in 1-year survival rate of two recipient groups ( P=0.201); statistically significant inter-group difference in 3-year survival rate between two recipient groups ( P=0.041) . Conclusion:Low albumin and leukopenia are risk factors for MDRO infection. Infection with MDRO has some impact on the survival of recipients.

Purpose: Oligometastatic non–small cell lung cancer (NSCLC) patients have been increasingly regarded as a distinct group that could benefit from local treatment to achieve a better clinical outcome. However, current definitions of oligometastasis are solely numerical, which are imprecise because of ignoring the biological heterogeneity caused by genomic characteristics. Our study aimed to profile the molecular alterations of oligometastatic NSCLC and elucidate its potential difference from polymetastasis. Materials and Methods: We performed next-generation sequencing to analyze tumors and paired peripheral blood from 77 oligometastatic and 21 polymetastatic NSCLC patients to reveal their genomic characteristics and assess the genetic heterogeneity. Results: We found ERBB2, ALK, MLL4, PIK3CB, and TOP2A were mutated at a significantly lower frequency in oligometastasis compared with polymetastasis. EGFR and KEAP1 alterations were mutually exclusive in oligometastatic group. More importantly, oligometastasis has a unique significant enrichment of apoptosis signaling pathway. In contrast to polymetastasis, a highly enriched COSMIC signature 4 and a special mutational process, COSMIC signature 14, were observed in the oligometastatic cohort. According to OncoKB database, 74.03% of oligometastatic NSCLC patients harbored at least one actionable alteration. The median tumor mutation burden of oligometastasis was 5.00 mutations/Mb, which was significantly associated with smoking, DNA damage repair genes, TP53 mutation, SMARCA4 mutation, LRP1B mutation, ABL1 mutation. Conclusion Our results shall help redefine oligometastasis beyond simple lesion enumeration that will ultimately improve the selection of patients with real oligometastatic state and optimize personalized cancer therapy for oligometastatic NSCLC.

Objective:To summarize the clinical characteristics and risk factors of acute rejection(AR)of transplanted pancreas and kidney after simultaneous pancreas-kidney transplantation(SPK)and explore the effects of AR on the survival of transplanted pancreas, kidney and recipients.Methods:From September 2016 to July 2022, the relevant clinical data were retrospectively reviewed for 218 recipients undergoing SPK.According to whether or not AR occurred after SPK, they were assigned into two groups of AR(n=53)and non-AR(n=165). The relevant clinical data were compared for two groups of donors and recipients and the risk factors of AR analyzed by binary Logistic regression.Kaplan-Meier method was employed for comparing the survival rates of recipients/transplanted pancreas and kidneys in two groups.Results:A total of 53 cases(24.3%)developed ARs of transplanted pancreas(n=31, 14.2%)(5 of 2 ARs), transplanted kidney(n=15, 6.9%)(1 of 2 ARs)and transplanted pancreas & kidney AR(n=11, 5.0%)(2 of 2 ARs). Tacrolimus blood levels in AR and non-AR groups were(5.8±1.2)and(6.3±1.6)μg/L and failed to attain targets in 36(67.9%)and 78(47.3%)cases.During follow-ups, the incidence of pneumonia and urinary tract infections in AR group versus non-AR group were[43.4%(23/53)vs.27.3%(45/165)and 39.6%(21/53)vs.18.8%(31/165)]and the differences were statistically significant( P=0.028 & 0.002). The results of multifactorial regression analysis revealed that sub-optimal blood level of tacrolimus was an independent risk factor for an occurrence of AR in grafts of SPK recipients( OR=2.254, 95% CI: 1.167-4.353, P=0.016). Comparisons of 1/5-year postoperative survival rates between recipients in AR and no-AR group(98.1% vs.93.9% and 92.1% vs.92.4%)indicated that the differences were not statistically significant( P=0.233 & 0.806). Through comparing 1/5-year survival rates of transplanted pancreas in AR and non-AR groups(94.3% vs.100%, 89.4% vs.98.6%), the differences were statistically significant( P=0.003 & 0.004). And 1/5-year survival rates of transplanted kidneys in AR and non-AR groups(92.5% vs.100% and 90.2% vs.100%)were compared and the differences were statistically significant(all P<0.001). Conclusions:The incidence of AR is higher in transplanted pancreas and kidney after SPK.And the incidence of pneumonia and urinary tract infection is higher in AR group than that in non-AR group.Sub-optimal blood level of tacrolimus is an independent risk factor for the occurrence of AR.The 1/5-year survival rates of transplanted pancreas and transplanted kidney are lower in AR group than those in non-AR group.It has some effect on the survival of transplanted pancreas and kidney.

Objective:To explore the clinical efficacy of aspirin plus low molecule heparin for pancreatic thrombosis during simultaneous pancreas and kidney transplantation (SPK).Methods:A total of 129 patients aged 18 years or higher underwent SPK between September 2016 and March 2020.They were divided retrospectively into two groups of aspirin ( n=60) and heparin ( n=69) according to different anticoagulant regimens.The aspirin group received only aspirin 100 mg/d at Day 1 post-operation.The heparin group received subcutaneous injection of enoxaparin 2 000 AxaIU daily for 7 days and followed by aspirin and clopidogrel.Outcomes and complication rates were compared between two groups. Results:All operations were successful without any mortality.In aspirin group, there were 5 cases of pancreatic thrombosis and one patient underwent pancreatectomy.There was no pancreatic thrombosis in heparin group ( P=0.014). There were 8 cases of intestinal anastomotic bleeding in aspirin group and 19 cases in heparin group.Statistically significant inter-group difference existed ( P=0.048). However, no significant inter-group difference existed in delayed recovery or rejection. Conclusions:Heparin anticoagulation can significantly lower the incidence of pancreatic thrombosis after SPK.Despite a higher incidence of intestinal anastomotic bleeding, no serious complication occurs after conservative meaures.

Objective:To explore the association between the spontaneous neural activity and memory function in depressive patients with different sleep quality.Methods:Totally 58 patients with depressive disorder and 58 gender-, age-, education-matched healthy controls (HC) completed 3.0 T MRI Scanning and clinical assessment including Wechsler memory scale (WMS), 24 Hamilton depression scale(HAMD-24) and Pittsburgh sleep quality index (PSQI). According to the score of PSQI, patients were divided into poor sleep quality group (PS, n=38) and good sleep quality group (GS, n=20). Amplitude of low frequency fluctuations (ALFF) were calculated and compared among three groups.Correlation analyses between the brain activity and the score of WMS were conducted as well. Results:Memory quotient of WMS showed differences among three groups( F=14.163, P<0.01), and the lowest score was found in patients with low sleep quality.The brain areas showed significant differences among three groups located in the left medial superior frontal gyrus (lmSFG, MNI: x=-10, y=30, z=58; K=56), right orbital inferior frontal gyrus (roIFG, MNI: x=26, y=20, z=-26; K=24) and left middle frontal gyrus (lMFG, MNI: x=-40 y=32, z=42; K=25) (voxel size P<0.001, cluster size P<0.05, GRF corrected). Compared with GS group, the ALFF of PS group showed significantly increased in the lmSFG, which was negatively correlated with memory quotient ( r=-0.327, P=0.045) and short term memory( r=-0.388, P=0.016). Compared with HC group, the ALFF of PS group showed increased in the lmSFG and lMFG, GS group showed increased ALFF in the roIFG. Conclusion:The impairment of memory function is more serious in patients with depression of low sleep quality, and the activity of frontal lobe is abnormally increased, which is related to memory function.Their association suggests that poor sleep quality in depressive patients may impair memory function by disrupting neural plasticity and synaptic pruning in the frontal lobes.

Objective    To study the clinical results of Mini Maze procedure in atrial fibrillation patients with impaired left ventricular systolic function. Methods    From June 2010 to December 2017, 86 atrial fibrillation patients with impaired left ventricular systolic function received Mini Maze procedure including 54 males and 32 females, with an average age of 60.7±5.9 years. Among them, 12 were with paroxysmal, 27 were with persistent and 47 were with long-standing persistent atrial fibrillation. The mean atrial fibrillation duration was 6.5±4.8 years. CHA2DS2-VASc score was 2.2±1.1. The mean diameter of left atrium was 46.9±3.8 mm. The mean diameter of left ventricle was 51.7±4.6 mm. The preoperative ejection fraction was 42.2%±4.7%. All patients received Mini Maze procedure after general anesthesia. The ablation included 3 annular ablations and 3 linear ablations. The left atrial appendage was excised by Endo-Gia. Ablation of Marshall ligament and epicardial autonomic ganglions were made by an ablation pen. Results    Eighty-six patients successfully completed the procedure without transition to thoracotomy. There was no death during the perioperative period. Seventy-seven patients (89.5%) maintained sinus rhythm at discharge. Eighty patients were followed up for 27.2±12.1 months and 72 patients maintained sinus rhythm. The overall postoperative left ventricular ejection fraction was 47.1%±6.2%. The ejection fraction of the postoperative sinus rhythm group was 48.2%±5.8%, and the ejection fraction of the non-sinus group was 41.6%±5.8% (P<0.05). Multivariate regression analysis showed a left atrial diameter (HR=1.485, 95%CI 1.157-1.906, P<0.05) and an increase in ejection fraction over 10% (HR=18.800, 95%CI 1.674-189.289, P<0.05) were closely related to postoperative recurrence. Kaplan-Meier curve analysis showed that the recurrence rate of atrial fibrillation was significantly lower in patients with an increase in postoperative ejection fraction over 10% (P<0.05). Conclusion    Mini Maze procedure is safe and effective in the treatment of atrial fibrillation patients with left ventricular systolic dysfunction, which helps to improve left ventricular function to prevent the vicious circle of atrial fibrillation and heart failure.

Objective To explore the influence of rs1360780 T risk allele of FK506-binding protein 5 (FKBP5) gene on the brain function under resting-state and its association with clinical symptoms as well as immune function in patients with major depressive disorder (MDD).Methods Totally 147 MDD patients and 61 gender-,age-,and education-matched healthy controls were scanned with 3.0T MRI Scanner and genotyped.The peripheral serum immunoglobulin and complement were measured.The main effect of the disease,the genotype and their interaction effects were analyzed using regional homogeneity (ReHo) by two-way ANOVA.Abnormal brain activity was identified in T risk allele carriers of rs1360780 and non-risk CC individuals in MDD using post hoc analyses.Correlation analyses were performed between ReHo values of significant brain regions and the total score,five-factor scores of Hamilton rating scale for depression (HAMD-17),serum levels of immunoglobulin and plasma complement component in MDD patients.Results (1) The results of 2x 2 ANOVA showed the interaction effects located in the left opercular part of inferior frontal gyrus (MNI:x,y,z =-42,6,9;F=10.83),right opercular part of inferior frontal gyrus (MNI:x,y,z =30,6,33;F=15.05),left medial superior frontal gyrus (MNI:x,y,z=-9,54,0;F=9.17) and left pallidum (MNI:x,y,z =-12,6,-6;F=11.37) (Alphasim corrected,P＜ 0.05).(2) In post-hoc analyses for the main effect of genotype,T+ carriers with MDD showed increased ReHo values in the right opercular part of inferior frontal gyrus (MNI:x,y,z=60,12,6;t=2.88) compared with CC carriers;for the effect of diseaseby-genotype interaction,T+ carriers with MDD showed increased ReHo values in the right opercular part of inferior frontal gyrus (MNI:x,y,z=30,6,33;t=2.96) and decreased ReHo values in the left orbital part of inferior frontal gyrus (MNI:x,y,z =-21,9,-18;t =-3.21) (Alphasim corrected,P＜ 0.05) in contrast to CC carriers.(3)Pearson's correlation showed that the average ReHo values of the right opercular part of inferior frontal gyrus negatively correlated with the content of immunoglobulin G (r=-0.528,P=O.0016,Bonferroni corrected) and positively correlated with anxiety/somatization factor score (r=0.421,P＜0.001,Bonferroni corrected) in T + carrìers with MDD.Conclusion The results of this study suggest that rs1360780 T-risk allele of FKBP5 gene is involved in the changes of local neural activity in the right opercular part of inferior frontal gyrus of depressed patients and could potentially indicate a neuropathological mechanism of anxiety somatic symptoms and immune dysfunction in depression.

Objective To preliminarily explore the clinical efficacy of ipsilateral simultaneous pancreas and kidney transplantation (SPK) .Methods Ipsilateral SPK was performed in 40 patients from September 2016 to August 2018 .During a follow-up period of 6 to 29 months ,we summarized the efficacy and complications of the technique .Results Up to now ,38 patients achieved an exceelent clinical efficacy with no major surgical complications .However ,two patients died of severe pneumonia .The postoperative serum levels of creatinine at 3 ,6 ,12 ,24 months were 107 ,102 ,107 ,110 umol/L ;creatinine clearance rate 64 ,67 ,64 ,63 ml/min;fasting glucose 4 .6 ,5 .1 ,4 .6 ,5 .2 mmol/L ;glycated hemoglobin 4 .8％ , 5 .4％ ,4 .9％ ,5 .2％ respectively .And 1/2-year pancrea and kidney graft survival rates both were 92％ . Complications included kidney graft rejection (n= 11) ,pancreas graft rejection (n= 12) ,simultaneous renal & pancreas graft rejection (n=6) ,renal graft DGF (n=1) ,pulmonary infection (n=14) ,urinary tract infections (n=18) ,gastrointestinal bleeding (n=10) diarrhea (n=6) ,splenic venous thrombosis (n=2) ,incomplete ureteric obstruction of renal allograft (n=3) ,urine leakage (n=1) and pancreas allograft dysfunction (n= 2) .There were no severe surgical complications .After aggressive interventions ,all postoperative complications were cured and none required excision of kidney or pancreas .Conclusions Ipsilateral SPK has definite therapeutic efficacy and it is worth wider popularization .

Objective To determine the effects of resecting the lower half of left stellate ganglion (LSG) on fast ventricular rate (VR) in persistent atrial fibrillation (AF) and its mechanism. Methods Twelve mature healthy male beagle dogs (15–25 kg) were studied. They were randomly divided into two groups (an experimental group and a control group, 6 dogs in each group). The control group were merely performed with rapid left atrial pacing to induce persistent AF. The experimental group were disposed with rapid left atrial pacing and received resection of the lower half of LSG after the persistent AF was documented. Simultaneously the ventricular rates were monitored separately before anesthesia, after anesthesia, 30 minutes and one month after LSG resection. The forward passing effective refractory period (ERP) of the canine atrioventricular node (AVN) was also measured. Results Each dog was documented with persistent AF after 3–6 weeks’ left atrial pacing. After resecting the lower half of LSG for 30 minutes (the control group was only observed for 30 minutes without LSG resection), the average VR of the control group attained 144.5±4.2 beats/min, while that of the experimental group was 121.5±8.7 beats/min (P<0.001). After resecting the lower half of LSG for one month (the control group was observed for one month without LSG resection), the average VR of the control group was 139.2±5.6 beats/min, while that of the experimental group was 106.5±4.9 beats/min (P<0.001). Meantime, the forward passing ERP of AVN of the experimental group was significantly prolonged than that of the control group (265.6±7.8 msvs.251.1±4.6 ms, P=0.003). Conclusion Resection of the lower half of LSG is efficient in reducing VR in canines with persistent AF, one of the mechanisms of which may be prolonging the forward passing ERP of AVN.