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 compare the clinical effect of buttress plate fixation and cannulated screw fixation of Regan-Morrey type II ulnar coronoid fractures.Methods:A retrospective case control study was made on 53 patients with Regan-Morrey type II ulnar coronoid fractures admitted to Wuxi No.9 People 's Hospital from April 2015 to January 2018，including 36 males and 17 females，aged from 21 to 63 years［（36.3±7.1）years］. Among them，24 patients were treated using buttress plates（plate group），and 29 patients using cannulated screws（screw group）. The operation time and fracture healing time were documented. The visual analogue score（VAS），range of motion of elbow flexion and extension and forearm rotation and Mayo elbow performance score（MEPS）were assessed at postoperative 1，3，6 months and at the last follow-up. The incidence of complications was observed as well. Results:All patients were followed up for 15-18 months［（15.9±1.3）months］. The operation time in plate group［（150.6±24.2）minutes］was longer than that in screw group［（126.8±18.3）minutes］（ P<0.05）. There was no significant difference in fracture healing time or VAS between the two groups（ P>0.05）. After 1，3，6 months and during the last follow-up，the range of motion of elbow joint flexion and extension in plate group［（87.2±5.8）°，（109.2±7.1）°，（121.3±6.2）°，（127.3±5.4）°］was higher than that in screw group［（70.5±9.1）°，（90.2±4.5）°，（108.3±5.1）°，（116.2±4.6）°］，the range of motion of forearm rotation in plate group［（78.3±9.1）°，（98.7±8.6）°，（130.2±7.1）°，（139.2±6.7）°］was higher than that in screw group［（60.1±5.1）°，（80.6±8.7）°，（116.1±5.5）°，（127.3±4.1）°］，and the MEPS in plate group［（30.6±7.6）points，（68.1±6.1）points，（90.2±4.3）points，（95.2±2.1）points］was higher than that in screw group［（27.2±8.1）points，（54.1±7.1）points，（82.1±5.3）points，（88.2±5.2）points］（all P<0.05）. In plate group，one patient sustained superficial wound infection at postoperative 1 week，which was healed uneventfully after surgical debridement and antibiotic therapy；two patients had heterotopic ossification without addition surgery. In screw group，three patients presented screw loosening and fracture redisplacement during early movement，which was healed by reducing the intensity of elbow functional exercise and prolonging the protection time of brace；four patients had heterotopic ossification，among which one combined with elbow stiffness showed improved range of motion of the elbow after elbow release at postoperative 12 months. The incidence of complications in plate group［13%（3/24）］was lower than that in screw group［26%（7/29）］（ P<0.05）. Conclusion:For Regan-Morrey type II ulnar coronoid fractures，the buttress plate fixation is superior to the cannulated screw fixation in fixation strength，recovery of elbow function and incidence of complications in regardless of longer operation time.

Objective:To explore the clinical application and long-term safety of hydroxychloroquine sulfate (HCQ) in the treatment of rheumatic diseases.Methods:A multi-center cross-sectional study was conducted between August 2017 and August 2018 in a random sample of eleven medical institutions of rheumatology and immunology in China. Patients who took HCQ for more than 3 months were enrolled into this study. The cumulative dose and long-term side effects of HCQ were recorded. The changes of laboratory indexes before and after treatment with HCQ were analyzed. Categorical variables were presented with counts and proportions, and evaluated by Chi-square test. Continuous parametric data were presented as Mean±standard deviation, and evaluated by Student's t test or Mann-Whitney U test. P-values less than 0.05 were considered statistically significant. Results:A total of 886 patients with rheumatic diseases were enrolled into this study, including 505 cases with systemic lupus erythematosus (57.0%), 210 cases with rheumatoid arthritis (23.7%), 80 cases with Sj?gren's syndrome (9.0%), 57 cases with undifferentiated connective tissue disease (6.4%), 12 cases of systemic vasculitis (1.4%), 10 cases of mixed connective tissue disease (1.1%), 7 cases of myositis (0.8%) and 5 cases with systemic sclerosis (0.6%). The most common long-term side effects of HCQ was skin or mucous lesions (12.4%) and vision problems (8.0%). Other adverse reactions included problems of digestive system (3.0%), nervous system (2.1%), musculoskeletal system (1.1%) and cardiovascular system (0.9%). 140 cases (15.8%) had stopped taking HCQ during the treatment. More than half of them decided to stop taking medicine by themselves. Fifty-four patients (6.1%) stopped using HCQ due to side effects while 24 of them took it again, and another 12 patients (1.4%) stopped the drug due to remission of illness. Patients were divided into three groups according to the cumulative dose of HCQ: less than 500 g, 500-1 000 g and more than 1 000 g respectively. There was significant difference in the incidence of long-term side effects among the three groups ( χ2=6.382, P=0.041). The last group (more than 1 000 g) suffered the highest incidence of long-term adverse reactions (37.1%). No severe adverse drug reactions were observed in this study. Conclusion:Hydroxychloroquine is widely used in the treatment of rheumatic diseases. The incidence of long-term side effects is 20.4%, is 6.1% lead to drug withdrawal, which are especially related to the cumulative doses. It should be adjusted properly according to the clinical application.

Objective Colon-targeting capsules based on gastric pellets and enteric pellets were prepared from Baizhu Huanglian prescription. The formulation composition and preparation process were optimized and the in-vitro release characteristics were investigated. Methods Optimum formulation composition and process parameters of Baizhu Huanglian pellets were screened out by single factor experiment and orthogonal design. The pellets core were prepared by extrusion-spheronization technique and coated in the fluid bed using bottom spray coating technique. To investigate the effect of coating level of the isolation layer, the proportion of polymer, the amount of plasticizer and weight gain of enteric coating on the release behavior of the enteric pellets. The pellets release behavior was fitted by model as well. Results The prescription of gastric pellets was drug loading 50%, PVPP 5%, MCC to lactose 1∶2 and wetting agent 40%. The process parameters were extrusion frequency 20 Hz, rounding speed 500 r/min and rounding time 5 min. The prescription of enteric pellets was drug loading 27%, PVPP 5%, MCC to lactose 5∶2, wetting agent 30% and adhesive 20%. The process parameters were extrusion frequency 20 Hz, rounding speed 700 r/min and rounding time 7 min. For enteric coating layer, the coating mixture of EUDRAGIT®L30D-55 to EUDRAGIT® FS30D was 1∶2. The amount of plasticizer was 10%. The increased weight of coating layer was 15%. The release time of enteric pellets in-vitro was up to 24 hours. The release behavior of the pellets conforms to the Higuchi model. Conclusion The colon targeting capsule of Baizhu Huanglian pellets were successfully prepared and showed the characteristics of sustained release and colon targeting.

Objective:To observe and analyze the risk factors related to vitreous re-hemorrhage (PVH) after anti-VEGF drugs combined with vitrectomy (PPV) in patients with proliferative diabetic retinopathy (PDR).Methods:Retrospective analysis study. From April 2017 to July 2018, 100 eyes of 87 PDR patients who were diagnosed in Jiaxing Eye Hospital and received anti-VEGF drugs combined with 25G PPV were included in the study. Among them, there were 44 eyes in 38 males and 56 eyes in 49 females. The age ranged from 26 to 83 years, with an average age of 57.72±8.82 years. All patients were type 2 diabetes, with an average duration of diabetes 10.84±6.03 years. All affected eyes were assisted by the same doctor with a non-contact wide-angle lens under the standard three-channel 25G PPV of the flat part of the ciliary body. Five to 7 days before the operation, intravitreal injection of ranibizumab or conbercept 0.05 ml (10 mg/ml) was performed. The incidence of PVH was observed. The age of PVH patients, duration of diabetes, vision before operation, average fasting blood glucose and average postprandial blood glucose before operation, systolic blood pressure and diastolic blood pressure before surgery, laser treatment before surgery, lens removal during operation, intraocular filling during operation, retinal laser points during operation, and fundus lesions during operation (hyperplasia film, Retinal hemorrhage, vascular occlusion, proliferative retinal traction, retinal hiatus, retinal detachment, exudation, neovascularization) were analyzed to find out the cause of PVH. Spearman bivariate correlation analysis and binary logistic regression analysis were performed on the data.Results:Of the 100 eyes of 87 patients, PVH occurred in 17 eyes (17%). There were statistically significant differences in the number of eyes with vascular occlusion and proliferative traction during surgery in patients with and without PVH ( χ2=5.741, 8.103; P<0.05). There was no significant difference in age ( t=-1.364), duration of diabetes ( t=0.538), preoperative vision ( t=1.897), preoperative fasting blood glucose level ( t=1.938), preoperative postprandial blood glucose level ( t=1.508), preoperative systolic blood pressure ( t=-0.571), preoperative diastolic blood pressure ( t=0.275), whether received laser treatment ( χ2=2.678), the number of laser points during operation ( t=0.565), whether received lens removal during operation ( χ2=0.331), whether found new blood vessels during operation ( χ2=2.741) and whether received intraocular filling during operation ( χ2=0.060) between the patients with and without PVH ( P>0.05). Spearman's bivariate correlation analysis showed that patients with low vision, poor control of fasting blood glucose levels, vascular occlusion and proliferative retinal traction during the operation were related risk factors for PVH ( rs=0.208, 0.229, 0.240, 0.285; P<0.05). Binary logistic regression analysis showed that fundus vascular occlusion and hyperplastic retinal traction may be independent risk factors for PVH during surgery ( OR=5.175, 13.915; P<0.05). Conclusion:Fundus vascular occlusion and retinal traction caused by fibrovascular membrane hyperplasia in PPV may be independent risk factors for PVH in patients with PDR after anti-VEGF drugs combined with PPV.

Objective To study the surgical treatment of hepatic hemangiomas and the timing of surgery.Methods A retrospective study was conducted on 908 patients with giant hemangiomas who underwent surgery between December 1997 and December 2017.The clinical data,surgical indications,surgical outcomes,lesion size,and the effect of TAE were compared.Results The diameter (mean + /-S.D.)of the resected hepatic cavernous hemangiomas was (11.1 ± 6.2) cm (the longest diameter was 60 cm).585 patients (64.4％) underwent enucleation of hepatic hemangiomas and 323 patients (35.6％) underwent anatomical hepatectomy.Six patients died perioperatively (mortality rate 0.7％).The incidence of severe complication (Clavien-Dindo grade 3 ～ 5) was 3.8％.The incidence of severe postoperative complication for enucleation (2.7％) was significantly less than anatomic liver resection (5.6％,P ＜0.05).When the lesion was more than 20 cm,the complication and mortality rates were significantly higher than those less than 20 cm (P ＜ 0.05).The complication and mortality rates in patients who underwent TAE before surgery were significantly higher than those without TAE (P ＜ 0.05).Conclusions Surgical enucleation of hemangiomas was superior to anatomical hepatectomy.With increase in tumor size,the risk of surgery increased.Surgical treatment was safe and effective for giant hepatic hemangiomas.For giant hepatic hemangiomas with significant increase in size,prompt surgical treatment is recommended.

Objective To explore the feasibility,safety and efficacy of laparoscopy assisted ultrasound guided radiofrequency ablation (RFA) in the treatment of hepatocellular carcinoma (HCC) beneath the diaphragm.Methods Twentythree consecutive patients with solitary HCC beneath the diaphragm were treated by laparoscopy assisted ultrasound guided RFA in the Chinese PLA General Hospital from January 2013 to March 2016.We observed the p erioperative complications and followedup long-term effect.Results All the 23 patients successfully underwent laparoscopy assisted ultrasound guided radiofrequency ablation.No serious complications such as massive hemorrhage,biliary fistula and severe pleural effusion,hemopneumothorax occurred in the patients during perioperative period.CT examination 2-3 days after the operation revealed that the tumor was completely covered by the ablation area.Besides,the survival condition was satisfactory during follow-up period of 9-38 months.Conclusion Laparoscopy-assisted ultrasound-guided radiofrequency ablation is effective and safe for HCC beneath the diaphragm.

OBJECTIVE To compare the difference of methods for active systemic anaphylactic reaction induced by breviscapine injection between ″Pharmacopoeia″ 2010 edition, an Attached ⅫG in Traditional Chinese Medicine lnjection Safety Test Application Guidelines ″ Anaphylactic Reaction Test″(thereafter referred to as the method of ″Pharmacopoeia″) and the Traditional Chinese Medicine, Natural Medicine lmmune Toxicity (Anaphylaxis, Anaphylactic Reaction of Light) Technology Guiding Principles in the 2005 Version (thereafter referred to as the method of ″Guiding Principle″) and provide reference for non-clinical safety evaluation of drugs. METHODS According to the methods of ″Pharmacopoeia″and ″Guiding Principle″, respectively, the effect of breviscapine injection on active systemic anaphylactic reaction of guinea pigs was investigated. The guinea pigs were divided into four groups, negative control group, positive control group, breviscapine injection 5 and 50 mg.kg-1 groups. ln the sensitization phase, the guinea pigs were ip administrered with breviscapine injection 0.5 mL each every other day for 3 times. The dose was 5 and 50 mg.kg-1 , respectively. For the method of ″Pharmacopoeia″, on the 14th and 21st days after the first sensitization, the guinea pigs were iv administrered with breviscapine injec-tion 1 mL. For the method of ″Guiding Principle″, the guinea pigs were provocated on the 12th day after the first sensitization. Each group was studied by observing the symptom of anaphylactic reaction and immune time. RESULTS For the method of ″Pharmacopoeia″, on the 14th day after the first sensitization, there was 1 guinea pig with sneezing and (or) the nose-scratching at different time in the 5 mg.kg-1 group. ln the 50 mg.kg-1 group, there was one or two cases of sneezing and (or) 1 case of nose-scratc-hing. The 5 and 50 mg.kg-1 dose groups conformed to the regulations. On the 21st day after the first sensitization, trembling occurred in the 5 mg.kg-1 group, with 1 or 2 guinea pigs sneezing and ( or) scratching the nose. There were 4 guinea pigs (4/ 4) with sneezing 1 and 3 times, cough once or twice, 1 scratching nose and urination at different time, and 1 guinea pigs (1/ 4) appeared 3 times consecutive sneezing and shivering in 50 mg.kg-1 group. The 5 mg.kg-1 group conformed to the regulations, while the 50 mg.kg-1 group did not. For the method of ″Guiding Principle″, the 5 mg.kg-1 group was weak positive or positive, with different degrees of symptoms of an anaphylactic reaction, including 3 guinea pigs scratched nasal symptoms. And the 50 mg.kg-1 group of anaphylactic symptoms including scratc-hing nose, sneezing, coughing and (or) urination, showed positive. CONCLUSION During the active systemic anaphylactic reaction of drugs non-clinical safety evaluation of drugs the advantage of either method should be brought into play. The method of ″ Pharmacopoeia″ may be used for preliminary screening of test samples. ln case pf suspected reactions, the method of ″Guiding Principle″ should be used for more detailed observations.

This study was aimed to observe the effect ofYang-Xue Qing-Nao(YXQN) granules on expressions of glycogen synthase kinase-3β (GSK-3β) andβ-catenin in CA1 area of hippocampus among vascular dementia (VD) rats. A total of 72 SD rats were randomly divided into the sham operation group, VD group (model group) and the YXQN granules treatment group (treatment group). The VD rat model was prepared by modified Pulsineli’s four-vessel occlusion. The expressions of GSK-3β andβ-catenin in CA1 area of hippocampus were detected by immunohistochemistry and western blotting at the 1st week, 2nd week, 4th weeks and 8th week after VD model operation. The results showed that expressions of GSK-3βwere increased in the model group at different time points, which were many quantities of expression at the 1st week, and a large number of expressions at the 2nd week. It reached peak at the 4th week; and began to decline but still higher at the 8th week. Compared with the sham operation group, the expression of GSK-3β was significantly increased in the model group at different time points (P < 0.01). The expression ofβ-catenin was increased in the model group at different time points. However, there was no statistical significance compared with the sham operation group (P > 0.05). Compared with the model group, expressions of GSK-3β andβ-catenin were significantly increased in the treatment group at different time points (P < 0.01). It was concluded that YXQN granules upregulated the expression of GSK-3β andβ-catenin, which may be helpful to VD treatment.

Objective To observe dynamic variation of neural precursor cells in dentate gyrus of hippocampus and effect of Yangxue Qingnao Granule on it in vascular dementia rats. Methods 72 Sprague-Dawley rats were randomly divided into sham group (n=24), vascular dementia group (model group, n=24) and Yangxue Qingnao Granule group (treatment group, n=24). The vascular dementia model was established with modified Pulsineli's four-vessel occlusion. The expression of Nestin was detected with Western blotting, the expression of 5-bromodeoxyuridine (BrdU) and BrdU/Nestin were detected with immunofluorescence in dentate gyrus of hippocampus 1, 2, 4 and 8 weeks after modeling. Results The expression of Nestin, BrdU and BrdU/Nestin increased in the model and treatment groups with time, peaked at 4 weeks after modeling, and it was more than that of the sham group on all the time points (P<0.01). However, it was more in the treatment group than in the model group on all the time points (P<0.01). Conclusion Yangxue Qingnao Granule promotes the proliferation of neural precursor cells in dentate gyrus of hippocampus in vascular dementia rats.