The paper is to explore how to carry out post-market technical evaluation of dietary supplements in China by referring to the experiences at home and abroad. Experiences of major countries and regions in the post-market evaluation of similar products of dietary supplements and China’s experience in drugs were systematically reviewed. Combined with the actual situation of the health food industry in China， suggestions were put forward for the post-market technical evaluation of health foods in China. There are many useful experiences worth learning from， such as the mandatory reporting responsibility of enterprises in the United States， a special scientific committee which provides long-term technical support in the European Union， post-market monitoring by enterprises in Australia， the establishment of relevant monitoring systems in Taiwan， the relatively mature regulatory system， evaluation system and management system in the field of drugs and medical devices， and the establishment of adverse reaction monitoring bases in the field of cosmetics， the responsibility of post-mark adverse reaction monitoring of food for special medical purposes by medical institutions， and the post-market management in various fields giving priority to safety. In combination with the current situation of China’s health food industry， five specific suggestions， such as promoting the construction of laws and regulations， are put forward.

To investigate whether chemotherapy could prolong the postoperative survival time in patients with early stages pancreatic ductal adenocarcinoma (PDAC). A total of 5280 stage ⅠA -ⅡB PDAC patients diagnosed from 2010 to 2015 were selected from surveillance，epidemiology，and end results (SEER) database. Propensity score matching (PSM) analysis was adopted to reduce the baseline differences between the groups. Univariate survival analysis was conducted with the Kaplan-Meier method. Multivariate survival analysis was performed with the Cox proportional hazards model. Univariate and multivariate survival analyses showed that age, differentiation, stage, chemotherapy were independent risk factors for the survival of PDAC patients. After PSM, it is found that adjuvant chemotherapy could prolong the median overall survival time (mOS) for stage ⅠB, ⅡA and ⅡB patients. However, for stage ⅠA patients, there were no significant differences in 3-year survival rate and mOS between patients with chemotherapy (=283) and without chemotherapy (=229) (57.4% vs 55.6%, vs all >0.05). Further analyses show that among 101 patients with well differentiated PDAC and 294 patients with moderately differentiated PDAC, there were no significant differences in survival rate and mOS between patients with and without chemotherapy (all >0.05). Among 117 patients with low-differentiated + undifferentiated PDAC, 3-year survival rate and mOS in patients with chemotherapy were significantly better than those without chemotherapy (48.5% vs 34.1%, vs all <0.05). Chemotherapy regimen used currently is not beneficial for patients with moderately and well differentiated stage ⅠA PDAC, but it is an independent prognostic factor for low-differentiated + undifferentiated PDAC patients.
Adenocarcinoma/pathology* ; Carcinoma, Pancreatic Ductal/surgery* ; Chemotherapy, Adjuvant ; Humans ; Neoplasm Staging ; Pancreatic Neoplasms/drug therapy* ; Prognosis ; Propensity Score

Objective: To analyze clonal evolution and clinical significance of trisomy 8 in patients with acquired bone marrow failure. Methods: The clinical data of 63 patients with acquired bone marrow failure accompanied with isolated trisomy 8 (+8) from June 2011 to September 2018 were analyzed retrospectively, the clonal evolution patterns and relationship with immmunosuppressive therapy were summarized. Results: Totally 24 male and 39 female patients were enrolled, including 39 patients with aplastic anemia (AA) and 24 patients with relatively low-risk myelodysplastic syndrome (MDS) . Mean size of+8 clone in MDS patients[65% (15%-100%) ]was higher than that of AA patients[25% (4.8%-100%) , z=3.48, P=0.001]. The patients were was divided into three groups (<30%, 30%-<50%,and ≥50%) according to the proportion of+8 clone. There was significant difference among the three groups between AA[<30%:55.6% (20/36) ; 30-50%: 22.2% (8/36) ; ≥50%22.2% (8/36) ]and MDS patients[<30%:19.0% (4/21) ; 30%-<50%:19.0% (4/21) ; ≥50%61.9% (13/21) ] (P=0.007) . The proportion of AA patients with+8 clone <30% was significantly higher than that of MDS patients (P=0.002) ; and the proportion of AA patients with+8 clone ≥50%was significantly lower than that of MDS patients (P=0.002) . The median age of AA and MDS patients was respectively 28 (7-61) years old and 48.5 (16-72) years old. Moreover, there was no correlation between age and+8 clone size in AA or MDS (r_s=0.109, P=0.125; r_s=-0.022, P=0.924, respectively) . There was statistical difference in total iron binding capacity, transferrin and erythropoietin between high and low clone group of AA patients (P=0.016, P=0.046, P=0.012, respectively) , but no significant difference in MDS patients. The immunosuppressive therapy (IST) efficacy of AA and MDS patients was respectively 66.7% and 43.8% (P=0.125) . Comparing with initial clone size (27.3%) , the +8 clone size (45%) of AA patients was increased 1-2 year after IST, but no statistical difference (z=0.83, P=0.272) . Consistently, there was no significant change between initial clone size (72.5%) and 1-2 year clone size (70.5%) after IST in MDS patients. There was no significant difference in IST efficient rate between +8 clone size expansion and decline group of in AA patients at 0.5-<1, 1-2 and>2 years after IST. We found four dynamic evolution patterns of +8 clone, which were clone persistence (45%) , clone disappearance (30%) , clone emergence (10%) and clone recurrence (15%) . Conclusions AA patients had a low clone burden, while MDS patients had a high burden of +8 clone. The +8 clone of AA patients didn’t significantly expanded after IST, and the changes of +8 clone also had no effect on IST response.

Objective: To determine the valuable hemolytic characteristics in differential diagnosis of paroxysmal nocturnal hemoglobinuria (PNH), autoimmune hemolytic anemia (AIHA) and hereditary spherocytosis (HS). Method: The clinical and hemolytic characteristics of 108 PNH patients, 127 AIHA patients and 172 HS patients diagnosed from January 1998 to April 2017 were compared. Results: ①Reticulocyte percentage (Ret%) of PNH patients [6.70% (0.14%-22.82%)] was significantly lower than that of AIHA [14.00%(0.10%-55.95%), P<0.001] and HS patients [11.83%(0.60%-57.39%), P<0.001]. The Ret% in PNH patients were significantly lower than those in AIHA and HS patients at the same levels of anemia, except for in mild anemia between PNH and AIHA patients. However, when comparing the Ret% between AIHA and HS patients, there was significant difference only in mild anemia [7.63%(1.87%-29.20%)% vs 11.20%(3.31%-22.44%), z=-2.165, P=0.030]. ②The level of TBIL in HS patients was significantly higher than that in AIHA and PNH patients [79.3 (11.2-244.0) μmol/L vs 57.6 (7.6-265.0) μmol/L, z=5.469, P<0.001; 79.3(11.2-244.0) μmol/L vs 26.2(4.6-217.7) μmol/L, z=-2.165, P<0.001], and the proportion of HS patients with TBIL more than 4 times the upper limit of normal (ULN) (64.1%) was significantly higher than that of AIHA (37.7%, χ²=19.896, P<0.001) and PNH patients (4.6%, P<0.001). ③The LDH level of PNH patients was significantly higher than that of AIHA and HS [1 500 (216-5 144) U/L vs 487 (29-3 516) U/L, z=-9.556, P<0.001; 1 500 (216-5 144) U/L vs 252 (132-663) U/L, z=-11.518, P<0.001], and the proportion of PNH patients with LDH more than 1 000 U/L (79.1%) was significantly higher than that of AIHA patients (13.0%, χ²=93.748, P<0.001) and HS patients (0, P<0.001). ④Splenomegaly occurred in 43.5% of PNH patients, including 16.0% with severe splenomegaly. In contrast, the occurrence of splenomegaly was 98.6% in AIHA patients and 100.0% in HS patients (P<0.001), and 63.0% of AIHA patients (P<0.001) and 90.4% of HS patients (P<0.001) were with severe splenomegaly. ⑤The prevalence of cholelithiasis in HS patients was up to 43.1%, significantly higher than that in AIHA patients (10.5%, P<0.001) and PNH patients (2.9%, P<0.001). Conclusion The comprehensive assessment of the five hemolytic characteristics is simplified, practical and efficient, with great clinical significance, providing specific indicators for differential diagnosis and efficient approach for making further work-up.

Objective From the perspective of traditional Chinese medicine (TCM) syndrome differentiation to investigate the blood glucose control strategies of patients with different etiological factors and treated by mechanical ventilation.Methods One hundred and twenty-six mechanical ventilation patients admitted to the Department of Intensive Care Unit (ICU) of Hangzhou Third People's Hospital from February 2016 to February 2017 were enrolled, they were divided into a heart failure group (64 cases) and a pneumonia group (62 cases) according to the cause of disease. Altogether 4 cases due to death, giving up the treatment or being transferred to other hospital were excluded in each group, thus, 60 cases in heart failure group and 58 cases in pneumonia group were finally enrolled. Both groups received at least 4 days of formal blood glucose monitoring and control program. The differences in TCM syndromes, the number of patients necessary to use insulin to control the blood glucose, the daily use of insulin dosage, the incidence of hypoglycemia and prognosis of patients were compared between the two groups.Results According to TCM syndrome differentiation, deficiency was the primary syndrome in the heart failure group, while in the pneumonia group, excess was the primary syndrome, the proportion of deficiency syndrome in heart failure group was significantly higher than that in the pneumonia group [63.33% (38/60) vs. 31.03% (18/58),P < 0.05]. Within 4 days, the incidence of hyperglycemia [50.0% (29/58) vs. 13.3% (8/60)], daily insulin dose (U/d: 85.35±6.35 vs. 20.13±8.20) in pneumonia group were higher than those in the heart failure group (bothP < 0.05). The incidence of hypoglycemia in heart failure group was higher than that in pneumonia group [16.67% (10/60) vs. 3.45% (2/58),P < 0.01].Conclusions It is necessary to use different blood glucose control strategies in patients with heart failure and pneumonia to undergo mechanical ventilation, and the TCM syndrome differentiation can provide theoretical references.

OBJECTIVETo explore the clinical characteristics, and the effect of paroxysmal nocturnal hemoglobinuria (PNH) clone size and its evolution on response and survival in aplastic anemia (AA) patients.

METHODSThe clinical data of 90 AA cases with PNH clones from 316 AA patients between January 2011 and September 2014 were retrospectively reviewed, their clinical characteristics were analyzed, and the influence of PNH clone evolution and size on response and survival were explored.

RESULTS① Of 316 patients, 90 cases (28.5%) with PNH clones. Of 83 cases with long-term follow-up data available, the complete (CR) and partial response (PR) rates were 43.4% and 33.7% respectively, with the overall responsive rate of 77.1%. The 3-year and 5-year overall survival (OS)rates were 79.4% and 76.1% respectively. ② After immunosuppressive therapy (IST), the PNH clone changed from negative to positive in 24 cases, persistently positive PNH clones were observed in 22 cases, disappeared in 10 cases. There were no significant differences in terms of overall responsive rates, survival rates, absolute reticulocyte value, TBIL, IBIL and LDH among the three groups (P >0.05). Ten cases became AA-PNH after a median time of 15.6 months, no significant differences were found in overall responsive and survival rates between the 10 cases and the other 46 cases who were monitored for PNH clones (P values were 0.896, 0.688, respectively). ③ According to univariate analysis, age≥55, infection, VSAA, ANC <0.5 × 10(9)/L and absolute reticulocyte value <0.012 × 10(12)/L had significant influence on survival (P values were 0.026, 0.000, 0.001, 0.000 and 0.010, respectively). Cox regression model analysis identified that age, infection and ANC were independent prognostic factors affecting survival (P values were 0.050, 0.012 and 0.050, respectively). The PNH clone size had no significant influence on response and survival based on univariate and Cox analyses.

CONCLUSIONThe PNH clone size and its evolution had no significant influence on response and survival.

Anemia, Aplastic ; complications ; pathology ; Clone Cells ; Hemoglobinuria, Paroxysmal ; complications ; pathology ; Humans ; Immunosuppression ; Reticulocytes ; Retrospective Studies

OBJECTIVETo explore the efficacy and safety of deferasirox in aplastic anemia (AA)patients with iron overload.

METHODSA single arm, multi- center, prospective, open- label study was conducted to evaluate absolute change in serum ferritin (SF)from baseline to 12 months of deferasirox administration, initially at a dose of 20 mg·kg(-1)·d(-1), and the safety in 64 AA patients with iron overload.

RESULTSAll patients started their deferasirox treatment with a daily dose of 20 mg · kg(-1) ·d(-1). The mean actual dose was (18.6±3.60) mg · kg(-1)·d(-1). The median SF decreased from 4 924 (2 718- 6 765)μg/L at baseline (n=64) to 3 036 (1 474- 5 551)μg/L at 12 months (n=23) with the percentage change from baseline as 38%. A median SF decrease of 651 (126-2 125)μg/L was observed at the end of study in 23 patients who completed 12 months' treatment, the median SF level decreased by 1 167(580-4 806)μg/L [5 271(3 420-8 278)μg/L at baseline; 3 036(1 474-5 551)μg/L after 12 months' treatment; the percentage change from baseline as 42% ] after 12 months of deferasirox treatment. The most common adverse events (AEs) were increased serum creatinine levels (40.98%), gastrointestinal discomfort (40.98%), elevated liver transaminase (ALT: 21.31%; AST: 13.11%)and proteinuria (24.59%). The increased serum creatinine levels were reversible and non-progressive. Of 38 patients with concomitant cyclosporine use, 12(31.8%)patients had two consecutive values >ULN, 10(26.3%)patients had two consecutive values >1.33 baseline values, but only 1(2.6%)patient's serum creatinine increased more than 1.33 baseline values and exceeded ULN. For both AST and ALT, no patients experienced two post- baseline values >5 ×ULN or >10 × ULN during the whole study. In AA patients with low baseline PLT count (less than 50 × 10(9)/L), there was no decrease for median PLT level during 12 months' treatment period.

CONCLUSIONSAA patients with iron overload could achieve satisfactory efficacy of iron chelation by deferasirox treatment. The drug was well tolerated with a clinically manageable safety profile and no major adverse events.

Anemia, Aplastic ; drug therapy ; Benzoates ; therapeutic use ; Blood Transfusion ; China ; Ferritins ; blood ; Humans ; Iron ; blood ; Iron Chelating Agents ; therapeutic use ; Iron Overload ; drug therapy ; Liver ; Prospective Studies ; Triazoles ; therapeutic use

ObjectiveTo establish a method for content determination of total iridoid compounds and baldrinal and 11-ethoxyviburtinal from Valerianae Jatamansi Rhizoma et Radix; To determine the contents of total iridoid compounds and baldrinal and 11-ethoxyviburtinal in Valerianae Jatamansi Rhizoma et Radix from three medicinal origins.Methods UV spectrophotometry was applied, 11-ethoxyviburtinal (cyclopentane-pyran-7-formaldehyde, 4-ethoxy methyl) was set as the reference substance, and the content of total iridoid compounds was determined at 288 nm. HPLC method was used to simultaneously determine the contents of baldrinal and 11-ethoxyviburtinal. The HPLC analysis was performed on a Phenomenex Luna C18 column (250 mm×4.6 mm, 5μm). The mobile phase was composed of acetonitrile-water in gradient elution at a flow rate of 0.95 mL/min. The detection wavelength was 288 nm and the column temperature was 30℃.Results The total iridoid compounds, baldrinal and 11-ethoxyviburtinal were in good linearity within the ranges of 2.088–14.616μg/μL, 74.88–224.64μg, and 41.6–249.6μg, respectively. This method was precise, and with good repeatability, stability and recovery rate.Conclusion The method is accurate, simple, rapid, which can be used for the quality control of Valerianae Jatamansi Rhizoma et Radix.

Objective To evaluate the clinical efficacy of small endoscopic sphincterotomy combined large-bal-loon dilation in treatment of common bile duct stones 1.0~2.5 cm in diameter. Methods 426 patients with large common bile duct (CBD) stones 1.0~2.5 cm in size were reviewed in our hospital between June 2010 and June 2014. They were randomized underwent small endoscopic sphincterotomy combined large-balloon dilation (SESPLBD) (n=218) or endoscopic sphincterotomy (EST) ( n= 208) for lithotripsy. The therapeutic outcome and complications were reviewed and compared. Results SESPLBD had higher complete duct clearance in one session (95.41 % vs. 93.75%), but there was no statistical significant difference. Bleeding was much less occurred in SESPLBD than in EST (2.29 % vs. 7.69 %, P= 0.025), especially when the stones were bigger than 1.5 cm in diameter. Mechanical lithotripsy was performed less in SESPLBD (13.76%vs 25.96 %, P=0.002), especially when the stones were 1.5 ~2.0 cm in diameter. There was no statistical significant difference in the incidence rate of post-ERCP pancreatitis (9.17 % vs. 6.73 %,P = 0.452), hyperamylasemia (19.72 % vs. 18.27 %,P = 0.796), perforation and death. Conclusions SESPLBD could be a safe method for large bile duct stones 1.0~2.5 cm in size. Compared with routine EST, it had less bleeding rate and mechanical lithotripsy requirement without increasing the incidence rate of post-ERCP pancreatitis or hyperamylasemia.