Objectives:Fenofibric acid is extracted from the widely used hypolipemic fenofibrate,nowadays being approved for marketing around numerous nations and regions,nonetheless not in China.Present trial evaluated the efficacy and safety in the Chinese hypertriglyceridemia population. Methods:This is a multi-center,randomized,double-blind,placebo-controlled phase Ⅲ clinical trial.Patients from 3 different cohorts,including severe hypertriglyceridemia(HTG),moderate HTG and mixed-dyslipidemia(MD),were randomized at 1:1 ratio to receive fenofibric acid 135 mg or placebo daily for 12 weeks.The primary endpoint was the percentage change of triglyceridemia(TG)from baseline at week 12.Secondary endpoints were the percentage changes of other blood lipid indexes.At the same time,the incidence of medical adverse events was observed. Results:Among the three cohorts of patients with severe HTG(n=52),moderate HTG(n=23)and MD(n=52),the TG levels in the fenofibric acid-treated group decreased by(49.12±29.19)%,(49.95±25.19)%and(49.79±19.28)%,respectively from baseline to 12 weeks,while the corresponding placebo groups decreased by(18.88±40.69)%,(8.11±29.86)%and increased by(10.42±73.04)%,respectively from baseline to 12 weeks.The differences between treatment and placebo groups were statistically significant(P<0.017 for severe HTG cohort,P<0.05 for moderate and MD cohort).The high-density lipoprotein cholesterol(HDL-C)in the fenofibric acid-treated group increased by(25.51±21.45)%,(24.55±24.73)%,and(23.60±27.38)%,and the placebo group increased by(1.91±20.42)%,(2.40±9.32)%and(7.13±19.12)%,respectively,the differences between the two groups were statistically significant(all P<0.05).In the fenofibric acid group,adverse events with incidence>5%included upper respiratory tract infection(10.9%),abdominal pain(6.3%),and increased serum creatinine levels(6.3%),rates of adverse events were similar between the two groups(P>0.05). Conclusions:Fenofibric acid can significantly reduce triglycerides and elevate HDL-C levels safely in Chinese patients with severe to moderate HTG without statin or MD patients on top of statin therapy.

OBJECTIVE：To analyze the clinical manifestations and characteristics of adverse drug reactions （ADR）induced by EGFR-TKI，and to provide reference for safe use of drugs in clinic. METHODS ：The relevant data of EGFR-TKI-induced ADR reports which were reported to Shandong ADR Monitoring Center from January 2018 to December 2020 were summarized ，and analyzed statistically in respects of age ，gender，drug variety ，ADR classification ，usage and dosage ，occurrence time ，involved organs/systems，clinical manifestations and prognosis of patients. RESULTS & CONCLUSIONS ：A total of 120 ADR reports induced by EGFR-TKI were included ，involving 120 patients. Among 120 patients，the female （60.83％）was more than the male （39.17％），and the age was mainly 50-79 years old （79.16％）. A total of 5 drugs including gefitinib ，ositinib，afatinib，ektinib and erlotinib were involved. ADR occurred in 72，11，15，6 and 16 patients using the above drugs respectively ；the main ADR was general ADR （70.83％），followed by severe ADR （22.50％），new general ADR （5.00％）and new severe ADR （1.67％）. All patients were given drugs orally ，off-label use was found in 2 patients who used ektinib ，and the rest met the medication requirements of the drug instructions. ADR occurred in 61 patients（50.83％）within 1 month after medication ，34 patients （28.33％）within 1-3 months after medication ，25 patients（20.83％）within 4-12 months after medication ，and no ADR occurred after 12 months. ADR of organs/systems involved were mainly the lesion of skin and its appendant injury，gastrointestinal system injury and hepatobiliary system injury. The main clinical manifestations were rash ，diarrhea and abnormal liver function ；in addition，some patients developed severe or new severe ADR such as interstitial pneumonia ，bone marrow suppression ，tongue swelling and cerebral infarction. Totally 102 patients recovered or improved after drug withdrawal or symptomatic treatment ，12 patients had unknown outcome ，and 6 patients did not improve. It is suggested that pharmaceutical care should be strengthened within 1 month after EGFR-TKI administration ，so as to guard against the occurrence of new and serve ADR and ensure the safety of clinical medication.

OBJECTIVE：To investigate the occurrence and characteristics of new adverse drug reactions （ADR）in Shandong province，so as to provide reference for the safety of drug use in the clinic. METHODS ：The data of new ADR reports were collected from Spontaneous Reporting System of Shandong ADR Monitoring Center during Oct. 2019 to Mar. 2020. Those reports were analyzed statistically in respects of report types ，reporting institution ，reporters’occupation，gender and age of patients ，drug type ，organs/ systems involved ，clinical manifestations. RESULTS & CONCLUSIONS ：A total of 8 566 new ADR reports were screened out ， accounting for 10.81％ of the effective ADRs. Among them ，there were 7 961 new and general ADR （92.94％）and 605 new and serious ADRs （7.06％）. For the new ADR ，the reporting institutions were mainly medical institutions （98.42％），and the reporters ’ occupation were mainly doctors （78.44％）. Female （4 860 cases）was slightly more than male （3 698 cases）；most of them were 45 years old and above （70.00％），and intravenous drip （47.67％）was the main route of administration. The top five ADR suspected drugs were TCM preparations （34.50％），anti-microbials（13.75％），circulatory system drugs （11.41％），nervous system drugs （6.39％）and blood system drugs （4.81％），involving 517，91，64，53，50 types，respectively，among which Levofloxacin injection caused the most serious ADR （24 cases）. The new and general ADR mainly involved gastrointestinal system ，skin and its appendant ； their clinical manifestations were nausea ，vomiting，rash，etc. New and serious ADR mainly caused systemic damage ；their clinical manifestations were anaphylactic shock ，chest tightness and shivering ，etc. It is suggested to strengthen the ADR monitoring of TCM preparations，anti-microbials，circulatory system drugs and other drugs ，so as to ensure the safety of clinical drug use.

Multi-modal therapeutics are emerging for simultaneous diagnosis and treatment of cancer. Polymeric carriers are often employed for loading multiple drugs due to their versatility and controlled release of these drugs in response to a tumor specific microenvironment. A theranostic nanomedicine was designed and prepared by complexing a small gadolinium chelate, conjugating a chemotherapeutic drug PTX through a cathepsin B-responsive linker and covalently bonding a fluorescent probe pheophorbide a (Ppa) with a branched glycopolymer. The branched prodrug-based nanosystem was degradable in the tumor microenvironment with overexpressed cathepsin B, and PTX was simultaneously released to exert its therapeutic effect. The theranostic nanomedicine, branched glycopolymer-PTX-DOTA-Gd, had an extended circulation time, enhanced accumulation in tumors, and excellent biocompatibility with significantly reduced gadolinium ion (Gd

Background and Objectives: Bronchopulmonary dysplasia (BPD) has major effects in premature infants. Although previous literature has indicated that mesenchymal stem cells (MSCs) can alleviate lung pathology in BPD newborns and improve the survival rate, few research have been done investigating significantly differentially expressed genes in the lungs before and after MSCs therapy. The aim of this study is to identify differentially expressed genes in lung tissues before and after hAD-MSC treatment. Methods: and Results: Human amnion-derived MSCs (hAD-MSCs) were cultured and met the MSCs criteria for cell phenotype and multidirectional differentiation. Then we confirmed the size of hAD-MSCs-EXOs and their expressed markers. An intratracheal drip of living cells showed the strongest effect on NHLI compared to cellular secretions or exosomes, both in terms of ameliorating pulmonary edema and reducing inflammatory cell infiltration. Through gene chip hybridization, PCR, and western blotting, acylaminoacyl-peptide hydrolase (APEH) expression was found to be significantly decreased under hyperoxia, and significantly increased after hAD-MSC treatment. Conclusions The intratracheal transplantation of hAD-MSCs ameliorated NHLI in neonatal rats through APEH.

Objective: To build an automatic bone age assessment system based on China 05 Bone Age Standard and the latest deep learning technology, and preliminary clinical verification was carried out. Methods: The left-hand radiographs of 5 000 children with suspected metabolic disorders were acquired from Wuxi Children′s Hospital. Among these cases, 2 351 patients were randomly chosen as training set, and 101 patients were randomly used as validation set. Four professional pediatric radiologists annotated the development stage according to the China 05 RUS-CHN standard with double-blind method. The mean value of the bone age assessed by experts was the reference standard which was used to train and validate the deep learning mothods based artificial intelligence (AI) model. Accuracy, mean absolute error (MAE), root mean squared error (RMSE) and time efficiency of bone age assessment were compared by using Chi-square test and t test and F test between resident doctors and AI model in the validation set. Results: The MAE and RMSE was (0.37±0.35) years and 0.50 years between AI model and reference standard, respeactively. When the error range was within ±1.0, ±0.7 and ±0.5 years, the accuracy of model on the validation set was 94.1% (95/101), 89.1% (90/101), 74.3% (75/101) respectively. The accuracy between two resident doctors and AI prediction wasn′t statistical significant (P>0.05). Conclusion The AI model of bone age assessment based on deep learning is feasible and has the characteristics of high accuracy and efficiency.

Objective To evaluate the correlation of different fractionation schedules in radiotherapy with the local control ( LC) and overall survival ( OS) rates in patients with extensive?stage small cell lung cancer ( ES?SCLC ) , and to figure out the relationship between different fractionation schedules in radiotherapy and the prognosis of ES?SCLC. Methods One hundred and ten patients newly diagnosed with ES?SCLC from February 2010 to March 2015 received chemoradiotherapy. According to the radiation dose, all patients were divided into hypo?fractionation group ( 30?45 Gy/3 Gy/10?15 f, n=31) and conventional fractionation group ( 54?60 Gy/1?8?2?0 Gy/27?30 f, n=79) . In all patients, 90?9% had stageⅣSCLC;21 patients had brain metastasis;39 patients were treated with prophylactic cranial irradiation ( PCI ) . The Kaplan?Meier method was used to calculate the survival time and log?rank test was used for between?group comparison. Between?group comparison of categorical data was made by χ2 test. Results The number of patients followed?up were 85 at 2?years. In all patients, the 2?year OS, progression?free survival ( PFS) , and LC rates were 27?7%, 17?5%, and 38?9%, respectively. The hypo?fractionation group had similar prognosis to the conventional fractionation group. There were no significant differences in the 2?year OS, PFS, and LC rates between the two groups ( 35% vs. 26%, P=0?886;18% vs. 16%, P=0?560;67% vs. 36%, P=0?159) . There was also no significant difference in the 2?year OS rate between patients treated with and without PCI (44% vs. 18%, P=0?044). In 84 patients with treatment failure, 11 had local recurrence, 41 had distant metastasis, and 32 had local recurrence plus distant metastasis. Conclusions The hypofractionated radiotherapy has similar efficacy but substantially shortened radiation time compared with conventionally fractionated radiotherapy. The palliative hypofractionated radiotherapy requires further study for ES?SCLC.

ObjectiveTo objectively evaluate the clinical efficacy of three-step acupuncture-cupping therapy for cervicogenic headache.MethodSixty patients were randomly allocated to treatment and control groups. The treatment group received three-step acupuncture-cupping therapy and the control group, conventional acupuncture based on “Acupuncture Therapeutics”. Both groups were treated for three courses (10 days as acourse with two days of rest between two courses) and then the clinical therapeutic effects were evaluated. The evaluation included the overall therapeutic effect on the symptoms, the VASscore and the follow-up recurrence rate at six months after treatment.ResultThe total efficacy rate was 96.7% in the treatment group and 83.3% in the control group; there was a statistically significant difference between the two groups (P<0.01). A follow-up of six months after treatment in the two groups showed that the recurrence rate was 16.7% in the treatment group and 46.7% in the control group;there was a statistically significant difference between the two groups (P<0.05).ConclusionThree-step acupuncture-cupping therapy has a definite effect on cervicogenic headache. Its immediate and long-term effects are superior to those of conventional acupuncture. The recurrence rate in six months is lower in this therapy than in conventionalacupuncture.

We established methods to isolate human amniotic fluid-derived progenitor cells (hAFPCs), and analyze the ability of hAFPCs to secrete human coagulation factor IX (hFIX) after gene modification. The hAFPCs were manually isolated by selection for attachment to gelatin coated culture dish. hFIX cDNA was transfected into hAPFCs by using a lentiviral vector. The hFIX protein concentration and activity produced from hAFPCs were determined by enzyme-linked immunosorbent assay (ELISA) and clotting assay. The isolated spindle-shaped cells showed fibroblastoid morphology after three culture passages. The doubling time in culture was 39.05 hours. Immunocytochemistry staining of the fibroblast-like cells from amniotic fluid detected expression of stem cell markers such as SSEA4 and TRA1-60. Quantitative PCR analysis demonstrated the expression of NANOG, OCT4 and SOX2 mRNAs. Transfected hAFPCs could produce and secrete hFIX into the culture medium. The observed concentration of secreted hFIX was 20.37% +/- 2.77% two days after passage, with clotting activity of 16.42% +/- 1.78%. The amount of hFIX:Ag reached a plateau of 50.35% +/- 5.42%, with clotting activity 45.34% +/- 4.67%. In conclusion, this study established method to isolate and culture amniotic fluid progenitor cells. Transfected hAFPCs can produce hFIX at stable levels in vitro, and clotting activity increases with higher hFIX concentration. Genetically engineered hAFPC are a potential method for prenatal treatment of hemophilia B.
Amniotic Fluid ; cytology ; Blood Coagulation ; Cell Culture Techniques ; Cell Separation ; methods ; DNA, Complementary ; Factor IX ; biosynthesis ; Genetic Engineering ; Genetic Vectors ; Humans ; Stem Cells ; cytology ; metabolism ; Transfection

We developed a three-dimensional mini-type permanent magnetic resonance imaging (MRI) device in our lab. The purposes of this study were (1) for further development of MRI technologies, (2) for support of broadening practices of animal test modeling in medical research, and (3) for training more specialists from colleges or universities in the field of MRI. This paper describes the research and development at our lab(s), especially stressing on the design of the main magnet, the gradient coil and the radio frequency coil. In addition, the specific methodologies used in our lab(s) and the related data are emphasized. The 3D MRI technologies have met the needs of using small animals, super thin sections of live animal body and high imaging resolutions. MRI images of mice head and abdominal have been obtained successfully by using the imager that we developed. The imaging results and analyses have also been discussed.
Animals ; Equipment Design ; Imaging, Three-Dimensional ; instrumentation ; Magnetic Resonance Imaging ; instrumentation ; methods ; Mice