Dear Health Care Provider (DHCP) letters promptly are directed to doctors and other demanders by manufacturer or FDA to communicate change of description drug labeling,which are divided into three types-Important Drug Warning Letters,Important Prescribing Information Letters,and Important Correction of Drug Information Letters.FDA issued Guidance for Industry and FDA Staff Dear Health Care Provider Letters:Improving Communication of Important Safety Information in February 2017,described in detail the contents and format of the three letters;and listed the models.This paper introduces the main contents of the guidance.Call on China's pharmaceutical production enterprises and regulatory agency from the FDA experience establish the corresponding mechanism in line with China's national conditions,so that doctors and other demanders can be timely access to important new information of labeling to ensure clinical safe and effective medication.

The European Union released Guideline on the assessment of clinical safety and efficacy in the preparation of European Union herbal monographs for well-established and traditional herbal medicinalproducts rev.1 in July 2016.It is noteworthy in the guideline that the test data can be replaced by the literature when the herbal medicine products are applied for registration and according to the scientific strength of the literature,different indications can be approved.This paper introduces the main contents of the guideline and is expected to inspire the research and supervision of Chinese materia medica and phytomedicine in China.

FDA in August 2016 released Microbiology Data for Systemic Antibacterial Drugs —— Development,Analysis,and Presentation Guidance for Industry,which introduced requirements of the whole process of the research on the microbiology of systemic antimicrobial drugs by FDA.Therefore,the guidance of FDA has an important reference value for the research and supervision of the systemic antimicrobial drugs in our country.The following are particularly noteworthy:requirements for the in vitro AST methods,the QC parameters and the AST interpretive criteria;Requirements for the format and content of the labeling microbiology portion;requirements for periodic evaluation and update of the in vitro AST methods,the QC parameters,and the AST interpretive criteria in postmarketing labeling;Requirements for the number of isolates and the characteristics of pathogenic bacteria for in vitro sensitivity test.

FDA issued Considerations for Use of Histopathology and Its Associated Methodologies to Support Biomarker Qualification Guidance for Industry in May 2016.The guideline outlined the characteristics of nonclinical biomarker of histopathology,and explained the scientific standards for the use of histopathological methods in the nonclinical biomarker qualification.This paper introduces the main contents of the guideline,and it is expected to be helpful to the research and supervision in our country.

FDA released Clinical Pharmacology Data to Support a Demonstration of Biosimilarity to a Reference Product Guidance for Industry in December,2016.The guidance describes the requirements of the trial designs and trial methods for the biosimilar clinical pharmacological studies,and especially points out the problems that should be paid special attention to in the studies.However there is no similar guidance in China.This paper introduces the guidance of FDA,which is beneficial to the research and regulation in China.

FDA issued the Clinical Pharmacology Section of Labeling for Human Prescription Drug and Biological Products — Content and Format Guidance for Industry (final guidance)in December 2016.The Guidance stipulated that clinical pharmacology section must contain three subsections—echanism of action,pharmacodynamics,and pharmacokinetics;If necessary,it can be added to microbiology and pharmacogenomics subsections etc.,as well as explained that the contents of each subsection should be included,also discussed the writing general principles and the format of the section.This paper introduces the main contents of the guidance,with the hope of helping writing and supervision on our country labeling.

Primary testicular lymphoma comprises 1% to 9% of testicular neoplasms and represents 1% to 2% of all non-Hodg-kin lymphomas. Histologically, the majority of the tumor consists of diffuse large B-cell non-Hodgkin lymphomas that are of intermedi-ate- or high-grade neoplasm. Clinically, the disease typically presents as a painless testicular swelling that develops over a span of weeks to months. B symptoms such as fever, weight loss, and anorexia are present in 25% to 41% of the patients. This tumor is an ag-gressive type, with frequent invasion of the epididymis, spermatic cord, and scrotum, as well as a marked tendency to relapse, especial-ly in the CNS. The treatment is mainly based on orchiectomy (mostly in stages ⅠE and ⅡE) regardless of its association with prophy-lactic irradiation of the scrotum and administration of intrathecal chemotherapy, cyclophosphamide, doxorubicin, vincristine, and pred-nisone regimen chemotherapy plus rituximab (R-CHOP) (stages ⅢE and ⅣE) and radiotherapy. The multi-modality treatment marked-ly improved progression-free and overall survival. We introduce as reference one case that received a multidisciplinary comprehensive discussion in the Department Lymphoma, Tianjin Medical University Cancer Hospital.

OBJECTIVE： To mine and evaluate the post-marketing safety alert signals of pegaspargase （PEG-ASP） and L-asparaginase （L-ASP），and compare the safety differences between them ，so as to provide reference for clinical safe and rational drug use. METHODS ： The adverse drug event （ADE） reports of PEG-ASP and L-ASP issued by FDA adverse event reporting system from Jan. 1st，2004-Jun. 30th，2020 were retrieved. BCPNN method was used to mine the safety signals of these two drugs under the condition that the lower limit of information component （IC－2SD）＞0 and the number of events ≥3. The medium and strong signals of two drugs with IC －2SD≥1.5 were evaluated and compared in 8 system organ class，such as gastrointestinal system ，hepatobiliary system ，blood and lymphatic system ，blood vessels and lymphatic vessels ， nervous system ，immune system ，metabolism and nutrition ，various examinations. IC value of specific ADE signal and its 95％ confidence interval were analyzed by time scanning spectrum. RESULTS & CONCLUSIONS ：The reports of PEG-ASP and L-ASP as suspected drugs were 2 324 and 3 824；67 and 68 medium and strong signals were included ，respectively. In gastrointestinal system，the common strong signal of PEG-ASP and L-ASP was necrotic pancreatitis. In hepatobiliary system ，both of them showed strong signal in venoocclusive liver disease ，and this ADE was not included in the drug instruction. In blood and lymphatic system ， common strong signals of the two drugs were febrile neutropenia ，coagulation disorder ，neutropenia and febrile bone marrow regeneration disorder ；in blood vessels and lymphatic vessels ，in addition to haemodynamic instability ，IC values of other signals of L-ASP were higher than those of PEG-ASP. In nervous system ，IC values of other signals of L-ASP were higher than those of PEG-ASP except for intracranial haemorrhage. In immune system ，anaphylactic reaction was a medium signal for L-ASP but was a strong signal for PEG-ASP. In metabolism and nutritional diseases ，except for tumor lysis syndrome ，IC values of other signals of L-ASP were higher than those of PEG-ASP. The results of time scanning spectrum showed that the signals of necrotic pancreatitis and coagulation disorder of PEG-ASP were stable ，while the signals of veno occlusive liver disease and hypersensitivity were unstable and needed to be observed ；above four signals of L-ASP were stable signals. When using PEG-ASP or L-ASP clinically ， close attention should be paid to the safety problems such as hypersensitivity ，coagulation disorder ，thrombosis，necrotic pancreatitis，venoocclusive liver disease and hypoproteinemia.

Cell migration is defined as the directional movement of cells toward a specific chemical concentration gradient, which plays a crucial role in embryo development, wound healing and tumor metastasis. However, current research methods showed low flux and are only suitable for single-factor assessment, and it was difficult to comprehensively consider the effects of other parameters such as different concentration gradients on cell migration behavior. In this paper, a four-channel microfluidic chip was designed. Its characteristics were as follows: it relied on laminar flow and diffusion mechanisms to establish and maintain a concentration gradient; it was suitable for observation of cell migration in different concentration gradient environment under a single microscope field; four cell isolation zones (20 μm width) were integrated into the microfluidic device to calibrate the initial cell position, which ensured the accuracy of the experimental results. In particular, we used COMSOL Multiphysics software to simulate the structure of the chip, which demonstrated the necessity of designing S-shaped microchannel and horizontal pressure balance channel to maintain concentration gradient. Finally, neutrophils were incubated with advanced glycation end products (AGEs, 0, 0.2, 0.5, 1.0 μmol·L ^-1), which were closely related to diabetes mellitus and its complications. The migration behavior of incubated neutrophils was studied in the 100 nmol·L ^-1 of chemokine (N-formylmethionyl-leucyl-phenyl-alanine) concentration gradient. The results prove the reliability and practicability of the microfluidic chip.
Cell Movement ; Chemotaxis ; Equipment Design ; Lab-On-A-Chip Devices ; Microfluidic Analytical Techniques ; Microfluidics ; Neutrophils ; Reproducibility of Results