Objective: To evaluate the safety of enterovirus 71（EV71）inactivated vaccines produced by Wuhan Institute of Bio Products through learning the incidence of adverse events following immunization（AEFI）in children aged 6 months to 3 years old after vaccination. Methods: According to the national requirement for vaccine safety monitoring program，data of AEFI cases after inoculated EV71 vaccines from September 2017 to October 2018 in Zhejiang Province was collected by combining active and passive monitoring. Demographic characteristics，space distribution，dose and incidence of AEFI were analyzed. Results: A total of 107 503 children were included in this study，of which 27 173 were actively monitored and 80 330 were passively monitored. The monitoring results showed that 288 cases of AEFI occurred after inoculated EV71 vaccines，the reported incidence rate was 267.90/100 000. Of 288 cases，266 cases had common reactions（247.43/100 000），14 cases had abnormal reactions（13.02/100 000）and 8 cases had complications（7.44/100 000）；145 cases were passively monitored（180.51/100 000）and 143 cases were actively monitored（526.26/100 000）；150 cases were males and 138 cases were females，with the males to females ratio of 1.09∶1. The AEFI of EV71 vaccines were reported in all the cities of Zhejiang Province，with Jinhua，Taizhou and Hangzhou ranking the top three and accounting for 50.69% of all the reported cases. About 202 cases of AEFI（70.14%）occurred after the first dose of EV71 vaccines，and 163 cases（56.60%）occurred on the day of inoculation.Most of common reactions were fever，swelling and sclerosis. The harm of the reported abnormal reactions was mild，with 8 cases of anaphylactic rash and no other serious abnormal reactions were found. Conclusion The reported incidence rate of AEFI of the domestic EV71 vaccine in children aged from 6 months to 3 years is 267.90/100 000，without serious abnormal reactions，suggesting that the EV71 vaccine is safe.

Objective: To explore the use of supporting guide wire to exclude the PICC catheter refolding malposition,and reduce the number of the catheter resetting and the average time of catheter resetting,while reducing the mechanicalness phlebitis and the incidence of symptomatic thrombosis. Methods: A total of 3 513 patients who received PICC from September 2016 to August 2018 were enrolled. The patients were divided into control group (1 757 cases) and observation group (1 756 cases) by random number table method.The control group was treated with conventional B-ultrasound guided modified Sadinger technique PICC. After the observation group was finished on the basis of the control group, the support guide wire was partially withdrawn and re-sent, according to whether the guide wire was re-supplied or not, to determine whether the catheter has a partial fold in the body. The incidence of catheter refolding malposition, the number of reductions, the time of reduction, and the incidence of mechanicalness phlebitis and symptomatic thrombosis were compared between the two groups. Results: The refolding malposition rate of the observation group and the control group were 0 and 3.47%(61/1 757), respectively. The difference was statistically significant (χ²=59.943, P<0.01). Among the 74 patients in the observation group who underwent catheter resetting, 63 patients were reset ≤1 times, 9 patients were reset twice, 2 patients were reset≥third; among the 61 patients in the control group who underwent catheter resetting, 24 patients were reset≤1 times, 6 patients were reset twice, 31 patients were reset≥third, the number of the resetting in two groups were compared,the difference was statistically significant(χ²=42.712, P<0.05). The average reset time of the observation group was (49.66±25.45) s, and the average reset time of the control group was (610.41±206.23) s, the difference was statistically significant (t=18.636, P<0.01).The incidence of mechanical phlebitis in the observation group and the control group were 1.31%(23/1 756) and 3.76%(66/1 757), respectively. The incidence of mechanical phlebitis in the two groups was statistically significant (χ²=20.241, P<0.01). The incidence of symptomatic thrombosis in the observation group and the control group were 0.34%(6/1 756), 1.20%(21/1 757), respectively. The incidence of symptomatic thrombosis in the two groups was statistically significant (χ²=8.261, P<0.05). Conclusions The use of the supportting guide wire to withdraw and re-feed during the catheterization process can effectively eliminate the PICC catheter refolding malposition, reduce the number of catheter reposition and the average reposition time, and reduce the incidence of mechanicalness phlebitis and symptomatic thrombosis. This method is simple and easy to use, it is worthy of clinical application.

Objective: To evaluate the post-marketing safety of inactivated Enterovirus type 71 (EV-A71) vaccine (human diploid cell) . Methods: A total of 20 191 healthy children aged 6 to 59 months were invited to receive 2 doses of EV-A71 vaccine in Zhejiang Province from September 2016 to December 2017. Child caregivers were followed up on the 4^th or 5^th day after each EV-A71 vaccination, and the incidence of local, systemic, and other adverse events within 3 days after vaccination was recorded to assess vaccine safety. Describe the differences in adverse events among children with different characteristics. Results: A total of 32 230 doses were observed in this study, of which 20 191 and 12 039 were vaccinated for the first and the second dose, respectively; and the incidence of adverse events within 3 days was 2.045% (413 doses) and 1.611% (194 doses), respectively. After the first and the second dose, the number of systemic adverse events was the highest, 371 and 175 cases, respectively, with an incidence of 1.837% and 1.454%, respectively; the number of local adverse events was the lowest, 14 and 2 doses, respectively, with an incidence of 0.069% and 0.017%. Local adverse events occurred after vaccination were generally mild, and only 2 patients had level of 3; among the systemic adverse events, 39 patients had a fever level of 3 or higher, accounting for 8.2% of the total fever. Most of the symptoms in the local adverse events did not require treatment, only 3 cases of vaccination site rash and 2 cases of pruritus were self-purchased drugs or outpatient treatment; except for 5 cases of fever, the other symptoms were not hospitalized in the case of systemic adverse events. Conclusion The incidence of adverse events within 3 days after vaccination with EV-A71 vaccine was low in children, mainly systemic adverse events, and the prognosis was good.

Premature infants with younger gestational age are more susceptible to a variety of risk factors, such as ischemia, hypoxia, infection and inflammatory damage.These risk factors will lead to white matter damage and cause neurological sequelae.In recent years, multimodality MRI such as diffusion weighted imaging, diffusion tensor imaging, magnetic resonance spectroscopy and susceptibility weighted imaging have developed rapidly, which provide evidence not only for the location and nature of brain damage, but also for the pathophysiology, tissue blood supply, cell metabolism.This review summarizes the application of multimodality MRI in premature infants with white matter damage.

AIM: To explore the pharmacokinetic interactions between sorafenib and dapagliflozin in rats and to provide some theoretical basis for the rational clinical use of the two drugs. METHODS: An ultra -performance liquid chromatography-tandem mass spectrometry (UPLC / MS / MS) method was developed for the simultaneous determination of sorafenib and dapagliflozin. Male SD rats were randomly divided into 5 groups (6 rats in each group), including 100 mg / kg sorafenib group, 0.5 mg / kg dapagliflozin group, 1 mg / kg dapagliflozin group, and 100 mg/kg sorafenib combined with 0.5 mg/kg dapagliflozin group and 100 mg/kg sorafenib combined with 1 mg / kg dapagliflozin group, for sorafenib and dapagliflozin drug interaction study. All samples were analyzed using a validated UPLC/ MS/MS method, and the main pharmacokinetic parameters were calculated by compartment model. RESULTS: 1 mg/kg dapagliflozin increased the C

Palbocicril, the first cyclin-dependent kinases 4 and 6 inhibitors, is a crucial milestone in the development history of antineoplastic drugs. It combined with aromatase inhibitor or fulvestrant as first-line, second-line or post-line therapy has good efficacy and safety for hormone receptor-positive, human epidermal growth factor receptor-2 negative locally advanced or metastatic breast cancer, which has a good application prospect. This article summarizes the clinical trials and safety studies related to palbociclib.

Drug-drug interactions (DDI) of tyrosine kinase inhibitors (TKIs) mediated by metabolic enzymes and transporters have become an important issue in clinical practice recently. In addition to CYP450 enzymes, uridine diphosphate glucuronidases (UGTs) are another class of metabolic enzymes involved in the metabolism of TKIs, and most TKIs can inhibit the UGTs in vitro. Potential clinically meaningful DDIs may occur with the co-administration of TKIs and substrates or inhibitors of UGTs. This paper will mainly focus on the UGTs-mediated drug-drug and the effect of UGT1A genotype on the drug interactions of TKIs and explores strategies to address, aiming to provide clinicians and pharmacists with references for the safe and rational application of TKIs.

Liver fibrosis is a key step in the progression of chronic liver diseases to liver cirrhosis and even liver cancer. In recent years， a large number of studies have shown the necessity of intervening in the process of liver fibrosis， and various anti-liver fibrosis drugs and active ingredients have been discovered. Non-coding RNAs also play an important role in the process of liver fibrosis， and searching for upstream non-coding RNAs that can regulate signaling pathways can provide new insights for anti-liver fibrosis treatment. This article introduces the process of liver fibrosis mediated by the TGF-β， Wnt/β-catenin， PI3K/Akt/mTOR， NF-κβ， Hippo， and MAPK signaling pathways， lists the latest anti-liver fibrosis drugs or active components in each signaling pathway， and summarizes the research advances in anti-liver fibrosis targets and drugs mediated by related non-coding RNAs， so as to provide new research ideas and treatment methods for anti-liver fibrosis treatment.

OBJECTIVETo study the high risk factors of the third level of lymphatic metastasis in breast cancer patients to guide clinical practice.

METHODSThe clinical data of 746 breast cancer patients (all female, aged from 33 to 80 years with a median of 46 years) received radical or modified mastectomy between 2001 and 2011 was analyzed retrospectively. Eleven individual variables were selected to investigate high risk factors of the third level of lymphatic metastasis in different conditions.

RESULTSAxillary nodes metastasis status (OR = 4.541, 95%CI:3.569-5.776), tumor site (OR = 1.437, 95%CI:1.029-2.007), external nodes involved (OR = 3.809, 95%CI:1.683-8.618) and estrogen receptor (OR = 0.740, 95%CI:0.569-0.964) were high risk factors of the third level of lymphatic metastasis. Further analysis found that it is prone to happen a metastasis, especially when the tumor with a size over 5 cm and located at the lateral quadrant. Negative estrogen receptor was a risk factor of the third level lymphatic metastasis along with the tumor stage.

CONCLUSIONFor preoperative tumor biopsy shows Negative estrogen receptor of tumor stage T3 and over stage T3 when considering suspicious lymph node metastasis or external tissues metastasis intraoperatively should take in account into third level axillary lymph node dissection actively.

Adult ; Aged ; Aged, 80 and over ; Axilla ; pathology ; Breast Neoplasms ; pathology ; surgery ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Mastectomy ; methods ; Middle Aged ; Prognosis ; Retrospective Studies ; Risk Factors

Objectives: To evaluate the safety of inactivated enterovirus A71(EV-A71) vaccines after large-scale immunization in the community. Methods: We selected EV-A71 susceptible people (healthy children) aged 6-59 months in vaccination clinics from 89 counties in Zhejiang Province between April 2016 and March 2018. All local and systematic adverse actions were collected by 30 min on-site inspection, within 3 days and 4-30 days follow-up. Chi-square test and Fisher′s exact test were used to compare the difference of AEs incidence in various characteristics among two groups. Results: A total of 71 663 doses of vaccines were included for active safety analysis, which included 37 331 doses in boys and 34 332 doses in girls. Among all the doses, children aged 6 to 11 months, 12 to 23 months and 24 to 59 months were received 13 707, 32 639 and 25 317 doses respectively. The incidence of adverse reactions within 30 min, 3 days and 4-30 days were 0.33% (239 doses), 1.58% (1 133 doses) and 0.34% (244 doses) respectively. Adverse reactions within 3 days were 1 372 doses, with a incidence of 1.91%; among all the cases, 539 doses (0.75%) were grade 1, 677 doses (0.94%) were grade 2 and 156 doses (0.22%) were grade 3, no grade-4 adverse reaction was reported. The common local adverse reactions were redness, swelling and pruritus, with the incidence rates were 0.05% (39 doses), 0.02% (16 doses) and 0.02% (12 doses), respectively, while the most common systemic adverse reaction was pyrexia with an incidence of 1.19% (856 doses), followed by diarrhea and anorexia with the incidence rates were 0.15% (104 doses) and 0.13% (90 doses) respectively. Conclusion Most adverse actions of EV-A71 vaccines were mild and moderate and majority of them were common adverse actions. No new adverse reactions were found in the study.