Background and purpose:For patients with advanced lung adenocarcinoma harboring an activating EGFR gene mutation, the current standard of care is EGFR-TKI alone. This study aimed to compare efficacy and safety of gefitinib plus chemotherapy with gefitinib or chemotherapy alone for treating advanced lung adenocarcinoma with an activatingEGFR gene mutation.Methods:This study included 61 patients with lung adenocarcinoma harboring an acti-vatingEGFR gene mutation (19 exons deletion and exon 21 L858R mutations) whose ECOG performance status was 0 or 1. Patients were randomly divided into 3 groups. Group A (n=20) were given carboplatin/pemetrexed of a 4-week cycle, six cycles at most, plus gefitinib (pemetrexed 500 mg/m2, d1; carboplatin AUC 5, d1; gefitinib 250 mg/d, d 5-21), and then re-ceived pemetrexed of a 4-week cycle plus gefitinib as maintenance therapy; Group B (n=20) were given carboplatin/peme-trexed of a 4-week cycle, six cycles at most (pemetrexed 500 mg/m2, d1; carboplatin AUC 5, d1), then received pemetrexed as maintenance therapy; Group C (n=21) were given gefitinib (gefitinib 250 mg/d). Patients continued to receive therapy until disease progression or unacceptable toxicity or death. The primary end point was middle PFS and 12 months PFS rate. The secondary end points included objective response rate and adverse events.Results:Groups A and C both lost 1 case during follow-up. Median PFS for patients was 20.1 months (95%CI:18.0-22.2) in group A, 5.5 months (95%CI:3.9-7.2) in group B, and 9.8 months (95%CI:6.8-12.8) in group C. PFS rates of 12 months for groups A, B and C were 78.9%, 15.0% and 40.0%, respectively. The overall objective response rates for groups A, B and C were 84.2%, 35.0% and 65.0%, respectively. Serious adverse events were reported by 36.8% for group A, 30.0% for group B, and 5.0% for group C. The most common grade 3/4 adverse events were neutropenia (3 cases in group A, 4 cases in group B), fatigue (2 cases in group A, 2 cases in group B) and liver function impairment (2 cases in group A, 1 case in group C).Conclusion:Among patients withEGFR mutant lung adenocarcinoma, combination of chemotherapy with gefitinib as first-line treatment demonstrates an improvement in PFS. Long-term survival results will be further followed up.

BACKGROUND: Our previous findings have shown that poly(lactic acid)/hydroxyapatite (PLA/HA) composite biomaterials prepared by the supercritical carbon dioxide method have good physiochemical properties and biocompatibility. However, the composite materials only have osteoconductivity but no osteoinductivity. OBJECTIVE: To prepare icariin-PLA/HA (IC-PLA/HA) composite biomaterials with good osteoconduction and osteoinduction. METHODS: The supercritical carbon dioxide method was used to prepare IC-PLA/HA composite biomaterials containing 10-4, 10-5, 10-6mmol/g IC, named as IC-PLA/HA(1 000), IC-PLA/HA(100) and IC-PLA/HA(10). PLA/HA composite material served as controls. Biomechanical properties, porosity, sustained release characteristics were detected, and scanning electron microscope observation was performed, in order to screen out the optimal IC content in the composite materials. RESULTS AND CONCLUSION: (1) Compressive strength and elastic modulus of IC-PLA/HA(1 000), IC-PLA/HA(100) and IC-PLA/HA(10) showed no difference from those of PLA/HA. (2) The porosity of all the composite materials was over 75%, and there was still no difference among groups. (3) The IC release from IC-PLA/HA was faster within the first 3 days, and then reduced gradually. However, after 7 days, the IC release plateaued, and the IC release amount from the IC-PLA/HA(100) was close to 10-7mol/L that had been confirmed to be an effective and safe concentration in the previous experiments. (4) Under the scanning electron microscope, HA and PLA were mixed homogeneously and IC was difficult to be identified. The pore size of the IC-PLA/HA(100) ranged from 50 μm to 150 μm. Overall, the IC-PLA/HA composite biomaterials have good mechanical and sustained-release properties.

OBJECTIVETo explore the effects of prenatal exposure to low level lead on learning and memory of rat's offspring.

METHODSThe pregnant rats were randomizedly divided into 4 groups and provided with doubly evaporated water in the control group and 125, 250 and 500 mg/L lead acetate solution via drinking water in three exposed groups respectively during the pregnancy. The learning and memory ability of 21-day old and 60-day old offsprings were tested by the Morris water maze and the shuttling and avoiding dark box respectively.

RESULTSThe blood and hippocampus lead concentrations of 1-day old and 21-day old offspring in the 3 lead-exposed groups were significantly increased compared with the control group (P < 0.05), while at the period of 60-day old there was no significant difference between them. The time to find the platform in Morris water maze for 21-day old and 60-day old offsprings of the 3 lead in the exposed groups was significantly increased compared with the control group during the 4 days training (P < 0.05). The times of initiative avoiding in the shuttling and avoiding dark box for 21-day old and 60-day old offsprings in the 3 lead-exposed groups were significantly decreased, while the latency of the initiative avoiding and latency of the passive avoiding were significantly increased compared with the control group (P < 0.05).

CONCLUSIONPrenatal exposure to low level lead impaired the space learning and memory ability of offsprings of the rats, and this kind of influence will continue till the offspring's maturity.

Animals ; Dose-Response Relationship, Drug ; Female ; Hippocampus ; drug effects ; metabolism ; Lead ; toxicity ; Maze Learning ; drug effects ; Memory ; drug effects ; Pregnancy ; Prenatal Exposure Delayed Effects ; Random Allocation ; Rats ; Rats, Wistar

Fear memories are temporarily suppressed after repeated retrieval, a phenomenon known as memory extinction.How to reduce or even eliminate fear memory is the key to the treatment of fear related diseases such as post-traumatic stress disorder(PTSD). A single extinction training based on Pavlov's fear regulation task could only inhibit the expression of conditioned fear memory traces, but it could not eliminate the acquired conditioned fear memory. However, according to the reconsolidation theory based on memory, the retrieval-extinction paradigm has a more lasting effect on the erasure and rewriting of fear memory, and can effectively prevent the return of fear memory. Studies have shown that extraction-regression is closely related to a variety of neurotransmitter receptors such as glutamate receptor(GluR), dopamine receptor(DAR), L-type voltage-gated calcium channels(LVGCs) and cannabinoid. Moreover, its effect is closely related with factors such as retrieval-extinction memory stage. At present, most of the researches on extracted boundary conditions only stay at the level of behavior, with little understanding and exploration on the level of molecular mechanism. From the perspective of molecular neurobiology, with different stages of memory and different types of receptors and molecular mechanisms, this research reviewed the mechanisms of retrieval-extinction in recent years.It provided valuable signaling pathways, molecular targets and research directions for the treatment of fear-related diseases such as PTSD.

ObjectiveTo investigate the clinical features of liver function and coagulation function in patients with Alongshan virus (ALSV) infection. MethodsClinical data were collected from 27 patients with ALSV infection who were admitted to Inner Mongolia General Forestry Hospital from May 2018 to September 2019, among whom there were 18 male patients and 9 female patients. Related data were extracted, and a database of relevant case reports was established. The descriptive epidemiological method was used to analyze the clinical features of liver function and coagulation markers, and the features of liver injury caused by ALSV infection were analyzed. ResultsFor the 27 patients, the abnormal rates of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), cholinesterase, and total bile acid were 25.9%, 33.3%, 25.9%, 40.7%, 8%, and 8%, respectively; among the 27 patients, 4 (14.8%) had an ALT level of ＞2×upper limit of normal (ULN), 3 (11.1%) had an AST level of ＞2×ULN, 1 (3.7%) had an ALP level of ＞2×ULN, and 5 (18.5%) had a GGT level of ＞2×ULN. Among the 27 patients, 25 (17 male patients and 8 female patients) had the results of bilirubin test, among whom 1 had a reduction in total bilirubin (TBil) (3.30 μmol/L) and 3 had an increase in TBil (23.7 μmol/L, 26.2 μmol/L, and 32 μmol/L, respectively). The abnormal rates of the coagulation markers international normalized ratio, activated partial thromboplastin time, and fibrinogen were 3.7%, 11.1%, and 22.2%, respectively. ConclusionThere is a certain degree of liver injury in patients with ALSV infection, generally with mild symptoms.

Objective To explore the changes of functional connectivity of anterior cingulate cortex (ACC) in online game addicts during the resting state,and to analyze the function of ACC in the pathogenesis of online game addiction from a perspective of resting-state functional connectivity.Methods Seventeen online game addicts treated in our hospital from March 2011 to October 2011 were recruited as addiction group and 17 healthy controls at the same period were recruited as HC group.The baseline characteristics of all 34 subjects were investigated and compared between the addiction group and the HC group.All fMRI data were preprocessed after a resting-state fMRI scan,and then,the left and right anterior cingulate cortexes were selected as regions of interest (ROIs) to calculate the linear correlation between the ACC and the entire brain to compare the differences between the online game addicts and normal controls.Results Obvious differences between the addiction group and HC group were noted in hours and days of online game using and degree of thirst to play online games (P＜0.05);within the functional connectivity of ACC during the resting state,in contrast to the controls,the online game addicts showed increased connectivity with posterior cingulate,medium cingulate,midbrain,nucleus accumbens and supplementary motor area,but reduced connectivity with prefrontal cortex,temporal lobe and occipital lobe (P＜0.05).Conclusion Altered functional connectivity of the ACC reflects the dysfunction in ACC of online game addicts,which may be linked to the forming and maintaining of the online game addiction.

OBJECTIVETo examine the effects of niacin on lysophosphatidylcholine (LPC)-induced intercellular adhesion molecule-1 (ICAM-1), and gained insight to the mechanisms.

METHODHuman umbilical vein endothelial cell line was cultured using Medium 200 medium in incubator at 37 °C and 5% CO2 condition.Experimental groups:(1) the negative control group:medium; (2) LPC different time groups:the medium added with 20 µmol/L final concentration of LPC, were cultured for 10 min and 8 h, 24 h; (3) LPC+ p38-mitogen-activated protein kinase (p38MAPK) inhibitor (SB203580) group:the medium added with 10 µmol/L p38MAPK inhibitor (SB203580) was cultured for 1 h, then human umbilical vein endothelial cells (HUVECs) added with the LPC were cultured for 10 min, 8 h and 24 h.(4) LPC+different niacin dose group:after separately adding with 0.25, 0.5, 1 mmol/L niacin, the cells were cultured for 18 h, then HUVECs added with the LPC were cultured for 10 min, 8 h and 24 h. Cell concentration in each group was 5×10(5)/ml, inoculated in 6-well plates, each well 1 ml. Detected by Western blot analysis of pp38MAPK, ICAM-1 protein content, real-time quantitative PCR to detect endothelial cell ICAM-1 mRNA expression, cell immunofluorescence to detect LPC-induced ICAM-1 protein expression.

RESULTIn LPC 24 h group, the expression of ICAM-1 protein was significantly increased 0.786 ± 0.02, the LPC+niacin group, ICAM-1 protein levels (0.487 ± 0.015) was significantly lower than the LPC 24 h group (P < 0.01), in LPC+SB203580 intervention group, ICAM-1 protein levels (0.461 ± 0.011) was significantly lower than that of the LPC 24 h group (P < 0.01), but did not reach the level of the control group. Adding LPC to culture for 10 min, phosphorylation of p38MAPK (pp38MAPK) reached its peak (0.47 ± 0.02), niacin could reduce the pp38MAPK (0.07 ± 0.02), SB203580 could also reduce its activity (0.11 ± 0.02). Adding LPC to culture for 8 h, ICAM-1 mRNA expression (8.16 ± 0.15) compared with the control group (1.00 ± 0.02) had a significant increase (t = 24.34, P < 0.01). Compared with the LPC 8 h, niacin reduced LPC-induced ICAM-1 mRNA expression (3.85 ± 0.14), and showed a dose-dependent manner (F = 8.06, P < 0.01), while SB203580 could not effectively reduce the ICAM-1 mRNA (8.09 ± 0.11).

CONCLUSIONNiacin prevented LPC-induced endothelial dysfunction by reducing expression of ICAM-1. These mechanisms appeared to be at least partly mediated by suppression of the pp38MAPK in endothelial cells. These pleiotropic effects of niacin may potentially contribute to the beneficial effects of risk reduction for atherosclerotic disease.

Atherosclerosis ; metabolism ; prevention & control ; Cell Adhesion ; drug effects ; Cells, Cultured ; Enzyme Inhibitors ; administration & dosage ; pharmacology ; Gene Expression Regulation ; drug effects ; Human Umbilical Vein Endothelial Cells ; drug effects ; metabolism ; Humans ; Imidazoles ; administration & dosage ; pharmacology ; Intercellular Adhesion Molecule-1 ; genetics ; metabolism ; Lysophosphatidylcholines ; administration & dosage ; pharmacology ; Niacin ; administration & dosage ; pharmacology ; Pyridines ; administration & dosage ; pharmacology ; RNA, Messenger ; genetics ; metabolism ; Real-Time Polymerase Chain Reaction ; Signal Transduction ; p38 Mitogen-Activated Protein Kinases ; antagonists & inhibitors ; metabolism

OBJECTIVE: To analyze clinical feature and information of medication to explore the risk signals of preparations containing Psoraleae Fructus (BGZP) related with hepatobiliary adverse drug reactions (ADR), in order to reinforce pharmacovigilance. METHODS: A retrospective study was conducted based on hepatobiliary ADR related with BGZP from the China Adverse Drug Reaction Monitoring System in years from January 2012 to December 2016. Serious and general ADRs were analyzed and assessed. RESULTS: There were 355 cases of hepatobiliary ADR related to BGZP. Both the amount of cases and the proportion of serious ADR showed an increasing growth by years (P<0.05). It was found that 10.43% of 355 cases may be involved with irrational drug use, including overdose, repeated medication, and combination of multiple drugs. There were 190 cases which used BGZP (non-combination), and they were mainly for common in diseases caused by abnormal immune activation (accounting for 40.53% of the total cases). Especially at the age group with the most cases with age of 41-50 years, the cases associated with immunological diseases of female were obviously more than that of male (P<0.05). The latency of hepatobiliary ADR related to BGZP ranged from 1 to 386 days, and the median latency was 27.5 days, along with the range of cumulative dose (0.45-520.02 g) as well as the daily dose (0.09-2.64 g/d) after the conversion. CONCLUSIONS Cases of hepatobiliary ADR related to BGZP showed significant individual differences, and there was no correlation between drug usage duration and dosage and the occurrence of hepatobiliary ADR. It may be similar with idiosyncratic drug-induced liver injury, and recommended that BGZP should be used with more caution under monitoring liver function, especially in female patients with immunological diseases.
Adult ; Adverse Drug Reaction Reporting Systems ; Chemical and Drug Induced Liver Injury/etiology* ; Drug-Related Side Effects and Adverse Reactions ; Female ; Humans ; Male ; Middle Aged ; Pharmacovigilance ; Retrospective Studies

As a representative variety of hypertoxic herbs, aconite has a very high medicinal value but certain security risks. With the advance of urbanization and industrial transfer and upgrading, traditional geo-authentic regions and emerging regions have gradually coexisted. However, there are significant differences in the geographical distribution, ecological environment and growing cycle in these areas, which may cause intraspecific variations in chemical components, and then affect herb quality and clinical efficacy. Furthermore, there was still lack of in-depth study on characteristic constituents of aconite genuineness. In this paper, an UPLC-Q-TOF-MS was used to investigate the chemical ingredients in Jiangyou aconite, Hanzhong aconite, Butuo aconite and Weishan aconite. The results suggested that using unsupervised PCA method, Jiangyou aconite was similar with Hanzhong aconite in chemical ingredients, but significantly different from ones in emerging regions. Using PLS-DA method, seven characteristic constituents were identified, in which Butuo aconite and Weishan aconite had higher contents of mesaconitine and fuziline, while Jiangyou aconite and Hanzhong aconite had higher contents of hypaconitine, neoline, carmichaeline, and songorine. Based on basic toxicity of each ingredient, we can find that hypaconitine and mesaconitine were the key toxicity factors to distinguish Jiangyou aconite, Butuo aconite, and Weishan aconite. The toxicity of geo-authentic Jiangyou aconite was lower than that of Butuo aconite and Weishan aconite. The lower toxicity in geo-authentic Jiangyou aconite was beneficial for ensuring clinical drug safety, which may be one of the important reasons for the formation of genuine aconite. These results provide new reference data to reveal the formation mechanism of genuine aconite from the perspective of plant secondary metabolite diversity.

To systematically evaluate the efficacy and safety of Gongxuening Capsules in the treatment of abnormal vaginal bleeding after medical abortion. CNKI, Wanfang, SinoMed, VIP, PubMed, Cochrane Library and EMbase databases were retrieved to comprehensively collect the clinical randomized controlled trials(RCTs) of Gongxuening Capsules for treatment of abnormal vaginal bleeding after medical abortion from the establishment of the databases to October 10, 2020. Literature screening, data extraction and quality evaluation were conducted independently by two system reviewers according to the inclusion and exclusion criteria. Cochrane Handbook bias risk assessment tool was used for the literature methodology quality evaluation, RevMan 5.3 software was used for Meta-analysis, and the evidence quality of outcomes was evaluated by the evidence quality grading system(GRADE). A total of 16 RCTs were inclu-ded. The results of Meta-analysis showed that as compared with the western medicine treatment alone, the addition of Gongxuening Capsules to the western medicine treatment can reduce the amount of vaginal bleeding(RR=1.23, 95%CI[1.19, 1.27], P<0.000 01), shorten vaginal bleeding time(RR_(≤15 d number of people)=1.39, 95%CI[1.31, 1.48], P<0.000 01; MD_(number ofdays)=-1.20, 95%CI[-1.66,-0.74],P<0.000 01). However, there was no obvious advantage in abortion effect(RR=1.02, 95%CI[0.99, 1.06], P=0.14) and menstrual recovery(MD=-0.35, 95%CI[-0.96, 0.25], P=0.25). The results of GRADE showed that the grading level was low for vaginal bleeding volume and vaginal bleeding time, and extremely low for abortion effect and mens-trual recovery. In terms of safety, 16 studies reported adverse events. Only one study showed no adverse events and the rest showed transient nausea, vomiting, stomach burning, upper abdominal discomfort and other gastrointestinal symptoms. The results show that the addition of Gongxuening Capsules to the application of western medicine in treatment of drug abortion can reduce the amount of vaginal bleeding and shorten vaginal bleeding time, but the abortion effect and menstrual recovery have no obvious advantages. The use of Gongxuening Capsules helps to achieve less adverse reactions and higher safety. Due to the small sample size of the included studies and many methodological quality problems, no conclusions with clinical guidance value can be obtained. Large sample-zise, high-qua-lity randomized controlled trials are still needed for further verification.
Abortion, Induced/adverse effects* ; Capsules ; Drugs, Chinese Herbal/adverse effects* ; Female ; Humans ; Male ; Pregnancy ; Uterine Hemorrhage