AIM: To investigate the effects of 0.01% atropine eye drops on macular blood flow density and retinal thickness in children with different degrees of myopia. METHODS: This was a prospective case-control study. Sixty-four patients (112 eyes) diagnosed with myopia for the first time with 0.01% atropine eye drops before and 6 months after medication were investigated with the uncorrected distance visual acuity (UCVA), axial length (AL), spherical equivalent (SE), macular ganglion cell-inner plexiform layer thicknes (mGCIPL) using slit lamp examination and optical coherence tomography (OCT), vascular density in the macular area and the area of the avascular in the fovea using optical coherence tomography angiography (OCTA) . Changes in various indicators before and after medication were compared. RESULTS: Compared with before medication, the AL of the three groups of myopia patients increased significantly (P<0.01), the difference in low to moderate myopia group was significantly smaller than that in high myopia group. Compared with before medication, SE increased in all three groups of myopia patients, yet there was no statistically significant difference in the low - grade myopia group (P>0.05). The difference was statistically significant between the moderate myopia group and the high myopia group (P< 0.01). Compared with before medication, there was no change in intraocular pressure (IOP) among the three groups of myopic patients (P>0.05). After 6 months of medication, the central circle macular vessel density (cCVD) increased in the low myopia group and moderate myopia group (P<0.01), there was no statistically significant difference in the high myopia group (P>0.05). Before and after medication, there was no significant difference in outer circle macular vessel density (oCVD), inner circle macular vessel density (iCVD), and whole circle macular vessel density (wCVD) among the three myopia groups (P>0.05). The increase in mGCIPL was statistically significant in the low myopia group (P<0.01), but there was no statistically significant difference in the moderate myopia and high myopia groups (P>0.05). There was no significant difference in foveal avascular zone (FAZ) among the three myopia groups before and after medication (P>0.05). There was no correlation between CVD, AL, and SE in the three myopia groups (P>0.01). There was a low correlation between CVD and mGCIPL in the low myopia group (r=0.442, P<0.05), there was no correlation between CVD and mGCIPL in the moderate myopia and high myopia groups (P >0.01). CONCLUSION: 0.01% atropine can significantly reduce the rate of axial and refractive growth in children with low to moderate myopia, increase the density of central macular vessels, and increase the thickness of mGCIPL in children with low to moderate myopia.

Palliative care,as the most special way to treat malignant tumors,is not only conducive to improving the quality of life and life value of patients,as well as alleviating the physical and mental pain of patients and their families,but also can help to relieve their financial burden and effectively avoid the waste of limited public resources.However,in the actual promotion of palliative care services,various ethical issues are encountered,such as the dignity of death,the need for psychological care,and the patient's right to independent decision-making.From the perspective of bioethics,by analyzing different types of practical disputes,this paper revealed their inherent ethical problems,and proposed specific countermeasures from the aspects of defending patient dignity,breaking the limitations of traditional cognition,and establishing a field model for joint decision-making between doctors and patients,so as to build a palliative care service model that suits China's national conditions and safeguard the patients'life rights and interests with malignant tumors.

[Objective]To investigate the effects of traditional Chinese medicine acupuncture combined with 0.01%atropine eye drops on macular vascular density and retinal thickness in children with low myopia.[Methods]A total of 84 children(156 eyes)newly diagnosed as low myopia were randomly divided into an experimental group and a control group.The experimental group received traditional Chinese medicine acupuncture combined with 0.01%atropine eye drops,while the control group was treated with 0.01%atropine eye drops alone.Ophthalmic examinations were performed before and after six months of treatment,including uncorrected distance visual acuity(UCVA),axial length(AL),spherical equivalent(SE),and slit-lamp examination.Optical coherence tomography(OCT)was used in routine mode to measure macular ganglion cell-inner plexiform layer(mGCIPL)thickness,and optical coherence tomography angiography(OCTA)was employed to measure macular vascular density and the area of the foveal avascular zone(FAZ).Changes in various indicators before and after treatment were compared between the two groups.[Results]After six months of treatment,both groups showed significant increases in AL and SE compared with that before treatment(P<0.01).The differences in AL and SE were significantly smaller in the experimental group than in the control group(P<0.05).No significant changes in intraocular pressure(IOP)were observed in either group before and after treatment(P>0.05).Compared to before treatment,both groups exhibited significant increases in mGCIPL thickness(P<0.01,P<0.05).Central circle macular vessel density(cCVD)increased in the experimental group(P<0.01),while there was no significant changes in outer circle macular vessel density(oCVD),inner circle macular vessel density(iCVD),whole circle macular vessel density(wCVD)or FAZ(P>0.05).After six months of treatment,no correlation was found between cCVD and AL or SE in the experimental group(P>0.05),but cCVD was positively correlated with mGCIPL thickness(r=0.448,P<0.05).[Conclusion]Traditional Chinese medicine acupuncture combined with 0.01%atropine eye drops can further reduce the growth rate of AL and diopter in children with low myopia.Additionally,this combined treatment increases cCVD and mGCIPL thickness in these children.

OBJECTIVE To explore whether diterpenoid 12-deoxyphorbol-13-palmitate （DP） from Euphorbia fischeriana can exert anti-leukemia effects through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signal pathway， and to provide experimental evidence for developing it into a new anti-leukemia drug. METHODS Using LY294002 （PI3K specific inhibitor） as tool drug， the effects of 24 h DP treatment on the proliferation and apoptosis of human myeloid leukemia HL60 cells were detected by MTT method， Annexin Ⅴ-FITC/PI staining and AO-EB staining. ELISA method was used to detect lactic dehydrogenase （LDH） release and the activities of cysteinyl aspartate specific proteinase 3 （caspase-3） and caspase-9. The transcriptional level of caspase-3， caspase-9， forkhead box O3a （FoxO3a） and B cell lymphoma 2 interacting mediator of cell death （Bim） mRNA were detected by real-time quantitative polymerase chain reaction （qRT-PCR）. The protein expression of phosphorylated FoxO3a （p- FoxO3a） and phosphorylated Akt （p-Akt） were detected by Western blot method. The nuclear translocation of FoxO3a protein was detected by immunostaining combined with laser confocal microscopy. RESULTS 10 μmol/L DP and 10 μmol/L DP+LY294002 could inhibit the proliferation and induce the apoptosis of HL60 cells （P＜0.01）. After treatment of 5， 10， 20 μmol/L DP， HL60 cells showed typical morphological characteristics of apoptosis； DP could significantly increase the levels of LDH release and the activities of caspase-3 and caspase-9 （P＜0.05 or P＜0.01）， in dose-dependent manner. After treatment of 10 μmol/L DP and 10 μmol/L DP+LY294002， the transcriptional levels of caspase-3， caspase-9 and Bim mRNA were increased significantly （P＜0.05 or P＜0.01）， and transcriptional level of FoxO3a mRNA and protein expressions of p-FoxO3a and p-Akt were decreased significantly （P＜0.05 or P＜0.01）. Nuclear translocation changes were observed in FoxO3a protein in 10 μmol/L DP+LY294002 group， and the change was more significant than that of LY294002 group. CONCLUSIONS DP can inhibit the proliferation and induce the apoptosis of HL60 cells via inhibiting PI3K/Akt signaling pathway.

This paper reviews the investigation of examining a child without protective equipment exposed to an exceptionally large radiation field, in order to provide a reference for the investigation and handling of similar cases in the future. Based on the analysis of the way of obtaining evidence and the application of law, the authors put forward some suggestions, such as improving the standards, laws, and regulations related to radiation, enhancing the protective facilities, standardizing the law enforcement procedures, and strengthening the publicity and training of radiation hygiene. The health-related rights and interests of the examinees shall be effectively protected.

BACKGROUND: Low-density computed tomography (LDCT) improved early lung cancer diagnosis but introduces an excess of false-positive pulmonary nodules data. Hence, accurate diagnosis of early-stage lung cancer remains challenging. The purpose of the study was to assess the feasibility of using circulating tumour cells (CTCs) to differentiate malignant from benign pulmonary nodules. METHODS: 122 patients with suspected malignant pulmonary nodules detected on chest CT in preparation for surgery were prospectively recruited. Peripheral blood samples were collected before surgery, and CTCs were identified upon isolation by size of epithelial tumour cells and morphological analysis. Laser capture microdissection, MALBAC amplification, and whole-exome sequencing were performed on 8 samples. The diagnostic efficacy of CTCs counting, and the genomic variation profile of benign and malignant CTCs samples were analysed. RESULTS: Using 2.5 cells/5 mL as the cut-off value, the area under the receiver operating characteristic curve was of 0.651 (95% confidence interval: 0.538-0.764), with a sensitivity and specificity of 0.526 and 0.800, respectively, and positive and negative predictive values of 91.1% and 30.3%, respectively. Distinct sequence variations differences in DNA damage repair-related and driver genes were observed in benign and malignant samples. TP53 mutations were identified in CTCs of four malignant cases; in particular, g.7578115T>C, g.7578645C>T, and g.7579472G>C were exclusively detected in all four malignant samples. CONCLUSIONS CTCs play an ancillary role in the diagnosis of pulmonary nodules. TP53 mutations in CTCs might be used to identify benign and malignant pulmonary nodules.
Humans ; Lung Neoplasms ; Exome Sequencing ; Multiple Pulmonary Nodules ; Carcinoma ; DNA Repair

In traditional Chinese medicine herbs (TCM), including Radix Salviae Miltiorrhizae (Danshen), Radix Puerariae Lobatae (Gegen), Radix Angelicae Sinensis (Danggui), and Rhizoma Chuanxiong (Chuanxiong) are widely used for the prevention and treatment of cardiovascular diseases and also often co-administered with Western drugs as a part of integrative medicine practice. Carboxylesterase 1 (CES1) plays a pivotal role in the metabolisms of pro-drugs. Since (S)-2-(2-(6-dimethylamino)-benzothiazole)-4,5-dihydro-thiazole-4-carboxylate (NLMe) has recently been identified by us as a selective CES1 bioluminescent sensor, we developed a rapid method using this substrate for the direct measurement of CES1 activity in rats. This bioluminescence assay was applied to determine CES1 activity in rat tissues after a two-week oral administration of each of the four herbs noted above. The results demonstrated the presence of CES1 enzyme in rat blood and all tested tissues with much higher enzyme activity in the blood, liver, kidney and heart than that in the small intestine, spleen, lung, pancreas, brain and stomach. In addition, the four herbs showed tissue-specific effects on rat CES1 expression. Based on the CES1 biodistribution and its changes after treatment in rats, the possibility that Danshen, Gegen and Danggui might alter CES1 ac-tivities in human blood and kidney should be considered. In summary, a selective and sensitive biolu-minescence assay was developed to rapidly evaluate CES1 activity and the effects of orally administered TCMs in rats.

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.

Mammalian carboxylesterases (CEs) are key enzymes from the serine hydrolase superfamily. In the human body, two predominant carboxylesterases (CES1 and CES2) have been identified and extensively studied over the past decade. These two enzymes play crucial roles in the metabolism of a wide variety of endogenous esters, ester-containing drugs and environmental toxicants. The key roles of CES in both human health and xenobiotic metabolism arouse great interest in the discovery of potent CES modulators to regulate endobiotic metabolism or to improve the efficacy of ester drugs. This review covers the structural and catalytic features of CES, tissue distributions, biological functions, genetic polymorphisms, substrate specificities and inhibitor properties of CES1 and CES2, as well as the significance and recent progress on the discovery of CES modulators. The information presented here will help pharmacologists explore the relevance of CES to human diseases or to assign the contribution of certain CES in xenobiotic metabolism. It will also facilitate medicinal chemistry efforts to design prodrugs activated by a given CES isoform, or to develop potent and selective modulators of CES for potential biomedical applications.

Objective To investigate the effects of penehyclidine hydrochloride (PHCD)on cerebral ischemia-reperfusion injury induced by intrauterine distress in fetal rats.Methods Eighty mature fetal rats weighing 4.52-4.81 g were randomly divided into four groups (n =20):sham opera-tion group(group S),PHCD control group (group S+ P),cerebral IR group (group IR),PHCD treatment group(group IR+P).Fetal rat intrauterine distress model was set up by clamping bilateral uterine horn vessels of pregnant rats.PHCD 2 mg/kg was injected in pregnant rat’s gluteus at 30 min before intrauterine distress model was set up in group IR+P,the same volume saline was injected in pregnant rat’s gluteus before shame operation in group S,the same volume PHCD was injected in pregnant rat’s gluteus before shame operation in group S+P.Fetal rats were decapitated at 12 h after the reperfusion,the peripheral blood of fetal rats was detected by blood gas analysis (including PH, PaO 2 ,PaCO 2 ,Lac);the infarct volume and the infarct volume fraction were detected by TTC stai-ning;pathological changes in lung tissue were observed by HE staining;the TNF-α,IL-6 content in the brain were detected by ELISA;the expression of NF-κB mRNA was detected by quantitative Real-time PCR,the expression of NF-κB p65 protein was detected by Western-blotting.Results The blood PH,PaO 2 in group IR and IR+P were lower than group S and S+P,the blood PH,PaO 2 in group IR+P was higher than group IR.Compared with group S and group S+P,the blood PaCO 2 , Lac,the infarct volume and the infarct volume fraction,the concentration of TNF-αand IL-6,the ex-pression of NF-κB mRNA and protein were significantly increased in group IR and IR+P (P <0.05), and those in group IR+P were lower than group IR (P <0.05 ).The pathological changes in brain tissue were significantly attenuated in group IR + P (P < 0.05 ).Conclusion Pretreatment with PHCDcouldattenuatecerebralischemia-reperfusioninjuryoffetalratsinducedbyintrauterinedistress. ThemechanismscouldrelatetotheinhibitionofNF-κBsignalingpathwayinbraintissues.