OBJECTIVE To prepare an intelligent responsive liposome-hydrogel nanopreparation co-loaded with gambogic acid （GA）， and characterize its antitumor activity in vitro . METHODS GA-ICG-Lip-gel was prepared by ethanol injection and cold dissolution， incorporating GA and the photosensitizer indocyanine green （ICG）. The appearance and microscopic morphology of GA-ICG-Lip-gel were observed， its encapsulation efficiency and drug loading capacity were measured， and its photothermal conversion performance， photothermal stability， and infrared imaging properties were investigated， along with the determination of its in vitro release profile. Human breast cancer MCF-7 cells were used as objects to investigate the effects of GA-ICG-Lip-gel （or with near-infrared light irradiation） on cell viability， migration ability， and the cellular uptake capacity of GA-ICG-Lip-gel. RESULTS GA-ICG-Lip-gel existed in a solution state at room temperature and transformed into a gel state at 37 ℃. Its microstructure was dense with small pores， and its encapsulation efficiency and drug loading were （96.07±0.86） % and （6.28±1.16） %， respectively. After exposure to near-infrared light， the temperature of GA-ICG-Lip-gel rose above 42 ℃， with no significant attenuation observed in the heating curve. The heating efficiency was dependent on both the irradiation time and drug concentration. Compared to media without gelatinase， the cumulative release rate of GA-ICG-Lip-gel increased in media containing gelatinase. In vitro studies showed that GA-ICG-Lip-gel could be efficiently taken up by MCF-7 cells； GA-ICG-Lip-gel significantly inhibited the viability and migration ability of MCF-7 cells （ P ＜0.05）， and this inhibitory effect was further enhanced under near-infrared light irradiation. CONCLUSIONS This study successfully prepares GA-ICG-Lip-gel， which exhibits favorable photothermal conversion properties and temperature/enzyme dual-responsive drug release characteristics， and demonstrates significant inhibitory effects on the proliferation and migration of breast cancer cells.

Objective To investigate the characteristics of human papillomavirus (HPV) prevalence and genotype distribution of 18 535 cases in Yuncheng . Methods A sample of 18535 residents who underwent HPV testing in our hospital from August 2020 to September 2023 were enrolled, and HPV genotyping was done to all samples. Then the rate of HPV infection, age distribution, genotype distribution, and multiple infections were statistically analyzed. Results Of the 18,535 subjects included, a total of 4,639 tested positive for HPV, demonstrating a positive rate of 25.03%. The positive rate of HPV infection varied among different age groups (χ²=29.587, P<0.05), with higher rates found in <25 years old group (29.61%) and >60 years old group (25.89%). Overall, 23 genotypes, covering 5315 viruses, were detected. There were 5 low-risk genotypes with the highest percentage of HPV42 (9.29%), and there were 18 high-risk genotypes with HPV52, HPV58, HPV66 and HPV53, subtypes as the most frequent subtypes, accounting for 13.64%, 8.97%, 7.41% and 7.04%, respectively. The type of HPV infection was predominantly single infections, with an overall single infection rate of 21.62% (4008/18535), which accounted for 86.40% (4 008/4 639) of all positive cases, and a multiple genotype infections rate of 3.40% (631/18535). The 25-34 year old group accounted for the largest proportion of single infections (25.12%), while the <25 year old group accounted for the largest proportion of multiple genotype infections (30.74%). Conclusion The prevalence rate of HPV infection in Yuncheng is 25.03%, with a higher positive rate in the <25 years age group and the >60 years age group. A total of 23 HPV genotypes are detected, of which the main genotypes are HPV42, HPV58, HPV66 and HPV53, and the type of infection is dominated by single infections.

AIM:Autophagy levels in lung cancer cisplatin-resistant A549/DDP cells and cisplatin-sensitive A549 cells were compared.The effects of microRNA-126(miRNA-126)on autophagy in lung cancer cisplatin-resistant cells were assessed,and the role of miRNA-126 in lung cancer cisplatin-resistant cells was discussed.METHODS:An MTT assay was used to detect the half maximal inhibitory concentration of cisplatin.The miRNA-126 expression was de-tected by RT-qPCR.Autophagolysosomes were observed under a fluorescence microscope using acridine orange staining.Protein levels of autophagy-associated molecule microtubule-associated protein 1 light chain 3(LC3)in lung cancer cells were determined by Western blot.RESULTS:Autophagy was significantly elevated in A549/DDP cells compared with A549 cells(P<0.01).The expression level of miRNA-126 was significantly elevated in A549/DDP cells after transfection with miRNA-126(P<0.01).miRNA-126 reversed cisplatin resistance of A549/DDP cells,and the level of intracellular acid dye follicular bright red fluorescence in the A549/DDP cells was significantly reduced after transfection with miRNA-126(P<0.01).The LC3-Ⅱ protein level in A549/DDP cells was significantly reduced after transfection with miRNA-126(P<0.01),and inhibition of cell autophagy by 3-methyladenine(3-MA)enhanced cisplatin sensitivity of A549/DDP cells(P<0.01).Compared with 3-MA+NC group,miRNA-126 combined with 3-MA further increased cisplatin sensitivity of A549/DDP cells(P<0.01).CONCLUSION:miRNA-126 reverses the cisplatin resistance in lung cancer A549/DDP cells by inhibiting autophagy.

AIM: To study the effect of growth hormone (GH) and vitamin E (Vit.E) combined in the treatment of endometrial thinning. METHODS: Twenty female SD rats were randomly divided into four groups: control group, model group, GH group and treatment group, with 5 rats in each group. Control group was routinely fed; Rats in model group, GH group and treatment group were injected intrauterine with 95%ethanol during estrus stage to construct a thin endometrial model. Six to eight hours after operation, rats in model group were injected intrauterine with 0.2 mL normal saline, rats in GH group and treatment group were injected with the same amount of GH, and the treatment group was given intragastric treatment of 60 mg/kg Vit.E. The rats were sacrificed 3 estrus cycles (about 2 weeks) after the operation. HE staining was performed on the uterine tissue to identify the model, and the levels of Cytokeratin 19 and Vimentin in the endometrium were detected by immunohistochemical color. RESULTS: The endometrial thickness of the model group was significantly thinner than that of the model group, and the endometrial thickness of the treatment group was significantly higher than that of the control group, but the endometrial thickness of the GH group was slightly lower than that of the control group. The expression levels of keratin and vimentin in model group were lower than those in GH group, control group and treatment group, and the differences were statistically significant. CONCLUSION: Endometrial-related proliferation indexes were significantly increased after GH and vitamin E treatment, and GH and vitamin E could effectively promote the proliferation of endometrial cells.

Objective:To analyze the molecular epidemiological characteristics of measles virus (MV) in Beijing from 2015 to 2019, and to provide laboratory basis for measles elimination.Methods:Measles virus-positive throat swab samples were collected through the Beijing Measles Laboratory network from 2015 to 2019. After the viral nucleic acid was extracted, 450 nucleotide fragments of the C terminal of the N gene of MV were amplified by RT-PCR. Nucleotide sequencing was performed for the amplified products. The phylogenetic tree was constructed with the representative strains of WHO measles virus genotype D8 genotype reference strains in China and other countries. Genotype identification was conducted and the nucleotide and amino acid homology analysis was carried out. A descriptive analysis of measles cases with D8 and B3 genotypes was conducted.Results:From 2015 to 2019, the genotypes of 546 MV were identified in the city, including 531 of H1a genotype, five vaccine strains, one of B3 genotype, and nine of D8 genotype, among which eight were epidemic strains in 2019. The homology of indigenous H1a genotype MV nucleotide and amino acid was 91.5%-100.0% and 73.6%-100.0%.In 2019, all eight cases of D8 genotype measles were adults, with two being an outbreak and the remaining six sporadic cases.Conclusions:The imported D8 genotype had become the main MV genotype in Beijing in 2019. With the decrease of measles incidence in 2019, native genotype H1a was no longer dominant, while other different genotypes were imported, forming a mixed epidemic trend. It was suggested that in the elimination of measles in Beijing, efforts should be made not only to block the transmission of local measles virus, but also to prevent and control the import and continuous transmission of non-local genotype virus, so as to avoid the risk of establishing local transmission by gradually evolving into a dominant strain.

OBJECTIVE：To pre pare Glycyrrhetinic acid-modified docetaxel magnetic nanoparticles （GA-DTX-NGO/IONP- NPs），and to evaluate its physicochemical properties. METHODS ：Magnetic nano graphene oxide （NGO/IONP）was chosen as the anti-tumor drug carrier ，docetaxel（DTX）as the model drug and glycyrrhetinic acid （GA）as the target molecule. Firstly ，NGO/ IONP was synthesized by hydrothermal method and GA-CS was synthesized by amidation reaction. Fourier IR spectrometer ，DSC and vibration sample magnetic measuring instrument were used to characterize NGO/IONP and GA-CS. GA-DTX-NGO/IONP-NPs Huperzine A in the nicotinic acetylcholine receptor alleviates Aβ -induced 1-42 treatment of Alzheimer ’s disease and vascular dementia ：a neurotoxicity via downregulation of p 38 and JNK MAPK meta-analysis[J]. Evid Based Complement Alternat Med ， signaling pathways[J]. Neurochem Int ，2018. DOI ：10. 2014. DOI ：10.1155/2014/363985. 1016/j.neuint.2018.09.005. were prepared by the ion gelation method. TEM and particle size analyzer were used to observe and determine the morphology ， particle size and Zeta potential of GA-DTX-NGO/IONP-NPs ；the ultrafiltration-centrifugation method was used to determine encapsulation efficiency and drug loading amount ；the magnetic properties were investigated by investigating the state with or without external magnetic field ；the photothermal conversion test was carried out with laser irradiation of 808 nm. RESULTS ：NGO/ IONP and GA-CS were successfully synthesized ，and NGO/IONP exhibited superparamagnetism characteristics. GA-DTX-NGO/ IONP-NPs were spherical under TEM ，the particle size was （262.8±4.23）nm and the Zeta potential was （13.6±1.51）mV. The encapsulation rate and drug loading amount were （94.29±0.50）％ and（17.12±0.12）％，respectively. GA-DTX-NGO/IONP-NPs were black in appearance and evenly dispersed. Under the external magnetic field ，the magnetic nanoparticles could move directionally，showing good magnetic properties. GA-DTX-NGO/IONP-NPs showed a good concentration- and time-dependent photothermal conversion effect under 808 nm laser irradiation. CONCLUSIONS ：GA-DTX-NGO/IONP-NPs are successfully prepared. This study could provide some theoretical basis for the combined treatment of magnetic heating-chemotherapy for liver tumors.

Aim To explore the effects of chrysin on endothelial dysfunction induced by acute high glucose.Methods ① The effects of chrysin on normal isolated aortic at contraction induced by PE and on endothelial dysfunction induced by high glucose were tested in the following medium: normal group,chrysin group;normal-glucose group: glucose 11mmol·L-1 in Krebs' solution;high-glucose group: glucose 44 mmol·L-1 in Krebs' solution;mannitol group: mannitol 33 mmol·L-1 in Krebs' solution and chrysin group: 44 mmol·L-1 Glu+chrysin 1.0 μmol·L-1 in Krebs' solution.② The effects of chrysin on HUVEC cell viability after incubated in high glucose were observed in the following groups: normal-glucose group: glucose 5.5 mmol·L-1 in culture solution;high-glucose group: glucose 33.3 mmol·L-1 in culture solution;mannitol group: mannitol 27.8 mmol·L-1 in culture solution and chrysin group: chrysin(25,50 μmol·L-1)in culture solution.And the NO release was also testd in these groups.Results ① Chrysin could induce vaso-dilation in a dose-dependent manner at normal glucose.The Emax was(58.94±9.61)％,and the EC50 value was 51.9 μmol·L-1.After incubating the aortic rings with high glucose(44 mmol·L-1)for 4 h,there were significant differences in ACh-induced vascular relaxation between the normal glucose group and the high glucose group.The Emax was(32.12±3.92)％and the EC50 value was 78.0 μmol·L-1 of high glucose group(P<0.01).The endothelium-independent relaxation induced by SNP was not significantly different between the two groups.And chrysin(1.0 μmol·L-1)could reverse the decline of ACh-induced vasorelaxation response induced by high glucose(44 mmol·L-1).The Emax was(70.7±3.87)％and the EC50 value was 0.852 μmol·L-1.② The cell viability of HUVEC was depressed after incubated in high glucose,and chrysin could reverse the decline in a concentration-dependent way.And chrysin in defferent concentrations could increase the cell NO release.Conclusion Chrysin could prevent the acute high glucose-induced vascular endothelial dysfunction and could increase the NO release.

AIM:To investigate the effects of curcumin on the abilities of migration and invasion in the lung cancer PC-9 cells, and to observe the relationship between curcumin and nectin-4 expression.METHODS:The viability, migration and invasion of lung cancer PC-9 cells treated with curcumin or transfected with siNectin-4 were measured by MTT assay, wound healing test and Transwell assay , respectively.The protein levels of nectin-4, p-AKT and AKT in the PC-9 cells treated with curcumin or transfected with siNectin-4 were detected by Western blot .RESULTS:Curcumin in-hibited the viability of PC-9 cells.The wound healing rates and the numbers of the transmembrane cells in curcumin 10μmol/L and 20 μmol/L groups were decreased compared with control group without curcumin treatment .The expression level of nectin-4 was reduced after curcumin treatment for 24 h.The viability of the PC-9 cells was significantly inhibited after transfected with siNectin-4 for 48 h or 72 h (P<0.01), and the wound healing rates was decreased in siNectin-4 group compared with NC group (P<0.01).The numbers of the transmembrane cells in siNectin-4 group was significantly reduced (P<0.01).Curcumin and knockdown of nectin-4 suppressed the activation of AKT pathway in PC-9 cells.In si-Nectin-4+curcumin group , the cell viability reduced compared with curcumin group , and wound healing rates , cell inva-sive ability and AKT phosphorylation levels were decreased .CONCLUSION:Curcumin inhibits migration and invasion of the lung cancer PC-9 cells via down-regulation of nectin-4 expression and inhibition of AKT pathway .

Objective To analyze the genotypes and the variation trend of rubella virus strains circulating in Beijing and to provide a scientific guidance for the prevention and control of rubella.Methods The viral nucleic acids were extracted from diagnostic pharyngeal swab specimens collected by Beijing rubella laboratory.The 739 nucleotides of rubella E1 gene were amplified by reverse transcription-polymerase chain reaction ( RT-PCR) .The amplified products were sequenced and analyzed.Genotypes of the rubella virus strains circulating in Beijing and variations in their nucleotides and amino acids were analyzed by comparing with those of the WHO recommended rubella virus reference strains.Results The target nucleotide se-quences of 10 rubella virus strains were obtained for molecular epidemiological study.All of the 10 strains belonged to 2B genotype and formed an independent branch according to the phylogenetic tree based on the 739 nucleotide fragments of E1 gene.Most of the nucleotide mutations occurred in the 10 strains were non-sense mutations.The amino acid sequences of the circulating strains were highly conservative.No significant mutations in the antigenic sites were identified in the rubella virus strains circulating in Beijing except that one amino acid mutation from Ser to Phe in the No.282 amino acid of E1 protein was identified in the hemag-glutination inhibition and neutralizing site of one strain.Conclusion This study indicated that the rubella virus genotype 2B epidemic strains were isolated in Beijing.

Objective To evaluate the value of fetal dual Doppler ultrasonography in the diagnosis of fetal arrhythmias.Methods 77 53 1 fetuses were examined by echocardiography.If fetal arrhythmias were found,information of pulsed wave Doppler signals in hepatic vein(HV) and descending aorta(DAo) using dual Doppler were collected simultaneously.Results On dual Doppler examination,13 1 of the fetuses showed signals of cardiac dysrhythmias,including 60 fetuses with irregular fetal heart rhythm but having normal heart rate,45 with tachyarrhythmias and 26 with bradyarrhythmias.Sixteen and 2 with tachy- or bradyarrhythmias fetuses complicated fetal malformation or severely maternal systemic diseases.Eighteen and 3 with tachy- or bradyarrhythmias fetuses revealed intrauterine death or intermediate pregnancy induction.The three main kinds of fetal arrhythmias had statistical differences in complicating with fetal malformation,maternal diseases,intrauterine fetal demise or intermediate pregnancy induction(all P <0.05).There was a significant difference in the accuracy of diagnosing rhythm abnormalities in the fetus between conventional ultrasonography and dual Doppler ultrasonography(k = 0.562,P < 0.05).Sixty cases of irregular fetal heart rhythm,42 cases of fetal tachyarrhythmias,and 8 cases of fetal bradyarrhythmias were changed to normal rhythm at the third-pregnancy or prenatal period through appropriate treatment.All surviving fetuses were examined by echocardiography within 3 days,without any combination of congenital heart disease,and 1 months after the delivery,the ECG were shown as sinus rhythm.Conclusions Dual Doppler ultrasonography is a precise and rapid method of assessing various types of fetal arrhythmias.Different types of fetal arrhythmias have different fetal prognosis.