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.

Hemp seed oil serves as the core pharmacodynamic part of hemp seed， containing various active constituents including fatty acids and their esters （such as linoleic acid， methyl linolenate， etc.）， tocopherols （such as α -tocopherol， β -tocopherol， etc.）， polyphenols （such as caffeic acid， quercetin， etc.）， and cannabinoids （such as cannabidiolic acid， cannabinol， etc.）. Pharmacological studies demonstrate that hemp seed oil exerts anti-oxidation and anti-aging， blood-lipid-lowering and anti-atherosclerotic， neuroprotective， anti-inflammatory effects， as well as functions in regulating intestinal microecology and improving intestinal mucosal barrier function. Its mechanisms are related to scavenging free radicals， activating endogenous antioxidant enzymes， improving the function of central cholinergic system， mitigating neuroinflammatory responses， regulating the balance of inflammatory factors， interfering with inflammatory signaling pathways， and optimizing the structure of intestinal microbiota. In future studies， a correlation network of “chemical component group-multi-target pharmacodynamic effect” can be constructed according to the chemical characteristics of hemp seed oil， and its pharmacodynamic evaluation for chronic diseases can be expanded， so as to promote its in-depth development and clinical transformation.

Long-term spaceflight,characterized by drastic changes in spatial position,disrupts the Earth's inherent environmental periodic signals,such as the day-night light-dark cycle.This leads to a misalignment between the external environmental cycles and the body's endogenous biological rhythms.The cumulative effect of this persistent"time difference"severely disrupts the core biological pathways that regulate the circadian rhythm.It triggers a series of neuroendocrine and behavioral stress responses,exemplified by sleep-wake disorders,which have become a core medical problem constraining the success of long-term space missions and astronaut health.Traditional Chinese Medicine(TCM)posits that aligning with the rhythmic changes of heaven,earth,day,night,and the four seasons,and maintaining the dynamic balance and harmonious functioning of the body's Yin and Yang vital energies,are fundamental principles for safeguarding vitality and resisting external pathogens and internal injuries.However,in the prolonged weightlessness,confinement,and abnormal lighting environment of deep space flight,the bond between the human body and natural rhythms is forcibly severed.Yin and Yang Qi become difficult to sustain,the mechanisms of ascent,descent,exit,and entry are obstructed,the visceral Qi transformation functions are impaired,and the circulation of Qi and Blood becomes disordered,ultimately leading to the onset of various disorders.This paper,grounded in the TCM temporal medicine perspective of"correspondence between heaven and human"(tian ren xiang ying)and the theories of Yin-Yang and Qi-Blood,meticulously reviews the historical classics and modern research on acupoint intervention strategies for addressing rhythm disorders and harmonizing Yin and Yang.Building upon this foundation,it innovatively proposes and argues for an integrated acupoint prescription strategy:the"Bei Xin Wu Xue"combined with the classic paired points Zhaohai(KI6)-Shenmai(BL62)on the lower limbs to regulate the dynamic balance of the Yin and Yang Heel Vessels(Yin/Yang Qiao Mai),and the classic paired points Taichong(LR3)-Yongquan(KI1)to guide Qi downward.This combination aims to work at multiple levels-"Heart-Brain,Yin-Yang,Liver-Kidney"-to calm the Heart Spirit,clear the Brain Mansion,and tonify the Liver and Kidney.The goal is to restore Yin and Yang Qi to an orderly and coordinated state,thereby assisting the disordered biological rhythm system in regaining homeostasis.This provides a novel TCM-inspired approach of"rhythm regulation and equilibrium restoration"(tiao shi fu heng)to safeguard the long-term in-orbit health of astronauts.

Objective To investigate the influence of intrahepatic cholestasis of pregnancy (ICP) on adverse pregnancy outcomes of hepatitis B virus (HBV)-infected pregnant women. Methods A retrospective analysis was performed for 232 pregnant women with chronic HBV infection who were admitted to Beijing YouAn Hospital, Capital Medical University, from March 2018 to March 2021. According to the presence or absence of ICP, the patients were divided into HBV infection group with 100 patients and HBV+ICP group with 132 patients; according to the severity of ICP, the patients in the HBV+ICP group were further divided into HBV+mild ICP group with 86 patients and HBV+severe ICP group with 46 patients. The above groups were compared in terms of the incidence rates of maternal complications during pregnancy, such as premature delivery, premature rupture of membranes, gestational diabetes mellitus, hypertensive disorder complicating pregnancy, and postpartum hemorrhage (PPH), as well as the adverse outcomes of fetus/neonate, such as intrauterine fetal death, neonatal asphyxia, amniotic fluid pollution degree Ⅲ(AFⅢ), neonatal respiratory distress syndrome, small-for-gestational-age (SGA), admission to the neonatal intensive care unit, pneumonia, and mother-to-child transmission (MTCT) of HBV. A one-way analysis of variance was used for comparison between multiple groups; the chi-square test, the chi-square test with continuity correction or the Fisher's exact test was used for comparison of categorical data between multiple groups. Results Compared with the HBV infection group in terms of maternal complications in late pregnancy, the HBV+ICP group had significantly higher incidence rates of premature delivery and PPH ( χ 2 =4.169 and 5.448, P =0.041 and 0.020), and in terms of the adverse outcomes of neonates, the HBV+ICP group had significantly higher incidence rates of neonatal asphyxia, AFⅢ, and SGA than the HBV infection group ( χ 2 =5.448, 16.567, and 11.053, P =0.020, P < 0.001, and P =0.002). In terms of the adverse outcomes of neonates, the HBV+severe ICP group had significantly higher incidence rates of AFⅢ and SGA than the HBV+mild ICP group ( χ 2 =4.200 and 4.511, P =0.040 and 0.034). Conclusion Compared with the pregnant women with HBV infection alone, the pregnant women with HBV infection and ICP have significantly higher incidence rates of adverse pregnancy outcomes in mothers and neonates, and the incidence rate of adverse outcomes in neonates increases with the increase in the severity of ICP. However, ICP has no influence on HBV MTCT.

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 observe the characteristics of the phagocytosis and bactericidal function of multidrug-resistant Mycobacterium tuberculosis(MDR- Mtb)-infected macrophage model, and the changes of the immune response and metabolic function in the process of phagocytosis and bactericidal function, aiming to provide reference for studying the role and mechanism of macrophages in the occurrence and development of multidrug-resistant tuberculosis(MDR-TB). Methods:We established MDR- Mtb and H37Rv-infected macrophage models, and used the colony-forming unit (CFU), Magnetic Luminex ? Assay and Cholesterol Assay kit to observe the effects on phagocytosis and bactericidal function, the secretion of Th1(IL-12/23 p40, IL-27 and TNF-α) and Th2 cytokines (IL-6 and IL-10) and cholesterol metabolism. The data were analyzed by SPSS25.0 software. The data were expressed as Mean± SD and analyzed by t test or F test. P<0.05 was considered statistically significant. Results:(1) After MDR- Mtb-infected macrophages, the intracellular CFU gradually increased and reached the highest at 24 h, while the extracellular CFU gradually decreased and reached the lowest at 24 h. The intracellular CFU at 48 h was lower than that at 24 h, while the extracellular CFU was higher than that at 24 h ( P<0.05). Both intracellular and extracellular CFU at 48 h were close to those at 4 h ( P>0.05). The intracellular CFU was lower than the H37Rv group at 8-48 h, while the extracellular CFU was higher than the H37Rv group ( P<0.05). (2) The level of IL-12/23 p40, IL-27, TNF-α, IL-6 and IL-10 of MDR-TB group were higher than those of blank group ( P<0.05), but the level of TNF-α and IL-6 at 24 h and 48 h were higher than that at 4 h ( P<0.05). IL-12/23 p40 and TNF-α at 48 h and IL-6 at 24 h were lower than those of the H37Rv group, while IL-27 at 48 h was higher than that of the H37Rv group ( P<0.05). (3) The levels of cholesterol of MDR-TB group at 24 h and 48 h were lower than those of 4 h and blank group ( P<0.05), but the level of cholesterol was similar to the H37Rv group at any time ( P>0.05). (4) TNF-α reached the highest when the intracellular CFU reached the highest at 24 h, and IL-6 reached the highest when the intracellular CFU decreased at 48 h. With the decreasing of cholesterol expression, the intracellular CFU increased and then decreased. Conclusions:MDR- Mtb could induce the phagocytosis and bactericidal function of macrophages, increase the expression of Th1 and Th2 cytokines and promote the utilization and consumption of cholesterol, but this function was weaker than that of H37Rv 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.

OBJECTIVE： To establish a methaod for content determination of doxorubicin hydrochloride nano-liposomes， and to optimize its preparation technology. METHODS： The contents of doxorubicin hydrochloride nano-liposomes was determined by UV spectrophotometry. The membrane dispersion method was used to prepare doxorubicin hydrochloride nano-liposomes. Using particle size， encapsulation efficiency and drug-loading amount as indexes， the weight ratio of phospholipid to drug （mg/mg）， the weight ratio of phospholipid to cholesterol （mg/mg） and ultrasonic time （min） as factors， central composite design-response surface methodology was used to optimize the preparation technology. The photothermal conversion effect of doxorubicin hydrochloride nano-liposomes was investigated by near infrared irradiation. RESULTS： The linear range of doxorubicin hydrochloride were 1.01-16.16 μg/mL（r＝0.999 7）； precision， stability and reproducibility tests were all in line with the requirments of Chinese Pharmacopoeia. The optimal preparation technology included that the weight ratio of phospholipid to drug was 13.30 ∶ 1（mg/mg）； the weight ratio of phospholipid to cholesterol was 4.09 ∶ 1 （mg/mg）； the ultrasonic time was 10 min. Under this technology， the particle size and drug-loading amount of doxorubicin hydrochloride nano-liposomes were （200.5±25.1） nm and （11.02±0.20）％， relative errors of which to predicted value （196.3 nm， 10.68％） were 1.82％ and 1.63％. The consistency between measured value and predicted value was good. Doxorubicin hydrochloride nano-liposomes exhibited concentration- dependent and time-dependent photothermal conversion characteristics under near infrared irradiation at 808 nm. CONCLUSIONS： Established method is simple and good accuracy. The optimized preparation technology is simple and feasible.

OBJECTIVE： To establish the fingerprint of Maizao yishen granules， and to provide scientific basis for its further development. METHODS： HPLC method was adopted to establish the fingerprint by using 10 batches of Maizao yishen granules sa samples. The determination was performed on Venusil XBP C18（L） column with mobile phase consisted of acetonitrile-0.2％ phosphoric acid （gradient elution） at the flow rate of 1→0.7 mL/min at 7-10 min， 0.7→1 mL/min at 10-15 min and 1 mL/min at the rest of time. The detection wavelengths were set at 284 nm （0-7 min）， 330 nm （7-32 min） and 360 nm （32-45 min）. The column temperature was 25 ℃， and sample size was 10 μL. The fingerprint of Maizao yishen granules was established， and the similarity evaluation was performed by using “Similarity Evaluation System of TCM Chromatographic Fingerprints” （2004 A edition） software. Then， the common peaks were assigned and identified by comparing reference substance and control medicinal materials. RESULTS： The precision， stability （24 h） and repeatability of the methodological investigation were all good [RSD values of relative retention time and relative peak area of each chromatographic peak were less than 3％ （n＝6）]. The similarity of 10 batches of samples were all above 0.900. Seventeen common peaks were identified， of which common peak 1 and 6 came from Semen Raphani； common peak 7， 9， 14， 15 and 16 from Citrus reticulata； common peak 5， 10， 11， 12 and 13 came from Glycyrrhiza uralensis； common peak 2 came from C. reticulata， G. uralensis and Ziziphus jujuba； peak 3 came from G. uralensis and Semen Raphani； peak 8 came from Hordeum vulgare and Semen Raphani； peak 4 and 17 came from C. reticulata and G. uralensis. Peak 1 was identified as hesperidin and the peak 9 was identified as sinapine. CONCLUSIONS： Established fingerprint of Maizao yishen granules is accurate and reliable， and can be used for quality control of Maizao yishen granules.

OBJECTIVE： To prepare Adriamycin hydrochloride （DOX） magnetic thermosensitive liposome （MTSL）， investigate its physicochemical properties， magnetic effect and photothermal effect， so as to provide reference for tumor chemo- therapy and photodynamic/photothermal therapy. METHODS： Using DOX as model drug， TiO2@Fe3O4 as photosensitizers and magnetic materials， DOX-TiO2@Fe3O4-MTSL was prepared with membrane dispersion method. The morphology and dispersibility were observed； particle size and Zeta potential were detected； encapsulation efficiency of the liposome were determined by centrifugal ultrafiltration and HPLC. Its paramagnetism property was also detected by magnetometer. Compared with DOX solution， in vitro release behavior of the liposome was investigated by dialysis method， and the release curves at different temperatures （at 37， 43 ℃） were compared. The photothermal conversion effect of the liposome and the production of reactive oxygen species （ROS） in human breast cancer MCF-7 cells were investigated by near infrared laser irradiation at 808 nm. RESULTS： Prepared DOX-TiO2@Fe3O4-MTSL was brown-black with good water dispersion， and was spherical in shape and uniform in size under electron microscopy. Average particle size was 250.6 nm； polydispersity index was 0.107； Zeta potential was （－7.76±3.41）mV； encapsulation efficiency was （92.3±3.2）％. Under the external magnetic field， the liposome could move in a directional direction and had obvious paramagnetism. Compared with DOX solution， the liposomes released slowly and showed obvious sustained- release characteristics. Compared with at 37 ℃， the drug release of liposome speeded up significantly at 43 ℃.With the increase of laser （808 nm） irradiation time， the temperature of the liposome kept rising， which had obvious photothermal conversion effect and could induce the increase of ROS in MCF-7 cells. CONCLUSIONS： DOX-TiO2@Fe3O4-MTSL is prepared succe- ssfully， which has uniform appearance， good physical and chemical properties. It has obvious paramagnetism sustained release effect and photothermal conversion efficiency， and can promote ROS production in MCF-7 cells under near infrared laser irradiation at 808 nm.