Ankylosing spondylitis is a chronic immunoinflammatory disease that mainly affects the spine and the sacroiliac joint， the mechanism of which is closely related to signaling pathways， such as osteoprotegerin （OPG）/receptor activator of nuclear factor-κB （RANK）/RANK ligand， mitogen-activated protein kinase （MAPK）， Wnt/β-catenin （β-catenin）， phosphoinositide 3- kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR）. Traditional Chinese medicine has the characteristics of multiple components and targets， and is widely used for the treatment of autoimmune diseases due to its low toxicity， strong specificity， and high efficacy. This review found that monomers and compounds of traditional Chinese medicine can exert anti ankylosing spondylitis effects by intervening in the aforementioned signaling pathways， regulating immune inflammatory responses， and inhibiting biological processes such as bone destruction， ectopic osteogenic differentiation， cell apoptosis， and autophagy.

Objective To explore the mechanism of microRNA(miRNA)-365a-3p affecting the function of vascular endothelial cells involved in the pathogenesis of preeclampsia(PE).Methods Primary human umbilical vein endothelial cells(HUVECs)were set as a NC group(transfected miR-365a-3p NC),a mimics group(trans-fected miR-365a-3p mimics)and a inhibitor group(transfected miR-365a-3p inhibitor).Logarithmic HUVECs cells were set as the blank group.The cell proliferation,migration and angiogenesis in each group were detected.Dual luciferin assay verified the targeting relationship between miR-365a-3p and downstream gene.The protein expressions of TGF-β1,Smad4 and Smad7 in each group were detected.Results Compared with the blank group and the NC group,the absorbance value and mobility of 24,48 and 72 h were decreased(P＜0.05),the number of tubular structures per field were decreased in the mimics group(P＜0.05),the absorbance value and mobility of 24,48 and 72 h were increased(P＜0.05),and the number of tubular structures per field were increased in the inhibitor group(P＜0.05).Dual luciferin assay showed that Smad7 was a target gene of miR-365a-3p.Compared with the blank group and the NC group,the protein expressions of TGF-β1 and Smad4 in the mimics group were increased(P＜0.05),while the protein expression of Smad7 was decreased(P＜0.05).The protein expression levels of TGF-β1 and Smad4 in the inhibitor group were decreased(P＜0.05),while the protein expression levels of Smad7 were increased(P＜0.05).Conclusion miR-365a-3p may affect the function of vascular endothelial cells by regulating the downstream TGF-β signaling pathway,and thus participate in the pathogenesis of PE.

AIM:To investigate the pathological mechanism by which abnormal activation of sphingosine-1-phosphate(S1P)/S1P receptor 2(S1PR2)signaling pathway induces pericyte loss and subsequently affects blood-brain barrier dysfunction in neuropsychiatric systemic lupus erythematosus(NPSLE)mice using MRL/lpr mouse model.METHODS:Behavioral changes in female MRL/lpr mice from 6 weeks of age were assessed using open-field test(OFT),novel object recognition test(NORT)and forced swimming test(FST).The mice with neurobehavioral changes exceeding 20％compared with baseline were defined as NPSLE mice,and were randomly divided into 3 groups,each with 6 mice:NPSLE-S1P antagonist group,NPSLE-S1PR2 blocker group,and NPSLE saline treatment group.Additional 6 mice with no abnormal behavioral changes served as control group.The mice in NPSLE-S1P antagonist group were treated with S1P antagonist FTY720(2 mg/kg,orally),those in NPSLE-S1PR2 blocker group received treatment with S1PR2 blocker JTE-013(8 mg/kg,intraperitoneally),while those in NPSLE saline treatment group and control group received an equivalent volume of saline.Treatments were conducted 3 times per week for 3 weeks.Behavioral changes were reassessed using OFT,NORT and FST.Enzyme-linked immunosorbent assay(ELISA)was used to detect serum levels of S1P,interleukin-6(IL-6)and interferon-α(IFN-α).Blood-brain barrier permeability changes were evaluated by Evans blue staining.He-matoxylin-eosin(HE)staining was employed to observe brain tissue inflammation,Nissl staining was used to examine neu-ronal damage,and immunofluorescence staining was performed to assess the expression of pericyte marker neural/glial an-tigen 2(NG2)and endothelial cell marker CD31 in microvessels.Western blot analysis was conducted to detect the ex-pression levels of S1P,S1PR2,platelet-derived growth factor receptor-β(PDGFR-β)and zonula occludens-1(ZO-1)in brain tissues,while RT-qPCR was utilized to measure S1PR2 and PDGFR-β mRNA levels.RESULTS:Compared with model group,the mice in S1P antagonist and S1PR2 blocker groups exhibited reduced latency and immobility time in the water(P<0.05)and increased central zone exploration distance(P<0.05).There was reduced inflammatory exudation and neuronal damage in the ventricles,along with attenuated retention of pericytes(NG2,green)and endothelial cells(CD31,red).Serum levels of S1P,IL-6 and IFN-α were significantly decreased(P<0.05).The S1PR2 mRNA expres-sion was significantly reduced,whereas PDGFR-β mRNA expression was significantly increased(P<0.05).Protein ex-pression levels of S1P and S1PR2 were significantly decreased,while PDGFR-β and ZO-1 protein levels were significantly increased(P<0.05).CONCLUSION:Inhibition of the S1P/S1PR2 pathway attenuates neurobehavioral symptoms,re-duces blood-brain barrier permeability,and suppresses inflammation in NPSLE mice.

ObjectiveTo investigate the willingness of middle school students to engage in medicine and its influencing factors during COVID-19 pandemic in Lanzhou， so as to provide references for the early career planning education on middle school students. MethodsConvenient sampling method was used to choose 1 795 middle school students from 5 schools in Lanzhou from July 21 to July 31， 2022 for this study where an online questionnaire survey was distributed to collect data. A self-compiled questionnaire was used to gather the general information， assess the willingness to engage in medicine and seek the underlying reasons. The psychological resilience level of students was assessed using Resilience Scale for Adolescents. Then multivariate Logistic regression analysis was conducted to screen the factors associated with the willingness of middle school students to engage in medicine. ResultsAfter the local outbreak of COVID-19 in Lanzhou， 835 （46.52%） middle school students demonstrated their willingness to engage in medicine， and the top three reasons for their willingness were being affected by medical staff during the pandemic （75.69%）， having interests in medical sciences （67.31%）， and the potential increase of attention to national medical development after the epidemic （43.23%）. Logistical regression analysis showed that female gender （OR=1.438， P<0.01）， family members engaged in the medical and health industry （OR=1.574， P<0.01） and having a high psychological resilience score （OR=1.011， P<0.01） were related to the clear willingness to engage in medicine， while studying in senior middle school （OR=0.473， P<0.01） and excessive exposure （≥50%） to negative information during the epidemic （OR=0.797， P<0.05） were related to declining willingness to engage in medicine. ConclusionAfter the COVID-19 outbreak in Lanzhou， a large proportion of local middle school students show their willingness to engage in medicine， especially among those of female gender， having family members engaged in the medical and health industry and having high level of psychological resilience. Whereas students studying in senior middle school and with excessive exposure to negative information during the outbreak indicate low willingness to engage in medicine.

BACKGROUND: Endocrine therapy (ET) and ET-based regimens are the preferred first-line treatment options for hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (HR+/HER2- MBC), while chemotherapy (CT) is commonly used in clinical practice. The aim of this study was to investigate the efficacy and clinical outcome of ET and CT as first-line treatment in Chinese patients with HR+/HER2- MBC. METHODS: Patients diagnosed with HR+/HER2-MBC between January 1st, 1996 and September 30th, 2018 were screened from the Chinese Society of Clinical Oncology Breast Cancer database. The initial and maintenance first-line treatment, progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: Among the 1877 included patients, 1215 (64.7%) received CT and 662 (35.3%) received ET as initial first-line treatment. There were no statistically significant differences in PFS and OS between patients receiving ET and CT as initial first-line treatment in the total population (PFS: 12.0 vs. 11.0 months, P = 0.22; OS: 54.0 vs . 49.0 months, P =0.09) and propensity score matched population. For patients without disease progression after at least 3 months of initial therapy, maintenance ET following initial CT (CT-ET cohort, n = 449) and continuous schedule of ET (ET cohort, n = 527) had longer PFS than continuous schedule of CT (CT cohort, n = 406) in the total population (CT-ET cohort vs. CT cohort: 17.0 vs . 8.5 months; P <0.01; ET cohort vs . CT cohort: 14.0 vs . 8.5 months; P <0.01) and propensity score matched population. OS in the three cohorts yielded the same results as PFS. CONCLUSIONS ET was associated with similar clinical outcome to CT as initial first-line treatment. For patients without disease progression after initial CT, switching to maintenance ET showed superiority in clinical outcome over continuous schedule of CT.
Humans ; Female ; Breast Neoplasms/metabolism* ; Receptor, ErbB-2/metabolism* ; Progression-Free Survival ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Disease Progression ; Treatment Outcome

Cancer is one of the malignant diseases threatening human. In recent years, nanotechnology is becoming the hope the cancer treatment, as it can take the drugs targeting to tumor sites, with enhanced efficacy and reduced toxicity. Chitosan is the only alkaline polysaccharide in nature with good biocompatibility and biodegradability. Moreover, chitosan has many reaction sites to make derivatives with different properties. Chitosan and its derivatives are widely used for drug delivery systems and tissue engineering scaffolds. Hence, they are valuable in the field of biomedicine. In this paper, the recent advances chitosan nanoparticles as drug delivery system for delivering anticancer drugs are reviewed, especially the advances of the preparation, passive targeting, active targeting, and stimuli-responsive drug delivery systems of chitosan nanoparticles.

Objective:To establish a disease risk prediction model for the newborn screening system of inherited metabolic diseases by artificial intelligence technology.Methods:This was a retrospectively study. Newborn screening data ( n=5 907 547) from February 2010 to May 2019 from 31 hospitals in China and verified data ( n=3 028) from 34 hospitals of the same period were collected to establish the artificial intelligence model for the prediction of inherited metabolic diseases in neonates. The validity of the artificial intelligence disease risk prediction model was verified by 360 814 newborns ' screening data from January 2018 to September 2018 through a single-blind experiment. The effectiveness of the artificial intelligence disease risk prediction model was verified by comparing the detection rate of clinically confirmed cases, the positive rate of initial screening and the positive predictive value between the clinicians and the artificial intelligence prediction model of inherited metabolic diseases. Results:A total of 3 665 697 newborns ' screening data were collected including 3 019 cases ' positive data to establish the 16 artificial intelligence models for 32 inherited metabolic diseases. The single-blind experiment ( n=360 814) showed that 45 clinically diagnosed infants were detected by both artificial intelligence model and clinicians. A total of 2 684 cases were positive in tandem mass spectrometry screening and 1 694 cases were with high risk in artificial intelligence prediction model of inherited metabolic diseases, with the positive rates of tandem 0.74% (2 684/360 814)and 0.46% (1 694/360 814), respectively. Compared to clinicians, the positive rate of newborns was reduced by 36.89% (990/2 684) after the application of the artificial intelligence model, and the positive predictive values of clinicians and artificial intelligence prediction model of inherited metabolic diseases were 1.68% (45/2 684) and 2.66% (45/1 694) respectively. Conclusion:An accurate, fast, and the lower false positive rate auxiliary diagnosis system for neonatal inherited metabolic diseases by artificial intelligence technology has been established, which may have an important clinical value.

Objective: To understand the possible transmission route of a family cluster of COVID-19 in Zhengzhou and the potential infectivity of COVID-19 in incubation period, and provide scientific evidence for the timely control of infectious source and curb the spread of the epidemic. Methods: Epidemiological investigation was conducted for a family cluster of COVID-19 (8 cases) with descriptive epidemiological method, and respiratory tract samples of the cases were collected for the nucleic acid detection of 2019-nCoV by RT-PCR. Results: Two primary cases, which occurred on 31 January and 1 February, 2020, respectively, had a common exposure history in Wuhan. The other six family members had onsets on 30 January, 31 January, 1 February (three cases) and 3 February, 2020. Conclusions In this family cluster of COVID-19, six family members were infected through common family exposure to the 2 primary cases. Five secondary cases had onsets earlier than or on the same day as the primary cases, indicating that COVID-19 is contagious in incubation period, and the home isolation in the early phase of the epidemic might lead to the risk of family cluster of COVID-19.

Microemulsions are promising drug delivery systems for the oral administration of poorly water-soluble drugs. However, the evolution of microemulsions in the gastrointestinal tract is still poorly characterized, especially the structural change of microemulsions under the effect of lipase and mucus. To better understand the fate of microemulsions in the gastrointestinal tract, we applied small-angle X-ray scattering (SAXS) and fluorescence resonance energy transfer (FRET) to monitor the structural change of microemulsions under the effect of lipolysis and mucus. First, the effect of lipolysis on microemulsions was studied by SAXS, which found the generation of liquid crystalline phases. Meanwhile, FRET spectra indicated micelles with smaller particle sizes were generated during lipolysis, which could be affected by CaCl, bile salts and lecithin. Then, the effect of mucus on the structural change of lipolysed microemulsions was studied. The results of SAXS and FRET indicated that the liquid crystalline phases disappeared, and more micelles were generated. In summary, we studied the structural change of microemulsions in simulated gastrointestinal conditions by SAXS and FRET, and successfully monitored the appearance and disappearance of the liquid crystalline phases and micelles.

Objective To explore the relationship between syncope and risk of death in patients with cardiovascular emergencies including acute myocardial infarction(AMI), arrhythmia, acute heart failure(AHF), pulmonary thromboembolism(PTE) and aortic dissection(AD) rupture. Methods Data from 2 789 patients with cardiovascular emergency admitted from June 2010 to June 2016 in the Emergency Department, Air Force General Hospital, PLA was retrospectively analyzed. Difference in gender, age and motality were compared between patients with syncope and those without syncope. Among fi ve kinds of cardiovascular emergency events with syncope, difference in mortality were compared. Difference in mortality were also analyzed by the CHM corrected chi square test when difference of disease, gender and age were taken into consideration. Syncope, the type of cardiovascular emergency, gender and age were analyzed as potential risk/protective factors for death by the multiple logistic regression analysis. Results The mortalities of the fi ve diseases accompanied with syncope were 50%, 30.43%, 26.53%, 20% and 7.04% respectively in arterial dissection, pulmonary embolism, acute myocardial infarction, acute heart failure and arrhythmia.There was a statistically signifi cant difference in mortality among the fi ve kinds of cardiovascular emergencies accompanied with syncope(P<0.05).The mortalities of patients with syncope were significantly higher than those without syncopein AMI patients(26.53% vs.11.20%,P<0.05) and cardiac arrhythmias patients(7.04% vs.0.36%,P<0.05).The results of the CHM corrected chi square test showed that there was signifi cant difference in mortality between the syncope group and non-syncope group, when the differences in disease type, age and gender were adjusted (χ2=35.876, P<0.01). The mortality of syncope group was higher than that of non-syncope group.When age, gender and disease type were considered as covariates, the multiple logistic regression analysis showed that syncope signifi cantly increased the risk of mortality(OR=3.876,95% CI:2.362-6.359,P<0.01).Conclusion Syncope is an independent risk factor of death in patients with cardiovascular emergencies.