Lysosomes represent a promising target for cancer therapy and reducing drug resistance. However, the short treatment time and low efficiency of lysosomal targeting have limited the application in lysosome-targeting anticancer drugs. In this study, we proposed an adhesive-bandage approach and synthesized a new lysosomal targeting drug, namely long-term lysosome-targeting anticancer drug (LLAD). It contains a SLC38A9-targeting covalently bound moiety and an alkaline component both to prolong the inhibition of SLC38A9 in lysosomes and alkalinize lysosomes. Upon short term and low-dose treatment of HeLa cells, at passage 0, with LLAD, it rapidly alkalinized lysosomes and also can be detected in lysosomes even at passage 15. LLAD induced apoptosis in HeLa cells through long-term lysosomal damage, and showed better long-term anticancer effect than cisplatin in vivo. Overall, our study paves the way for developing long-term lysosomal targeting drugs to treat cancer and overcome the drug resistance of cancer cells, and also provides a candidate drug, LLAD, for treating cancer.

It was a cross-sectional study. Six myocardial infarction patients with non-obstructive coronary artery disease (MINOCA group) admitted to Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2021 to August 2022 were enrolled in the study and 78 healthy subjects were selected as control group. The patients and healthy controls were selected with 1∶1 propensity score matching according to age, gender, body mass index, occupation and marriage status; and 5 study subjects of each group were finally enrolled in the study. The general clinical data and magnetocardiographic (MCG) results were collected from the hospital′s electronic medical record system. Compared with control group, MINOCA group showed abnormal QR rotation, discrete changes in positive and negative magnetic poles in TT segment, and disordered current direction. The analysis of MCG data revealed 35 parameters with statistically significant difference between the two groups, involving TT interval, QRS complex, RS interval and QR interval. This study explored the magnetocardiographic characteristics of MINOCA, which suggest that MCG may be conducive for diagnosis of MINOCA in the future.

ObjectiveTo investigate the effect and potential mechanism of Dihuangyin on 2， 4-dinitrochlorobenzene （DNCB） -induced model mice with atopic dermatitis （AD）. MethodA mouse model with AD was established by repeatedly stimulating the back skin of mice with DNCB. After successful modeling， the mice were randomly divided into model group， Runzao group （0.78 g·kg^-1）， and high， medium， and low dose （40.30， 20.15， and 10.08 g·kg^-1） groups of Dihuangyin， with 12 mice in each group， and the blank group consisted of 12 mice， 72 in total. The administration groups were given the corresponding liquid by dose， and the blank group and model group were given the same dose of pure water by intragastric administration， once a day. The skin lesions and scratching times of mice were observed after continuous administration for two weeks. The back skin lesions of mice were stained with hematoxylin-eosin （HE） and toluidine blue to observe the pathology. The contents of serum immunoglobulin E （IgE）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， and interferon-γ （IFN-γ） were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression levels of IFN-γ， IL-4， IL-6， Janus kinase 1 （JAK1）， and transcriptional activator 3 （STAT3） in skin lesion tissue were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expressions of JAK1， phosphorylation（p）-JAK1， STAT3， and p-STAT3 proteins in skin lesion tissue were detected by Western blot. ResultCompared with the blank group， the back skin of the model group showed large-scale scab， dryness， erosion， hypertrophy with scratching， epidermal hyperplasia with hyperkeratosis and parakeratosis， hyperacanthosis with edema， and a large number of mast cell infiltration in the dermis， some of which were degranulated. The contents of IgE， IL-4， IL-6， and IFN-γ in the serum of mice were significantly increased （P<0.01）， and the protein expression levels of p-JAK1， STAT3， and p-STAT3 and mRNA expressions of IL-4， IL-6， IFN-γ， JAK1， and STAT3 in skin lesion tissue were significantly increased （P<0.01）. Compared with the model group， only a small amount of dryness and desquamation were observed in the back skin of mice in each administration group， and cell edema was reduced. The inflammatory infiltration was significantly reduced， and the number of mast cell infiltration was significantly decreased. The serum IgE， IL-4， IL-6， and IFN-γ of mice were decreased to varying degrees （P<0.05， P<0.01）. The protein expression levels of p-JAK1， STAT3， and p-STAT3 and mRNA expressions of IL-4， IL-6， IFN-γ， JAK1， and STAT3 in skin lesion tissue were significantly decreased， and the effect of high dose group of Dihuangyin was the best （P<0.01）. ConclusionDihuangyin can improve skin lesions and pruritus in mice with AD， and its mechanism may be related to the effective regulation of cytokines on the helper T cells （Th1）/Th2 axis by interfering with the JAK1/STAT3 signaling pathway and affecting skin barrier function.

OBJECTIVE To explore the improvement effect and mechanism of acacetin on juvenile asthma rats based on the silence information regulator 1 （SIRT1）/AMP-activated protein kinase （AMPK） signaling pathway. METHODS Juvenile SD rats were randomly divided into control group， asthma group， acacetin group （13.33 mg/kg， gavage）， SIRT inhibitor EX-527 group （1 mg/kg， intraperitoneal injection） and acacetin+EX-527 group （13.33 mg/kg acacetin， gavage+1 mg/kg EX-527， intraperitoneal injection）， with 12 rats in each group （half male and half female）. Except for the control group， the other groups were sensitized by intraperitoneal injection of ovalbumin and nebulized inhalation of ovalbumin to induce the asthma model. After modeling， rats in each drug group were orally administered or （and） intraperitoneally injected with the corresponding medication once a day for 2 weeks. After the last administration， the total number of cells， the proportion of eosinophils， and the levels of interleukin-5 （IL-5）， IL-4 and tumor necrosis factor-α （TNF-α） in the bronchoalveolar lavage fluid （BALF） were measured. The pathological changes and abnormal proliferation of goblet cells in lung tissue were observed， the levels of malondialdehyde （MDA） and superoxide dismutase （SOD） in lung tissue and the protein expressions of SIRT1, AMPK and peroxisome proliferator activated receptor-gamma co-activator factor-1α（PGC-1α） were detected. RESULTS Compared with control group， there was a large number of inflammatory cell infiltration and obvious goblet cell dysplasia in the lung tissue of rats in asthma group； the total number of cells in BALF， the proportion of eosinophils， the levels of IL-5， IL-4 and TNF-α in BALF， PAS score and MDA level in the lung tissue were significantly increased （P＜0.05）； the SOD level， protein expressions of SIRT1 and PGC-1α and protein phosphorylation level of AMPK in lung tissue were significantly decreased in asthma group （P＜0.05）. Compared with the asthma group， the pathological changes of lung tissue and goblet cell dysplasia of rats were reduced， and all quantitative indexes were significantly improved in acacetin group （P＜0.05）， while the pathological changes of lung tissue and goblet cell dysplasia of rats were increased， and all quantitative indexes were significantly worsened in EX-527 group （P＜ 0.05）. The combination of EX-527 could significantly reverse the effects of acacetin on oxidative stress and airway inflammation in juvenile asthma rats. CONCLUSIONS Acacetin can inhibit oxidative stress and airway inflammation in juvenile asthma rats，which may be related to the activation of the SIRT1/AMPK jinanlvshishen@163.com signaling pathway.

Objective:To evaluate the consistency of the Chinese three-dimensional anterior visual field analysis system (Scansys), the anterior segment analyzer (Pentacam), the frequency-domain anterior segment optical coherence tomography system (CASIA SS-1000), and a new ultra-high frequency digital ultrasound scanning system (Arcscan Insight100) to measure central vault after implantable collamer lens (ICL) implantation in myopic eyes with crystalline lenses.Methods:A diagnostic test study was conducted.Fifty-six myopic patients (56 eyes) who underwent ICL V4c implantation from June to December 2019 were included.Scansys, Pentacam, CASIA and Arcscan were used to measure the central vault after surgery.The vault measurements were compared.Correlations between the measurements of the four instruments were analyzed using Pearson correlation analysis, and consistency comparisons were analyzed using the Bland-Altman method.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2021[13]). Written informed consent was obtained from each subject.Results:The central vault measurements by Scansys, Pentacam, CASIA and Arcscan were (481.8±191.6), (476.4±190.6), (619.3±207.5) and (534.0±221.2)μm, respectively, with a statistically significant overall difference ( F=143.301, P<0.001). The vault measurements by Scansys and Pentacam were significantly lower than CASIA and Arcscan, and Arcscan was lower than CASIA, with statistically significant differences (all at P<0.001). There were strong positive correlations in vault measurements between Arcscan and CASIA, Arcscan and Pentacam, Arcscan and Scansys, CASIA and Pentacam, CASIA and Scansys, Pentacam and Scansys ( r=0.982, 0.933, 0.931, 0.942, 0.941, 0.989; all at P<0.001). Intraclass correlation coefficients of vault measurements by Scansys, Pentacam, CASIA and Arcscan were 0.985, 0.975, 0.998, 0.992, respectively.The 95% limits of agreement of vault measurements differences were -170 to 0, 0 to 280, 0 to 280, -110 to 210, -100 to 220 μm, between CASIA and Arcscan, CASIA and Scansys, CASIA and Pentacam, Arcscan and Scansys, Arcscan and Pentacam, respectively, and the maximum absolute value of the difference was beyond the clinically acceptable range, showing poor agreement.The 95% limits of agreement of vault measurement difference was -60 to 50 μm between Scansys and Pentacam, showing a good agreement. Conclusions:The repeatability of the vault after ICL V4c implantation in myopic eyes measured by the four instruments is good.Among them, the vault measurements of Scansys and Pentacam are smaller, showing good consistency, and their results could be substituted for each other.The measurement of CASIA is the largest, followed by Arcscan, which have a large difference from each other, and their results can not be substituted for each other, which should be comprehensively analyzed with the actual situation in clinical work.

With the development of space technology,the health risks for astronauts in space have also increased,which has made the application value of telemedicine technology in space exploration more prominent.In the outer space environment,various exogenous and endogenous factors may affect human health in multiple ways.As deep space exploration advances and space technology develops,the risks of astronauts'health issues in space increase,and telemedicine technology has important application value in space exploration,which is related to astronauts'lives,health,and the success of missions.This article summarizes the research progress of telemedicine technology in recent years,analyzes remote medical diagnosis and treatment,intelligent surgical robots,and the application of artificial intelligence,discusses the latest progress in related fields at home and abroad,and provides a reference for the medical support of long-term space flight.

In the field of space exploration,the importance of microorganisms to human health cannot be ignored,and they will play a crucial role in maintaining astronaut health,ensuring habitat sustainability,and ensuring the success of the entire mission.Microorganisms may have negative impacts on space missions,but they also have practical value.This article reviews research progress in recent years on the effects of space environments on microorganisms,the current status of microbial contamination in space environments,detection methods,and the application of microorganisms in the field of space health.It clarifies that research on the impact of microorganisms and microbial ecosystems in space exploration is not only helpful in safeguarding the survival and health of astronauts,but also provides valuable reference for future space exploration projects.

Objective To evaluate the stability,safety and immune enhancement and anti-tumor effects of Wilms'tumor gene 1(WT1)peptide combined with AddaVaxTM emulsion vaccine for acute myeloid leukemia.Methods The stability of WT1 peptide in the adjuvant vaccine was evaluated using MALDI-TOF-MS time-of-flight mass spectrometry.Female C57BL/6 mice were randomly divided into PBS group,WT1 peptide group,and WT1 peptide+AddaVaxTMemulsion adjuvant vaccine group.The immunization was performed at a dose of 50 μg/mouse for antigen and 50 μg/mouse for adjuvant,with intramuscular injection on days 0,14,and 28.HE staining was used to assess the toxicity of intramuscular vaccination on mouse organ tissues.Cytokine levels were detected by ELISA,and the number of IFN-γ-secreting splenocytes was measured by ELISpot.Flow cytometry was employed to detect the maturation of bone marrow-derived dendritic cells(BMDCs)promoted by the vaccine in vitro and the promotion for lymphocyte activation,and H-2Db WT1 tetramer was utilized to detect the proportion of specific CD8+T cells.After establishing a mouse leukemia tumor model using the C1498-mWT1 stable cell line,the anti-tumor effects of the vaccine for prevention and treatment were evaluated.Results The WT1 peptide stably existed in the vaccine without causing significant organ tissue changes in mice after intramuscular injection.Compared to the mice immunized with WT1 aqueous solution,the mice after intramuscular injection of the WT1 peptide emulsion adjuvant vaccine showed stronger immune responses of Th1 cells,including IFN-γ and TNF-α,as well as Th17 cells of IL-17A(P＜0.05),and the mice had not only promoted number of IFN-γ secreting splenocytes(P＜0.01)but also enhanced maturation of BMDCs,as indicated by an increase in the proportions of CD40+/CD11c+and CD86+CD80+/CD11c+ cells(P＜0.05).Additionally,there were increases in both the proportion of CD4+/CD3+T and CD69+/CD8+T cells(P＜0.05)and the proportion of specific CD8+T cells(P＜0.05).In the anti-tumor effect study using the C1498-mWT1 mouse model,the median survival time of the WT1+AddaVaxTM group was extended by 6 d compared to the WT1 aqueous solution group.At day 50,the survival rate of mice in the WT1+AddaVaxTM group was still 28.5％,while all mice in the other groups had died(P＜0.05).Conclusion The vaccine with the WT1 peptide and AddaVaxTM emulsion adjuvant exhibits good immunological and anti-tumor effects.

Objective To compare the effectiveness and safety of semaglutide with dulaglutide in patients diagnosed with type 2 diabetes.Methods A multicenter retrospective cohort study was conducted to include patients with type 2 diabetes who received semaglutide or dulaglutide treatment at three hospitals between April 2021 and July 2023 in the study.The patients were divided into the semaglutide group(SEMA group)and the dulaglutide group(DULA group)based on their treatment.Propensity score matching was used to pair the two groups in a 1:1 ratio,aligning them based on baseline characteristics such as gender,age,body mass index,blood glucose levels,duration of diabetes,and complications.Various parameters including fasting blood glucose,2-hour postprandial blood glucose,glycosylated hemoglobin(HbA1c),serum creatinine,urea nitrogen levels,estimated glomerular filtration rate(eGFR),urinary albumin/creatinine ratio(UACR),and occurrences of adverse reactions were assessed at 3,6,9,and 12 months after the treatment.Results After propensity score matching,98 patients were included in both the SEMA and DULA groups,showing no statistically significant differences in baseline characteristics between the groups(P＞0.05).At each follow-up point,the fasting blood glucose,2-hour postprandial blood glucose,and HbA1c levels of both groups showed a significant decrease compared to the baseline(P≤0.05).The inter-group comparison revealed no statistically significant differences in the changes in fasting blood glucose,2-hour postprandial blood glucose,and HbA1c levels between the two groups(P＞0.05).At the 6th month,the SEMA group exhibited a statistically significant higher rate of HbA1c＜7％compared to the DULA group(P＜0.05).In the SEMA group,serum creatinine and urea nitrogen decreased significantly at the 6th month compared to baseline,while eGFR showed an increase at the 3rd and 6th month,and UACR decreased,all with statistical significance(P＜0.05).In the DULA group,there was a statistically significant increase in serum creatinine and decrease at the 3rd and 6th months in eGFR,respectively.Additionally,urea nitrogen levels decreased significantly at the 9th month,all differences were statistically significant(P＜0.05).The inter-group comparison revealed that at the 3rd and 6th month,the SEMA group exhibited a greater reduction in serum creatinine levels compared to the DULA group.Additionally,the SEMA group demonstrated a more pronounced increase in eGFR levels than the DULA group,with statistical significance(P＜0.05).At the 6th month,the SEMA group exhibited a significantly greater decrease in UACR and a significantly lower incidence of renal insufficiency compared to the DULA group(P＜0.05).There were no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Semaglutide and dulaglutide can significantly improve blood glucose control,exhibit comparable effectiveness and safety in lowering blood glucose levels,and semaglutide has a potentially protective effect on renal function.

Objective    To analyze the surgical efficacy and influencing factors of myasthenia gravis (MG) patients with thymic atrophy after thymectomy. Methods    The clinical data of MG patients with thymic atrophy undergoing thymectomy between October 2014 and May 2018 in Daping Hospital of Army Medical University and Shijiazhuang People Hospital were retrospectively analyzed. Results    A total of 71 patients were collected, including 40 males and 31 females with a mean age of 45.17±12.42 years. All patients received the surgery successfully. After the surgery, 20 (28.17%) patients were stable remission, 12 (16.90%) patients were minimal manifestation status,19 (26.76%) patients were improved, 5 (7.04%) patients showed no change, 3 (4.23%) patients were worsened, 10 (14.08%) patients were exacerbated and 2 (2.82%) patients were dead. Multivariate logistic regression analysis showed that the preoperative illness duration (OR=4.61, 95%CI 1.13-18.85, P=0.03), and postoperative pyridostigmine combined with immunosuppressive (OR=0.12, 95%CI 0.03-0.45, P=0.00) were independent risk factors for long-term efficacy of thymectomy for MG patients with thymic atrophy. Conclusion    Early surgery after diagnosis of MG and postoperative pyridostigmine combined with immunosuppressive treatment is beneficial to the prognosis of MG patients with thymic atrophy.