In In recent years, small-molecule targeted protein degraders inducing protein degradation have been developing rapidly. These molecules are attracting substantial interest from researchers since they can overcome such limitations of traditional small-molecule inhibitors as their inapplicability to ‘undruggable’ targets and tendency to induce drug resistance. Compared with other targeted protein degraders, small-molecule hydrophobic tags (HyTs) may have a smaller number of hydrogen bond donors/acceptors, smaller molecular weights, and better pharmacokinetic profiles, thus attracting extensive attention from researchers. This review focuses on the possible mechanisms and popular types of HyTs, with special attention to the potential application value of adamantane, a typical hydrophobic tag, in the fields of cancer and neurodegeneration. In general, there are still some problems like fewer types of hydrophobic tags and insufficient research on degradation mechanisms, which still need to be further explored. This review is expected to provide researchers working in the fields of small-molecule targeted protein degraders with some valuable reference.

Objective To investigate the impact of various health education intervention strategies on the proper use of personal respiratory protective equipment (RPE) among workers exposed to dust. Methods Dust-exposed workers were recruited from 60 selected enterprises in Guangdong Province using cluster random sampling method. They were randomly allocated to the control, low-intensity intervention, and high-intensity intervention groups, with 358, 346, and 371 workers in each group, respectively. Workers in the control group received no designed intervention. Workers in the low-intensity intervention group received traditional plus mobile health education on the proper use of RPE. Workers in the high-intensity intervention group received all components of the low-intensity intervention, supplemented with peer education. The intervention lasted for six months. RPE usage was compared among the three groups of workers before and after the intervention. Results Workers in the control, low-intensity intervention, and high-intensity intervention groups showed higher rates of both RPE wearing and correct RPE wearing after the intervention than before it within their respective groups (RPE wearing rate: 94.1% vs 99.2%, 95.7% vs 100.0%, 94.6% vs 100.0%, all P<0.01; correct RPE wearing rate: 66.8% vs 91.1%, 67.3% vs 95.7%, 66.6% vs 96.5%, all P<0.01). Post-intervention correct RPE wearing rates were highest in the high-intensity intervention group, followed by the low-intensity intervention group, and the control group, with the percentage of 96.50%, 95.66% and 91.06%, respectively (P<0.01). Binary logistic regression analysis result showed that different intervention strategies affected the correct use of personal RPE among dust-exposed workers after adjusting for gender, age, and other confounding factors (P<0.05). Compared with the control group, the rates of correct RPE use increased in the low-intensity intervention group and the high-intensity intervention group (odd ratio was 2.14 and 3.01; 95% confidence interval was 1.12 - 4.10 and 1.53 - 5.91, respectively). Conclusion The implementation of traditional plus mobile health education interventions on the proper use of RPE can promote correct RPE utilization among dust-exposed workers, and integrating peer education further enhances the intervention effectiveness.

Objective:To investigate the common viral pathogen spectrum of acute respiratory infection (ARI) cases in Changshu city.Methods:Nasopharyngeal swab samples from outpatients and inpatients in five sentinel hospitals in Changshu city from January 2022 to October 2023 were collected. Real-time fluorescent quantitative polymerase chain reaction was used to detect the nucleic acids of influenza virus (Flu) and respiratory syncytial virus (RSV), adenovirus (AdV), human rhinovirus (HRV), human parainfluenza virus (HPIV), enterovirus (EV), human coronavirus (HCoV), human metapneumovirus (HMPV), and human bocavirus (HBoV).Results:Of the 1 936 ARI cases, 18.1% (350/1 936) were tested positive for viral nucleic acid. Flu had the highest detection rate (7.1%), followed by HBoV (3.7%), AdV (1.9%) and RSV (1.6%). The virus detection rate was significantly different among different age groups and seasons. In March 2023, the total virus detection rate was the highest (47.6%), mainly Flu. Flu showed unimodal prevalence in spring and winter. The prevalence trend of HBoV and HCoV was consistent, and the detection rate of HBoV (5.43%) was higher than that of HCoV (2.45%), both of which peaked in summer. RSV prevalence peaks in autumn (4.5%). The detection rate of children aged 0-5 years was the highest, reaching 33.3%.Conclusions:The main ARI pathogens in Changshu city from 2022 to 2023 were Flu, HBoV, AdV and RSV.

In the context of high-quality development in medical institutions, the supply-processing-distribution(SPD) management mode has gradually been widely applied. The authors described in detail the procurement, supply, inventory, distribution, and settlement management of medical consumables and in vitro diagnostic reagents in a certain hospital under the SPD mode. It was found that SPD was conducive to strengthening the supervision of medical consumables and in vitro diagnostic reagents in the hospital, ensuring quality and safety of use, reducing hospital operating costs, and improving hospital′s competitiveness. However, attention should be paid to preventing data security risks, strengthening operational management, and improving the cost-benefit analysis of in vitro diagnostic reagents.

[Purpose]To analyze the trend of incidence and mean age at diagnosis of lymphoma in cancer registration areas of Jiangsu Province from 2009 to 2019.[Methods]Continuous and com-pleted data of cancer incidence from 2009 to 2019 were collected from 16 cancer registries in Jiangsu Province,and all indicators meeting the requirements.Joinpoint 4.7.0.0 software was used to analyze the trend of lymphoma incidence,the average annual percentage change(AAPC)and 95％confidence interval(CI)were calculated.A birth cohort was built from 1929 to 2019,to ana-lyze the change trend of lymphoma incidence rate among people born in different periods.[Re-sults]From 2009 to 2019,the AAPC of lymphoma incidence rate in cancer registration areas of Jiangsu Province was 5.74％,5.55％for men and 5.02％for women.The AAPC in urban areas was higher than that in rural areas(6.26％vs 4.90％).The age-standardized incidence rate(ASIR)of lymphoma increased by 3.40％annually on average.The rising amplitude of ASIR of women(3.16％)was higher than that of men(3.05％),and the rising amplitude of ASIR of lymphoma in urban areas(3.39％)was higher than that in rural areas(2.43％).The birth cohort analysis showed that the incidence rate of lymphoma fluctuated greatly before the age of 40,and there was no sig-nificant trend of change,while the incidence rate in age groups of 40 years old and above showed an overall upward trend.The average age at onset of lymphoma showed an upward trend from 2009 to 2019,with an average annual increase of 0.35 years old(P＜0.001).The standardized average age at onset for lymphoma still showed a significant upward trend,with an average annual increase of 0.15 years old(P=0.016).Compared with 2009,the standardized age specific incidence of lym-phoma in 2019 showed an overall backward trend,while the standardized incidence in all age groups after 60 years old(except for the age group of 70～74 years old)increased.The proportion of lymphoma in people above 60 years old was 56.16％in 2019,which was higher than that in 2009(52.57％).[Conclusion]The incidence rate of lymphoma in Jiangsu Province was increasing year by year from 2009 to 2019.The age at onset tended to shift back,and the trend was more pronounced in male than female.

Objective To preliminarily investigate the anti-tumor effects of phytosphingosine(PHS)and the involvement of inducing apoptosis of leukemia cells.Methods Cellular model of leukemia was established in leukemia cell lines K562 and SUP-B15.CCK-8 assay and EdU assay were used to measure the viability and DNA synthesis of K562 and SUP-B15 cells.RNA-seq was carried out to verify the differentially expressed genes(DEGs)after PHS treatment.Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were applied to analyze the involved functions and signaling pathways.Comparative Toxicogenomics Database(CTD)and Discovery Studio software were employed to predict the underlying targets of PHS and molecular docking.Cell apoptosis was detected by flow cytometry,mitochondrial membrane potential was evaluated by JC-1 probe,and protein expression of key molecules was validated by Western blotting.Results PHS inhibited the proliferation of K562 and SUP-B15 cells in a time-and dose-dependent manner.The half-maximal inhibitory concentration(IC50)of K562 cells was 17.67 and 12.52 pmol/L for 24 and 48 h,respectively,and the IC50 value of SUP-B15 cells was 17.58 and 14.86 μmol/L for 24 and 48 h,respectively.PHS treatment at a dose of 20 μmol/L for 48 h resulted in significant inhibition of DNA synthesis.GO enrichment analysis of the K562 cells showed that PHS might be involved in positive regulation of apoptotic process,plasma membrane and its integral components,and protein kinase binding and activity.Reverse predictive analysis showed that BCL-2 protein was the most likely target of PHS.PHS significantly increased the apoptotic rate of leukemia cells(P＜0.05)in a dose-dependent manner,reduced the mitochondrial membrane potential,and down-regulated BCL-2 level(P＜0.05)and up-regulated the levels of Cleaved caspase-3 and Cleaved caspase-9(P＜0.05).Conclusion PHS may inhibit the proliferation of leukemia cells by inducing mitochondria-dependent apoptosis,possibly through PHS and BCL-2 interaction.

Objective:To explore the genes related to primary myelofibrosis (PMF) and signaling pathways as well as the possible clinical significance.Methods:A total of 3 mRNA expression datasets of PMF (GSE26049, GSE61629 and GSE53482) were downloaded from Gene Expression Omnibus (GEO) database, including the data of peripheral blood samples from 55 PMF patients and 58 controls. The differentially expressed genes (DEG) between PMF patients and the controls were identified by using online tool GEO2R. Gene ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the common DEG of the 3 datasets, and then protein interaction (PPI) network was constructed. The key nodes of the common DEG in PPI network were calculated by using MCC method and Degree method in cytoHubba program; finally the top 10 hub genes were selected and the hub genes shared by the 2 methods were obtained. Peripheral blood samples of 25 PMF patients and 10 controls (normal hematopoietic stem cell transplant donors or iron deficiency anemia patients) admitted to the Second Hospital of Shanxi Medical University from September 2017 to June 2021 were retrospectively collected. Reverse transcription-fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of 10 screened common hub genes in each sample, and the expressions of all genes at transcriptional level of the two groups were compared.Results:A total of 239 common DEG between PMF patients and the controls were screened out in the 3 datasets, including 153 downregulated DEG and 86 upregulated DEG. The GO enrichment analysis showed that the common downregulated DEG were significantly enriched in negative regulation of transcription, translation and fibroblast proliferation, while the upregulated DEG were mainly enriched in protein ubiquitination and ubiquitin-dependent protein catabolic process. The KEGG pathway analysis indicated that the upregulated common DEG and downregulated common DEG were both enriched in PI3K/Akt signaling pathway, cancer pathways and transcriptional misregulation in cancer. There were 8 common hub genes shared by the 2 methods among the top 10 genes ranked by MCC and Degree methods, including 6 downregulated common DEG (TP53, MYC, ATM, FYN, PTPRC and ATRX) and 2 upregulated common DEG (VEGFA and FOXO3). These above 8 common hub genes were mainly involved in PI3K/Akt signaling pathway, cell cycle and cancer transcriptional regulation signaling pathways. RT-qPCR detection of clinical peripheral blood samples showed that the relative expression levels of mRNA in 6 downregulated common DEG of PMF patients were lower compared with those in controls, while the differences were not statistically significant (all P > 0.05); the relative expression levels of mRNA in 2 upregulated common DEG of PMF patients were higher compared with those in controls, and the differences were statistically significant ( U value was 33.00, 36.00, respectively; P value was 0.021, 0.033, respectively). Conclusions:Bioinformatics and clinical sample verification show that VEGFA and FOXO3 are up-regulated in PMF patients, which are mainly involved in the PI3K/Akt signaling pathway, cell cycle and cancer transcriptional regulation signaling pathway. Both genes may be related to the development of PMF and may become potential therapeutic targets.

Background and purpose:Outcomes for cancer patients with steroid-resistant immune checkpoint inhibitor-associated myocarditis(srICIAM)are poor.Intensified immunosuppressive therapies,including tofacitinib,a novel Janus kinase(JAK)inhibitor,may have some therapeutic benefits.However,due to the lack of sufficient clinical data,the effectiveness of such treatments and their impact on cardiovascular outcomes remain unclear.This study aimed to investigate the therapeutic effect of tofacitinib on srICIAM.Methods:This retrospective case-control study included 36 malignant tumor patients who received immune checkpoint inhibitor treatment at Zhongshan Hospital affiliated to Fudan University from July 2019 to May 2022 and developed srICIAM.Patients receiving corticosteroids in combination with tofacitinib were assigned to the tofacitinib group(n=19),while those not treated with tofacitinib were allocated to the control group(n=17).The study compared clinical characteristics,laboratory findings,and imaging results between the two groups.Additionally,follow-up was conducted to monitor the incidence of cardiovascular endpoints in these patients.The research plan was approved by the Ethics Committee of Zhongshan Hospital Affiliated to Fudan University(Approval Number:B2021-275R).This study was conducted in accordance with the ethical guidelines of the Helsinki Declaration.Results:Compared to the control group,and with no significant difference in the cumulative dose and duration of corticosteroids(P＜0.05),the tofacitinib group showed a shorter myocarditis recovery time(median recovery time:86.5 days vs 126.5 days,P=0.021).The myocarditis-related mortality rate was significantly lower in the tofacitinib group than in the control group(5%vs 35%,P=0.025).Conclusion:Tofacitinib may reduce mortality and promote cardiac recovery in srICIAM patients without impeding the anti-tumor effect.It may become one of the potential treatment strategies in the future.

Drug resistance presents one of the major causes for the failure of cancer chemotherapy. Cancer stem-like cells (CSCs), a population of self-renewal cells with high tumorigenicity and innate chemoresistance, can survive conventional chemotherapy and generate increased resistance. Here, we develop a lipid-polymer hybrid nanoparticle for co-delivery and cell-distinct release of the differentiation-inducing agent, all-trans retinoic acid and the chemotherapeutic drug, doxorubicin to overcome the CSC-associated chemoresistance. The hybrid nanoparticles achieve differential release of the combined drugs in the CSCs and bulk tumor cells by responding to their specific intracellular signal variation. In the hypoxic CSCs, ATRA is released to induce differentiation of the CSCs, and in the differentiating CSCs with decreased chemoresistance, DOX is released upon elevation of reactive oxygen species to cause subsequent cell death. In the bulk tumor cells, the drugs are released synchronously upon the hypoxic and oxidative conditions to exert potent anticancer effect. This cell-distinct drug release enhances the synergistic therapeutic efficacy of ATRA and DOX with different anticancer mechanism. We show that treatment with the hybrid nanoparticle efficiently inhibit the tumor growth and metastasis of the CSC-enriched triple negative breast cancer in the mouse models.

OBJECTIVE To study the correlation between color and inner quality during the processing of Prunus mume carbon， and provide reference for the determination of processing end point of P. mume carbon. METHODS The chromaticity value of P. mume carbon powder was measured by colorimeter， and the inner quality of P. mume carbon was measured by selecting the contents of water， water-soluble extract， citric acid and tannin. The dynamic change trend of the chromaticity value， water， water- soluble extract， the contents of citric acid and tannin in P. mume carbon under different processing time was analyzed. The correlation between color and the above indexe contents was analyzed， and the regression equation of inner quality-chromaticity value was established. Combined with principal component analysis （PCA）， hierarchical cluster analysis （CA） and partial least squares discriminant analysis （PLS-DA）， the difference of P. mume carbon at different processing times was analyzed to determine the processing end point. RESULTS With the extension of processing time， the sample color gradually deepened； the chromaticity values L* and E* of the samples increased at first and then decreased， the chromaticity values a* and b* decreased， and finally all tended to be stable. The content of water-soluble extract， citric acid and tannin in the sample increased at first and then decreased， the water content of the sample decreased with time and finally stabilized. Correlation analysis showed that water， water-soluble extract， citric acid and tannin were positively correlated with L*， a*， b* and E*（P＜0.001）. PCA and HCA showed that P. mume carbon under different processing time could be clustered into two categories： the processed samples of 0-30 min and those of 40-60 min. PLS-DA showed that water and water-soluble extract were important quality indexes and b* was an important chrominance index in the processing of P. mume carbon. The chromaticity value of the samples processed for 50 min and 60 min were not significantly different. The contents of water， water- soluble extract， citric acid and tannin in the samples processed for 60 min were less than those processed for 50 min. CONCLUSIONS There is a certain correlation between the color and the inner quality of P. mume carbon. The processing time of P. mume carbon should be 40-50 min.