Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer, although it is limited by the low tumor delivery efficacy of anticancer drugs. Bacterial therapy is emerging for cancer treatment due to its high immune stimulation effect; however, excessively generated immunogenicity will cause serious inflammatory response syndrome. Here, we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts (LP@BG@CCM) by layer-by-layer encapsulation for the treatment of metastatic lung cancer. The preparation processes were simple, only involving film formation, electroporation, and pore extrusion. LP@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer cells. In the 4T1 breast cancer metastatic lung cancer mouse models, the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance, the reduced lung weight, the clear lung tissue structure, and the enhanced cancer cell apoptosis compared to its precursors. Moreover, several major immune factors were improved after administration of LP@BG@CCM, including the CD4⁺/CD8a⁺ T cells in the spleen and the TNF-α, IFN-γ, and IL-4 in the lung. LP@BG@CCM exhibits the optimal synergistic chemo-immunotherapy, which is a promising medication for the treatment of metastatic lung cancer.

Objective To explore the context and hotspot changes of forensic mixed stain research through bibliometric approach.Methods The literature of forensic mixed stain included in the core col-lection of Web of Science database from 2011 to 2022 were collected as the study object,and the an-nual publication number,countrie(region),institution,journal,keywords,etc.were bibliometrically and visually analyzed using the R-based Bibliometrix 1.1.6 package and VOSviewer 1.6.18 software.Re-sults A total of 732 articles on forensic mixed stain were included from 2011 to 2022,with the an-nual number of articles published and the annual citation frequency showing a steady increase year by year.Among the 59 countries(regions)with the most published articles,the United States ranked first with 246 articles,followed by China with 153 articles.The literature came from 104 journals,and the total number of articles published in the top 10 journals was 633.FORENSIC SCI INT GENET ranked first with 307 articles.Visual analysis using VOSviewer software showed that keywords could be divided into four research clusters,namely the genetic marker development group(blue),the mixed stain typing analysis theory group(red),the sequencing analysis group(yellow),and the case sample research group(green).It can be divided into four development stages in terms of different time peri-ods:early development(2011-2013),middle development(2014-2016),rapid development(2017-2020)and latest development(2021-2022).Conclusion The number of publications by domestic and foreign scholars in the study of mixed stain in forensic science is showing a relatively stable trend.Machine learning,next generation sequencing and other research have been the hottest topics that have attracted the most attention in recent years,which is expected to further develop the theory of mixed stain typing and sequencing analysis in forensic mixed stain research.

Corneal transplantation is an effective treatment for corneal blindness, and it is the only hope for patients with corneal blindness. Cornea has no blood vessels and no lymphatic vessels, which is called immune privilege organ, so the success rate of corneal transplantation is significantly higher than that of other organ transplantation, but the rejection reaction after corneal transplantation is still the main reason for the failure of corneal transplantation. The directional movement of immune cells to lymphoid tissue and inflammatory sites is the mainly immune response after organ transplantation. And the regulatory T cells(Treg)play a key role in immune regulation, which can induce immune tolerance by regulating and inhibiting the activation of effector T cells and reduce the rejection reaction after corneal transplantation. In addition, this review also discussed the effectiveness of applying cordyceps sinensis extract FTY720 to enhance the function of Treg. Based on this, we briefly reviewed the sources, mechanism of action and treatment of Treg after corneal transplantation, so as to provide some reference for the subsequent clinical application transformation and basic research.

This experiment aims to study the taste-masking effects of different kinds of corrigent used individually and in combination on ibuprofen oral solution, in order to optimize the taste-masking formulation. Firstly, a wide range of corrigent and the mass fractions were extensively screened using electronic tongue technology. Subsequently, a combination of sensory evaluation, analytic hierarchy process (AHP)-fuzzy mathematics evaluation, and Box-Behnken experimental design were employed to comprehensively assess the taste-masking effects of different combinations of corrigent on ibuprofen oral solution, optimize the taste-masking formulation, and validate the results. The study received ethical approval from the Review Committee of the Beijing University of Chinese Medicine (ethical code: 2024BZYLL0102). The results showed that corrigent fractions and types were screened separately through single-factor experiments. Subsequently, a Box-Behnken response surface design combined with AHP and fuzzy mathematics evaluation was used to fit a functional model: Z = 688.310 11 - 3 023.722 22X₁ - 11.477 00X₂ + 62.721 67X₃ + 14.600 00X₁X₂ - 179.666 67X₁X₃ - 3.152 00X₂X₃ + 4 031.111 11X₁² + 0.525 28X₂² + 9.772 00X₃². This model is stable and reliable, determining the optimal taste-masking formulation to be 3.9 g·L^-1 of stevioside, 100 g L^-1 of xylitol, and 30 g L^-1 of methyl-β-cyclodextrin. The comprehensive score of the verification test is 88.14, with a relative RSD of 0.39%, indicating the feasibility of this model. This study achieved the improvement of the taste of ibuprofen oral solution through a combination of objective and subjective methods. Three types of corrigent were identified for enhancing drug taste, leading to the selection of the optimal taste-masking formulation for ibuprofen oral solution. This significantly enhanced the taste of the original formulation, improved patient compliance, and offered a new approach to mitigating the undesirable taste of formulations.

Objective To explore the protective mechanism of icariin on neuronal oxidative damage,providing a basic pharmacological basis for the treatment of cognitive impairment.Methods Glutamate was used to induce oxidative stress injury in HT22 cells.HT22 cells were divided into control group(normal cultured cells),model group(glutamate injury model)and experimental-L,-M,-H groups(5,10 and 20 μmol·L-1 icariin pretreatment for modeling,respectively).Cell proliferation was detected by cell counting kit-8(CCK-8)method;cytotoxicity was detected by lactate dehydrogenase(LDH)method;reactive oxygen species(ROS)levels were detected by flow cytometry;superoxide dismutase(SOD)levels were detected by biochemical kits;the expression levels of Kelch-like epichlorohydrin-related protein-1(Keap1),nuclear factor E2-related factor 2(Nrf2)were detected by Western blotting;the corresponding mRNA expression was detected by real-time fluorescence quantification polymerose chain reaction.Results The cell viability of control group,model group and experimental-L,-M,-H groups were(100.00±1.31)％,(66.38±2.44)％,(72.07±4.95)％,(82.41±3.57)％and(87.97±4.98)％;LDH release were(0.48±0.52)％,(18.82±2.09)％,(15.32±1.17)％,(10.37±1.39)％and(6.51±0.87)％;ROS level were(14.23±1.13)％,(41.74±1.60)％,(35.69±1.08)％,(33.28±1.69)％and(30.32±2.03)％;SOD levels were(54.84±1.17),(37.95±1.13),(48.02±1.28),(50.56±1.34)and(52.55±1.04)U·mg-1;Keap1 protein levels were 0.36±0.01,0.52±0.03,0.46±0.04,0.39±0.09 and 0.35±0.12;Nrf2 protein levels were 0.29±0.02,0.13±0.08,0.18±0.03,0.21±0.11 and 0.26±0.04;catalase(CAT)mRNA levels were 1.01±0.08,0.81±0.06,0.90±0.04,1.05±0.15 and 1.33±0.26;SOD mRNA levels were 1.09±0.12,0.83±0.03,0.86±0.08,0.94±0.08 and 1.09±0.16.Among the above indicators,the differences between the model group and the control group were statistically significant(all P＜0.01);the differences between the experimental-M,-H groups and the model group were statistically significant(P＜0.01,P＜0.05).Conclusion Icariin may activate the Keap1/Nrf2/antioxidant response element(ARE)signaling pathway,regulate the expression of related proteins,and reduce the level of ROS to effectively alleviate oxidative stress injury in neuronal cells.

Objective:To explore the impact of rehabilitation exercise intervention mode based on cardiac function classification on clinical effect and quality of life(QOL)in patients with chronic heart failure(CHF).Methods:A total of 160 CHF patients who visited our hospital from Dec 2021 to Jan 2023 were selected,and 154 cases were fi-nally enrolled.According to the random number table method,patients were divided into study group and control group with 77 cases in each group.Control group received routine nursing program,while the study group received rehabilitation exercise intervention based on cardiac function classification on the basis of control group,both groups were intervened for three months.Clinical total effective rate,and cardiopulmonary function,serum oxidative stress indicators and MLHFQ score before and after intervention were compared between two groups.Results:Total effective rates of study subgroups of class Ⅱ and Ⅲ were significantly higher than those of control group(class Ⅱ:100.00％vs.83.78％;class Ⅲ:97.37％vs.80.00％)(P＜0.05 both).Compared with control subgroup of classⅢ after intervention,there were significant rise in peak VO2[(16.98±2.03)ml·min-1·kg-1 vs.(18.61±2.41)ml·min-1·kg-1],LVEF[(41.73±4.53)％vs.(48.03±5.22)％]and 6MWD[(351.34±61.00)m vs.(391.53±64.42)m](P＜0.01 all);and significant reductions in LVEDd[(57.55±3.91)mm vs.(53.18±3.07)mm],LVESd[(35.90±2.91)mm vs.(30.50±2.67)mm],levels of LPO[(6.00±0.99)mg/L vs.(3.95±0.61)mg/L],MPO[(3.83±0.58)mg/L vs.(2.03±0.28)mg/L],and MLHFQ total score[(57.05±4.57)points vs.(45.29±3.94)points]in study subgroup of class Ⅲ(P=0.001 all).Compared with control subgroup of class Ⅱ after intervention,there were significant rise in peak VO2,LVEF and 6MWD,and significant reductions in LVEDd,LVESd,levels of LPO,MPO and MLHFQ score in study subgroup of class Ⅱ,P＜0.05 or＜0.01.There was no significant difference in the incidence rate of adverse events during follow-up between two groups(3.90％vs.6.49％,P=0.717).Conclusion:Rehabilitation exercise intervention based on cardiac function classifi-cation can significantly improve cardiopulmonary function,inhibit oxidative stress response in vivo and improve quality of life in CHF patients,which is worthy of promotion and application in clinical practice.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Aim To study the regulation and mechanism of phloroglucinol in bladder smooth muscle spasm. Methods In vitro the experiment used bladder muscle strip to verify the relieving effect of phloro-glucinol on bladder spasm by different drugs. At the same time,RT-qPCR and Western blot were used to detect the expression levels of genes involved in the calcium signaling pathway caused by the antispasmodic effect of phloroglucinol. Results Phloroglucinol could relieve bladder spasm, and the antispasmodic effect was enhanced with the increase of concentration, and the expression of calponin 1 and MYLK3 in tissue cells increased. The results of RT-qPCR showed that the expression of Gprc5b G,Ppp2r5a, Chptl, Prkar2b ,Abcd2 and Rasdl genes in mouse bladder tissue significantly decreased, which was consistent with the sequencing results of RNA-seq.Conclusions Phloroglucinol can relieve bladder smooth muscle spasm, and its mechanism is related to calcium signaling pathway. Meanwhile, phloroglucinol also inhibits the expression of Rasdl gene, suggesting that it may be related to cell cycle , protein phosphorylation, choline metabolism, ATP synthesis and tumor-related pathways.

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

The articles on alarm management of clinical medical equipment from January 2000 to January 2023 were collected with common databases in the world as search sources.CiteSpace software was used for trend drawing of annual publication distribution,author cooperation network mapping,country/institution cooperation network mapping and keyword knowledge mapping,and for analyzing related issues in depth.The annual publication of medical equipment alarm management research showed a fluctuating upward trend,the authors had good cooperative relationship with the organizations,the hotspots included ventilator,alarm and alarm fatigue in Chinese and alarm fatigue,intensive care unit and patient safety in English,and the research frontier involved in alarm fatigue,false alarm and alarm management.References were provided for conducting related research in China.