Targeting drug delivery systems mediated by nanoparticles has shown great potential in the diagnosis and treatment of cancer. However, influences of different tumor progressions on the accumulation of nanoparticles, especially the ligand-modified active targeting nanoparticles are seldom exploited. In this work, the accumulation and penetration of RGD-modified gold nanoparticles (active AuNPs) with different sizes were investigated in orthotopic breast cancer with different tumor progressions. The results showed that the smallest active AuNPs had better accumulation and permeation effects in early tumor tissues with the relatively looser extracellular matrix, larger gaps, lower interstitial fluid pressure, and less receptor expression, which was due to size effects. However, the larger active AuNPs had better accumulation and penetration effects in late tumor tissues with highly expressed target receptors integrin α _v β ₃ because of the multivalent interactions between larger active nanoparticles and integrin α _v β ₃. In the midterm, tumor accumulation of active AuNPs was equally influenced by size effects and multivalent interactions. Therefore, RGD-modified nanoparticles with sizes of 7 and 90 nm accumulated more in tumors. This study will guide a rational design of active targeting nanoparticles for enhancing the diagnosis and treatment of tumors based on their progressions.

ObjectiveBased on modern analytical techniques and a depressed mouse model established by chronic unpredictable mild stress（CUMS）， to evaluate the quality marker（Q-Marker） and pharmacodynamic difference of Baihe Dihuangtang prepared by different processes. MethodsHigh performance liquid chromatography（HPLC） was used to establish the characteristic profiles of Baihe Dihuangtang， and determine the content of Q-Marker in the samples prepared by ancient and modern processes. Seventy C57BL/6J mice were randomly divided into the normal group， model group， fluoxetine group（3 mg·kg^-1）， low and high dose groups of ancient process（6.5， 26 g·kg^-1）， and low and high dose groups of modern process（6.5， 26 g·kg^-1）， with 10 mice in each group. Except for the normal group， CUMS was used to induce depression in mice from the other groups for 28 d. After successful modeling， administration groups were given the corresponding drugs by gavage every day， and the normal and model groups were given an equal volume of pure water by gavage for 21 consecutive days. Change in body mass of mice was recorded， tail suspension test and open field test were used to evaluate the depressive behavior of mice， and enzyme-linked immunosorbent assay（ELISA） was employed to determine the contents of tumor necrosis factor-α（TNF-α）， interleukin（IL）-1β and IL-6 in serum. ResultsCharacteristic profiles of Baihe Dihuangtang prepared by the two processes were established， the similarity between the two was 0.951， and 8 characteristic peaks were recognized with the reference peak of regaloside A. The results of quantitative analysis showed that the Q-Marker content was similar in Baihe Dihuangtang prepared by ancient and modern processes. The results of pharmacodynamics showed that， compared with the normal group， the model group showed increased immobility time in the tail suspension test， reduced total movement distance in the open field test， and elevated IL-1β， IL-6 and TNF-α levels in the serum（P<0.01）. Compared with the model group， the behavioral indicators of mice in the Baihe Dihuangtang treatment group were significantly improved in terms of tail suspension time and open field exercise， and the levels of IL-1β， IL-6 and TNF-α in serum were significantly reduced（P<0.05， P<0.01）. Baihe Dihuangtang prepared by the two processes both had antidepressant effects， and the difference between the two was not statistically significant in improving depressive symptoms. ConclusionQ-Marker of Baihe Dihuangtang prepared by modern and ancient methods are equivalent in content， and the pharmacological effects are consistent， indicating that dried Lilii Bulbus can replace fresh products in the preparation of Baihe Dihuangtang. This study provides a scientific basis for the development of new drugs of Baihe Dihuangtang and a reference for its rational application and clinical use.

ObjectiveBased on modern analytical techniques and a depressed mouse model established by chronic unpredictable mild stress（CUMS）， to evaluate the quality marker（Q-Marker） and pharmacodynamic difference of Baihe Dihuangtang prepared by different processes. MethodsHigh performance liquid chromatography（HPLC） was used to establish the characteristic profiles of Baihe Dihuangtang， and determine the content of Q-Marker in the samples prepared by ancient and modern processes. Seventy C57BL/6J mice were randomly divided into the normal group， model group， fluoxetine group（3 mg·kg^-1）， low and high dose groups of ancient process（6.5， 26 g·kg^-1）， and low and high dose groups of modern process（6.5， 26 g·kg^-1）， with 10 mice in each group. Except for the normal group， CUMS was used to induce depression in mice from the other groups for 28 d. After successful modeling， administration groups were given the corresponding drugs by gavage every day， and the normal and model groups were given an equal volume of pure water by gavage for 21 consecutive days. Change in body mass of mice was recorded， tail suspension test and open field test were used to evaluate the depressive behavior of mice， and enzyme-linked immunosorbent assay（ELISA） was employed to determine the contents of tumor necrosis factor-α（TNF-α）， interleukin（IL）-1β and IL-6 in serum. ResultsCharacteristic profiles of Baihe Dihuangtang prepared by the two processes were established， the similarity between the two was 0.951， and 8 characteristic peaks were recognized with the reference peak of regaloside A. The results of quantitative analysis showed that the Q-Marker content was similar in Baihe Dihuangtang prepared by ancient and modern processes. The results of pharmacodynamics showed that， compared with the normal group， the model group showed increased immobility time in the tail suspension test， reduced total movement distance in the open field test， and elevated IL-1β， IL-6 and TNF-α levels in the serum（P<0.01）. Compared with the model group， the behavioral indicators of mice in the Baihe Dihuangtang treatment group were significantly improved in terms of tail suspension time and open field exercise， and the levels of IL-1β， IL-6 and TNF-α in serum were significantly reduced（P<0.05， P<0.01）. Baihe Dihuangtang prepared by the two processes both had antidepressant effects， and the difference between the two was not statistically significant in improving depressive symptoms. ConclusionQ-Marker of Baihe Dihuangtang prepared by modern and ancient methods are equivalent in content， and the pharmacological effects are consistent， indicating that dried Lilii Bulbus can replace fresh products in the preparation of Baihe Dihuangtang. This study provides a scientific basis for the development of new drugs of Baihe Dihuangtang and a reference for its rational application and clinical use.

To investigate the infection status of two arboviruses,akabane orthobunyavirus(AKAV)and bluetongue virus(BTV),in cattle herds of Guizhou Province,we employed the indirect ELISA method to detect AKAV and BTV antibody levels in the present experiment.A total of 1504 bovine serum samples from 37 large-scale farms and 88 free-range households from 26 districts or coun-ties of 7 cities(prefectures)of Guizhou Province were collected to detect AKAV antibody levels.Additionally,1 241 serum samples from 30 large-scale farms and 15 free-range households in 19 districts or counties of 3 cities(prefectures)were tested for BTV antibody levels.Moreover,two influencing factors,breeding mode and sampling season,were statistically analyzed for their effects.The results showed that the overall positive rate of AKAV antibodies was 11.64％(175/1 504),with individual positive rates of 13.20％(123/934)and 9.12％(52/570)in large-scale farms and free-range households,respectively.No significant differences were observed between the two groups.However,the farm positive rate(64.86％,24/37)in large-scale farms was significantly higher than that(26.14％,23/88)in free-range households.Seasonal statistics showed that the positive rate was highest during the summer season at 60.00％(12/20).The total positive rate of BTV antibodies was 25.42％(222/1 241).The farm positive rate and individual positive rate in free-range households were 66.67％(10/15)and 41.91％(57/136),respectively.For large-scale farms,these rates were 60.00％(18/30)and 14.93％(165/1 105),respectively.The individual pos-itive rate in free-range households was significantly higher than that in large-scale farms.Seasonal statistics showed that the positive rates in summer and autumn seasons were 50.00％(5/10)and 72.41％(21/29),respectively,both of which were significantly higher than those in winter and spring seasons.All these findings indicated that both AKAV and BTV were present to a certain ex-tent in Guizhou Province,with seasonality.Furthermore,differences were observed between the different breeding modes.Our results could provide a data reference for the formulation of preven-tion and control measures for the two insect-borne diseases.

To establish a rapid visual detection method for Akabane virus(AKAV)on site,specific primers and probes based on the S fragment of AKAV were designed in this experiment.Corre-sponding groups were added to the primers or probes to fulfil the requirement of the combination of recombinase polymerase amplification(RPA)with lateral flow dipstick(LFD).The reaction temperature and time,concentrations of the primer and probe were optimized to establish the RPA-LFD method for detecting AKAV.After that,the specificity,sensitivity and clinical reliability of the method were evaluated.The results showed that after 20 minutes of reaction at 37 ℃,the test results could be read on LFD paper.There was no cross reaction against blue tongue virus,Pasteurella multocida,bovine infectious rhinotracheitis virus and bovine Mycoplasma bovis,and the detection limit was 2.5 × 100 copies/μL of standard plasmid.Detection of clinical samples showed a consistent results with that by RT-PCR method.These findings indicated that the RPA-LFD method established had the advantages of good specificity,high sensitivity,simple operation and visualization,and could be applied to clinical detection,which provides new technical support for the rapid diagnosis and prevention and control of AKAV.

Gastrointestinal (GI) cancers are a leading cause of cancer morbidity and mortality worldwide. Despite advances in treatment, cancer relapse remains a significant challenge, necessitating novel therapeutic strategies. In this study, we engineered nanobody-based chimeric antigen receptor (CAR) natural killer (NK) cells targeting cadherin 17 (CDH17) for the treatment of GI tumors. In addition, to enhance the efficacy of CAR-NK cells, we also incorporated CV1, a CD47-SIRPα axis inhibitor, to evaluate the anti-tumor effect of this combination. We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner. CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47-signal regulatory protein α (SIRPα) axis inhibitor CV1, likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment. Collectively, our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers. The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy. Further investigations are warranted to speed up the clinical translation of these findings.

Objective To investigate the status quo of indwelling needles use in the hospitals at all lev-els in Chongqing city,and to evaluate the normalization and safety of indwelling needles use by referring to Nursing Practice Standards for Intravenous Therapy.Methods A self-designed questionnaire was used in July 2023 to conduct a cross-sectional survey on the use of indwelling needles in the hospitals at all levels in Chongqing city.Results A total of 30 807 patients in 77 hospitals were included,among them 62.67%used indwelling needles.The closed type indwelling needles accounted for 88.87%and the safety type indwelling needles accounted for 41.74%.Non-needle infusion connectors accounted for 37.78%,and steel needle con-nected with heparin caps accounted for 51.69%.95.66%of puncture site was in the upper limb,the non-cor-rosive drug infusion accounted for 87.57%,and the complications occurrence rate was 2.46%.Among the 6 419 surveyed nurses,75.51%removed indwelling needles based on clinical indications.There were statistically significant differences in the usage rates of closed type indwelling needles and non-needle infusion connectors among hospitals at different levels(P<0.05).There were also statistically significant differences in the inci-dence rates of complication and phlebitis(P<0.05).Conclusion The overall application of indwelling needles in the hospitals at all levels in Chongqing city is generally standardized,but the use of safety type indwelling needles and needle-free infusion connectors still needs to be improved.

To investigate the infection status of two arboviruses,akabane orthobunyavirus(AKAV)and bluetongue virus(BTV),in cattle herds of Guizhou Province,we employed the indirect ELISA method to detect AKAV and BTV antibody levels in the present experiment.A total of 1504 bovine serum samples from 37 large-scale farms and 88 free-range households from 26 districts or coun-ties of 7 cities(prefectures)of Guizhou Province were collected to detect AKAV antibody levels.Additionally,1 241 serum samples from 30 large-scale farms and 15 free-range households in 19 districts or counties of 3 cities(prefectures)were tested for BTV antibody levels.Moreover,two influencing factors,breeding mode and sampling season,were statistically analyzed for their effects.The results showed that the overall positive rate of AKAV antibodies was 11.64％(175/1 504),with individual positive rates of 13.20％(123/934)and 9.12％(52/570)in large-scale farms and free-range households,respectively.No significant differences were observed between the two groups.However,the farm positive rate(64.86％,24/37)in large-scale farms was significantly higher than that(26.14％,23/88)in free-range households.Seasonal statistics showed that the positive rate was highest during the summer season at 60.00％(12/20).The total positive rate of BTV antibodies was 25.42％(222/1 241).The farm positive rate and individual positive rate in free-range households were 66.67％(10/15)and 41.91％(57/136),respectively.For large-scale farms,these rates were 60.00％(18/30)and 14.93％(165/1 105),respectively.The individual pos-itive rate in free-range households was significantly higher than that in large-scale farms.Seasonal statistics showed that the positive rates in summer and autumn seasons were 50.00％(5/10)and 72.41％(21/29),respectively,both of which were significantly higher than those in winter and spring seasons.All these findings indicated that both AKAV and BTV were present to a certain ex-tent in Guizhou Province,with seasonality.Furthermore,differences were observed between the different breeding modes.Our results could provide a data reference for the formulation of preven-tion and control measures for the two insect-borne diseases.

To establish a rapid visual detection method for Akabane virus(AKAV)on site,specific primers and probes based on the S fragment of AKAV were designed in this experiment.Corre-sponding groups were added to the primers or probes to fulfil the requirement of the combination of recombinase polymerase amplification(RPA)with lateral flow dipstick(LFD).The reaction temperature and time,concentrations of the primer and probe were optimized to establish the RPA-LFD method for detecting AKAV.After that,the specificity,sensitivity and clinical reliability of the method were evaluated.The results showed that after 20 minutes of reaction at 37 ℃,the test results could be read on LFD paper.There was no cross reaction against blue tongue virus,Pasteurella multocida,bovine infectious rhinotracheitis virus and bovine Mycoplasma bovis,and the detection limit was 2.5 × 100 copies/μL of standard plasmid.Detection of clinical samples showed a consistent results with that by RT-PCR method.These findings indicated that the RPA-LFD method established had the advantages of good specificity,high sensitivity,simple operation and visualization,and could be applied to clinical detection,which provides new technical support for the rapid diagnosis and prevention and control of AKAV.

Palliative and hospice care is an emerging medical care model for the development of modern medicine,and its emergence is not only a sign of social demand and the development of human civilization,but also an important manifestation of the change in the modern medical model.Hospice care is the final stage of palliative care,which is of great significance for the end-of-life treatment of incurable diseases.Palliative and hospice care has become an independent discipline in many countries,and its development has been rapid.However,the develop-ment of hospice and palliative care in China is not satisfactory,and the lack of money and human resources are the main reasons limiting its development.Many scholars have carried out a lot of useful practices in this regard.How to explore a road of hospice and palliative care development suitable for China′s national conditions is an urgent problem to be solved.By reviewing domestic and foreign literature,this paper summarizes the development mode and payment method of palliative and hospice care abroad,identifies the challenges encountered in the practice of hospice care in China,and draws on the development experience of palliative and hospice care in foreign countries.We aimed to identify pain points and difficulties faced in developing palliative and hospice care in China,so as to better serve patients at the end of life,gradually promote the concept of palliative and hospice care,and contribute to the sustainable development of palliative and hospice care in China.