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.

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 explore the impact of suture configuration and fixation type on the biome-chanical strength of rotator cuff repair,using a factorial design study.Methods Sixteen fresh-frozen porcine shoulder samples were randomized into an anchorless double-row suture bridge transosseous su-tures(DS)group,an anchored double-row suture bridge transosseous-equivalent(DE)group,an an-chorless X-BOX construct transosseous sutures(XS)group,and an anchored X-BOX construct transos-seous-equivalent(XE)group,each of four,according to suture configuration(double-row suture bridge,traditional X-BOX construct)and fixation type(suture anchors,transosseous sutures).Then,their fatigue resistance(first-cycle excursion,gap length difference ratio,and the percentage of ex-posed footprints)and the failure strength(the maximum failure load and the re-tear type)were mea-sured using a biomechanical material testing machine.Results Different suture configurations affected failure strength(F=39.559,P<0.001),with the double-row suture bridge groups(693.07±58.35 N,746.76±138.57 N)showing significantly higher failure strength,compared to the traditional X-BOX groups(462.90±18.91 N,421.43±90.76 N).However,the fixation type did not significantly im-pact failure strength(F=1.161,P=0.302).Moreover,the suture configuration influenced the gap differ-ence ratio(F=7.781,P=0.016),but had no significant correlation with other fatigue resistance indica-tors(P>0.05).Meanwhile,failure strength and fatigue resistance were not correlated with fixation type,and the interaction between suture and fixation type(P>0.05).The incidence of failure types for the four suture configurations was as follows:Type I tendon tear:XS>XE>DS=DE;type II tendon tear:DS>XE>XS=DE;fixing material-related failure:DE>DS=XE=XS.Conclusion The failure strength and gap formation ratio in rotator cuff repair under fatigue loading are influenced by suture configuration,whereas no significant association has been observed with respect to fixation method,whether using transosseous sutures or suture anchors.

Objective:To explore the application effect of fine skin care in patients with psoriasis, and provide evidence-based theoretical basis for the development of skin care in patients with psoriasis.Methods:A randomized controlled trial was conducted. Patients with psoriasis admitted to the People′s Hospital of Wenshan Zhuang and Miao Autonomous Prefecture, Yunnan Province from December 2022 to March 2024 were selected as the research subjects by the convenience sampling method and divided into the control group and the experimental group by the random number table method. The control group was given routine care. The experimental group was given fine skin care on the basis of control group. Before and after the intervention, the itching symptoms, skin lesions, comfort and quality of life were evaluated using 12-item Pruritus Severity Scale (12-PSS), Psoriasis Area and Severity Index (PASI), General Comfort Questionnaire (GCQ), 36-item Short Form (SF-36) and compared between the two groups. The incidence of complications and recurrence rate in the two groups were counted 3 months after intervention.Results:Finally, 96 patients were included in the study, including 48 patients in the experimental group, 28 males and 20 females, aged (59.31 ± 17.31) years old; 48 cases in the control group, 29 males and 19 females, aged (61.54 ± 18.11) years old. Before the intervention, there were no statistically significant differences in the scores of 12-PSS, PASI, GCQ and SF-36 between the two groups (all P>0.05). After the intervention, the scores of 12-PSS and PASI in the experimental group were (3.65 ± 2.96), (5.08 ± 1.15) points respectively, which were lower than (8.29 ± 2.00), (7.37 ± 1.34) points in the control group, the differences were statistically significant ( t=9.00, 8.99, both P<0.05). The scores of GCQ and SF-36 in the experimental group were (41.42 ± 4.01), (95.08 ± 4.47) points respectively, which were higher than (33.94 ± 5.74) and (84.19 ± 8.52) points in the control group, the differences were statistically significant ( t=7.40, 7.84, both P<0.05). The total incidence of complications and recurrence rate in the experimental group were 4.17% (2/48), 2.08% (1/48) respectively, which were lower than 18.75% (9/48), 14.58% (7/48) in the control group, the differences were statistically significant ( χ2=5.03, 4.91, both P<0.05). Conclusions:Fine skin care can improve the itching symptoms of patients with psoriasis and reduce the severity of skin lesions. It can also improve the comfort and quality of life of patients and reduce the incidence of complications and recurrence rate, and the clinical application effect is good.

Objective To explore the impact of suture configuration and fixation type on the biome-chanical strength of rotator cuff repair,using a factorial design study.Methods Sixteen fresh-frozen porcine shoulder samples were randomized into an anchorless double-row suture bridge transosseous su-tures(DS)group,an anchored double-row suture bridge transosseous-equivalent(DE)group,an an-chorless X-BOX construct transosseous sutures(XS)group,and an anchored X-BOX construct transos-seous-equivalent(XE)group,each of four,according to suture configuration(double-row suture bridge,traditional X-BOX construct)and fixation type(suture anchors,transosseous sutures).Then,their fatigue resistance(first-cycle excursion,gap length difference ratio,and the percentage of ex-posed footprints)and the failure strength(the maximum failure load and the re-tear type)were mea-sured using a biomechanical material testing machine.Results Different suture configurations affected failure strength(F=39.559,P<0.001),with the double-row suture bridge groups(693.07±58.35 N,746.76±138.57 N)showing significantly higher failure strength,compared to the traditional X-BOX groups(462.90±18.91 N,421.43±90.76 N).However,the fixation type did not significantly im-pact failure strength(F=1.161,P=0.302).Moreover,the suture configuration influenced the gap differ-ence ratio(F=7.781,P=0.016),but had no significant correlation with other fatigue resistance indica-tors(P>0.05).Meanwhile,failure strength and fatigue resistance were not correlated with fixation type,and the interaction between suture and fixation type(P>0.05).The incidence of failure types for the four suture configurations was as follows:Type I tendon tear:XS>XE>DS=DE;type II tendon tear:DS>XE>XS=DE;fixing material-related failure:DE>DS=XE=XS.Conclusion The failure strength and gap formation ratio in rotator cuff repair under fatigue loading are influenced by suture configuration,whereas no significant association has been observed with respect to fixation method,whether using transosseous sutures or suture anchors.

Objective:To explore the application effect of fine skin care in patients with psoriasis, and provide evidence-based theoretical basis for the development of skin care in patients with psoriasis.Methods:A randomized controlled trial was conducted. Patients with psoriasis admitted to the People′s Hospital of Wenshan Zhuang and Miao Autonomous Prefecture, Yunnan Province from December 2022 to March 2024 were selected as the research subjects by the convenience sampling method and divided into the control group and the experimental group by the random number table method. The control group was given routine care. The experimental group was given fine skin care on the basis of control group. Before and after the intervention, the itching symptoms, skin lesions, comfort and quality of life were evaluated using 12-item Pruritus Severity Scale (12-PSS), Psoriasis Area and Severity Index (PASI), General Comfort Questionnaire (GCQ), 36-item Short Form (SF-36) and compared between the two groups. The incidence of complications and recurrence rate in the two groups were counted 3 months after intervention.Results:Finally, 96 patients were included in the study, including 48 patients in the experimental group, 28 males and 20 females, aged (59.31 ± 17.31) years old; 48 cases in the control group, 29 males and 19 females, aged (61.54 ± 18.11) years old. Before the intervention, there were no statistically significant differences in the scores of 12-PSS, PASI, GCQ and SF-36 between the two groups (all P>0.05). After the intervention, the scores of 12-PSS and PASI in the experimental group were (3.65 ± 2.96), (5.08 ± 1.15) points respectively, which were lower than (8.29 ± 2.00), (7.37 ± 1.34) points in the control group, the differences were statistically significant ( t=9.00, 8.99, both P<0.05). The scores of GCQ and SF-36 in the experimental group were (41.42 ± 4.01), (95.08 ± 4.47) points respectively, which were higher than (33.94 ± 5.74) and (84.19 ± 8.52) points in the control group, the differences were statistically significant ( t=7.40, 7.84, both P<0.05). The total incidence of complications and recurrence rate in the experimental group were 4.17% (2/48), 2.08% (1/48) respectively, which were lower than 18.75% (9/48), 14.58% (7/48) in the control group, the differences were statistically significant ( χ2=5.03, 4.91, both P<0.05). Conclusions:Fine skin care can improve the itching symptoms of patients with psoriasis and reduce the severity of skin lesions. It can also improve the comfort and quality of life of patients and reduce the incidence of complications and recurrence rate, and the clinical application effect is good.

Objective:To explore the predictive value of the neutrophil-to-lymphocyte ratio (NLR) combined with blood glucose at admission for a positive blood culture for sepsis.Methods:A single-center retrospective cohort study was conducted. According to the 2016 American Society of Critical Care/European Society of Critical Care Medicine (SCCM/ESICM) and diagnostic criteria for sepsis and septic shock-3.0 (sepsis-3.0), patients with sepsis were admitted to the Emergency Department of Fujian Medical University Union Hospital for more than 24 h from January 2019 to December 2021 were enrolled. Age, gender, sequential organ failure assessment, source of infection, NLR, and blood culture results were recorded. Based on the blood culture results, patients were divided into a blood culture positive group (Gram-positive group, Gram-negative group) and blood culture negative group, and the differences between the groups were compared. The risk factors for a positive blood culture were analyzed using multivariate logistic regression. A receiver operating characteristic analysis was performed for the NLR combined with the blood glucose measurement.Results:A total of 265 patients with sepsis were included, of which 62 were positive in blood culture (15 Gram-positive patients, 37 Gram-negative patients and 10 fungal patients). The positive rate of blood culture was 23.4%. The number of patients with history of diabetes, neutrophil count, procalcitonin, blood glucose, and NLR in the positive blood culture group were significantly higher than those in the negative blood culture group (all P<0.001). Multivariate logistic regression analysis revealed that random admission blood glucose ( OR=1.116, 95% CI: 1.051~1.186, P<0.001) and NLR ( OR=1.039, 95% CI: 1.015~1.064, P=0.001) were independent risk factors for blood culture positivity in sepsis patients. For patients with blood culture positive, and with Gram-negative bacterial bloodstream infections, the AUC of the NLR combined with the admission blood glucose level was 0.819 (95% CI: 0.761-0.877, P<0.001) and 0.871 (95% CI: 0.813-0.928, P<0.001), respectively. Conclusions:The combination of NLR and random admission blood glucose could provide a good predictive value for blood culture positive and gram-negative bacterial bloodstream infections in sepsis patients.

In the course of pathophysiology,we gave full play to the advantages of network teaching platform to integrate teaching resources,broaden students' learning pathways,and enhance the interaction,which could benefit teachers as well as students.The traditional teaching mode and concept were changed by using Computer Aided Instruction (CAI) and relying on the network platform to carry out multi-level teaching methods such as flipped classroom and Task-Based Leaming (TBL).We gradually conducted formative assessment to promote learning.Thus,the interest and the enthusiasm of students in learning were elevated and the independent learning capability were cultivated.

OBJECTIVE:To establish a method for the determination of related substances in lorcaserin hydrochloride.METHODS:HPLC method was adopted.The determination was performed on Welch ultimate XB-ODS column with mobile phase consisted of Sodium dihydrogen phosphate (pH =6.5)-acetonitrile (gradient elution) at the flow rate of 1.0 mL/min.The detection wavelength was set at 220 nm,and column temperature was 35 ℃.The sample size was 20 μL.RESULTS:The linear ranges of impurity 1,2,3 were 0.075 60-7.560 μg/mL(r=0.999 9),0.081 40-8.140 μg/mL(r=0.999 9),0.099 24-9.924 μg/mL(r=0.999 9),respectively.The limits of quantification were 0.075 60,0.081 40,0.099 25 μg/mL.The limits of detection were 0.022 68,0.024 42,0.029 77 μg/mL.RSD of precision test was lower than 2.0％.Impurity 1 was found in stability test and reproducibility test,RSD＜2.0％.The recoveries were 98.53％-102.45％ (RSD=1.06％,n=9),98.26％-101.64％ (RSD=1.03 ％,n=9),100.08％-102.10％ (RSD=0.70％,n=9),respectively.CONCLUSIONS:The method is sensitive,rapid,accurate and reliable,which can be used to determine the related substances of lorcaserin hydrochloride.

Comparing the definition,classification,quantity,core capacity construction and the supervision mode of Chinese and the United States specialist nurses,there was a gap between them.The training for the specialist nurses in China was at the initial stage.The advanced experience should be learned from America to provide the reference for building the core capacity and supervision mode of the specialist nurses.