Although cancer immunotherapy has made great strides in the clinic, it is still hindered by the tumor immunosuppressive microenvironment (TIME). The stimulator of interferon genes (STING) pathway which can modulate TIME effectively has emerged as a promising therapeutic recently. However, the delivery of most STING agonists, specifically cyclic dinucleotides (CDNs), is performed intratumorally due to their insufficient pharmacological properties, such as weak permeability across cell membranes and vulnerability to nuclease degradation. To expand the clinical applicability of CDNs, a novel pH-sensitive polycationic polymer-modified lipid nanoparticle (LNP-B) system was developed for intravenous delivery of CDNs. LNP-B significantly extended the circulation of CDNs and enhanced the accumulation of CDNs within the tumor, spleen, and tumor-draining lymph nodes compared with free CDNs thereby triggering the STING pathway of dendritic cells and repolarizing pro-tumor macrophages. These events subsequently gave rise to potent anti-tumor immune reactions and substantial inhibition of tumors in CT26 colon cancer-bearing mouse models. In addition, due to the acid-sensitive property of the polycationic polymer, the delivery system of LNP-B was more biocompatible and safer compared with lipid nanoparticles formulated with an indissociable cationic DOTAP (LNP-D). These findings suggest that LNP-B has great potential in the intravenous delivery of CDNs for tumor immunotherapy.

Cold tumors have a poor response to tumor immunotherapy due to low immune cell infiltration and the ability to evade immune attacks. Converting cold tumors into hot tumors can enhance the clinical effectiveness of anti-tumor immunotherapy. High-intensity focused ultrasound (HIFU) as a non-invasive treatment can damage tumors through mechanical effects, but there is a lack of research on its cytotoxic mechanisms at the cellular level and its role in inducing anti-immune responses. In this study, the role of HIFU in triggering tumor ferroptosis by disrupting the GSH/GSSG balance through mechanochemical action and the associated anti-tumor immune priming effect were investigated. The use of a nano-enhancer loaded with PFOB combined with HIFU could enhance ferroptosis in triple-negative breast cancer at a specific stage of tumor growth (UTGR = 0) while promoting the conversion of a cold tumor into a hot tumor, thereby improving the immune response. Overall, this provides valuable guidance for the clinical application of HIFU in tumor immunotherapy.

ObjectiveTo analyze the quantity-quality transfer of standard decoction of Ginseng Radix et Rhizoma（GRR） decoction pieces produced by fresh and traditional cutting， and to provide reference for quality control and application development of the decoction pieces produced by fresh cutting. MethodTen batches of representative GRR decoction pieces produced by fresh and traditional cutting and their standard decoctions were prepared by standard process， and high performance liquid chromatography（HPLC） fingerprint of the standard decoction was established and performed on an Agilent EC-C₁₈ column（4.6 mm×150 mm， 2.7 μm） with acetonitrile（A）-0.1% phosphoric acid aqueous solution（B） as the mobile phase for gradient elution（0-23 min， 18%-21%A； 23-35 min， 21%-28%A； 35-80 min， 28%-32%A）， and the detection wavelength was 203 nm. Then similarity evaluation， principal component analysis（PCA） and partial least squares-discriminant analysis（PLS-DA） of fingerprint of the standard decoction were performed to screen the differential components with variable importance in the projection（VIP） value>1. Quantitative analysis was carried out on the screened known differential components， and combined with the indicators of the dry extract rate and the transfer rate， to explore the differences in the quantity-quality transfer between the standard decoction of GRR decoction pieces produced by fresh and traditional cutting. ResultThe fingerprint similarity of the standard decoction of GRR decoction pieces produced by fresh and traditional cutting was more than 0.950， and 18 common peaks were identified， including 9 identified common peaks. The results of PCA and PLS-DA showed that there were some differences in the contents of index components between the two standard decoctions. The contents of ginsenoside Rg₁， Re and Ro in GRR decoction pieces produced by fresh cutting were higher than those in traditional decoction pieces， while the contents of ginsenoside Rb₁， Rc ， Rb₂ and Rd were lower than those in traditional decoction pieces. The contents of ginsenoside Rg₁， Re， Rb₁ and Ro in the standard decoction of GRR decoction pieces produced by fresh cutting were higher than those in the standard decoction of traditional decoction pieces， while the contents of ginsenoside Rc ， Rb₂ and Rd were comparable between the two standard decoctions. Compared with the standard decoction of the traditional decoction pieces， the average transfer rates of ginsenoside Rg₁， Rb₁， Rc， Rb₂ and dry extract rate of the standard decoction of GRR decoction pieces produced by fresh cutting were significantly increased（P<0.05）， and the average transfer rate of ginsenoside Re and Rd also increased， but the difference was not statistically significant. ConclusionThe dry extract rate， content and transfer rate of index components of standard decoction of GRR decoction pieces produced by fresh cutting are better than those of the standard decoction of traditional decoction pieces， which can provides data support for the subsequent clinical application of fresh cutting products.

ObjectiveTo analyze and determine the differential components of freeze-dried and sun-dried Panacis Quinquefolii Radix（PQR）， and to compare the differences in their pro-angiogenic activities. MethodFingerprints of freeze-dried and sun-dried PQR were established based on ultra performance liquid chromatography（UPLC）， and chemometrics methods such as principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were combined to determine the differential saponin composition of the two decoction pieces， and six representative saponins were selected and their contents in freeze-dried and sun-dried PQR were determined by UPLC. Transgenic zebrafish line Tg（fli1a∶EGFP） embryos fertilized for 24 h were selected， and different doses of 70% methanol extracts of freeze-dried and sun-dried PQR（10， 30 mg·L^-1） were used to intervene in normal zebrafish and in a zebrafish model of intersegmental vascular（ISV） injury induced by vascular endothelial growth factor（VEGF） receptor tyrosine kinase inhibitor Ⅱ（PTK787）， then the development of subintestinal vein（SIV） and ISV of zebrafish was observed， SIV diameter， mean number of crossings and mean number of germinations were determined， and the ISV vascular index was calculated， in order to compare the pro-angiogenic activities of the two decoction pieces. ResultThe similarity of the fingerprints of freeze-dried and sun-dried PQR decoction pieces was>0.950， and 17 common peaks were identified， of which 6 common peaks were designated as peak 6（ginsenoside Rg₁）， peak 7（ginsenoside Re）， peak 8（ginsenoside Rb₁）， peak 11（ginsenoside Rc）， peak 13（ginsenoside Rb₂）， and peak 16（ginsenoside Rd）， respectively. A total of 11 differential saponin components were screened by PCA and OPLS-DA， indicating that there were some differences in the contents of the components in the two decoction pieces. The results of determination showed that the contents of ginsenosides Rg₁， Re， Rb₁ and Rb₂ in freeze-dried PQR were higher than those in sun-dried PQR， while the contents of ginsenosides Rc and Rd were lower than those in sun-dried PQR（P<0.05， P<0.01）. In the study of the pro-angiogenic effect on normal zebrafish embryos， compared with the blank group， and the SIV vessel diameter， mean germination rate and mean crossover rate were significantly higher in the high-dose groups of freeze-dried and sun-dried PQR（P<0.01）， and the vessel diameter， mean numbers of crossings and germinations in the freeze-dried PQR group were higher than those of the sun-dried PQR group（P<0.05）. In the study of the pro-angiogenic effect on zebrafish embryos with ISV injury， the development of ISV in the model group was significantly inhibited when compared with the blank group， compared with the model group， different dose groups of freeze-dried and sun-dried PQR could promote the growth and sprouting of ISV， and the number of normal blood vessels in the freeze-dried PQR group was significantly higher than that in the sun-dried PQR group at the same dosage（P<0.05）. ConclusionFreeze-drying can effectively avoid the loss and secondary transformation of ginsenosides in PQR， and its angiogenic activity is better than that of sun-dried PQR， which can provide a reference for the production and development of high-quality PQR decoction pieces.

Objective: To explore the causal relationship between adolescent school connectedness and the co-occurrence with health risk behaviors among junior high school students, so as to provide the reference for reducing the occurrence of adolescents health risk behaviors among junior high school students. Methods: A total of 924 students from two junior high schools in Jishou City were selected by the convenience sampling and cluster sampling methods, and two follow up surveys were conducted at 6 month intervals in April (T1) and October (T2) of 2023 using the Adolescent Health Risk Behavior Questionnaire and the School Connection Scale. The scores of the co-occurrence of school connectedness and health risk behaviors among junior high school students were compared by different survey periods and genders using the t-test, and cross lagged analyses were performed using Mplus 8.3 software. Results: School connectedness scores among junior high school students in T1 and T2 surveys were (38.86±7.46) (37.87± 7.71 ) and co-occurrence of health risk behaviors scores were (1.64±0.68) (1.83±0.53), respectively, and the differences between the scores of the 2 surveys were statistically significant ( t=4.24, -4.14, P <0.05). The correlation between school connectedness and co-occurrence of health risk behaviors were statistically significant in both surveys ( r =-0.46 to -0.33, P <0.05). Cross lagged analyses showed that school connectedness in T1 negatively predicted the co-occurrence of health risk behaviors in T2 ( β =-0.08), and the co-occurrence of health risk behaviors in T1 negatively predicted the school connectedness in T2 ( β =-0.15) ( P <0.05). Conclusions There is a longitudinal causal relationship between school connectedness and co-occurrence of health risk behaviors among junior high school students. School connectedness should be improved through various ways to reduce the co-occurrence of health risk behaviors.

Objective:To observe any effect of electroacupuncture pretreatment (EP) on the function of cerebral microvascular endothelial cells in mice with middle cerebral artery obstruction (MCAO), and to explore the role of miRNA-155 RNA and the p53 pathway in determining it.Methods:Forty-two mice were randomly divided into a sham operation group, a model group, an EP group, an miR-155 inhibitor (MI) group, an miR-155 agonist (MA) group, an miR-155 inhibitor negative control (MIN) group and an miR-155 agonist negative control (MAN) group. Each group had 6 rats. All except the sham-operated and model groups received EP, followed by injecting into the corresponding lateral ventricles inhibitor and agonist in groups MI and MA, and placebos in group MIN and MAN. All 7 groups were subjected to MCAO modeling 48 hours after the EP. Twenty-four and 72 hours after the modeling, neurological deficits were quantified using modified neurological severity scoring (mNSS). All of the mice were then sacrificed and any brain tissue damage was observed using hematoxylin-eosin (HE) staining. Terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) was used to observe any apoptosis of endothelial cells, and enzyme-linked immunosorbent assays (ELISA) were employed to detect the level of intercellular cell adhesion molecule-1 (ICAM-1) in the serum. Apoptotic endothelial cells in the cerebral microbleed and ICAM-1, Bcl-2 and Bax positive cells were detected using immunofluorescence. Quantitative real-time polymerase chain reactions (qRT-PCR) were carried to observe the expressions of miRNA-155 RNA and YY1 and p53 proteins in the ischemia/reperfusion (I/R) region.Results:Twenty-four and 72 hours after the MCAO the average mNSS score of the EP group was significantly lower than the model group′s average. HE staining showed that the cell morphology of the EP group was more regular. The number of apoptotic cells, the expression of ICAM-1, the relative expression of ICAM-1, the Bax/Bcl-2 ratio, as well as the relative expression of miRNA-155 RNA and YY1 and p53 proteins were all then significantly lower in the EP group than in the model group, on average.The expression of miRNA-155 RNA, p53 protein and ICAM-1, as well as the Bax to Bcl-2 ratio in the MI group was then significantly lower than in the MIN group, on average.Conclusion:Electroacupuncture pretreatment improves microvascular endothelial cell functioning in the cerebrum after ischemia and reperfusion (at least in mice) and may attenuate cerebral cell injury by down-regulating the miRNA-155-mediated YY1/p53 pathway.

Objective:To observe the clinical and imaging features of patients with retinal vein occlusion (RVO) complicated with retinal artery occlusion (RAO).Methods:A retrospective clinical study. Fifteen patients with 15 eyes with RVO combined with RAO and macular edema diagnosed by ophthalmology examination in the Department of Ophthalmology, First People's Hospital of Xianyang City during 2 years from February 1, 2022 to January 31, 2024 were included in the study. Branch retinal vein occlusion (BRVO) combined with branch retinal artery occlusion (BRAO) occurred in 3 cases and 3 eyes. Central retinal vein occlusion (CRVO) complicated with central retinal artery occlusion (CRAO) in 12 eyes. Best corrected visual acuity (BCVA), intraocular pressure, scanning laser ophthalmoscope, optical coherence tomography (OCT), fluorescein fundus angiography (FFA) and serum homocysteine were all performed. OCT angiography (OCTA) was performed in 6 eyes. All eyes were treated with intravitreal injection of anti-vascular endothelial growth factor drugs. After the initial 1 treatment, dosage was assessed as needed. Follow-up was performed every month for 12 months after treatment. FFA inspection was performed at 3 months. During follow-up, it was found that there were no perfusion areas of capillaries, and retinal laser photocoagulation therapy was given in time. Fundus manifestations, FFA, OCT, OCTA characteristics and causes of disease were analyzed retrospectively.Results:There were 15 eyes in 15 cases, 9 eyes in 9 males; 6 women with 6 eyes. Age was (61.0±9.7) years. All complained of painless vision loss in one eye. All eyes were positive for relative afferent pupillary disorder. Contralateral congenital optic disc defect was in 1 case; hypertension was in 6 cases; hyperhomocysteinemia was in 2 cases; cerebral infarction was in 3 cases; coronary heart disease was in 1 case. CRVO combined with CRAO was in 12 eyes BCVA light sensitivity-0.25. The BCVA of BRVO combined with BRAO were 0.1, 0.4 and 0.25, respectively. All the patients had retinal edema in the posterior pole of the eye, venous sinuous, dilated, thin arteries and stiff shape. The retina presents with flaky or flame-like bleeding. Posterior polar retinal lint patch was in 13 eyes. In 12 eyes with CRVO combined with CRAO, optic disc edema was observed and the boundary was not clear. In 3 eyes with BRVO combined with BRAO, no obvious abnormality was found in the optic disc, and the boundary was clear. FFA examination showed no or prolonged arterial filling, delayed retinal vein laminar flow, relatively slow or even no capillary filling, macular arteriole atretosis to varying degrees, arch ring structure destruction, optic disc telangiectasia and fluorescein leakage. OCT examination showed that the middle and inner layers of the retina were thickened to varying degrees, the diffuse reflex was enhanced, the interlayer structure was unclear, and the reflex of the lower retinal tissue was weakened. The blood flow density of superficial capillary plexus and deep capillary plexus (DCP) decreased in 6 eyes undergoing OCTA examination. Decreased or interrupted blood flow in the vascular bed of DCP. During the follow-up period, there were 13 eyes with no perfusion area of retinal capillary. The time of occurrence was (1.14±0.95) (0-2) months, and the area was 10-75 disc area. Optic nerve atrophy occurred in 5 eyes. At the last follow-up, visual acuity increased, unchanged and decreased in 12, 2 and 1 eyes, respectively.Conclusions:The pathogenesis of RVO-RAO is complicated. Most RVO and RAO occurred simultaneously, and a few RVO occurred several days after RAO. Although the RAO manifestations are not typical, the radiographic features are both RVO and RAO. Compared with BVRO combined with BRAO, the prognosis of visual acuity in CRAO patients with CRVO is worse.

Objective:To deeply explore the experience of lactation mastitis women, so as to provide a basis for formulating reasonable support measures.Methods:This study was a qualitative study. From November to December 2022, purposive sampling was used to select 13 patients with lactation mastitis who visited the Breast Specialist Nursing Clinic of Dongfang Hospital, Beijing University of Chinese Medicine as the research subject. This study used semi-structured interviews to collect data, and applied the Colaizzi 7-step analysis method to analyze, summarize, and extract themes.Results:The experience of lactation mastitis patients were mainly summarized as self-emotional experience and interpersonal relationship experience. Self-emotional experiences included feelings of anxiety, stress, helplessness, and self-blame. Interpersonal relationship experiences consisted of feelings of helplessness, useless, decision-making difficulties, desire for help and understanding.Conclusions:Lactation mastitis patients face various negative psychological experiences and burdens. Medical and nursing staff, family caregivers, and society should jointly pay attention to the patients' feelings and provide targeted support measures.

Spinal microglia and astrocytes are both involved in neuropathic and inflammatory pain, which may display sexual dimorphism. Here, we demonstrate that the sustained activation of spinal astrocytes and astrocyte-derived interleukin (IL)-17A promotes the progression of mouse bone cancer pain without sex differences. Chemogenetic or pharmacological inhibition of spinal astrocytes effectively ameliorates bone cancer-induced pain-like behaviors. In contrast, chemogenetic or optogenetic activation of spinal astrocytes triggers pain hypersensitivity, implying that bone cancer-induced astrocytic activation is involved in the development of bone cancer pain. IL-17A expression predominantly in spinal astrocytes, whereas its receptor IL-17 receptor A (IL-17RA) was mainly detected in neurons expressing VGLUT2 and PAX2, and a few in astrocytes expressing GFAP. Specific knockdown of IL-17A in spinal astrocytes blocked and delayed the development of bone cancer pain. IL-17A overexpression in spinal astrocytes directly induced thermal hyperalgesia and mechanical allodynia, which could be rescued by CaMKIIα inhibitor. Moreover, selective knockdown IL-17RA in spinal Vglut2 ⁺ or Vgat ⁺neurons, but not in astrocytes, significantly blocked the bone cancer-induced hyperalgesia. Together, our findings provide evidence for the crucial role of sex-independent astrocytic signaling in bone cancer pain. Targeting spinal astrocytes and IL-17A/IL-17RA-CaMKIIα signaling may offer new gender-inclusive therapeutic strategies for managing bone cancer pain.

Moral distress generally exists in the nursing interns and has a far-reaching impact. This paper analyzed and summarized the current situation, influencing factors and coping strategies of the nursing interns at home and abroad, in order to provide reference for promoting the professional development of nursing students, strengthening their professional beliefs and stabilizing the nursing team.