Objective To construct lentivirus containing CXCR4 gene and transfect MCF-7 cells , and obtain CXCR4 high-expressing MCF-7 cells. Methods CXCR4 gene was amplified by RT-PCR to construct CXCR4/pSin-EF2, which was transfected into HEK293T cells with psPAX2 and pMD2G vector for lentivirus packing. Packaged lentivirus was used to transfect human breast cancer cells MCF-7, with empty lentivirus as control. CXCR4 mRNA and protein expression levels were detected by RT-PCR and Western blot before and after transfection. And flow cytometry was used to detecte cell surface CXCR4 expression. Results The recombinant plasmid CXCR4/pSin-EF2 was constructed successfully,identified by double digestion and sequencing, and transfected into HEK293T cells to obtain high-titer lentivirus. RT-PCR and Western blot confirmed that the expression of CXCR4 in MCF-7 cells increased significantly after CXCR4 lentivirus transfection. Flow cytometry results showed that the CXCR4 positive rate increased from 26.78% to 99.29%, while there is no significant difference in CXCR4 expression between vector-transfected MCF-7 cells and non-transfected MCF-7 cells. Conclusion CXCR4 lentivirus and the breast cancer cell line with high and stable expression of CXCR4 (MCF-7CXCR4) were successfully constructed.

Objective To observe the influences of sonophoresis of Fufang Sanqi Xiaotong (Compound Notoginseng Pain-relieving) Ointment on changes of synovial morphology and expressions of chondrocyte caspase-9 and X-linked inhibitor of apoptosis protein (XIAP) in rabbits with knee osteoarthritis (KOA).Methods New Zealand white rabbits (n =32,6 months old) were randomly divided into group of sonophoresis of Fufang Sanqi Xiaotong (sonophoresis group),group of coupling agent ultrasound treatment (coupling agent group),model group and normal group (each n =8).Except of normal group,other groups received anterior cruciate ligament transaction (ACLT).After 6 weeks,sonophoresis group and coupling agent group were given corresponding therapies for 2 treatment courses and model group and normal group were not given any interventions.The changes of synovial histomorphology were observed with light microscope after HE staining,and expressions of caspase-9 and XIAP were detected by using immunohistochemistry technique in all groups after 2 treatment courses.Results The degeneration degree of synovial membrane under light microscope showed an ascending order in all groups as follows:normal group,sonophoresis group,coupling agent group and model group.The value of integral optical density (IOD) of caspase-9 was higher,and IOD value of XIAP was lower in sonophoresis group,coupling agent group and model group than those in normal group.The IOD value of caspase-9 was lower,and IOD value of XIAP was higher in sonophoresis group and coupling agent group than those in model group.The IOD value of caspase-9 was lower,and IOD value of XIAP was higher in sonophoresis group than those in coupling agent group.Conclusion The sonophoresis of Fufang Sanqi Xiaotong is superior to ultrasound treatment,and has the protective effect on cartilage and relief effect on synovial inflammation,and can delay KOA development.The mechanism may be related to decrease of caspase-9 expression and increase of XIAP expression.

Objective:To integrate the best evidence of sexual health management for colorectal cancer patients both domestically and internationally, so as to provide guidance for clinical practice.Methods:Evidence on sexual health management of colorectal cancer patients in domestic and foreign databases and websites was systematically searched, and evidence from literature that met quality evaluation standards was extracted and summarized. The search period was from July 2003 to July 2023.Results:A total of 16 articles were included, including five clinical decisions, six clinical practice guidelines, three expert consensus/group standards, and two systematic reviews. Thirty-four recommended opinions were formed, including eight aspects of evaluation and screening, assessment tools, manifestations of sexual dysfunction, coping strategies for sexual problems, psychological intervention, measures for fertility protection, health education, and follow-up management.Conclusions:This study summarizes the best evidence for sexual health management in colorectal cancer patients. It is necessary to selectively apply evidence based on the evaluation of patient conditions by medical and nursing staff and clinical situations to ensure effective and scientific sexual health management strategies for patients, and promote the translation of best evidence into clinical practice.

A major challenge facing photodynamic therapy (PDT) is that the activity of the immune-induced infiltrating CD8⁺ T cells is subject to the regulatory T lymphocytes (Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment (TME), a supramolecular photodynamic nanoparticle (DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated β-cyclodextrin (DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration (Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile β-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs. The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.

Considering that photodynamic therapy (PDT)-induced oxygen consumption and microvascular damage could exacerbate hypoxia to drive more glycolysis and angiogenesis, a novel approach to potentiate PDT and overcome the resistances of hypoxia is avidly needed. Herein, morpholine-modified PEGylated bilirubin was proposed to co-deliver chlorin e6, a photosensitizer, and diclofenac (Dc). In acidic milieu, the presence of morpholine could enable the nanocarriers to selectively accumulate in tumor cells, while PDT-generated reactive oxidative species (ROS) resulted in the collapse of bilirubin nanoparticles and rapid release of Dc. Combining with Dc showed a higher rate of apoptosis over PDT alone and simultaneously triggered a domino effect, including blocking the activity and expression of lactate dehydrogenase A (LDHA), interfering with lactate secretion, suppressing the activation of various angiogenic factors and thus obviating hypoxia-induced resistance-glycolysis and angiogenesis. In addition, inhibition of hypoxia-inducible factor-1α (HIF-1α) by Dc alleviated hypoxia-induced resistance. This study offered a sequentially responsive platform to achieve sufficient tumor enrichment, on-demand drug release and superior anti-tumor outcomes in vitro and in vivo.

As known, the benefits of photothermal therapy (PTT) are greatly limited by the heat tolerance of cancer cells resulting from overexpressed heat shock proteins (HSPs). Then HSPs further trigger the formation of stress granules (SGs) that regulate protein expression and cell viability under various stress conditions. Inhibition of SG formation can sensitize tumor cells to PTT. Herein, we developed PEGylated pH (low) insertion peptide (PEG-pHLIP)-modified hollow copper sulfide nanoparticles (HCuS NPs) encapsulating the SG inhibitor ISRIB, with the phase-change material lauric acid (LA) as a gate-keeper, to construct a pH-driven and NIR photo-responsive controlled smart drug delivery system (IL@H-PP). The nanomedicine could specifically target slightly acidic tumor sites. Upon irradiation, IL@H-PP realized PTT, and the light-controlled release of ISRIB could effectively inhibit the formation of PTT-induced SG to sensitize tumor cells to PTT, thereby increasing the antitumor effect and inducing potent immunogenic cell death (ICD). Moreover, IL@H-PP could promote the production of reactive oxygen species (ROS) by tumor-associated macrophages (TAMs), repolarizing them towards the M1 phenotype and remodeling the immunosuppressive microenvironment. In vitro/vivo results revealed the potential of PTT combined with SG inhibitors, which provides a new paradigm for antitumor and anti-metastases.