Objective: To explore the effect of miR-3591-3p targeting P53 on cisplatin resistance of ovarian cancer (OC) SKOV3/DDP cells. Methods: Target prediction and dual luciferase assay were used to validate miR-3591-3p targeting P53. SKOV3/DDP cells were divided into control group, DDP group, miR-3591-3p knockdown group (anti-miR-3591-3p), miR-3591-3p knockdown control group (anti-miR-NC), cisplatin+miR-3591-3p knockdown group (DDP+anti-miR-3591-3p), cisplatin+control group (DDP+anti-miR-NC), cisplatin+miR-3591-3p knockdown+P53 knockdown group (DDP+anti-miR-3591-3p+sh-P53), cisplatin+miR-3591-3p knockdown+P53 knockdown control group (DDP+anti-miR-3591-3p+sh-NC). CCK-8 assay was used to detect cell survival rate and IC50 value; Flow cytometry were used to detect cell cycle and apoptosis; RT-qPCR was used to detect miR-3591-3p and P53 mRNA levels in cells; Western blot was used to detect P53, P-gp, MRP1, Ki-67, CyclinD1, Bcl-2, and Bax protein levels in cells. Nude mice were divided into control group, DDP group, miR-3591-3p knockdown group (anti-miR-3591-3p), miR-3591-3p knockdown control group (anti-miR-NC), and cisplatin+miR-3591-3p knockdown group (DDP+anti-miR-3591-3p). Subcutaneous injection of SKOV3/DDP cells was used to prepare transplanted tumor model. Tumor volume, mass, miR-3591-3p, P53 mRNA and protein levels in tumor tissue were detected. Results: MiR-3591-3p and P53 had binding sites. After overexpression of miR-3591-3p, wild-type P53 luciferase activity was decreased (P＜0.05); However, there was no significant difference in the luciferase activity of mutant P53 (P＞0.05). After DDP treatment or knockdown of miR-3591-3p expression, miR-3591-3p level in cells was decreased, the mRNA and protein levels of P53 were increased; the cell survival rate and IC50 value were decreased [DDP group 24, 36, 48 h IC50 (21.26±2.95)mg/L,(17.38±1.93)mg/L and (13.76±1.46)mg/L, control group (41.06±4.39)mg/L, (36.15±3.46)mg/L and(29.87±1.39)mg/L; anti-miR-3591-3p group 24,36,48 h IC50 (19.96±2.19)mg/L, (17.62±3.52)mg/L and (13.05±1.53)mg/L,anti-miR-NC group (43.37±3.83)mg/L, (40.47±2.82)mg/L and (31.41±0.73)mg/L], the proportion of S phase was decreased, the proportion of G0/G1 phase and cell apoptosis rate [DDP group (27.00±2.00)%, Control group (3.33±1.53)%; anti-miR-3591-3p group (28.98±3.14)%, anti-miR-NC group (4.05±1.96)%] were increased; P-gp, MRP1, Ki-67, CyclinD1, Bcl-2 protein levels were decreased, while Bax protein level was increased (all P＜0.05). Knocking down miR-3591-3p could enhance the impact of DDP on the above indicators (all P＜0.05). Knocking down P53 expression could inhibit the impact of miR-3591-3p deletion on the above indicators (all P＜0.05). After DDP treatment or knockdown of miR-3591-3p, the tumor volume and weight of nude mice were decreased [DDP group 14,21,28 d volume (284.26±24.51)mm3,(563.21±44.17)mm3 and (741.32±72.01)mm3,control group (384.25±41.25)mm3, (840.32±71.27)mm3 and (1 242.47±100.54)mm3; anti-miR-3591-3p group 14,21,28 d volume (274.47±27.77)mm3, (584.68±61.14)mm3 and (815.24±73.19)mm3, anti-miR-NC group (355.47±46.84)mm3, (804.24±79.54)mm3 and (1 350.47±108.37)mm3; DDP group weight (0.85±0.15)g,control group (1.34±0.12)g; anti-miR-3591-3p group (0.88±0.14)g, anti-miR-NC group (1.34±0.10)g],miR-3591-3p level in tumor tissue was decreased, and the mRNA and protein levels of P53 were increased (all P＜0.05); Knocking down miR-3591-3p could enhance the effect of DDP on the above indicators (all P＜0.05). Conclusion: MiR-3591-3p targeting P53 enhances cisplatin resistance in SKOV3/DDP cells.

For patients with advanced non-small cell lung cancer (NSCLC) harboring sensitive epidermal growth factor receptor (EGFR) mutations, guidelines prioritize the use of third-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs), which offer higher objective response rate (ORR), longer progression-free survival (PFS), and better quality of life. However, due to the low proportion of elderly patients enrolled in clinical trials, the existing evidence is insufficient to fully guide clinical practice. This review examines the efficacy and safety differences of third-generation EGFR-TKIs as monotherapy or in combination in the elderly NSCLC by integrating subgroup analyses or pre-specified research objectives from prospective and retrospective studies. The results show that third-generation EGFR-TKIs have comparable efficacy in elderly patients to younger populations and are well-tolerated. Although combination therapies may extend survival time, the associated increased toxicity necessitates careful risk-benefit assessment.
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This study investigated the mechanism of Croci Stigma in treating immune checkpoint inhibitor(ICI)-associated myocarditis based on network pharmacology and molecular docking. Network pharmacology was employed to screen the active ingredients and molecular targets of Croci Stigma in treating ICI-associated myocarditis. The "drug-ingredient-target-disease" network and protein-protein interaction network were constructed to screen the key ingredients and core targets. Gene Ontology functional enrichment analysis showed that the mechanism was related to the regulation of inflammation and apoptosis. The Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the treatment was related to the advanced glycation end product-receptor for advanced glycation end products(AGE-RAGE) signaling pathway. Molecular docking result showed that crocins had close associations with RAC-alpha serine/threonine-protein kinase 1(AKT1), signal transducer and activator of transcription 3, and matrix metalloproteinase 9. Crocins were then selected as the therapeutic drug. The mouse model of ICI-associated myocarditis was established by subcutaneous injection of porcine cardiac myosin combined with intraperitoneal injection of pembrolizumab. The results suggested that Croci Stigma reduced the spleen index but had no effect on the heart index. The electrocardiogram showed that Croci Stigma increased the heart rate and shortened PR and QRS intervals. Echocardiographic data indicated that Croci Stigma increased the left ventricular stroke volume, cardiac output, ejection fraction, and fractional shortening. Hematoxylin-eosin and Masson staining results showed that Croci Stigma decreased the number of inflammatory cells infiltrating in the myocardium and alleviated myocardial fibrosis. Enzyme-linked immunosorbent assay results showed that Croci Stigma decreased the serum levels of inflammatory cytokines including tumor necrosis factor-alpha, interleukin-6, interleukin-12, and regulated on activation, normal T-cell expressed and secreted and lowered the levels of creatine kinase and creatine kinase isoenzyme MB. Biochemical data suggested that Croci Stigma inhibited the activities of superoxide dismutase and lactate dehydrogenase. Western blot result showed that Croci Stigma regulated the expression of myocardial AKT. The findings demonstrate that Croci Stigma may regulate AKT expression to effectively protect the cardiac tissue from ICI-associated myocarditis through antagonizing immune responses and inflammation, inhibiting oxidative stress, alleviating cardiac fibrosis, relieving cardiac block, and improving the cardiac function.

This study primarily investigates the effect of Liuwei Dihuang Pills on the activation and proliferation of female germline stem cells(FGSCs) in the ovaries and cortex of mice with premature ovarian failure(POF), and how it improves ovarian function. ICR mice were randomly divided into the control group, model group, Liuwei Dihuang Pills group, Liuwei Dihuang Pills double-dose group, and estradiol valerate group. A mouse model of POF was established by intraperitoneal injection of cyclophosphamide. After successful modeling, the mice were treated with Liuwei Dihuang Pills or estradiol valerate for 28 days. Vaginal smears were prepared to observe the estrous cycle and body weight. After the last administration, mice were sacrificed and sampled. Serum levels of estradiol(E_2), follicle-stimulating hormone(FSH), luteinizing hormone(LH), and anti-Müllerian hormone(AMH) were measured by enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe ovarian morphology and to count follicles at all stages to evaluate ovarian function. Immunohistochemistry was used to detect the expression of mouse vasa homolog(MVH), a marker of ovarian FGSCs. Immunofluorescence staining, using co-labeling of MVH and proliferating cell nuclear antigen(PCNA), was used to detect the expression and localization of specific markers of FGSCs. Western blot was employed to assess the protein expression of MVH, octamer-binding transcription factor 4(Oct4), and PCNA in the ovaries. The results showed that compared with the control group, the model group exhibited disordered estrous cycles, decreased ovarian index, increased atretic follicles, and a reduced number of follicles at all stages. FSH and LH levels were significantly elevated, while AMH and E_2 levels were significantly reduced, indicating the success of the model. After treatment with Liuwei Dihuang Pills or estradiol valerate, hormone levels improved, the number of atretic follicles decreased, and the number of follicles at all stages increased. MVH marker protein and PCNA proliferative protein expression in ovarian tissue also increased. These results suggest that Liuwei Dihuang Pills regulate estrous cycles and hormone disorders in POF mice, promote the proliferation of FGSCs, improve follicular development in POF mice, and enhance ovarian function.

Lung cancer is the cancer with the highest incidence and mortality rate worldwide. In addition to the diversified treatment and prolonged lifespan in view of the development of medical technology, the side effect of medicine should not be ignored. Drug-induced interstitial lung disease (DI-ILD) is also commonly encountered during this process, and ILD triggered by the treatment of lung cancer characterized by the inflammation and scarring of lung tissue after the antitumor treatment in lung cancer leads to a poor prognosis and high mortality. The diagnosis and treatment of ILD caused by anti-lung cancer agents remains challenging in clinical settings and requires joint efforts from multidisciplinary team (MDT). This review systematically updates the epidemiology, molecular pathogenesis, genomics/genetics study, diagnosis and treatment of ILD related to anti-lung cancer agents. By the integration of the latest evidences, the paper offers clinical work references for early diagnosis of ILD related to anti-lung cancer agents to enhance the survival and quality of life of the lung cancer patients.
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The application of small molecule targeted drugs for lung cancer has significantly improved the survival of lung cancer patients. However, these drugs have a wide variety of types, fast development and market launch of new drugs, complex adverse reactions, and are mostly used at home, which increases the risk of irrational drug use. At the same time, insufficient monitoring of efficacy and safety is also prone to occur, ultimately affecting treatment outcomes. This consensus focuses on 43 small molecule targeted drugs or combinations for lung cancer, providing standardized recommendations for rational drug use and monitoring of efficacy/adverse reactions in clinical practice. The recommendations are regarding drug selection, dosage adjustment, efficacy monitoring, adverse reaction monitoring, and improvement of patient compliance. This consensus aims to improve the rational use and efficacy/safety monitoring quality of small molecule targeted drugs for lung cancer, ensure the effectiveness and safety of drug treatment, prolong the survival of lung cancer patients and improve their quality of life.
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Peritoneal metastasis is a common form of distant metastasis in patients with colorectal cancer, and it is typically associated with a poor prognosis. The development of peritoneal metastasis involves complex molecular mechanisms and multifactorial regulation of the tumor microenvironment. Due to the presence of the blood-peritoneal barrier, only a small amount of systemic medication reaches the peritoneal cavity, resulting in limited efficacy against peritoneal metastasis. Intraperitoneal administration shows significant therapeutic advantages as it can directly target the tumor microenvironment, maintain high local drug concentrations, and reduce systemic toxicity. Intraperitoneal chemotherapy, especially hyperthermic intraperitoneal chemotherapy, has become a cornerstone therapeutic strategy in the clinical treatment of peritoneal metastasis. When selecting chemotherapy drugs and drug combinations, pharmacokinetic properties, efficacy, and safety must be comprehensively considered to optimize the treatment outcomes. In addition, the unique microenvironment of the peritoneal cavity provides new treatment approaches for biological treatment strategies, including antitoxins, vaccines, immune checkpoint inhibitors, etc. Techniques such as pressurized intraperitoneal aerosol chemotherapy and novel drug delivery systems demonstrate potential for enhanced efficacy, offering promising alternatives to improve patient outcomes. This article will review peritoneal barrier characteristics, intraperitoneal drug transport, intraperitoneal chemotherapy, and intraperitoneal biological therapies, thereby establishing a theoretical framework for precision therapy in colorectal cancer peritoneal metastasis.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is an emerging therapeutic modality for peritoneal carcinomatosis. This review aims to evaluate the safety, efficacy, and current clinical application of PIPAC in the treatment of peritoneal metastases originating from gastrointestinal malignancies. This review outlines the technical principles, historical development, procedural steps, commonly used drugs, and administration protocols of PIPAC; analyses the current clinical application status of PIPAC technology; discusses the current challenges and future directions of PIPAC; suggests that PIPAC technology still needs to conduct more high-quality and large-sample clinical trials to further establish the safety and efficacy of PIPAC, optimize its indications and formulate standardized operation specifications. In the future, multi-centre cooperation, multi-disciplinary cooperation, precision medicine strategies and new drug research and development will promote the clinical transformation and standardized application of PIPAC technology.

Objective: Exploring the efficacy and safety of the combination of programmed cell death protein 1 (PD-1) inhibitors with chemotherapy for the treatment of local recurrence at the primary tumor site of esophageal squamous cell carcinoma (ESCC) following definitive chemoradiotherapy. Methods: Seventy-six patients with local recurrence at the primary tumor site of ESCC following definitive chemoradiotherapy, who were treated at the Cancer Hospital Affiliated with Nanjing Medical University from January 2019 to January 2024. All patients received treatment with a PD-1 inhibitor combined with chemotherapy, and the short-term efficacy, long-term efficacy, and adverse reactions were observed. Univariate and multivariate Cox regression models were employed to identify the factors influencing overall survival (OS) and after-recurrence survival (ARS). Results: Among the 76 patients, 7 achieved partial response, 35 had stable disease, and 34 experienced progressive disease. The objective response rate was 9.2% (7/76), and the disease control rate was 55.3% (42/76). With a median follow-up time of 23.1 months, 33 out of 76 patients died. The median survival time was 38.5 months (95% CI: 29.6-47.3 months); the 1-year, 2-year, and 3-year OS were 94.5%, 66.6%, and 51.7%, respectively. The median ARS was 14.7 months (95% CI: 10.4-19.1 months); the 6-month, 12-month, and 24-month ARS were 85.8%, 59.6%, and 25.7%, respectively. Univariate analysis showed that the initial radiation dose, the Eastern Cooperative Oncology Group (ECOG) performance status of patients after recurrence, the recurrence-free interval (RFI), and the approach to chemotherapy treatment following local esophageal recurrence were factors affecting OS and ARS (P＜0.05). Multivariate analysis showed that initial radiotherapy dose (HR=0.268, 95% CI: 0.100-0.720), the ECOG performance status after recurrence (HR=4.106, 95% CI: 1.228-13.728), and RFI (HR=0.248, 95% CI: 0.106-0.582) were independent prognostic factors for OS. Additionally, the initial radiation dose (HR=0.289, 95% CI: 0.098-0.853) and the ECOG performance status after recurrence (HR=5.143,95% CI:1.404-18.838) were independent prognostic factors for ARS. The incidence of treatment-related adverse-reactions was 85.5% (65/76). Grade 3 or higher treatment-related adverse reactions primarily included anemia in 4 cases, leukopenia in 8 cases, neutropenia in 9 cases, thrombocytopenia in 2 cases, liver function abnormalities in 4 cases, and elevated troponin T in 2 cases. There were no cases of treatment-related mortality. Conclusions: The combination of PD-1 inhibitors with chemotherapy is safe and effective for local recurrence at the primary tumor site of ESCC following definitive chemoradiotherapy and can provide survival benefits for patients. This approach can be considered as a therapeutic option for local recurrence at the primary tumor site of ESCC following definitive chemoradiotherapy.

Objective: We aimed to investigate the relationship between CYP2D6*10 gene polymorphisms and adverse reactions associated with tamoxifen treatment in breast cancer patients, and assess the value of CYP2D6*10 gene polymorphism testing in guiding the use of medications in endocrine therapy for breast cancer. Methods: 177 breast cancer patients with HR-positive and postoperative tamoxifen were admitted to the First Affiliated Hospital of Nanjing Medical University from November 2012 to December 2021. Their clinicopathologic data were collected for follow-up observation of adverse reactions related to tamoxifen treatment. After two years of tamoxifen treatment, finger blood of these patients was taken for CYP2D6 gene polymorphism detection. Moreover, databases including RNAfold, QTLbase, 3DSNP v2.0, RegulomeDB 2.2, and HaploReg v4.2 were used to predict the annotation of proximal and distal interactions of CYP2D6 polymorphic sites between genes and regulatory elements. Results: Genotyping analysis revealed 40 patients (22.6%) with the CC genotype, 79 (44.6%) with the CT genotype, and 58 (32.8%) with the TT genotype. Common adverse reactions to tamoxifen included abnormal liver function (58), fatty liver (81), uterine fibroids (12), and endometrial surgery for endometrial thickening (17). Univariate and multivariate logistic regression analyses showed that there were no significant statistical differences between the CC and CT+TT genotypes in terms of liver damage, new-onset fatty liver, uterine fibroids, or tumor recurrence and metastasis (P＞0.05). Notably, endometrial thickening was more significant in patients with the CT+TT genotype (4.37±3.82 mm) than in those with the CC genotype (2.43±2.96 mm), with a statistically significant difference between them (P＜0.01). Bioinformatic analysis suggested that in breast tissues, the CYP2D6*10 polymorphic locus had a significant expression quantitative trait locus (eQTL) effect with CYP2D6, and its genetic variations could affect the binding of CYP2D6 to transcription factors, which might modulate the expression of CYP2D6 through changes in secondary structure and chromatin modifications, etc., and thus affect the tamoxifen drug sensitivity. Further eQTL analysis showed significant correlation between CYP2D6 expression levels with different genotypes of the CYP2D6 rs1065852 polymorphism in breast tissues (P＜0.01). Conclusion: Tamoxifen remains a primary therapeutic agent for premenopausal HR-positive breast cancer patients, and its efficacy is influenced by polymorphisms in the CYP2D6*10. It is recommended that for breast cancer patients carrying the CYP2D6 CT and TT genotypes, endometrial monitoring should be strengthened during treatment with tamoxifen, and the medication should be adjusted in a timely manner.

Objective: To prepare mesothelin-loaded paclitaxel (PTX) phase change nanoparticles and evaluate their targeting effect and therapeutic effect on ovarian cancer. Methods: PTX-loaded phase-change nanoparticles PTX-NPs were prepared by the thin-film hydration method, and targeted mesothelin-loaded PTX phase-change nanoparticles Ab-PTX-NPs were prepared by attaching anti-mesothelin antibody to the nanoparticles using the biotin-affinity method. Zeta potential and particle size were determined by applying a zeta potential and a particle size analyzer, and the encapsulation rate and the amount of drug loading of PTX was measured by applying a UV spectrophotometer. Flow cytometry was used to detect the connectivity of anti-mesothelin antibody with PTX-NPs. The phase transition of Ab-PTX-NPs was induced by low-power focused ultrasound, and its ultrasonography imaging was observed; laser scanning confocal microscopy and flow cytometry were used to detect the targeting ability of Ab-PTX-NPs on ovarian cancer SKOV3 cells. The targeting and killing ability of Ab-PTX-NPs on ovarian cancer SKOV3 cells was observed by in vitro targeting assay and apoptosis detection assay. The ovarian cancer model of BALB/c nude mice was constructed to observe the distribution of Ab-PTX-NPs in vivo as well as the effects on blood biochemistry and important organs of nude mice. Results: Ab-PTX-NPs were successfully prepared with a zeta potential of -(8.37±2.71) mV, a diameter of (690.46±28.75) nm, an encapsulation rate of (88.2±4.4)% for PTX, a drug loading capacity of (27.3±0.9)%, and a linkage rate of (94.9±2.8)% between anti-mesothelin antibody and PTX-NPs. Low-intensity focused ultrasound could successfully induce phase transition of Ab-PTX-NPs to realize ultrasonography imaging, and 6 W was the optimal excitation power for low-intensity focused ultrasound. Ab-PTX-NPs showed excellent targeting and killing ability to SKOV3 cells, and the apoptosis and necrosis rate of SKOV3 cells in the Ab-PTX-NPs group reached 79.6%. In vivo imaging showed that the fluorescence intensity at the tumor site of nude mice in the Ab-PTX-NPs group was significantly higher than that in the PTX-NPs group. Biosafety assay showed that 15 d after Ab-PTX-NPs administration, the serum aspartate aminotransferase, alanine aminotransferase, creatine kinase, low-density lipoprotein, blood creatinine, and urea nitrogen concentrations of nude mice were (174.163±20.596)U/L, (33.297±2.573)U/L, (1 959.978±72.212)U/L, (22.033±5.030)μmol/L, (0.393±0.058)mmol/L, and (26.405±4.957)mmol/L, which were not significantly different from those of the phosphate buffer solution (PBS) group, the NPs group, and the PTX-NPs group. The organs such as the heart, the liver, the spleen, the lungs and the kidneys remained intact, and what was seen by the naked eye and microscope was similar with those of the PBS group, NPs group and PTX-NPs group. Conclusion: Ab-PTX-NPs were successfully prepared, which had good ovarian cancer targeting ability and killing effect and effectively reduced the toxicity of PTX.

This study aims to investigate the anti-tumor effect and mechanism of Guiqi Yiyuan Ointment combined with cisplatin on Lewis lung carcinoma-bearing mice via the protein kinase RNA-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2α(eIF2α)/activated transcription factor 4(ATF4)/C/EBP homologous protein(CHOP) signaling pathway. Sixty SPF-grade male C57BL/6 mice were selected and assigned into a blank group and a modeling group by the random number table method. After modeling of the Lewis lung carcinoma, the mice in the modeling group were randomized into model, cisplatin(5 mg·kg~(-1), once a week), and low-, medium-, and high-dose(1.7, 3.5, and 7.05 g·kg~(-1), respectively, once a day) Guiqi Yiyuan Ointment+cisplatin(5 mg·kg~(-1)) groups(n=10). After 14 days of continuous intervention, the spleen, thymus, and tumor samples of the mice were collected, weighed, and recorded, and the spleen index, thymus index, and tumor suppression rate were calculated. Hematoxylin-eosin(HE) staining was employed to observe the pathological changes in the tumor tissue. The morphological changes of the endoplasmic reticulum of tumor cells were observed by transmission electron microscopy. The positive expression of phosphorylated eIF2α(p-eIF2α) and ATF4 in the tumor tissue was detected by immunofluorescence. Western blot was employed to determine the protein levels of phosphorylated PERK(p-PERK), p-eIF2α, ATF4, CHOP, B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cyclin-dependent kinase inhibitor 1A(p21), and cyclinD1 in the tumor tissue. Real-time fluorescent quantitative PCR was employed to determine the mRNA levels of PERK, eIF2α, ATF4, CHOP, Bax, Bcl-2, p21, and cyclinD1 in the tumor tissue. Compared with the blank group, the model group showed decreases in spleen index and thymus index(P<0.05). Compared with the model group, the cisplatin group showed decreases in spleen index and thymus index(P<0.05), and the medium-and high-dose Guiqi Yiyuan Ointment+cisplatin groups presented increases in spleen index and thymus index(P<0.05). In addition, the treatment groups all showed decreased tumor mass(P<0.05), increased tumor cell lysis and nuclear rupture, widened gap between rough endoplasmic reticulum, enhanced average fluorescence intensity of p-eIF2α and ATF4(P<0.05), up-regulated protein levels of p-PERK/PERK, p-eIF2α/eIF2α, ATF4, CHOP, Bax, and p21(P<0.05), down-regulated protein and mRNA levels of Bcl-2 and cyclinD1(P<0.05), and up-regulated mRNA levels of PERK, eIF2α, ATF4, CHOP, Bax, and p21(P<0.05). Compared with the cisplatin group, the combination groups showed increases in spleen index and thymus index(P<0.05) as well as mean optical density(P<0.05), and the high-dose Guiqi Yiyuan Ointment+cisplatin group showed decreased tumor mass(P<0.05). In addition, the medium-and high-dose Guiqi Yiyuan Ointment+cisplatin groups showcased enhanced average fluorescence intensity of p-eIF2α and ATF4(P<0.05), up-regulated protein levels of p-PERK/PERK, p-eIF2α/eIF2α, ATF4, CHOP, Bax, and p21(P<0.05), down-regulated protein and mRNA levels of Bcl-2 and cyclinD1(P<0.05), and up-regulated mRNA levels of PERK, eIF2α, ATF4, CHOP, Bax, and p21(P<0.05). In conclusion, Guiqi Yiyuan Ointment combined with cisplatin can effectively inhibit the growth of Lewis lung carcinoma in mice by regulating the expression of proteins related to the PERK/eIF2α/ATF4/CHOP signaling pathway and promoting cell cycle arrest and apoptosis.

Metal ion-promoted chemodynamic therapy(CDT) combined with photodynamic therapy(PDT) offers broad application prospects for enhancing anti-tumor effects. In this study, glycyrrhizic acid(GA), copper ions(Cu~(2+)), and norcantharidin(NCTD) were co-assembled to successfully prepare a natural small-molecule, carrier-free hydrogel(NCTD Gel) with excellent material properties. Under 808 nm laser irradiation, NCTD Gel responded to the tumor microenvironment(TME) and acted as an efficient Fenton reagent and photosensitizer, catalyzing the conversion of endogenous hydrogen peroxide(H_2O_2) within the tumor into oxygen(O_2), and hydroxyl radicals(·OH, type Ⅰ reactive oxygen species) and singlet oxygen(~1O_2, type Ⅱ reactive oxygen species), while depleting glutathione(GSH) to stabilize reactive oxygen species and alleviate tumor hypoxia. In vitro and in vivo experiments demonstrated that NCTD Gel exhibited significant CDT/PDT synergistic therapeutic effects. Further safety evaluation and metabolic testing confirmed its good biocompatibility and safety. This novel hydrogel is not only simple to prepare, safe, and cost-effective but also holds great potential for clinical transformation, providing insights and references for the research and development of metal ion-mediated hydrogel-based anti-tumor therapies.

To investigate the mechanism of Qitu Erzhi Decoction(QTEZ) in ameliorating chemotherapy-induced myelosuppression and the focus of its decomposed formulae on the effects of hematopoietic cells of the three lineages, respectively. Ultra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS) was used to identify the components of QTEZ intestinal absorption liquid and obtain the target sites, which were intersected with chemotherapy-induced myelosuppression targets collected from several databases, including OMIM, and an interaction network was established based on network pharmacology for Gene Ontology(GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. Hematopoietic stem cells of mice were taken after intraperitoneal injection of 5-fluorouracil for myelosuppression modeling and randomly divided into the model group, Qitu Erzhi group, Astragali Radix-Angelicae Sinensis Radix group, Ligustri Lucidi Fructus-Ecliptae Herba group, Psoraleae Fructus-Cuscutae Semen group, and positive drug group, which were given the corresponding traditional Chinese medicine intestinal absorption liquid and the positive drug granulocyte colony-stimulating factor, respectively. The normal hematopoietic stem cells were taken as the control group and were given the intervention of normal saline. The proliferation of hematopoietic progenitor cells of three lineages was observed by flow cytometry, and the cell cycle and colony formation assay were observed. Western blot was used to verify the effect of QTEZ on the pathway proteins including phosphoinositide 3-kinase(PI3K), phosphorylated PI3K(p-PI3K), protein kinase B(AKT), and phosphorylated AKT(p-AKT). RT-qPCR and Western blot were used to detect the effects of QTEZ on cell cycle-related targets such as CDK inhibitor 1(P21), cyclin D1(CCND1), and cyclin-dependent kinase 4(CDK4). The results showed that a total of 158 components were identified by QTEZ, and 375 component and disease intersecting targets were obtained, 21 core components and 40 core targets were obtained after constructing the network, and GO and KEGG enrichment showed signaling pathways such as PI3K/AKT. QTEZ and its decomposed formulae could promote the 5-fluorouracil-blocked cell cycle to resume operation, and all of them had different degrees of restoration effects on the set of colonies, among which QTEZ had the best restoration effect, and the Astragali Radix-Angelicae Sinensis Radix group had a focused effect on colony forming unit-erythrocyte. Western blot results indicated that there was no significant difference in the expression levels of pathway proteins among the groups. RT-qPCR and Western blot results showed that QTEZ could down-regulate P21 and up-regulate the protein and mRNA expression of CDK4 and CCND1. In conclusion, QTEZ and its decomposed formulas can exert a protective effect on hematopoietic stem cells with 5-fluorouracil-induced myelosuppression by promoting the normal operation of the cell cycle and colony formation, and the mechanism may be related to the down-regulation of the cell cycle-related targets of P21 and the up-regulation of CDK4 and CCND1. In addition, Astragali Radix-Angelicae Sinensis Radix can have a targeted protective effect on erythrocytes.

Antineoplastic drugs have clear health hazards to the human body. In recent years, the scale of use of antineoplastic drugs had continued to expand, and the occupational exposure risk of medical personnel had also increased, which had attracted widespread attention. Taking effective measures to prevent occupational exposure can protect the health of medical personnel. This article reviewed the laws, regulations, guidelines, and industry guidance documents on occupational exposure prevention and control of antineoplastic drugs issued by relevant departments and associations in China. It summarized the scientific management experience of antineoplastic drugs in China, with the aim of reducing the occupational exposure risk of antineoplastic drugs in the future, and assisting the healthy development of China's medical and health industry.

Background: To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex® in Chinese patients with premenopausal breast cancer. Methods: From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex® every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results: A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex®. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex®. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex® group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion: LY01005 is as effective as Zoladex® in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective: To investigate whether F.nucleatum affects the chemotherapy resistance of colorectal cancer by regulating ABC subfamily G subtype 2 (ABCG2), in view of the fact that the correlation between the two has not been reported. Methods: Oxaliplatin was used to interfere with colorectal cancer cells and co-cultured with F.nucleatum to establish a chemotherapy-induced model of microbial infection. Calcein AM/PI cell staining, trypan blue staining, and cell counting kit 8 (CCK-8) method were used to detect cell activity. Real-time fluorescence quantitative polymerase chain reaction and western blot were used to detect ABCG2 mRNA and protein expression levels in colorectal cancer cells. The target gene was knocked down by constructing shRNA plasmids. The HCT-116 cell F.nucleatum infection model was constructed and transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analyses were performed to determine the differential gene expression enrichment pathways. Genistein (GST) was used as an E-cadherin blocker, and triclabendazole sulfoxide (TCBZSO) was used as an ABCG2 blocker. Immunofluorescence was used to detect E-cadherin and β-catenin protein expressions and intracellular localization levels. The subcutaneous xenograft model of nude mice was constructed in vivo, and the expression level of ABCG2 protein in tissues was detected by immunohistochemical staining. Results: CCK-8 results showed that F. nucleatum+oxaliplatin group [HT-29, (92.26±1.66)%; HCT-116, (82.13±1.84)%] cell relative survival rate was higher than that of oxaliplatin group [HT-29, (79.64±3.72)%; HCT-116, (67.56±2.96)%; P＜0.001]. The relative survival rate of oxaliplatin and F. nucleatum co-culture group with ABCG2-knockdown HCT-116 cells [(61.44±1.48)%] was lower than that of F. nucleatum and oxaliplatin co-cultured with HCT-116 cells [(69.29±4.45)%, P=0.015]. GO enrichment analysis showed that HCT-116 cells co-cultured with F.nucleatum were significantly enriched in "β-catenin binding", "cadherin binding" and "regulation of Wnt signaling pathway". RT-qPCR results showed that the relative expression of ABCG2 mRNA in F.nucleatum + genistein group was significantly lower than that in F.nucleatum group (P＜0.001). The results in vivo showed that the tumor weight in the F.n+L-OHP+TCBZSO group [(0.12±0.02)g] was lower than that in the F.n+L-OHP group [(0.33±0.05)g, P＜0.001]. Immunohistochemistry suggested that the promotion of ABCG2 protein expression by F. nucleatum was blocked after TCBZSO intervention. Conclusion:F. nucleatum up-regulates ABCG2 expression through E-cadherin/β-catenin signaling pathway to promote colorectal cancer resistance to oxaliplatin.

Moxibustion therapy is an important traditional non-pharmacological treatment in traditional medicine for improving chemotherapy-induced bone marrow suppression. By reviewing recent studies on moxibustion intervention for chemotherapy-induced bone marrow suppression, this article summarized and analyzed the current research status. In clinical studies, moxibustion therapy that tonifies the spleen, nourishes the kidneys, warms yang, and nourishes blood has been verified to be effective for chemotherapy-induced bone marrow suppression, but the efficacy may vary among individuals receiving different chemotherapy regimens. Experimental studies have shown that moxibustion therapy primarily improves chemotherapy-induced bone marrow suppression by repairing bone marrow tissue structure, increasing the amounts of hematopoietic stem cells, improving bone marrow hematopoietic microenvironment, repairing bone marrow cell DNA, and regulating signaling pathways such as Notch, Wnt, phosphatidylinositol 3-kinase/protein kinase B/ mammalian target protein of rapamycin and other signaling pathways. Future research can further systematically reveal the mechanisms of moxibustion therapy, such as alleviating hematopoietic stem cell aging induced by chemotherapy, regulating miRNAs to improve bone marrow suppression, and investigate the sensitivity of patients with bone marrow suppression caused by different chemotherapy regimens to moxibustion therapy, in order to complete and standardize the application protocols of moxibustion.

To investigate the biological activity and antitumor effect of pegylated recombinant human interleukin 2 (PEG-rhIL-2) obtained by site-specific conjugation of polyethylene glycol (PEG) with non-natural amino acids, and to explore its antitumor mechanism.