Evaluation of the Efficacy of Postoperative Adjuvant Therapy for HER2-Positive Ductal Carcinoma in Situ with Microinvasion.

A retrospective study on 90 eligible HER2+ ductal carcinoma in situ with microinvasion (DCIS-MI) patients was performed with a median follow-up time of 57 months. The baseline was consistent between the 4-cycle and 6-cycle chemotherapy groups. There were more patients with multiple foci of micrometastasis in the target therapy group in the two groups with or without target therapy (p < 0.01). Postoperative chemotherapy with a 4-cycle regimen can achieve the expected therapeutic effect in patients with HER2+ DCIS-MI, but the role of target therapy in HER2+ DCIS-MI patients has not been confirmed.

Body Mass Index and Breast Cancer-Related Lymphedema: A Retrospective Cohort Study.

OBJECTIVE: This study aims to evaluate the association between body mass index (BMI) and the incidence of breast cancer-related lymphedema (BCRL). METHODS: This retrospective cohort study analyzed data from 1464 breast cancer patients treated at The Third Hospital of Nanchang between 2018 and 2021. Patients were categorized based on BMI (<25, 25 to < 30, ≥ 30 kg/m²). Variables such as axillary lymph node dissection, infections, radiotherapy, and comorbidities were taken into account. RESULTS: The incidence of BCRL was 23.4%. Higher BMI was associated with increased risk of BCRL, with significant incidence rates observed at 1, 2, and 3 years in the higher BMI groups. Multivariate analysis confirmed BMI as an independent risk factor for BCRL. CONCLUSION: Elevated BMI is associated with increased BCRL risk and decreased BCRL-free survival, underscoring the significance of weight management in breast cancer care.

Comparison of minimal access and open breast surgery: a propensity score-matched study on postoperative immune function in breast cancer.

BACKGROUND: Minimal access breast surgery (MABS) is commonly employed in the management of breast cancer, but there is limited research on the postoperative immune function associated with MABS. OBJECTIVE: This study aimed to assess the postoperative immune function in breast patients who underwent MABS or conventional open breast surgery (COBS). METHODS: We retrospectively analyzed the medical records of 829 breast cancer patients treated with either MABS or COBS at a single hospital between January 2020 and June 2023. Among them, 116 matched pairs were obtained through 1:1 propensity score matching (PSM). Flow cytometry was used to measure the percentages of CD3+, CD4+, and CD8+ cells, as well as the CD4+/CD8+ ratio, on three different time points: preoperative day 1 (PreD1), postoperative day 1 (PostD1), and postoperative day 7 (PostD7). RESULTS: Both the MABS and COBS groups demonstrated a significant reduction in the percentages of CD3+, CD4+, and CD8+ cells, along with the CD4+/CD8+ ratio, from PreD1 to PostD1. Interestingly, the MABS group showed a reversal of these parameters, returning to preoperative levels by PostD7. Conversely, the COBS group showed an increase in these parameters from PostD1 to PostD7, but they still remained significantly lower than preoperative levels at PostD7. CONCLUSION: MABS treatment may result in reduced postoperative immune suppression and faster recovery of preoperative immune function compared to COBS in patients.

Current career situations of Chinese pharmacovigilance professionals working for pharmaceutical companies: an exploratory survey.

BACKGROUND: Pharmacovigilance in China has experienced rapid development in the past 30 years. The implementation of Good Pharmacovigilance Practice in China since the end of 2021 heralds a new era of pharmacovigilance affairs, which puts forward higher requirements for the quantity and quality of pharmacovigilance personnel. This study aimed to preliminarily explore the current career situations of pharmacovigilance professionals working in China for pharmaceutical companies. METHODS: A questionnaire was adapted from research in the USA and Europe with the help of several pharmacovigilance experts. Snowball sampling was used to conduct an exploratory survey to obtain the frequency of basic demographic information, work status, and career expectations of pharmacovigilance professionals working for pharmaceutical companies. RESULTS: The personnel engaged in pharmacovigilance work for pharmaceutical companies were mainly medical or pharmaceutical undergraduates within 3 years of graduation. Their work intensity and pressure were relatively high. The training provided by their universities and enterprises could not well meet their needs to improve their job competence. Although they were optimistic about pharmacovigilance and will not change their career, most of them were planning to change their employers. CONCLUSION: There was a gap between the demand and supply of pharmacovigilance personnel. Relevant regulatory authorities and industry associations should guide higher education institutions to collaborate with pharmacovigilance specialists to strengthen pharmacovigilance education for medical or pharmaceutical students, on the basis of which pharmacovigilance certification courses and continuing education courses can be developed. Meanwhile, pharmaceutical enterprises should consider reasonably adjusting work intensity and income to avoid a high turnover rate.

Discovery of a Novel Inhibitor Structure of Mycobacterium tuberculosis Isocitrate Lyase.

Tuberculosis remains a global threat to public health, and dormant Mycobacterium tuberculosis leads to long-term medication that is harmful to the human body. M. tuberculosis isocitrate lyase (MtICL), which is absent in host cells, is a key rate-limiting enzyme of the glyoxylic acid cycle and is essential for the survival of dormant M. tuberculosis. The aim of this study was to evaluate natural compounds as potential MtICL inhibitors through docking and experimental verification. Screening of the TCMSP database library was done using Discovery Studio 2019 for molecular docking and interaction analysis, with the putative inhibitors of MtICL, 3-BP, and IA as reference ligands. Daphnetin (MOL005118), with a docking score of 94.8 and -CDOCKER interaction energy of 56 kcal/mol, was selected and verified on MtICL in vitro and M. smegmatis; daphnetin gave an IC50 of 4.34 µg/mL for the MtICL enzyme and an MIC value of 128 µg/mL against M. smegmatis, showing enhanced potential in comparison with 3-BP and IA. The interactions and essential amino acid residues of the protein were analyzed. In summary, natural daphnetin may be a promising new skeleton for the design of inhibitors of MtICL to combat dormant M. tuberculosis.

Analysis of 246 sentinel lymph node biopsies of patients with clinical primary breast cancer by application of carbon nanoparticle suspension.

AIM: This study aims to explore the accuracy, specificity and laws of axillary lymph node metastasis predicted by sentinel lymph node biopsy (SLNB) by comparing axillary lymph node status via SLNB and axillary lymph node dissection (ALND) with nanocarbon as the tracer. METHODS: Forty six patients were retrospectively analyzed. These patients underwent SLNB with nanocarbon as the tracer from March 2013 to April 2014. RESULTS: Two hundred and forty six patients of sentinel lymph node (SLN) were successfully detected. Among these patients, 8 patients had 1 SLN (3.25%), 33 patients had 2 SLN (13.41%), 46 patients had 3 SLN (18.70%), 51 patients had 4 SLN (20.73%), 40 patients had 5 SLN (16.26%), 24 patients had 6 SLN (9.76%) and 24 patients had 7 or more SLN (9.76%). The SLNB success rate of nanocarbon staining in the 246 cases was 99.59%, accuracy rate was 97.06% and sensitivity was 93.22%. Furthermore, false negatives were found in four patients, and the false-negative rate was 6.78%. The number of lymph node metastasis in the SLNB and ALND of early-stage breast cancer was analyzed. When the number of SLN dissection was 1, 2, 3, 4, 5, 6 or 7, the coincidence rate of lymph node metastasis for SLNB and ALND was 80.00, 84.36, 78.57, 88.89, 90.48, 80.00, 73.68 and 78.36, respectively. CONCLUSION: Sentinel lymph node biopsy performed using the nanocarbon staining method is simple, easy and reliable, and it can be used to predict the axillary status of breast cancer in the early stage.

Novel Transforming Growth Factor-Beta Receptor 1 Antagonists through a Pharmacophore-Based Virtual Screening Approach.

As new drugs for the treatment of malignant tumors, transforming growth factor-beta receptor 1 (TGFßR1) antagonists have attracted wide attention. Based on the crystal structure of TGFßR1-BMS22 complex, the pharmacophore model A02 with two hydrogen bond acceptors (HBAs) and four hydrophobic (HYD) properties was constructed. From the common features of active ligands reported in the literature, pharmacophore model B10 was also generated, which has two aromatic ring centers (RAs) and two HYD properties. The two models have high sensitivity and specificity to the training set, and they are highly consistent in spatial structure. Combining the two pharmacophore models, two novel skeleton structures with potential activity were selected by virtual screening from the DruglikeDiverse, MiniMaybridge, and ZINC Drug-Like databases. Four compounds (YXY01⁻YXY04) with potential anti-TGFßR1 activity were designed based on the new skeleton structures. In combination with Lipinski's rules; absorption, distribution, metabolism, excretion, and toxicity (ADMET); and, toxicological properties predicted in the study, YXY01-03 with the novel skeleton, good drug-like properties, and potential activity were finally discovered and may have higher safety relative to BMS22, which may be valuable for further research.

A prognostic nomogram for recurrence survival in post-surgical patients with varicose veins of the lower extremities.

Varicose veins of the lower extremities (VVLEs) are prevalent globally. This study aims to identify prognostic factors and develop a prediction model for recurrence survival (RS) in VVLEs patients after surgery. A retrospective analysis of VVLEs patients from the Third Hospital of Nanchang was conducted between April 2017 and March 2022. A LASSO (Least Absolute Shrinkage and Selection Operator) regression model pinpointed significant recurrence predictors, culminating in a prognostic nomogram. The model's performance was evaluated by C-index, receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). The LASSO regression identified seven predictors for the nomogram predicting 1-, 2-, and 5-year RS. These predictors were age, body mass index (BMI), hypertension, diabetes, the Clinical Etiological Anatomical Pathophysiological (CEAP) grade, iliac vein compression syndrome (IVCS), and postoperative compression stocking duration (PCSD). The nomogram's C-index was 0.716, with AUCs (Area Under the Curve scores) of 0.705, 0.725, and 0.758 for 1-, 2-, and 5-year RS, respectively. Calibration and decision curve analyses validated the model's predictive accuracy and clinical utility. Kaplan-Meier analysis distinguished between low and high-risk groups with significant prognostic differences (P < 0.05). This study has successfully developed and validated a nomogram for predicting RS in patients with VVLEs after surgery, enhancing personalized care and informing clinical decision-making.

Comprehensive assessment of body mass index effects on short-term and long-term outcomes in laparoscopic gastrectomy for gastric cancer: a retrospective study.

To examine the influence of Body Mass Index (BMI) on laparoscopic gastrectomy (LG) short-term and long-term outcomes for gastric cancer. A retrospective analysis was conducted on gastric cancer patients undergoing LG at the Third Hospital of Nanchang City from January 2013 to January 2022. Based on WHO BMI standards, patients were categorized into normal weight, overweight, and obese groups. Factors such as operative time, intraoperative blood loss, postoperative complications, and overall survival were assessed. Across different BMI groups, it was found that an increase in BMI was associated with longer operative times (average times: 206.22 min for normal weight, 231.32 min for overweight, and 246.78 min for obese), with no significant differences noted in intraoperative blood loss, postoperative complications, or long-term survival among the groups. The impact of BMI on long-term survival following LG for gastric cancer was found to be insignificant, with no notable differences in survival outcome between different BMI groups. Although higher BMI is associated with increased operative time in LG for gastric cancer, it does not significantly affect intraoperative blood loss, postoperative complications, recovery, or long-term survival. LG is a feasible treatment choice for obese patients with gastric cancer.

Development and validation of a nomogram for breast cancer-related lymphedema.

To establish and validate a predictive model for breast cancer-related lymphedema (BCRL) among Chinese patients to facilitate individualized risk assessment. We retrospectively analyzed data from breast cancer patients treated at a major single-center breast hospital in China. From 2020 to 2022, we identified risk factors for BCRL through logistic regression and developed and validated a nomogram using R software (version 4.1.2). Model validation was achieved through the application of receiver operating characteristic curve (ROC), a calibration plot, and decision curve analysis (DCA), with further evaluated by internal validation. Among 1485 patients analyzed, 360 developed lymphedema (24.2%). The nomogram incorporated body mass index, operative time, lymph node count, axillary dissection level, surgical site infection, and radiotherapy as predictors. The AUCs for training (N = 1038) and validation (N = 447) cohorts were 0.779 and 0.724, respectively, indicating good discriminative ability. Calibration and decision curve analysis confirmed the model's clinical utility. Our nomogram provides an accurate tool for predicting BCRL risk, with potential to enhance personalized management in breast cancer survivors. Further prospective validation across multiple centers is warranted.

Impact of neoadjuvant chemotherapy on perioperative immune function in breast cancer patients: a propensity score-matched retrospective study.

To evaluate the impact of neoadjuvant chemotherapy on perioperative immune function in breast cancer patients, focusing on CD3+, CD4+, CD8+, and natural killer (NK) cells, as well as the CD4+/CD8+ ratio. We retrospectively reviewed medical records of breast cancer patients who underwent surgery with or without neoadjuvant chemotherapy at our medical center from January 2020 to December 2022. Patients were matched 1:1 based on propensity scores. Immune cell proportions and the CD4+/CD8+ ratio were compared on preoperative day one and postoperative days one and seven. Among matched patients, immune cell proportions and the CD4+/CD8+ ratio did not significantly differ between those who received neoadjuvant chemotherapy and those who did not at any of the three time points. Similar results were observed in chemotherapy-sensitive patients compared to the entire group of patients who did not receive neoadjuvant chemotherapy. However, chemotherapy-insensitive patients had significantly lower proportions of CD4+ and NK cells, as well as a lower CD4+/CD8+ ratio, at all three time points compared to patients who did not receive neoadjuvant chemotherapy. Neoadjuvant chemotherapy may impair immune function in chemotherapy-insensitive patients, but not in those who are sensitive to the treatment.

Synergistic effect of bovine cateslytin-loaded nanoparticles combined with ultrasound against Candida albicans biofilm.

Purpose: To investigate the synergistic effect of bovine cateslytin-loaded nanoparticles (bCAT-NPs) combined with ultrasound against Candida albicans biofilm and uncover the underlying mechanism. Methods: bCAT-NPs were prepared by the double emulsion method, and toxicity was observed by the hemolysis ratio. The metabolic activity and viable cell biomass, morphology and membrane permeability of C. albicans biofilm were observed. The expression of ALS3 mRNA, the content of reactive oxygen species, was detected. Finally, bCAT structure was analyzed. Results & conclusion: The hemolysis ratio of the bCAT-NPs group was significantly lower than that of the bCAT group. bCAT-NPs combined with ultrasound significantly reduced biofilm metabolic activity, inhibited the formation of hyphae, decreased the expression of ALS3 mRNA and increased the intracellular reactive oxygen species content. In the in vivo experiments, the colony-forming units/ml in the ultrasound+bCAT-NPs group decreased, and a few planktonic fungal cells were observed.

Discovery of Inhibitors for Mycobacterium Tuberculosis Peptide Deformylase Based on Virtual Screening in Silico.

Tuberculosis has been the serious disease threatening human health and public safety due to the emergence of MDR and XDR-TB. Mycobacterium tuberculosis peptide deformylase (MtPDF) is a valuable target for antituberculotics. In order to discover new potential inhibitor candidates of MtPDF as leads for antituberculotics, Discovery Studio (DS) 2019 was used to perform molecular docking for virtual screening in silico with the bioactive compound library-I (L1700) against MtPDF. Six compounds with high docking scores and favourable ligand-protein interactions by LibDock and CDOCKER were selected for the evaluation of the inhibition potencies against MtPDF and Mycobacterium smegmatis. GST-6×His tagged MtPDF was recombinant expressed and purified firstly by Glutathione Sepharose 4B, and secondly by Ni Sepharose 6 FF after the cleavage of human rhinovirus 3C protease. These compounds showed IC50 values from 0.5 µmol/L to 112 µmol/L against MtPDF, among which CUDC-101 bearing hydroxamic acid exhibited IC50 of 0.5 µmol/L on MtPDF and MIC against Mycobacterium smegmatis of 32 µg/mL, and Ixazomib Citrate with IC50 of 63 µmol/L and MIC of 16 µg/mL. CUDC-101 and Ixazomib Citrate are promising as the potential leads for antituberculotics.

Non-islet cell tumor hypoglycemia caused by breast tumor: A case report.

INTRODUCTION: Non-islet cell tumor hypoglycemia (NICTH) generally refers to hypoglycemia caused by tumors other than islet cell tumors. Although hypoglycemia is a common clinical emergency, NICTH rarely occurs in patients with breast cancer. PATIENT CONCERNS: A 47-year-old woman presented with repeated hypoglycemia hypoglycemia caused by a lobulated breast tumor. DIAGNOSES: Hypoglycemic symptoms occurred many times during fasting and in the early morning. Insulin and C-peptide levels were decreased; insulin-like growth factor (IGF)-II: IGF-I was greater than 10. Postoperative pathology revealed a lobulated tumor in the breast. After excluding other causes of hypoglycemia, the patient was diagnosed with NICTH due to breast cancer. INTERVENTIONS: Total mastectomy of right breast was performed. OUTCOMES: After 3 years of follow-up, hypoglycemia did not recur. CONCLUSION: Patients with breast cancer may experience recurrent hypoglycemia. After exclusion of insulinomatous and pancreatic origin of hypoglycemia, the possibility of NICTH should be considered, and surgical resection of the primary tumor should be performed as soon as possible.

Synthesis, In Vitro Antitumor Activity and Molecular Mechanism of Novel Furan Derivatives and their Precursors.

BACKGROUND: Compounds featuring furan nucleus exhibit diverse biological properties. Lots of furan derivatives have been explored as pharmaceutical compounds. Hence it is of great interest to explore furan derivatives and their precursors as antitumor agents. OBJECTIVE: A series of novel furan derivatives and their precursors (1-36) were synthesized from α-haloketones and ß-dicarbonyl compounds. METHODS: The reactions between ß-dicarbonyl compounds and α-haloketones under basic conditions produced tricarbonyls or dihydrofurans, which were then condensed into their corresponding furan products. Their potential antiproliferative activity in vitro against two human tumor cell lines-cervical (HeLa) and colorectal (SW620) was evaluated using CCK-8 assay. Compounds 1 and 24 were selected for Western blot analysis. RESULTS: Pronounced anti-proliferative effect in the micromolar level was observed for compounds (1, 4, 17, 20, 21, 24, 27, 31 and 32) in HeLa cells, with their IC50 values ranging from 0.08 to 8.79µM. Additionally, furan compounds (24, 26, 32 and 35) had moderate to potent anti-proliferative activity against the SW620 cell line. Furthermore, the possible targets of these compounds were explored by Western blot analysis. The results indicated that the candidates (compounds 1 and 24) exhibited excellent antiproliferative activity, which may be mediated by promoting the activity of PTEN to suppress PI3K/Akt and Wnt/ß-catenin signaling. CONCLUSION: Most of the furan derivatives and their precursors reported herein exhibited moderate to excellent anti-proliferative activity against HeLa cell line and/or SW620 cell line. Compounds 1 and 24, as well as their analogues may be developed as promising anti-cancer agents.

PSMB5 is associated with proliferation and drug resistance in triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, characterized by advanced disease stage and poor prognosis. Moreover, due to the lack of therapeutic markers, TNBC patients can't benefit fully from currently available targeted therapies. METHODS: To fully understand the molecular basis of TNBC, we used gene set enrichment analysis (GSEA) to screen out the most altered functional module in TNBC, from publicly available microarray data and studied the association of the candidate gene with TNBC development. RESULTS: We found that the proteasome was significantly activated in TNBC. As compared with other breast cancer subtypes and normal tissue, proteasome subunit beta 5 (PSMB5), the key regulator of proteasome function, was overexpressed in TNBC tissue and predictive of poor prognosis. Moreover, we also found that PSMB5 knockdown induced TNBC apoptosis and significantly enhanced cancer cell sensitivity to the chemotherapeutic agents bortezomib and paclitaxel. CONCLUSIONS: Our results suggest a potential role for PSMB5 as a biomarker and therapeutic target for TNBC.

The formation of a host-guest inclusion complex system between ß-cyclodextrin and baicalin and its dissolution characteristics.

OBJECTIVES: Baicalin (BCL) has potential therapeutic benefits, but its clinical outcomes are restricted mainly because of low water solubility. This study sought to improve the water solubility of BCL by the formation of inclusion complex with ß-cyclodextrin (ß-CD). METHODS: The inclusion complex was studied by solubility test, differential scanning calorimeter (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), 1 H Nuclear magnetic resonance (1 HNMR) and scanning electron microscopy (SEM). Molecular docking was conducted to verify the experimental findings. The dissolution rate was determined by dialysis membrane method. In vivo absorption studies in rats were conducted and high-performance liquid chromatography (HPLC) was used to analyse the plasma level of BCL after oral administration. KEY FINDINGS: The DSC, FTIR, XRD, 1 HNMR and SEM findings suggested the formation of inclusion complex between BCL and ß-CD in 1 : 1 stoichiometry. Molecular docking demonstrated the insertion of benzene ring of BCL into ß-CD cavity by hydrophobic interactions and possible H-bond formation. Moreover, ß-CD markedly improved the solubility of BCL and displayed AL -type phase diagrams. The improvement in dissolution rate of the inclusion complex was reflected in the earlier Tmax , higher Cmax and larger AUC0-t than that of BCL after oral administration. CONCLUSIONS: ß-cyclodextrin complex can be used as an effective formulation strategy for development of BCL-loaded delivery system with better therapeutic outcomes.

Interleukin-12 activated CD8+ T cells induces apoptosis in breast cancer cells and reduces tumor growth.

During the past two decades, cytokines have emerged as key molecules to modulate innate and adaptive immunity and mediate anti-tumor activity. Although multiple cytokine types are implicated for such anti-tumor activity in several cancer types, it remains largely unknown in breast cancer. In this study, cytokines that are prior known for antitumor activity in different cancer types were examined against breast cancer using a 4T1 cells based xenograft-model. Our results showed Interleukin-12 (IL-12) (500ng/mouse) significantly suppressed the growth of tumors, while other cytokines showed minimal suppression. Subsequent molecular analysis by flow cytometry and immunohistochemistry confirmed the CD8+ cells infiltration and Interferon-γ (IFN-γ) production by them in tumor environment. In addition, we observed that IFN-γ production by activated CD8+ cells directly induced apoptosis in tumor cells, which together indicate that IL-12 causes CD8+ cells to infiltrate and secrete IFN-γ in tumor environment, which induce apoptosis in them and causes tumor growth suppression. Furthermore, we showed that lower dosage of IL-12 and chemotherapy drug tamoxifen combinations enhanced the tumor suppression as opposed to single treatments, and thereby propose an alternate option for high dosage associated effects for both drug and cytokine treatments.