Cytokinin signaling localized in phloem noncell-autonomously regulates cambial activity during secondary growth of Populus stems.

The regulation of cytokinin on secondary vascular development has been uncovered by modulating cytokinin content. However, it remains unclear how cytokinin enriched in developing secondary phloem regulates cambium activity in poplar. Here, we visualized the gradient distribution of cytokinin with a peak in the secondary phloem of poplar stem via immunohistochemical imaging, and determined the role of phloem-located cytokinin signaling during wood formation. We generated transgenic poplar harboring cytokinin oxidase/dehydrogenase (CKX)2, a gene encoding a cytokinin degrading enzyme, driven by the phloem-specific CLE41b promoter, indicating that the disruption of the cytokinin gradient pattern restricts the cambial activity. The RNA interference-based knockdown of the histidine kinase (HK) genes encoding cytokinin receptors specifically in secondary phloem significantly compromised the division activity of cambial cells, whereas the phloem-specific expression of a type-B response regulator (RR) transcription factor stimulated cambial proliferation, providing evidence for the noncell-autonomous regulation of local cytokinin signaling on the cambial activity. Moreover, the cambium-specific knockdown of HKs also led to restricted cambial activity, and the defects were aggravated by the reduced cytokinin accumulation. Our results showed that local cytokinin signaling in secondary phloem regulates cambial activity noncell-autonomously, and coordinately with its local signaling in cambium.

Genistein attenuates isoflurane-induced neurotoxicity and improves impaired spatial learning and memory by regulating cAMP/CREB and BDNF-TrkB-PI3K/Akt signaling.

Anesthetics are used extensively in surgeries and related procedures to prevent pain. However, there is some concern regarding neuronal degeneration and cognitive deficits arising from regular anesthetic exposure. Recent studies have indicated that brain-derived neurotrophic factor (BDNF) and cyclic AMP response element-binding protein (CREB) are involved in learning and memory processes. Genistein, a plant-derived isoflavone, has been shown to exhibit neuroprotective effects. The present study was performed to examine the protective effect of genistein against isoflurane-induced neurotoxicity in rats. Neonatal rats were exposed to isoflurane (0.75%, 6 hours) on postnatal day 7 (P7). Separate groups of rat pups were orally administered genistein at doses of 20, 40, or 80 mg/kg body weight from P3 to P15 and then exposed to isoflurane anesthesia on P7. Neuronal apoptosis was detected by TUNEL assay and FluoroJade B staining following isoflurane exposure. Genistein significantly reduced apoptosis in the hippocampus, reduced the expression of proapoptotic factors (Bad, Bax, and cleaved caspase-3), and increased the expression of Bcl-2 and Bcl-xL. RT-PCR analysis revealed enhanced BDNF and TrkB mRNA levels. Genistein effectively upregulated cAMP levels and phosphorylation of CREB and TrkB, leading to activation of cAMP/CREB-BDNF-TrkB signaling. PI3K/Akt signaling was also significantly activated. Genistein administration improved general behavior and enhanced learning and memory in the rats. These observations suggest that genistein exerts neuroprotective effects by suppressing isoflurane-induced neuronal apoptosis and by activating cAMP/CREB-BDNF-TrkB-PI3/Akt signaling.

The Treatment of Pelvic Locoregional Recurrence of Cervical Cancer After Radical Surgery With Intensity-Modulated Radiation Therapy Compared With Conventional Radiotherapy: A Retrospective Study.

OBJECTIVE: The aim of this study was to investigate the therapeutic response and toxicity of intensity-modulated radiation therapy (IMRT) or conventional radiotherapy (c-RT) as adjuvant therapy in patients with pelvic locoregional recurrence of cervical cancer after radical surgery. METHODS: This retrospective study included 161 patients with unresectable pelvic locoregional recurrence of cervical cancer after radical surgery between March 2003 and May 2012. All patients were initially diagnosed with International Federation of Gynecology and Obstetrics stage IB-IIA cervical cancer and received radical hysterectomy and pelvic lymphadenectomy. A total of 82 patients were treated with c-RT, whereas the remaining 79 patients underwent IMRT. Intracavitary brachytherapy and concurrent chemotherapy were performed during external irradiation. RESULTS: The mean dose delivered to the planning target volume was significantly higher in the IMRT group than in the c-RT group (61.8 vs 50.3 Gy, P = 0.029). Intensity-modulated radiation therapy plans yielded better dose sparing of small bowel, bladder, and rectum than did c-RT (P < 0.05). Moreover, the IMRT patients experienced less acute and chronic toxicities (P < 0.05) and better short-term effects (complete response + partial response) than did those treated with c-RT (89.9% vs 63.4%, P = 0.03). Three- and 5-year overall survival rates were significantly higher in the IMRT group than in the c-RT group (3-year: 58.4% vs 39.1%, P = 0.012; 5-year: 35.4% vs 21.4%, P = 0.007). Furthermore, 5-year progression-free survival rates were significantly higher in the IMRT group than in the c-RT group (26.1% vs 15.1%, P = 0.031). CONCLUSIONS: Intensity-modulated radiation therapy achieved outcomes superior to c-RT in patients with pelvic locoregional recurrence of cervical cancer after radical surgery. The acute and chronic toxicities were acceptable, and the adjacent organs at risk were well protected.

Preparation of ZnO:Eu3+ nanospheres via a micro-emulsion method and analysis of the photoluminescence properties.

ZnO:Eu3+ nanospheres were prepared via a micro-emulsion method with hexadecyl trimethyl ammonium bromide as the primary surfactant, butanol as the cosurfactant and octane as the oil phase. The X-ray diffraction (XRD) pattern suggests that the Eu3+ ions have entered into the ZnO lattices. Scanning electron microscopy (SEM) images show that large scale-shaped nanospheres about 200-500 nm in size were formed. The photoluminescence (PL) spectra suggest that the Eu3+ ions doped into ZnO have located at the non-inversion center positions because only the 612 nm peak (5D0 --> 7F2) occurred in the emission spectra. A schematic drawing for the possible mechanisms of electron transitions in the PL excitation and emission spectra is also proposed.

Gene expression changes after ionizing radiation in endothelial cells derived from human endometrial cancer-preliminary outcomes.

BACKGROUND: Accumulating evidence has demonstrated that death of microvascular endothelial cells plays a decisive role in the tumor response against radiotherapy. Nevertheless, radiation-induced gene alterations on cancer-associated endothelial cells of human endometrial carcinoma remain poorly understood. The purpose of this study was to elucidate the gene expression changes after X-ray radiation in human endometrial carcinoma vascular endothelial cells and to provide new targets for combined treatment of radiation and anti-angiogenesis in human endometrial carcinoma. MATERIALS AND METHODS: Endometrial cancer-derived endothelial cells, which obtained before and 4 h after 400 cGy X-ray radiation from four endometrial carcinomas, were analyzed by gene expression profile. The selected meaningful genes from gene microarray experiments were validated by real-time quantitative PCR. RESULTS: Microarray analyses showed 49 significantly changed genes which were common to all the microarray experiments. There into, 14 genes were found to be in persistent up-regulation and 14 in persistent down-regulation 4 h after X-ray radiation when compared with the control group. These genes were involved in cell cycle and growth regulation, cell-apoptosis, chemokine, cell signaling, cellular stress response, angiogenesis, DNA synthesis and repair and cell adhesion. Eight randomly selected genes were validated by real-time PCR. DISCUSSION: The genes of cancer-derived endothelial cells regulated by X-ray radiation as well as their related signal pathways, which obtained from gene expression profiling data, were relevant to radiosensitivity of endometrial cancer. This study shows that the identified genes and their related signaling pathways are candidated biomarkers for radiation and anti-angiogenesis of human endometrial carcinoma.

Fluorescence imaging-guided surgery: current status and future directions.

Surgery is one of the most important paradigms for tumor therapy, while fluorescence imaging (FI) offers real-time intraoperative guidance, greatly boosting treatment prognosis. The imaging fidelity heavily relies on not only imaging facilities but also probes for imaging-guided surgery (IGS). So far, a great number of IGS probes with emission in visible (400-700 nm) and near-infrared (NIR 700-1700 nm) windows have been developed for pinpointing disease margins intraoperatively. Herein, the state-of-the-art fluorescent probes for IGS are timely updated, with a special focus on the fluorescent probes under clinical examination. For a better demonstration of the superiority of NIR FI over visible FI, both imaging modalities are critically compared regarding signal-to-background ratio, penetration depth, resolution, tissue autofluorescence, photostability, and biocompatibility. Various types of fluorescence IGS have been summarized to demonstrate its importance in the medical field. Furthermore, the most recent progress of fluorescent probes in NIR-I and NIR-II windows is summarized. Finally, an outlook on multimodal imaging, FI beyond NIR-II, efficient tumor targeting, automated IGS, the use of AI and machine learning for designing fluorescent probes, and the fluorescence-guided da Vinci surgical system is given. We hope this review will stimulate interest among researchers in different areas and expedite the translation of fluorescent probes from bench to bedside.

The state-of-art polyurethane nanoparticles for drug delivery applications.

Nowadays, polyurethanes (PUs) stand out as a promising option for drug delivery owing to their versatile properties. PUs have garnered significant attention in the biomedical sector and are extensively employed in diverse forms, including bulk devices, coatings, particles, and micelles. PUs are crucial in delivering various therapeutic agents such as antibiotics, anti-cancer medications, dermal treatments, and intravaginal rings. Effective drug release management is essential to ensure the intended therapeutic impact of PUs. Commercially available PU-based drug delivery products exemplify the adaptability of PUs in drug delivery, enabling researchers to tailor the polymer properties for specific drug release patterns. This review primarily focuses on the preparation of PU nanoparticles and their physiochemical properties for drug delivery applications, emphasizing how the formation of PUs affects the efficiency of drug delivery systems. Additionally, cutting-edge applications in drug delivery using PU nanoparticle systems, micelles, targeted, activatable, and fluorescence imaging-guided drug delivery applications are explored. Finally, the role of artificial intelligence and machine learning in drug design and delivery is discussed. The review concludes by addressing the challenges and providing perspectives on the future of PUs in drug delivery, aiming to inspire the design of more innovative solutions in this field.

[Application value of reduced field intensity modulated radiation therapy for advanced cervical cancer].

OBJECTIVE: To explore the clinical value and efficacy of reduced field intensity modulated radiation therapy (RF-IMRT) for patients with advanced cervical cancer. METHODS: Seventy-one patients with stage IIB-IIIB cervical cancer, who underwent reduced field IMRT (RF-IMRT group) and 72 patients treated with conventional radiotherapy (c-RT group) in Shandong Cancer Hospital between 2005 August and 2011 August, were enrolled in this study. The RF-IMRT plans were as follows: whole pelvic IMRT plan was performed to deliver an initial dose of 30 Gy, then the irradiated volume was reduced to lymphatic drainage region as well as paracervix and parametrium for an additional 30 Gy boost. Conventional 2-field RT plan was performed in these patients using ADAC Pinnacle 3 planning system, to be given the same prescription dose, and to compare the irradiation dose of organs at risk (OARs). At the same time, conventional 2-field RT was performed in 72 patients of the c-RT group. Concurrent chemotherapy and intracavitary brachytherapy were also performed in the two groups. The treatment response, toxicities, normal tissue avoidance, and survival were assessed. RESULTS: Sixty-six patients of the RF-IMRT group and 65 patients of the c-RT group fulfilled the treatment plan. IMRT plans yielded better dose conformity to the target (0.711 ± 0.057 vs. 0.525 ± 0.062, P = 0.032) and better sparing of the rectum, bladder and small intestine (rectum: 41.6 ± 6.8 vs. 50.8 ± 3.2, P = 0.016; bladder: 40.2 ± 2.9 vs. 51.4 ± 1.8, P = 0.007; small intestine: 22.3 ± 2.6 vs. 35.8 ± 3.9, P = 0.004). The mean dose delivered to the planning target volume (PTV) was significantly higher in the RF-IMRT group than that in the c-RT group (60.8 vs. 51.2 Gy, P = 0.006). The RF-IMRT patients experienced significantly lower acute and chronic toxicities with comparable short-term effects than did those treated with conventional RT (P > 0.05). No significant differences were found between the two groups for 1-, 3-, and 5-year overall survival (OS) rates, while a significantly higher progression-free survival (PFS, 65.2% vs. 46.2%, P = 0.031) rate was observed in the RF-IMRT group. CONCLUSIONS: RF-IMRT yields higher dose distributions and lower toxicities compared with conventional RT, and both the tumor target volume and pelvic lymphatic drainage region achieve curative dose irradiation, the adjacent organs at risk are well protected, and with tolerable adverse reactions. Yet, RF-IMRT provides comparable clinical outcomes and higher PFS.

[Clinical study of sentinel lymph node detection guided radical abdominal trachelectomy].

OBJECTIVE: To evaluate the clinical value of sentinel lymph nodes (SLN) in predicting pelvic lymph node status for early cervical squamous cell carcinoma, and approach the clinical significance of SLN detection for guiding radical abdominal trachelectomy (RAT).Outcomes of follow up and fertility were also observed. METHODS: A total of 31 patients with stageIa2-Ib1 squamous cell carcinoma planned to be given RAT and pelvic lymphadenectomy were enrolled. (99m)Tc-labeled phytate was injected before surgery.Intraoperatively, SLN were identified, excised, and submitted to fast frozen section.Systematic bilateral pelvic lymphadenectomy was performed, and then RAT was performed in patients with negative SLN. All nodes were sent for routine pathological examination and immunostained with anti-cytokeratin antibody to detect micrometastases. RESULTS: SLN were detected in all patients (100%,31/31). A total of 109 SLN were identified with a mean number of 3.5 per patient.Of these, SLN of 2 patients were positive on frozen sections and proved to be metastasis by final pathologic examination and quitted the RAT. No missed micrometastasis was found using immunohistochemical staining in SLN and other lymph nodes using histologically node-negative cases. No false negative cases was found and the negative value was 100% (31/31). The sensitivity, accuracy, and false negative rates were 100%, 100%, and 0, respectively. Perioperative complications occurred in 5 patients including 2 cases of bladder injury and 3 cases of uterine artery injury.No relapses occurred during follow-up.Five of 19 patients with procreative desire conceived pregnancies (4 spontaneous abortion and 1 premature birth) after surgery. CONCLUSIONS: The identification of SLN using (99m)Tc-labeled phytate could predict the pelvic lymph node status in early stage cervical cancer. Under the guidance of SLN detection, RAT is a feasible operative modality with well prognosis and low complications for young patients who desire to preserve reproductive function.

Comparative efficacy of acupuncture-related interventions for tubal obstructive infertility: A systematic review and Bayesian meta-analysis of randomized controlled trials.

BACKGROUND: Tubal obstructive infertility (TOI) is a challenging condition affecting many women worldwide. Acupuncture and herbal medicine have emerged as potential therapeutic options for enhancing fertility outcomes in these patients. However, the evidence regarding their efficacy remains inconclusive, necessitating a comprehensive systematic review and meta-analysis. METHOD: Computer searches were conducted in PubMed, Cochrane, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), VIP Information, Wanfang Database, and China Biology Medicine (CBM) databases to retrieve relevant literature on the efficacy and safety of acupuncture and related therapies for the treatment of tubal obstructive infertility. The search period extended from the inception of the databases to December 2022. Two researchers independently screened the literature based on strict inclusion criteria, extracted relevant data, and utilized Cochrane Collaboration tools and the Jadad scale to comprehensively assess the quality of the included studies. Subsequently, pairwise meta-analysis and network meta-analysis were performed using statistical software such as StataSE and Rstudio, and graphical representations were generated to present the results. RESULT: The network meta-analysis included 1580 articles, with 23 meeting the criteria. These studies involved 2355 patients and explored 13 intervention measures. Acupuncture-related therapies outperformed control interventions in improving pregnancy rates, tubal patency rates, and overall effectiveness while demonstrating a lower incidence of adverse events. EA+CHM was identified as the most effective for pregnancy rates, MOX for tubal patency rates, and MOX+AP for overall effectiveness. The safety profile of acupuncture-related interventions was acceptable. These findings support acupuncture-related therapies as effective and safe options for tubal obstructive infertility management. Further high-quality research is needed to validate and expand upon these results. CONCLUSION: These findings offer novel treatment strategies for acupuncture-related interventions, providing practitioners with evidence-based guidance. Addressing limitations through future research is crucial, including diverse literature, emphasizing higher-quality RCTs, and exploring a broader range of interventions with long-term follow-up data. Systematic assessment of adverse events, standardized techniques, and robust ranking methods should be considered.

Immunity and reproduction protective effects of Chitosan Oligosaccharides in Cyclophosphamide/Busulfan-induced premature ovarian failure model mice.

Introduction: Premature ovarian failure (POF) is a major cause of infertility among women of reproductive age. Unfortunately, there is no effective treatment available currently. Researchers have shown that immune disorders play a significant role in the development of POF. Moreover, growing evidence suggest that Chitosan Oligosaccharides (COS), which act as critical immunomodulators, may have a key role in preventing and treating a range of immune related reproductive diseases. Methods: KM mice (6-8 weeks) received a single intraperitoneal injection of cyclophosphamide (CY, 120mg/kg) and busulfan (BUS, 30mg/kg) to establish POF model. After completing the COS pre-treatment or post-treatment procedures, peritoneal resident macrophages (PRMs) were collected for neutral erythrophagocytosis assay to detect phagocytic activity. The thymus, spleen and ovary tissues were collected and weighed to calculate the organ indexes. Hematoxylin-eosin (HE) staining was performed to observe the histopathologic structure of those organs. The serum levels of estrogen (E2) and progesterone (P) were measured via the enzyme-linked immunosorbent assay (ELISA). The expression levels of immune factors including interleukin 2 (IL-2), interleukin 4 (IL-4), and tumor necrosis factor α (TNF-α), as well as germ cell markers Mouse Vasa Homologue (MVH) and Fragilis in ovarian tissue, were analyzed by Western blotting and qRT-PCR. In addition, ovarian cell senescence via p53/p21/p16 signaling was also detected. Results: The phagocytic function of PRMs and the structural integrity of thymus and spleen were preserved by COS treatment. The levels of certain immune factors in the ovaries of CY/BUS- induced POF mice were found to be altered, manifested as IL-2 and TNF-α experiencing a significant decline, and IL-4 presenting a notable increase. Both pre-treatment and post-treatment with COS were shown to be protective effects against the damage to ovarian structure caused by CY/BUS. Senescence-associated ß-galactosidase (SA-ß-Gal) staining results showed that COS prevents CY/BUS-induced ovarian cell senescence. Additionally, COS regulated estrogen and progesterone levels, enhanced follicular development, and blocked ovarian cellular p53/p21/p16 signaling which participating in cell senescence. Conclusion: COS is a potent preventative and therapeutic medicine for premature ovarian failure by enhancing both the ovarian local and systemic immune response as well as inhibiting germ cell senescence.

Intensity-modulated radiation therapy for advanced cervical cancer: a comparison of dosimetric and clinical outcomes with conventional radiotherapy.

OBJECTIVE: The aim of this study is to evaluate the dosimetry, efficacy and toxicity of reduced field intensity-modulated radiation therapy (RF-IMRT) for patients with advanced cervical cancer. METHODS: From August 2005 to August 2010, 60 patients with stage IIB-IIIB cervical cancer underwent reduced field IMRT (RF-IMRT group) and 62 patients treated with conventional radiotherapy (c-RT group) were enrolled. The RF-IMRT plans were as follows: whole pelvic IMRT plan was performed to deliver a dose of 30Gy firstly, then the irradiated volume was reduced to lymphatic drainage region as well as paracervix and parametrium for an additional 30Gy boost. Intracavitary brachytherapy and concurrent chemotherapy were performed during external irradiation. The tumor coverage and normal tissue avoidance were evaluated. Treatment response, toxicities and survival were assessed. RESULTS: The mean dose delivered to the planning target volume was significantly higher in RF-IMRT group than in c-RT group (61.5 vs. 50.8Gy, P=0.046). IMRT plans yielded better dose conformity to the target and better sparing of the rectal, bladder and small intestine. The RF-IMRT patients experienced significantly lower acute and chronic toxicities with comparable short-term effects than did those treated with conventional RT (CR: 87.7% vs. 88.3%, P=0.496; PR: 7.0% vs. 6.7%, P=0.440). No significant differences were found between treatment groups for 1year, 3year, and 5year overall survival (OS) levels, although the latter approached statistical significance in favor of IMRT, while a significantly higher progression-free survival (PFS; P=0.031) was seen for IMRT. CONCLUSIONS: RF-IMRT yields improved dose distributions, with lower toxicities, while providing comparable clinical outcomes. The increased PFS may be an advantage.

[Isolation, purification and characterization of endothelial cells from endometrial cancer and normal endometrial tissue].

OBJECTIVE: To immunopurify human endometrial endothelial cells (HEEC) from fresh surgical specimens of endometrial cancers and normal endometrial tissues, and investigate their biological characteristics. METHODS: Endothelial cells of endometrial cancers and normal endometrial tissues were isolated using anti-CD31 conjugated magnetic microbeads. The isolated endothelial cells were cultured in vitro and their origins were identified. Their angiogenic characteristics were observed by MTT, wound healing, Transwell cell invasion and tube formation assays. RESULTS: Flow cytometry revealed that the immunopurification technique yielded endothelial cell purity of > 95% in all samples. All purified HEEC were characterized as endothelial cells on the basis of expression of the classical endothelial markers vWF and CD31 as shown by immunofluorescence examination. Although the tumor-associated HEEC didn't show more rapid proliferation than normal HEEC, they exhibited enhanced migration ability (P = 0.006), potent invasiveness (P = 0.033), and elevated tube formation in vitro (P = 0.029). CONCLUSIONS: Human endometrial endothelial cells can be efficiently isolated from endometrial cancer and normal endometrial tissues by immunomagnetic methods. Tumor-associated HEEC exhibit enhanced migratory ability, potent invasiveness, and elevated tube formation in vitro.

[Angiogenesis related gene expression profiles of human endometrial endothelial cells isolated from tissue of endometrial cancer].

OBJECTIVE: To identify and verify the different genes expression pattern between human endometrial endothelial cells (HEEC) isolated from endometrial cancer and normal endometrium. METHODS: Endothelial cells were isolated from 5 patients with endometrial cancer (endometrial cancer group 1) and 5 patients with normal endometria tissue (control group 1) admitted from June to November 2007 in Shandong Cancer Hospital. Global expression patterns of endothelial cells were examined using oligonucleotide microarrays. Tissues from 36 patients with endometrial cancer (endometrial cancer group 2) and 10 normal endometrial tissues (control group 2) admitted from January 2007 to April 2008 were selected to verify the expression of different genes, in which up-regulated genes including ESM1, MMP-10, SPP1 and HMGB1 were tested by quantitative real-time PCR and immunohistochemistry. RESULTS: Microarray analyses revealed 317 genes that exhibited > 2-fold or < 0.5 differences were identified (including 191 genes up-regulated and 126 down-regulated). Pathway analysis showed that these genes involved cell cycle, cell adhesion molecules, and extracellular matrix-receptor interaction were obviously predominant. Of them, 97 up-regulated genes and 44 down-regulated genes were related to angiogenesis. The mRNA expression of ESM1, MMP-10, SPP1 and HMGB1 in endometrial cancer group 2 were 0.898, 3.890, 1.433 and 1.881, respectively. Positive expression of SPP1, MMP-10, ESM1 and HMGB1 was observed in endometrial cancer group 2. However, the SPP1, ESM1 and HMGB1 was negative expressed in control group 2. CONCLUSION: It shows that there are the different angiogenesis related genes between endometrial cancer and normal endothelium, which will provide insights into the anti-angiogenesis therapy for endometrial cancers.

PCMT1 Is a Potential Prognostic Biomarker and Is Correlated with Immune Infiltrates in Breast Cancer.

Background: Protein-L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1) is involved in the occurrence and development of a variety of malignant tumors. However, the prognostic value of PCMT1 in breast cancer remains unclear. Methods: Based on the Cancer Genome Atlas database, we assessed the correlation between the expression of PCMT1 and prognosis, immune invasion, and tumor mutation burden in a variety of cancers. The expression level, mutation, immune correlation, and coexpression of PCMT1 in breast cancer were studied using the following databases: UALCAN database, Human Protein Atlas database, cBioPortal database, TIMER database, and LinkedOmics database. Kaplan-Meier Plotter was used for survival analysis. Receiver operating characteristic (ROC) curves and nomograms were drawn using the R software package. P < 0.05 was considered statistically significant. Results: Pancancer analysis showed that PCMT1 is highly expressed in a variety of cancers and is significantly related to the prognosis of a variety of cancers. PCMT1 is significantly related to the tumor mutation burden of a variety of cancers. PCMT1 is significantly high in breast cancer, and it is significantly related to the abundance of immune infiltration. Survival analysis revealed that high PCMT1 expression is significantly associated with shorter overall survival (OS), relapse-free survival (RFS), and postprogression survival (PPS) in breast cancer patients. ROC curves and nomograms verify the effectiveness of PCMT1 as a prognostic biomarker for breast cancer. Conclusions: PCMT1 can be used as a potential prognostic biomarker of breast cancer, and it is significantly related to the abundance of breast cancer immune infiltration.

BAG family proteins contributes to autophagy-mediated multidrug resistance of tumor.

Multidrug resistance (MDR) is a significant cause of tumor treatment failure. Accumulating evidence suggests that autophagy plays a significant role in the development of MDR. Autophagy is a conserved mechanism that maintains tumor homeostasis by removing damaged mitochondria. However, the specific regulatory mechanism is unclear. Here, we summarize recent studies on the role of autophagy in the development of MDR and the initiation of mitophagy by Bcl-2-associated athanogene (BAG) family proteins. Additionally, this mini-review emphasizes the regulatory role of BAG family proteins, which maintain mitochondrial homeostasis by regulating the PINK1/Parkin pathway. Elucidation of the regulatory mechanisms of mitophagy may foster the development of clinical therapeutic strategies for MDR tumors.

Sentinel lymph node biopsy as guidance for radical trachelectomy in young patients with early stage cervical cancer.

BACKGROUND: The purpose of this study was to assess the feasibility and accuracy of sentinel lymph nodes (SLNs) detection using 99mTc phytate in predicting pelvic lymph nodes status for radical abdominal trachelectomy (RAT) in patients with early stage cervical cancer. METHODS: Sixty-eight women with stage IA2-IB1 cervical cancer and scheduled to undergo fertility-sparing surgery enrolled in this study. 99mTc-labeled phytate was injected before surgery. Intraoperatively, SLNs were identified, excised, and submitted to fast frozen section. Systematic bilateral pelvic lymphadenectomy and/or para-aortic lymph node dissection was performed. Then RAT was performed in patients with negative SLNs. All nodes were sent for routine pathological examination and immunostained with anti-cytokeratin antibody to detect micrometastases. Outcomes of follow up and fertility were observed. RESULTS: SLNs were identified in 64 of 68 patients (94.1%). Of these, SLNs of 8 patients (11.8%) were positive on frozen sections and proved to be metastasis by final pathologic examination. The sensitivity, accuracy, and false negative rates were 100%, 100%, and 0%, respectively. All 60 patients with negative SLN underwent RAT successfully. Two relapses occurred and no one died of tumor progression during follow-up. Five of the 15 patients with procreative desire conceived 8 pregnancies (3 term delivery, 2 premature birth, 1 spontaneous abortion, and 2 were still in the duration of pregnancy) after surgery. CONCLUSIONS: The identification of SLN using 99mTc-labeled phytate is accurate and safe to assess pelvic nodes status in patients with early cervical cancer. SLNs biopsy guided RAT is feasible for patients who desire to have fertility preservation.

Improving the catalytic activity of hyperthermophilic Pyrococcus prolidases for detoxification of organophosphorus nerve agents over a broad range of temperatures.

Prolidase isolated from the hyperthermophilic archaeon Pyrococcus furiosus has potential for application for decontamination of organophosphorus compounds in certain pesticides and chemical warfare agents under harsh conditions. However, current applications that use an enzyme-based cocktail are limited by poor long-term enzyme stability and low reactivity over a broad range of temperatures. To obtain a better enzyme for OP nerve agent decontamination and to investigate structural factors that influence protein thermostability and thermoactivity, randomly mutated P. furiosus prolidases were prepared by using XL1-red-based mutagenesis and error-prone PCR. An Escherichia coli strain JD1 (lambdaDE3) (auxotrophic for proline [DeltaproA] and having deletions in pepQ and pepP dipeptidases with specificity for proline-containing dipeptides) was constructed for screening mutant P. furiosus prolidase expression plasmids. JD1 (lambdaDE3) cells were transformed with mutated prolidase expression plasmids and plated on minimal media supplemented with 50 muM Leu-Pro as the only source of proline. By using this positive selection, Pyrococcus prolidase mutants with improved activity over a broader range of temperatures were isolated. The activities of the mutants over a broad temperature range were measured for both Xaa-Pro dipeptides and OP nerve agents, and the thermoactivity and thermostability of the mutants were determined.

Intensity-modulated radiation therapy versus para-aortic field radiotherapy to treat para-aortic lymph node metastasis in cervical cancer: prospective study.

AIM: To compare dosimetry, efficacy, and toxicity of intensity-modulated radiation therapy (IMRT) with para-aortic field radiotherapy in patients with para-aortic lymph node (PALN) metastasis of cervical cancer. METHODS: This prospective study examined 60 patients with cervical cancer with PALN metastasis who underwent whole-pelvis radiotherapy followed by brachytherapy between November 1, 2004 and May 31, 2008. After 3 cycles of chemotherapy, patients were serially allocated into two groups and treated with IMRT or para-aortic field RT at doses of 58-68 Gy and 45-50 Gy, respectively. Treatment response was evaluated and toxicities were assessed. Patients in the IMRT group were treated with both para-aortic field RT and IMRT in order to compare the exposure dose of organs at risk. RESULTS: In the IMRT group, the mean dose delivered to the planning target volume was 67.5 Gy. At least 99% of the gross tumor volume received effective coverage and radical dose (median, 63.5 Gy; range, 54.5-66) during treatment. IMRT plans yielded better dose conformity to the target and better sparing of the spinal cord and small intestine than para-aortic field RT. The IMRT patients experienced less acute and chronic toxicities. The IMRT group also had higher 2- and 3-year survival rates than the para-aortic RT group (2-year, 58.8% vs 25.0%, P = 0.019; 3-year, 36.4% vs 15.6%, P = 0.016). However, no significant difference was found in 1-year survival (67.7% vs 51.3%, P =0.201). The median survival in the IMRT group was 25 months (range, 3 to 37 months). The actuarial overall survival, disease-free survival, and locoregional control rates at 2 years were 67%, 77%, and 88%, respectively, in the IMRT group. CONCLUSIONS: IMRT provides better clinical outcomes than para-aortic field radiotherapy in patients with PALN metastasis. However, cervical local and distal recurrence remain a problem. Long-term follow-up and studies involving more patients are needed to confirm our results.

[Gemcitabine based combination chemotherapy, a new salvage regimen for recurrent platinum resistant epithelial ovarian cancer].

OBJECTIVE: To evaluate the efficacy and toxicities of gemcitabine combined with ifosfamide and anthracycline chemotherapy for recurrent platinum resistant ovarian epithelial cancer. METHODS: Gemcitabine 800 mg/m(2) (day 1, 8), ifosfamide 1.5 g/m(2) (day 1 - 3), adriamycin 40 mg/m(2) or epirubicin 60 mg/m(2) (day 1) or mitoxantrone 10 mg/m(2) (day 1, 8) were used in recurrent platinum resistant/refractory ovarian cancer patients, the cycle was repeated at interval of 21 to 28 days. RESULTS: A total of 60 patients received 172 cycles combined chemotherapy. There were no one cases complete response, while partial response 22 (37%, 22/60), stable 23 (38%, 23/60) and progression 15 (25%, 15/60) were observed, with clinical benefit rate 75% (45/60). The median time of progression-free survival was 7 months, and the median overall survival time was 20 months. The main side effect was hematologic toxicity with leukopenia rate of 82% (49/60), among which III-IV accounted for 31% (15/49). Digestive reaction was all in I-II, accounted for 42% (25/60). CONCLUSION: The regimen of gemcitabine combined with ifosfamide and anthracycline is feasible, tolerable and effective in patients with recurrent platinum resistant/refractory epithelial ovarian cancer.