Nomogram for Predicting Survival in Locally Advanced Cervical Cancer with Concurrent Chemoradiotherapy plus or Not Adjuvant Chemotherapy: A Retrospective Analysis Based on 2018 FIGO Staging.

Background: The comprehensive treatment mode of combining concurrent chemoradiotherapy (CCRT) with adjuvant chemotherapy (AC) is a commonly used mainstream model in the clinical practice of locally advanced cervical cancer (LACC). However, the necessity for AC after CCRT lacks sufficient evidence-based medical support. This study constructs a predictive model for the survival time dependence of CCRT ± AC for LACC based on the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging with internal validation, the prognosis was assessed with intensity-modulated radiotherapy (IMRT) and concurrent cisplatin, and provides guidance for future stratified treatment. Materials and Methods: The retrospective analysis included 482 patients with LACC who CCRT from January 2016 to January 2023. Patients who used the 2009 FIGO staging were all standardized for the 2018 FIGO staging. The 482 patients with LACC were divided into a training set (n = 290) and a validation set (n = 192) at a ratio of 6:4. COX multivariate regression model and LASSO regression were used to screen for independent prognostic factors affecting progression-free survival (PFS) and overall survival (OS), and a nomogram clinical prediction model was constructed based on these factors. Evaluate the effectiveness of the model through the receiver operating characteristic curve, calibration curve, decision curve, risk heat map, and survival curves for risk stratification. Results: The PFS and OS independent prognostic risk factors affecting the 2018 FIGO staging of LACC during CCRT were validated to be similar to the 2009 FIGO staging prediction model reported in previous literature. In the training cohort, area under the curve (AUC) values at 1, 3, and 5 years were 0.941, 0.882, and 0.885 for PFS, and 0.946, 0.946, and 0.969 for OS, respectively. When applied to a test cohort, the model also showed accurate prediction result (AUC at 1, 3, and 5 years were 0.869, 0.891, and 0.899 for PFS, and 0.891, 0.941 and 0.878 for OS, respectively). Subgroup analysis suggests that patients with LACC, adenocarcinoma, stage IVA, pelvic lymph node metastasis, pretreatment hemoglobin ≤100 g/l and residual tumor diameter >2 cm, who received CCRT in the 2018 FIGO stage, may benefit more from adjuvant chemtherapy. Conclusions: Based on the 2018 FIGO staging, a nomogram prediction model for PFS and OS in patients with LACC undergoing CCRT was developed. The model, established by combining weighted clinical and pathological factors, can provide more personalized treatment predictions in clinical practice. For patients with high-risk factors such as residual tumor diameter > 2 cm after CCRT for LACC, AC may bring benefits.

Relationship between chorioamnionitis or funisitis and lung injury among preterm infants: meta-analysis involved 16 observational studies with 68,397 participants.

BACKGROUND: Chorioamnionitis (CA) can cause multiple organ injuries in premature neonates, particularly to the lungs. Different opinions exist regarding the impact of intrauterine inflammation on neonatal respiratory distress syndrome (NRDS) and bronchopulmonary dysplasia (BPD). We aim to systematically review the relationship between CA or Funisitis (FV) and lung injury among preterm infants. METHODS: We electronically searched PubMed, EMbase, the Cochrane library, CNKI, and CMB for cohort studies from their inception to March 15, 2023. Two reviewers independently screened literature, gathered data, and did NOS scale of included studies. The meta-analysis was performed using RevMan 5.3. RESULTS: Sixteen observational studies including 68,397 patients were collected. Meta-analysis showed CA or FV increased the lung injury risk (OR = 1.43, 95%CI: 1.06-1.92). Except for histological chorioamnionitis (HCA) (OR = 0.72, 95%CI: 0.57-0.90), neither clinical chorioamnionitis (CCA) (OR = 1.86, 95%CI: 0.93-3.72) nor FV (OR = 1.23, 95%CI: 0.48-3.15) nor HCA with FV (OR = 1.85, 95%CI: 0.15-22.63) had statistical significance in NRDS incidence. As a result of stratification by grade of HCA, HCA (II) has a significant association with decreased incidence of NRDS (OR = 0.48, 95%CI: 0.35-0.65). In terms of BPD, there is a positive correlation between BPD and CA/FV (CA: OR = 3.18, 95%CI: 1.68-6.03; FV: OR = 6.36, 95%CI: 2.45-16.52). Among CA, HCA was positively associated with BPD (OR = 2.70, 95%CI: 2.38-3.07), whereas CCA was not associated with BPD (OR = 2.77, 95%CI: 0.68-11.21). HCA and moderate to severe BPD (OR = 25.38, 95%CI: 7.13-90.32) showed a positive correlation, while mild BPD (OR = 2.29, 95%CI: 0.99-5.31) did not. CONCLUSION: Currently, evidence suggests that CA or FV increases the lung injury incidence in premature infants. For different types of CA and FV, HCA can increase the incidence of BPD while decreasing the incidence of NRDS. And this "protective effect" only applies to infants under 32 weeks of age. Regarding lung injury severity, only moderate to severe cases of BPD were positively correlated with CA.

The extracellular polysaccharide inhibit porcine epidemic diarrhea virus with extract and gene editing Lacticaseibacillus.

Lacticaseibacillus is one of the predominant microorganisms in gut from human and animal, and the lacticaseibacillus have effective applications against the viral diarrhea of piglets in the farm. However, the function and the concrete cell single pathways of the active ingredient from lacticaseibacillus was not clear within anti-infection in the postbiotics research. Here, we compared the biological function of extracellular polysaccharides (EPS) purified from lacticaseibacillus casei (L. casei) and gene editing lacticaseibacillus casei with the CRISPER-Cas9 technology, which were with the ability of antioxidation and anti-inflammation, and the EPS could also inhibit the ROS production within the Porcine Small Intestinal Epithelial Cells-J2 (IPEC-J2). Interestingly, we found that both of EPS and genome editing lacticaseibacillus casei could specifically target the IFN-λ expression in the IPEC-J2, which was beneficial against the PEDV infection in the virus replication and production with the qRT-PCR and indirect immunofluorescence methods. Finally, the STAT3 cell single pathway was stimulated to transcribe IFN-λ with the EPS to elucidate the detailed mechanism of activating type III IFN signals receptor of IL-10R2, which play the function between anti-inflammation and anti-virus in the PEDV infection. Taken together, our research linked a postbiotics of EPS with the antiviral infection of PEDV, which suggest that the lacticaseibacillus itself still have displayed the potential immunomodulatory activities, and highlight the immunomodulatory potential of EPS-producing microbes.

Comparative study on the clinical outcomes and prognosis of endovascular embolization and craniotomy clipping for the treatment of cerebral aneurysms.

Objective: To investigate the safety and outcomes of endovascular embolization and craniotomy clipping in the treatment of cerebral aneurysms. Methods: We collected the clinical data of 106 patients with cerebral aneurysm who underwent surgical treatment (endovascular embolization, Group-A, n=55; craniotomy clipping, Group-B, n=51) in the First People's Hospital of Yichang from January 2020 to May 2021. We compared surgical treatment indexes, treatment costs, neurological function before and after the treatment, incidence of postoperative complications and the prognosis after one-year follow-up between the two groups. Results: Endovascular embolization (Group-A) was associated with a shorter mean operation time and hospital stay, a lower mean intraoperative bleeding amount, and a higher mean treatment cost than craniotomy clipping (Group-B) (P<0.05). Compared with the pre-operative neurological function scores, the scores of both groups decreased after the surgery, and the mean post-operative score of Group-A was significantly lower than that of Group-B (P<0.05). Compared with Group-B , patients in Group-A had a lower overall complication rate (P < 0.05. Higher proportion of patients in Group-A had a good prognosis (P < 0.05). Conclusion: Endovascular embolization for the treatment of cerebral aneurysms is safe as it can shorten the operation time and hospital stay, reduce the incidence of neurological injury and complications, and have a favorable prognosis. However, the treatment is more expensive. Endovascular embolization can be selected for the treatment of cerebral aneurysms when economic conditions allow it.

Preparation of sustainable mineral oil-free offset printing ink with vegetable oil esters.

Mineral oils are used in substantial quantities for the production of varnishes and inks due to their abundance and versatility. However, as part of the production process, some of mineral oil components are separated as waste material, whereupon they can mix with air, water, or soil and become potentially harmful to the environment. Almost all these waste materials are volatile organic compounds (VOCs), chemicals that can easily evaporate at room temperature and have toxic effect. Therefore, a novel green, mineral oil-free offset printing ink was produced using vegetable oil esters as bio-renewable raw materials. Accompanying varnishes were prepared with linseed oil, methyl oleate, octyl stearate, and four types of resin (A, B, C, and D). The application of these varnishes to magenta color offset ink was subsequently studied to screen out the best combination of resin and ester in terms of setting time. Meanwhile, dyeing force tests were conducted to evaluate the ink's printability, while rheological analysis was done via viscosity and flowability tests. The setting time of the magenta color offset ink made by varnish A was observed to be considerably shorter than that of the ink samples prepared using varnishes B, C, and D. Furthermore, varnish A proved to be a good alternative varnish for the production of yellow, cyan, and black color offset printing inks. Samples of these inks were printed on coated paper, and their printability was contrasted against that of vegetable oil-based (pure vegetable oil), mineral oil-based, and other mineral oil-free offset printing inks. Results determined that the varnishes produced with linseed oil, methyl oleate, and octyl stearate can replace mineral oil-based varnishes for the production of offset printing ink.

The efficacy of stereotactic minimally invasive thrombolysis at different catheter positions in the treatment of small- and medium-volume basal ganglia hemorrhage (SMITDCP I): a randomized, controlled, and blinded endpoint phase 1 trial.

Objective: The aim of this study was to evaluate the effects of stereotactic minimally invasive puncture with different catheter placement positions when combined with urokinase thrombolysis for the treatment of small- and medium-volume basal ganglia hemorrhage. Our goal was to identify the best minimally invasive catheter placement position to enhance therapeutic efficacy for patients with cerebral hemorrhage. Methods: The stereotactic minimally invasive thrombolysis at different catheter positions in the treatment of small- and medium-volume basal ganglia hemorrhage (SMITDCPI) was a randomized, controlled, and endpoint phase 1 trial. We recruited patients with spontaneous ganglia hemorrhage (medium-to-small and medium volume) who were treated in our hospital. All patients received stereotactic, minimally invasive punctures combined with an intracavitary thrombolytic injection of urokinase hematoma. A randomized number table method was used to divide the patients into two groups concerning the location of catheterization: a penetrating hematoma long-axis group and a hematoma center group. The general conditions of the two groups of patients were compared, and the data were analyzed, including the time of catheterization, the dosage of urokinase, the amount of residual hematoma, the hematoma clearance rate, complications, and the National Institute of Health stroke scale (NIHSS) score data at 1 month after surgery. Results: Between June 2019 and March 2022, 83 patients were randomly recruited and assigned to the two groups as follows: 42 cases (50.60%) to the penetrating hematoma long-axis group and 41 cases (49.40%) to the hematoma center group. Compared with the hematoma center group, the long-axis group was associated with a significantly shorter catheterization time, a lower urokinase dose, a lower residual hematoma volume, a higher hematoma clearance rate, and fewer complications (P < 0.05). However, there were no significant differences between the two groups in terms of the NIHSS scores when tested 1 month after surgery (P > 0.05). Conclusion: Stereotactic minimally invasive puncture combined with urokinase for the treatment of small- and medium-volume hemorrhage in the basal ganglia, including catheterization through the long axis of the hematoma, led to significantly better drainage effects and fewer complications. However, there was no significant difference in short-term NIHSS scores between the two types of catheterization.

Bulk Polymerization of Thermoplastic Shape Memory Epoxy Polymer for Recycling Applications.

Conventional epoxy polymers are thermo-set and difficult to recycle and reuse. In this study, a series of linear thermoplastic epoxy polymers (EPx) with shape memory properties were prepared by using a bifunctional monoamine diglycolamine (DGA) as a curing agent and an equivalent amount of bifunctional rigid epoxy resin (E-51) and bifunctional flexible epoxy resin (polypropylenglycol diglycidyl ether, PPGDGE) in a bulk polymerization reaction. The results showed that these samples can fully react under the curing process of, 60 °C/2 h, followed by 80 °C/2 h, followed by 120 °C/2 h. The introduction of different contents of PPGDGE can adjust the Tg of the material to adapt to different environmental requirements, and can significantly increase the fracture strain of the material and improve its micro-phase separation structure. Thus, Rf of the material is close to 100%, and Rr is increased from 87.98% to 97.76%. Importantly, this linear chain structure allows the material to be easily recycled and reprocessed by dissolving or melting, and also means the material shows potential for 3D printing or other thermoplastic remolding.

Identification and validation of DNA methylation markers to predict axillary lymph node metastasis of breast cancer.

BACKGROUND: Axillary lymph node metastasis (ALNM) is one of the most important prognostic factors for breast cancer patients, and DNA methylation is involved in ALNM of breast cancer. However, the methylation profile of breast cancer ALNM remains unknown. METHODS: Breast cancer tissues were collected from patients with and without ALNM. We investigated the genome-wide DNA methylation profile in breast cancer with and without ALNM using reduced representation bisulfite sequencing (RRBS). Then, differentially methylated regions (DMRs) were verified by targeted bisulfite sequencing. RESULTS: A total of 21491 DMRs were identified between the lymph node positive group and negative group. Compared to the LN-negative breast cancer, LN-positive breast cancer had 10,920 hypermethylated DMRs and 10,571 hypomethylated DMRs. Then, 10 DMRs in the gene promoter region were detected by targeted bisulfite sequencing, these gene included HOXA5, PTOV1-AS1, RHOF, PAX6, GSTP1, RASGRF2, AKR1B1, BNIP3, CRMP1, ING5. Compared with negative lymph node, the promoter methylation levels of RASGRF2, AKR1B1 and CRMP1 increased in positive lymph node, while the promoter methylation level of RHOF decreased in positive lymph node. In addition, Cancer Genome Atlas (TCGA) data showed that RASGRF2, AKR1B1 and CRMP1 were low expressed in breast Cancer tissues, while RHOF was high expressed in breast Cancer tissues. Furthermore, in addition to highly methylated AKR1B1, RASGRF2 and CRMP1 gene promoters, BNIP3, GSTP1, HOXA5 and PAX6 gene promoters were also methylated in ER-positive and HER2-negative breast cancer with ALNM. CONCLUSIONS: When compared to negative lymph node breast cancer, the positive lymph node breast cancer has a differential methylation status. Promoter methylation of RASGRF2, AKR1B1, CRMP1 and RHOF in lymph node positive breast cancer tissues was significantly different from that in lymph node negative breast cancer tissues. AKR1B1, RASGRF2, CRMP1, BNIP3, GSTP1, HOXA5 and PAX6 genes were methylated in ER-positive and HER2-negative breast cancer with ALNM. The study provides an important biological base for understanding breast cancer with ALNM and developing therapeutic targets for breast cancer with ALNM.

Tumor-associated macrophages promote migration and invasion via modulating IL-6/STAT3 signaling in renal cell carcinoma.

Tumor-associated macrophages (TAMs) promote tumor cell growth and metastasis in various human cancers. However, the role of TAMs in renal cell carcinoma (RCC) is rarely investigated. Herein, we observed that the infiltration of TAMs was obviously elevated in RCC tumor tissues, high infiltration of TAMs was closely associated with tumor progression and poor prognosis in RCC patients. In vitro assays further indicated that the conditioned medium of TAMs (TAMs CM) facilitated migration, invasion, and epithelial-mesenchymal transition (EMT) in RCC cells. Moreover, we found that IL-6 was involved in the functions of TAMs in RCC; IL-6 neutralizing antibody (IL-6NA) partly abolished the effect of TAMs on RCC cells. In addition, we demonstrated that TAMs might exert their roles by activating STAT3 signaling in RCC, and IL-6 was responsible for TAMs-induced STAT3 signaling activation. In conclusion, our results revealed that high infiltration of TAMs may promote RCC cells migration, invasion, and EMT via modulating IL-6/STAT3 signaling, further suggesting a potential of novel treatment strategies targeting TAMs or IL-6 for metastatic RCC.

Non-drug efflux function of ABCC5 promotes enzalutamide resistance in castration-resistant prostate cancer via upregulation of P65/AR-V7.

Drug resistance is responsible for castration-resistant prostate cancer (CRPC)-associated mortality. While ATP binding cassette subfamily C member 5 (ABCC5) has been reported to regulate multiple drug resistance, its drug-efflux function may not be the main reason underlying resistance to enzalutamide, an androgen receptor inhibitor. Here, we aimed to determine whether the non-drug efflux function of ABCC5 affects enzalutamide resistance. The ABCC5 expression data in patients with prostate cancer (PCa) were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus, and their correlation with disease prognosis was analyzed. Immunohistochemical staining was performed on a cohort of 80 patient samples. Proliferation of enzalutamide-resistant 22RV1 and C4-2B cells was investigated using CCK-8, EdU, and colony formation assays. The effect of ABCC5 silencing on enzalutamide resensitization was evaluated in vitro and in vivo. Functional assays indicated that ABCC5 depletion resensitized enzalutamide-resistant cells to inhibit cell growth and impeded xenograft tumor proliferation. Mechanistically, luciferase and ChIP assays confirmed that P65 regulated AR expression and activity by binding to its promoter, while ABCC5-mediated resistance effected by AR-V7 (one of the widely studied AR splicing variants that meditate AR antagonist resistance) upregulation could be reversed by P65 knockdown. Furthermore, activation of the NF-κB pathway reversed the effects of ABCC5 knockdown by extra AR-V7 expression. Thus, ABCC5 might be a novel target for enzalutamide-resistant CRPC treatment.

Analysis of risk factors and preventive strategies for intracranial infection after neuroendoscopic transnasal pituitary adenoma resection.

OBJECTIVE: To analyse the risk factors for intracranial infection after neuroendoscopic transnasal pituitary adenoma resection (NTPAR) to provide a reference for the prevention and treatment of postoperative intracranial infection. METHODS: The clinical data of 387 patients who underwent NTPAR in the Department of Neurosurgery of the First People's Hospital of Yichang from March 2013 to March 2021 were retrospectively analysed. The patients were divided into an infected group and a noninfected group according to the occurrence of intracranial infection. The detailed clinical data of the two groups were collected. Univariate and multivariate logistic regression was used to analyse the risk factors for intracranial infection after NTPAR. RESULTS: Among the 387 surgical patients, 32 patients (8.27%) were in the intracranially infected group and 355 patients (91.73%) were in the noninfected group. The results of the univariate analysis suggested that age > 45 years, tumour size > 1 cm, operation time > 240 min, blood loss > 400 ml, Kelly Grade of cerebrospinal fluid (CSF) leakage > Grade 2, postoperative CSF leakage, lumbar cistern drainage and blood transfusion were the influencing factors for postoperative intracranial infection, while the results of multivariate logistic regression analysis implied that intraoperative CSF leakage (Kelly Grade > 2) and postoperative CSF leakage were independent influencing factors for intracranial infection after NTPAR, and perioperative use of antibiotics was an independent protective factor for postoperative intracranial infection. CONCLUSIONS: There are a variety of risk factors for intracranial infection after NTPAR, which indicates that it is necessary to develop different repair strategies for CSF leakage according to the Kelly Grade, timely treatment of postoperative CSF leakage and perioperative use of antibiotics. These measures have been shown to effectively reduce the probability of intracranial infection after NTPAR.

Systematic analysis of the potential off-target activities of osimertinib by computational target fishing.

Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor used to treat non-small cell lung cancer. However, its off-targets are obscure, and systematic analysis of off-target activities remains to be performed. Here, we identified the off-targets of osimertinib using PharmMapper and DRAR-CPI and analyzed the intersected targets using the GeneMANIA and DAVID servers. A drug-target-pathway network was constructed to visualize the associations. The results showed that osimertinib is associated with 31 off-targets, 40 Kyoto Encyclopedia of Genes and Genomes pathways, and 9 diseases. Network analysis revealed that the targets were involved in cancer and other physiological processes. In addition to EGFR, molecular docking analysis showed that seven proteins, namely Janus kinase 3, peroxisome proliferator-activated receptor alpha, renin, mitogen-activated protein kinases, lymphocyte-specific protein tyrosine kinase, cell division protein kinase 2 and proto-oncogene tyrosine-protein kinase Src, could also be potential targets of osimertinib. In conclusion, osimertinib is predicted to target multiple proteins and pathways, resulting in the formation of an action network via which it exerts systematic pharmacological effects.

Intravitreal conbercept for diabetic macular oedema: 2-year results from a randomised controlled trial and open-label extension study.

BACKGROUND: To demonstrate the efficacy and safety of intravitreal injections of conbercept versus laser photocoagulation in the treatment of diabetic macular oedema (DME). METHODS: A 12-month multicentre, randomised, double-masked, double-sham, parallel controlled, phase III trial (Sailing Study), followed by a 12-month open-label extension study. Patients with centre-involved DME were randomly assigned to receive either laser photocoagulation followed by pro re nata (PRN) sham intravitreal injections (laser/sham) or sham laser photocoagulation followed by PRN 0.5 mg conbercept intravitreal injections (sham/conbercept). Patients who entered the extension study received PRN conbercept treatment. The primary endpoint was the changes in best-corrected visual acuity (BCVA) from baseline. RESULTS: A total of 248 eyes were included in the full analysis set and 157 eyes continued in the extension study. Significant improvement in mean change in BCVA from baseline to month 12 was observed in the sham/conbercept group (8.2±9.5 letters), whereas no improvement was observed in the laser/sham group (0.3±12.0 letters). Patients in the laser/sham group showed a marked improvement in BCVA after the switch to conbercept in the extension study, and there was no difference in BCVA between the two groups at the end of the extension study. CONCLUSION: The use of a conbercept PRN intravitreal injection regimen improved the BCVA of patients with DME, and its efficacy was better than that of laser photocoagulations, and the same efficacy was observed when the eyes treated with laser alone were switched to conbercept. TRIAL REGISTRATION NUMBER: NCT02194634.

Predictive Value of ERCC1 mRNA Level from Receiver-Operator Characteristic and Pretreatment EBV-DNA Virus Load in Stage II Nasopharyngeal Carcinoma Patients Receiving Intensity-Modulated Radiotherapy with Concurrent Cisplatin.

Background: The molecular mechanisms underlying chemoresistance are still poorly understood in nasopharyngeal cancer. The protein expression of ERCC1 in DNA repair genes has been reported related to resistance platinum and predicting treatment outcomes in various malignant carcinomas, but the benefit for predicting outcomes with optimal cutoff value of ERCC1mRNA is controversial. The level of plasma Epstein-Barr virus (EBV) DNA is positively correlated with clinical stages of nasopharyngeal carcinoma (NPC). The predictive value of ERCC1mRNA from receiver-operator characteristic (ROC) and EBV-DNA level for stratified treatment with stage II NPC is exactly unclear. This study aims to assess the predictive value of combined EBV-DNA and ERCC1 in stage II nasopharyngeal cancer (NPC) patients treated with intensity-modulated radiotherapy (IMRT) with concurrent cisplatin, and provide guidance for future stratified treatment. Methods: A total of 86 stage II NPC patients who received IMRT and concurrent cisplatin-based chemotherapy with or without cisplatin-based adjuvant chemotherapy had measurements of ERCC1 mRNA, and pretreatment EBV-DNA levels were analyzed by real-time PCR (RT-PCR). Associations of ERCC1 mRNA and pretreatment EBV-DNA levels with clinical characteristics and survivals were evaluated. Results: Cutoff value of ERCC1 mRNA obtained from ROC curve was used, and there were significant differences in progression-free survival (PFS) and overall survival (OS) and overall response rate (ORR) between high expression group and low expression group (p = 0.021 and 0.030 and 0.000, respectively). Patients with pretreatment EBV-DNA <2000 copies/mL had significantly better PFS and ORR (p = 0.024 and 0.043, respectively) and a marginally significant impact on OS (p = 0.062) than those with pretreatment EBV-DNA ≥2000 copies/mL. Patients were divided into three groups by combination of ERCC1 mRNA and EBV-DNA level: ERCC1 mRNA low expression/pre-EBV-DNA <2000 copies/mL, ERCC1 mRNA low expression/pre-EBV-DNA ≥2000 copies/mL, and ERCC1 mRNA high expression/pre-EBV-DNA ≥2000 copies/mL. There were significant differences in ORR among the three groups (p = 0.005). The median follow-up was 62 months (range 22-84) with a follow-up rate of 90.70%. In these groups by combination of ERCC1 mRNA and EBV-DNA level, 1, 3, 5-year OS were 100%, 100%, 100%; 100%, 94.1%, 90.9%; and 100%, 85%, 72.9%, respectively (p = 0.038); 1, 3, 5-year PFS were 100%, 100%, 100%; 97.1%, 91.2%, 84.8%; and 95%, 85%, 71.4%, respectively (p = 0.028). Multivariate analysis showed that combination of ERCC1 mRNA and EBV-DNA levels remained independent prognostic factor but not ERCC1 mRNA and EBV-DNA alone. Conclusions: Combined ERCC1 mRNA and pre-EBV-DNA is a better prognostic biomarker in stage II NPC patients treated with concurrent chemoradiation. Patients with ERCC1 mRNA high expression/pre-EBV-DNA ≥2000 copies/mL may benefit from more aggressive treatment.

Comparison of the curative effect and prognosis of stereotactic drainage and conservative treatment for moderate and small basal ganglia haemorrhage.

BACKGROUND: Minimally invasive surgery has achieved good results in the treatment of cerebral haemorrhage.However, no large-scale clinical study has demonstrated that surgical treatment of cerebral haemorrhages less than 30 ml can improve the curative effect. Our study explored the efficacy and complication of stereotactic drainage based on the amount of cerebral hemorrhage (15-30 ml) in hypertensive basal ganglia. METHOD: Sixty patients with hypertensive basal ganglia haemorrhages were divided into a control group and an experimental group with 30 patients in each group. Patients in the control group were treated conservatively. In contrast, those in the experimental group received stereotactic drainage, and urokinase was injected into the haematoma cavity after the operation. The haematoma volume at admission and 1, 3, 7 and 30 days after treatment and National Institute of Health stroke scale(NIHSS) score data were recorded. Complications after treatment in the two groups of data were compared and analysed. RESULT: No significant differences in age, sex, time of treatment after onset, admission blood pressure, admission haematoma volume or admission NIHSS score were noted between these two groups (P > 0.05). After treatment, significant differences in haematoma volume were noted between the two groups on the 1st, 3rd, 7th and 30th days after treatment (P < 0.05). The amount of hematoma of patients in the experimental group was significantly reduced compared with that in the control group, and the NIHSS scores were significantly different on the 3rd, 7th and 30th days after treatment. The neurological deficit scores of patients in the experimental group were significantly reduced compared with those in the control group, and the incidence of pulmonary infection and venous thrombosis in the lower limbs of patients in the experimental group were significantly reduced (P < 0.05). ROC curve analysis showed that stereotactic drainage affected the early neurological function of patients with small and medium basal ganglia haemorrhages. CONCLUSION: For patients with small and medium basal ganglia haemorrhages, stereotactic drainage can be used due to the faster drainage speed of haematomas after operation, which is beneficial to the recovery of neurological function and reduce complications.

Mechanisms of Fritillariae Thunbergii Flos in lung cancer treatment from a systems pharmacology perspective.

ETHNOPHARMACOLOGICAL RELEVANCE: Fritillariae Thunbergii Flos (FTF) included in the Chinese Pharmacopoeia (1977 Edition) is a Chinese medicinal herb traditionally used to treat bronchitis. In recent years, it has been applied in the treatment of lung cancer. However, the molecular mechanism remains largely unknown. METHODS: The screening of bioactive compounds, acquisition of drug targets, network construction, and experimental validation in vivo were combined to explored the mechanism of FTF in the treatment of lung carcinoma with regards to systems pharmacology. RESULTS: The network Lung Cancer Pathway consisted of 114 nodes (44 compounds and 70 potential targets) and 361 edges, as well as modules that included inflammatory response, angiogenesis, negative regulation of the apoptotic process, and positive regulation of cell proliferation and migration. It was examined by conducting experiments that involved the administration of ethanol-based extracts of FTF in Lewis lung carcinoma mice. The extracts exerted excellent anti-lung cancer effects in vivo by significantly inhibiting tumor proliferation, thereby extending the survival period of tumor-bearing mice. Moreover, FTF induced the downregulation of PIK3CG, Bcl-2, eNOS, VEGF, p-STAT3, and STAT3 genes in tumor-bearing mice. CONCLUSIONS: The findings of the present study verify the therapeutic effects and mechanism of FTF on lung cancer and provide a theoretical basis to support the comprehensive utilization of FTF resources.

MicroRNA-4500 Inhibits Migration, Invasion, and Angiogenesis of Breast Cancer Cells via RRM2-Dependent MAPK Signaling Pathway.

With the consideration of the dynamic role of microRNAs (miRNAs) in breast cancer, miRNAs may serve as therapeutic targets, helping to prevent development of therapy resistance, maintain stable disease, and prohibit metastatic spread. We identified the differentially expressed breast cancer-related gene ribonucleotide reductase subunit M2 (RRM2) as the study focus through microarray expression profiles. Next, the upstream regulatory microRNA (miR)-4500 of RRM2 was predicted using bioinformatics website analysis, and their binding was verified by a dual luciferase reporter gene assay. The regulatory effects of miR-4500 on breast cancer cell proliferation, apoptosis, migration, invasion, and capillary-like tube formation of endothelial cells were assessed by gain- and loss-of-function experiments. The experimental data revealed that miR-4500 was downregulated, whereas RRM2 was upregulated in breast cancer cells. Mechanistic analysis revealed that miR-4500 downregulated the RRM2 expression to inactivate the mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, miR-4500 exerted anti-tumor effects by targeting RRM2 through suppression of the MAPK signaling pathway in vitro, evidenced by attenuated cancer cell migration and invasion and capillary-like tube formation of endothelial cells. The in vivo experiments further corroborated in vitro results. Collectively, overexpressed miR-4500 could downregulate RRM2 and inhibit activation of the MAPK signaling pathway, thus attenuating breast cancer cell proliferation, invasion, migration, and angiogenesis and promoting breast cancer cell apoptosis.

Correlation between UGT1A1 gene polymorphism and irinotecan chemotherapy in metastatic colorectal cancer: a study from Guangxi Zhuang.

BACKGROUND: There are obviously ethnic differences between the UGT1A1 gene polymorphisms. Due to the difference of genetic background and environment, the treatment with colorectal cancer patients of Guangxi Zhuang should not completely follow the Euramerican or Chinese han patients. The study aimed to explore the correlation of UGT1A1 gene polymorphism of Guangxi Zhuang metastatic colorectal cancer (mCRC) with irinotecan -based chemotherapy, in order to develop an individualized irinotecan regimen for mCRC patients of Guangxi Zhuang. METHODS: From June 2013 and June 2015, a total of 406 patients of Guangxi who were histologically diagnosed as metastatic colorectal cancer with 102 patients of this cohort with three generations of Zhuang, and 86 patients that conformed to inclusion and exclusion criteria were competitively enrolled. The distribution of UGT1A1 gene polymorphism was analyzed-retrospectively in all patients. Pyrosequencing method was used to detect the UGT1A1*28 and*6 gene polymorphism in the 86 Guangxi Zhuang mCRC patients. After first-line chemotherapy with FOLFIRI regimen, the relationship between gene polymorphism of UGT1A1 and adverse reactions, and efficacy of Irinotecan were analyzed with χ2 test and Kaplan-Meier method. RESULTS: UGT1A1*28 wild-type (TA6/6), heterozygous mutant (TA6/7) and homozygous mutant (TA7/7) accounted for 69.8, 30.2 and 0%, respectively. UGT1A1*6 wild type (G/G), heterozygous mutation type (G/A) and homozygous mutant (A/A) accounted for 76.7%, 20.9 and 2.3%, respectively. UGT1A1*28 TA6/7 type could increase the risk of grade 3~4 diarrhea (p = 0.027), which did not increase the risk of grade 3~4 neutropenia (p = 0.092). UGT1A1*6G/A and A/A type could increase the risk of grade 3~4 diarrhea and neutropenia (p = 0.001; p = 0.017). After chemotherapy with FOLFIRI, there was no significant difference in response rate (RR) (p = 0.729; p = 0.745) or in median progression-free survival (mPFS) between the wild-type, mutant treatment of UGT1A1*28 and UGT1A1*6 (7.0 m vs 7.4 m, p = 0.427; 6.9 m vs 7.0 m p = 0.408). CONCLUSIONS: The distribution of UGT1A1*28 and UGT1A1*6 gene polymorphism in Guangxi Zhuang patients were differed from the existing reported of European people and Chinese Han population. The UGT1A1 gene polymorphism with irinotecan chemotherapy-associated diarrhea and neutropenia were closely related. There was no significant association between UGT1A1 gene polymorphism and therapeutic efficacy of irinotecan.

MicroRNA-145 suppresses epithelial to mesenchymal transition in pancreatic cancer cells by inhibiting TGF-ß signaling pathway.

TGF-ß signaling plays a critical role in tumor progression and many approaches have been made to inhibit its functions. MicroRNA is one of the approaches that inhibit TGF-ß signaling and can be used as a promising treatment for cancer. This study explored the role of miRNA-145 in pancreatic cancer (PC) development. The expression of miRNA-145 in PC tissues and paired adjacent normal tissues was examined by qRT-PCR. The expression of miRNA-145 in PC cells and the ability of cell migration and invasion were detected both in vivo and in vitro. The results showed that miRNA-145 was down-regulated in PC tissues and PC cells. Increasing the expression of miRNA-145 in PC cells inhibited the TGF-ß signaling pathway and epithelial-mesenchymal transition (EMT) process. Scratch assay and transwell assay showed that miRNA-145 inhibited the migration and invasion in PC cells. In vivo experiments confirmed that miRNA-145 mimics delayed the growth of PC xenografts comparing with miRNA-145 inhibitor. Our results suggested that miRNA-145 can inhibit epithelial to mesenchymal transition (EMT) and tumor growth by suppressing TGF-ß signaling pathway. Thus, miRNA-145 could be a potential therapeutic for targeting TGF-ß signaling in PC treatment.

Citrate-based fluorophore-modified cellulose nanocrystals as a biocompatible fluorescent probe for detecting ferric ions and intracellular imaging.

In this contribution, citrate-based fluorophore (CF)-modified cellulose nanocrystals (CNCs) were prepared in a facile manner using sulfuric acid hydrolysis of citric acid/cysteine-treated microcrystalline celluloses. These rod-like CNCs have an average length of 156 nm and an average width of 7.9 nm. Because of conjugated CFs, these CNCs exhibit typical fluorescence characteristics, including a maximum excitation wavelength at 350 nm, maximum emission wavelength at 435 nm, high quantum yield of 83%, and good photostability. More importantly, these fluorescent CNCs exhibit a selective quenching effect toward Fe3+ ions; meanwhile, these CNCs exhibit negligible cytotoxicity and were internalized by cells. Therefore, these CNCs can be used as a fluorescence probe for detecting Fe3+ ions in living cells.