Development and validation of a nomogram for predicting poor operative visibility during FESS in Chinese adult patients with CRS.

Objective: The purpose of this study is to develop and evaluate a nomogram that is capable of predicting poor operative visibility during functional endoscopic sinus surgery. Method: To identify potential risk factors, patients with chronic rhinosinusitis who underwent functional endoscopic sinus surgery (FESS) between January 2019 and December 2022 were selected from our hospital's electronic medical record system. Data on general patient information, clinical manifestations, clotting-related test indices, Lund-Machay score of sinuses CT scanning, Lund-kennedy score of nasal endoscopies, anesthesia methods, intraoperative blood pressure and heart rate, and Boezaart bleeding score were collected. Minimum absolute convergence and selection operator (LASSO) regression, as well as multivariate logistic regression, were used to determine the risk factors. A nomogram was developed in order to predict poor operating visibility during FESS, and its performance was evaluated utilizing both the training and verification datasets via various measures including receiver operating characteristic (ROC) curve analysis, area under the curve (AUC), Hosmer-Lemeshow goodness-of-fit test, calibration curve, and decision curve analysis. Results: Of the 369 patients who met the inclusion criteria, 88 of them exhibited POV during FESS. By deploying LASSO and multivariate logistic regression analyses, six risk factors were identified and used to construct a nomogram for predicting POV during FESS. These factors include prothrombin time (PT), prothrombin activity (PTA), Lund-Mackay score (LMS), Lund-Kennedy score (LKS), anesthetic method, and intraoperative hypertension. The AUC of the training set was found to be 0.820 while that of the verification set was 0.852. The Hosmer-Lemeshow goodness-of-fit test and calibration curve analysis revealed good consistency between predicted and actual probabilities. Also, the decision curve demonstrated that the nomogram had a high degree of clinical usefulness and net benefit. Conclusion: The constructed nomogram has a strong ability to predict the poor intraoperative field in patients with chronic rhinosinusitis, which can help preoperative judgment of high-risk patients and provide evidence for perioperative management and preoperative plan formulation.

Expansion of human megakaryocyte-biased hematopoietic stem cells by biomimetic Microniche.

Limited numbers of available hematopoietic stem cells (HSCs) limit the widespread use of HSC-based therapies. Expansion systems for functional heterogenous HSCs remain to be optimized. Here, we present a convenient strategy for human HSC expansion based on a biomimetic Microniche. After demonstrating the expansion of HSC from different sources, we find that our Microniche-based system expands the therapeutically attractive megakaryocyte-biased HSC. We demonstrate scalable HSC expansion by applying this strategy in a stirred bioreactor. Moreover, we identify that the functional human megakaryocyte-biased HSCs are enriched in the CD34+CD38-CD45RA-CD90+CD49f lowCD62L-CD133+ subpopulation. Specifically, the expansion of megakaryocyte-biased HSCs is supported by a biomimetic niche-like microenvironment, which generates a suitable cytokine milieu and supplies the appropriate physical scaffolding. Thus, beyond clarifying the existence and immuno-phenotype of human megakaryocyte-biased HSC, our study demonstrates a flexible human HSC expansion strategy that could help realize the strong clinical promise of HSC-based therapies.

Efficacy and Safety of Anlotinib Combined with PD-1 Blockades for Patients with Previously Treated Epithelial Ovarian Cancer: A Retrospective Study.

Purpose: This study was to investigate the efficacy and safety of anlotinib combined with programmed cell death protein 1 (PD-1) blockades for patients with previously treated advanced epithelial ovarian cancer (EOC). Patients and Methods: Present study was designed as a retrospective study, a total of 32 patients with advanced EOC who progressed after at least two lines previously available standard therapy were included in this study. All the patients were administered with anlotinib combined with PD-1 blockades administration. Clinical activity was implemented and analyzed, which was assessed according to the change of target lesion by imaging evidence and all the subjects were followed up regularly. Safety profile were collected and documented during the treatment. Univariate analysis was carried out using log rank test and multivariate analysis were adjusted by Cox regression analysis. Results: The best overall response suggested that partial response was noted in 12 patients, stable disease was observed in 14 patients, progressive disease was found in 6 patients. Therefore, the objective response rate (ORR) of the 32 patients was 37.5% (95% CI: 21.1-56.3%), disease control rate (DCR) of the patients was 81.3% (95% CI: 63.6-92.8%). The median follow-up duration of this study was 17.5 months (follow-up range: 0.9-33.5 months). And the median PFS and OS of the 32-patient cohort was 6.8 months (95% CI: 2.64-10.96) and 18.5 months (95% CI: 14.08-22.92), respectively. The most common treatment-related adverse reactions were fatigue (68.8%), nausea and vomiting (56.3%), hypertension (50.0%) and diarrhea (40.6%). Multivariate Cox regression analysis for PFS indicated that ECOG performance status and FIGO stage were independent factors to predict PFS of patients with previously treated EOC. Conclusion: Anlotinib combined with PD-1 blockades demonstrated promising efficacy and tolerable safety profile for patients with previously treated advanced EOC preliminarily. The conclusion should be confirmed in more patients with advanced EOC subsequently.

Observation on the effect of periodontal treatment on patients with combined periodontal-pulpal lesions.

OBJECTIVE: To evaluate the effect of periodontal treatment on combined periodontal-pulpal lesions. METHODS: A total of 327 patients with periodontal-pulpal lesions (360 affected teeth) were selected, and all affected teeth were treated with a complete root canal, and assigned into group A (periodontal treatment group, 180 affected teeth) and group B (non-periodontal treatment group, 180 affected teeth). Group A received periodontal basic treatment for 2 weeks after the completion of root canal treatment; 6 weeks later, if there were still more than 5 mm periodontal pockets and bleeding after detection, flap treatment was performed. Group B received root canal treatment and supragingival scaling. Follow-up was conducted at 3, 6, 12 and 24 months after surgery by observing the periodontal depth (PD), alveolar bone resorption and tooth mobility (TM). RESULT: In group A, the PDs before operation and 2 years after operation were (5.966±1.877) mm and (5.133±1.935) mm, and the PD was significantly decreased. In group B, the PDs before operation and 2 years after operation were (5.533±1.856) mm and (6.167±1.927) mm, and the PD was increased. There was no statistical difference in preoperative TM between the two groups (P>0.05). Two years after operation, TM in group A was significantly lower than that in group B (P<0.05). In terms of X-ray performance, there was no significant change in alveolar bone resorption in group A two years after operation compared with that before operation (P>0.05); two years after operation, alveolar bone resorption in group B was significantly reduced compared with that before operation (P<0.05). CONCLUSION: Periodontal treatment is a promising technique for patients with combined periodontal-pulpal lesions.

Characterization of type I and type II diacylglycerol acyltransferases from the emerging model alga Chlorella zofingiensis reveals their functional complementarity and engineering potential.

BACKGROUND: The green alga Chlorella zofingiensis has been recognized as an industrially relevant strain because of its robust growth under multiple trophic conditions and the potential for simultaneous production of triacylglycerol (TAG) and the high-value keto-carotenoid astaxanthin. Nevertheless, the mechanism of TAG synthesis remains poorly understood in C. zofingiensis. Diacylglycerol acyltransferase (DGAT) is thought to catalyze the committed step of TAG assembly in the Kennedy pathway. C. zofingiensis genome is predicted to possess eleven putative DGAT-encoding genes, the greatest number ever found in green algae, pointing to the complexity of TAG assembly in the alga. RESULTS: The transcription start site of C. zofingiensis DGATs was determined by 5'-rapid amplification of cDNA ends (RACE), and their coding sequences were cloned and verified by sequencing, which identified ten DGAT genes (two type I DGATs designated as CzDGAT1A and CzDGAT1B, and eight type II DGATs designated as CzDGTT1 through CzDGTT8) and revealed that the previous gene models of seven DGATs were incorrect. Function complementation in the TAG-deficient yeast strain confirmed the functionality of most DGATs, with CzDGAT1A and CzDGTT5 having the highest activity. In vitro DGAT assay revealed that CzDGAT1A and CzDGTT5 preferred eukaryotic and prokaryotic diacylglycerols (DAGs), respectively, and had overlapping yet distinctive substrate specificity for acyl-CoAs. Subcellular co-localization experiment in tobacco leaves indicated that both CzDGAT1A and CzDGTT5 were localized at endoplasmic reticulum (ER). Upon nitrogen deprivation, TAG was drastically induced in C. zofingiensis, accompanied by a considerable up-regulation of CzDGAT1A and CzDGTT5. These two genes were probably regulated by the transcription factors (TFs) bZIP3 and MYB1, as suggested by the yeast one-hybrid assay and expression correlation. Moreover, heterologous expression of CzDGAT1A and CzDGTT5 promoted TAG accumulation and TAG yield in different hosts including yeast and oleaginous alga. CONCLUSIONS: Our study represents a pioneering work on the characterization of both type I and type II C. zofingiensis DGATs by systematically integrating functional complementation, in vitro enzymatic assay, subcellular localization, yeast one-hybrid assay and overexpression in yeast and oleaginous alga. These results (1) update the gene models of C. zofingiensis DGATs, (2) shed light on the mechanism of oleaginousness in which CzDGAT1A and CzDGTT5, have functional complementarity and probably work in collaboration at ER contributing to the abundance and complexity of TAG, and (3) provide engineering targets for future trait improvement via rational manipulation of this alga as well as other industrially relevant ones.

Differential responses of the green microalga Chlorella zofingiensis to the starvation of various nutrients for oil and astaxanthin production.

Chlorella zofingiensis has been proposed as a potential producer of lipids and the high-value carotenoid astaxanthin. In this study, the responses of photoautotrophic C. zofingiensis with respect to growth, lipid profiles and astaxanthin accumulation were investigated upon the starvation of N (NS), P (PS) and S (SS). NS and SS stimulated triacylglycerol (TAG) accumulation, which reached 27% and 21% of dry weight (DW), respectively. Stresses also stimulated astaxanthin accumulation greatly, reaching 3.9 mg/g DW by NS. SS led to the highest TAG productivity (52.4 mg L-1 d-1) while NS gave rise to the highest astaxanthin productivity (0.624 mg L-1 d-1). In combination with transcriptional analysis, a working model for stress-associated TAG and astaxanthin biosynthesis was proposed. Taken together, these detailed data shed light on the elucidation of differential responses to nutrient stresses and may provide insights into future engineering of this promising alga for improving TAG and astaxanthin production.

Malignant changes in adenomyosis in patients with endometrial adenocarcinoma: A case series.

The aim of the study is to describe the clinical characteristics and prognosis of malignant transformation of adenomyosis in patients with endometrial cancer.In this retrospective descriptive study, the clinical data of patients with endometrial cancer (n = 127) who were admitted at our hospital between January 2006 and December 2013 were evaluated.Among the 127 patients with endometrial cancer, 24 patients had endometrial cancer concurrently with adenomyosis. Among these 24 patients, 3 were diagnosed with malignant transformation of adenomyosis. Postoperative pathological investigations in the cancer+adenomyosis group revealed endometrial adenocarcinoma of Grade I (n = 21) and II (n = 3). The patients with malignant transformation of adenomyosis were relatively younger than the other patients. In those 3 patients, both the estrogen and progesterone receptors were strongly expressed in eutopic endometrium and were weakly positive in ectopic endometrium.Although adenomyosis is usually benign, it might also be a precursor of malignant disease. As the incidence of adenomyosis malignant transformation is low, and its clinical manifestations are nonspecific, it may only be confirmed by postoperative pathological examination. Further investigations on larger sample size may provide additional data about prognosis of adenomyosis malignant transformation.

Association of CYP1A1 and GSTM1 Polymorphisms With Oral Cancer Susceptibility: A Meta-Analysis.

Our meta-analysis was aimed to evaluate the association of CYP1A1 and glutathione-S-transferase M1 (GSTM1) polymorphisms with oral cancer susceptibility.The related articles were searched in PubMed, Embase, and CNKI databases. Fifty eligible studies were included in our meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the relationship of CYP1A1 (rs4646903 and rs1048943) and GSTM1 polymorphisms with oral cancer risk. A random-effects model or fixed-effects model was employed depending on the heterogeneity.In overall analysis, CYP1A1 rs4646903 polymorphism was associated with the risk of oral cancer (CC vs TT: OR 1.65, 95% CI 1.33-2.05; CC vs TC+TT: OR 1.77, 95% CI 1.48-2.11; C vs T: OR 1.17, 95% CI 1.07-1.28), whereas rs1048943 showed no obvious association with oral cancer susceptibility. Moreover, subgroup analysis by ethnicity demonstrated that rs4646903 and rs1048943 both related with increased risk of oral cancer in Asians. Moreover, the analysis based on source of control suggested that rs4646903 could increase the risk for oral cancer in both population- and hospital-based populations, whereas no remarkable relationship of rs1048943 with oral cancer susceptibility was observed. For GSTM1 gene, null genotype appeared to be a risk factor for oral cancer (null vs present: OR 1.23, 95% CI 1.12-1.34), which was also proved in the subgroup analysis.The results demonstrated that CYP1A1 rs4646903 and null genotype of GSTM1 polymorphisms might serve as risk factors for oral cancer.