Predicting the Prognosis and Immunotherapeutic Response of Triple-Negative Breast Cancer by Constructing a Prognostic Model Based on CD8+ T Cell-Related Immune Genes.

Objective: Triple-negative breast cancer (TNBC) poses a significant challenge for treatment efficacy. CD8+ T cells, which are pivotal immune cells, can be effectively analyzed for differential gene expression across diverse cell populations owing to rapid advancements in sequencing technology. By leveraging these genes, our objective was to develop a prognostic model that accurately predicts the prognosis of patients with TNBC and their responsiveness to immunotherapy. Methods: Sample information and clinical data of TNBC were sourced from The Cancer Genome Atlas and METABRIC databases. In the initial stage, we identified 67 differentially expressed genes associated with immune response in CD8+ T cells. Subsequently, we narrowed our focus to three key genes, namely CXCL13, GBP2, and GZMB, which were used to construct a prognostic model. The accuracy of the model was assessed using the validation set data and receiver operating characteristic (ROC) curves. Furthermore, we employed various methods, including Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, immune infiltration, and correlation analyses with CD274 (PD-L1) to explore the model's predictive efficacy in immunotherapeutic responses. Additionally, we investigated the potential underlying biological pathways that contribute to divergent treatment responses. Results: We successfully developed a model capable of predicting the prognosis of patients with TNBC. The areas under the curve (AUC) values for the 1-, 3-, and 5-year survival predictions were 0.618, 0.652, and 0.826, respectively. Employing this risk model, we stratified the samples into high- and low-risk groups. Through KEGG enrichment analysis, we observed that the high-risk group predominantly exhibited enrichment in metabolism-related pathways such as drug and chlorophyll metabolism, whereas the low-risk group demonstrated significant enrichment in cytokine pathways. Furthermore, immune landscape analysis revealed noteworthy variations between (PD-L1) expression and risk scores, indicating that our model effectively predicted the response of patients to immune-based treatments. Conclusion: Our study demonstrates the potential of CXCL13, GBP2, and GZMB as prognostic indicators of clinical outcomes and immunotherapy responses in patients with TNBC. These findings provide valuable insights and novel avenues for developing immunotherapeutic approaches targeting TNBC.

Aesthetic Preferences for Beautiful Buttocks in Female: A Study on the Chinese Population.

BACKGROUND: Many theories referring to the conception of a beautiful buttock have been put forward, but little has been proved, especially in the Asian group. OBJECTIVE: To analyse the aesthetic preference for aesthetically pleasing characteristics in the Chinese population. METHODS: In the survey, we computerized the buttock image of a Chinese female through the Photoshop software (Adobe Photoshop CS5; Adobe Systems, Inc., San Jose, Calif), and buttocks with and without four features were attained. An online questionnaire was made to rank the most aesthetic buttocks. The data for the various demographic groups were compared using the Pearson Chi-square test. A value of p < 0.05 was used for statistical significance. RESULTS: In total, 2348 responses were collected. Over half of the respondents prefer without supragluteal fossettes (56.9%), V-shaped crease (60.4%) and lateral depression (90.1%). The most attractive infragluteal fold option was short type (34.9%), followed by median infragluteal fold (32.7%) and long infragluteal fold (32.4%). Supragluteal fossettes, median or long infragluteal fold and V-shaped crease were more preferred among young people. CONCLUSION: Supragluteal fossettes, V-shaped crease and lateral depressions were not preferred in over half of the respondents. The aesthetic preference was influenced by the gender and age. The plastic surgeons should consider the variabilities above when establishing aesthetic aim for beautiful buttocks in gluteoplasty. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Probabilistic Presurgical Language Functional MRI Atlas of Brain Tumor Patients.

BACKGROUND AND PURPOSE: Patients with brain tumors have high intersubject variation in putative language regions, which may limit the utility of straightforward application of healthy-subject brain atlases in clinical scenarios. The purpose of this study was to develop a probabilistic functional brain atlas that consolidates language functional activations of sentence completion and silent word generation language paradigms using a large sample of patients with brain tumors. MATERIALS AND METHODS: The atlas was developed using retrospectively collected fMRI data from patients with brain tumors who underwent their first standard-of-care presurgical language fMRI scan at our institution between July 18, 2015, and May 13, 2022. 317 patients (861 fMRI scans) were used to develop the language functional atlas. An independent presurgical language fMRI dataset of 39 patients with brain tumors from a previous study was used to evaluate our atlas. Family-wise error corrected binary functional activation maps from sentence completion, letter fluency, and category fluency presurgical fMRI were used to create probability overlap maps and pooled probabilistic overlap map in Montreal Neurological Institute standard space. Wilcoxon signed-rank test was used to determine significant difference in the maximum Dice coefficient for our atlas compared to a meta-analysis-based template with respect to expert-delineated primary language area activations. RESULTS: Probabilities of activating left anterior primary language area and left posterior primary language area in temporal lobe were 87.9% and 91.5%, respectively, for sentence completion, 88.5% and 74.2%, respectively, for letter fluency, and 83.6% and 67.6%, respectively, for category fluency. Maximum Dice coefficients for templates derived from our language atlas were significantly higher than the meta-analysis-based template in left anterior primary language area (0.351 and 0.326, respectively, P < .05) and left posterior primary language area in temporal lobe (0.274 and 0.244, respectively, P < .005). CONCLUSIONS: Brain tumor patient-and paradigm-specific probabilistic language atlases were developed. These atlases had superior spatial agreement with fMRI activations in individual patients than the meta-analysis-based template. ABBREVIATIONS: SENT = sentence completion, LETT = letter fluency, CAT = category fluency, PLA = primary language area, aPLA = anterior PLA, pPLAT = posterior PLA in the temporal lobe, pPLAP = posterior PLA in the parietal lobe, SMA = supplementary motor area, DLPFC = dorsolateral prefrontal cortex, BTLA = basal temporal language area.

Effect of contrast agent on T2-weighted fat-suppressed imaging and diffusion-weighted imaging in the diagnosis of breast tumors.

Background: Although previous studies have shown that the injection of contrast agents can improve image quality, the specific impact of this on T2-weighted fat-suppressed (T2 FS) and diffusion-weighted imaging (DWI) sequences in the diagnosis of breast cancer remains incompletely understood. In particular, there is insufficient research on how contrast agents affect the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC) values within these sequences, and how these changes influence the diagnosis of benign and malignant breast tumors. Methods: Breast magnetic resonance images (MRI) were obtained from 178 consecutive patients on a 3T scanner. The SNR and CNR of lesions on T2 FS sequence were calculated before and after contrast agent injection and compared. Differences between pre- and post-contrast ADC in identifying different tumor types were compared using the Kruskal-Wallis H-test and the paired comparison test. The accuracy of ADC values between pre- and post-contrast in distinguishing benign and malignant breast masses was assessed using receiver operating characteristic (ROC) curves. Results: The SNR and CNR of T2 FS sequence increased after contrast injection, and especially for invasive cancer and benign tumor, the increase was significant. For DWI, there was a slight increase or decrease of ADC values after contrast injection, but the ADC values before and after contrast had a similar effect in identifying different types of tumors. In the ROC curve analysis for assessing benign and malignant breast tumors, the area under the curve (AUC) before and after contrast showed similar results. Conclusions: Contrast agent injection can improve the SNR and CNR of T2 FS sequence, thus providing higher quality images for the diagnosis of breast lesions. Furthermore, injection of contrast agent had little effect on the ability of ADC values to identify different types of lesions and both ADC values before and after the contrast agent were able to distinguish between benign and malignant tumors with almost the same accuracy.

Preparation of iron oxide-modified digestate biochar and effect on anaerobic digestion of kitchen waste.

Two kinds of Fe2O3-modified digestate-derived biochar (BC) were prepared and their effects on anaerobic digestion (AD) of kitchen waste (40.0 g VS/L) were investigated, with BC and Fe2O3 addition used as a comparison. The results showed that Fe2O3-modified BC (Fe2O3-BC1 prepared by co-precipitation and Fe2O3-BC2 by impregnation) significantly increased methane yield (20.8 % and 16.4 %, respectively) and reduced volatile fatty acid concentration (35.6 % and 29.6 %, respectively). Microbial high-throughput analysis revealed that Fe2O3-modified BC selectively enriched Clostridium (47.3 %) and Methanosarcina (72.2 %), suggesting that direct interspecies electron transfer contributing to improved biogas production performance was established and enhanced. Correlation analysis indicated that biogas production performance was improved by the larger specific surface area (83.4 m2/g), pore volume (0.101 cm3/g), and iron content (97.4 g/Kg) of the BC. These results offer insights for enhancing the efficacy of AD processes using Fe2O3-modified BCs as additives.

Enhancement of methane production from anaerobic digestion of Erigeron canadensis via O2-nanobubble water supplementation.

Malignant invasive Erigeron canadensis, as a typical lignocellulosic biomass, is a formidable challenge for sustainable and efficient resource utilization, however nanobubble water (NBW) coupled with anaerobic digestion furnishes a prospective strategy with superior environmental and economic effectiveness. In this study, influence mechanism of various O2-NBW addition times on methanogenic performance of E. canadensis during anaerobic digestion were performed to achieve the optimal pollution-free energy conversion. Results showed that supplementation of O2-NBW in digestion system could significantly enhance the methane production by 10.70-16.17%, while the maximum cumulative methane production reached 343.18 mL g-1 VS in the case of one-time O2-NBW addition on day 0. Furthermore, addition of O2-NBW was conducive to an increase of 2-90% in the activities of dehydrogenase, α-glucosidase and coenzyme F420. Simultaneously, both facultative bacteria and methanogenic archaea were enriched as well, further indicating that O2-NBW might be responsible for facilitating hydrolytic acidification and methanogenesis. Based on Kyoto Encyclopedia of Genes and Genomes (KEGG) cluster analysis, provision of O2-NBW enhanced the metabolism of carbohydrate and amino acid, translation as well as membrane transport of bacteria and archaea. This study might offer the theoretical guidance and novel insights for efficient recovery of energy from lignocellulosic biomass on account of O2-NBW adhibition in anaerobic digestion system, progressing tenor of carbon-neutral vision.

Prenatal ultrasound diagnosis and prognosis of fetus with isolated filar cyst: a retrospective analysis.

Objective: This study aimed to investigate the prenatal ultrasonographic diagnosis and prognosis of fetuses with isolated filar cysts (FCs). Methods: The ultrasonographic features, reasons for missed diagnosis, and prognosis of eight isolated FCs diagnosed using ultrasound were analyzed retrospectively through follow-up. Results: Eight isolated FCs showed round or fusiform cystic anechoic areas at the end of the conus medullaris. Among them, six cases were prenatally diagnosed and the other two cases were diagnosed after birth. Of the six cases diagnosed prenatally, four (66.7%) disappeared during pregnancy, and the shortest time to disappearance was 1 month after the first diagnosis. All patients were followed up without any clinical symptoms or functional abnormalities. Conclusion: Isolated FCs may exhibit physiological variations that disappear spontaneously during pregnancy and usually have no clinical symptoms. They are usually benign and have a good prognosis. Ultrasonography is helpful for the diagnosis and follow-up of FCs.

Medical financial hardship between young adult cancer survivors and matched individuals without cancer in the United States.

BACKGROUND: Young adult cancer survivors face medical financial hardships that may lead to delaying or forgoing medical care. This study describes the medical financial difficulties young adult cancer survivors in the United States experience in the post-Patient Protection and Affordable Care Act period. METHOD: We identified 1009 cancer survivors aged 18 to 39 years from the National Health Interview Survey (2015-2022) and matched 963 (95%) cancer survivors to 2733 control individuals using nearest-neighbor matching. We used conditional logistic regression to examine the association between cancer history and medical financial hardship and to assess whether this association varied by age, sex, race and ethnicity, and region of residence. RESULTS: Compared with those who did not have a history of cancer, young adult cancer survivors were more likely to report material financial hardship (22.8% vs 15.2%; odds ratio = 1.65, 95% confidence interval = 1.50 to 1.81) and behavior-related financial hardship (34.3% vs 24.4%; odds ratio = 1.62, 95% confidence interval = 1.49 to 1.76) but not psychological financial hardship (52.6% vs 50.9%; odds ratio = 1.07, 95% confidence interval = 0.99 to 1.16). Young adult cancer survivors who were Hispanic or lived in the Midwest and South were more likely to report psychological financial hardship than their counterparts. CONCLUSIONS: We found that young adult cancer survivors were more likely to experience material and behavior-related financial hardship than young adults without a history of cancer. We also identified specific subgroups of young adult cancer survivors that may benefit from targeted policies and interventions to alleviate medical financial hardship.

GPX2 acts as an oncogene and cudraflavone C has an anti-tumor effect by suppressing GPX2-dependent Wnt/ß-catenin pathway in colorectal cancer cells.

Colorectal carcinoma (CRC) is a common cancer associated with poor prognosis, and cudraflavone C (Cud C) is a natural flavonol with reported anti-CRC capacity. However, the precise mechanisms underlying the anti-CRC effect require further demonstration. The aim of present study was to evaluate the impact of Cud C on the cell viability and apoptosis of CRC cells and to determine the underlying mechanisms. The Human Protein Atlas (THPA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases were used to analyze the expression status of glutathione peroxidase 2 (GPX2) in CRC. Cell viability was examined using cell counting kit-8 (CCK-8) assay. Flow cytometry was utilized to evaluate apoptosis. The levels of gene transcription and protein expression of GPX2, caspase-3, cleaved caspase-3), ß-catenin, and c-Myc were determined by RT-qPCR and Western blotting. Our results showed that GPX2 was overexpressed in CRC as compared to normal tissue and the extent of GPX2 overexpression is greatest in CRC when compared with other cancers according to GEPIA and THPA databases. GPX2 knockdown significantly suppressed the cell viability, induced apoptosis of CRC cell lines, and restrained the activity of Wnt/ß-catenin pathway. Cud C treatment decreased cell viability, induced apoptosis in CRC cell lines, and diminished the expression level of GPX2-dependent activation of Wnt/ß-catenin pathway, while such effects can be abolished by GPX2 overexpression. In conclusion, Cud C suppressed GPX2-dependent Wnt/ß-catenin pathway to exert anti-CRC function.

Long-term outcomes of vulvar or vaginal cancer patients undergoing laparoendoscopic single-site inguinal lymphadenectomy.

INTRODUCTION: Laparoendoscopic single-site inguinal lymphadenectomy (LESS-IL), a minimally invasive technique, has been reported in patients with vulvar or vaginal cancer regarding its safety and feasibility. However, the long-term outcomes, especially oncologic outcomes, are still lacking. We aimed to evaluate the long-term outcomes of LESS-IL to confirm its safety further. PATIENTS AND METHODS: Data were prospectively collected from patients with vulvar or vaginal cancer who underwent LESS-IL at our institution between July 2018 and June 2021. The patients were followed up for at least 12 months. All procedures were performed according to treatment standards. Short- and long-term complications and oncologic outcomes were analysed. RESULTS: A total of 16 patients undergoing 28 LESS-IL procedures were identified, amongst whom 4 underwent unilateral LESS-IL. The median numbers of excised groin lymph nodes were 9.0 (6.5-11.8) and 10.5 (8.3-12.0) in each left and right groin, respectively. Short-term complications occurred in 4 (25%) patients, including 18.7% lymphocele and 6.3% wound infection. Long-term complications regarding lower-limb lymphoedema appeared in 6 (37.5%) patients. Most short- and long-term complications were Clavien-Dindo 1 or 2, accounting for 90% of all post-operative issues. After a median follow-up of 27 (21.3-35.8) months, only 1 (6.3%) patient had isolated inguinal recurrence at 13 months postoperatively. No local or distant recurrence occurred. CONCLUSION: Our results suggest that LESS-IL is associated with little incidence of complications and promising oncologic outcomes, further demonstrating the safety and feasibility of the LESS-IL technique in patients requiring IL.

Molecular typing and prognostic risk models for ovarian cancer: a study based on cell differentiation trajectory.

Ovarian cancer is a heterogeneous disease with different molecular phenotypes. We performed molecular typing of ovarian cancer using cell differentiation trajectory analysis and proposed a prognostic risk scoring model. Using the copy number variation provided by inferCNV, we identified malignant tumor cells. Then, ovarian cancer samples were divided into four subtypes based on differentiation-related genes (DRGs). There were significant differences in survival rates, clinical features, tumor microenvironment scores, and the expression levels of ICGs among the subtypes. Based on nine DRGs, a prognostic risk score model was generated (AUC at 1 year: 0.749; 3 years: 0.651). Then we obtained a nomogram of the prognostic variable combination, including risk scores and clinicopathological characteristics, and predicted the 1-, 3- and 5-year overall survival. Finally, we explored some issues of immune escape using the established risk model. Our study demonstrates the significant influence of cell differentiation on predicting prognosis in OV patients and provides new insights for OV treatment and potential immunotherapeutic strategies.

Comparing vagus nerve stimulation and resective surgery outcomes in patients with co-occurring autism and epilepsy to patients with epilepsy alone: A population-based study.

Autism and epilepsy commonly co-occur. Understanding trends in healthcare utilization and in-hospital outcomes amongst patients with autism and epilepsy can help optimize care and reduce costs. We compared hospital outcomes amongst patients with autism and epilepsy to those with epilepsy alone undergoing vagus nerve stimulation (VNS) and resective/disconnective surgery. Differences in discharge status, in-hospital mortality, mean length of stay (LOS), cost and surgical/medical complications were examined. Elective surgical admissions amongst patients with epilepsy alone and co-occurring autism and epilepsy were identified in the 2003-14 National Inpatient Sample (NIS) using previously validated ICD-9-CM case definitions. One patient with co-occurring epilepsy and autism was matched to three epilepsy patients for age, sex and (1) VNS and (2) resective/disconnective surgery. Multinomial logistic regressions were performed to examine the outcomes of interest. Data were collected on: (1) VNS-52 (mean age: 12.79 ± 1.03; 19.27% female) hospital admissions in persons with comorbid autism and epilepsy, 156 (mean age: 12.84 ± 0.71; 19.31% female) matched controls with epilepsy alone; (2) resective/disconnective surgery-113 (mean age: 12.99 ± 0.84; 24.55% female) with comorbid autism and epilepsy, 339 (mean age: 13.37 ± 0.68; 23.86% female) matched controls with epilepsy alone. Compared to patients with epilepsy alone, patients with autism and epilepsy who underwent either surgery showed no differences for in-hospital mortality, discharge status, mean LOS, hospitalization cost, and surgical/medical complications. Our study shows the feasibility and safety of epilepsy VNS and resective surgery in those with ASD do not differ with those with epilepsy alone, contrary to the prevalent safety concerns of epilepsy surgery in patients with ASD.

[Clinicopathological Features of Primary Small Cell Neuroendocrine Carcinoma of the Bladder].

Objective To investigate the clinicopathological features,immunohistochemical features,diagnosis,and relationship with sporadic prostate cancer in primary small cell neuroendocrine carcinoma of the bladder. Methods We retrospectively analyzed the clinical characteristics of 12 patients with primary small cell neuroendocrine carcinoma of the bladder diagnosed at Beijing Chao-Yang Hospital affiliated to Capital Medical University from January 2013 to September 2022.The histological features of primary small cell neuroendocrine carcinoma of the bladder were re-evaluated by two pathologists according to the 2022 revision of the World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs.Electronic medical records were retrieved,and telephone follow-up was conducted from the time of histopathological diagnosis to the death or the end of the last follow-up until January 31,2023. Results The 12 patients include 7 patients in pT3 stage and 1 patient in pT4 stage.Eight patients were complicated with other types of tumors,such as high-grade urothelial carcinoma of the bladder and squamous cell carcinoma.Five patients had sporadic prostate cancer.Immunohistochemical staining showed that 12 (100.0%),10 (83.3%),and 8 (66.7%) patients were tested positive for CD56,Syn,and CgA,respectively.The Ki67 proliferation index ranged from 80% to 90%.Five patients with urothelial carcinoma were tested positive for CK20,GATA3,and CK7.P504S was positive in all the 5 patients with prostate cancer,while P63 and 34ßE12 were negative.The follow-up of the 12 patients lasted for 3-60 months.Eight of these patients died during follow-up,with the median survival of 15.5 months.Four patients survived. Conclusions Primary small cell neuroendocrine carcinoma of the bladder is a rare urological tumor with high aggressiveness and poor prognosis.In male patients with bladder prostatectomy,all prostate tissue should be sampled.If prostate cancer is detected,the prostate-specific antigen level should be monitored.

The Accurate Interpretation and Clinical Significance of Morphological Features of Fine Needle Aspiration Cells in Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) is the most common malignant neoplasm of the thyroid gland; fine needle aspiration cytology is the most basic and reliable diagnostic method before PTC operation. However, it is not clear which cell morphological changes can be used as a reliable standard for the diagnosis of PTC. A retrospective analysis was performed on 337 patients with PTC confirmed by postoperative histology. An additional 197 randomly selected patients with benign thyroid lesions were included in the study and used as a control group. True papillary arrangements, swirl arrangements, and escape arrangements had high specificity, all of which were 100%, but only swirl arrangements had ideal sensitivity (77.61%). The nuclear volume characteristics had a high sensitivity of more than 90%, but the specificities of both nuclear crowding and nuclear overlap were too low, only 16.34% and 23.35%. The sensitivities of five nuclear structural characteristics were more than 90%, but only the specificity of intranuclear cytoplasmic pseudoinclusions (INCIs) reached 100%, nuclear contour irregularity and pale nuclei with powdery chromatin also had ideal interpretation value except for grooves and marginally placed micronucleoli. Although the sensitivity of psammoma bodies (PBs) was low, the specificity was 100%. In terms of preparation methods, the method of liquid-based preparation (LBP) is obviously better than that of conventional smears. The diagnostic efficiency by the combined detection method of parallel tests showed that without reducing the specificity, the sensitivity increased with the increase of the number of morphological characteristics and finally reached 98.81%. The INCIs and swirl arrangements are the most common and important indicators for the diagnosis of PTC, whereas papillary-like arrangements, the crowding and overlap of nuclear, grooves, marginally placed micronucleoli, and multinucleated giant cells are of little significance for the diagnosis of PTC.

Surgical Treatment for Chest "Lock" Keloid Using Autologous Split-Thickness Skin Grafting and Postoperative Radiotherapy.

BACKGROUND: The treatment of chest "lock" keloids is challenging due to skin defects and a high recurrence rate. OBJECTIVE: Evaluation of the effectiveness of autologous split-thickness skin graft with local radiotherapy for treating chest "lock" keloids. METHODSAND MATERIALS: Fifty-seven patients with chest "lock" keloids were treated from July 2018 to September 2020. The skin defects were closed with an autologous split-thickness skin graft (STSG) and vacuum sealing drainage. The donor and the recipient sites received the first session of radiotherapy 72 hours postoperation for 3 consecutive days. Patients underwent follow-up examinations 12 months after surgery. The Patient and Observer Scar Assessment Scale (POSAS) was used to assess the treatment outcome. RESULTS: Except for the complaints of pain, which did not improve in the patients' assessments (p = .368), POSAS improved significantly after treatment (p < .0001). The cure rate (including cured and partially cured scars) was 100%. No keloid recurrence was observed during the follow-up period. CONCLUSION: The procedure of treating chest "lock" keloid by keloid debulking and autologous STSG followed by postoperational radiotherapy is a novel combined methodology for treating keloids.

The efficacy and safety of nanoparticle albumin bound-paclitaxel-based regimen as second- or third-line treatment in patients with advanced esophageal squamous cell carcinoma.

BACKGROUND: There are limited reports on nanoparticle albumin bound-paclitaxel (nab-paclitaxel) regimens as second- or third-line treatments for advanced esophageal squamous cell carcinoma (ESCC). Additionally, its safety and efficacy in ESCC patients after failure of first-line programmed cell death protein-1 (PD-1) blockade plus chemotherapy have not been reported. In this study, we aimed to assess the efficacy and tolerability of nab-paclitaxel regimens as second- or later-line treatment in advanced ESCC. METHODS: We retrospectively reviewed clinical data of advanced ESCC patients who participated in a randomized phase III clinical study and received serplulimab or placebo plus chemotherapy at our institution, and consecutive patients who received subsequent nab-paclitaxel-based regimens as second- or later-line treatment were included for data collection and analysis. RESULTS: A total of 39 patients were included, 25 (64.1%) received serplulimab plus chemotherapy and 14 (35.9%) received chemotherapy alone as first-line treatment. Treatment strategies included nab-paclitaxel monotherapy (7/39, 17.9%), or in combination with other chemotherapy (19/39, 48.7%), with anti-PD-1 antibodies (12/39, 30.8%) or with nimotuzumab (1/39, 2.6%). Overall, the objective response rate (ORR) and disease control rate (DCR) were 33.3% (13/39) and 61.5% (24/39), respectively. With a median follow-up of 9.7 months, the median progression-free survival and median overall survival were 5.0 and 7.9 months, respectively. The most common adverse events were neuropathy peripheral (30.8%), anemia (30.8%), neutrophil count decreased (23.1%), and nausea (20.5%). CONCLUSIONS: Nab-paclitaxel-based regimen could be a safe and effective option as second- or later-line treatment in patients with advanced ESCC, regardless of their previous exposure to PD-1 inhibitors.

Analysis of Significant Genes and Pathways in Esophageal Cancer Based on Gene Expression Omnibus Database.

Objective To screen antigen targets for immunotherapy by analyzing over-expressed genes, and to identify significant pathways and molecular mechanisms in esophageal cancer by using bioinformatic methods such as enrichment analysis, protein-protein interaction (PPI) network, and survival analysis based on the Gene Expression Omnibus (GEO) database.Methods By screening with highly expressed genes, we mainly analyzed proteins MUC13 and EPCAM with transmembrane domain and antigen epitope from TMHMM and IEDB websites. Significant genes and pathways associated with the pathogenesis of esophageal cancer were identified using enrichment analysis, PPI network, and survival analysis. Several software and platforms including Prism 8, R language, Cytoscape, DAVID, STRING, and GEPIA platform were used in the search and/or figure creation.Results Genes MUC13 and EPCAM were over-expressed with several antigen epitopes in esophageal squamous cell carcinoma (ESCC) tissue. Enrichment analysis revealed that the process of keratinization was focused and a series of genes were related with the development of esophageal cancer. Four genes including ALDH3A1, C2, SLC6A1,and ZBTB7C were screened with significant P value of survival curve.Conclusions Genes MUC13 and EPCAM may be promising antigen targets or biomarkers for esophageal cancer. Keratinization may greatly impact the pathogenesis of esophageal cancer. Genes ALDH3A1, C2, SLC6A1,and ZBTB7C may play important roles in the development of esophageal cancer.

Analysis of Patient-Reported Outcomes After Breast Reconstruction: A Retrospective Study.

OBJECTIVE: This study aimed to investigate the effects of surgical timing, procedure, and age, on complication rates, health-related quality of life, and postoperative satisfaction, in patients who underwent breast reconstruction. METHODS: The data of 80 patients who underwent breast reconstruction surgery between August 2004 and June 2018 were reviewed. Patients were grouped according to surgical timing, procedure, and age. The evaluation indicators included complications and BREAST-Q scores. The statistical methods used included the Mann-Whitney U test and analyses of variance and covariance. RESULTS: The incidence of complications was 15.0% (12/80). The complication rates were similar in each group ( P > 0.05). The postsurgical scores of patient satisfaction with breast, psychosocial well-being, and sexual well-being were higher than the presurgical scores ( P < 0.05). The postoperative psychosocial and sexual well-being scores of patients in the immediate group were higher than those in the delayed group ( P < 0.05). The satisfaction with the outcome in the abdominal flap group was higher than that in the other group, whereas the sexual well-being score of the abdominal flap group was lower than that of the other group ( P < 0.05). The scores of the postoperative physical well-being of the chest and abdomen in the younger group were higher than that in the older group ( P < 0.05). CONCLUSIONS: Breast reconstruction can significantly improve patients' health-related quality of life and satisfaction. Immediate breast reconstruction can reduce the adverse psychological and physical effects that breast loss exerts on patients, leading to better postoperative satisfaction. Patients who underwent breast reconstruction with abdominal flaps had higher postoperative satisfaction. Breast reconstruction in elderly patients was associated with considerable postoperative satisfaction.

Effects of lactate on metabolism and differentiation of CD4+T cells.

BACKGROUND: Lactate accumulation caused by abnormal tumor metabolism can induce the formation of an inhibitory immune microenvironment through a variety of pathways, which is characterized by regulatory T cells (Treg) infiltration and effector T cells (Teff) depletion. Studies have found that the key reason why Treg cells can survive in harsh environments lies in their flexible metabolic mode, which can use lactate in tumor microenvironment (TME) as an alternative energy substance to maintain their inhibitory activity. In addition, lactate could also promote the differentiation of CD4+T cells into Treg, but the mechanism was not completely clear. The purpose of this study was to investigate the possible mechanism by which lactate is utilized by CD4+T cells to influence Th17/Treg ratio. METHODS: Basal cytokines (anti-CD3, anti-CD28, TGF-ß) and 10 mM lactate was added into Naïve CD4+T cells basal medium for 3 days. After TCR stimulation, Naïve CD4+T converted to CD4+T. Flow cytometry was used to detect the proportion of Treg cells; ELISA was used to detect the activity of LDHA, LDHB and NADH and the amount of α -Ketoglutaric Acid (α-KG) and 2-Hydroxyglutaric Acid (2HG) after lactate entered the cells; Western Blot and RT-PCR were used to detect the protein and gene expression of Foxp3, RORγt, LDHA and LDHB. In the validation experiment, lactate uptake inhibitor AZD3965, LDHA inhibitor GSK2837808A and NADH conversion inhibitor Rotenone were added respectively to observe the differentiation ratio of Treg cells and confirm the key points of metabolism; the degradation of Treg cell transcription factor Foxp3 was interfered with ubiquitination inhibitors to observe whether it co-ubiquitinated with HIF-1α; the expression and activity of LDHA, LDHB and NADH in mitochondria and cytoplasm were detected to confirm cell localization. RESULTS: When basal cytokines (anti-CD3, anti-CD28, TGF-ß) stimulated, lactate was added to the culture medium, and CD4+T cells absorbed a large amount of lactate not only through MCT1 (monocarboxylic acid transporter), but also increased the expression of lactate dehydrogenase and accelerated the intracellular metabolism of lactate. LDHB in cytoplasm mainly catalyzed the dehydrogenation of lactate to pyruvate, accompanied by the transformation reaction between NAD+ and NADH. The latter further entered the mitochondria and participates in the tricarboxylic acid cycle metabolism. In addition, lactate could significantly increase the level of LDHA in mitochondria and promote the transformation of α-KG to 2HG, accompanied by the transformation of NADH to NAD+. These metabolic changes eventually led to an increase in the intracellular 2HG/α-KG ratio. Abnormal 2HG increased the proportion of Treg by inhibiting ATP5B-mediated phosphorylation of mTOR and the synthesis of HIF-1α, causing it not be enough to ubiquitinate and degrade with Foxp3. CONCLUSIONS: Lactate plays an important role in regulating the differentiation of Treg cells, inducing the expression and function of LDHA and promoting the transformation of α-KG to 2HG may be an important mechanism.

Pleural fluid soluble Fas ligand and tuberculous pleural effusion: a prospective diagnostic test accuracy study.

Background: The diagnosis of tuberculous pleural effusion (TPE) is challenging for pulmonologists. Adenosine deaminase (ADA), interferon-gamma (IFN-γ), and interleukin-27 (IL-27) have some limitations for diagnosing TPE. Soluble Fas ligand (sFasL) had a high diagnostic value for TPE. However, it remains unknown: (I) whether sFasL has an additional diagnostic value to the traditional markers (e.g., ADA); (II) whether sFasL provides a net benefit in patients with undiagnosed pleural effusion; (III) factors affecting the diagnostic accuracy of sFasL for TPE. This study aimed to evaluate the additional diagnostic value and benefit of pleural fluid sFasL for TPE. Methods: We prospectively enrolled 211 patients with undiagnosed pleural effusion. The concentration of sFasL in pleural fluid was measured by an enzyme-linked immunosorbent assay (ELISA). The diagnostic accuracy and net benefit of sFasL and ADA for TPE were analyzed by a receiver operating characteristic (ROC) curve, decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discriminant improvement (IDI). Results: The area under the ROC curves (AUCs) of sFasL and ADA were 0.74 (95% CI: 0.65-0.83) and 0.80 (95% CI: 0.71-0.90), respectively. The decision curve of sFasL revealed net benefit. The continuous NRI and IDI of sFasL were 0.36 (0.00-0.72, P=0.05) and 0.02 (-0.01-0.06, P=0.18), respectively. Conclusions: Pleural fluid sFasL has moderate diagnostic accuracy for TPE.