Objective:To compare the survival outcomes of different subsequent treatment regimens in patients with locally advanced hypopharyngeal squamous cell carcinoma (HPSCC) who achieved partial response (PR) after neoadjuvant chemotherapy based on the gross tumor volume regression rate (GTVRR).Methods:This retrospective study included patients with locally advanced HPSCC treated at the Department of Head and Neck Surgery, Beijing Tongren Hospital, from January 2011 to December 2023. The cohort included 135 males and 3 females, aged from 35 to 77 years. All patients received 2-3 cycles of TPF regimen (paclitaxel+cisplatin+5-fluorouracil) neoadjuvant chemotherapy. Subsequent treatments included concurrent chemoradiotherapy or surgery combined with postoperative adjuvant radiotherapy. The impacts of different subsequent treatment modalities on the survivals and prognoses of patients were compared based on GTVRR thresholds of 50% and 70%. The χ 2 test was used to analyze influencing factors; survival analysis and intergroup comparisons were performed using the Kaplan-Meier method and Log-rank test; prognostic factors were assessed using univariate and multivariate Cox regression analyses. Results:The 5-year OS and PFS rates were 56.5% and 47.9%, respectively, while, the 10-year OS and PFS rates were 25.8% and 21.2%, respectively. The median OS was 75 months, and the median PFS was 48 months. The laryngeal function preservation rate for the entire cohort was 83.3%. The patients who underwent surgery combined with postoperative radiotherapy had significantly better OS and PFS outcomes than those treated with concurrent chemoradiotherapy ( P<0.05). Stratification based on GTVRR revealed that the surgery plus postoperative radiotherapy regimen was particularly effective for PR patients with a GTVRR of 30%-70%, showing significantly better OS and PFS compared to the concurrent chemoradiotherapy group ( P<0.05). Conclusion:The optimal subsequent treatment for PR-HPSCC may be surgery-based comprehensive treatment, particularly for patients with a GTVRR of 30%-70%. This study offers valuable insights for the stratified treatment of HPSCC, which could contribute to improving overall patient prognosis.

Objective:To compare the survival outcomes of different subsequent treatment regimens in patients with locally advanced hypopharyngeal squamous cell carcinoma (HPSCC) who achieved partial response (PR) after neoadjuvant chemotherapy based on the gross tumor volume regression rate (GTVRR).Methods:This retrospective study included patients with locally advanced HPSCC treated at the Department of Head and Neck Surgery, Beijing Tongren Hospital, from January 2011 to December 2023. The cohort included 135 males and 3 females, aged from 35 to 77 years. All patients received 2-3 cycles of TPF regimen (paclitaxel+cisplatin+5-fluorouracil) neoadjuvant chemotherapy. Subsequent treatments included concurrent chemoradiotherapy or surgery combined with postoperative adjuvant radiotherapy. The impacts of different subsequent treatment modalities on the survivals and prognoses of patients were compared based on GTVRR thresholds of 50% and 70%. The χ 2 test was used to analyze influencing factors; survival analysis and intergroup comparisons were performed using the Kaplan-Meier method and Log-rank test; prognostic factors were assessed using univariate and multivariate Cox regression analyses. Results:The 5-year OS and PFS rates were 56.5% and 47.9%, respectively, while, the 10-year OS and PFS rates were 25.8% and 21.2%, respectively. The median OS was 75 months, and the median PFS was 48 months. The laryngeal function preservation rate for the entire cohort was 83.3%. The patients who underwent surgery combined with postoperative radiotherapy had significantly better OS and PFS outcomes than those treated with concurrent chemoradiotherapy ( P<0.05). Stratification based on GTVRR revealed that the surgery plus postoperative radiotherapy regimen was particularly effective for PR patients with a GTVRR of 30%-70%, showing significantly better OS and PFS compared to the concurrent chemoradiotherapy group ( P<0.05). Conclusion:The optimal subsequent treatment for PR-HPSCC may be surgery-based comprehensive treatment, particularly for patients with a GTVRR of 30%-70%. This study offers valuable insights for the stratified treatment of HPSCC, which could contribute to improving overall patient prognosis.

Endo-beta-N-acetylglucosaminidase (ENGase) is widely distributed in various organisms. The first reported ENGase activity was detected in Diplococcus pneumoniae in 1971. The protein (Endo D) was purified and its peptide sequence was determined in 1974. Three ENGases (Endo F1-F3) were discovered in Flavobacterium meningosepticum from 1982 to 1993. After that, the activity was detected from different species of bacteria, yeast, fungal, plant, mice, human, etc. Multiple ENGases were detected in some species, such as Arabidopsis thaliana and Trichoderma atroviride. The first preliminary crystallographic analysis of ENGase was conducted in 1994. But to date, only a few ENGases structures have been obtained, and the structure of human ENGase is still missing. The currently identified ENGases were distributed in the GH18 or GH85 families in Carbohydrate-Active enZyme (CAZy) database. GH18 ENGase only has hydrolytic activity, but GH85 ENGase has both hydrolytic and transglycosylation activity. Although ENGases of the two families have similar (β/α)8-TIM barrel structures, the active sites are slightly different. ENGase is an effective tool for glycan detection andglycan editing. Biochemically, ENGase can specifically hydrolyze β‑1,4 glycosidic bond between the twoN-acetylglucosamines (GlcNAc) on core pentasaccharide presented on glycopeptides and/or glycoproteins. Different ENGases may have different substrate specificity. The hydrolysis products are oligosaccharide chains and a GlcNAc or glycopeptides or glycoproteins with a GlcNAc. Conditionally, it can use the two products to produce a new glycopeptides or glycoprotein. Although ENGase is a common presentation in cell, its biological function remains unclear. Accumulated evidences demonstrated that ENGase is a none essential gene for living and a key regulator for differentiation. No ENGase gene was detected in the genomes of Saccharomyces cerevisiae and three other yeast species. Its expression was extremely low in lung. As glycoproteins are not produced by prokaryotic cells, a role for nutrition and/or microbial-host interaction was predicted for bacterium produced enzymes. In the embryonic lethality phenotype of the Ngly1-deficient mice can be partially rescued by Engase knockout, suggesting down regulation of Engase might be a solution for stress induced adaptation. Potential impacts of ENGase regulation on health and disease were presented. Rabeprazole, a drug used for stomach pain as a proton inhibitor, was identified as an inhibitor for ENGase. ENGases have been applied in vitro to produce antibodies with a designated glycan. The two step reactions were achieved by a pair of ENGase dominated for hydrolysis of substrate glycoprotein and synthesis of new glycoprotein with a free glycan of designed structure, respectively. In addition, ENGase was also been used in cell surface glycan editing. New application scenarios and new detection methods for glycobiological engineering are quickly opened up by the two functions of ENGase, especially in antibody remodeling and antibody drug conjugates. The discovery, distribution, structure property, enzymatic characteristics and recent researches in topical model organisms of ENGase were reviewed in this paper. Possible biological functions and mechanisms of ENGase, including differentiation, digestion of glycoproteins for nutrition and stress responding were hypothesised. In addition, the role of ENGase in glycan editing and synthetic biology was discussed. We hope this paper may provide insights for ENGase research and lay a solid foundation for applied and translational glycomics.

Objective:To analyze the impact of muscle mass reduction on the prognosis of patients and to observe the differences in prognosis among patients with different types of tumors affected by muscle mass reduction.Method:Tumor patients with available muscle mass data from the National Health and Nutrition Examination Survey,NHANES(NHANES)database(1999～2006 and 2011～2018)were selected as study subjects.Patients were divided into a muscle mass reduction group and a non-muscle mass reduction group based on differences measured by Dual-energy X-ray Absorptiometry(DXA).A Cox regression multivariate analysis was conducted to evaluate the impact of muscle mass reduction on the prognosis of tumor patients,and a subgroup analysis was performed based on different tumor locations to analyze the differences in overall survival(OS)and cancer-specific survival(CSS)associated with muscle mass reduction.Result:A total of 1 663 tumor patients were included in the study,comprising 64 with head and neck tumors,478 with skin tumors,237 with breast tumors,39 with lung tumors,138 with digestive system tumors,253 with urological system tumors,264 with gynecological tumors,64 with hematological system tumors,and 103 with tumors in other locations.There were 517 patients in the muscle mass reduction group and 1,146 in the non-muscle mass reduction group.Patients in the muscle mass reduction group showed significantly lower OS and CSS compared to the non-muscle mass reduction group(OS,HR=1.358;CSS,HR=2.109).Muscle mass reduction was significantly associated with OS in head and neck tumor patients(HR=4.060)and both OS and CSS were significantly worse in urinary system tumor patients in the muscle mass reduction group(OS,HR=1.625;CSS,HR=2.311),whereas no significant differences were observed in other tumors.Conclusion:Tumor patients with muscle mass reduction have significantly worse OS and CSS compared to those with normal muscle mass,and the prognosis varies across different tumor sites.Special attention should be given to muscle mass status in patients with head and neck tumors and urinary system tumors,with timely interventions as needed.

This study explored a new model of Prostate Imaging Reporting and Data System (PIRADS) and adjusted prostate-specific antigen density of peripheral zone (aPSADPZ) for predicting the occurrence of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). The demographic and clinical characteristics of 853 patients were recorded. Prostate-specific antigen (PSA), PSA density (PSAD), PSAD of peripheral zone (PSADPZ), aPSADPZ, and peripheral zone volume ratio (PZ-ratio) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The calibration and discrimination abilities of new nomograms were verified with the calibration curve and area under the ROC curve (AUC). The clinical benefits of these models were evaluated by decision curve analysis and clinical impact curves. The AUCs of PSA, PSAD, PSADPZ, aPSADPZ, and PZ-ratio were 0.669, 0.762, 0.659, 0.812, and 0.748 for PCa diagnosis, while 0.713, 0.788, 0.694, 0.828, and 0.735 for csPCa diagnosis, respectively. All nomograms displayed higher net benefit and better overall calibration than the scenarios for predicting the occurrence of PCa or csPCa. The new model significantly improved the diagnostic accuracy of PCa (0.945 vs 0.830, P < 0.01) and csPCa (0.937 vs 0.845, P < 0.01) compared with the base model. In addition, the number of patients with PCa and csPCa predicted by the new model was in good agreement with the actual number of patients with PCa and csPCa in high-risk threshold. This study demonstrates that aPSADPZ has a higher predictive accuracy for PCa diagnosis than the conventional indicators. Combining aPSADPZ with PIRADS can improve PCa diagnosis and avoid unnecessary biopsies.
Male ; Humans ; Prostate/pathology* ; Prostate-Specific Antigen/analysis* ; Prostatic Neoplasms/diagnostic imaging* ; Biopsy ; Nomograms ; Retrospective Studies

Aged ; Antiviral Agents/therapeutic use* ; COVID-19/drug therapy* ; China/epidemiology* ; Cohort Studies ; Female ; Hospital Mortality ; Hospitalization ; Humans ; Male ; Middle Aged ; Patient Acuity ; SARS-CoV-2 ; Treatment Outcome

N-methyl-D-aspartate receptor (NMDAR),an important ionic glutamate receptor and a ligand and voltage-gated ion channel characterized by complex composition and functions and wide distribution,plays a key role in the pathological and physiological process of diseases or stress states.NMDAR can mediate apoptosis through different pathways such as mitochondrial and endoplasmic reticulum damage,production of reactive oxygen species and peroxynitrite,and activation of mitogen-activated protein kinase and calpain.This paper reviews the structure,distribution,and biological characteristics of NMDAR and the mechanisms of NMDAR-mediated apoptosis.
Apoptosis ; Humans ; Mitogen-Activated Protein Kinases/metabolism* ; Reactive Oxygen Species/metabolism* ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Signal Transduction

ObjectiveTo investigate the role of lncRNA-PVT1/miR-15a/ Bmi-1 pathway in the proliferation of HGC-27 gastric cancer cells in vitro. MethodsGastric cancer cell line HGC-27 was cultured in vitro and divided into the following groups： （1） blank control， si-PVT1 and si-PVT1 NC. The si-PVT1 and si-PVT1 NC groups were transferred with PVT1 siRNA and PVT1 siRNA scramble， respectively. （2） blank control， miR-15a and miR-15a NC. （3） blank control， si-Bmi-1 and si-Bmi-1 NC. Cell proliferation was evaluated by using MTS. The expression of PVT1， miR-15a and Bmi-1 was detected in the condition of PVT1 inhibition. In order to validate the relationship between miR-15a and Bmi-1， miR-15a mimic was transfected into HGC-27 gastric cancer cell line， and the expression of miR-15a and Bmi-1 was examined. The potential complementary binding sites of PVT1 and miR-15a， and miR-15a and Bmi-1 were predicted by bioinformatics. Dual-luciferase reporter assay was performed to detect luciferase activity of the different groups of cells in order to verify the relationship between PVT1 and miR-15a and miR-15a and Bmi-1. Relevant rescue experiment was conducted in order to further validate the mutual relationship of lncRNA-PVT1， miR-15a and Bmi-1. ResultsOD₄₉₀ value and cell proliferation rate were significantly decreased in the condition of PVT1 or Bmi-1 inhibition， or miR-15a overexpression （P<0.01）. The expression of Bmi-1 was decreased in si-PVT1 group， whereas miR-15a was increased （P<0.01）. miR-15a was increased after transfection， whereas the expression of Bmi-1 was decreased （P<0.01）. The dual luciferase reporter assay indicated that both the PVT1 and Bmi-1 reporter gene luciferase activity were decreased significantly in miR-15a mimics group， down-regulating 56% and 32%， respectively （P<0.01）. The expression of PVT1 and Bmi-1 was elevated in the condition of PVT1 knockdown and miR-15a inhibition， whereas both of their expression were further decreased in the condition of PVT1 knockdown and miR-15a transfection. ConclusionLncRNA-PVT1 could upregulate Bmi-1 （lncRNA-PVT1/miR-15a/Bmi-1 pathway） to promote the proliferation of gastric cancer cells in vitro by inhibiting miR-15a.

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

Objective Circulating tumor cells (CTCs) have potential value in the clinical application of various tumors. This study was to investigate the role of CTCs and their chemokine receptor CCR9 in the invasion and metastasis of non-small cell lung cancer (NSCLC). Methods From May 2018 to June 2019, a total of 62 patients with NSCLC in the clinical oncology center of The People's Hospital of Guangxi Zhuang Autonomous Region were enrolled in this study. The CanpatrolTM CTC technique was used to detected the expressions of CTCs and CCR9 in CTCs in peripheral blood of patients. Furthermore, the relationships between expression levels of CTCs, CCR9 and clinical, pathological characteristics of NSCLC patients were analyzed. Results CTCs were detected in 56 of 62 (90.3%) NSCLC patients. CTCs counts were associated with TNM stage, lymph node metastasis and distant metastasis of NSCLC (P<0.05). In the analysis of clinical correlation between CTC subtypes and NSCLC, epithelial CTCs counts were related to TNM stage and distant metastasis of NSCLC (r=0.296 and r=0.273, P<0.05). Additionally, counts of mixed type CTCs were also correlative with NSCLC tumor metastasis (r =0.253, P =0.047). Finally, we found that the positive rate of CCR9 in mixed type CTCs was associated with distant metastasis of NSCLC (r=0.353, P=0.038). Conclusion CTCs counts and subtypes were correlated with TNM stage and metastasis of NSCLC. The expression level of CCR9 on CTC was expected to be a biomarker to evaluate the risk of tumor metastasis in NSCLC.