Lung cancer poses a serious threat to global public health security.Chemotherapy,as the main strategy for cancer treatment,faces challenges such as high toxicity and drug resistance.Anticancer peptides have the potential of being developed into new anticancer drugs due to their advantages of broad-spectrum anticancer activity,rapid action,and difficulty in generating drug resistance,but they also face shortcomings such as weak activity and strong toxic side effects.The weakly acidic microenvironment of tumors(pH 6.5-6.8)provides a good idea for the design of anticancer peptides of high-efficiency and low-toxicity.Previously,we designed the acid-sensitive antibacterial peptide pHly-1 using the wolf spider(Lycosa singoriensis)toxin Lycosin-Ⅰ as a template.In this study,we found that pHly-1 also had acid-sensitive anticancer activity.Further alanine scanning analysis of pHly-1 was carried out,and we ob-tained a mutant pHTP-2 with better acid sensitivity,whose IC50(half maximal inhibitory concentration)against A549 cells was 15.68 μmol/L at pH 6.6 and was greater than 100 μmol/L at pH 7.4.At pH 6.6,pHTP-2 could act on various lung cancer cell lines and induce the death of A549 cells by rapid ly-sis;at pH 7.4,500 μmol/L pHTP-2 had weak toxicity to red blood cells(the hemolysis rate was ap-proximately 38％)and primary myocardial cells(the inhibition rate was 49.7％,with P＜0.05).Analy-sis of its charge,particle size,morphology,and secondary structure showed that at pH 6.6,the histidine in the sequence of pHTP-2 was protonated,increasing the positive charge(P＜0.01),decreasing the hy-drated particle size(P＜0.05)and forming an α-helical structure to induce membrane lysis of A549 cells.At pH 7.4,it was deprotonated,the positive charge decreases,a β-sheet structure was formed and self-aggregation occurred,limiting its effect on the A549 cell membrane and showing weak activity.In summary,pHTP-2 could respond to the weakly acidic microenvironment of tumors to exert selective cyto-toxic activity,effectively overcoming the shortcomings of anticancer peptides such as low efficiency and high toxicity.Our findings suggest that it is a high-quality lead molecule for anticancer drugs.

Objective:To investigate the value of gadoxetate disodium-enhanced MRI combined with T 1 mapping in preoperative prediction of cytokeratin 19 (CK19) and glypican-3 (GPC3) positive dual-phenotype hepatocellular carcinoma (DPHCC). Methods:This case-control study included retrospectively enrolled patients with pathologically confirmed HCC from Central People′s Hospital of Zhanjiang (training set, n=85; December 2020 to July 2022) and the Second Affiliated Hospital, School of Medicine, South China University of Technology (test set, n=35; April 2023 to April 2024). Patients were categorized into CK19 and GPC3 positive DPHCC group (training set=19, test set=11) and non-DPHCC group (training set=66, test set=24) based on postoperative immunohistochemical staining. All patients received preoperative MRI scans, including gadoxetate disodium-enhanced imaging and T 1 mapping. Clinical data were collected, qualitative MRI features were evaluated, and quantitative parameters were measured, including signal intensity, T 1 values, apparent diffusion coefficient (ADC), tumor-to-liver ADC ratio (rADC), tumor-to-liver signal intensity ratio, and T 1 relaxation time reduction rate (ΔT 1%). Statistical comparisons between groups were performed using independent t-tests, Mann-Whitney U tests, or χ2 tests. Multivariate logistic regression identified independent predictors of CK19 and GPC3 positive DPHCC, and a combined model was constructed. Predictive performance was evaluated using area under the receiver operating characteristic curve (AUC), with DeLong test comparing model performance. Results:Significant intergroup differences were observed in alpha-fetoprotein (AFP), total bilirubin, direct bilirubin, DWI target sign, rADC, hepatobiliary-phase T 1 (T 1HBP), and ΔT 1% ( P<0.05). Multivariate analysis identified AFP>20 ng/ml ( OR=5.835, 95% CI 1.019-33.397, P=0.048), DWI target sign ( OR=13.408, 95% CI 2.216-81.131, P=0.005), and ΔT1%≤31% ( OR=14.429, 95% CI 2.166-96.125, P=0.006) as independent predictors of DPHCC. The AUC values of the aforementioned three independent predictors and the combined model for predicting DPHCC were 0.641 (95% CI 0.530-0.742), 0.679 (95% CI 0.569-0.777), 0.740 (95% CI 0.634-0.829), and 0.886 (95% CI 0.799-0.945) in the training set, and 0.568 (95% CI 0.390-0.743), 0.669 (95% CI 0.490-0.818), 0.689 (95% CI 0.511-0.843), and 0.824 (95% CI 0.658-0.931) in the test set, respectively. The DeLong test results showed that in the training set, the diagnostic performance of the combined model was superior to those of the three individual features ( Z=3.68, P<0.001; Z=3.15, P=0.002; Z=3.15, P=0.002). In the test cohort, the combined model demonstrated better diagnostic performance than AFP>20 ng/ml and ΔT 1%≤31% ( Z=2.15, P=0.032; Z=2.12, P=0.034), while no statistically significant difference was observed compared with the DWI target sign ( Z=1.77, P=0.076). Conclusion:The integrated model incorporating clinical data, gadoxetate disodium-enhanced MRI, and T 1 mapping parameters effectively predicts CK19 and GPC3 positive DPHCC.

Lung cancer poses a serious threat to global public health security.Chemotherapy,as the main strategy for cancer treatment,faces challenges such as high toxicity and drug resistance.Anticancer peptides have the potential of being developed into new anticancer drugs due to their advantages of broad-spectrum anticancer activity,rapid action,and difficulty in generating drug resistance,but they also face shortcomings such as weak activity and strong toxic side effects.The weakly acidic microenvironment of tumors(pH 6.5-6.8)provides a good idea for the design of anticancer peptides of high-efficiency and low-toxicity.Previously,we designed the acid-sensitive antibacterial peptide pHly-1 using the wolf spider(Lycosa singoriensis)toxin Lycosin-Ⅰ as a template.In this study,we found that pHly-1 also had acid-sensitive anticancer activity.Further alanine scanning analysis of pHly-1 was carried out,and we ob-tained a mutant pHTP-2 with better acid sensitivity,whose IC50(half maximal inhibitory concentration)against A549 cells was 15.68 μmol/L at pH 6.6 and was greater than 100 μmol/L at pH 7.4.At pH 6.6,pHTP-2 could act on various lung cancer cell lines and induce the death of A549 cells by rapid ly-sis;at pH 7.4,500 μmol/L pHTP-2 had weak toxicity to red blood cells(the hemolysis rate was ap-proximately 38％)and primary myocardial cells(the inhibition rate was 49.7％,with P＜0.05).Analy-sis of its charge,particle size,morphology,and secondary structure showed that at pH 6.6,the histidine in the sequence of pHTP-2 was protonated,increasing the positive charge(P＜0.01),decreasing the hy-drated particle size(P＜0.05)and forming an α-helical structure to induce membrane lysis of A549 cells.At pH 7.4,it was deprotonated,the positive charge decreases,a β-sheet structure was formed and self-aggregation occurred,limiting its effect on the A549 cell membrane and showing weak activity.In summary,pHTP-2 could respond to the weakly acidic microenvironment of tumors to exert selective cyto-toxic activity,effectively overcoming the shortcomings of anticancer peptides such as low efficiency and high toxicity.Our findings suggest that it is a high-quality lead molecule for anticancer drugs.

Objective:To investigate the value of gadoxetate disodium-enhanced MRI combined with T 1 mapping in preoperative prediction of cytokeratin 19 (CK19) and glypican-3 (GPC3) positive dual-phenotype hepatocellular carcinoma (DPHCC). Methods:This case-control study included retrospectively enrolled patients with pathologically confirmed HCC from Central People′s Hospital of Zhanjiang (training set, n=85; December 2020 to July 2022) and the Second Affiliated Hospital, School of Medicine, South China University of Technology (test set, n=35; April 2023 to April 2024). Patients were categorized into CK19 and GPC3 positive DPHCC group (training set=19, test set=11) and non-DPHCC group (training set=66, test set=24) based on postoperative immunohistochemical staining. All patients received preoperative MRI scans, including gadoxetate disodium-enhanced imaging and T 1 mapping. Clinical data were collected, qualitative MRI features were evaluated, and quantitative parameters were measured, including signal intensity, T 1 values, apparent diffusion coefficient (ADC), tumor-to-liver ADC ratio (rADC), tumor-to-liver signal intensity ratio, and T 1 relaxation time reduction rate (ΔT 1%). Statistical comparisons between groups were performed using independent t-tests, Mann-Whitney U tests, or χ2 tests. Multivariate logistic regression identified independent predictors of CK19 and GPC3 positive DPHCC, and a combined model was constructed. Predictive performance was evaluated using area under the receiver operating characteristic curve (AUC), with DeLong test comparing model performance. Results:Significant intergroup differences were observed in alpha-fetoprotein (AFP), total bilirubin, direct bilirubin, DWI target sign, rADC, hepatobiliary-phase T 1 (T 1HBP), and ΔT 1% ( P<0.05). Multivariate analysis identified AFP>20 ng/ml ( OR=5.835, 95% CI 1.019-33.397, P=0.048), DWI target sign ( OR=13.408, 95% CI 2.216-81.131, P=0.005), and ΔT1%≤31% ( OR=14.429, 95% CI 2.166-96.125, P=0.006) as independent predictors of DPHCC. The AUC values of the aforementioned three independent predictors and the combined model for predicting DPHCC were 0.641 (95% CI 0.530-0.742), 0.679 (95% CI 0.569-0.777), 0.740 (95% CI 0.634-0.829), and 0.886 (95% CI 0.799-0.945) in the training set, and 0.568 (95% CI 0.390-0.743), 0.669 (95% CI 0.490-0.818), 0.689 (95% CI 0.511-0.843), and 0.824 (95% CI 0.658-0.931) in the test set, respectively. The DeLong test results showed that in the training set, the diagnostic performance of the combined model was superior to those of the three individual features ( Z=3.68, P<0.001; Z=3.15, P=0.002; Z=3.15, P=0.002). In the test cohort, the combined model demonstrated better diagnostic performance than AFP>20 ng/ml and ΔT 1%≤31% ( Z=2.15, P=0.032; Z=2.12, P=0.034), while no statistically significant difference was observed compared with the DWI target sign ( Z=1.77, P=0.076). Conclusion:The integrated model incorporating clinical data, gadoxetate disodium-enhanced MRI, and T 1 mapping parameters effectively predicts CK19 and GPC3 positive DPHCC.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Robotic surgery is known as the"third technological revolution"in the field of surgery,and is an important milestone in the development of modern surgery.However,our country's innovative surgical robot industry is still in its early stages,and it is only being utilized in certain surgical fields.To explore the effectiveness of the application of do-mestic surgical robot in oral and maxillofacial surgery,the author successfully completed a case of benign parotid tumor resection with the assistance of a domestic autonomous robot.The operation was successful,facial nerve function was preserved,and postoperative wound healing was good.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Objective: To investigate current use of oral anticoagulant (OAC) therapy and influencing factors among coronary artery disease (CAD) patients with nonvalvular atrial fibrillation (NVAF) in China. Methods: Results of this study derived from "China Atrial Fibrillation Registry Study", the study prospectively enrolled atrial fibrillation (AF) patients from 31 hospitals, and patients with valvular AF or treated with catheter ablation were excluded. Baseline data such as age, sex and type of atrial fibrillation were collected, and drug history, history of concomitant diseases, laboratory results and echocardiography results were recorded. CHA₂DS₂-VASc score and HAS-BLED score were calculated. The patients were followed up at the 3rd and 6th months after enrollment and every 6 months thereafter. Patients were divided according to whether they had coronary artery disease and whether they took OAC. Results: 11 067 NVAF patients fulfilling guideline criteria for OAC treatment were included in this study, including 1 837 patients with CAD. 95.4% of NVAF patients with CAD had CHA₂DS₂-VASc score≥2, and 59.7% of patients had HAS-BLED≥3, which was significantly higher than NVAF patients without CAD (P<0.001). Only 34.6% of NVAF patients with CAD were treated with OAC at enrollment. The proportion of HAS-BLED≥3 in the OAC group was significantly lower than in the no-OAC group (36.7% vs. 71.8%, P<0.001). After adjustment with multivariable logistic regression analysis, thromboembolism(OR=2.48,95%CI 1.50-4.10,P<0.001), left atrial diameter≥40 mm(OR=1.89,95%CI 1.23-2.91,P=0.004), stain use (OR=1.83,95%CI 1.01-3.03, P=0.020) and β blocker use (OR=1.74,95%CI 1.13-2.68,P=0.012)were influence factors of OAC treatment. However, the influence factors of no-OAC use were female(OR=0.54,95%CI 0.34-0.86,P=0.001), HAS-BLED≥3 (OR=0.33,95%CI 0.19-0.57,P<0.001), and antiplatelet drug(OR=0.04,95%CI 0.03-0.07,P<0.001). Conclusion: The rate of OAC treatment in NVAF patients with CAD is still low and needs to be further improved. The training and assessment of medical personnel should be strengthened to improve the utilization rate of OAC in these patients.
Humans ; Female ; Male ; Atrial Fibrillation/drug therapy* ; Coronary Artery Disease/complications* ; Anticoagulants/therapeutic use* ; Platelet Aggregation Inhibitors/therapeutic use* ; Risk Factors ; China ; Administration, Oral ; Stroke

OBJECTIVE: To explore the potential mechanism of Yishen Qutong Granules (YSQTG) for the treatment of esophageal cancer using network pharmacology and experimental research. METHODS: The effective components and molecular mechanism of YSQTG in treating esophageal cancer were expounded based on network pharmacology and molecular docking. The key compound was identified by high-performance liquid chromatography and mass spectrometry (HPLC-MS) to verify the malignant phenotype of the key compounds in the treatment of esophageal cancer. Then, the interaction proteins of key compounds were screened by pull-down assay combined with mass spectrometry. RNA-seq was used to screen the differential genes in the treatment of esophageal cancer by key compounds, and the potential mechanism of key compounds on the main therapeutic targets was verified. RESULTS: Totally 76 effective compounds of YSQTG were found, as well as 309 related targets, and 102 drug and disease interaction targets. The drug-compound-target network of YSQTG was constructed, suggesting that quercetin, luteolin, wogonin, kaempferol and baicalein may be the most important compounds, while quercetin had higher degree value and degree centrality, which might be the key compound in YSQTG. The HPLC-MS results also showed the stable presence of quercetin in YSQTG. By establishing a protein interaction network, the main therapeutic targets of YSQTG in treating esophageal cancer were Jun proto-oncogene, interleukin-6, tumor necrosis factor, and RELA proto-oncogene. The results of cell function experiments in vitro showed that quercetin could inhibit proliferation, invasion, and clonal formation of esophageal carcinoma cells. Quercetin mainly affected the biological processes of esophageal cancer cells, such as proliferation, cell cycle, and cell metastasis. A total of 357 quercetin interacting proteins were screened, and 531 genes were significantly changed. Further pathway enrichment analysis showed that quercetin mainly affects the metabolic pathway, MAPK signaling pathway, and nuclear factor kappa B (NF- κ B) signaling pathway, etc. Quercetin, the key compound of YSQTG, had stronger binding activity by molecular docking. Pull-down assay confirmed that NF- κ B was a quercetin-specific interaction protein, and quercetin could significantly reduce the protein level of NF- κ B, the main therapeutic target. CONCLUSION YSQTG can be multi-component, multi-target, multi-channel treatment of esophageal cancer, it is a potential drug for the treatment of esophageal cancer.
Humans ; Network Pharmacology ; Quercetin ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Esophageal Neoplasms ; Drugs, Chinese Herbal

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.