BACKGROUND: Durvalumab after chemoradiotherapy (CRT) failed to bring survival benefits to patients with epidermal growth factor receptor ( EGFR ) mutations in PACIFIC study (evaluating durvalumab in patients with stage III, unresectable NSCLC who did not have disease progression after concurrent chemoradiotherapy). We aimed to explore whether locally advanced inoperable patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs) and the optimal treatment regimen. METHODS: We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from inception to December 31, 2022 and performed a meta-analysis based on a Bayesian framework, with progression-free survival (PFS) and overall survival (OS) as the primary endpoints. RESULTS: A total of 1156 patients were identified in 16 studies that included 6 treatment measures, including CRT, CRT followed by durvalumab (CRT-Durva), TKI monotherapy, radiotherapy combined with TKI (RT-TKI), CRT combined with TKI (CRT-TKI), and TKI combined with durvalumab (TKI-Durva). The PFS of patients treated with TKI-containing regimens was significantly longer than that of patients treated with TKI-free regimens (hazard ratio [HR] = 0.37, 95% confidence interval [CI], 0.20-0.66). The PFS of TKI monotherapy was significantly longer than that of CRT (HR = 0.66, 95% CI, 0.50-0.87) but shorter than RT-TKI (HR = 1.78, 95% CI, 1.17-2.67). Furthermore, the PFS of RT-TKI or CRT-TKI were both significantly longer than that of CRT or CRT-Durva. RT-TKI ranked first in the Bayesian ranking, with the longest OS (60.8 months, 95% CI = 37.2-84.3 months) and the longest PFS (21.5 months, 95% CI, 15.4-27.5 months) in integrated analysis. CONCLUSIONS: For unresectable stage III EGFR mutant NSCLC, RT and TKI are both essential. Based on the current evidence, RT-TKI brings a superior survival advantage, while CRT-TKI needs further estimation. Large randomized clinical trials are urgently needed to explore the appropriate application sequences of TKI, radiotherapy, and chemotherapy. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022298490.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; ErbB Receptors/genetics* ; Lung Neoplasms/drug therapy* ; Mutation/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Chemoradiotherapy ; Antibodies, Monoclonal/therapeutic use*

Objective:To investigate the relationship between the Palatopharyngeal Arch Staging System（PASS） and the severity of Obstructive Sleep Apnea（OSA）, as well as the patterns of airway collapse, while further assessing its clinical applicability. Methods:A total of 98 patients diagnosed with OSA at the Department of Otorhinolaryngology Head and Neck Surgery, Shenzhen University Affiliated Shenzhen Hospital, were recruited for this study. Data collected included basic demographic information, oropharyngeal laryngoscopy videos, results from awake laryngoscopy Muller tests, and indicators from sleep respiratory monitoring. The distribution of each PASS stage among patients with varying severities of OSA was compared. Additionally, both objective and subjective sleep indicators along with occurrences of airway collapse in OSA patients across different PASS stages were analyzed. Results:In total, 98 patients participated in this study. Statistically significant differences were observed in neck circumference, weight, Body Mass Index（BMI）, tongue position, and PASS stage when comparing mild-to-moderate OSA patients to those with severe OSA（P<0.05）. Furthermore, there were statistically significant variations in Apnea-Hypopnea Index（AHI）, minimum blood oxygen saturation levels, average blood oxygen saturation levels, oxygen desaturation index values, and total oxygen desaturation indices among OSA patients categorized by different PASS stages. Multiple comparisons revealed statistically significant differences in AHI as well as minimum and average blood oxygen saturation levels between patients at PASS 1 versus those at PASS 3（P<0.05）. Additionally, notable differences regarding oropharyngeal collapse rates among OSA patients across various PASS stages were identified; specifically between those at PASS stage 1 and those at PASS stage 3. Conclusion:The proportion of PASS stages for OSA varies across different severity levels. The severity of OSA and the degree of airway collapse in patients with varying PASS stages also exhibit significant differences. Patients classified as PASS 3 demonstrate a more severe form of OSA compared to those at PASS 1, with stage 3 being more susceptible to oropharyngeal collapse than its stage 1 counterpart. This assessment system is anticipated to address the current limitations in evaluating the lateral pharyngeal wall within the oropharynx.
Humans ; Sleep Apnea, Obstructive/pathology* ; Male ; Severity of Illness Index ; Female ; Middle Aged ; Polysomnography ; Adult ; Pharynx/physiopathology* ; Aged

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant solid tumor of the digestive system, characterized by rapid progression and difficulties of early diagnosis. Five-year survival rate of the patients is less than 9%. With the acceleration of global population aging and lifestyle change, the incidence of PDAC has been increasing annually. Currently, surgical treatment and chemotherapy remain the standard treatment options for PDAC patients. Early symptoms of PDAC are so undetectable that most patients miss the optimal opportunity for radical surgical resection. Even among those who undergo surgery, the high recurrence rate remains a major problem. PDAC is known for its unique tumor microenvironment. The cellular and non-cellular components in the tumor microenvironment account for as much as 90% of the tumor stroma, presenting many potential targets for PDAC therapy. Activated pancreatic stellate cells within PDAC tissue express specific proteins and secrete various cytokines and metabolites, which directly contribute to the proliferation, invasion, and metastasis of PDAC cells. These elements are critical in extracellular matrix production, connective tissue hyperplasia, immune tolerance, and drug resistance. Immune cells, such as macrophages and neutrophils, exert immunosuppressive and tumor-promoting roles in PDAC progression. The extracellular matrix, which serve as a natural physical barrier, induces interstitial hypertension and reduces blood supply, thereby hindering the delivery of drugs to the tumor. Additionally, it helps the metastasis and differentiation of PDAC cells, reducing the efficacy of clinical chemotherapy and immunotherapy. Although chemotherapeutic agents like gemcitabine have been used in the clinical treatment of PDAC for more than 20 years, the curative effect is obstructed by their poor stability in the bloodstream, low cellular uptake, and poor targeting. While small-molecule inhibitors targeting mutations such as KRAS^G12C, BRCA, and NTRK fusion have shown great potential for molecular targeted treatments and gene therapies of PDAC, their broader application is limited by side effects and restricted scope of patients. The advancement of nanotechnology brings new strategies for PDAC treatment. By virtue of unique size characteristics and actual versatility, different drug-delivery nanosystems contribute to overcome the dense stromal barrier, prolong the circulation time of therapeutics and realize precise PDAC treatment by targeted drug delivery. Clinical nanodrugs such as albumin-bound paclitaxel (nab-paclitaxel) and irinotecan liposome greatly improve the pharmacokinetics of conventional chemotherapeutics and promote drug accumulation inside the tumor, thereby are applying to the first-line treatment of PDAC. It is noteworthy that none nanodrugs with active targeting design have been approved for clinical treatment yet, though many are in clinical trials. In this review, we discuss promising targeting strategies based on different nanodrug delivery systems for treatment of PDAC. One major nanostrategy focuses on the tumor cell targeting and its applications in chemotherapy, molecular targeting therapy, gene therapy, and immunotherapy of PDAC. Another nanostrategy targets the tumor microenvironment, which highlights the nanosystems specifically regulating pancreatic stellate cells, immune cells and the extracellular matrix. Recent progress of developing new nanotheraputics for breakthrough in the fight of PDAC are elaborated in this review. We also provide our perspectives on the challenges and opportunities in the field.

Objective To explore the feasibility of radiomics features combined with different machine learning methods based on CT scans to predict lymphovascular and perineural invasion in patient with gastric cancer.Methods A total of 142 patients with gas-tric cancer lymphovascular confirmed by operative pathological examination were retrospectively selected.Among all patients,there were 96 positive cases and 46 negative cases.Among 137 patients with perineural invasion,there were 76 positive cases and 61 nega-tive cases.The 3D-Slicer package was used for delineation,and the Pyradiomics package was used to extract radiomics features.All data were randomly divided into training set and test set in an 8∶2 ratio.Intraclass correlation coefficient(ICC),Pearson correla-tion analysis,least absolute shrinkage and selection operator(LASSO)algorithm were used for feature selection.Support vector machine(SVM),K-nearest neighbor(KNN),decision tree(DT),random forest(RF),extreme tree(ET),extreme gradient boosting(XGBoost),and LightGBM were used to compare the models of lymphovascular and perineural invasion,respectively.Receiver operating characteris-tic(ROC)curve and area under the curve(AUC)were used to evaluate the predictive performance of these models.Results The lymphovascular group AUC of SVM,KNN,DT,RF,ET,XGBoost,and LightGBM in the training set were 0.926,0.753,1.000,0.999,1.000,1.000,and 0.917,and the AUC in the test set were 0.894,0.692,0.456,0.678,0.753,0.650,and 0.650,respectively.The perineural invasion group AUC of SVM,KNN,DT,RF,ET,XGBoost,and LightGBM in the training set were 0.864,0.794,1.000,1.000,1.000,1.000,and 0.866,and the AUC in the test set were 0.861,0.706,0.700,0.672,0.731,0.667,and 0.678,respectively.Conclusion Based on venous phase CT radiomics features combined with machine learning methods,it is feasible to predict lymphovascu-lar and perineural invasion of gastric cancer preoperatively.Among the variousmachine learning methods,SVM shows the best predictive performance for lymphovascular and perineural invasion in patient with gastric cancer.

Objective : To investigate the occupational exposure to blood-borne pathogens among medical workers in a tertiary general hospital in Hangzhou City from 2010 to 2022, so as to provide the evidence for improving occupational protective measures among medical workers. Methods: The registration and follow-up data of occupational exposure to blood-borne pathogens among medical workers from 2010 to 2022 were collected from the blood-borne occupational exposure monitoring system in a tertiary general hospital in Hangzhou City. The population distribution, occurrence, protection and disposal of occupational exposure to blood-borne pathogens were analyzed using a descriptive epidemiological method. Results: A total of 1 230 cases were reported with occupational exposure to blood-borne pathogens among medical workers in the study hospital from 2010 to 2022, with the highest incidence in 2021 (4.67%) and the lowest incidence in 2010 (0.99%). The incidence of occupational exposure to blood-borne pathogens appeared a tendency forwards a rise from 2010 to 2022 (P<0.05). Of all cases with occupational exposure to blood-borne pathogens, there were 934 women (75.93%), 656 nurses (53.33%), and 514 cases with working experiences of one year and shorter (41.79%). Hand was the predominant site of occupational exposure to blood-borne pathogens (92.03%) and ward was the predominant place of exposure (35.37%), while scalp needle was the predominant mode of exposure (32.68%), and removal of needle was the predominant procedure of exposure (32.36%). A total of 1 106 cases were tested for the blood-borne pathogens in the exposure sources, and 448 cases were tested positive for blood-borne pathogens, with a detection rate of 40.51%. Hepatitis B virus, treponema pallidum and human immunodeficiency virus were the three most common blood-borne pathogens, and there were 739 cases (60.08%) with personal protective equipment during exposure. Following the follow-up surveillance for more than 6 months post-exposure, no infections occurred. Conclusions Junior nurses and hand exposure were predominant among medical workers with occupational exposure to blood-borne pathogens in the study hospital from 2010 to 2022, and hepatitis B virus was the predominant blood-borne pathogen. No post-exposure infections occurred.

OBJECTIVE: To evaluate the safety and efficacy of catheter-directed thrombolysis (CDT) versus systemic thrombolysis (ST) in the treatment of pulmonary embolism (PE). METHODS: The Cochrane Library, PubMed, and Embase databases were searched to collect the literature on the comparison of the results of CDT and ST in the treatment of PE from the beginning of their records to May 2020, and meta-analysis was performed by STATA software (version 15.1). Using standardized data-collection forms, the authors screened the studies and independently extracted data, and assessed the quality of the studies using the Newcastle-Ottawa Scale for cohort studies. Cohort studies that examined the following results were included in the current study: in-hospital mortality, all-cause bleeding rate, gastrointestinal bleeding rate, intracranial hemorrhage rate, the incidence of shock, and hospital length of stay. RESULTS: A total of eight articles, with 13,242 participants, involving 3962 participants in the CDT group and 9280 participants in the ST group were included. CDT compared with ST in the treatment of PE can significantly affect in-hospital mortality rate [odds ratio (OR) = 0.41, 95% CI: 0.30-0.56, P < 0.05], all-cause bleeding rate (OR = 1.20, 95% CI: 1.04-1.39, P = 0.012), gastrointestinal bleeding rate (OR = 1.43, 95% CI: 1.13-1.81, P = 0.003), the incidence of shock (OR = 0.46, 95% CI: 0.37-0.57, P < 0.05), and hospital length of stay [standard mean difference (SMD) = 0.16, 95% CI: 0.07-0.25, P < 0.05]. However, there was no significant effect on intracranial hemorrhage rate in patients with PE (OR = 0.70, 95% CI: 0.47-1.03, P = 0.070). CONCLUSIONS CDT is a viable alternative to ST in the treatment of PE, as it can significantly reduce in-hospital mortality rate, all-cause bleeding rate, gastrointestinal bleeding rate, and incidence of shock. However, CDT may prolong hospital length of stay to a certain extent. Further research is needed to evaluate the safety and efficacy of CDT and ST in the treatment of acute PE and other clinical outcomes.

Objective:To evaluate the value of B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation detection in the differentiating malignant from benign with Bethesda system for reporting thyroid cytopathology (BSRTC) categories Ⅰ and Ⅲ nodules. Methods:From January 2019 to December 2020, a total of 264 nodules from 263 patients (79 males, 184 females; median age 46 years) were retrospectively enrolled and all patients underwent BRAF V600E mutation detection, fine-needle aspiration cytology (FNAC) and thyroid nodulectomy in the Affiliated Drum Tower Hospital of Nanjing University Medical School. Thirteen nodules of 12 patients had repeat aspirate samples and 51 nodules were examined with multiple genes assay in formalin fixed paraffin embedded tissues. Taken the postoperative histopathological results as the gold standard, the diagnostic efficiency of BRAF V600E mutation was analyzed by comparing the results of multiple genes assay and BRAF V600E mutation detection of repeated puncture samples. Results:Of 264 nodules, 230 were malignant (papillary thyroid cancer (PTC)) and 34 were benign, with BSRTC categories Ⅰ (nondiagnostic) and Ⅲ (follicular lesion) nodules of 58 and 206. The sensitivities of BRAF V600E mutation detection in BSRTC categories Ⅰ and Ⅲ nodules were 77.1%(37/48) and 78.0%(142/182), the specificities were 9/10 and 91.7%(22/24), the positive predictive values were 97.4%(37/38) and 98.6%(142/144), the negative predictive values were 45.0%(9/20) and 35.5%(22/62), and the accuracy rates were 79.3%(46/58) and 79.6%(164/206). The diagnostic concordance of BRAF V600E mutation detection was 90.2%(46/51) in the preoperative and postoperative samples of 51 nodules with preoperative BRAF V600E wild type but postoperative pathology confirmed as PTC and was 11/13 in repeat puncture samples. Conclusion:BRAF V600E mutation detection is an effective diagnostic method for BSRTC categories Ⅰ and Ⅲ nodules.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

Our previous study has shown that p66^Shc plays an important role in the process of myocardial regeneration in newborn mice, and p66^Shc deficiency leads to weakened myocardial regeneration in newborn mice. This study aims to explore the role of p66^Shc protein in myocardial injury repair after myocardial infarction in adult mice, in order to provide a new target for the treatment of myocardial injury after myocardial infarction. Mouse myocardial infarction models of adult wild-type (WT) and p66^Shc knockout (KO) were constructed by anterior descending branch ligation. The survival rate and heart-to-body weight ratio of two models were compared and analyzed. Masson's staining was used to identify scar area of injured myocardial tissue, and myocyte area was determined by wheat germ agglutinin (WGA) staining. TUNEL staining was used to detect the cardiomyocyte apoptosis. The protein expression of brain natriuretic peptide (BNP), a common marker of myocardial hypertrophy, was detected by Western blotting. The results showed that there was no significant difference in survival rate, myocardial scar area, myocyte apoptosis, and heart weight to body weight ratio between the WT and p66^ShcKO mice after myocardial infarction surgery. Whereas the protein expression level of BNP in the p66^ShcKO mice was significantly down-regulated compared with that in the WT mice. These results suggest that, unlike in neonatal mice, the deletion of p66^Shc has no significant effect on myocardial injury repair after myocardial infarction in adult mice.
Animals ; Mice ; Body Weight ; Cicatrix/metabolism* ; Mice, Knockout ; Myocardial Infarction/genetics* ; Oxidative Stress ; Shc Signaling Adaptor Proteins/metabolism* ; Src Homology 2 Domain-Containing, Transforming Protein 1/metabolism*