Background and Aims:Pancreatic ductal adenocarcinoma(PDAC)is the most common pathological type of pancreatic cancer,with a poor long-term prognosis and a lack of individualized prognostic assessment tools.This study was conducted to construct a prognostic nomogram for PDAC patients based on large-sample real-world data from the SEER database using machine learning algorithms to provide precise and individualized prognostic evaluations to inform clinical decision-making. Methods:The clinical and prognostic data of PDAC patients pathologically diagnosed from 2000 to 2018 were extracted from the SEER database based on inclusion and exclusion criteria.The data were randomly divided into training(70％)and validation(30％)sets.In the training set,independent prognostic factors were identified using univariate and multivariate Cox proportional hazards models,LASSO regression,and random survival forests.A nomogram was developed to predict 6,12,and 36-month cancer-specific survival(CSS)and overall survival(OS).The model was then validated and assessed in both training and validation sets using the concordance index(C-index),receiver operating characteristic(ROC)curve,calibration curve,survival curves,and decision curve analysis. Results:A total of 4 237 patients were included,with 2 965 in the training set and 1 272 in the validation set,showing comparable baseline characteristics.The median follow-up time was 18(9-36)months for the training set and 18(9-37)months for the validation set.The multivariate Cox model indicated that age,T stage,N stage,M stage,differentiation,surgery,systemic therapy,and chemotherapy were independent factors for OS(all P＜0.05).For CSS,age,T stage,N stage,M stage,differentiation,surgery,and chemotherapy were independent factors(all P＜0.05).The LASSO regression model found that age,differentiation,T stage,N stage,M stage,chemotherapy,surgery,lymph node dissection,radiotherapy,and systemic therapy were associated with OS,while T stage,N stage,M stage,chemotherapy,surgery,lymph node dissection,radiotherapy,and systemic therapy were linked to CSS.The random survival forest model identified the top five variables affecting OS as systemic therapy,differentiation,N stage,chemotherapy,and T stage;and for CSS,they were systemic therapy,differentiation,N stage,chemotherapy,and AJCC stage.Based on the analyses from the multivariate Cox,LASSO,and random survival forest model,along with clinical significance,a prediction model was successfully constructed using seven clinical features:age,T stage,N stage,M stage,differentiation,surgery,and chemotherapy to predict OS and CSS at 6,12,and 36 months.The validation results showed C-indexes of 0.692(95％CI=0.681-0.704)and 0.680(95％CI=0.664-0.698)for OS in the training and validation sets,respectively,and 0.696(95％CI=0.684-0.707)and 0.680(95％CI=0.662-0.698)for CSS.ROC curves indicated good predictive value,and calibration curves closely matched the ideal 45° reference line. Conclusion:Age,TNM stage,differentiation,surgery,and chemotherapy are independent prognostic factors for PDAC patients.The prognostic model based on these variables has high discrimination and accuracy,assisting clinicians in developing precise and personalized treatment and follow-up plans for PDAC patients.

Due to the limitations of current anti-HBV therapies, the HBV core (HBc or HBcAg) protein assembly modulators (CpAMs) are believed to be potential anti-HBV agents. Therefore, discovering safe and efficient CpAMs is of great value. In this study, we established a HiBiT-based high-throughput screening system targeting HBc and screened novel CpAMs from an in-house marine chemicals library. A novel lead compound 8a, a derivative of the marine natural product naamidine J, has been successfully screened for potential anti-HBV activity. Bioactivity-driven synthesis was then conducted, and the structure‒activity relationship was analyzed, resulting in the discovery of the most effective compound 11a (IC₅₀ = 0.24 μmol/L). Furthermore, 11a was found to significantly inhibit HBV replication in multiple cell models and exhibit a synergistic effect with tenofovir disoproxil fumarate (TDF) and IFNa2 in vitro for anti-HBV activity. Treatment with 11a in a hydrodynamic-injection mouse model demonstrated significant anti-HBV activity without apparent hepatotoxicity. These findings suggest that the naamidine J derivative 11a could be used as the HBV core protein assembly modulator to develop safe and effective anti-HBV therapies.

As the utilization of computed tomography in lung cancer screening becomes more prevalent in the post-pandemic era, the incidence of multiple primary lung cancer (MPLC) has surged in various countries and regions. Despite the continued application of advanced histologic and sequencing technologies in this research field, the differentiation between MPLC and intrapulmonary metastasis (IM) remains challenging. In recent years, the specific mechanisms of genetic and environmental factors in MPLC have gradually come to light. Lobectomy still predominates in the treatment of MPLC, but the observation that tumor-specific sublobar resection has not detrimentally impacted survival appears to be a viable option. With the evolution of paradigms, the amalgamated treatment, primarily surgical, is an emerging trend. Among these, stereotactic ablative radiotherapy (SABR) and lung ablation techniques have emerged as efficacious treatments for early unresectable tumors and control of residual lesions. Furthermore, targeted therapies for driver-positive mutations and immunotherapy have demonstrated promising outcomes in the postoperative adjuvant phase. In this manuscript, we intend to provide an overview of the management of MPLC based on the latest discoveries.
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Humans ; Lung Neoplasms/therapy* ; Early Detection of Cancer ; Lung/surgery* ; Treatment Outcome ; Radiosurgery/methods* ; Neoplasms, Multiple Primary/pathology*

Humans ; COVID-19/genetics* ; SARS-CoV-2/genetics* ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; CRISPR-Cas Systems/genetics* ; RNA, Viral/genetics*

Background Preterm birth-related complications are the leading cause of death in newborns and children under the age of 5 years. Maternal heat exposure has been associated with both sleep status during pregnancy and the increased risk of preterm birth. However, whether sleep status could mediate the association between heat exposure and preterm birth remains unclear. Objective To evaluate the association between maternal heat exposure in early pregnancy and preterm birth, and to further explore potential mediation effect of sleep status on the association between heat exposure and preterm birth. Methods A birth cohort was established in Guangzhou Panyu Maternal Child Health Hospital (Guangzhou Panyu District He Xian Memorial Hospital) from 2017 until now. Pregnant women (with gestational age between 8 and 13 weeks) were included in this study when they presented to the hospital for their first prenatal care visit and signed an informed consent. Then they were followed up until delivery. A total of 3 268 pregnant women were included for the final analysis. Questionnaires were distributed to collect the demographic characteristics, lifestyles, and sleep status of pregnant women. Daily meteorological data during the study period were collected from meteorological monitoring stations in Guangzhou and the average ambient mean temperature of four weeks before the survey was calculated and assigned for each pregnancy. The 75th, 80th, 85th, 90th, and 95th percentiles (P₇₅, P₈₀, P₈₅, P₉₀, and P₉₅) of the average ambient temperature of all pregnant women were used as the thresholds to define heat exposure. Logistic regression was used to evaluate the effects of heat exposure in different definitions on preterm birth and sleep status (sleep duration, night sleep timing, and wake up timing). The mediation effects of sleep status on the relationship between heat exposure and preterm birth were also analyzed. Results Among all the included participants, 165 newborns were preterm births with an incidence rate of 5.0%. Heat exposures with thresholds of P₉₀ and P₉₅ increased the risk of preterm birth, with ORs (95%CIs) of 1.66 (1.04-2.57) and 1.90 (1.03-3.33), respectively (P<0.05). Heat exposures with thresholds of P₇₅, P₈₀, P₈₅, P₉₀, and P₉₅ decreased the sleep duration (<9 h vs. ≥9 h, control group: ≥9 h), and the ORs (95%CIs) were 1.51 (1.25-1.83), 1.44 (1.17-1.77), 1.35 (1.08-1.70), 1.43 (1.09-1.87), and 1.45 (1.00-2.13), respectively. Heat exposures with P₇₅ and P₈₀ thresholds resulted in earlier wake up timing (<8: 00 vs. ≥8: 00, control group: <8: 00), with ORs (95%CIs) of 0.77 (0.63-0.93) and 0.76(0.61-0.93), respectively. No significant association was observed between heat exposure and night sleep timing. The mediation analyses showed that under heat exposure with P₉₀ threshold, a statistically significant mediation effect was observed for sleep duration, and the proportion mediated was 6.07% (95%CI: 0.17%-25.00%) (P<0.05). No significant mediation effect was observed for night sleep timing and wake up timing. Conclusion An elevated risk of preterm birth after heat exposure in early pregnancy may be partly mediated through reducing sleep duration.

TSCI have dyskinesia and sensory disturbance that can cause various life-threaten complications. The patients with traumatic spinal cord injury (TSCI), seriously affecting the quality of life of patients. Based on the epidemiology of TSCI and domestic and foreign literatures as well as expert investigations, this expert consensus reviews the definition, injury classification, rehabilitation assessment, rehabilitation strategies and rehabilitation measures of TSCI so as to provide early standardized rehabilitation treatment methods for TSCI.

Direct-acting antivirals (DAAs) play a critical role for the therapy of chronical hepatitis B. DAAs can decrease the production of viral progeny of hepatitis B virus (HBV), breaking the viral dynamic equilibrium between: (1) virion production from hepatocytes and clearance from circulation; (2) replenishment and decay of covalently closed circular (ccc)DNA pool inside infected hepatocytes. Nucleos(t)ide analogues can potently shift the first balance to undetectable viremia in the blood, but have limited or no effect on the second one, thus making it imperative to develop new agents targeting additional step(s) of HBV life cycle. We herein briefly introduce the DAAs currently in development by classifying them as agents affecting the replenishment or the decay of cccDNA pool.

Objective? To explore the effects of enteral nutrition program based on intensive ultrasound monitoring gastric residual on patients receiving lung transplantation. Methods? Totally 100 patients who received lung transplantation in a Class Ⅲ Grade A hospital between January and December 2016 were selected and divided into the treatment group (n=50) and the control group (n=50) according to the random number table. Patients in the treatment group received enteral nutrition based on intensive ultrasound monitoring gastric residual, while patients in the control group received conventional enteral nutrition. The indicators of enteral nutrition application and complications were observed in both groups. Results? The gastric residual of the treatment group was (130.32±40.44) ml; the nutrition interruption rate was 6%; the time for achieving the target feed volume was (3.47±0.62) d, lower than those of the control group (t/χ2=-2.341, 8.575, 2.193;P＜ 0.05), which were (198.13±40.25) ml, 28% and (5.59±0.71) d. The dripping speed of the treatment group was (87.00±10.59) ml/h, higher than that of the control group (t=6.121, P＜0.05). The incidence rate of aspiration of the treatment group was 4%, and there was no statistically significant difference compared with that of the control group (χ2=0.298; P＞0.05), which was 6%. The incidence rates of enteral nutrition reflux, diarrhea and reintubation rates of the treatment group were 10%, 10% and 8%, respectively, lower than those of the control group (33%,26%,24%) (χ2=6.250, 4.336, 4.762; P＜ 0.05) . Conclusions? The enteral nutrition program based on intensive ultrasound monitoring gastric residual conforms to target-oriented nursing care for patients receiving lung transplantation, which helps to achieve the target feed volume more quickly and ameliorate enteral nutrition-related complications.

Objective? To investigate the effect and safety of high-flow nasal cannula (HFNC) oxygen therapy for patients after extubation in lung transplantation. Methods? A retrospective study was conducted on 60 hospitalized patients with lung transplant during January 2017 to December 2017 in Wuxi People＇s Hospital. According to the different methods of respiratory support prescribed after extubation, the patients were divided into two groups: observation group (n=28, via HFNC) and control group (n=32, via nasal oxygen tube) . The two groups were compared in terms of the clinical indicators including their blood gas analysis(oxygenation index, lactic acid, partial pressure of carbon dioxide) , viscosity of sputum and comfort, etc. Results? Six hours after extubation and before transferring to other departments, the observation group＇s oxygenation index was(263.70±48.97)and(273.22±43.26)mmHg, which were statistically different from those of the control group with (217.83±77.30)and(229.08±68.64)mmHg respectively (P＜ 0.05). Before transferring to other departments, the partial pressure of carbon dioxide in the observation group was (37.04±8.56)mmHg, lower than the control group with (42.43±6.14)mmHg with a statistical difference (P＜0.05); the viscosity of sputum in the obseration group was lower than the control group with statistical difference (P＜0.05); the patients＇ comfort in the observation group achieved (7.72±1.06)points, higher than the control group＇s (4.39±0.82)points with statistical difference (P＜ 0.05). Conclusions? HFNC oxygen therapy for the patients after extubation in lung transplantation has good effects, is safe and reliable, and can be widely applied in clinical practice.

Objective To summarize the experiences of postoperative care of 7 patients with lung transplantation patients receiving high flow nasal cannulae oxygen therapy. Methods The key points to ensure the success of operation were oxygen therapy waiting for lung transplantation,sequential treatment after tracheal intubation, assisted by fiberoptic bronchoscopy, nasal high flow oxygen therapy failed to switch to non-invasive treatment or re intubation. Results All 7 patients got through the intensive care period successful. Conclusions High flow nasal cannulae can improve the comfort and compliance of lung transplant patients,and easy to operate.