ObjectivePrimary liver cancer, predominantly hepatocellular carcinoma (HCC), is a significant global health issue, ranking as the sixth most diagnosed cancer and the third leading cause of cancer-related mortality. Accurate and early diagnosis of HCC is crucial for effective treatment, as HCC and non-HCC malignancies like intrahepatic cholangiocarcinoma (ICC) exhibit different prognoses and treatment responses. Traditional diagnostic methods, including liver biopsy and contrast-enhanced ultrasound (CEUS), face limitations in applicability and objectivity. The primary objective of this study was to develop an advanced, light-weighted classification network capable of distinguishing HCC from other non-HCC malignancies by leveraging the automatic analysis of brightness changes in CEUS images. The ultimate goal was to create a user-friendly and cost-efficient computer-aided diagnostic tool that could assist radiologists in making more accurate and efficient clinical decisions. MethodsThis retrospective study encompassed a total of 161 patients, comprising 131 diagnosed with HCC and 30 with non-HCC malignancies. To achieve accurate tumor detection, the YOLOX network was employed to identify the region of interest (ROI) on both B-mode ultrasound and CEUS images. A custom-developed algorithm was then utilized to extract brightness change curves from the tumor and adjacent liver parenchyma regions within the CEUS images. These curves provided critical data for the subsequent analysis and classification process. To analyze the extracted brightness change curves and classify the malignancies, we developed and compared several models. These included one-dimensional convolutional neural networks (1D-ResNet, 1D-ConvNeXt, and 1D-CNN), as well as traditional machine-learning methods such as support vector machine (SVM), ensemble learning (EL), k-nearest neighbor (KNN), and decision tree (DT). The diagnostic performance of each method in distinguishing HCC from non-HCC malignancies was rigorously evaluated using four key metrics: area under the receiver operating characteristic (AUC), accuracy (ACC), sensitivity (SE), and specificity (SP). ResultsThe evaluation of the machine-learning methods revealed AUC values of 0.70 for SVM, 0.56 for ensemble learning, 0.63 for KNN, and 0.72 for the decision tree. These results indicated moderate to fair performance in classifying the malignancies based on the brightness change curves. In contrast, the deep learning models demonstrated significantly higher AUCs, with 1D-ResNet achieving an AUC of 0.72, 1D-ConvNeXt reaching 0.82, and 1D-CNN obtaining the highest AUC of 0.84. Moreover, under the five-fold cross-validation scheme, the 1D-CNN model outperformed other models in both accuracy and specificity. Specifically, it achieved accuracy improvements of 3.8% to 10.0% and specificity enhancements of 6.6% to 43.3% over competing approaches. The superior performance of the 1D-CNN model highlighted its potential as a powerful tool for accurate classification. ConclusionThe 1D-CNN model proved to be the most effective in differentiating HCC from non-HCC malignancies, surpassing both traditional machine-learning methods and other deep learning models. This study successfully developed a user-friendly and cost-efficient computer-aided diagnostic solution that would significantly enhances radiologists’ diagnostic capabilities. By improving the accuracy and efficiency of clinical decision-making, this tool has the potential to positively impact patient care and outcomes. Future work may focus on further refining the model and exploring its integration with multimodal ultrasound data to maximize its accuracy and applicability.

Objective To investigate the effects of raddeanin A(RA)on the proliferation and apoptosis of HCT116 cells and on the β-catenin/c-Myc pathway.Methods Human colon cancer HCT116 cells were divided into four groups:Control group,experimental-L group,experimental-M group and experimental-H group.Experimental-L,experimental-M,experimental-H groups were treated with 5,10 and 20 μmol·L-1raddeanin A,and the control group was given the same amount of normal saline,respectively.The inhibitory effect of RA on the proliferation of HCT116 cells of colon cancer was detected by cell counting kit-8(CCK-8)method.Cell nucleus morphology change was observed with the fluorescence;the apoptosis rate was detected by flow cytometry;and the expression of related proteins of β-catenin/c-Myc signaling pathway was detected by western blot.Results After 48 h,the cell inhibitory rates of the control group,experimental-L,experimental-M,experimental-H groups were 0,(19.15±0.65)％,(35.11±0.40)％and(49.93±1.13)％,respectively;the cell apoptosis rates were(0.16±0.18)％,(9.26±0.42)％,(17.87±2.54)％and(38.10±2.70)％,respectively;the protein expression levels of β-catenin were 0.74±0.03,0.69±0.01,0.33±0.02 and 0.16±0.04,respectively;the protein expression levels of c-Myc were 0.89±0.01,0.54±0.03,0.29±0.03 and 0.13±0.04,respectively;the protein expression levels of Cyclin D1 were 0.84±0.04,0.66±0.01,0.48±0.06 and 0.21±0.03,respectively;the expression levels of Cleaved-Caspase3 protein were 0.19±0.03,0.26±0.04,0.45±0.04 and 0.78±0.01,respectively.The above indicators in the experimental-L,experimental-M,experimental-H groups showed statistically significant differences compared to those of control group(all P＜0.05).Conclusion RA can inhibit the proliferation of HCT116 cells and induce apoptosis,which may be related to the inhibition of β-catenin/c-Myc signaling pathway.

Objective To study the pharmacokinetic characteristics of lamotrigine tablets in Chinese healthy subjects under fasting and fed conditions,and to evaluate the bioequivalence and safety profiles between the domestic test preparation and the original reference preparation.Methods Twenty-four Chinese healthy male and female subjects were enrolled under fasting and fed conditions,18 male and 6 female subjects under fasting conditions,17 male and 7 female subjects under fed conditions.A random,open,single-dose,two preparations,two sequences and double-crossover design was used.Plasma samples were collected over a 72-hour period after give the test or reference preparations 50 mg under fasting and fed conditions.The concentration of lamotrigine in plasma was detected by liquid chromatography-tandem mass spectrometry,and the main pharmacokinetic parameters were calculated to evaluate the bioequivalence by WinNonLin 8.1 program.Results The main pharmacokinetic parameters of single-dose the tested and reference preparations were as follows:The fasting condition Cmax were(910.93±248.02)and(855.87±214.36)ng·mL-1;tmax were 0.50(0.25,4.00)and 1.00(0.25,3.50)h;t1/2 were(36.1±9.2)and(36.0±8.2)h;AUC0_72h were(27 402.40±4 752.00)and(26 933.90±4 085.80)h·ng·mL-1.The fed condition Cmax were(701.62±120.67)and(718.95±94.81)ng·mL-1;tmax were 4.00(1.00,5.00)and 4.00(0.50,5.00)h;t1/2 were(44.2±12.4)and(44.0±12.0)h;AUC0-72h were(30 253.20±7 018.00)and(30 324.60±6 147.70)h·ng·mL-1.The 90％confidence intervals of the geometric mean ratios of Cmax and AUC0-72 hfor the test preparation and reference preparation were all between 80.00％and 125.00％under fasting and fed conditions.Conclusion Two kinds of lamotrigine tablets are bioequivalent,and have similar safety in Chinese healthy male and female subjects under fasting and fed conditions.

BACKGROUND: There are few multi-city studies on the association between temperature and mortality in basin climates. This study was based on the Sichuan Basin in southwest China to assess the association of basin temperature with non-accidental mortality in the population and with the temperature-related mortality burden. METHODS: Daily mortality data, meteorological and air pollution data were collected for four cities in the Sichuan Basin of southwest China. We used a two-stage time-series analysis to quantify the association between temperature and non-accidental mortality in each city, and a multivariate meta-analysis was performed to obtain the overall cumulative risk. The attributable fractions (AFs) were calculated to access the mortality burden attributable to non-optimal temperature. Additionally, we performed a stratified analyses by gender, age group, education level, and marital status. RESULTS: A total of 751,930 non-accidental deaths were collected in our study. Overall, 10.16% of non-accidental deaths could be attributed to non-optimal temperatures. A majority of temperature-related non-accidental deaths were caused by low temperature, accounting for 9.10% (95% eCI: 5.50%, 12.19%), and heat effects accounted for only 1.06% (95% eCI: 0.76%, 1.33%). The mortality burden attributable to non-optimal temperatures was higher among those under 65 years old, females, those with a low education level, and those with an alternative marriage status. CONCLUSIONS Our study suggested that a significant association between non-optimal temperature and non-accidental mortality. Those under 65 years old, females, and those with a low educational level or alternative marriage status had the highest attributable burden.
Female ; Humans ; China/epidemiology* ; Cities ; Cold Temperature ; Hot Temperature ; Mortality ; Temperature ; Time Factors ; Middle Aged ; Male

Objective:To investigate the prognosis of patients with initially resectable gastric cancer liver metastasis (GCLM) who were treated by different modalities, and analyze the influencing factors for prognosis of patients.Methods:The retrospective cohort study was conducted. The clinicopathological data of 327 patients with initially resectable GCLM who were included in the database of a nationwide multicenter retrospective cohort study on GCLM based on real-world data from January 2010 to December 2019 were collected. There were 267 males and 60 females, aged 61(54,68)years. According to the specific situations of patients, treatment modalities included radical surgery combined with systemic treatment, palliative surgery combined with systemic treatment, and systemic treatment alone. Observation indicators: (1) clinical characteristics of patients who were treated by different modalities; (2) prognostic outcomes of patients who were treated by different modalities; (3) analysis of influencing factors for prognosis of patients with initially resectable GCLM; (4) screening of potential beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard regression model. The propensity score matching was employed by the 1:1 nearest neighbor matching method with a caliper value of 0.1. The forest plots were utilized to evaluate potential benefits of diverse surgical combined with systemic treatments within the population. Results:(1) Clinical characteristics of patients who were treated by different modalities. Of 327 patients, there were 118 cases undergoing radical surgery plus systemic treatment, 164 cases undergoing palliative surgery plus systemic treatment, and 45 cases undergoing systemic treatment alone. There were significant differences in smoking, drinking, site of primary gastric tumor, diameter of primary gastric tumor, site of liver metastasis, and metastatic interval among the three groups of patients ( P<0.05). (2) Prognostic outcomes of patients who were treated by different modalities. The median overall survival time of the 327 pati-ents was 19.9 months (95% confidence interval as 14.9-24.9 months), with 1-, 3-year overall survival rate of 61.3%, 32.7%, respectively. The 1-year overall survival rates of patients undergoing radical surgery plus systemic treatment, palliative surgery plus systemic treatment and systemic treatment alone were 68.3%, 63.1%, 30.6%, and the 3-year overall survival rates were 41.1%, 29.9%, 11.9%, showing a significant difference in overall survival rate among the three groups of patients ( χ2=19.46, P<0.05). Results of further analysis showed that there was a significant difference in overall survival rate between patients undergoing radical surgery plus systemic treatment and patients undergoing systemic treatment alone ( hazard ratio=0.40, 95% confidence interval as 0.26-0.61, P<0.05), between patients undergoing palliative surgery plus systemic treatment and patients under-going systemic treatment alone ( hazard ratio=0.47, 95% confidence interval as 0.32-0.71, P<0.05). (3) Analysis of influencing factors for prognosis of patients with initially resectable GCLM. Results of multivariate analysis showed that the larger primary gastric tumor, poorly differentiated tumor, larger liver metastasis, multiple hepatic metastases were independent risk factors for prognosis of patients with initially resectable GCLM ( hazard ratio=1.20, 1.70, 1.20, 2.06, 95% confidence interval as 1.14-1.27, 1.25-2.31, 1.04-1.42, 1.45-2.92, P<0.05) and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy were independent protective factors for prognosis of patients with initially resectable GCLM ( hazard ratio=0.60, 0.39, 0.46, 95% confidence interval as 0.42-0.87, 0.25-0.60, 0.30-0.70, P<0.05). (4) Screening of potentinal beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Results of forest plots analysis showed that for patients with high-moderate differentiated GCLM and patients with liver metastasis located in the left liver, the overall survival rate of patients undergoing radical surgery plus systemic treatment was better than patients undergoing palliative surgery plus systemic treatment ( hazard ratio=0.21, 0.42, 95% confidence interval as 0.09-0.48, 0.23-0.78, P<0.05). Conclusions:Compared to systemic therapy alone, both radical and palliative surgery plus systemic therapy can improve the pro-gnosis of patients with initially resectable GCLM. The larger primary gastric tumor, poorly differen-tiated tumor, larger liver metastasis, multiple hepatic metastases are independent risk factors for prognosis of patients with initial resectable GCLM and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy are independent protective factors for prognosis of patients with initially resectable GCLM.

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

Objective To predict the potential geographic distribution of Oncomelania hupensis in Yunnan Province using random forest (RF) and maximum entropy (MaxEnt) models, so as to provide insights into O. hupensis surveillance and control in Yunnan Province. Methods The O. hupensis snail survey data in Yunnan Province from 2015 to 2016 were collected and converted into O. hupensis snail distribution site data. Data of 22 environmental variables in Yunnan Province were collected, including twelve climate variables (annual potential evapotranspiration, annual mean ground surface temperature, annual precipitation, annual mean air pressure, annual mean relative humidity, annual sunshine duration, annual mean air temperature, annual mean wind speed, ≥ 0 ℃ annual accumulated temperature, ≥ 10 ℃ annual accumulated temperature, aridity and index of moisture), eight geographical variables (normalized difference vegetation index, landform type, land use type, altitude, soil type, soil textureclay content, soil texture-sand content and soil texture-silt content) and two population and economic variables (gross domestic product and population). Variables were screened with Pearson correlation test and variance inflation factor (VIF) test. The RF and MaxEnt models and the ensemble model were created using the biomod2 package of the software R 4.2.1, and the potential distribution of O. hupensis snails after 2016 was predicted in Yunnan Province. The predictive effects of models were evaluated through cross-validation and independent tests, and the area under the receiver operating characteristic curve (AUC), true skill statistics (TSS) and Kappa statistics were used for model evaluation. In addition, the importance of environmental variables was analyzed, the contribution of environmental variables output by the models with AUC values of > 0.950 and TSS values of > 0.850 were selected for normalization processing, and the importance percentage of environmental variables was obtained to analyze the importance of environmental variables. Results Data of 148 O. hupensis snail distribution sites and 15 environmental variables were included in training sets of RF and MaxEnt models, and both RF and MaxEnt models had high predictive performance, with both mean AUC values of > 0.900 and all mean TSS values and Kappa values of > 0.800, and significant differences in the AUC (t = 19.862, P < 0.05), TSS (t = 10.140, P < 0.05) and Kappa values (t = 10.237, P < 0.05) between two models. The AUC, TSS and Kappa values of the ensemble model were 0.996, 0.954 and 0.920, respectively. Independent data verification showed that the AUC, TSS and Kappa values of the RF model and the ensemble model were all 1, which still showed high performance in unknown data modeling, and the MaxEnt model showed poor performance, with TSS and Kappa values of 0 for 24%(24/100) of the modeling results. The modeling results of 79 RF models, 38 MaxEnt models and their ensemble models with AUC values of > 0.950 and TSS values of > 0.850 were included in the evaluation of importance of environmental variables. The importance of annual sunshine duration (SSD) was 32.989%, 37.847% and 46.315% in the RF model, the MaxEnt model and their ensemble model, while the importance of annual mean relative humidity (RHU) was 30.947%, 15.921% and 28.121%, respectively. Important environment variables were concentrated in modeling results of the RF model, dispersed in modeling results of the MaxEnt model, and most concentrated in modeling results of the ensemble model. The potential distribution of O. hupensis snails after 2016 was predicted to be relatively concentrated in Yunnan Province by the RF model and relatively large by the MaxEnt model, and the distribution of O. hupensis snails predicted by the ensemble model was mostly the joint distribution of O. hupensis snails predicted by RF and MaxEnt models. Conclusions Both RF and MaxEnt models are effective to predict the potential distribution of O. hupensis snails in Yunnan Province, which facilitates targeted O. hupensis snail control.

Objective To investigate the effects of acetylshikonin on proliferation,invasion and migration of oxaliplatin-resistant human colon cancer HCT116 cells(HCT116/L-OHP).Methods HCT116/L-OHP cells were divided into blank group,control group,experimental-L group,experimental-M group and experimental-H group.The control group was treated with 10 μmol·L-1 oxaliplatin.The experimental-L,experimental-M,experimental-H groups were treated with 1.25,2.50 and 5.00 μmol·L-1 acetylshikin and 10 μmol·L-1 oxaliplatin,respectively.The blank group was given routine culture.The changes of HCT116/L-OHP cell proliferation were detected by cell counting kit-8(CCK-8)method;flow cytometry was used to evaluate the apoptosis of cells;Transwell assay was used to detect the changes of cell migration and invasion ability;Western blot was used to detect the expressions of P-glycoprotein(P-gp),matrix metallo-proteinases 2(MMP2),nuclear factor kappa-B(NF-κB)/and hypoxia induced factor-1 α(HIF-1α)proteins.Results The cell inhibition rates of the blank group,control group and experimental-L,-M,-H groups were 0,(8.27±0.01)％,(10.53±0.02)％,(34.17±0.01)％and(48.47±0.05)％;cell apoptosis rates were(0.13±0.02)％,(1.37±1.04)％,(9.73±0.87)％,(26.71±4.26)％and(40.75±4.70)％;invading cells were 130.70±9.81,127.10±9.21,71.83±3.57,28.83±1.87 and 19.63±6.11;the number of migration cells was 150.50±10.17,148.40±8.13,94.58±4.09,63.98±5.09 and 31.85±5.50;the relative expression levels of P-gp protein were 0.91±0.01,0.89±0.02,0.75±0.04,0.61±0.07 and 0.25±0.03;the relative expression levels of MMP2 protein were 1.24±0.01,1.22±0.02,0.96±0.01,0.53±0.01 and 0.16±0.02;the relative expression levels of NF-κB-p65 were 1.12±0.12,1.07±0.01,0.78±0.01,0.64±0.02 and 0.31±0.03;the relative expression levels of HIF-1 α were 0.65±0.04,0.52±0.03,0.41±0.02,0.35±0.03 and 0.09±0.01,respectively.The above indicators in the experimental-L,-M,-H groups showed statistically significant differences compared to those of blank group(all P＜0.05).Conclusion Acetylshikonin combined with oxaliplatin can significantly inhibit the proliferation,invasion and migration of HCT116/L-OHP cells,and induce cell apoptosis,which may be related to the inhibition of P-gp and MMP2 expression and the activation of NF-κB/HIF-1 α signal.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.