[Experimental study on the artificial infection of common freshwater snails with Angiostrongylus cantonensis in Dali Bai Autonomous Prefecture, Yunnan Province].

OBJECTIVE: To evaluate the potential risk of transmission of angiostrongyliasis by common freshwater snails in Dali Bai Autonomous Prefecture, Yunnan Province, so as to provide insights into local surveillance of angiostrongyliasis. METHODS: Common freshwater snails were collected from Dali Bai Autonomous Prefecture, Yunnan Province from March to April, 2020, and identified and bred in laboratory. SD rats were infected with third-stage larvae of Angiostrongylus cantonensis that were isolated from commercially available Pomacea canaliculata snails in Dali Bai Autonomous Prefecture, and freshwater snails were infected with the first-stage larvae of A. cantonensis that were isolated from the feces of SD rats 39 days post-infection at room temperature. The developmental process and morphological characteristics of worms in hosts were observed, and the percentages of A. cantonensis infections in different species of freshwater snails were calculated. Then, SD rats were infected with the third-stage larvae of A. cantonensis that were isolated from A. cantonensis-infected freshwater snails, and the larval development and reproduction was observed. RESULTS: More than 3 000 freshwater snail samples were collected from farmlands, ditches and wetlands around Erhai Lake in Dali Bai Autonomous Prefecture, and Cipangopaludina chinensis, P. canaliculata, Parafossarulus striatulus, Oncomelania hupensis robertsoni, Galba pervia, Physa acuta, Radix swinhoei, Assiminea spp., Tricula spp. and Bellamya spp. were morphologically identified. A total of 105 commercially available P. canaliculata snails were tested for A. cantonensis infections, and 2 P. canaliculata snails were found to be infected with A. cantonensis, in which the third-stage larvae of A. cantonensis were isolated. Ten species of freshwater snails were artificially infected with the third-stage larvae of A. cantonensis, and all 10 species of freshwater snails were found to be infected with A. cantonensis, with the highest positive rate of A. cantonensis infections in Bellamya spp. (62.3%, 137/204), and the lowest in C. chinensis (35.5%, 11/31). After SD rats were infected with the third-stage larvae of A. cantonensis isolated from different species of freshwater snails, mature adult worms of A. cantonensis were yielded. CONCLUSIONS: Multiple species of freshwater snails may serve as intermediate hosts of A. cantonensis under laboratory conditions in Dali Bai Autonomous Prefecture of Yunnan Province. Further investigations on natural infection of A. cantonensis in wild snails in Dali Bai Autonomous Prefecture seem justified.

[Role of CTGF and PI3K/Akt signaling pathway in paraquat-induced mesenchymal changes in alveolar epithelial cells].

Objective: To investigate the role of connective tissue growth factor (CTGF) and PI3K/Akt signaling pathways in paraquat (PQ) -induced alterations in alveolar epithelial cell mesenchymalization (EMT) . Methods: In February 2023, RLE-6TN cells were divided into 2 groups, which were set as uncontaminated group and contaminated group (200 µmol/L PQ), and cellular EMT alteration, CTGF and PI3K/Akt signaling pathway related molecules expression were detected by cell scratch assay, qRT-PCR and western-blot assay. Using shRNA interference technology to specifically inhibit the expression of CTGF, RLE-6TN cells were divided into four groups: control group, PQ group (200 µmol/L PQ), interference group (transfected with a plasmid with shRNA-CTGF+200 µmol/L PQ), and null-loaded group (transfected with a plasmid with scramble- CTGF+200 µmol/L PQ), qRT-PCR and western blot were used to examine the alteration of the cellular EMT and the expression of molecules related to the activity of PI3K/Akt pathway. The PI3K/Akt signaling pathway was blocked by the PI3K inhibitor LY294002, and the expression of EMT-related molecules in cells of the control group, PQ group (200 µmol/L PQ), and inhibitor group (200 µmol/L PQ+20 µmol/L LY294002) was examined by qRT-PCR and western blot.The t-test was used to compare the differences between the two groups, while the analysis of variance (ANOVA) was applied to compare the differences among multiple groups. For further pairwise comparisons, the Bonferroni method was adopted. Results: The results of cell scratch test showed that compared with the uncontaminated group, RLE-6TN cells in the contaminated group had faster migration rate, lower mRNA and protein expression levels of E-Cadherin, and higher mRNA and protein expression levels of α-SMA, CTGF, PI3K and Akt, with statistical significance (P<0.05). After specific inhibition of CTGF expression, the mRNA and protein expression of CTGF, PI3K, Akt, and α-SMA in the cells of the interference group were significantly lower than that of the PQ group and the null-loaded group (P<0.05/6), whereas that of E-Cadherin was higher than that of the PQ group and the null-loaded group (P<0.05/6). Specifically blocking the PI3K/Akt signaling pathway, the mRNA and protein expression of PI3K, Akt and α-SMA in the cells of the inhibitor group was decreased compared with that of the PQ group (P<0.05/3), while the expression of E-Cadherin was elevated compared with that of the PQ group (P<0.05/3) . Conclusion: CTGF may promote PQ-induced alveolar epithelial cell EMT through activation of the PI3K/Akt signaling pathway. Inhibition of CTGF expression or blockade of PI3K/Akt signaling pathway activity can alleviate the extent of PQ-induced alveolar epithelial cell EMT.

SWI/SNF family mutations in advanced NSCLC: genetic characteristics and immune checkpoint inhibitors' therapeutic implication.

BACKGROUND: SWItch/Sucrose NonFermentable (SWI/SNF) mutations have garnered increasing attention because of their association with unfavorable prognosis. However, the genetic landscape of SWI/SNF family mutations in Chinese non-small-cell lung cancer (NSCLC) is poorly understood. In addition, the optimal treatment strategy has not yet been determined. PATIENTS AND METHODS: We collected sequencing data on 2027 lung tumor samples from multiple centers in China to comprehensively analyze the genomic characteristics of the SWI/SNF family within the Chinese NSCLC population. Meanwhile, 519 patients with NSCLC from Sun Yat-sen University Cancer Center were enrolled to investigate the potential implications of immunotherapy on patients with SWI/SNF mutations and to identify beneficial subpopulations. We also validated our findings in multiple publicly available cohorts. RESULTS: Approximately 15% of Chinese patients with lung cancer harbored mutations in the SWI/SNF chromatin remodeling complex, which were mutually exclusive to the EGFR mutations. Patients with SWI/SNFmut NSCLC who received first-line chemoimmunotherapy had better survival outcomes than those who received chemotherapy alone (median progression-free survival: 8.70 versus 6.93 months; P = 0.028). This finding was also confirmed by external validation using the POPLAR/OAK cohort. SWI/SNFmut NSCLC is frequently characterized by high tumor mutational burden and concurrent TP53 or STK11/KEAP mutations. Further analysis indicated that TP53 and STK11/KEAP1 mutations could be stratifying factors in facilitating personalized immunotherapy and guiding patient selection. CONCLUSIONS: This study provides a step forward in understanding the genetic and immunological characterization of SWI/SNF genetic alterations. Moreover, our study reveals substantial benefits of immunotherapy over chemotherapy for SWI/SNF-mutant patients, especially the SWI/SNFmut and TP53mut subgroups.

[The ninth edition of TNM staging for lung cancer: precise staging for precise diagnosis and treatment].

The ninth edition of TNM staging for lung cancer has been announced at the 2023 World Lung Cancer Congress and implemented from January 1, 2024. The focus of the ninth TNM staging change is dividing N2 into N2a and N2b, as well as M1c into M1c1 and M1c2. Although the T staging has not changed, it has played an important role in verifying the eighth edition of the T staging. The subdivision of stage N2 has led some patients with ⅢA of the eighth edition to experience ascending or descending stages, which will more accurately help to assess the condition and prognosis of patients with mediastinal lymph node metastasis, as well as the design of related clinical studies. Modifying the M1c staging will help define oligometastasis and explore new treatment models in the future. The ninth edition of the TNM staging system provides a more detailed division of different tumor loads, but there is no clear explanation for the staging of lung cancer after neoadjuvant therapy. Further data analysis is needed, and it is expected to be answered in the tenth edition of TNM staging.

[Recent research advances of angiogenesis in temporomandibular joint osteoarthritis].

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease of temporomandibular joint, which has a high incidence and affects the quality of patients' life. While the pathogenesis of TMJOA remains unclear. It has been found that angiogenesis is involved in the development of TMJOA and it is closely related to the degradation of articular cartilage matrix, subchondral ossification, osteophyte formation and pain. This article reviews the recent advances in the study of angiogenesis in TMJOA, and provides a prospect for the treatment of TMJOA.

[A multiscale carotid plaque detection method based on two-stage analysis].

OBJECTIVE: To develop a method for accurate identification of multiscale carotid plaques in ultrasound images. METHODS: We proposed a two-stage carotid plaque detection method based on deep convolutional neural network (SM-YOLO).A series of algorithms such as median filtering, histogram equalization, and Gamma transformation were used to preprocess the dataset to improve image quality. In the first stage of the model construction, a candidate plaque set was built based on the YOLOX_l target detection network, using multiscale image training and multiscale image prediction strategies to accommodate carotid artery plaques of different shapes and sizes. In the second stage, the Histogram of Oriented Gradient (HOG) features and Local Binary Pattern (LBP) features were extracted and fused, and a Support Vector Machine (SVM) classifier was used to screen the candidate plaque set to obtain the final detection results. This model was compared quantitatively and visually with several target detection models (YOLOX_l, SSD, EfficientDet, YOLOV5_l, Faster R-CNN). RESULTS: SM-YOLO achieved a recall of 89.44%, an accuracy of 90.96%, a F1-Score of 90.19%, and an AP of 92.70% on the test set, outperforming other models in all performance indicators and visual effects. The constructed model had a much shorter detection time than the Faster R-CNN model (only one third of that of the latter), thus meeting the requirements of real-time detection. CONCLUSION: The proposed carotid artery plaque detection method has good performance for accurate identification of carotid plaques in ultrasound images.

[Introduction to the 9th edition of TNM classification for lung cancer].

Lung cancer is the second commonly diagnosed cancer and remained the leading cause of cancer-related death, with an estimated 1.8 million deaths in 2020. The identification of driver gene mutation and administration of corresponding tyrosine kinase inhibitor have improved overall survival and quality of life in advanced lung cancer patients. Check point inhibitor has revolutionized treatment strategy of driver gene negative advanced NSCLC patients. TNM staging system is the most widely used classification method, providing an international common language during academic communication and important tool for predicting prognosis and subsequent treatment decision making. Accumulating knowledge about prognostic factors in lung cancer promotes the update of TNM classification. In the World Conference on Lung Cancer (WCLC) held in Singapore, September, 2023, International Association for Study of Lung Cancer (IASLC) released the forthcoming 9th edition of TNM classification for lung cancer, which is supposed to be adopted at January, 2024. The manuscript discussed the history, data resource and limitation of the TNM staging system.

Imaging features of temporomandibular joint synovial chondromatosis with associated osseous degenerative changes.

Synovial chondromatosis (SC) of the temporomandibular joint (TMJ) is a rare benign disease associated with the formation of multiple cartilaginous nodules in the synovial tissue of the TMJ. This can result in pain, swelling, clicking, limited mouth opening, and osseous degenerative joint changes. A retrospective cross-sectional study was performed to summarize the clinical features, radiographic findings, and surgical and histopathological findings of TMJ SC patients who underwent open surgery over a 24-year period. A radiographic scoring system was used to evaluate osseous changes and correlate condyle and joint fossa degeneration. The study included 38 patients and focused on 38 joints. All 38 of these joints showed degenerative changes in the condyle, while 37 showed osseous degenerative changes in the articular fossa. The degree of condylar degenerative changes was related to the duration of the chief complaints (r = 0.342, P = 0.036) and the histopathological stage of the TMJ SC (r = 0.440, P = 0.006), while the degree of joint fossa degenerative changes was associated with the radiographic extent of the SC (r = 0.504, P = 0.001), type of calcification (r = 0.365, P = 0.024), and the histopathological stage (r = 0.458, P = 0.004).

Gelanxinning capsule improves coronary microvascular dysfunction by inhibiting inflammation and restoring endothelial function.

OBJECTIVE: Gelanxinning capsule (GXSC) is a Chinese medicine to cure coronary artery disease (CAD) and a compound of Pueraria lobata, hawthorn extract, and gypenosides. However, whether GXSC could improve coronary microvascular dysfunction (CMD) is unknown. We aimed to demonstrate the therapeutic effect of GXSC on CMD and its underlying mechanisms in CAD patients. PATIENTS AND METHODS: This was a single-center, randomized control trial. A total of 78 patients diagnosed by selective coronary angiography (CAG) participated in this study. Patients' demographics, medical history, medications, and results of laboratory testing were collected. The index of microcirculatory resistance (IMR) and coronary flow reserve (CFR) were obtained by CAG and single-photon emission computed tomography (SPECT) separately. Fasting blood samples were obtained on the morning following the admission day. Concentrations of several molecules of inflammation, endothelial function, and coronary microvascular function were measured by ELISA. Patients were followed-up two months after discharge and fasting blood samples were also acquired. RESULTS: All patients were randomly divided into 2 groups: GXSC, 38 (48.7%), and control, 40 (51.3%). The intergroup comparison revealed no significant differences with respect to all baseline variables. As for inflammation biomarkers, proinflammatory NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and interleukin (IL)-1 were significantly decreased in GXSC compared with the control group (0.71±0.08 vs. 1.04±0.07, p<0.01 and 7.16±0.59 vs. 10.93±1.04, p<0.01). Anti-inflammatory adropin was increased in the GXSC group (7.75±0.59 vs. 5.71±0.68, p=0.03). As for indexes of endothelial function, the concentrations of syndecan (SDC) 1, SDC4 and heparan sulphates (HS) were significantly downregulated in 2 months GXSC treatment (3.31±0.28 vs. 4.85±0.43, p<0.01, 3.79±0.56 vs. 5.69±0.68, p=0.03 and 21.31±2.79 vs. 35.18±4.11 p<0.01). In addition, the level of SIRTUIN 1 (SIRT1), which is a vascular protective protein, was upregulated in GXSC group (5.63±0.30 vs. 4.22±0.37, p<0.01). As for molecules of coronary microvascular function, endocan, soluble urokinase plasminogen activator receptor (suPAR), and growth differentiation factor (GDF)-15 were significantly decreased consistently in GXSC compared with the control group (0.09±0.01 vs. 0.19±0.03, p<0.01, 4.44±0.40 vs. 5.73±0.40, p=0.03 and 2.08±0.17 vs. 2.69±0.18, p=0.02). CONCLUSIONS: In conclusion, GXSC could improve CMD by inhibiting inflammation and restoring endothelial function. GXSC might be an effective drug in CAD patients without obstructive epicardial coronary arteries but suffering from angina.

[Prediction of microvascular invasion in hepatocellular carcinoma with magnetic resonance imaging using models combining deep attention mechanism with clinical features].

OBJECTIVE: To investigate the consistency and diagnostic performance of magnetic resonance imaging (MRI) for detecting microvascular invasion (MVI) of hepatocellular carcinoma (HCC) and the validity of deep learning attention mechanisms and clinical features for MVI grade prediction. METHODS: This retrospective study was conducted among 158 patients with HCC treated in Shunde Hospital Affiliated to Southern Medical University between January, 2017 and February, 2020. The imaging data and clinical data of the patients were collected to establish single sequence deep learning models and fusion models based on the EfficientNetB0 and attention modules. The imaging data included conventional MRI sequences (T1WI, T2WI, and DWI), enhanced MRI sequences (AP, PP, EP, and HBP) and synthesized MRI sequences (T1mapping-pre and T1mapping-20 min), and the high-risk areas of MVI were visualized using deep learning visualization techniques. RESULTS: The fusion model based on T1mapping-20min sequence and clinical features outperformed other fusion models with an accuracy of 0.8376, a sensitivity of 0.8378, a specificity of 0.8702, and an AUC of 0.8501 for detecting MVI. The deep fusion models were also capable of displaying the high-risk areas of MVI. CONCLUSION: The fusion models based on multiple MRI sequences can effectively detect MVI in patients with HCC, demonstrating the validity of deep learning algorithm that combines attention mechanism and clinical features for MVI grade prediction.

[Advances on pathogenesis of acquired peritoneal ultrafiltration failure in peritoneal dialysis].

Peritoneal ultrafiltration failure is a common reason for peritoneal dialysis (PD) withdrawal as well as mortality in PD patients. Based on the three-pore system, inter-cellular small pores and trans-cellular ultra-small pores (aquaporin-1) are mainly responsible for water transfer across the peritoneum. Both small and ultra-small pores-dependent water (free water) transport decline accompanied with time on PD, with more significant decrease in free water, resulting in peritoneal ultrafiltration failure. The reduction of free water transport is associated with fast peritoneal solute transfer, reduced crystalloid osmotic gradient due to increased interstitial glucose absorption, and declined osmotic conductance to glucose resulted from impaired aquaporin-1 function and peritoneal interstitial fibrosis. The decline of small pore-based water is mainly because of fast loss of crystalloid osmotic gradient, decrease of hydrostatic pressure mediated by peritoneal vasculopathy, as well as reduced absolute number of small pores. The current review discusses the advance on pathogenesis of acquired peritoneal ultrafiltration failure in long-term PD.

[Advances in the arthroscopic methods in managing temporomandibular joint disorders].

Temporomandibular joint disorders are common diseases characterized by joint clicking, limited mouth opening and pain, which have a huge impact on the patients' daily life. Conservative methods include medicine, physiotherapy and occlusal application. With the advancement of medical technology, the arthroscopy is becoming popular for its minimally invasion and high efficiency. This review focuses on the common arthroscopic methods, and provides an outlook of the arthroscopic surgery.

[Fetal ECG extraction using temporal convolutional encoder-decoder network].

OBJECTIVE: To extract weak fetal ECG signals from mixed ECG signals recorded from maternal abdominal wall for accurate analysis of fetal heart rate and fetal ECG patterns. METHODS: By exploiting the superior nonlinear mapping ability of deep convolutional network, we developed a nonlinear adaptive noise cancelling (nonlinear ANC) extraction framework based on a temporal convolutional encoder-decoder network for extracting fetal ECG signals. We first constructed a deep temporal convolutional network (TCED-Net) model for fetal ECG signal extraction, and with the maternal chest ECG signal as the reference signal, the maternal ECG component in the abdominal mixed signal was estimated using this model. The estimated maternal ECG component was subtracted from the mixed abdominal ECG signals to obtain the fetal ECG component. Experimental analyses were performed using synthetic ECG signals (FECGSYNDB) and clinical ECG signals (NIFECGDB, PCDB) to test the performance of the propose method. RESULTS: The results of experiments on the FECGSYNDB dataset showed that the proposed approach achieved good performance in F1-score (98.89%), mean-square-error (MSE; 0.20) and quality signalto-noise ratio (qSNR; 7.84). The F1- score reached 99.1% on the NIFECGDB dataset and 98.61% on the PCDB dataset. The R peak detection accuracy index of the proposed method was higher than the existing best-performing algorithms such as EKF (F1=93.84%), ES-RNN (F1=97.20%) and AECG-DecompNet (F1=95.43%) by 5.05%, 1.9% and 3.18%, respectively. CONCLUSION: The fetal ECG signals extracted using the proposed method are clearer than those by the existing algorithms, suggesting the potential value this method for effective fetal health monitoring during pregnancy.

Research on red tide short-time prediction using GRU network model based on multi-feature Factors--A case in Xiamen sea area.

Red tide caused severe impacts on marine fisheries, ecology, economy and human life safety. The formation mechanism of the red tide is rather complicated; thus, red tide prediction and forecasting have long been a research hotspot around the globe. This study collected ocean monitoring data before and after the occurrence of red tides in Xiamen sea area from 2009 to 2017. The Pearson correlation coefficient method was used to obtain the associated factors of red tide occurrence, including water temperature, saturated dissolved oxygen, dissolved oxygen, chlorophyll-aand potential of hydrogen. Then, we built a short-time red tide prediction model based on the combination of multiple feature factors. chlorophyll-a, dissolved oxygen, saturated dissolved oxygen, potential of hydrogen, water temperature, salinity, turbidity, wind speed, wind direction and Air pressure were used as the input variables, building a short-time prediction model based on the combination of multiple feature factors to forecast red tide in the next 6 h by using the monitoring data. The accuracy of different forecast models with different feature combinations was compared. Results show that the distinguishing factors which have the most significant influence on red tide prediction in Xiamen are chlorophyll-a, dissolved oxygen, saturated dissolved oxygen, potential of hydrogen, and water temperature. the convergence speed of the Gated Recurrence Unit (GRU) prediction model based on the main feature factor proposed in this paper was faster and obtained the expected result, and the accuracy rates of the buoys are above 92%. The research shows the feasibility to use GRU network model to predict the occurrence of red tide with multi-feature factors as input parameters. the paper provides an effective method for the red tide early warning in Xiamen sea area.

Early on-treatment tumor growth rate (EOT-TGR) determines treatment outcomes of advanced non-small-cell lung cancer patients treated with programmed cell death protein 1 axis inhibitor.

BACKGROUND: Tumor growth rate (TGR), denoted as percentage change in tumor size per month, is a well-established indicator of tumor growth kinetics. The predictive value of early on-treatment TGR (EOT-TGR) for immunotherapy remains unclear. We sought to establish and validate the association of EOT-TGR with treatment outcomes in patients with advanced non-small-cell lung cancer (aNSCLC) undergoing anti-PD-1/PD-L1 (programmed cell death protein 1/programmed death-ligand 1) therapy. PATIENTS AND METHODS: This bicenter retrospective cohort study included a training cohort, a contemporaneously treated internal validation cohort, and an external validation cohort. Computed tomography images were retrieved to calculate EOT-TGR, denoted as tumor burden change per month during a period between baseline and the first imaging evaluation after immunotherapy. Kaplan-Meier methodology and Cox regression analysis were conducted for survival analyses. RESULTS: In the pooled cohort (n = 172), 125 patients (72.7%) were males; median age at diagnosis was 58 (range 28-79) years. Based on the training cohort, we determined the optimal cut-off value for EOT-TGR as 10.4%/month. Higher EOT-TGR was significantly associated with inferior overall survival [OS; hazard ratio (HR) 2.93, 95% confidence interval (CI) 1.47-5.83; P = 0.002], worse progression-free survival (PFS; HR 2.44, 95% CI 1.46-4.08; P = 0.001), and lower objective response rate (3.3% versus 20.9%; P = 0.040) and durable clinical benefit rate (6.7% versus 41.9%; P = 0.001). Results were reproducible in the two validation cohorts for OS and PFS. Among 43 patients who had a best response of progressive disease in the training cohort, those with high EOT-TGR had worse OS (HR 2.64; P = 0.041) and were more likely to progress due to target lesions at the first tumor evaluation (85.2% versus 0.0%; P <0.001). CONCLUSIONS: Higher EOT-TGR was associated with inferior OS and immunotherapeutic response in patients with aNSCLC undergoing anti-PD-1/PD-L1 therapy. This easy-to-calculate radiologic biomarker may help evaluate the abilities of immunotherapy to prolong survival and assist in tailoring patients' management. TRIAL REGISTRATION: ClinicalTrials.govNCT04722406; https://clinicaltrials.gov/ct2/show/NCT04722406.

[A time-series study on the association of ambient temperature with daily outpatient visits of eczema in Huizhou city].

Objective: To explore the impact of environmental temperature exposure on eczema visits. Methods: Eczema clinic data from January 1, 2016 to December 31, 2019 were collected from the Huizhou Dermatology Hospital, and data on meteorological factors (average daily temperature and relative humidity) for the same period were derived from 86 meteorological stations of the Guangdong Provincial Climate Center. A distributed lag nonlinear model (DLNM) was used to assess the lagged effect of environmental temperature exposure on eczema, and a natural smooth spline function was used to control the nonlinear confounding of humidity. Results: There were 254 053 eczema outpatient visits at the Huizhou Dermatology Hospital within four years, with an average of 173.89 visits per day. The relationship between daily average temperature and the number of visits was non-linear (U shape). The risk of eczema increased by 2.20% (1.19%-3.21%) for every 1 ℃ decrease for the low temperature, and increased by 2.35% (1.24%-3.5%) for every 1 ℃ increase for the high temperature. The effect of high temperature was greater than that of low temperature. In all cases, 1.60% (0.44%-2.68%) of eczema outpatient visits were attributed to low temperature and the attributable number was 4 065 (1 128-6 798), while 6.33% (1.40%-10.87%) of eczema outpatient visits were due to high temperature and the attributable number was 16 082 (3 557-27 616). Conclusion: Both high temperature and low temperature are associated with increased risk of eczema.