Objective To investigate the epidemiological characteristics and spatial distribution characteristics of Clonorchis sinensis human infections in Guangdong Province from 2016 to 2022, so as to provide insights into formulation of the clonorchiasis control measures in the province. Methods Xinhui District of Jiangmen City, Longmen County of Huizhou City and Wengyuan County of Shaoguan City in Guangdong Province were selected as fixed surveillance sites for human clonorchiasis from 2016 to 2022, and additional 10% to 15% counties (districts) endemic for clonorchiasis were sampled from Guangdong Province as mobile surveillance sites each year from 2016 to 2022. A village (community) was randomly selected from each surveillance site according to the geographical orientations of east, west, south, north and middle, and subjects were randomly sampled from each village (community). C. sinensis eggs were detected in subjects’ stool samples using the Kato-Katz technique, and the prevalence and intensity of C. sinensis infections were calculated. In addition, subjects’ gender, age, ethnicity, educational level and occupation were collected. The Guangdong Provincial 1:1 million electronic map in vector format was downloaded from the National Geomatics Center of China, and kernel density analysis and spatial autocorrelation analysis of C. sinensis human infections in Guangdong Province from 2016 to 2022 were performed using the software ArcGIS 10.7. Results A total of 153 188 residents were tested for C. sinensis infections in Guangdong Province from 2016 to 2022, including 75 596 men (49.35%) and 77 592 women (50.65%), and there were 5 369 residents infected with C. sinensis, with 3.50% overall prevalence of infections. The prevalence rates of severe, moderate and mild C. sinensis infections were 0.76%, 7.26% and 91.97% among C. sinensis-infected residents in Guangdong Province from 2016 to 2022, and there were age-, gender-, ethnicity-, occupation- and educational level-specific prevalence of C. sinensis human infections (χ² = 2 578.31, 637.33, 52.22, 2 893.28 and 1 139.33, all P values < 0.05). Global spatial autocorrelation analysis showed a cluster in the prevalence of C. sinensis human infections in Guangdong Province (Moran’s I = 0.63, Z = 27.31, P < 0.05). Kernel density analysis showed that the prevalence of C. sinensis human infections with a high kernel density in Guangdong Province was mainly distributed along the Zhujiang River basin in Pearl River Delta areas, followed by in eastern and northern Guangdong Province. In addition, local spatial autocorrelation analysis identified 73 high-high clusters of the prevalence of C. sinensis human infections in Guangdong Province. Conclusions The prevalence of C. sinensis human infections was high in Guangdong Province from 2016 to 2022, and mild infection was predominant among all clonorchiasis cases, with spatial clusters identified in the prevalence of C. sinensis human infections. Targeted clonorchiasis control measures are required among high-risk populations and areas.

Objective:To investigate the clinical, pathological and immunophenotypic features, and differential diagnosis of angioimmunoblastic T-cell lymphoma (AITL) with B-cell proliferation or neoplasms.Methods:Eight qualified cases were collected from the Department of Pathology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China from January 2019 to July 2023. One case was diagnosed with AITL and diffuse large B-cell lymphoma (DLBCL) and the other seven cases were diagnosed with AITL and B-cell proliferation. Clinical characteristics and pathological morphology were summarized. Immunohistochemical analysis, fluorescence in situ hybridization and gene rearrangement detection were performed.Results:The patients′ average age was 58 years. Five of them were male. Biopsies of the enlarged cervical lymph nodes showed structural destruction and exhibited various histologic patterns. Some cases revealed Burkitt-like morphology, a moderate tumor volume and slightly irregular nuclei. Some cases showed prominent nucleoli. High endothelial venules and expanded follicular dendritic cells were detected. Tumor cells derived from T-follicular helper (TFH) cells were positive for two or more TFH biomarkers. Nodular or diffuse patchy proliferation of B cells was noted around the tumor tissue, which was initially considered as B-cell lymphoma. All of the 8 cases showed monoclonal rearrangements of the T-cell receptor genes while 5 of them also showed clonal rearrangements of the Ig genes. Seven of the 8 cases were subject to the detection of C-MYC gene breakage and were all negative. EBV-positive cells were seen in 6 cases. Neoplastic B cells were positive for C-MYC (>40%), while proliferative B cells were negative for C-MYC (<40%).Conclusions:The histological morphology of AITL with B-cell proliferation or lymphoma may be different from AITL. An integrated analysis, incorporating clinical, morphologic, immunophenotypic, and molecular assessment, helps reach an accurate diagnosis. This group of cases demonstrated the clinical and pathological characteristics of AITL accompanied by B-cell proliferation and B-cell lymphoma. The findings suggest that C-MYC maybe a feasible indicator for distinguishing B-cell proliferation from B-cell lymphoma, and provide a simple and feasible immunohistochemical marker for the diagnosis and research of composite lymphoma.

Objective·To develop a machine learning approach for early identification of metabolic syndromes associated with inflammatory metabolic state changes in breast cancer patients after neoadjuvant therapy,using common laboratory and transthoracic echocardiography indices.Methods·Female patients with primary invasive breast cancer diagnosed at the Department of Breast Surgery,Renji Hospital,Shanghai Jiao Tong University School of Medicine,between September 2020 and September 2022,were included.General patient information,laboratory test results,and transthoracic echocardiography data were collected.After feature extraction,five machine learning algorithms,including random forest(RF),gradient boosting(GB),support vector machine(SVM),K-nearest neighbor(KNN),and decision tree(DT),were applied to construct a prediction model for the changes of the patients' metabolic state after neoadjuvant therapy,and the prediction performances of the five models were compared.Results·A total of 232 cases with valid clinical data were included,comprising 135 cases before neoadjuvant therapy and 97 cases after completing 4 cycles of neoadjuvant therapy.Feature extraction identified five key features:white blood cell count,hemoglobin,high-density lipoprotein(HDL),interleukin-2 receptor,and interleukin-8.In the multi-feature analysis,the area under the receiver operating characferistic curve(AUC)was higher in the combination of white blood cell count,hemoglobin and HDL compared to the combination of interleukin-2 receptor and interleukin-8(RF:0.928 vs 0.772,GB:0.900 vs 0.792,SVM:0.941 vs 0.764,KNN:0.907 vs 0.762,DT:0.799 vs 0.714).The RF,SVM,and GB models showed higher AUC(0.928,0.941,0.900)and accuracy(0.914,0.897,0.776).The SVM model exhibited superior accuracy in the training data compared to the RF and GB models(P=0.394,0.122 and 0.097,respectively).Conclusion·The SVM model can be used to establish a prediction model for identifying breast cancer patients at high risk of developing inflammatory metabolic state-related metabolic syndrome after neoadjuvant therapy by incorporating five common clinical indicators,namely,white blood cell count,hemoglobin,high-density lipoprotein,interleukin-2 receptor,and interleukin-8.SVM modeling may be useful for clinicians to establish individualized screening protocols based on a patient's inflammatory metabolic state.

Objective:To analyze the risk factors which may lead to tracheostomy in patients receiving invasive mechanical ventilation (IMV) in emergency intensive care unit (EICU).Methods:A case-control study was adopted to retrospectively analyze the clinical data of patients hospitalized in EICU receiving IMV from August 2016 to August 2019. The clinical data of patients were extracted through the electronic medical record system of the hospital information database. Patients were divided into the tracheostomy group and successful extubation group according to whether they received tracheostomy during hospitalization. The different clinical characteristics of the two groups were compared, and logistic regression was used to analyze the independent risk factors of tracheostomy.Results:A total of 109 patients were included in this study, among which, 53 patients underwent tracheotomy and 56 patients were successfully extubated. Logistic regression showed that GCS score ≤ 8 ( OR=5.10, 95% CI: 1.68-15.42, P < 0.01), cervical spinal cord injury ( OR=10.32, 95% CI: 2.74-38.82, P < 0.01), and sepsis ( OR=3.45, 95% CI: 1.39-8.54, P<0.01) were independent risk factors of tracheostomy for patients receiving IMV in EICU. Conclusions:If patients receiving IMV have GCS score ≤ 8, cervical spinal cord injury, or sepsis, they should be given more attention, because they may need early tracheostomy to save lives and improve the prognosis.

Objective:To analyze the relationship between preoperative deep vein thrombosis (DVT) and parameters of conventional coagulation tests (CCTs) and thromboelastography (TEG) in patients with acute trauma, and to establish a prediction model to screen out high-risk patients with preoperative DVT.Methods:The clinical data of patients with acute traumatic fracture admitted to the Emergency Intensive Care Unit of Shanghai Sixth People’s Hospital from January 2021 to June 2021 were retrospectively collected. According to whether preoperative DVT occurred, the patients were divided into the DVT group and non-DVT group. The differences of CCTs and TEG parameters at the same time were compared between the two groups. Logistic regression analysis was applied to identify independent risk factors for DVT after trauma. The receiver-operating characteristic curve analysis was employed to analyze the clinical value of those parameters to predict preoperative DVT.Results:Among 123 patients with acute traumatic fracture, 101 patients were treated with anticoagulation before operation, and 51 patients were diagnosed with DVT. There were significant differences in activated partial thromboplastin time, fibrinogen (Fib), D-Dimer, fibrinogen degradation products (FDPs), reaction time, clotting time, α angle, maximum amplitude (MA) and coagulation index between the DVT and non-DVT groups. D-Dimer and MA were independent risk factors for preoperative DVT in patients with traumatic fracture. Logistic regression equation was used to establish a prediction model: the predicting index = 0.101×D-Dimer +0.241×MA + (-18.190). The α angle (AUC=0.833, P<0.001), MA (AUC=0.904, P<0.001), coagulation index (AUC=0.914, P<0.001) of TEG versus Fib (AUC=0.684, P=0.001), D-Dimer (AUC=0.685, P<0.001) and FDPs (AUC=0.656, P=0.003) of CCTs had a higher diagnostic efficacy in developing DVT of lower extremity in patients with traumatic fracture, and of all the coagulation index was the best. However, the predictor of D-Dimer combined with MA had a better predictive value (AUC=0.926, P<0.001), and the best cut-off value was 0.32 with a sensitivity and specificity of 90.2% and 79.8%, respectively. Conclusions:Compared with CCTs, TEG has more advantages in predicting preoperative DVT in patients with traumatic fracture, and the predictor of D-Dimer combined with MA can screen out patients with high risk of DVT, which can be recommended for clinical application.

Peptide‒drug conjugates (PDCs) are drug delivery systems consisting of a drug covalently coupled to a multifunctional peptide via a cleavable linker. As an emerging prodrug strategy, PDCs not only preserve the function and bioactivity of the peptides but also release the drugs responsively with the cleavable property of the linkers. Given the ability to significantly improve the circulation stability and targeting of drugs in vivo and reduce the toxic side effects of drugs, PDCs have already been extensively applied in drug delivery. Herein, we review the types and mechanisms of peptides, linkers and drugs used to construct PDCs, and summarize the clinical applications and challenges of PDC drugs.

Patients with small-cell lung cancer (SCLC) relapse within months after completing previous therapies. This study aimed to investigate the efficacy and safety of anlotinib as third- or further-line therapy in patients with short-term relapsed SCLC from ALTER1202. Patients with short-term relapsed SCLC (disease progression within 3 months after completing ⩾ two lines of chemotherapy) in the anlotinib (n = 67) and placebo (n = 34) groups were analyzed. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival, objective response rate (ORR), disease control rate, and safety. Anlotinib significantly improved median PFS/OS (4.0 vs. 0.7 months, P < 0.0001)/(7.3 vs. 4.4 months, P = 0.006) compared with placebo. The ORR was 4.5%/2.9% in the anlotinib/placebo group (P = 1.000). The DCR in the anlotinib group was higher than that in the placebo group (73.1% vs. 11.8%, P < 0.001). The most common adverse events (AEs) were hypertension (38.8%), loss of appetite (28.4%), and fatigue (22.4%) in the anlotinib group and gammaglutamyl transpeptidase elevation (20.6%) in the placebo group. No grade 5 AEs occurred. For patients with short-term relapsed SCLC, third- or further-line anlotinib treatment was associated with improved survival benefit. Further studies are warranted in this regard.
Humans ; Lung Neoplasms/drug therapy* ; Treatment Outcome ; Neoplasm Recurrence, Local/chemically induced* ; Quinolines/adverse effects*

LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
Animals ; Cell Differentiation ; Embryo, Mammalian/metabolism* ; Embryonic Development ; Mice ; Pluripotent Stem Cells/metabolism* ; RNA, Messenger/genetics* ; RNA, Ribosomal ; RNA-Binding Proteins/metabolism* ; Transcription Factors/metabolism* ; Zygote/metabolism*

Objective To evaluate the rupture risk of carotid atherosclerotic plaque under cervical rotatory manipulation. Methods The fluid-structure interaction (FSI) model of carotid atherosclerotic plaque was established, and tensile deformation of the plaque and lumen under cervical rotatory manipulation was simulated.Mechanical parameters such as the maximum flow shear stress(FSS), the maximum wall shear stress (WSS), the maximum plaque wall stress (PWS), wall tensile stress (WTS) and wall pressure (WP) of the plaque and lumen were recorded. Results Under 16% carotid tensile deformation, the maximum WSS of the plaque was 40.54 Pa. The maximum PWS was 66.16 kPa, which was far smaller than the threshold of plaque rupture.The maximum WTS of fiber cap and the maximum strain were 156.75 kPa and 0.56, which were larger than the fracture strain range. The maximum WTS of the lumen was 1 040.30 kPa, which approached the threshold of medial membrane rupture and might cause vascular injury. Conclusions When the cervical spine rotates to the end range of motion, large carotid artery stretch may cause damage to epidermal tissues of the plaque, leading to abscission. Lesions, ulcers, bleeding and vascular damage may form inside the plaque, which will affect stability of the plaque. Cervical rotatory manipulation should be performed cautiously in patients with cervical diseases who also have carotid atherosclerotic plaques.The finite element assessment of plaques before manipulation may be an effective safety screening method.

Objective:To explore the value of stress hyperglycemia ratio (SHR) in predicting the prognosis of patients with acute heart failure (AHF).Methods:AHF patients admitted to the Emergency Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital from December 2016 to January 2019 were retrospectively included. Clinical data were recorded and SHR was calculated. According to the survival of the patients within 1 year, they were divided into the death group ( n=89) and the survival group ( n=218). Logistic regression analysis was used to analyze the risk factors of mortality. Kaplan-Meier analysis was used to evaluate the correlation between SHR and the prognosis of AHF patients. Results:A total of 307 patients aged 83 ( range 74-87) years old who met the inclusion criteria were included in this study, including 153 males and 104 females. The age, SHR and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in the death group were higher than those in the survival group [84 (78, 88) vs 82 (72, 86), 1.11 (0.91, 1.51) vs 1.02 (0.86, 1.27), 5 351 (2 098, 14 039)μg/L vs 4 243 (2 294, 7 565)μg/L ]. The left ventricular ejection fraction (LVEF) in the death group was significantly lower than that of the survival group [53 (45, 57) % vs 58 (44, 64) %, P< 0.05]. Logistic regression analysis showed that SHR was an independent risk factor for death in AHF patients ( OR=2.397, 95% CI: 1.285-4.471, P< 0.05). Median SHR was used to draw the survival curve. Patients with high SHR had a lower cumulative survival rate, and the difference was statistically significant ( P<0.05). Conclusion:SHR can identify critically ill patients and is an independent risk factor for death in AHF patients.