Humans ; Consensus ; Pancreatic Neoplasms/therapy* ; Neuroendocrine Tumors/therapy*

The coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection. So far, a few small-molecule antiviral drugs, including nirmatrelvir-ritonavir (Paxlovid), remdesivir, and molnupiravir have been marketed for the treatment of COVID-19. Nirmatrelvir-ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19. However, the existing treatment options have limitations, and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still needed. To date, four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in China. These drugs include azvudine, simnotrelvir-ritonavir (Xiannuoxin), leritrelvir, and mindeudesivir (VV116). Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for progression. In this review, we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19. These findings will expand our understanding and highlight the potential widespread application of China's homegrown anti-COVID-19 drugs.
Humans ; Ritonavir/therapeutic use* ; COVID-19 ; Antiviral Agents/therapeutic use* ; China ; Nitriles ; Lactams ; Proline ; Adenosine/analogs & derivatives* ; Leucine

Pregnancy in patients with Eisenmenger syndrome (ES) is associated with high maternal mortality rates of 30%‒50%, or even up to 65% in the case of a cesarean section (Yuan, 2016). Here, we report a case of term pregnancy complicated with ES and severe pulmonary artery hypertension (PAH), which was managed by a multidisciplinary team (MDT) and resulted in an uncomplicated delivery via elective cesarean section. The goal of this study is to emphasize the importance of multidisciplinary approach in the management of pregnancy with ES, which can profoundly improve maternal and infant outcomes.
Female ; Humans ; Pregnancy ; Cesarean Section ; Eisenmenger Complex/therapy* ; Hypertension, Pulmonary/therapy* ; Maternal Mortality ; Pregnancy Complications, Cardiovascular/therapy* ; Pregnancy Outcome

Accurate segmentation of whole slide images is of great significance for the diagnosis of pancreatic cancer. However, developing an automatic model is challenging due to the complex content, limited samples, and high sample heterogeneity of pathological images. This paper presented a multi-tissue segmentation model for whole slide images of pancreatic cancer. We introduced an attention mechanism in building blocks, and designed a multi-task learning framework as well as proper auxiliary tasks to enhance model performance. The model was trained and tested with the pancreatic cancer pathological image dataset from Shanghai Changhai Hospital. And the data of TCGA, as an external independent validation cohort, was used for external validation. The F1 scores of the model exceeded 0.97 and 0.92 in the internal dataset and external dataset, respectively. Moreover, the generalization performance was also better than the baseline method significantly. These results demonstrate that the proposed model can accurately segment eight kinds of tissue regions in whole slide images of pancreatic cancer, which can provide reliable basis for clinical diagnosis.
Humans ; China ; Pancreatic Neoplasms/diagnostic imaging* ; Learning

Objective:The tumor-stroma ratio(TSR)is considered an independent prognostic factor for gastric cancer.Traditionally,TSR as-sessments have relied on the visual evaluation of surgical specimens,which is a method that lacks objectivity.This study was conducted to investigate whether the TSR in preoperative biopsy specimens can be automatically quantified using deep learning methods and whether the TSR value can be used to predict the efficacy of neoadjuvant chemotherapy(NAC)in patients with gastric cancer.Methods:In total,148 preoperative biopsy slides and 43 surgical resection slides from patients with gastric cancer who underwent NAC treatment at Yunnan Can-cer Hospital between March 2013 and March 2020 were used in the study.Tumor region segmentation and epithelial-stromal segmentation models were developed.The surgical resection slides were used to trained and evaluate the model,and the biopsy slides were used to test their predictive abilities.The TSR values were determined on the basis of the intersection of predictions from both models.The postoperat-ive pathological tumor regression grade(TRG)was used to categorize patients into good responders(TRG 0-1)and poor responders(TRG 2-3).Univariate and multivariate Logistic regression analyses were conducted to determine the correlation between the TSR value and the ef-ficacy of NAC in gastric cancer.Results:The intersection over union(IOU)value was 0.94 for the tumor tissue segmentation model and 0.88 for the epithelial-stromal segmentation model.Using cutoff values of 44.93％and 70.22％,patients were classified into low,intermediate,and high TSR groups.The proportion of good responders was significantly different among these groups(P＜0.05).Multivariate Logistic re-gression analysis indicated that the TSR was an independent predictor of NAC response in gastric cancer(OR=0.10,95％CI:0.03-0.32).When the TSR three-category classification was added as a predictor of treatment response alongside conventional clinical information,the area under curve(AUC)increased from 0.71 to 0.85.Conclusions:This deep learning model is capable of automatically segmenting tumor,epi-thelial,and stromal regions based on pathological slides,accurately calculating TSR value,and predicting the efficacy of NAC on the basis of the automatically computed TSR values.

OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNP) of aquaporin 7 ( AQP7) and aquaporin 9 ( AQP9) genes and type 2 diabetes mellitus (T2DM) among ethnic Han Chinese population. METHODS: A case-control study involving 1194 subjects with T2DM and 1274 non-diabetic mellitus (NDM) subjects were enrolled. Genotypes of three SNPs (rs3758269 of AQP7 gene, rs16939881 and rs57139208 of AQP9 gene) were determined by using a MassArray method. The association of the three SNPs with T2DM was assess, and the correlation of glucose and lipid metabolism parameters with various SNP genotypes in the NDM group was analyzed. RESULTS: The allelic and genotypic frequencies of the three SNPs did not differ significantly between the two groups (P>0.05). Nor was there significant difference between the two groups with different genetic models (P>0.05). No significant association of genotypes of AQP7 gene rs3758269, AQP9 gene rs16939881 and rs57139208 with glucose and lipid metabolism parameters were observed in the NDM group (P>0.05). CONCLUSION The rs3758269 in AQP7 gene and rs16939881 and rs57139208 in AQP9 gene are not associated with the genetic susceptibility of T2DM among ethnic Han Chinese population.
Aquaporins/genetics* ; Case-Control Studies ; China ; Diabetes Mellitus, Type 2/genetics* ; Genetic Predisposition to Disease ; Humans ; Polymorphism, Single Nucleotide

Tumor-targeted immunotherapy is a remarkable breakthrough, offering the inimitable advantage of specific tumoricidal effects with reduced immune-associated cytotoxicity. However, existing platforms suffer from low efficacy, inability to induce strong immunogenic cell death (ICD), and restrained capacity of transforming immune-deserted tumors into immune-cultivated ones. Here, an innovative platform, perfluorooctyl bromide (PFOB) nanoemulsions holding MnO₂ nanoparticles (MBP), was developed to orchestrate cancer immunotherapy, serving as a theranostic nanoagent for MRI/CT dual-modality imaging and advanced ICD. By simultaneously depleting the GSH and eliciting the ICD effect via high-intensity focused ultrasound (HIFU) therapy, the MBP nanomedicine can regulate the tumor immune microenvironment by inducing maturation of dendritic cells (DCs) and facilitating the activation of CD8⁺ and CD4⁺ T cells. The synergistic GSH depletion and HIFU ablation also amplify the inhibition of tumor growth and lung metastasis. Together, these findings inaugurate a new strategy of tumor-targeted immunotherapy, realizing a novel therapeutics paradigm with great clinical significance.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, and its prevalence has been increasing during the recent years, which has posed a great impact on the families of the patients and society. Epidemiological studies have found that environmental exposure factors have an important impact on the occurrence and development of ASD, including pesticides, heavy metals, poly- and perfluoroalkyl substances, phenols, and air pollution. This paper focused on the relationship between environmental exposure to the above mentioned typical environmental exposure factors and the occurrence of ASD, in order to provide reference for related research of ASD.

A new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has recently been proposed. We aim to examine the associations of MAFLD, particularly its discordance from non-alcoholic fatty liver disease (NAFLD), with the progression of elevated brachial-ankle pulse wave velocity (baPWV) and albuminuria in a community-based study sample in Shanghai, China. After 4.3 years of follow-up, 778 participants developed elevated baPWV and 499 developed albuminuria. In comparison with the non-MAFLD group, the multivariable adjusted odds ratio (OR) of MAFLD group for new-onset elevated baPWV was 1.25 (95% confidence interval (CI) 1.01-1.55) and 1.35 (95% CI 1.07-1.70) for albuminuria. Participants without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria (OR 1.77; 95% CI 1.07-2.94). Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or albuminuria. In conclusion, MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index, waist circumference, and hip circumference. Individuals without NAFLD but diagnosed as MAFLD had high risk of albuminuria, supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.
Humans ; Pulse Wave Analysis ; Albuminuria ; Ankle Brachial Index ; Non-alcoholic Fatty Liver Disease/diagnosis* ; Vascular Stiffness ; Prospective Studies ; Risk Factors ; China/epidemiology*