Acute-on-chronic liver failure （ACLF） is a form of acute hepatic insufficiency that occurs in the context of a chronic liver disease， with a relatively high mortality rate. To improve the prognosis of ACLF patients， it is essential to early identify the patients with pre-ACLF and constantly optimize and innovate treatment regimens for the disease in the progressive stage. With more than 10 years of research， the Chinese CLIF consortium has developed an early warning model for ACLF and established a system for transferring high-risk patients to tertiary hospitals. At present， the real-world study has also confirmed the consistency between the early warning model and actual conditions in clinical practice， making contributions to the early screening， diagnosis， and treatment of ACLF. The treatment options for the progressive stage of ACLF are also expanding， from the development of innovative pharmaceuticals to the use of artificial liver support and stem cell therapy， and such treatment modalities have made significant achievements in clinical studies and are expected to be implemented in the near future. The development of a more efficient diagnostic system and novel treatment modalities has led to a significant improvement in the diagnosis and treatment of ACLF.

ObjectiveThis paper proposes a novel real-time bedside pulmonary ventilation monitoring method for the diagnosis of chronic obstructive pulmonary disease (COPD), based on electrical impedance tomography (EIT). Four indicators—center of ventilation (CoV), global inhomogeneity index (GI), regional ventilation delay inhomogeneity (RVDI), and the ratio of forced expiratory volume in one second to forced vital capacity (FEV₁/FVC)—are calculated to enable the spatiotemporal assessment of COPD. MethodsA simulation of the respiratory cycles of COPD patients was first conducted, revealing significant differences in certain indicators compared to healthy individuals. The effectiveness of these indicators was then validated through experiments. A total of 93 subjects underwent multiple pulmonary function tests (PFTs) alongside simultaneous EIT measurements. Ventilation heterogeneity under different breathing patterns—including forced exhalation, forced inhalation, and quiet tidal breathing—was compared. EIT images and related indicators were analyzed to distinguish healthy individuals across different age groups from COPD patients. ResultsSimulation results demonstrated significant differences in CoV, GI, FEV₁/FVC, and RVDI between COPD patients and healthy individuals. Experimental findings indicated that, in terms of spatial heterogeneity, the GI values of COPD patients were significantly higher than those of the other two groups, while no significant differences were observed among healthy individuals. Regarding temporal heterogeneity, COPD patients exhibited significantly higher RVDI values than the other groups during both quiet breathing and forced inhalation. Moreover, during forced exhalation, the distribution of FEV₁/FVC values further highlighted the temporal delay heterogeneity of regional lung function in COPD patients, distinguishing them from healthy individuals of various ages. ConclusionEIT technology effectively reveals the spatiotemporal heterogeneity of regional lung function, which holds great promise for the diagnosis and management of COPD.

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin ( 1) and variecolactone ( 2) was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues ( 5- 7). Analysis of the compounds' anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities, 5 was associated with significantly reduced toxic side effects in cancer-bearing mice, indicating its potentially broader therapeutic window. Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

Objective To summarize and explore the individualized surgical treatment strategy and prognosis of anomalous aortic origin of coronary artery (AAOCA). Methods The clinical data of children with AAOCA admitted to Shanghai Children's Medical Center from March 2018 to August 2021 were retrospectively analyzed. Results A total of 17 children were enrolled, including 13 males and 4 females, with a median age of 88 (44, 138) months and a median weight of 25 (18, 29) kg. All patients received operations. The methods of coronary artery management included coronary artery decapitation in 9 patients, coronary artery transplantation in 5 patients and coronary artery perforation in 3 patients. One patient with severe cardiac insufficiency (left ventricular ejection fraction 15%) received mechanical circulatory assistance after the operation for 12 days. No death occurred in the early postoperative period, the average ICU stay time was 4.3±3.0 d, and the total hospital stay was 14.4±6.1 d. All the children received regular anticoagulation therapy for 3 months after discharge. The median follow-up time was 15 (13, 24) months. All patients received regular anticoagulation therapy for 3 months after discharge. No clinical symptoms such as chest pain and syncope occurred again. The cardiac function grade was significantly improved compared with that before operation. Imaging examination showed that the coronary artery blood flow on the operation side was unobstructed, and no restenosis occurred. Conclusion AAOCA is easy to induce myocardial ischemia and even sudden cardiac death. Once diagnosed, operation should be carried out as soon as possible. According to the anatomic characteristics of coronary artery, the early effect of individualized surgery is satisfactory, and the symptoms of the children are significantly improved and the cardiac function recovers well in the mid-term follow-up.

Cryoablation therapy with explicit anti-tumor mechanisms and histopathological manifestations has a long history.A large number of clinical practice has shown that cryoablation therapy is safe and effective,making it an ideal tumor treatment method in theory.Previously,its efficacy and clinical application were constrained by the limitations of refrigerants and refrigeration equipment.With the development of the new generation of cryoablation equipment represented by argon helium knives,significant progress has been made in refrigeration efficien-cy,ablation range,and precise temperature measurement,greatly promoting the progression of tumor cryoablation technology.This consensus systematically summarizes the mechanism of cryoablation technology,indications for oral mucosal melanoma(OMM)cryotherapy,clinical treatment process,adverse reactions and management,cryotherapy combination therapy,etc.,aiming to provide reference for carrying out the standardized cryoablation therapy of OMM.

Objective:To evaluate the value of detection of serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in opportunistic screening of liver cancer in Chinese population with a meta-analysis.Methods:Literatures on combined screening of liver cancer by AFP, CEA and CA19-9 were retrieved from CNKI, Wanfang Database, Chongqing VIP database, PubMed, Embase and Cochrane Library from the establishment of the databases to June 2023. The Quality Assessment Tool of Diagnostic Accuracy Studies (QUADAS-2) was used to evaluate the quality of the literature. Stata 17.0 statistical software was used for meta-analysis, and Deeks funnel plot was used to analyze publication bias.Results:A total of 24 literatures met the inclusion criteria, including 1 471 patients with liver cancer and 2 150 controls. The overall sensitivity of AFP in liver cancer diagnosis (screening) was 0.71 (95% CI: 0.66-0.75), the total specificity was 0.86 (95% CI: 0.80-0.90), and the area under summary receiver operating characteristic (sROC) curve (AUC) was 0.82 (95% CI: 0.78-0.85). The total sensitivity of CEA in liver cancer diagnosis (screening) was 0.48 (95% CI: 0.40-0.56), the total specificity was 0.85 (95% CI: 0.79-0.89), and the AUC of sROC was 0.74 (95% CI: 0.70-0.77). The total sensitivity of CA19-9 in liver cancer diagnosis (screening) was 0.56 (95% CI: 0.50-0.61), the total specificity was 0.80 (95% CI: 0.73-0.85), and the AUC was 0.69 (95% CI: 0.65-0.73). AFP has the highest sensitivity and specificity among the three. The overall sensitivity of combined detection of AFP, CEA and CA19-9 for liver cancer diagnosis (screening) was increased to 0.89 (95% CI: 0.85-0.92), the overall specificity was 0.77 (95% CI: 0.70-0.82), and the AUC was 0.91 (95% CI: 0.88-0.93). No publication bias was found in either individual or combined test of the biomarkers. Conclusions:Detection of AFP alone has high sensitivity and specificity, and it is a tumor marker that can be used for the opportunistic screening of liver cancer. When combined tests of AFP, CEA and CA19-9 are used to screen liver cancer, the results should be interpreted more carefully.