Metabolic dysfunction-associated steatohepatitis (MASH), a severe type of metabolic dysfunction-associated steatotic liver disease (MASLD), is a leading etiology of end-stage liver disease worldwide, posing significant health and economic burdens. microRNA-320 (miR-320), a ubiquitously expressed and evolutionarily conserved miRNA, has been reported to regulate lipid metabolism; however, whether and how miR-320 affects MASH development remains unclear. By performing miR-320 in situ hybridization with RNAscope, we observed a notable downregulation of miR-320 in hepatocytes during MASH, correlating with disease severity. Most importantly, miR-320 downregulation in hepatocytes exacerbated MASH progression as demonstrated that hepatocyte-specific miR-320 deficient mice were more susceptible to high-fat, high-fructose, high-cholesterol diet (HFHC) or choline-deficient, amino acid-defined, high-fat diet (CDAHFD)-induced MASH compared with control littermates. Conversely, restoration of miR-320 in hepatocytes ameliorated MASH-related steatosis and fibrosis by injection of adeno-associated virus 8 (AAV8) carrying miR-320 in different types of diet-induced MASH models. Mechanistic studies revealed that miR-320 specifically regulated fibroblast growth factor 1 (FGF1) production in hepatocytes by inhibiting regulator factor X1 (RFX1) expression. Notably, knockdown of Rfx1 in hepatocytes mitigated MASH by enhancing FGF1-mediated AMPK activation. Our findings underscore the therapeutic potential of hepatic miR-320 supplementation in MASH treatment by inhibiting RFX1-mediated FGF1 suppression.

Objective:To evaluate the efficacy of acute T-cell lymphoblastic leukemia(T-ALL)in children and explore the prognostic risk factors.Methods:The clinical data of 127 newly diagnosed children with T-ALL admitted to five hospitals in Fujian province from April 2011 to December 2020 were retrospectively analyzed,and compared with children with newly diagnosed acute precursor B-cell lymphoblastic leukemia(B-ALL)in the same period.Kaplan-Meier analysis was used to evaluate the overall survival(OS)and event-free survival(EFS),and COX proportional hazard regression model was used to evaluate the prognostic factors.Among 116 children with T-ALL who received standard treatment,78 cases received the Chinese Childhood Leukemia Collaborative Group(CCLG)-ALL 2008 protocol(CCLG-ALL 2008 group),and 38 cases received the China Childhood Cancer Collaborative Group(CCCG)-ALL 2015 protocol(CCCG-ALL 2015 group).The efficacy and serious adverse event(SAE)incidence of the two groups were compared.Results:Proportion of male,age ≥ 10 years old,white blood cell count(WBC)≥ 50 × 109/L,central nervous system leukemia,minimal residual disease(MRD)≥ 1％during induction therapy,and MRD ≥ 0.01％at the end of induction in T-ALL children were significantly higher than those in B-ALL children(P＜0.05).The expected 10-year EFS and OS of T-ALL were 59.7％and 66.0％,respectively,which were significantly lower than those of B-ALL(P＜0.001).COX analysis showed that WBC ≥ 100 x 109/L at initial diagnosis and failure to achieve complete remission(CR)after induction were independent risk factors for poor prognosis.Compared with CCLG-ALL 2008 group,CCCG-ALL 2015 group had lower incidence of infection-related SAE(15.8％vs 34.6％,P=0.042),but higher EFS and OS(73.9％vs 57.2％,PEFS=0.090;86.5％vs 62.3％,PoS=0.023).Conclusions:The prognosis of children with T-ALL is worse than children with B-ALL.WBC ≥ 100 × 109/L at initial diagnosis and non-CR after induction(especially mediastinal mass has not disappeared)are the risk factors for poor prognosis.CCCG-ALL 2015 regimen may reduce infection-related SAE and improve efficacy.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

Due to the limitations of current anti-HBV therapies, the HBV core (HBc or HBcAg) protein assembly modulators (CpAMs) are believed to be potential anti-HBV agents. Therefore, discovering safe and efficient CpAMs is of great value. In this study, we established a HiBiT-based high-throughput screening system targeting HBc and screened novel CpAMs from an in-house marine chemicals library. A novel lead compound 8a, a derivative of the marine natural product naamidine J, has been successfully screened for potential anti-HBV activity. Bioactivity-driven synthesis was then conducted, and the structure‒activity relationship was analyzed, resulting in the discovery of the most effective compound 11a (IC₅₀ = 0.24 μmol/L). Furthermore, 11a was found to significantly inhibit HBV replication in multiple cell models and exhibit a synergistic effect with tenofovir disoproxil fumarate (TDF) and IFNa2 in vitro for anti-HBV activity. Treatment with 11a in a hydrodynamic-injection mouse model demonstrated significant anti-HBV activity without apparent hepatotoxicity. These findings suggest that the naamidine J derivative 11a could be used as the HBV core protein assembly modulator to develop safe and effective anti-HBV therapies.

Background: and Purpose Intravenous tenecteplase (TNK) efficacy has not been well demonstrated in acute ischemic stroke (AIS) beyond 4.5 hours after onset. This study aimed to determine the effect of intravenous TNK for AIS within 4.5 to 24 hours of onset. Methods: In this pilot trial, eligible AIS patients with diffusion-weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch were randomly allocated to intravenous TNK (0.25 mg/kg) or standard care within 4.5–24 hours of onset. The primary endpoint was excellent functional outcome at 90 days (modified Rankin Scale [mRS] score of 0–1). The primary safety endpoint was symptomatic intracranial hemorrhage (sICH). Results: Of the randomly assigned 80 patients, the primary endpoint occurred in 52.5% (21/40) of TNK group and 50.0% (20/40) of control group, with no significant difference (unadjusted odds ratio, 1.11; 95% confidence interval 0.46–2.66; P=0.82). More early neurological improvement occurred in TNK group than in control group (11 vs. 3, P=0.03), but no significant differences were found in other secondary endpoints, such as mRS 0–2 at 90 days, shift analysis of mRS at 90 days, and change in National Institutes of Health Stroke Scale score at 24 hours and 7 days. There were no cases of sICH in this trial; however, asymptomatic intracranial hemorrhage occurred in 3 of the 40 patients (7.5%) in the TNK group. Conclusion This phase 2, randomized, multicenter study suggests that intravenous TNK within 4.5–24 hours of onset may be safe and feasible in AIS patients with a DWI-FLAIR mismatch.

China ; Manganese/toxicity* ; Stainless Steel

There are 200-500 species of Potentilla(Rosaceae) worldwide, among which 90 species are widely distributed in China and have a long history of ethnic medicinal use. According to our statistics, a total of 367 compounds have been isolated and identified from plants of this genus, including terpenoids, flavonoids, phenolic acids, tannins, and phenylpropanoids. The medicinal materials made from these plants mainly have antioxidative, blood sugar-lowering, anti-inflammatory, anti-tumor, cardiovascular system-protecting, neuroprotective, and hepatoprotective activities. This study systematically reviews the research progress on chemical constituents and pharmacological activities of Potentilla plants to provide a basis for further research and clinical application.
Anti-Inflammatory Agents/pharmacology* ; Antioxidants/pharmacology* ; Drugs, Chinese Herbal/pharmacology* ; Plant Extracts/pharmacology* ; Potentilla

Objective: This study analyzed the correlation between genetic mutation and prognostic significance in childhood acute lymphoblastic leukemia (ALL) . Methods: Targeted exome by next-generation sequencing (NGS) technology was used to carry out molecular profiling of untreated 141 children with ALL in Fujian Medical University Union Hospital from November 2016 to December 2019. Correlation of genetic features and clinical features and outcomes was analyzed. Results: Among the 141 pediatric patients with ALL, 160 somatic mutations were detected in 83 patients (58.9% ) , including 37 grade Ⅰ mutations and 123 grade Ⅱ mutations. Single nucleotide variation was the most common type of mutation. KRAS was the most common mutant gene (12.5% ) , followed by NOTCH1 (11.9% ) , and NRAS (10.6% ) . RAS pathway (KRAS, FLT3, PTPN11) , PAX5 and TP53 mutations were only detected, and NRAS mutations was mainly found in B-ALL while FBXW7 and PTEN mutations were only found, and NOTCH1 mutation was mainly detected in T-ALL. The average number of mutations detected in each child with T-ALL was significantly higher than in children with B-ALL (4.16±1.33 vs 2.04±0.92, P=0.004) . The children were divided into mutation and non-mutation groups according to the presence or absence of genetic variation. There were no statistically significant differences in sex, age, newly diagnosed white blood cell count, minimal or measurable residual disease monitoring results, expected 3-year event-free survival (EFS) and overall survival (OS) between the two groups (P>0.05) . On the other hand, the proportion of T-ALL and fusion gene negative children in the mutant group was significantly higher than the non-mutation group (P=0.021 and 0.000, respectively) . Among the patients without fusion gene, the EFS of children with grade I mutation was significantly lower than children without grade I mutation (85.5% vs 100.0% , P=0.039) . Among children with B-ALL, the EFS of those with TP53 mutation was significantly lower than those without TP53 mutation (37.5% vs 91.2% , P<0.001) . Conclusion: Genetic variation is more common in childhood ALL and has a certain correlation with clinical phenotype and prognosis. Therefore, targeted exome by NGS can be used as an important supplement to the traditional morphology, immunology, cytogenetics, and molecular biology classification.
Child ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Prognosis ; Technology

Objective: To explore the clinical application value of two longitudes three transverses method in the location of the perforator of thoracodorsal artery perforator and deep wound repair. Methods: The retrospectively observational study was conducted. From December 2018 to June 2020, 17 patients with deep wounds who were admitted to the Affiliated Hospital of Zunyi Medical University met the inclusion criteria and were included in this study, including 7 males and 10 females, aged 12 to 72 years. The wound areas of patients after debridement were 7 cm×3 cm to 11 cm×7 cm. Two longitudinal lines were located through the midpoint of the armpit, the posterior superior iliac spine, and the protruding point of the sacroiliac joint, and three transverse lines were located 5, 10, and 15 cm below the midpoint of the armpit between the two longitudinal lines, i.e. two longitudes three transverses method, resulting in two trapezoidal areas. And then the thoracodorsal artery perforators in two trapezoidal areas were explored by the portable Doppler blood flow detector. On this account, a single or lobulated free thoracodorsal artery perforator flap or flap that carrying partial latissimus dorsi muscle, with an area of 7 cm×4 cm to 12 cm×8 cm was designed and harvested to repair the wound. The donor sites were all closed by suturing directly. The number and location of thoracodorsal artery perforators, and the distance from the position where the first perforator (the perforator closest to the axillary apex) exits the muscle to the lateral border of the latissimus dorsi in preoperative localization and intraoperative exploration, the diameter of thoracodorsal artery perforator measured during operation, and the flap types were recorded. The survivals of flaps and appearances of donor sites were followed up. Results: The number and location of thoracodorsal artery perforators located before operation in each patient were consistent with the results of intraoperative exploration. A total of 42 perforators were found in two trapezoidal areas, with 2 or 3 perforators each patient. The perforators were all located in two trapezoid areas, and a stable perforator (the first perforator) was located and detected in the first trapezoidal area. There were averagely 1.47 perforators in the second trapezoidal area. The position where the first perforator exits the muscle was 2.1-3.1 cm away from the lateral border of the latissimus dorsi. The diameters of thoracodorsal artery perforators were 0.4-0.6 mm. In this group, 12 cases were repaired with single thoracodorsal artery perforator flap, 3 cases with lobulated thoracodorsal artery perforator flap, and 2 cases with thoracodorsal artery perforator flap carrying partial latissimus dorsi muscle. The patients were followed up for 6 to 16 months. All the 17 flaps survived with good elasticity, blood circulation, and soft texture. Only linear scar was left in the donor area. Conclusions: The two longitudes three transverses method is helpful to locate the perforator of thoracodorsal artery perforator flap. The method is simple and reliable. The thoracodorsal artery perforator flap designed and harvested based on this method has good clinical effects in repairing deep wound, with minimal donor site damage.
Adolescent ; Adult ; Aged ; Arteries ; Child ; Female ; Humans ; Male ; Middle Aged ; Perforator Flap ; Reconstructive Surgical Procedures/methods* ; Retrospective Studies ; Skin Transplantation ; Soft Tissue Injuries/surgery* ; Treatment Outcome ; Young Adult

Objective:To analyze the role of preoperative circulating tumor cell(CTC) and circulating tumor vascular endothelial cells (CTEC) in the diagnosis of gastric cancer and its correlation with the clinicopathological characteristics of gastric cancer.Methods:Sixty-two gastric cancer patients and 11 patients of benign gastric diseases were enrolled. Subtraction enrichment (SE) and immunofluorescence staining-chromosome fluorescence in situ hybridization (i·FISH) were used to integrate the unique SE-i ·FISH technology platform detecting patients′ CTC and CTEC.Results:The number of CTC in the gastric cancer group was significantly higher than that in the control group ( t=2.693, P=0.009); the number of CTEC in the gastric cancer group was higher than the control group ( t=2.015, P=0.048). With the cut-off value being set at 9 cells/6 ml in blood, the sensitivity of CTC in the diagnosis of gastric cancer is 84%, and the specificity is 82% (AUC=0.876, 95% CI, 0.792-0.963, P<0.01); When set at 6 cells/6 ml, the sensitivity of CTEC in the diagnosis of gastric cancer is 50%, and the specificity is 100%(AUC=0.727, 95% CI, 0.603-0.851, P=0.02). CTC positive is closely related to tumor location(χ 2=4.292, P=0.038 ) and TNM stage(CTC≥10, χ 2=4.848, P=0.028; CTC≥11, χ 2=6.234, P=0.013). CTEC positive is closely related to serum CA19-9(χ 2=4.858, P=0.028) and serum CA724 (χ 2=4.108, P=0.043 ) . Conclusion:SE-i·FISH technology has high sensitivity and specificity in the detection of CTC and CTEC of gastric cancer.