Objective This clinical study aimed to evaluate the accuracy of a fully digital technique for mea-suring sagittal condylar inclination(SCI),as well as vali-dating whether differences existed between the left and right SCI values of the same participant,to provide a ref-erence for clinical practice.Methods Ten participants with good occlusal relationship and normal temporomandibular joint were recruited.Three methods were used to mea-sure the SCI values of the participants,namely,A(mechanical facebow transferring and mechanical articulator-based measuring method with physical protrusive interocclusal registration),B(face scan-based virtual facebow and virtual ar-ticulator-based measuring method with digital protrusive interocclusal registration),and C(jaw motion tracking system-based measuring method).With the group subjected to methods A and C as the control,the SCI values obtained by the three methods were statistically analyzed.The left and right SCI values of the same participant were also compared.Re-sults The left and right SCI values measured by method A were 41.70°±7.09° and 42.80°±8.62°,those by method B were 35.09°±12.49° and 37.63°±12.10°,and those by method C were 39.43°±8.72° and 38.45°±6.91°.No significant dif-ference existed among the SCI values measured by the three methods(P>0.05).Meanwhile,no statistical difference existed between the SCI values on the left and right sides of the same participant(P>0.05).Conclusion The accuracy of the virtual facebow and digital protrusive occlusal registration based SCI measuring method was the same as that of mechanical facebow based and jaw motion tracking system-based methods.The SCI values on the left and right sides of the same participant were similar.Clinically,an appropriate SCI measurement and setting strategy can be selected based on the actual situations.

Objective This clinical study aimed to as-sess the trueness of three intraoral scanners for the recor-ding of the maximal intercuspal position(MIP)to provide a reference for clinical practice.Methods Ten participants with good occlusal relationship and healthy temporomandibular joint were recruited.For the control group,facebow transferring procedures were performed,and bite registrations at the MIP were used to transfer maxillary and mandibular casts to a mechanical articulator,which were then scanned with a laboratory scanner to obtain digital cast data.For the experimental groups,three intraoral scanners(Trios 3,Carestream 3600,and Aoralscan 3)were used to obtain digital casts of the participants at the MIP following the scanning workflows endorsed by the corresponding manufacturers.Sub-sequently,measurement points were marked on the control group's digital casts at the central incisors,canines,and first molars,and corresponding distances between these points on the maxillary and mandibular casts were measured to calcu-late the sum of measured distances(DA).Distances between measurement points in the incisor(DI),canine(DC),and first molar(DM)regions were also calculated.The control group's maxillary and mandibular digital casts with the added mea-surement points were aligned with the experimental group's casts,and DA,DI,DC,and DM values of the aligned control casts were determined.Statistical analysis was performed on DA,DI,DC,and DM obtained from both the control and ex-perimental groups to evaluate the trueness of the three intraoral scanners for the recording of MIP.Results In the con-trol group,DA,DI,DC,and DM values were(39.58±6.40),(13.64±3.58),(14.91±2.85),and(11.03±1.56)mm.The Trios 3 group had values of(38.99±6.60),(13.42±3.66),(14.55±2.87),and(11.03±1.69)mm.The Carestream 3600 group showed values of(38.57±6.36),(13.56±3.68),(14.45±2.85),and(10.55±1.41)mm,while the Aoralscan 3 group had val-ues of(38.16±5.69),(13.03±3.54),(14.23±2.59),and(10.90±1.54)mm.Analysis of variance revealed no statistically sig-nificant differences between the experimental and control groups for overall deviation DA(P=0.96),as well as local devi-ations DI(P=0.98),DC(P=0.96),and DM(P=0.89).Conclusion With standardized scanning protocols,the three intra-oral scanners demonstrated comparable trueness to traditional methods in recording MIP,fulfilling clinical requirements.

Lipocalin-2 (LCN2) is a secreted glycoprotein originally purified from mouse kidney cells infected with simian virus 40 and plays a key role in the control of cellular homeostasis during inflammation and the response to cellular stress or injury, and it is considered a potential biomarker for rheumatic diseases, cancer, liver diseases, and inflammatory diseases. Studies have shown that LCN2 is expressed in hepatic parenchymal and nonparenchymal cells and is secreted into the bloodstream, and it is closely associated with the development and progression of acute liver injury, liver cirrhosis, viral hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease, and hepatocellular carcinoma. This article summarizes the animal experiments and clinical studies on the association of LCN2 with the pathogenesis of liver diseases, in order to provide new ideas and therapeutic targets for the prevention and treatment of liver diseases.

Hepatocellular carcinoma (HCC) is an aggressive human cancer with increasing incidence worldwide. Multiple efforts have been made to explore pharmaceutical therapies to treat HCC, such as targeted tyrosine kinase inhibitors, immune based therapies and combination of chemotherapy. However, limitations exist in current strategies including chemoresistance for instance. Tumor initiation and progression is driven by reprogramming of metabolism, in particular during HCC development. Recently, metabolic associated fatty liver disease (MAFLD), a reappraisal of new nomenclature for non-alcoholic fatty liver disease (NAFLD), indicates growing appreciation of metabolism in the pathogenesis of liver disease, including HCC, thereby suggesting new strategies by targeting abnormal metabolism for HCC treatment. In this review, we introduce directions by highlighting the metabolic targets in glucose, fatty acid, amino acid and glutamine metabolism, which are suitable for HCC pharmaceutical intervention. We also summarize and discuss current pharmaceutical agents and studies targeting deregulated metabolism during HCC treatment. Furthermore, opportunities and challenges in the discovery and development of HCC therapy targeting metabolism are discussed.

Acute myeloid leukaemia (AML) is the most common form of acute leukaemia in adults, with increasing incidence with age and a generally poor prognosis. Almost 20% of AML patients express mutant isocitrate dehydrogenase 2 (mIDH2), which leads to the accumulation of the carcinogenic metabolite 2-hydroxyglutarate (2-HG), resulting in poor prognosis. Thus, global institutions have been working to develop mIDH2 inhibitors. SH1573 is a novel mIDH2 inhibitor that we independently designed and synthesised. We have conducted a comprehensive study on its pharmacodynamics, pharmacokinetics and safety. First, SH1573 exhibited a strong selective inhibition of mIDH2 R140Q protein, which could effectively reduce the production of 2-HG in cell lines, serum and tumors of an animal model. It could also promote the differentiation of mutant AML cell lines and granulocytes in PDX models. Then, it was confirmed that SH1573 possessed characteristics of high bioavailability, good metabolic stability and wide tissue distribution. Finally, toxicological data showed that SH1573 had no effects on the respiratory system, cardiovascular system and nervous system, and was genetically safe. This research successfully promoted the approval of SH1573 for clinical trials (CTR20200247). All experiments demonstrated that, as a potential drug against mIDH2 R140Q acute myeloid leukaemia, SH1573 was effective and safe.

Alanine-serine-cysteine transporter 2 (ASCT2) is reported to participate in the progression of tumors and metabolic diseases. It is also considered to play a crucial role in the glutamate-glutamine shuttle of neuroglial network. However, it remains unclear the involvement of ASCT2 in neurological diseases such as Parkinson's disease (PD). In this study, we demonstrated that high expression of ASCT2 in the plasma samples of PD patients and the midbrain of MPTP mouse models is positively correlated with dyskinesia. We further illustrated that ASCT2 expressed in astrocytes rather than neurons significantly upregulated in response to either MPP⁺ or LPS/ATP challenge. Genetic ablation of astrocytic ASCT2 alleviated the neuroinflammation and rescued dopaminergic (DA) neuron damage in PD models in vitro and in vivo. Notably, the binding of ASCT2 to NLRP3 aggravates astrocytic inflammasome-triggered neuroinflammation. Then a panel of 2513 FDA-approved drugs were performed via virtual molecular screening based on the target ASCT2 and we succeed in getting the drug talniflumate. It is validated talniflumate impedes astrocytic inflammation and prevents degeneration of DA neurons in PD models. Collectively, these findings reveal the role of astrocytic ASCT2 in the pathogenesis of PD, broaden the therapeutic strategy and provide a promising candidate drug for PD treatment.