[Chinese expert guidance on overall application of lenvatinib in hepatocellular carcinoma].

Lenvatinib mesylate is an oral receptor tyrosine kinase inhibitor against targets of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor α, stem cell growth factor receptor, and rearranged during transfection, et al. Lenvatinib has been approved by the National Medical Products Administration of China on September 4, 2018, for the first-line treatment of patients with unresectable hepatocellular carcinoma who have not received systematic treatment before. Up to February 2023, Lenvatinib has been listed in China for more than 4 years, accumulating a series of post-marketing clinical research evidences. Based on the clinical practice before and after the launch of lenvatinib and referring to the clinical experience of other anti-angiogenesis inhibitors, domestic multidisciplinary experts and scholars adopt the Delphi method to formulate the Chinese Expert Guidance on Overall Application of Lenvatinib in Hepatocellular Carcinoma after repeated discussions and revisions, in order to provide reference for reasonable and effective clinical application of lenvatinib for clinicians.

[Expert consensus on the biobank development of oral genetic diseases and rare diseases and storage codes of related biological samples from craniofacial and oral region].

The biological samples of oral genetic diseases and rare diseases are extremely precious. Collecting and preserving these biological samples are helpful to elucidate the mechanisms and improve the level of diagnose and treatment of oral genetic diseases and rare diseases. The standardized construction of biobanks for oral genetic diseases and rare diseases is important for achieving these goals. At present, there is very little information on the construction of these biobanks, and the standards or suggestions for the classification and coding of biological samples from oral and maxillofacial sources, and this is not conducive to the standardization and information construction of biobanks for special oral diseases. This consensus summarizes the background, necessity, principles, and key points of constructing the biobank for oral genetic diseases and rare diseases. On the base of the group standard "Classification and Coding for Human Biomaterial" (GB/T 39768-2021) issued by the National Technical Committee for Standardization of Biological Samples, we suggest 76 new coding numbers for different of biological samples from oral and maxillofacial sources. We hope the consensus may promote the standardization, and smartization on the biobank construction as well as the overall research level of oral genetic diseases and rare diseases in China.

[Clinical and pathological features and differential diagnosis of fibro-osseous tumors and dysplasias].

Fibro-osseous lesions is a class of diseases with obvious similarities in clinical manifestations and pathological features, which has been attracting the attention of clinicians and pathologists. The latest WHO 2022 Classification (5th edition) included six of these diseases (cemento-osseous dysplasia, segmental odontomaxillary dysplasia, fibrous dysplasia, juvenile trabecular ossifying fibroma, psammomatoid ossifying fibroma and familial gigantiform cementoma) in the " fibro-osseous tumours and dysplasias ", and put forward new ideas on the diagnosis and treatment of these diseases. According to the latest WHO 2022 Classification (5th edition), the clinical and pathological features, diagnosis and differential diagnosis of these six diseases were described.

[Diagnosis and differentiation diagnosis of primary temporomandibular joint cartilage and giant cell related tumor lesions].

Cartilage and giant cell-related neoplastic lesions originating in the temporomandibular joint region have similar clinical, imaging and pathological manifestations, making the diagnosis of these disorders challenging to varying degrees. Diagnostic findings can influence treatment procedures and a definitive pathological diagnosis is important for the prognosis of these conditions. In this article, we discuss the pathological diagnosis and differentiation of four benign cartilage and giant cell related tumors and tumor-like lesions that occur in the temporomandibular joint, namely synovial chondromatosis, tumoral calcium pyrophosphate deposition disease, pigmented villonodular synovitis and chondroblastoma, taking into account their clinical features and histological manifestations, with a view to providing a basis for clinical management.

[Precise combination of systemic therapy and hepatic surgery].

In China, the mortality rate of primary liver cancer ranks third among malignant tumors, so it is an imperative health issue. Surgery has always been an ideal treatment for early liver cancer, and an alternative treatment for some intermediate and advanced stage liver cancers. In recent years, significant progress has been made in the treatment of liver cancer, and relevant experts have begun to combine existing treatment methods into the early and intermediate-stage to explore drug treatment methods. Here, we will discuss the surgical and drug treatment issues, as well as the combination of the both, and their impact on future liver cancer treatment models.

[Predictive value of two-dimentional shear wave elastography in posthepatoectomy liver failure].

Objective: To investigate the value of two-dimensional shear wave elastography (2D SWE) combined with clinical biochemical data in predicting posthepatoectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC). Methods: A total of 274 HCC patients who underwent hepatectomy in Zhongshan Hospital Fudan University from January 2015 to January 2016 were retrospectively collected, including 235 males and 39 females, age 19-80 (56±11) years. All patients were confirmed to be HCC by postoperative pathology. The preoperative 2D SWE examination, laboratory examination results and intraoperative indicators were analyzed. According to the occurrence of PHLF after surgery, single factor analysis and multiple logistic regression analysis were performed on the above indicators to obtain a binary logistic regression model, and evaluate the diagnostic effect of the model on PHLF. In addition, 103 HCC patients from October 2019 to January 2020 were retrospectively collected as an external validation set, including 89 males and 14 females, age 23-80 (55±11) years old. Results: The liver stiffness measurement (LSM) obtained from 2D SWE, INR and Laminin (LN) were independent predictors of PHLF. The formula of prediction model PM=-15.451+0.095×LSM+11.7×INR+0.012×LN was obtained by combining above three factors. The area under the curve (AUC) of PHLF was 0.82, which was higher than that of end-stage liver disease model (MELD) score and Child-Pugh grading diagnosis of PHLF. The AUC of PHLF predicted by PM in the external validation group was 0.81. Conclusion: 2D SWE is helpful for clinicians to evaluate liver reserve function preoperatively and to predict the occurrence of PHLF in patients with HCC.

[Pathological features of immune-mediated hepatitis due to immune checkpoint inhibitors and anti-angiogenesis targeted therapy].

Objective: To compare the histologic features of immune-mediated hepatitis (IMH) due to immune checkpoint inhibitors (ICIs) monotherapy and combined ICIs anti-angiogenesis tyrosine kinases (TKIs) targeted therapy. Methods: Twenty-one IMH patients who had liver biopsy during ICIs treatment in Zhongshan Hospital of Fudan University from 2015 to 2019 were included. Among them, ten were treated with ICIs monotherapy, and 11 were treated with combined ICIs and anti-angiogenesis targeted therapy. The histologic features of IMH were assessed by HE staining and PD-L1/2 was evaluated by immunohistochemical staining. Results: Patients treated with monotherapy ICIs presented with different levels of lobular hepatitis and portal inflammation. Besides, there were also cholangitis, endothelialitis, Kupffer cells activation and peliosisi hepatitis. Eight cases (8/10) showed mild and two cases (2/10) showed moderate hepatic injury. As for patients receiving combined ICIs and TKIs therapy, the extent of IMH was more severe, with four cases (4/11) showing moderate-severe liver injury, with confluent or bridging necrosis, portal inflammation, cholangitis, interface hepatitis. Among these, one patient developed acute severe hepatitis with massive hepatocyte necrosis and died of multisystem dysfunction. In those cases with severe liver injury, many CD8 positive lymphocytes aggregated in the portal area and hepatic sinusoid, and PD-L1 was expressed in many endothelial cells. There were both 2 cases of death in ICIs monotherapy and combination therapy group. Among the latter group, 1 patient developed acute severe hepatitis with massive hepatocyte necrosis and died of multisystem dysfunction. Conclusion: Compared with ICIs monotherapy, combined ICIs and anti-angiogenesis targeted TKIs therapy may cause overlapping hepatic injury, leading to severe IMH.

An adaptable soft-mold embossing process for fabricating optically-accessible, microfeature-based culture systems and application toward liver stage antimalarial compound testing.

Advanced cell culture methods for modeling organ-level structure have been demonstrated to replicate in vivo conditions more accurately than traditional in vitro cell culture. Given that the liver is particularly important to human health, several advanced culture methods have been developed to experiment with liver disease states, including infection with Plasmodium parasites, the causative agent of malaria. These models have demonstrated that intrahepatic parasites require functionally stable hepatocytes to thrive and robust characterization of the parasite populations' response to investigational therapies is dependent on high-content and high-resolution imaging (HC/RI). We previously reported abiotic confinement extends the functional longevity of primary hepatocytes in a microfluidic platform and set out to instill confinement in a microtiter plate platform while maintaining optical accessibility for HC/RI; with an end-goal of producing an improved P. vivax liver stage culture model. We developed a novel fabrication process in which a PDMS soft mold embosses hepatocyte-confining microfeatures into polystyrene, resulting in microfeature-based hepatocyte confinement (µHEP) slides and plates. Our process was optimized to form both microfeatures and culture wells in a single embossing step, resulting in a 100 µm-thick bottom ideal for HC/RI, and was found inexpensively amendable to microfeature design changes. Microfeatures improved intrahepatic parasite infection rates and µHEP systems were used to reconfirm the activity of reference antimalarials in phenotypic dose-response assays. RNAseq of hepatocytes in µHEP systems demonstrated microfeatures sustain hepatic differentiation and function, suggesting broader utility for preclinical hepatic assays; while our tailorable embossing process could be repurposed for developing additional organ models.

[Application of biological factor in cementum regeneration].

At the present day, curettage and periodontal surgery comprise the main strategy for the treatment of periodontitis, however, these methods are limited in regenerating cementum. It has been found that some biological factors such asenamel matrix derivative (EMD), transforming growth factor-ß (TGF-ß) and insulin-like growth factor (IGF) could promote cementum regeneration. In the cementum regenerationstudies, there has been a lack of criteria to distinguish cementum from alveolar bone and other types of cementum. Therefore, this article will briefly review the biological factors that affect the cementum regeneration and the molecular markers used to judge the regenerating cementum.

[Vascular endothelial growth factor-loaded microspheres promote dental pulp regeneration and vascularization].

Objective: To evaluate the effect of vascular endothelial growth factor (VEGF)-loaded microspheres on dental pulp tissue regeneration and vascularization in vivo. Methods:In vitro release experiment and human umbilical vein endothelial cell migration experiment were conducted with VEGF loaded microspheres. The dental pulp stem cells (DPSC) were co-cultured with VEGF microspheres to observe the compatibility between the cells and the microspheres. DPSC and VEGF loaded microspheres were injected into the root lumen through the apical foramen, which were then transplanted subcutaneously into nude mice. Histological and immunohistochemical features were observed after nine weeks. Results: DPSCs attached and spread on the surface of the microspheres. HE staining showed that the regenerated pulp-like tissue fulfilled the whole apex and middle third of the root. Differentiated odontoblast-like cells aligned with the existing tubular root dentin. Conclusions: VEGF-loaded microspheres promoted the regeneration of pulp-like tissues and formation of blood vessels.

In-situ tensile testing of ZrCu-based metallic glass composites.

ZrCu-based bulk metallic glass composites (BMGCs) are well known for their plastic deformability, superior to traditional metallic glasses (MGs), which is attributed to a unique dual-phases structure, namely, the glassy matrix and unstable B2 phase. In the present study, in-situ tensile testing is used to trace the deformation process of a ZrCu-based BMGC. Three deformation stages of the BMGC, i.e., the elastic-elastic stage, the elastic-plastic stage, and the plastic-plastic stage are identified. In the elastic-elastic and elastic-plastic stages, the yield strength and elastic limit are major influenced by the volume fraction of the B2 crystals. In the plastic-plastic stage, the B2 phase stimulates the formation of multiple shear bands and deflects the direction of shear bands by disturbing the stress field in front of the crack tip. The deformation-induced martensitic transformation of the metastable B2 phase contributes to the plasticity and work hardening of the composite. This study highlights the formation and propagation of multiple shear bands and reveals the interactions of shear bands with structural heterogeneities in situ. Especially, the blocking of shear bands by crystals and the martensitic transformation of the B2 phase are critical for the mechanistic deformation process and illustrate the function of the B2 phase in the present BMGCs.

[Analysis of gene mutation and clinical characteristics in patients with idiopathic epilepsy].

Objective: To explore the association between gene mutations and clinical characteristics in Chinese patients with epilepsy. Methods: A total of twenty-three patients with idiopathic epilepsy admitted to the Xuanwu Hospital of Capital Medical University from January 2014 to July 2016 were included.The age at onset of epilepsy ranged from 8 months to 31 years.All patients were screened for mutations by next-generation of sequencing (NGS), using a targeted capture panel of epilepsy and related seizures to screen forgene causative for or related to epilepsy.Some mutations were verified for inheritance by Sanger sequencing of two generations in the family.The differences in clinical characteristics among different mutation carriers were compared. Results: A total of 38 mutations were identified in 23 patients.Most of the patients presented with tonic-clonic seizures, and most were not accompanied by mental retardation.Causative genes were dominated by those encoding ion channel, enzyme and proteins with special functions.Although mutation carriers for genes encoding ion channel proteins and those with special functions were not significantly different in age at onset, types of seizure, family history or complications(P>0.05), patients presenting with tonic-clonic seizures had higher frequency of mutations in genes encoding ion channel (15/15)than those encoding proteins with special function(16/20)(P=0.066). Conclusions: NGS is a useful technology in detecting mutations in patients with various types of epilepsy and aiding in etiological diagnosis of the disease.Tonic-clonic seizures may correlate with mutations in genes encoding ion channel.

[The treatment of early-stage liver cancer].

Although the diagnostic rate of early-stage liver cancer is low, only these patients have a chance of radical treatment, and thus related treatment modalities deserve attention. Surgical resection is the preferred choice for the treatment of early-stage liver cancer. For patients with high selectivity, local treatment including radiofrequency ablation can achieve satisfactory outcomes. Liver transplantation is the preferred choice for patients with decompensated liver cirrhosis. Early-stage liver cancer has a high postoperative recurrence rate, and the research and development of postoperative adjuvant therapy should be taken seriously.

[Advances in basic and clinical research on hepatocellular carcinoma in 2016].

Hepatocellular carcinoma (HCC) is still one of common malignant cancers worldwide, with increasing incidence and mortality rates. Early diagnosis and effective treatment for HCC remain to be explored. This article introduces the research advances in the early specific diagnosis and effective therapies for HCC in 2016, such as molecular markers in the specific diagnosis and targeted therapy for HCC, main therapeutic regimens, robot-assisted liver resection, and no-touch radiofrequency ablation.

Moderate swimming suppressed the growth and metastasis of the transplanted liver cancer in mice model: with reference to nervous system.

Physical activity has been shown to suppress tumor initiation and progression. The neurotransmitter dopamine (DA) is closely related to movement and exhibits antitumor properties. However, whether the suppressive effects of physical activity on tumors was mediated by the nervous system via increased DA level remains unknowns. Here we show that regular moderate swimming (8 min/day, 9 weeks) raised DA levels in the prefrontal cortex, serum and tumor tissue, suppressed growth, reduced lung metastasis of transplanted liver cancer, and prolonged survival in a C57BL/6 mouse model, while overload swimming (16 and 32 min/day, 9 weeks) had the opposite effect. In nude mice that were orthotopically implanted with human liver cancer cell lines, DA treatment significantly suppressed growth and lung metastasis by acting on the D2 receptor (DR2). Furthermore, DR2 blockade attenuated the suppressive effect of moderate swimming on liver cancer. Both moderate swimming and DA treatment suppressed the transforming growth factor-beta (TGF-ß1)-induced epithelial-mesenchymal transition of transplanted liver cancer cells. At the molecular level, DR2 signaling inhibited extracellular signal-regulated kinase phosphorylation and expression of TGF-ß1 in vitro. Together, these findings demonstrated a novel mechanism by which the moderate exercise suppressed liver cancer through boosting DR2 activity, while overload exercise had the opposite effect, highlighting the possible importance of the dopaminergic system in tumor growth and metastasis of liver cancer.

Clinical analysis of gastroenteropancreatic neuroendocrine tumor with liver metastasis, compared with primary hepatic neuroendocrine tumor.

OBJECTIVE: The objective was to study the clinicopathologic features, grading, treatment protocols, and prognostic of gastroenteropancreatic neuroendocrine tumor (NET) with liver metastasis and primary hepatic NET. MATERIALS AND METHODS: The clinical data of 34 patients with hepatic NET were retrospectively reviewed. According to the primary tumor location and 2010 World Health Organization classification, the cases were categorized to analyze the clinicopathologic features, treatment condition, and prognostic factors. RESULTS: There was a marked male predominance either in gastroenteropancreatic NET liver metastasis group or primary group. Primary hepatic NET is mostly single nodule located in the right lobe of liver, and the metastatic hepatic NET is mostly from pancreas with multiple nodules and metastasizes to both lobes of the liver, with a high degree of malignancy and poor prognosis. There are 17 cases (50%) of NET and 17 cases (50%) of neuroendocrine carcinoma (NEC) in all the 34 patients of this study. The mitotic figure and Ki-67 proliferation index are both higher in NEC group than in NET group, which indicated highly malignancy of the NEC. The 5-year disease-free survival (DFS) rates for primary group and metastatic group were 30% and 40%, respectively (P > 0.05), while the 5-year survival rates were 35% and 66%, respectively (P > 0.05). Different tumor grade was found closely associated with 5-year DFS (P < 0.05) and overall survival (OS) (P < 0.05) in both groups. Furthermore, we found 5-year DFS of patients with primary site of the tumor located in the gastrointestinal tract was much lower than that located in pancreas (P < 0.05), while the 5-year OS showed no significant differences between two groups (P > 0.05). CONCLUSIONS: Surgery is an effective method for the treatment of hepatic NET; tumor grading is an important determinant factor of prognosis.

Prognostic value of peritumoral heat-shock factor-1 in patients receiving resection of hepatocellular carcinoma.

BACKGROUND: The cross-talk of hepatocellular carcinoma (HCC) cells and abnormal metabolic signals in peritumoral microenvironment modifies our knowledge of hepatocarcinogenesis. As an indispensable modulator of various stresses, the clinical significance of heat-shock transcription factor-1 (HSF1) in HCC microenvironment has never been defined. METHODS: Hepatocellular carcinoma and matched peritumoral liver tissues (n=332) were semiquantitatively analysed for HSF1 expression, followed by correlation with clinicopathological parameters (patient outcomes). Moreover, the effects of HSF1 deficiency in L02 on monocarboxylate transporter-4 (MCT4) and HCC cells' colonisation and proliferation were investigated. RESULTS: High expression of HSF1 in peritumoral tissue but not in HCC tissue was associated with poorer overall survival (OS) and time to recurrence (TTR), especially early recurrence (ER), which was further reconfirmed in validation cohort. Multivariate analysis showed that prognostic performance of peritumoral HSF1 was independent of other clinicopathological factors (hazard ratio for OS=2.60, P=0.002, for TTR=2.52, P<0.001). Notably, downregulation of HSF1 in L02 decreased MCT4 expression significantly. The supernatant from L02-shRNA-HSF1 in hypoxia, NOT normoxia condition, inhibited HCC cell colonisation and proliferation. Moreover, the combination of peritumoral HSF1 and MCT4 was the best predictor for ER and OS. CONCLUSION: High peritumoral HSF1 expression can serve as a sensitive 'readout' for high-risk HCC ER, and could be a potential metabolic intervention target following curative resection.

Broadband antireflection and absorption enhancement by forming nano-patterned Si structures for solar cells.

In this letter, we report the antireflection and light absorption enhancement by forming sub-wavelength nano-patterned Si structures via nano-sphere lithography technique. It is found that the surface reflection can be significantly suppressed in a wide spectral range (400-1000 nm) and the weighted mean reflection is less than 5%. Meanwhile, the broad band optical absorption enhancement is achieved consequently. Heterojunction solar cells are prepared by depositing ultrathin amorphous Si film on the nano-patterned Si structures, the short circuit current density increases to 37.2 mA/cm(2)and the power conversion efficiency is obviously improved compared to the reference cell on flat Si substrate.

A prognostic scoring system based on clinical features of intrahepatic cholangiocarcinoma: the Fudan score.

BACKGROUND: The objectives of this study were to propose a clinical prognostic scoring system applicable for intrahepatic cholangiocarcinoma (ICC) and to evaluate the prognostic validity of the American Joint Committee on Cancer (AJCC) 7th edition staging system. PATIENTS AND METHODS: Retrospective univariate and multivariate survival analyses were conducted for 344 patients with ICC who underwent hepatectomy. A simple clinical prognostic scoring system (Fudan score) was developed based on the independent predictors. The prognostic validity was assessed in 74 patients with unresected tumors and compared with the AJCC 6th and 7th edition systems. RESULTS: In the training set, serum alkaline phosphatase level, carbohydrate antigen 19-9 level, tumor boundary type, tumor size, and number of intrahepatic tumors were independent predictive factors of survival in ICC and were incorporated into the Fudan score. Three hundred forty-four patients were categorized into four subsets with 5-year overall survival rates of 48.6%, 25.6%, 10.3%, and 0.0% for low-, intermediate-, high-, and extremely high-risk groups, respectively. The discriminative ability of the Fudan score was better than that of the AJCC staging system and well applied in the unresected patient set. CONCLUSIONS: A Fudan score based on clinical factors may provide a relatively accurate prognostic prediction for ICC patients regardless of resection status.