Chronic liver diseases with common causes including viral infections， alcohol abuse， and autoimmune diseases. Alkaloids， as a class of plant-derived compounds， have shown significant potential in regulating chronic liver diseases. Recent studies have shown that alkaloids are able to exert a therapeutic effect on chronic liver diseases through multiple pathways. These compounds have a regulatory effect on key pathological processes such as liver fibrosis， inflammatory response， oxidative stress， and cell apoptosis， and they also regulate the metabolic homeostasis of hepatocytes by modulating multiple signaling pathways， thereby playing a role in regulating chronic liver diseases. This article reviews the role and mechanism of alkaloids in the treatment of chronic liver diseases， in order to provide new ideas and directions for the treatment of chronic liver diseases.

Objective: To investigate the mechanism of action of curcumol on mitochondrial autophagy in hepatic stellate cells and its molecular mechanism against liver fibrosis. Methods : Hepatic stellate cells were divided into blank group, model group(lipopolysaccharide 5 mg/L), and low, medium and high curcumol group(12.5, 25 and 50 mg/L); Thiazolyland(MTT) was used to detect the effects of curcumol on the viability of hepatic stellate cells; flow cytometry was used to detect the effects of curcumol on apoptosis of hepatic stellate cells; 5,5′,6,6′-Tetrachloro-1,1′,3,3′-tetraethylimidacarbocyanine iodide(JC-1) was used to detect the mitochondrial membrane potential; effects of curcumol on mitochondrial morphology and autophagosome were detected by transmission electron microscopy; effect of curcumol on mitochondrial localisation were detected by fluorescent probe; Immunoblotting assay was performed to detect the effects of curcumin on PTEN-induced putative kinase 1(PINK1), Parkinson's disease protein(Parkin), microtubule-associated protein light chain 3(LC3), autophagy-associated protein(Beclin1), mitochondrial inner membrane translocase 23(Timm23), mitochondrial outer membrane translocase 20(Tomm20), Bcl-2 associated X protein(Bax), B lymphocytoma-2(Bcl2), cleaved-cysteine protease 3(Caspase3), α-smooth muscle actin(ɑ-SMA), collagen type Ⅰ(Collagen Ⅰ), and collagen type Ⅲ(Collagen Ⅲ) protein expression. Results : Compared with the blank control group, cell proliferation rate, Caspase3, Bcl2, LC3Ⅱ, Beclin1, PINK1, Parkin, ɑ-SMA, CollagenⅠ, CollagenⅢ proteins significantly increased in the model group(P<0.01), co-localisation of mitochondria and lysosomes increased, and the number of mitochondrial autophagosome significantly increased(P<0.01), while Timm23 and Tomm20 proteins, mitochondrial membrane potential decreased significantly(P<0.01), apoptosis rate decreased, and Bax protein expression decreased. Compared with the model group, after curcumol intervention, cell proliferation rate, Bcl2, Timm23, Tomm20, α-SMA, CollagenⅠ and CollagenⅢ protein expression significantly decreased in the curcumol low-, medium-and high-concentration groups(P<0.01), and the mitochondrial membrane potential significantly decreased(P<0.01), whereas apoptosis rate, Caspase3, Bax, LC3Ⅱ, Beclin1, PINK1 and Parkin proteins significantly increased(P<0.05), the co-localisation of mitochondria and lysosomes increased, and the number of mitochondrial autophagosome significantly increased(P<0.01). Conclusion Curcumol exerts ameliorative effects on hepatic fibrosis by modulating mitochondrial hyperautophagy mediated by the PINK1/Parkin signaling pathway, and promoting hepatic stellate cell apoptosis.

Chronic liver disease(CLD)tends to have a high incidence rate and impose a serious burden on society and families.Studies have shown that metal ion metabolism is closely associated with CLD,and some Chinese herbal medicines can play a role in the prevention and treatment of CLD by regulating metal ion metabolism.At present,the synthetic drugs currently used for the treatment of CLD fail to achieve a satisfactory effect,and therefore,a variety of Chinese herbal medicines are being used as supplementary and alternative therapies for CLD.This article introduces the role of metal ion metabolism in CLD and the regulatory effect of Chinese herbal medicines and their active components on CLD,and the analysis shows that metal ion metabolism is expected to provide new ideas for the research on CLD and a theoretical basis for the clinical treatment of CLD.For the role of metal ion metabolism in the treatment of CLD,more prospective clinical study data are needed in the future to provide effective and safe treatment regimens for patients with CLD.

BACKGROUND:In recent years,the development of liver organoids has made it a hot spot in the field of international liver disease research,but there is still no article on the bibliometric analysis of liver organoids. OBJECTIVE:To explore the hot trends in liver organoids in the last 20 years based on bibliometrics and visualization analysis. METHODS:We searched the articles about liver organoids in the Web of Science Core Collection from January 1,2002 to November 12,2022.Origin,Office,and CiteSpace software were used for bibliometrics and visualization analysis.We statistically analyzed the number of annually published articles,countries,institutions,authors,journals,and keywords of the articles by generating charts. RESULTS AND CONCLUSION:The number of articles,citation frequency,institutions and personnel involved in the research about liver organoids showed an overall upward trend in the last 20 years,indicating that the field was growing rapidly and attention was increasing.The USA had published the most papers and had the strongest influence in this field.Although it had invested a lot of time and energy,the number of papers published by a single research institution in the USA was not the highest among many research institutions.China was second only to the USA in the number of publications,with the Chinese Academy of Sciences and Fudan University leading the list.Utrecht University in the Netherlands was the institution with the most publications.Clevers H was the author with the highest number of articles.The article with the highest co-citation frequency was"Long-term culture of genome-stable bipotent stem cells from adult human liver".The main fields of study for liver organoids were Molecular Science,Biology,and Immunology.The most frequently occurring keywords were stem cell,in vitro,and culture.The research hotspots in the liver organoids field were mainly focused on in vitro stem cell three-dimensional culture,differentiation and gene expression.

Objective To study the application value of CAD/CAM technology in the teaching of inlay manufacturing.Methods A total of 60 undergraduates interned in the Department of Stomatology,Yan'an Hospital,Kunming Medical University were randomly divided into an experimental group(n=30)and a control group(n=30).We selected appropriate clinical cases for students to prepare for mandibular molar's proximal occlusal inlays.The instructor guided the results of the first preparation in different ways,and the students made the second modification and preparation,and the assessment team scored and evaluated the five aspects of the final preparation,the shape of the preparation,the shape of the occlusal surface,the dovetail retention,and the adjacent surface.Results The scores of all detection indexes in the experimental group were higher than those in the control group(P<0.05).Conclusion The application of CAD/CAM technology in inlay manufacturing teaching can effectively improve students'clinical hands-on ability and achieve better teaching effects than traditional teaching methods.

Objective To investigate the role of miR-125b on hepatic angiogenesis,with the hope of providing new targets for the prevention and treatment of liver fibrosis.Methods The human hepatic sinusoidal endothelial cells were transfected with miR-125b mimics and inhibitors,and the mRNA and protein expression of vascular endotheli-al growth factor(VEGF),cluster of differentiation antigens 31(CD31),von Willebrand factor(vWF),collagenⅣ,and laminin(LN)were detected by qRT-PCR and ELISA,and the expression of nitric oxide(NO)was detec-ted by fluorescent probe,scanning electron microscopy detected the alteration of the window holes on the surface of human hepatic sinusoidal endothelial cells,angiogenesis assay was performed to observe the neovascularization of each group,and dual luciferase reporter gene assay was performed to validate the targeting relationship between miR-125b and VEGF.Results qRT-PCR and ELISA showed that compared with the negative control group,the mRNA and protein expressions of VEGF,CD31,vWF,Collagen Ⅳ,and LN significantly decreased after miR-125b mimic transfection(P＜0.05),while the mRNA and protein expressions of VEGF,CD31,vWF,CollagenⅣ,and LN were significantly increased after transfection with miR-125 b mimics(P＜0.05);fluorescent probe detection showed that compared with the negative control group,the average fluorescence of intensity expression NO decreased significantly(P＜0.05),while the average fluorescence intensity expression of NO increased significant-ly after miR-125b inhibitor transfection(P＜0.05);the number of fenestrations on the surface of human liver sinu-soidal endothelial cells significantly increased after miR-125b mimic transfection(P＜0.05),while the number of fenestrations on the surface of human liver sinusoidal endothelial cells decreased significantly after miR-125 b inhibi-tor transfection(P＜0.05);angiogenesis assay showed that compared with the negative control group,the number of angiogenesis significantly decreased after miR-125b mimic transfection(P＜0.05),while the number of angio-genesis significantly increased after miR-125b inhibitor transfection(P＜0.05);dual luciferase reporter gene assay showed that compared with negative control group,the expression of relative fluorescence intensity after transfection of miR-125b mimics in VEGF wild-typ significantly decreased(P＜0.05),while the expression of relative fluores-cence intensity after transfection of miR-125b mimics in VEGF mutant significantly decreased(P＞0.05).Con-clusion miR-125b can inhibit liver angiogenesis and thus play an anti-fibrosis role,which can provide a new ref-erence for the prevention and treatment of chronic liver disease and the development of new drugs.

An increasing number of studies have demonstrated that exosomes are closely associated with liver fibrosis and mediate the process of liver fibrosis by participating in cytokine secretion, macrophage activation, extracellular matrix remodeling, and hepatic stellate cell activation. This article summarizes that the resolution of liver fibrosis requires the reduction of pro-inflammatory and fibrotic cytokines, the reduction of extracellular matrix protein production, the increase of collagenase activity, and finally the loss of activated myofibroblasts. It is believed that exosomes play an important role in the treatment of liver fibrosis and are potential markers for diagnosis and treatment, and in future studies, it is necessary to improve exosome extraction techniques and standardization of treatment quantification.

Objective:To analyze the effect and safety of plerixafor combined with G-CSF mobilization in plasma cell disease.Methods:The clinical baseline data, success rate of collection, and adverse reactions of consecutive cases of plasma cell disease were analyzed retrospectively, where the patients received plerixafor combined with G-CSF for autologous hematopoietic stem cell mobilization in Peking University People's Hospital from January 2018 to December 2019.Results:Forty-nine patients with plasma disease were included, of which 39 (79.6% ) were multiple myeloma, 8 (16.3% ) were amyloidosis, and 2 (4.1% ) were monoclonal gammopathy of renal significance. A total of 16 patients (32.7% ) had renal insufficiency, and 7 patients (14.3% ) had previous collection failure. The median times of apheresis was 1 (1-3) , median days of apheresis was 2 (1-3) days, 47 patients (95.9% ) were successfully collected for once, and the success rate of collection for twice was 100% after using plerixafor for mobilization. In 16 patients with renal insufficiency, collection was successful in 5 patients (31.3% ) on the first day, while aphresis was required in 8 patients (50% ) on the second day and 3 (18.8% ) on the third day. The main adverse reactions were fatigue, insomnia, abdominal pain, diarrhea, dizziness, and arthralgia. A total of 37 patients underwent autologous hematopoietic stem cell transplantation with 11 (8-13) days for neutrophil engraftment, and 11 (9-26) days for platelet engraftment.Conclusions:Plerixafor combined with G-CSF has a high success rate in mobilizaion of autologous hematopoietic stem cells in patients with plasma cell disease with minimum side effects, even in patients with renal insufficiency.

Objective To investigate the efficacy of lateral decubitus intramedullary nailing for treatment of subtrochanteric fractures of the femur.Methods From January 2012 to December 2015,23 patients with simple femoral subtrochanteric fracture were treated at Department of Orthopedic Trauma,Changhai Hospital.They were 15 males and 8 females,aged from 19 to 77 years (average,48.3 years).According to the Seinsheimer classification,there were 6 cases of type ⅡB,8 cases of type ⅡC,6 cases of type Ⅲ A,and 3 cases of type ⅢB.Their injuries were caused by traffic accident in 10 cases,falling from a height in 5 cases,and sprain in 8 cases.All patients were treated by closed reduction and anterograde intrarnedullary nailing at lateral decubitus.Their operative time,bleeding volume,fluoroscopic frequency,fracture healing time,functional recovery and complications were recorded and analyzed.Results Their operative time ranged from 55 to 80 min,averaging 65.7 min;their bleeding volumes ranged from 240 to 420 mL,averaging 304.3 mL;their fluoroscopic frequency ranged from 30 to 60 times,averaging 42.7 times.This cohort was followed up for 12 to 28 months (average,17.9 months).Their fracture healing time ranged from 4 to 10 months,averaging 5.5 months.Nonunion occurred in one patient but was cured by secondary operation.The HSS evaluation at the final follow-ups showed 17 excellent cases and 6 good ones,yielding an excellent to good rate of 100％.All the wounds healed by the first intention.No infection,deep vein thrombosis or implant failure was observed.Conclusion As lateral decubitus intramedullary nailing can achieve satisfactory clinical efficacy for subtrochanteric fractures of the femur,the body position of lateral decubitus may be a good alternative.

OBJECTIVE:To optimize the extraction technology of garlic oil. METHODS:Using extraction rate of garlic oil as index,based on single factor test,Box-Behnken response surface method was used to optimize conditions of steam distillation method for the extraction of garlic as fermentation time,solid to liquid ratio,fermentation temperature and the verification test were made for the optimized technology. RESULTS:The optimal extraction technology was as follows as fermentation time of 4.5 h,solid to liquid ratio of 1:7,fermentation temperature of 55 ℃. The average extraction rate of garlic oil in verification test was 0.32%(RSD=1.43%,n=3);the relative error between the measured value and predicted value was 0.06%. CONCLUSIONS:Box-Behnken response surface method is simple,reasonable and feasible to optimize the extraction technology of garlic oil,which can provide a scientific basis for industrial production.