ObjectiveTo study the characteristics of the five tones of Parkinson's disease （PD） patients based on the theory of "five-viscera phonology"， and provide references for the syndrome differentiation and treatment of PD. MethodsA total of 272 cases of PD patients were collected as the PD group， and 240 individuals， including patient family members and hospital staff， were recruited as the control group. The 25-tone analyzer was used to collect the five-tone characteristics of both PD patients and control group participants. The participants were then stratified into three age groups， 41~55， 56~70， and 71~85 years old， and categorized by gender （male and female） for analysis. The frequency and composition ratio of the five tones were analyzed for both groups across the different age ranges and genders. Additionally， the average voice frequency of each participant was calculated to compare differences between groups， stratified by age range and gender. ResultsIn the 41~55 and 56~70 age groups， male participants in the PD group and the control group exhibited the highest frequency of Yu （羽） tone， with the PD group showing a significantly higher composition ratio of Yu tone compared to the control group （P＜0.05）； for males in the 56~70 age group， the composition ratios of Shang （商） and Zhi （徵） tone in the PD group were lower than those in the control group （P＜0.05）. For males in the 71~85 age group， both the PD group and the control group had the highest frequency of Yu tone， but there was no statistically significant difference in the composition ratios of the five tones between groups （P＞0.05）. For female participants in the PD group across all age groups， Yu tone was the most frequent， whereas for the control group， Jue （角） tone was the most frequent in all age groups， and the composition ratio of Yu tone in the PD group was significantly higher than that in the control group across all age groups （P＜0.05）； in the 56~70 age group， the composition ratio of Jue tone was lower in the PD group compared to that in the control group （P＜0.05）. Regarding voice frequency， males in the PD group aged 41~55 and 56~70 had higher voice frequency than those in the control group of the same age range， and similarly， females in the PD group aged 56~70 and 71~85 had higher voice frequency than their counterparts in the control group （P＜0.05）. ConclusionPD patients have a voice with a higher frequency and an increased proportion of Yu tone in their five-tone distribution. According to the theory of five-viscera phonology， PD patients may have disease mechanism of kidney essence deficiency.

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.

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.

ObjectiveTo observe the effect of modified Tianwang Buxindan （MTBD） on the skin of sleep-deprived （SD） mice and investigate its mechanism. MethodSixty 2-month-old female Kunming mice were randomly divided into a blank group， a model group， a vitamin C （VC， 0.08 g·kg^-1）， and MTBD low-， medium-， and high-dose groups （6.5， 12.5， 25 g·kg^-1）. Except for the blank group， the other groups were subjected to SD mouse model induction （using multiple platform water environment method for 18 hours of sleep deprivation daily from 15：00 to next day 9：00）， continuously for 14 days， and caffeine （CAF， 7.5 mg·kg^-1） was injected intraperitoneally from the 2nd week onwards， continuously for 7 days. While modeling， the blank group and the model group were administered with normal saline （0.01 mL·g^-1）， and the other groups received corresponding drugs for treatment. On the day of the experiment， general observations were recorded （such as body weight， spirit， fur， and skin）. After sampling， skin tissue pathological changes were observed under an optical microscope using hematoxylin-eosin （HE） and Masson staining methods. Skin thickness and skin moisture content were measured. Biochemical assay kits were used to detect skin hydroxyproline （HYP） content， skin and serum superoxide dismutase （SOD） activity， and malondialdehyde （MDA） content. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum interleukin （IL）-6， tumor necrosis factor （TNF）-α， and IL-1β levels in mice. Western blot was used to detect skin tissue type Ⅰ collagen （ColⅠ）， type Ⅲ collagen （ColⅢ）， phosphatidylinositol 3-kinase （PI3K）， phosphorylated （p）-PI3K， protein kinase B （Akt）， p-Akt， nuclear factor E₂-related factor 2 （Nrf2）， heme oxygenase （HO）-1， and nuclear factor （NF）-κB protein expression. ResultCompared with the blank group， the model group showed varying degrees of changes. In general， signs of aging such as reduced body weight （P<0.01）， listlessness， dull fur color， and formation of wrinkles on the skin appeared. Tissue specimen testing revealed skin thinning， flattening of the dermoepidermal junction （DEJ）， and reduced collagen fibers under the optical microscope. Skin thickness and moisture content decreased， skin tissue HYP content significantly decreased （P<0.01）， skin and serum SOD activity significantly decreased （P<0.01）， and MDA content significantly increased （P<0.01）. Serum IL-6， TNF-α， and IL-1β levels significantly increased （P<0.01）. Skin ColⅠ， ColⅢ， p-PI3K/PI3K， p-Akt/Akt， Nrf2， and HO-1 protein expression significantly decreased （P<0.05， P<0.01）， and NF-κB expression increased （P<0.01）. Compared with the model group， the VC group and the MTBD low-dose group showed increased skin moisture content， HYP content， SOD activity， and ColⅠ， ColⅢ， p-PI3K/PI3K protein expression （P<0.05， P<0.01）， and decreased serum MDA content （P<0.05）. In addition， a decrease in serum IL-6 and IL-1β levels was detected in the MTBD low-dose group （P<0.05）， while the above indicators in the MTBD medium- and high-dose groups improved （P<0.05， P<0.01）. ConclusionSleep deprivation accelerates the aging process of the skin in SD model mice. MTBD can improve this phenomenon， exerting anti-inflammatory and antioxidant effects， and its mechanism of action may be related to the activation of the PI3K/Akt/Nrf2 signaling pathway.

Cognitive dysfunction is the impairment of higher brain functions.Cognitive impairment caused by neuropsychiatric diseases has caused serious impact on patients'quality of life and the outcome of the disease.The transcranial alternating current stimulation(tACS)improves cognitive function by modulating neural oscillations of specific frequencies,affecting the release of neurotransmitters such as serotonin and dopamine,and enhancing local and distal synchronization of brain networks.Specific frequencies of tACS can improve the cognitive impairment caused by Alzheimer disease(AD),schizophrenia,and depression,among which the gamma and theta frequencies of tACS have the most significant effects on cognitive function.tACS has high safety and low operational difficulty,and has great potential to improve cognitive function.

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.

Objective To analyse the effect of baseline serum vascular endothelial growth factor(VEGF)level on clinical factors,pathological features and prognosis of patients with non-triple-negative breast cancer.Methods A total of 120 patients with non-triple-negative breast cancer admitted to the hospital from January 2019 to December 2020 were selected as the study objects.According to the TNM stage of the tumor,the stud-y objects were divided into 80 patients with TNM stage Ⅰ and Ⅱ(group A)and 40 patients with TNM stageⅢ(group B).Serum VEGF levels,clinical factors and pathological features were compared between the two groups.Receiver operating characteristic(ROC)curve was used to analyze the optimal cut-off value of serum VEGF level in predicting stage Ⅲ breast cancer.Survival curves for overall survival and disease-free survival were plotted using the Kaplan-Meier method,and comparisons were made using the Log-rank test.The effects of baseline serum VEGF levels on overall survival and disease-free survival in non-triple-negative breast cancer were investigated by multivariate Cox regression model.Results Serum VEGF,D-dimer,fibrinogen(FIB),fi-brin degradation products(FDP),cancer antigen 125(CA-125)and cancer antigen 15-3(CA15-3)in group B were significantly different from those in group A(P＜0.05).ROC curve analysis showed that the area under the curve of serum VEGF in TNM stage Ⅲ of non-triple-negative breast cancer was 0.875,95％CI(0.802-0.948),P＜0.001.The levels of D-dimer,FIB,FDP,CA-125 and CA15-3 in serum VEGF≥180.40 pg/mL patients were higher than those in serum VEGF＜180.40pg/mL patients,and the differences were statistically significant(P＜0.05).In patients with serum VEGF＜180.40 pg/mL,the proportion of tumor T1 stage,tumor N0 and N1 stage,TNM stage Ⅰ/Ⅱ,and Luminal type A were higher than those with serum VEGF≥180.40 pg/mL patients,and the differences were statistically significant(P＜0.05).The disease-free survival rate of serum VEGF＜180.40 pg/mL patients was significantly higher than that of serum VEGF≥180.40 pg/mL patients,and the difference was statistically significant(P＜0.001).After correction,VEGF≥180.40 pg/mL was a risk factor for recurrence and metastasis of non-triple-negative breast cancer[HR=2.563,95％CI(1.772-3.708),P＜0.001].Conclusion High baseline VEGF levels are associated with progression of non-triple-negative breast cancer and are an influential factor in its prognosis.

Objective:To summarize the clinical manifestations and prognostic factors of patients with hepatic amyloidosis in a single center.Methods:The clinical data of 28 primary systemic light chain amyloidosis cases with liver involvement in our center from October 2012 to January 2023 were retrospectively analyzed. The main clinical manifestations and prognostic factors were studied. Statistical analysis were performed using the χ 2 test, Fisher's exact test, Wilcoxon rank test, or Kaplan-Meier survival curve log-rank test according to the different data. Results:The main clinical manifestations of patients with liver involvement were abdominal distension, hepatomegaly, and edema. CD56 and chemokine receptor 4 protein expression accounted for 52% (13/25) and 56% (14/25). 64.3% (9/14) patients were combined with t (11,14), and 21.4% (3/14) patients were positive for 1q21 (+), and no patients were detected with del(17p). Univariate analysis showed that Mayo 2004 and 2012 stages and total bilirubin (TBil) ≥34.2 μmol/L were associated with progression-free survival and overall survival. The median progression-free survival and overall survival were significantly inferior in patients with TBil≥34.2μmol/L group (0.178 years, 0.195 years) than with the TBil<34.2μmol/L group (0.750 years, 3.586 years) ( P ?

Currently， evidence on the efficacy and risk of traditional Chinese medicine （TCM） injections is seriously insufficient， and it is difficult to evaluate TCM injections comprehensively， truly and objectively using available efficacy evaluation indicators. Therefore， establishing a clinical efficacy evaluation system that can effectively reflect TCM injections is imperative. Core outcome set （COS） has played an important role in screening TCM efficacy evaluation indicators， however， there are still certain problems， such as large differences in efficacy indicators， non-standardization， and lack of featured and specific TCM indicators. Mixed method research （MMR） has the advantages of looking at problems from both quantitative and qualitative perspectives. It is thereby proposed to use COS and MMR integrated model to establish a clinical efficacy evaluation indicator system that not only fully considers the cha-racteristics of TCM injections， but also highlights the efficacy and advantages of TCM injections from the perspective of TCM intervention. Simultaneously， an indicator screening method using MMR to optimize COS research model is formulated， which can provide ideas for the research on efficacy evaluation indicators of TCM injections.

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.