ObjectiveTo investigate the effects of rhizosphere organic acids secreted by the roots of Salvia miltiorrhiza on continuous cropping obstacles. MethodsThe mixed solution of organic acids in the rhizosphere of S. miltiorrhiza in continuous cropping and rotation cropping was added to the hairy roots subcultured for 21 days， and samples were collected on days 0， 2， 4， 6， 8， and 10. The changes of biomass， effective components， primary metabolites， secondary metabolites， antioxidant enzymes， and hormones in hairy roots of S. miltiorrhiza were observed and determined. ResultsCompared with the rotation cropping group and the blank control group， the simulation of organic acid secretion from the roots of S. miltiorrhiza had a significant inhibitory effect on the growth of hairy roots and decreased the content of effective components as well as total sugar and total protein in primary metabolites. Compared with the blank control group， the rotation cropping group and the continuous cropping group showed total sugar and total protein content decreases of 33.9% and 5.1%， respectively. On the other hand， the secretion of organic acids from S. miltiorrhiza roots significantly promoted the accumulation of total phenolic acids and total tanshinone， which showed increases of 14.6% and 1.6%， respectively， in continuous cropping group and rotation cropping group compared with the blank control group. ConclusionThe organic acid environment under continuous cropping significantly inhibited the growth of hairy roots and the accumulation of primary metabolites， while promoting the synthesis and accumulation of secondary metabolites of S. miltiorrhiza.

Objective To evaluate the safety and efficacy of transcatheter arterial chemoembolization(TACE)combined with lenvatinib and camrelizumab in the treatment of advanced hepatocellular carcinoma(HCC).Methods The clinical data of a total of 63 patients with advanced HCC,who received TACE combined with lenvatinib and camrelizumab(triple therapy)or TACE combined with lenvatinib(dual therapy)at the Jingmen Municipal People's Hospital of China between April 2020 and December 2021,were retrospectively analyzed.Triple therapy group had 30 patients,and dual therapy group had 33 patients.The post-treatment tumor response,disease progression-free survival(PFS),overall survival(OS),and the incidence of adverse drug reactions were recorded.Results The median follow-up period of the two groups was 14 months(range of 4-26 months).Compared with the dual therapy group,in the triple therapy group the objective response rate(ORR)was remarkably higher(83.3%vs.57.6%,P=0.026),the disease control rate(DCR)was obviously higher(93.3%vs.69.7%,P=0.039),the median PFS was significantly longer(8.0 months vs.5.0 months,P＜0.01),and the median OS was strikingly longer(24.0 months vs.12.0 months,P=0.004).No statistically significant difference in the incidence of adverse drug reactions existed between the two groups(P＞0.05).Conclusion For the treatment of advanced HCC,TACE combined with lenvatinib and camrelizumab is clinically safe and effective.(J Intervent Radiol,2024,32:57-62)

Wilson's disease, also known as hepatolenticular degeneration, is an inherited disorder of copper metabolism caused by homozygous or compound heterozygous variants in the ATP7B gene, which is mainly clinically manifested as liver disease and/or neurological/psychological disorders, and Kayser-Fleischer ring in the peripheral cornea. Patients with Wilson's disease are currently treated with lifelong use of chelating agents that promote copper ion excretion and/or zinc agents that reduce copper absorption, but there is still an unmet clinical need because some patients who receive treatment have poor efficacy, disease progression, or serious adverse drug reactions. In recent years, new therapeutic drugs have been developed rapidly. This article will summarize the advances in drug treatment of Wilson's disease, shedding new light on the treatment of Wilson's disease.

Objective To investigate the impact of the change in anti-hepatitis B virus (HBV) therapy indication on treatment rate and the features of the population requiring treatment. Methods The treatment-naïve patients with chronic hepatitis B (CHB) in the China Registry of Hepatitis B (CR-HepB) database were selected as subjects, and related demographic, virological, hematological, and biochemical data were collected. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. Results A total of 3640 treatment-naïve CHB patients were included in this study, among whom 64.4% were male, 68.7% had an age of 30-59 years, and 46.8% had an indeterminate clinical stage. According to the 2015 and 2019 editions of Guidelines for the prevention and treatment of chronic hepatitis B and the 2022 edition of expert consensus, the number of patients who had the indication for antiviral therapy was 625(17.2%), 1333(36.6%), and 2890(79.4%), respectively. The number of patients requiring treatment was increased by 1557 according to the 2022 edition of expert consensus, among whom 1424(91.5%) met the treatment threshold of alanine aminotransferase (ALT) > 30 U/L for male patients or ALT > 19 U/L for female patients. The additional patients requiring treatment according to the 2022 edition of expert consensus had significantly higher levels of ALT and HBV DNA and significantly lower scores of APRI and FIB-4 than the additional patients requiring treatment according to the 2019 edition of Guidelines (all P < 0.05). Conclusion The expansion of antiviral therapy indications for CHB may significantly increase the proportion of CHB patients receiving antiviral treatment and help mild CHB patients at the risk of disease progression to receive timely treatment and achieve the improvement in long-term prognosis.

Objective To describe the characteristics and registration status of clinical trials of new drugs for nonalcoholic steatohepatitis (NASH), and to provide a reference for the design and implementation of clinical trials of new drugs for NASH. Methods The U.S. Clinical Trials Database, China Clinical Trial Registry, and Center for Drug Evaluation, National Medical Products Administration, were searched for clinical trials of new drug registration and interventional studies with NASH as the indication published up to August 6, 2021, using NASH in English and Chinese characters as the keywords, and liver cirrhosis was excluded. Two researchers independently searched and screened the articles to extract relevant information. Results A total of 196 clinical trials of new drug registration or interventional studies for NASH were included, among which there were 174 trials registered abroad and 22 trials registered in China, and the number of registrations tended to increase year by year. The numbers of phase Ⅰ, phase Ⅰ/Ⅱ(including Ⅰb/Ⅱa), phase Ⅱ, phase Ⅱ/Ⅲ, and phase Ⅲ clinical trials were 45(23.0%), 8(4.1%), 112(57.1%), 4(2.0%), and 19(9.7%), respectively. The main drug types included farnesoid X receptors, fibroblast growth factors, peroxisome proliferator-activated receptor agonists, and glucagon-like peptide-1, with numbers of 16(8.16%), 14(7.14%), 11(5.61%), and 13(6.63%), respectively. The clinical trials of innovative drugs for NASH initiated by the sponsors in European and American regions accounted for the highest proportion, and there was a gradual increase in the number of clinical trials of innovative drugs in China in recent years, with a similar distribution of single-center and multicenter clinical trials. As for the trials with NASH patients as subjects, the numbers of trials with pathology, imaging, and clinical diagnosis as the main inclusion criteria were 125, 66, and 42, respectively. Phase Ⅰ clinical trials used safety, tolerability, and pharmacokinetic parameters as the main assessment indices, while phase Ⅱ and phase Ⅲ clinical trials often used safety and efficacy as the main assessment indices. The number of clinical trials for the registration of innovative drugs for NASH was relatively low but kept increasing in China, and there were fewer clinical trials of innovative traditional Chinese medicine drugs compared with innovative chemical drugs. Conclusion There is a significant increase in the registration of international clinical trials of innovative drugs for NASH, and most of these trials are in the early phases, with large differences in inclusion criteria and assessment indices, a lack of unified evaluation indices, and relatively few trials with new designs. There are fewer clinical trials of innovative drugs for NASH in China than in European and American countries, and the number of such trials is gradually increasing in China.

Continuous cropping obstacle is the bottleneck of medicinal plant cultivation, which seriously affects the quality and yield of medicinal materials. The research on the mechanism of continuous cropping obstacle has evolved from soil physical and chemical properties and allelopathy in the 1970s to the changes of rhizosphere microenvironment and plant response mechanism at present. According to the available studies in this field and our previous research work, we systematically analyzed the mechanism of rhizosphere exudate-mediated microbial community reconstruction in the soil of the medicinal plants in continuous cropping. Specifically, rhizosphere exudates, providing the carbon source and energy for microbial growth, act as inducers or repellents to induce microbial growth or transfer, thereby changing the physicochemical properties (such as acidity) of rhizosphere soil and further altering the structure of rhizosphere microbial community. Further, we comprehensively discussed the ways of synergism between rhizosphere exudates and soil microorganisms in causing harm to the medicinal plants in continuous cropping. That is, rhizosphere exudates mediate the infection of the rhizosphere by pathogenic microorganisms, increase the susceptibility of the nearby plants, inhibit the defense of the host plants, and protect the pathogens to occupy the dominant niche. The synergistic interaction results in the release of more pathogenic factors such as mycotoxins by rhizosphere pathogens, enhanced toxicity of rhizosphere allelochemicals, and deterioration of soil physical and chemical properties. This paper summarizes the role of interaction between rhizosphere exudates and soil microorganisms in the formation of continuous cropping obstacles, aiming to provide a new research idea for revealing the formation mechanism as well as the theoretical support for overcoming continuous cropping obstacles of medicinal plants.

Objective:To understand and compare the differences between age, sex and liver diseases-related mortality risk in patients with hepatitis B virus-related liver cirrhosis.Methods:Based on the front-page inpatient medical record database and the death registration system of Beijing patients with hepatitis B-related liver cirrhosis from 2008 to 2015 were included. The survival information of all patients were traced up to the occurrence of liver disease-related mortality event or until December 31, 2019. Kaplan-Meier method was used to calculate the cumulative incidence of liver disease-related mortality in patients with liver cirrhosis. Cox regression model was used to analyze the effect of age-gender interaction on liver disease-related mortality risk.Results:A total of 16 738 patients with hepatitis B-related liver cirrhosis were included, of which 13 969 cases (83.46%) were in compensated stage and 2 769 cases (16.54%) were in decompensated stage. Liver cirrhosis complications mortality risk in patients with compensated stage cirrhosis at 3, 5, and 8 years were 10.84%, 12.70%, and 14.37%, respectively; while in decompensated stage patients, the mortality risk was 16.70%, 19.02%, and 20.73%, respectively. The 3, 5, and 8-year liver cancer mortality rates of patients with compensated stage liver cirrhosis were 5.24%, 7.49%, and 10.25%, respectively; while those with decompensated stage liver cancer mortality rates were 9.01%, 11.16%, and 13.50%, respectively. Liver disease-related mortality risk was increased with age in patients with liver cirrhosis. Liver cirrhosis complications mortality risk in female patients with liver cirrhosis at age < 60 years was lower than that of male patients. Liver cirrhosis complications mortality risk in male and female patients aged 60-69 years were similar. Liver cirrhosis complications mortality risk in female patients aged ≥70 years was higher than that of male patients. However, female patients had a lower risk of liver cancer mortality than male patients in utmost age groups.Conclusion:Age is positively correlated with liver diseases-related mortality risk in patients with hepatitis B-related liver cirrhosis. Female sex is a protective factor for liver cancer mortality in patients with liver cirrhosis, and the protective effect on liver cirrhosis complications mortality risk gradually disappears with age.

Objective: To investigate the occurrence and risk factors of deep venous thrombosis (DVT) in adult burn patients. Methods: The clinical data of 1 219 adult burn patients admitted to the Department of Burns of Zhengzhou First People′s Hospital from January 1, 2015 to August 31, 2016, conforming to the study criteria, were analyzed retrospectively by the method of case-control study, including 811 males and 408 females, aged 18-102 years. According to whether DVT occurred during hospitalization or not, the patients were divided into group DVT (n=12) and non-DVT group (n=1 207). The incidence of DVT, the diagnosis time of DVT, affected limbs, and DVT classification were counted and recorded. The gender, age, total burn area, D-dimer, lower limb burn, full-thickness burn, femoral vein indwelling central venous catheter (CVC) , inhalation injury, sepsis/infection shock, surgical operation, and infusion of concentrated red blood cells of patients between the two groups were compared with chi-square test, and then the indicators with statistically significant differences between the two groups were processed by multivariate binary logistic regression analysis to screen the independent risk factors of DVT in the adult burn patients. Results: (1) The incidence of DVT of adult burn patients was 0.98% (12/1 219), and DVT was diagnosed 24-138 days after injury, with a median of 61.5 days. DVT occurred in the right lower limb of 2 patients, left lower limb of 8 patients, and bilateral lower limbs of 2 patients, and DVT classification included 6 cases of mixed type and 6 cases of peripheral type. (2) There were no statistically significant differences in gender, age, and full-thickness burn of patients between the two groups ( χ²=1.524, 0.021, 3.115, P>0.05). There were statistically significant differences in total burn area, lower limb burn, inhalation injury, sepsis/infection shock, D-dimer, femoral vein indwelling CVC, surgical operation, and infusion of concentrated red blood cells among patients between the two groups (χ²=17.975, 6.206, 3.987, 8.875, 5.447, 15.124, 10.735, 14.031, P<0.05 or P<0.01). (3) Total burn area, D-dimer, and femoral vein indwelling CVC were independent risk factors for DVT in adult burn patients (odds ratio=10.927, 4.762, 9.394, 95% confidence interval=3.078-38.789, 1.197-18.934, 2.631-33.540, P<0.05 or P<0.01). Conclusions The incidence of DVT in adult burn patients is relatively low, and the diagnosis time of DVT is 3 weeks after burn, with DVT classification of mixed type and peripheral type. The total burn area, femoral vein indwelling CVC, and D-dimer are independent risk factors for predicting DVT in adult burn patients.