Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

OBJECTIVE: To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment. METHODS: ApoE^-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation. RESULTS: Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36. CONCLUSION Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.
Animals ; MicroRNAs/genetics* ; Exosomes/drug effects* ; Plaque, Atherosclerotic/genetics* ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Blood Platelets/drug effects* ; Apolipoproteins E/deficiency* ; Thrombospondin 1/metabolism* ; CD36 Antigens/metabolism* ; Platelet Activation/drug effects* ; Male ; Mice ; Mice, Inbred C57BL

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Objective:To evaluate the clinical efficacy of Fried Licorice Decoction Plus-minus in combination with PD-1 therapy for patients with advanced non-small cell lung cancer(NSCLC)with Qi-Yin deficiency.Methods:From December 2020 to December 2022,72 patients diagnosed with advanced NSCLC with Qi-Yin deficiency were enrolled in this study.The patients were recruited from Jilin Provincial Cancer Hospital and the Affiliated Hospital of Changchun University of Chinese Medicine.The patients were randomly assigned into two groups,with 36 patients in each group.The control group received PD-1 treatment alone,and the treatment group received PD-1 combined with Fried Licorice Decoction Plus-minus.The measures of primary outcomes included immune function(CD3+,CD3+/CD4+,and CD3+/CD8+)and quality of life score(Kamofsky,KPS).The measures of secondary outcomes included the objective response rate(ORR);traditional Chinese medicine(TCM)symptom score;serum tumor marker carcinoembryonic antigen(CEA);neuron-specific enolase(NSE);cytokeratin fragment(CYFRA211);and incidence of immune-related adverse events such as gastrointestinal toxicity,pulmonary toxicity,hepatotoxicity,and thyroid toxicity.Results:Regarding immune function regulation,a significant improvement was observed in CD3+,CD3+/CD4+,and CD3+/CD8+.Furthermore,at T3 and T4 time points,an improvement was observed in patient quality of life indicators such as the tumor markers CEA and CY211.In addition,symptoms related to TCM syndrome,including coughing,fatigue,palpitations,and diarrhea were significantly reduced compared to the baseline levels.Moreover,the treatment group exhibited superior outcomes compared to those of the control group in terms of reducing immune-associated pneumonia and diarrhea(P<0.05).The ORR for both groups was similar;36%for those receiving com-bination therapy vs.25%for those receiving PD-1 monotherapy.Therefore,no significant differences between these two groups were ob-served(P>0.05).Conclusions:The combination of Fried Licorice Decoction Plus-minus and PD-1 in the treatment of patients with advanced NSCLC showed a significant enhancement in immune function,improvement in clinical efficacy,reduction in immune-related adverse reac-tions,and had an excellent safety profile.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

The incidence and detection rates of benign and low-grade malignant pancreatic tumors have risen yearly.For patients with such tumors,traditional radical resection procedures often result in excessive loss of normal pancreatic parenchyma,leading to complications such as postoperative insufficiency of both exocrine and endocrine functions.Studies have shown that functional-preserving surgeries,such as minimally invasive enucleation or partial resection surgeries,can maximize the protection of patients'pancreatic function and improve long-term quality of life.However,for some tumors deep within the pancreatic parenchyma,accurately locating the tumor and protecting the pancreatic duct pose challenges.Intraoperative ultrasound(IOUS)has become an ideal intraoperative imaging tool,often referred to as the surgeon's"third eye"because of its portability,ability to provide real-time high-resolution information,non-reliance on ionizing radiation,and the fact that it does not require special patient preparation.With advancements in technology,the application scope of IOUS has expanded beyond its initially limited diagnostic role to various surgical applications,including identifying non-palpable lesions,guiding surgical strategies,and staging tumors.In the current era of minimally invasive and precision surgery,the proficiency of surgeons in using IOUS has become an important issue.This article reviews the history of IOUS applications,summarizes the advantages and basic usage methods of robotic IOUS,and shares techniques for applying IOUS in robot-assisted precise resection of pancreatic tumors.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

COVID-19 is caused by a novel coronavirus-severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which has being spreading around the world, posing a serious threat to human health and lives. Neutralizing antibodies and small molecule inhibitors for virus replication cycle are the main antiviral treatment for novel coronavirus recommended in China. To further promote the rational use of antiviral therapy in clinical practice, the National Center for Infectious Diseases (Beijing Ditan Hospital Capital Medical University and the First Affiliated Hospital, Zhejiang University School of Medicine) invited experts in fields of infectious diseases, respiratory and intensive care to develop an Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( trial version 10) and experiences in the diagnosis and treatment of COVID-19 in China. The consensus is concise, practical and highly operable, hopefully it would improve the understanding of antiviral therapy for clinicians and provide suggestions for standardized medication in treatment of COVID-19.

OBJECTIVE: To determine the thermic effect of food (TEF) in a Chinese mixed diet in young people. METHODS: During the study, the participants were weighed and examined for body composition every morning. The total energy expenditure (TEE) of the participants was measured by the doubly labeled water method for 7 days, and during this period, basal energy expenditure was measured by indirect calorimetry and physical activity energy expenditure was measured by an accelerometer. The value obtained by subtracting basal energy expenditure and physical activity energy expenditure from TEE was used to calculate TEF. RESULTS: Twenty healthy young students (18-30 years; 10 male) participated in the study. The energy intake of the participants was not significantly different from the Chinese Dietary Reference Intake of energy ( P > 0.05). The percentage of energy from protein, fat and carbohydrate were all in the normal range. The intakes of fruits, milk and dietary fiber of the participants were significantly lower than those in the Chinese Dietary Guidelines ( P < 0.05). There was no significant difference in the body weight of the participants during the experiment ( P > 0.05). When adjusted for body weight, there was no significant difference in either TEE or basal energy expenditure between the male and female participants ( P > 0.05). In addition, there was no significant difference in physical activity energy expenditure and TEF between the male and female participants ( P > 0.05). The percentage of TEF in TEE was 8.73%. CONCLUSION The percentage of TEF in TEE in a Chinese mixed diet in young people was significantly lower than 10% ( P < 0.001). A value of 10% is usually considered to be the TEF in mixed diets as a percentage of TEE.
Adolescent ; Female ; Humans ; Male ; Body Composition ; Body Weight ; Diet ; East Asian People ; Energy Intake ; Energy Metabolism ; Exercise ; Young Adult ; Adult

Objective To investigate the prevalence of mountain-type zoonotic visceral leishmaniasis (MT-ZVL) in Yangquan City, Shanxi Province from 2015 to 2020, so as to provide the scientific evidence for formulating the MT-ZVL control strategy. Methods The epidemiological data pertaining to MT-ZVL cases in Yangquan City from 2015 to 2020 were collected and descriptively analyzed. A Joinpoint regression model was created to analyze the trend in the MT-ZVL incidence in Yangquan City from 2015 to 2020 using annual percent change (APC). The sandflies surveillance data and the prevalence of Leishmania infections in dogs were collected in Yangquan City in 2020, and the regional distribution of sandflies density and sero-prevalence of Leishmania infections in dogs were calculated. In addition, the associations of sandflies density and sero-prevalence of Leishmania infections in dogs with the incidence of human MT-ZVL were examined using the linear correlation analysis. Results A total of 162 MT-ZVL cases were reported in Yangquan City, Shanxi Province from 2015 to 2020, with annual mean incidence of 1.9/10⁵, and there were 4, 7, 16, 27, 33 cases and 75 cases with MT-ZVL reported from 2015 to 2020, appearing a tendency towards a rapid rise (APC = 72.79%, t = 11.10, P < 0.01). MT-ZVL cases were reported across the five counties (districts) of Yangquan City, and the cases predominantly occurred in Jiaoqu District (35.2%, 57/162) and Pingding County (33.3%, 54/162). MT-ZVL cases were predominantly detected in residents at ages of 15 years and older (71.6%, 116/162) and at ages of 0 to 2 years (22.2%, 36/162), with farmers (37.4%, 61/162) and diaspora children (24.5%, 40/162) as predominant occupations. The mean density of Phlebotomus chinensis was 6.3 sandflies per trap per night in Yangquan City from during the period from May to September, 2020, with the highest density observed in Jiaoqu District (12.6 sandflies per trap per night) and the lowest in Yuxian County (1.1 sandflies per trap per night), and there was a region-specific mean density of Ph. chinensis in Yangquan City (H = 17.282, P < 0.01). The sero-prevalence of serum anti-Leishmania antibody was 7.4% (2 996/40 573) in domestic dogs in Yangquan City, with the highest sero-prevalence seen in Jiaoqu District (16.6%, 1 444/8 677), and the lowest in Yuxian County (2.3%, 266/11 501), and there was a region-specific sero-prevalence rate of anti-Leishmania antibody in domestic dogs in Yangquan City (χ² = 1 753.74, P < 0.01). The sero-prevalence of anti-Leishmania antibody was significantly higher in stray dogs (20.0%, 159/794) than in domestic dogs (χ² = 176.63, P < 0.01). In addition, there were significant associations among the sandflies density, sero-prevalence of anti-Leishmania antibody in domestic dogs and the incidence of human MT-ZVL (r = 0.832 to 0.870, all P values < 0.05). Conclusions The prevalence of MT-ZVL appeared a tendency towards a rapid rise in Yangquan City from 2015 to 2020, and systematic interventions are urgently needed for MT-ZVL control.