Ganoderic acid is a class of lanostane-type triterpenoids found in Ganoderma species, and is one of the most important pharmacologically active components in G. lucidum, exhibiting antioxidant, anti-neuropsychiatric, anti-tumor, and immune-enhancing properties. The content of ganoderic acid in G. lucidum is very low, and the traditional extraction process is complex, yielding minimal amounts at high cost. The biosynthetic pathway of G. lucidum triterpenoids(GLTs), including the synthesis of different structural forms of ganoderic acid from lanosterol, as well as the molecular regulatory mechanisms involving key regulatory enzyme genes and their functions, are not yet fully understood. With the continuous development of synthetic biology technologies, there has been a deeper understanding of the biosynthesis and metabolic regulation pathways of ganoderic acid and its derivatives at the molecular level. Research has explored the key regulatory enzyme genes related to ganoderic acid biosynthesis and their functions. Moreover, through the optimization of synthetic biology and culture conditions, large-scale production and preparation of GLTs at the cellular level have been achieved. This paper reviews and analyzes the latest research progress on the biosynthesis pathways and metabolic regulation of GLTs, focusing on the configuration of ganoderic acid and its derivatives, the biosynthetic pathways, key enzyme genes, transcription factors related to ganoderic acid biosynthesis, signal transduction mechanisms, and factors affecting triterpenoid biotransformation. This review is expected to provide a theoretical basis and technical reference for improving the efficient production of triterpenoid pharmacological components and the exploitation and utilization of G. lucidum resources.
Triterpenes/chemistry* ; Reishi/chemistry* ; Biosynthetic Pathways ; Lanosterol

OBJECTIVE: Huachansu injection (HCSI), a promising anti-cancer Chinese medicine injection, has been reported to have the potential for reducing the toxicity of chemotherapy and improving the quality of life for colorectal cancer (CRC) patients. The objective of this study is to explore the synergistic and detoxifying effects of HCSI when used in combination with irinotecan (CPT-11). METHODS: To investigate the effect of HCSI on anti-CRC efficacy and intestinal toxicity of CPT-11, we measured changes in the biological behavior of LoVo cells in vitro, and anti-tumor effects in LoVo cell xenograft nude mice models in vivo. Meanwhile, the effect of HCSI on intestinal toxicity and the uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) expression was investigated in the CPT-11-induced colitis mouse model. Subsequently, we measured the effect of HCSI and its 13 constituent bufadienolides on the expression of UGT1A1 and organic anion transporting polypeptides 1B3 (OATP1B3) in HepG2 cells. RESULTS: The combination index (CI) results showed that the combination of HCSI and CPT-11 exhibited a synergistic effect (CI < 1), which significantly suppressing the LoVo cell migration, enhancing G2/M and S phase arrest, and inhibiting tumor growth in vivo. Additionally, the damage to intestinal tissues was attenuated by HCSI in CPT-11-induced colitis model, while the increased expression of UGT1A1 in HepG2 cells and in mouse was observed. CONCLUSION The co-therapy with HCSI alleviated the intestinal toxicity induced by CPT-11 and exerted an enhanced anti-CRC effect. The detoxifying mechanism may be related to the increased expression of UGT1A1 and OATP1B3 by HCSI and its bufadienolides components. The findings of this study may serve as a theoretical insights and strategies to improve CRC patient outcomes. Please cite this article as: Jiang B, Meng ZY, Hu YJ, Chen JJ, Zong L, Xu LY, Zhang XQ, Zhang JX, Han YL. Huachansu injection enhances anti-colorectal cancer efficacy of irinotecan and alleviates its induced intestinal toxicity through upregulating UGT1A1-OATP1B3 expression in vitro and in vivo. J Integr Med. 2025; 23(5):576-590.
Irinotecan/therapeutic use* ; Animals ; Glucuronosyltransferase/genetics* ; Humans ; Colorectal Neoplasms/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Nude ; Mice ; Up-Regulation/drug effects* ; Male ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Hep G2 Cells ; Cell Line, Tumor ; Intestines/drug effects* ; Amphibian Venoms

Mytilus is one of bivalves with great economic and ecological values.The innate immune de-fense of Mytilus shows great significance in the study of marine biological immunology.Hemolymph is the main immune tissue for Mytilus.The Nanopore full-length transcriptome of Mytilus coruscus hemocytes,and the serum differential proteomics based on SDS-PAGE analysis were performed to identify key pro-teins involving in the immune response of Mytilus hemolymph in response of different bacteria and fungi stresses.A total of 44 proteins were identified in the serum induced by different microorganisms.Among them,26 proteins showed significant differential expression level in response to different microbial stres-ses,and their functions were involved in protein folding protection,cell autophagy and apoptosis regula-tion,reactive oxygen species production,energy metabolism regulation,cell detoxification,and immune regulation.The changes in expression levels of these proteins varied in response to different bacterial and fungal stresses,suggesting that Mytilus has different immune response strategies to different bacterial and fungal stresses.The results provide a new scientific basis for understanding the differential immune mech-anism of Mytilus innate immune system in response to different types of microbial invasion,as well as the screening of specific biomarker proteins for microbial infection,and provide ideas for the healthy develop-ment and disease prevention of shellfish aquaculture.

Objective To establish the pharmacokinetic model of linezolid in neonates,and to optimize the administration regimen. Methods A prospective study was conducted among 64 neonates with sepsis who received linezolid as anti-infective therapy,and liquid chromatography-tandem mass spectrometry was used to measure the plasma concentration of the drug. Clinical data were collected,and nonlinear mixed effects modeling was used to establish a population pharmacokinetic (PPK) model. Monte Carlo simulation and evaluation was performed for the optimal administration regimen of children with different features. Results The pharmacokinetic properties of linezolid in neonates could be described by a single-compartment model with primary elimination,and the population typical values for apparent volume of distribution and clearance rate were 0.79 L and 0.34 L/h,respectively. The results of goodness of fit,visualization verification,and the Bootstrap method showed that the model was robust with reliable results of parameter estimation and prediction. Monte Carlo simulation results showed that the optimal administration regimen for linezolid in neonates was as follows:6 mg/kg,q8h,at 28 weeks of gestational age (GA);8 mg/kg,q8h,at 32 weeks of GA;9 mg/kg,q8h,at 34-37 weeks of GA;11 mg/kg,q8h,at 40 weeks of GA. Conclusions The PPK model established in this study can provide a reference for individual administration of linezolid in neonates. GA and body weight at the time of administration are significant influencing factors for the clearance rate of linezolid in neonates.

Objective:To investigate the effects of bunched cognitive behavior intervention on disease fear and psychological security in patients with glioma.Methods:A total of 92 patients with glioma who underwent surgical treatment from January 2022 to June 2023 were selected.According to the order of enrollment, all subjects were divided into research group( n=44)and control group( n=48). The patients in control group received routine medical and nursing intervention, and patients the research group adopted glioma bunched cognitive behavior intervention on the basis of routine medical and nursing intervention, including 4 intervention cycles.At enrollment, 2 weeks after intervention, and 4 weeks after intervention, all subjects were evaluated by the fear of progression questionnaire-short form (FoP-Q-SF), safety questionnaire (SQ), self-rating anxiety scale (SAS) and self-rating depression scale (SDS). All the data in this study were processed by SPSS 26.0 statistical software.The scores of FoP-Q-SF, SQ, SAS and SDS before and after intervention were compared by repeated measures ANOVA between the two groups. Results:(1)The total FoP-Q-SF score, physiological health dimension scores, and social family dimension scores of the two groups showed significant interaction effects before and after intervention ( F=254.839, 52.738, 12.237, all P<0.05). Further simple effect analysis showed that after 2 and 4 weeks of intervention, the FoP-Q-SF scores of the research group (2 weeks after intervention: 33.80±4.94, 36.48±4.04; 4 weeks after intervention: 31.25±4.55, 35.94±4.47) and social family dimensions (2 weeks after intervention: 15.32±2.56 points, 17.06±2.14; 4 weeks after intervention: 14.05±2.59, 16.96±1.99) were lower than those of the control group (all P<0.05). The physiological health dimension score of the research group was lower than that of the control group after 4 weeks of intervention (4 weeks after intervention: 17.30±2.92, 19.06±2.38) ( P<0.05). After 4 weeks of intervention, the FoP-Q-SF score, physiological health dimension score, and social family dimension score of the research group were all lower than those at 2 weeks after intervention and before intervention (all P<0.05). (2)The total SQ score, interpersonal security dimension score and the determined control score of the two groups showed significant interaction effects before and after intervention( F=193.129, 54.706, 44.015, all P<0.05). Further simple effect testing showed that after 2 and 4 weeks of intervention, the total SQ score and interpersonal security score of the research group were higher than those of the control group (all P<0.05). The determined control score of the research group was higher than that of the control group after 4 weeks of intervention ( P<0.05). After 2 and 4 weeks of intervention, the total SQ score, interpersonal security score, and determination control score of the research group were higher than before intervention (all P<0.05), and the total SQ score and interpersonal security score of the research group were higher than 2 weeks after intervention (both P<0.05). (3)The SAS score and SDS score of the two groups showed significant interaction effects before and after intervention( F=237.867, 282.882, both P<0.05). Further simple effect analysis showed that after 2 and 4 weeks intervention, the SAS and SDS scores of the research group were lower than those of the control group (all P<0.05). The SAS and SDS scores of the research group were lower after 2 weeks and 4 weeks intervention than before intervention (all P<0.05). The SAS and SDS scores of the research group at 4 weeks after intervention were lower than those at 2 weeks after intervention (both P<0.05). Conclusion:Bundled cognitive behavioral intervention can improve disease fear and negative emotions in patients with glioma, and enhance psychological security.

AIM To analyze the constituents absorbed into blood and brain from Zhishe Tongluo Capsules.METHODS Sixteen rats were randomly assigned into four groups and given intragastric administration(3.1 g/kg),after which the cerebral ischemia-reperfusion injury(MACO)model was established,the blood and brain tissues were collected,and UHPLC-Q Exactive Focus MS/MS was adopted in the identification of prototype constituents.RESULTS Total 70 constituents were identified,20 of which were found in the blood,mainly including flavonoids,tanshinones and Ligusticum chuanxiong phthalides,and 7 of them could enter the brain through blood-brain barrier.Compared with the normal administration group,the MACO administration group demonstrated added constituents absorbed into blood containing 3-hydroxybenzoic acid,calycosin-7-glucoside,curcumenol,senkyunolide B,dihydrotanshinone I and cryptotanshinone;removed constituents absorbed into brain containing puerarin,elemicin,sedanolide,and added those containing salvianolic acid A,senkyunolide I,dihydrotanshinone I in the left brain tissues(infarcted side).CONCLUSION The constituents absorbed into blood and brain from Zhishe Tongluo Capsules,along with the enhanced absorptions of phthalides,quinones and phenols in MACO rats in vivo may be the active substances for treating cerebral infarction.

Objective To observe the clinical efficacy of levofloxacin combined with levofloxacin scheme in the treatment of pulmonary tuberculosis patients with positive hepatitis B surface antigen(HBsAg)and its impact on drug-induced liver injury.Methods Pulmonary tuberculosis patients with positive HBsAg were divided into treatment group and control group according to the anti-tuberculosis treatment plan.The treatment group received 2HLZE/4HLE anti-tuberculosis regimen(levofloxacin 0.6 g,twice a week+isoniazid 0.3 g,qd+ethambutol hydrochloride 0.75 g,qd+pyrazinamide 0.5 g,tid)for 6 months,and the control group received 2HRZE/4HRE anti-tuberculosis regimen(levofloxacin 0.6 g,qd+isoniazid 0.3 g,qd+ethambutol hydrochloride 0.75 g,qd+pyrazinamide 0.5 g,tid)for 6 months.The sputum smear conversion rate,liver function indicators[glutamate pyruvate transaminase(GPT),glutamate oxaloacetate transaminase(GOT),serum total bilirubin(TBIL)],clinical efficacy,drug-induced liver injury,as well as the incidence of adverse drug reactions were compared between the two groups.Results A total of 41 patients were enrolled in the treatment group and 39 patients in the control group.After treatment,the clinical total effective rates in the treatment and control groups were 97.56％and 79.49％,which showed statistically significant difference(P＜0.05).After 4 months of treatment,the sputum smear conversion rates in the treatment group and the control group were 90.24％and 71.79％,respectively;after 6 months of treatment,the sputum smear conversion rates in the treatment group and the control group were 95.12％and 79.49％,respectively,both showing statistically significant differences(all P＜0.05).After 6 months of treatment,the GPT levels in the treatment group and the control group were(87.39±17.26)and(101.49±23.48)U·L-1,the GOT levels were(97.54±19.25)and(119.63±21.57)U·L-1,and the TBIL levels were(31.53±9.35)and(38.27±9.64)μmol·L-1,respectively,all showing statistically significant differences(all P＜0.05).The incidence of drug-induced liver injury in the treatment group and the control group was 19.51％and 41.03％respectively,and the time of liver injury occurrence was(12.98±2.26)and(10.23±1.95)days,both showing statistically significant differences(all P＜0.05).The total incidences of adverse reactions in the treatment group and the control group was 29.27％and 64.10％respectively,with statistically significant differences(P＜0.05).Conclusion Compared with the levofloxacin scheme,the levofloxacin combined with levofloxacin scheme can reduce the incidence and severity of drug-induced liver injury and improve the clinical treatment efficacy in pulmonary tuberculosis patients with positive HBsAg.

Humans ; Retrospective Studies ; Tetanus/epidemiology* ; China/epidemiology*

OBJECTIVE: Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery. METHODS: We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated. RESULTS: A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery. CONCLUSION These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.
Female ; Humans ; Male ; Middle Aged ; Brucellosis ; COVID-19 ; Retrospective Studies ; SARS-CoV-2 ; Treatment Outcome ; Case Reports as Topic

Melatonin,an endocrine hormone synthesized by the pineal gland,plays an important role in the reproduction.The growth and development of follicles is the basis of female mammalian fertility.Follicles have a high concentration of melatonin.Melatonin receptors exist on ovarian granulosa cells,follicle cells,and oocytes.It regulates the growth and development of these cells and the maturation and atresia of follicles,affecting female fertility.This paper reviews the protective effects and regulatory mechanisms of melatonin on the development of ovarian follicles,granulosa cells,and oocytes and makes an outlook on the therapeutic potential of melatonin for ovarian injury,underpinning the clinical application of melatonin in the future.
Animals ; Female ; Melatonin/pharmacology* ; Ovarian Follicle ; Oocytes ; Granulosa Cells/physiology* ; Mammals