OBJECTIVE To evaluate the influence of gene polymorphism on plasma minimum concentration （cmin） of voriconazole （VRZ） in patients with invasive fungal infection. METHODS The Cochrane Library， Embase， PubMed， Web of Science， China Biomedical Literature Database， CNKI， VIP and Wanfang Data were searched for literature on the correlation between gene polymorphisms and cmin of VRZ from inception to April 2024. After screening the literature， extracting data， and evaluating the quality of the literature， meta-analysis was performed using R 4.3.2 software. RESULTS A total of 21 studies with 2 454 patients were included. The results of meta-analysis showed that the VRZ cmin of CYP2C19 IM and PM types was significantly higher than EM type， and the VRZ cmin of IM type was significantly lower than PM type （P＜0.01）. The VRZ cmin of CYP2C9 rs1057910 AA type was significantly higher than AC/CC type， and that of CYP3A5 rs776746 CC type was significantly higher than TT type （P＜0.01）. The VRZ cmin of POR rs10954732 GG type was significantly higher than GA and AA types， and that of POR rs1057868 CT type was significantly lower than TT type （P＜0.01）. The VRZ cmin of ABCB1 rs1045642 CC type was significantly higher than TT type （P＜0.05）. The VRZ cmin of NR1I2 rs2472677 CT type was significantly higher than TT type， and rs7643645 AA type was significantly higher than AG type （P＜0.05）. The VRZ cmin of ABCC2 rs717620 CC type was significantly lower than CT type and TT type， and the CT type was significantly lower than TT type （P＜0.01）. CONCLUSIONS Mutant alleles in CYP2C19， CYP2C9 rs1057910， CYP3A5 rs776746， POR rs10954732， ABCB1 rs1045642 and NR1I2 rs7643645 can lead to a decrease in VRZ plasma concentration， and mutant allele in ABCC2 rs717620 can lead to an increase in VRZ plasma concentration.

OBJECTIVE To evaluate the influence of gene polymorphism on plasma minimum concentration （cmin） of voriconazole （VRZ） in patients with invasive fungal infection. METHODS The Cochrane Library， Embase， PubMed， Web of Science， China Biomedical Literature Database， CNKI， VIP and Wanfang Data were searched for literature on the correlation between gene polymorphisms and cmin of VRZ from inception to April 2024. After screening the literature， extracting data， and evaluating the quality of the literature， meta-analysis was performed using R 4.3.2 software. RESULTS A total of 21 studies with 2 454 patients were included. The results of meta-analysis showed that the VRZ cmin of CYP2C19 IM and PM types was significantly higher than EM type， and the VRZ cmin of IM type was significantly lower than PM type （P＜0.01）. The VRZ cmin of CYP2C9 rs1057910 AA type was significantly higher than AC/CC type， and that of CYP3A5 rs776746 CC type was significantly higher than TT type （P＜0.01）. The VRZ cmin of POR rs10954732 GG type was significantly higher than GA and AA types， and that of POR rs1057868 CT type was significantly lower than TT type （P＜0.01）. The VRZ cmin of ABCB1 rs1045642 CC type was significantly higher than TT type （P＜0.05）. The VRZ cmin of NR1I2 rs2472677 CT type was significantly higher than TT type， and rs7643645 AA type was significantly higher than AG type （P＜0.05）. The VRZ cmin of ABCC2 rs717620 CC type was significantly lower than CT type and TT type， and the CT type was significantly lower than TT type （P＜0.01）. CONCLUSIONS Mutant alleles in CYP2C19， CYP2C9 rs1057910， CYP3A5 rs776746， POR rs10954732， ABCB1 rs1045642 and NR1I2 rs7643645 can lead to a decrease in VRZ plasma concentration， and mutant allele in ABCC2 rs717620 can lead to an increase in VRZ plasma concentration.

ObjectiveTo investigate the mechanism of ferroptosis mediated by long-chain acyl-CoA synthetase 4 （ACSL4） signalling pathway in rats with coronary heart disease with blood stasis syndrome and the intervention effect of Xuefu Zhuyutang. MethodsSPF male SD rats were randomly divided into normal group， sham-operation group， model group， trimetazidine group （5.4 mg·kg^-1）， low-， medium-， and high-dose group （3.51， 7.02，14.04 g·kg^-1） of Xuefu Zhuyutang. The coronary artery left anterior descending ligation method was used to prepare a model of coronary heart disease with blood stasis syndrome， and continuous treatment for 7 d was conducted， while the sham-operation group was only threaded and not ligated. The general macroscopic symptoms of the rats were observed， and indicators such as electrocardiogram， echocardiography， and blood rheology were detected. The pathological morphology of myocardial tissue was observed by hematoxylin-eosin （HE） staining， and the changes in mitochondria in myocardial tissue were observed by transmission electron microscopy. The level of iron deposition in myocardial tissue was observed by Prussian blue staining. The levels of 12-hydroxyeicosatetraenoic acid （12-HETE） and 15-HETE were detected in serum by enzyme-linked immunosorbent assay. A biochemical colourimetric assay was used to detect the levels of Fe²⁺， lipid peroxidation （LPO）， glutathione （GSH）， and T-GSH/glutathione disulfide （GSSG） in myocardial tissue. DCFH-DA fluorescence quantitative assay was employed to detect the levels of reactive oxygen species （ROS）. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was adopted to detect the protein and mRNA expressions of glutathione peroxidase 4 （GPX4）， ferritin heavy chain 1 （FTH1）， ACSL4， and ly-sophosphatidylcholine acyltransferase3 （LPCAT3） in myocardial tissue. ResultsCompared with those in the normal group， the rats in the model group were poor in general macroscopic symptoms. The electrocardiogram showed widened QRS wave amplitude and increased voltage， bow-back elevation of the ST segments， elevated T waves， J-point elevation， and accelerated heart rate. Echocardiography showed a significant reduction in left ventricular ejection fraction （LVEF） and left ventricular fraction shortening （LVFS） （P<0.01）. Blood rheology showed that the viscosity of the whole blood （low， medium， and high rate of shear） was significantly increased （P<0.01）. HE staining showed an abnormal structure of myocardial tissue. There was a large area of myocardial necrosis and inflammatory cell infiltration and a large number of connective tissue between myocardial fibers. Transmission electron microscopy showed that the mitochondria were severely atrophy or swelling. The cristae were reduced or even broken， and the matrix was flocculent or even vacuolated. Prussian blue staining showed that there were a large number of iron-containing particles， and the iron deposition was obvious. The content of 12-HETE and 15-HETE in the serum was significantly increased （P<0.01）. The content of Fe²⁺， LPO， and ROS in myocardial tissue was significantly increased （P<0.01）. The content of GSH was significantly decreased （P<0.01）， and T-GSH/GSSG was decreased （P<0.01）. The protein and mRNA expressions of GPX4 and FTH1 in myocardial tissue were both significantly decreased （P<0.05， P<0.01）， while those of ACSL4 and LPCAT3 increased significantly （P<0.01）. Compared with the model group， the general macroscopic symptoms and electrocardiogram results of rats in low-， medium- and high-dose groups of Xuefu Zhuyutang were alleviated， and the differences in LVEF/LVFS ratios were all significantly increased （P<0.05， P<0.01）. The differences in whole-blood viscosity （low， medium， and high rate of shear） were all significantly decreased （P<0.01）. The results of HE staining and transmission electron microscopy showed that the morphology， structure， and mitochondria of cardiomyocytes were improved. The content of 12-HETE and 15-HETE in serum was reduced to different degrees in low-， medium-， and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）. The content of Fe²⁺， LPO， and ROS was significantly reduced in the medium- and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）， and the content of GSH and T-GSH/GSSG was significantly increased （P<0.05， P<0.01）. The protein and mRNA expressions of GPX4 and FTH1 were significantly increased to varying degrees in the medium- and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）， and ACSL4 and LPCAT3 were decreased to different degrees in the low-， medium-， and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）. ConclusionXuefu Zhuyutang can regulate iron metabolism and anti-lipid oxidation reaction to mediate ferroptosis through the ACSL4 signalling pathway， thus exerting a protective effect on rats with coronary heart disease with blood stasis syndrome.

ObjectiveTo clarify the protective effect of Danlou tablet， a representative traditional Chinese medicine of the stagnation of phlegm and blood stasis co-treatment method， on vascular endothelial function in patients with atherosclerosis （AS）. MethodsA randomized controlled trial was conducted. From September 2023 to November 2023， a total of 72 patients who were diagnosed at Guang'anmen Hospital， China Academy of Chinese Medical Sciences and met the inclusion and exclusion criteria for carotid atherosclerosis （CAS） combined with coronary atherosclerotic heart disease （CHD） and stable angina pectoris （SAP） were enrolled. The patients were randomly divided into a control group （receiving conventional Western medicine treatment） and an observation group （receiving Danlou tablet combined with conventional Western medicine treatment）， with 36 cases in each group. The intervention lasted for 12 weeks. The frequency of angina pectoris attacks was recorded to evaluate the clinical efficacy of Danlou tablet. Peripheral blood samples were collected from patients， and the expression levels of serum endothelial injury markers before and after treatment were detected by enzyme-linked immunosorbent assay （ELISA）. The nitrate reductase method was employed to evaluate the protective effect of Danlou tablet on vascular function. The expression levels of serum inflammatory factors and lipoproteins were determined by ELISA and an automatic biochemical analyzer （dynamic timed scatter turbidimetry and enzymatic method） to assess the anti-inflammatory and lipid-regulating effects of Danlou tablet. ResultsIn terms of angina pectoris attacks， compared with that in the control group， the frequency of attacks in the observation group was reduced （P<0.05）. In terms of endothelial injury markers， compared with the levels before treatment within the same group， the levels of endothelin-1 （ET-1）， intercellular adhesion molecule-1 （ICAM-1）， and vascular cell adhesion molecule-1 （VCAM-1） in the peripheral blood of the observation group were decreased （P<0.05）， while the levels of nitric oxide （NO） and vascular endothelial growth factor （VEGF） were increased （P<0.05）. Compared with the control group after treatment， the differences in ET-1， NO， ICAM-1， and VCAM-1 were significant （P<0.05）. In terms of serum inflammatory factors， after treatment， the interleukin-6 （IL-6） level in the observation group was decreased significantly （P<0.05）. Compared with the control group after treatment， the IL-6 level in the observation group was decreased significantly （P<0.01）. In terms of serum lipoproteins， after treatment， the level of low-density lipoprotein cholesterol （LDL-C） in the observation group was decreased （P<0.05）. After treatment， the level of high-density lipoprotein cholesterol （HDL-C） in the observation group was significantly higher than that in the control group （P<0.05）. In terms of safety evaluation， no serious adverse events occurred in either group during the intervention period. ConclusionDanlou tablet applied to patients with CAS combined with CHD can improve endothelial function， reduce inflammatory indicators， alleviate symptoms， improve the quality of life of patients， and demonstrate good safety.

ObjectiveTo clarify the protective effect of Danlou tablet， a representative traditional Chinese medicine of the stagnation of phlegm and blood stasis co-treatment method， on vascular endothelial function in patients with atherosclerosis （AS）. MethodsA randomized controlled trial was conducted. From September 2023 to November 2023， a total of 72 patients who were diagnosed at Guang'anmen Hospital， China Academy of Chinese Medical Sciences and met the inclusion and exclusion criteria for carotid atherosclerosis （CAS） combined with coronary atherosclerotic heart disease （CHD） and stable angina pectoris （SAP） were enrolled. The patients were randomly divided into a control group （receiving conventional Western medicine treatment） and an observation group （receiving Danlou tablet combined with conventional Western medicine treatment）， with 36 cases in each group. The intervention lasted for 12 weeks. The frequency of angina pectoris attacks was recorded to evaluate the clinical efficacy of Danlou tablet. Peripheral blood samples were collected from patients， and the expression levels of serum endothelial injury markers before and after treatment were detected by enzyme-linked immunosorbent assay （ELISA）. The nitrate reductase method was employed to evaluate the protective effect of Danlou tablet on vascular function. The expression levels of serum inflammatory factors and lipoproteins were determined by ELISA and an automatic biochemical analyzer （dynamic timed scatter turbidimetry and enzymatic method） to assess the anti-inflammatory and lipid-regulating effects of Danlou tablet. ResultsIn terms of angina pectoris attacks， compared with that in the control group， the frequency of attacks in the observation group was reduced （P<0.05）. In terms of endothelial injury markers， compared with the levels before treatment within the same group， the levels of endothelin-1 （ET-1）， intercellular adhesion molecule-1 （ICAM-1）， and vascular cell adhesion molecule-1 （VCAM-1） in the peripheral blood of the observation group were decreased （P<0.05）， while the levels of nitric oxide （NO） and vascular endothelial growth factor （VEGF） were increased （P<0.05）. Compared with the control group after treatment， the differences in ET-1， NO， ICAM-1， and VCAM-1 were significant （P<0.05）. In terms of serum inflammatory factors， after treatment， the interleukin-6 （IL-6） level in the observation group was decreased significantly （P<0.05）. Compared with the control group after treatment， the IL-6 level in the observation group was decreased significantly （P<0.01）. In terms of serum lipoproteins， after treatment， the level of low-density lipoprotein cholesterol （LDL-C） in the observation group was decreased （P<0.05）. After treatment， the level of high-density lipoprotein cholesterol （HDL-C） in the observation group was significantly higher than that in the control group （P<0.05）. In terms of safety evaluation， no serious adverse events occurred in either group during the intervention period. ConclusionDanlou tablet applied to patients with CAS combined with CHD can improve endothelial function， reduce inflammatory indicators， alleviate symptoms， improve the quality of life of patients， and demonstrate good safety.

Sennoside A (SA), a typical prodrug, exerts its laxative effect only after its transformation into rheinanthrone catalyzed by gut microbial hydrolases and reductases. Hydrolases have been identified, but reductases remain unknown. By linking a photoreactive group to the SA scaffold, we synthesized a photoaffinity probe to covalently label SA reductases and identified SA reductases using activity-based protein profiling (ABPP). From lysates of an active strain, Bifidobacterium pseudocatenulatum (B. pseudocatenulatum), 397 proteins were enriched and subsequently identified using mass spectrometry (MS). Among these proteins, chromate reductase/nicotinamide adenine dinucleotide (NADH) phosphate (NADPH)-dependent flavin mononucleotide (FMN) reductase/oxygen-insensitive NADPH nitroreductase (nfrA) was identified as a potent SA reductase through further bioinformatic analysis and The Universal Protein Resource (UniProt) database screening. We also determined that recombinant nfrA could reduce SA. Our study contributes to further illuminating mechanisms of SA transformation to rheinanthrone and simultaneously offers an effective method to identify gut bacterial reductases.

Gastric cancer (GC) is characterized by high morbidity and mortality rates. Chinese agarwood comprises the resin-containing wood of Aquilaria sinensis (Lour.) Gilg., traditionally utilized for treating asthma, cardiac ischemia, and tumors. However, comprehensive research regarding its anti-GC effects and underlying mechanisms remains limited. In this study, Chinese agarwood petroleum ether extract (CAPEE) demonstrated potent cytotoxicity against human GC cells, with half maximal inhibitory concentration (IC₅₀) values for AGS, HGC27, and MGC803 cells of 2.89, 2.46, and 2.37 μg·mL^-1, respectively, at 48 h. CAPEE significantly induced apoptosis in these GC cells, with B-cell lymphoma-2 (BCL-2) associated X protein (BAX)/BCL-2 antagonist killer 1 (BAK) likely mediating CAPEE-induced apoptosis. Furthermore, CAPEE induced G₀/G₁ phase cell cycle arrest in human GC cells via activation of the deoxyribonucleic acid (DNA) damage-p21-cyclin D1/cyclin-dependent kinase 4 (CDK4) signaling axis, and increased Fe²⁺, lipid peroxides and reactive oxygen species (ROS) levels, thereby inducing ferroptosis. Ribonucleic acid (RNA) sequencing, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blotting analyses revealed CAPEE-mediated upregulation of heme oxygenase-1 (HO-1) in human GC cells. RNA interference studies demonstrated that HO-1 knockdown reduced CAPEE sensitivity and inhibited CAPEE-induced ferroptosis in human GC cells. Additionally, CAPEE administration exhibited robust in vivo anti-GC activity without significant toxicity in nude mice while inhibiting tumor cell growth and promoting apoptosis in tumor tissues. These findings indicate that CAPEE suppresses human GC cell growth through upregulation of the DNA damage-p21-cyclin D1/CDK4 signaling axis and HO-1-mediated ferroptosis, suggesting its potential as a candidate drug for GC treatment.
Animals ; Humans ; Mice ; Antineoplastic Agents, Phytogenic ; Apoptosis/drug effects* ; Cell Line, Tumor ; Cyclin D1/genetics* ; Cyclin-Dependent Kinase 4/genetics* ; DNA Damage/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Ferroptosis/drug effects* ; G1 Phase Cell Cycle Checkpoints/drug effects* ; Heme Oxygenase-1/genetics* ; Mice, Inbred BALB C ; Mice, Nude ; Plant Extracts/pharmacology* ; Stomach Neoplasms/physiopathology* ; Thymelaeaceae/chemistry* ; Up-Regulation/drug effects*

Objective To apply ultrasound to monitor cardiac function changes after anthracycline exposure in children with acute leukemia,in order to obtain the indicators of early changes in their cardiac function.Methods Children with acute leukemia from 2018 March to December 2020 in the Children's Hospital of Kunming Medical University were enrolled according to the inclusion and exclusion criteria,their routine cardiac ultrasound and tissue Doppler condition were recorded,and the changes in systolic function were evaluated by Tei index including TeiS,TeiRL,TeiM and TeiT.Results The mean values of LVEF in the normal and the experimental group were both above 60%.FS,SV,and EDV were all in the normal range.While common indicant,the index of TDI or Tei was not statistically significant(P>0.05).The levels of TeiM,TeiRL and TieT in the groups that received a total dose of 200 mg/m2 anthracyclines and 250 mg/m2 were significantly different from that before treatment(P<0.05).Conclusion Tei index can be utilized as a sensitive indicator for early changes in left and right heart function after children with acute leukemia are exposed to anthracyclines.

Objective To analyze the clinical characteristics of 310 patients with anti-tuberculosis drug-induced liver injury(ATB-DILI),to explore prognostic influencing factors,and to provide reference for its prevention and treatment.Methods Primary tuberculosis patients hospitalized in the Department of Tuberculosis of the Third People's Hospital of Kunming from November 2020 to November 2022 who met the diagnosis of ATB-DILI were enrolled.Statistics by gender,age,history,type of tuberculosis,co-morbidities,frequency of anti-tuberculosis regimens leading to liver injury,use of hepatoprotective drugs,and management and regression were performed to analyze the clinical characteristics of the patients and the factors influencing their prognosis.Results 310 patients were included,male,148(47.74%)and female,162(52.26%).The mean age was 44.33±17.47 years.Thirty-four patients had a history of allergy.The combination of isoniazid,rifampicin,pyrazinamide,and ethambutol(244 patients,78.71%)was the anti-tuberculosis regimen that resulted in the highest number of cases of hepatic injury.The median time between initiation of the tuberculosis regimen and the development of hepatic injury in patients with ATB-DILI was 30 d,and the mean duration of hospitalization was 16.39±7.01 d.The most used hepatoprotective drug was reduced glutathione(154 patients,49.68%),and most patients used a combination of 2 hepatoprotective drugs(128 patients,41.29%).Liver injury improved in 257 cases(82.90%)and failed in 53 cases(17.10%).The differences in alcohol consumption,severity,clinical staging,TT,ALP,TBIL,DBIL,IBIL,and GGT were statistically significant compared to those who did not recover(P<0.05),and severity and high ALP were independent risk factors for poor prognosis.Conclusions Patients should be carefully asked if they have a history of basic liver disease and alcoholism before using anti-tuberculosis drugs.In the course of anti-tuberculosis treatment,the combined use of anti-tuberculosis drugs is more serious than the use of single drugs to cause liver damage.Drugs that may cause liver damage should be used with caution and improved anti-tuberculosis programs should be explored.At the same time,liver function should be monitored regularly during anti-tuberculosis treatment,especially 30 days after medication,in order to reduce the occurrence of adverse reactions.

Objective:To analyze the acupoint selection law in treating insomnia with warming-needle moxibustion using data mining technology.Methods:The clinical research literature on warming-needle moxibustion in treating insomnia was retrieved from the databases of CNKI, VIP, Wanfang Data, China Medical Journal Full-text Database, SinoMed, PubMed from the establishment of the databases to June 30, 2023. Acupuncture prescriptions were extracted and a database was established. Descriptive analysis was carried out on the intervention measures, the number of moxibustion numbers, the total effective rate, and the relevant information of acupoint selection. Clustering analysis and association rule analysis by using SPSS Statistics 26.0, SPSS Modeler 18.0 were performed on the high-frequency acupoints used in body acupuncture and warming acupuncture, respectively.Results:A total of 67 articles about warming-needle moxibustion for insomnia were included. The main intervention was single warming-needle moxibustion, followed by combined auricular acupuncture. Moxibustion with moxa sticks of 1 to 2 cm in length was often used. The total effective rate was mostly between 92% and 94%. A total of 85 prescriptions were obtained, involving 55 acupoints (569 times in frequency), among which Baihui (DU 20) (55 times), Shenmen (HT 7) (54 times) and Sanyinjiao (SP 6) (45 times) were widely used. The selected acupoints were mainly distributed on the head, face, back and waist, and the affiliated meridians were mainly bladder meridian, Governor Vessel and heart meridian. The specific acupoints were mainly crossing points, followed by back-shu acupoints. Clustering analysis of high-frequency acupoints obtained three effective groups, including "Xinshu (BL 15)- Pishu (BL 20) - Shenshu (BL 23) - Ganshu (BL 18)", etc. Baihui (DU 20) and Shenmen (HT 7) were the most relevant acupoint combinations. A total of 44 acupoints (frequency 272 times) were involved in the selection of warming acupuncture, among which Sanyinjiao (SP 6) (32 times), Xinshu (BL 15) (23 times) and Pishu (BL 20) (23 times) were more frequently used. Clustering analysis of high-frequency acupoints obtained three effective groups, including "Xinshu (BL 15)- Pishu (BL 20) - Shenshu (BL 23) - Ganshu (BL 18)", etc. Pishu (BL 20) and Xinshu (BL 15) were the most relevant acupoint combinations.Conclusions:Warming-needle moxibustion for the treatment of insomnia focuses on the application of acupoints on the bladder meridian on the back and waist, cooperates with the selection of acupoints on the head and face, and attaches importance to the application of intersection points in specific acupoints. The selection of acupoints by warming-needle moxibustion is mainly based on the back-shu acupoints of zang-fu organs, which plays the role of balancing yin and yang, regulating zang-fu organs, tonifying deficiency and tranquilizing mind to help sleep.