Objective To study the effects of scutellarin on endometrial carcinoma Ishikawa cells,and analyze the correlation between the effects and phosphatidyl inositol 3 kinase(PI3 K)/protein kinase B(Akt)signaling pathway.Methods Ishikawa cells were divided into blank group and experimental-L,-M,-H groups,each group was treated with complete medium containing 0,5,10 and 20 μmol·L-1 scutellarin,respectively.Cell viability,clonal formation ability,metastatic ability,invasion,apoptosis and protein expression were detected by cell counting kit-8(CCK-8),plate cloning,scratch,Transwell,flow cytometry and Western blot assay,respectively.Results The cell viability of blank group and experimental-L,-M,-H groups at 48 h were(100.00±0.00)％,(78.51±7.54)％,(52.93±4.91)％and(41.62±5.33)％;the clone formation rate were(100.00±0.00)％,(56.59±6.34)％,(35.23±4.62)％and(10.66±1.91)％;the scratch healing rate were(53.70±6.19)％,(40.59±4.75)％,(34.25±4.40)％and(15.78±2.14)％;the number of invasive cells were 189.70±14.06,106.82±12.67,84.37±8.13 and 53.74±6.78;the relative expression levels of matrixmetallo proteinase-2 were 0.96±0.10,0.73±0.06,0.68±0.08 and 0.42±0.05;tissue inhibitor of MMP-1(TIMP-1)were 0.35±0.04,0.51±0.05,0.74±0.08 and 1.20±0.14;the apoptosis rates were(4.21±0.53)％,(15.83±2.42)％,(22.72±3.85)％and(34.41±4.67)％;the relative expression levels of B cell lymphoma-2(Bcl-2)were 1.38±0.15,0.90±0.10,0.56±0.06 and 0.24±0.03;Bcl-2 associated X protein(Bax)were 0.31±0.02,0.44±0.04,0.93±0.11 and 1.26±0.14;the relative expression levels of PI3Kp85 were 0.67±0.05,0.42±0.04,0.36±0.02 and 0.28±0.03;phosphorylated Akt(p-Akt)were 0.78±0.06,0.53±0.04,0.46±0.05 and 0.42±0.03.Compared with the blank group,the above indexes in the experimental-L,-M,-H groups were statistically significant(P＜0.05 or P＜0.01).Conclusion Scutellarin can inhibit the proliferation,metastatic ability and invasion of endometrial carcinoma Ishikawa cells and promote apoptosis by regulating PI3K/Akt signaling pathway.

Objective To observe the clinical efficacy and safety of esketamine injection combined with sufentanil injection for patient-controlled intravenous analgesia(PCIA)after fracture surgery in children.Methods Children scheduled for elective limb fracture incision and internal fixation were randomly divided into control group and treatment group.The control group was given 2 μg·kg-1 sufentanil for PCIA;the treatment group was given 1.0 mg·kg-1 esketamine combined with 1.5 μg·kg-1 sufentanil for PCIA.Background dose of 2 groups:2 mL·h-1,single dose of 2 mL each time,locking time of 15 min,total volume of 100 mL.The facial expression,leg movement,mobility,crying,consolability scale(FLACC)scores and Ramsay sedation scores,analgesic drug consumption and PCIA compression times within 48 h after operation,and adverse drug reactions were compared between the two groups at different time points after operation.Results Forty subjects enrolled in the treatment group,1 dropped out,and 39 were finally included in the statistical analysis;40 subjects enrolled in the control group,2 dropped out,and 38 were finally included in the statistical analysis.After treatment,the FLACC scores of treatment group at 2,4,6,12,24 and 48 h after operation were(4.75±0.93),(2.50±0.97),(1.75±0.93),(2.06±1.18),(1.13±0.62)and(0.50±0.63)points,which in control group were(6.13±1.13),(3.80±1.21),(2.87±0.64),(3.47±1.13),(1.87±0.92)and(1.27±0.80)points,and there were significant differences in the two groups(all P＜0.05).The Ramsay sedation scores of treatment and control groups at 2 hours after operation were(2.25±0.45)and(1.47±0.52)points;the number of effective PCIA compressions within 24 hours was 4.25±3.94 and 8.13±5.71;the amount of analgesic drugs used within 24 hours after surgery was(52.38±9.11)and(61.47±12.82)mL;the amount of analgesic drugs used within 48 hours after surgery was(88.81±14.31)and(94.60±5.93)mL,respectively;and the differences were statistically significant(all P＜0.05).The adverse drug reactions of two groups were mainly dizziness,nausea and vomiting.The total incidences of adverse drug reactions in treatment and control groups were 53.85％and 84.21％with significant difference(P＜0.05).Conclusion Esketamine injection combined with sufentanil injection can reduce postoperative pain intensity,improve analgesic sedation effect and reduce the incidence of adverse reactions of analgesic pump after fracture surgery in children.

Aim To explore the effect of baicalin on respiratory syncytial virus in vitro and its effect on cell metabolism. Methods The anti-RSV effect of baicalin in vitro was verified by antiviral cell experiment, and the cellular metabolic mechanism of baicalin against RSV was explored by cell metabolomics. Results Baicalin had an inhibitory effect on all stages of RSV infection, and the condition of CPE was significantly improved, which may mainly play a role in the adsorption and proliferation of RSV. A total of 19 differential metabolites were screened by cell metabolomics, which were mainly glycerol phospholipids, nucleosides and fatty acids. Seven metabolic pathways were obtained by enrichment analysis, which were mainly related to glycerol-phospholipid metabolism, fatty acid metabolism (arachidonic acid metabolism, α-linolenic acid metabolism, linoleic acid metabolism), amino acid metabolism and purine metabolism. Conclusions Baicalin has significant inhibitory effect on the adsorption and proliferation of RSV, which may be related to fatty acid metabolism, glycerol phospholipid metabolism, amino acid and purine metabolism.

OBJECTIVE: Jiedu Recipe (JR), a Chinese herbal remedy, has been shown to prolong overall survival time and decrease recurrence and metastasis rates in patients with hepatocellular carcinoma (HCC). This work investigated the mechanism of JR in HCC treatment. METHODS: The chemical constituents of JR were detected using liquid chromatography-mass spectrometry. The potential anti-HCC mechanism of JR was screened using network pharmacology and messenger ribonucleic acid (mRNA) microarray chip assay, followed by experimental validation in human HCC cells (SMMC-7721 and Huh7) in vitro and a nude mouse subcutaneous transplantation model of HCC in vivo. HCC cell characteristics of proliferation, migration and invasion under hypoxic setting were investigated using thiazolyl blue tetrazolium bromide, wound healing and Transwell assays, respectively. Image-iT™ Hypoxia Reagent was added to reveal hypoxic conditions. Stem cell sphere formation assay was used to detect the stemness. Epithelial-mesenchymal transition (EMT) markers like E-cadherin, vimentin and α-smooth muscle actin, and pluripotent transcription factors including nanog homeobox, octamer-binding transcription factor 4, and sex-determining region Y box protein 2 were analyzed using Western blotting and real-time polymerase chain reaction. Western blot was performed to ascertain the anti-HCC effect of JR under hypoxia involving the Wnt/β-catenin pathway. RESULTS: According to network pharmacology and mRNA microarray chip analysis, JR may potentially act on hypoxia and inhibit the Wnt/β-catenin pathway. In vitro and in vivo experiments showed that JR significantly decreased hypoxia, and suppressed HCC cell features of proliferation, migration and invasion; furthermore, the hypoxia-induced increases in EMT and stemness marker expression in HCC cells were inhibited by JR. Results based on the co-administration of JR and an agonist (LiCl) or inhibitor (IWR-1-endo) verified that JR suppressed HCC cancer stem-like properties under hypoxia by blocking the Wnt/β-catenin pathway. CONCLUSION JR exerts potent anti-HCC effects by inhibiting cancer stemness via abating the Wnt/β-catenin pathway under hypoxic conditions. Please cite this article as: Guo BJ, Ruan Y, Wang YJ, Xiao CL, Zhong ZP, Cheng BB, Du J, Li B, Gu W, Yin ZF. Jiedu Recipe, a compound Chinese herbal medicine, inhibits cancer stemness in hepatocellular carcinoma via Wnt/β-catenin pathway under hypoxia. J Integr Med. 2023; 21(5): 474-486.
Animals ; Mice ; Humans ; Carcinoma, Hepatocellular/genetics* ; beta Catenin/pharmacology* ; Liver Neoplasms/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; RNA, Messenger/therapeutic use* ; Cell Line, Tumor ; Cell Proliferation ; Cell Movement ; Gene Expression Regulation, Neoplastic

Humans ; Multiple Myeloma ; Leukemia, Myeloid, Acute ; Melphalan

Abstract: Objective　To evaluate the potential transmission risk of schistosomiasis in Yunnan Province, and to provide strategic basis for the prevention and control. Methods　Based on the prevalence of schistosomiasis, the social and environmental factors that may lead to the epidemic, 1-3 villages from 3 provincial-level and 15 county-level counties (cities and districts) were selected as the evaluated villages in 2021. The risk of schistosomiasis spread was analyzed comprehensively by consulting, reviewing and collecting routine surveillance data of schistosomiasis in the villages, combined with snail and wild feces survey. The risk level was evaluated for the positive snails, positive wild feces, resident infection, average density of live snails and snail frame occurrence rate. Results　Totally 7 snail counties schistosomiasis transmission was blocked of 18 epidemic counties and the rest were eliminated counties. A total of 152 447 snail frames were investigated and 3 043 frames with snails, 15 895 snails were captured and included 15 727 live snails in the 32 evaluated villages. The total area of snail was 58.87 hm2 and the area of reoccurrence was 34.19 hm2 with snail frame occurrence rate of 2.00% and average density of live snails 0.103 2/0.11 m2, and no positive snails were found by loop-mediated isothermal amplification (LAMP) assay. A total of 1 374 wild feces were collected in 27 evaluated villages of 14 epidemic counties, mainly from cattle, dogs, sheep, equine animals, pigs and so on, all of which were negative. According to the risk assessment of epidemic spread, Yongle Village and Yongsheng Village in Eryuan County, Zhiming Village in Chuxiong City were Ⅱ risk, and the rest were Ⅲ risk. Conclusions　Although the risk of transmission is low in Yunnan Province, the risk of transmission and spread still exists. It is necessary to strengthen the risk monitoring, control of snail and effective management of livestock to prevent the rebound of the epidemic.

Objective To investigate the morphological variation of Oncomelania hupensis shells in Yunnan Province, so as to provide insights into the understanding of O. hupensis genetic evolution and control. Methods According to the O. hupensis density, geographical location, altitude, water system and environmental type, 12 administrative villages were sampled from 10 schistosomiasis-endemic counties (districts) in 3 prefectures (cities) of Yunnan Province as snail collection sites. From December 2021 to January 2022, about 200 snails were collected from each collection site, among which thirty adult snails (6 to 7 spirals) were randomly selected from each site, and the 11 morphological indexes of snail shells were measured and subjected to cluster analysis and principal component analysis. Results Of O. hupensis snails from 12 localities of Yunnan Province, the longest shell (7.33 mm) was detected in snails from Yongle Village, Eryuan County, with the shortest (4.68 mm) in Dongyuan Village, Gucheng District, and the largest angle of apex (59.47°) was measured in snails from Caizhuang Village, Midu County, with the smallest (41.40°) in Qiandian Village, Eryuan County. The mean coefficient of variation was 9.075% among O. hupensis snails from 12 localities of Yunnan Province, with the largest coefficient of variation seen in the thickness of the labra brim (29.809%). Among O. hupensis snails from 12 localities of Yunnan Province, the mean Euclidean distance was 2.26, with the shortest Euclidean distance seen between O. hupensis snails from Qiandian Village of Eryuan County and Wuxing Village of Dali City (0.26), and the largest found between O. hupensis snails from Caizhuang Village of Midu County and Cangling Village of Chuxiong County (8.17). Cluster analysis and principal component analysis classified O. hupensis snails from 12 localities of Yunnan Province into three categories, including the O. hupensis snail samples from Caizhuang Village of Midu County, O. hupensis snail samples from Cangling Village of Chuxiong County, and O. hupensis snail samples from Qiandian Village of Eryuan County, Wuxing Village of Dali City, Yangwu Village of Yongsheng County, Xiaoqiao Village of Xiangyun County, Yongle Village of Eryuan County, Xiaocen Village of Dali City, Anding Village of Nanjian County, Dongyuan Village of Gucheng District, Lianyi Village of Heqing County, and Dianzhong Village of Weishan County. The variations in these three categories of snail samples were mainly measured in the principal component 2 related to the angle of apex and the thickness of the labra brim. Conclusions The variations in the Euclidean distance and morphological features of shells of O. hupensis from 12 localities of Yunnan Province gradually rise with the decrease in the latitude of the collection sites. The angle of apex is an indicator for the growth of O. hupensis whorl.

Objective To investigate the relationship between gait spatiotemporal parameters and balance function in stroke hemiplegic patients. Methods From September, 2018 to March, 2020, 76 stroke hemiplegic patients (38 in Brunnstrom Ⅳ and V, respectively) were assessed balance function with Active Balancer EAB-100 and Star Excursion Balance Test (SEBT), and gait parameters of speed, cadence and asymmetry, named step length asymmetry ratio (SLA), swing time asymmetry ratio (SWTA), stance time asymmetry ratio (STA), maximum flexion angle ratio (MFA) of hip and knee. The correlation among gait parameters and balance function was analysed. Results The balance and gait parameters were better in those in Brunnstrom V than in Brunnstrom Ⅳ (|t| > 2.268, P < 0.05). The speed and cadence correlated with the most balance indexes (|r| > 0.335, P < 0.05). SLA correlated with SEBT in Brunnstrom Ⅳ patients (r = -0.467~-0.613, P < 0.01), while it correlated with medial-lateral (M-L) stability limits in Brunnstrom V patients (r = -0.356, P = 0.028). SWTA correlated with stability limit of Anterior-Posterior (A-P) (r = -0.335, P = 0.040) and M-L (r = 0.510, P = 0.001), and most of SEBT (r = -0.330~ -0.445, P < 0.05) in Brunnstrom Ⅳ patients. MFA of hip and knee correlated with balance indexes in Brunnstrom Ⅳ patients (|r| > 0.326, P < 0.05), while MFA of knee correlated with most balance indexes in Brunnstrom V patients (r > 0.329, P < 0.05), and MFA of hip correlated with A-P stability limit (r = 0.369, P = 0.023). Conclusion Both speed and cadence of steps can well respond to the balance function in stroke hemiplegic patients. For the asymmetry, it is related with balance in patients with poorer recovery.

A new polyketide, coptaspin A(1), along with two known compounds 4-acetyl-3,4-dihydro-6,8-dihydroxy-3-methoxy-5-methylisocoumarin(2), and cytochalasin Z_(12)(3), was isolated from the endophytic fungi Aspergillus sp. ZJ-58, which was isolated from the genuine medicinal plant Coptis chinensis in Chongqing after solid-state fermentation on rice and silica gel, MCI, and HPLC-based separation. Their structures were elucidated by MS, NMR, IR, UV, and ECD. The newly isolated compound 1 showed moderate inhibitory activities against LPS-induced NO production in RAW264.7 macrophages with the IC_(50) value of 58.7 μmol·L~(-1), suggesting its potential anti-inflammatory activity.
Anti-Inflammatory Agents/pharmacology* ; Aspergillus/chemistry* ; Coptis chinensis ; Plants, Medicinal ; Polyketides/pharmacology*

OBJECTIVE: To investigate the efficacy, safety and the risk factors affecting prognosis of high-risk acute myeloid leukemia (AML) patients treated by cladribine-based intensified conditioning regimen. METHODS: The clinical data of 28 patients with high-risk AML treated by cladribine in combination with busulfan plus cyclophosphamide (BuCy) intensified conditioning regimen before allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Zhujiang Hospital, Southern Medical University from October 2016 to June 2020 were analyzed retrospectively. The overall survival (OS) rate, cumulative progression-free survival (PFS) rate, relapse rate, non-relapse mortality (NRM), regimen related toxicity (RRT) and risk factors affecting prognosis of the patients were analyzed. RESULTS: The 1-year OS and PFS of the patients after implantation was (78.8±8.6)% and (79.8±8.1)%, while the 1-year cumulative relapse rate and NRM of the patients was 9.3% and 22.0%, respectively. The 1-year expected OS of MRD^- high-risk patients before HSCT was 100%. The 1-year expected OS and PFS of the patients in pre-transplant relapse group was (46.9±18.7)% and (50.0±17.7)%, respectively. The incidence of I/II grade RRT was 39.3%. NO III/IV grade RRT were found in 28 patients. Multivariate analysis showed that pre-transplant relapse was the independent risk factor affecting OS and PFS of the patients. CONCLUSION The intensified conditioning regimen of cladribine in combination with BuCy can reduce the relapse rate of high-risk AML transplantation, and its RRT is mild, exhibiting good safety. MRD^- high-risk patients before HSCT can achieve better transplant benefits, but the prognosis of patients with relapse before transplantation is not significantly improved. Therefore, for non-relapsed high-risk AML patients, this intensified conditioning regimen deserves to be considered.
Busulfan ; Cladribine ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute/therapy* ; Retrospective Studies ; Transplantation Conditioning