1.Acupuncture at Weizhong (BL40) attenuates acetic acid-induced overactive bladder in rats by regulating brain neural activity through the modulation of mast cells and tibial nerves.
Xin LIU ; Chao-Yue ZHANG ; Xiu-Yu DU ; Shan-Shan LI ; Yu-Qing WANG ; Yi ZHENG ; Han-Zhi DENG ; Xiao-Qin FANG ; Jia-Ying LI ; Zu-Qing WANG ; Shi-Fen XU ; Yi-Qun MI
Journal of Integrative Medicine 2025;23(1):46-55
OBJECTIVE:
The present study evaluated the effects of deep acupuncture at Weizhong acupoint (BL40) on bladder function and brain activity in a rat model of overactive bladder (OAB), and investigated the possible mechanisms around the acupuncture area that initiate the effects of acupuncture.
METHODS:
Adult female Sprague-Dawley rats were randomly divided into six groups, comprising a control group, model group, group treated with deep acupuncture at BL40, group treated with shallow acupuncture at BL40, group treated with acupuncture at non-acupoint next to BL40, and group treated with acupuncture at Xuanzhong (GB39). Urodynamic evaluation was used to observe the urination, and functional magnetic resonance imaging was used to observe the brain activation. The mechanism of acupuncture at BL40 in regulating bladder function was explored by toluidine blue staining and enzyme-linked immunosorbent assay, and the mechanism was verified by stabilizing mast cells (MCs) or blocking tibial nerve.
RESULTS:
Deep acupuncture at BL40 significantly increased the intercontraction interval in OAB rats and enhanced the mean amplitude of low frequency fluctuation of primary motor cortex (M1), periaquaductal gray matter (PAG), and pontine micturition center (PMC). It also increased the zero-lag functional connectivity between M1 and PAG and between PAG and PMC. Shallow acupuncture at BL40 and acupuncture at non-acupoint or GB39 had no effect on these indexes. Further studies suggested that deep acupuncture at BL40 increased the number and degranulation rate of MCs as well as the contents of 5-hydroxytryptamine, substance P, and histamine in the tissues around BL40. Blocking the tibial nerve by lidocaine injection or inhibiting MC degranulation by sodium cromoglycate injection obstructed the effects of acupuncture on restoring urinary function and modulating brain activation in OAB rats.
CONCLUSION
Deep acupuncture at BL40 may be more effective for inhibiting OAB by promoting degranulation of MCs around the acupoint and stimulating tibial nerve, thereby regulating the activation of the brain area that controls the lower urinary tract. Please cite this article as: Liu X, Zhang CY, Du XY, Li SS, Wang YQ, Zheng Y, Deng HZ, Fang XQ, Li JY, Wang ZQ, Xu SF, Mi YQ. Acupuncture at Weizhong (BL40) attenuates acetic acid-induced overactive bladder in rats by regulating brain neural activity through the modulation of mast cells and tibial nerves. J Integr Med. 2025; 23(1): 46-55.
Animals
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Urinary Bladder, Overactive/physiopathology*
;
Mast Cells/physiology*
;
Rats, Sprague-Dawley
;
Female
;
Acupuncture Therapy
;
Acupuncture Points
;
Rats
;
Brain/physiopathology*
;
Tibial Nerve/physiopathology*
;
Acetic Acid
;
Urinary Bladder/physiopathology*
2.Thermal sensitization of acupoints in patients with knee osteoarthritis: A cross-sectional case-control study.
Jian-Feng TU ; Xue-Zhou WANG ; Shi-Yan YAN ; Yi-Ran WANG ; Jing-Wen YANG ; Guang-Xia SHI ; Wen-Zheng ZHANG ; Li-Na JIN ; Li-Sha YANG ; Dong-Hua LIU ; Li-Qiong WANG ; Bao-Hong MI
Journal of Integrative Medicine 2025;23(3):289-296
OBJECTIVE:
Varied acupoint selections represent a potential cause of the uncertainty surrounding the efficacy of acupuncture for knee osteoarthritis (OA). Skin temperature, a guiding factor for acupoint selection, may help to address this issue. This study explored thermal sensitization of acupoints used for the treatment of knee OA.
METHODS:
This cross-sectional case-control study enrolled cases aged 45-75 years with symptomatic knee OA and age- and gender-matched non-knee OA controls in a 1:1 ratio. All participants underwent infrared thermographic imaging. The primary outcome was the relative skin temperature of acupoint (STA), and the secondary outcome was the absolute STA of 11 acupoints. The Z test was used to compare the relative and absolute STAs between the groups. Principal component analysis was used to extract the common factors (CFs, acupoint cluster) in the STAs. A general linear model was used to identify factors affecting the STA in the knee OA cases. For the group comparisons of relative STA, P < 0.0045 (adjusted for 11 acupoints through Bonferroni correction) was considered to indicate statistical significance. For other analyses, P < 0.05 was used as the threshold for statistical significance.
RESULTS:
The analysis included 308 participants, consisting of 151 cases (mean age: [64.58 ± 6.67] years; male: 25.83%; mean body mass index: [25.70 ± 3.16] kg/m2) and 157 controls (mean age: [63.37 ± 5.96] years; male: 26.11%; mean body mass index: [24.47 ± 2.84] kg/m2). The relative STAs of ST34 (P = 0.0001), EX-LE2 (P < 0.0001), EX-LE5 (P = 0.0006), SP10 (P < 0.0001), BL40 (P = 0.0012) and GB39 (P = 0.0037) were higher in the knee OA group. No difference was found in the STAs of ST35, ST36, SP9, GB33 and GB34. Four CFs were identified for relative STA in both groups. The acupoints within each CF were consistent between the groups. The mean values of the relative STAs across each CF were higher in the knee OA group. In the knee OA cases, no factors were observed to affect the relative STA, while age and gender were found to affect the absolute STA.
CONCLUSION
Among patients with knee OA, thermal sensitization occurs in the acupoints of the lower extremity, exhibiting localized and regional thermal consistencies. The thermally sensitized acupoints that we identified in this study, ST34, SP10, EX-LE2, EX-LE5, GB39 and BL40, may be good choices for the acupuncture treatment of knee OA. Please cite this article as: Tu JF, Wang XZ, Yan SY, Wang YR, Yang JW, Shi GX, Zhang WZ, Jing LN, Yang LS, Liu DH, Wang LQ, Mi BH. Thermal sensitization of acupoints in patients with knee osteoarthritis: A cross-sectional case-control study. J Integr Med. 2025; 23(3): 289-296.
Humans
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Osteoarthritis, Knee/physiopathology*
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Male
;
Cross-Sectional Studies
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Middle Aged
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Female
;
Acupuncture Points
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Case-Control Studies
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Aged
;
Skin Temperature
;
Acupuncture Therapy
3.Identification and expression analysis of cellulose synthase family genes in Aquilaria sinensis
Xin-yu MI ; Hai-ling QIU ; Fan-yuan GUAN ; Yu-yan ZHENG ; Xiao-hui WANG ; She-po SHI
Acta Pharmaceutica Sinica 2024;59(1):253-264
Cellulose synthase (CesA), one of the key enzymes in the biosynthesis of cellulose in plants, plays an important role in plant growth and plant resistance. In this study, a total of 21
4.Design and implementation of low-code platform for data services
Ren-Xin DING ; Tao ZHENG ; Mi-Ye WANG ; Qing-Ke SHI
Chinese Medical Equipment Journal 2024;45(4):13-19
Objective To design a low-code platform for data services to reduce the data interface service development costs and improve the development efficiency.Methods The platform was developed with Browser/Server(B/S)architecture,which used JAVA Spring Boot as its main framework and MySQL as the backend database system and had the functions for data source management,service catalog management,service management,service testing,service release management and service subscription management.Results The platform decreased the costs for interface development,operation and maintenance,lowered the technical threshold of interface development,unified the interface standard and enhanced hospital data security.Conclusion The platform developed provides support for hospital data interface service,digitalization and data services.[Chinese Medical Equipment Journal,2024,45(4):13-19]
5.Hepatocyte apoptosis fragment product cytokeratin-18 M30 level and non-alcoholic steatohepatitis risk diagnosis: an international registry study.
Huai ZHANG ; Rafael S RIOS ; Jerome BOURSIER ; Rodolphe ANTY ; Wah-Kheong CHAN ; Jacob GEORGE ; Yusuf YILMAZ ; Vincent Wai-Sun WONG ; Jiangao FAN ; Jean-François DUFOUR ; George PAPATHEODORIDIS ; Li CHEN ; Jörn M SCHATTENBERG ; Junping SHI ; Liang XU ; Grace Lai-Hung WONG ; Naomi F LANGE ; Margarita PAPATHEODORIDI ; Yuqiang MI ; Yujie ZHOU ; Christopher D BYRNE ; Giovanni TARGHER ; Gong FENG ; Minghua ZHENG
Chinese Medical Journal 2023;136(3):341-350
BACKGROUND:
Liver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and possible sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in diagnosing NASH, but results across studies have been inconsistent. We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH.
METHODS:
Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and in all patients, circulating CK-18 M30 levels were measured. Individuals with a NAFLD activity score (NAS) ≥5 with a score of ≥1 for each of steatosis, ballooning, and lobular inflammation were diagnosed as having definite NASH; individuals with a NAS ≤2 and no fibrosis were diagnosed as having non-alcoholic fatty liver (NAFL).
RESULTS:
A total of 2571 participants were screened, and 1008 (153 with NAFL and 855 with NASH) were finally enrolled. Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL (mean difference 177 U/L; standardized mean difference [SMD]: 0.87 [0.69-1.04]). There was an interaction between CK-18 M30 levels and serum alanine aminotransferase, body mass index (BMI), and hypertension ( P < 0.001, P = 0.026 and P = 0.049, respectively). CK-18 M30 levels were positively associated with histological NAS in most centers. The area under the receiver operating characteristics (AUROC) for NASH was 0.750 (95% confidence intervals: 0.714-0.787), and CK-18 M30 at Youden's index maximum was 275.7 U/L. Both sensitivity (55% [52%-59%]) and positive predictive value (59%) were not ideal.
CONCLUSION
This large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for non-invasively diagnosing NASH.
Humans
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Non-alcoholic Fatty Liver Disease/diagnosis*
;
Keratin-18
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Biomarkers
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Biopsy
;
Hepatocytes/pathology*
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Apoptosis
;
Liver/pathology*
6.Use of indocyanine green fluorescence navigation in laparoscopic anatomical hepatectomy.
Zi Qi HOU ; Qing Yun XIE ; Ming Heng LIAO ; Chang LIU ; Guo Teng QIU ; Zhao Xing JIN ; Shi Zheng MI ; Ji Wei HUANG
Chinese Journal of Surgery 2023;61(5):368-374
Objective: To examine the clinical value of fluorescence-guided indocyanine green (ICG) laparoscopic anatomical hepatectomy in the treatment of primary hepatocellular carcinoma. Methods: Data from patients diagnosed with hepatocellular carcinoma and who underwent laparoscopic hepatectomy with ICG fluorescence navigation in the Department of Liver Surgery and Liver Transplantation Center of West China Hospital between September 2020 and May 2022 were retrospectively collected. There were 53 males and 19 females, with an age of (55.5±12.9)years(range:42.6 to 68.4 years). Among them, 13 of the cases underwent laparoscopic anatomical liver resection(LALR) guided by tans-arterial ICG,43 of the cases received LAIR guided by portal vein negative ICG, and 16 of the cases received LALR positive by portal vein. Comparison among the three groups was performed by one-way ANOVA; and the rank sum test was used for comparison between groups. The counting data was expressed as percentage,and the χ2 test or Fisher's exact probability method was used for comparison between groups. Results: (1) Postoperative pathology: Resection R0 was achieved in all operations. The maximum tumor diameter of the patients in the arterial staining group, the reverse staining group, and the positive staining group(M (IQR)) was 2.5 (2.4) cm, 3.0 (2.5) cm and 3.0(2.4) cm,respectively. There were no statistically significant differences in the maximum tumor diameter between the three groups (P=0.364). The minimum tumor margin was 1.1 (1.1) cm, 1.0 (1.0) cm, 1.1 (1.6) cm in the the arterial staining group, reverse staining group and the positive staining group, respectively. There was no significant difference in the margin among the three groups (P=0.878). (2) Operation conditions: the operation time of the arterial staining group, the negative staining group, and the positive portal staining group was (348±93)minutes,(277±112)minutes,and (295±116)minutes,respectively. There were no significant differences in operation time among the three groups (P=0.134). The intraoperative blood loss of the three groups was 80(150)ml,200(350)ml,and 100(150)ml,respectively. There was no statistically significant difference in intraoperative bleeding volume between the three groups(P=0.743). All cases were not transfused during the operation and were not converted to laparotomy. ALT in the arterial staining group was higher than in the negative staining group in the first two days after the operation ((559±398)IU/L307(257) IU/L, q=235.5,P=0.004;(611±389)IU/L(331±242) IU/L, q=265.2, P=0.002). There was only one case of a grade III complication (Clavien-Dindo grading system) postoperative complication in the negative and positive staining group of the portal vein, respectively. Tumor markers in all patients decreased to the normal range after 2 months of operation. Conclusion: Laparoscopic anatomical hepatectomy guided by ICG fluorescence through arterial staining and portal vein staining is safe and feasible for primary hepatocellular carcinoma treatment.
7.Comparison of drug susceptibility of and drug resistance mutations in fluconazole-resistant Candida albicans strains from superficial and deep infections
Tiantian DING ; Baohong CUI ; Shuhong MI ; Yang ZHANG ; Hailin ZHENG ; Jihai SHI ; Weida LIU
Chinese Journal of Dermatology 2022;55(10):874-878
Objective:To compare the in vitro susceptibility of fluconazole-resistant Candida albicans strains from superficial and deep infections to 8 antifungal drugs, and to compare drug resistance mutations in these strains. Methods:According to the Clinical and Laboratory Standards Institute (CLSI) protocol M27-A4, 26 deep infection-derived and 33 superficial infection-derived drug-resistant Candida albicans strains were tested for in vitro susceptibility to 8 antifungal drugs (fluconazole, voriconazole, itraconazole, posaconazole, amphotericin B, fluorocytosine, terbinafine, and micafungin) alone or in combination. DNA was extracted from all drug-resistant strains, and mutations in 3 drug resistance genes, including ERG3, ERG11 and FUR1, were detected by PCR. Normally distributed measurement data with homogeneous variance were compared between two groups by using two-independent-sample t test, non-normally distributed measurement data with non-homogeneous variance were compared using Mann-Whitney U test, and enumeration data were compared using chi-square test. Results:The minimum inhibitory concentrations (MICs) of fluconazole, itraconazole, voriconazole, posaconazole and fluorocytosine all significantly differed between the superficial infection group and deep infection group (all P < 0.05) , while there was no significant difference in the MIC of amphotericin B or micafungin between the two groups (both P > 0.05) . The MIC of terbinafine was >64 μg/ml in 96.6% of the above strains, so could not be compared between groups. As combination drug susceptibility testing revealed, the combination of terbinafine with azoles (fluconazole, voriconazole, itraconazole or posaconazole) showed synergistic inhibitory effects against 15 Candida albicans strains (7 strains from deep infections, 8 strains from superficial infections) , with fractional inhibitory concentration (FIC) indices being 0.033 to 0.187; no marked synergistic effect was observed in the combinations between fluorocytosine and azoles, between fluorocytosine and amphotericin B, or between amphotericin B and fluconazole, with the FIC indices being 0.56 to 1.125. The missense mutation V351A in the ERG3 gene was identified in all the 33 (100%) superficial infection-derived strains, as well as in 13 (50%) deep infection-derived strains, and the mutation A353T in the ERG3 gene was identified in 4 (15%) deep infection-derived strains; as for the ERG11 gene, missense mutations identified in the superficial infection-derived strains included I437V (32 strains, 97%) , Y132H (23 strains, 70%) , T123I (16 strains, 48%) , K128T (6 strains, 18%) , D116E (5 strains, 15%) , A114S (4 strains, 12%) , E266D (2 strains, 6%) , G448E (2 strains, 6%) , and G465S (2 strains, 6%) , while missense mutations identified in the deep infection-derived strains included I437V (23 strains, 88%) , E266D (13 strains, 50%) , E260G (5 strains, 19%) , and V488I (4 strains, 15%) ; the missense mutation R101C in the FUR1 gene was identified in 11 (33%) superficial infection-derived strains, but not identified in deep infection-derived strains. Conclusion:The drug susceptibility and drug resistance mutations differed to some extent between superficial infection- and deep infection-derived fluconazole-resistant Candida albicans strains.
8.Investigation on the Serum NGAL Reference Range of Healthy Populations in Xi'an
Ruijie SHI ; Futang YAN ; Wenkang LIU ; Hua ZHANG ; Jun YUAN ; Peng MI ; Shuling HU ; Xiao ZHENG
Journal of Modern Laboratory Medicine 2017;32(4):130-132
Objective To establish serum NGAL reference range of healthy populations in Xi'an Area.Methods 2 665 cases (aged 6 to 95 years old,male 1 370,female 1 295) of health-check people were collected from March 2014 to October 2016 in Medical Examination Center of Shaanxi Provincial People's Hospital,and 682 cases (aged 0 to 6 years old,male 356,female 326) were collected from preschool children of prevention.Serum NGAL concentration of them were analysed by immunoturbidimetry method with the Automatic Biochemical Analysis Assembly Line of Beckman-AU5800,and the detection data for statistical analysis.Then established the reference range of serum NGAL population of different age and different sex in Xi'an.Results The serum NGAL levels in healthy subjects showed a skewed distribution,which were preschool children under 6 years of age 37.66±23.12 ng/ml,6~15 years 39.25±25.34 ng/ml,16~49 years 46.68±27.06 ng/ml,and 50~ 69 years 57.82±29.13 ng/ml.Compared the first two with the latter,there was a significant difference (t=0.589,P< 0.05).The serum NGAL levels of over 70 years were 61.87 ± 32.64 ng/ml,and there was a significant difference between the ages of 15 and 49 and over 70 years (t=8.529,P<0.01).At the same time,the serum NGAL was closely correlated with age (r=0.298,P<0.01).But there was no significant difference in serum NGAL level between male and female (t=0.263~0.542,all P>0.05).87ng/ml was the upper limit of the reference value for the age of 50 years.Conclusion The level of serum NGAL was related to age and increased with age,but not with gender.
9.A multi-center clinical study of a novel controlled attenuation parameter for assessment of fatty liver.
Feng SHEN ; Ruidan ZHENG ; Yuqiang MI ; Junping SHI ; Guofeng CHEN ; Jianneng CHEN ; Liang XU ; Qin PAN ; Leiming XU ; Jiangao FAN
Chinese Journal of Hepatology 2014;22(12):926-931
OBJECTIVETo evaluate the controlled attenuation parameter (CAP) assessment of fatty liver and choose a cut-off value of hepatic steatosis more than 5%.
METHODSConsecutive patients, 18 years or older, who had undergone percutaneous liver biopsy and CAP measurement were recruited from five liver healthcare centers in China. All enrollees were categorized as hepatic steatosis grade S0 (<5%) or S1 (5%). An M-probe equipped FibroScan 502 was used to capture CAP values. Receiver operating characteristic (ROC) curves were plotted, and the areas under (AU) the curves were calculated to determine the diagnostic efficacy. The CAP cut-off values at the optimal thresholds were defined by maximum Youden indices; sensitivity and specificity were also calculated.
RESULTSA total of 332 patients were enrolled in the study, including 67 patients with non-alcoholic fatty liver disease (NAFLD) and 265 with chronic hepatitis B (CHB) viru: infection. The median age (inter quartile range, IQR) of the study cohort was 39.0 (32.0-50.5) years-old. There were 46 males (68.7%) in the NAFLD group, with a median age of 37.0 (28.0-45.0) years-old, and 182 males (68.7%) in the CHB group; the differences between the two groups in median age and male: female ratio did not reach statistical significance. Multivariate linear regression analysis identified steatosis grade and body mass index (BMI) as independently associated with CAP. The median (IQR) CAP values among patients with S0 and S1 grade steatosis were 215.0 (190.0-241.0) dB/m and 294.0 (255.0-325.5) dB/m (P<0.001), respectively. For all patients, when BMI was <25 kg/m2, the ability of the AUROC of the CAP to discriminate hepatic steatosis more than or equal to 5% was 0.853, and the optimal cut-off value was 244.5 dB/m; however, when BMI≥25 kg/m2, the AUROC was 0.835 and the optimal cut-off value 269.5 dB/m.
CONCLUSIONCAP can identify hepatic steatosis more than or equal to 5% and is applicable for the diagnosis of fatty liver if it is adjusted for BMI.
Adult ; Area Under Curve ; Bile ; Biopsy ; Body Mass Index ; China ; Fatty Liver ; Female ; Hepatitis B, Chronic ; Humans ; Linear Models ; Male ; Middle Aged ; Multivariate Analysis ; ROC Curve ; Tissue Extracts
10.Analysis of testosterone, estradiol, progesterone and PSA expression in prostate cancer cells LNCaP and DU145 in vitro after atractylodes mmacrocephala koidz volatile oil treatment
Weigui SUN ; Zhangqun YE ; Hongzhi WANG ; Kun JIANG ; Qichuan ZHENG ; Tianliang SHI ; Cunzhi HAN ; Zhenguo MI
Chinese Journal of Urology 2012;(12):947-950
Objective To study the antitumor effects on human prostate cancer cell lines of a traditional Chinese medicine named atractylodes macrocephala koidz volatile oil in vitro.Methods LNCaP and DU145 cell lines were normally cultured and were divided into 4 control groups including:Blank culture without serum and without cell (group A),Blank culture with serum but without cell (group B),LNCaP cell culture with serum (group C),DU145 cell culture with serum (group D).In the meanwhile,there were 6 experimental groups:adding 50 μg/ml of atractylodes macrocephala koidz volatile oil in culture of group C1 and group D1,250ug/ml in group C2 and group D2,and 500ug/ml in group C3 and group D3.All of the 10 groups were simultaneously cultured in 24-well-plates for 48 hrs,and each group was repeatedly studied for three times.Forty-eight hours later,every 2 × 106 cells of LNCaP or DU145 was seeded into each well and atractylodes macrocephala koidz volatile oil was added in 6 experimental groups,and saline water was added into 4 control groups.Another 48 hrs later,the culture solutions of the 10 groups were separately collected for testosterone (T),estradiol (E2),progesterone (P),vascular endothelial growth factor (VEGF),basic fibroblast growth factor (b-FGF),total prostate specific antigen (tPSA) and free prostate specific antigen (fPSA) analysis with enzyme-linked immunoassay kits.The experiment was repeated for 3 times,and the mean data were statistically analyzed by SPSS One-way ANOVA.Results The growth of cultured cells was found to have been effectively inhibited in group C1 and group D2.The inhibition severity of LNCaP cells was positively related with the drug concentration and time,while DU145 cells could only be highly inhibited (60.96%) after 24hrs drug treatments.In group C and group D,we found that both T were in very low level (0 ng/ml) whereas both E2 were in high levels (269 pg/ml and 239.81 pg/ml,P < 0.05),no distinct differences showed in P; In addition,VEGF,b-FGF and fPSA were all in high values,whose values were 102.96 pg/ml and 1763.40 pg/ml,0.26 ng/ml and 6.41 ng/ml,0.16 ng/ml and 0.44 ng/ml,respectively; DU145 cells had higher values than LNCaP cells (P < 0.05).As regard to the 6 experimental groups,in the groups C1,C2,C3 and D3,we found that T had been unexpectedly increased from 0 to 0.37 ng/ml (P < 0.05),E2 continuously elevated from 239.81 pg/ml to 649.90 pg/ml (P <0.05),surprisingly P were also increased from 0.98 ng/ml to 9.83 ng/ml (P <0.01).On the contrary,VEGF,b-FGF and fPSA levels were all graduallydecreased,dropping down to 47.79 pg/ml and 59.56pg/ml,0 and 1.79 ng/ml,0 and 0.11 ng/ml,respectively; nevertheless,in group C2 and group D2,fPSA values were surprisingly increased from 0 and 0.04 ng/ml up to 1.78 ng/ml and 0.23 ng/ml respectively.Conclusions Atractylodes macrocephala koidz volatile oil has certain anti-tumor effects on human prostate cancer.Compared with LNCaP cells,DU145 cells have many different characteristics in sex hormone,cytokine and PSA expressions.

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