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Objective:To analyze the diagnostic and prognostic value of routine bone marrow examination in patients with extranodal NK/T-cell lymphoma (ENKTCL) based on PET-CT staging.Methods:Clinical data of 186 patients who received bone marrow biopsy and bone marrow aspiration in Fujian Medical University Union Hospital from 2013 to 2021 were retrospectively analyzed. All patients were divided into bone marrow biopsy + bone marrow aspiration group ( n=186) and PET-CT + bone marrow biopsy group ( n=139). The sensitivity, specificity, positive and negative predictive values were compared between two groups. The data were analyzed and plotted. Survival analysis was performed using Kaplan-Meier method and log-rank test. Results:In the whole cohort, 45 patients were positive for bone marrow biopsy, and 30 of them were positive for bone marrow aspiration. A total of 141 patients who were negative for bone marrow biopsy also achieved negative results for bone marrow aspiration. A total of 139 patients completed PET-CT staging and bone marrow biopsy. And 30 patients were diagnosed with positive bone marrow by PET-CT, in which 22 of them were confirmed positive by bone marrow biopsy. Among 109 patients diagnosed with negative bone marrow by PET-CT, 5 of them were confirmed positive by bone marrow biopsy. All these cases were classified as stage Ⅳ due to distant metastases. PET-CT had a diagnostic sensitivity of 81.5%, a specificity of 92.9%, a positive predictive value of 73.3%, and a negative predictive value of 95.4%. Among early stage (Ⅰ-Ⅱ stage) patients diagnosed with PET-CT, all of them were negative for bone marrow biopsy (the negative predictive value was 100%). In stage Ⅳ patients ( n=55), the 1-year overall survival of patients with bone marrow involvement by bone marrow biopsy or PET-CT ( n=35) compared with their counterparts with the involvement of other organs ( n=20) was 28.7% vs.42.0% ( P=0.13), and 1-year progression free survival rates was 23.2% vs. 23.3% in ( P=0.94). Conclusions:Routine bone marrow biopsy does not change the original staging of patients with early stage ENKTCL based on PET-CT staging. Advanced stage patients with positive bone marrow biopsy tend to obtain worse prognosis, indicating that bone marrow biopsy still has certain value.
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OBJECTIVE：To establish th e fingerp rint and c onduct cluster analysis of Hefu zhiyang decoction （HFZYD），and establish the method for content determination of 8 components，so as to provide reference for the quality control of HFZYD. METHODS：UPLC method was adopted. The determination was performed on ACQUITY UPLC BEH C 18 column with mobile phase consisted of acetonitrile- 0.1％ glacial acetic acid solution （gradient elution ）at the flow rate of 0.25 mL/min. The column temperature maintained at 30 ℃，and detection wavelength was 236 nm. The sample size was 5 μL. The fingerprint of 10 batches of HFZYD was established with Similarity Evaluation System of TCM Chromatographic Fingerprints （2012 edition）. Compared with substance control ，the common peaks were identified. The similarity evaluation was conducted. SPSS 21.0 software was used to conduct cluster analysis of 10 batches of samples. The contents of 8 components such as gallic acid in 10 batches of samples were determined by above UPLC. RESULTS ：There were 34 common peaks in the UPLC fingerprint of 10 batches of HFZYD ， identified as peak 1 was gallic acid ，peak 10 was ferulic acid ，peak 13 was astilbin ，peak 23 was paeonol ，peak 28 was dictamnine，peak 31 was obacunone ，peak 32 was fraxinellone ，and peak 34 was osthole. Its similarity with the control fingerprint was 0.923-0.979. Among 10 batches of samples ，S1，S2，S5，S6，S7，S8 and S 10 were clustered into one category ，and S 3，S4 and S 9 were clustered into one category. The average contents of above 8 components were 0.596-0.714，0.262-0.321，7.647-9.859， 0.113-0.644，0.170-0.202，0.854-1.281，0.631-0.857，3.243-3.548 mg/g，respectively. CONCLUSIONS ：UPLC fingerprint and the method for content determination of 8 components in HFZYD are established successfully.
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Objective:To evaluate the clinical efficacy of radiotherapy in the treatment of extracranial metastatic breast cancer, and to investigate the significance and prognostic factors of whole-lesion radiotherapy (WLRT).Methods:Clinical data of 85 patients with extracranial metastatic breast cancer treated with radiotherapy between 2014 and 2019 were retrospectively analyzed. Thirty-six patients were assigned into the WLRT group and 49 in the non-WLRT group. The local control (LC), progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan- Meier method, log-rank test and univariate prognostic analysis. Cox proportional hazards model was used for multivariate prognostic analysis. Results:The median follow-up time was 26.7 months. The 2-year LC, PFS, OS rates were 77%, 26%, 77%, respectively. The 2-year LC (91% vs. 67%, P=0.001), PFS (47% vs. 8%, P<0.001), OS rates (84% vs. 71%, P=0.010) in the WLRT group were significantly higher than those in the non-WLRT group, respectively. Multivariate analysis demonstrated that WLRT was an independent favorable prognostic factor for the LC, PFS and OS. Furthermore, bone metastasis alone was associated with improved LC and positive hormone receptor status was correlated with improved OS. Conclusions:WLRT has the potential to prolong the survival of patients with extracranial metastatic breast cancer. The patients with bone metastases alone obtain better LC, whereas those with negative hormone receptor status has worse OS.
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Objective:To evaluate the efficacy and safety of comprehensive treatment based on radiotherapy for patients with leptomeningeal metastases (LM) in this prospective study.Methods:A total of 93 patients diagnosed with LM admitted to our hospital undergoing whole brain radiotherapy (WBRT) or craniospinal irradiation (CSI) with or without simultaneous boost from 2014 to 2017 were enrolled. The dynamic changes of clinical signs and symptoms, enhanced magnetic resonance imaging (MRI), cerebrospinal fluid cytology and liquid biopsy detection were recorded. The primary endpoint was overall survival (OS), the secondary endpoints were local control (LC), intracranial progress-free survival (IPFS), brain metastasis specific survival (BMSS) and toxicity.Results:The major primary disease was non-small cell lung cancer. The whole cohort received WBRT with boost (40 Gy in 20 fractions (f) for WBRT and 60 Gy in 20 f for boost), focal radiation to LM, WBRT and CSI (40 Gy in 20 f or 50 Gy in 25 f for WBRT and 36 Gy in 20 f for CSI). For 20 patients, tumor cells were identified and intrathecal chemotherapy was performed. Sixty-three patients received target therapy. The median follow-up time was 33.8 months. The 1-year OS, LC and IPFS was 62.4%, 77.2% and 52.6%, respectively. The median survival time was 15.9 months, and the median BMSS was 42.2 months. Treatment-related grade 3-4 adverse events were rare and only 8 cases was observed to have grade 3 hematological toxicity.Conclusion:Reasonable comprehensive treatment including precise radiotherapy, intrathecal chemotherapy and targeted therapy can be well tolerated and prolong the survival time of LM patients.
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Objective:To evaluate the efficacy and safety of hypofractionated radiotherapy for lung metastases (LMs).Methods:From March 2007 to April 2019, 193 patients with 317 LMs including 124 male and 69 female admitted to our hospital were enrolled. The median age was 58 years old and the median KPS was 80. The primary tumors were mainly distributed in the lung (33.7%), colorectum (21.2%), head and neck (13.5%) and breast (10.9%), respectively. The clinical efficacy and side effects of hypofractionated radiotherapy for LMs were evaluated.Results:The median follow-up time was 59.9 months (95% CI: 55.1-64.6 months). Among 193 patients with 317 LMs, 90.7% of them were treated with 4D-CT, 69.4% for intensity-modulated radiation therapy (IMRT), 28.0% for volumetric-modulated arc therapy (VMAT) and 2.6% for tomotherapy (TOMO), respectively. The median gross tumor volume (GTV) and planning target volume (PTV) were 5.0 cm 3(0.2-142.3 cm 3) and 12.0 cm 3(1.0-200.1 cm 3). The prescription dose regimen was 60 Gy in 4 to 15 fractions. The median dose for PTV was 60 Gy (45-70 Gy) and biological effective dose was 96 Gy (60-150 Gy), respectively. The 1-, 3-and 5-year local control rates (LCR) were 95.7%, 91.3% and 89.9%, respectively. The median time from primary cancer diagnosis to lung metastases was a prognostic factor for LCR ( P=0.027). The overall survival (OS) and progression-free survival (PFS) rates were 90.1%, 60.8%, 46.2%, and 54.3%, 30.3%, 19.9%, respectively. The median time from primary cancer diagnosis to lung metastases and extrapulmonary metastases was the prognostic factor for OS and PFS. No Grade 3 toxicities were seen. Conclusion:Image-guided hypofractionated precision radiotherapy is an efficacious and safe treatment for LMs.
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Objectives To evaluate the clinical efficacy and safety of hypofractionated radiotherapy for cancer patients with hepatic metastases. Methods From May 2007 to November 2016,45 patients ( male:female=20:25) with inoperable hepatic metastases were enrolled in this investigation. The median age was 58 years old ( range:25-83).The median Karnofsky performance score ( KPS) was 80.Primary colorectal cancer was detected in 14 patients,primary breast cancer in 9 and primary lung cancer in 6 cases. Twenty-one patients had extrahepatic metastases. A total of 52 lesions were treated. Thirty-four cases received radiotherapy for one single lesion. The fractional dose was 45 Gy/3 fractions and 60 Gy/10-15 fractions. The median gross tumor volume (GTV) was 10. 1 cm3(0. 3-175. 2 cm3) and 29. 8 cm3(5. 0-209. 6 cm3) for planning target volume ( PTV).Seventeen CT images were fused with MRI and IMRT was adopted in 43 cases. The median dose of PTV was 60 Gy (40-60 Gy) and 90 Gy (60-132 Gy) for bioequivalent dose (BED). Results The median follow-up time was 23. 5 months and the median survival time was 26. 0 months (95%CI:21.4-30.6 months).The 1-year local control (LC),disease-free survival (DFS) and overall survival ( OS ) were 94%, 27% and 91%, respectively. Six cases died of liver metastases and abnormal liver function. Conclusion Hypofractionated radiotherapy is an efficacious and safe local treatment for inoperable hepatic metastases.
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Objective To retrospectively analyze the dosimetry and efficacy of whole-brain irradiation (WBRT) with simultaneous integrated boost (SIB) by helical tomotherapy (HT) in the treatment of multiple brain metastases (BMs),and to evaluate the feasibility,efficacy,and safety of HT.Methods From 2014 to 2017,a total of 43 patients with multiple BMs (no less than 3 lesions) were enrolled as subjects.A dose of 40 Gy was delivered to the whole brain in 20 fractions,while a dose of 60 Gy was delivered to the gross target volume (GTV) in 20 fractions.Patients were reexamined by magnetic resonance imaging during treatment.The radiation field would be shrunk if GTV was reduced.Target coverage (TC),conformity index (CI),prescription isodose/target volume (PITV) ratio,and homogeneity index (HI) were assessed.Clinical indices included local recurrence-free survival (LRFS),intracranial progression-free survival (IPFS),progression-free survival (PFS),overall survival (OS),and toxicities.Results The median lesion number was 6(3-36) and the median total volume of GTV was 8.74 cm3.The TC,CI,PITV,and HI for GTV were 0.96±0.028,0.51±0.164,2.09±1.245,and 0.12±0.066,respectively,while the TC and HI for the whole brain were 0.95±0.033 and 0.43±0.161,respectively.In all the patients,26％ had replarming during treatment.The two-stage treatment reduced the radiation dose to organs at risk.The 1-year LRFS,IPFS,PFS,and OS rates were 96％,80％,39％,and 86％,respectively.No grade ≥3 toxicities were observed.Conclusions WBRT with SIB by HT achieves satisfactory conformity,homogeneity,efficacy,and safety,which is a recommended treatment plan for multiple BMs.Replanning during treatment can better protect normal tissue.
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Objective To retrospectively analyze and compare the clinical efficacy and safety between fractionated stereotactic radiotherapy (FSRT) combined with and without temozolomide in the treatment of large brain metastases.Methods Between 2009 and 2017,84 patients with large brain metastases (tumor size ≥ 6 cm3) were recruited and assigned into the CRT group (concurrent TMZ and FSRT,n=42) and RT group (FSRT alone,n=42).The radiation dose was 52.0 Gy in 13 fractions or 52.5 Gy in 15 fractions.Patients were reexamined by magnetic resonance imaging (MRI) during treatment.The radiation field would be shrunk if the gross target volume (GTV) was reduced.The clinical efficacy was evaluated at postoperative 2 to 3 months.The primary end-point event was local recurrence-free survival (LRFS) and the secondary end-point events included intracranial progression-free survival (IPFS),progression-free survival (PFS),overall survival (OS),brain metastasis-specific survival (BMSS) and adverse events.The survival rates were assessed with Kaplan-Meier method and log-rank test and monovariate analysis.Results The median GTV in the CRT and RT groups was 16.9 cm3 and 15.7 cm3.During the treatment,75％ of the lesions in the CRT group were reduced compared with 34％ in the RT group (P=0.000).The local control (LC) rate in the CRT and RT groups was 100％ and 98％.The median follow-up time was 16.1 months (range,2.1-105.7 months).In the CRT group,the LRFS (P=0.040),IPFS (P=0.022),PFS (P=0.045),OS (P=0.013) and BMSS (P=0.006) were significantly better than those in the RT group,respectively.In the CRT group,the incidence of grade Ⅰ-Ⅱ gastrointestinal adverse events was 33％,significantly higher compared with 26％ in the RT group (P=0.006).No grade Ⅳ-Ⅴ adverse events occurred in both groups.Conclusion Combined application of temozolomide and FSRT can further enhance the LC and survival rates and do not increase the risk of severe adverse events in patients diagnosed with large brain metastases.
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Objective To study the changes of activities of phase Ⅰ and Ⅱ drug-metabolic enzymes in the spleen of rats with spleen-kidney yang deficiency syndrome.Methods The rat model of spleen-kidney yang deficiency syndrome was established by gastric gavage of Radix et Rhizoma Rhei decoction combined with injection of hydrocortisone for 17 continuous days.And then we detected the activities of 6 kinds of phase Ⅰ drug-metabolic enzymes of CYP2C19,CYP2D6,CYP2C9,CYP1A2,CYP2C8,CYP3A4,and 4 kinds of phase Ⅱ drugmetabolic enzymes of phenol sulfotransferase (PST),uridine diphosphate glucuronosyl transferase 1 (UGT1),glutathione transferase (GST),estrogen sulfotransferase (SULT1E1) in the spleen.Results Compared with the normal control group,the activities of PST,UGT1,GST and SULT1E1 in the model group were significantly decreased (P ＜ 0.05 or P ＜ 0.01),and the activity of CYP1A2 was significantly increased (P ＜ 0.01),while CYP2C19,CYP2D6,CYP2C8,CYP3A4,CYP2C9 enzymes showed no obvious changes(P ＞ 0.05).Conclusion The activities of splenic drug-metabolic enzymes,in particular the phase Ⅱ enzymes,are significantly varied under the state of spleen-kidney yang deficiency.
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Objective To analyze the efficacy and safety of hypofractionated stereotactic radiotherapy ( FSRT ) combined with temozolomide ( TMZ ) for large brain metastases ( BMs ) in a prospective phaseⅡclinical trial.Methods From 2010 to 2015, a total of 33 patients were enrolled as subjects.The median Karnofsky Performance Status scores before and after treatment were 70 and 80, respectively.The major primary tumor was non-small cell lung cancer (57.6%).The brain metastasis had a diameter of≥3 cm or a volume of ≥6 cm3 .The radiation dose was 52 Gy in 13 fractions or 52.2 Gy in 15 fractions.Patients received TMZ at a dose of 75 mg/m2 per day concurrently.The radiotherapy was followed by 6 cycles of adjuvant treatment with TMZ (150 mg/m2, days 1-5, 28 days per cycle).Patients were reexamined by magnetic resonance imaging ( MRI) during the treatment.The radiation field would be shrunk if the gross target volume ( GTV) was reduced by≥20%.The treatment outcomes were evaluated by MRI at 2-3 months after treatment.Results The total numbers of tumors and GTVs were 95 and 38, respectively. Twenty-four (63%) out of the 38 GTVs had a volume larger than 10 cm3 and the median GTV was 15.3 cm3 (5.7-142.8 cm3).Twenty-two (67%) out of the 33 patients achieved field shrinking during the treatment, and the median reduction rate of GTV was 44%( 21%-88%) .The median total dose was 59.5 Gy, and 100%and 21.2%of patients completed the concurrent and adjuvant treatment with TMZ, respectively.In all patients, the overall response rate was 97.0%;the 1-year local control, intracranial progression-free survival, and overall survival rates were 97%, 70%, and 62%, respectively;the median survival time was 15.3 months.The main adverse reactions were grade 1-2 nausea and vomiting.One patient got grade 3 liver function impairment.Conclusions FSRT combined with TMZ is a safe and effective approach for treating large BMs.More than 50%of patients can achieve field shrinking to shorten treatment duration and reduce toxicity.Clinical Trial Registry ClinicalTrials.gov,registration number:NCT02654106.
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Objective To compare the pharmacokinetics difference of methotrexate ( MTX) alone or MTX combined with the decoction of Radix Salviae Miltiorrhizae ( RSM) in rats, and to investigate the possible impact of RSM on the efficacy and pharmacokinetics of MTX after oral administration. Methods Sprague-Dawley rats were given MTX (7 mg/kg) alone or MTX together with RSM (3.085 g/kg) respectively. At different time points, blood was sampled from orbital venous plexus and then was precipitated by perchloric acid. The serum concentration of MTX was determined by using high performance liquid chromatography ( HPLC) method. Chromatographic separation was achieved on a reversed-phase Diamonsil C18 (2) column with the mobile phase of methanol-formic acid water solution (formic acid in volume fraction of 0.1%) in gradient elution. The column temperature was 27 ℃, flow rate was 1 mL/min, detection wavelength was 302 nm, and the injection volume was 10 μL. The results were analyzed by pharmacokinetic software DAS ( 2.1.1) by non-compartment model. Results The linearity of the calibration curve for MTX was good in the range of 0.097 6 ~ 12.5 mg/L, the detection limit was 0.097 6 mg/L and the recovery was in the range of 77.5% ~ 86.6%. Compared with MTX group, the peak-arriving time of MTX-RSM group was advanced, and the clearance of MTX was delayed. Area under concentration-time curve at 0-t (AUC(0-t)) was increased by 0.609 times, and AUC(0-∞) was increased by 0.786 times. Conclusion The decoction of RSM exerts an effect on promoting the absorption of MTX, delaying the clearance of MTX and enhancing the bioavailability of MTX in vivo.
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<p><b>OBJECTIVE</b>To establish a SPE-HPLC method for analyzing astilbin in rats serum and explore the effects of Yinxieling (YXL) prescription and Smilacis Glabrae Rhizoma on the pharmacokinetic characteristics of effective components.</p><p><b>METHOD</b>Male Sprague-dawley rats were administrated YXL and Smilacis Glabrae Rhizoma respectively. At different time points, serum concentration of astilbin was extracted by Solid Phase Extraction (SPE) and determined using HPLC method. Chromatographic separation was achieved on a reversed-phase Phenomenex C18 column with the mobile phase of methanol-acetonitrile-formic acid water solution (0.05% formic acid) and gradient elution, temperature of bar was 24 degrees C, flow rate was 0.8 mL x min(-1).</p><p><b>RESULT</b>The method showed excellent linearity over the concentration range 0.266-53.1 mg x L(-1) of astilbin (r = 0.996). The extract recoveries were from 79.0% to 89.1%. Significant diffenerce in pharmacokinetic parameter of astilbin including t1/2, Cmax, AUC(0-t), AUC(0-infinity) and MRT were obtained through non-compartment model after oral administration of YXL prescription comparing with Smilacis Glabrae Rhizoma.</p><p><b>CONCLUSION</b>The method was applied to a pharmacokinetic study of astilbin. It indicated that the bioavailability of astilbin in YXL enhanced in rats and one of the reasons may be that components of prescription affect the pharmacokinetics of astilbin in vivo.</p>
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Animals , Male , Rats , Administration, Oral , Drugs, Chinese Herbal , Chemistry , Flavonols , Blood , Pharmacokinetics , Rats, Sprague-Dawley , Reproducibility of ResultsABSTRACT
OBJECTIVE: To optimize the extraction conditions of plumula nelumbinis. METHODS: The semi - bionic extraction (SBE) conditions were optimized by homogeneous design while total alkaloids and dry extract were adopted as markers. Factors of extraction time, solute quantity and the pH values were evaluated for their effects on extraction process. RESULTS: Optimal parameters were as follows: plumula nelumbinis was extracted in water 8 times as much as it for 3 times; the pH values of the water for the 1st, 2nd and 3rd decoctions were 5.0,6.0 and 8.0, respectively; the boiling lasted 4 hours. CONCLUSION: The method prouides theoretical reference for the extraction plumula nelumbinis.
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OBJECTIVE: To establish the method for the determination of emodin, resveratrol, polydatin and gentiopicrin in the Compound Polygonum cuspidatum semisolid matrix capsule in order to provide basis of its quality control. METHODS: TLC scanning method was used to determine emodin and resveratrol at same plate and the developer was petroleum ether-butyl acetate-methanol-glacial acetic acid(4∶1∶0.7∶0.03) with determination wavelength of 285 nm and 293 nm respectively. Polydatin and gentiopicrin were determined at same plate and the developer was chloroform-methanol(7 ∶ 2)with determination wavelength of 313 nm and 270 nm respectively. RESULTS: All target components were separated and the standard curves of emodin, resveratrol, polydatin and gentiopicrin showed good linearity. Average recoveries of them were 100.1%(RSD=0.86%),99.6%(RSD=2.86%), 101.4%(RSD=0.99%),98.5%(RSD=2.89%),respectively. CONCLUSION: Established method is rapid, simple for the quality control of Compound P. cuspidatum semisolid matrix capsule.
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OBJECTIVE:To optimize the extraction craft of gentiopicrin from gentian.METHODS:The extraction craft was optimized by orthogonal test with gentiopicrin as an index,and the content of gentiopicroside was determined by TLC scanning method.RESTLUTS:The quantity of menstruum and the extraction times of gentiopicrin had significant influence in the gentiopicrin extraction(P
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AIM: To establish the method of determining ginsenoside Rg1 and notoginsenoside R1,and control the quality of Yiqi Gushen Dialysis Liquid(Radix et Rhizoma Notoginseng,Radix Astragali,etc.) METHODS: Sample was pretreated with solid phase extraction using ODS C_13 cartridges.Ginsenoside Rg1 and Notoginsenoside R1 were separated with TLC method.The mobile phase was chloroform-methanol-water(3∶0.8∶0.1),developed twice.The coloration was 10% sulphuric acid ethanol solution.The detection wavelength was 560 nm. RESULTS: The calibration curves for ginsenoside Rg1 and notoginsenoside R1 were A=113.4 C-34.976,(r=0.997),A=92.14 C-13.597,(r=0.997),respectively,the linear ranges were between 2.64-13.2 mg and 0.85-8.5 mg,and the detection limit was 0.88 mg and 0.65 mg,respectively.The average recoveries were 100.31% and 98.72%,respectively.The contents of the sample were between 5.683-5.764mg,1.528-1.599 mg per 10 mL,respectively. CONCLUSION: The proposed method for estimating ginsenoside Rg1 and notoginsenoside R1 is simple,precise,specific,sensitive and accurate and can be used for quality control of Yiqi Gushen Dialysis Liquid.
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OBJECTIVE:To establish a HPLC method for determination of anthraquinone free derivatives from Chinese herbal in dog serum METHODS:With Hypersil BDS C18 column,the mobile phase was methanol-0 5% acetic acid(80∶20) The sample was extracted with methanol and dried at room temperature The residue was reconstituted by methanol and analyzed at 430nm RESULTS:The five components can be separated well The linear ranges were Aloe-emodin(0 15～6 0?g/ml,r=0 9 996) Rhein(0 14～5 6?g/ml,r=0 9 982);Emodin(0 13～5 2?g/ml,r=0 9 990);Chrysophanol(0 2～8 0?g/ml,r=0 9 991);Physcion(0 1～4 0?g/ml,r=0 9 994) CONCLUSION:This method can provide the basis for vivo analysis of anthraquinone free derivatives and bioavailability study of Rheum palmatum preparations