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1.  Paclitaxel-coated balloons for the treatment of patients with in-stent restenosis: A meta-analysis of angiographic and clinical data 
Paclitaxel-coated balloons (PCBs) have become attractive alternative treatment options for patients with in-stent restenosis (ISR); however, the safety and efficacy of PCBs in comparison with those of conventional therapies are less well defined. The aim of this meta-analysis was to systematically review the efficacy and safety of PCBs for patients with ISR using comparisons with control groups. Electronic databases, such as MEDLINE, Embase and the Cochrane Central Register of Controlled Trials, were searched, and eligible studies that compared PCBs with uncoated balloons (UCBs) or drug-eluting stents (DESs) in patients with ISR were considered. Subgroup analyses were performed with different control groups. Nine studies (1,488 patients, 1,608 lesions) were included in the meta-analysis. Compared with patients who underwent UCB angioplasty, those who underwent PCB angioplasty exhibited a clear superiority in late lumen loss (LLL) [weighted mean difference (WMD), −0.46; 95% confidence interval (CI), (−0.59)-(−0.34); P<0.00001] and major adverse cardiac events (MACEs) [odds ratio (OR), 0.21; 95% CI, 0.13–0.33; P<0.00001]. The OR for myocardial infarction (MI) (OR, 0.46; 95% CI, 0.15–1.47; P=0.19) did not reach statistical significance. PCBs were associated with similar outcomes when compared with DESs with regard to LLL (WMD, −0.04; 95% CI, −0.18–0.10; P=0.57), MACEs (OR, 0.74; 95% CI, 0.36–1.53; P=0.42) and the ORs for all endpoints, including total mortality, target lesion revascularization, MI, stent thrombosis and binary restenosis, and no statistically significant differences were found. This meta-analysis showed that PCBs are associated with superior outcomes when compared with UCBs in the management of ISR, and are at least as efficacious and as well tolerated as DESs.
PMCID: PMC4473663  PMID: 26136975
paclitaxel-coated balloon; drug-eluting stent; in-stent restenosis; meta-analysis
2.  The genus Pseudolathra Casey in China: new species and new records (Coleoptera, Staphylinidae, Paederinae) 
ZooKeys  2013;1-9.
Two new species of the genus Pseudolathra Casey from mainland China are described and attributed to their respective species groups, P. cylindrata sp. n. from Hubei and Sichuan, and P. superficiaria sp. n. from Yunnan. Pseudolathra pulchella (Kraatz, 1859), P. transversiceps Assing, 2013 and P. bipectinata Assing, 2013 from Yunnan are reported from China for the first time. The history of the exploration of the Chinese fauna of Pseudolathra is summarized.
PMCID: PMC3867107  PMID: 24363571
New species; Pseudolathra; Paederinae; Staphylinidae; China
3.  Transcription Expression and Clinical Significance of Dishevelled-3 mRNA and δ-Catenin mRNA in Pleural Effusions from Patients with Lung Cancer 
Objective. To evaluate diagnostic utility of Dishevelled-3 (DVL-3) mRNA and δ-catenin mRNA expression in pleural effusions of patients with lung cancer. Methods. DVL-3 mRNA and δ-catenin mRNA levels were assessed by performing RT-PCR on pleural effusion specimens from patients with lung cancer (n = 75) and with lung benign disease (n = 51). Results. The expressions of DVL-3 mRNA and δ-catenin mRNA were significantly higher in malignant than in benign lung disease (P < 0.01) and were obviously higher than cytology in adenocarcinoma (P < 0.01). In single use, DVL-3 mRNA had the highest specificity (94.1%) and PPV (95.7%), whereas δ-catenin mRNA had the highest sensitivity (92.0%) and NPV (88.5%). When combinations of markers were evaluated together, DVL-3 mRNA and δ-catenin mRNA gave a high-diagnostic performance: sensitivity of 100.0%, NPV of 100.0%, and accuracy of 96.0%, respectively. Conclusion. As molecular markers of detecting pleural micrometastasis, DVL-3 mRNA and δ-catenin mRNA are helpful to diagnose the cancer cells in pleural effusions of patients with lung cancer.
PMCID: PMC3296179  PMID: 22461838
4.  Study on the optical property and biocompatibility of a tissue engineering cornea 
To study the optical property and biocompatibility of a tissue engineering cornea.
: The cross-linker of N-(3-Dimethylaminoropyl)-N'ethylcarbodiimide hydrochloride (EDC)/N-Hydroxysuccinimide (NHS) was mixed with Type I collagen at 10% (weight/volume). The final solution was molded to the shape of a corneal contact lens. The collagen concentrations of 10%, 12.5%, 15%, 17.5% and 20% artificial corneas were tested by UV/vis-spectroscopy for their transparency compared with normal rat cornea. 10-0 sutures were knotted on the edges of substitute to measure the corneal buttons's mechanical properties. Normal rat corneal tissue primary culture on the collagen scaffold was observed in 4 weeks. Histopathologic examinations were performed after 4 weeks of in vitro culturing.
The collagen scaffold appearance was similar to that of soft contact lens. With the increase of collagen concentration, the transparency of artificial corneal buttons was diminished, but the toughness of the scaffold was enhanced. The scaffold transparency in the 10% concentration collagen group resembled normal rat cornea. To knot and embed the scaffold under the microscope, 20% concentration collagen group was more effective during implantation than lower concentrations of collagen group. In the first 3 weeks, corneal cell proliferation was highly active. The shapes of cells that grew on the substitute had no significant difference when compared with the cells before they were moved to the scaffold. However, on the fortieth day, most cells detached from the scaffold and died. Histopathologic examination of the primary culture scaffold revealed well grown corneal cells tightly attached to the scaffold in the former culturing.
Collagen scaffold can be molded to the shape of soft contact corneal lens with NHS/EDC. The biological stability and biocompatibility of collagen from animal species may be used as material in preparing to engineer artificial corneal scaffold.
PMCID: PMC3340846  PMID: 22553753
tissue engineering; collagen cross-linking scaffold; primary culture in vitro; optical property; biocompatibility
5.  (E)-3-Nitro-N′-(3-nitro­benzyl­idene)­benzohydrazide 
In the title compound, C14H10N4O5, the mol­ecule exists in a trans conformation with respect to the methyl­idene unit. The dihedral angle between the benzene rings is 9.8 (2)°. In the crystal, mol­ecules are linked through N—H⋯O hydrogen bonds to form chains along the c axis.
PMCID: PMC3295476  PMID: 22412587
6.  (E)-N′-(3-Fluoro­benzyl­idene)-3-nitro­benzohydrazide 
In the title compound, C14H10FN3O3, the mol­ecule exists in a trans conformation with respect to the methyl­idene unit. The dihedral angle between the benzene rings is 5.1 (2)°. In the crystal, mol­ecules are linked through N—H⋯O hydrogen bonds, forming chains along the c axis.
PMCID: PMC3295477  PMID: 22412588
7.  (E)-2-Chloro-N′-(4-hy­droxy­benzyl­idene)­benzohydrazide 
The title hydrazone mol­ecule, C14H11ClN2O2, has a trans conformation with respect to the methyl­idene unit. The dihedral angle between the two benzene rings is 37.6 (3)°. In the crystal, the presence of O—H⋯O, O—H⋯N and N—H⋯O hydrogen bonds leads to the formation of a three-dimensional network. The title compound crystallized in the chiral ortho­rhom­bic space group P212121 and was refined as an inversion twin [Flack parameter = −0.20 (18)].
PMCID: PMC3295484  PMID: 22412595
8.  (E)-4-Hy­droxy-N′-(2-hy­droxy-3,5-diiodo­benzyl­idene)-3-meth­oxy­benzohydrazide methanol monosolvate 
In the title compound, C15H12I2N2O4·CH3OH, the hydrazone mol­ecule exists in an E conformation with respect to the C=N bond. The dihedral angle between the rings is 11.9 (2)°. There is one intra­molecular O—H⋯N hydrogen bond in the hydrazone mol­ecule. In the crystal, the hydrazone and methanol mol­ecules are linked through O—H⋯O and N—H⋯O hydrogen bonds and C—H⋯O inter­actions to form two-dimensional networks lying parallel to (001).
PMCID: PMC3295446  PMID: 22412557
9.  (E)-4-Nitro-N′-(3-nitro­benzyl­idene)benzohydrazide 
The title compound, C14H10N4O5, has an E conformation with respect to the C=N bond. The dihedral angle between the benzene rings is 2.41 (14)°. In the crystal, mol­ecules are linked through N—H⋯O hydrogen bonds to form chains along the c axis. C—H⋯O inter­actions are also present, linking the chains to form a three-dimensional network.
PMCID: PMC3295447  PMID: 22412558
10.  N′-[(1E)-(2-Hy­droxy­naphthalen-1-yl)methyl­idene]-2-meth­oxy­benzohydrazide 
There are three independent mol­ecules in the asymmetric unit of the title compound, C19H16N2O3, in which the dihedral angles between the naphthalene ring system and the benzene ring are 7.52 (16), 18.15 (18), and 13.9 (2)°. All the mol­ecules exist in the trans configuration with respect to the methyl­idene units. In each mol­ecule there is one O—H⋯N and one N—H⋯O intra­molecular hydrogen bond. In the crystal, two of the mol­ecules are linked via a bifurcated N—H⋯(O,O) hydrogen bond. All three mol­ecules are further linked via C—H⋯O inter­actions.
PMCID: PMC3201446  PMID: 22065731
11.  (E)-N′-(5-Bromo-2-hy­droxy-3-meth­oxy­benzyl­idene)-1H-indole-3-carbo­hydrazide 
There are three independent mol­eculesi n the asymmetric unit of the title compound, C18H16BrN3O3, in which the dihedral angles between the indole and benzene rings are 76.9 (2), 4.9 (2), and 70.9 (2)°. All three mol­ecules exist in a trans configuration with respect to the methyl­idene units. In each mol­ecule, there is one intra­molecular O—H⋯N hydrogen bond. In the crystal, N—H⋯O hydrogen bonds occur.
PMCID: PMC3201537  PMID: 22065413
12.  (E)-N′-(5-Bromo-2-meth­oxy­benzyl­idene)-2-chloro­benzohydrazide 
In the title compound, C15H12BrClN2O2, the dihedral angle between the two substituted aromatic rings is 77.8 (3)°. The mol­ecule exists in a trans conformation with respect to the methyl­idene unit. In the crystal structure, inversion dimers linked by pairs of N—H⋯O hydrogen bonds generate R 2 8(8) loops.
PMCID: PMC3200979  PMID: 22065403
13.  (E)-N′-(3,5-Dichloro-2-hy­droxy­benzyl­idene)-2-meth­oxy­benzohydrazide 
In the title compound, C15H12Cl2N2O3, the dihedral angle between the two substituted aromatic rings is 5.4 (4)°. Intra­molecular O—H⋯N and N—H⋯O hydrogen bonds affect the planarity of the molcular conformation, with a mean deviation from the plane defined by the non-H atoms of 0.062 (2) Å. The mol­ecule exists in a trans configuration with respect to the methyl­idene unit. In the crystal, mol­ecules are linked by N—H⋯O inter­actions.
PMCID: PMC3151996  PMID: 21837171
14.  Clinical significance of tumor-associated macrophage infiltration in supraglottic laryngeal carcinoma 
Chinese Journal of Cancer  2011;30(4):280-286.
Tumor-associated macrophages (TAMs) can elicit contrasting effects on tumor progression, depending on different tumor microenvironment. This study aimed to explore the correlation between TAM infiltration and clinicopathologic characteristics, metastasis, and prognosis of supraglottic laryngeal carcinoma. TAMs in intratumoral and peritumoral regions of 84 specimens of supraglottic laryngeal carcinoma tissues were detected by immunohistochemical staining with monoclonal CD68 antibody. The density of peritumoral CD68+ TAMs in recurrence cases (9/11) and in dead cases (17/23) were significantly higher than those in non-recurrence cases (33/73) and in survival cases (25/61), with significant differences (P = 0.024 and 0.007, respectively). The Kaplan-Meier survival analysis showed a significant relationship between the infiltration of both intratumoral and peritumoral CD68+ TAMs and the overall survival of patients. The 5-year survival rate was significantly lower in the group with a high density of intratumoral CD68+ TAMs than in the group with a low density (39.6% vs. 82.5%, P < 0.05). Similarly, the 5-year survival rate was significantly lower in the group with a high density of peritumoral CD68+ TAMs than in the group with a low density (50.6% vs. 73.1%, P < 0.05). Cox regression analysis revealed that T classification, distant metastasis, and intratumoral or peritumoral CD68+ TAMs were independent factors for disease-free survival, whereas T classification and intratumoral CD68+ TAMs were independent factors for overall survival. The results indicate that TAM infiltration in supraglottic laryngeal carcinoma can be used to predict metastasis and prognosis and is an independent factor for prognosis.
PMCID: PMC4013355  PMID: 21439250
Laryngeal neoplasm; squamous cell carcinoma; tumor-associated macrophages; prognostic factor
15.  Oral PSORI-CM01, a Chinese herbal formula, plus topical sequential therapy for moderate-to-severe psoriasis vulgaris: pilot study for a double-blind, randomized, placebo-controlled trial 
Trials  2016;17:140.
To provide evidence that the Chinese herbal medicine (CHM) PSORI-CM01 combined with Western medicine reduces the relapse rate of psoriasis vulgaris (PV), we plan to conduct a large-scale randomized control trial (RCT). In order to improve and perfect the RCT, this pilot study was designed to determine the feasibility and the potential of a modified protocol for the full-scale RCT.
Eligible patients with psoriasis vulgaris (PV) were enrolled into a randomized comparison in which all subjects received topical sequential therapy and PSORI-CM01 or placebo for 12 weeks. The primary outcome measure was the relapse rate. Treatment response was computed from Psoriasis Area and Severity Index (PASI), body surface area (BSA), and Dermatology Life Quality Index (DLQI). The secondary outcome measures included time to relapse, time to onset, rebound rate, PASI score, pruritus scores on the Visual Analog Scale (VAS), BSA, DLQI and SF-36 (short form health survey), and incidence of serious adverse events (SAEs).
Six of 7 (86 %) subjects reached the PASI-50 in the CHM group compared with nine of 10 (90 %) in the placebo group during the treatment period. Among the subjects who reached PASI-50, one out of six subjects (17 %) relapsed in the CHM group during the treatment period compared with six out of nine patients in the placebo group (67 %). No subjects met the rebound criteria. Changes to baseline in the PASI scores were not significantly different between the two groups (t = 1.764, P = 0.098).
Oral PSORI-CM01 combined with topical sequential treatment showed a smaller recurrence rate (P = 0.118) than placebo combined with the same topical therapy for moderate-to-severe PV in this pilot study.
Trial registration
Chinese Clinical Trial Registry ( ChiCTR-TRC-13003233; date of registration: 15 April 2013.
Electronic supplementary material
The online version of this article (doi:10.1186/s13063-016-1272-x) contains supplementary material, which is available to authorized users.
PMCID: PMC4793560  PMID: 26983642
Psoriasis vulgaris; pilot randomized controlled trial; PSORI-CM01; Chinese herbal medicine; topical sequential treatment
16.  Prevalence and risk factors of organ failure in patients with severe acute pancreatitis 
This study was undertaken to determine the prevalence of organ failure and its risk factors in patients with severe acute pancreatitis (SAP).
A retrospective analysis was made of 186 patients with SAP who were had been hospitalized in the intensive care unit of Jinzhong First People’s Hospital between March 2000 and October 2009. The patients met the diagnostic criteria of SAP set by the Surgical Society of the Chinese Medical Association in 2006. The variables collected included age, gender, etiology of SAP, the number of comorbidit, APACHEII score, contrast-enhanced CT (CECT) pancreatic necrosis, CT severity index (CTSI) , abdominal compartment syndrome (ACS) , the number of organ failure, and the number of death. The prevalence and mortality of organ failure were calculated. The variables were analyzed by unconditional multivariate logistic regression to determine the independent risk factors for organ failure in SAP.
Of 186 patients, 96 had organ failure. In the 96 patients, 47 died. There was a significant association among the prevalence of organ failure and age, the number of comorbidity, APACHEII score, CECT pancreatic necrosis, CTSI, and ACS. An increase in age, the number of comorbidity, APACHEII score, CECT pancreatic necrosis were correlated with increased number of organ failure. Age, the number of comorbidity, APACHEII score, CECT pancreatic necrosis, CTSI and ACS were assessed by unconditional multivariate logistic regression.
Organ failure occurred in 51.6% of the 186 patients with SAP. The mortality of SAP with organ failure was 49.0%. Age, the number of comorbidity, APACHEII score, CECT pancreatic necrosis, CTSI and ACS are independent risk factors of organ failure.
PMCID: PMC4129688  PMID: 25214968
Severe acute pancreatitis; Organ failure; Prevalence; Risk factor; Age; Comorbidity; APACHE; Pancreatic necrosis; Abdominal compartment syndrome
17.  Evaluation of HCPTd1, d14-double passaged intervening chemotherapy protocol for hepatocellular carcinoma 
AIM: To establish a kind of standardization of the clinical chemotherapeutic prototypes for unresectable hepatocellular carcinomas (HCC).
METHODS: 10-Hydroxycamptothecin (HCPT) was applied through transcatheter arterial embolization (TAE) to HCC patients who were categorized into three groups: (1) test group: treatment with HCPT twice (HCPT d1 and 14) through TAE and portal venous embolization. (2) Control I: treatment with anticancer drugs without HCPT. (3) Control II: treatment with HCPT as a major component in anticancer drugs once (HCPT d1). A set of comparisons between test groups and control I and II groups were performed before and after the treatment to study the effectiveness of each treatment, in terms of tumor volumes, dynamic variations in serum alpha-fetoprotein (AFP), gamma-glutamyl transferase hepatoma-specific band (GGT-II), patient survival and adverse events.
RESULTS: The general effectiveness rate of the test group reached 62.1% (72/116), remarkably higher than that of control I (32.1%, 40/124) and control II (54.7%, 47/56), (P<0.01 and P<0.05, respectively). Especially, the reduction rate or disappearance of the portal vein tumor emboli was as high as 88.4% (61/69) in the test group, in contrast with 13.9% (10/72) in control I and 35.9% (18/51) in control II (P<0.01 and P<0.01, respectively). After treatment, AFP decreased or turned to negative levels at 52.3% (34/65) in control I, 67.3% (35/52) in control II, and 96.8% (60/62) in the test group. Also GGT-II declined or became negative at 37.8% (28/74) in control I, 69.5% (57/82) in control II, and 94.7% (89/94) in test group (P<0.01 and P<0.05, respectively).
CONCLUSION: We have designed a good protocol (test group) to treat HCC with excellent advantages of high efficiency, low cost, low toxicity and low adverse events and easy application. It could be recommended as one of the standardizations for HCC treatment in clinical practice.
PMCID: PMC4320400  PMID: 16127757
Hydroxycamptothecin; Transcatheter arterial embolization; Portal venous embolization; Hepatocellular carcinoma
18.  Histone methyltransferases: novel targets for tumor and developmental defects 
Histone lysine methylation plays a critical role in epigenetic regulation of eukaryotes. To date, studies have shown that lysine residues of K4, K9, K27, K36 and K79 in histone H3 and K20 in histone H4 can be modified by histone methyltransferases (HMTs). Such histone methylation can specifically activate or repress the transcriptional activity to play a key role in gene expression/regulation and biological genetics. Importantly, abnormities of patterns or levels of histone methylation in higher eukaryotes may result in tumorigenesis and developmental defects, suggesting histone methylation will be one of the important targets or markers for treating these diseases. This review will outline the structural characteristics, active sites and specificity of HMTs, correlation between histone methylation and human diseases and lay special emphasis on the progress of the research on H3K36 methylation.
PMCID: PMC4697697  PMID: 26807165
Histone lysine methylation; histone methyltransferases; epigenetic modification
19.  Dexamethasone intravitreal implant in previously treated patients with diabetic macular edema: subgroup analysis of the MEAD study 
BMC Ophthalmology  2015;15:150.
Dexamethasone intravitreal implant 0.7 mg (DEX 0.7) was approved for treatment of diabetic macular edema (DME) after demonstration of its efficacy and safety in the MEAD registration trials. We performed subgroup analysis of MEAD study results to evaluate the efficacy and safety of DEX 0.7 treatment in patients with previously treated DME.
Three-year, randomized, sham-controlled phase 3 study in patients with DME, best-corrected visual acuity (BCVA) of 34–68 Early Treatment Diabetic Retinopathy Study letters (20/200–20/50 Snellen equivalent), and central retinal thickness (CRT) ≥300 μm measured by time-domain optical coherence tomography. Patients were randomized to 1 of 2 doses of DEX (0.7 mg or 0.35 mg), or to sham procedure, with retreatment no more than every 6 months. The primary endpoint was ≥15-letter gain in BCVA at study end. Average change in BCVA and CRT from baseline during the study (area-under-the-curve approach) and adverse events were also evaluated. The present subgroup analysis evaluated outcomes in patients randomized to DEX 0.7 (marketed dose) or sham based on prior treatment for DME at study entry.
Baseline characteristics of previously treated DEX 0.7 (n = 247) and sham (n = 261) patients were similar. In the previously treated subgroup, mean number of treatments over 3 years was 4.1 for DEX 0.7 and 3.2 for sham, 21.5 % of DEX 0.7 patients versus 11.1 % of sham had ≥15-letter BCVA gain from baseline at study end (P = 0.002), mean average BCVA change from baseline was +3.2 letters with DEX 0.7 versus +1.5 letters with sham (P = 0.024), and mean average CRT change from baseline was −126.1 μm with DEX 0.7 versus −39.0 μm with sham (P < 0.001). Cataract-related adverse events were reported in 70.3 % of baseline phakic patients in the previously treated DEX 0.7 subgroup; vision gains were restored following cataract surgery.
DEX 0.7 significantly improved visual and anatomic outcomes in patients with DME previously treated with laser, intravitreal anti-vascular endothelial growth factor, intravitreal triamcinolone acetonide, or a combination of these therapies. The safety profile of DEX 0.7 in previously treated patients was similar to its safety profile in the total study population.
Trial registration NCT00168337 and NCT00168389, registered 12 September 2005
PMCID: PMC4628378  PMID: 26519345
Corticosteroid; Dexamethasone; Diabetic retinopathy; Drug delivery; Implant; Macular edema
20.  Effects of electroacupuncture therapy for Bell’s palsy from acute stage: study protocol for a randomized controlled trial 
Trials  2015;16:378.
Although many patients with facial paralysis have obtained benefits or completely recovered after acupuncture or electroacupuncture therapy, it is still difficult to list intuitive evidence besides evaluation using neurological function scales and a few electrophysiologic data. Hence, the aim of this study is to use more intuitive and reliable detection techniques such as facial nerve magnetic resonance imaging (MRI), nerve electromyography, and F waves to observe changes in the anatomic morphology of facial nerves and nerve conduction before and after applying acupuncture or electroacupuncture, and to verify their effectiveness by combining neurological function scales.
A total of 132 patients with Bell’s palsy (grades III and IV in the House-Brackmann [HB] Facial Nerve Grading System) will be randomly divided into electroacupuncture, manual acupuncture, non-acupuncture, and medicine control groups. All the patients will be given electroacupuncture treatment after the acute period, except for patients in the medicine control group. The acupuncture or electroacupuncture treatments will be performed every 2 days until the patients recover or withdraw from the study. The primary outcome is analysis based on facial nerve functional scales (HB scale and Sunnybrook facial grading system), and the secondary outcome is analysis based on MRI, nerve electromyography and F-wave detection. All the patients will undergo MRI within 3 days after Bell’s palsy onset for observation of the signal intensity and facial nerve swelling of the unaffected and affected sides. They will also undergo facial nerve electromyography and F-wave detection within 1 week after onset of Bell’s palsy. Nerve function will be evaluated using the HB scale and Sunnybrook facial grading system at each hospital visit for treatment until the end of the study. The MRI, nerve electromyography, and F-wave detection will be performed again at 1 month after the onset of Bell’s palsy.
Trial registration
Chinese Clinical Trials Register identifier: ChiCTR-IPR-14005730. Registered on 23 December 2014.
PMCID: PMC4548841  PMID: 26303741
Acupuncture; Bell’s palsy; Electromyography; F Wave test; Magnetic resonance imaging
21.  Analysis on the psychological characteristics of patients with acute iridocyclitis 
PMCID: PMC4458677  PMID: 26086022
22.  Immunochemotherapy for primary central nervous system lymphoma with rituximab, methotrexate, cytarabine and dexamethasone: Retrospective analysis of 18 cases 
Molecular and Clinical Oncology  2015;3(4):949-953.
The incidence of primary central nervous system lymphoma (PCNSL) has increased in the last two decades and the clinical research regarding the treatment for PCNSL patients has also increased. However, the optimal induction chemotherapy has not been fully established. In the present retrospective study, the aim was to analyze the outcome in PCNSL patients treated with the combination of rituximab, methotrexate (MTX), cytarabine (Ara-C) and dexamethasone (R-MAD). Eighteen patients from Beijing Tiantan Hospital (Beijing, China) between January 2010 and March 2014 were newly diagnosed with PCNSL [diffuse large B-cell lymphoma (DLBCL) type] and received R-MAD as first-line treatment. The dosage was as follows: 375 mg/m2 rituximab was administered on day 0, 3.5 g/m2 MTX was administered on day 1, 1 g/m2 Ara-C was administered on day 2 and 10 mg dexamethasone was administered on days 1–3, every 3 weeks. After 6 cycles, the overall response rate was 94.5%. Ten (55.6%) patients achieved complete response (CR), 7 (38.9%) achieved partial response (PR) and 1 (5.6%) had progressive disease (PD). Patients were followed up from the start of the treatment, median 24.2 months (range 6–48). The overall survival (OS) rate was 94.5% and progression-free survival rate was 94.5%. The median OS was 22 months (95% confidence interval, 19.4–24.6). The high level of serum lactate dehydrogenase (LDH) concentration was associated with a poor outcome. Among 5 patients with an abnormally high LDH concentration, 1 achieved CR, 3 had PR and 1 had PD. None of the patients experienced any grade 4 toxicity. These results indicated that the R-MAD immunochemotherapy regimen is effective in PCNSL patients without serious toxicity. A prospective investigation with more patients should be administered in order to understand the more accurate effect of the regimen.
PMCID: PMC4486824  PMID: 26171213
primary central nervous system lymphoma; immunochemotherapy; rituximab; retrospective analysis; serum lactate dehydrogenase
23.  Comparison of the proliferation, cytotoxic activity and cytokine secretion function of cascade primed immune cells and cytokine-induced killer cells in vitro 
Molecular Medicine Reports  2015;12(2):2629-2635.
The present study aimed to compare the antitumor effects of cascade primed immune (CAPRI) cells and cytokine-induced killer (CIK) cells in vitro, through investigating cell morphology, proliferation, cytotoxic activity to tumor cells and the ability of these cells to secrete cytokines. Peripheral blood samples (50 ml) were obtained from three healthy volunteers and peripheral blood mononuclear cells (PBMCs) were obtained from each via Ficoll-Conray density gradient centrifugation. Each suspension of PBMCs (1×106/ml) was divided into two parts; CAPRI cells were obtained from one part through a series of induction, amplification and cytokine cultures, while CIK cells were obtained from the other part through induction with different cytokines. During the culture process, the proliferation and morphological changes were observed for the two cell types using Trypan blue staining. At day 14, the cytotoxic activity of the two cell types was examined through determining lactate dehydrogenase release in the presence of K562 leukemia cells and MCF-7 breast cancer cells. In addition, secretory levels of interferon (IFN)-γ and interleukin (IL)-2 were detected using enzyme-linked immunospot (ELISPOT) technology. The results revealed that at day 5 and 14 of culture, there were significantly fewer CAPRI cells compared with CIK cells (P<0.001), although the survival rate of each cell type was >95%. The cytotoxic activity of CAPRI cells towards the K562 cell line was effector-target ratio-dependent (40:1 and 20:1) with values of 55.1±3.25 and 35.0±2.65%, respectively, which were significantly reduced compared with the corresponding data in CIK cells, 60.0±3.03 and 39.7±3.42% (P=0.004 and 0.005, respectively). Furthermore, the cytotoxic activity of CAPRI cells towards MCF-7 cells were 71.5±3.06, 56.0±3.76 and 40.2±2.90% at effector-target ratios 40:1, 20:1 and 10:1, respectively. These data were significantly higher than the corresponding values in CIK cells, 65.4±3.86, 49.5±3.91 and 36.1±3.73% (P=0.002, 0.003 and 0.02, respectively). As determined using ELISPOT technology at different cell concentrations (1×106/ml and 5×105/ml), IFN-γ secretion levels, determined by the number of spot-forming cells, of CAPRI cells were 126.2±10.31 and 48.8±10.99, respectively, which were significantly reduced compared with those of CIK cells, 409.3±7.76 and 159.3±15.45, respectively (P<0.001). IL-2 secretion levels in CAPRI cells were 325.1±16.24 and 113.8±11.29 at 1×106/ml and 5×105/ml, respectively, which were significantly increased compared with CIK cells, 212.0±16.58 and 70.7±10.57, respectively (P<0.001). In conclusion, the present study demonstrated that CAPRI cells had a reduced proliferation rate compared with CIK cells as well as a less potent cytotoxic effect on K562 cells; however, the two cell types had potent cytotoxic activity towards solid tumor MCF-7 cells. In addition, CAPRI cells secreted lower levels of IFN-γ and increased levels of IL-2 compared with CIK cells. These results indicated that antitumor activities of CAPRI and CIK cells proceeded via different mechanisms.
PMCID: PMC4464195  PMID: 25955083
cascade primed immune cells; cytokine-induced killer cells; proliferation; cytotoxic activity; cytokine
24.  Efficacy and safety of nerve growth factor for the treatment of neurological diseases: a meta-analysis of 64 randomized controlled trials involving 6,297 patients 
Neural Regeneration Research  2015;10(5):819-828.
China is the only country where nerve growth factor is approved for large-scale use as a clinical medicine. More than 10 years ago, in 2003, nerve growth factor injection was listed as a national drug. The goal of this article is to evaluate comprehensively the efficacy and safety of nerve growth factor for the treatment of neurological diseases.
A computer-based retrieval was performed from six databases, including the Cochrane Library, PubMed, EMBASE, Sino Med, CNKI, and the VIP database, searching from the clinical establishment of nerve growth factor for treatment until December 31, 2013. The key words for the searches were “nerve growth factor, randomized controlled trials” in Chinese and in English.
Inclusion criteria: any study published in English or Chinese referring to randomized controlled trials of nerve growth factor; patients with neurological diseases such as peripheral nerve injury, central nerve injury, cranial neuropathy, and nervous system infections; patients older than 7 years; similar research methods and outcomes assessing symptoms; and measurement of nerve conduction velocities. The meta-analysis was conducted using Review Manager 5.2.3 software.
The total effective rate, the incidence of adverse effects, and the nerve conduction velocity were recorded for each study.
Sixty-four studies involving 6,297 patients with neurological diseases were included. The total effective rate in the group treated with nerve growth factor was significantly higher than that in the control group (P < 0.0001, RR: 1.35, 95%CI: 1.30–1.40). The average nerve conduction velocity in the nerve growth factor group was significantly higher than that in the control group (P < 0.00001, MD: 4.59 m/s, 95%CI: 4.12–5.06). The incidence of pain or scleroma at the injection site in the nerve growth factor group was also higher than that in the control group (P < 0.00001, RR: 6.30, 95%CI: 3.53–11.27), but such adverse effects were mild.
Nerve growth factor can significantly improve nerve function in patients with nervous system disease and is safe and effective.
PMCID: PMC4468778  PMID: 26109961
nerve regeneration; neurological diseases; nerve growth factor; randomized controlled trials; meta-analysis; adverse effects; nerve conduction velocity; neural regeneration
25.  MicroRNA100 Inhibits Self-Renewal of Breast Cancer Stem–like Cells and Breast Tumor Development 
Cancer research  2014;74(22):6648-6660.
miRNAs are essential for self-renewal and differentiation of normal and malignant stem cells by regulating the expression of key stem cell regulatory genes. Here, we report evidence implicating the miR100 in self-renewal of cancer stem-like cells (CSC). We found that miR100 expression levels relate to the cellular differentiation state, with lowest expression in cells displaying stem cell markers. Utilizing a tetracycline-inducible lentivirus to elevate expression of miR100 in human cells, we found that increasing miR100 levels decreased the production of breast CSCs. This effect was correlated with an inhibition of cancer cell proliferation in vitro and in mouse tumor xenografts due to attenuated expression of the CSC regulatory genes SMARCA5, SMARCD1, and BMPR2. Furthermore, miR100 induction in breast CSCs immediately upon their orthotopic implantation or intracardiac injection completely blocked tumor growth and metastasis formation. Clinically, we observed a significant association between miR100 expression in breast cancer specimens and patient survival. Our results suggest that miR100 is required to direct CSC self-renewal and differentiation.
PMCID: PMC4370193  PMID: 25217527

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