Objective To evaluate the efficacy of rituximab in treating chronic lymphocytic leukemia (CLL). Methods The clinical data of CLL patients receiving fludarabine,cyclophosphamide±rituximab (with or without rituximab) regimen or cyclophosphamide,vincristine,and prednisone±doxorubicin±rituximab regimen in our hospital from March 2000 to February 2015 were analyzed retrospectively. Therapeutic efficacies and survivals of patients treated with different regimens were evaluated and compared. Results The complete response (CR) rate and the overall response rate (ORR) in 72 patients (43.6%) treated with rituximab were significantly higher than those treated without rituximab (38.9% vs. 21.5%,P=0.015;83.3% vs. 60.2%,P=0.001). The median PFS and OS for patients treated with rituximab were 53.0 (27.0-79.0) months and 112.0 (81.1-142.9) months,and the median PFS and OS for patients treated without rituximab were 28.0 (18.3-37.7) months and 89.0(72.0-106.0),but the results were not statistically significant (P=0.094,P=0.109). According to the cytogenetic features,patients were further divided into high-risk subgroup (with chromosome 17p deletion or 11q deletion) and non-high-risk subgroup. And in the high-risk subgroup,the ORR of patients treated with rituximab was 86.4%,which was significantly higher than that in patients treated without rituximab (53.3%)(P=0.012);in the non-high-risk subgroup,the PFS was marginally prolonged in patients treated with rituximab,but the difference was not statistically significant(P=0.050). Conclusions Compared with traditional chemotherapy,the chemoimmunotherapies with rituximab result in higher CR rate and ORR in CLL patients. In patients without 17p deletion or 11q deletion,the use of rituximab can marginally prolong PFS.

Compound Yizhihao, consists of Radix isatidis, Folium isatidis, Artemisia rupestris, has a significant therapeutic effect on the treatment of influenza and fever. However, the mechanism of its action is still unclear. In this investigation, we collected the key target molecule of influenza disease and the chemical constituents of Compound Yizhihao, and developed Naïve Bayesian classification models based on the input molecular fingerprints and molecule descriptors. The built models were further applied to construct classifiers for predicting the effective constituents. We used the professional network-building software to build the constituent-target network and target-pathway network, which revealed the network pharmacology of the effective constituents in Compound Yizhihao. It will contribute to the further research of mechanism of Compound Yizhihao.

The study was designed to explore the drug-drug interactions mechanisms mediated by OATP1B1 between traditional Chinese medicine Danshensu and rosuvastatin. First, the changes of rosuvastatin pharmacokinetics were investigated in presence of Danshensu in rats. Then, the primary rat hepatocytes model was established to explore the effects of Danshensu on the uptake of rosuvastatin by hepatocytes. Finally, HEK293T cells with overexpression of OATP1B1*a and OATP1B1*5 were established using a lentiviral delivery system to explore the effects of Danshensu on the uptake of rosuvastatin. Rosuvastatin pharmacokinetic parameters of C(max0, AUCO(0-t), AUC(0-∞) were increased about 123%, 194% and 195%, by Danshensu in rats, while the CL z/F value was decreased by 60%. Uptake of rosuvastatin in the primary rat hepatocytes was decreased by 3.13%, 41.15% and 74.62%, respectively in the presence of 20, 40 and 80 μmol x L(-1) Danshensu. The IC50 parameters was (53.04 ± 2.43) μmol x L(-1). The inhibitory effect of Danshensu on OATP1B1 mediated transport of rosuvastatin was related to the OATP1B1 gene type. In OATP1B1*5-HEK293T mutant cells, transport of rosuvastatin were reduced by (39.11 ± 4.94)% and (63.61 ± 3.94)%, respectively, by Danshensu at 1 and 10 μmol x L(-1). While transport of rosuvastatin was reduced by (8.22 ± 2.40)% and (11.56 ± 3.04)% and in OATP1B1*1a cells, respectively. Danshensu significantly altered the pharmacokinetics of rosuvastatin in rats, which was related to competitive inhibition of transport by OATPJBI. Danshensu exhibited a significant activity in the inhibition of rosuvastatin transport by OATP1B1*5-HEK293T, but not by OATP1B1*1a, suggesting a dependence on OATP1B1 sequence.
Animals ; Drug Interactions ; Drugs, Chinese Herbal ; pharmacology ; HEK293 Cells ; Hepatocytes ; drug effects ; metabolism ; Humans ; Lactates ; pharmacology ; Organic Anion Transporters ; metabolism ; Rats ; Rosuvastatin Calcium ; pharmacology ; Solute Carrier Organic Anion Transporter Family Member 1b1

The study was designed to explore the drug-drug interactions mechanisms mediated by OATP1B1 between traditional Chinese medicine Danshensu and rosuvastatin. First, the changes of rosuvastatin pharmacokinetics were investigated in presence of Danshensu in rats. Then, the primary rat hepatocytes model was established to explore the effects of Danshensu on the uptake of rosuvastatin by hepatocytes. Finally, HEK293T cells with overexpression of OATP1B1*a and OATP1B1*5 were established using a lentiviral delivery system to explore the effects of Danshensu on the uptake of rosuvastatin. Rosuvastatin pharmacokinetic parameters of C(max0, AUCO(0-t), AUC(0-∞) were increased about 123%, 194% and 195%, by Danshensu in rats, while the CL z/F value was decreased by 60%. Uptake of rosuvastatin in the primary rat hepatocytes was decreased by 3.13%, 41.15% and 74.62%, respectively in the presence of 20, 40 and 80 μmol x L(-1) Danshensu. The IC50 parameters was (53.04 ± 2.43) μmol x L(-1). The inhibitory effect of Danshensu on OATP1B1 mediated transport of rosuvastatin was related to the OATP1B1 gene type. In OATP1B1*5-HEK293T mutant cells, transport of rosuvastatin were reduced by (39.11 ± 4.94)% and (63.61 ± 3.94)%, respectively, by Danshensu at 1 and 10 μmol x L(-1). While transport of rosuvastatin was reduced by (8.22 ± 2.40)% and (11.56 ± 3.04)% and in OATP1B1*1a cells, respectively. Danshensu significantly altered the pharmacokinetics of rosuvastatin in rats, which was related to competitive inhibition of transport by OATPJBI. Danshensu exhibited a significant activity in the inhibition of rosuvastatin transport by OATP1B1*5-HEK293T, but not by OATP1B1*1a, suggesting a dependence on OATP1B1 sequence.

The study was designed to explore the drug-drug interactions mechanisms mediated by OATP1B1 between traditional Chinese medicine Danshensu and rosuvastatin. First, the changes of rosuvastatin pharma­cokinetics were investigated in presence of Danshensu in rats. Then, the primary rat hepatocytes model was established to explore the effects of Danshensu on the uptake of rosuvastatin by hepatocytes. Finally, HEK293T cells with overexpression of OATP1B1*1a and OATP1B1*5 were established using a lentiviral delivery system to explore the effects of Danshensu on the uptake of rosuvastatin. Rosuvastatin pharmacokinetic parameters of C_max, AUC_0-t, AUC_0-∞ were increased about 123%, 194% and 195%, by Danshensu in rats, while the CL_z/F value was decreased by 60%. Uptake of rosuvastatin in the primary rat hepatocytes was decreased by 3.13%, 41.15% and 74.62%, respectively in the presence of 20, 40 and 80 μmol·L^-1 Danshensu. The IC₅₀ parameters was (53.04 ± 2.43) μmol·L^-1. The inhibitory effect of Danshensu on OATP1B1 mediated transport of rosuvas­tatin was related to the OATP1B1 gene type. In OATP1B1*5-HEK293T mutant cells, transport of rosuvastatin were reduced by (39.11 ± 4.94) % and (63.61 ± 3.94) %, respectively, by Danshensu at 1 and 10 μmol·L^-1. While transport of rosuvastatin was reduced by (8.22 ± 2.40) % and (11.56 ± 3.04) % and in OATP1B1*1a cells, respectively. Danshensu significantly altered the pharmacokinetics of rosuvastatin in rats, which was related to competitive inhibition of transport by OATP1B1. Danshensu exhibited a significant activity in the inhibition of rosuvastatin transport by OATP1B1*5-HEK293T, but not by OATP1B1*1a, suggesting a dependence on OATP1B1 sequence.

Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Pancreatic Neoplasms ; diagnosis ; Solitary Fibrous Tumors ; diagnosis

OBJECTIVETo investigate whether there are different stromal compositions in the prostate tissue of patients with benign prostatic hyperplasia (BPH) and evaluate their significance in the course of the disease.

METHODSForty-three surgical or bioptic prostatic specimens of BPH and 5 autoptic normal prostatic specimens were stained by the Masson method to display the elements of the muscle fiber and collagen. The relationship of the changes in the prostatic stromal composition was analyzed with the degree of bladder outlet obstruction (BOO) , IPSS and medication results.

RESULTSThe mean ratio of muscle fiber to collagen in the normal prostate tissue was (3.2 +/- 0.2):1, significantly higher than that of the BPH patients (1: [4.7 +/- 3.1] ) (P < 0.01); that in the BPH patients with BOO was 1: (5.4 +/- 3.7) markedly lower than in those without BOO (1: [2.5 +/- 1.1] ) (P = 0.02); that in the BPH patients with severe prostatic symptoms was 1: (9.1 +/- 2.9), remarkably lower than in those with moderate (1: [5.3 +/- 3.4]) and mild prostatic symptoms (1: [2.8 +/- 1.7]) (P < 0.01); and that in the BPH patients with satisfactory medicinal therapeutic results was 1:(2.3 +/- 1.9), significantly higher than in those with poor therapeutic results (1: [7.6 +/- 4.3]) (P < 0.01).

CONCLUSIONThe stromal composition in the prostatic tissue of BPH patients undergoes different degrees of changes. More obvious BPH symptoms and poorer therapeutic results are associated with a bigger proportion of collagens and a smaller proportion of muscle fibers in the prostatic tissue. These changes may play an important role in the development and progression of BPH.

Aged ; Aged, 80 and over ; Case-Control Studies ; Fibrosis ; Humans ; Male ; Middle Aged ; Prostate ; pathology ; Prostatic Hyperplasia ; pathology ; Urinary Bladder Neck Obstruction ; pathology

OBJECTIVETo explore the efficacy of neuromodulation (including sacral neuromodulation and dorsal penile/clitoral nerve neuromodulation) for the treatment to neurogenic bowel dysfunction due to spinal cord injury.

METHODSFrom January 2006 to April 2008, 9 patients with neurogenic constipation after spinal cord injury underwent the therapy of neuromodulation, 1 patient underwent the therapy of sacral neuromodulation, 8 patients underwent the therapy of dorsal penile/clitoral nerve neuromodulation. The therapeutic efficacy was evaluated and followed up by means of Wexner constipation score.

RESULTSOne patient received permanent electrode and neurostimulator implantation and constipation were improved continuously. A significant improvement in the Wexner constipation score was observed compared with the preoperative baseline level (preoperative baseline: median 22; after implantation: median 9). Four patients were effective after the therapy of dorsal penile/clitoral nerve neuromodulation. Wexner constipation score decrease from 19 to 11 after 12 weeks dorsal penile/clitoral nerve neuromodulation. Patients also showed a significant improvement in their symptoms and quality of life during follow up.

CONCLUSIONSSacral neuromodulation and dorsal penile/clitoral nerve neuromodulation may be effective for some neurogenic constipation. However there are no methods successfully identify the candidate who will be beneficial before the procedure. Good quality research data are needed to evaluate the effects of sacral neuromodulation and dorsal penile/clitoral nerve neuromodulation for these conditions.

Constipation ; etiology ; therapy ; Electric Stimulation Therapy ; methods ; Electrodes, Implanted ; Female ; Follow-Up Studies ; Humans ; Male ; Spinal Injuries ; complications ; Treatment Outcome

OBJECTIVETo compare the effect between lumbar backwards flexion manipulation and rotating manipulation for treating lumbar intervertebral disc herniation.

METHODSTwo hundred and nine patients of lumbar intervertebral disc herniation, male 131, female 78, the age from 20 to 79 years old, 58 cases of all these patients age above 50. According to diagnosis the ladder of the 92 cases bulging type, 69 hernia type, 48 cases free type. The patients were randomly divided into treatment group (107 cases) and control group (102 cases). All the patients were treated with the three-dimensional computer-controlled traction therapeutic apparatus, with continued traction for 30 minutes. After traction, lumbar backwards flexion manipulation and rotating manipulation were respectively adopted in treatment group and control group (on alternate days one time, 3 times as a course of treatment). The symptoms and signs (including back pain and discomfort, lower limb pain and numbness, powerless urination and defecation, numbness in perineum, straight-leg raising degree, ability of lower extremity walking, work and live) of patients were observed after treatment.

RESULTSAll the patients were followed up from 1 to 6 months with an average of 3.2 months. After treatment, the symptoms and signs of patients have markedly improved (P < 0.01), but the lower back pain and discomfort, lower limb walking ability in treatment group were better than control group (P < 0.05). According therapeutic criteria, the effect of treatment group was better than of control group (P < 0.01). In cases with bulging type, 47 in treatment group and 45 in control group, the effect of treatment group was better than of control group (P < 0.05); in cases with hernia type, 35 in treatment group and 34 in control group, there was no significantly difference in effect between two groups (P > 0.05); in cases of free type, 25 in treatment group and 23 in control group, there was no significantly difference in effect between two groups (P > 0.05).

CONCLUSIONThe global effect of lumbar backwards flexion manipulation was satisfactory than rotating manipulation for treating lumbar intervertebral disc herniation. But rotating manipulation suited to free type.

Adult ; Aged ; Female ; Follow-Up Studies ; Humans ; Intervertebral Disc Displacement ; surgery ; therapy ; Lumbar Vertebrae ; pathology ; Male ; Manipulation, Orthopedic ; methods ; Middle Aged ; Treatment Outcome

BACKGROUNDYupingfeng, a traditional Chinese complex prescription, has been used efficaciously in China for the cure and prevention of inflammatory diseases related to immunodeficiency such as allergic rhinitis and chronic bronchitis. However, the active components of this prescription remain unclear. The present study focused on investigating the antiinflammatory and immunoregulatory effects of the glucosidic extract from Yupingfeng.

METHODSWe tested animal models for ear swelling induced by dimethylbenzene in mice; palm swelling induced by carregeenin and granuloma induced by cotton pellet in rats; level of haemolysin, antibody generation by the splenic cells, delayed hypersensitivity and T cell subsets in spleen of immunosuppressed mice.

RESULTSGlucosidic extract of 24 mg/kg, 48 mg/kg and 96 mg/kg significantly inhibited mice's ear swelling induced by dimethylbenzene. Similarly glucosidic extract of 16 mg/kg, 32 mg/kg and 64 mg/kg inhibited rats' palm swelling induced by carregeenin and granuloma induced by cotton pellet. Glucosidic extract of 24 mg/kg, 48 mg/kg and 96 mg/kg improved the IgM level in serum and level of haemolysin in splenocytes in mice immunosuppressed by cyclophosphamide. Delayed hypersensitivity in mice suppressed by cyclophosphamide was enhanced by glucosidic extract of 24 mg/kg, 48 mg/kg and 96 mg/kg. These results suggested that Yupingfeng could recover humoral and cellular immune function in mice with immunosuppression. Glucosidic extract of 48 mg/kg and 96 mg/kg significantly resisted the immunosuppressive mice ear swelling and maintained it at nearly normal level. The enhanced, delayed hypersensitivity actions of glucosidic extract, suppressed by cyclophosphamide, might be brought about by inducing TH cell and regulating T lymphocytes subset.

CONCLUSIONSThe glucosidic extract from Yupingfeng has antiinflammatory and immunoregulation action, suggesting that these glucosides are the principal active components of the traditional Chinese prescription Yupingfeng.

Animals ; Anti-Inflammatory Agents ; therapeutic use ; Carrageenan ; toxicity ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Glucosides ; therapeutic use ; Granuloma ; chemically induced ; drug therapy ; Guinea Pigs ; Immunosuppressive Agents ; therapeutic use ; Mice ; Mice, Inbred BALB C ; Otitis ; chemically induced ; drug therapy ; Rats ; Rats, Sprague-Dawley ; Xylenes ; toxicity