OBJECTIVETo analyze the factors affecting pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients.

METHODSA retrospective cohort study was carried out to analyze the clinical data of 141 breast cancer patients treated with neoadjuvant chemotherapy. The factors affecting pCR and the changes of tumor receptor status before and after treatment were analyzed.

RESULTSAmong all the 141 patients, 21 patients (14.9%) achieved pCR. The rate of pCR achieved by regimens of anthracycline combined with taxane was higher (16.8%, 19/113) than that by anthracycline-containing regimens (7.1%, 1/14). The dose intensity of anthracycline had a significant correlation with pCR rate (P < 0.05). The pCR rate in the relative dose intensity of taxane ≥ 0.85 arm was higher than that of < 0.85 arm (P = 0.02). Eighty patients (56.7%) had completed more than 4 cycles of chemotherapy and the median time to achieve pCR was 6 (3 to 10) cycles. The pCR rate had a significant difference between patients < 6 and ≥ 6 cycles (7.1% vs. 22.5%,P = 0.01). Multivariate analysis showed that tumor size measured by palpation ≤ 5 cm and ≥ 6 chemotherapy cycles were significantly related with pCR rate (P < 0.05). In all the 21 pCR patients, the pre-treatment ER(-), PR(-), HER-2(-) statuses were in 14, 14 and 17 patients, respectively. The status of ER, PR, HER-2 of most patients (74.2%, 69.7% and 87.7%, respectively) was not changed after treatment. Among the patients with changes in receptor status, ER changed from negative to positive was in the majority (37.1%, 13/35 vs. 12.9%, 4/31, P < 0.05), and the percentage of changes in PR and HER-2 status had no significant differences.

CONCLUSIONSThe regimens of anthracycline combined with taxane can achieve a higher pCR rate. The lymph node and receptor status before therapy have no significant correlation with pCR. Patients who have primary tumor size ≤ 5 cm, ≥ 6 chemotherapy cycles and enough dose intensity are easier to achieve pCR. The receptor status before and after therapy should be determined, and according to any positive results, physicians can chose HER-2 targeted therapy and/or endocrine therapy after surgery to benefit the patients.

Adult ; Aged ; Aged, 80 and over ; Anthracyclines ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Bridged-Ring Compounds ; administration & dosage ; Chemotherapy, Adjuvant ; Dose-Response Relationship, Drug ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoadjuvant Therapy ; methods ; Proportional Hazards Models ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Remission Induction ; Retrospective Studies ; Taxoids ; administration & dosage ; Tumor Burden

Carnosol has been proved to have anti-breast cancer effect in previous research. But its ER subtype's specific regulation and mediation mechanisms remain unclear. The aim of this study is to observe the effect of carnosol on cell proliferation and its estrogen receptor α and β's specific regulation and mediation mechanisms with ER positive breast cancer T47D cell. With estrogen receptor α and β antagonists MPP and PHTPP as tools, the MTT cell proliferation assay was performed to observe the effect of carnosol on T47D cell proliferation. The changes in the T47D cell proliferation cycle were detected by flow cytometry. The effect of carnosol on ERα and ERβ expressions of T47D cells was measured by Western blot. The findings showed that 1 x 10(-5)-1 x 10(-7) mol x L(-1) carnosol could significantly inhibit the T47D cell proliferation, which could be enhanced by MPP or weakened by PHTPP. Meanwhile, 1 x 10(-5) mol x L(-1) or 1 x 10(-6) mol x L(-1) carnosol could significantly increase ERα and ERβ expressions of T47D cells, and remarkably increase ERα/ERβ ratio. The results showed that carnosol showed the inhibitory effect on the proliferation of ER positive breast cancer cells through target cell ER, especially ERβ pathway. In the meantime, carnosol could regulate expressions and proportions of target cell ER subtype ERα and ERβ.
Blotting, Western ; Breast Neoplasms ; metabolism ; pathology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Diterpenes, Abietane ; chemistry ; pharmacology ; Dose-Response Relationship, Drug ; Estrogen Receptor Modulators ; pharmacology ; Estrogen Receptor alpha ; antagonists & inhibitors ; metabolism ; Estrogen Receptor beta ; antagonists & inhibitors ; metabolism ; Female ; Flow Cytometry ; Humans ; Molecular Structure ; Pyrazoles ; pharmacology ; Pyrimidines ; pharmacology

OBJECTIVETo evaluate the short-term efficacy and safety of Bushen Shuji Granule (BSG) in treating ankylosing spondylitis (AS) patients.

METHODSA prospective randomized controlled clinical trial was carried out in 62 active stage AS patients with Shen deficiency Du-channel cold syndrome (SDDCS), who were randomly assigned to the BSG group (treated with BSG) and the control group (treated with Celecoxib Capsule). Twelve weeks consisted of one therapeutic course. Therapeutic effects were evaluated by ASAS20 and ASAS40 (set by Assessments in Ankylosing Spondylitis working group) , BASDA150, Chinese medical (CM) syndrome efficacy evaluation standards. BASDAI, the Bath Ankylosing Spondylitis Functional Index (BASFI), the Bath AS Metrology Index (BASMI), scores for spine pain, scores for pain at night, patient global assessment (PGA) , erythrocyte sedimentation rate (ESR) , and C reactive protein (CRP) were observed before and after treatment.

RESULTSAfter three-month treatment by BSG, ASAS20 standard rate was 63. 33% (19/30 cases) in the BSG group and 66.67% (20/30 cases) in the control group with no significant difference between the two groups (χ2 = 0.073, P > 0.05). The efficacy for CM syndromes was 70.00% (21/30 cases) in the BSG group, higher than that in the control group [40.00% (12/30 cases), χ2 = 5.455, P < 0.05]. Scores for CM syndromes, BASDAI, night pain index, spinal pain index, PGA, CRP were improved in the BSG group (P < 0.05, P < 0.01). The incidence of adverse events in the BSG group was lower than that of the control group.

CONCLUSIONBSG based on Shen supplementing, Du-channel strengthening, blood activating, and channels dredging method had good short-term clinical efficacy and safety in treating AS.

Asian Continental Ancestry Group ; Biomedical Research ; Blood Sedimentation ; C-Reactive Protein ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Pain ; Prospective Studies ; Safety ; Spondylitis, Ankylosing ; drug therapy

OBJECTIVETo evaluate the clinical efficacy and safety of bushen quhan zhiwang decoction (BQZD) combined methotrexate (MTX) in treating rheumatoid arthritis (RA).

METHODSA prospective, randomized controlled study was carried out. RA patients of Shen deficiency and cold invading syndrome in the treatment group (120 cases) were treated with BQZD and MTX (10 mg/week), while those in the control group (120 cases) were treated with MTX (10 mg/week) alone. The therapeutic course for all was 24 weeks. The efficacy and safety indices were evaluated at the baseline and 24 weeks after treatment, including clinical signs and symptoms, condition assessment, Health Assessment Questionnaire (HAQ), disease activity index 28 (DAS28), laboratory parameters of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), safety indicators, and Chinese medical syndrome integrals.

RESULTSThe total effective rate was 80. 0% in the treatment group, better than that of the control group (66.7%), showing statistical difference (P <0.01). In the two groups significant improvement of clinical signs and symptoms, ESR, CRP, visual analogue scale (VAS) by both physicians and patients, HAQ, DAS28, and Chinese medical syndrome integrals after treatment were shown (P <0.01). Better effects were obtained in the treatment group in lessening tender joint numbers and swollen joint numbers, VAS by both physicians and patients, DAS28, and Chinese medical syndrome integrals (P < 0.05). Besides, adverse reactions occurred less in the treatment group than in the control group (P < 0.05).

CONCLUSIONSBQZD had roles in relieving symptoms, improving joint functions, signs, ESR, and CRP. It was an effective herb for RA patients of Shen deficiency and cold invading syndrome. It could enhance the efficacy and reduce adverse reactions of MTX through synergistic effects with MTX.

Adult ; Aged ; Arthritis, Rheumatoid ; diagnosis ; drug therapy ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Methotrexate ; adverse effects ; therapeutic use ; Middle Aged ; Prospective Studies ; Treatment Outcome

Objective To assess the changes on the whole night polysomnography (PSG) in patients with chronic fatigue syndrome(CFS). Methods The whole night PSGs were recorded from 24 patients with CFS and 33 normal subjects. Results Compared with normal subjects, patients with CFS showed significantly reduced total sleep duration ([488.7?21.7]min vs [515.9?31.7]min, P

Autophagy acts as an important homoeostatic mechanism by degradation of cytosolic constituents and plays roles in many physiological processes. Recent studies demonstrated that autophagy can also regulate the production and secretion of the proinflammatory cytokine interleukin-1β (IL-1β), which plays a critical role in the development and maintenance of neuropathic pain. In the present study, the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were significantly decreased after spinal nerve ligation (SNL), and the changes were accompanied by inhibited autophagy in the spinal microglia and increased mRNA and protein levels of IL-1β in the ipsilateral spinal cord. We then investigated the antinociceptive effect of rapamycin, a widely used autopahgy inducer, on SNL-induced neuropathic pain in rats and found that treatment with intrathecal rapamycin significantly attenuated the mechanical allodynia and thermal hyperalgesia. Moreover, rapamycin significantly enhanced autophagy in the spinal microglia, whereas it reduced the mRNA and protein levels of IL-1β in the ipsilateral spinal cord. Our results showed that rapamycin could ameliorate neuropathic pain by activating autophagy and inhibiting IL-1β in the spinal cord.
Animals ; Autophagy ; drug effects ; Immunosuppressive Agents ; Interleukin-1beta ; antagonists & inhibitors ; metabolism ; Male ; Neuralgia ; drug therapy ; metabolism ; pathology ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Sirolimus ; pharmacology ; Spine ; metabolism ; pathology

OBJECTIVETo explore the role of cytokines and keratinocytes in the survival mechanism of mixed auto and allogeneic skin grafting.

METHODSThirty-six SD rats were employed in the study. The rat model with mixed auto and allogeneic skin grafting and mixed human epithelial and lymphocytic culture (MELC) model were established. The change of IL-10 in the serum and the supernatant of the cultured tissue sample from the local wound was observed after the mixed skin grafting in scalded rats. And the role of epithelium in the induction of immunosuppression in vitro was monitored.

RESULTSThe serum IL-10 content in the rats with mixed skin grafting (25.89 +/- 2.82 ng/L) at 7 postoperative day (POD) was evidently higher than that in normal rats (14.20 +/- 2.43 ng/L) (P < 0.05). The IL-10 content in the culture supernatant of rat tissue samples exhibited evident different during 4-14 PODs (P < 0.05-0.01), while which was no difference to that in normal rat on 21st and 28th POD. The inhibiting effects of autologous epithelia and keratinocytes in MELC system were correlated with their dosage. After the adding of autologous keratinocytes to MELC system the cytokines secreted from Th1 could induce the secretion of cytokines from Th2 by IL-10 mediation. This effect could be corrected by the addition of monoclonal antibody of IL-10.

CONCLUSIONThe keratinocytes inlayed in the autoskin during mixed grafting could increase the local IL-10 level by activating Th2 cells, which might be one of the important reasons of the survival of mixed skin grafting.

Animals ; Burns ; immunology ; surgery ; Cytokines ; metabolism ; Giant Cells, Langhans ; cytology ; Graft Survival ; immunology ; Humans ; Interleukin-10 ; metabolism ; Keratinocytes ; cytology ; Lymphocyte Culture Test, Mixed ; Male ; Rats ; Rats, Sprague-Dawley ; Skin Transplantation ; immunology ; Th2 Cells ; metabolism ; Transplantation, Autologous ; Transplantation, Homologous

OBJECTIVETo study the biomechanical properties of self-designed calcaneal anatomical plate and pre-cut gudgeon system and its efficacy for calcaneal fracture fixation.

METHODSSixteen fresh foot specimens were randomly divided into experimental group and the control group. Axial compressive load were applied to all specimens in order to create a calcaneal fracture model, and the maximum load and the maximum arch displacement of experimental group were recorded. In experimental group, self-designed intenal fixation system were utilized, while the AO plate internal fixation system were utilized in the control group. Axial compressive test were applied again to both groups, and the maximum load, the foot arch displacement and calcanus broadens were measured and recorded.

RESULTSComparison between before and after fixing the calcaneus fracture by self-designed internal fixation system in experimental group, the difference of the maximum load was significant (P<0.01), but there was no significant difference (P>0.05) of the maximum arch displacement. All parameters were significantly different (P<0.01) between the experimental group and the control group.

CONCLUSIONThe fractured calcaneus will be able to regain normal foot biomechanical function after treated by self-designed internal fixation system, and able to support foot arch to bear great load. The self-designed internal fixation and pre-cut gudgeon system is considered to outperform the conventional AO internal fixation system with its better effectiveness and outcome in treating calcaneus fractures.

Adolescent ; Adult ; Biomechanical Phenomena ; Bone Plates ; Calcaneus ; injuries ; physiopathology ; Female ; Fracture Fixation, Internal ; methods ; Fractures, Bone ; physiopathology ; surgery ; Humans ; Male ; Middle Aged ; Young Adult

BACKGROUNDPostoperative knee soft tissue irritation is a common complication after retrograde nail fixation of femoral fractures. Distal locking screw prominence is one of the causes for soft tissue irritation. This study aimed to determine whether the use of the femoral condyles tangential views improve the diagnostic accuracy compared with anteroposterior (A-P) view in detecting distal locking screw penetrations during retrograde femoral nailing.

METHODSThe angle between the sagittal plane and lateral aspect of the condyle and the angle between the sagittal plane and medial aspect of condyle were measured on computed tomography (CT) images. After the angles were measured and recorded, cadaveric femurs were used in a simulated surgical procedure. The retrograde femoral nail was inserted into the femur and placed distal locking screws, which were left 2, 4, and 6 mm proud of the medial and lateral condyles for each femur. A-P view, lateral condyle tangential view and medial condyle tangential view were obtained. All fluoroscopic images were recorded and sent to three observers blinded to the experimental procedure to determine whether screws penetrated the condyle cortex or not.

RESULTSAccording to the results of CT scan, the lateral condyle view was 20.88 ± 0.98° and the medial condyle view was 40.46 ± 3.14°. In the A-P view, we detected 0% at 2 mm penetration, 16.7% (lateral condyle screw) and 25.0% (medial condyle screw) at 4 mm, and 41.7% (lateral condyle screw) and 58.3% (medial condyle screw) at 6 mm. In the lateral tangential view, we detected 91.7% at 2 mm penetration of the lateral condyle and 100% at 4 mm and 6 mm. In the medial tangential view, we detected 66.7% at 2 mm penetration of the medial condyle and 100% at 4 mm and 6 mm. The femoral condyle tangential views provided significant improvement in detecting screw penetrations at all lengths (2, 4, and 6 mm) compared with the A-P view (P < 0.05).

CONCLUSIONSThe femoral condyles tangential views increased the accuracy of detecting screw penetrations on the medial and lateral condyles. Routine clinical use of the femoral condyles tangential views has the potential to increase accuracy in detecting distal locking screw penetration during retrograde femoral nailing.

Bone Screws ; Femoral Fractures ; diagnostic imaging ; surgery ; Fracture Fixation, Internal ; Fracture Fixation, Intramedullary ; Humans ; Tomography, X-Ray Computed

The purpose of this study was to investigate the vasorelaxing effect of vasonatrin peptide (VNP) on human intramammary artery (HIMA).The vasorelaxing effect of VNP on HIMA was measured by means of perfusion in vitro. The effects of HS-142-1, TEA, 8-Br-cGMP and methylene blue (MB) were also observed. It was found that VNP caused a concentration-dependent relaxation in HIMA which was independent of the endothelium. 8-Br-cGMP (0.1-1000 micromol/L) also caused a concentration-dependent relaxation in HIMA. The vasorelaxing effect of VNP disappeared in the presence of HS-142-1 (20 micromol/L), an antagonist of the natriuretic peptide guanylate cyclase (GC) receptor. MB (10 micromol/L), an inhibitor of GC, not only blocked completely the relaxation of HIMA, but also enhanced the vascular contraction induced by norepinephrine. TEA (1 mmol/L), an antagonist of calcium activated potassium channels (K(Ca)), reduced but not completely blocked the vasorelaxing effect of VNP. These findings suggest that VNP can relax HIMA, which is independent of the endothelium. This effect is possibly achieved by the binding of VNP with the natriuretic peptide GC receptors in the smooth muscle cells (SMCs), leading to an increase in intracellular cGMP level. Moreover, the vasorelaxing effect of VNP is associated with K(Ca).
Aged ; Atrial Natriuretic Factor ; pharmacology ; Dose-Response Relationship, Drug ; Humans ; In Vitro Techniques ; Mammary Arteries ; drug effects ; physiology ; Middle Aged ; Potassium Channels, Calcium-Activated ; metabolism ; Receptors, Guanylate Cyclase-Coupled ; metabolism ; Vasodilation ; drug effects ; physiology