OBJECTIVE To prepare and characterize curcumin nanomicelles （hereinafter referred to as Cur/mPEG-PBLA micelles）， and to evaluate the in vitro hepatoprotective activity against alcohol liver disease （ALD）. METHODS Cur/mPEG-PBLA micelles were prepared with the dialysis method using methoxy-poly（ethylene glycol）-poly（β-benzyl-L-aspartate） （mPEG-PLGA） as the carrier. The appearance and microscopic morphology of Cur/mPEG-PBLA micelles were observed， and particle size， polydispersity index， Zeta potential， encapsulation efficiency and drug loading content were all detected. The in vitro release， pH stability， thermal stability， dilution stability， storage stability， plasma stability tests， and hemolysis experiments were all performed. The cell model of ALD was established with anhydrous ethanol intervention using human liver cancer cells and normal liver cells as objects， Cur reference solution as reference， to evaluate in vitro preventive and ameliorative effects of Cur/mPEG- PBLA micelles on ALD. RESULTS The prepared Cur/mPEG-PBLA micelles exhibited a pale-yellow milky light， with a spherical shape and uniform distribution. The average particle size was about 140 nm， and the polydispersity index was less than 0.3. Zeta potential was （－8.15±0.05） mV； the encapsulation efficiency was （73.26±3.16）%， and the drug loading content was （4.87± 0.42）%. The cumulative release of Cur reference substance was close to 80% at 10 h； the cumulative release of Cur/mPEG-PBLA micelles at 8 h was 28.94% and only 48.25% at 48 h. pH stability and thermal stability of Cur/mPEG-PBLA micelles were better than those of Cur reference solution； Cur/mPEG-PBLA micelles showed good dilution stability， storage stability and plasma stability， and would not cause hemolysis. Cur reference solution and Cur/mPEG-PBLA micelles had varying degrees of in vitro preventive and ameliorative effects on ALD in two types of cells； after 48 h of application， the above effects of Cur/mPEG-PBLA micelles were significantly better than those of Cur reference solution at the same mass concentration （P＜0.05）. CONCLUSIONS Cur/mPEG-PBLA micelles can improve pH stability and thermal stability of Cur， delayits degradation rate， and have better in vitro hepatoprotective activity against ALD.

Humans ; Granuloma, Pyogenic/pathology* ; Hemangioma, Capillary

OBJECTIVES: Stably expressed transforming growth factor -beta 1(TGF-β1)MCs were obtained and the effects of centellaasiatica (CA) granule on the expressions of Smad 2/3, Smad 7 and collagen Ⅳ and the level of Smad 2/3 phosphorylation were observed. METHODS: Lipofectin method was used to transfect TGF-β1 vector into MC, and the stably expressed TGF-β1 cell lines were selected by G418. The cells were divided into three groups. Control group:normal MC + RPMI 1640 + 10% normal rat serum; TGF-β1 group:stably expressed TGF-β1 MC + RPMI 1640 + 10% normal rat serum; CA group:stably expressed TGF-β1 MC + RPMI 1640 + 10% rat serum containing high CA. The experiments were repeated for five times. The contents of TGF-β1 and collagen Ⅳ in the culture medium were detected with ELISA, the expressions of mRNA and protein of TGF-β1, Smad 2/3, Smad 7 and the level of Smad 2/3 phosphorylation were detected by using real time quantitative polymerase chain reaction and Western blot. RESULTS: The contents of TGF-β1 and collagen Ⅳ in the culture medium of stably-expressed TGF-β1 MC were increased significantly, and the CA could reverse the effects of TGF-β1. The expressions of mRNA and protein of TGF-β1, Smad 2/3 and the level of Smad 2/3 phosphorylation were increased significantly in TGF-β1 transfected MC, and CA could dramatically reduce the expressions of mRNA and protein of TGF-β1, Smad 2/3 and the level of Smad 2/3 phosphorylation. The high expression of TGF-β1 decreased the expression of Smad 7 mRNA and protein, and the CA could antagonize the effect of mRNA expression. CONCLUSIONS The MCs stably-expressed TGF-β1 can activate the TGF-β1/Smad signal pathway and increase the expression of collagen Ⅳ. CA can decrease the occurrence of diabetic nephropathy(DN) by reducing the production of collagen Ⅳ through inhibiting the TGF-β1/Smad signal pathway.
Animals ; Cells, Cultured ; Centella ; chemistry ; Collagen Type IV ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Mesangial Cells ; drug effects ; metabolism ; Rats ; Signal Transduction ; Smad Proteins ; metabolism ; Smad2 Protein ; metabolism ; Smad3 Protein ; metabolism ; Smad7 Protein ; metabolism ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVE: To investigate the effects of centella asiatica (CA) granule on the expression of transform growth factor-β(TGF-β) and related down-stream signals in rats with early diabetic nephropathy(DN) and to clarify the molecular mechanisms of CA molecular mechanism of on preventing and curing early diabetic kidney disease DN by studying the effects of centella asiatica on TGF-β expression and related down-stream signals. METHODS: Sixty male SD rats were divided into control group(=10) and DN model group(=50). The model rats were made a right nephrectomy. One week later, diabetic nephropathy was induced by intraperitoneal injection of streptocozin(30 mg/kg) for three consecutive days. High blood glucose level of Tail vein (fasting glucose ≥ 16.7 mmol/L) and high urinary protein level(total protein level in DN group was more than twice higher than the control group) were measured to confirm early DN in rats. In the sham operation group, the right renal capsule was damaged and the corresponding amount of saline was injected. The model rats were administrated by the means of intragastric administration. The DN model group were divided into DN group, DN+fosinopril group(1.6 mg/kg·d), DN+high CA group(16.8 mg/kg·d), DN+medium CA group(11.2 mg/kg·d) and DN+low CA group(5.6 mg/kg·d), and each group was intragastric administration one time every morning last for 16 weeks. The expressions of mRNA and protein of TGF-β, TβR1, TβR2, Smad2/3, Smad7 and the level of Smad2/3 phosphorylation were detected by using real time quantitative polymerase chain reaction and Western blot. RESULTS: The expressions of mRNA and protein of TGF-β, TβR1, TβR2, Smad2/3 and the level of Smad2/3 phosphorylation were significantly increased, the expressions of mRNA and protein of Smad7 were dramatically decreased. The fosinopril and high dosage CA could reverse the effects of DN. CONCLUSIONS CA plays an important role in preventing and curing DN through regulating the TGF-β/Smad signaling pathways.
Animals ; Centella ; chemistry ; Diabetes Mellitus, Experimental ; Diabetic Nephropathies ; chemically induced ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Kidney ; physiopathology ; Male ; Rats ; Rats, Sprague-Dawley ; Receptor, Transforming Growth Factor-beta Type I ; metabolism ; Receptor, Transforming Growth Factor-beta Type II ; metabolism ; Signal Transduction ; Smad2 Protein ; metabolism ; Smad3 Protein ; metabolism ; Smad7 Protein ; metabolism ; Transforming Growth Factor beta1 ; metabolism

Objective To investigate the clinicopathological features,survival,and the impact of postoperative adjuvant radiotherapy on the ovarian function in patients less than or equal to 35 years of age with stage ⅠB-ⅡA cervical cancer.Methods One hundred and eighty-six patients who were admitted to our hospital from 2000 to 2011 were retrospectively analyzed.An equal number of patients older than 35 years of age with cervical cancer within the same period were used as stage-marched controls.The Kaplan-Meier method was used to calculate the survival rates,and the log-rank test was used for pairwise comparison and univariate prognostic analyses.The Cox proportional hazards model was used for multivariate prognostic analyses.Results The patients less than or equal to 35 years of age had a significantly higher incidence of non-squamous carcinoma but significantly lower incidence rates of deep stromal invasion and lymph-vascular space invasion (LVSI) compared with the control group (P =0.000;P =0.008;P =0.000).Though young patients had significantly higher 5-year disease-free survival (DFS) and overall survival (OS) rates than the control group (93.7％ vs.84.5％,P=0.005;96.1％ vs.89.5％,P=0.033),age was not an independent prognostic factor (P =0.202;P =0.950).Among patients less than or equal to 35 years of age,lymph node metastasis and LVSI were independent prognostic factors for DFS (P =0.000;P =0.000),while LVSI and initial tumor size were independent prognostic factors for OS (P =0.000;P =0.000).There was no significant difference in the incidence of normal ovarian function between young patients treated with and without adjuvant radiotherapy after ovarian transposition (63％ vs.73％,P =0.422).Conclusions Patients less than or equal to 35 years of age with stage ⅠB-ⅡA cervical cancer have a better prognosis than the control group.However,age is not an independent prognostic factor.Postoperative adjuvant radiotherapy will not impair the function of transposed ovaries.

Objective:To approach the clinicopathologic characteristics, treatment modalities, and prognosis of the patients with double primary carcinoma of endometrial carcinoma and colorectal carcinoma and analyze the relationship between this disease and Lynch syndrome. Methods:The clinicopathologic and follow-up data of 34 cases with double primary carcinoma of endometrial carci-noma and colorectal carcinoma treated in Cancer Hospital of Chinese Academy of Medical Sciences were reviewed. Results:The medi-an age of the 34 patients was 51.5 years old (ranging from 39 to 76). Twenty-two of the total cases (22/34, 64.7%) had tumor family his-tory. The pathologic results indicated that 79.4%(27/34) was endometrioid adenocarcinoma. In the 34 cases, 33 were treated by surgical procedure. Of the 33 cases undergoing surgery, 17 patients with endometrial carcinoma and 19 with colorectal carcinoma received fur-ther adjuvant treatment of chemotherapy and/or radiotherapy. The 2-and 5-year survival rates were 84.3%and 63.1%in the 34 cases, respectively. Conclusion:The age of onset is earlier in the patients with double primary carcinoma than in those with sporadic colorec-tal carcinoma. Some cases have cancer family history, and their survival rates are similar to those of the patients with sporadic colorec-tum carcinoma. Diagnosis of some patients with double primary carcinoma may be in line with Lynch syndrome.

Objective To evaluate the effects of posterior segmental pedicle screw instrumentation and augmentation using calcium sulphate cement in treatment of Denis type B thoracolumbar burst fractures.Methods Forty patients with Denis type B thoracolumbar burst fracture treated between January 2011 and December 2012 were reviewed retrospectively.Twenty patients received posterior short-segment pedicle screw fixation in conjunction with screw placement at the level of fracture and calcium sulphate augmentation without posterolateral fusion (combined treatment group),but 20 patients underwent traditional short-segment pedicle screw fixation (conventional treatment group).Radiographs and CT scans evaluated local kyphotic angle on the spot of injury,anterior height of the injured vertebra,and canal encroachment before and after operation and at final follow-up.Meanwhile,visual analogue score (VAS),Oswestry disability index (ODI),and neurologic status based upon ASIA 2000 were assessed.Results Mean follow-up period was 15 months (range,12-24 months).Vertebral height restoration was equivalent of the two groups immediately after operation,but better result of kyphosis correction was found in treatment group than in control group (P ＜ 0.05).Anterior vertebral height and kyphotic angle significantly improved in treatment group compared to control group at final follow-up (P ＜ 0.05).Clinical and neurologic outcome evaluation were similar between the two groups.No implant failure occurred at follow-up.Conclusion For Denis type B thoracolumbar burst fractures,posterior segmental pedicle screw fixation augmented with calcium sulphate is effective for reducing correction loss and implant failure,compensating for the deficiencies of conventional fixation.

BACKGROUNDNerve-sparing radical hysterectomy (NSRH) was developed in an attempt to minimize complications after radical hysterectomy. Since 2008, a modified NSRH-nerve plane-sparing radical hysterectomy (NPSRH) has been developed at the Cancer Hospital, Chinese Academy of Medical Sciences. The aim of this study was to investigate the role of NPSRH in improving postoperative pelvic visceral dysfunctions.

METHODSEighty-three patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB1-IIA2 cervical cancer received NPSRH (the study group) from January 2008 to October 2012. One hundred and sixty-six patients who underwent conventional radical hysterectomy (CRH) were randomly selected as the control group. Age, pathological type and stage were matched between the two groups. The safety of surgery was assessed by duration of operation and blood transfusion rate. Postoperative short-term bladder function was analyzed by duration of catheterization. Long-term bladder, anorectal and sexual function were evaluated with questionnaires.

RESULTSSeventy-eight patients (94.0%) in the NPSRH group and one hundred and sixty patients (96.4%) in the CRH group completed the study. Median follow-up time was 31.9 months and 31.0 months respectively (P = 0.708). There was no significant difference between the two groups in terms of age, body mass index, FIGO stage, pathologic type, preoperative and postoperative therapy (P > 0.05). The blood transfusion rate shared no difference between two groups (P = 0.364). The operation time in the NPSRH group was significantly longer than CRH group (P < 0.01). But the duration of catheterization and hospitalization in the NPSRH group was significantly reduced compared with CRH group (P < 0.01). In addition, the incidence of long-term urinary frequency, urinary incontinence, urinary retention, straining to void, constipation and diarrhea was significantly lower in the NPSRH group (P < 0.05). However, there was no significant difference regarding sexual function (P > 0.05).

CONCLUSIONSThe current evidence indicated that NPSRH improved long-term bladder function compared to CRH. Moreover, it may improve long-term anorectal function as well.

Anal Canal ; physiology ; Female ; Follow-Up Studies ; Humans ; Hysterectomy ; methods ; Rectum ; physiology ; Urinary Bladder ; physiology ; Uterine Cervical Neoplasms ; surgery

Objective To evaluate efficacy,safety and complication of percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fracture (OVCF) in≥90 years patients.Methods Clinical data of 56 cases aged ≥ 90 years with osteoporotic vertebral compression fracture undergoing percutaneous kyphoplasty were retrospectively analyzed.Visual analog scale (VAS) score,analgesics administration score,locomotor activity score,bone cement leakage and incidence of refracture were evaluated before and 3 days after treatment,and at the last follow-up.Results The mean follow-up was 18.6 months (6-32 months) in all patients.The mean VAS score was (7.1 ±2.1) before treatment,(2.6±1.1) at 3 days after the procedure,and (1.8±0.7) at last follow-up,respectively (F=455.794,P＜0.001).Analgesics administration score were (2.0±1.7),(1.4±0.5) and (1.1±0.7) respectively before and 3 days after treatment,and at the last follow-up (F=9.631,P＜0.001).Locomotor activity score were (2.5±0.6),(1.2±0.5) and (1.0±0.3)before and 3 days after treatment,and at the last follow-up (F=63.254,P＜ 0.001) respectively.Bone cement leakage occurred in 10 cases(17.9％),recurrent fracture in 6 cases(10.7％),cerebrospinal leak in 3 cases (5.3％),and nerve root stimulation in2 cases(3.6％).Total complication rate was 33.9％(19/56),and all complications were transient and well tolerated.Conclusions Kyphoplasty for osteoporotic vertebral compression fracture in the very elderly is effective and safe.It alleviates fracture-induced pain,reduces analgesic drug use and improves spinal activity,and provides a better choice for minimal invasive treatment for nonagenarian OVCF patients.

Objective To investigate the safety of ovarian preservation for stage Ⅰ endometrial carcinomas in women aged 40 years and younger.Methods Seventy-five cases of stage Ⅰ endometrial cancer aged 40 years and younger from Jan 1999 to Jan 2012 were treated in Cancer Hospital , Chinese Academy of Medical Sciences.They were further divided into two groups:20 patients who underwent ovarian preservation (group A) and 55 patients who underwent oophorectomy (group B).Clinical and pathological recordings of these patients were reviewed and compared.Results In the group A , there were 13 patients preserved both ovaries , and 7 patients preserved a single ovary.While there were no significant differences in the age, body mass index, surgical staging, histology, grade, cytology of peritoneal lavage or ascites , and postoperative treatment between two groups ( all P>0.05 ).The differences in the level of CA 125 [ 25%(5/20) versus 18%(10/55)] and number of patients underwent pelvic lymphadenectomy [35% (7/20) versus 84%(46/55)] were statistically significant between two groups (all P<0.05).Of seventy-five cases, only two patients relapsed and all survived after a median follow-up time of 31.7 months ( range:0 to 160 months).Kaplan-Meier analysis revealed no difference in overall survival (100.0% versus 100.0%) and disease free survival ( 90.0% versus 95.5%) between two groups ( P =0.579 ).Conclusions Ovarian preservation has no statistically significant impact on the survival of young patients with stage Ⅰa, well differentiated endometrial cancer.Large-scale, prospective clinical studies are needed to validate the safety of ovarian preservation for those patients.