OBJECTIVES: Glioma is the most common primary intracranial tumor and there is still no ideal treatment at present. Gene therapy, as one of the new methods for treating glioma, has attracted attention in recent years. But its application in treating glioma is very limited due to lack of effective delivery vectors. This study aims to investigate the feasibility of biomimetic nanomaterials made from glioma cells-derived extracellular vesicles (EV) for targeted delivery of signal transducers and activators of transcription 3 (STAT3)-small interfering RNA (siRNA) in treating glioma. METHODS: First, U251 glioma cells-derived extracellular vessel (EVU251) was extracted by ultra-centrifugal method. Nanoparticle tracking analysis was used to characterize the particle size distribution, the transmission electron microscope was used to analyze the morphology, and Western blotting was used to verify the expression of srface characteristic protein. The homing ability was verified by cell uptake assay after labeling EVU251 with membrane dye kit PKH67; the EVU251 contents were removed by a low permeability method and then EVMU251 was prepared through a microporous membrane. Finally, the biomimetic nanomaterials EVMU251@STAT3-siRNA were prepared by loading STAT3-SiRNA with electro-dyeing method. The real-time quantitative PCR was used to quantify the successful encapsulation of siRNA, and the encapsulation and drug loading rate was calculated; then Cy5-labeled siRNA was used to evaluate the ability of biomimetic nanomaterials (EVMU251@CY5-siRNA) to target U251 cells. Lysosomal escape ability of the biomimetic nanomaterial was evaluated by lysosomal dye lyso-tracker green. At last, the ability of EVMU251@STAT3-siRNA to knock down STAT3 gene and selective killing of U251 cells was detected by cell experiments in vitro. RESULTS: The size of EVU251 ranged from 50 nm to 200 nm with a natural disc shape. The expression of extracellular vesicle marker proteins could be detected on the membrane of EVU251. The cell uptake assay demonstrated that it had homing ability to target U251 cells. After EVU251 was prepared as EVMU251@STAT3-siRNA, the particle size was (177.9±5.0) nm, the siRNA loading rate was (33.5±2.2)% and the drug loading rate was (3.24±0.21)%. The biomimetic nanomaterial EVMU251@STAT3-siRNA still had the ability to target U251 cells and successfully deliver siRNA to the cytoplasm without lysosomal degradation. The EVMU251@STAT3-siRNA can effectively knock down the expression of STAT3 gene and produce selective killing ability in U251 cells. CONCLUSIONS The biomimetic nanomaterials EVMU251@STAT3-siRNA made from glioma U251 cells-derived extracellular vesicles can knock down STAT3 gene of U251 cells and produce selective killing effect, which can provide a new idea for the treatment of glioma.
Humans ; RNA, Small Interfering/genetics* ; Biomimetics ; Cell Line, Tumor ; Glioma/therapy* ; Nanostructures ; Cell Proliferation ; STAT3 Transcription Factor/metabolism*

Cardiac Rehabilitation ; Exercise Therapy ; Heart Failure/surgery* ; Heart Transplantation ; Humans

Adult ; Cesarean Section/statistics & numerical data* ; China/epidemiology* ; Female ; Humans ; Pregnancy ; Pregnancy Outcome/epidemiology* ; Risk Factors ; Trial of Labor ; Young Adult

OBJECTIVE: To compare the clinical effect of the combined treatment of acupuncture, moxibustion, Chinese herbal medicine and western medication and simple western medication on polycystic ovary syndrome (PCOS) of kidney deficiency and blood stagnation pattern and explore the effect on endometrial receptivity and the expression of serum homeobox gene A10 (HOXA10). METHODS: A total of 60 patients with PCOS of kidney deficiency and blood stagnation pattern were randomized into a combined treatment group and a western medication group, 30 cases in each one. In the western medication group, on the fifth day of menstruation, clomiphene citrate tablets were taken orally, 50 mg each time, once daily, consecutively for 5 days. On the day when the follicle diameter was ≥ 18 mm, chorionic gonadotrophin for muscular injection, a dose of 10 000 U was given. Before sleep, the aspirin enteric-coated tablets were taken orally, 50 mg (except during menstruation). In the combined treatment group, on the base of the treatment as the western medication group, acupuncture and moxibustion were adopted and the Chinese herbal for tonifying the kidney and activating blood circulation was taken orally. The acupoints were Guanyuan (CV 4), Qihai (CV 6), Zusanli (ST 36), Sanyinjiao (SP 6), Zigong (EX-CA 1), etc. Acupuncture was remained for 30 min each time, once every two days and discontinued during menstruation. Chinese herbal was given from the 3rd day of menstruation till the onset of the next menstruation, one dose each day. After consecutive treatment for 3 menstrual cycles in the two groups, the real-time polymerase chain reaction (RT-PCR) method was adopted to determine the expression of serum HOXA10 before and after treatment in the patients of the two groups. The endometrial thickness at ovulatory phase, uterine arterial flow 7 days after ovulation [including uterine arterial pulsatility index (PI), resistance index (RI), peak systolic velocity (PSV)/end diastolic velocity (EDV), meaning S/D], pregnancy rate and the score of Chinese medicine symptoms before and after treatment were compared in the patients between the two groups. RESULTS: ① After treatment, the expression of serum HOXA10 was higher than that before treatment in the patients of the two groups ( CONCLUSION The combined treatment with acupuncture, moxibustion and medication effectively improves endometrial receptivity and uterine arterial flow in the patients with PCOS of kidney deficiency and blood stagnation pattern and increases pregnancy rate. The therapeutic effect is better than the simple western medication and its mechanism is probably related to the regulation of serum HOXA10 expression.
Acupuncture Points ; Acupuncture Therapy ; Female ; Genes, Homeobox ; Homeobox A10 Proteins ; Humans ; Kidney ; Moxibustion ; Polycystic Ovary Syndrome/genetics* ; Pregnancy

Objective:To evaluate the effects of aquatic exercise on lower-limb motor function and activities of daily living for patients with stroke. Methods:The randomized controlled trials (RCTs) about effects of aquatic therapeutic exercise on stroke patients were recalled from the databases of Cochrane Library, PEDro, PubMed, EMBASE, Web of Knowledge, Web of Science, OVID, EBSCO, CMCI, CNKI, Wanfang and VIP. The methodological quality of the included RCTs was evaluated. The data were extracted, and analysed with RevMan 5.3. Results:A total of 23 RCTs that represented 861 participants were evaluated. Compared with the control group, aquatic exercise significantly improved the performance of Berg Balance Scale (WMD = 2.69, 95%CI 1.21 to 4.16,P < 0.001), Timed Up and Go Test (WMD = -1.56, 95%CI -3.07 to -0.05,P < 0.05), Functional Reach Test (WMD = 2.69, 95%CI 1.21 to 4.16,P < 0.001), sway velocity of center of pressure (SVCOP) (left/right) (WMD = -1.38, 95%CI -2.72 to -0.05,P < 0.05), SVCOP (anteroposterior) (WMD = -1.64, 95%CI -3.10 to 　-0.18,P < 0.05), walking speed (SMD = 0.33, 95%CI 0.07 to 0.58,P < 0.05), Two Minute Walk Test (WMD = 12.75, 95%CI 4.17 to 21.34,P < 0.01), Functional Ambulation Category (WMD = 0.94, 95%CI 0.67 to 1.20,P < 0.001), muscle strength of knee extensor (WMD = 4.30, 95%CI 1.53 to 7.07,P < 0.01), muscle strength of knee flexor (WMD = 4.80, 95%CI 0.29 to 9.32,P < 0.05), and Functional Independence Measurement (WMD = 6.12, 95%CI 3.98 to 8.27,P < 0.001), but not significantly in the score of modified Barthel Index (WMD = 2.92, 95%CI -6.74 to 12.58,P = 0.55). Conclusion:Aquatic exercise can improve balance, walking and muscle strength of lower extremities of stroke patients, but do not for activities of daily living.

Objective:To explore the application of mobile medical technology in aquatic rehabilitation assessment for patients with spinal cord injury. Methods:From November, 2017 to April, 2018, 72 patients with spinal cord injury accepted aquatic exercise were randomly divided into control group (n = 36) and experimental group (n = 36). All the patients were assessed with Water Orientation Assessment of Alyn (WOTA), using paper scale for the control group, mobile scale for the experimental group, twice. The time for assessment and for recall was recorded. The accuracy of results and variety between assessment was compared. Results:The time for assessment and for recall was less in the experimental group than in the control group (t > 10.492, P < 0.001), with more accuracy of standard total score, the variety of total score and standard total score (χ² > 4.545, P < 0.05). Conclusion:Compared with the paper-based assessment, the assessment based on mobile technology may improve work efficiency.

Objective To evaluate the curative value of the tauroursodeoxycholic acid (TUDCA) and Danning table (DN) in the prevention of bile duct stones recurrence after ERCP. Methods 210 patients with Choledocholithiasisby ERCP were randomly divided into 3 groups. The patients in the control group were not given any medicine. The patients in the TUDCA group took TUDCA every night. The patients in the DN group took Danning tablets of three times a day. The course of medication and followed up for the patients was 24 months after the operation. All the patients would be examined regularly by Biliary color doppler ultrasound and MRCP. The recurrence rates of Choledocholithiasis, cholesterol saturation index and serum lipid were recorded and compared statistically between the three groups. Results In total, 190 patients completed the treatment and follow-up according to the experimental design. The recurrence rates of the control, TUDCA and DN group were 17.46%(11/63), 6.34% (4/63) and 10.94% (7/64). The recurrence rates in the TUDCA and DN group were significantly lower than those the control group (P < 0.05).The recurrence rate in the TUDCA group was significantly lower than that in the DN group; On the tenth days after the operation, the CSI in the TUDCA were significantly lower than those the control group and the DN group (P < 0.05). There was no statistically significant difference between the DN group and the control group (P > 0.05); To the patients without recurrence, the level of TC, LDL in the TUDCA group were significantly lower than those the control group and and the DN group (P < 0.05). The level of HDL in the TUDCA group were significantly higher than those the control group and and the DN group (P < 0.05). There was no statistically significant difference on the level of HDL between the DN groupand the control group (P > 0.05). Conclusion The application of TUDCA and DN for patients with Choledocholithiasis after ERCP can effectively reduce the recurrence rates, the curative effect of TUDCA more than DN.

OBJECTIVETo explore the effect difference between acupuncture combined with Chinese medicine of artificial cycle therapy on the basis of western medication and simple western medication for polycystic ovarian syndrome (PCOS) of phlegm damp type with insulin resistance, and to explore its mechanism.

METHODSSixty patients were randomly assigned into an observation group and a control group, 30 cases in each group. Patients of the control group began to take letrozole and metformin orally on the third menstrual day. Patients of the observation group were treated with acupuncture combined with Chinese medicine of artificial cycle therapy on the basis of the treatment of the control group. The main acupoints were Guanyuan (CV 4), Qihai (CV 6) and bilateral Zigong (EX-CA 1), Luanchao (Extra), Fenglong (ST 40), Yinlingquan (SP 9), Zusanli (ST 36), Sanyinjiao (SP 6). Dahe (KI 12) was matched in the follicular phase, and warm acupuncture was applied at Guanyuan (CV 4) and Qihai (CV 6); Zhongji (CV 3) and Xuehai (SP 10) were matched in the ovulatory phase, and electroacupuncture were used at Qihai (CV 6) and Zhongji (CV 3), Xuehai (SP 10) and Yinlingquan (SP 9), 2 Hz and continuous wave; The acupoints in the luteal phase were the above main acupoints, at the same time, moxibustion was used at Guanyuan (CV 4) and Qihai (CV 6), the treatment was given once every other day, 30 min a time. There was no treatment in the menstrual phase. Chinese medicine was applied for tonifying kidney and nourishing blood, strengthening spleen and eliminating phlegm. The patients of the two groups were treated for continuous three menstrual cycles. The indexes before and after treatment were detected, including serum microRNA-29 (miR-29) expression, TCM symptom score, insulin (INS), blood-sugar content and homeostasis model assessment-insulin resistance (HOMA-IR) index, the endocrine hormone values of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), LH/FSH ratio, prolactin (PRL). The pregnancy rates of the two groups were compared.

RESULTSAfter treatment the expressions of miR-29 and TCM symptom scores of the two groups were lower than those before treatment (<0.01,<0.05), with better results in the observation group (<0.01,<0.05). The levels of LH LH/FSH and T of the observation group were lower than those before treatment (<0.01,<0.05), and the T value in the control group decreased after treatment (<0.05). The changes of LH and LH/FSH in the observation group were better than those in the control group (both<0.05). After treatment, The INS, blood-sugar content and HOMA-IR were lower than those before treatment in the two groups (<0.05,<0.01), with better results for INS and HOMA-IR improvements in the observation group (both<0.05). The pregnancy rate in the observation group was 56.7% (17/30), which was significantly higher than 30.0% (9/30) in the control group (<0.05).

CONCLUSIONAcupuncture combined with Chinese medicine of artificial cycle therapy can improve the endocrine levels and insulin resistance of PCOS with phlegm damp type. At the same time, the pregnancy rate is improved. By the view of molecular biology, there may be a pathway trough changing serum miR-29 expression.

The study is aimed to test the effect of Huangqin Tang (HQT) on serum metabolic profile in rats with ulcerative colitis, and explore its possible action mechanism for ulcerative colitis (UC) rats. The model of UC rats with cell immunoreactivity was made using a compound method (trinitrobenzene sulfonic acid plus ethanol). Rats were randomly divided into the control group, the model group, and HQT group. Ultra performance liquid chromatography tandem mass spectrometry (UHPLC-MS), principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were employed to analyze the metabolic profile among normal group, the model group, HQT group. Potential biomarkers were screened in the serum based on the variable importance projection (VIP) value > 1, P< 0.05. As compared with the normal group, 16 potential biomarkers such as valine, tryptophan, lactic acid and urea were found and identified in the serum of model group rats. As compared with the model group, a part of the biomarkers were restored nearly to a normal state after HQT administration for 10 days. Metabolomic analysis revealed that the HQT has a certain therapeutic effect in UC rats, and the mechanism may be related to regulation of lipid metabolism, amino acid metabolism and energy metabolism.

This study was designed to investigate the effect of Huangqin Tang (HQT) on TLR4/Myd88 pathway and the downstream cytokines in rats with ulcerative colitis (UC) to explore its underlying mechanisms of action. The model of UC rats with cell immunoreactivity was made using a compound method (trinitrobenzene sulfonic acid plus ethanol). Rats were randomly divided into the control group, the model group, the salazosulfapyridine (SASP) group, high, medium and low dose (20, 10, 5 g·kg^-1) of HQT groups. After a three-day treatment, production of NO in serum was detected by Griess assay, the levels of interleukin (IL)-4, IL-10, IL-17 and prostaglandin E₂ (PGE₂) in serum were detected by ELISA. After a five-day treatment, the positive protein expressions of COX-2 and iNOS in the colon tissue were determined by ICH method, the protein expressions of TLR4 and MyD88 in colon tissue were determined by Western blot. Compared with the control group, the levels of NO, IL-17, PGE₂, the protein expressions of TLR4, MyD88 and the protein positive expressions of COX-2, iNOS were apparently higher in the model group. Compared with model group, the above indexes were significantly improved in the SASP and high-dose HQT groups (P<0.05). These results show that HQT has a definite effect on UC in rats. Its mechanisms of action may be achieved by inhibiting the activity of TLR4/MyD88/NF-κB signal pathway and down-regulation of NO, IL-17 and PGE 2 production.