Biomacromolecule drugs have been increasingly used in clinical practice due to their distinct advantages, including precise targeting, small dose, high safety and activity. However, owing to their high molecular weight, strong hydrophilicity, and poor stability in the gastrointestinal tract, the oral bioavailability of the biomacromolecule drugs remains extremely poor. As a novel and innovative technology for active drug delivery, gastrointestinal microneedles hold immense potential in the oral delivery of biomacromolecule drugs because of their low-invasive nature and high permeation enhancement effects. This review primarily summarizes the actuating force, design strategies, fabrication techniques, and applications of gastrointestinal microneedles for the oral delivery of biomacromolecule drugs. Additionally, the challenges and further perspectives in the development this technology are presented, aiming to promote the subsequent research and clinical translation of gastrointestinal microneedles, and to provide a new efficient and safe strategy for oral delivery of biomacromolecule drugs.

OBJECTIVETo explore the clinical effects of Dynesys system for the treatment of multiple segment lumbar degenerative disease.

METHODSA total of 28 patients with lumbar degenerative disc disease treated with Dynesys system from December 2008 to May 2011 were retrospectively reviewed. There were 16 males and 12 females, aged from 27 to 75 years old with an average of 49.1 years. Thirteen patients with multiple segmental lumbar intervertebral disc protrusion, including L3-L5 in 7 cases, L2-L4 in 1 case and L4-S1 in 5 cases. Fifteen patients with multiple segmental lumbar spinal stenosis, including L3-L5 in 10 cases, L4-L5 in 4 cases and L2-S1 in 1 case. The symptoms of lumbago and (or) intermittent claudication in all patients were treated with conservative treatments for more than 6 months and these methods did not work. Visual analogue scale (VAS) was used to analyze the lumbar and leg pain, imaging data were used to measure the intervertebral space height and intervertebral motion of fixed segment and upper adjacent segment, Oswestry Disability Index (ODI) was used to evaluate the clinical effect.

RESULTSAll operations were successful and the patients were followed up from 38 to 65 months with an average 50.6 months. At final follow-up, ODI and VAS of the low back pain and leg pain were (25.10±6.52)%, (1.25±0.70) points and (1.29±0.89) points, respectively and were decreased compared with preoperative (P<0.05). Postoperative intervertebral space heights were increased and intervertebral motions were decreased in fixed segment compared with preoperative (P<0.05). There were no significant differences in intervertebral space heights and intervertebral motions of upper adjacent segment between preoperative and postoperative (P>0.05).

CONCLUSIONDynesys system may obtain long-term clinical curative effect in treating multiple lumbar degenerative disease. It can partially preserve the intervertebral motions of the fixed segments, have little effect on adjacent segments. The long-term clinical effect of Dynesys still need longer time follow-up observation.

Adult ; Aged ; Female ; Follow-Up Studies ; Humans ; Intervertebral Disc Degeneration ; pathology ; surgery ; Joint Instability ; Lumbar Vertebrae ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Visual Analog Scale

Objective To investigate the effects of Houpupaiqi mixture on the recovery of gastrointestinal function after open gastrointestinal surgery,and evaluate the efficacy and safety of Houpupaiqi mixture.Methods A total of 144 selected patients who underwent open gastrointestinal surgery were enrolled into the multi-center prospective randomized double-blind controlled clinical trial from October 2010 to September 2011.Of the 144 patients,66 were from People's Hospital of Peking University,72 were from Beijing Friendship Hospital of Capital University of Medical Sciences,and 6 were from People's Hospital of Guangdong Province.All the patients were randomly divided into 2 groups (test group:96 patients,control group:48 patients) at the ratio of 2∶1 according to the random number table.Five patients who did not meet the criteria were excluded from the study,and then there were 92 patients in the test group and 47 patients in the control group.The study was assessed by the ethics committees,and all the patients signed the informed consent form.Houpupaiqi mixture (50 ml) or placebo (50 ml) were administered in the test group and control group at postoperative 16 and 20 hours,respectively.Parenteral and enteral nutritional support were given after pulling out of gastric tube.A standard intravenous analgesia was applied in the 2 groups,and agents which stimulate or suppress gastrointestinal motility were prohibited.The time for the recovery of regular bowel sounds,the first exhaust and first defecation time,and the time of first solid food intake of the 2 groups were recorded.Vital signs were recored before operation and after drug administration.Blood and urinary routine test,hepatic and renal function test,electrocardiogram examination,record of adverse drug event were carried out at postoperative day 6.The time for the indexes above and relevant frequencies were calculated,and the survival curve were drawn by Kaplan-Meier method.All the time points were analyzed using the Log-rank test.The measurement data were analyzed using the t test or rank-sum test,and the enumeration data were analyzed using the chi-square test or Fisher exact probability.Results The median time for the recovery of regular bowel sounds,median time for first exhaust and defecation were 21.4 (20.0,23.7)hours,45.0 (40.0,54.0) hours and 65.5 (54.7,74.0) hours in the test group,and 47.5 (44.0,56.5) hours,91.0 (87.0,93.8)hours,98.0 (94.0,113.5)hours in the control group,there were significant differences between the 2 groups (Log-rank values =21.67,53.15,11.81,P＜0.05).The median time of first solid food intake were 72.5 (66.2,110.5) hours of the test group and 116.3 (114.8,117.3) hours of the control group,with no significant difference between the 2 groups (Log-rank value =13.70,P ＞ 0.05).There were no significant differences in the body temperature,respiration,heart rate,systolic blood pressure and diastolic blood pressure before and after medication between the 2 groups (Z =0.03,0.68,0.97,0.22,0.72,P ＞ 0.05).There were no significant differences in the number of patients with abnormal results of blood test,hepatic function,renal function and electrocardiogram between the 2 groups (P ＞ 0.05).No severe adverse event was observed in the clinical trial.Conclusion Houpupaiqi mixture significantly promotes the recovery of gastrointestinal function of the patients who underwent open gastrointestinal surgery with relatively low adverse events.

Objective The present study aims to explore the optimal combination of growth factors, including TGF-?_1,IGF-I and BMP-2,for the induction of ehondrogenesis of MSCs in vitro monolayer culture. Methods MSCs were induced to differentiate into ehondrocytes in the medium with the following growth fac- tors:TGF-?_1,BMP-2 and IGF-I,either alone or in combination.We detected two cartilage specific markers in differentiated cells.Alcian blue stain was used for aggreean and RT-PCR for collagen type II mRNA.Results The level of Collagen typeⅡmRNA of group BMP-2+IGF-I,TGF-?_1,TGF-?_1+IGF-I,TGF-?_1+BMP-2 and TGF-?_1+IGF-I+BMP-2 was 0.147?0.062,0.478?0.069,0.489?0.022,0.653?0.013,0.807?0.051 respectively. Alcian blue stain in all gruups were positive.Conclusion The TGF-?_1+IGF-I+BMP-2 group is the most ef- fective combination in chondrogenesis induction.

Objective To investigate the activation of NF-κB and regulation by ubiquitin (Ub)-proteasome pathway in the aorta of rats with chronic renal failure(CRF).Methods The CRF rat model was established by right nephreetomy and left branch renal artery ligation.The CRF rats were were randomly divided into simple CRF group(n=20)and CRF+M used as control group(CON).The NF-κB and the Ub mRNA expression were detected by RT-PCR,and its protein expression was analyzed by immunohistochemistry method.The activity of NF-κBwas mesured by EMSA method.The concentration of IL-1 and TNF-α was detected by ELISA.Results Compared with the CON group,the concentration of serum IL-1 and TNF-α was increased significantly in CRF group [IL-1:(9.02±1.29) vs (2.74±0.96)mg/L,P＜0.01;TNF-α:(50.02±9.52) vs (14.04±1.29)mg/L,P＜0.01]at month 4 after operation.The mRNA expression of NF-κB and Ub in the aorta of CRF group was 1.38 and 1.29 times as that of CON group(P＜0.01).and the protein expression of NF-κB and Ub was 3.75 and 20.5 times as that of CON group(P＜0.01).Compared with the CON group,the activity of NF-κB in the aorta of rats of CRF group was elevated markedly at month 4 after operation(P＜0.01).All the indices were further increased at month 6 after operation.Compared with CRF group,the concentrations of serum IL-1and TNF-α were decreased significantly in CRF+M group[IL-1:(2.94±0.33)mg/L,P＜0.01;TNF-α:(12.80±2.12)mg/L,P＜0.01].The mRNA and protein expression of NF-κB and Ub were also decreased markedly(P＜0.01),and the activity of NF-κB was decreased significantly at month 4 to 6 after operation(P＜0.01).But the amount of ubiquitnative protein was increased significantly in the aorta of CRF+M group as compared to CRF group(P＜0.01). Conclusion The inflammatory signal pathway of ubquitin-proteasome-NF-κB pathway was activated in the aorta of CRF rats,and the proteasome was probablely an important pharmacological intervention target to regulate the activation of NF-κB.

Objective To evaluate the safety and effectiveness of the treatment by selective β 1 receptor blockers on patients with chronic obstructive pulmonary disease (COPD).Methods Eighty cases of COPD Ⅲ (stable period) inpatient with or without coronary heart disease were collected in The Second People's Hospital of Shanghai from September 2012 to November 2013.The patients were randomly divided into testing group (Metoprolol treatment group) and control group (regular treatment group) with 40 cases for each group.Metoprolol group therapy based on the use of conventional metoprolol tablets,an initial dose of metoprolol 12.5 mg/d,titrated to the appropriate dose based on heart rate and tolerance of the morning resting heart rate of 55 to 60 times/min that reached the target dose of metoprolol continuous medication for 12 months.Blood gas analysis were recorded before and after treatment,pulmonary function,and 6 min walk test (6MWT) and were chronic lung disease Assessment Test (CAT) Rating.The control group was administrated regular treatment while the testing group added small dose of Metoprolol with titration to an appropriate dose on this basis.12 months in a row,and assessed the end stage.Results (1) After the application of selective β receptor blockers on testing group,no statistically significant difference (P＞0.05) in the values of FEV1 in anticipation value％ (testing group:(45.45 ± 4.68) ％ vs.(43.32 ± 4.84) ％;control group:(44.23 ± 4.68) ％ vs.(42.58 ±4.24)％),PaO2(testing group:(75.92± 10.78) mmHg vs.(74.86± 11.21) mmHg;control group:(70.23 ±6.45) mmHg vs.(72.36±7.28) mmHg) and PaCO2(testing group:(46.28±8.28) mmHg vs.(47.46±10.22) mmHg);control group:(44.54 ± 8.89) mmHg vs.(42.36 ± 7.45) mmHg) before and after treatment.But the 6MWD (testing group:(287 ± 23) m vs.(384± 34) m;control group:(284 ± 25) m vs.(295 ±21) m) and COPD appraisal test(CAT) (testing group:(21±7) score vs.(17±6) score);control group:(22 ±5) score vs.(20± 6) score) had improved significantly compared with that before treatment,with significant difference(t=4.903,4.784;P＜0.05).Conclusion Selective β receptor blockers have no effect on the airway resistance of COPD patients and reduction on pulmonary function.It can also increase the exercise tolerance and enhance the living quality for improving clinical prognosis.

BACKGROUND:During the healing of fractures, removal of sciatic nerve can result in insufficient mechanical rigidity of newborn woven bone. However, there are less reports concerning the denervation effects during distraction osteogenesis. OBJECTIVE:To observe the effect of removal of the sciatic nerve on bone regeneration and the expression of Runt-related transcription factor 2 (Runx2) protein during distraction osteogenesis in a rabbit model. METHODS:Twenty-four adult male New Zealand rabbits were selected and underwent left tibial osteodistraction to construct animal models of distraction osteogenesis. Before distraction, the animals were randomly divided into group R (resecting the left sciatic nerve) and group I (intact left sciatic nerve). Six weeks after completion of distraction, the animals were kil ed and the lengthened tibias were harvested for radiography, three-dimensional CT reconstruction, histological evaluation, connectivity density (Conn.D) evaluation. RESULTS AND CONCLUSION:New regenerated bone was present and Runx2 protein was expressed in the distraction gaps of al animals at the end of the study, as revealed by radiography, three-dimensional CT reconstruction, and histological observation. However, less new bone formation and a lower degree of mineralization and expression of Runx2 protein were observed in group R compared with group I. The results suggest that the denervation appears to have an inhibitory effect on bone formation and the expression of Runx2 protein during distraction osteogenesis.

Objective To analyze the effects of adenohypophysis function after treating with thyrotropin releasing hormone and its clinical significance in patients with brain trauma. Methods There were 22 cases with traumatic brain injuries from July 2010 to September 2012 in Chinese people's Liberation Army nine eight hospital,after injuried within 4 to 12 hours,then 1 1 cases who were given thyrotropin-releasing hormone(TRH)were selected as experimental group,while 1 1 cases who were given the same amount of isotonic saline were selected as control group,then the score of GCS, ICS,RLS85 and the improvement of adenohypophysis function were observed. Results After treatment,the score of glasgow coma scale (GCS ), innsbruck coma scale (ICS),and the reaction level scale (RLS85)between two groups were significantly increased in three days compared with before treatment,and within three days after injury situation,the improvements of ICS and RLS85 in experimental group were better than control group(P<0.05 ). Compared with control group,the levels of each gland pituitary hormone in experimental group were significantly increased(P<0.05 ),and on the third day,the growth hormone (GH)was reduced significantly,finally 50%of that in control group. Conclusion Patients with brain injury treated with thyrotropin releasing hormone,has no significant adverse reactions,with the characteristics of safe and effective.

In order to summarize and perfect the basic skill practicing method in acupuncture teaching and form a characteristic teaching, the research on skill training and technique improving of acupuncture and tuina major was carried out. The undergraduate students in acupuncture and tuina major from College of Acupuncture-Moxibustion and Tuina were randomly divided into an experimental group and a control group. Students from both groups received the basic courses of acupuncture-moxibustion and tuina as requested in the syllabus and the special teaching was added to the experimental group, namely "three practice" (strength practice, coordination practice, targeted practice of acupuncture basic skills) and "three enlightenment" (technique enlightenment, mind and qi enlightenment, efficacy enlightenment). During and after the courses, the teaching effectiveness was evaluated on the basis of needling manipulation. The peacetime score in the experimental group was superior to that in the control group (38.03 +/- 1.14 vs 33.25 +/- 1.31, P < 0.05), the total score in the experimental group was superior to that in the control group (84.03 +/- 6.30 vs 78.05 +/- 6.55, P < 0.05). The special teaching method of "three practice" and "three enlightenment" can improve the effect of skill training teaching method. It highlights the unique feature of central plains by integrating the essence of Shaolin internal qigong and Chen-style Taiji, it can also provide new ideas for the practical teaching of TCM professional courses and the construction of characteristic professionals.
Acupuncture ; education ; manpower ; Acupuncture Therapy ; methods ; Humans ; Students ; Teaching

ObjectiveTo investigate the effects of Chinese compound Sheng-wu Capsule on learning-memory ability and histology including the neurons, astrocytes and expression of nerve growth factor(NGF) and its receptor (TrkA) in hippocampus CA1 of aged rats. MethodsSheng-wu Capsule consists of 6 kinds of Chinese medicinal herbs such as polygonum multiflorum,ginseng, and Rhizoma Acori Tatarinowii.The water-soluble component of polygonum multiflorum,2,3,5,4'- tetrahydroxystibane-2-O-β-D-glucoside was the quality standard of Sheng-wu Capsule.Aged Wistar rats(22 months old) were orally administrated with Sheng-wu Capsule(1.8g/kg and 0.9g/kg) for 2 months. Positive control drug was Piracetam(0.56g/kg). The learning and memory ability was tested by passageway water maze; the number and morphology of neurons was detected by HE staining; the proliferation of astrocytes was detected by immuno-histochemistry for glial fibrillary acidic protein(GFAP); the expression of neurotrophic substance was detected by immuno-histochemistry for NGF and TrkA receptor by ABC method. Image analysis to determine average cell number, size(area) and staining density in hippocampal CA1 region was achieved by VISILOG 5.0 image pattern analyser.ResultsBoth NGF and TrkA-immunoreactive neurons in aged rats significantly decreased as well as cell number, size and staining density in CA1 region of hippocampus(P<0.01). Aged rats showed damage of neurons and increase of GFAP positive cells in the same area,model rats indicated learning-memory deficit too. In Sheng-wu Capsule administrated groups,the significant little decrease in cell number, size and staining density of NGF and TrkA-immunoreactive neurons in CA1 region of hippocampus was observed(P<0.01-0.05). The loss of Neurons and proliferation of astrocytes were inhibited and learning-memory ability was also improved in Sheng-wu groups.Conclusions Chinese compound Sheng-wu Capsule significantly promotes the expression of NGF and TrkA in aged rats and it relieves the damage of hippocampus.This may be the mechanism by which Sheng-wu Capsule improves the learning and memory ability. Enhancing endogenous neurotrophic substance plays an important role in the treatment of Alzheimer's disease.