AIM: To explore the transport and delivery of active drug from dexamethasone-angelica sinensis polysaccharides prodrug in the gastrointestinal tract of rats. METHODS: Dexamethasone and the prodrug were orally administered to rats at the dose of 1.96 mg?kg~ -1 (calculated by carried dexamethasone). The drugs in the plasma and contents of different parts of the rats' gastrointestinal tract were determined by high performance liquid chromatography (HPLC). RESULTS: Dexamethasone carried by the prodrug was mainly released in the contents and mucosa of cecum and colon after oral administration of the prodrug. The absorption of released dexamethasone was reduced significantly. The peak time, peak concentration and AUC were 7.2 h , 42 ?g?L~ -1 and 334 ?g?h?L~ -1 , respectively. However, free dexamethasone was found mainly in the contents and mucosa of the stomach, proximal and distal small intestine after oral administration. The peak time, peak concentration and AUC were 2.2 h, 2 120 ?g?L~ -1 and 11 875 ?g?h?L~ -1 , respectively. CONCLUSION: Dexamethasone can be specifically delivered to the cecum and colon by using dexamethasone- angelica sinensis polysaccharides prodrug. The absorption of dexamethasone was reduced significantly and the drug concentration in colon was increased significantly. The prodrug has a potential in the treatment of colitis.

AIM:To explore the therapeutic effect of dexamethasone Angelica sinensis polysaccharide prodrug(DEX-AP) on trinitrobenzene sulfonic acid(TNBS) induced ulcerative colitis(UC) in rats and its side effects.METHODS: The experimental UC rats were induced by clusis of the solution of TNBS in 45% alcoho1(50(mg?ml~(-1))).The UC rats were orally administrated with(0.25)(?mol?kg~(-1)?d~(-1)) DEX and(0.05),(0.25),(1.25)(?mol?kg~(-1)?d~(-1)) DEX-AP(calculated by carried DEX in DEX-AP) for 7 days,respectively.The rats were killed after the amount of peripheral blood lymphocyte was counted,then the spleen,thymus and colon were separated and weighted.After the ulcerative area of colon was calculated,the colonic myeloperoxidase(MPO) activity was determined and parts of colon were paraffin sectioned and examined under light microscope by HE stain.RESULTS: After the UC rats were administrated with different doses of DEX-AP for 7 days,the ulcerative area,the weight and the MPO activity of colon reduced significantly.The reduction of MPO activity was correlated to the dose of DEX-AP and the MPO activity with DEX-AP at the doses of(0.25),(1.25)(?mol?kg~(-1)?d~(-1)) reduced more significantly than that with DEX at the the dose of(0.25)(?mol?kg~(-1)?d~(-1)).The number of peripheral blood lymphocyte,spleen weight and thymus weight of UC rats reduced significantly at the dose of(0.25)(?mol?kg~(-1)?d~(-1)) DEX(P

Objective To establish a scald-induced pain model using a constant-temperature electrical scald instrument in rats.Methods Thirty-six pathogen-free male Sprague-Dawley rats, weighing 200-250 g, were randomly divided into 4 groups (n =9 each) using a random number table: control group (group C), scald for 5 s group (group S5), scald for 10 s group (group S10), and scald for 15 s group (group S15).The rats were anesthetized with intraperitoneal chloral hydrate.In S5, S10 and S15 groups, the plantar surface of the left hindpaw of rats were exposed to a constant-temperature electrical scald instrument (85 ℃) for 5, 10 and 15 s, respectively.The plantar surface of the left hindpaw of rats was exposed to an electrical scald instrument (room temperature) for 10 s in group C.At 1 day before treatment (T0),and 1, 3, 5, 7 and 14 days after treatment (T1-5), the mechanical and thermal pain thresholds were measured.Immediately after treatment, and at 24 h after treatment, the total body condition, wound color, and shape of the margin of the wound were observed and recorded.At 24 h after treatment, 3 rats were randomly sacrificed, and the skin from the plantar surface of the left hindpaw was removed for microscopic examination.Results Compared with group C, the thermal pain threshold at T1-2, and the mechanical pain threshold at T1-3 were significantly decreased in group S5, and the thermal pain threshold,and mechanical pain threshold were significantly decreased at T1-4 in group S10 (P＜0.05).The thermal pain threshold ＞ 25 s, and the mechanical pain threshold ＞30 g at T1-5 in group S15.The swelling in foot was bovious, burn blister appeared, and the degree of damage was aggravated in group S10 compared with S5 and S15 groups.Conclusion The scald-induced pain model is successfully established using a constant-temperature electrical scald instrument in rats.

BACKGROUND: Inhibiting the degradation of extracellular matrix in the intervertebral disc can delay the degenerative process of intervertebral disc. Matrix metalloproteinases-3 (MMP3) is considered as a key enzyme for degradation of extracelular matrix components such as type II collagen and aggrecan.
OBJECTIVE:To construct the short hairpin RNA lentiviral vector targeting human MMP3 gene and to detect its efficiency of gene silence by infecting human degenerative nucleus pulposus cells.
METHODS:According to the human MMP3 mRNA (NM_002422.4) sequence, four groups of the short hairpin RNA gene sequences targeting MMP3 were designed, synthesized and annealed to form double stranded DNA fragments, which were connected with the LV3 vectors digested by BamHI andEcoRI enzymes, and then transfected into the competent cels. The positive clones were identified by PCR, and analyzed by sequencing. The packaging and titer of lentivirus were determined after transfecting 293T cells. Human degenerative nucleus pulposus cels were infected with lentivirus vector, and the transfection efficiency of each group was observed under inverted fluorescence microscope. The interfering efficiency was detected by real time-PCR and western blot at 72 and 96 hours.
RESULTS AND CONCLUSION:The ds-oligo DNA was successfully inserted into the lentiviral vector as confirmed by electrophoresis and sequence analysis. The recombinant lentivirus was harvested from 293T cels with a viral titer of 1-5 ×108 TU/mL. RNA interference targeting the GCC AGG CTT TCC CAA GCA AAT sequences with the highest interfering efficiency in MMP3 gene at 72 and 96 hours resulted in suppression of MMP3 mRNA expression by 98% and 72%, respectively; and at 96 hours, the interfering efficiency of protein expression was 57.2%. The recombinant lentivirus vector containing RNA interference targeting MMP3 gene is successfuly constructed, which lays a foundation for further studies on the MMP3 function and gene therapy.

Objective:To introduce a novel ridge preservation technique with micro-titanium plate avoiding the use of bone grafting materials,and evaluate the potential horizontal bone preservation effect of this new technique,applied on single maxillary central incisors after tooth extraction for future implant restoration.Methods:Nine patients (six women and three men),mean age (26.0 ±5.7)years(from 1 8 to 34 years)referred to the Department of Oral Implantology,Peking University School and Hospital of Stomotology,were selected and diagnosed with unsalvageable single middle incisor with fine general con-ditions,no signs of acute local inflammation,no ongoing or previous periodontitis,healthy neighboring teeth and intact buccal bone walls.Tooth extraction,delayed implant placement and implant-supported single crown restoration were selected as treatment plan.The teeth were extracted atraumatically with lo-cal anesthesia,followed by a reflection of a minor flap to exposed 2-3 mm of the buccal bone plate.Af-ter that,a micro-titanium plate was trimmed and bended to fit the convexity of the labial bone and fixed by two mini pins with intent to support the labial soft tissue.The flap was then repositioned over the micro titanium plate and secured with two single sutures.No bone grafting materials or releasing incisions were needed.The sockets were left to heal without any intention of primary wound closure.Cone-beam compu-ted tomographic (CBCT)scans were obtained before and four months after tooth extraction.Horizontal ridge widths were measured with CBCT software,and the preservation effects were calculated and recor-ded by the percentage of horizontal ridge alteration.Results:The nine extraction sockets were healed un-eventfully.The average socket width before extraction was (7.51 ±0.48)mm (6.92-7.82 mm).The average alveolar ridge labial-palatal width at the control point of the edentulous area was (6.81 ±0.44) mm (6.04-7.38 mm)4 months after tooth extraction,the mean percentage of ridge width preserved was 90.87%±2.91%(87.28%-95.60%).Conclusion:This novel ridge preservation method by the usage of a micro-titanium plate did not interfere with the natural socket healing process,and at the same time,largely preserved the width of alveolar ridge without any bone grafting procedures.Long term results remain to be seen.

Objective To explore the correlation between TCM constitution and sleep status in escort troops. Methods Standardized TCM Constitution Questionnaire and Pittsburgh Sleep Quality Index (PSQI) were used to investigate escort troops. Factors of PSQI and constitution types were analyzed. Results The results of PSQI showed the number of escort troops who had bad sleeping (PSQI>7) was 64, which accounted for 46%of the escort troops, among which, 45 people (70.3%) were justified as biased constitution, while 19 were normal constitution (29.7%). The top three biased constitution in bad sleeping were:qi deficiency, phlegm-dampness and dampness-heat. PSQI factors such as sleep disorder, daytime dysfunction and total score had positive correlation with qi deficiency, yang deficiency, yin deficiency, dampness-heat and blood stasis, and negative correlation with normal constitution. Conclusion Sleep condition of escort troops has correlation with TCM constitution, which indicates that sleep status could be improved by regulating TCM constitution.

Objective:To analyze the intervention effect of rehabilitation platform-based online psycho-education on patients with bipolar disorder (BD) in remission stage.Methods:In this randomized controlled study, 91 patients with BD in remission stage who attended the community health center in Xicheng District, Beijing from July to August 2021 were randomly divided into a test group (46 cases) and a control group (45 cases) according to a 1∶1 ratio using the random number table. Baseline data were collected from both groups, and the control group received conventional medication and community telephone follow-up, while the test group was given online mental health education in the form of a WeChat subscription number on this basis, including BD mental health education course push (twice a week) and disease self-management (daily recording of mood, sleep, medication, exercise and gratitude diary), and the intervention period was 6 months in both groups. During the intervention, one patient in the test group was admitted to hospital due to exacerbation of mental illness and the trial was terminated. A total of 90 cases were included in the study. The scores of Medication Adherence Rating Scale (MARS), Hamilton Depression Scale (HAMD), Young Mania Rating Scale (YMRS) and Perceived Devaluation-Discrimination Scale (PDD) were assessed at baseline, after 3 months and 6 months of intervention in both groups, respectively. And the differences in baseline data between the two groups were compared using two independent samples t test and χ2 test, and the repeated-measures ANOVA was used to compare the differences in MARS, HAMD, YMRS, and PDD scores between the two groups before and after the intervention, and to analyze the intervention effects of network mental health education based on the rehabilitation platform on patients in remission stage of BD. Results:After 6 months of intervention, MARS scores in the test group was significantly higher than that in the control group [(8.47±1.75) vs (7.47±1.85)], and was significantly higher than that at baseline (7.36±2.13) and after 3 months of intervention (8.04±1.68) (all P<0.05). YMRS and PDD scores in the test group were significantly lower than those at baseline after 3 and 6 months of intervention [YMRS, 2.0(1.0,4.0),2.0(0,3.0) vs 3.0(1.0,5.5); PDD, (31.18±4.65), (30.13±4.76) vs (32.51±4.51)] (all P<0.05); the differences in YMRS and PDD scores in the control group were not statistically significant (all P>0.05). There was no statistically significant difference in HAMD scores between the two groups before and after the intervention (all P>0.05). Conclusion:Combining mental health education based on rehabilitation platform with conventional medication and community management can significantly improve the medication compliance of patients with BD in remission stage, and improve their manic symptoms and reduce the stigma of the disease.

【Objective:】 To deeply understand the current situation and hotspots of drug clinical trials risk management in China. 【Methods:】 Co-word analysis and social network analysis were used to sort out the study results of risk management in drug clinical trials in China. 【Results:】 The trend of risk research of drug clinical trials in China was generally on the rise. The research hotspots focused on four areas: drug supervision and pharmacovigilance, risk management of drug clinical trial institutions, ethical review of drug clinical trials, and risk management of drug clinical trials. 【Conclusion:】 In the future, China should gradually improve the risk management system and supervision system of drug clinical trials, explore to establish a risk-based quality management and ethical review system of drug clinical trials, and enhance the risk assessment and coping ability of institutions.

【Objective:】 To sort out the influencing factors of drug clinical trial risks and improve the risk management level of drug clinical trials in China. 【Methods:】 The literature analysis method was used to sort out the literature related to the risk management of drug clinical trials in China, and the text analysis method was used to summarize and refine the influencing factors of drug clinical trial risks. 【Results:】 The risk categories of drug clinical trials were divided into 5 parts, namely drug clinical trial institution management, ethics committee management, clinical trial designs, researchers, and subjects, involving 13 main risk influencing factors and 21 specific risk points. 【Conclusion:】 By strengthening the construction of drug clinical trial institutions and ethical management capabilities, optimizing research protocol design, enhancing researchers’ awareness and ability, and establishing a subject management system to improve the quality of drug clinical trials.

Objective:To explore the effects of foraging exercise (FE) on depressive-like behaviors and expression of transforming growth factor-β1 (TGF-β1) in hippocampus of rats with ischemic stroke after chronic stress.Methods:The right middle cerebral artery occlusion (MCAO) model was used in 30 male adult clean grade SD rats by suture method.According to the body weight, rats were evenly divided into stroke group ( n=10) and chronic unpredictable mild stimulation (CUMS) group ( n=20). Rats of CUMS group received stress induction 1 week after operation and lasted for 3 weeks. Then, according to random number generator of SPSS 24.0 software, the depression rats were divided into post-stroke depression (PSD) group( n=10) and FE groups ( n=10). The FE group received free FE intervention for 4 weeks. Body weight, water maze test, novelty inhibition feeding test (NSFT) and sucrose preference test (SPT) were performed at the end of the 1st, 4th and 8th week, respectively. The expression of TGF-β1 in hippocampus was detected by Immunohistochemistry (IHC) and Western blot (WB), and the levels of TGF-β1 and TNF-α in serum were detected by ELISA. SPSS 24.0 software was used for statistical analysis. The behavioral data were compared by two factor repeated measurement analysis of variance. One way ANOVA was used for comparison among groups, and LSD test was used for further pairwise comparison. Results:(1) The interaction between group and time had statistical significance on body weight, latency and food intake of NSFT and sucrose preference index(SPI) ( F=2.936-12.098, all P<0.05). After 4 weeks, compared with the stroke group((343.80±19.34)g, (12.10±6.97)s, (0.75±0.09)%), the body weight((307.80±17.23)g, (305.30±24.39)g), and SPI((0.52±0.06)%, (0.53±0.07)%) of PSD group and FE group were lower and the NSFT latency((21.70±7.02)s, (22.40±0.84)s) was longer (all P<0.05). After 8 weeks, SPI in FE group was higher than that in PSD group ( P=0.045). There were significant differences in body weight of three groups, NSFT latency and SPI of PSD group and FE group, and food intake of stroke and FE group ( F=8.478-196.548, all P<0.05). There was no interaction between group and time in the water maze test. Main effect of time ( P=0.034) and main effect of group ( P<0.01) had statistical significance on escape latency. The escape latency after 4 weeks was longer than that after 1 week ( P=0.003). The latency of PSD group was longer than that of stroke group ( P=0.005), and latency of FE group was shorter than that of the PSD group ( P<0.01). The main effect of group had statistical significance in the number of crossing quadrant ( P<0.01). The number of crossing quadrant of FE group was less than that of PSD group ( P<0.01). (2) Immunohistoche mistry staining showed that compared with the stroke group, the expression of TGF-β1 was down-regulated in 3 areas of hippocampus of PSD group (CA1, CA3 and DG) ( t=5.449-9.353, all P<0.01). Compared with stroke group, the expression of TGF-β1 of CA1 ( t=7.433, P<0.01) in FE group was down-regulated, but was up-regulated in CA3 ( t=3.342, P<0.05) of FE group. Compared with the PSD group, the expression of TGF-β1 was up-regulated in CA3 and DG of FE group ( t=7.811, 8.790, both P<0.01). (3) Western blot results: Compared with stroke group, the expression of TGF-β1 in hippocampus of PSD group was down-regulated ( t=3.255, P<0.01). Compared with the PSD group, the expression of TGF-β1 in hippocampus of FE group was up-regulated ( t=2.906, P<0.05). (4) ELISA detection showed that compared with the stroke group, the levels of TGF-β1 decreased ( t=2.224, P<0.05), but TNF-α increased ( t=6.127, P<0.01) in PSD group.Compared with the PSD group, the expression of TGF-β1 in FE group increased significantly ( t=4.417, P<0.01). Conclusion:Foraging exercise can improve the depressive behavior symptoms of ischemic stroke rats after chronic stress, and its mechanism may be related to the increasing expression of TGF-β1, which can alleviate the inflammatory reaction in hippocampus.