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.

The peripherally inserted central catheter (PICC) in neonates has solved the long-term venous access needs of hospitalized infants in the Neonatal Intensive Care Unit (NICU) . The application of technology is accompanied by the risk of complications. Providing safe and high-quality vascular access for neonates through standardized operations is of great significance. The National Association of Neonatal Nurses (NANN) has formulated the Practice Guideline for PICC in Neonates and revised it into the the Practice Guideline for Peripherally Inserted Central Catheter in Neonates (Third Edition) in 2015, aiming to support the bedside nursing practice of neonatal PICC, reduce the occurrence of complications, and promote neonatal safety. This article interprets the recommended points for early identification, management, and prevention of complications after neonatal PICC catheterization in the guidelines.

Objective To construct and validate a risk prediction model for delayed healing of venous leg ulcer(VLU),so as to provide a reference basis for early identification of people at high risk of delayed healing.Methods Using a convenience sampling method,331 VLU patients attending vascular surgery departments in 2 tertiary A hospitals in Sichuan Province from January 2018 to December 2022 were selected as a modeling group and an internal validation group,and 112 patients admitted to another tertiary A hospital were selected as an external validation group.Risk factors for delayed healing in VLU patients were screened using univariate analysis,LASSO regression,and multivariate logistic regression analysis,and a risk prediction model was constructed using R software,and the predictive effects of the models were examined using the area under the receiver operating characteristic curve,the Hosmer-Lemeshow test,decision curve,and the bootstrap resampling for internal validation and spatial external validation were performed,respectively.Results The predictors that ultimately entered the prediction model were diabetes(OR=4.752),deep vein thrombosis(OR=4.104),lipodermatosclerosis(OR=5.405),ulcer recurrence(OR=3.239),and ankle mobility(OR=5.520).The model had good discrimination(AUC:0.819 for internal validation and 0.858 for external validation),calibration(Hosmer-Lemeshow test:χ2=13.517,P=0.095 for internal validation and χ2=3.375,P=0.909 for external validation)and clinical validity.Conclusion The model constructed in this study has good differentiation and calibration,and it can effectively predict people at high risk of delayed healing of VLU,which facilitates targeted clinical interventions to improve ulcer outcomes and reduce the risk of delayed ulcer healing.

Objective To explore the related risk factors of hypokalemia in elderly patients with acute cerebral hemorrhage(ACH),and construct a risk prediction model based on logistic regres-sion.Methods A total of 190 elderly ACH patients treated in Foshan Hospital of Traditional Chi-nese Medicine from June 2022 to May 2024 were enrolled as study objects,and were divided into hypokalemic group(potassium＜3.5 mmol/L,n=51)and normal group(potassium 3.5-5.5 mmol/L,n=139)according to whether hypokalemia occurred.Logistic regression model was used to analyze the risk factors of hypokalemia in the elderly ACH patients.Based on the identified risk factors,a comprehensive index model was constructed.ROC curve was drawn to analyze the diag-nostic value of the index for occurrence of hypokalemia in the patients.Results Larger female ra-tio,higher NIHSS score at admission,elevated urea nitrogen and blood creatinine at admission,and higher glomerular filtration rate(GFR)≤60 ml/min,and ratio of using hydrochlorothiazide＞20 mg/d were observed in the hypokalemic group than the normal group(P＜0.01).Univariate logistic regression analysis showed that female,NIHSS score at admission,urea nitrogen at ad-mission,serum creatinine at admission,GFR ≤60 ml/min,and hydrochlorothiazide dose＞20 mg/d were risk factors for hypokalemia in the ACH patients(P＜0.05,P＜0.01).Multivariate lo-gistic regression analysis indicated that female,NIHSS score at admission,GFR ≤60 ml/min,and hydrochlorothiazide dose＞20 mg/d were independent risk factors for hypokalemia in the elderly ACH patients(OR=6.393,95％CI:2.138-19.112,P=0.001;OR=3.123,95％CI:2.161-4.513,P=0.000;OR=3.327,95％CI:1.137-9.736,P=0.028;OR=3.111,95％CI:1.083-8.933,P=0.035).ROC curve analysis revealed that the AUC values of female,NIHSS score at admission,GFR,hydrochlorothiazide dose and comprehensive index in predicting hypokalemia in elderly ACH patients were 0.621,0.897,0.601,0.613 and 0.857,with a sensitivity of 52.90％,76.50％,49.00％,54.90％and 72.50％,and a specificity of 71.20％,88.50％,71.20％,67.60％and 87.80％,respectively.Conclusion Female,NIHSS score at admission,GFR ≤60 ml/min,and hydrochlorothiazide dose＞20 mg/d may affect the occurrence of hypokalemia in elderly ACH pa-tients,and our comprehensive index model based on these risk factors has high performance in predicting the occurrence of hypokalemia in elderly ACH patients.

Objective:To explore the effect of foraging exercise (FE) on the behavior of rats with post-stroke depression (PSD) and the expression of 5-Hydroxytryptamine 1A (5-HT1A) receptor and transforming growth factor β1 (TGF-β1) in their frontal lobes.Methods:Thirty-six healthy male Sprague-Dawley rats were randomly divided into an ischemia-reperfusion (I/R) group, a PSD group and a PSD+ FE (FE) group, each of 12. The right middle cerebral artery of each was occluded using the thread occlusion method with 1.5h of ischemia. In the PSD and FE groups, mild stimulation was administered at unpredictable intervals over 3 weeks beginning 1 week after the successful modeling. The rats in the I/R group were raised in a group. Those in the PSD group were raised in individual cages. Those in the FE group were raised in a single cage and foraged freely for a total of 4 weeks. Four and eight weeks after the modeling, the body weights were measured, and the open field, social interaction (SIT) and sugar preference tests were administered to all of the groups. Four weeks later, all of the rats were sacrificed and their brains were sliced and stained. The expression of 5-HT1A receptor and TGF-β1 in the frontal lobe was detected using western blotting.Results:One week after modeling, there was no significant difference in average body weight or the average behavioral scores among the three groups. After four weeks the PSD and FE groups had significantly lower average body weight than the I/R group, fewer counts of rearing and grid crossing, longer SIT latency, less interaction time and lower average sugar preference (all significant differences). After eight weeks the average body weight had increased in each group. SIT latency had shortened and interaction time had increased in the FE group, and the rearing and grid crossing counts and sugar preference had increased in the PSD and FE groups. At that point the FE group had significantly greater average body weight than the PSD group, more counts of rearing and grid crossing, shorter SIT latency, increased interaction time, and greater sugar preference. The ratio of residual brain volume in the right hemisphere of the PSD and FE groups was significantly lower on average than in the I/R group. However, there was no significant difference in the right residual brain volume ratio between the PSD and FE groups. Staining revealed that the pathological changes in the frontal lobes of the FE group had been significantly relieved compared with the PSD group. Eight weeks after the operation the increases in average 5-HT 1A receptor and TGF-β1 levels in the FE group were significantly greater than in the PSD group.Conclusion:Foraging can relieve the depressive symptoms of rats modeling post-stoke depression. The mechanism may be related to alleviating the pathological damage and increasing the expression of 5-HT1AR and TGF-β1 in the frontal lobe. Early chronic stress may increase the volume of cerebral infarction, at least in rats.