Skin modeling of transdermal drug delivery system refers to experimental models that mimic the structure and function of human skin to explore and evaluate absorption,penetration,and efficacy of medicines in transdermal drug delivery.It provides an alternative to traditional human skin experiments and reduces the use of human skin in medical research,which is convenient,controllable,and cost effective.For skin models of transdermal drug delivery systems,this article introduces commonly used animal skin models,artificial skin models,and recombinant human skin models from the perspective of the transdermal absorption pathway of medicines,and analyzes their advantages,disadvantages,and applications so provide references the research and development of transdermal formulations and topical therapies.

Methods: This study enrolled 51 patients with LDK out of 382 patients with adult degenerative spinal deformity. Baseline information was reviewed including demographic data and complications. Sagittal spinopelvic alignments and global imbalance parameters were assessed on full-length X-ray images of the spine. Muscularity and the fatty infiltration area of the ES and multifidus (MF) were measured at the L4/5 level on preoperative magnetic resonance image to evaluate the lumbar erector muscle atrophy. Stratification by sagittal vertical axis (SVA) was performed: group 1 with SVA <100 mm and group 2 with SVA >100 mm, and these groups were compared. Spearman correlation and multivariable logistic regression analyses were performed to analyze and define risk factors of postoperative proximal junctional kyphosis (PJK). Results: Group 2 had lower ES and MF muscularity than group 1. ES muscularity correlated with SVA (r=−0.510, p<0.003), lumbar lordosis (r=−0.415, p<0.018), and postoperative PJK (r=−0.508, p<0.022). MF muscularity did not correlate with the above parameters. Multivariable logistic regression analysis verified ES muscularity (odds ratio [OR], 0.001; p<0.039) and SVA (OR, 1.034; p<0.048) as the risk factors for postoperative PJK. Conclusions ES atrophy, besides the MF, is an important predictor in distinguishing decompensated LDK from well-compensated ones. It plays an important role in compensatory mechanism, not only correlates with global sagittal imbalance but also ties to PJK after deformity corrective surgery.

Methods: A cohort of 54 consecutive patients with DLS and RO was included in the study. All the included patients underwent selective RO fusion and at least 2 years of follow-up. They were divided into two groups: group 1 with a curve <30° and group 2 with a curve ≥30°. The clinical outcomes were evaluated by the Oswestry Disability Index (ODI) and Numerical Rating Scale. The radiological assessment included RO location, offset and subluxated-disc orientation, Cobb angle, and coronal as well as sagittal alignments. Results: The offset value was greater in group 2 than in group 1 (13.4±4.7 mm vs. 9.3±3.5 mm, p<0.001). The subluxated disc was mainly oriented to the concave side in group 2 (15/21) but to the convex side in group 1 (20/33) (p =0.022). Group 2 had a higher rate of postoperative adjacent RO than group 1 (14/21 vs. 1/33, p<0.001). The ODI was comparable between both groups preoperatively but higher at the final follow-up in group 2 (34.9±9.5) than in group 1 (24.4±6.2). In the multiple logistic regression analysis, the thoracolumbar/lumbar curve was identified as the risk factor for postoperative adjacent RO (odds ratio, 1.400; p=0.007). The receiver operating characteristic analysis verified it with an area under the curve of 0.960 (p<0.001). Conclusions The clinical and radiological outcomes were maintained well in group 1 but not in group 2. Selective RO fusion in DLS with a lumbar curve <30° is a rational option. However, it should be avoided in those with a lumbar curve >30° because of a higher complication rate and a worse clinical outcome at the final follow-up.

Methods: This study included 60 patients with Lenke 1 AIS who underwent selective thoracic fusion surgery. Coronal spinal alignment parameters were analyzed preoperatively, postoperatively, and at the final follow-up. The postoperative FMS was divided into two groups: the balanced group (FMS ≤20 mm) and the unbalanced group (FMS >20 mm). An independent t-test was used to compare quantitative data between groups, and a chi-square test was used for qualitative data. Furthermore, binary logistic regression and receiver operating characteristics curve analyses were used to identify the risk factors for postoperative distal adding-on in AIS. Results: At 2-year follow-up, the unbalanced group was more likely to have adding-on (17 of 24 patients) than the balanced group (six of 36 patients; p<0.001). Twenty-three patients with distal adding-on had significantly greater preoperative and postoperative lower instrumented vertebrae (LIV) rotation, FMS, and FMS angle (FMSA) than those without postoperative distal adding-on. Binary logistic regression analysis selected three independent risk factors for adding-on incidence after surgery: FMS (odds ratio [OR], 1.115; 95% confidence interval [CI], 1.049–1.185; p<0.001), FMSA (OR, 1.590; 95% CI, 1.225–2.064; p<0.001), and postoperative LIV rotation (OR, 6.581; 95% CI, 2.280–19.000; p<0.001). Conclusions Achieving a balanced fusion mass intraoperatively is important to avoid postoperative distal adding-on, with FMS of <20 mm and FMS angle of <4.5°. Furthermore, correcting LIV rotation helps to decrease the incidence of postoperative distal addingon.

Objective To analyze the levels of IgE,TNF-α and FeNO in children with acute attack of bronchial asthma and their correlation with the severity of bronchial asthma, so as to provide theoretical basis for clinical evaluation of bronchial asthma. Methods A total of 547 children with acute bronchial asthma treated in Chengdu Women and Children's Central Hospital from January 2020 to December 2020 were selected and divided into mild group (n=287), moderate group (n=186) and severe group (n=74) according to the severity of their disease. All the children's symptoms were controlled after treatment. The serum IgE, TNF-α and FeNO levels in the experimental group were compared between the acute attack stage and the clinical control stage. Spearman correlation analysis was used to analyze the correlation between the serum IgE, TNF-α and FeNO levels and the severity of the disease. ROC curve of children with bronchial asthma was drawn to analyze the differential diagnosis value of serum IgE, TNF-α and FeNO levels in children with acute bronchial asthma. Results The levels of IgE, TNF-α and FeNO in acute stage were significantly higher than those in clinical control stage (P<0.05). The levels of serum IgE, TNF-α and FeNO in severe group were higher than those in mild and moderate groups significantly (P<0.05). The levels of serum IgE, TNF-α and FeNO in moderate group were higher than those in mild group significantly (P<0.05). Spearman correlation analysis showed that serum IgE, TNF-α and FeNO water were positively correlated with the severity of bronchial asthma (r=0.419 , 0.438 , 0.502 , P<0.05). ROC curve analysis showed that the AUC, sensitivity, accuracy and specificity of serum IgE, TNF-α and FeNO levels combined in diagnosing the severity of bronchial asthma in patients with acute attack was 0.938 (95% CI: 0.912-0.982 ), 83.47%, 92.06%, 94.28%. Conclusion The level of serum IgE, TNF-α and FeNO in children with acute attack of bronchial asthma is closely related to the severity of the disease, and combined detection of the three can be used to evaluate the severity of the disease in children.

Objective:To explore the consistency of peripheral whole blood and venous serum procalcitonin (PCT) levels, and the value of peripheral whole blood PCT in evaluating pediatric bacterial infection.Methods:This multicenter cross-sectional parallel control study was conducted in 11 children′s hospital. All the 1 898 patients older than 28 days admitted to these hospitals from March 2018 to February 2019 had their peripheral whole blood and venous serum PCT detected simultaneously with unified equipment, reagent and method. According to the venous serum PCT level, the patients were stratified to subgroups. Analysis of variance and chi-square test were used to compare the demographic characteristics among groups. And the correlation between the peripheral blood and venous serum PCT level was investigated by quantitative Pearson correlation analysis.The PCT resultes were also converted into ranked data to further test the consistency between the two sampling methods by Spearman′s rank correlation test. Furthermore, the ranked data were converted into binary data to evaluate the consistency and investigate the best cut-off of peripheral blood PCT level in predicting bacterial infection.Results:A total of 1 898 valid samples were included (1 098 males, 800 females),age 27.4(12.2,56.7) months. There was a good correlation between PCT values of peripheral whole blood and venous serum ( r=0.97 , P<0.01). The linear regression equation was PCT?venous serum=0.135+0.929×PCT peripheral whole blood. However, when stratified to 5 levels, PCT results showed diverse and unsatisfied consistency between the two sampling methods ( r=0.51-0.92, all P<0.01). But after PCT was converted to ordinal categorical variables, the stratified analysis showed that the coincidence rate of the measured values by the two sampling methods in each boundary area was 84.9%-97.1%. The dichotomous variables also showed a good consistency (coincidence rate 96.8%-99.3%, Youden index 0.82-0.89). According to the severity of disease, the serum PCT value was classified into 4 intervals（<0.5、0.5-<2.0、2.0-<10.0、≥10.0 μg/L）, and the peripheral blood PCT value also showed a good predictive value (AUC value was 0.991 2-0.997 9). The optimal cut points of peripheral whole blood PCT value 0.5、1.0、2.0、10.0 μg/L corresponding to venous serum PCT values were 0.395, 0.595, 1.175 and 3.545 μg/L, respectively. Conclusions:There is a good correlation between peripheral whole blood PCT value and the venous serum PCT value, which means that the peripheral whole blood PCT could facilitate the identification of infection and clinical severity. Besides, the sampling of peripheral whole blood is simple and easy to repeat.

ABSTRACT OBJECTIVE：To study the improvement effect of Periplaneta americana extract Ento-A on damp-heat ulcerative colitis（UC）model rats. METHODS：Totally 70 rats were randomly divided into normal control group（n＝8）and modeling group （n＝62）. The damp-heat UC model was induced in modeling group by high sugar，high fat，spicy diet combined with 2，4， 6-trinitrobenzene sulfonic acid enema. 48 modelrats were randomly divided into model control group，mesalazine group （300 mg/kg），Changyanning group（300 mg/kg）and Ento-A low-dose，medium-dose and high-dose（50，100，200 mg/kg，calculated by the extract），with 8 rats in each group. Normal control group and model control group were given normal saline intrsgastrically，and other groups were given relevant medicine intragastrically，once a day，for consecutive 14 days. After last administration， disease activity index （DAI）， colonic mucosal injury index （CMDI） and histopathological score （HS）of rats were determined. The spleen index，liver index and colon index in rats were determined. The serum levels of IL-8，IL-17，SOD and MDA，colonic levels of IL-2，PGE2 and MPO were detected by ELISA. RESULTS：Compared with normal control group，the DAI score，CMDI score，HS score，colonic index，the serum levels of IL-8，IL-17 and MDA， colonic levels of MPO and PGE2 were increased significantly（P＜0.01）；serum level of SOD and colonic level of IL-2 were decreased significantly （P＜0.01）. Compared with model control group，DAI score，CMDI score，serum levels of IL-17 and MDA，colonic levels of PGE2 were decreased significantly in Ento-A high-dose groups（P＜0.05 or P＜0.01），while serum level of SOD and colonic level of IL-2 were increased significantly（P＜0.01）. CMDI score and HS score，serum levels of IL-8，IL-17 and MDA，colonic levels of PGE2 and MPO were decreased significantly in Ento-A medium-dose group（P＜0.05 or P＜0.01）， while colonic level of IL-2 was increased significantly（P＜0.01）. HS score，serum levels of IL-17 and MDA，colonic levels of MPO and PGE2 were decreased significantly in Ento-A low-dose group（P＜0.05 or P＜0.01），while serum level of IL-2 was increased significantly（P＜0.01）. CONCLUSIONS：P. americana extract Ento-A may play improvement effect on damp-heat UC rats by regulating immune system balance and reducing inflammatory damage.

OBJECTIVE：To study the spectrum-ef fect relationship of anti-hepatoma effect of C Ⅱ-3 extract from Periplaneta americana，and to preliminarily clarify the anti-hepatoma active components of it. METHODS ：Based on UHPLC fingerprints of 10 batches of C Ⅱ-3 samples，with the help of UHPL C-Q-TOF/MS，the compounds corresponding to each chromatographic peak were identified qualitatively by standard substances and related literatures. Using the IC 50 value of each batch of C Ⅱ-3 sample against human hepatoma cells HepG 2 as anti-hepatoma activity index ，the spectrum-effect relationship of fingerprint and anti-hepatoma effect was established and analyzed by the combination of grey relational analysis （GRA）and orthogonal partial least squares（OPLS）. RESULTS ：There were 25 common peaks in UHPLC fingerprints of 10 batches of C Ⅱ-3 samples，and 10 chemical compounds were identified ，which were cyclo- （Tyr-Pro）（peak 24），cyclo-（Gly-Phe）（peak 15），hypoxanthine（peak 3）， adenine（peak 7），phenylalanine（peak 10），inosine（peak 11），N-acetyldopamine（peak 16），cyclo-（Pro-Ala）（peak 13），2-hydroxy propionyl（peak 22），cyclo-（Pro-Ser）（peak 6）. The IC 50 of 10 batches of C Ⅱ-3 samples to HepG 2 cells was 70.550-200.303 μg/mL. Among 25 common peaks ，the order of GRA correlation （r）of anti-hepatoma activity was peak 20＞23＞24＞15，all of r values were greater than 0.7；the order of variable importance projection （VIP）of OPLS analysis was peak 23＞18＞15＞24＞7＞14＞6＞ 2＞20，all of VIP values were greater than 1. The standard regression coefficients of peak 7，15，20，23，24 were all greater than 0；while the standard regression coefficients of peak 2，6，14，18 were all less than 0. Conjoint analysis shows that the order of anti-hepatoma activity was peak 20＞23＞24＞15. CONCLUSIONS：unknown chemical ingredients （peak 20， ），cyclo-（Tyr-Pro）（peak 24）and cyclo- （Gly-Phe）（peak 15） in C Ⅱ-3 may be main anti-hepatoma active components.

OBJECTIVE： To study the improvement effects of Bee venom（BV） plastics on experimental cerebral thrombosis in rats. METHODS： Totally 96 SD rats were randomly divided into sham operation group （normal saline）， model group （plastics blank matrix）， Nimodipine group （positive drug， 4.00 mg/kg） and BV plastics low-dose， medium-dose， high-dose groups （1.67， 3.33， 6.67 mg/kg）， with 16 rats in each group. Rats in sham operation group and Nimodipine group were given medicine intragastrically， while rats in model group and BV plastics groups were given medicine by transdermal smearing. After 5 days of continuous administration， the experimental cerebral thrombosis model was established by ligating the right external carotid artery and pterygomandibular artery， and injecting compound thrombus inducer into the internal carotid artery. The wet mass ratio of right brain to left brain was measured to investigate the degree of brain edema on the infarcted side. The content of Evans blue （EB） in the left and right hemispheres of rats was determined by ultraviolet spectrophotometry to investigate the cerebral vascular permeability. Blood rheology and coagulation function indicators of rats were measured. The pathological changes of brain tissue in rats were observed by HE staining， and the number of survival neuron cells was counted. RESULTS： Compared with the indexes of sham operation group， the cerebral thrombosis model was established successfully. Compared with model group， the area of blue staining in the right brain （infarcted side） of rats in BV plastics groups was significantly reduced， and the right brain/left brain wet mass ratio and the content of EB in the right brain tissue were significantly reduced （P＜0.05 or P＜0.01）. The whole blood viscosity and Casson viscosity of rats in BV plastics groups， and the plasma viscosity of rats in BV plastics medium-dose and high-dose groups decreased significantly （P＜0.01）. PT and APTT of rats were prolonged significantly in BV plastics medium-dose group （P＜0.01）. The pathological changes of brain tissue in rats in BV plastics groups were significantly alleviated. The arrangement of neuron cells was more orderly， the shape and structure of cells were clear， the nucleolus was clear， the membrane was intact， and the number of survival neuron cells was significantly increased （P＜0.01）. CONCLUSIONS： BV plastics can alleviate brain edema， inhibit cerebral vascular permeability， improve hemorheology and coagulation function indicators of rats after the formation of cerebral thrombosis， and alleviate nerve cell injury after ischemia.

OBJECTIVE： To investigate the acute toxicity， long-term toxicity， skin irritation and anaphylaxis of Bee venom （BV） plastics， and to evaluate its preclinical safety. METHODS： The acute toxicity of BV plastics to rats was investigated after administration of high-dose， medium-dose and low-dose （144， 96， 48 mg/kg） of BV plastics. The long-term toxicity of BV plastics was investigated by continuous administration of high-dose， medium-dose and low-dose （72， 48， 24 mg/kg） of BV plastics for 28 days. The irritation of intact and damaged skin in rabbits with 8 mg/kg BV plastics was investigated by using the self-control method of left and right homologous body. The skin anaphylaxis of guinea pig were investigated after sensitized with 15 mg/kg BV plastics on the left back （on 0， 7th， 14th day） and stimulated with 15 mg/kg BV plastics on the right back. RESULTS： During the acute toxicity experiment with BV plastic，the weight of rats and the changes of viscera were normal，and there was no relevant toxic reaction. Long-term toxicity test results showed that no significant pathological changes were observed at 24 h after the last administration； the spleen index  of rats in BV low-dose group， testicular index in middle-dose group and epididymis index in high-dose and middle-dose groups were significantly increased， while PT in plasma of rats in BV medium-dose and low-dose groups was significantly prolonged （P＜0.05）. There were no abnormal changes in organ appearance， other organ index， coagulation index and blood biochemical index. All above indexes became normal at the end of 2-week recovery period. Skin irritation test showed that BV plastics could cause slight erythema and obvious scab on the skin of rabbits which along with little irritation on intact or damaged skin. Skin anaphylaxis test showed that BV plastics produced mild erythema in the skin of guinea pigs， belonging to light allergy. CONCLUSIONS： No acute or long-term toxicity is observed after transdermal administration of BV plastics， which is safe and only causes mild irritation and irritability to skin， indicating there is good safety of the plastic under experiment doses.