Compared with conventional transdermal drug delivery systems, dissolving microneedles significantly enhance drug bioavailability by penetrating the stratum corneum barrier and achieving intradermal drug delivery. In order to improve the transdermal bioavailability of dexmedetomidine hydrochloride, in this study, a novel microneedle delivery system was developed for dexmedetomidine hydrochloride based on 3D printing combined with micro-molding. By systematically optimizing the microneedle geometrical parameters, array arrangement, and preparation process parameters, we determined the optimal ratio of drug-carrying matrix as 15% PVP (polyvinyl pyrrolidone) K90. The microneedles exhibited significant drug loading gradients, with mean content of (209.99±27.56) μg/patch, (405.31±30.31) μg/patch, and (621.61±34.43) μg/patch. They showed a regular pyramidal structure under SEM and handheld electron microscopy, and their mechanical strength allowed effective penetration into the stratum corneum. The surface contact angles were all < 90°, indicating excellent hydrophilicity. The microneedles dissolved completely within 10 min after skin insertion, achieving a cumulative release rate of 90% (Higuchi model, r=0.996) during 2 hours of in vitro transdermal permeation. The cytotoxicity test and hemolysis test verified good biocompatibility. Pharmacodynamic evaluation showed that the microneedle group demonstrated pain-relieving effect within 15 min, with the pain threshold at the time point of 60 min being 3 times that in the transdermal cream group. The microneedle system developed in this study not only offers an efficient drug delivery option for patients but also establishes an innovative platform for rapid percutaneous delivery of hydrophilic drugs, demonstrating significant potential in perioperative pain management.
Dexmedetomidine/pharmacokinetics* ; Printing, Three-Dimensional ; Needles ; Drug Delivery Systems/methods* ; Administration, Cutaneous ; Animals ; Microinjections/instrumentation* ; Skin Absorption ; Skin/metabolism*

Objective To investigate the correlation between amide proton transfer-weighted(APTw)value derived from APTw imaging and Ki-67 expression in hepatocellular carcinoma.Methods Sixty patients with hepatic occupations underwent preoperative upper abdominal MRI scanning,including APTw and diffusion weighted imaging(DWI)sequences.Thirty-two patients with hepatocellular carcinoma proved by pathological results were enrolled in the prospective study.The APTw and apparent diffusion coefficient(ADC)values of the lesions were measured from the corresponding APTw and ADC images,respectively.Mann-Whitney U test or independent sample t test was used to analyze the differences in APTw and ADC values between the high and low Ki-67 expression groups.Pearson correlation analysis was used to evaluate the correlation between APTw value,ADC value and Ki-67 expression level of hepatocellular carcinoma.The receiver operating characteristic(ROC)curve was used to evaluate the diagnostic efficacy of amide proton transfer(APT)parameter in differentiating high and low Ki-67 expression groups.Results The APTw values of high Ki-67 expression group(n=24)was higher than that of low Ki-67 expression group(n=8)[(1.33±0.77)％vs(0.64±0.58)％,P=0.026].There was no significant difference in ADC values between the two groups(0.82×10-3 mm2/s vs 0.86×10-3 mm2/s,P=0.679).The APTw values were positively correlated with Ki-67 expression(r=0.377,P=0.035),and the area under the curve(AUC)of APTw value＞1.24％for the diagnosis of high Ki-67 expression was 0.794,with a sensitivity of 67％and a specificity of 88％.Conclusion The APTw value of hepatocellular carcinoma is positively correlated with Ki-67 expression,which has certain diagnostic value for predicting the expression status of Ki-67.

Objective To investigate the value of extracellular volume fraction(ECV)based on CT for predicting macrotrabecular-massive hepatocellular carcinoma(MTM-HCC).Methods Data of 23 MTM-HCC(MTM-HCC group)and 56 non-MTM-HCC(nMTM-HCC group)patients were retrospectively analyzed,and CT manifestations were compared between groups.CT values of abdominal aorta(P-CTabdominal aorta,E-CTabdominal aorta),tumors(P-CTtumor,E-CTtumor)and non-tumor liver parenchyma(P-CTliver,E-CTliver)in plain phase(P)and enhancement equilibrium phase(E)CT were measured,then ECV of tumors and liver parenchyma were calculated,and ECV-related parameters were compared between groups.Receiver operating characteristic curves were drawn,and area under the curve(AUC)was calculated to evaluate the predictive efficacy of ECV-related parameters for predicting MTM-HCC.Results No significant difference of CT manifestations was found between groups(all P＞0.05).E-CTtumor,Δltumor(absolute enhancement CT value of the tumor area)and ECVtumor in MTM-HCC group were all lower than those in nMTM-HCC group(all P＜0.01).The AUC of E-CTtumor,Δtumor and ECVtumor for predicting MTM-HCC was 0.74,0.77 and 0.87,respectively,and the AUC of ECVtumor was higher than that of E-CTtumor and Δtumor(Z=2.271,2.557,P=0.023,0.011).Conclusion ECV based on CT could be used to effectively predict MTM-HCC.

Objective To discuss the clinical value of systemic immune-inflammation index(SII)in predicting the prognosis of patients with extrahepatic cholangiocarcinoma(ECCA)treated with biliary stenting combined with 125I seeds implantation.Methods A total of 128 patients with unresectable ECCA,who received biliary stenting combined with 125I seeds implantation at the Interventional Department of the Affiliated Hospital of Xuzhou Medical University of China between August 2018 and August 2021,were enrolled in this study.The peripheral blood routine testing was performed within 3 days before operation,based on which the SII was calculated.Receiver operating characteristic(ROC)curve was applied to determine the optimal cut-off value of SII,based on which the patients were divided into high-SII group and low-SII group.Cox regression model was used to analyze the independent factors affecting patient prognosis.The Kaplan-Meier curve was plotted to analyze the one-year survival.Results The optimal cut-off value of SII was 1 050,the sensitivity was 66.0％,the specificity was 69.3％,and the area under ROC curve of SII was 0.676.The one-year survival rate of patients with ECCA in the high-SII group was significantly lower than that in the low-SII group(P＜0.05).Univariate Cox regression analysis indicated that vascular invasion,T stage,adjuvant chemotherapy,CA19-9,and preoperative SII were the important factors affecting the prognosis of patients with ECCA.Multivariate Cox regression analysis revealed that T stage,CA19-9,and preoperative SII were the independent risk factors for patient prognosis,while adjuvant chemotherapy was a protective factor.The Kaplan-Meier curves showed that the one-year survival rate in high-SII group was remarkably lower than that in the low-SII group.Conclusion Preoperative SII has an important value in evaluating the prognosis of patients with ECCA who are treated with biliary stenting combined with 125I seed implantation.(J Intervent Radiol,2023,32:1221-1225)

Objective:To investigate the safety and efficacy of robot-guided ventricular partition puncture drainage in severe intraventricular hemorrhage.Methods:A total of 23 patients with severe intraventricular hemorrhage who underwent robot-guided ventricular partition puncture drainage (experimental group) and 19 patients who underwent robot-guided bilateral ventricular puncture drainage (control group) at Department of Neurosurgery, People's Hospital of Baise from January 2021 to December 2021 were included. The differences in residual hematoma volume within 24 h of surgery, drainage tube retention time, mortality rate within 30 d of surgery, incidence of complications (re-bleeding, intracranial infection, pulmonary infection, hydrocephalus) within 6 months of surgery, and scores of Glasgow coma scale (GCS), activity of daily living (ADL), and National Institutes of Health stroke scale (NIHSS) at 6 months after surgery were compared between the 2 groups.Results:Compared with the control group, the experimental group had significantly lower residual hematoma volume within 24 h of surgery ([8.854±3.519] mL vs. [5.668±2.873] mL), shorter drainage tube retention time ([6.580±1.981] d vs. [4.910±2.763] d), lower incidence of hydrocephalus within 6 months of surgery (42.105% vs. 8.696%), and significantly higher GCS and ADL scores and lower NIHSS scores at 6 months after surgery (8.790±2.898 vs. 11.610±2.948; 69.470±12.899 vs. 78.480±12.861; 13.950±5.265 vs. 9.870±4.124, P<0.05). Conclusion:Robot-guided ventricular partition puncture drainage is a safe and effective surgical method for severe intraventricular hemorrhage.

OBJECTIVE：To i nvestigate the spectrum-effect relationship of analgesic and anti-inflammatory effects of ethyl acetate extract from Zhuang medicine Stahlianthus involucratus from different habitats. METHODS ：Ten batches of S. involucratus from different habitats were used as samples to investigate the anti-inflammatory and analgesic activities of ethyl acetate extracts by xylene induced ear swelling test and acetic acid induced writhing test in mice. HPLC fingerprints of 10 batches of ethyl acetate extract from S. involucratus were established and their similarity was evaluated by using Similarity Evaluation System of TCM Chromatogram Fingerprint （2012 edition），and the common peaks were identified by comparison with the control. The spectrum-effect relationship of anti-inflammatory and analgesic effects of ethyl acetate extract from S. involucratus were analyzed on the basis of Pearson correlation coefficient （auricle swelling degree and writhing times in 15 min as pharmacodynamic indexes ）and Grey relational analysis （inhibition rate of ear swelling and analgesic rate as pharmacodynamic indexes ）. RESULTS ： batches of ethyl acetate extract from S. involucratus had obvious anti-inflammatory and analgesic effects ； inhibition rates of ear swelling in mice were 46.43％-55.16％，and the analgesic rates of mice were 45.56％-52.72％. A total of 18 common peaks were identified in 10 batches of samples ，andthe similarity between them and the control fingerprint was 0.994-0.997. Compared with substance control ，the pea ks 1，2 and 4 were identified as protocatechuic acid ， p-hydroxy- 0771-4953513。E-mail：liangjie1101@126.com benzoic acid and p-hydroxybenzaldehyde，respectively. Results of Pearson correlation analysis showed that peak 10 and peak 18 were significantly negative correlated with auricle swelling degree and writhing times in 15 min（r were values －0.853，－0.738，P values were 0.002，0.015，respectively）. Results of Gray correlation degree analysis showed that the correlation degree of 18 common peaks with inhibition rate of ear swelling and analgesic rate were all greater than 0.65；among them ，peaks 14，1（protocatechuic acid ），17，9，4（p-hydroxybenzaldehyde），2（p-hydroxybenzoic acid ）， 16，7 and 6 showed the relatively high correlation degree （correlation degree ＞0.7）；peak 1（protocatechuic acid ），17，14，9，16，2 （p-hydroxybenzoic acid ）and 4（p-hydroxybenzaldehyde）showed the relatively high correlation degree （correlation degree ＞0.7）. CONCLUSIONS：The ethyl acetate extract of S. involucratus show good anti-inflammatory and analgesic effects. Peak 1 （protocatechuic acid ），2（p-hydroxybenzoic acid ），10，14，17，18 may be its main active ingredients.

Objective: To investigate the expression of macrophage migration inhibitory factor (MIF) in pulmonary tissues from patients with chronic obstructive pulmonary disease (COPD) and the relationship with its clinical features. Methods: One hundred and eighty patients who underwent pulmonary bullectomy lobectomy due to pneumatocele from January 2015 to September 2018 in Longgang Central Hospital were enrolled and classified into patients without COPD (control group)and patients with COPD (COPD group), with 90 patients each group. According to the lung function parameters, 90 patients with COPD were divided into the mild COPD group, the moderate COPD group, and the severe COPD group. The levels of mRNA and protein of MIF were measured with RT-PCR, ELISA and Western blot. One-way ANOVA, Pearson correlation analysis and SNK-q test were used to analyze the results with SPSS 18.0, and P<0.05 was considered statistically significant. Results: The level of MIF in pulmonary tissues from the control group was obviously lower than those in the COPD group (P<0.05). The level of MIF in pulmonary tissues in the severe COPD group was obviously higher than those in pulmonary tissues in the mild COPD, moderate COPD and control groups (P<0.05). MIF was positively correlated with the lung function parameters (P<0.05). Conclusion The high expression of MIF in pulmonary tissues is closely related to the severity of COPD.

Objective :To explore influence of intra—arterial thrombolysis combined hyperbaric oxygen on serum levels of soluble intercellular adhesion molecule—1 (sICAM—1) and calcitonin gene related peptide (CGRP) in patients with severe ischemic stroke .Methods : A total of 96 patients with severe ischemic stroke in our hospital were randomly and equally divided into thrombolysis group and combined treatment group (received intra—arterial thrombolysis +hyperbaric oxygen therapy ).United States National Institutes of Health Stroke score (NIHSS) was used to assess neurological function recovery , and modified Rankin rating score (mRS) was used to assess recovery of clinical symptoms.After two—week treatment ,clinical therapeutic effect etc .were compared between two groups .Results :Compared with thrombolysis group after treatment ,there was significant rise in total effective rate (77.08% vs. 93. 75%, P＝0.021) ;significant reductions in scores of NIHSS [ (8.10 ± 3.45) scores vs .(5.36 ± 2.11) scores] and mRS [ (2.58 ± 0. 80) scores vs .(1.81 ± 0.76) scores] ;significant reduction in serum sICAM—1 level [ (237.31 ± 18. 04) ng／ml vs.(220.25 ± 16.40) ng／ml] ,and significant rise in serum CGRP level [ (27.02 ± 6.06) pg／ml vs. (35.24 ± 6.13) pg／ml] in combined treatment group , P＝0.001 all.There was no significant difference in revascu—larization within two weeks between two groups , P＝0.551. Conclusion : Intra—arterial thrombolysis combined hy—perbaric oxygen possesses significant therapeutic effect on patients with severe ischemic stroke .It can relieve clinical symptoms ,recover cognitive function ,improve revascularization rate in these patients .

Objective To evaluate the clinical presentations,pathologic characteristics,and the diagnosis and treatment of eosinophilic cystitis.Methods Two cases of eosinophilic cystitis were analyzed,and the relevant literature was reviewed.Case 1,a 63-year-old man,complained of voiding urgency and frequency,dysuria,intermittent hematuria,and lower abdominal pain.Cystoscopic examination showed that an about 5cm?3cm abnormal focus was 0.2-0.4 cm above bladder mucosa at the fundus of the bladder.Case 2,a 42-year-old woman,complained of voiding urgency and frequency,dysuria,and suprapubic pain with intermittent hematuria.Cystoscopic examination showed that about 4 cm?3 cm?2 cm abnormal foci of cauliflower-like were 0.3-0.4 cm above bladder mucosa at the fundus and neck of the bladder.Imaging examinations(Bultrasound,CT and IVU) showed diffuse thickening of bladder wall and tumor-like lesions.They both underwent transurethral resection of the lesions and were treated with oral steroids and antibiotics.Results Postoperative pathology confirmed eosinophilic cystitis in both cases.The follow-up was 6 months.The voiding symptoms disappeared,and imaging examinations showed no space-occupying lesions of the bladder in them.Up to now,there has no evidence of relapse.Conclusions Eosinophilic cystitis is a very rare tumor-like inflammatory disease.It is easily misdiagnosed as bladder neoplasm.Cystoscopy and biopsy are gold standard for the diagnosis.Current treatment modalities include transurethral resection of the bladder lesion along with nonspecific medical therapy.

Satisfaction questionnaires for emergency patients were developed in the present study and face to face surveys were conducted. The rate of effective retrieval was 96.8% and the response rate was 96.2%. The ? coefficient for internal consistency was fairly high (0.7099～0.9217) and there was a fairly strong correlation between the various items and the subordinate factors (0.744～0.912, with the exception of B15). A factor analysis indicated that the factor load and structure were basically consistent with the contents of the questionnaire. A statistical analysis showed that the satisfaction questionnaire for emergency patients, which had both credibility and validity, could be used for evaluating emergency patient satisfaction and could provide hospitals with the basis for measuring medical quality.