BACKGROUND:Gold nanoparticles are of great significance in the development of multifunctional transdermal drug delivery systems.Smaller gold nanoparticles can penetrate the dermis through the intercellular pathway,but are limited to their easy agglomeration and colloidal morphology,which makes it difficult to exert effects on low delivery efficiency. OBJECTIVE:To develop an ultrasound-optimized hydrogel delivery system by combining phase change nanodroplets with bio-adhesive hydrogel for percutaneous delivery of gold nanoparticles. METHODS:The ultrasound-responsive nanodroplets loaded with gold nanoparticles were prepared by the emulsion solvent evaporation method and loaded into the polydopamine-modified methylacryloyl gelatin hydrogel to prepare a composite hydrogel scaffold.The structure and chemical composition of the ultrasound-responsive nanogold carrier were characterized.The microstructure,porosity,permeability,rheology,in vitro hemostasis,and antibacterial properties of the composite hydrogel were characterized.The cell compatibility of the hydrogel scaffold was evaluated by live/dead staining,and the optimization effects of low-intensity pulsed ultrasound on the permeability,porosity,and mechanical properties of hydrogel were evaluated. RESULTS AND CONCLUSION:(1)Transmission electron microscopy and ultraviolet-visible spectroscopy proved the successful construction of nanogold carriers.The particle size and potential results demonstrated that the synthesized nanoscaled ultrasonic responsive carrier had good stability.(2)Live/dead cell staining proved that the prepared composite hydrogel scaffold had certain biocompatibility.(3)Scanning electron microscopy exhibited that the prepared composite hydrogel scaffold had a porous network structure,and numerous pores of about 2 μm appeared inside the macropores after the addition of nanodroplets and ultrasonic irradiation.The permeability experiment displayed that low-intensity pulsed ultrasound could optimize the porosity and permeability of hydrogel materials.The hemostatic performance of the composite hydrogel scaffold was better than that of the hemostatic sponge and polydopamine@methylacrylylated gelatin hydrogel scaffold.Under the irradiation of low-intensity pulsed ultrasound,the composite hydrogel scaffolds had good antioxidant effects and antibacterial properties.(4)Thermal imaging results manifested that gold nanoparticles were encapsulated in ultrasound-responsive nanobubbles,and more uniform dispersion could be obtained under ultrasonic excitation.(5)The results of the mechanical property test demonstrated that the storage modulus of the hydrogel increased before and after loading gold nanoparticles-nanodroplets,which showed stronger mechanical properties.The elongation at break was 122%,and the ductility was better than that without gold nanoparticles-nanodroplets(P<0.05).(6)These findings indicate that the composite hydrogel scaffold has good biocompatibility,antibacterial property,oxidation resistance,and hemostatic effect.

Objective To compare the accuracy of the original-mirror alignment algorithm and a landmark-indepen-dent method in constructing the midsagittal plane(MSP)of the cone beam computed tomography in patients with facial deformities,so as to provide a theoretical basis for symmetric analysis.Methods The study was approved by the hospi-tal ethics committee.Cone beam computed tomography data of 30 patients with facial deformities were obtained,and the output was saved in DICOM format.The scan data were imported into Mimics 21.0;after segmentation,three-dimension-al(3D)skull models were reconstructed.Furthermore,the 3D scan data of skulls were transformed into mirror skull models using Geomagic Studio 2014 reverse engineering software.The MSP of each skull was generated using both the original-mirror alignment algorithm and the landmark-independent method.Original-mirror alignment algorithm:the original skull model and its mirror model were combined,and the new data to calculate the MSP(S1)of the original data in Geomagic Studio 2014 were obtained.Landmark-independent method:the following anatomical landmarks were deter-mined using Mimics 21.0:nasion(N),crista galli(CG),sella(S),basion(Ba),vomer(V),posterior nasal spine(PNS),in-cisive foramen(IF),and anterior nasal spine(ANS).The MSP(S2)of best fit was then found by minimizing the mean square distance of these eight anatomical landmarks to a plane in Geomagic Studio 2014.The results of the S1 and S2 models constructed using the original-mirror alignment algorithm and the landmark-independent method,respectively,were scored subjectively by five senior maxillofacial surgeons,and a paired t-test was performed for the two groups.The internal consistency analysis was performed based on secondary experiments to verify the repeatability of the expert evaluation method.Results The average scores of the S1 and S2 models were 65.73 and 75.90,respectively.The aver-age score of the model constructed using the landmark-independent method was significantly higher than that of the model constructed using the original-mirror alignment algorithm(P＜0.01).Furthermore,the results of the internal con-sistency analysis showed that the expert evaluation method had good reliability and validity.Conclusion In patients with facial deformities,the MSP constructed using the landmark-independent method is superior to that constructed us-ing the original-mirror alignment algorithm.This study provides a theoretical basis for maxillofacial symmetry analysis in clinical settings and is clinically feasible.

Objective:To explore the potential of thrombus-targeted nanoprobes for ultrasound/near-infrared bimodal imaging and their synergistic therapeutic effects on thrombosis in vitro.Methods:Nanoprobes loaded with arginine-glycine-aspartate peptide (RGD), perfluoropentane (PFP) and indocyanine green (ICG) were prepared by ultrasonic vibration and carbodiimide method with mesoporous silica nanoparticle (MSN) as the carrier. The probe morphology was observed by scanning and transmission electron microscopy. The loading of RGD and ICG was detected by Bicinchoninic Acid Assay (BCA) and UV-Visible-NIR spectroscopy respectively. The imaging performance and photothermal response of the nanoprobe under near infrared light (NIR) irradiation were studied in vitro. Its biological safety was tested by cytotoxicity test and hemolysis test. The phase transformation was studied under ultrasound and NIR irradiation. The nanoprobe was incubated with fresh arterial thrombus, and its target-seeking ability was observed by frozen section. Ultrasound and NIR irradiation were used to evaluate its thrombolytic ability by the weight changes of thrombus before and after irradiation.Results:The prepared nanoprobe had regular morphology and uniform size. The particle diameter was (156.83±5.05)nm, and the surface potential was (11.47±0.25)mV. The RGD coupling rate was (77.67±4.50)%, which could mediate the targeting of nanoprobe to fresh extracorporeal arterial thrombus. UV-Visible-NIR spectroscopy confirmed the successful loading of ICG, and its encapsulation rate was (80.47±0.05)%. After ultrasound and NIR irradiation, the nanoprobe could undergo acoustically induced phase transition, thermally induced phase transition and enhance the ultrasonic development effect. With the increase of the concentration of the nanoprobe solution, the NIR signal gradually increased, and the temperature rose in a concentration-dependent and intensity-dependent manner after NIR irradiation. The cytotoxicity test and hemolysis test showed that the nanoprobe had good biological safety, and it could play a thrombolytic role under the combined irradiation of ultrasound and NIR, and the weight of thrombus was significantly reduced after the treatment ( P<0.01). Conclusions:In this study, the nanoprobe (RGD/ICG/PFP@MSN) were successfully prepared possesses excellent dual mode imaging capabilities of ultrasound and NIR, excellent phase transition ability and photothermal conversion efficiency, as well as efficient targeted penetration and therapeutic effects against thrombosis. This study provides strong in vitro experimental evidence and new strategies for the integration of diagnosis and treatment of thrombotic diseases under the cooperation of ultrasound and NIR.

Talaromycosis marneffei has been increasing in recent years. Our understanding of this disease has gradually deepened through extensive basic and clinical research, but there are still many limitations. In this article, by incorporating the latest research advancements, we discuss important issues in managing Talaromycosis marneffei trends, aiming to guide effective prevention and control of the disease, improving public health, and reducing the healthcare burden.

Objective:To evaluate and summarize the best evidence for exercise scheme after bariatric and metabolic surgery in obese patients at home and abroad.Methods:We used "obesity" " bariatric and metabolic surgery" "sleeve gastrectomy" "gastric bypass surgery" "banding surgery" "exercise" "physical activity" "exercise therapy" "guideline" "expert consensus" "systematic review" "Meta-analysis" and "evidence summary" as keywords, and searched databases such as UpToDate, Cochrane Library, PubMed, China National Knowledge Infrastructure (CNKI) , Wanfang Data, and the guide network and professional association platforms by computer. Literature retrieved included guidelines, expert consensus, best clinical practice, clinical decision-making, systematic reviews, and the search time limit was from the database establishment to July 18, 2020. Two researchers evaluated the quality of literature and extracted evidence, and the evidence was revised and perfected through expert consultation.Results:A total of 4 systematic reviews and Meta-analysis articles, 2 clinical decision-making articles, 4 guidelines, and 1 expert consensus were included. The evidence was collected from 7 aspects, namely the importance of exercise, pre-exercise evaluation, exercise style, exercise intensity and duration, exercise safety, exercise follow-up, exercise effect evaluation, and finally 33 best evidences were summed up.Conclusions:Evidence of exercise scheme after bariatric and metabolic surgery in obese patients is comprehensive. Medical institutions and clinical medical and nursing staff can combine the institutional environment to transform and apply the evidence.

Metabolic bariatric surgery (MBS) is the most effective treatment for severe obesity. In order to achieve and maintain a good weight loss effect after MBS and prevent short-term and long-term postoperative complications, postoperative diet and nutrition management is very necessary. This article summarizes the importance of diet and nutrition management, management status, intervention status, and diet management tools for obese patients after MBS, and puts forward the problems to be solved in my country's current diet and nutrition management, so as to provide a reference for future research on diet and nutrition management after MBS.

OBJECTIVE:To establish the method for simultaneous determination of berberine hydrochloride and baicalin in Jianpi zhixiening granules. METHODS:HPLC switching walvelength method was adopted. The determination was performed on Hypersil BDS C18 column with mobile phase consisted of methanol-0.45％ phosphoric acid solution-triethylamine(50:49:1,V/V/V) at the flow rate of 1.0 mL/min. The detection wavelength was set at 265 nm(berberine hydrochloride)and 280 nm(baicalin). The column temperature was set at 30 ℃,and sample size was 10 μL. RESULTS:The linear range of berberine hydrochloride and baicalin were 60.3-312.8 ng(r=0.9997)and 81.5-368.9 ng(r=0.9999). The limits of quantitation were 0.6668,0.7740 ng,andthe limits of detection were 0.2226,0.2580 ng,respectively. RSDs of intermediate precision,stability and repeatability tests were all lower than 1.0％. The recoveries were 96.48％-99.30％(RSD=1.06％,n=6) and 95.20％-99.39％(RSD=1.66％,n=6), respectively. RSDs of durability test were all lower than 2.0％. CONCLUSIONS:The method is simple, precise, stable, reproducible,accurate and durable. It can be used for simultaneous determination of berberine hydrochloride and baicalin in Jianpi zhixiening granules.

Objective To establish the blood Septin9 methylation detection system for early screening of colorectal cancer based on fluorescence PCR technology .Methods The PCR primer of Septin9 was designed by searching the CpG island site of Septin9 methylation in the NCBI database .The high methylation site of Septin9 gene promoter region was confirmed by PCR amplification and sequencing after extracting DNA from colorectal cancer and para-carcinoma tissues .The fluorescence PCR and TaqMan probe detection technique was designed by aiming at high methylation site for constructing the plasma sample methylation detection sys-tem .Then its accuracy ,specificity ,repeatability and minimum detectable amount were performed the assess-ment and analysis .The SETP9 methylation detection was performed in plasma samples from 57 cases of color-ectal cancer and 30 healthy persons .Results The high methylation site of Septin9 gene in tissue samples was confirmed by sequencing .This site served as the target for designing fluorescence PCR detection system .After assessment ,the accuracy ,specificity and repeatability of this detection system were 100％ ,the lowest detection amount reached 0 .1 ng/μL .Among the plasma samples in 57 cases of colorectal cancer ,the positive rate of Septin9 methylation site detection was 71 .92％ (41/57) and the positive rate of in the patients with pathologi-cal stage Ⅰ and Ⅱ of colorectal cancer reached 64 .2％ .But Septin9 gene had no methylation in plasma of healthy population .Conclusion The plasma fluorescence PCR detection system with Septin9 gene methylation as the target has the characteristics of high sensitivity ,high specificity and high accuracy ,which is the reliable detection technique for the early screening of colorectal cancer and has good clinical application prospect .

Objective To study the pharmacokinetics and detection window of clozapine and its metabolites in human blood, so as to provide experimental basis for forensic cases of identification of clozapine poisoning. Methods 29 Taiyuan Han people's elbow venous blood was collected after given oral administration of 12.5mg clozapine at different time point, in which clozapine and its metabolites were extracted with solid phase extraction (SPE) and determined by HPLC-MS-MS. The qualitative analysis was based on retention time and MRM ions. The quantitative analysis was based on an internal standard method and calibration curve. Using the 3p97 pharmacokinetic software, pharmacokinetic equation of clozapine in the blood were imitated from the C-T data, and pharmacokinetic parameters were calculated. Results The pharmacokinetics of clozapine met a two compartment open model with a first kinetics absorption. The Tmax of clozapine(CLP), demethylclozapine(DMCLP), N-oxidation-clozapine(NO-CLP) respectively were 2.96±1.32h, 8.65±3.00h, 9.31±26.38h; The Cmax of CLP, DMCLP, NO-CLP respectively were 34.68±9.32ng/mL, 11.16±4.15ng/mL, 9.62±13.88ng/mL;The t1/2 of CLP, DMCLP, NO-CLP respectively were 17.02±23.63h, 27.06±12.58h, 41.27±29.75h; The detection window of CLP, DMCLP, NO-CLP respectively were 81.72±26.19h, 93.21±29.40h and 19.93±14.62h. Conclusion The pharmacokinetics of clozapine in blood of Han people is consistent with two compartment open model with a first kinetics absorption. The pharmacokinetics model and parameters of clozapine can provide expirimental basis for forensic identification of clozapine poisoning cases.

Objective To investigate the significance of the combined detection of several serum tumor markers with high-risk human papillomavirus (HR-HPV) in the diagnosis of cervical cancer.Methods Chemiluminescent microparticle immunoassay(CMIA) was employed to measure the levels of serum CA125,CA19-9,SCCA and CEA in peripheral blood samples collected from 249 patients with cervical cancer,30 patients with cervix intraepithelial neoplasia(CIN),and 60 healthy controls.The levels of serum CA72-4,HE4 were measured by electrochemiluminescence immunoassay(ECLI).Flow-through hybridization and gene chip technology (HybriMax) was employed to measure the HPV genotypes in all the 339 cases of women.Results Serum CA72-4 level in the cervical cancer group [3.13 (2.25,7.63) ng/mL] was significantly higher than that in the C IN group [2.37 (1.98,6.25) ng/mL] and the control group [2.69 (2.35,3.35) ng/mL] (P =0.028;P =0.003).Serum CEA level in the cervical cancer group 3.08 (2.28,4.75) ng/mL was significantly higher than that in the CIN group [1.45 (1.00,1.83) ng/mL] and the control group [2.13 (1.45,2.67) ng/mL] (P =0.000;P =0.000).Serum CA 125 level in the cervical cancer group [24.4(20.30,44.15) U/mL] was significantly higher than that in the CIN group[12.85(7.90,16.23)U/mL] and the control group[12.33 (11.26,17.11) U/mL] (P =0.000;P =0.000).Serum CA19-9 level in the cervical cancer group[27.05(18.48,38.01) U/mL] was significantly higher than that in the CIN group[13.01 (8.79,17.12) U/mL] and the control group[12.83 (10.89,17.93) U/mL] (P =0.000;P =0.000).Serum SCCA level in the cervical cancer group [1.7 (0.90,4.75) ng/mL] was significantly higher than that in CIN group [0.8 (0.60,1.10) ng/mL] and the control group [0.6 (0.50,0.70) ng/mL] (P =0.000;P =0.000).However,there was no significant difference of HE-4 among three groups (P ＞ 0.05).The HR-HPV infection rates in the cervical cancer (92.4％) and CIN patients (90.0％) were significantly higher than that in controls (15.0％)(x2 =46.875,P =0.000;x2 =165.178,P =0.000).In the cervical cancer patients,the levels of serum tumor marker was associated with Federation International of Gynecology and Obstetrics (FIGO) stage (P ＜ 0.05).ROC curves showed HR-HPV was the most sensitive in the diagnosis of cervical cancer.The sensitivity of the diagnosis of cervical cancer by serum tumor markers combined with HR-HPV(97.99％) was significantly higher than that of single marker,CA724 25.30％,CEA 20.89％,CA125 27.71％,CA199 24.90％,SCCA 52.61％,HPV 92.37％ (x2 =278.237,P =0.000;x2 =307.036,P =0.000;x2 =263.348,P =0.000;x2 =280.769,P =0.000;x2 =137.864,P =0.000;x2 =8.580,P =0.003).Conclusion Serum tumor markers combined with HR-HPV check can improve the detection rate of cervical cancer and has important clinical value.