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 repair effect of bone marrow mesenchymal stem cells(BMSCs)on interferon gamma(IFN-γ)induced ovarian granulosa cell immune injury.Methods:A model of IFN-γ-induced ovarian granulosa cell immune injury was estab-lished.KGN cells after modeling were co-cultured with human BMSCs(hBMSCs)and divided into three groups:negative control(NC)group,IFN-γ group,and BMSC group.After co-culture,cell proliferation was determined by a cell counting kit 8 assay for 3 consecu-tive days.Cell apoptosis was determined using an Annexin V-FITC apoptosis detection kit and a CytoFLEX flow cytometer.The estra-diol level and the mRNA expression levels of aromatase CYP19A1 and FSHR were measured to evaluate the hormone synthesis ability.The level of lactate dehydrogenase(LDH),mRNA expression levels of NLRP3,caspase-1(CASP1),and interleukin-1β,and protein expression levels of NLRP3,CASP1,and gasdermin-D were determined to evaluate cell pyroptosis.Results:The proliferation rate of granulosa cells in the IFN-γ group and the BMSC group was lower than that in the NC group at 24 h,48 h and 72 h,and that in the IFN-γ group was lower than that in the BMSC group(P<0.001).The number of apoptotic granulosa cells in the INF-γ group and the BMSC group was higher than that in the NC group,and that in the INF-γ group was higher than that in the BMSC group(P<0.001).The estradiol level in the INF-γ group and the BMSC group was lower than that in the NC group,and that in the INF-γ group was lower than that in the BMSC group(P<0.001).Compared with the IFN-γ group,the mRNA expression of CYP19A1 and FSHR in the BMSC group decreased(P<0.001).Compared with the IFN-γ group,the BMSC group had significantly decreased LDH level,mRNA expression levels of NLRP3 and CASP1,and protein expres-sion level of CASP1.Conclusion:hBMSCs repair the immune in-jury of KGN cells induced by IFN-γ by restoring cell proliferation,inhibiting cell apoptosis,repairing endocrine function,and reducing pyroptosis.

Objective To analyze the status quo and high-risk factors of hemorrhagic transformation(HT)in patients with acute cerebral infarction(ACI)treated with alteplase(rt-PA).Methods A total of 462 patients with ACI who were admitted to Hai'an People's Hospital and treated with rt-PA from June 2019 to June 2023 were retrospectively emrolled.According to the occurrence of HT,the patients were assigned to HT group(n=31)or non-HT group(n=431).The clinical data of the two groups were compared,and high-risk factors of HT in ACI patients treated with rt-PA were analyzed.Results The incidence of HT was 6.71%(31/462).Multivariate logistic analysis showed that increased systolic blood pressure(SBP),severe cerebral small vessel disease(CSVD),and increased neutrophil-to-lymphocyte ratio(NLR)were the high-risk factors of HT in patients with ACI after treatment with rt-PA(P＜0.05).Conclusion There is a high incidence of HT in patients with ACI after treatment with rt-PA,the levels of SBP,CSVD and NLR are the influencing factors,and they can provide a basis for prediction and clinical intervention.

Objective To explore the protective effect of 7,8-dihydroxyflavone(7,8-DHF)on the retina of diabetic rats and its mechanism.Methods A total of 18 SPF-grade male Sprague-Dawley(SD)rats were selected and randomly divided into three groups:the normal group,the model group,and the experimental group,with six rats in each group.Rats in the normal group were fed with a normal diet,while those in the remaining two groups were fed with a high-fat emulsion through oral gavage continuously for 2 weeks to establish a diabetes model.Rats in the experimental group were provided with 7,8-DHF(5 mg?kg-1)by continuous intraperitoneal injection,while those in the normal and model groups were provided with an equal volume of normal saline.The rats in all groups received intervention once a day for 2 weeks.The changes in the body mass and fasting blood glucose(FBG)were observed before and after modeling.Besides,the changes in the retina of rats in each group were observed by fundus fluorescence angiography(FFA)after 2 weeks.Moreo-ver,the changes and apoptosis of retinal neuronal cells were detected by hematoxylin and eosin(HE)staining,CD31 im-munofluorescence,and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assays.Results After 2 weeks of continuous intervention,compared with the normal group,the body mass of rats in the model and experimental groups decreased(both P＜0.05),and the FBG increased significantly(both P＜0.05);compared with the model group,the experimental group showed an increase in the body mass(P＜0.05)and a decrease in the FBG(P＜0.05).The fundus photography and FFA of rats in the three groups did not reveal any fundus features of diabetic retinopathy.The HE staining results showed that the retina of rats in the normal and experimental groups was structurally intact,with neatly arranged cells and uniform thickness;the retinal structure of rats in the model group remained clear.However,the thickness of the inner layers of the retina of rats in the model group was thinner compared with the normal and experimental groups,exhibi-ting significant differences(both P＜0.05).The CD31 immunofluorescence assay results indicated that the CD31 immuno-fluorescence intensity values of rats in the three groups were roughly comparable,without significant differences(all P＞0.05).The TUNEL assay results suggested that the apoptosis of retinal neurons increased in rats in the model group com-pared with the normal group,exhibiting significant differences(P＜0.001);compared with the model group,the apoptosis of retinal neurons of rats in the experimental group decreased significantly,displaying significant differences(P＜0.001).Conclusion The apoptosis of retinal neurons in diabetic rats may precede vascular endothelial cell injury.7,8-DHF can improve the body mass,decrease the blood glucose level,and protect the retinal neurons in diabetic rats.

Hot melt extrusion(HME)technology employs thermodynamic and kinetic principles to mix pharmaceutical polymers with crystalline drugs at high temperatures and extrude them,embedding drug molecules within the polymer matrix to form solid dispersions.Due to its solvent-free nature,capability for one-step processing,and support for continuous operation,HME has garnered significant attention in the pharmaceutical industry in recent years.This article introduced the basic principles and development history of HME technology and its marketed drugs.It reviewed the research progress of HME technology in improving drug solubility,masking taste,controlled release,targeted release,oral dispersible films,implant formulations,semi-solid formulations,and 3D printed formulations.Additionally,the article summarized the advantages and limitations of HME technology and provided an outlook on its future development.

Objective To explore the protective effect of 7,8-dihydroxyflavone(7,8-DHF)on the retina of diabetic rats and its mechanism.Methods A total of 18 SPF-grade male Sprague-Dawley(SD)rats were selected and randomly divided into three groups:the normal group,the model group,and the experimental group,with six rats in each group.Rats in the normal group were fed with a normal diet,while those in the remaining two groups were fed with a high-fat emulsion through oral gavage continuously for 2 weeks to establish a diabetes model.Rats in the experimental group were provided with 7,8-DHF(5 mg?kg-1)by continuous intraperitoneal injection,while those in the normal and model groups were provided with an equal volume of normal saline.The rats in all groups received intervention once a day for 2 weeks.The changes in the body mass and fasting blood glucose(FBG)were observed before and after modeling.Besides,the changes in the retina of rats in each group were observed by fundus fluorescence angiography(FFA)after 2 weeks.Moreo-ver,the changes and apoptosis of retinal neuronal cells were detected by hematoxylin and eosin(HE)staining,CD31 im-munofluorescence,and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assays.Results After 2 weeks of continuous intervention,compared with the normal group,the body mass of rats in the model and experimental groups decreased(both P＜0.05),and the FBG increased significantly(both P＜0.05);compared with the model group,the experimental group showed an increase in the body mass(P＜0.05)and a decrease in the FBG(P＜0.05).The fundus photography and FFA of rats in the three groups did not reveal any fundus features of diabetic retinopathy.The HE staining results showed that the retina of rats in the normal and experimental groups was structurally intact,with neatly arranged cells and uniform thickness;the retinal structure of rats in the model group remained clear.However,the thickness of the inner layers of the retina of rats in the model group was thinner compared with the normal and experimental groups,exhibi-ting significant differences(both P＜0.05).The CD31 immunofluorescence assay results indicated that the CD31 immuno-fluorescence intensity values of rats in the three groups were roughly comparable,without significant differences(all P＞0.05).The TUNEL assay results suggested that the apoptosis of retinal neurons increased in rats in the model group com-pared with the normal group,exhibiting significant differences(P＜0.001);compared with the model group,the apoptosis of retinal neurons of rats in the experimental group decreased significantly,displaying significant differences(P＜0.001).Conclusion The apoptosis of retinal neurons in diabetic rats may precede vascular endothelial cell injury.7,8-DHF can improve the body mass,decrease the blood glucose level,and protect the retinal neurons in diabetic rats.

Hot melt extrusion(HME)technology employs thermodynamic and kinetic principles to mix pharmaceutical polymers with crystalline drugs at high temperatures and extrude them,embedding drug molecules within the polymer matrix to form solid dispersions.Due to its solvent-free nature,capability for one-step processing,and support for continuous operation,HME has garnered significant attention in the pharmaceutical industry in recent years.This article introduced the basic principles and development history of HME technology and its marketed drugs.It reviewed the research progress of HME technology in improving drug solubility,masking taste,controlled release,targeted release,oral dispersible films,implant formulations,semi-solid formulations,and 3D printed formulations.Additionally,the article summarized the advantages and limitations of HME technology and provided an outlook on its future development.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.