OBJECTIVE: To explore the early clinical efficacy of a three-stage external treatment with traditional Chinese medicine (TCM) in the treatment of talar bone contusion caused by acute ankle sprain. METHODS: A retrospective analysis was performed on 360 patients with primary lateral ankle sprain admitted from September 2021 to July 2024. Patients with talar bone contusion were selected based on MRI examination, and 73 cases were finally included. According to different treatment methods, they were divided into the observation group and the control group. The observation group consisted of 35 cases, including 16 males and 19 females, aged 24 to 37 years old with an average of (30.34±2.68) years old, and received the three-stage external TCM treatment combined with the "POLICE" protocol. The control group included 38 cases, including 18 males and 20 females, aged 24 to 35 years old with an average of (29.87±2.57) years old, and was treated with the "POLICE" protocol alone. The volume of bone marrow edema (BME) area shown by MRI before treatment and 6 weeks after treatment was measured using 3D Slicer software, and the BME improvement rate was calculated. The "Figure of 8" measurement method was used to assess ankle swelling before treatment and at 1 and 3 weeks after treatment. The visual analogue scale (VAS) was used to evaluate ankle pain before treatment and at 1 and 6 weeks after treatment. At 6 weeks after treatment, the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and Karlsson ankle function score system were used to evaluate the improvement of ankle function. RESULTS: A total of 73 patients with talar bone contusion caused by ankle sprain completed the 6-week follow-up. At 6 weeks after treatment, the BME improvement rate in the observation group was (39.18±0.06)%, which was higher than (26.75±0.03)% in the control group, with a statistically significant difference (P<0.05). After 1 week of treatment, the VAS score in the observation group was (2.89±0.72) points, lower than (3.37±0.79) points in the control group, and the difference was statistically significant (P<0.05). The ankle swelling degree in the observation group was (50.20±3.19) cm, lower than (52.00±3.60) cm in the control group, with a statistically significant difference (P<0.05). After 3 weeks of treatment, there was no statistically significant difference in ankle swelling between the two groups. At 6 weeks after treatment, there was no statistically significant difference in VAS scores between the two groups. At 6 weeks after treatment, the AOFAS ankle-hindfoot score and Karlsson score in the observation group were (87.43±4.18) and (82.77±5.93) points, respectively, which were higher than (82.92±4.87) and (76.45±6.85) points in the control group, with statistically significant differences (P<0.05). According to the AOFAS ankle-hindfoot score, 8 cases were excellent and 27 cases were good in the observation group;2 cases were excellent, 33 cases were good, and 3 cases were fair in the control group. The difference between the two groups was statistically significant (χ²=7.089, P=0.029). CONCLUSION The three-stage external TCM treatment combined with the "POLICE" protocol has a significant early clinical efficacy. It can significantly reduce ankle pain and swelling in patients with bone contusion caused by acute lateral ankle sprain, promote the absorption of bone marrow edema, and accelerate the recovery of ankle function.
Ankle Injuries/drug therapy* ; Drugs, Chinese Herbal/administration & dosage* ; Talus/injuries* ; Retrospective Studies ; Administration, Cutaneous ; Magnetic Resonance Imaging ; Humans ; Male ; Female ; Young Adult ; Adult ; Contusions/etiology* ; Visual Analog Scale ; Musculoskeletal Pain/etiology* ; Recovery of Function/drug effects* ; Treatment Outcome ; Follow-Up Studies

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*

Atopic dermatitis (AD) is a chronic inflammatory skin condition. Natural products have gained traction in AD treatment due to their accessibility, low toxicity, and favorable pharmacological properties. However, their application is primarily constrained by poor solubility, instability, and limited permeability. The transdermal drug delivery system (TDDS) offers potential solutions for transdermal delivery, enhanced penetration, improved efficacy, and reduced toxicity of natural drugs, aligning with the requirements of modern AD treatment. This review examines the application of hydrogels, microneedles (MNs), liposomes, nanoemulsions, and other TDDS-carrying natural products in AD treatment, with a primary focus on their effects on penetration and accumulation in the skin. The aim is to provide valuable insights into the treatment of AD and other dermatological conditions.
Animals ; Humans ; Administration, Cutaneous ; Biological Products/pharmacokinetics* ; Dermatitis, Atopic/drug therapy* ; Drug Delivery Systems ; Hydrogels/chemistry* ; Skin/metabolism* ; Skin Absorption

Conventional administration methods have problems including low bioavailability, complex operation process, and discomfort of patients with fear of needles. Transdermal delivery can avoid these problems, whereas most drugs are difficult to directly penetrate the skin cuticle and reach the diseased site. Microneedling is an emerging method of local drug delivery, enabling the drug penetration through the stratum corneum of the skin in a minimally invasive manner and delivering the drug directly to the diseased site, thereby improving the treatment effect. Stimuli-responsive microneedles have attracted much attention because of the spatiotemporal controllability, high drug delivery efficiency, and mild potential side effects. This review introduced the commonly used materials and various types of stimuli-responsive microneedles and the drug release mechanisms. In addition, this paper expounded the biomedical applications of stimuli-responsive microneedles as drug delivery systems in response to different stimuli and discusses the challenges and potential solutions for stimuli-responsive microneedles.
Needles ; Drug Delivery Systems/instrumentation* ; Microinjections/instrumentation* ; Humans ; Administration, Cutaneous

Rheumatoid arthritis(RA) is a chronic degenerative joint disease characterized by inflammation. Due to the complex causes, no specific therapy is available. Non-steroidal anti-inflammatory agents and corticosteroids are often used(long-term, oral/injection) to interfere with related pathways for reducing inflammatory response and delaying the progression of RA, which, however, induce many side effects. Microneedle, an emerging transdermal drug delivery system, is painless and less invasive and improves drug permeability. Thus, it is widely used in the treatment of RA and is expected to be a new strategy in clinical treatment. This paper summarized the application of microneedles in the treatment of RA, providing a reference for the development of new microneedles and the expansion of its clinical application.
Humans ; Drug Delivery Systems ; Administration, Cutaneous ; Pharmaceutical Preparations ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use* ; Arthritis, Rheumatoid/drug therapy* ; Needles

Huoluo Xiaoling Dan is a classical prescription commonly used for blood circulation and pain relief in clinic with obvious effects. To make it directly treat lesion and improve the effect, this research optimized the preparation process of Huoluo Xiaoling gel paste and further evaluated its in vitro transdermal absorption performance, so as to provide a scientific basis for its development and utilization. Using primary viscosity, holding viscosity, and sensory score as evaluation indexes, the matrix amount of gel paste was determined by the single factor test and Box-Behnken response surface method. The ultra-performance liquid chromatography(UPLC) method was established to determine the content of eight active ingredients, including Danshensu, ferulic acid, salvianolic acid B, salvianolic acid A, ligustilide, tanshinone Ⅱ_A, 11-keto-β-boswellic(KBA), and 3-acetyl-11-keto-β-boswellic acid(AKBA). A mo-dified Franz diffusion cell method was used to evaluate and compare the absorption properties of the gel paste without volatile oil and with volatile oil microemulsion. The results showed that the optimal prescription for Huoluo Xiaoling gel paste matrix was NP700(1.35 g), glycerol(7.00 g), micropowder silica gel(1.25 g), sodium carboxymethyl cellulose(0.20 g), tartaric acid(0.06 g), and glyceryl aluminum(0.04 g). The mass fractions of eight active ingredients in the paste were successively 0.48, 0.014, 0.95, 0.39, 0.57, 0.055, 0.35, and 0.97 mg·g~(-1). The results of the in vitro transdermal absorption test showed that the addition of the volatile oil or the volatile oil microemulsion promoted the transdermal absorption of the active ingredients, and the law of drug penetration conformed to the zero equation or the Higuchi equation. The gel paste prepared by the optimal prescription has good appearance and adhesion, with no residue, and has the characteristics of skeletal slow-release preparation, which is easy to reduce the number of administration, la-ying a foundation for the development of new external dosage forms of Huoluo Xiaoling Dan.
Administration, Cutaneous ; Skin Absorption ; Chromatography, Liquid ; Oils, Volatile ; Viscosity

OBJECTIVE: To compare the clinical efficacy between auricular point sticking combined with transcutaneous electrical acupoint stimulation (TEAS) and nicotine patch for smoking cessation. METHODS: Two hundred patients who voluntarily quit smoking were randomly divided into a combination group and a nicotine patch group, 100 cases in each group. In the combination group, auricular point sticking (Shenmen [TF₄], Neifenmi [CO₁₈], Pizhixia [AT₄], Jiaogan [AH_6a], etc., once every other day) combined with TEAS（Lieque [LU 7] and Zusanli [ST 36], with continuous wave, 20 Hz in frequency, 1 mA in current intensity, 30 min each time, once a day) were applied. In the nicotine patch group, nicotine patch was applied. Both groups were treated for 8 weeks. The immediate withdrawal rate and persistent withdrawal rate 8 weeks into treatment and in follow-up of 16 weeks after treatment in the two groups were compared; before treatment, 8 weeks into treatment and in follow-up of 16 weeks after treatment, the degree of nicotine dependence was evaluated by using Fagerström test for nicotine dependence (FTND); 1 week into treatment, 8 weeks into treatment and in follow-up of 16 weeks after treatment, the withdrawal symptoms and smoking craving were evaluated by using Minnesota nicotine withdrawal scale (MNWS); the safety and compliance (dropped off rate and treatment completeness) were evaluated in the two groups. RESULTS: There was no statistical significance of the differences in the immediate withdrawal rate and persistent withdrawal rate 8 weeks into treatment and during follow-up between the two groups (P>0.05). The FTND scores were decreased 8 weeks into treatment and during follow-up in the two groups compared with those before treatment (P<0.01); the FTND score during follow-up in the combination group was lower than the nicotine patch group (P<0.05). The MNWS scores were decreased 8 weeks into treatment and during follow-up in the two groups compared with those 1 week into treatment (P<0.05); the changes of MNWS scores 8 weeks into treatment and during follow-up in the combination group were greater than the nicotine patch group (P<0.05, P<0.01). There were no serious adverse reactions in either group. Eight weeks into treatment and during follow-up, the dropped off rates were all 16.0% (16/100) in the combination group, which were 20.0% (20/100) and 23.0% (23/100) in the nicotine patch group, there was no statistical significance of the differences in the two groups (P>0.05). There was no significant difference in treatment completeness between the two groups (P>0.05). CONCLUSION Auricular point sticking combined with TEAS could effective decrease the degree of nicotine dependence, improve withdrawal symptoms in smokers, its effect is superior to nicotine patch.
Humans ; Smoking Cessation ; Tobacco Use Disorder ; Acupuncture Points ; Administration, Cutaneous ; Nicotine ; Substance Withdrawal Syndrome/drug therapy*

Microneedle percutaneous immunization is achieved by puncturing the stratum corneum of the skin with microneedles so that the vaccine is efficiently recognized by antigen-presenting cells to induce a specific immune response. Due to the advantages of efficient induction of immune response, low pain and easy storage, transdermal immunization by microneedles has been widely used for immunization of various vaccines in recent years. This review summarizes the materials of microneedles, application for transcutaneous immunization, as well as the challenges that need to be addressed.
Administration, Cutaneous ; Drug Delivery Systems ; Needles ; Vaccination ; Vaccines

Objective: To explore the clinical features and treatment of pyoderma gangrenosum (PG). Methods: A retrospective observational study was conducted. From January 2012 to July 2021, 25 patients with PG who met the inclusion criteria were admitted to Beijing Fucheng Hospital, including 16 males and 9 females, with the age of onset of disease being 14 to 75 years. Among them, the classification of PG identified 17 cases of ulcerative type, 6 cases of pustular type, 1 case of proliferative type, and 1 case of bullous type. Six patients were accompanied with systemic diseases, while 19 patients were not accompanied with systemic diseases. At the same time of systemic treatment with glucocorticoids, dressing changes or surgical skin grafting was performed on the wounds. The results of laboratory and histopathological examinations, the overall curative effects and follow-up of patients, the wound healing time of patients with negative and positive microbial culture results of wound secretion specimens, and the curative effects of patients with and without systemic diseases were analyzed. Results: The results of blood routine examination of 19 patients were abnormal, and all the immunological indexes were normal in all the patients; the microbial culture results of wound secretion specimens were positive in 14 patients; and the histopathological examination results of ulcer boundary tissue in 15 patients with rapid wound progress were mainly local tissue inflammatory changes. The wounds were cured in 17 patients, mostly healed in 7 patients, and not healed in 1 patient. After one-year's follow-up, the PG in 3 patients relapsed due to self-discontinuation of medication after discharge, and the wounds were healed gradually after adjustment of medication, while the remaining patients had no relapse. The days of wound healing in 14 patients with positive microbial culture results of wound secretion specimens were 21-55 days, and the days of wound healing in 11 patients with negative microbial culture results in wound secretion specimens were 20-54 days. In the 6 patients with systemic diseases, the wounds of 3 patients were cured, and the wounds of the other 3 patients were mostly healed. In the 19 patients without systemic diseases, the wounds of 14 patients were cured, the wounds of 4 patients were mostly healed, and the wound of 1 patient was not healed. Conclusions: The laboratory examination and pathological manifestations of patients with PG lacks characteristics, and their clinical manifestations are rich and diverse, thus PG can be easily misdiagnosed. The glucocorticoids combined with immunosuppressive therapy have good effects on PG. Surgical intervention can be performed on the wounds. Specifically, excessive debridement is not recommended in the acute phase, but skin grafting can be performed in the contraction phase.
Administration, Cutaneous ; Adolescent ; Adult ; Aged ; Female ; Glucocorticoids ; Humans ; Male ; Middle Aged ; Pyoderma Gangrenosum/therapy* ; Skin Transplantation ; Wound Healing ; Young Adult

This study aims to establish a rapid and sensitive UPLC-MS/MS method for simultaneously determining the content of strychnine and paeoniflorin in plasma and brain tissue of rats, and compare the pharmacokinetic behavior and brain tissue distribution of paeoniflorin combined with normal and toxic doses of strychnine in rats after percutaneous administration. Compared with those in the toxic-dose strychnine group, the AUC_(0-t), AUC_(0-∞), and C_(max) of strychnine decreased by 51.51%, 45.68%, and 46.03%, respectively(P<0.01), and the corresponding values of paeoniflorin increased by 91.41%, 102.31%, and 169.32%, respectively(P<0.01), in the compatibility group. Compared with the normal-dose strychnine group, the compatibility group showed insignificantly decreased C_(max), AUC_(0-t), and AUC_(0-∞) of strychnine, increased C_(max) and T_(max) of paeoniflorin(P<0.01), 66.88% increase in AUC_(0-t), and 70.55% increase in AUC_(0-∞) of paeoniflorin. In addition, the brain tissue concentration of strychnine decreased and that of paeoniflorin increased after compatibility. The combination of paeoniflorin with normal dose and toxic dose of strychnine can inhibit the percutaneous absorption of strychnine, and greatly promote the percutaneous penetration of paeoniflorin, whereas the interaction mechanism remains to be explored. The UPLC-MS/MS method established in this study is easy to operate and has good precision. It is suitable for in vivo study of pharmacokinetic behavior and brain tissue distribution of paeoniflorin and strychnine after percutaneous administration in rats, which provides reference for the safe and rational clinical use of strychnine and the combined use of drugs, and lays a solid foundation for the development of external preparations containing Strychni Semen.
Administration, Cutaneous ; Animals ; Brain ; Bridged-Ring Compounds/pharmacology* ; Chromatography, Liquid/methods* ; Glucosides ; Monoterpenes ; Rats ; Rats, Sprague-Dawley ; Strychnine ; Tandem Mass Spectrometry/methods* ; Tissue Distribution