[Rapamycin and HPPH Co-Loaded Nanodrug Delivered via Dissolvable Microneedles to Treat Port-Wine Stains]. / å ±è½½é›·å¸•éœ‰ç´ å’Œå ‰å ‹æ´›çš„çº³ç±³è¯ç‰©å¤åˆå¯æº¶è§£å¾®é’ˆæ²»ç–—é²œçº¢æ–‘ç—£çš„å®žéªŒç ”ç©¶.

Objective: Port-wine stains are a kind of dermatological disease of congenital capillary malformation. Based on the biological characteristics of port-wine stains and the advantages of microneedle transdermal administration, we intend to construct a nanodrug co-loaded with rapamycin (RPM), an anti-angiogenesis drug, and photochlor (HPPH), a photosensitizer, and integrate the nanodrug with dissolvable microneedles (MN) to achieve anti-angiogenesis and photodynamic combination therapy for port-wine stains. Methods: First, RPM and HPPH co-loaded nanoparticles (RPM-HPPH NP) were prepared by the emulsification solvent-volatilization method, and its ability to generate reactive oxygen species (ROS) was investigated under 660 nm laser irradiation. Mouse hemangioendothelioma endothelial cells (EOMA) were used as the subjects of the study. The cellular uptake behaviors were examined by fluorescence microscopy and flow cytometry. The cytotoxicity effects of RPM-HPPH NP with or without 660 nm laser irradiation on EOMA cells were examined by MTT assays (with free RPM serving as the control). Then, hyaluronic acid (HA) dissolvable microneedles loaded with RPM-HPPH NP (RPM-HPPH NP@HA MN) were obtained by compounding the nanodrug with HA dissolvable microneedle system through the molding method. The morphological characteristics and mechanical properties of RPM-HPPH NP@HA MN were investigated by scanning electron microscope and electronic universal testing machine. The penetration ability of RPM-HPPH NP@HA MN on the skin of nude mice was evaluated by trypan blue staining and H&E staining experiment. Results: The RPM-HPPH NP prepared in the study had a particle size of 150 nm and generated large amounts of ROS under laser irradiation. At the cellular level, RPM-HPPH NP was taken up by EOMA cells in a time-dependent manner. The cytotoxicity of RPM-HPPH NP was higher than that of free RPM with or without laser irradiation. Under laser irradiation, RPM-HPPH NP exhibited stronger cytotoxic effects and the difference was statistically significant (P<0.05). The height of the needle tip of RPM-HPPH NP@HA MN was 600 µm and the mechanical property of a single needle was 0.75048 N. Trypan blue staining and HE staining showed that pressing on the microneedles could produce pores on the skin surface and penetration of the stratum corneum. Conclusion: RPM-HPPH NP@HA MN can deliver RPM-HPPH NP percutaneously to the lesion tissue and realize the synergistic treatment of port-wine stains with anti-angiogenic therapy and photodynamic therapy, providing a new strategy for the construction of nanodrug-loaded microneedle delivery system and the clinical treatment of port-wine stains.

Novel valve-in-surgical bioprosthetic transcatheter aortic valve replacement: Undermining iatrogenic coronary obstruction with radiofrequency needle (UNICORN).

An 86-year-old female with history of surgical aortic valve replacement presented with clinical signs of heart failure. Echocardiography revealed a reduction in left ventricular systolic function and severe bioprosthetic aortic valve dysfunction. This is the first reported case of valve-in-valve transcatheter aortic valve replacement with concomitant undermining iatrogenic coronary obstruction with radiofrequency needle procedure in a surgical bioprosthetic valve.

SERS-Based Microneedle Biosensor for In Situ and Sensitive Detection of Tyrosinase.

Tyrosinase (TYR) emerges as a key enzyme that exerts a regulatory influence on the synthesis of melanin, thereby assuming the role of a critical biomarker for the detection of melanoma. Detecting the authentic concentration of TYR in the skin remains a primary challenge. Distinguished from ex vivo detection methods, this study introduces a novel sensor platform that integrates a microneedle (MN) biosensor with surface-enhanced Raman spectroscopy (SERS) technology for the in situ detection of TYR in human skin. The platform utilized dopamine (DA)-functionalized gold nanoparticles (Au NPs) as the capturing substrate and 4-mercaptophenylboronic acid (4-MPBA)-modified silver nanoparticles (Ag NPs) acting as the SERS probe. Here, the Au NPs were functionalized with mercaptosuccinic acid (MSA) for DA capture. In the presence of TYR, DA immobilized on the MN is preferentially oxidized to dopamine quinone (DQ), a process that results in a decreased density of SERS probes on the platform. TYR concentration was detected through variations in the signal intensity emitted by the phenylboronic acid. The detection system was able to evaluate TYR concentrations within a linear range of 0.05 U/mL to 200 U/mL and showed robust anti-interference capabilities. The proposed platform, integrating MN-based in situ sensing, SERS technology, and TYR responsiveness, holds significant importance for diagnosing cutaneous melanoma.

Minoxidil Nanosuspension-Loaded Dissolved Microneedles for Hair Regrowth.

Minoxidil (MIN) is used topically to treat alopecia. However, its low absorption limits its use, warranting a new strategy to enhance its delivery into skin layers. The objective of this study was to evaluate the dermal delivery of MIN by utilizing dissolved microneedles (MNs) loaded with MIN nanosuspension (MIN-NS) for hair regrowth. MIN-NS was prepared by the solvent-antisolvent precipitation technique. The particle size of MIN-NS was 226.7 ± 9.3 nm with a polydispersity index of 0.29 ± 0.17 and a zeta potential of -29.97 ± 1.23 mV. An optimized formulation of MIN-NS was selected, freeze-dried, and loaded into MNs fabricated with sodium carboxymethyl cellulose (Na CMC) polymeric solutions (MIN-NS-loaded MNs). MNs were evaluated for morphology, dissolution rate, skin insertion, drug content, mechanical properties, ex vivo permeation, in vivo, and stability studies. MNs, prepared with 14% Na CMC, were able to withstand a compression force of 32 N for 30 s, penetrate Parafilm M® sheet at a depth of 374-504 µm, and dissolve completely in the skin within 30 min with MIN %recovery of 95.1 ± 6.5%. The release of MIN from MIN-NS-loaded MNs was controlled for 24 h. MIN-NS-loaded MNs were able to maintain their mechanical properties and chemical stability for 4 weeks, when kept at different storage conditions. The in vivo study of the freeze-dried MIN-NS and MIN-NS-loaded MNs proved hair regrowth on rat skin after 11 and 7 days, respectively. These results showed that MIN-NS-loaded MNs could potentially improve the dermal delivery of MIN through the skin to treat alopecia.

Pseudomyopia treated with auricular point sticking combined with periocular needle-embedding therapy and prevention of true myopia: a multicenter randomized controlled trial. / è€³ç©´è´´åŽ‹è”åˆçœ¼å‘¨æ¿é’ˆæŠ€æœ¯é¢„é˜²å‡æ€§è¿‘è§†å‘çœŸæ€§è¿‘è§†è¿›å±•ï¼šå¤šä¸­å¿ƒéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To observe the clinical effect and safety of auricular point sticking combined with periocular needle-embedding therapy for pseudomyopia and prevention of true myopia. METHODS: A total of 269 children with pseudomyopia were randomized into an observation group (134 cases, 2 cases dropped out) and a control group (135 cases, 5 cases dropped out). In the control group, the healthy education was provided. In the observation group, besides the intervention as the control group, the auricular point sticking was delivered at gan (CO12), pi (CO13), xin (CO15) and yan (LO5) on one ear in each treatment, combined with periocular needle-embedding technique at bilateral Cuanzhu (BL 2), Yuyao (EX-HN 4) and Sibai (ST 2). There were 2 weeks of interval after 4 weeks of treatment. One course of treatment was composed of 6 weeks and 2 courses were required. Separately, before treatment, after 6 and 12 weeks of treatment, and after 12 weeks (the 1st follow-up visit) and 24 weeks (the 2nd follow-up visit) of treatment completion, the spherical equivalent (SE), SE progression, axial length (AL) progression, accommodative amplitude (AMP), the score of the TCM symptom and the general symptom were observed in the two groups. The safety and compliance were evaluated in the two groups. RESULTS: After 6 and 12 weeks of treatment, and in the 1st and 2nd follow-up visits, SE increased when compared with that before treatment in the two groups (P<0.05), and AMP was larger than that before treatment in the observation group (P<0.05). After 12 weeks of treatment, and in the 1st and 2nd follow-up visits, the progression of SE was slower in the observation group compared with that in the control group (P<0.01, P<0.001). After 6 and 12 weeks of treatment, and in the 1st and 2nd follow-up visits, the progression of AL in the observation group was lower than that of the control group (P<0.05, P<0.01, P<0.001); and in the 1st and 2nd follow-up visits, AMP of the observation group was larger when compared with that in the control group (P<0.05, P<0.001). After 6 and 12 weeks of treatment, and in the 1st and 2nd follow-up visits, the total scores of TCM symptom and general symptom were reduced in comparison with those before treatment in the observation group (P<0.05); after 6 and 12 weeks of treatment, the total scores of TCM symptom and general symptom were lower than those before treatment in the control group (P<0.05). In the 1st and 2nd follow-up visits, the difference of the total score of TCM symptom and general symptom in the observation group was larger than that of the control group (P<0.05). In the observation group, compared with the control group, the scores for pale/dark complexion in the 1st and 2nd follow-up visits and that for lassitude in the 2nd follow-up visit were lower (P<0.05), the score for poor concentration after 12 weeks of treatment and that for poor sleep and memory in the 2nd follow-up visit were lower (P<0.05). There were no adverse reactions in the two groups. The compliance was 98.5% in the observation group and was 96.3% in the control group, without statistical difference (P>0.05). CONCLUSIONS: On the basis of health education, auricular point sticking combined with periocular needle-embedding therapy can effectively prevent from true myopia, control the increase of SE, delay the growth of AL and improve AMP in children with pseudomyopia. This compound therapeutic regimen can relieve the general symptom and comprehensively prevent from myopia through multiple approaches, with high safety and satisfactory compliance.

A novel biopsy scheme for prostate cancer: targeted and regional systematic biopsy.

PURPOSE: To explore a novel biopsy scheme for prostate cancer (PCa), and test the detection rate and pathological agreement of standard systematic (SB) + targeted (TB) biopsy and novel biopsy scheme. METHODS: Positive needles were collected from 194 patients who underwent SB + TB (STB) followed by radical prostatectomy (RP). Our novel biopsy scheme, targeted and regional systematic biopsy (TrSB) was defined as TB + regional SB (4 SB-needles closest to the TB-needles). The McNemar test was utilized to compare the detection rate performance for clinical significant PCa (csPCa) and clinical insignificant PCa (ciPCa). Moreover, the accuracy, positive predictive value (PPV) and negative predictive value (NPV) were investigated. The agreement between the different biopsy schemes grade group (GG) and RP GG were assessed. The concordance between the biopsy and the RP GG was evaluated using weighted κ coefficient analyses. RESULTS: In this study, the overall detection rate for csPCa was 83.5% (162 of 194) when SB and TB were combined. TrSB showed better NPV than TB (97.0% vs. 74.4%). Comparing to STB, the TB-detection rate of csPCa had a significant difference (p < 0.01), while TrSB showed no significant difference (p > 0.999). For ciPCa, the overall detection rate was 16.5% (32 of 194). TrSB showed better PPV (96.6% vs. 83.3%) and NPV (97.6% vs. 92.9%) than TB. Comparing to STB, the detection rate of both schemes showed no significant difference (p = 0.077 and p = 0.375). All three schemes GG showed poor agreement with RP GG (TB: 43.3%, TrSB: 46.4%, STB: 45.9%). Using weighted κ, all three schemes showed no difference (TB: 0.48, TrSB: 0.51, STB: 0.51). In our subgroup analysis (PI-RADS = 4/5, n = 154), all three schemes almost showed no difference (Weighted κ: TB-0.50, TrSB-0.51, STB-0.50). CONCLUSION: Our novel biopsy scheme TrSB (TB + 4 closest SB needles) may reduce 8 cores of biopsy compared with STB (standard SB + TB), which also showed better csPCa detection rate than TB only, but the same as STB. The pathological agreement between three different biopsy schemes (TB/TrSB/STB) GG and RP GG showed no difference.

An integrated wearable differential microneedle array for continuous glucose monitoring in interstitial fluids.

Monitoring biomarkers in human interstitial fluids (ISF) using microneedle sensors has been extensively studied. However, most of the previous studies were limited to simple in vitro demonstrations and lacked system integration and analytical performance. Here we report a miniaturized, high-precision, fully integrated wearable electrochemical microneedle sensing device that works with a customized smartphone application to wirelessly and in real-time monitor glucose in human ISF. A microneedle array fabrication method is proposed which enables multiple individually addressable, regionally separated sensing electrodes on a single microneedle system. As a demonstration, a glucose sensor and a differential sensor are integrated in a single sensing patch. The differential sensing electrodes can eliminate common-mode interference signals, thus significantly improving the detection accuracy. The basic mechanism of microneedle penetration into the skin was analyzed using the finite element method (FEM). By optimizing the structure of the microneedle, the puncture efficiency was improved while the puncture force was reduced. The electrochemical properties, biocompatibility, and system stability of the microneedle sensing device were characterized before human application. The test results were closely correlated with the gold standard (blood). The platform can be used not only for glucose detection, but also for various ISF biomarkers, and it expands the potential of microneedle technology in wearable sensing.

A novel multifunctional microneedle patch for synergistic photothermal- gas therapy against maxillofacial malignant melanoma and associated skin defects.

Considering the high recrudescence and the long-lasting unhealed large-sized wound that affect the aesthetics and cause dysfunction after resection of maxillofacial malignant skin tumors, a groundbreaking strategy is urgently needed. Photothermal therapy (PTT), which has become a complementary treatment of tumors, however, is powerless in tissue defect regeneration. Therefore, a novel multifunctional sodium nitroprusside and Fe2+ ions loaded microneedles (SNP-Fe@MNs) platform was fabricated by accomplishing desirable NIR-responsive photothermal effect while burst releasing nitric oxide (NO) after the ultraviolet radiation for the ablation of melanoma. Moreover, the steady releasing of NO in the long term by the platform can exert its angiogenic effects via upregulating multiple related pathways to promote tissue regeneration. Thus, the therapeutic dilemma caused by postoperative maxillofacial skin malignancies could be conquered through promoting tumor cell apoptosis via synergistic PTT-gas therapy and subsequent regeneration process in one step. The bio-application of SNP-Fe@MNs could be further popularized based on its ideal bioactivity and appealing features as a strategy for synergistic therapy of other tumors occurred in skin.

Swellable microneedle-coupled light-addressable photoelectrochemical sensor for in-situ tracking of multiple pesticides pollution in vivo.

In vivo monitoring of multiple pesticide contamination is of great significance for evaluating the health risks of different pesticides, agricultural production safety, and ecological and environmental assessment. Here, we report a hydrogel microneedle array coupled light-addressable photoelectrochemical sensor for tracking multiple pesticide uptake and elimination in living animals and plants, holding three prominent merits: i) enables in-situ detection of in vivo pesticides, avoiding cumbersome and complex sample transportation and handling processes; ii) allows repeated in vivo sampling of the same organism, improving tracking test controllability and accuracy; iii) avoids lethal sampling, providing a better understanding of the pesticides fate in living organisms. The coupled sensor is mechanically robust for withstanding more than 0.35 N per needle and highly swellable (800 %) for timely extraction of sufficient in vivo solution for analysis. For proof-of-concept, it achieves in-situ detection of atrazine, acetamiprid, and carbendazim efficiently and quantitatively in artificial agarose skin models, mouse skin interstitial fluids, and plant leaves with little inflammatory reaction. This simple, highly integrated, minimally invasive, and high-throughput in vivo monitoring method is ideal for future field environmental monitoring and plant and animal disease diagnosis.

A mechanics-based model for predicting flexible needle bending with large curvature in soft tissue.

Percutaneous insertion is one of the most common minimally invasive procedures. Compared with traditional straight rigid needles, bevel-tipped flexible needle can generate curved trajectories to avoid obstacles and sensitive organs. However, the nonlinear large deflection problem challenges the bending prediction of the needle, which dramatically influences the surgical success rate. This paper analyzed the mechanism of needle-tissue interaction, and established a mechanics-based model of the needle bending during an insertion. And then, a discretization of the bending model was adopted to accurately predict the large bending of the needle in soft tissue. Insertion experiments were conducted to validate the bending prediction model. The results showed that the large needle bending was predicted with the mean/RMSE/maximumu error of 0.42 mm / 0.26 mm / 1.08 mm, which was clinically acceptable. This proved the rationality and accuracy of the proposed model.

Investigation of Presumptive HIV Transmission Associated with Receipt of Platelet-Rich Plasma Microneedling Facials at a Spa Among Former Spa Clients - New Mexico, 2018-2023.

HIV transmitted through cosmetic injection services via contaminated blood has not been previously documented. During summer 2018, the New Mexico Department of Health (NMDOH) was notified of a diagnosis of HIV infection in a woman with no known HIV risk factors who reported exposure to needles from cosmetic platelet-rich plasma microneedling facials (vampire facials) received at a spa in spring 2018. An investigation of the spa's services began in summer 2018, and NMDOH and CDC identified four former spa clients, and one sexual partner of a spa client, all of whom received HIV infection diagnoses during 2018-2023, despite low reported behavioral risks associated with HIV acquisition. Nucleotide sequence analysis revealed highly similar HIV strains among all cases. Although transmission of HIV via unsterile injection practices is a known risk, determining novel routes of HIV transmission among persons with no known HIV risk factors is important. This investigation identified an HIV cluster associated with receipt of cosmetic injection services at an unlicensed facility that did not follow recommended infection control procedures or maintain client records. Requiring adequate infection control practices and maintenance of client records at spa facilities offering cosmetic injection services can help prevent the transmission of HIV and other bloodborne pathogens and ensure adequate traceback and notification in the event of adverse clinical outcomes, respectively.

Computational fluid dynamics investigation on the irrigation of a real root canal with a side-vented needle.

BACKGROUND: Root canal therapy is one of the main treatments for root canal diseases, and effective irrigation is the key to successful treatment. Side-vented needle is one of the commonly used needle types in clinic. In the real root canal, due to the influence of the curvature of the root canal, the irrigation flow field in different needle directions shows obvious differences. At the same time, changes in root canal curvature and working depth will lead to changes in irrigation efficiency and the flow field. Both the mainstream of the irrigation flow and the shear stress near the wall changes significant. Consequently, either the replacement in the root canal or the removal efficiency of the smear layers is apparently modified. MATERIALS AND METHODS: In this paper, the permanent root canal of the maxillary first molar prepared until 15/04 were scanned by micro-CT, and then imported into the software for 3D reconstruction. The key parameters of flushing efficiency of 30G side needle at different working depths of 4.75 mm, 5 mm, 5.25 mm and 5.5 mm were compared. Meanwhile, the simulated models with different curvatures of 0°, 5°, 10°, 20° and 30° based on the real root canal were reconstructed to investigate the curvature effect on the irrigation efficiency. RESULTS: The results show that moderate working depth (such as 4.75 mm and 5.25 mm in present paper) helps to improve the replacement capacity of irrigation flow. At the same time, the apical pressure decreased as the working depth increased. The curvature of the root canal seriously affects the removal depth of the smear layers of the root canal. A root canal with a large curvature (especially 20° and 30°) can significantly improve the difficulty of irrigation. CONCLUSIONS: (1) Moderate working depth helps to improve the displacement capacity, the ERD of the irrigation flow is generally improved at the working depths of 4.75 mm and 5.25 mm, and the apical pressure will decrease with the increase of working depth. (2) The large curvature of the root canal can significantly improve the difficulty of irrigation. The curvature of the root canal can severely influence the removal depth of the smear layer on the wall. It can be found both the span and the depth of the ESS for little curvatures (5° and 10°) root canals are higher than those for large curvatures (20° and 30°).

Protein-based microneedles for biomedical applications: A systematic review.

Microneedles are minimally-invasive devices with the unique capability of bypassing physiological barriers. Hence, they are widely used for different applications from drug/vaccine delivery to diagnosis and cosmetic fields. Recently, natural biopolymers (particularly carbohydrates and proteins) have garnered attention as safe and biocompatible materials with tailorable features for microneedle construction. Several review articles have dealt with carbohydrate-based microneedles. This review aims to highlight the less-noticed role of proteins through a systematic search strategy based on the PRISMA guideline from international databases of PubMed, Science Direct, Scopus, and Google Scholar. Original English articles with the keyword "microneedle(s)" in their titles along with at least one of the keywords "biopolymers, silk, gelatin, collagen, zein, keratin, fish-scale, mussel, and suckerin" were collected and those in which the proteins undertook a structural role were screened. Then, we focused on the structures and applications of protein-based microneedles. Also, the unique features of some protein biopolymers that make them ideal for microneedle construction (e.g., excellent mechanical strength, self-adhesion, and self-assembly), as well as the challenges associated with them were reviewed. Altogether, the proteins identified so far seem not only promising for the fabrication of "better" microneedles in the future but also inspiring for designing biomimetic structural biopolymers with ideal characteristics.

Parallel needling technique for peripheral facial paralysis with qi deficiency and blood stasis: a randomized controlled trial. / å¹³è¡Œå¯¹åˆºæ³•æ²»ç–—æ°”è™šè¡€ç˜€åž‹å‘¨å›´æ€§é¢ç˜«ï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To observe the clinical efficacy of the parallel needling technique for peripheral facial paralysis with qi deficiency and blood stasis. METHODS: Sixty-two patients with peripheral facial paralysis of qi deficiency and blood stasis were randomly assigned to a parallel needling group and a conventional acupuncture group, with 31 patients in each group. The conventional acupuncture group received needling at Yangbai (GB 14), Quanliao (SI 18), Jiache (ST 6), Dicang (ST 4), Yifeng (TE 17) on the affected side, Hegu (LI 4) on the healthy side, and bilateral Zusanli (ST 36), Sanyinjiao (SP 6), Xuehai (SP 10) and Qihai (CV 6) etc. The parallel needling group, in addition to the conventional acupuncture points, received parallel needling at three additional groups of acupoints, i.e. forehead wrinkle group, mid-face group, and corner of the mouth group. Both groups retained needles for 30 min, with one session every other day and a total of three sessions per week, lasting for four weeks. The House-Brackmann (H-B) facial nerve function grading, physical function (FDIP) and social function (FDIS) scores of facial disability index (FDI), TCM syndrome score before and after treatment were compared between the two groups, and the clinical efficacy was assessed. RESULTS: Compared with before treatment, after treatment, both groups showed improvements in H-B facial nerve function grading (P<0.05), FDIP total scores and sub-item scores were increased (P<0.05), FDIS total scores, sub-item scores, and TCM syndrome scores were decreased (P<0.05). After treatment, the parallel needling group showed the higher FDIP total score and eating sub-item score and lower FDIS total score and insomnia sub-item score compared with those in the conventional acupuncture group (P<0.05). The total effective rate was 90.3% (28/31) in the parallel needling group and 87.1% (27/31) in the conventional acupuncture group, with no statistically significant difference between the two groups (P>0.05). CONCLUSIONS: The parallel needling technique combined with conventional acupuncture, is as effective as conventional acupuncture alone in treating facial paralysis with qi deficiency and blood stasis. However, the parallel needling technique combined with conventional acupuncture shows advantages in the improvement of food intake and sleep quality.

A mechanics-based model for a tendon-driven active needle navigating inside a multiple-layer tissue.

Percutaneous minimally invasive procedures such brachytherapy and biopsy require a flexible active needle for precise movement inside tissue and accurate placement at target positions for higher success rates for diagnosis and treatment, respectively. In a previous work, we presented a tendon-driven active needle to navigate inside tissue. This work presents a new model to predict the deflection of the tendon-driven needle while steering in a multiple-layer soft tissue. A multi-layer phantom tissue with different localized stiffness was developed for needle insertion tests followed by indentation tests to identify its mechanical properties. Using a robot that inserts and actively bends the tendon-driven needle inside the soft tissue while simultaneously tracking the needle through ultrasound imaging, various experiments were conducted for model validation. The proposed model was verified by comparing the simulation results to the empirical data. The results demonstrated the accuracy of the model in predicting the tendon-driven needle deflection in multiple-layer (different stiffness) soft tissue.

Single-Incision Laparoscopic Cholecystectomy Using a Set of Novel Needle Instruments.

BACKGROUND: Although the technique of single-incision laparoscopic cholecystectomy (SILC) has improved remarkably, problems such as limited exposure and instrument collision persist. We describe a new SILC technique that uses a set of specially-designed needle instruments. METHODS: Fifty-six patients with benign gallbladder disease underwent SILC using the newly-designed needle assembly instruments (NAIs). The NAIs comprise an needle assembly exposing hook for operative field exposure and an needle assembly electrocoagulation hook for dissection. During the operation, the NAIs were assembled and disassembled before and after gallbladder removal within the abdominal cavity. The operative efficacy and postoperative complications of this procedure were evaluated. RESULTS: SILC was completed successfully in 52 cases, and four cases (7.14%) required an additional trocar. There were no conversions to open surgery. The mean operative time was 48.2 ± 21.8 min, and the mean operative bleeding volume was 10.5 ± 12.5 mL. Minor postoperative complications occurred in 3 cases, including 2 cases of localized fluid accumulation in the abdominal cavity and 1 case of pulmonary infection, and all of them recovered after conservative treatment. There was no occurrence of bile leak, abdominal bleeding, bile duct injury and incisional hernia. The medical cost of each case was saved by approximately $200. The abdominal scars produced by the needle instruments were negligible. CONCLUSION: NAIs can make SILC safer, more convenient, and less expensive.

Cyclodextrin microneedles for the delivery of a nanoparticle-based peptide antigen vaccine.

In recent years, microneedles (MNs) have gained considerable interest in drug formulation due to their non-invasive and patient-friendly nature. Dissolving MNs have emerged as a promising approach to enhance drug delivery across the skin in a painless manner without generating sharp waste and providing the possibility for self-administration. Cyclodextrins, a group of cyclic oligosaccharides, are well-established in pharmaceutical products due to their safety and unique ability to form inclusion complexes with various drug molecules. In this manuscript, we report the development and characterization of dissolving MNs composed of cyclodextrins for intradermal delivery of a cyclodextrin-based nanoparticulate vaccine. Different cyclodextrins were tested and the most promising candidates were fabricated into MNs by micromolding. The MNs' piercing effectiveness and drug permeation across the skin were tested ex vivo. Furthermore, in vivo studies were carried out to assess the skin's tolerance to cyclodextrin-based MNs, and to evaluate the immune response using a model peptide antigen in a mouse model. The data revealed that the MNs were well-tolerated and effective, even leading to dose-sparing effects. This study highlights the potential of cyclodextrin-based dissolving MNs as a versatile platform for intradermal vaccine delivery, providing a compatible matrix for nanoparticulate formulations to enhance immune responses.

Use of the lateral arm in tomosynthesis-guided SCOUT Reflector placement procedures.

Preoperative localization procedures are important for guiding surgical excision of non-palpable findings in the breast. The SCOUT Reflector (Merit Medical, South Jordan UT, USA) is a non-wire-based localization device that has been incorporated into clinical use with great success. SCOUT Reflectors can be placed using several imaging modalities, including tomosynthesis. One drawback to SCOUT Reflector placement under tomosynthesis guidance is an inability to directly visualize the introducer needle tip, a factor that limits precision. In this brief communication, we describe the use of a lateral arm attachment for tomosynthesis guided SCOUT Reflector placement. Precise SCOUT Reflector placement can be achieved using the lateral arm due to the ability to clearly visualize the introducer needle and the SCOUT Reflector within the introducer needle bore prior to deployment.

Kirchhoff's law-based velocity-controlled motion models to predict real-time cutting forces in minimally invasive surgeries.

A theoretical framework, united by a "system effect" is formulated to model the cutting/haptic force evolution at the cutting edge of a surgical cutting instrument during its penetration into soft biological tissue in minimally invasive surgery. Other cutting process responses, including tissue fracture force, friction force, and damping, are predicted by the model as well. The model is based on a velocity-controlled formulation of the corresponding equations of motion, derived for a surgical cutting instrument and tissue based on Kirchhoff's fundamental energy conservation law. It provides nearly zero residues (absolute errors) in the equations of motion balances. In addition, concurrent closing relationships for the fracture force, friction coefficient, friction force, process damping, strain rate function (a constitutive tissue model), and their implementation within the proposed theoretical framework are established. The advantage of the method is its ability to make precise real-time predictions of the aperiodic fluctuating evolutions of the cutting forces and the other process responses. It allows for the robust modeling of the interactions between a medical instrument and a nonlinear viscoelastic tissue under any physically feasible working conditions. The cutting process model was partially qualitatively verified through numerical simulations and by comparing the computed cutting forces with experimentally measured values during robotic uniaxial biopsy needle constant velocity insertion into artificial gel tissue, obtained from previous experimental research. The comparison has shown a qualitatively similar adequate trend in the evolution of the experimentally measured and numerically predicted cutting forces during insertion of the needle.

A Hollow Microneedle Equipped with a Micropillar for Improved Needle Insertion and Injection of Drug Solution.

PURPOSE: Hollow-type microneedles (hMNs) are a promising device for the effective administration of drugs into intradermal sites. Complete insertion of the needle into the skin and administration of the drug solution without leakage must be achieved to obtain bioavailability or a constant effect. In the present study, several types of hMN with or without a rounded blunt tip micropillar, which suppresses skin deformation, around a hollow needle, and the effect on successful needle insertion and administration of a drug solution was investigated. Six different types of hMNs with needle lengths of 1000, 1300, and 1500 µm with or without a micropillar were used. METHODS: Needle insertion and the disposition of a drug in rat skin were investigated. In addition, the displacement-force profile during application of hMNs was also investigated using a texture analyzer with an artificial membrane to examine needle factors affecting successful insertion and administration of a drug solution by comparing with in vivo results. RESULTS: According to the results with the drug distribution of iodine, hMN1300 with a micropillar was able to successfully inject drug solution into an intradermal site with a high success rate. In addition, the results of displacement-force profiles with an artificial membrane showed that a micropillar can be effective for depth control of the injected solution as well as the prevention of contact between the hMN pedestal and the deformed membrane. CONCLUSION: In the present study, hMN1300S showed effective solution delivery into an intradermal site. In particular, a micropillar can be effective for depth control of the injected solution as well as preventing contact between the hMN pedestal and the deformed membrane. The obtained results will help in the design and development of hMNs that ensure successful injection of an administered drug.