As a relatively novel technique for drug delivery, the needle-free injection technique is characterized by transporting the drug liquid to the designated subcutaneous position through a high-speed micro-jet. Although this technique has been applied in many fields, the research on its drug dispersion mechanism and injection performance is insufficient. The presented study aims to identify critical parameters during the injection process and describe their influence on the injection effect. The injection completion rate and performance of a needle-free injector under various operating conditions were compared based on mouse experiments. The results show that the nozzle diameter imposes a more significant influence on jet characteristics than other injection parameters. Moreover, the injection completion rate increases with the nozzle diameter. The nozzle diameters of 0.14 mm and 0.25 mm correspond to injection completion rates of 89.7% and 95.8%, respectively. Furthermore, by analyzing the rate of blood glucose change in the tested mice, it is found that insulin administration through the needle-free injection can achieve a drug effect duration longer than 120 min, which is better than that obtained using conventional needle-syringe technique. In summary, the obtained conclusions can provide an important reference for the optimal design and extending application of the air-powered needle-free injector.
Animals ; Mice ; Insulin/administration & dosage* ; Needles ; Injections, Subcutaneous/methods* ; Injections, Jet/instrumentation* ; Drug Delivery Systems/instrumentation* ; Blood Glucose/analysis* ; Equipment Design

Objective: To analyze the factors affecting the efficacy of mite subcutaneous immunotherapy (SCIT) in allergic asthma patients aged 5-18 years, and to find the best predictive model for the curative effect. Methods: The data of 688 patients aged 5-18 years with allergic asthma who completed more than 3 years of mite SCIT from December 2006 to November 2021 in the Department of Respiratory Medicine, Children's Hospital Affiliated to Nanjing Medical University were retrospectively analyzed. Male, results of skin prick test (SPT), age, daily medication score (DMS), visual analogue scale (VAS) score, and enrollment season were defined as independent variables. R language models, including Logistic regression model, random forest model and extreme gradient boosting (XGboost) model, were used to analyze the impact of these independent variables on the outcomes. The receiver operating characteristic curve was applied to compare the predictive ability of the models. Hypothesis testing of the area under curve (AUC) of the 3 models was performed using DeLong test. Results: There were 435 males and 253 females in the 688 patients. There were 349 patients aged 5-<8 years, 240 patients aged 8-<11 years, and 99 patients aged 11-18 years. SPT showed that 429 cases (62.4%) were only allergic to mite, and 259 cases (37.7%) were also allergic to other allergens. According to the efficacy after 3 years of SCIT, 351 cases (51.0%) discontinued the treatment and 337 cases (49.0%) required continued treatment. The DMS was 4 (3, 6) at initiation, 3 (2, 5) at 3 months, 3 (2, 5) at 4 months, 2 (1, 3) at 12 months, and 0 (0, 1) at 3 years of SCIT treatment. The VAS was 3.5 (2.5, 5.2) at initiation, 3.2 (2.2, 4.8) at 3 months, 2.6 (1.4, 4.1) at 4 months, 1.0 (0.6, 1.8) at 12 months, and 0.5 (0, 1.2) at 3 years of treatment. At 3, 4, and 12 months, the rate of decline in DMS was 0 (0, 20%), 16.7% (0, 33.3%), and 50.0% (31.0%, 75.0%), respectively; and the VAS decreased by 7.1% (3.2%,13.8%), 27.6% (16.7%,44.4%), and 70.2% (56.1%, 82.3%), respectively. Regarding the enrollment season, 99 cases were in spring, 230 cases in summer, 171 cases in autumn, and 188 cases in winter. The R language Logistic regression model found that DMS>3 points at 3 months (OR=-3.5, 95%CI:-4.3--2.7, P<0.01), male (OR=-1.7, 95%CI:-2.3--1.0), P<0.01), DMS decline rate>16.7% at 4 months (OR=-1.6, 95%CI:-2.3--0.8, P<0.01) and DMS decline rate>0 at 3 months (OR=-0.7, 95%CI:-1.3--0.2, P<0.05) had higher possibility of drug discontinuation; whereas, the decline rate of DMS at 12 months>50.0% (OR=0.7, 95%CI: 0.1-1.3, P<0.05), VAS at 12 months>1.0 points (OR=0.9, 95%CI: 0.3-1.6, P<0.05), and initial VAS<4.0 points (OR=1.0, 95%CI: 0.4-1.6, P<0.01) had lower possibility of drug discontinuation. Both the random forest model and the XGboost model showed that DMS>3 points at 3 months (mean decrease accuracy=30.9, importance=0.45) had the greatest impact on drug discontinuation. The AUC of the random forest model was the largest at 0.900, with an accuracy of 78.2% and a sensitivity of 84.5%. Logistic regression model had AUC of 0.891, accuracy of 80.0%, and sensitivity of 80.0%; XGboost model had AUC of 0.886, accuracy of 76.9%, and sensitivity of 84.5%. The AUC of the pairwise comparison model by DeLong test found that all three models could be used for the prediction of this data set (all P>0.05). Conclusions: The more drugs used to control the primary disease, and the more careful reduction of the control medicine after starting SCIT treatment, the more favorable it is to stop all drugs after 3 years. The random forest model is the best predictive model for the efficacy of mite SCIT in asthmatic children.
Adolescent ; Allergens ; Animals ; Asthma/therapy* ; Child ; Child, Preschool ; Desensitization, Immunologic/methods* ; Female ; Humans ; Immunotherapy/methods* ; Injections, Subcutaneous ; Male ; Mites ; Retrospective Studies

PURPOSE: Ultra-rush schedule of subcutaneous allergen immunotherapy (UR-SCIT) administering maximum maintenance dose of allergen extract within one day can save time and effort for allergen immunotherapy in patients with allergic disease. However, UR-SCIT is associated with an increased risk of systemic reaction (SR) and typically has been conducted in a hospital admission setting. To overcome disadvantages of UR-SCIT, we evaluated the safety of UR-SCIT conducted in an outpatient clinic in patients with atopic dermatitis (AD) and allergic rhinitis (AR). METHODS: UR-SCIT was performed in 538 patients with AD and/or AR sensitized to house dust mite (HDM). A maximum maintenance dose of tyrosine-adsorbed HDM extract (1 mL of maintenance concentration) was divided into 4 increasing doses (0.1, 0.2, 0.3, and 0.4 mL) and administered to the patients by subcutaneous injection at 2-hour intervals for 8 hours in an outpatient clinic. SRs associated with UR-SCIT were classified according to the World Allergy Organization grading system. RESULTS: SR was observed in 12 of 538 patients (2.2%) with AD and/or AR during UR-SCIT. The severity grades of the observed SRs were mild-to-moderate (grade 1 in 7 patients, grade 2 in 4 patients, and grade 3 in 1 patient). The scheduled 4 increasing doses of HDM extract could be administered in 535 of 538 patients (99.4%) except 3 patients who experienced SR before administration of the last scheduled dose. SR was observed within 2 hours in 11 patients after administration of the scheduled doses of HDM extract except one patient who experienced a grade 2 SR at 5.5 hours after administration of the last scheduled dose. CONCLUSIONS: UR-SCIT with tyrosine-adsorbed HDM extract conducted in an outpatient clinic was tolerable in patients with AD and AR. UR-SCIT can be a useful method to start a SCIT in patients with AD and AR.
Ambulatory Care Facilities ; Appointments and Schedules ; Dermatitis, Atopic ; Desensitization, Immunologic ; Dust ; Humans ; Hypersensitivity ; Injections, Subcutaneous ; Methods ; Outpatients ; Pyroglyphidae ; Rhinitis, Allergic

This study was to investigate the effect of subcutaneous injection of the adipose stem cells (ASCs) with conditioned media (CM) in the treatment of acne vulgaris scar. We used Adult male New Zealand white rabbit ears as an animal model and induced acne formation by Kignman method. Adipose tissue was isolated and harvested from the scapula of rabbits, and ASCs were cultured and expanded until passage 1. There have four groups in our experiment, include phosphate buffered saline (PBS), ASCs with PBS (ASC + PBS), CM, and ASCs with CM (ASC + CM) group. This solution of 0.6 ml injected to subcutaneous in each group. ASC + PBS and ASC + CM groups were containing ASCs of 5.0 × 106 cells/ml. We analyzed the treatment of 4 groups to scar tissue after 2 and 4 weeks by hematoxylin and eosin stain, immunohistochemistry, and RNA expression level of tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), and matrix metalloproteinase-2 (MMP-2). Also, the expression of keratin 16 (K16) was detected by western blot analysis. H&E stain showed that infiltration of inflammation cells was significantly reduced at 2 and 4 weeks, as well as re-epithelialization was improved in the ASC + CM group. The ASC + CM gourp was reduced both expression levels of TNF-α, IL-1α, and MMP-2 and K16 protein level. In conclusion, the ASCs with CM has a significant curative effect on acne vulgaris scar, more to the point, the CM has a key role on treatment. It could be applied to a therapeutic approach to regenerate to treat acne vulgaris scar.
Acne Vulgaris ; Adipose Tissue ; Adult ; Blotting, Western ; Cicatrix ; Culture Media, Conditioned ; Ear ; Eosine Yellowish-(YS) ; Hematoxylin ; Humans ; Immunohistochemistry ; Inflammation ; Injections, Subcutaneous ; Keratin-16 ; Male ; Matrix Metalloproteinase 2 ; Methods ; Models, Animal ; Necrosis ; New Zealand ; Rabbits ; Re-Epithelialization ; RNA ; Scapula ; Stem Cells

BACKGROUND: Acellular dermal matrix (ADM) helps wound healing by stimulating angiogenesis, acting as a chemoattractant for endothelial cells, providing growth factors, and permitting a substrate for fibroblasts to attach. The current standard for using paste-type ADM (CG Paste) in wound healing is direct application over the wounds. The major concerns regarding this method are unpredictable separation from the wounds and absorption into negative-pressure wound therapy devices. This study aimed to investigate the effects of subcutaneous injection of paste-type ADM on wound healing in rats. METHODS: Full-thickness skin defects were created on the dorsal skin of rats. Eighteen rats were randomly divided into three groups and treated using different wound coverage methods: group A, with a saline dressing; group B, standard application of CG Paste; and group C, injection of CG Paste. On postoperative days 3, 5, 7, 10, and 14, the wound areas were analyzed morphologically. Histological and immunohistochemical tissue analyses were performed on postoperative days 3 and 7. RESULTS: Groups B and C had significantly less raw surface than group A on postoperative days 10 and 14. Collagen fiber deposition and microvessel density were significantly higher in group C than in groups A and B on postoperative days 3 and 7. CONCLUSIONS: This study showed comparable effectiveness between subcutaneous injection and the conventional dressing method of paste-type ADM. Moreover, the injection of CG Paste led to improved wound healing quality through the accumulation of collagen fibers and an increase in microvessel density.
Absorption ; Acellular Dermis* ; Animals ; Bandages ; Collagen ; Endothelial Cells ; Fibroblasts ; Injections, Subcutaneous* ; Intercellular Signaling Peptides and Proteins ; Methods ; Microvessels ; Negative-Pressure Wound Therapy ; Ointments ; Rats ; Skin ; Wound Healing* ; Wounds and Injuries*

Vaccination is the most efficient method for infectious disease prevention. Parenteral injections such as intramuscular, intradermal, and subcutaneous injections have several advantages in vaccine delivery, but there are many drawbacks. Thus, the development of a new vaccine delivery system has long been required. Recently, microneedles have been attracting attention as new vaccination tools. Microneedle is a highly effective transdermal vaccine delivery method due to its mechanism of action, painlessness, and ease of use. Here, we summarized the characteristics of microneedles and the possibilities as a new vaccine delivery route.
Communicable Diseases ; Injections, Subcutaneous ; Methods* ; Vaccination ; Vaccines*

The efficiency of dendritic cell-activated and cytokine-induced killer cell (DC-CIK) therapy on children with acute myeloid leukemia (AML) after chemotherapy was investigated. Mononuclear cells were collected from children achieving complete remission after chemotherapy, cultured in vitro and transfused back into the same patient. Interleukin-2 (IL-2) was injected subcutaneously every other day 10 times at the dose of 1 × 10(6) units. Peripheral blood lymphocyte subsets and minimal residual disease (MRD) were detected by flow cytometry. Function of bone marrow was monitored by methods of morphology, immunology, cytogenetics and molecular biology. The side effects were also observed during the treatment. The average follow-up period for all the 22 patients was 71 months and relapse occurred in two AML patients (9.1%). The percentage of CD3(+)/CD8(+) cells in peripheral blood of 15 patients at the 3rd month after DC-CIK treatment (36.73% ± 12.51%) was dramatically higher than that before treatment (29.20% ± 8.34%, P < 0.05). The MRD rate was >0.1% in 5 patients before the treatment, and became lower than 0.1% 3 months after the treatment. During the transfusion of DC-CIK, side effects including fever, chills and hives appeared in 7 out of 22 (31.82%) cases but disappeared quickly after symptomatic treatments. There were no changes in electrocardiography and liver-renal functions after the treatment. MRD in children with AML can be eliminated by DC-CIK therapy which is safe and has fewer side effects.
Adolescent ; Antineoplastic Agents ; therapeutic use ; Bone Marrow ; drug effects ; immunology ; pathology ; Child ; Child, Preschool ; Cytokine-Induced Killer Cells ; cytology ; immunology ; transplantation ; Dendritic Cells ; cytology ; immunology ; transplantation ; Female ; Humans ; Immunotherapy, Adoptive ; methods ; Injections, Subcutaneous ; Interleukin-2 ; therapeutic use ; Leukemia, Myeloid, Acute ; immunology ; pathology ; therapy ; Male ; Neoplasm, Residual ; Primary Cell Culture ; Recurrence ; Remission Induction ; Treatment Outcome

Preoperative localization is necessary prior to video assisted thoracoscopic surgery for the detection of small or deeply located lung nodules. We compared the localization ability of a mixture of lipiodol and methylene blue (MLM) (0.6 mL, 1:5) to methylene blue (0.5 mL) in rabbit lungs. CT-guided percutaneous injections were performed in 21 subjects with MLM and methylene blue. We measured the extent of staining on freshly excised lung and evaluated the subjective localization ability with 4 point scales at 6 and 24 hr after injections. For MLM, radio-opacity was evaluated on the fluoroscopy. We considered score 2 (acceptable) or 3 (excellent) as appropriate for localization. The staining extent of MLM was significantly smaller than methylene blue (0.6 vs 1.0 cm, P<0.001). MLM showed superior staining ability over methylene blue (2.8 vs 2.2, P=0.010). Excellent staining was achieved in 17 subjects (81%) with MLM and 8 (38%) with methylene blue (P=0.011). An acceptable or excellent radio-opacity of MLM was found in 13 subjects (62%). An appropriate localization rate of MLM was 100% with the use of the directly visible ability and radio-opacity of MLM. MLM provides a superior pulmonary localization ability over methylene blue.
Animals ; Ethiodized Oil/*administration & dosage ; Fluoroscopy ; Injections, Subcutaneous ; Lung/*radiography/surgery ; Methylene Blue/*administration & dosage ; Preoperative Care ; Rabbits ; Solitary Pulmonary Nodule/*surgery ; Staining and Labeling/methods ; Thoracic Surgery, Video-Assisted/*methods ; Thoracoscopy/methods ; Tomography, X-Ray Computed

OBJECTIVETo investigate the efficacy and safety of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in the salvage therapy for the grade IV neutropenia induced by concurrent chemoradiotherapy, and to provide evidence for its clinical rational application.

METHODS114 malignant tumor patients suffered with grade IV neutropenia induced by concurrent chemoradiotherapy were treated in the following groups. In the P-50 group, 42 patients received a single subcutaneous injection of 50 µg/kg PEG-rhG-CSF. In the P-100 group, 30 patients received a single subcutaneous injection of 100 µg/kg PEG-rhG-CSF. In the P+R group, 22 patients received a single subcutaneous injection of 50 µg/kg PEG-rhG-CSF and multiple subcutaneous injections of 5 µg×kg(-1)×d(-1) rhG-CSF, until the absolute neutrophil count (ANC) ≥ 2.0×10(9)/L. In the R group, 20 patients received multiple subcutaneous injections of 5 µg×kg(-1)×d(-1) rhG-CSF, until ANC ≥ 2.0×10(9)/L. The P-50, P-100 and P+R groups were experimental groups, and the R group was defined as control group. In each group, the neutrophil proliferation rate and the neutrophil counts at different time points, the period of neutropenia symptom relief, and the rate of adverse reactions induced by above drugs were analyzed.

RESULTSBoth neutrophil proliferation rates and neutrophil counts in the patients of experimental groups at different time points were significantly higher than those in the control group. In the experimental groups the period of the clinical effect began in 12-24 hours, and the conditions of neutropenia were improved in 36 hours. In the experimental groups, the period of the symptom relief such as fever and skeletal muscle pain was (30.00 ± 7.48) hours and (30.00 ± 5.10) hours, respectively, significantly shorter than (72.00 ± 17.89) hours and (59.00 ± 11.46) hours in the control group (P < 0.05). The adverse drug reaction rate was 26.1% in the experimental groups and 25.0% in the control group (P > 0.05).

CONCLUSIONSFor the treatment of grade IV neutropenia induced by concurrent chemoradiotherapy, PEG-rhG-CSF is effective and safe. The recommend dose of this drug for the salvage therapy for those patients is a single hypodermal injection of 50 µg/kg. Usually it becomes effective in 12-24 hours.

Chemoradiotherapy ; Granulocyte Colony-Stimulating Factor ; genetics ; metabolism ; Humans ; Injections, Subcutaneous ; Leukocyte Count ; Neutropenia ; chemically induced ; Neutrophils ; Recombinant Proteins ; Salvage Therapy ; methods

OBJECTIVETo evaluate the therapeutic efficacy of 3-year subcutaneous immunotherapy (SCIT) in asthmatic children allergic to mite.

METHODSNinety asthmatic children allergic to house dust mite (with or without allergic rhinitis) and aged 5-14 years were randomized into SCIT treatment group (n=45) and control group (n=45). The SCIT treatment group received SCIT combined with standardized treatment for asthma, while the control group received the standardized treatment alone. The therapeutic effects were assessed based on the daytime and nighttime symptom scores, mean daily doses of inhaled corticosteroids (ICS), skin prick test results, peak expiratory flows and total serum IgE at baseline and in the 3-year treatment.

RESULTSIn both groups, the daytime and nighttime symptom scores in the first, second, and third years of treatment were significantly lower than the baseline values (P<0.01), and the scores decreased year by year during the 3-year treatment (P<0.01). Also, the mean daily doses of ICS in the first, second, and third years of treatment were significantly lower than the baseline values (P<0.01), and the doses decreased year by year during the 3-year treatment (P<0.01). The mean daily dose was significantly lower in the SCIT treatment group than in the control group in the second and third years of treatment (P<0.05). After 3-year treatment, the SCIT treatment group had a significantly higher proportion of children who discontinued use of ICS due to remission of symptoms compared with the control group (29% vs 20%, P<0.05). At the end of the 3-year treatment, the total serum IgE was significantly lower than the baseline value in the SCIT treatment group (P<0.01), and it was significantly lower in the SCIT treatment group than in the control group (P<0.05).

CONCLUSIONSThree-year SCIT is effective in asthmatic children allergic to house dust mite and allows reduction in the dosage of ICS.

Adrenal Cortex Hormones ; administration & dosage ; Animals ; Asthma ; immunology ; therapy ; Child ; Desensitization, Immunologic ; adverse effects ; methods ; Female ; Humans ; Immunoglobulin E ; blood ; Injections, Subcutaneous ; Male ; Pyroglyphidae ; immunology