Factors influencing agitation during anesthesia recovery after laparoscopic hernia repair under total inhalation combined with caudal block anesthesia

BACKGROUND Laparoscopic hernia repair is a minimally invasive surgery,but patients may experience emergence agitation(EA)during the post-anesthesia recovery period,which can increase pain and lead to complications such as wound reopening and bleeding.There is limited research on the risk factors for this agitation,and few effective tools exist to predict it.Therefore,by integrating clinical data,we have developed nomograms and random forest predictive models to help clinicians predict and potentially prevent EA.AIM To establish a risk nomogram prediction model for EA in patients undergoing laparoscopic hernia surgery under total inhalation combined with sacral block anesthesia.METHODS Based on the clinical information of 300 patients who underwent laparoscopic hernia surgery in the Nanning Tenth People’s Hospital,Guangxi,from January 2020 to June 2023,the patients were divided into two groups according to their sedation-agitation scale score,i.e.,the EA group(≥5 points)and the non-EA group(≤4 points),during anesthesia recovery.Least absolute shrinkage and selection operator regression was used to select the key features that predict EA,and incorporating them into logistic regression analysis to obtain potential pre-dictive factors and establish EA nomogram and random forest risk prediction models through R software.RESULTS Out of the 300 patients,72 had agitation during anesthesia recovery,with an incidence of 24.0%.American Society of Anesthesiologists classification,preoperative anxiety,solid food fasting time,clear liquid fasting time,indwelling catheter,and pain level upon awakening are key predictors of EA in patients undergoing laparoscopic hernia surgery with total intravenous anesthesia and caudal block anesthesia.The nomogram predicts EA with an area under the receiver operating characteristic curve(AUC)of 0.947,a sensi-tivity of 0.917,and a specificity of 0.877,whereas the random forest model has an AUC of 0.923,a sensitivity of 0.912,and a specificity of 0.877.Delong’s test shows no significant difference in AUC between the two models.Clinical decision curve analysis indicates that both models have good net benefits in predicting EA,with the nomogram effective within the threshold of 0.02 to 0.96 and the random forest model within 0.03 to 0.90.In the external model validation of 50 cases of laparoscopic hernia surgery,both models predicted EA.The nomogram model had a sensitivity of 83.33%,specificity of 86.84%,and accuracy of 86.00%,while the random forest model had a sensitivity of 75.00%,specificity of 78.95%,and accuracy of 78.00%,suggesting that the nomogram model performs better in predicting EA.CONCLUSION Independent predictors of EA in patients undergoing laparoscopic hernia repair with total intravenous anesthesia combined with caudal block include American Society of Anesthesiologists classification,preoperative anxiety,duration of solid food fasting,duration of clear liquid fasting,presence of an indwelling catheter,and pain level upon waking.The nomogram and random forest models based on these factors can help tailor clinical decisions in the future.

Efficacy of budesonide/formoterol inhalation powder in treating viral pneumonia in children

BACKGROUND Respiratory viruses are increasingly detected in children with communityacquired pneumonia.Further strategies to limit antibiotic use in children with viral pneumonia are warranted.AIM To explore clinical efficacy of budesonide/formoterol inhalation powder for viral pneumonia in children and its impact on cellular immunity and inflammatory factor production.METHODS A total of 60 children with viral pneumonia were recruited:30 receiving budesonide/formoterol inhalation powder and 30 conventional symptomatic treatment.Outcome measures included peripheral blood levels of inflammatory cytokines,CD4^(+),CD8^(+),Th1,Th2,Th17 and Treg,clinical efficacy,and incidence of adverse reactions.RESULTS Compared with the control group,the observation group showed a significant reduction in interleukin-6 and high-sensitivity C-reactive protein levels after treatment.Compared with the control group,the observation group showed a significant increase in CD4^(+)/CD8^(+)and Th1/Th2 levels,and a decrease in Th17/Treg levels after treatment.The total effective rates in the observation group and the control group were 93.75%and 85.00%,respectively,which was a significant difference(P=0.003).CONCLUSION Budesonide/formoterol inhalation powder significantly improved therapeutic efficacy for viral pneumonia in children.The mechanism of action may be related to downregulation of the inflammatory response and improved cellular immune function.

Clinical Efficacy Analysis of Tiotropium Bromide Combined with Budesonide and Formoterol Inhalation in Treating COPD

Objective:To analyze the clinical efficacy of tiotropium bromide(TB)combined with budesonide formoterol(BUD/FM)inhalation in treating chronic obstructive pulmonary disease(COPD).Methods:62 COPD patients admitted to the hospital between June 2020 and December 2022 were selected as samples for this study.The patients were divided into a combination group and a conventional group using the random number table method,with 31 cases in each group.The patients in the combination group were treated with TB combined with BUD/FM inhalation,whereas the patients in the conventional group were treated with BUD/FM inhalation only.The treatment efficacy and changes in lung function indicators of both groups were compared.Results:The total efficacy of treatment in the combined group was higher than that in the conventional group,and the difference was statistically significant(P<0.05).Before treatment,there was no difference in pulmonary function indicators between the two groups(P>0.05).After three months of treatment,all lung function indicators of the combined group were higher than those of the conventional group,and the difference was statistically significant(P<0.05).Conclusion:Combining TB with BUD/FM inhalation therapy increases the efficacy of treatment for patients with COPD.Besides,it also improves lung function and leads to a better prognosis.

Recent progress of respiratory inhalation drug delivery systems

With the influence of many factors such as the aging of the population,the younger smokers,and the serious air pollution,the incidence of chronic respiratory diseases is increasing year by year.In the treatment of respiratory diseases,clinical intervention is still mainly based on drug control of pulmonary symptoms.However,systemic drugs have disadvantages such as many adverse reactions and severe systemic side effects.In recent years,the research and development of local drug delivery systems for the respiratory tract has brought new changes to the treatment of respiratory diseases.Locally delivered drugs can directly act on the airways and have the characteristics of fast onset,good curative effect and small side effects.It is a simple,efficient and safe treatment method,which has a very significant effect,and has become a hot topic of current research and promotion.This paper briefly reviews the development track and latest research progress of respiratory local drug delivery systems at home and abroad,in order to provide reference for clinical workers in drug selection and application.

Inhalation therapy for pulmonary fibrosis:chemical medicines and herbal medicines

Pulmonary fibrosis(PF)is a chronic,progressive,and irreversible pulmonary interstitial disease with unclear pathogenesis.Currently,there are few treatment options for managing PF.Inhalation therapy,as a routine treatment for respiratory diseases,is being used to study the treatment of PF.Some herbal medicines and their active ingredients have been reported to have anti-PF effects.This review aims to provide an overview of the latest developments in inhalation therapy,focusing on the utilization of chemical medicines and herbal medicines for the treatment of PF in both clinical practice and basic research.The inhalation of chemical drugs such as pirfenidone,nintedanib,N-acetylcysteine,and interferon-γhas been shown to demonstrate anti-PF effects.Additionally,the inhalation of various natural products derived from herbal medicines,encompassing polyphenols,alkaloids,flavonoids,saponins,terpenoids,and herbal extracts,contributes to the therapeutic management of PF through diverse mechanisms.The inhalation of both chemical and herbal medicines presents promising advantages in the treatment of PF.Further clinical trials are required to investigate the effectiveness,safety,and mechanism of action of inhalation therapy utilizing natural products derived from herbal medicines.

The Effect of Nebulized Budesonide Inhalation in Treating Children with Asthma and its Influence on Immune Indexes

Objective:To explore and analyze the effect of nebulized budesonide inhalation on children with asthma and its influence on immune indexes.Methods:300 children who were with asthma admitted to the Pediatric Respiratory Department of our hospital from January 2021 to January 2023 were selected as the research subjects.The patients were divided into a nebulization group(n=150)and a reference group(n=150)by drawing lots.The nebulization group received routine treatment along with budesonide nebulization inhalation therapy,while the reference group only received routine treatment.The treatment effect,the immune indicators,the time taken for the disappearance of symptoms,and the pulmonary function indicators of both groups were compared.Results:The total efficacy of treatment received in the nebulization group was significantly higher than that in the reference group(P<0.05).Before treatment,there was no statistically significant difference in the CD4^(+),CD8^(+),CD4^(+)/CD8^(+),between the two groups(P>0.05);after treatment,the nebulization group’s CD4^(+),CD8^(+),CD4^(+)/CD8^(+)and other immune indicators were significantly better than the reference group(P<0.05).The time taken for the disappearance of symptoms like wheezing,coughing,crackles,shortness of breath,and other symptoms in the nebulization group was significantly shorter than in the reference group(P<0.05).Before treatment,there was no statistically significant difference in the pulmonary function indexes such as FEV1,PEF,and FVC between the two groups(P>0.05);after treatment,the pulmonary function indexes of the patients in the nebulization group were significantly better than those in the reference group(P<0.05).Conclusion:Nebulized budesonide inhalation therapy has shown significant efficacy in the treatment of pediatric asthma,with notable improvements in immune indicators.Therefore,it is worthy of recommendation and further promotion.

TREATMENT OF 50 CASES OF SENILE DEMENTIA BY ACUPUNCTURE COMBINED WITH INHALATION OF HERBAL DRUGS AND OXYGEN

Clinical DataCase selection: 100 cases who met thediagnostic criteria of senile dementiaformulated by American Association ofPsychiatry in Handbook of Diagnosis andStatistics (DSM-Ⅲ-R, 3rd revised edition)

Combined early fluid resuscitation and hydrogen inhalation attenuates lung and intestine injury

AIM:To study the effects of combined early fluid resuscitation and hydrogen inhalation on septic shockinduced lung and intestine injuries.METHODS:Wistar male rats were randomly divided into four groups:control group(Group A,n = 15);septic shock group(Group B,n = 15);early fluid resuscitation-treated septic shock group(Group C,n = 15);and early fluid resuscitation and inhalation of 2% hydrogentreated septic shock group(Group D,n = 15).The activity of hydroxyl radicals,myeloperoxidase(MPO),superoxide dismutase(SOD),diamine oxidase(DAO),and the concentration of malonaldehyde(MDA) in the lung and intestinal tissue were assessed according to the corresponding kits.Hematoxylin and eosin staining was carried out to detect the pathology of the lung and intestine.The expression levels of interleukin(IL)-6,IL-8,and tumor necrosis factor(TNF)-α in lung and intestine tissue were detected by enzyme-linked immunosorbent assay method.The expression levels of Fas and Bcl2 in lung tissues were determined by immunohistochemistry and Western blotting.RESULTS:Septic shock elicited a significant increase in the levels of MDA(10.17 ± 1.12 nmol/mg protein vs 2.98 ± 0.64 nmol/mg protein) and MPO(6.79 ± 1.02 U/g wet tissue vs 1.69 ± 0.14 U/g wet tissue) in lung tissues.These effects were not significantly decreased by Group C pretreatment,but were significantly reduced by Group D pretreatment(MDA:4.45 ± 1.13 nmol/mg protein vs 9.56 ± 1.37 nmol/mg protein;MPO:2.58 ± 0.21 U/g wet tissue vs 6.02 ± 1.16 U/g wet tissue).The activity of SOD(250.32 ± 8.56 U/mg protein vs 365.78 ± 10.26 U/mg protein) in lung tissues was decreased after septic shock,and was not significantly increased by Group C pretreatment,but was significantly enhanced by Group D pretreatment(331.15 ± 9.64 U/mg protein vs 262.98 ± 5.47 U/mg protein).Histological evidence of lung hemorrhage,neutrophil infiltration and overexpression of IL-6,IL-8,and TNF-α was observed in lung tissues,all of which were attenuated by Group C and further alleviated by Group D pretreatment.Septic shock also elicited a significant increase in the levels of MDA,MPO and DAO(6.54 ± 0.68 kU/L vs 4.32 ± 0.33 kU/L) in intestinal tissues,all of which were further increased by Group C,but significantly reduced by Group D pretreatment.Increased Chiu scoring and overexpression of IL-6,IL-8 and TNF-α were observed in intestinal tissues,all of which were attenuated by Group C and further attenuated by Group D pretreatment.CONCLUSION:Combined early fluid resuscitation and hydrogen inhalation may protect the lung and intestine of the septic shock rats from the damage induced by oxidative stress and the inflammatory reaction.

Inhalation of nanoparticle-based drug for lung cancer treatment:Advantages and challenges

Ever since the success of developing inhalable insulin,drug delivery via pulmonary administration has become an attractive route to treat chronic diseases.Pulmonary delivery system for nanotechnology is a relatively new concept especially when applicable to lung cancer therapy.Nano-based systems such as liposome,polymeric nanoparticles or micelles are strategically designed to enhance the therapeutic index of anti-cancer drugs through improvement of their bioavailability,stability and residency at targeted lung regions.Along with these benefits,nano-based systems also provide additional diagnostic advantages during lung cancer treatment,including imaging,screening and drug tracking.Nevertheless,delivery of nanobased drugs via pulmonary administration for lung cancer therapy is still in its infancy and numerous challenges are expected.Pharmacology,immunology,toxicology and largescale manufacturing(stability and activity of drugs)are some aspects in nanotechnology that should be taken into consideration for the development of inhalable nano-based chemotherapeutic drugs.This review will focus on the current inhalable nano-based drugs for lung cancer treatment.

Histomorphological and Histochemical Alterations Following Short-term Inhalation Exposure to Sulfur Mustard on Visceral Organs of Mice

Toxic effects of inhaled sulfur mustard (SM) on the histology of visceral organs was investigaed by exposing mice to 84. 6mg/m3 for 1h duration, using controlled single exposure conditions. A progressive fall in body weight from third day onwards was noticed. Light microscopic examination of the pulmonary tissue of these animals at 6 h post exposure revealed that the tracheobronchial epithelium remained intact, but was infiltrated by inflammatory cells. By 24 h post exposure, the mucosecretory cells were destroyed. The indanunatory reaction was maximum at 48 h. By 7th day post exposure there was swelling and vacuolation of lung parenchymal cells and thrombi formation. In addition SM caused congestion and hemorrhage at alveolar level. SM also caused granulovacuolar degeneration with perinuclear clumping of the cytopasm of hepatocytes and renal parenchymal cells. Renallesions were chazacterized by congestion and hemorrhage. Among visceral tissues, maximum atrophywas observed in spleen. Distribution of lesions increased with post exposure period. The maximum lesions were observed at 7th day post-exposure.

Potentially fatal electrolyte imbalance caused by severe hydrofluoric acid burns combined with inhalation injury: A case report

BACKGROUND Hydrofluoric acid(HF)is one of the most common causes of chemical burns.HF burns can cause wounds that deepen and progress aggressively.As a result,HF burns are often severe even if they involve a small area of the skin.Published cases of HF burns have mostly reported small HF burn areas.Few cases of HF inhalation injury have been reported to date.CASE SUMMARY A 24-year-old man suffered from extensive hydrofluoric acid burns covering 60%of the total body surface area(TBSA),including deep second degree burns on 47%and third degree burns on 13%of the TBSA,after he fell into a pickling pool containing 15%HF.Comprehensive treatments were carried out after the patient was admitted.Ventricular fibrillation occurred 9 times within the first 2 h,and the lowest serum Ca2+concentration was 0.192 mmol/L.A dose of calcium gluconate(37 g)was intravenously supplied during the first 24 h,and the total amount of calcium gluconate supplementation was 343 g.Extracorporeal membrane oxygenation(ECMO)was applied for 8 d to handle the acute respiratory distress syndrome(ARDS)induced by the HF inhalation injury.The patient was discharged after 99 d of comprehensive treatment,including skin grafting.CONCLUSION Extensive HF burns combined with an inhalation injury led to a potentially fatal electrolyte imbalance and ARDS.Adequate and timely calcium supplementation and ECMO application were the keys to successful treatment of the patient.

Effects of bone marrow-derived mesenchymal stemcells engraftment on vascular endothelial cell growthfactor in lung tissue and plasma at early stage of smoke inhalation injury

BACKGROUND： This study was undertaken to determine the effect of mesenchymal stem cells （MSCs） engraftment on vascular endothelial cell growth factor （VEGF） in lung tissue, plasma and extravascular lung water at early stage of smoke inhalation injury.METHODS： A rabbit smoke inhalation injury model was established using a home-made smoke inhalation injury generator, and rabbits were divided into two groups randomly： a control group （S group, n=32） and a MSCs treatment group （M group, n=32）. 10 ml PBS was injected via the ear marginal vein immediately at injury into the S group. Third generation MSCs with a concentration of 1×107/10 ml PBS were injected via the ear marginal vein immediately at injury into the M group. VEGF in peripheral blood and lung tissue were measured at 0 （baseline）, 2, 4 and 6 hours after injection respectively and analyzed. The right lungs of rabbits were taken to measure lung water mass fraction.RESULTS： In the lung tissue, VEGF decreased gradually in the S group （P〈0.05） and signi？ cantly decreased in the M group （P〈0.05）, but it increased more signi？ cantly than the values at the corresponding time points （P〈0.05）. In peripheral blood, VEGF increased gradually in the S group （P〈0.05） and markedly increased in the M group （P〈0.05）, but it decreased more signi？ cantly than the values at corresponding time points （P〈0.05）.CONCLUSION： MSCs engraftment to smoke inhalation injury could increase VEGF in lung tissue, decrease VEGF in plasma and reduce extravascular lung water, indicating its protective effect on smoke inhalation injury.

Critical physicochemical attributes of chitosan nanoparticles admixed lactose-PEG 3000 microparticles in pulmonary inhalation

Chitosan nanoparticles are exhalation prone and agglomerative to pulmonary inhalation.Blending nanoparticles with lactose microparticles(~5 μm) could mutually reduce their agglomeration through surface adsorption phenomenon. The chitosan nanoparticles of varying size, size distribution, zeta potential, crystallinity, shape and surface roughness were prepared by spray drying technique as a function of chitosan, surfactant and processing conditions. Lactose-polyethylene glycol 3000(PEG3000) microparticles were similarly prepared. The chitosan nanoparticles, physically blended with fine lactose-PEG3000 microparticles, exhibited a comparable inhalation performance with the commercial dry powder inhaler products(fine particle fraction between 20% and 30%). Cascade impactor analysis indicated that the aerosolization and inhalation performance of chitosan nanoparticles was promoted by their higher zeta potential and circularity, and larger size attributes of which led to reduced inter-nanoparticulate aggregation and favored nanoparticles interacting with lactose-PEG3000 micropaticles that aided their delivery into deep and peripheral lungs.

Pharmacological treatment of inhalation injury after nuclear or radiological incidents: The Chinese and German approach

Inhalation injury is often associated with burns and significantly increases morbidity and mortality. The main toxic components of fire smoke are carbon monoxide, hydrogen cyanide, and irritants. In the case of an incident at a nuclear power plant or recycling facility associated with fire, smoke may also contain radioactive material. Medical treatments may vary in different countries, and in this paper, we discuss the similarities and differences in the treatments between China and Germany. Carbon monoxide poisoning is treated by 100% oxygen administration and,if available, hyperbaric oxygenation in China as well as in Germany. In addition, antidotes binding the cyanide ions and relieving the respiratory chain are important. Methemoglobin-forming agents(e.g., nitrites, dimethylaminophenol)or hydroxocobalamin(Vitamin B12) are options. The metabolic elimination of cyanide may be enhanced by sodium thiosulfate. In China, sodium nitrite with sodium thiosulfate is the most common combination. The use of dimethylaminophenol instead of sodium nitrite is typical for Germany, and hydroxocobalamin is considered the antidote of choice if available in cases of cyanide intoxications by fire smoke inhalation as it does not further reduce oxygen transport capacity. Systematic prophylactic use of corticosteroids to prevent toxic pulmonary edema is not recommended in China or Germany. Stable iodine is indicated in the case of radioiodine exposure and must be administered within several hours to be effective. The decorporation of metal radionuclides is possible with Ca(DTPA)or Prussian blue that should be given as soon as possible. These medications are used in both countries, but it seems that Ca(DTPA) is administered at lower dosages in China. Although the details of the treatment of inhalation injury and radionuclide(s) decorporation may vary, the general therapeutic strategy is very similar in China and Germany.

Pulmonary Toxicity of a Formulated Preparation of Fenvalerate in Rats Subchronically Exposed by Nose Only Inhalation for 90 Days

Objective The pulmonary toxicity of a commercially available formulated preparation of Fenvalerate (Fen), a synthetic pyrethroid has been studied in rats following subchronic nose only inhalation exposure route. Method Adult male rats were exposed to Fen for 4h/day, 5 days a week for 90 days by using Flow Past Dynamic Nose only Inhalation Chamber. Results Fen exposed rats showed a significant increase in enzymatic activities of lactate dehydrogenase (LDH), acid phosphatase (ACP), alkaline phosphatase (ALP) and γ-glutamyl transferase (γ-GT) which are considered as biochemical indicators of pulmonary damage. The concomitant histopathological examination of Fen exposed rats' lung revealed inflammatory changes viz., influx of mononuclear cells admixed with a few giant cells in alveolar lumen, hypetrophied bronchiolar and alveolar epithelial lining cells and presence of edematous fluid in alveolar lumen alongwith congested parenchymatous blood vessels. Conclusion These results for the first time indicate the pulmonary toxic effects of a commonly used formulated Fen preparation by using rat model and nose only inhalation as the route of exposure.

Inhalation properties of water-soluble drug loaded liposomes atomized by nebulizer

The pulmonary route presents several advantages in designing drug delivery systems in both systemic and topical administration.The use of particulate carriers is an attractive method for designing pulmonary drug delivery systems,because such carriers could control drug release and selective drug targeting when the carriers reach the target site in the lung.The prevention of local irritation,reduced drug toxicity,and improved drug stability are also preferable results of utilizing such carrier systems.Among a number of particulate carriers,liposomes have an advantage in safety,because they consist of phospholipids,which are bio-components.

Effect of Inhalational Anesthetics on Cytotoxicity and Intracellular Calcium Differently in Rat Pheochromocytoma Cells (PC12)

Isoflurane, a commonly used inhaled anesthetic, induces apoptosis in rat pheochromocytoma cells （PC12） in a concentration- and time-dependent manner with unknown mechanism. We hypothesized that isoflurane induced apoptosis by causing abnormal calcium release from the endoplasmic reticulum （ER） via activation of inositol 1,4,5-trisphosphate （IP3） receptors. Alzheimer＇s presenilin-1 （PS 1） mutation increased activity of IP3 receptors and therefore rendered cells vulnerable to isoflurane-induced cytotoxicity. Sevoflurane and desflurane had less ability to disrupt intracellular calcium homeostasis and thus being less potent pared the cytotoxic effects of various inhaled to cause cytotoxicity. This study examined and com-anesthetics on PC12 cells transfected with the Alzheimer＇s mutated PS 1 （L286V） and the disruption of intracellular calcium homeostasis. PC 12 cells transfected with wild type （WT） and mutated PS 1 （L286V） were treated with equivalent of 1 MAC of isoflurane, sevoflurane and desflurane for 12 h. MTT reduction and LDH release assays were performed to evaluate cell viability. Changes of calcium concentration in cytosolic space （[Ca^2＋]c） were determined after exposing different types of cells to various inhalational anesthetics. The effects of IP3 receptor antagonist xestospongin C on isoflurane-induced cytotoxicity and calcium release from the ER in L286V PC12 cells were also determined. The results showed that isoflurane at 1 MAC for 12 h induced cytoxicity in L286V but not WT PC12 cells, which was also associated with greater and faster elevation of peak [Ca^2＋]c in L286V than in the WT cells. Xestospongin C significantly ameliorated isoflurane cytotoxicity in L286V cells, as well as inhibited the calcium release from the ER in L286V cells. Sevoflurane and desflurane at equivalent exposure to isoflurane did not induce similar cytotoxicity or elevation of peak [Ca^2＋]c in L286V PC 12 cells. These results suggested that isoflurane induced cytoxicity by partially causing abnormal calcium release from the ER via activation of IP3 receptors in L286V PC12 cells. Sevoflurane and desflurane at equivalent exposure to isoflurane did not induce similar elevation of [Ca^2＋]c or neurotoxicity in PC 12 cells transfected with the Alzheimer＇s PS 1 mutation.

Inhalation treatment of lung cancer: the influence of composition, size and shape of nanocarriers on their lung accumulation and retention

Objective： Various nanoparticles have been designed and tested in order to select optimal carriers for the inhalation delivery ofanticancer drugs to the lungs. Methods： q-he following nanocarriers were studied： micelles, liposomes, mesoporous silica nanoparticles （MSNs）, poly propyleneimine （PPI） dendrimer-siRNA complexes nanoparticles, quantum dots （QDs）, and poly （ethylene glycol） polymers. All particles were characterized using the following methods： dynamic light scattering, zeta potential, atomic force microscopy, in vitro cyto- and genotoxicity. In vivo organ distribution of all nanopartides, retention in the lungs, and anticancer effects of liposomes loaded with doxorubicin were examined in nude mice after the pulmonary or intravenous delivery. Results： Significant differences in lung uptake were found after the inhalation delivery of lipid-based and non-lipid-based nanoparticles. The accumulation ofliposomes and miceUes in lungs remained relatively high even 24 h after inhalation when compared with MSNs, Q Ds, and PPI dendrimers. There were notable differences between nanoparticle accumulation in the lungs and other organs 1 and 3 h after inhalation or intravenous administrations, but 24 h after intravenous injection all nanoparticles were mainly accumulated in the liver, kidneys, and spleen. Inhalation delivery of doxorubicin by liposomes significantly enhanced its anticancer effect and prevented severe adverse side effects of the treatment in mice bearing the orthotopic model of lung cancer. Conclusion： The results of the study demonstrate that lipid-based nanocarriers had considerably higher accumulation and longer retention time in the lungs when compared with non-lipid-based carriers after the inhalation delivery. These particles are most suitable for effective inhalation treatment of lung cancer.

Nitrogen monoxide vector of ultrasonic atomizing inhalation improves vertebro-basilar artery insufficiency Hemodynamic changes are detected by transcranial Doppler test

BACKGROUND： Latest researches at home and abroad indicate that glycerol trinitrate plays its function because it can metabolize into nitrogen monoxide （NO） in vivo. OBJECTIVE： To study the therapeutic effects of NO vector of ultrasonic atomizing inhalation on vertebro-basilar artery insufficiency （VBI） through transcranial Doppler （TCD） detection and serum NO content and indirect effect of TCD on cerebral blood flow changes. DESIGN： Randomized grouping and controlled clinical study. SETTING： Department of Neurology, the Fourth People＇s Hospital of Jinan. PARTICIPANTS： A total of 130 patients who were diagnosed as VBI were selected from Department of Neurology, the Fourth People＇s Hospital of Jinan from December 2001 to December 2005. The involved inpatients were checked by CT and MRI, and met the VBI diagnostic standard enacted by the Fourth National Academic Meeting of Cerebrovascular Disease in 1995. All patients and their relatives provided the confumed consent. They were randomly divided into low-dose treatment group （n =60）, high-lose treatment group （n =30） and control group （n =40）. METHODS： Patients in the low-dose and high-dose treatment groups were given ultrasonic atomizing inhalation of 3 mg and 5 mg glycerol trinitrate, respectively, for 20 minutes, once a day. In addition, ligustrazine and energy mixture were used once a day for three days in a course. Cases in the control group were only given ligustrazine and energy mixture. All selected cases accepted TCD, blood NO content was checked at the time of beginning, after the first time and after a period of treatment. According to the TCD test, VBI patients were divided into two groups （high-low flow velocity）. The vertebral artery （VA） and basal artery （BA） of left or right sides were detected by 2 Hz detector via occipital window. MAIN OUTCOME MEASURES： ①Blood flow velocity of systolic phase, blood flow velocity of diastole phase and vascular resistance in left and right VA and BA detected by using TCD before treatment, after treatment for one course; ②content of serum NO indirectly measured by using nitric acid disoxidation technique. RESULTS： All 130 VBI patients were involved in the final analysis. ①Changes of hemodynamic indexes： Systolic phase of VA and diastole phase of BA were higher in low-dose treatment group than that in the control group after first treatment, and there was significant difference （P 〈 0.05）; meanwhile, systolic phase and diastole phase of VA and systolic phase of BA were also higher in treatment group than that in the control group after one course （P 〈 0.05）. However, both systolic phase and diastole phase of VA and BA were lower in high-dose treatment group than that in the control group after first treatment and one course, and there was significant difference （P 〈 0.05）. ②Content of serum NO： After first treatment, there was no significant difference between low-dose treatment group and high-dose treatment group （P 〉 0.05）; but both groups were higher than control group, and there was significant difference （P 〈 0.05, 0.01）. CONCLUSION： NO vector of ultrasonic atomizing inhalation can improve VBI so as to improve cerebral blood-supply state.

The influence of amino acids on aztreonam spray-dried powders for inhalation

The dry powder inhalation of antibiotics for the treatment of lung infections has attracted drastically increasing attention as it offers rapid local therapy at lower doses and minimal side effects.In this study,aztreonam(AZT)was used as the model antibiotic and spraydried to prepare powders for inhalation.Amino acids of glycine(GLY),histidine(HIS)and leucine(LEU)were used as excipients to modify the spray-dried particles.It was demonstrated that the GLY-AZT spray-dried powders formed huge agglomerates with the size of 144.51μm,which made it very difficult to be delivered to the lungs(FPF:0.29%w/w only).In comparison with the AZT spray-dried powders,HIS-modified spray-dried powders showed increased compressibility,indicating larger distance and less cohesion between particles;while the LEU-modified spray-dried particles showed a hollow structure with significantly decreased densities.The fine particle fraction for HIS-and LEU-modified powders was 51.4%w/w and 61.7%w/w,respectively,and both were significantly increased(one-way ANOVA,Duncan’s test,P<0.05)compared to that of AZT spray-dried powders(45.4%w/w),showing a great potential to be applied in clinic.