Background Nanoemulsions (NEs) is one of the most popular ophthalmic colloidal drug delivery system due to its long-term stability, low toxicity and irritancy, considerable capacity for solubilization of lipophilic drug molecules and great potential in bioavailability improvement.The cornea pathway is the main route of intraocular absorption after topical use of NEs.Though NEs possess numerous physiological and physicochemical advantages,the use of NEs cannot always obtain satisfactory results.Objective This study was to investigate the impacts of epithelium and stroma on the corneal permeation of topical ophthalmic terbinafine hydrochloride nanoemulsions (TH-NEs).Methods TH-NEs was prepared by the self-emulsification method.The size and Zeta potential of the oil droplets in the formulation were analyzed using a dynamic light-scattering particle size analyzer.The high performance liquid chromatography (HPLC) was used for the in vitro release study.Sixty New Zealand albino rabbits were randomly divided into intact cornea group and cornea epithelium debrided group.The cornea epithelium of the left eyes was debrided in the cornea epithelium debrided group.The TH-NEs were instilled into the lower conjunctival sac of left eyes.Six rabbits were executed from each group 15,30,60,120 and 240 minutes after dosing,respectively.The corneas were collected and analyzed by HPLC.The fluorescein diacetate (FDA) was used to label the TH-NEs.Two C57BL/6 mice with left cornea epithelium debrided and 2 normal mice were used for the fluorescence tracing study.The fluorescence distribution of FDA labeled TH-NEs was observed by a two-photon laser confocal scanning microscope 30 minutes and 60 minutes after single instillation.Results The average size and Zeta potential of the oil droplets were 51.37 nm and-0.232 7 mV respectively,and 0.482％ of encapsulated drugs was released from the TH-NEs after 12 hours.The peak concentrations of TH in the intact cornea and epithelium debrided cornea were (17.85 ± 2.79) μg/g and (4.40± 1.75) μg/g respectively, which occurred 15 minutes postdose.The drug concentrations in the intact cornea were significantly higher than that in the debrided cornea 15,30,60 and 120 minutes after dosing, with significant differences between them (t =9.998,8.658,6.903,7.576;all at P=0.000).The fluorescence was observed in the cornea epithelium when the cornea was intact.The fluorescence intensity in the superior layer of corneal epithelium was obviously higher than that in the deep layers of corneal epithelium 30 minutes and 60 minutes after dosing.No fluorescence was observed in the cornea stroma of both eyes.Conclusions The cornea epithelium is the main of absorption and distribution position of TH-NEs.The cornea stroma is the dominating permeation barrier for the intraocular transportation of the TH-NEs.The cornea stroma may stop the permeation of TH-NEs by molecular exclusion mechanism.

Background Macrogol 15 hydroxystearate (HS15) is a novel soft non-ionic surfactant and is widely used to solubilize the poorly soluble drugs due to high drug loading and enhancing permeability ability to hydrophobic drug.However,the delivering effects to cornea of HS15 on terbinafine hydrochloride (TH),a insoluble antifungal agents,is unclear.Objective This study was to investigate the promoting corneal absorption effects of HS15 micelles (HNMs) on TH.Methods TH-HNMs was prepared by a co-solvent method.The hydrodynamic droplet size,polydispersity index,and Zeta potential of TH-HNMs were measured by using a Zetasizer.The shape of the micelles was observed under the transmission electron microscope.The high performance liquid chromatography (HPLC) was employed to detect the in vitro cumulative releasing level of TH in the TH-HNMs and drug entrapment efficiency.TH-HNMs was topically adninistered in eyes of 5 healthy male New Zealand rabbits to evaluate the ocular irritation response.Ninety rabbits were randomized into experimental group and control group,and 50 μl of 0.5％ TH-HNMs and 0.5％ oily TH were topically administered in the right eyes of the animals in the experimental group and contral group,respectively.The animals were sacrificed 5,15,30,60,90,120,180,240,360 minutes after eye dropping by over anesthetization way and the corneas were harvested,and the TH content in the cornea was detected using HPLC.The study protocal was approved by Life Science Ethic Committee of Henen Eye Hospital.Results The average size and polyolis persital index of TH-HNMs were 13.32 nm and 0.046,respectively,and its average Zeta potential was-0.133 mV.The drug entrapment efficiency was 100％.The release level of TH from the micelles presented a pH-dependent manner.The release level of TH was (95.20±3.20)％ in the phosphate buffer with pH 5.0 and (0.17± 0.01)％ in the phosphate buffer with pH 7.4.The ocular irritation score was 2,and no visible damage was found around experimental eyes after instillation of TH-HNMs.The peak content of TH in the rabbit cornea 5 minutes was (20.26±2.26)pg/g in the experimental group,which was significantly higher than (1.40± 0.44)μg/g in the control group (t =18.926,P=0.000).The area under the curve (AUC)0.360min of drug concentration-time curve in the experimental group was 1 292.25 μg/(g · min),which was 15.6 times more than the control group.Conclusions TH-HNMs is an ideal agent with a simple preparing process,high drug entrapment efficiency,small size and low ocular irritation.Compared with oily TH,TH-HNMs can effectively enhance the corneal absorption of TH.

Objective To investigate the corneal permeability of cyclosprin A (CsA) loaded on polymeric vector after topical application.Methods The grafted copolymer chitosan-graft-cyclodextrin (CS-g-CD) was synthesized,and the physicochemical structures of the polymer were investigated using nuclear magnetic resonance spectroscopy (NMR) and fourier transform infrared spectroscopy (FT-IR).A novel CsA eye drop was prepared using the grafted copolymer as carrier material.The physicochemical properties of eye drop,including drug-loading content,osmotic pressure and viscosity were investigated by high performance liquid chromatography-mass spectrometry (HPLC-MS),osmotic pressure gauge and viscometer,respectively.New Zealand albino rabbits were randomly divided into intact cornea CsA group,epithelium debrided CsA group and epithelium debrided control group.The corneal epithelia of the left eyes was debrided in the cornea epithelium debrided group.Cornea irritation test was performed on New Zealand albino rabbits.The aqueous humor was taken and the corneas were collected at 0.5 hour and 1 hour after instilled.The concentration of CsA was measured by HPLC-MS.Cy5 labeled vector loaded with Coumarin 6 served as model copolymers system,the penetration capabilities of the double fluorescent labeling copolymers system were monitored in vivo using two-photon scanning fluorescence microscopy on murine corneas after topical application.The use and care of the animals complied with Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.Results The polymer of CS-g-CD was successfully synthesized and confirmed using NMR and FT-IR.The drug loading of CsA in eye drop solution was 0.06 ％;the osmotic pressure was 305 mOsmol/kg and the viscosity was 36.5 cP.The CsA drug delivery system had a reversible temperature-sensitive drug release behavior and had no obvious irritation on the eyes of New Zealand rabbits.One hour after treatment,the concentration of CsA in the cornea and aqueous humor of epithelium debrided CsA group was (5.88 ± 1.46) μg/g and (149.19 ± 3.93) ng/ml,respectively,which was significantly higher than (3.98 ±0.95) μg/g and (30.25± 11.43) ng/ml in epithelium debrided control group (both at P＜0.05);the concentration of CsA in the aqueous humor of intact cornea CsA group was (7.23 ± 1.31)ng/ml,which was significantly lower than that in epithelium debrided CsA group (P＜0.05).Polymer vectors were mainly retained in the corneal epithelium,and coumarin 6 gradually diffused into the deep corneal stroma with time.Conclusions The grafted copolymer can load CsA,and the eye drop can effectively overcome the corneal barrier and increase the corneal permeability of CsA.

Objective To investigate the corneal permeability of cyclosprin A (CsA) loaded on polymeric vector after topical application. Methods The grafted copolymer chitosan.graft.cyclodextrin ( CS.g.CD ) was synthesized, and the physicochemical structures of the polymer were investigated using nuclear magnetic resonance spectroscopy ( NMR) and fourier transform infrared spectroscopy ( FT.IR) . A novel CsA eye drop was prepared using the grafted copolymer as carrier material. The physicochemical properties of eye drop,including drug.loading content, osmotic pressure and viscosity were investigated by high performance liquid chromatography.mass spectrometry ( HPLC.MS) ,osmotic pressure gauge and viscometer,respectively. New Zealand albino rabbits were randomly divided into intact cornea CsA group, epithelium debrided CsA group and epithelium debrided control group. The corneal epithelia of the left eyes was debrided in the cornea epithelium debrided group. Cornea irritation test was performed on New Zealand albino rabbits. The aqueous humor was taken and the corneas were collected at 0. 5 hour and 1 hour after instilled. The concentration of CsA was measured by HPLC.MS. Cy5 labeled vector loaded with Coumarin 6 served as model copolymers system, the penetration capabilities of the double fluorescent labeling copolymers system were monitored in vivo using two.photon scanning fluorescence microscopy on murine corneas after topical application. The use and care of the animals complied with Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission. Results The polymer of CS.g.CD was successfully synthesized and confirmed using NMR and FT.IR. The drug loading of CsA in eye drop solution was 0. 06 ％;the osmotic pressure was 305 mOsmol/kg and the viscosity was 36. 5 cP. The CsA drug delivery system had a reversible temperature.sensitive drug release behavior and had no obvious irritation on the eyes of New Zealand rabbits. One hour after treatment,the concentration of CsA in the cornea and aqueous humor of epithelium debrided CsA group was (5. 88±1. 46)μg/g and (149. 19±3. 93)ng/ml,respectively,which was significantly higher than (3. 98±0. 95)μg/g and (30. 25±11. 43)ng/ml in epithelium debrided control group (both at P<0. 05);the concentration of CsA in the aqueous humor of intact cornea CsA group was ( 7. 23 ± 1. 31 ) ng/ml, which was significantly lower than that in epithelium debrided CsA group ( P<0. 05 ) . Polymer vectors were mainly retained in the corneal epithelium, and coumarin 6 gradually diffused into the deep corneal stroma with time. Conclusions The grafted copolymer can load CsA,and the eye drop can effectively overcome the corneal barrier and increase the corneal permeability of CsA.

BACKGROUND: Chronic cough after pulmonary resection is one of the most common complications, which seriously affects the quality of life of patients after surgery. Therefore, the aim of this study is to explore the risk factors of chronic cough after pulmonary resection and construct a prediction model. METHODS: The clinical data and postoperative cough of 499 patients who underwent pneumonectomy or pulmonary resection in The First Affiliated Hospital of University of Science and Technology of China from January 2021 to June 2023 were retrospectively analyzed. The patients were randomly divided into training set (n=348) and validation set (n=151) according to the principle of 7:3 randomization. According to whether the patients in the training set had chronic cough after surgery, they were divided into cough group and non-cough group. The Mandarin Chinese version of Leicester cough questionnare (LCQ-MC) was used to assess the severity of cough and its impact on patients' quality of life before and after surgery. The visual analog scale (VAS) and the self-designed numerical rating scale (NRS) were used to evaluate the postoperative chronic cough. Univariate and multivariate Logistic regression analysis were used to analyze the independent risk factors and construct a model. Receiver operator characteristic (ROC) curve was used to evaluate the discrimination of the model, and calibration curve was used to evaluate the consistency of the model. The clinical application value of the model was evaluated by decision curve analysis (DCA). RESULTS: Multivariate Logistic analysis screened out that preoperative forced expiratory volume in the first second/forced vital capacity (FEV1/FVC), surgical procedure, upper mediastinal lymph node dissection, subcarinal lymph node dissection, and postoperative closed thoracic drainage time were independent risk factors for postoperative chronic cough. Based on the results of multivariate analysis, a Nomogram prediction model was constructed. The area under the ROC curve was 0.954 (95%CI: 0.930-0.978), and the cut-off value corresponding to the maximum Youden index was 0.171, with a sensitivity of 94.7% and a specificity of 86.6%. With a Bootstrap sample of 1000 times, the predicted risk of chronic cough after pulmonary resection by the calibration curve was highly consistent with the actual risk. DCA showed that when the preprobability of the prediction model probability was between 0.1 and 0.9, patients showed a positive net benefit. CONCLUSIONS Chronic cough after pulmonary resection seriously affects the quality of life of patients. The visual presentation form of the Nomogram is helpful to accurately predict chronic cough after pulmonary resection and provide support for clinical decision-making.
Humans ; Chronic Cough ; Cough/etiology* ; Lung Neoplasms ; Pneumonectomy/adverse effects* ; Quality of Life ; Retrospective Studies

Hypertension is the primary disease that endangers human health. A convenient and accurate blood pressure measurement method can help to prevent the hypertension. This paper proposed a continuous blood pressure measurement method based on facial video signal. Firstly, color distortion filtering and independent component analysis were used to extract the video pulse wave of the region of interest in the facial video signal, and the multi-dimensional feature extraction of the pulse wave was preformed based on the time-frequency domain and physiological principles; Secondly, an integrated feature selection method was designed to extract the universal optimal feature subset; After that, we compared the single person blood pressure measurement models established by Elman neural network based on particle swarm optimization, support vector machine (SVM) and deep belief network; Finally, we used SVM algorithm to build a general blood pressure prediction model, which was compared and evaluated with the real blood pressure value. The experimental results showed that the blood pressure measurement results based on facial video were in good agreement with the standard blood pressure values. Comparing the estimated blood pressure from the video with standard blood pressure value, the mean absolute error (MAE) of systolic blood pressure was 4.9 mm Hg with a standard deviation (STD) of 5.9 mm Hg, and the MAE of diastolic blood pressure was 4.6 mm Hg with a STD of 5.0 mm Hg, which met the AAMI standards. The non-contact blood pressure measurement method based on video stream proposed in this paper can be used for blood pressure measurement.
Humans ; Blood Pressure/physiology* ; Blood Pressure Determination/methods* ; Algorithms ; Hypertension/diagnosis* ; Sexually Transmitted Diseases