Objective:To discuss the medication, prescription law and academic thoughts of doctors in the Ming and Qing Dynasties for the treatment of abdominal tympanites based on the Yi An Lei Ju. Methods:The medical records of doctors in the Ming and Qing Dynasties for the treatment of tympanites contained in Yi An Lei Ju were retrieved, and the prescription information was extracted. Based on R4.2.1 and the TCM inheritance calculation platform V3.0, the frequency, property and taste, and meridian tropism, and efficacy categories of drugs were counted, and association rules analysis and clustering analysis were performed. Results:A total of 214 prescriptions were included, involving 239 kinds of Chinese materia medica, with a total frequency of 2 080 times. The high-frequency drugs (frequency≥30) were Poria, Citri Reticulatae Pericarpium, Alismatis Rhizoma, Atractylodis Macrocephalae Rhizoma, Aconiti Lateralis Radix Praeparata, etc. The medicinal properties of the drugs were mainly warm, neutral and cold. The flavors were mainly pungent, sweet and bitter. The meridians were mainly spleen, liver and kidney meridians. The efficacy categories were mainly tonic drugs, diuresis and dampness drugs, and qi-regulating drugs. Association rule analysis found that the most frequently used drug pair was Poria-Citri Reticulatae Pericarpium. Clustering analysis showed that drugs (frequency≥20) could be divided into 4 clusters.Conclusions:Doctors in the Ming and Qing Dynasties treated abdominal tympanites with the basic treatment methods of invigorating the spleen and promoting diuresis, soothing the liver and regulating qi, warming the kidney and resolving fluid retention. The medication took into account the ascending and descending of qi, the combination of attack and supplement, the combination of cold and heat, and the harmony of qi and blood.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Objective:To investigate the clinical characteristics of choledocholithiasis com-bined with periampullary diverticulum and influencing factor for difficult cannulation of endoscopic retrograde cholangiopancreatography (ERCP).Methods:The retrospective case-control study was conducted. The clinical data of 1 920 patients who underwent ERCP for choledocholithiasis in 15 medical centers, including the First Hospital of Lanzhou University, et al, from July 2015 to December 2017 were collected. There were 915 males and 1 005 females, aged (63±16)years. Of 1 920 patients, there were 228 cases with periampullary diverticulum and 1 692 cases without periampullary diverticulum. Observation indicators: (1) clinical characteristics of patients with choledocholithiasis; (2) intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis; (3) influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and com-parison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Logistic regression model was used for univariate and multivariate analyses. Results:(1) Clinical characteristics of patients with choledocholithiasis. Age, body mass index, cases with complications as chronic obstructive pulmonary disease, diameter of common bile duct, cases with diameter of common bile duct as <8 mm, 8?12 mm, >12 mm, diameter of stone, cases with number of stones as single and multiple were (69±12)years, (23.3±3.0)kg/m 2, 16, (14±4)mm, 11, 95, 122, (12±4)mm, 89, 139 in patients with choledocholithiasis combined with periampullary diverticulum, versus (62±16)years, (23.8±2.8)kg/m 2, 67, (12±4)mm, 159, 892, 641, (10±4)mm, 817, 875 in patients with choledocholithiasis not combined with periampullary diver-ticulum, showing significant differences in the above indicators between the two groups ( t=?7.55, 2.45, χ2=4.54, t=?4.92, Z=4.66, t=?7.31, χ2=6.90, P<0.05). (2) Intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis. The balloon expansion diameter, cases with intraoperative bleeding, cases with hemorrhage management of submucosal injection, hemostatic clip, spray hemostasis, electrocoagulation hemostasis and other treatment, cases with endoscopic plastic stent placement, cases with endoscopic nasal bile duct drainage, cases with mechanical lithotripsy, cases with stone complete clearing, cases with difficult cannulation, cases with delayed intubation, cases undergoing >5 times of cannulation attempts, cannulation time, X-ray exposure time, operation time were 10.0(range, 8.5?12.0)mm, 56, 6, 5, 43, 1, 1, 52, 177, 67, 201, 74, 38, 74, (7.4±3.1)minutes, (6±3)minutes, (46±19)minutes in patients with choledocholithiasis combined with periampullary diverticulum, versus 9.0(range, 8.0?11.0)mm, 243, 35, 14, 109, 73, 12, 230, 1 457, 167, 1 565, 395, 171, 395, (6.6±2.9)minutes, (6±5)minutes, (41±17)minutes in patients with choledocholithiasis not combined with periampullary diverticulum, showing significant differences in the above indicators between the two groups ( Z=6.31, χ2=15.90, 26.02, 13.61, 11.40, 71.51, 5.12, 9.04, 8.92, 9.04, t=?3.89, 2.67, ?3.61, P<0.05). (3) Influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Results of multivariate analysis showed total bilirubin >30 umol/L, number of stones >1, combined with periampullary diverticulum were indepen-dent risk factors for difficult cannulation in patients with periampullary diverticulum who underwent ERCP for choledocholithiasis ( odds ratio=1.31, 1.48, 1.44, 95% confidence interval as 1.06?1.61, 1.20?1.84, 1.06?1.95, P<0.05). Results of further analysis showed that, of 1 920 patients undergoing ERCP for choledocholithiasis, the incidence of postoperative pancreatitis was 17.271%(81/469) and 8.132%(118/1 451) in the 469 cases with difficult cannulation and 1 451 cases without difficult cannula-tion, respectively, showing a significant difference between them ( χ2=31.86, P<0.05). In the 1 692 patients with choledocholithiasis not combined with periampullary diverticulum, the incidence of postopera-tive pancreatitis was 17.722%(70/395) and 8.250%(107/1 297) in 395 cases with difficult cannula-tion and 1 297 cases without difficult cannulation, respectively, showing a significant difference between them ( χ2=29.00, P<0.05). In the 228 patients with choledocholithiasis combined with peri-ampullary diverticulum, the incidence of postoperative pancreatitis was 14.865%(11/74) and 7.143%(11/154) in 74 cases with difficult cannulation and 154 cases without difficult cannulation, respectively, showing no significant difference between them ( χ2=3.42, P>0.05). Conclusions:Compared with patients with choledocholithiasis not combined with periampullary divertioulum, periampullary divertioulum often occurs in choledocholithiasis patients of elderly and low body mass index. The proportion of chronic obstructive pulmonary disease is high in choledocholithiasis patients with periampullary diverticulum, and the diameter of stone is large, the number of stone is more in these patients. Combined with periampullary diverticulum will increase the difficult of cannulation and the ratio of patient with mechanical lithotripsy, and reduce the ratio of patient with stone complete clearing without increasing postoperative complications of choledocholithiasis patients undergoing ERCP. Total bilirubin >30 μmol/L, number of stones >1, combined with periampullary diverticulum are independent risk factors for difficult cannulation in patients of periampullary diverticulum who underwent ERCP for choledocholithiasis.

Objective : To investigate the effects of gestational diabetes mellitus (GDM) on birth outcome and umbilical artery (UA) blood flow parameters in the third trimester, and to analyze the role of UA blood flow parameters in GDM and birth outcome. Methods : Based on the birth cohort from Wuhu , Anhui , China , 189 pregnant women with GDM were collected as the case group. The non⁃GDM pregnant women were matched 1 ∶ 1 according to age and pre⁃pregnancy body mass index , and 189 normal pregnant women were selected as the control group. Pregnant women with GDM were divided into poorly controlled group and well controlled group according to fasting blood glucose in the third trimester. The UA blood flow parameters and fetal birth outcomes in the third trimester were tracked. Results : Compared with the control group , UA parameters in poorly controlled and well controlled groups significantly increased (F = 6. 63 , P < 0. 05 ; F = 4. 43 , P < 0. 05 ; F = 5. 57 , P < 0. 05) . Poor glycemic control of GDM was associated with increased birth weight and risk of larger than gestational age. The multi⁃factor linear regression model showed that the Z score of the peak systolic velocity/end diastolic velocity (S/D) in the poorly controlled group was negatively correlated with birth weight (β = - 209. 78 , 95% CI: - 301. 48 - 118. 07) . S/D index Z score mediated the relationship between poor blood glucose control and birth weight. The intermediate effect value was - 58. 41 (95% CI: - 106. 40 ~ - 19. 65) , accounting for 25. 98% of the total effect. Conclusion Poor glycemic control in GDM is a risk factor for fetal weight gain , and UA function plays a partial mediating role in influencing neonatal birth weight. GDM pregnant women should strictly control blood glucose level to better protect maternal and infant health.

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.

To establish an injectable hydrogel containing Prussian blue (PB) nanospheres for photothermal therapy against cancer, PB nanospheres were prepared by one-pot synthesis and the thermosensitive Pluronic F127 was used as the hydrogel matrix. The PB nanospheres and the hydrogel were characterized by shape, particle size, serum stability, photothermal performance upon repeated 808 nm laser irradiation, as well as the rheological features. The effect of the PB nanospheres and the hydrogel were evaluated qualitatively and quantitatively in 4T1 mouse breast cancer cells. The retention, photothermal efficacy, therapeutic effects and systemic toxicity of the hydrogel were assessed in a tumor-bearing mouse model. The PB nanospheres had a diameter of about 150 nm and exhibited satisfactory serum stability, photo-heat convert ability and repeated laser exposure stability. The hydrogel encapsulation did not negatively influence the above features of the photothermal agent. The nanosphere-containing hydrogel showed a phase transition at body temperature and, as a result, a long retention time . The photothermal agent-embedded hydrogel displayed promising photothermal therapeutic effects in the tumor-bearing mouse model with little-to-no systemic toxicity after peritumoral administration.

Objective To compare the effects of bone transport versus induced membrane technique for large segmental tibial defects.Methods The clinical data were analyzed retrospectively of 89 patients with large segmental tibial defect who had been treated at Department of Orthopaedics,Wuxi No.9 People's Hospital from June 2005 to February 2017 using bone transport or induced membrane technique.They were 58males and 31 females,aged from 13 to 74 years (average,38.0 years).The bone transport group had 59cases and the induced membrane technique group 30 cases.The 2 groups were compared in terms of preoperative general data and postoperative bone nonunion,bone healing time,complications and functional recovery of the adjacent joint.Results There were no statistically significant differences between the 2groups in terms of age,gender,cause or type of defects,associated injury,course of disease,functionary scores of the adjacent joint or number of operations,showing compatibility between the 2 groups (P ＞ 0.05).All the patients were followed up for 12 to 48 months (average,20 months).The bone transport group had significandy longer clinical healing time (14.7 ± 5.4 months) and significantly higher incidences of major complications (50.8％),minor complications (57.6％) and overall complications (83.1％) than the induced membrane technique group (11.2 ± 2.8 months,16.7％,26.7％ and 30.0％,respectively) (P ＜ O.05),but significantly lower functionary scores of the adjacent joint (86.4 ± 5.0 points) than the induced membrane technique group (88.8 ± 4.9 points) (P ＜ 0.05).Conclusions Both bone transport and induced membrane technique are effective repairs for large segmental tibial defects.However,induced membrane technique may be superior to bone transport in terms of bone healing,complications and functional recovery.

Objective: To summarize the measures and experience of treatment in mass extremely severe burn patients. Methods: The clinical data and treatment of 8 extremely severe burn patients in August 2 Kunshan factory aluminum dust explosion accident who were admitted in the 100th Hospital of PLA on August 2nd, 2014, were retrospectively analyzed. There were 4 males and 4 females, aging 22-45 (34±7) years, with total burn area of 55%-98% [(89±15)%] total body surface area (TBSA) and full-thickness burn area of 45%-97% [(80±21)%] TBSA. All the 8 patients were accompanied with severe shock, inhalation injury, and blast injury. According to the requirements of former PLA General Logistics Department and Nanjing Military Command, a treatment team was set up including a special medical unit and a special care unit, with Chai Jiake from the First Affiliated Hospital of PLA General Hospital as the team leader, Zheng Qingyi from the 175th Hospital of PLA (the Affiliated Dongnan Hospital of Xiamen University) as the deputy leader, the 100th Hospital of PLA as the treatment base, and burn care, respiratory, nephrology, nursing specialists from the First Affiliated Hospital of PLA General Hospital, and the burn care experts and nursing staff from the 180th Hospital of PLA, 118th Hospital of PLA, 98th Hospital of PLA, and 175th Hospital of PLA, and nurses from the 85th Hospital of PLA, 455th Hospital of PLA, 101th Hospital of PLA, 113th Hospital of PLA as team members. Treatment strategies were adopted as unified coordination by the superior, unified responsibility of team leader, division of labor and cooperation between team members, and multidisciplinary cooperation led by department of burns. With exception of one patient who received deep vein catheterization before admission, the other 7 patients were treated with deep vein catheterization 0.5 to 3.0 hours after admission to correct hypovolemic shock as soon as possible. Eight patients received tracheotomy, and 7 patients were treated with mechanical ventilation by ventilator in protective ventilation strategy with low tide volume and low volume pressure to assist breathing. Fiberoptic bronchoscopy was done one to three times for all the 8 patients to confirm airway injuries and healing status. Escharectomy and Meek dermatoplasty in the extremities of all the 8 patients were performed 3 to 6 days after injury for the first time. Escharectomy, microskin grafting, and covering of large pieces of allogeneic skin on the trunks of 4 patients were performed 11 to 16 days after injury for the second time. The broad-spectrum antibiotics were uniformly used at first time of anti-infective therapy, and then the antibiotics species were adjusted in time. The balance of internal environment was maintained and the visceral functions were protected. One special care unit was on responsibility of only one patient. Psychological intervention was performed on admission. The rehabilitative treatment was started at early stage and in company with the whole treatment. Results: Acute renal injury occurred in 5 patients within 36 hours after injury and their renal function was restored to normal 4 days after injury due to active adjustment of fluid resuscitation program. No pulmonary complications, such as severe pulmonary infection and ventilator-associated pneumonia, occurred in the survived patients. One of the 8 patients died, and the other 7 patients were cured successfully. The wounds were basically healed in 2 patients in 26 or 27 days by 2 or 3 times of operation, and in 5 patients by 4 or 5 times of operation. The basic wound healing time was 26-64 (48±15) days for all the 7 patients. Conclusions Treatment strategies of unified coordination by the superior, unified responsibility of team leader, division of labor and cooperation between team members, and multidisciplinary cooperation led by department of burns are the bases to successful treatment. Correcting shock as soon as possible is the prerequisite and closing wound as soon as possible is the key to successful treatment. Comprehensive treatment measures, such as maintaining and regulating the function of viscera, improving the body immunity, and preventing and treating the complications, are the important components to successful treatment. It is emphasized that in the treatment of mass extremely severe burn patients, specialist burn treatment should always be in the dominant position, and other related disciplines may play a part in auxiliary function.

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 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.