Objective To prepare naloxone hydrochloride nasal spray and evaluate the ciliotoxicity and pharmacokinetics of the formulation. Methods The stability of naloxone hydrochloride was studied in pH3.5-5.5. Penetration promoting effects of absorp-tion enhancers on the naloxone hydrochloride were evaluated. Nasal ciliotoxicity studies were carried out using isolated toad palate. Rats were treated with naloxone hydrochloride solution by intramuscular injection of nasal drops to evaluate the pharmacokinetics. Results Naloxone hydrochloride solution was stable in pH3.5-5.5. Disodium ethylenediaminetetraacetic acid(0.2%,W/V)had the best penetration promoting effect on naloxone hydrochloride. Naloxone hydrochloride nasal spray did not exhibit obvious nasal ciliotox-icity compared to the negative control. The nasal spray had a faster therapeutic effect and its bioavailability was similar to that of the in-tramuscular injection. Conclusion Naloxone hydrochloride nasal spray prepared in this research is stable with no obvious nasal cilio-toxicity,has faster therapeutic effect,and good bioavailability,so may have a broad application prospect.

Objective To establish male rat models for fertility following liver transplantation. Methods Male Sprague-Dawley (SD) rats were used as the donors and recipients of liver transplantation. The donor liver was transplanted with two-cuff technique. Liver transplantation was performed in 15 male SD rats. At 3 weeks after liver transplantation, 5 rats were randomly sacrificed for detection of sperm deformity rate. The remaining male rats were mixed bred and mated with healthy female SD rats at a ratio of 1︰2. General conditions of the rats undergoing liver transplantation were recorded. Liver function parameters were detected after liver transplantation. Postoperative sperm deformity rate was observed. The pregnant status of female rats and health situation of their offsprings was monitored. Results All 15 rats (100%) underwent liver transplantation successfully. Nine rats (9/10) survived longer than 8 weeks. Liver function parameters were normal in male rats following liver transplantation. The sperm deformity rate was ranged from 0.5% to 1.3%. Ten male rats undergoing liver transplantation were mixed bred with female rats at a ratio of 1︰2 for 1 week. All female rats were successfully mated and delivered their offsprings after 3 weeks. The offsprings had no evident physiological deformity. Conclusions Male rat models for fertility are successfully established after liver transplantation, which serve as an animal model to evaluate the fertility performance in male patients undergoing liver transplantation.

Objective:To explore the effect of double-eyelid blepharoplasty by continuously double W-shape buried suture method through skin and conjunctiva.Methods:The data of patients received double-eyelid blepharoplasty by continuously double W-shape buried suture method through skin and conjunctiva in Department of Medical Aesthetic Surgery, People’s Hospital of Rizhao, and Department of Plastic Surgery, Yimeitiancheng’s Cosmetic and Plastic Hospital of Rizhao from January 2021 to June 2022 were retrospectively analyzed. Before the operation, the double eyelid line was designed and 5 points were evenly marked along the line as A, B, C, D and E (from the lateral to the internal). During the operation, 10 ml needle was used to puncture the 5 points marked on the double eyelid line. Starting from the outermost point A, the needle was inserted obliquely inward on the skin surface, and then the upper eyelid was turned over, and the stitches was stabed-out from the conjunctival surface of the upper margin of tarsus. The stitches was inserted again from the original point pierced on the conjunctival surface, and the stitches was stabed-out diagonally inward through the skin surface at the point B. The same method was used to penetrate points C, D and E successively. Then E, D, C, B and A points were penetrated in turn from the inside to the outside. The two suture ends were passed through the 3/8 arc round stitches, which was inserted from the point A and stabed-out skin surface of the outer orbital margin above the double eyelid line through the deep. The tightness was adjusted and tied the knotted. After the surgery, the surgical results and complications were observed, and patients’ satisfaction was evaluated before and 6 months after the surgery, which included four factors: eyelid curvature, width, smoothness, and symmetry, with a maximum score of 100. Higher scores indicated greater patients’ satisfaction. Measurement data were expressed as Mean±SD, and paired sample t-test was used to compare the satisfaction of the same patient before and after surgery. P<0.05 indicated statistically significant difference. Results:A total of 82 patients with 160 eyes were included, including 75 females and 7 males. The age ranged from 18 to 32 years old, with a mean of 25.4 years old. 78 cases were treated with both eyes and 4 with one eye. In the early postoperative period, 8 patients had local cyanosis and slight swelling of eyelid, which was improved after routine cold compress treatment. Two cases reported a foreign body sensation in the eyeball, which improved with application of levofloxacin for 1 week. The remaining patients had good eyelid morphology with no significant swelling or foreign body sensation. A total of 60 patients were followed up for 6 months, and their eyelid morphology appeared natural and aesthetically pleasing. The eyelid crease was smooth when opened, and there were no obvious surgical scars when closed. Only one patient had a shallow eyelid crease, which was satisfactorily repaired with additional suturing. None of the patients experienced external suture exposure or subcutaneous nodules. The patient satisfaction score was (58.15±5.07) before operation and (98.68±1.69) 6 months after operation, the difference was statistically significant ( t=-70.33, P<0.001). Conclusion:Double-eyelid blepharoplasty by continuously double W-shape buried suture method through skin and conjunctiva has the advantages of minimally invasion, simple performence, direct vision operation, with natural appearance of double eyelid, and high patient satisfaction.

Objective:To explore the effect of double-eyelid blepharoplasty by continuously double W-shape buried suture method through skin and conjunctiva.Methods:The data of patients received double-eyelid blepharoplasty by continuously double W-shape buried suture method through skin and conjunctiva in Department of Medical Aesthetic Surgery, People’s Hospital of Rizhao, and Department of Plastic Surgery, Yimeitiancheng’s Cosmetic and Plastic Hospital of Rizhao from January 2021 to June 2022 were retrospectively analyzed. Before the operation, the double eyelid line was designed and 5 points were evenly marked along the line as A, B, C, D and E (from the lateral to the internal). During the operation, 10 ml needle was used to puncture the 5 points marked on the double eyelid line. Starting from the outermost point A, the needle was inserted obliquely inward on the skin surface, and then the upper eyelid was turned over, and the stitches was stabed-out from the conjunctival surface of the upper margin of tarsus. The stitches was inserted again from the original point pierced on the conjunctival surface, and the stitches was stabed-out diagonally inward through the skin surface at the point B. The same method was used to penetrate points C, D and E successively. Then E, D, C, B and A points were penetrated in turn from the inside to the outside. The two suture ends were passed through the 3/8 arc round stitches, which was inserted from the point A and stabed-out skin surface of the outer orbital margin above the double eyelid line through the deep. The tightness was adjusted and tied the knotted. After the surgery, the surgical results and complications were observed, and patients’ satisfaction was evaluated before and 6 months after the surgery, which included four factors: eyelid curvature, width, smoothness, and symmetry, with a maximum score of 100. Higher scores indicated greater patients’ satisfaction. Measurement data were expressed as Mean±SD, and paired sample t-test was used to compare the satisfaction of the same patient before and after surgery. P<0.05 indicated statistically significant difference. Results:A total of 82 patients with 160 eyes were included, including 75 females and 7 males. The age ranged from 18 to 32 years old, with a mean of 25.4 years old. 78 cases were treated with both eyes and 4 with one eye. In the early postoperative period, 8 patients had local cyanosis and slight swelling of eyelid, which was improved after routine cold compress treatment. Two cases reported a foreign body sensation in the eyeball, which improved with application of levofloxacin for 1 week. The remaining patients had good eyelid morphology with no significant swelling or foreign body sensation. A total of 60 patients were followed up for 6 months, and their eyelid morphology appeared natural and aesthetically pleasing. The eyelid crease was smooth when opened, and there were no obvious surgical scars when closed. Only one patient had a shallow eyelid crease, which was satisfactorily repaired with additional suturing. None of the patients experienced external suture exposure or subcutaneous nodules. The patient satisfaction score was (58.15±5.07) before operation and (98.68±1.69) 6 months after operation, the difference was statistically significant ( t=-70.33, P<0.001). Conclusion:Double-eyelid blepharoplasty by continuously double W-shape buried suture method through skin and conjunctiva has the advantages of minimally invasion, simple performence, direct vision operation, with natural appearance of double eyelid, and high patient satisfaction.

ObjectiveTo explore the construction of mouse model of liver implanted tumor after hepatectomy by implantation of liver tumor tissue.MethodsH22 hepatocellular carcinoma (HCC) cells of mice were implanted to the scapula of 2 BALB/c (nu/nu) nude mice and tumors developed in 2 weeks. Eighteen nude mice were divided into three groups according to random number table method: non-hepatectomy group (group A), 30% hepatectomy group (group B) and 70% hepatectomy group (group C) with 6 mice in each group. The hepatectomy model of nude mice was established. The left lateral lobe and middle lobe were dissected for the nude mice in group A. The tissues of left lateral lobe were ligated and resected in group B. And the tissues of left lateralobe and middle lobe were ligated and resected in group C. The tumor tissues incised from the scapula were implanted to the livers of nude mice in three groups. The tumor formation rate and the volume of implanted tumors of three groups were compared. The tumor formation rate was compared using Fisher's exact probability test, and the volume of implanted tumors was compared using Kruskal-Wallis test and Bonferroni method.ResultsThe tumor formation rate of group A, B and C after 2 weeks was respectively 6/6, 6/6 and 5/6, and no signiifcant difference was observed (P=1.000). The median volume of implanted tumors in group A, B and C was respectively 19(6-33), 22(8-44) and 150(58-186) mm3. The median volume of implanted tumors in group C was signiifcantly larger than those in group A and B (Z=9.03, 7.12;P<0.0167). The implanted tumors in three groups were all conifrmed as HCC and with different degrees of necrosis and inlfammatory cell inifltration by histopathological examination.ConclusionsImplantation of liver tumor tissue can be used to construct an ideal mouse model of liver implanted tumor after major hepatectomy with the advantages of short experimental period, high tumor formation rate and good stability.

This study aims to prepare altrenogest extended-release tablets,evaluate their quality and establish a content determination method.The hydrophilic gel skeleton type,dosage and core thick-ness of altrenogest extended-release tablets were used as the investigating factors,and the release degree of the tablets was used as the investigating index,the prescription process of altrenogest ex-tended-release tablets was optimized by one-factor screening and central combinatorial design re-sponse surface method,and quality evaluation was carried out,the in vitro release model was es-tablished,and a high-performance liquid chromatography(HPLC)assay method was set up for the determination of altrenogest extended-release tablets.The results showed that the optimal pre-scription of altrenogest extended-release tablets was 2％as the main drug,70％as the solubilizer,0.5％as the lubricant,19.1％as the filler,8.4％as the hydrophilic gel skeleton material,and the thickness of the tablets was 3.8 mm.The in vitro drug release conformed to the Higuchi model,and the altrenogest showed a good linear relationship with the R2=0.999 98 in the range of 10-80 mg/L.The optimized process for the extended-release tablets was stable and had a good quality.The extended-release tablets were stable and had significant slow-release effect.The HPLC method is accurate and reliable and can be used for the determination of altrenogest in extended-release tablets.

Albendazole sulfoxide and ivermectin compound pouring agent were prepared with dime-thyl sulfoxide and 1,2-propanediol as solvents.The central composite design response surface method was used to optimize the formula of pouring agent.Franz diffusion cell method was used to investigate the transdermal performance of pouring agent in vitro.The permeation amounts of the two drugs were determined by HPLC.The best formula of pouring agent was ivermectin 0.5％,al-bendazole sulfoxide 5％,dimethyl sulfoxide 52％,propylene glycol 39％,and the rest was 100％anhydrous ethanol.The cumulative permeation amounts of ivermectin and albendazole sulfoxide were up to 20.78 μg/cm2 and 249.02 μg/cm2,respectively.The in vitro release model of the two drugs accords with the first-order kinetic equation.There is a good linear relationship between al-bendazole sulfoxide and ivermectin in the range of 1-100 mg/L and the peak area.The precision and stability RSD of the two methods are less than 2％.The preparation process of albendazole sul-foxide compound pouring agent is simple,stable and easy to pour.The established HPLC method is simple and accurate,and can be used for the determination of albendazole sulfoxide and ivermectin in pouring agent.