ObjectiveTo investigate the effects of artemisinin （ART） on histopathological damage and salivary secretion in the submandibular gland （SMG） of mice with Sjögren's syndrome （SS） model，and on the expression of aquaporin 5 （AQP5） in SMG cells. MethodsThe NOD/Ltj mice were used as a model of SS and randomly divided into the SS model group，the ART group，and the hydroxychloroquine sulfate （HCQ） group，with six mice per group. Another 6 female BALB/c mice at the same week were selected as the control group. Mice in the ART group was fed with the ART solution daily in the dosage of 50 mg·kg^-1，and mice in the HCQ group was given with the HCQ solution （1 300 mg·kg^-1）. Mice in the SS model and control groups were given saline daily. The treatment lasted for 8 weeks. The 24-hour average water intake，salivary flow rate，SMG pathology scores of mice in each group were measured，as well as the expression levels of AQP5 protein and gene in the SMG tissues. ResultsCompared with the control group，the 24-hour average water intake of mice in the model group was significantly increased （P<0.01），and the saliva flow rate was significantly decreased （P<0.01）. Compared to the SS model group，the 24-hour average water intake of mice in the ART and HCQ groups was significantly reduced （P<0.01），and the salivary flow rate was significantly increased in the ART group（P<0.01），comparisons between groups showed that the ART was superior to the HCQ in reducing water intake and improving saliva flow rate in SS model mice （P<0.05）. The HE staining results showed that，compared with the normal group，the number of lymphocyte infiltration foci in SMG tissue in the model group increased，and the pathological score increased （P<0.01）. Compared to the SS model group，after the intervention of the ART and HCQ，the number of lymphocytic infiltration foci in the SMG tissue decreased，the area of the lymphocytic infiltration foci was reduced，and the pathology score of the SMG tissues was lowered in the ART group（P<0.01）. However，there was no difference in pathological scores between the ART and HCQ groups . The results of IHC，Western blot，and Real-time PCR showed that，compared with the normal group，the expression levels of AQP5 protein and gene in SMG tissue in the model group significantly decreased （P<0.05）. Comparing with the SS model group，the ART and HCQ groups could significantly up-regulated the expression levels of AQP5 protein and mRNA in the SMG tissue，and the treatment effect was better than that of HCQ. ConclusionART was able to ameliorate SMG structural damage and salivary secretion function in SS model mice，and its mechanism of action may be related to the up-regulation of AQP5 protein and gene expression levels in SMG cells.

Objective To explore the effects of modulating the Hippo-YAP/TAZ pathway using Huashi Runzao Prescription(HRP)on the apoptosis and salivary secretion function of submandibular gland cells in a naive non-obese diabetic(NOD/Ltj)mouse model of Sj?gren's syndrome(SS).Methods Eight-week-old female BALB/c mice were selected as the blank group.Eight-week-old female NOD/Ltj were randomly divided into the model,HRP-L,HRP-M,HRP-H,and hydroxychloroquine sulphate(HCQ)groups.After eight weeks of drug administration,the water consumption and salivary flow rate of each group were recorded.The histopathological damage of the submandibular gland in each group was determined using hematoxylin and eosin staining,the apoptosis rate of the submandibular gland was determined using TUNEL staining,and AQP5,Bax,Bcl-2,beclin-1,YAP,p-YAP,and TAZ expressions in submandibular gland tissues were determined using immunohistochemistry and Western blotting.Results Compared with the blank group,the Hippo-YAP/TAZ pathway was inhibited in the submandibular gland tissues of the model group,lymphocyte infiltration increased,water consumption increased,salivary flow rate decreased,AQP5 expression decreased,and submandibular gland cells apoptosis rate increased(P<0.05).Compared with all other administered groups,in the HRP-M group,the Hippo-YAZ/TAZ pathway was significantly activated,lymphocyte infiltration in submandibular gland tissues was reduced,water consumption was reduced,the salivary flow rate and AQP5 expression were increased,and the apoptosis rate of submandibular gland cells was reduced(P<0.05).Conclusion HRP reduced the pathological damage and apoptosis of submandibular gland cells in SS model mice.It improved the overall secretory function of submandibular gland tissues,which may be related to Hippo pathway activation and downregulating YAP/TAZ expression.

Objective To explore the effects of modulating the Hippo-YAP/TAZ pathway using Huashi Runzao Prescription(HRP)on the apoptosis and salivary secretion function of submandibular gland cells in a naive non-obese diabetic(NOD/Ltj)mouse model of Sj?gren's syndrome(SS).Methods Eight-week-old female BALB/c mice were selected as the blank group.Eight-week-old female NOD/Ltj were randomly divided into the model,HRP-L,HRP-M,HRP-H,and hydroxychloroquine sulphate(HCQ)groups.After eight weeks of drug administration,the water consumption and salivary flow rate of each group were recorded.The histopathological damage of the submandibular gland in each group was determined using hematoxylin and eosin staining,the apoptosis rate of the submandibular gland was determined using TUNEL staining,and AQP5,Bax,Bcl-2,beclin-1,YAP,p-YAP,and TAZ expressions in submandibular gland tissues were determined using immunohistochemistry and Western blotting.Results Compared with the blank group,the Hippo-YAP/TAZ pathway was inhibited in the submandibular gland tissues of the model group,lymphocyte infiltration increased,water consumption increased,salivary flow rate decreased,AQP5 expression decreased,and submandibular gland cells apoptosis rate increased(P<0.05).Compared with all other administered groups,in the HRP-M group,the Hippo-YAZ/TAZ pathway was significantly activated,lymphocyte infiltration in submandibular gland tissues was reduced,water consumption was reduced,the salivary flow rate and AQP5 expression were increased,and the apoptosis rate of submandibular gland cells was reduced(P<0.05).Conclusion HRP reduced the pathological damage and apoptosis of submandibular gland cells in SS model mice.It improved the overall secretory function of submandibular gland tissues,which may be related to Hippo pathway activation and downregulating YAP/TAZ expression.

Objective To explore the effects of modulating the Hippo-YAP/TAZ pathway using Huashi Runzao Prescription(HRP)on the apoptosis and salivary secretion function of submandibular gland cells in a naive non-obese diabetic(NOD/Ltj)mouse model of Sj?gren's syndrome(SS).Methods Eight-week-old female BALB/c mice were selected as the blank group.Eight-week-old female NOD/Ltj were randomly divided into the model,HRP-L,HRP-M,HRP-H,and hydroxychloroquine sulphate(HCQ)groups.After eight weeks of drug administration,the water consumption and salivary flow rate of each group were recorded.The histopathological damage of the submandibular gland in each group was determined using hematoxylin and eosin staining,the apoptosis rate of the submandibular gland was determined using TUNEL staining,and AQP5,Bax,Bcl-2,beclin-1,YAP,p-YAP,and TAZ expressions in submandibular gland tissues were determined using immunohistochemistry and Western blotting.Results Compared with the blank group,the Hippo-YAP/TAZ pathway was inhibited in the submandibular gland tissues of the model group,lymphocyte infiltration increased,water consumption increased,salivary flow rate decreased,AQP5 expression decreased,and submandibular gland cells apoptosis rate increased(P<0.05).Compared with all other administered groups,in the HRP-M group,the Hippo-YAZ/TAZ pathway was significantly activated,lymphocyte infiltration in submandibular gland tissues was reduced,water consumption was reduced,the salivary flow rate and AQP5 expression were increased,and the apoptosis rate of submandibular gland cells was reduced(P<0.05).Conclusion HRP reduced the pathological damage and apoptosis of submandibular gland cells in SS model mice.It improved the overall secretory function of submandibular gland tissues,which may be related to Hippo pathway activation and downregulating YAP/TAZ expression.

Objective To explore the effects of modulating the Hippo-YAP/TAZ pathway using Huashi Runzao Prescription(HRP)on the apoptosis and salivary secretion function of submandibular gland cells in a naive non-obese diabetic(NOD/Ltj)mouse model of Sj?gren's syndrome(SS).Methods Eight-week-old female BALB/c mice were selected as the blank group.Eight-week-old female NOD/Ltj were randomly divided into the model,HRP-L,HRP-M,HRP-H,and hydroxychloroquine sulphate(HCQ)groups.After eight weeks of drug administration,the water consumption and salivary flow rate of each group were recorded.The histopathological damage of the submandibular gland in each group was determined using hematoxylin and eosin staining,the apoptosis rate of the submandibular gland was determined using TUNEL staining,and AQP5,Bax,Bcl-2,beclin-1,YAP,p-YAP,and TAZ expressions in submandibular gland tissues were determined using immunohistochemistry and Western blotting.Results Compared with the blank group,the Hippo-YAP/TAZ pathway was inhibited in the submandibular gland tissues of the model group,lymphocyte infiltration increased,water consumption increased,salivary flow rate decreased,AQP5 expression decreased,and submandibular gland cells apoptosis rate increased(P<0.05).Compared with all other administered groups,in the HRP-M group,the Hippo-YAZ/TAZ pathway was significantly activated,lymphocyte infiltration in submandibular gland tissues was reduced,water consumption was reduced,the salivary flow rate and AQP5 expression were increased,and the apoptosis rate of submandibular gland cells was reduced(P<0.05).Conclusion HRP reduced the pathological damage and apoptosis of submandibular gland cells in SS model mice.It improved the overall secretory function of submandibular gland tissues,which may be related to Hippo pathway activation and downregulating YAP/TAZ expression.

Objective To explore the effects of modulating the Hippo-YAP/TAZ pathway using Huashi Runzao Prescription(HRP)on the apoptosis and salivary secretion function of submandibular gland cells in a naive non-obese diabetic(NOD/Ltj)mouse model of Sj?gren's syndrome(SS).Methods Eight-week-old female BALB/c mice were selected as the blank group.Eight-week-old female NOD/Ltj were randomly divided into the model,HRP-L,HRP-M,HRP-H,and hydroxychloroquine sulphate(HCQ)groups.After eight weeks of drug administration,the water consumption and salivary flow rate of each group were recorded.The histopathological damage of the submandibular gland in each group was determined using hematoxylin and eosin staining,the apoptosis rate of the submandibular gland was determined using TUNEL staining,and AQP5,Bax,Bcl-2,beclin-1,YAP,p-YAP,and TAZ expressions in submandibular gland tissues were determined using immunohistochemistry and Western blotting.Results Compared with the blank group,the Hippo-YAP/TAZ pathway was inhibited in the submandibular gland tissues of the model group,lymphocyte infiltration increased,water consumption increased,salivary flow rate decreased,AQP5 expression decreased,and submandibular gland cells apoptosis rate increased(P<0.05).Compared with all other administered groups,in the HRP-M group,the Hippo-YAZ/TAZ pathway was significantly activated,lymphocyte infiltration in submandibular gland tissues was reduced,water consumption was reduced,the salivary flow rate and AQP5 expression were increased,and the apoptosis rate of submandibular gland cells was reduced(P<0.05).Conclusion HRP reduced the pathological damage and apoptosis of submandibular gland cells in SS model mice.It improved the overall secretory function of submandibular gland tissues,which may be related to Hippo pathway activation and downregulating YAP/TAZ expression.

Objective To explore the effects of modulating the Hippo-YAP/TAZ pathway using Huashi Runzao Prescription(HRP)on the apoptosis and salivary secretion function of submandibular gland cells in a naive non-obese diabetic(NOD/Ltj)mouse model of Sj?gren's syndrome(SS).Methods Eight-week-old female BALB/c mice were selected as the blank group.Eight-week-old female NOD/Ltj were randomly divided into the model,HRP-L,HRP-M,HRP-H,and hydroxychloroquine sulphate(HCQ)groups.After eight weeks of drug administration,the water consumption and salivary flow rate of each group were recorded.The histopathological damage of the submandibular gland in each group was determined using hematoxylin and eosin staining,the apoptosis rate of the submandibular gland was determined using TUNEL staining,and AQP5,Bax,Bcl-2,beclin-1,YAP,p-YAP,and TAZ expressions in submandibular gland tissues were determined using immunohistochemistry and Western blotting.Results Compared with the blank group,the Hippo-YAP/TAZ pathway was inhibited in the submandibular gland tissues of the model group,lymphocyte infiltration increased,water consumption increased,salivary flow rate decreased,AQP5 expression decreased,and submandibular gland cells apoptosis rate increased(P<0.05).Compared with all other administered groups,in the HRP-M group,the Hippo-YAZ/TAZ pathway was significantly activated,lymphocyte infiltration in submandibular gland tissues was reduced,water consumption was reduced,the salivary flow rate and AQP5 expression were increased,and the apoptosis rate of submandibular gland cells was reduced(P<0.05).Conclusion HRP reduced the pathological damage and apoptosis of submandibular gland cells in SS model mice.It improved the overall secretory function of submandibular gland tissues,which may be related to Hippo pathway activation and downregulating YAP/TAZ expression.

Objective To explore the effects of modulating the Hippo-YAP/TAZ pathway using Huashi Runzao Prescription(HRP)on the apoptosis and salivary secretion function of submandibular gland cells in a naive non-obese diabetic(NOD/Ltj)mouse model of Sj?gren's syndrome(SS).Methods Eight-week-old female BALB/c mice were selected as the blank group.Eight-week-old female NOD/Ltj were randomly divided into the model,HRP-L,HRP-M,HRP-H,and hydroxychloroquine sulphate(HCQ)groups.After eight weeks of drug administration,the water consumption and salivary flow rate of each group were recorded.The histopathological damage of the submandibular gland in each group was determined using hematoxylin and eosin staining,the apoptosis rate of the submandibular gland was determined using TUNEL staining,and AQP5,Bax,Bcl-2,beclin-1,YAP,p-YAP,and TAZ expressions in submandibular gland tissues were determined using immunohistochemistry and Western blotting.Results Compared with the blank group,the Hippo-YAP/TAZ pathway was inhibited in the submandibular gland tissues of the model group,lymphocyte infiltration increased,water consumption increased,salivary flow rate decreased,AQP5 expression decreased,and submandibular gland cells apoptosis rate increased(P<0.05).Compared with all other administered groups,in the HRP-M group,the Hippo-YAZ/TAZ pathway was significantly activated,lymphocyte infiltration in submandibular gland tissues was reduced,water consumption was reduced,the salivary flow rate and AQP5 expression were increased,and the apoptosis rate of submandibular gland cells was reduced(P<0.05).Conclusion HRP reduced the pathological damage and apoptosis of submandibular gland cells in SS model mice.It improved the overall secretory function of submandibular gland tissues,which may be related to Hippo pathway activation and downregulating YAP/TAZ expression.

Objective To explore the effects of modulating the Hippo-YAP/TAZ pathway using Huashi Runzao Prescription(HRP)on the apoptosis and salivary secretion function of submandibular gland cells in a naive non-obese diabetic(NOD/Ltj)mouse model of Sj?gren's syndrome(SS).Methods Eight-week-old female BALB/c mice were selected as the blank group.Eight-week-old female NOD/Ltj were randomly divided into the model,HRP-L,HRP-M,HRP-H,and hydroxychloroquine sulphate(HCQ)groups.After eight weeks of drug administration,the water consumption and salivary flow rate of each group were recorded.The histopathological damage of the submandibular gland in each group was determined using hematoxylin and eosin staining,the apoptosis rate of the submandibular gland was determined using TUNEL staining,and AQP5,Bax,Bcl-2,beclin-1,YAP,p-YAP,and TAZ expressions in submandibular gland tissues were determined using immunohistochemistry and Western blotting.Results Compared with the blank group,the Hippo-YAP/TAZ pathway was inhibited in the submandibular gland tissues of the model group,lymphocyte infiltration increased,water consumption increased,salivary flow rate decreased,AQP5 expression decreased,and submandibular gland cells apoptosis rate increased(P<0.05).Compared with all other administered groups,in the HRP-M group,the Hippo-YAZ/TAZ pathway was significantly activated,lymphocyte infiltration in submandibular gland tissues was reduced,water consumption was reduced,the salivary flow rate and AQP5 expression were increased,and the apoptosis rate of submandibular gland cells was reduced(P<0.05).Conclusion HRP reduced the pathological damage and apoptosis of submandibular gland cells in SS model mice.It improved the overall secretory function of submandibular gland tissues,which may be related to Hippo pathway activation and downregulating YAP/TAZ expression.

Objective:To evaluate the efficacy and safety of micropulse transscleral cyclophotocoagulation (MP-TSCPC) for refractory glaucoma.Methods:A prospective multicenter observational case series study was conducted.A total of 63 refractory glaucoma patients (67 eyes) who underwent MP-TSCPC treatment were enrolled at Zhongshan Ophthalmic Center, Sun Yat-sen University, Chengdu First People's Hospital (Chengdu Integrated TCM& Western Medicine Hospital), and Changsha Aier Eye Hospital from August 2022 to April 2023.Among these cases, there were 40 eyes (59.7%) with unreduced intraocular pressure (IOP) after glaucoma surgery, 4 eyes (6.0%) with secondary glaucoma after vitrectomy, 2 eyes (3.0%) with secondary glaucoma after keratoplasty, 8 eyes (11.9%) with neovascular glaucoma, 3 eyes (4.5%) with secondary glaucoma due to iridocorneal endothelial syndrome, 6 eyes (9.0%) with primary open-angle glaucoma and 4 eyes (6.0%) with primary angle-closure glaucoma.Best corrected visual acuity (BCVA) was measured using the ETDRS chart and the IOP was measured using the Goldmann applanation tonometry before and 6 months after the surgery.The usage of anti-glaucoma medications before and after surgery and postoperative complications were recorded.Surgical success rate was calculated and surgical success was defined as an IOP reduction of more than 20% from baseline or a reduction in the number of ocular hypotensive medications with no change in IOP.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Zhongshan Ophthalmic Center, Sun Yat-sen University (No.2022KYPJ225).Written informed consent was obtained from each subject.Results:There was a statistically significant overall difference in IOP at different time points before and after surgery ( F=60.10, P<0.001), and the IOP at different time points after surgery was significantly lower than that before surgery, with statistically significant differences (all at P<0.001).IOP reduction at 6 months after surgery was (43.7±20.7)%.The number of anti-glaucoma medications used postoperatively was 2(0, 3) types, which was significantly less than the 3(2, 3) types used preoperatively ( Z=-2.70, P=0.007).The 6-month postoperative BCVA (LogMAR) was 1.40(0.52, 2.70), which showed no significant change compared to the preoperative 1.40(0.70, 2.70) ( Z=-0.10, P=0.952).The surgical success rate was 83.6%(56/67) at 6 months postoperatively.Postoperative complications included mydriasis (11/67), conjunctival hemorrhage (11/67), mild anterior chamber inflammation (1/67), mild ciliary body detachment (3/67), local choroidal detachment (1/67), and cystoid macular edema (1/67), all of which were reversible after treatment. Conclusions:MP-TSCPC appears to be a safe and effective treatment option for refractory glaucoma.