Objective:To investigate the expressions of MUC1, MUC4, MUC5AC and MUC16 in patients with first diagnosis of dry eye and their correlation with dry eye symptoms and signs.Methods:A cross-sectional study was conducted.Sixty-nine dry eye patients (69 eyes) as dry eye group and 40 normal volunteers (40 eyes) as normal control group were recruited in Xiamen Eye Center of Xiamen University, Beijing Tongren Hospital, West China Hospital of Sichuan University and Shanghai Puotuo District Center Hospital from December 2016 to May 2018.Symptoms were evaluated by Chinese dry eye questionnaire, Ocular Surface Disease Index (OSDI) and Dry Eye-Related Quality-of-Life Score Questionnaire (DEQS). Signs were assessed by tear film breakup time (TBUT), keratoconjunctival fluorescein sodium staining, and Schirmer I test.Conjunctival cells were collected by conjunctival impression cytology.The expression levels of MUC1, MUC4, MUC5AC and MUC16 mRNA in the two groups were determined by real-time fluorescence quantitative PCR.The correlation between the mRNA levels of conjunctival mucins and dry eye symptoms and signs were analyzed by Spearman correlation analysis.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committees of Xiamen Eye Center of Xiamen University (No.2017003), Beijing Tongren Hospital, Capital Medical University (No.TREC2016-29), West China Hospital of Sichuan University (No.2016310) and Shanghai Puotuo District Center Hospital (No.PTEC-A-2016-18-1). Written informed consent was obtained from each subject before any medical examination.Results:The expression levels of MUC1 and MUC16 mRNA in dry eye patients were 3.277(0.568, 5.790) and 1.815(1.048, 3.694), which were higher than 1.055(0.550, 2.010) and 1.024(0.541, 1.965) in normal control group (Z=819.00, P=0.008; Z=861.00, P=0.002). According to OSDI scores, MUC1 was mainly increased to 3.277(1.161, 6.226) in mild to moderate (12-32 points) dry eye patients (Z=9.04, P=0.029), and MUC16 was mainly increased to 1.968(1.074, 3.726) in severe (>32 points) dry eye patients (Z=12.24, P=0.007). MUC1 expression was positively correlated with TBUT, and was negatively correlated with corneal staining scoring and keratoconjunctival staining scoring ( r s=0.270, P=0.025; r s=-0.331, P=0.006; r s=-0.325, P=0.007). MUC16 expression was positively correlated with TBUT, and was negatively correlated with blurred vision scoring, symptom exacerbation scoring during reading, impact scoring of driving at night, impact scoring of computer and impact scoring of TV use ( r s=0.249, P=0.039; r s=-0.359, P=0.047; r s=-0.370, P=0.034; r s=-0.558, P=0.016; r s=-0.498, P=0.006; rs=-0.515, P=0.002). Conclusions:The gene expressions of MUC1 and MUC16 are higher in conjunctiva of dry eye patients.MUC1 mRNA expression is related to patients' signs.MUC16 mRNA expression is related to the quality of life of patients.

Objective:To explore the characteristics of ovarian torsion in in vitro fertilization-embryo transfer (IVF-ET) cycles and identify factors that may affect the outcome. Methods:Patients who underwent surgery for ovarian torsion during IVF treatment in the Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital from January 2010 to December 2019 were included. The general information, IVF cycle characteristics, and intraoperative findings of patients were retrospectively analyzed. The diagnosis and treatment process were summarized. The pregnancy outcomes were followed up, and the possible influencing factors were analyzed.Results:There were 141 539 cycles of controlled ovarian stimulation (COS) and 75 585 cycles of frozen-thawed embryo transfer (FET) during the study period. A total of 50 patients were diagnosed with ovarian torsion and treated surgically, 90.0% of them occurred in the COS cycles (39 cases in fresh embryo transfer cycles and 6 cases in embryo freezing cycles), and 10.0% (5/50) occurred in the FET cycles (endometrial preparation in natural cycles or ovulation induction cycles). About 86.0% (43/50) of the patients occurred during pregnancy assisted with IVF-ET and 81.4% (35/43) occurred in the first trimester of pregnancy. All patients except one had abdominal pain as the first symptom, only 34.0% (17/50) of the patients had definite inducements, and all patients had signs of tenderness in the lower abdomen and adnexal area. Preoperative ultrasound examination showed that the average diameter of the torsional ovaries was (78.17±15.98) mm, compared with (48.69±15.96) mm in the controls, with an average difference of (30.13±19.69) mm (-3.5-80.0 mm). About 76.2% (32/42) of the torsional ovaries showed blood flow signals by color doppler ultrasound. All patients underwent surgery, and the coincidence rate between the preoperative diagnosis and the surgical diagnosis was 96%. Totally 22 torsional ovaries (44%) were found to be purplish-black, of which 16 cases underwent adnexectomy by laparoscopy or laparotomy. Totally 34 cases (68%) underwent ovarian detorsion. The average torsional degree of ovaries in the adnexectomy group was higher than that in the ovarian detorsion group [(727.50±206.54)° vs. (477.35±262.92)°, P=0.002]. There were no statistical differences between the two groups in the duration from onset to operation and the ratio of ovarian blood signal deficiency (all P>0.05). Among 44 patients with the embryo transfer, 84.1% (37/44) of patients obtained live birth, 1 case had implantation failure, and 6 cases had a spontaneous abortion. Patients with an adverse pregnancy outcome and patients with a live birth did not have significantly different ovarian torsion time, surgical methods, the duration from onset to operation, and other factors. Conclusion:Ovarian torsion in patients with IVF-ET treatment mostly occurs in the first trimester of pregnancy after fresh embryo transfer. Abdominal pain accompanied by differential enlargement of bilateral ovaries may suggest the possibility of ovarian torsion. We are unable to rule out ovarian torsion by observation of ovarian blood flow with color Doppler ultrasound. Active surgery was helpful to make a clear diagnosis and protect the fertility of patients. Patients with long torsional durations, purplish-black ovaries, or ovarian blood deficiency still have the opportunity to retain the torsional ovary. The pregnancy outcome of patients with ovarian torsion was satisfactory after surgical treatment.

Objective:To explore the characteristics of ovarian torsion in in vitro fertilization-embryo transfer (IVF-ET) cycles and identify factors that may affect the outcome. Methods:Patients who underwent surgery for ovarian torsion during IVF treatment in the Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital from January 2010 to December 2019 were included. The general information, IVF cycle characteristics, and intraoperative findings of patients were retrospectively analyzed. The diagnosis and treatment process were summarized. The pregnancy outcomes were followed up, and the possible influencing factors were analyzed.Results:There were 141 539 cycles of controlled ovarian stimulation (COS) and 75 585 cycles of frozen-thawed embryo transfer (FET) during the study period. A total of 50 patients were diagnosed with ovarian torsion and treated surgically, 90.0% of them occurred in the COS cycles (39 cases in fresh embryo transfer cycles and 6 cases in embryo freezing cycles), and 10.0% (5/50) occurred in the FET cycles (endometrial preparation in natural cycles or ovulation induction cycles). About 86.0% (43/50) of the patients occurred during pregnancy assisted with IVF-ET and 81.4% (35/43) occurred in the first trimester of pregnancy. All patients except one had abdominal pain as the first symptom, only 34.0% (17/50) of the patients had definite inducements, and all patients had signs of tenderness in the lower abdomen and adnexal area. Preoperative ultrasound examination showed that the average diameter of the torsional ovaries was (78.17±15.98) mm, compared with (48.69±15.96) mm in the controls, with an average difference of (30.13±19.69) mm (-3.5-80.0 mm). About 76.2% (32/42) of the torsional ovaries showed blood flow signals by color doppler ultrasound. All patients underwent surgery, and the coincidence rate between the preoperative diagnosis and the surgical diagnosis was 96%. Totally 22 torsional ovaries (44%) were found to be purplish-black, of which 16 cases underwent adnexectomy by laparoscopy or laparotomy. Totally 34 cases (68%) underwent ovarian detorsion. The average torsional degree of ovaries in the adnexectomy group was higher than that in the ovarian detorsion group [(727.50±206.54)° vs. (477.35±262.92)°, P=0.002]. There were no statistical differences between the two groups in the duration from onset to operation and the ratio of ovarian blood signal deficiency (all P>0.05). Among 44 patients with the embryo transfer, 84.1% (37/44) of patients obtained live birth, 1 case had implantation failure, and 6 cases had a spontaneous abortion. Patients with an adverse pregnancy outcome and patients with a live birth did not have significantly different ovarian torsion time, surgical methods, the duration from onset to operation, and other factors. Conclusion:Ovarian torsion in patients with IVF-ET treatment mostly occurs in the first trimester of pregnancy after fresh embryo transfer. Abdominal pain accompanied by differential enlargement of bilateral ovaries may suggest the possibility of ovarian torsion. We are unable to rule out ovarian torsion by observation of ovarian blood flow with color Doppler ultrasound. Active surgery was helpful to make a clear diagnosis and protect the fertility of patients. Patients with long torsional durations, purplish-black ovaries, or ovarian blood deficiency still have the opportunity to retain the torsional ovary. The pregnancy outcome of patients with ovarian torsion was satisfactory after surgical treatment.

Objective:To analyze the clinical manifestations and signs of the first diagnosed dry eye patients, and to explore the concordance between the Chinese dry eye diagnostic criteria and the Asian dry eye diagnostic criteria.Methods:A cross-sectional multicenter study was conducted.One hundred and forty-one eyes of 141 patients who were diagnosed as dry eye for the first time were included in Xiamen Eye Center of Xiamen University, Beijing Tongren Hospital, West China Hospital of Sichuan University and Shanghai Putuo District Center Hospital from December 2016 to May 2018.All patients completed the Chinese Dry Eye Questionnaire, Ocular Surface Disease Index (OSDI) and Dry Eye-Related Quality-of-life Score Questionnaire (DEQS) to evaluate the symptoms of dry eye.Tear film breakup time (BUT), keratoconjunctival fluorescein staining, meibomian gland morphology and function examination, and Schirmer Ⅰ test were performed to evaluate dry eye signs and the association between dry eye symptoms and signs.The eyes were divided into corneal staining positive and negative group according to the presence or absence of corneal fluorescein staining, and the dry eye symptoms of the two groups were assessed by the three questionnaires.The eyes were divided into tear-deficient dry eye, evaporative dry eye, mixed dry eye and abnormal tear dynamics dry eye to compare the difference of dry eye signs among the groups.This study adhered to the Declaration of Helsinki.The study protocol complied with Chinese regulations and rules on clinical trial research and was approved by Ethics Committees of Xiamen Eye Center of Xiamen University (No.2017003), Beijing Tongren Hospital, Capital Medical University (No.TREC2016-29), West China Hospital of Sichuan University (No.2016310) and Shanghai Putuo District Center Hospital (No.PTEC-A-2016-18-1). Written informed consent was obtained from patients before entering the cohort.Results:The total score of Chinese Dry Eye Questionnaire, OSDI questionnaire and DEQS questionnaire was 12.00(7.00, 16.00), 25.00(17.50, 36.93) and 32.02(15.77, 52.34), respectively.It was found that 130 eyes (92.2%) had dryness, and 109 eyes (77.3%) had ocular fatigue and 108 eyes (76.6%) had foreign body sensation.Dryness, foreign body sensation, photophobia and poor vision were weakly positively correlated with corneal staining ( r=0.177、0.297、0.172, all at P<0.05). Pain, photophobia and poor vision were negatively correlated with tear secretion ( r=-0.178, -0.197, -0.174; all at P<0.05). It was found that 43.3% of dry eye patients had used visual display terminals.Among the 141 eyes, 75 eyes (53.2%) were with over evaporation dry eye, 43 eyes (30.5%) with mixed dry eye, 18 eyes (12.8%) with aqueous-deficient dry eye and 3 eyes (2.1%) with abnormal tear dynamics dry eyes. Conclusions:Initial diagnosis of dry eye patients is mainly mild to moderate.Dry eye signs and symptoms are correlated.Over evaporation dry eye is the most common type of dry eye.The concordance between the Chinese dry eye diagnostic criteria and the Asian Dry Eye Society diagnostic criteria reaches 97.2%.

Objective:To study the change in serum fibroblast growth factor 21(FGF21)level and its correlation with liver functions in elderly patients with hepatitis B virus(HBV)-related cirrhosis.Methods:A total of 150 elderly patients with HBV infection admitted to Beijing Ditan Hospital and China-Japan Friendship Hospital from January 2019 to December 2020 were selected and divided into chronic hepatitis B(CHB)group(n=70)and HBV-related cirrhosis group(n=80). Healthy subjects were selected as the control group(n=50). Serum FGF21 was determined by ELISA method.Clinical data, clinical laboratory indicators and FGF21 as a core parameter of this study were collected and compared among control group, CHB group, HBV-related cirrhosis group.The correlations of FGF21 level with several liver function indexes were analyzed by Pearson correlation analysis.Results:The levels of total bilirubin(TBil)and total biliary acid(TBA)were significantly higher in HBV-related cirrhosis group than in CHB group.The levels of aspartate transaminase(AST), alanine transaminase(ALT), glutamyl transpeptadase(GGT), serum albumin, cholinesterase, FGF21 and HBV-DNA were significantly lower in HBV-related cirrhosis group than in CHB group(all P<0.05). The levels of serum FGF21 were(108.6 ± 7.3)ng/L, (92.5 ± 7.6)ng/L and(75.8 ± 6.3)ng/L in Child-Pugh A, B and C patients, respectively.The level of FGF21 was statistically significantly decreased with the increase of Child-Pugh grading( F=18.290, P=0.000). Serum FGF21 level was positively correlated with AST, ALT, TBil, cholin-esterase and albumin levels( r=0.652, 0.579, 0.609, 0.558, 0.613, all P<0.05). Conclusions:The level of serum FGF21 is significantly decreased in elderly patients with HBV-related cirrhosis, and is positively correlated with liver function indexes.

Objective:To evaluate the safety and efficacy of metal clips combined with endoscopic histoacryl injection for gastric varices with spontaneous portosystemic shunts.Methods:The clinical data and complications of 32 patients who were treated with metal clips combined with endoscopic histoacryl injection at Beijing Ditan Hospital of Capital Medical University from May 2016 to October 2018 were collected and analyzed.Results:Hemostasis was achieved in all patients, and the median volume of histoacryl was 3.8 mL. Varices were eradicated or disappeared in 9 cases, and the degree of varices were lessened in 23 cases. No rebleeding was found at 72 h, 7 d, 14 d and 6 weeks after operation in any patient. No ectopic embolism occurred.Conclusion:Metal clips combined with endoscopic histoacryl injection is effective and safe to treat gastric varices with spontaneous portosystemic shunts.

Objective To evaluate the efficacy of 0.3％ sodium hyaluronate ophthalmic solution in mild-to-moderate dry eye patients.Metbods A prospective,multicenter,and self-controlled clinical trial was performed on 200 patients who were diagnosed as mild-to-moderate dry eye from January 2015 to June 2017 in Eye Institute of Xiamen University,Eye & ENT Hospital of Fudan University,Zhongshan Ophthalmic Center,Xiangya Hospital Central South University,Eye Hospital of Wenzhou Medical University,and Beijing Tongren Hospital,Capital Medical University.The study protocol was approved by the Ethics Committees of Eye Institute of Xiamen University,written informed consent was obtained from each patient prior to any medical examination.All patients were treated with 0.3％ sodium hyaluronate ophthalmic solution 6 times per day (one drop each time) for 28 days.Corneal fluorescein sodium staining,tear film break-up time (BUT),Schirmer Ⅰ test (S Ⅰ t),degree of conjunctival hyperemia,eyelid margin,meibomian gland secretion,secretory capacity of meibomian gland and subjective symptoms were assessed at baseline,on the 14th day and 28th day after treatment.Bulbar impression cytology was evaluated at baseline and on the 28th day after treatment.Irritation of 0.3％ sodium hyaluronate ophthalmic solution was estimated on the 14th day and 28th day after treatment.Results The total score of subjective symptoms,BUT,S Ⅰ t,degree of conjunctival hyperemia were significantly different among different treatment time points (F =108.969,27.598,16.838,36.750;all at P＜0.01).Compared with before treatment,the total score of subjective symptoms was significantly decreased,the degree of conjunctival hyperemia and the total corneal fluorescein sodium staining point number were significant decreased on the 14th day and 28th day after treatment.The total score of subjective symptoms,degree of conjunctival hyperemia and total corneal fluorescein sodium staining point number on the 28th day after treatment were significant lower than those on the 14th day after treatment.Compared with before treatment,the BUT was significantly longer and the S Ⅰ t scores were significantly increased on the 14th day and 28th day after treatment.The BUT on the 28th day after treatment was significantly longer than that on the 14th day after treatment;no significant difference in S Ⅰ t was observed between the 28th day and the 14th day after treatment.The scores of palpebral margin change,meibomian gland secretory ability and secretion characteristics were not significantly different among different treatment time points(H=0.255,2.356,0.294;all at P＞0.05).The impression cytology grade on the 28th day after treatment was 1.08±0.74,which was significantly lower than 1.53±0.76 before treatment (t =5.979,P＜0.01).The number of goblet cells on the 28th day after treatment was significantly higher than that before treatment (U =1 806.500,P＜ 0.01).On the 14th day after treatment,70％ of the patients indicated that the drug was non-irritating,and no patient had intolerable irritation affecting daily lives.All patients had good tolerance to this drug.Conclusions The use of 0.3％ sodium hyaluronate eye drops can improve the symptoms and signs of mild to moderate dry eye,which can be widely used for mild-to-moderate dry eye patients in clinic.

Objective: The aim of this study was to evaluate the value for CBL and LBL teaching method in the training of refresher doctors in reproductive medicine. Methods: A questionnaire survey was conducted among 186 refresher doctors who had studied in the reproductive medicine center at Peking University Third Hospital from January 2016 and December 2017 one year after their graduation. We tested 33 refresher doctors in observe group and 33 refresher doctors in the CBL+LBL group who graduated at the same period. Results: Ninety-two refresher doctors responded to the investigation. The questionnaire survey showed that 84.78% of the refresher doctors thought that CBL and LBL teaching method could improve their learning abilities, clinical problem analysis and solving skills, and surgical techniques, which was conducive to promoting their assisted reproductive technology. Besides, 63.04% of refresher doctors believed this method improved their research abilities. In CBL+LBL group, examination scores of theoretical knowledge were significantly higher than the observe group (P<0.05). Conclusion The combination of CBL and LBL is effective and feasible in the training of refresher doctors in reproductive medicine.

Objective To evaluate the efficacy of 0. 3％ sodium hyaluronate ophthalmic solution in mild.to. moderate dry eye patients. Methods A prospective,multicenter,and self.controlled clinical trial was performed on 200 patients who were diagnosed as mild.to.moderate dry eye from January 2015 to June 2017 in Eye Institute of Xiamen University,Eye &ENT Hospital of Fudan University,Zhongshan Ophthalmic Center,Xiangya Hospital Central South University, Eye Hospital of Wenzhou Medical University, and Beijing Tongren Hospital, Capital Medical University. The study protocol was approved by the Ethics Committees of Eye Institute of Xiamen University,written informed consent was obtained from each patient prior to any medical examination. All patients were treated with 0. 3％ sodium hyaluronate ophthalmic solution 6 times per day ( one drop each time) for 28 days. Corneal fluorescein sodium staining,tear film break.up time (BUT),SchirmerⅠtest (SⅠt),degree of conjunctival hyperemia,eyelid margin,meibomian gland secretion,secretory capacity of meibomian gland and subjective symptoms were assessed at baseline,on the 14th day and 28th day after treatment. Bulbar impression cytology was evaluated at baseline and on the 28th day after treatment. Irritation of 0. 3％ sodium hyaluronate ophthalmic solution was estimated on the 14th day and 28th day after treatment. Results The total score of subjective symptoms,BUT,SⅠt,degree of conjunctival hyperemia were significantly different among different treatment time points( F=108. 969,27. 598,16. 838,36. 750;all at P<0. 01). Compared with before treatment,the total score of subjective symptoms was significantly decreased, the degree of conjunctival hyperemia and the total corneal fluorescein sodium staining point number were significant decreased on the 14th day and 28th day after treatment. The total score of subjective symptoms,degree of conjunctival hyperemia and total corneal fluorescein sodium staining point number on the 28th day after treatment were significant lower than those on the 14th day after treatment. Compared with before treatment,the BUT was significantly longer and the SⅠt scores were significantly increased on the 14th day and 28th day after treatment. The BUT on the 28th day after treatment was significantly longer than that on the 14th day after treatment;no significant difference in SⅠt was observed between the 28th day and the 14th day after treatment. The scores of palpebral margin change,meibomian gland secretory ability and secretion characteristics were not significantly different among different treatment time points(H=0. 255,2. 356,0. 294;all at P>0. 05). The impression cytology grade on the 28th day after treatment was 1. 08±0. 74,which was significantly lower than 1. 53±0. 76 before treatment (t=5. 979, P<0. 01). The number of goblet cells on the 28th day after treatment was significantly higher than that before treatment(U=1806. 500,P<0. 01). On the 14th day after treatment,70％ of the patients indicated that the drug was non.irritating,and no patient had intolerable irritation affecting daily lives. All patients had good tolerance to this drug. Conclusions The use of 0. 3％ sodium hyaluronate eye drops can improve the symptoms and signs of mild to moderate dry eye,which can be widely used for mild.to.moderate dry eye patients in clinic.

Objective To investigate the effect of expressions of endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) in the ischemic cortex on ischemic cerebral injury in rats with diabetes mellitus.Methods A total of 36 healthy male Sprague-Dawley rats were divided into 3 groups:a shamoperation group,a cerebral ischemic group,and a diabetic cerebral ischemic group according to the random number table method.A diabetes model was induced by injection of streptozocin,and then,a permanent focal cerebral ischemic model was induced by the suture method.At 24 h after ischemia,the neurological deficit scores were conducted.The triphenyl tetrazolium chloride staining was used to measure the infarct volume.TUNEL was used to detect the apoptotic cells.Real-time fluorescence quantitative polymerase chain reaction was used to detect the expression levels of VEGF and VEGFR2 mRNAs.Western blot was used to detect the expression levels of VEGF and VEGFR2 proteins.Results In the sham operation group,there were no neurological deficit and infarcts,and there were only a few apoptotic cells and a few expressions of VEGF,VEGFR2 mRNAs and protein.The neurological function score (4.25 ±0.54 vs.2.86 ±0.73);t =5.303,P＜0.001),infarct volume (51.69 ±2.26 mm3 vs.30.15 ±2.08 mm3;t =23.166,P＜0.001),and the number of apoptotic cells (24.22 ± 1.34/HP vs.13.28 ±0.37/HP;t =27.261,P＜0.001) in the diabetic cerebral ischernia group were significantly increased than those in the cerebral ischemic group,while VEGF,VEGFR2 mRNA,and protein expression level were significantly decerased (VEGF mRNA:4.74 ± 0.54 vs.6.71 ± 0.91,P ＜ 0.001;VEGFR2 mRNA:4.06 ± 0.60 vs.6.16 ± 0.96,P ＜ 0.001,VEGF protein:0.99 ± 0.13 vs.1.55 ± 0.23,P ＜ 0.001;VEGFR2 protein:4.12 ± 0.74 vs.6.23 ± 0.76,P ＜ 0.001) compare with the cerebral ischemic group.Conclusions VEGF/VEGFR2 signal pathway participates in diabetes aggravating ischemic cerebral injury.The downregulating of VEGF/VEGFR2 may be one of the mechanisms of diabetes aggravating ischemic cerebral injury.