Polycystic ovary syndrome is a common endocrine disorder characterized by hyperandrogenemia and menstrual disorders. Patients not only have a high incidence of insulin resistance and metabolic syndrome, but also a high incidence of sleep disorders, especially obstructive sleep apnea. Obesity, hyperandrogenemia, insulin resistance,and other factors are responsible for the high prevalence of sleep apnea in women with polycystic ovary syndrome.

Diabetic macular edema(DME)and age-related macular degeneration(ARMD)are the leading causes of visual impairment and blindness worldwide, and their common pathological features are increased vascular permeability and abnormal neovascularization, in which cytokines such as vascular endothelial growth factor(VEGF)and angiopoietin-2(Ang-2)play an important role. Intravitreal injection of anti-VEGF agents significantly changed the clinical management of DME and ARMD, but limitations such as the non-responsive cases, the treatment burden and risks caused by frequent injections need to be overcome. Faricimab, a novel bispecific monoclonal antibody that simultaneously targets VEGF-A and Ang-2, can effectively reduce vascular permeability, decrease the number of neovascularization and alleviate retinal edema. Registered clinical studies have shown that Faricimab is effective in improving vision and reducing retinal edema, which is non-inferior to Aflibercept and Ranibizumab, maintains a long dosing interval, and has a high safety profile. This article reviews the latest advances in the treatment of DME and ARMD with Faricimab.

Objective To analyze the outcomes of radiotherapy for 74 patients with intracranial ger-minoma. Methods Between 1990 and 2007,74 patients with intracranial germinoma(9 pathologically diag-nosed and 65 clinically diagnosed) were treated with radiotherapy in our hospital. The median age at diagno-sis was 15 (range 5-45) years. Radiation treatment fields varied among patients, including craniospinal irra-diation(CSI), whole brain irradiation, whole ventricular irradiation with primary tumor boost, and involved-field irradiation only to the primary tumor plus margin. The dose was 38.5 -50.0 Gy to the tumor,18-25 Gy to the whole brain/ventricular,and 21-25 Gy to the whole spinal cord in fractions of 1.6-2.0 Gy per day,5 fractions per week. Results The median follow-up time was 80(range 12-168) months and the fol-low-up rate was 97%. Fourteen patients had been followed up for over 10 years. The 1-,5- and 10-year o-verall survival rates were 99% ,96% and 93%. The corresponding disease free survival rates were 97%, 90% and 83%, respectively. Relapses occurred in 9 patients. For the 6 patients with in-field relapse, the dose to the tumor was 38.5-40.0 Gy in 3 patients, 41-45 Gy in 2 and 46-50 Gy in 1. Relapse in the spinal cord was found in 3 patients and none of them received spinal irradiation. Twenty-one patients re-quired hormonal replacement therapy because of radiation induced hypofunction of prehypophysis. Conclu-sions Radiotherapy alone is a curative treatment for intracranial germinoma. The proper dose should be de-termined by tumor numbers and the examination of cerebrospinal fluid.

Objective To study the efficacy,late complications and prognostic factors of postopera-tive radiotherapy for bladder cancer: Methods Between July 1995 and January 21307,109 patients with primary bladder cancer who had received adjuvant pelvic radiation therapy were retrospectively analyzed. The age ranged from 41 to 94 (median 68) years. There were 29 patients with T1 disease,60 with T2,17 with T3, 3 with T4, and 7 with positive lymph node. Three-dimensional radiotherapy was given with a median total dose of 49.2 Gy(39.3 -62.2 Gy) in conventional fractionation after surgery. Field-in-field intensity modu-lated radiotherapy was given to 57 patients. Results The total follow-up rate was 98% ,with a median fol-low up time of 36(2-144) months. The 1-,3- and 5-year local control rate was 63% ,47% and 42% ,respec-tively. The 1-,3- and 5-year overall survival rate was 80% ,48% and 37% ,respectively. Among the 109 pa-tients,33 died of tumor progression or metastasis,42 showed local recurrence,and 22 had lymph node metas-tasis. According to the RTOG criteria,grade 1,2,3 and 4 radiation related early urological side effects were 22% ,59% ,12% and 1% ,respectively;The corresponding late urological side effects were 29% ,28% ,2% and 1%, respectively. Two patients underwent whole bladder cystectomy due to the radiation related side effects. Conclusions Postoperative three-dimensional radiotherapy, achieving high response rate with tol-erable side effects, can be offered as an alternative option to the radical cystectomy in the bladder conserving treatment.

Objective To observe the efficacy and safety of preoperative concurrent chemoradiotherapy or radiotherapy alone in patients with T3,T4 or lymph node-positive rectal cancer.Methods 141 rectal cancer patients with locally advanced or node-positive based on imaging from 2000 to 2009 were retrospective analyzed.Ninety-seven patients received preoperative concurrent chemoradiotherapy and 44 received preoperative radiotherapy alone.Two-dimensional or three-dimensional radiation technique and four types of chemotherapy regimens were used.Results The following-up rate was 91.5％.106 patients were followed up for at least 3 years and 68 patients for at least 5 years.The 3-and 5-year overall survival rates were 85.8％ and 65.7％,respectively.The 3-and 5-year local recurrence rates were 9.2％ and 14.1％,respectively.The 3-and 5-year metastasis rates were 33.8％ and 45.8％,respectively.The downstaging rate was up to 59.0％ (82/139) and the rate of sphincter preservation was 65.5％ (91/139).The median disease-free survival in patients treated with preoperative concurrent chemoradiotherapy was superior to radiotherapy alone (51 months vs 31 months,x2 =12.88,P =0.000).The time to metastasis in patients with downstaging was significantly delayed than that in patients without downstaging (60 months vs 29 months,x2 =14.65,P =0.000).Most acute toxicity was grade 1 and grade 2.The incidence of delayed wound healing and anastomotic leakage was very low.Conclusions Preoperative concurrent chemoradiotherapy or radiotherapy alone has excellent tumor downstaging effect and helps in sphincter preservation,with tolerable side effects.

Objective To evaluate treatment results and prognostic factors of 47 patients withprimary urethral transitional cell carcinoma treated with post-operative adjuvant radiotherapy. Methods From October 1998 to October 2008, 47 patients with primary urethral transitional cell carcinoma received postoperative adjuvant radiotherapy. Thirty-one patients had stage T_3/T_4 disease, 7 had lymph node metastasis. Thirty-nine patients had G3 tumor, 13 had stump-positive. The median radiotherapy dose was 60 Gy (36-64 Gy). 81% patients (38/47) were treated with regional irradiation. Results The median follow-up time was 21 months (6 -88 months). The follow-up rate was 92%. The median overall survival time was 35 months (5 -88 months). The 2-and 5-year overall survival rates were 57% and 49%, respectively. In univariate analysis, the median overall survival time was better in patients with stage T_1 or T_2 compared with stage T_3 or T_4 tumor (42 months vs. 19 months,Χ~2 =7. 28,P=0. 007), with age of ≤65 years compared with >65 years (28 mouths vs 18 months,Χ~2 =8.23 ,P =0. 004). There was no significantdifference in the long term survival in patients with non-radical surgery compared with radical mastectomy (21 months vs. 20 months, Χ~2 = 0. 90, P = 0. 344). In multivariate analysis, the stage T_3 or T_4 (Χ~2 = 7. 89, P =0. 005), >65 years old (Χ~2 = 4.85, P = 0. 028), renal pelvis involvement (Χ~2= 5.65, P = 0. 018), and tumor located in the mid or inferior segment (Χ~2=6. 08 ,P =0. 014) were factors associated with poorer prognosis. Conclusions Postoperative adjuvant radiotherapy can improve the efficacy of patients with locally advanced urethral transitional cell carcinoma. Advanced T stage and > 65 years age are associated with poorer prognosis.

Objective To analyze the efficacy,late complications and prognostic factors of post-op-erative radiotherapy for cervical cancer. Methods From Nov. 1999 to Feb. 2005,114 patients with cervi-cal cancer received adjuvant pelvic radiotherapy after radical hysterectomy and pelvic lymphadenectomy. The median age was 42.5 (24 to 72) years old. According to the FIGO staging system,6,51,18,26 and 13 pa-tients had stage ⅠA, Ⅰb1, Ⅰb2, ⅡA and ⅡBdisease. The pathological type was squamous cell carcinoma,ade-nocarcinoma, squamous-adenocarcinoma and undifferentiated carcinoma in 92,19,2 and 1 patients, respec-tively. The whole-pelvic external beam irradiation of 50 Gy (40 to 60 Gy) was given with 6 MV or 15 MV X-ray beams using four-field box technique. Eighty-one patients received intravaginal brachytherapy of 16 Gy (4 -30 Gy in 1 -6 fractions) 4 weeks after the beginning of radiotherapy, with the referrence point being at 0.5 cm under the vaginal mucosa. Eighty-seven patients received preoperative and/or concurrent chemother-apy. The survival and independent prognostic factors were analyzed by Log-rank method and Cox model. Results The median follow-up time was 26.0 (5 - 75) months. The overall survival rate, disease-free sur-rival rate and local control rate were 93.1%, 88.1% and 94.6% at 2-year, and 75.7%, 62.3% and 85.6% at 5-year,respectively. The independent prognostic factors were lymph node metastasis and positive surgical margin for overall survival, positive surgical margin for local control, and stage, uterine body invasion and positive surgical margin for disease-free survival. Sixteen patients ( 14% ) had distant metastasis, and the most common sites were the lung,inguinal region,bone,liver and brain. According to RTOG grading sys-tem, the incidence of late gastrointestinal side effects of grade 1,2 and 3 was 11.4%, 11.4% and 3.5%. The corresponding genitourinary side effects were 14.0% ,6.1% and 0.9%, respectively. The incidence of leg lymphedema was 7 % . Conclusions Post - operative radiotherapy can achieve good local control in cervical cancer with acceptable late side effects. Distant metastasis is the main cause of death.

Objective To investigate the treatment outcomes of 41 patients with suprasellar and pineal germinoma who are treated in our department in recent 18 years,and to explore related therapeutic strategies.Methods A total of 41 patients with concurrent suprasellar and pineal germinoma who were treated in our department from January 1996 to August 2013 were enrolled.There were 35 male patients and 6 female patients,and the median age was 16 years (range 5-39 years).Five patients had pathologically confirmed germinoma and 36 patients had clinically diagnosed germinoma.Conventional radiotherapy was performed for 33 patients, and intensity-modulated radiotherapy was performed for 8 patients.Combined-modality chemoradiotherapy was performed for the 5 patients with pathologically diagnosed germinoma.The 6 MV X-ray was applied for radiotherapy;6 patients received whole ventricular irradiation and a boost in tumor region, 16 received whole-brain radiotherapy and a boost in tumor region,and 19 received craniospinal irradiation and a boost in tumor region.The median radiation dose for tumor region was 45.0 Gy (37.8-50.0 Gy),and the median dose for prophylactic irradiation was 25.0 Gy (17.8-35.0 Gy).The survival was caculated using Kaplan-Meier method.Results The number of patients followed were 26 at 5-years.The 5-year overall survival rate and relapse-free survival rate were 95% and 85%,respectively.Relapse and metastasis were noted in 8 patients,and 3 of them died.There were 4 patients with spinal cord metastasis,1 patient with ventricular dissemination,and 3 patients with periventricular relapse.Among the 22 patients who did not undergo spinal irradiation,4(18.2%) experienced spinal cord metastasis,and all the other 19 patients who underwent spinal irradiation did not experience spinal cord metastasis.The 8 patients undergoing intensity-modulated radiotherapy and the 5 patients undergoing combined-modality chemoradiotherapy did not experience treatment failure during follow-up.Conclusions Radiotherapy for intracranial germinoma has a good therapeutic effect,and the patients with suprasellar and pineal germinoma who do not undergo spinal cord irradiation have a high failure rate.It is suggested to perform spinal cord irradiation for patients with suprasellar and pineal lesions.

Aim: To investigate the pathological changes in NTBC[2-(2-nitro-4-trifluoro-methyl-benzoyl) -1,3 cy-clohexanedione]-induced hepatic injury in mice and in the repopulation of adult hepatocytes in Fah~(-/-) mouse. Methods: Autogenous hepatic injuries in Fah~(-/-) mice were induced by the treatment of NTBC. Injection of hepatocytes obtained from wild-type mice to spleen were transplanted into the Fah~(-/-) mice. Then, changes to body weight and the likelihood of the transplanted Fah~(-/-) mice, and hepatic immunohistochemistry were ob-served. In addition, pathological changes to liver damage induced by NTBC treatment were analyzed under HE-staining microscopy and electron microscopy. Results: The surviving Fah~(-/-) mice subjected to hepatocyte trans-plantation were found to be healthy and in stable body weight. liver repopulation reached to 90% in the 8th week. Repopulating hepatocytes caused no alteration to histological structure of the recipient liver, and subacute hepatic injury occurred in the Fah~(-/-) mice after NTBC treatment. Electronic microscopy observations indicated that necrosis in the hepatocytes occurred at early stage and that apoptosis gradually appeared. It was also shown both necrosis and apoptosis co-existed in the same samples of interest at the following stages of the induced liver injury. Conclusion: Transplanted hepatocytes proliferated in Fah~(-/-) mice allow 90% of the hepatocytic repopula- tion. Repopulation renders normal hepatic function and structure in the recipient Fah~(-/-) mice, as a model of liver repopulation, could be applicable in study of stem cell derived hepatic cells in transplantation assay.

Objective To study the modulation in number and function of endothelial progenitor cell ( EPC ) in multiple organ dysfunction syndrome ( MODS ) after trauma in swine, and to investigate its pathogenesis. Methods Forty pigs were divided into sham group and MODS group ( each, n = 20 ). The model of MODS of two-hit injury, namely hemorrhagic shock and endotoxemia, was reproduced. The peripheral blood was collected before hemorrhage ( T1 ) and endotoxin injection ( T2 ), and 1 hour ( T3 ), 24 hours ( T4 ), 48 hours ( T5 ) after endotoxin injection. Phosphorylation of p38 mitogen-activated protein kinase ( p-p38MAPK ) in mononuclear cell was determined by Western Blot, the content of tumor necrosis factor-α ( TNF-α) was determined with enzyme linked immunosorbent assay ( ELISA ), and the number of EPC was determined with flow cytometry. Results Model of MODS was successfully reproduced in 17 pigs. In model group, the expression of p-p38MAPK ( A value ) peaked at T3 ( 4.83±0.52 ), and gradually declined at T4 and T5 ( 4.36±0.43, 1.93±0.33 ), and the expression of p-p38MAPK at T3-T5 was significantly higher than that at T1 ( 1.00±0.22, all P<0.01 ). The plasma concentration of TNF-α( ng/L ) at T3 in MODS group was obviously elevated compared with that of sham group ( 532.43±52.17 vs. 129.03±20.45, t=31.163, P<0.001 ), and it peaked at T3, it then gradually lowered, and it was significantly higher at T4 and T5 than that in sham group ( T4: 398.93±35.75 vs. 131.12±29.53, t = 26.562, P < 0.001; T5: 287.48±27.26 vs. 126.44±26.96, t=17.861, P<0.001 ). The number of EPC ( ×107/L ) was apparently increased in MODS group at T3 compared with sham group ( 4.832±0.624 vs. 3.545±0.363, t=9.542, P<0.001 ), and it peaked at T3, then gradually decreased, and the number of EPC at T4 and T5 was significantly lower than that in sham group ( T4:2.628±0.627 vs. 3.442±0.325, t=5.043, P<0.001;T5:2.203±0.711 vs. 3.471±0.323, t=2.972, P<0.001 ). Conclusion Phosphorylation of p38MAPK could increase the plasma concentration of TNF-αand decrease the quantity of EPC in MODS,which may be one of the mechanisms of MODS.