Research progress and considerations on non-clinical studies of the drugs administered through the ocular vitreous body / 药学学报

In recent years, with the development of ophthalmic therapeutic drugs, the vitreous body, as a channel for the treatment of ophthalmic diseases, especially fundus diseases, has opened up a new therapeutic approach for various choroidal neovascular diseases, macular edema, uveitis and other diseases associated with fundus diseases, which is represented by wet age-related macular degeneration (wAMD). The drugs administered through the vitreous body mainly include ocular anti-vascular endothelial growth factor (VEGF) injections, microplasmin and hormones. For this kind of ophthalmic products, there are no clear technical guidelines and norms for non-clinical research at home and abroad. This article combines review practices and cases of marketed products to sort out the research progress and considerations on non-clinical studies of ophthalmic drugs dosing through the ocular vitreous body, in order to provide references for the research and evaluation of such drugs.

Identification and preservation of arm lymphatics in axillary lymph node dissection to prevent arm lymphedema: a single center randomized controlled trial / 中华肿瘤杂志

Objective: To evaluate the feasibility of identification and preservation of arm lymphatics (DEPART) in axillary lymph node dissection (ALND) for breast cancer to prevent arm lymphedema. Methods: A randomized controlled study method was used. Two hundred and sixty-five patients who underwent breast cancer surgery at the Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University from November 2017 to June 2018 were included, and the patients were randomly divided into ALND+ DEPART group (132 patients) and standard ALND group (133 patients) by random number table method. In the ALND+ DEPART group, indocyanine green and methylene blue were injected as tracers before surgery, and the arm sentinel nodes was visualized by staged tracing during intraoperative dissection of axillary lymph nodes. Partial frozen sections were made of arm lymph nodes >1 cm in length and hard and suspicious of metastasis, and arm lymph nodes and lymphatic vessels were selectively preserved. Patients in the standard ALND group underwent standard ALND. Objective and subjective indexes of arm lymphedema were evaluated by 5-point circumference measurement and Norman questionnaire. Results: Among 132 breast cancer patients in the ALND+ DEPART group, 121 (91.7%) completed DEPART. There were no statistically significant differences in age, body mass index, pathological type, dissection number of axillary lymph node, N stage, TNM stage, molecular typing, and regional radiotherapy between the ALND+ DEPART and standard ALND groups (P>0.05). At a median follow-up of 24 months, assessment by the 5-point circumference measurement showed that the incidence rates of lymphedema in the ALND+ DEPART and standard ALND groups were 5.0% (6/121) and 15.8% (21/133), respectively, with statistically significant differences (P=0.005). Assessment by the Norman questionnaire showed that the incidence rates of lymphedema in the ALND+ DEPART and standard ALND groups were 5.8% (7/121) and 21.8% (29/133), respectively, with a statistically significant difference (P<0.001). No local regional recurrence was observed in either group during the follow-up period. Conclusion: For breast cancer patients with positive axillary lymph nodes, the administration of DEPART during ALND can reduce or avoid the occurrence of arm lymphedema without compromising oncology safety.

Parathyroid hormone assay with eluent of aspirated tissues in parathyroidectomy / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the values of intraoperative fine-needle aspiration (IFNA) and parathyroid hormone (PTH) detection in the eluate of aspirated tissue during parathyroidectomy. Methods: Fifty-four patients with secondary hyperparathyroidism (SHPT) including 24 males and 30 females, aged 20-83 years, admitted to Zhongnan Hospital of Wuhan University from January 2019 to October 2019, were included. All patients received subtotal parathyroidectomy with autologous transplantation, during surgery, IFNA and PTH detection in the eluate of aspirated tissue were performed, and also routine postoperative pathological examination was performed. The results of PTH detection in the eluate of aspirated tissue and postoperative pathological examinations were compared and analyzed by SPSS and R software for evaluating of the sensitivity, specificity, positive predictive value, negative predictive value, misdiagnosis rate, missed diagnosis and accuracy. Results: Surgery was completed successfully in all patients. After surgery, the symptoms were improved in the patients except two who were asymptomatic. None had any serious postoperative complications such as hypocalcaemia or hoarseness. A total of 231 aspirated tissue samples were tested, of which 216 were identified as parathyroid and 15 non-parathyroid based on intraoperative PTH detection in tissue eluate; while 217 were confirmed as parathyroid tissues and 14 non-parathyroid tissues with postoperative pathological examinations. The specificity and sensitivity of intraoperative IFNA and PTH detection in tissue eluate for identifying parathyroid tissues were 99.5% and 100.0%, respectively. Conclusion: The IFNA and PTH detection in tissue eluate is a rapid, simple, and accurate procedure, which helps the surgeon to identify parathyroid tissue and to ensure the endocrine activity of preserved or autografted parathyroid tissue during parathyroidectomy.

Application value of intraoperative neuromonitoring plus "classification of EBSLN" to protect the external branch of the superior laryngeal nerve / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the application efficacy of the "classification of external branch of superior laryngeal nerve (EBSLN)" combined with intraoperative neuromonitoring (IONM) in the dissection of EBSLN for protecting the nerve from injuery, compared with ligation of branches of the superior thyroid vessels without attempts to visually identify the nerve. Methods: A prospective randomized controled study was performed in our center. Patients subjected to thyroidectomy from January 2017 to June 2019 were randomly divided into 2 groups, patients in experimental group underwent thyroidectomy and "classification of EBSLN" with IONM to dissect EBSLN, and patients in control group received synchronous surgery without attempts to visually identify the nerve. The anatomical subtypes of EBSLN in experimental group were recorded. The voice handicap index 10 (VHI-10) score was evaluated and the movement of bilateral vocal cords was examined by laryngoscope before surgery, 1 month, 3 months, and 6 months after surgery, respectively. SPSS 26.0 statistical software was used for statistical analysis. Results: Among the 1 377 EBSLN from 827 patients (317 males and 510 females, aged 24-58 years old), 691 EBSLNs in experimental group and 686 EBSLNs in control group. Totally 98.3% of EBSLNs in experimental group were identified by IONM including 16.4% (113/691) for type Ⅰ, 21.3% (147/691) for type Ⅱa, 31.4% (217/691) for type Ⅱb, 10.4% (72/691) for type Ⅲa, 3.9% (27/691) for type Ⅲb, 16.6% (115/691) for type Ⅲc. There was no statistical significance difference in baseline data between 2 groups (all P>0.05). All patients were followed up for more than 6 months. The postoperative nerve injury rate of experimental group was significantly lower than that of control group (1.2% vs. 7.5%, χ²=12.659, P<0.001), and the VHI-10 scores and laryngoscope results of experimental group were better than those of control group in three follow-up visits (P<0.001). With postoperative laryngoscope examination, 3 patients in the experimental group and 23 patients in the control group showed vocal cord relaxation, bilateral oblique asymmetry and other phenomena, which were considered as the results of permanent injury. Other patients with symptoms were relieved to varying degrees during the follow-up, and their symptoms were considered as the results of temporary injury. Conclusion: IONM combined with "classification of EBSLN" can reduce significantly the risk of EBSLN injury in thyroidectomy, which is better than direct ligation of branches without attempts to visually identify the nerve.

Associations of psychological resilience with family cohesion and non-suicidal self-injury of middle school students in Fujian Province / 中国学校卫生

Objective@#To explore the relationship between family cohesion, psychological resilience and non-suicidal self-injury among middle school students.@*Methods@#By using the stratified random cluster sampling method, 2 065 students from 4 middle school from Fujian province were investigated with family cohesion scale, adolescent psychological resilience scale and adolescent self-injury behavior questionnaire.@*Results@#The report rate of self-injury was 40.34%, which differed by childhood migration experiences, parenting style as well as academic pressure (χ2=11.66，29.45，12.48，P<0.01). Total scores and dimensional scales in family cohesion and psychological resilience showed significant differences in students with or without self-injury (t=-8.33，-12.08，-7.29，-11.53，-3.38，-7.37，-7.68，P<0.01). The family cohesion was positively correlated with the psychological resilience and each dimension (r=0.27-0.56, P<0.01), but negatively correlated with non-suicidal self-injury (r=-0.18, P<0.01). The psychological resilience and each dimension were negatively correlated with non-suicidal self-injury (r=-0.24--0.14, P<0.01). Psychological resilience had a partial mediating effect between family cohesion and non-suicidal self-injury, with mediating effect accounting for 61.11% of the total effect.@*Conclusion@#Psychological resilience played a mediating role between family cohesion and non-suicidal self-injury. By promoting family cohesion to improve psychological resilience, it is helpful to prevent non-suicidal self-injury among middle school students.

Effect and Mechanism of Yishen Simiaotang on Gouty Nephropathy with Renal Failure / 中国实验方剂学杂志

Objective: To analyze the therapeutic effect and mechanism of Yishen Simiaotang on gouty nephropathy (GN) complicated with renal failure (RF). Method: Totally 96 cases of GN with RF treated at our hospital from March 2015 to December 2017 were divided into the control group (48 cases) and the observation group (48 cases) according to the random control principle. In addition to the basic therapy, allopurinol was added to the control group, and Yishen Simiaotang was added to observation group. After 2 months of treatment, the clinical efficacy and safety of two groups were compared. The urinary levels of β2-microglobulin (β2-MG), α1-microglobulin (α1-MG), 24 h urine protein (24 hUpro) and glomerular filtration rate (eGFR) were compared between two groups before and after treatment, and the levels of serum albumin (ALB), urea nitrogen (BUN), serum creatinine (SCr) and uric acid (UA) were detected and compared before and after the treatment. The serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and hypersensitivity C reactive protein (hs-CRP) were compared before and after treatment between two groups. Result: The total effective rate of observation group was 89.58%, which was significantly higher than 72.92%of control group (χ2=4.376,PPβ2-MG, α1-MG, 24 hUpro in both groups decreased significantly (PPα, hs-CRP and IL-6 in both groups were significantly lower than those before treatment, and the decrease in observation group was more obvious than that in control group (PConclusion: Yishen Simiaotang is effective in the treatment of GN combined with RF, and can reduce renal tubule injury, improve renal function, regulate the state of micro-inflammation, with a high safety.

Effect of Eylea on recombinant AAV2-VEGF-induced choroidal neovascularization / 中华实验眼科杂志

Objective To evaluate the effect of Eylea (aflibercept) on recombinant adeno-associated virus 2 (AAV2)-vascular endothelial growth factor (VEGF)-induced choroidal neovascularization (CNV).Methods Two normal cynomolgus monkeys were used in this study.Recombinant AAV2-VEGF was delivered by subretinal injection (60 μl/eye,7.0×1011 IU/ml) into both eyes for each cynomolgus monkey.Both eyes of one animal were treated with single intravitreal injection of Eylea (50 μl/eye,40 mg/ml) 3 weeks after AAV2-VEGF injection,and the two eyes of the other animal were untreated.Optical coherence tomography (OCT),electroretinography (ERG),fluorescein angiography (FFA) and ocular photography were conducted.The experiment was approved by the Institutional Animal Care and Use Committee (IACUC) at JOINN Laboratories (Suzhou) (IACUC serial number:ACU15-1112).Results OCT showed that subretinal hyperreflective material,retinal edema,choroid edema and local pigment epithelial detachment were found after injection of recombinant AAV2-VEGF.All of those symptoms were relieved after treated with Eylea,but aggravated after 4 weeks treated with Eylea.FFA showed that the area of fluorescein leakage expanded obviously after 2 weeks treated with AAV2-VEGF,and it was observed at the whole of fundus posterior pole at 5 weeks after injection.After 1 week treated with Eylea,the area of fluorescein leakage decreased obviously,but increased gradually after 4 weeks treated with Eylea.ERG results showed that the amplitude of ERG decreased gradually after injection of recombinant AAV2-VEGF.After intravitreal injection of Eylea,the amplitude of ERG increased gradually,but it decreased again after 4 weeks treated with Eylea.Conclusions Injection of recombinant AAV2-VEGF is capable of inducing CNV and pathological retinal in cynomolgus monkey.Eylea can prevent the development of clinically relevant CNV,but the effect just lasts for a period.

Effects of short-chain acyl-CoA dehydrogenase on hypertensive vascular remodeling / 中国病理生理杂志

AIM:To investigate the changes of short-chain acyl-CoA dehydrogenase(SCAD)in hypertensive vascular remodeling and to explore the relationship between SCAD and vascular remodeling in hypertension.METHODS:The spontaneously hypertensive rats(SHR;24 weeks old)and Wistar rats(24 weeks old)were used as experimental con-trol groups.The SHR and Wistar rats of 16 weeks old were trained by swimming as experimental groups.The systolic pres-sure was measured periodically.The thickness of vascular wall and the diameter of the vascular lumen were measured.The contents of ROS and ATP,the enzyme activity of SCAD, and the expression of SCAD at mRNA and protein levels in the aorta were determined.The free fatty acid in the serum and aorta was also measured.RESULTS:Compared with Wistar group,the diameter of vascular lumen decreased in SHR group.The thickness of vascular wall,the ratio of vascular wall and the diameter of vascular lumen,and the blood pressure in SHR group were increased significantly(P<0.05).Com-pared with SHR group,the diameter of vascular lumen increased in SHR +swim group.The thickness of vascular wall,the ratio of vascular wall and the diameter of vascular lumen,and the blood pressure in SHR +swim group were decreased sig-nificantly.Compared with control group, the expression of SCAD at mRNA and protein levels, the enzyme activity of SCAD,and the content of ATP were decreased in SHR group.However,the free fatty acid in the serum and aorta,and the content of ROS in the aorta were increased in SHR group.The expression of SCAD at mRNA and protein levels,the en-zyme activity of SCAD,the content of ATP were increased in Wistar +swim group and SHR +swim group.However, the free fatty acid in serum and aorta,and the content of ROS in the aorta were decreased in Wistar +swim group and SHR+swim group.CONCLUSION: Decrease in SCAD expression may be associated with hypertensive vascular remodeling. Swimming training can reverse hypertensive vascular remodeling by increasing the expression of SCAD in the aorta.

A retrospective study of diabetes in middle-aged and elderly urban population in Hainan, south China

Objective:To investigate the distribution characteristics and epidemic trends of diabetes in middle-aged and elderly urban Hainanese, and to explore the correlations between diabetes and hypertension or hyperlipidemia in this kind of people.Methods:Middle-aged and elderly urban Hainanese (35–74 years old) were examined at the Medical Center of the Second Affiliated Hospital of Hainan Medical University from 2013 to 2017. According to the World Health Organiza-tion (WHO) Diabetes Diagnostic Criteria 1999, subjects with fasting blood glucose (FBG) level ⩾7.0 mmol/L (126 mg/dL) were diagnosed as diabetes. The retrospective analysis of the collected cleared data was conducted by using chi-square test, single factor correlation analysis and multiple linear regression analysis methods [gender: X1 (male=1, female=2); age: X2 (35–44=1, 45–54=2, 55–64=3, 65–74=4). The test level was set as 0.05. All data were standardized by age according to the 6th National Census Data 2010.Results:A total of 69 077 middle-aged and elderly observations’ data in 2013–2017 were collected. The detection rates of diabetes were 8.28%, 8.89%, 10.71%, 8.29%, and 9.21% respectively by year (χConclusions:The detection rate of diabetes in middle-aged and elderly urban Hainanese increased in the past five years and it was linearly related with gender and age; weak correlations between diabetes and hypertension or hyperlipidemia were observed. Further prospective studies should be done in the future.

Clinical analysis of cerebellar infarction with vertebral artery hypoplasia / 中国医师进修杂志

Objective To summarize the clinical features and vascular lesions in patients who suffered from cerebellar infarction with vertebral artery hypoplasia(VAH). Methods Retrospective analysis was used in the research. The selected patients suffered from cerebellar infarction with VAH or stenosis (stenosis rate≥50%). Seventy-one patients with cerebellar infarction were enrolled. There were 34 patients in VAH group and 37 patients in vertebral artery stenosis group. The age, sex, risk factors, clinical manifestations and characteristics of vascular examination were compared. Results The age, sex, risk factors between two groups had no significant differences (P>0.05). The scores of National Institutes of Health Stroke Scale (NIHSS) between two groups had no significant difference (P>0.05). The proportion of early neurological deterioration in VAH group (41.2%, 14/34) was higher than that in vertebral artery stenosis group (18.9%, 7/37), χ2=4.21, P<0.05. There were more patients with anterior circulation artery stenosis in the VAH group (35.3%, 12/34), compared with that in artery stenosis group (13.5%, 5/37),χ2=4.62, P<0.05. Except the ipsilateral vertebral artery, other arteries stenosis in VAH group (44.1%, 15/34) was significantly higher than that in vertebral artery stenosis group (13.5%, 5/37),χ2=8.20, P<0.05. Conclusions Cerebellar infarction with vertebral artery hypoplasia is more likely to have multiple cerebral arterial stenosis (stenosis rate ≥50%). The patients who suffered from cerebellar infarction with vertebral artery hypoplasia might be prone to early neurological deterioration.