Background The penetration of bacterial agents into the vitreous cavity is difficult because of the existence of blood-retina barrier.So conventional drug therapy is not enough effective on endophthalmitis.Drug delivery systems can decrease drug dose and reduce the drug toxicity.To construct nano controlled-release system of anti-bacterial agents is very important for the treatment of intraocular infectious diseases.Objective This study was to investigate the toxicology and intraocular pharmacoklnetics of intravitreal PNIPAAm-PEO loaded norvancomycin nanoparticles (NV-PNIPAAm-PEO) in normal rabbit eyes.Methods NV-PNIPAAm-PEO was constructed with the drug-loading rate about 22％,and then the drug gelatin solution (20 g/L) was prepared using normal saline solution.Forty-one New Zealand albino rabbits were randomized divided into experimental group and control group.20 g/L drug gelatin solution 0.1 ml was monocularly injected into the vitreous cavity in the experimental group,and the equal volume of sterilized normal saline solution was used in the control group.In 1 day,2,3,7,14,21 and 28 days after injection,ocular anterior and posterior segments were examined by slit lamp microscope and Bsonography,and electroretinogram (ERG) was recorded and the histopathological examination was performed to evaluate the biotoxicity of the drug.Norvancomycin contents in the cornea homogenate,aqueous humor,vitreous,retinochoroid homogenate were detected by high performance liquid chromatography (HPLC) system.Results The anterior and posterior segments were normal by the slit lamp microscope and B-sonography 1-28 days after injection of NV-PNIPAAm-PEO.In 7,14,21 and 28 days after injection,there were no statistically significant difference in the a-wave latency and amplitude of max-ERG between the two groups,as well as the b-wave amplitude(P＞0.05).The histopathological examination showed that the retinal structure was normal in both groups.HPLC assay showed that the norvancomycin level was gradually declined in different eye tissues from 1 day through 28 days after injection.Norvancomycin was undetectable in the cornea during the observing duration.The maximal norvancomycin content in the blood plasma was (0.34 ± 0.11) mg/L in the second day,and norvancomycin content ranged (0.08 ± 0.04)-(2.16±0.07) mg/L in the aqueous humor,(0.11 ±0.22)-(2.54 ±0.38) μg/g in the chorioretina,respectively.The drug concentration was (5.65 ± 1.14)-(406.69 ± 21.05) mg/L in the vitreous,which was higher than the minimal inhibitory concentration (MIC) to the most gram-positive bacteria.Conclusions The intravitreal injection of 22％ NV-PNIPAAm-PEO maintains the therapeutic drug concentration till 21 days in vitreous without the toxic effect on eye tissues,suggesting a great treating potential for intraocular infecting diseases.

To better understand the drugs, frequency and other factors involved in the drug-induced renal failure, 227 cases of renal failure reported in the Chinese medical and pharmaceutical journals were statistically analyzed. Our results showed that the drugs that tend to cause renal failure are antibiotics, involving 80 cases, followed by antituberculosis agents(38 eases)and dehydration agents. Gentamycin (47 cases) and rifrimactane(36 cases) were among the drugs with highest incidence. There were 58 cases of death due to drug-related renal failure.

Objective To explore the pregnancy outcome and obstetric management of pregnancy and delivery after vaginal radical trachelectomy (VRT).Methods Forty-two cases of VRT from December 2003 to May 2012 in Peking Union Medical College Hospital were analyzed retrospectively.Among them ten cases got pregnant successfully.Results The average age of patient at VRT surgery was (30.6 ± 3.7) years old and average follow-up time was 29.5 months.There were 31 patients attempted conception.Ten of them got fourteen conceptions successfully.Overall conception rate was 45％ (14/31).There were four cases of first trimester abortion.Among them,two were miscarriage,two were elective abortion.There was one case of ectopic pregnancy operation and non of second trimester loss.Nine cases reached the third trimester.The total preterm delivery rate was 4/9.There were two cases delivered before 32 gestational weeks (2/9).Cesarean section was performed through a transverse incision in all of nine cases.No uterine rupture and postpartum hemorrhage occurred.All newborns had good outcomes.The average follow-up time after postpartum was 22.9 months.All cases were disease-free.Conclusions The conception rate of patients after VRT in our series is 45％.The preterm birth rate of pregnancy after VRT is higher.Routine cerclage of cervix during VRT procedure and pregnancy is not necessary.Cesarean section shortly after full term pregnancy through a transverse incision should be considered as a suitable and safe procedure.

Objective:To investigate the detection rate of motoric cognitive risk(MCR)syndrome and explore the possible risk factors at different age groups.Methods:A total of 561 patients from geriatric outpatient clinic of Hubei Provincial Hospital of Traditional Chinese Medicine from November 2018 to December 2019 were divided into two age groups under 70 years old(n=241)and 70 years old and above(n=320). The general information, Pittsburgh Sleep Quality Index, Geriatric Depression Scale-15(GDS-15), 4-meter walking test, Mini-Mental State Examination and Morse Fall Scale were collected.Patients with MCR were screened out according to the MCR diagnostic criteria.Logistic multiple regression analysis was used to analyze the associated risk factors.Results:7 cases(7/241, 2.9%)met the MCR diagnostic criteria in age<70 years group, and 34 cases(34/320, 10.7%)in age ≥ 70 years group.The proportion of hearing impairment complaints and GDS-15 scores of MCR patients were higher than those of the non-MCR group in age<70 years group, and the Morse Fall Scale of MCR patients was higher than that of the non-MCR group in age ≥70 years old group( P<0.05). After adjusting for associated confounding factors, multiple logistic regression analysis showed that hearing impairment complaints( OR=26.394, P<0.05)and GDS-15( OR=1.385, P<0.05)were independent risk factors for MCR in age<70 years group.And female( OR=0.445, P<0.05)was a protective factor for MCR in age ≥70 years old group. Conclusions:Motoric cognitive risk syndrome has different risk factors in different age groups, which may indicate that the causes and predictive significance of MCR in these two different age groups are different.

This study aimed to establish human IFN-gamma (hIFN-gamma) in vitro release assay and to apply it in diagnosis of human tuberculosis. Human IFN-gamma gene was cloned and expressed in Escherichia coli. The recombinant hIFN-gamma was purified and used as immunogen to immunize mice and rabbits respectively. Monoclonal and polyclonal antibodies were respectively developed and a sandwich ELISA was established. The heparized whole blood from 111 active tuberculosis patients and 292 clinical healthy controls were collected. The blood was stimulated with tuberculosis specific fused antigen ESAT-6/CFP-10 and the plasma was collected for IFN-gamma detection. The sensitivity for tuberculosis diagnosis was 95.5%, whereas the positive detection rate for the healthy controls was 16.7%. There was a significant difference between the patients and healthy controls (P<0.01) indicating that this assay had a high sensitivity and specificity, and thus could be promising in tuberculosis diagnosis.
Animals ; Antibodies, Monoclonal ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Interferon-gamma ; immunology ; secretion ; Mice ; Mice, Inbred BALB C ; Mycobacterium tuberculosis ; immunology ; Rabbits ; T-Lymphocytes ; immunology ; Tuberculosis ; diagnosis ; immunology

Objective To investigate risk factors for and clinical features of steroid-induced diabetes mellitus due to glucocorticoid treatment.Methods Clinical data were collected from 798 patients who received systemic glucocorticoid treatment in Department of Dermatology of Hangzhou Third People's Hospital from 2013 to 2016,and analyzed retrospectively.Logistic regression analysis was performed to analyze the factors influencing the occurrence of steroid-induced diabetes mellitus (SDM),repeatedmeasures analysis of variance to compare peripheral blood glucose levels of patients with SDM after breakfast,lunch and dinner,and t test to compare the levels of fasting blood glucose and glycosylated hemoglobin (HbA1 c) between patients with SDM and those with type 2 diabetes mellitus.Results Of the 798 patients,38 developed SDM due to glucocorticoid treatment.The average age was significantly older in the patients with SDM ([66.86 ± 13.30] years,n =38) than in those without SDM ([39.95 ± 17.01] years,n =760;t =8.86,P ＜ 0.01),but there was no significant difference in the gender ratio between the patients with and thhose without SDM (x2 =1.61,P =0.20).The prevalence of fatty liver,hyperlipidemia,hypertension,abnormal liver function and family history of diabetes mellitus was significantly higher in the patients with SDM than in those without SDM (x2 =12.25,19.25,32.69,21.47,16.70 respectively,all P ＜0.01).Logistic regression analysis showed that age,fatty liver,hyperlipidemia,hypertension,abnormal liver function,dosage of glucocorticoids,duration of glucocorticoid therapy,use of immunosuppressive agents and family history of diabetes mellitus were risk factors for SDM (all P ＜ 0.05).There were no significant differences in fasting blood glucose levels or postprandial peripheral blood glucose levels among the SDM patients receiving glucocorticoid therapy at different dosages of 0.50-0.74,0.75-0.99,1.00-1.25 mg·kg-1· d-1 (P ＞ 0.05).The peripheral blood glucose levels after breakfast,lunch and dinner were (11.50 ± 2.90),(16.02 ± 5.81) and (16.81 ± 4.52) mmol/L respectively in the patients with SDM.The levels of fasting blood glucose and glycosylated HbA 1 c were both significantly lower in the patients with SDM than in those with type 2 diabetes mellitus (t =3.74,9.92 respectively,both P ＜ 0.001).Conclusions The risk factors for SDM are age,dosage of glucocorticoids,duration of glucocorticoid therapy,fatty liver,hyperlipidemia,hypertension,abnormal liver function,use of immunosuppressive agents and family history of diabetes mellitus.The patients with SDM showed obviously elevated blood glucose levels mostly after lunch and dinner,but slightly increased levels of fasting blood glucose and glycosylated HbA 1c,which can be used to distinguish between SDM and type 2 diabetes mellitus.

Objective To analyze the clinocopathological characteristics of infectious granulomas.Methods The clinical features,histopathological manifestations of 39 patients with infectious granulomas were analyzed retrospectively.Results Among 39 cases of infectious granulomas,there were 15 males and 24 females,and 17 cases of fungal granuloma and 22 cases of tuberculous granuloma.There was no statistically significant difference in gender and age between fungal granulomas and tuberculous granulomas.The mean course of tuberculous granuloma aud tuberculous granuloma was (0.88 ± 0.67) years and (5.54 ± 3.49) years,respectively (t =4.51,P =0.00);there was no significant difference in mean age of onset in fungal granuloma patients and tuberculous granuloma patients [(54.6 ± 19.6) vs.(47.6 ± 18.1) years,P ＞0.05)].There were 4 and 18 cases of fungal and tuberculous granulomatosis at the face,and 13 and 3 cases at the extremities (all P =0.00);the lesions occurred in the trunk in one case of tuberculous granuloma.The clinical manifestations of fungal and tuberculous granulomas as plaques/nodules were in 14 cases aud 22 cases (P =0.08);as ulcers and pus exudates were in 10 and 2 cases,respectively (P =0.00).The histopathological features showed epidermal hyperplasia in 12 and 4 cases,infiltrative patterns in 4 and 21 cases,infiltration of neutrophils in 14 and 3 cases,infiltration of plasma cells in 15 and 5 cases,infiltration of eosinophils in 10 and 0 cases,necrosis in 1 and 10 cases in fungal granulomas and tuberculous granulomas,respectively (P =0.00,0.00,0.00,0.00,0.00,0.01).Conclusion Fungal granuloma and tuberculous granuloma are different in the lesion sites,clinical manifestations and histopathological features.

ObjectiveTo explore the mechanism of modified Shuyuwan in treating vascular dementia （VaD） complicated with depression in mice. MethodThe VaD model was established by bilateral carotid artery stenosis （BCAS） in seven 3-month-old male C57/BL6 mice. The regional cerebral blood flow （rCBF） of mice was measured by laser speckle imaging before and after BCAS surgery. Then， the BCAS method was combined with chronic unpredictable mild stress （CUMS） to establish a mouse model of VaD complicated with depression. BCAS/CUMS mice were assigned into BCAS/CUMS， fluoxetine （0.01 g·kg^-1）， and high-， medium-， and low-dose （20， 10， 5 g·kg^-1， respectively） modified Shuyuwan groups. The shame group underwent sham operation without CUMS （n=10）. The tail suspension test and sucrose preference test were carried out to examine the depressive behaviors of mice. The distribution and expression of myelin-associated glycoprotein （MAG）， myelin basic protein （MBP）， neurofilament heavy polypeptide （NF200）， and anti-non-phosphorylated neurofilament epitope antibody （SMI32） in the corpus callosum （CC） were detected by the immunofluorescence assay. Western blot was employed to determine the protein levels of monocarboxylate transporter 1 （MCT1）， MBP， MAG， oligodendrocyte glycoprotein （MOG）， amyloid precursor protein （APP）， NF200， contactin-associated protein （Caspr）， and voltage-gated sodium channel （Nav1.6） in the corpus callosum. The level of lactic acid in the serum was measured by the lactic acid assay kit， and the ultrastructure of myelin was observed by ultraprojective electron microscope. ResultLaser speckle imaging showed that rCBF decreased immediately 10 min after BCAS surgery （P<0.01）， and the rCBF was still cerebral hypoperfusion and did not return to the preoperative level 2 weeks after surgery. Behavioral test results showed that compared with the sham group， the BCAS/CUMS group presented decreased percentage of sucrose preference （P<0.01） and prolonged immobile time in the tail suspension test （P<0.01）. Compared with the BCAS/CUMS group， fluoxetine and modified Shuyuwan increased the percentage of sucrose preference （P<0.01） and shortened the immobile time in the tail suspension test （P<0.01）. The level of lactic acid was the highest in the BCAS/CUMS mice （P<0.01）， and modified Shuyuwan lowered the lactic acid level （P<0.01）. Immunofluorescence results showed that compared with the sham group， the BCAS/CUMS group presented decreased fluorescence intensity of MAG， MBP and NF200 and increased fluorescence intensity of SMI32 in the corpus callosum， and such changes were reversed by modified Shuyuwan at different doses and fluoxetine. Western blot results showed that compared with the sham group， the BCAS/CUMS modeling down-regulated the protein levels of MCT1， MBP， MOG， MAG， NF20， and Caspr （P<0.05， P<0.01） and up-regulated the protein levels of APP and Nav1.6 in the corpus callosum， and the above trends were reversed by modified Shuyuwan （P<0.05， P<0.01）. Compared with the sham group， BCAS/CUMS modeling led to myelin ultrastructure damage and axon atrophy， which were alleviated by modified Shuyuwan. ConclusionModified Shuyuwan can ameliorate the transport disorder of lactic acid between myelin sheath and axon by upregulating the expressin of MCT1， promote the regeneration of myelin sheath in the corpus callosum， and improve the integrity of myelin sheath structure， thereby alleviating depression in VaD mice.