The preclinical safety assessment of hepatotoxicity drugs has a low sensitivity and low specificity. Related tests often generate false negative results and unexpected toxicity,which is one of the major reasons for the cessation of development and withdrawal from the market. Proteomics enjoys advantages of rapidness,high sensitivity and high throughout,and therefore can be used in the search for new biomarkers of hepatotoxicity in preclinical studies,leading to the development of safer drugs and a more efficient drug discovery process. In this review,the current preclinical biomark?ers of liver toxicity and development of proteomic technologies in the discovery and validation of bio?markers of drug-induced liver injury are described,in general the application of proteomics to Chinese medicine-induced liver toxicity in particular. Compared with traditional methods,proteomic technologies show promising results for the discovery of novel hepatotoxic markers. Proteomics,in conjugation with other omics techniques,will play a major role in the early stage of hepatotoxicity screening and will prove to be a good bridge in clinics in the future.

Objective To explore the high risk factors of brain injury in preterm infants,and to reduce its morbidity and improve the developmental outcome.Methods One hundred and thirty preterm infants,who were admitted to our neonatal intensive care unit(NICU)between Aug.2005 and Aug.2007,were scanned by echo in 1,3,4,7,15 days,and 1,3 and 6 months after birth,respectively.Those who had intraventricular hemorrhage(IVH)of grade Ⅰor Ⅱ were regarded as mild brain injury,whereas those who had IVH of grade Ⅲ or Ⅳ or periventricular leukomalacia(PVL)were regarded as severe brain injury.Logistic regression was adopted to analyze 17 factors:gestational age,birth weight,hypertension syndrome during pregnancy,premature rupture of membranes,modalities of delivery,fetal distress,asphy-xiate,resuscitation,surfactant,apnea,seizures,hypoxia,hypercarbia,hypocarbia,acidosis,use of oxygen,nasal constant positive airway pressure or mechanical ventilation.Results Among 130 preterm infants,88 cases(66.7%)were detected with brain injury,which included 29 cases(33%)with mild brain injury(5 cases with IVH of grade Ⅰ,24 cases with IVH of grade Ⅱ)and 59 cases(67%)with severe brain injury(53 cases with IVH of grade Ⅲ,1 case with IVH of grade Ⅳ and 5 cases with PVL).Gestational age and birth weight were the fundamental factors of brain injury in premature infants.The smaller the gestational age and the lower the birth weight,the highter the brain injury rate.Resuscitation,hypoxia,the use of auxiliary ventilation were also important high risk factors of brain injury in preterm infants.All these high risk factors could influence the autoregulation of cerebral blood and trigger or aggravate brain injury of preterm infants.Conclusions Smaller gestational age,lower birth weight,resuscitation,hypoxia,the use of auxiliary ventilation were all the high risk factors of brain injury in premature infants,which could influence the parameters of cerebral blood dynamics by influencing cerebral blood autoregulation of preterm infants and lead to the occurrence of brain injury in premature.

OBJECTIVE: To study the preparation of carboxylated multi-walled carbon nanotubes loaded with podophyllotoxin (PPT-CNTs-COOH) as well as the characteristics of the in vitro transdermal penetration. METHODS: PPT-CNTs-COOH was prepared by freezing milling method; IR, UV, XRD, and TGA were used to characterize the PPT-CNTs-COOH; HPLC method was used for determination of the content of podophyllotoxin loaded in the carboxylated multi-walled carbon nanotubes; franze diffusion cells method was used to determine the drug transdermal penetration rate. RESULTS: The IR spectrum of PPT-CNTs-COOH showed the main absorption peaks of PPT and CNTs-COOH and the peaks changed obviously. Compared with free PPT, the UV absorption peaks of PPT-CNTs-COOH changed obviously. The PPT content in the CNTs-COOH gel was 58.0 μg·mg-1; the transdermal penetration rate of PPT gel was 7.08 μg·cm-2·h-1 and that of the PPT-CNTs-COOH gel was 3.03 μg·cm-2·h-1; the skin retention of PPT-CNTs-COOH gel was 3.04 μg·cm-2, far less than the 1.52 μg·cm-2 of PPT gel. Mild irritation developed within 24 h following removal of the PPT-CNTs-COOH gel, and disappears after 72 h. CONCLUSION: Podophyllotoxin can successfully be loaded into the carboxylated multi-wall carbon nanotubes by using the frozen ball milling method. The product has remarkable sustained release effect in vitro and high retention in skin, which is beneficial to transdermal delivery.

Abstract: Objective To analyze the application effect of rapid diagnostic techniques in Shaanxi from 2016 to 2020,and to provide basis for further optimizing the process of tuberculosis detection and formulating prevention and control strategies. Methods A total of 104 437 cases of tuberculosis patients registered in Shaanxi Province from 2016-2020 were exported from the Tuberculosis Information Management System (The subsystem of China Disease Prevention and Control Information System) according to first management unit, and the laboratory test results of sputum smear, sputum culture and molecular tests were collected to statistically analyzed the positive rate of etiology, sputum smear, sputum culture, molecular biology testing rate, and indicators of positive testing rate of tuberculosis patients. Results From 2016 to 2020, the etiology�positive rate of tuberculosis in Shaanxi province were 13.49% (2 664/19 754), 22.68% (5 081/22 401), 35.99% (8 232/22 876), 48.14% (10 438 / 21 682), 52.65% (9 332 / 17 724), respectively, with an increasing trend (χ2 trend=9 473.12, P<0.001) year by year; the proportion of molecular tests positive only in etiology-positive pulmonary tuberculosis (PTB) were 0 (0/2 664), 0.16% (8/5 081), 15.44% (1 271/8 232), 27.58% (2 879/10 438), 31.52% (2 941/9 332), respectively, with an increasing trend year by year (χ2 trend=2 971.44, P<0.001); the molecular test rates of the 5 years were 0.01% (2 / 19 754), 0.38%(85 / 22 401), 21.11% (4 828/22 876), 52.42%(11 365/21 682), 55.18%(9 780/17 724), respectively, with an increasing trend year by year (χ2 trend = 28 269.23, P<0.001). The rate of molecular test in sputum smear-negative was 22.72%(17 976 / 79 130). The proportion of patients with only molecular test-positive was 33.43% (4 032/12 062) in municipal designated hospitals, and 11.99%(2 279/ 19 014) in county-level designated hospitals, the difference was statistically significant (χ2 =2 096.46, P<0.001). Conclusions The rate of molecular biology testing in Shaanxi Province from 2016 to 2020 showed a year-on-year increase. Through the application of rapid molecular tests, the etiology-positive rates of tuberculosis have been increased significantly,but the current molecular test detection rate is not high compared with other provinces, especially in county-level designated hospitals and smear-negative patients, so we should make a big promotion in application of rapid molecular technique.

Objective:To investigate the correlation between hyperreflective dots (HRD) and lipid levels and systemic inflammatory factors in patients with branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO).Methods:A cross-sectional clinical study. From December 2016 to June 2020, 118 eyes of 118 patients with retinal vein occlusion diagnosed in the Department of Ophthalmology, Central Theater Command Hospital of People's Liberation Army were included in the study. Among them, 67 cases of BRVO and 51 cases of CRVO were divided into CRVO group and BRVO group accordingly. Peripheral venous blood was drawn from the patients within 3 days after the eye examination to detect the percentage of neutrophils, monocytes, hypersensitive C-reactive protein (CRP), total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and lipoprotein(a). The ratio of monocytes to high-density lipoprotein (MHR) was also calculated. The 3D OCT-2000 instrument from Topcon (Japan) was used to measure the central retinal thickness (CRT) and the numbers of HRD. According to the different distribution position, HRD is divided into inner retina HRD, outer retina HRD, and total retina HRD.The independent sample t test was used to compare the continuous variables of the two groups, and the χ2 test was used to compare the rates. The correlation between HRD counts and blood lipid levels and peripheral blood inflammation indicators in patients with different types of RVO was analyzed by Spearman correlation analysis. Results:The average age of patients in the BRVO group and CRVO group were 60.1±9.5 and 53.6±15.7 years, respectively; the prevalence of hypertension was 53.7% (36/67) and 24.5% (12/51), respectively. Comparison of age ( t=2.634) and prevalence of hypertension ( χ2=11.298) between the two groups showed statistically significant differences ( P<0.05). Gender ( χ2=2.000), course of disease ( t=-1.101), prevalence of diabetes ( χ2=1.315), eye category ( χ2=1.742), baseline visual acuity ( t=1.792), intraocular pressure ( t=0.708), CRT ( t=1.318), and peripheral blood include the percentage of neutrophils, the absolute number of monocytes, CRP, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, lipoprotein(a), MHR ( t=-0.559, 1.126, 0.579, 1.299, -0.134, 0.556, 1.230, -0.267, 0.483), the difference was not statistically significant. Correlation analysis showed that the HRD counts in the outer retina of BRVO patients were positively correlated with total cholesterol ( r=0.289, P=0.036); the HRD in the inner retina and total HRD counts of CRVO patients were positively correlated with CRP ( r=0.406, 0.343; P=0.004, 0.014). There was no correlation between HRD counts and percentage of neutrophils, absolute number of monocytes, triglycerides, high-density lipoprotein, low-density lipoprotein, lipoprotein(a), and MHR ( P>0.05). Conclusion:The number of HRD is related to the blood lipid level in BRVO patients and CRP (an inflammatory index) in CRVO patients.

Eustachian Tube ; abnormalities ; surgery ; Humans ; Laser Therapy ; Male ; Middle Aged ; Prosthesis Implantation ; Stents ; Tympanoplasty

BACKGROUND: Current research of mechano growth factor (MGF) mainly focuses on the muscles and nerve damage and repair, and it has bean confirmed that MGF can promote muscle cell hypertrophy and nerve repair significantly. Regarding its role in fracture healing is unclear. OBJECTIVE: To investigate the effect of MGF on radial fracture healing in rabbits. METHODS: By using random digital table method, 12 New Zealand rabbits were divided into 3 groups: blank control group, low-dose MGF group and high-dose MGF group. The models with 5 mm bone defect were produced in the middle of the left radius in rabbits. At 3 days after the surgical operation, the defective areas were given 0.2 mL PBS or 0.2 mL MGF (0.36 and 0.72 g/L) injected into the ends of fracture areas, respectively, once per day for continuous 5 days. At 4, 6, 8 weeks after operation, X-ray photography was used to evaluate the healing of fracture, and the histological examinations were performed at the 8~(th) weak to observe the call morphology at the fracture lesion. RESULTS AND CONCLUSION: At 1 day after operation, the activities of rabbits were reduced, with slightly reduced food intake, at 2 days they almost recovered to normal activities and diet. At 3 days, the surgical incision slightly swelled with a small amount of bleeding and without obvious signs of infection. All 12 rabbits entered the final analysis. X-rays showed that two fracture ends have basically combined in the high-dose MGF group at 4 weeks post-surgery, cortical bone was continuous and fracture lines were unclear. At 6 weaks the bone medullary cavity almost run through and fully run through at 8 weeks. The healing time in the high-dose MGF group was remarkably shorter than that in blank control group and low-dose MGF group, the healing was in high quality. At 8 weeks after operation, a large number of osteoid tissues were observed in the blank control group, a small amount of woven bone formed, at a transition period from the fibrous bone callus to the bony bone callus; a large number of woven bone formed inthe low-dose MGF group, at bony bone callus period; in the high-dose MGF group, a large number of woven bones converted into mature lamellar bone, at the callus rebuilding phase, which was consistent with imaging results. It is indicated that MGF can accelerate fracture healing significantly in a rabbit model and shows a dose-dependent manner in a certain range.

The Epstein-Barr virus latent membrane protein 1 (LMP1) oncopro tein causes multiple cellular changes, including activation of the NF-κB trans cription factor. To elucidate its possible mechanism, the interaction between LM P1 and the tumor necrosis factor receptor associated factor (TRAF) molecules was detected by the immunoprecipitation-Western blotting assay. Results showed tha t LMP1 was co-precipitated with TRAF1,2,3 in the LMP1-HNE2 cell line. In the m eantime, κB reporter gene analysis revealed that over expression of TRAF1 or TR AF2 augmented LMP1-mediated NF-κB activation from LMP1, suprisingly, overexpr ession of either TRAF3 or an dominant negative TRAF3 inhibited the NF-κB activ ation, indicating that TRAF1 or TRAF2 is a positive modulator of LMP1-mediated NF-κB activation, whereas,TRAF3 is a negative modulator. Rather both CTAR1 (carboxy-terminal activating region 1) and CTAR2 domains of LMP1 can independently activate NF-κB by interacting with TRAF proteins. These data indicate that LMP1 interacts TRAF1,2,3 which are important for LMP1-mediated N F-κB activation, and further suggest that signaling from TRAFs may be involved in the progression to malignancy in cells of epithelial origin such as nasophar yngeal carcinoma (NPC).

Mild-symptom erectile dysfunction (MSED) is commonly seen in clinical practice, but receives inadequate attention from both the patients and clinicians. Increasing researches have indicated that MSED is associated with not only unhealthy living habits and psychological factors but also the early progression of endothelial, metabolic and endocrine diseases. The diagnosis and treatment of MSED should be based on the relevant guidelines, with consideration of both its specific and common features. The therapeutic principle is a combination of integrated and individual solutions aimed at the causes of the disease. Drug intervention should be initiated if psychological therapy fails. Negligence of MSED may affect the quality of life of the patients and their partners, and what's more, might delay the management of some other severe underlying diseases. Adequate attention to the early diagnosis and treatment for MSED is of great significance for a deeper insight into the etiology of ED, the prevention of potential cardiovascular and metabolic diseases, and the improvement of the overall health of males.
Attention ; Erectile Dysfunction ; diagnosis ; etiology ; therapy ; Humans ; Male ; Quality of Life

There is no a systemic performance metrics for clinical data management. While the CDMC in China starts to develop the quality metrics for clinical data management, it is essential to think over the performance and pursue metrics implementation of clinical data management in China. This article provides the basic concept, development and implementation of the performance metric in clinical data management.
China ; Clinical Trials as Topic ; standards ; Data Collection ; standards ; Information Storage and Retrieval ; standards