ObjectiveTo study the clinical features and pathogenesis of ophthalmoplegia in senile patients with diabetes, and access the possibility of its development.MethodsBesides routine ophthalmologic and ocular muscle examination, general and laboratory examinations were also done. Some patients were diagnosed also with the help of image processing.ResultsMonocular involvement happened in all 21 patients. 12 patients suffered from oculomotor nerve paralysis, 5 abducent nerve paralysis, 3 trochlearis nerve paralysis, and 1 compound nerve paralysis. Among these patients with complete oculomotor nerve panalysis, no papillary change appeared.Conclusions Microvascular pathologic change may be the pathogenetic basis of ophthalmoplegia for senile diabetic patients. Its prognosis is favorable if reasonable treatment is made.

Objective To analyse the clinical and pathological characteristics of congenital adrenal hyperplasia (CAH) with adrenal myelolipoma (AML),and to improve the awareness of CAH.Methods The P450c17a gene in a pedigree with CAH and the clinical and pathological characteristics of three sisters of the pedigree with CAH and adrenal myelolipoma were studied;and the pertinent literatures reported abroad were analyzed and summarized.Results (1) A heterozygous point mutation 1178 base A to T in exon 6,and a heterozygous deletion mutation 1 457-1 465 bases TCGACTCTT of exon 8 were detected in P450c17 (CYP17) gene of three sisters of the pedigree with CAH.(2) The clinical characteristics of three sisters were hypertension,hypokalemia,primary amenorrhea,and gonadal dysgenesis.Without regular treatment after the diagnosis of CAH,the three sisters experienced many years of elevated serum ACTH levels,and developed AML.Conclusion The long-term high ACTH level plays an important role in the development of AML,although the exact mechanism of CAH with adrenal myelolipoma remains still unclear.CAH patients require long-term regular treatment.

Objective:To explore the applicability of depressor substances test and histamine test for the quality control of depro-teinized culf blood extractives injection. Methods: Depressor substances test and histamine test were carried out on 10 batches of deproteinized culf blood extractives injection samples. Results:Some samples showed positive reactions in the experiments. The correl-ative analysis showed positive correlation existed between the results of depressor substances test and histamine test. However, part of samples causing blood pressure decrease in anesthetized cats showed negative or relatively reduced results in histamine test. Conclu-sion:Deproteinized culf blood extractives injection may be contaminated by depressor substances. Part of these substances may not be histamine analogue, therefore, depressor substances test may be considered in the quality control of the product.

Objective: To investigate the association between single nucleotide polymorphisms (SNPs) of rs3130542 and rs4821116 in the HLA-C and UBE2L3 genes and the effect of telbivudine antiviral therapy during pregnancy in HBeAg-positive mothers through a large-sample control study, and to provide a basis for the development of individualized blocking strategies for pregnant women with a high viral load. Methods: The genotypes of rs3130542 and rs4821116 were determined for 312 pregnant women with a high viral load who received telbivudine antiviral therapy during the second or third trimester of pregnancy, and the dominant model, recessive model, and additive model were used to analyze the association between the genotypes of these two loci and the reduction in HBV DNA load. The Shapiro-Wilk test and the Levene test were used to evaluate data normality and homogeneity of variances, and the t-test or the non-parametric Mann-Whitney U test was selected based on data type and was used for the comparison of means between groups. The Hardy-Weinberg equilibrium was used to determine the genotype of SNPs, and the dominant model, recessive model, and additive model were used for analysis. Results: Mothers with an AA/AG genotype of rs3130542 in the HLA-C gene had a significantly higher probability of HBV DNA load ≥10³ IU/ml at the time of delivery (P < 0.05) and a significantly higher risk of failure in the prevention of mother-to-child transmission, no matter whether they started to take telbivudine at week 24 or 28 of pregnancy. The association between the genotype of rs4821116 in the UBE2L3 gene and the reduction in viral load in pregnant women needed to be confirmed by studies with a larger sample size. Conclusion Pregnant women with a high viral load and an AA/AG genotype of rs3130542 in the HLA-C gene tend to have poor response to antiviral therapy during pregnancy, and early antiviral intervention is recommended for such patients.

Objective To observe the dynamic characteristics of hepatitis B core antibody (anti-HBc) titers in chronic hepatitis B (CHB) patients treated with interferon and to explore the predictive value of anti-HBc for response to interferon.Methods The clinical information of the patients diagnosed with CHB in Department of Infectious Diseases , the First Affiliated Hospital of Xi′an Jiaotong University from October 2011 to October 2014 were collected.HBV DNA, liver function and HBV serological markers of CHB patients were tested dynamically during and after interferon treatment.The dynamic characteristics of anti-HBc titers in patients with different virological responses were analyzed.The predictive values of anti-HBc titer for the efficacy of interferon treatment of CHB patients were analyzed by binary logistic regression .Results Of the 42 CHB patients aging(30.8 ±10.1) years old, 34 patients were hepatitis B e antigen (HBeAg) positive and 8 were negative.All patients completed 48-week interferon treatment and 24-week follow-up after the end of treatment. Among them, 28.6%( 12/42), 26.2%( 11/42 ) and 45.2%( 19/42 ) of patients achieved sustained virological response (SVR), virological relapse ( VR) and non-response ( NR), respectively.Patients with different virological response presented various characteristics of anti -HBc titers.Compared with NR group, the anti-HBc titers at baseline and week 12 were significantly higher in SVR group (at baseline: [4.93 ±0.30] vs [4.70 ±0.33] lg IU/mL, t ＝2.147, P ＝0.013; at week 12: [4.83 ± 0.23] vs [4.44 ± 0.41] lg IU/mL, t＝3.032, P＝0.007).The anti-HBc titers in SVR group at week 12 and week 24 were significantly higher than those in VR group (at week 12: [4.83 ±0.23] vs [4.67 ±0.51] lg IU/mL, t＝2.400, P＝0.039; at week 24: [4.73 ±0.21] vs [4.55 ±0.50] lg IU/mL, t＝2.542, P＝0.039).By multivariate logistic regression analysis, the anti-HBc titer at baseline was the independent predictive factor for SVR in CHB patients treated with interferon (OR＝6.000, 95%CI: 1.118 -20.486, P＝0.037).The area under receiver operating characteristics curve was 0.753 and the optimal cutoff value of anti-HBc titer for the response to interferons in CHB patients was 5.03 lg IU/mL, with positive predictive value of 64.3%and negative predictive value of 89.3%.Conclusions Dynamic pattern of anti-HBc titers is correlated with different virological responses in CHB patients treated with interferon , and the baseline anti-HBc titer is the independent predictive factor for SVR.

With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.

Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China.

In recent years, modeling and simulation technology based on pharmacometrics has received increasing attention in the development of innovation drugs. In August of 2021, FDA issued a guidance named Pharmacokinetic-Based Criteria for Supporting Alternative Dosing Regimens of Programmed Cell Death Receptor-1 (PD-1) or Programmed Cell Death-Ligand 1 (PD-L1) Blocking Antibodies for Treatment of Patients with Cancer Guidance for Industry, claiming the necessity of using population PK-based simulation method for the optimization of dosing regimens, and the corresponding implementation standards. This article first summarized the existing therapeutic regimens of PD-1/PD-L1 blocking antibodies in clinic as well as the main content of the guidance, and then cited some actual examples where population PK-based simulation method did contribute to the approval of the alternative dosing regimens. Besides, some critical considerations for the dosing regimen optimization of PD-1/PD-L1 blocking antibodies were also analyzed. In our view, this guidance would have positive impacts on the development of PD-1/PD-L1 blocking antibodies in the future. We hope that this article may provide some references for the colleagues in China.

【Objective】 To investigate the environmental pollution of blood collection and supply institutions by using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and evaluate its application value. 【Methods】 Colonies of air from blood donation sites, skin puncture sites of blood donors, platelet storage boxes, platelet collection equipment, object surfaces of related experimental consumables and cuff surfaces of staff after disinfection were collected, and typical colonies after cultivation were selected for microbial identification by microbial mass spectrometry and then compared with bacteria results detected in blood components from May 2017 to May 2021. 【Results】 Aseptic growth, the number of colonies ≤4.0 CFU/ dish, and the number of colonies > 4.0 CFU/dish accounted for 21.20%, 62.20% and 16.60%, respectively. The qualified rate from high to low was platelet storage box, bacteria settling in the air of blood donation room after disinfection, platelet collection equipment, skin puncture site of blood donors after disinfection, the surface of platelet consumables and the surface of medical staff's overalls. After disinfection, the blood donors' skin puncture sites were compared with other collection sites, and the t values were 2.0371, 1.508, 2.109, 1.961 and 1.778, respectively, with no significant difference (P>0.05). Thirty cases of bacterial contamination of blood components were detected from May 2017 to May 2021, among which the detection rate of apheresis platelets was the highest, and the t values were 1.731 and 2.272, relative to the contamination frequency of erythrocytes and plasma bacteria (P>0.05), while the t value was 2.875, relative to concentrated platelets, with significant difference (P<0.05). 【Conclusion】 Bacterial contamination of blood components mostly come from air bacteria settling, blood donors' arms and skin after disinfection, and surfaces of related equipment and materials. Therefore, it is of clinical significance to conduct strict disinfection of working sites, establish disinfection monitoring methods and formulate disinfection hygiene standards in blood stations.

【Objective】 To observe the effect of hydrogen peroxide atomization sterilizer using low concentration hydrogen peroxide disinfectant on the environment and object surface of physical examination area (hereinafter referred to as " physical examination area" ) in blood centers, so as to provide a simple method which is safe, efficient, easy to operate, harmless to human body and has no corrosive effect on equipment. 【Methods】 The physical examination area was disinfected with atomized hydrogen peroxide sterilizer, and the difference of colony number between air and surface before and after disinfection was compared to evaluate the disinfection effect. 【Results】 After disinfection, the hydrogen peroxide residue was detected for 25 times at 5 points, and the results were (0.7~1)ppm, with no statistical difference (P>0.05). 25 tests were carried out at 5 points, and the quartile of the test results was (0~2)CFU/ dish, and the qualified rate was 100%. The test results of bacteria before and after disinfection were statistically significant (P<0.05), which met the requirements of Class Ⅱ environment in Hygienic Standard for Hospital Disinfection(GB15982-2012). After disinfection, the quartile of surface colony detection results of workbench, blood donor seat, screen and door handle were (0~24.1)CFU/cm^2, (1.6~55.4)CFU/cm^2, (0~7.2)CFU/cm² and (0~4.8)CFU/cm^2, with the qualified rate at 80%, 48%, 100% and 100%, respectively, which were in accordance with the requirements of Class Ⅲenvironment in GB15982-2012. The number of colonies after disinfection at the above detection sites decreased significantly compared with that before disinfection (P<0.05). The surface contact plate pressing method and cotton swab smearing method were used to detect the number of colonies on the surface of sterilized work tables and blood donor seats, and the detection rate of the former was higher than that of the latter, with statistical significance (P<0.05). 【Conclusion】 After disinfection by hydrogen peroxide atomization sterilizer, the hydrogen peroxide residue met the requirements specified in the manual. The terminal disinfection effect of air in the physical examination area environment can meet the Class Ⅱ environmental requirements of GB15982-2012. However, the number of microorganisms on object surface after terminal disinfection was significantly lower than that before disinfection.