Analysis of the progress of clinical trials for ophthalmic drug in China, 2022 / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the progress of clinical trials for ophthalmic drugs in China in 2022 and discuss its changes with 2014 to 2021, thus providing the latest data reference for the development of new drug and the implementation of clinical trials, and a basis for decision-making.METHODS: In this cross-sectional study, we retrieved the drug clinical trials registration and information disclosure platform of National Medical Products Administration database. Drug clinical trials for eye diseases registered from January 1 to December 31, 2022 were included. Number(proportion)was used to describe the characteristics of clinical trials for ophthalmic drug, the indication, the trial phase, the efficacy and the geographical distribution.RESULTS:A total of 55 clinical trials for ophthalmic drug were included, which accounted for 1.66% of all clinical trials, showing a steady growth trend. Main drug type was chemical drugs with the highest proportion of 58.18%. The top three indications with the most clinical trials were age-related macular degeneration, myopia and dry eye. Two gene drugs emerged in 2022, and 7 drugs carried out ≥2 trials, of which atropine sulfate and recombinant anti-vascular endothelial growth factor(VEGF)humanized monoclonal antibody were the most(7 and 5 respectively). Most trials were in phase I and phase III stages, accounting for 36.36% and 27.27% respectively. The median start-up time of phase I trials in 2022 was 2.72(0.77, 3.47)mo, which was significantly shorter than 3.87(3.00, 6.30)mo of 2014～2021(Z=-2.630, P=0.009), and there were no significant differences between BE, phase II, III, IV comparing with 2014～2021(P>0.05).CONCLUSIONS: In 2022, the number and implementation efficiency of clinical trials for ophthalmic drugs in China increased steadily. The indications are mainly fundus disease, myopia and dry eye. Most new drugs are in the early stage of research and development or close to market. Gene therapy drugs began to emerge.

Design, methodology, and preliminary results of the follow-up of a population-based cohort study in rural area of northern China: Handan Eye Study / 中华医学杂志(英文版)

Background@#Handan Eye Study (HES), a large population-based cohort study in rural area of northern China, was one of the few studies focusing on the major eye diseases of rural Chinese population. The aim of this study was to introduce the design, methodology and to assess the data quality of the follow-up phase of HES.@*Methods@#All participants were recruited in Yongnian county of Handan city between 2012 and 2013. Main outcomes were measured by visual quality scales and ocular examinations. We performed the Chi-square test to make comparison of categorical data among groups, One-way analysis of variance and Kruskal-Wallis test was applied to make comparison of continuous data among groups, a post-hoc test was done to make further pairwise comparison. Inter-class correlation coefficients (ICCs) and Kappa coefficients were used to evaluate the consistency between different operators. Logistic regression was used to explore the influence factors of death, odds ratio (OR) and 95% confidence interval (CI) were used to estimate the effect size of each influence factor.@*Results@#The follow-up rate was 85.3%. Subjects were classified into three groups: the follow-up group (n = 5394), the loss to follow-up group (n = 929), and the dead group (n = 507), comparison of their baseline information was done. Compared with the other two groups, age of the dead group (66.52 ± 10.31 years) was the oldest (Z = 651.293, P < 0.001), male proportion was the highest (59.0%) (χ2 = 42.351, P < 0.001), only 65.9% of the dead finished middle school education (Z = 205.354, P < 0.001). The marriage percentage, body mass index (BMI), best-corrected visual acuity (BCVA), and intra-ocular pressure of the dead group was the lowest either. Spherical equivalent error (SER) of the dead group was the highest. Besides, history of smoking, hypertension, diabetes, and heart disease were more common in the dead group. Multivariate analysis showed that age (OR = 1.901, 95% CI: 1.074–1.108), gender (OR = 0.317, 95% CI: 0.224–0.448), and BCVA (OR = 0.282, 95% CI: 0.158–0.503) were associated with death. While between the follow-up group and the loss to follow-up group, there was only difference on age, gender, BMI, systolic blood pressure and SER. The Cronbach coefficients of all scales used in the follow-up were ≥0.63 and the cumulative variances were ≥0.61, indicating good reliability and validity. The ICCs and Kappa coefficients between different operators were ≥0.69.@*Conclusions@#HES has a high follow-up rate and a low risk of loss to follow-up bias. Age, gender, and BCVA are influence factors of death. Specifically, male subjects are at a higher risk of death than female, age is a risk factor of death while BCVA is a protective factor for death.

Design, methodology, and preliminary results of the follow-up of a population-based cohort study in rural area of northern China: Handan Eye Study / 中华医学杂志(英文版)

BACKGROUND@#Handan Eye Study (HES), a large population-based cohort study in rural area of northern China, was one of the few studies focusing on the major eye diseases of rural Chinese population. The aim of this study was to introduce the design, methodology and to assess the data quality of the follow-up phase of HES.@*METHODS@#All participants were recruited in Yongnian county of Handan city between 2012 and 2013. Main outcomes were measured by visual quality scales and ocular examinations. We performed the Chi-square test to make comparison of categorical data among groups, One-way analysis of variance and Kruskal-Wallis test was applied to make comparison of continuous data among groups, a post-hoc test was done to make further pairwise comparison. Inter-class correlation coefficients (ICCs) and Kappa coefficients were used to evaluate the consistency between different operators. Logistic regression was used to explore the influence factors of death, odds ratio (OR) and 95% confidence interval (CI) were used to estimate the effect size of each influence factor.@*RESULTS@#The follow-up rate was 85.3%. Subjects were classified into three groups: the follow-up group (n = 5394), the loss to follow-up group (n = 929), and the dead group (n = 507), comparison of their baseline information was done. Compared with the other two groups, age of the dead group (66.52 ± 10.31 years) was the oldest (Z = 651.293, P < 0.001), male proportion was the highest (59.0%) (χ = 42.351, P < 0.001), only 65.9% of the dead finished middle school education (Z = 205.354, P < 0.001). The marriage percentage, body mass index (BMI), best-corrected visual acuity (BCVA), and intra-ocular pressure of the dead group was the lowest either. Spherical equivalent error (SER) of the dead group was the highest. Besides, history of smoking, hypertension, diabetes, and heart disease were more common in the dead group. Multivariate analysis showed that age (OR = 1.901, 95% CI: 1.074-1.108), gender (OR = 0.317, 95% CI: 0.224-0.448), and BCVA (OR = 0.282, 95% CI: 0.158-0.503) were associated with death. While between the follow-up group and the loss to follow-up group, there was only difference on age, gender, BMI, systolic blood pressure and SER. The Cronbach coefficients of all scales used in the follow-up were ≥0.63 and the cumulative variances were ≥0.61, indicating good reliability and validity. The ICCs and Kappa coefficients between different operators were ≥0.69.@*CONCLUSIONS@#HES has a high follow-up rate and a low risk of loss to follow-up bias. Age, gender, and BCVA are influence factors of death. Specifically, male subjects are at a higher risk of death than female, age is a risk factor of death while BCVA is a protective factor for death.

Design, synthesis and evaluation of a novel BRD4 protein inhibitors / 药学学报

Bromodomain-containing proteins (BCPs) can specifically recognize acetylated lysine (KAc) in histones and other substrate proteins. Recently, several kinase inhibitors were found to inhibit bromodomains, such as the PLK1 inhibitor BI-2536 and the JAK2 inhibitor TG101209, which bind to BRD4 with IC50 values of 25 nmol·L-1 and 130 nmol·L-1, respectively. To obtain potent BRD4 inhibitors from inhibitor BI-2536, we used dihydroquinoxalin-2(1H)-one to replace the 7,8-dihydropteridin-6(5H)-one in BI2536. By exploring the structure-activity relationships of the new dihydroquinoxalin-2(1H)-one structures, we obtained a novel phenyl side chain series of BRD4 inhibitors. We identified several potent BRD4 inhibitors, especially compounds 16, 22, 28 and 29, which had IC50 values below 100 nmol·L-1 in fluorescence anisotropy (FA) assays, indicating this series of compounds are worth to fruther investigation.

Phosphatase and tensin homologue genetic polymorphisms and their interactions with viral mutations on the risk of hepatocellular carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Chronic hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC). Some HBV mutants and dysregulation of phosphatase and tensin homolog (PTEN) may promote the development of HCC synergistically. We aimed to test the effects of PTEN genetic polymorphisms and their interactions with important HBV mutations on the development of HCC in HBV-infected subjects.</p><p><b>METHODS</b>Quantitative polymerase chain reaction was applied to genotype PTEN polymorphisms (rs1234220, rs2299939, rs1234213) in 1012 healthy controls, 302 natural clearance subjects, and 2011 chronic HBV-infected subjects including 1021 HCC patients. HBV mutations were determined by sequencing. The associations of PTEN polymorphisms and their interactions with HBV mutations with HCC risk were assessed using multivariate logistic regression analysis.</p><p><b>RESULTS</b>Rs1234220 C allele was significantly associated with HCC risk compared to healthy controls (adjusted odds ratio [AOR] = 1.35, 95% confidence interval [CI] = 1.07-1.69) and HCC-free HBV-infected subjects (AOR = 1.27, 95% CI = 1.01-1.57). rs1234220 C allele was significantly associated with increased frequencies of HCC-risk A1652G, C1673T, and C1730G mutations in genotype B HBV-infected subjects. Rs2299939 GT genotype was inversely associated with HCC risk in HBV-infected patients (AOR = 0.75, 95% CI = 0.62-0.92). The interaction of rs2299939 variant genotypes (GT+TT) with A3054T mutation significantly increased HCC risk (AOR = 2.41, 95% CI = 1.08-5.35); whereas its interaction with C3116T mutation significantly reduced HCC risk (AOR = 0.34, 95% CI = 0.18-0.66). These significant effects were only evident in males after stratification.</p><p><b>CONCLUSIONS</b>PTEN polymorphisms and their interactions with HBV mutations may contribute to hepatocarcinogenesis in males. The host-virus interactions are important in identifying HBV-infected subjects who are more likely to develop HCC.</p>

Multiplex real-time PCR method for rapid detection of Marburg virus and Ebola virus / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>Marburg virus and Ebola virus are acute infections with high case fatality rates. A rapid, sensitive detection method was established to detect Marburg virus and Ebola virus by multiplex real-time fluorescence quantitative PCR.</p><p><b>METHODS</b>Designing primers and Taqman probes from highly conserved sequences of Marburg virus and Ebola virus through whole genome sequences alignment, Taqman probes labeled by FAM and Texas Red, the sensitivity of the multiplex real-time quantitative PCR assay was optimized by evaluating the different concentrations of primers and Probes.</p><p><b>RESULTS</b>We have developed a real-time PCR method with the sensitivity of 30.5 copies/microl for Marburg virus positive plasmid and 28.6 copies/microl for Ebola virus positive plasmids, Japanese encephalitis virus, Yellow fever virus, Dengue virus were using to examine the specificity.</p><p><b>CONCLUSIONS</b>The Multiplex real-time PCR assays provide a sensitive, reliable and efficient method to detect Marburg virus and Ebola virus simultaneously.</p>

Geographical distribution of cancer mortality in China, 2004-2005 / 中华预防医学杂志

<p><b>OBJECTIVE</b>To describe geographical distribution and its transition of mortality of cancers in China.</p><p><b>METHODS</b>The information of 2 513 949 310 person years were collected in 1973-1975 and 142 660 482 person years in 2004-2005 respectively. Being standardizing the death rates of these two survey with 2000 national census population, the changes of mortality of main cancers was observed and the geographic distribution of cancers in 2004-2005 was analyzed.</p><p><b>RESULTS</b>A total of 1 865 445 cancer deaths were collected in 1973-1975, the standardized death rate was 99.61/100 000, and 193 839 cancer deaths were collected in 2004-2005, the standardized death rate was 123.72/100 000, with growth of 24.20%. District mortality analysis showed that the provincial standardized cancer death rates varied greatly, with the highest in Heilongjiang (7443 cases, 183.34/100 000), and the lowest in Yunnan (2454 cases, 61.03/100 000). The highest standardized death rate of esophageal cancer, gastric cancer, liver cancer, colon cancer, lung cancer, nasopharyngeal cancer, leukemia, female breast cancer, cervical cancer was in Henan (3535 cases, 32.95/100 000), Gansu (1333 cases, 59.35/100 000), Heilongjiang (1640 cases, 38.63/100 000), Shanghai (390 cases, 11.58/100 000), Heilongjiang (2382 cases, 60.15/100 000), Hainan (36 cases, 7.04/100 000), Tianjin (161 cases, 5.45/100 000), Heilongjiang (179 cases, 8.09/100 000), Xinjiang (131 cases, 10.69/100 000) respectively; the lowest standardized cancer death rate of above-mentioned cancers was in Yunnan (63 cases, 1.59/100 000), Beijing (235 cases, 5.95/100 000), Tianjin (454 cases, 10.86/100 000), Tibet (3 cases, 0.82/100 000), Tibet (12 cases, 3.29/100 000), Qinghai (0 case, 0.00/100 000), Tibet (1 cases, 0.28/100 000), Tibet (6 cases, 2.88/100 000), Chongqing (27 cases, 1.02/100 000) respectively.</p><p><b>CONCLUSION</b>Comparing the two surveys, the standardized mortality of cancers was increased. Most of cancers occurred obviously in cluster by geographical distribution.</p>

Economic burden of coronary heart disease and stroke attributable to hypertension in China / 中华流行病学杂志

<p><b>OBJECTIVE</b>1) To estimate annual direct medical costs of coronary heart disease (CHD) and stroke attributable to hypertension among Chinese adults aged 35-74 years in China, 2) to analyze the correlation between the hypertension awareness and hypertension treatment rate.</p><p><b>METHODS</b>2003 National Health Services Survey (n = 93 018) was used to derive direct medical costs including costs for outpatient visits, physician services, inpatient stays, rehabilitation services, nurses fees, and medications. The medical costs of CHD and stroke attributable to hypertension were estimated by multiplying population attributable risk proportion by corresponding disease costs. Using 2002 National Nutrition and Health Survey (n = 148 804), the prevalence of hypertension awareness and hypertension treatment rate in 132 survey sites were calculated. Correlation was used to analyze the correlation between the two variables.</p><p><b>RESULTS</b>The direct medical costs of hypertension, CHD and stroke were 20.2, 15.7 and 24.3 billion Yuan, respectively. The medical costs attributable to hypertension were estimated at 19.1 billion Yuan (RMB), accounting for 47.7% of the total medical costs of the two chronic diseases. The prevalence of hypertension awareness is highly correlated with hypertension treatment rate (r = 0.9777, P < 0.0001).</p><p><b>CONCLUSION</b>The economic burden of CHD and stroke attributable to hypertension is very high, reaching about 50% of the total medical costs of the two diseases. The prevalence of hypertension awareness could be used as an important indicator to evaluate the effectiveness of hypertension prevention and control at community level.</p>

The Role of Androgen in High-Salt Induced Hypertension in Rats / 中华高血压杂志

Objective To study the effects of high salt intake on blood pressure and renin-angiotensin in male rats with different plasm androgen levels.Methods Thirty male Wistar rats were randomized to sham(n=10)or operated(n=10),or castration(n=10),or testosterone replacement after castarion(26.7 mg/kg,n=10)and fed with 8% NaCl for 8 weeks.Tall arterial pressure were recorded before,4 and 8 weeks after experiment.Serum PRA,plasma angiotensin Ⅱ(Ang Ⅱ)and testosterone(T)were determined by radioimmunoassey respectively. Results After 8 weeks high salt dietary,blood pressure was significantly increased in sham and testosterone replace ment rats(Sham operation group:137.3?4.0 vs the basal line:117.5?5.9 mmHg,testosterone replacement group: 134.4?5.2 vs the basal line:116.6?7.7 mmHg,P0.05).Concomitantly,sham operation or testosterone re placement rats had higher PRA and plasm Ang Ⅱ content compared with castrated rats(PRA:Sham operation 5.90 ?0.77 vs testosterone replacement group:5.69?0.47 vs castrated rats:4.90?0.55 mol/(L?h),P

Research actuality and expectation on embryo toxicity of traditional Chinese medicine / 中国中药杂志

Traditional Chinese medicine with embryo toxicity has been named as abstinence medicine in cyesis in ancient times. Embryo toxicity is one of the key theories of traditional Chinese medicine. Based on history retrospective study and rhodern research, the paper expounded that the developing course of embryo toxicity of traditional Chinese medicine is from cyesis abstinence to inheritance toxicity and reproductive development toxicity, and overviewed the research of active components of traditional Chinese medicine in the domains of inheritance toxicity and reproductive development toxicity. Meanwhile, it pointed out that the main problem in the domain is about the definition of conception and category of traditional Chinese medicine with embryo toxicity and the foundation of relative assessment system. In the end, some suggestions were given to solve the problem including the control of poisonous traditional Chinese medicines, right processing, reasonable compatibility, extensional application, and utilizing modem science and technology.