Study on treatment of "cytokine storm" by anti-2019-nCoV prescriptions based on arachidonic acid metabolic pathway / 中国中药杂志

Since the outbreak of 2019-nCoV, the epidemic has developed rapidly and the situation is grim. LANCET figured out that the 2019-nCoV is closely related to "cytokine storm". "Cytokine storm" is an excessive immune response of the body to external stimuli such as viruses and bacteria. As the virus attacking the body, it stimulates the secretion of a large number of inflammatory factors: interleukin(IL), interferon(IFN), C-X-C motif chemokine(CXCL) and so on, which lead to cytokine cascade reaction. With the exudation of inflammatory factors, cytokines increase abnormally in tissues and organs, interfering with the immune system, causing excessive immune response of the body, resulting in diffuse damage of lung cells, pulmonary fibrosis, and multiple organ damage, even death. Arachidonic acid(AA) metabolic pathway is principally used to synthesize inflammatory cytokines, such as monocyte chemotactic protein 1(MCP-1), tumor necrosis factor(TNF), IL, IFN, etc., which is closely related to the occurrence, development and regression of inflammation. Therefore, the inhibition of AA metabolism pathway is benefit for inhibiting the release of inflammatory factors in the body and alleviating the "cytokine storm". Based on the pharmacophore models of the targets on AA metabolic pathway, the traditional Chinese medicine database 2009(TCMD 2009) was screened. The potential herbs were ranked by the number of hit molecules, which were scored by pharmacophore fit value. In the end, we obtained the potential active prescriptions on "cytokine storm" according to the potential herbs in the "National novel coronavirus pneumonia diagnosis and treatment plan(trial version sixth)". The results showed that the hit components with the inhibitory effect on AA were magnolignan Ⅰ, lonicerin and physcion-8-O-β-D-glucopy-ranoside, which mostly extracted from Magnoliae Officinalis Cortex, Zingiberis Rhizoma Recens, Lonicerae Japonicae Flos, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Scutellariae Radix, Gardeniae Fructus, Ginseng Radix et Rhizoma, Arctii Fructus, Dryopteridis Crassirhizomatis Rhizoma, Paeoniaeradix Rubra, Dioscoreae Rhizoma. Finally the anti-2019-nCoV prescriptions were analyzed to obtain the potential active prescriptions on AA metabolic pathway, Huoxiang Zhengqi Capsules, Jinhua Qinggan Granules, Lianhua Qingwen Capsules, Qingfei Paidu Decoction, Xuebijing Injection, Reduning Injection and Tanreqing Injection were found that may prevent 2019-nCoV via regulate cytokines. This study intends to provide reference for clinical use of traditional Chinese medicine to resist new coronavirus.

Study on screening potential traditional Chinese medicines against 2019-nCoV based on Mpro and PLP / 中国中药杂志

With the rapid outbreak of COVID-19, traditional Chinese medicine(TCM) has been playing an active role against the epidemic. However, the screening of TCM is limited by the development cycle and laboratory conditions, which greatly limits the screening speed. This study established optimization docking models and virtual screening to discovery potential active herbs for the prevention and treatment of the novel coronavirus based on molecular docking technology. The crystal structures of 3 CL protease(Mpro) and papain-like protease(PLP) were obtained from PDB database and homologous modeling respectively, and were used to conduct virtual screening of TCMD 2009 database by CDOCKER program. The ingredients scored in the top 100 were selected respectively, and the candidate herbs were ranked by the numbers of hit molecules. Based on Mpro inhibitors screening, 12 322 potential active components were obtained, and the representative active components included aster pentapeptide A, ligustrazine, salvianolic acid B, etc., and Zingiberis Rhizoma Recens, Asteris Radix et Rhizoma, Notoginseng Radix et Rhizoma, Chuanxiong Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Zingiberis Rhizoma, Dianthi Herba, Rhei Radix et Rhizoma, Cistanches Herba were obtained. While 11 294 potential active ingredients were obtained by PLP inhibitor screening, representative active ingredients included gingerketophenol, ginkgol alcohol, ferulic acid, etc., and Codonopsis Radix, Notopterygii Rhizoma et Radix, Zingiberis Rhizoma Recens, Ginkgo Semen, Chuanxiong Rhizoma, Trichosanthis Fructus, Paeoniae Radix Alba, Psoraleae Fructus, Sophorae Flavescentis Radix, Notoginseng Radix et Rhizoma, Angelicae Sinensis Radix were chosen. By combining the diagnosis and treatment scheme of Hunan province's and angiotensin converting enzyme 2(ACE2) inhibitors screening from literature, present study also discussed the rational application of candidate herbs to this epidemic situation. Trichosanthis Fructus obtained by PLP inhibitors screening and Fritillaria verticillata obtained by ACE2 inhibitors screening were parts of the Sangbei Zhisou Powder and Xiaoxianxiong Decoction, which might be applicable to the syndromes of cough and dyspnea. Rhei Radix et Rhizoma screened by Mpro and Trichosanthis Fructus screened by PLP were contained in Maxing Shigan Decoction and Xuanbai Chengqi Decoction, and could be applied to the syndromes of epidemic virus blocking lung. Mori Folium, Lonicerae Japonicae Flos and Forsythiae Fructus obtained by ACE2 inhibitors screening were included in the Sangju Decoction and Yinqiaosan, which might be applicable to the syndromes of warm pathogen attacking lung and cough and dyspnea. The results of this study are intended to provide a reference for the further development of traditional Chinese medicine to deal with the new epidemic.

The analysis of the active follow-up study of registered cancer patients between 2002 and 2005 in urban areas of Beijing / 中华预防医学杂志

<p><b>OBJECTIVE</b>To evaluate the results of the active follow-up among registered cancer patients in 2002 - 2005 in urban areas of Beijing.</p><p><b>METHODS</b>A number of 63 997 cancer patients diagnosed during 2002 - 2005 were selected from the surveillance database of Beijing Office for Cancer Prevention and Control. By matching the identity information of the patients with the death surveillance database built by the vital statistic department in Beijing, 29 223 patients were confirmed to be alive.1149 cases were removed from the study due to lack of exact key variables, such as address and telephone numbers. 28 074 patients were, at last, included in the active follow-up study. The investigators and the inspectors, who accepted standard training program, investigated each patient's status of census register and survival condition by phone calling, household interview and visits at local police station or residential committee. The loss ratio of follow-up and the constituent ratio of the withdrawal reasons were calculated.</p><p><b>RESULTS</b>Among the 28 074 patients selected in active follow-up, 21 696 patients were followed successfully; 1453 of whom didn't have the census register of Beijing, which accounted for 6.70%. Out of the other 20 243 Beijing residents, 4715 patients (23.29%) were already dead and 84.22% (3971/4715) of them replenished the failure to report by passive follow-up. Among all the 4715 dead cases, 4405 (93.43%) patients were died from cancer. The follow-up study helped to replenish the vital statistics in different districts, the ratio ranged from 4.87% and 8.85%. 6378 patients were withdrawn from the study. The loss ratio was 22.72% (6378/28 074), and the total loss ratio was 12.03% ((6378 + 1149)/(63 997 - 1453)). Of these withdrawal cases, 3041 (47.68%) were lost to follow-up in that the investigators can't find the patients or the relatives of the patients according to the registered phone number or address information. The other reasons included: the patients removed to other areas (1199 cases, 18.80%), the patients and their family members were temporarily not at home (127 cases, 1.99%), the patients and their family members rejected to answer the interview (292 cases, 4.58%), and other reasons (1719 cases, 26.95%).</p><p><b>CONCLUSION</b>The method of active follow-up towards registered cancer patients can replenish the missing information which could not be collected from passive follow-up procedure; and therefore effectively improve the quality of data in cancer registration.</p>

Incidence trends and pathological characteristics of lung cancer in urban Beijing during period of 1998 - 2007 / 中华预防医学杂志

<p><b>OBJECTIVE</b>To describe the incidence trends and pathological characteristics of lung cancer in urban Beijing, China.</p><p><b>METHODS</b>A total of 32 845 medical records of the residents diagnosed as lung cancer in urban Beijing from 1998 to 2007 were retrieved through the cancer registry system of Beijing Cancer Registry. Crude incidence rate, age-specific incidence rate, adjusted incidence rate by world standardized population, annual percentage change (APC) and histological categorized incidence rate by world standardized population were calculated in order to compare the differences of the incidence trends in different time periods, or among different gender and age groups.</p><p><b>RESULTS</b>A total of 32 845 newly diagnosed lung cancer patients between 1998 and 2007 were included in our study. The crude incidence rate was 47.81/100 000 (32 845/68 704 429), increasing by 38.80% from 39.30/100 000 in 1998 to 54.55/100 000 in 2007 with APC at 3.35% in urban Beijing (Z = 9.984, P < 0.001). While it changed to 28.95/100 000 with an APC at 0.27% (Z = 0.846, P = 0.422) when adjusted by world standardized population. For male, the crude incidence rate was 58.28/100 000 (20 342/34 906 580, adjusted rate at 37.03/100 000, APC at 0.38%, Z = 1.008, P = 0.343); while for female, the crude incidence rate was 36.99/100 000 (12 503/33 797 849, adjusted rate at 21.48/100 000, APC at 0.14%, Z = 0.431, P = 0.678). 17 920 lung cancer patients being diagnosed according to histological evidence, accounted for 54.56%. The respective proportion of the patients with histological diagnosis was 43.14% (1095/2538) in 1998 and 65.55% (2641/4029) in 2007, with a 51.95% increase (χ(2) = 859.152, P < 0.001) in decade. In terms of subtypes of lung cancer, the proportion of squamous cell carcinoma decreased annually, from 30.41% (333/1095) in 1998 to 24.16% (638/2641) in 2007; while the proportion of adenocarcinoma increased from 42.83% (469/1095) to 46.80% (1236/2641). As a result, the squamous cell carcinoma to adenocarcinoma ratio declined from 0.71 (333/469) to 0.52 (638/1236) (χ(2) = 50.214, P < 0.001). For women, the ratio declined more significantly and the proportion of the squamous cell carcinoma and adenocarcinoma were 14.77% (925/6262) and 60.83% (3809/6262), respectively in the period between 1998 and 2007.</p><p><b>CONCLUSION</b>No significant change was found in the incidence trend of lung cancer after the incidence rate adjusted by world standard population, but the proportion of the subtypes of lung cancer categorized by histological evaluation changed apparently.</p>

Analysis of the incidence and survival of female breast cancer in Beijing during the last 20 years / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To provide scientific evidence for breast cancer prevention and control through epidemiological analysis of the incidence, mortality and survival rate of female breast cancer in Beijing.</p><p><b>METHODS</b>The registration data of females in Beijing urban area from 1982 to 2001 were retrospectively reviewed. The incidence, mortality and survival rate of female breast cancer were analyzed using routine and life table statistical methods.</p><p><b>RESULTS</b>There was a trend of annual increase by an average of 4.6% and 4.9% in the Beijing urban incidence and world population standardized incidence of female breast cancer during the period of 1982 to 2001. The epidemiological features of Beijing urban female breast cancer showed: (1) The incidence curve of different age groups from 25 to 80 years elevated with two peaks at age of >or= 45 and >or= 70 years; (2) There was an elevation in each age group during the last 20 years; (3) The interception rate at age of 35 to 64 reached 95.3/100,000 population, which made the breast cancer become the number one cancer in female. The changes of survival rate showed: the 5-year observed survival rate (OSR) increased from 62.0% in 1982 - 1983 to 68.7% in 1987 - 1988, the relative survival rate (RSR) increased from 66.3% to 74.2%. The OSR and RSR in 1987 - 1988 were 60.3% and 65.1% at 10 years, and 57.7% and 61.3% 15 years, respectively. The mortality rate of breast cancer fluctuated at 8 to 10 per 10(5) population during the last 20 years.</p><p><b>CONCLUSION</b>There is a trend of an annual increase in female breast cancer in Beijing. The 5-year survival is being improved gradually while the mortality rate remains stable. The results demonstrate that the "early prevention, early diagnosis and early treatment" principles for breast cancer is effective in Beijing.</p>