OBJECTIVE To study the protective effect and mechanism of Shiyifang medicinal wine （SYF） on knee osteoarthritis（KOA）of rabbit induced by papain . METHODS Thirty-five rabbits were randomly divided into blank group ，model group，positive group （Diclofenac diethylamine emulsion 200 mg/kg），SYF high -dose group （386 mg/kg）and SYF low -dose group（97 mg/kg），with 7 rabbits in each group （all had 4 males and 3 females）. Except for the blank group ，the other groups ’ rabbits were injected 0.5 mL papain mixture （containing 2% papain and 0.03 mol/L L -cysteine）into the right knee cavity on day 1， 4 and 7，to replicate KOA model . Blank group was given constant volume of normal saline . From the 15th day ，drugs were applied to right hind knee joints of rabbits in each group ，twice a day for 20 days. At the same time ，the diameter of right knee joints of rabbits was measured by vernier calipers at day 0，8，14 and 35 to calculate swelling degree . After the experiment ，the levels of IL-1β，TNF-α and PGE 2 in synovial tissue were determined by enzyme -linked immunosorbent assay . Hematoxylin-eosin（HE） staining was used to prepare the sections of synovial tissue ，and the pathological changes were observed . The relative mRNA expressions of TLR 4，MyD88 and NF - кB p 65 in the TLR 4/MyD88/NF- кB signaling pathway were detected by real -time quantitative polymerase chain reaction . The relative protein expressions of TLR 4，MyD88，NF-кB p 65 and p -NF-кB p 65 were detect by Western blot . RESULTS Compared with blank group，the degree of knee swelling could be increased in model group ，the pathological damage of synovial tissue was more serious ，and the levels of IL -1β，TNF-α and PGE 2 were increased significantly in synovial tissue （P＜0.05）. The relative expression levels of TLR 4，MyD88，NF-кB p 65 mRNAs and TLR 4，MyD88，p-NF-кB p 65 proteins were significantly increased（P＜0.05）. Compared with model group ，swelling degree of right hind knee and the pathological injury degree of synovial tissue were significantly improved in each treatment group ，while the levels of IL -1β，TNF-α and PGE 2 in synovial tissue were significantly decreased （P＜0.05）. The relative mRNA expressions of TLR 4，MyD88 and NF -кB p 65 and relative protein expressions of TLR 4，MyD88（except for SYF low -dose group ）and p -NF-кB p 65 were all significantly decreased （P＜0.05）. CONCLUSIONS SYF shows protective effect on KOA induced by papain ，the mechanism of which is associated with decreasing the levels of IL -1β，TNF-α and PGE 2 and down -regulating TLR 4/MyD88/NF-кB signaling pathway .

OBJEC TIVE To investigate the status and clinical characteristics of adverse drug reactions （ADRs）induced by sintilimab in order to provide references for clinical rational drug use. METHODS The cases of ADR induced by sintilimab were retrieved from the databases of PubMed ，Embase，CNKI，VIP and Wanfang. RESULTS A total of 32 literature were included ， involving 33 patients among which there were 25 males（75.76％）and 8 females（24.24％）. The incidence of ADRs was higher in patients aged over 40 years（81.82％）. The dose of sintilimab was the drug instructions recommended dose （200 mg）for 30 patients and 100 mg for a patient. The earliest ADR occurred 1 h after the first medication ，the latest ADR occurred after 14 cycles of sintilimab. The 27 cases suffered from ADR cases （81.82％）within 4 months after medication ，and no reports of ADR occurred after 12 months of medication. The major manifestations of ADR were myocarditis ，diabetes mellitus ，checkpoint inhibitor pneumonitis（CIP），cytokine release syndrome （CRS）and hypothyroid myopathy （HM），etc. CRS and HM belonged to ADRs not recorded in the drug instructions. The 29 cases of recovery and 4 deaths occurred after symptomatic treatment. CONCLUSIONS ADR caused by sintilimab often occurs within 4 months after treatment ，and it is high in males and patients over 40 years old. In clinical application of sintilimab ，attention should be paid to the occurrence of myocarditis ，diabetes mellitus ，CIP，as well as CRS and HM not recorded in the drug instructions.

Chigger mites is a group of arthropods and some of them are vectors of scrub typhus. As a common synanthropic rodent species, the Brown rat (Rattus norvegicus) often harbors lots of ectoparasites including chigger mites. According to some “data mining” strategies, the present study took the advantage of the abundant original data from a long-term field ecological investigation between 2001 and 2015 to make a detailed analysis of chigger mites on R. norvegicus in Yunnan Province, Southwest of China. From 18 of 33 investigated counties, only 1414 chigger mites were collected from 1113 Brown rats with relatively low infestations. The 1414 individual chigger mites were identified as comprising 61 species, 11 genera and 2 subfamilies of the family Trombiculidae with a high species diversity (S=61, H’=3.13). Of 61 mite species, there were four main species, Walchia ewingi, Ascoschoengastia indica, W. koi and A. rattinorvegici, which accounted for 44.41% of the total mites. All the chigger mites were of aggregated distribution among different individuals of R. norvegicus. The Brown rats in the outdoor habitats harbored much more individuals and species of chigger mites with a higher mean abundance (MA=1.46) and mean intensity (MI=12.53) than in the indoor habitats (P<0.05). The overall infestation of the rats was significantly higher in the mountainous landscapes than in the flatland landscapes (P<0.001). The species similarity (Css) of the mites on the male and female rats reached 64.44% with sex biased infestations. The male rats harbored more species and individuals of the mites than the female rats. The adult rats harbored more species and individuals of the mites than the juvenile rats. The species abundance distribution of the mites was successfully fitted by Preston’s lognormal model with S ^ (R)=15e–[0.31(R–1)]2 (α=0.31, R2=0.95). On the basis of fitting the theoretical curve by Preston’s model, the total mite species on R. norvegicus was estimated to be 86 species, and 25 rare mite species were missed in the sampling field investigation. The curve tendency of the species-plot relationship indicates that R. norvegicus have a great potential to harbor many species of chigger mites, and more species of the mites would be collected if more rats are sampled.

Objective: To analyze the burden of disease (BOD) on diabetes attributable to high BMI in China from 1990 to 2016. Methods: Data based on population of the 2016 Global Burden of Disease Study for China were used to analyze the attributable fractions (PAF) of BOD for diabetes attributable to high BMI. Measurements for attributable BOD of diabetes included disability adjusted life years (DALY), years of lost life (YLL), years living with disability (YLD), death number and mortality rate. The average world population from 2010 to 2035 was used as a reference. Results: In 2016, death number of diabetes attributable to high BMI was 40 310, which was significantly higher than that in 1990 (15 008). Age-standardized death rate of diabetes attributable to high BMI increased from 2.01/100 000 in 1990 to 2.60/100 000 in 2016, which showed a more significant increasing trend in both males and people aged 15-49 years. DALYs of diabetes attributable to high BMI increased from 1.09 million person years to 3.30 million person years. YLL and YLD also showed increasing trends. The highest increasing rate of YLD was in people aged 15-49 years. High BMI was responsible for 26.01% of the diabetes deaths in 2016 in China, an increase of 39.39% compared with that in 1990 (18.66%). Most provinces in China experienced a sharp increase of DALY of diabetes attributable to high BMI from 1990 to 2016. Inner Mongolia, Xinjiang, Zhejiang, Macao SAR, Sichuan and Qinghai had the most significant increase tendency in terms of DALY rate during this period. Conclusions: There was a rapid increase of the deaths and mortality rate of diabetes attributable to high BMI, causing a heavy disease burden, in China from 1990 to 2016. The BOD varied in both different age and gender groups. More attention should be paid to males and people aged 15-49 years in the prevention and control programs of diabetes.
Adolescent ; Adult ; Body Mass Index ; China/epidemiology* ; Cost of Illness ; Diabetes Mellitus/ethnology* ; Disabled Persons ; Humans ; Macau ; Male ; Middle Aged ; Quality-Adjusted Life Years ; Sickness Impact Profile ; Young Adult

Objective: To analyze the effect of intervention programs and influencing factors regarding the community "5+1" staged diabetes target management on patients with type 2 diabetes mellitus (T2DM) and to provide evidence for improving the quality of life (QOL). Methods: A total of 12 community health service centers from Shanxi province, Jiangsu province, and Ningxia Hui autonomous region were selected as intervention group and control group, by stratified cluster sampling method. "5+1" model was used in intervention groups and basic public health services model was applied in control groups for this two-year follow-up. Data was collected through a questionnaire on demographic and disease-related information, while the QOL was measured with SF-36. Multiple linear regression and conducted by SAS 9.4. Results: A total of 2 467 subjects were included at baseline and 1 924 had completed a two-year-long management service. After intervention programs being implemented, the net effect of PCS score between the intervention and the control groups was 13.6, with the net effect of MCS score as 29.8. Results from the multiple linear regression showed that the main factors affecting PCS scores included age, type of medical insurance, baseline PCS score and regions of residency. Main factors related to MCS score included age, type of medical insurance, baseline MCS score, hypertension, and region of residency. Conclusion: Community "5+1" staged diabetes target management model presented favorable effect of improving the QOL on T2DM patients.
Community Health Services/organization & administration* ; Diabetes Mellitus, Type 2/therapy* ; Humans ; Hypertension ; Program Evaluation ; Quality of Life ; Self Care ; Self-Management ; Surveys and Questionnaires

The aim of this paper was to investigate the flavonoids of callus of transgenic and non-transgenic Saussurea involucrate and its antitumor activity on the esophageal cancer CaEs-17 cells. The species and content of mono-phenols were detected by high performance liquid chromatography. The growth of human esophageal cancer CaEs-17 cells was detected using CCK-8 assay, apoptosis morphology observation and flow cytometry. Expression of related apoptotic genes Bax and Bcl-2 were determined by qPCR. The results showed that the content of total flavonoids in the transgenic callus was 2.72 times that of the non-transgenic callus. The cyanidin-galactoside was detected in the transgenic callus, but not in the non-transgenic callus. The inhibitory effect of the extracts from the transgenic callus on CaEs-17 cells was more significant than that of the non-transgenic callus, and the IC₅₀ value had a decreased of 26.4%. Flow cytometry analysis results showed that the apoptosis induction effect of the extracts from the transgenic callus on CaEs-17 cells was significantly better than that of the non-transgenic callus. Fluorescence quantitative PCR analysis results showed that the extracts from the transgenic callus could up-regulate the expression of proapoptotic gene Bax and down-regulate the expression of apoptotic gene Bcl-2, and the regulation effect of the transgenic callus was more significant. Therefore, compared with the non-transgenic callus, the antitumor activity of the extracts from the callus of transgenic S. involucrate on the esophageal cancer CaEs-17 cells was significantly increased, which was closely related to the accumulation of cyanidin-galactoside and its metabolism-related flavonoid compounds in the transgenic callus.
Apoptosis ; Chromatography, High Pressure Liquid ; Flavonoids ; Humans ; Phenols ; Plant Extracts ; Saussurea

Objective: To verify the safety and efficacy of IONTRIS particle therapy system (IONTRIS) in clinical implementation. Methods: Between 6.2014 and 8.2014, a total of 35 patients were enrolled into this trial: 31 males and 4 females with a median age of 69 yrs (range 39-80). Ten patients had locally recurrent head and neck tumors after surgery, 4 cases with thoracic malignancies, 1 case with hepatocellular carcinoma, 1 case with retroperitoneal sarcoma, and 19 cases with non-metastatic prostate carcinomas. Phantom dose verification was mandatory for each field before the start of radiation. Results: Twenty-two patients received carbon ion and 13 had proton irradiation. With a median follow-up time of 1 year, all patients were alive. Among the 16 patients with head and neck, thoracic, and abdominal/pelvic tumors, 2, 1, 12, and 1 cases developed complete response, partial response, stable disease, or disease progression, respectively. Progression-free survival rate was 93.8% (15/16). Among the 19 patients with prostate cancer, biological-recurrence free survival was 100%. Particle therapy was well tolerated in all 35 patients. Twenty-five patients (71.4%) experienced 33 grade 1 acute adverse effects, which subsided at 1 year follow-up. Six (17.1%) patients developed grade 1 late adverse effects. No significant change in ECOG or body weight was observed. Conclusions IONTRIS is safe and effective for clinical use. However, long term follow-up is needed to observe the late toxicity and long term result.

In a real-world running of cancer screening programs or intervention strategies, multiple influencing factors need to be considered other than the effectiveness and cost-effectiveness. The articles in this special issue summarize the main findings related to sustainability of cancer screening program in urban China from four perspectives of cancer screening service, including actual supplier, potential supplier, actual demander and potential demander. These evidences are expected to provide references for decision-making on suitable strategies and running mechanism for large-scale cancer screening program in local populations.
China ; Cost-Benefit Analysis ; Early Detection of Cancer/methods* ; Health Services Administration ; Humans ; Mass Screening/organization & administration* ; Neoplasms/prevention & control* ; Urban Population

Objective: To investigate the second or third trimester pregnancy-related anxiety on small-for-gestational-age infants. Methods: This study was based on Ma'anshan Birth Cohort Study (MABC), with 3 040 maternal-singleton pairs finally selected for data analysis, from May 2013 to September 2014. The psychological state of pregnancy was evaluated according to a self-developed 'anxiety scale for gestation'. Small-for-gestational-age was defined as 'having birth weight below the 10(th) percentile at a particular gestational week', while large-for-gestational-age infants was defined as 'having birth weight above the 90(th) percentile'. Birth weight between the 10(th) and 90(th) percentile was classified as appropriate-for-gestational age infants. χ(2) test was used to compare the distribution of characteristics in pregnancy among three groups with different birth weights. Multivariate logistic regression models were conducted to evaluate the associations between third trimester pregnancy- related anxiety and birth weight. Results: The incidence rates of small- and large-gestational-age infants were 9.6% and 16.6%, respectively. Difference between women with only one of the second or third trimester pregnancy-related anxiety syndromes and small-for-gestational-age infants showed no statistical significance. Women with both second and third trimester pregnancy-related anxieties might increase the risk of small-for-gestational-age infants (OR=1.39, 95%CI: 1.04-1.87). However, there was no significant difference between pregnancy-related anxiety and large-for- gestational-age infants (OR=1.05, 95%CI: 0.81-1.35) noticed. Conclusion: Women with second and third trimester pregnancy-related anxiety appeared a risk factor for small-for-gestational-age infants.
Anxiety/psychology* ; Birth Weight ; China/epidemiology* ; Cohort Studies ; Female ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Infant, Small for Gestational Age ; Pregnancy ; Pregnancy Complications/psychology* ; Pregnancy Trimester, Third/psychology*

Objective: To analyze the trends on mortalities of all-cause and deaths caused by chronic and non-communicable diseases (NCDs) among Chinese labor force population during 2007 to 2016. Methods: Data on cause-of-death that collected from the National Mortality Surveillance System was used to analyze the age and area-related specific crude mortality rates, age-standardized mortality rates and component ratios of NCDs, among the Chinese labor force population, during 2007 to 2016. Trend of crude mortality rates and mortality component ratios of the three major diseases (infectious diseases, maternal and infant diseases, nutritional deficiency diseases; NCDs; injuries) were analyzed. Age-standardized mortality of cancer, COPD, cardiovascular and cerebrovascular diseases were also analyzed by gender. Age-standardized mortality was calculated based on the Year 2010 Population Census of China. Joinpoint regression model was used to obtain annual percentage change and 95%CI was set for assessing the trend. Results: In 2016, the age-standardized all-cause mortality rate was 217.23 per 100 000 among the Chinese labor force population, but decreased by -2.8% (95%CI: -3.8%- -1.7%) annually from 2007 to 2016. The gap between different gender and regions gradually narrowed. The proportion of deaths caused by NCDs increased annually by 0.8% (95%CI: 0.7%-0.9%). The age-standardized mortality rate of NCDs appeared as 171.89/100 000, among the Chinese labor force population in 2016, showing a downward trend by -2.4% (95%CI:-3.3% - -1.4%). However, in females, there appeared the greatest decrease, with an average annual change of -3.3% (95%CI:-4.0% - -2.5%). Diseases as cancer, COPD, cardiovascular and cerebrovascular diseases all showed downward trends in the whole country, with an average range of -2.0% (95%CI: -2.6%--1.3%), -8.0% (95%CI: -8.9% - -7.1%), -1.5% (95%CI: -2.9% - -0.1%), -2.3% (95%CI: -2.8% - -1.8%) in a ten-year period, respectively. Conclusion: All-cause and age-standardized mortality rates caused by NCDs among Chinese labor force population were decreasing during 2007 to 2016. However, the constituent ratios appeared increasing, year by year. Close attention needs to be paid on NCDs which affecting the health of the labor force population in China.
Cause of Death/trends* ; China ; Chronic Disease/epidemiology* ; Employment ; Female ; Humans ; Infant ; Mortality/trends* ; Noncommunicable Diseases/mortality*