[Clinical observation of the subthreshold micropulse laser combined with ranibizumab for treatment of diabetic macular edema].

Objective: To evaluate the efficacy and safety of the subthreshold micropulse laser (SMPL) combined with ranibizumab in treating diabetic macular edema (DME). Methods: This was a prospective randomized controlled study. Patients diagnosed with DME in the Ophthalmology Department of Beijing Hospital were enrolled from January 2020 to December 2022. Patients were randomized in a ratio of 1∶1 using a table of random numbers into the ranibizumab monotherapy group and the SMPL combined with ranibizumab therapy group. We compared the changes of best-corrected visual acuity, central macular thickness measured by optical coherence tomography and optical coherence tomography angiography parameters, including the vessel density of the superficial and deep capillary plexus (DCP), foveal avascular zone size and peripapillary vessel density, at baseline, 6 and 12 months after the treatment. After 12 months of follow-up, fundus fluorescein angiography results, adverse events, and the number of injections or laser therapies were recorded. The Fisher's exact test and group t-test were used for statistical analysis. Results: Seventy-two patients (72 eyes) were enrolled, with a mean age of (61.1±8.2) years. Patients in the combination therapy group included 19 males and 17 females, while patients in the ranibizumab monotherapy group were 17 males and 19 females. There was no statistically significant difference in baseline characteristics between the two groups (P>0.05). A significant improvement in best-corrected visual acuity was shown in both groups at 6 and 12 months [(58.5±12.9) and (58.2±12.2) ETDRS letters in the combination therapy group, and (63.3±13.1) and (63.8±12.5) ETDRS letters in the ranibizumab monotherapy group]. A significant reduction in central macular thickness was shown in both groups at 6 and 12 months [(451.0±185.5) and (380.4±159.3)µm in the combination therapy group, and (387.5±135.5) and (372.8±146.1)µm in the ranibizumab monotherapy group]. However, there was no significant difference between groups at each timepoint (all P>0.05). At 12 months, the vessel density of the superficial capillary plexus showed no statistical difference compared to the baseline value in each group or between groups (42.6%±5.9% in the ranibizumab monotherapy group and 42.2%±5.5% in the combination therapy group, P>0.05). The vessel density of the DCP in the combination therapy group significantly increased to 47.5%±5.6% at 12 months, significantly different from that in the ranibizumab group (43.4%±5.1%; P<0.05). The foveal avascular zone size in the ranibizumab monotherapy group reduced to (0.32±0.13) mm2, significantly different from that in the combination therapy group [(0.34±0.16) mm2] at 12 months (P<0.05). Patients in the ranibizumab monotherapy group received (7.3±2.5) intravitreal injections, while patients in the combination therapy group received 3 injections. No unfavorable outcomes on fundus fluorescein angiography or systemic or topical severe adverse events were observed during the follow-up. Conclusions: The SMPL combined with intravitreal ranibizumab injections was effective and safe in treating DME patients. The combination treatment significantly reduced the number of injections and improved the vessel density of the DCP and macular ischemia, compared to the ranibizumab monotherapy.

Site-directed mutation of ß-galactosidase from Streptococcus thermophilus for galactooligosaccharide-enriched yogurt making.

ß-Galactosidase is one of the most important enzymes used in dairy processing. It converts lactose into glucose and galactose, and also catalyzes galactose to form galactooligosaccharides (GOS), so-called prebiotics. However, most of the ß-galactosidases from the starter cultures have low transgalactosylation activities, the process that results in galactose accumulation in yogurt. Here, a site-directed mutation strategy was attempted, to genetically modify ß-galactosidase from Streptococcus thermophilus. Out of 28 Strep. thermophilus strains, a ß-galactosidase gene named bgaQ, encoded for high ß-galactosidase hydrolysis activity (BgaQ), was cloned from the strain Strep. thermophilus SDMCC050237. It was 3,081 bp in size, with 1,027 deduced amino acid residuals, which belonged to the GH2 family. After replacing the Tyr801 and Pro802 around the active sites of BgaQ with His801 and Gly802, the GOS synthesis of the generated mutant protein BgaQ-8012 increased from 20.5% to 26.7% at 5% lactose, and no hydrolysis activity altered obviously. Subsequently, the purified BgaQ or BgaQ-8012 was added to sterilized milk inoculated with 2 starters from Strep. thermophilus SDMCC050237 and Lactobacillus delbrueckii ssp. bulgaricus ATCC11842. The GOS yields with added BgaQ or BgaQ-8012 increased to 5.8 and 8.3 g/L, respectively, compared with a yield of 3.7 g/L without enzymes added. Meanwhile, the addition of the BgaQ or BgaQ-8012 reduced the lactose content by 49.3% and 54.4% in the fermented yogurt and shortened the curd time. Therefore, this study provided a site-directed mutation strategy for improvement of the transgalactosylation activity of ß-galactosidase from Strep. thermophilus for GOS-enriched yogurt making.

[Clinical observation of combined oral contraceptives drospirenone and ethinylestradiol tablets (â ¡) in the treatment of dysmenorrhea in Chinese women].

Objective: To evaluate the efficacy and safety of drospirenone and ethinylestradiol tablets (Ⅱ) in Chinese women with dysmenorrhea. Methods: This was a single-arm, open-label, interventional, multicenter, post-authorization safety/effectiveness study of drospirenone and ethinylestradiol tablets (Ⅱ) across 6 treatment cycles, a total of 526 patients were included in the dysmenorrhea subgroup. Visual analog scale (VAS) was used to assess the severity of menstrual pain. Secondary outcomes included unintended pregnancies, bleeding pattern, cycle control and safety. Results: After treated with drospirenone and ethinylestradiol tablets (Ⅱ), VAS of pain had decreased significantly compared with baselines [(49.5±23.7) vs (32.3±24.9) vs (20.7±19.4) vs (18.4±18.7) mm, P<0.01]. From the second cycle to the fifth cycle, the incidence of scheduled bleeding increased from 93.9% (450/479) to 96.4% (431/447). The duration of scheduled bleeding decreased from (5.7±2.7) to (5.4±1.8) days. The incidence of intermenstrual bleeding decreased from 9.0% (43/479) to 5.6% (25/447). 17.5% (92/526) patients reported adverse drug reactions, most frequently reported adverse events were breast pain, nausea, breast swelling, headache, and uterine bleeding. No death occurred during the study. Conclusion: Drospirenone and ethinylestradiol tablets (Ⅱ) is effective for the treatment of dysmenorrhea and has good safety.

Intestinal dysbacteriosis mediates the reference memory deficit induced by anaesthesia/surgery in aged mice.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is associated with increased morbidity and mortality and has become a major concern for patients and caregivers. POCD is most common in older patients. Previous studies demonstrated that the gut microbiome affects cognitive function and behaviour, and perioperative factors, including the operation itself, antibiotics, opioids or acid-inducing drugs, affect the gut microbiome. Thus, we hypothesised that intestinal dysbacteriosis caused by anaesthesia/surgery induces POCD. METHODS: Tibial fracture internal fixation was performed in 18-month-old C57BL/6 mice under isoflurane anaesthesia to establish the POCD model. The Morris water maze was used to measure reference memory after anaesthesia/surgery. High-throughput sequencing of 16S rRNA from faecal samples was used to investigate changes in the abundance of intestinal bacteria after anaesthesia/surgery. To confirm the role of the gut microbiome in POCD, we pretreated mice with compound antibiotics or mixed probiotics (VSL#3). Anaesthesia/surgery impaired reference memory and induced intestinal dysbacteriosis in aged mice. RESULTS: The 16S rRNA sequencing data revealed 37 genera (18 families) of bacteria that changed in abundance after anaesthesia/surgery. Pretreating mice with compound antibiotics or mixed probiotics (VSL#3) prevented the learning and memory deficits induced by anaesthesia/surgery. We further conducted quantitative real-time polymerase chain reaction (qRT-PCR) of 22 common types of bacteria among the 37 total types to verify the results of bacterial flora changes after anaesthesia/surgery. Numbers of 8 types of bacteria changed after anaesthesia/surgery but returned to normal after treatment with a mix of probiotics. CONCLUSIONS: Our data suggest that deficits in reference memory induced by anaesthesia/surgery are mediated by intestinal dysbacteriosis.

[Liver cancer epidemiology in China, 2015].

Objective: Using updated population-based cancer registration (PBCR) data, we estimated nation-wide liver cancer statistics overall, by sex and by areas in China. Methods: Qualified PBCR data of liver cancer in 2015 which met the data quality criteria were stratified by geographical locations, sex, and age groups. Age-specific incidence and mortality rates by sex and area were calculated. The burden of liver cancer was evaluated by multiplying these rates by the year of 2015 population. Chinese standard population in 2000 and World Segi's population were used for the calculation of age-standardized rates (ASR) of incidence and mortality. Results: Qualified 368 cancer registries covered a total of 309 553 499 populations in China, accounting for 22.52% of the national population. It is estimated that there were 370 000 new cases (274 000 males and 96 000 females) of liver cancer in China. The age-standardized incidence rates by Chinese standard population (ASR China) and World Segi's population (ASR World) were 17.64 per 100 000 and 17.35 per 100 000, respectively. Rural areas showed higher incidence (ASR China: 20.07 per 100 000, ASR World: 19.67 per 100 000) than urban areas (ASR China: 15.90 per 100 000, ASR world: 15.67 per 100 000). Subgroup analysis showed that western areas of China had highest incidence rate of liver cancer, with the ASR China of 20.65 per 100 000 and 20.22 per 100 000 for ASR world, respectively. For new cases of liver cancer deaths, there were 326 000 new deaths (242 000 males and 84 000 females) in China, with age-standardized mortality rate by Chinese standard population and World Segi's population of 15.33 per 100 000 and 15.09 per 100 000, respectively. Rural areas showed higher mortality (ASR China: 17.17 per 100 000, ASR world: 16.86 per 100 000) than urban areas (ASR China: 14.00 per 100 000, ASR World: 13.81 per 100 000). Conclusions: There is still a heavy burden of liver cancer in China. Rural residents have higher incidence and mortality of liver cancer compared with urban counterparts. It is likely that many factors such as hepatitis virus infection, and aflatoxin exposure play a dominating role. Prevention and control strategies should be enhanced in the future.

[Report of cancer epidemiology in China, 2015].

Objective: Data from local cancer registries were pooled to estimate cancer incidence and mortality in China, 2015. Methods: Data submitted from 501 cancer registries were checked & evaluated according to the criteria of data quality control, and 368 registries' data were qualified for the final analysis. Data were stratified by area (urban/rural), sex, age group and cancer sites, and combined with national population data to estimate cancer incidence and mortality in China, 2015. Chinese population census in 2000 and Segi's population were used for age-standardized. Results: Total population covered by 368 cancer registries were 309 553 499 (148 804 626 in urban and 160 748 873 in rural areas). The percentage of morphologically verified cases (MV) and the percentage of death certificate-only cases (DCO) accounted for 69.34% and 2.09%, respectively, and the mortality to incidence ratio was 0.61. About 3 929 000 new cancer cases were reported in 2015 and the crude incidence rate was 285.83 per 100 000 population (males and females were 305.47 and 265.21 per 100 000 population). Age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) were 190.64 and 186.39 per 100 000 population, respectively, with the cumulative incidence rate (0-74 age years old) of 21.44%. The cancer incidence and ASIRC were 304.96/100 000 and 196.09/100 000 in urban areas and 261.40/100 000 and 182.70/100 000 in rural areas, respectively. About 2 338 000 cancer deaths were reported in 2015 and the cancer mortality was 170.05/100 000 (210.10/100 000 in males and 128.00/100 000 in females). Age-standardized mortality rates by Chinese standard population (ASMRC) and by world standard population (ASMRW) were 106.72/100 000 and 105.84/100 000, respectively, with the cumulative incidence rate (0-74 age years old) of 11.94%. The cancer mortality and ASMRC were 172.61/100 000 and 103.65/100 000 in urban areas and 166.79/100 000 and 110.76/100 000 in rural areas, respectively. The most common cancer cases including lung, gastric, colorectal, liver and female breast, the top 10 cancer incidence accounted for about 76.70% of all cancer new cases. The most common cancer deaths including lung, liver, gastric, esophageal and colorectal, the top 10 cancer deaths accounted for about 83.00% of all cancer deaths. Conclusions: The burden of cancer showed a continuous upward trend in China. Cancer prevention and control faces the problem of the disparity in different areas and different cancer burden between men and women. The cancer pattern in China presents the coexistence of the cancer patterns in developed and developing countries. The situation of cancer prevention and control is still serious in China.

[Analysis of incidence and mortality of esophageal cancer in China, 2015].

Objective: To estimate the incidence and mortality rates of esophageal cancer in China in 2015. Methods: Based on the data quality review and assessment, the esophageal cancer data from 368 cancer registries in 31 provinces (autonomous regions and municipalities) in China were included in this study. According to the national population data in 2015, the nationwide incidence and mortality of the esophageal cancer were estimated. Chinese standard population in 2000 and world Segi's population were used to calculate the age-standardized (ASR) incidence and mortality rates (ASR China and world, respectively). Results: The 368 cancer registries covered a total of 309 553 499 populations in China, accounting for 22.52% of the national population. There were 245 651 new esophageal cancer cases estimated in China in 2015, with a crude incidence rate of 17.87/100 000. The ASR China and ASR world were 11.14/100 000 and 11.28/100 000, respectively. The estimated number of esophageal cancer death was 188 044 in China in 2015, with a crude mortality rate of 13.68/100 000; The ASR China and ASR world mortality rates were 8.33/100 000 and 8.36/100 000, respectively. The ASR China incidence and mortality of esophageal cancer in males were higher in males (16.50/100 000 and 12.66/100 000) than those in females (5.92/100 000 and 4.17/100 000), and they were higher in rural areas (15.95/1100 000 and 11.67/100 000) than those in urban areas (7.59/100 000 and 5.87/100 000). Conclusion: The incidence and mortality of esophageal cancer in China are higher than the global average. The disparity of the incidence and mortality rates of esophageal cancer significantly differed in genders and areas.

[Analysis on incidence and mean age at diagnosis for Global Cancer].

Objective: To analyze the age distribution characteristics of different cancers in the world according to the database from Cancer Incidence in Five Continents published by the International Association of Cancer Registries, and to compare the age differences of cancer incidence in different regions. Methods: Cancer incidence data from volume XI of Cancer Incidence in Five Continents including 339 population-based cancer registries in 65 countries during 2008-2012 have been extracted. The average age of cancer incidence in different regions, gender and cancer sites were analyzed and stratified according to the human development Index and the level of national or regional development UN Development. The Segi's world standard population (world standard) was standardized to calculate the average age of the cancer incidence and to analyze the effect of age structure of the population on the average age of cancer diagnosis. Results: This study included 4 812 008 148 person-years in the global population (including 2 367 458 302 men and 2 444 549 846 women), and 21 892 093 of the new cancer cases, including 11 450 515 men and 10 441 578 women. The analysis showed that the average age of cancer incidence in the world was 65.73 years, and men and women were 66.70 and 64.67 years old, respectively. Among them, the average incidence age of testicular cancer was the youngest, with an average age of 36.67 years, and that of gallbladder cancer was the highest with average age of 71.55 years. After adjusting for population structure, the average incidence age was highest in gallbladder cancer, followed with bladder cancer and prostate cancer, and the testicular was with the lowest average age of incidence, followed by bone cancer and brain tumor. The results showed that the average age of cancer incidence in developed countries or regions was 66.38 years old, and that in less developed countries or regions was 61.75 years old, but in China it was 63.47 years old. According to the human development index (HDI), the higher the country or region with HDI, the higher the average age of cancer incidence, and the difference is reduced after the adjustment of the age structure of the population. Conclusions: There are different characteristics of the age distribution for different cancer sites. In terms of the age of cancer incidence, those of gallbladder cancer and bladder cancer are relatively old, while those of the testis, bone and thyroid cancer are relatively young. The average age of cancer incidence in China is between developed and less developed countries. Prevention and control of cancer should be carried out according to the age distribution characteristics of different cancers.

[Report of Cancer Incidence and Mortality in China, 2014].

Objective: The registration data of local cancer registries in 2014 were collected by National Central Cancer Registry (NCCR)in 2017 to estimate the cancer incidence and mortality in China. Methods: The data submitted from 449 registries were checked and evaluated, and the data of 339 registries out of them were qualified and selected for the final analysis. Cancer incidence and mortality were stratified by area, gender, age group and cancer type, and combined with the population data of 2014 to estimate cancer incidence and mortality in China. The age composition of standard population of Chinese census in 2000 and Segi's population were used for age-standardized incidence and mortality in China and worldwide, respectively. Results: Total covered population of 339 cancer registries (129 in urban and 210 in rural) in 2014 were 288 243 347 (144 061 915 in urban and 144 181 432 in rural areas). The mortality verified cases (MV%) were 68.01%. Among them, 2.19% cases were identified through death certifications only (DCO%), and the mortality to incidence ratio was 0.61. There were about 3, 804, 000 new cases diagnosed as malignant cancer and 2, 296, 000 cases dead in 2014 in the whole country. The incidence rate was 278.07/100, 000 (males 301.67/100, 000, females 253.29/100, 000) in China, age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population were 190.63/100, 000 and 186.53/100, 000, respectively, and the cumulative incidence rate (0-74 age years old) was 21.58%. The cancer incidence and ASIRC in urban areas were 302.13/100, 000 and 196.58/100, 000, respectively, whereas in rural areas, those were 248.94/100, 000 and 182.64/100, 000, respectively. The cancer mortality in China was 167.89/100, 000 (207.24/100, 000 in males and 126.54/100, 000 in females), age-standardized mortality rates by Chinese standard population (ASMRC) and by world standard population were 106.98/100, 000 and 106.09/100, 000, respectively. And the cumulative incidence rate (0-74 age years old) was 12.00%. The cancer mortality and ASMRC in urban areas were 174.34/100, 000 and 103.49/100, 000, respectively, whereas in rural areas, those were 160.07/100, 000 and 111.57/100, 000, respectively. Lung cancer, gastric cancer, colorectal cancer, liver cancer, female breast cancer, esophageal cancer, thyroid cancer, cervical cancer, encephala and pancreas cancer, were the most common cancers in China, accounting for about 77.00% of the new cancer cases. Lung cancer, liver cancer, gastric cancer, esophageal cancer, colorectal cancer, pancreatic cancer, breast cancer, encephala, leukemia and lymphoma were the leading causes of death and accounted for about 83.36% of cancer deaths. Conclusions: The progression of cancer registry in China develops rapidly in these years, with the coverage of registrations is expanded and the data quality was improved steadily year by year. As the basis of cancer prevention and control program, cancer registry plays an important role in making the medium and long term of anti-cancer strategies in China. As China is still facing the serious cancer burden and the cancer patterns varies differently according to the locations and genders, effective measures and strategies of cancer prevention and control should be implemented based on the practical situation.

[Incidence and mortality of cervical cancer in China, 2014].

Objective: To estimate the incidence and mortality of cervical cancer in China based on the cancer registry data in 2014, collected by the National Central Cancer Registry (NCCR). Methods: There were 449 cancer registries submitted cervical cancer incidence and deaths in 2014 to NCCR. After evaluating the data quality, 339 registries' data were accepted for analysis and stratified by areas (urban/rural) and age group. Combined with data on national population in 2014, the nationwide incidence and mortality of cervical cancer were estimated. Chinese population census in 2000 and Segi's population were used for age-standardized incidence/mortality rates. Results: Qualified 339 cancer registries covered a total of 288 243 347 populations (144 061 915 in urban and 144 181 432 in rural areas). The percentage of morphologically verified cases and death certificate-only cases were 86.07% and 1.01%, respectively. The mortality to incidence ratio was 0.30. The estimates of new cases were about 102 000 in China in 2014, with a crude incidence rate of 15.30/100 000. The age-standardized incidence rates by China standard population (ASR China) and world standard population (ASR world) of cervical cancer were 11.57/100 000 and 10.61/100 000, respectively. Cumulative incidence rate of cervical cancer in China was 1.11%. The crude and ASR China incidence rates in urban areas were 15.27/100 000 and 11.16/100 000, respectively, whereas those were 15.34/100 000 and 12.14/100 000 in rural areas. The estimates of cervical cancer deaths were about 30 400 in China in 2014, with a crude mortality rate of 4.57/100 000. The ASR China and ASR world mortality rates were 3.12/100 000 and 2.98/100 000, respectively, with a cumulative mortality rate (0-74 years old) of 0.33%. The crude and ASR China mortality rates were 4.44/100 000 and 2.92/100 000 in urban areas, respectively, whereas those were 4.72/100 000 and 3.39/100 000 in rural areas. Conclusions: There is still a heavy burden of cervical cancer in China. The burden and patterns of cervical cancer shows different characters of urban and rural people. Prevention and control strategies should be implemented referring to local status.

[The incidence and mortality of lung cancer in China, 2014].

Objective: To estimate lung cancer incidence and mortality in China using population-based cancer registry data in 2014 collected by National Central Cancer Registry of China (NCCRC). Methods: 449 cancer registries submitted cancer registry data in 2014. All datasets were evaluated and 339 registries' data which met the quality control criteria of NCCRC were analyzed. Numbers of new lung cancer cases and deaths were estimated using calculated incidence and mortality rates and corresponding national population stratified by areas, sexes and age groups. The standard population of Chinese census in 2000 and world Segi' s population were applied to calculate age-standardized incidence and mortality rates in China and worldwide, respectively. Results: A total of 781, 500 new lung cancer cases were diagnosed in 2014. The crude incidence rate was 57.13 per 100 000 and the age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) were 36.71 per 100 000 and 36.63 per 100 000, respectively. The cumulative incidence rate (0-74 years old) was 4.50%. Lung cancer was the most common cancer in male (ASIRW: 50.04 per 100 000) and the second most common cancer in female (ASIRW: 23.63 per 100 000). The incidence rates were slightly similar in urban areas and in rural areas (ASIRW: 36.64 per 100 000 vs 36.56 per 100 000). A total of 626 400 lung cancer deaths were reported. The crude mortality rate was 45.80 per 100 000 and the age-standardized mortality rates by Chinese standard population (ASMRC) and by world standard population (ASMRW) were 28.49 per 100 000 and 28.31 per 100 000, respectively. The cumulative mortality rate (0-74 years old) was 3.32%. Lung cancer was the most common cause of cancer deaths both in male (ASMRW: 40.21 per 100 000) and female (ASMRW: 16.88 per 100 000). The mortality rate was slightly higher in rural areas than in urban areas (ASMRW: 28.63 per 100 000 vs 28.04 per 100 000). Both lung cancer incidence and mortality rates increased with age, and the peak age was 80-84 years group. Conclusions: The disease burden of lung cancer is heavy in China. Efficient national health policies and prevention and control strategies against lung cancer should be promoted.

[Trend analysis on incidence and age at diagnosis for lung cancer in cancer registration areas of China, 2000-2014].

Objective: To analyze the incidence trend and mean age at diagnosis for lung cancer in cancer registration areas of China from 2000 to 2014. Methods: The data of lung cancer incidence used in this study were from 22 registries submitted to National Central Cancer Registry with continuous data during 2000 and 2014, covering about 621 593 469 person-years. All cancer cases were coded as C33-C34 according to the International Classification of Diseases-10(th) Revision (ICD-10) were extracted for this analysis with about 343 663 patients. The incidence of different sex and regional population, the standardized incidence rate by Chinese population, the average annual change percentage (AAPC), the mean age and adjusted mean age of cancer incidence were calculated. The incidence of each year was described by regional and age groups, and the linear regression model was employed to analyze the relationship between mean age at onset and year. Results: The crude incidence rate and age-standardized incidence rate (ASR) of lung cancer for men in cancer registry areas in 2000 were 56.98 per 100 000 and 48.43 per 100 000, respectively. The rates were 89.51 per 100 000 and 46.85 per 100 000 in 2014, respectively. For women in the same areas, the rates were 27.77 per 100 000 and 20.17 per 100 000 in 2000; while 51.31 per 100 000 and 25.44 per 100 000 in 2014, respectively. The crude incidence rate increased along with the age. In 2000-2014, the trend of crude rate and ASR of lung cancer were significantly increased (CR: AAPC=3.8%, 95%CI: 3.5%-4.1%; ASR: AAPC=0.4%, 95%CI: 0.2%-0.7%). The rise of crude rate in females was higher than that in males (Male: AAPC=3.5%, 95%CI: 3.2%-3.7%; Female: AAPC=4.5%, 95%CI: 4.1%-5.0%). However, the rise of the ASR declined for both male and female (Male: AAPC=-0.2%, 95%CI:-0.4%-0.0%; Female: AAPC=1.4%, 95%CI: 1.0%-1.9%). The average age at diagnosis of lung cancer in rural areas was 64.35 years old in 2000, and increased to 65.97 years old in 2014 (ß=0.11, P<0.001), while adjusted mean age at onset remained stable in all areas and urban areas (P>0.05). And the average age at onset increased significantly over time in male (ß=-0.02, P=0.014), which was not seen in female (ß=-0.01, P=0.522). Conclusion: The crude incidence rate of lung cancer in cancer registry areas in China increased slowly during 2000-2014; and the standardized average age of male at diagnosis decreased slightly, while the age in rural areas increased during 2000-2014. Lung cancer will still be the focus of cancer prevention and control in the near future.

[Incidence trend and change in the age distribution of female breast cancer in cancer registration areas of China from 2000 to 2014].

Objective: To estimate the incidence trend and change in the age distribution of female breast cancer in cancer registry areas in China from 2000 to 2014. Methods: 22 cancer registries in China with continuous monitoring data from 2000 to 2014 were selected. All datasets were checked and evaluated based on data quality control criteria and were included in the analysis. The cancer registries covered 675 954 193 person-years, including 342 010 930 person-years of male and 333 943 263 person-years of female. Female breast cancer cases (International Classification of Diseases-10(th) Revision: C50) were extracted. Crude incidence rate (CR), age-standardized incidence rate by Chinese standard population(ASIRC), annual percent change (APC), crude and adjusted mean age at onset were calculated. Incidence rates stratified by regions and age groups were calculated. Results: Female breast cancer incidence rate significantly increased from 31.90/100 000 in 2000 to 63.30/100 000 in 2014. Incidence rate increased rapidly from 2000 to 2008 (CR: APC=6.5%, 95%CI: 5.3%-7.8%; ASIRC: APC=4.6%, 95%CI: 3.6%-5.7%). Its increment slowed down from 2008-2014 (CR: APC=3.2%, 95%CI: 1.4%-5.1%; ASIRC: APC=1.4%, 95%CI:-0.1%-2.9%). The crude mean age at onset increased from 54.4 in 2000 to 57.0 in 2014. Adjusted mean age at onset remained around 54.3 in 2014. Crude mean age at onset increased significantly over time in all registry areas (ß=0.192, P<0.001), urban (ß=0.205, P<0.001) and rural (ß=0.092, P=0.014) areas, while adjusted mean age at onset remained stable in all registry areas (ß=0.009, P=0.289), urban (ß=0.017, P=0.139) and rural (ß=-0.054, P=0.109) areas. Conclusion: Female breast cancer incidence rate in China increased from 2000 to 2014. Aging of the population resulted in a significant increase in crude mean age at onset. After age adjustment, no significant changes in age distribution were found.

[Analysis on the trend of prostate cancer incidence and age change in cancer registration areas of China, 2000 to 2014].

Objective: To analyze the trend of cancer incidence and age changes among men in cancer registration areas of China from 2000 and 2014. Methods: We select the information of national cancer registry with continuous data from 2000 to 2014, review and organize the monitoring data at the above registries. A total of 22 monitoring registries were included in this study. The covering population of male were about 314 330 648 person years. The information on the incidence of all male prostate cancer patients with C61 was extracted from the International Classification of Diseases-10(th) Revision (ICD-10). To understand the incidence of male prostate cancer in each year, the age-standardized rate by Chinese population (ASR), average annual percent change (AAPC), adjusted mean age at onset were calculated. Incidence rates stratified by regions and age groups were also calculated. The linear regression model was employed to analyze the relationship between mean age at onset and year. Results: The prostate cancer incidence in China increased by 11.5% (95%CI: 10.3%-12.7%) from 2000(4.62/100 000) to 2014(21.62/100 000), the age-standardized incidence rate increased by 7.1% (95%CI: 6.0%-8.1%) and the growth of rural was greater than that of urban. The age-specific incidence showed that the incidence rate increased significantly among the age group of 50 years; the incidence rates in men who have the same age but with different birth years showed a significant increase as birth years increased. The adjusted mean age at diagnosis of prostate cancer in cancer registry areas was 74.09 years old in the year of 2000, reduced by 0.13 year old to 72.35 years old in 2014 (ß=-0.13, P<0.001). The adjusted mean age at onset declined significantly over time in urban areas (ß=-0.13, P<0.001). Conclusion: The trend of prostate cancer incidence among men in cancer registry regions generally increased, and the average age at diagnosis declined slightly from 2000 to 2014.

[Analysis on the trend of cancer incidence and age change in cancer registry areas of China, 2000 to 2014].

Objective: To analyze the trends of cancer incidence and age changes in China with using cancer registration data, and to provide evidence for the development of cancer prevention and control. Methods: Twenty-two cancer registries with continuous (2000-2014) data were selected. The incidence of different sex and regional population, the standardized incidence rate by Chinese population, the average annual change percentage (AAPC) and annual change percentage(APC) were calculated. Age-period-cohort model were used to analyze the changes of cancer incidence, age-adjusted mean ages. The age-standardized proportion of 2000 and 2014 with were compared. Results: The cancer incidence in China increased by 3.9% (95%CI: 3.7%-4.1%) from 2000 to 2014 in APC, and the age-standardized incidence rate increased by 1.2% (95%CI: 1.0%-1.4%) in AAPC. The age-specific incidence showed that each age groups increased significantly in female, ranged between 0.9% to 6.0%. The APC in male aged from 60 years old showed decline trend, the APC in 60-69, 70-79, ≥80 years old were -0.2, -0.3, -0.3, while in the population aged 0-29, 30-39 years old increased dramatically, APC were 3.5, 2.0. Female under 60 also increased, and APC in 0-29, 30-39, 40-49, 0-59 years old were 5.7, 6.0, 3.4, 2.9, respectively. The mean age of patients diagnosed with cancer were increased during the past 15 years, with about 0.11 years per year increased. However, the mean age of the patients diagnosed with cancer showed decreased trend by 0.13 years after age structure adjusted. Conclusion: The trend of mean age for cancer incidence in China were getting younger than before, and the trend in women is more obviously than in man.

[Clinical application value of echocardiography combined with genetic testing in fetal cardiac rhabdomyoma].

OBJECTIVE: To investigate the clinical value of echocardiography combined with genetic testing in the fetal cardiac rhabdomyoma. METHODS: Thirty-three fetal cardiac rhabdomyoma cases diagnosed by fetal echocardiogram in Beijing Anzhen Hospital from Jan. 2011 to Oct. 2015 were enrolled in a retrospective analysis. The results of other examination and pregnancy outcomes of them were followed up, the genetic characteristics of cardiac rhabdomyoma were summarized on the basis of pathology and genetics examination results. RESULTS: The pregnancy outcomes: 24 cases were terminated pregnancy, 4 cases were born and 5 cases were lost. The results of ultrasound, pathology and genetic examination were detailed in 8 cases. Pathological examination: the typical characteristics of cardiac rhabdomyoma were found in the 8 cases with cardiac rhabdomyoma. The tumor tissue was composed of irregular and swelling shape of cardiomyocytes, and the cytoplasm was vacuole like, which was characteristic of " spider like cells" through microscopic observation. The geneticdetection results: 7 cases had tuberous sclerosis complex (TSC) gene mutation, TSC gene abnormalities were not detected in 1 case. Among the 7 cases with TSC gene mutations, 6 cases were with TSC2 gene mutation and the other 1 case was with TSC1 gene mutation. The family gene was investigated in the 5 cases, which including 3 cases of TSC gene mutation in mother passed on to the fetus (1 case with family of three generations of genetic) and 2 cases of spontaneous TSC gene mutation in the fetus. CONCLUSIONS: Prenatal echocardiography combined with genetic detection have important clinical significance, which not only can clear if cardiac rhabdomyomas were associated with TSC, but also can clear the TSC gene mutation source. So as to further guide the perinatal management.

The application of high definition flow imaging in fetal hemodynamics.

OBJECTIVE: This work aims to investigate the application of high definition flow imaging (HD-flow) in fetal hemodynamics, and establish reference range of hemodynamic parameters in fetal with different gestational ages. MATERIALS AND METHODS: A thousand of normal pregnant women were divided into five groups: 18-22, 23-27, 28-32, 33-37, and 38-40 gestational weeks. Color Doppler flow imaging (CDFI) and HD-flow were adopted to display the heart structure and measure the blood flow velocity. The pulmonary vein display results were scored. The results of HD-flow and CDFI were compared. RESULTS: The catheter peak velocity of fetal mitral, tricuspid, aortic, pulmonary artery, aortic arch, ductal arch, the inferior vena cava, pulmonary vein, and venous catheter increased continuously with the increase of gestational age, showing a linear correlation. HD-flow was superior to CDFI on the display of pulmonary vein in 18-22, 23-27, and 28-32 weeks (p < 0.05), but was not in 33-37 and 38-40 weeks. HD-flow was an accurate positioning method for the pulmonary veins. CONCLUSION: HD-flow can make accurate evaluation of fetal hemodynamics and the demonstration of low blood flow, such as pulmonary venous, is better than CDFI. Pulmonary veins can be accurately positioned with HD-flow. HD-flow can demonstrate the main blood vessels of the whole fetal circulation and can display the spatial relationship of the blood vessels. It is of important clinical significance in hemodynamic study.

[Periconceptional maternal homocysteine and birth weight outcomes in offspring: a prospective cohort study].

Objective: To quantify the associations between periconceptional maternal homocysteine (HCY) and offspring's birth weight and risk of small for gestational age (SGA) infant. Methods: The 19 984 mother-child pairs in this prospective cohort study were recruited from the Shanghai preconception cohort; the infants were delivered from 1st September 2016 to 11th November 2022. A standardized questionnaire was used to collect the mothers' demographic information, medical history, dietary supplement use, and maternal complications during pregnancy, and their serum samples were collected. Serum HCY, folate, and vitamin B12 were measured using chemiluminescent microparticle immunoassay based on serum sample drawn at enrollment. Birth weight data were obtained from medical records. Multiple imputation methods were applied to handle missing data in key variables. Multivariable linear regression and Poisson regression models were used to analyze the relationship between maternal HCY concentration during the periconceptional period and the birth weight and SGA risk of the offspring. Results: A total of 9 452 pairs were enrolled preconceptionally and the remaining 10 532 pairs were enrolled in early pregnancy. The proportion of mothers whose pregnancy age was greater than 35 years was 9.2% (1 832/19 984), the proportion of primiparous women was 76.5% (15 283/19 984), the proportion of pre-pregnancy overweight and obesity was 14.0% (2 804/19 984), the proportion of using folic acid supplements before pregnancy was 21.4% (4 272/19 984), and the proportion of those who supplemented with folic acid during early pregnancy was 85.2% (8 976/10 532); gestational diabetes mellitus was in 6.2% (1 245/19 984), gestational hypertensive syndrome in 3.6% (711/19 984). The birth weight of the offspring was (3 297±468) g, and there were 1 962 SGA children (9.8%). The HCY concentration in the overall population in appropriate for gestational age during the periconceptional period was (7.9±3.2) µmol/L, with (8.3±3.7) µmol/L in the preconception subgroup and (7.3±2.4) µmol/L in the early pregnancy subgroup. After adjustment for the covariates of perinatal demographic information, adverse pregnancy outcomes, serum folate and vitamin B12, increased maternal periconceptional HCY was significantly associated with lower offspring birth weight (ß=-2.30, 95%CI -4.43--0.16, P=0.035). Only the early pregnancy subgroup was significantly associated with lower offspring birth weight (ß=-7.39, 95%CI-11.50--3.21, P<0.001). No association was found between peripregnancy HCY and offspring SGA risk. However, elevated HCY in early pregnancy was associated with an increased risk of SGA in the offspring (RR=1.05, 95%CI 1.01-1.08, P=0.002). Periconceptional vitamin B12 was a mediator of the association between HCY and offspring birth weight, accounting for 16.5%, 41.2% and 5.4% of its total effect in the overall periconceptional population, the pre-pregnancy subgroup and the early pregnancy subgroup, respectively. Conclusions: Maternal periconceptional HCY level is associated with lower birth weight in offspring, but not with the risk of SGA. Elevated maternal HCY in early pregnancy subgroup may be associated with increased risk of SGA in offspring.

[Outcomes and care practices of extremely preterm infants at 22-25 weeks' gestation age from the Chinese Neonatal Network].

Objective: To describe the current status and trends in the outcomes and care practices of extremely preterm infants at 22-25 weeks' gestation age from the Chinese Neonatal Network (CHNN) from 2019 to 2021. Methods: This cross-sectional study used data from the CHNN cohort of very preterm infants. All 963 extremely preterm infants with gestational age between 22-25 weeks who were admitted to neonatal intensive care units (NICU) of the CHNN from 2019 to 2021 were included. Infants admitted after 24 hours of life or transferred to non-CHNN hospitals were excluded. Perinatal care practices, survival rates, incidences of major morbidities, and NICU treatments were described according to different gestational age groups and admission years. Comparison among gestational age groups was conducted using χ2 and Kruskal-Wallis tests. Trends by year were evaluated by Cochran-Armitage and Jonckheere-Terpstra tests for trend. Results: Of the 963 extremely preterm infants enrolled, 588 extremely preterm infants (61.1%) were male. The gestational age was 25.0 (24.4, 25.6) weeks, with 29 extremely preterm infants (3.0%), 88 extremely preterm infants (9.1%), 264 extremely preterm infants (27.4%), and 582 extremely preterm infants (60.4%) at 22, 23, 24, and 25 weeks of gestation age, respectively. The birth weight was 770 (680, 840) g. From 2019 to 2021, the number of extremely preterm infants increased each year (285, 312, and 366 extremely preterm infants, respectively). Antenatal steroids and magnesium sulfate were administered to 67.7% (615/908) and 51.1% (453/886) mothers of extremely preterm infants. In the delivery room, 20.8% (200/963) and 69.5% (669/963) extremely preterm infants received noninvasive positive end-expiratory pressure support and endotracheal intubation. Delayed cord clamping and cord milking were performed in 19.0% (149/784) and 30.4% (241/794) extremely preterm infants. From 2019 to 2021, there were significant increases in the usage of antenatal steroids, antenatal magnesium sulfate, and delivery room noninvasive positive-end expiratory pressure support (all P<0.05). Overall, 349 extremely preterm infants (36.2%) did not receive complete care, 392 extremely preterm infants (40.7%) received complete care and survived to discharge, and 222 extremely preterm infants (23.1%) received complete care but died in hospital. The survival rates for extremely preterm infants at 22, 23, 24 and 25 weeks of gestation age were 10.3% (3/29), 23.9% (21/88), 33.0% (87/264) and 48.3% (281/582), respectively. From 2019 to 2021, there were no statistically significant trends in complete care, survival, and mortality rates (all P>0.05). Only 11.5% (45/392) extremely preterm infants survived without major morbidities. Moderate to severe bronchopulmonary dysplasia (67.3% (264/392)) and severe retinopathy of prematurity (61.5% (241/392)) were the most common morbidities among survivors. The incidences of severe intraventricular hemorrhage or periventricular leukomalacia, necrotizing enterocolitis, and sepsis were 15.3% (60/392), 5.9% (23/392) and 19.1% (75/392), respectively. Overall, 83.7% (328/392) survivors received invasive ventilation during hospitalization, with a duration of 22 (10, 42) days. The hospital stay for survivors was 97 (86, 116) days. Conclusions: With the increasing number of extremely preterm infants at 22-25 weeks' gestation admitted to CHNN NICU, the survival rate remained low, especially the rate of survival without major morbidities. Further quality improvement initiatives are needed to facilitate the implementation of evidence-based care practices.