[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.

Review of research pertaining to the effect of tumor-derived exosomes on natural killer cells.

Tumor-derived exosomes (TDEs) play critical roles in many aspects of cancer progression. There have been several advances in cancer immunotherapy in recent years. A major challenge, however, has been addressed to the role of TDEs in tumor cell immune escape through their influence on the antitumor immunity of natural killer (NK) cells, a key type of immune cell. In this review, we present our overview of the effects of different TDEs on NK cell activation and NK cell toxicity. Studies on mechanism suggest that TDEs mainly affect the immune response of NK cells by inhibiting activated receptors on the surface of NK cells and downregulating the NK recognition ligand MICA/B on the tumor cell surface. In addition, a summary was documented on how to restore the cytotoxicity of NK cells and improve the drug's ability to recognize tumor cells, and a detailed explanation was also provided on the mechanism of action of the drug.

[Treatment of patent ductus arteriosus in very preterm infants in China].

Objective: To describe the current status and trends in the treatment of patent ductus arteriosus (PDA) among very preterm infants (VPI) admitted to the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) from 2019 to 2021, and to compare the differences in PDA treatment among these units. Methods: This was a cross-sectional study based on the CHNN VPI cohort, all of 22 525 VPI (gestational age<32 weeks) admitted to 79 tertiary NICU within 3 days of age from 2019 to 2021 were included. The overall PDA treatment rates were calculated, as well as the rates of infants with different gestational ages (≤26, 27-28, 29-31 weeks), and pharmacological and surgical treatments were described. PDA was defined as those diagnosed by echocardiography during hospitalization. The PDA treatment rate was defined as the number of VPI who had received medication treatment and (or) surgical ligation of PDA divided by the number of all VPI. Logistic regression was used to investigate the changes in PDA treatment rates over the 3 years and the differences between gestational age groups. A multivariate Logistic regression model was constructed to compute the standardized ratio (SR) of PDA treatment across different units, to compare the rates after adjusting for population characteristics. Results: A total of 22 525 VPI were included in the study, with a gestational age of 30.0 (28.6, 31.0) weeks and birth weight of 1 310 (1 100, 1 540) g; 56.0% (12 615) of them were male. PDA was diagnosed by echocardiography in 49.7% (11 186/22 525) of all VPI, and the overall PDA treatment rate was 16.8% (3 795/22 525). Of 3 762 VPI who received medication treatment, the main first-line medication used was ibuprofen (93.4% (3 515/3 762)) and the postnatal day of first medication treatment was 6 (4, 10) days of age; 59.3% (2 231/3 762) of the VPI had been weaned from invasive respiratory support during the first medication treatment, and 82.2% (3 092/3 762) of the infants received only one course of medication treatment. A total of 143 VPI underwent surgery, which was conducted on 32 (22, 46) days of age. Over the 3 years from 2019 to 2021, there was no significant change in the PDA treatment rate in these VPI (P=0.650). The PDA treatment rate decreased with increasing gestational age (P<0.001). The PDA treatment rates for VPI with gestational age ≤26, 27-28, and 29-31 weeks were 39.6% (688/1 737), 25.9% (1 319/5 098), and 11.4% (1 788/15 690), respectively. There were 61 units having a total number of VPI≥100 cases, and their rates of PDA treatment were 0 (0/116)-47.4% (376/793). After adjusting for population characteristics, the range of standardized ratios for PDA treatment in the 61 units was 0 (95%CI 0-0.3) to 3.4 (95%CI 3.1-3.8). Conclusions: From 2019 to 2021, compared to the peers in developed countries, VPI in CHNN NICU had a different PDA treatment rate; specifically, the VPI with small birth gestational age had a lower treatment rate, while the VPI with large birth gestational age had a higher rate. There are significant differences in PDA treatment rates among different units.

[Non-erythrocyte blood products transfusion in very preterm and extremely preterm infants in Chinese neonatal intensive care units].

Objective: To describe the use of non-erythrocyte blood products transfusion in very preterm and extremely preterm infants in the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) in 2019, to explore the disparity between different centers, and to further investigate the rationality and standardability of non-erythrocyte blood products transfusion. Methods: This was a cross-sectional study based on the CHNN cohort of very preterm and extremely preterm infants. All 6 598 infants with gestational age (GA)<32 weeks and admitted to the 57 NICU of CHNN within 24 h of life in 2019 were enrolled. Non-erythrocyte blood products included platelet, plasma, albumin, immunoglobulin, cryoprecipitate and prothrombin complex. Infants who received at least one type of non-erythrocyte blood products were defined in transfusion group. The comparison between infants with and without transfusion was done by t-test, rank-sum test or χ2 test as appropriate. Linear regression model was used to generate adjusted transfusion rate of each center, and to investigate the correlation between adjusted rate and center-level characteristics. Results: A total of 6 598 infants were enrolled in the study, with gestational age of 30.0 (28.7, 31.0) weeks and birth weight of (1 353±312) g, and 43.6 % (2 877) of them were female. Among them, 42.7% (2 816) infants were enrolled in transfusion group, with the times of transfusion as 3 (1, 6) times. Compared to the infants without any transfusion of non-erythrocyte blood products, those infants received transfusion had lower gestational age (Z=17.62, P<0.01), lower birth weight (t=18.64, P<0.01), higher proportion of small-for-gestation age (χ2=31.06, P<0.01), multiple birth (χ²=12.82, P<0.01) and intensive resuscitation in delivery room (χ²=287.52, P<0.01), as well as lower proportion of females (χ²=10.68, P<0.01) and even lower proportion of infants born in this hospital (χ²=78.23, P<0.01). Among the entire study population, albumin (25.4%, 1 674 cases), immunoglobulin (21.5%, 1 417 cases) and plasma (18.9%, 1 245 cases) were the most commonly used non-erythrocyte blood products. Overall, 60.4% (544/901) infants with gestational age <28 weeks received transfusion 4 (2, 8) times. A total of 39.9% (2 272/5 697) infants between 28-31weeks received non-erythrocyte blood products 3 (1, 6) times. The non-erythrocyte blood products transfusion rates of critically-ill and non-critically-ill infants were 62.2% (1 693/2 723) and 29.0% (1 123/3 875) respectively, and the transfusion times were 4 (2,7) and 2 (1,4) times. The transfusion rates varied significantly among different NICU, and the disparities remained obvious after adjustment (adjusted χ²=153.48, P<0.01). Conclusion: Near half of very preterm and extremely preterm infants admitted to Chinese NICU in 2019 receive non-erythrocyte blood products during hospitalization with significant disparities among different hospitals.

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.

LncRNA TTTY15 regulates hypoxia-induced vascular endothelial cell injury via targeting miR-186-5p in cardiovascular disease.

OBJECTIVE: Dysfunction of vascular endothelial cells was associated with diverse human diseases, including cardiovascular disease. Long noncoding RNAs (LncRNAs) were involved in the regulation of cell injury. We aimed to investigate the role of lncRNA testis-specific transcript, Y-linked 15 (TTTY15) in hypoxia-induced cell injury in human umbilical vein endothelial cells (HUVECs). MATERIALS AND METHODS: Cell counting kit-8 (CCK8) assay was used to check cell viability. Lactate dehydrogenase (LDH) assay kit and flow cytometry were utilized to evaluate the leakage rate of LDH and cell apoptosis, respectively. The protein levels of Cyclin D1 and B-cell lymphoma-2-Associated X (Bax) in hypoxia-induced HUVECs were measured by Western blot. Quantitative Real-time polymerase chain reaction (qRT-PCR) was conducted to detect the expression levels of TTTY15 and miR-186-5p in hypoxia-induced HUVECs. The starBase was utilized to predict the binding sites between TTTY15 and miR-186-5p and the dual-luciferase reporter assay was performed to verify the interaction. RESULTS: Hypoxia inhibited cell viability and promoted the release of LDH and cell apoptosis in HUVECs. Besides, hypoxia significantly decreased the protein level of Cyclin D1 and increased the protein level of Bax in HUVECs. In addition, the expression level of TTTY15 was obviously upregulated in hypoxia-induced HUVECs, opposite to the level of miR-186-5p. Meanwhile, knockdown of TTTY15 or upregulation of miR-186-5p mitigated hypoxia-induced cell injury in HUVECs. Further studies suggested that TTTY15 targeted miR-186-5p and regulated hypoxia-induced cell injury via interacting with miR-186-5p in HUVECs. CONCLUSIONS: Downregulation of TTTY15 ameliorated hypoxia-induced cell injury by targeting miR-186-5p in HUVECs.

[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.

[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.

MicroRNA-15a-5p down-regulation inhibits cervical cancer by targeting TP53INP1 in vitro.

OBJECTIVE: An increasing number of reports have shown that microRNAs (miRNAs) play a vital role in the occurrence and development of cancer by acting as tumor inhibitors or oncogenes. The purpose of this research was to explore whether the expression level of microRNA-15a-5p (miR-15a-5p) was related to TP53 regulated inhibitor of apoptosis 1 (TP53INP1) in cervical cancer, and to explore the role of miR-15a-5p in cervical cancer in vitro. PATIENTS AND METHODS: Human cervical cancer tissues and adjacent normal tissues were obtained from 30 cervical cancer patients. Firstly, we carried out the quantitative Real Time-PCR (qRT-PCR) assay to evaluate the level of miR-15a-5p in cervical cancer tissues and cell lines. The TargetScan and the Dual-Luciferase Reporter Assay were used to confirm the relationship between TP53INP1 and miR-15a-5p. Besides, the Cell Counting Kit-8 (CCK-8) and the flow cytometry analysis were performed to detect the effect of miR-15a-5p on cell proliferation and apoptosis in cervical cancer cells. RESULTS: Our results showed that the expression of miR-15a-5p was enhanced in cervical cancer tissues and cells lines. The data from the Dual-Luciferase Reporter Assay demonstrated that TP53INP1 was a direct target of miR-15a-5p. We also found that TP53INP1 was down-regulated in the cervical cancer tissues and cell lines compared with the adjacent normal tissues and normal cervical cells. Besides, the down-regulation of miR-15a-5p depressed cervical cancer cell proliferation and enhanced cell apoptosis. Our results clearly suggested that the down-regulation of TP53INP1 successfully impaired the tumor-inhibition effects of miR-15a-5p inhibitor in cervical cancer cells. CONCLUSIONS: Our findings indicated that miR-15a-5p functioned as a tumor-promoting gene in cervical cancer by directly targeting TP53INP1, indicating that miR-15a-5p might be a potential treatment target for cervical cancer patients.

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.

[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.

[The doctors and their works on history of medicine in early Chinese Society of Medical History].

The Chinese Society of Medical History of the Chinese Medical Association is one of the most important organizations for the study of history of medicine in China. Many of its early members were both doctors and medical historians. Using the name list of this society in the Republic of China, along with other materials like medical journals and popular newspapers, the author tried to present a brief introduction of their achievements in modern medicine and contributions to the history of medicine. Also, it is the author's wish to attract attentions of more doctors of modern medicine to the study of history of medicine.

[Epidemiological characteristics of gastric cancer in China, 2015].

Objective: To estimate the morbidity and mortality of gastric cancer and its distribution in China in 2015 and provide information for future cancer prevention and control study and policy decision. Methods: In 2018, a total of 501 cancer registry systems reported data to the office of National Central Cancer Registry, and the data from 368 cancer registry systems met the criteria. The overall, gender specific, age specific and area specific morbidity and mortality rates of gastric cancer in China were estimated based on national population data in 2015. Chinese standard population in 2000 and World Segi's population data were used to calculate the age-standardized rates (ASR) of morbidity and mortality, including ASR of China and the world. Results: In 2015, the qualified 368 cancer registry system covered a total of 309 553 499 population in China, including 156 934 140 males and 152 619 359 females. We estimated that there were 403 000 new gastric cancer cases, with the crude morbidity rate of 29.31 per 100 000, ASR China of 18.68 per 100 000, ASR world of 18.57 per 100 000, and a cumulative rate of 2.29% for 0-74 years. There were 290 900 new gastric cancer deaths, with the crude mortality rate of 21.16 per 100 000, ASR China of 13.08 per 100 000, ASR world of 12.92 per 100 000, and a cumulative rate of 1.5% for 0-74 years. Gastric cancer ranked second as the most common cancers and third as the most common cancer causes of death in China. In general, both the morbidity rate (ASR China, male: 26.54 per 100 000; female: 11.09 per 100 000; rural area: 21.82 per 100 000; urban area: 16.37 per 100 000) and mortality rate (ASR China, male: 18.75 per 100 000; female: 7.72 per 100 000; rural area: 15.84 per 100 000; urban area: 11.05 per 100 000) were higher in males than those in females, and higher in rural area than those in urban area. The morbidity and mortality rates of gastric cancer increased from the age of 40 years and peaked in age group of 80-years. The case number of gastric cancer significantly increased from the age group of 50-years, peaked at 60-70 years, and the majority of cases occured in age group of 55-80 years. There was an overall consistent trend of the age-specific morbidity and mortality rates across different subgroups by sex and geographic areas, with the rates were higher in males than those in females, and higher in rural area than that in urban area. Conclusions: The incidence of gastric cancer varied with sex, age and areas (urban area and rural area). The present analysis provides the latest data on the prevalence of gastric cancer in China, which can help optimize the current screening guidelines and the prevention and control strategies of gastric cancer to reduce the disease burden caused by gastric cancer in China.

[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.

Control of lactic acid production during hydrolysis and acidogenesis of food waste.

Lactate accumulation occurs frequently during the hydrolysis and acidogenesis of food waste and produces an unfavorable substrate for anaerobic digestion. The objective of the present study was to reduce lactic acid production during the hydrolysis and acidogenesis of food waste in leachate bed reactor for establishment of the two-phase anaerobic digestion system. The results showed that the hydrolysis and acidogenesis of food waste in batch feeding mode underwent two consecutive stages, namely lactic acid fermentation and mixed acid fermentation. In the lactic acid fermentation stage, lactate constituted 74.4-96.8% of the total organic acids in the leachate. However in semi-continuous mode the content of lactate in the leachate could be reduced less than 0-2% for leach bed reactors operated at feeding loads of 50-150g/d although lactate accumulation occurred at a feeding load of 200g/d. Furthermore the organic acid shifted to acetate and butyrate, providing ideal substrates for anaerobic digestion.

[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.

[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.