ObjectiveTo investigate the impact of early intervention with Yishen Huazhuo prescription （YHP） on the learning and memory of accelerated aging model mice， as well as its underlying mechanism. MethodForty-eight 3-month-old male SAMP8 mice were randomly assigned into four groups， including the model group， low-dose YHP group， high-dose YHP group， and donepezil group. Additionally， 24 SAMR1 mice of the same age were divided into a control group and a YHP treatment control group， each consisting of 12 mice. The YHP groups received YHP at doses of 6.24 g·kg^-1 and 12.48 g·kg^-1， while the donepezil group was treated with donepezil at a dose of 0.65 mg·kg^-1. The model group and control groups were given physiological saline. The mice were gavaged once daily for a duration of four weeks. Spatial learning and memory abilities of mice were assessed using the Morris water maze test. Immunofluorescence staining was employed to evaluate neuronal density as well as expression levels of M1 microglial （MG） polarization marker inducible nitric oxide synthase （iNOS） and M2 MG polarization marker arginase-1 （Arg-1） in the hippocampus region. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of pro-inflammatory factor interleukin 1β （IL-1β） and anti-inflammatory factor transforming growth factor-β₁ （TGF-β₁）. Furthermore， Western blot analysis was conducted to determine expressions of amyloid β peptide1-42 （Aβ_1-42） along with triggering receptor expressed on myeloid cells 2 （TREM2）/nuclear factor kappa B （NF-κB） signaling pathway-related proteins TREM2， phospho （p）-NF-κB p65， and phospho-inhibitory kappa B kinase β （IKKβ） in the hippocampus. ResultCompared with the control group， the model group exhibited a significantly prolonged escape latency （P<0.01）， a significant reduction in neuron-specific nuclear protein （NeuN） expression in the hippocampus， a significant increase in iNOS expression in MG， and a significant decrease in Arg-1 expression. The serum IL-1β content was significantly increased， while the TGF-β₁ content was significantly decreased. Additionally， there was a significant decrease in TREM2 expression in the hippocampus and significant increases in p-NF-κB p65， p-IKKβ， and Aβ_1-42 expressions （P<0.05， P<0.01）. However， no significant changes were observed in escape latency， times of crossing the platform， and hippocampal NeuN expression in the YHP treatment control group. Conversely， iNOS expression in MG as well as the hippocampal p-NF-κB p65， p-IKKβ， and Aβ_1-42 expressions were significantly decreased. Furthermore， TREM2 expression was significantly increased （P<0.05， P<0.01）. In comparison to the model group， the low-dose YHP group showed a significantly shortened escape latency and an increased number of crossing the platform （P<0.05， P<0.01）. In the high-dose YHP group， the escape latency was significantly shortened （P<0.05）. In the low-dose YHP group， high-dose YHP group， the expression of NeuN in the hippocampus was significantly increased， the expression of iNOS in MG was significantly decreased， and the expression of Arg-l was significantly increased. The serum IL-1β content was significantly decreased， while the TGF-β₁ content was significantly increased. Furthermore， the expression of TREM2 in the hippocampus was significantly increased， and the expressions of p-NF-κB p65， p-IKKβ， and Aβ_1-42 were significantly decreased （P<0.01）. ConclusionEarly YHP intervention may promote the transformation of hippocampal MG from M1 to M2 by regulating the TREM2/NF-κB signaling pathway， reduce the release of neuroinflammatory factors， protect hippocampal neurons， and reduce the deposition of Aβ_1-42， and finally delay the occurrence of learning and memory decline in SAMP8 mice.

The extremely low bioavailability of oral paclitaxel (PTX) mainly due to the complicated gastrointestinal environment, the obstruction of intestinal mucus layer and epithelium barrier. Thus, it is of great significance to construct a coordinative delivery system which can overcome multiple intestinal physicochemical obstacles simultaneously. In this work, a high-density PEGylation-based glycocholic acid-decorated micelles (PTX@GNPs) was constructed by a novel polymer, 9-Fluorenylmethoxycarbonyl-polyethylene glycocholic acid (Fmoc-PEG-GCA). The Fmoc motif in this polymer could encapsulate PTX via π‒π stacking to form the core of micelles, and the low molecular weight and non-long hydrophobic chain of Fmoc ensures the high-density of PEG. Based on this versatile and flexible carriers, PTX@GNPs possess mucus trapping escape ability due to the flexible PEG, and excellent intestine epithelium targeting attributed to the high affinity of GCA with apical sodium-dependent bile acid transporter. The in vitro and in vivo results showed that this oral micelle could enhance oral bioavailability of PTX, and exhibited similar antitumor efficacy to Taxol injection via intravenous route. In addition, oral PTX@GNPs administered with lower dosage within shorter interval could increase in vivo retention time of PTX, which supposed to remodel immune microenvironment and enhance oral chemotherapy efficacy by synergistic effect.

Objective To investigate the effect of Guizhi Fuling Capsule on NF-κB and MAPK signaling pathway in lipopolysaccharide(LPS)-induced rat endometritis model.Methods The rats were randomly divided into 6 groups according to body weight,namely sham-operation group,model group,positive group(dexamethasone,2.5 mg·kg-1),Guizhi Fuling Capsule high-dose,medium-dose and low-dose groups(0.54,0.27,0.14 g·kg-1),with 10 rats in each group.The sham operation group and the model group were given 0.5%CMC-Na by gavage,and the other groups were given corresponding drugs by gavage once a day for 7 consecutive days.One hour after the last administration,the animals were anesthetized by intraperitoneal injection of 10%chloral hydrate.The rats in the sham operation group only underwent laparotomy and abdominal closure.The left uterus of the rats in the other groups was scratched and injected with a syringe(1.0 μg·μL-1)LPS normal saline solution 0.25 mL.24 hours after LPS injection,the uterine tissues of rats were collected and the pathological changes and MPO,TNF-α,IL-1β,IL-6 were measured in uterine tissues.The expression levels of NF-κB p65,IκBα,ERK,p38 and their phosphorylated proteins were measured in uterine tissues.Results Compared with sham operation group,histopathological score,MPO,TNF-α,IL-1β and IL-6 levels in model group were significantly increased(P<0.01),and NF-κBp65,IκBα,ERK,p38 protein phosphorylation levels were significantly increased(P<0.01).Compared with model group,Guizhi Fuling capsule significantly decreased pathological score of uterus,TNF-α,IL-1β,and IL-6 levels(P<0.01),and significantly decreased NF-κBp65,IκBα,ERK,p38 protein phosphorylation levels(P<0.01).Conclusion Guizhi Fuling capsule plays an anti-inflammatory role in endometritis by inhibiting the transmission of NF-κB and MAPK signaling pathways and inhibiting the secretion of inflammatory factors IL-1β,TNF-α and IL-6 in uterine tissue.

Specnuezhenide(SNZ)is among the main components of Fructus Ligustri Lucidi,which has anti-inflammation,anti-oxidation,and anti-tumor effect.The low bioavailability makes it difficult to explain the mechanism of pharmacological effect of SNZ.In this study,the role of the gut microbiota in the metabolism and pharmacokinetics characteristics of SNZ as well as the pharmacological meaning were explored.SNZ can be rapidly metabolized by the gut microbiome,and two intestinal bacterial metabolites of SNZ,salidroside and tyrosol,were discovered.In addition,carboxylesterase may be the main intestinal bacterial enzyme that mediates its metabolism.At the same time,no metabolism was found in the incubation system of SNZ with liver microsomes or liver homogenate,indicating that the gut microbiota is the main part involved in the metabolism of SNZ.In addition,pharmacokinetic studies showed that salidroside and tyrosol can be detected in plasma in the presence of gut microbiota.Interestingly,tumor development was inhibited in a colorectal tumor mice model administered orally with SNZ,which indicated that SNZ exhibited potential to inhibit tumor growth,and tissue distribution studies showed that salidroside and tyrosol could be distributed in tumor tissues.At the same time,SNZ modulated the structure of gut microbiota and fungal group,which may be the mechanism governing the antitumoral activity of SNZ.Furthermore,SNZ stimulates the secretion of short-chain fatty acids by intestinal flora in vitro and in vivo.In the future,targeting gut microbes and the interaction between natural products and gut microbes could lead to the discovery and development of new drugs.

At present, clinical interventions for chronic kidney disease are very limited, and most patients rely on dialysis to sustain their lives for a long time. However, studies on the gut-kidney axis have shown that the gut microbiota is a potentially effective target for correcting or controlling chronic kidney disease. This study showed that berberine, a natural drug with low oral availability, significantly ameliorated chronic kidney disease by altering the composition of the gut microbiota and inhibiting the production of gut-derived uremic toxins, including p-cresol. Furthermore, berberine reduced the content of p-cresol sulfate in plasma mainly by lowering the abundance of g_Clostridium_sensu_stricto_1 and inhibiting the tyrosine-p-cresol pathway of the intestinal flora. Meanwhile, berberine increased the butyric acid producing bacteria and the butyric acid content in feces, while decreased the renal toxic trimethylamine N-oxide. These findings suggest that berberine may be a therapeutic drug with significant potential to ameliorate chronic kidney disease through the gut-kidney axis.

Objective:To analyze the epidemiological trends and major risk attribution of pancreatic cancer in China, Japan and South Korea from 1990 to 2019.Methods:The descriptive epidemiological method was conducted. The overall incidence rate, mortality rate, age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of pancreatic cancer in China, Japan and South Korea from 1990 to 2019 were collected from the Global Burden of Disease (GBD) Database. Age-standardized rates were calculated based on the worldwide standardized population structure provided by GBD Database 2019. Observation indicators: (1) incidence and motality of pancreatic cancer in China, Japan and South Korea in 2019; (2) age-period-cohort model analysis of incidence and mortality rates of pancreatic cancer in China, Japan and South Korea from 1990 to 2019; (3) trends of ASIR and ASMR of pancreatic cancer in China, Japan and South Korea from 1990 to 2019; (4) trends of major risk attribution of pancreatic cancer related death in China, Japan and South Korea from 1990 to 2019. Count data were represented as absolute numbers, percentages and ratios. Joinpoint V.4.7.0.0 software was used to calculate the annual percentage change (APC), the average annual percentage change (AAPC) of incidence and mortality rates of pancreatic cancer in different time periods and 95% confidence interval (95% CI). The age-period-cohort model in STATA V.15.0 software was used to analyze the influence of different ages, periods and birth cohorts on the risk of onset and death of pancreatic cancer after controlling the other two variables, with the risk effect size described as relative risk (95% CI). Results:(1) Incidence and motality of pancreatic cancer in China, Japan and South Korea in 2019. In 2019, the incidence rate of pancreatic cancer in China increased from 0.07/100,000 among 15-19 years old to 64.01/100,000 among 85-89 years old, with increasing from 0.09/100,000 to 94.71/100,000 in males and from 0.04/100,000 to 47.47/100,000 in females. The mortality rate of pancreatic cancer in China increased from 0.04/100,000 among 15-19 years old to 79.58/100,000 among 85-89 years old, with increasing from 0.05/100,000 to 116.50/100,000 in males and from 0.03/100,000 to 59.69/100,000 in females. The incidence rate of pancreatic cancer in Japan increased from 0.03/100,000 among 15-19 years old to 162.26/100,000 among 85-89 years old, with increasing from 0.03/100,000 to 177.67/100,000 in males and from 0.04/100,000 to 153.67/100,000 in females. The mortality rate of pancreatic cancer in Japan increased from 0.02/100,000 among 15-19 years old to 154.88/100,000 among 85-89 years old, with increasing from 0.02/100,000 to 170.93/100,000 in males and from 0.02/100,000 to 145.94/100,000 in females. The incidence rate of pancreatic cancer in South Korea increased from 0.04/100,000 among 15-19 years old to 136.78/100,000 among 85-89 years old, with increasing from 0.03/100,000 to 153.78/100,000 in males and from 0.04/100,000 to 129.73/100,000 in females. The mortality rate of pancreatic cancer in South Korea increased from 0.02/100,000 among 15-19 years old to 135.98/100,000 among 85-89 years old, with increasing from 0.02/100,000 to 156.21/100,000 in males and from 0.02/100,000 to 127.59/100,000 in females. The peak incidence and mortality of pancreatic cancer in China were found in males aged 65-69 years, and the overall incidence and mortality of males in different age groups were higher than those of females in the same age group. In Japan, the peak incidence of pancreatic cancer occurred in females aged 80-84 years and the peak mortality occurred in males aged 75-79 years. The morbidity and mortality of males aged <80 years were higher than those of females in the same age group, while the morbidity and mortality of males aged ≥80 years were lower than those of females in the same age group. In South Korea, the peak incidence of pancreatic cancer occurred in females aged 80-84 years, and the peak mortality occurred in males aged 70-74 years. The morbidity and mortality of males aged <75 years were higher than those of females in the same age group, while the morbidity and mortality of males aged ≥75 years were lower than those of females in the same age group. (2) Age-period-cohort model analysis of incidence and mortality rates of pancreatic cancer in China, Japan and South Korea from 1990 to 2019. Age effect: after adjustment for the period and cohort effects, the risk of incidence and mortality rates of pancreatic cancer in both males and females of China, Japan and South Korea increased with age, which is more obvious in females than males, and more obvious in Japanese than Chinese and Korean populations. Period effect: after adjustment for age and cohort effects, the risk of incidence and mortality rates of pancreatic cancer in both males and females of China, Japan and South Korea increased from 1990 to 2019, with the period effect more significant in the Chinese population. Cohort effect: after adjustment for age and period effects, the risk of morbidity and mortality rates of pancreatic cancer decreased with the passage of birth cohort in China, Japan and South Korea. (3) Trends of ASIR and ASMR of pancreatic cancer in China, Japan and South Korea from 1990 to 2019. The ASIR and ASMR of pancreatic cancer in China increased yearly from 1990 to 2019, and the ASIR and ASMR in 2019 were 1.82 times and 1.79 times those in 1990, respectively. The ASIR and ASMR of pancreatic cancer in Japan showed a slowly increasing trend, and the ASIR and ASMR in 2019 were 1.09 times and 1.05 times those in 1990, respectively. The ASIR and ASMR of pancreatic cancer in South Korea increased firstly, then decreased, and slowly increased. From 1990 to 2019, the AAPC of ASIR of pancreatic cancer in China was 2.08% (95% CI as 1.91% to 2.24%, P<0.05) and AAPC of ASMR was 2.02% (95% CI as 1.86% to 2.19%, P<0.05). The AAPC of ASIR of pancreatic cancer in Japan was 0.28% (95% CI as 0.15% to 0.42%, P<0.05) and AAPC of ASMR was 0.13% (95% CI as 0.03% to 0.24%, P<0.05). The AAPC of ASIR of pancreatic cancer in South Korea was 0.50% (95% CI as 0.21% to 0.80%, P<0.05) and AAPC of ASMR was 0.15% (95% CI as -0.10% to 0.40%, P>0.05). (4) Trends of major risk attribution of pancreatic cancer related death in China, Japan and South Korea from 1990 to 2019. The main risk factors for pancreatic cancer related death in China, Japan and South Korea from 1990 to 2019 were smoking, high fasting glucose and high body mass index (BMI). The trend of pancreatic cancer related death, mainly attributed to smoking, showed that the proportion of Chinese males increased from 31.4% in 1990 to 34.1% in 2000, then decreased to 31.1% in 2015, and then showed a slow increase to 31.7% in 2019. The proportion of Chinese females increased from 6.7% in 1990 to 10.4% in 2005 and then dropped to 8.7% in 2019. The proportion of Japanese males decreased from 38.8% in 1990 to 26.9% in 2019 and the proportion of Japanese females decreased from 20.9% in 1990 to 14.8% in 2019. The proportion of South Korean males decreased from 37.5% in 1990 to 30.3% in 2019 and the proportion of South Korean females decreased from 12.6% in 1990 to 10.0% in 2019. The trend of pancreatic cancer related death proportion, mainly attributed to high fasting blood glucose, showed that the proportion of Chinese males increased from 5.9% in 1990 to 7.1% in 2019 and the propor-tion of Chinese females increased from 6.2% in 1990 to 6.8% in 2019. The proportion of Japanese males increased from 7.0% in 1990 to 7.7% in 2019 and the proportion of females increased from 5.0% in 1990 to 5.5% in 2019. The proportion of South Korean males increased from 6.8% in 1990 to 9.7% in 2019 and the proportion of females increased from 6.1% in 1990 to 8.2% in 2019. The trend of pancreatic cancer related deaths proportion, attributed mainly to high BMI, showed that the proportion of Chinese males increased from 1.3% in 1990 to 3.0% in 2019 and the proportion of females increased from 2.1% in 1990 to 4.3% in 2019. The proportion of Japanese males increased from 2.0% in 1990 to 2.4% in 2019 and the proportion of females increased from 3.1% in 1990 to 3.4% in 2019. The proportion of South Korean males increased from 1.9% in 1990 to 3.1% in 2019 and the proportion of females increased from 3.4% in 1990 to 4.3% in 2019. Conclusions:The incidence of pancreatic cancer in China may continue to rise but to be stable in Japan and South Korea. The incidence of pancreatic cancer in females, especially elderly women, needs more attention. Smoking remains the most critical risk factor for pancreatic cancer. More attention should also be paid to the increased risk of pancreatic cancer associated with high BMI and high fasting plasma glucose.

Objective:To investigate the current situation of cardiopulmonary bypass(CPB) in China and analyze the causes, to guide the formulation and implementation of technology standard.Methods:The survey task force sent out a nationwide survey to obtain up-to-date information on perfusion practice by ChSECC(Chinese Society of Extracorporeal Circulation). The unit of analysis for the survey was the medical center performs CPB. The survey consisted 48 questions covering four topics of qualifications, including certification and education, policies and practices, device and equipment, techniques used.Results:There were 540 of the 714 centers for an overall response rate of 76%. According to the annual number of CPB, they were divided into 4 groups: group A(≤50 cases/year), group B(50-100 cases/year), group C(100-500 cases/year) and group D(≥500 cases/year). The response rate of center with more than group D last year was 100%. Most of the perfusionists had certification issued by ChSECC. Although there were more than 80% of group D performed regular training and assessment of perfusionist, the result was still not ideal enough. Low utilization of safety equipment was not depend on the annual operation volume in most of responding centers. Ultrafiltration and blood protection technology had high application rate in group D compared with group A and B.Conclusion:The certification rate of perfusionists are high. Lower the number of annual CPB cases, lower the proportion of regular evaluation and training, and lower rate of standards performance. No matter the amount of CPB, the application rate of safety equipment is not ideal. Higher the number of CPB cases, higher the utilization rate of CPB related technologies.

OBJECTIVE: To explore the effect of ultra-high frequency radiation on psychomotor neurological behavior in workers with exposure. METHODS: A total of 85 workers who exposed to 40.68 MHz radiofrequency were recruited as the exposure group by judgment sampling method. A group of 121 workers without occupational EMR exposure were recruited as the control group. Workers in both groups were from the same shoe factory. The electric field intensity(EFI) of ultra-high frequency radiation of workplace in the exposure group was measured. The computerized neurobehavioral evaluation system in Chinese version 3 was used to evaluate the psychomotor neurobehavioral function which included the neurobehavioral ability index(NAI) of simple visual reaction time(SVRT), digital screening and fit curve and the general NAI(GNAI) of the above 3 indexes. RESULTS: The median of the workplace EFI of ultra-high frequency radiation in the exposure group was 119.0 V/m, and all of them exceeded the national occupational exposure limit. NAI of digital screening in exposure group was lower than that in the control group(P<0.05). There is no statistically significant difference in the NAI of SVRT, fit curve and GNAI(P>0.05). Meanwhile, there is no statistically significant difference in abnormal rate of NAI of SVRT, digital screening, fit curve and GNAI(P>0.05). The results of multiple linear regression analysis showed that the ultra-high frequency radiation EFI exposure was negatively correlated with NAI of digital screening(P<0.05) after eliminating the influence of confounding factors such as age, working age, gender, education level, smoking, drinking and staying up late. CONCLUSION: The digital screening of psychomotor neurobehavioral function in the exposure workers was adversely affected by the ultra-high frequency radiation. The neural behavioral ability of eye-hand coordination and precise movement may be the specific performance.

OBJECTIVETo develop a rapid preimplantation genetic diagnosis method for -thalassemia SEA deletion based on blastocyst cell whole genome amplification (WGA) combined with short fragment Gap-PCR.

METHODSUsing multiple displacement amplification (MDA) WGA technique, we established a double-fluorescent PCR system of the housekeeping genes GAPDH and β-actin for WGA quality testing, and a genotyping PCR system of mutant and normal short sequences for α-thalassemia SEA deletion. The sensitivity and accuracy of this method for diagnosis of -thalassemia SEA deletion were evaluated by detecting lymphocyte samples containing different cell numbers from carriers of SEA deletion. The applicability of this method was evaluated by testing of 12 blastocyst biopsy samples.

RESULTSDetection of lymphocyte samples with different cell numbers using the method developed in this study revealed no ADO in 3-cell samples, and the product quantity of WGA became stable for 4-cell samples. Genotyping of the 10 blastocyst biopsy samples with successful WGA showed a genotype of --/ in 5 samples and / in the other 5 samples, which were consistent with the verification results.

CONCLUSIONSThe method developed in this study is a complete testing process for 4-6 blastocyst biopsy cells to allow rapid, accurate, and cost-effective PGD genotyping of -thalassemia SEA deletion using short fragment gap-PCR.

Objective:To develop a method for the quantitative determination of ambrisentan. Methods: 1 H NMR spectra were obtalned with a Bruker AscendTM 400 superconducting NMR spectrometer. For each sample, DMSO-D6 was used as the solvent, the pulse width was 10. 0 μs, the delay time was 5 s and the scanning time was 16. Results: The proton peaks of ambrisentan at δ6. 16 ppm and maleic acid atδ6. 28 ppm were used as the quantitative peaks. The linear regression equation of peak area and quality ratio was Y=0. 140 7X+0. 034 8 with the correlation coefficient of 0. 999 4. RSD was 0. 2%(n=6)in the repeated experiments. The absolute content of ambrisentan reference substance was 99. 9%. Conclusion: The results showed that 1 H NMR can be used in the quantitative determination of ambrisentan without reference substance. The method is reliable, rapid, accurate and simple.