Objective:To analyse the differences of related genes between serum alpha-fetoprotein (AFP) positive gastric cancer and AFP negative gastric cancer, and the relationship between related genes and prognosis of serum AFP positive gastric cancer.Methods:A total of 1 144 gastric cancer patients undergoing surgery at the 940th Hospital , Joint Logistic Support Force, People's Liberation Army from Jan 2013 to Dec 2018 were retrospectively analyzed. Of them, 47 cases were of AFP positive gastric cancer, and 47 serum AFP negative case were obtained by proper matching method.Results:Forty-seven patients with serum AFP positive gastric cancer, accounting for 4.1% of all gastric cancer patients during the same period. The prognosis of serum AFP negative gastric cancer is better than that of serum AFP positive gastric cancer. The 1-, 3- and 5-year cumulative survival rates were 95.6% vs. 63.8%, 48.9% vs. 23.4% and 26.7% vs. 14.9%, respectively. There were statistical differences in the immunohistochemistry of AFP, HER2, VEGF, GPC3, SALL4, P53 and Ki67 between the two groups ( χ2=67.758, P<0.001; χ2=4.004, P=0.044; χ2=19.299, P<0.001; χ2=5.232, P=0.022; χ2=6.359, P=0.012; χ2=6.224, P=0.013; χ2=5.232, P=0.022). The more co-positive expressions of AFP, GPC3, VEGF and SALL4, the more likely they were to affect pTNM stage, vascular invasion and liver metastasis ( χ2=5.328, P=0.021; P=0.013; χ2=5.887, P=0.015; χ2=3.923, P=0.048). Univariate and multivariate survival analysis of serum AFP positive gastric cancer showed:AFP, GPC3, VEGF and SALL4 were risk factors for AFP positive gastric cancer ( HR=3.700, P=0.036; HR=4.237, P=0.003; HR=3.916, P=0.004; HR=3.412, P=0.001). Conclusions:Serum AFP positive gastric cancer is a rare and highly invasive special type of gastric cancer. AFP, GPC3, VEGF and SALL4 are overexpressed in serum AFP positive gastric cancer, which is correlated with tumor stage, vascular invasion and liver metastasis. The final diagnosis of serum AFP positive gastric cancer still needs immunohistochemical examination. Preoperative serum AFP level is an important basis for AFP positive gastric cancer screening and AFP immunohistochemical examination.

Ischemic stroke is one of the leading causes of death and disability worldwide. In Han dynasty， HUA Tuo proposed the original preventive medicine idea that "with good blood circulation， the disease cannot be born"， which opened a broad space for the cross-research of blood-related mechanical factors and pharmacology. In the pathogenesis of ischemic stroke， mechanical factors comprehensively affect the function and crosstalk of platelets and endothelial cells. In recent years， as the well-known effects on thrombosis and stroke， more attention has been paid to hemodynamic factors as the participants involved in pathological mechanisms and potential therapeutic targets of ischemic stroke. The mechanical force ion channel Piezo1 widely exists on the surface of many types of cells. Besides being regulated by chemical and endogenous substances， Piezo1 responds to different mechanical conditions， regulates the opening and closing of channels， and activates different downstream signaling pathways. Piezo1 is now regarded as an important connection between mechanical and biochemical signals. A variety of Chinese medicine can affect the activity of Piezo1 protein， which may prevent and treat thrombotic diseases such as ischemic stroke through Piezo1 protein. In this paper， the effects of Piezo1 protein on the physiological and pathological functions of endothelial cells and platelet under different mechanical conditions and the role of Piezo1 in the process of thrombosis were reviewed， as well as the effects of Chinese medicine， chemical medicine， and endogenous substances targeting Piezo1 channel. These could provide new ideas for further exploring the mechanisms of Chinese medicines in activating blood circulation， developing new drugs， and deepening biomechanical-pharmacology research.

Objective:To investigate the regional homogeneity (ReHo) among the major depressive disorder patients without mixed features (MDD noMF), major depressive disorder with mixed features (MMF), bipolar disorder with mixed features (BMF) and bipolar disorder patients without mixed features (BD noMF) patients, and to explore the brain activity and functional connectivity patterns of the MMF and BMF patients. Methods:This was a cross-sectional study. The MDD noMF patients (MDD noMF group), MMF patients (MMF group), BMF patients (BMF group), BD noMF patients (BD noMF group), and age-and gender-matched healthy controls (HC group) were recruited from Beijing Anding Hospital, Capital Medical University between April, 2021 and June, 2022. All the participants underwent resting-state functional MRI scanning. The ReHo values was computed with the DPABI software based on the MATLAB. Firstly, the difference in ReHo among the patients with MDD noMF, MMF, BMF, BD noMF and HC group were estimated by the analysis of covariance and the post-hoc method (LSD or Games-Howell). And then, the brain regions with significant different ReHo values were selected as the seeds to calculate the functional connectivity with the whole brain. Results:A total of 29 cases in the MDD noMF group, 24 cases in the MMF group, 26 cases in the BMF group, 29 cases in the BD noMF group, and 42 in the HC group were included. The differences in ReHo values in the left fusiform and the left precuneus of the 5 groups were statistically significant ( P<0.05). Among of them, the ReHo values of the left fusiform were lower in the MMF, BMF and BD noMF groups compared with the HC group ( P<0.05), while the ReHo values of the left precuneus in MDD noMF, MMF, BMF and BD noMF groups were higher than that in the HC group ( P<0.05). The ReHo value of the left fusiform was lower in the MMF group compared with the MDD noMF group ( P=0.001); the ReHo value of the left fusiform was lower in the BMF group compared with the MDD noMF and BD noMF groups ( P<0.05). The functional connectivity between the left fusiform and vermis, left insula, right putamen, and left medial superior frontal gyrus, and functional connectivity between the left precuneus and right superior frontal gyrus (dorsolateral) showed significant difference among the MDD noMF, MMF, BMF, BD noMF and HC groups ( P<0.05). Compared with HC group, MDD noMF, MMF, BD noMF groups showed higher functional connectivity between the left fusiform and the vermis, and MDD noMF, MMF, BMF, BD noMF group showed higher functional connectivityy between the the left fusiform and the left insula, left medial superior frontal gyrus and right putamen ( P<0.05). Compared with the MDD noMF group, the MMF, BMF and BD noMF groups showed higher functional connectivity between the left fusiform and the left insula ( P<0.05). Compared with the MDD noMF group, the BMF and BD noMF groups had higher functional connectivity between the left fusiform and the left medial superior frontal gyrus ( P<0.05). The BMF group showed higher functional connectivity of the left fusiform with the right putamen than the MDD noMF and BD noMF groups. Additonally, the BMF and BD noMF groups showed higher functional connectivity between the left precuneus and the right superior frontal gyrus (dorsolateral) than HC, MDD noMF and MMF groups ( P<0.05). Conclusions:MMF and BMF patients have local abnormalities of functional activity synchronization in the left fusiform and precuneus and abnormal functional connectivity patterns with multiple brain regions. MMF and BMF patients have specific neuroimaging features compared to MDD noMF or BD noMF patients and also share similar neuroimaging pathogenesis.

ObjectiveBased on the inhibitory activity of phosphodiesterase （PDE）， a method for determining the anti-inflammatory activity of Qingjin Huatantang was established to supplement and improve the quality control system of this famous classical formula. MethodHigh performance liquid chromatography （HPLC） was used to determine the activity of PDE， and the dose-effect relationship of inhibiting PDE activity of Qingjin Huatantang was investigated. The mobile phase consisted of methanol-0.5% acetic acid aqueous solution （5∶95）， and the detection wavelength was 254 nm. By measuring the PDE inhibition rate of multiple batches of Qingjin Huatantang water extract lyophilized powder， biological activity was marked with the activity of the neutralizing enzyme in the international unit U. ResultWhen the concentration of reaction substrate （cyclic adenosine monophosphate） was 50 μmol·L^-1 and the reaction time was 60 min， the enzymatic reaction was stable with 4 U·mL^-1 of PDE. In this reaction system， when the concentration of Qingjin Huatantang water extract lyophilized powder was 0.11-3.0 g·L^-1， the inhibitory effect of PDE showed a concentration-dependent relationship. It was determined that the concentration of Qingjin Huatantang water extract lyophilized powder to be tested was 1 g·L^-1， which showed a significant and stable inhibitory effect on PDE， and the inhibitory rate was >45%， that is， 1 mg of Qingjin Huatantang water extract lyophilized powder could neutralize the activity of 1.8 U PDE at least. ConclusionThis study establishes a biological activity evaluation method of Qingjin Huatantang based on the inhibitory activity of PDE， and the anti-inflammatory activity of Qingjin Huatantang is characterized by international unit U of PDE activity， which can provide a new method for the determination of biological activity of traditional Chinese medicine compounds.

Alpha-fetoprotein producing gastric cancer (AFPGC) is a special type of gastric cancer. AFPGC is considered to be the most highly invasive tumor with a high degree of malignancy and prone to metastasis. As a consequence, it usually causes unsatisfied treatment effect and the prognosis is poor. At present, treatment methods and monitoring indicators have limited effect on AFPGC. VEGF, HER2, AFP, GPC3 and SALL4 are cogently associated with tumor genesis and development. If we can reasonably guide the treatment and prognosis of AFPGC patients, it will greatly improve the situation of patients and improve the survival of patients. This article reviews the research progress of the genes related to the treatment and prognosis of AFPGC.

Objective:To investigate the value of chromosomes 7 and 8 polysomy in circulating tumor cells (CTCs) for the diagnosis of non-small cell lung cancer, and the correlation of CTCs with clinical pathological characteristics and epidermal growth factor receptor (EGFR) mutations in cancer tissue.Methods:Fifty-seven patients with non-small cell lung cancer and 21 patients with benign lung diseases were enrolled at Beijing Chaoyang Hospital, Capital Medical University, Beijing, China from November 2017 to October 2020. Negative enrichment combined with immunofluorescence in situ hybridization (imFISH) was used to identify CTCs polysomy on chromosomes 7 and 8. EGFR mutations in 56 lung cancer patients was detected using ARMS-PCR.Results:CTCs were detected in 93.0% (53/57) of non-small cell lung cancers and 28.6% (6/21) benign lung lesions. The difference between lung cancer patients and the control cohort was statistically significant ( P<0.01). Receive operator curve (ROC) analyses showed that, when the cut-off value was 1 cell/3.2 mL, Youden index had the highest sensitivity of 93.0% and specificity of 71.4% (AUC=0.906, 95% CI:0.833-0.980, P<0.01). The positive rate of CTCs in stage Ⅲ-Ⅳ cancers was significantly higher than that in stage Ⅰ-Ⅱ ( P=0.023). No significant correlation was observed between positive rate of CTCs or chromosome polysomy and age, gender, smoking status, pathologic types and EGFR mutation status. The number of CTCs in EGFR mutated group was higher than that in the non-mutated group (6.5±1.1 vs. 3.7±0.7, P=0.045). The detection rate for CTCs ≥5 in the EGFR mutated group was also higher than the EGFR non-mutated group (52.0% vs. 19.4%, P=0.010). Conclusion:Detection of CTCs with chromosomes 7 and 8 polysomy has potential value in auxiliary diagnosis of non‐small cell lung cancer, and the number of CTCs is correlated to TNM stage and EGFR gene mutation status.

Objective To understand the prevalence of thyroid nodules of children lived in different water iodine areas in Cangzhou City. Methods From Oct. 2015 to Jan. 2017, 15 villages were selected as monitoring sites in Cangzhou,two drinking water samples were collected from each survey site(all had centralized water supply), and the water iodine content was determined. A total of 100 children aged 8 to 10 (half male and female) were examined for thyroid nodules, and at least 50 children (half male and half female) were selected to detect urinary iodine content. In the high iodine water counties, the monitoring sites of iodine salt was according to "National Iodine Deficiency Monitoring Program"; in the monitoring sites of iodine salt supplied counties, students in the monitored village were asked to detect urinary iodine and household salt samples were collected to monitor salt iodine. In the high iodine area, the salt iodine test was carried out by semi-quantitative method. In the non-high iodine area, the salt iodine content of the iodized salt monitoring sites was determined by direct titration, the salt iodine content of Chuan salt and other intensified edible salt was tested by arbitration(GB/T 13025.7-2012). Water iodine and urinary iodine were tested by arsenic and cerium catalytic spectrophotometry. Results Water iodine content was 28.2 - 1 128.0 μg/L in 15 villages; a total of 1 066 urine samples were examined, the median of uriary iodine in each village was 102.6-1 162.0 μg/L;a total of 1 575 children aged 8 to 10 years were examined,among them,125 cases of thyroid nodules were detected; thyroid nodules detection rate was 7.9%. The prevalence of male was 7.0% (61/871), and the prevalence of female was 9.1% (64/704), there was no significant difference in the detection rate of thyroid nodules between different sex (χ2=2.07,P>0.05); The detection rate of thyroid nodules were 4.5%(23/508),7.8%(4/51), 11.6%(59/507)in children with urinary iodine at the appropriate level (100 - <200 μg/L), the appropriate level (200 - < 300 μg/L) and iodine excess level (≥300 μg/L), the difference of thyroid nodules in children with different levels of urinary iodine detection rate was statistically significant (χ2=17.30, P < 0.01). The difference of prevalence of thyroid nodules in children aged 8 to 10 years with water iodine concentrations of 10 - < 100, 100 - < 300 and ≥300 μg/L was statistically significant[2.9%(13/448),7.9%(25/317), 10.7%(87/810),χ2=23.86,P<0.05].The patients with unilateral thyroid nodule accounted for 64.8% (81/125); the patients with multiple thyroid nodules counted for 58.4% (73/125), and 34.2%(13/38),69.0%(60/87)in areas with iodine content less than 300 μg/L and no less than 300 μg/L,the difference between the two was statistically significant (χ2= 13.14, P < 0.01). A total of 1 800 salt samples were collected from the high water iodine counties,of which 1 779 were iodine-free salt, the rate of iodine-free salt was 98.8%; a total of 190 salt samples were collected in student family, in the 4 iodized salt monitoring sites, the salt iodine median of resident's edible salt was 0.0 mg/kg. Conclusion The prevalence of thyroid nodules in children aged 8 - 10 years may be related to high water iodine in Cangzhou City; children with multiple thyroid nodules is also significantly higher in water iodine content greater than 300 μg/L areas.

Objective:To explore the adjustment factors to the migration and functional activity on macrophages in the uterine of inflammatory mice induced by LPS.Methods:150 Kunming female mouse were divided into control group (group A),LPS model group (group B),MCP-1 blocking-up group (group C),the mice uterines were extracted separately at hour 1,3,6,12,24.The number of CD14+ macrophages and the expression of CD14 macrophages were detected by Immunohistochemistry,ELISA detects the expression of TNF-α and MCP-1.Results:①Compared with group A,the number of CD14+ macrophages and the expression of CD14 in endometrium,myometrium,perimrtrium of group B were highly significantly increased (P<0.01) at every time points,the endometrium,myometrium of group C were closely to normal level at 1,3,6 h;compared with group B,the number of CD14+ macrophages and the expression of CD14 were highly significantly decreased(P<0.01)at 1,3,6 h of perimrtrium of group C and every time points of endometrium,myometrium of group C.②Compared with group A,the content of TNF-α and MCP-1 were highly significantly increased (P<0.01) at every time points of group B and 12,24 h of group C;compared with group B,the content of TNF-α and MCP-1 of group C were highly significantly decreased(P<0.01) at every time points.Conclusion:The migration of macrophages and the expression of CD14 and TNF-α in the uterine of inflammatory mice induced by LPS were regulated by MCP-1.

Objective To explore the efficacy of ganoderma lucidum preparation(Ling Zhi) in treating APP/PS-1 transgenic mouse models of Alzheimer's disease(AD).Methods APP/PS-1 transgenic mice of 4 months were randomly divided into model group,ganoderma lucidum treatment groups,including high [2250 mg/(kg·d)] and middle [750 mg/(kg·d)] dose groups,i.e.LZ-H and LZ-M groups,and the positive control group(treated with donepezil hydrochloride [2 mg/(kg·d)]).In addition,C57BL/6J wild mice were selected as normal group.The animals were administered for 4 months.Histopathological examinations including hematoxylin-eosin(HE) staining,immunohistochemistry,special staining,and electron microscopy were applied,and then the pathological morphology and structures in different groups were compared. Results The senile plaques and neurofibrillar tangles in the cerebrum and cerebellum were dissolved or disappeared in LZ-H and LZ-M groups.Decrease of amyloid angiopathy was found in LZ-H and LZ-M groups.The immature neurons appeared more in hippocampus and dentate nucleus of LZ-H and LZ-M groups than those in AD model and donepezil hydrochloride groups(hippcampus:F=1.738,P=0.016;dentate nucleus:F=1.924,P=0.026),and these immature neurons differentiated to be neurons.More Purkinje cells loss occurred in AD model mice than that in LZ-H and LZ-M groups(F=9.46,P=0.007;F=9.46,P=0.010).The LZ-H and LZ-M groups had more new neuron stem cells grown up in cerebellum.Electromicroscopic examination showed the hippocampal neurons in LZ-H and LZ-M group were integrated,the nuclear membrane was intact,and the mitochondria in the cytoplasm,endoplasmic reticulum,Golgi bodies,microtubules,and synapses were also complete.The microglial cell showed no abnormality.No toxicity appeared in the pathological specimens of mice treated with ganoderma lucidum preparation.Conclusion The ganoderma lucidum preparation can dissolve and decline or dismiss the senile plaques and neurofibrillar tangles in the brain of AD mice and also reduce the amyloid angiopathy.

Objective To evaluate the efficacy of Ganoderma lucidum preparation on the behaviors,biochemistry,and autoimmunity parameters of mouse models of APP/PS-1 double transgenic Alzheimer's disease(AD).Methods A total of 44 4-month-old APP/PS-1 double transgenic AD mice were randomly divided into AD model group,Aricept group,Ganoderma lucidum middle-dose(LZ-M)group,and Ganoderma lucidum high-dose(LZ-H)group,with 11 mice in each group.In addition,10 4-month-old C57BL/6 mice were used as the control group.Water maze test was conducted to observe the behavior changes,and the protein expressions in brain tissues were detected by Western blot analysis.The autoimmune indicators were detected by indirect immunofluorescence method.Results In the navigation experiment,the time of finding the platform was gradually shortened since the 2day in the control,LZ-H,and LZ-M groups,and the time of searching the platform in the AD model group gradually increased.On the 5day,the time of finding platform was significantly shorter in control group (t=5.607,P=0.000) and LZ-H group(t=2.750,P=0.010)than AD model group.In the space exploration experiment,the number of crossing the target platform(t=2.452,P=0.025)and the residence time in the target quadrant(t=2.530,P=0.020)in AD model group mice was significantly smaller/shorter than those in control group;in addition,the number of crossing the target platform in the AD model group was significantly smaller than that in LZ-H group(t=2.317,P=0.030)and LZ-M group(t=2.443,P=0.030),while the residence time in target quadrant decreased significantly(t=2.770,P=0.020)compared with LZ-H group;the number of crossing through the target platform quadrant(t=2.493,P=0.022)and residence time in the target quadrant(t=2.683,P=0.015)in LZ-H group were significantly higher than in Aricept group.Western blot analysis showed that the expression of ApoA1 in the brain tissues of mice in LZ-H and LZ-M groups were significantly higher than those in AD model group(P<0.01,P<0.05);Aβ-40 expression in LZ-H group was significantly lower than that in AD model group(P<0.05);the expressions of Syt1,ApoE,and ABCA1 in brain tissues of mice in LZ-H group were significantly higher than those in model group(P<0.01,P<0.05).The plasma IgG level in Aricept group(t=30.945,P=0.000),LZ-M group(t=25.639,P=0.000)and LZ-H group(t=4.689,P=0.001)were significantly higher than that in the control group.Conclusion Ganoderma lucidum preparation can improve behavior disorders of AD model mice,promote the expressions of ApoA1,ApoE and Syt1,inhibit the expression of Aβ-40 protein,and improve the autoimmune function.