OBJECTIVE: To observe the effect of electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) on hippocampal neuronal ferritinophagy mediated by the nuclear receptor coactivator 4 (NCOA4)/ferritin heavy chain 1 (FTH1) signaling pathway in vascular dementia (VD) rats, and to explore the potential mechanisms of electroacupuncture for VD. METHODS: A total of 60 male rats of SPF grade were randomly divided into a blank group (12 rats), a sham surgery group (12 rats) and a modeling group (36 rats). In the modeling group, the modified 4-vessel occlusion method was used to establish the VD model. The 24 successfully modeled rats were randomly divided into a model group and an electroacupuncture group, with 12 rats in each group. In the electroacupuncture group, electroacupuncture was applied at left and right "Sishencong" (EX-HN1), and bilateral "Fengchi" (GB20), with continuous wave, in frequency of 2 Hz and current intensity of 1 mA, 30 min a time, once daily for 21 consecutive days. The learning and memory abilities were assessed using the Morris water maze test before modeling, after modeling and after intervention, as well as the novel object recognition test after intervention. After intervention, the neuronal morphology in the hippocampus was observed by Nissl staining; the iron deposition was observed by Prussian blue staining; the reactive oxygen species (ROS) level was detected by dihydroethidium (DHE) fluorescence staining; the levels of iron, malondialdehyde (MDA) and superoxide dismutase (SOD) in the hippocampal tissue were measured by the colorimetric assay, TBA method, and WST-1 method, respectively; the positive expression of NCOA4, FTH1 and glutathione peroxidase 4 (GPX4) was detected by immunohistochemistry; the protein expression of NCOA4, FTH1, GPX4, and the ratio of microtubule-associated protein 1 light chain 3B (LC3B) Ⅱ/Ⅰ in the hippocampus were detected by Western blot. RESULTS: Compared with the sham surgery group, in the model group, the escape latency was prolonged, and the number of platform crossings reduced (P<0.01), the recognition index (RI) was decreased (P<0.01); the hippocampal neurons displayed a blurred laminar structure, disorganized cellular arrangement, and the number of Nissl bodies was decreased (P<0.01); the percentage of iron deposition area in the hippocampus was increased (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were increased (P<0.01), the SOD level, and the protein expression of FTH1 and GPX4 were decreased (P<0.01). Compared with the model group, in the electroacupuncture group, the escape latency was shortened and the number of platform crossings was increased (P<0.01), the RI was increased (P<0.01); the hippocampal neurons exhibited more regular morphology, better-organized cellular structure, and the number of Nissl bodies was increased (P<0.05); the percentage of iron deposition area in the hippocampus reduced (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were decreased (P<0.01, P<0.05), the SOD level, and the protein expression of FTH1 and GPX4 were increased (P<0.01). CONCLUSION Electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) can improve learning and memory abilities in VD rats, and its mechanism may be associated with the regulation of the hippocampal NCOA4/FTH1 signaling pathway, inhibition of ferritinophagy, and alleviation of oxidative stress damage.
Animals ; Electroacupuncture ; Dementia, Vascular/genetics* ; Male ; Rats ; Signal Transduction ; Humans ; Memory ; Rats, Sprague-Dawley ; Nuclear Receptor Coactivators/genetics* ; Ferritins/genetics* ; Learning ; Hippocampus/metabolism* ; Acupuncture Points

Background::Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease (PD) risk factors; however, no comprehensive analyses of these genes in patients with PD have been undertaken. Therefore, we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD.Methods::Whole-exome sequencing (WES) was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls. Additionally, whole-genome sequencing (WGS) was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls.Results::We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts, respectively. Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD. However, the significance did not pass the Bonferroni correction. Meanwhile, 72 and 1730 common variants were found in the WES and WGS cohorts, respectively. Unfortunately, single-variant logistic association analyses did not identify significant associations between common variants and PD. Conclusions::Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients. However, we highlight the complexity of PD and the need for extensive research elucidating its etiology.

Objective To investigate the effect of early combined use of liraglutide on cardiometa-bolic risk factors and prognosis in patients with T2DM and CMVD.Methods A total of 124 T2DM patients with concomitant CMVD admitted in our hospital from May 2021 to June 2023 were enrolled,and divided into the liraglutide group(n=59)and the non-liraglutide group(n=65)according to taking liraglutide or not.The main observation indicators were compared between the two groups,including cardiometabolic risk factors,such as Hcy,UA,FPG,eGFR,HbA1c,hs-CRP,WC,BMI,WWI,and echocardiographic indicators,such as LAD,LVEDD,LVPWT,IVST,E/e',e',LVEF,LAVI,LVMI,and RWT.And the incidence of adverse reactions and read-mission rates were recorded during follow-up.Results After treatment,in the liraglutide group,Hcy,UA,FPG,HbA1c,hs-CRP,WC,BMI,WWI,E/e',LAVI,LVMI,RWT,IVST and LVPWT values,and anteroposterior,transverse and long diameters of left atrium were all lower than before treatment,and eGFR and e'value were increased(P＜0.05,P＜0.01),and no significant difference was seen in LVEF and LVEDD(P＞0.05).The non-liraglutide group obtained lower HbA1c,FPG,BMI,E/e'and LAVI values,and transverse diameter of left atrium,elevated LVPWT and e'value(P＜0.05,P＜0.01),and no obvious changes in Hcy,UA,eGFR,hs-CRP,WC,WWI,BMI,LVEF,LVMI,RWT,LVEDD,IVST,and anteroposterior and long diameters of left atrium when compared with the indicators before treatment(P＞0.05).At the end of the fol-low-up,when compared with the non-liraglutide group,the liraglutide group had more significant decreases in E/e',LAVI,LVMI and RWT values and increase in e'value(P＜0.05,P＜0.01),and higher total effective rates(94.92％vs 72.31％,P＜0.01).What's more,the readmission rate due to adverse cardiovascular events was notably lower in the liraglutide group and the non-liraglutide group(3.39％vs 15.38％,P＜0.05).Conclusion Compared with BMI,WWI may be more sensi-tive in reflecting changes in cardiometabolic risk factors in T2DM patients with CMVD;Early combined application of liraglutide has good efficacy and safety,and exerts multiple cardiovascular protective effects,including reducing cardiometabolic risk factors,improving cardiac diastolic function and renal function,inhibiting chronic inflammation and decreasing the occurrence of ad-verse cardiovascular events in the patients.

OBJECTIVE: To explore the mechanism of electroacupuncture (EA) at "Fengchi" (GB 20) and "Sishencong" (EX-HN 1) on learning and memory impairment in vascular dementia (VD) rats by observing the influences on the N-methyl-D-aspartate receptor (NMDAR)/cyclic adenosine monophosphate response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway and the excitotoxicity induced by hippocampal calcium overload. METHODS: Thirty-two male SD rats of SPF grade were selected and randomized into a normal group (6 rats), a sham-operation group (6 rats) and an operation group (20 rats). VD model was established with the modified Pulsinelli's four-vessel occlusion (4-VO) method. Twelve rats after successfully modeled were assigned randomly into a model group and an EA group, 6 rats in each one. In the EA group, EA was delivered at bilateral "Fengchi" (GB 20) and "Sishencong" (EX-HN 1), with the continuous wave, the frequency of 2 Hz and the electric current of 1 mA. Stimulation intensity was adjusted depending on the slightly trembling of rat head. EA was given once daily, 30 min each time; and EA intervention was delivered for 21 days continuously. Using Morris water maze test, the learning and memory function was assessed. The neuronal morphology in the hippocampal CA1 was observed with HE staining; the level of glutamate (GLU) in serum and hippocampal tissue, as well as the activity of calcium pump (Ca²⁺-ATP) in the hippocampus were detected using colorimetric method. The protein expression of NMDAR, calmodulin-dependent protein kinase Ⅱ (CaMKⅡ), phosphorylated calmodulin-dependent protein kinase Ⅱ (p-CaMKⅡ), phosphorylated cyclic phosphoradenosine effector element binding proteins (p-CREB), CREB, and BDNF in the hippocampal CA1 was detected using immunohistochemistry. The protein expression of NMDAR, CREB, p-CREB and BDNF in the hippocampal tissue was detected using Western blot method. RESULTS: Compared to the sham-operation group, in the model group, the escape latency was prolonged and the platform crossing times of rats were reduced (P<0.01), the hippocampal neuron structure was damaged to different degrees, the structure in hippocampal CA1 was loosened, the arrangement disorganized, with clear grid-like structure; the neuronal morphology was irregular, pyknosis and even dissolution occurred, glial cells increased, blood capillary was dilated and the inflammatory cells were infiltrated and scattered. The level of GLU in the serum and hippocampal tissue and the protein expression of hippocampal NMDAR were elevated (P<0.01), the activity of Ca²⁺-ATP and the protein expression of CaMKⅡ, p-CaMKⅡ, CREB, p-CREB and BDNF were reduced (P<0.01, P<0.05); and the ratio of p-CaMKⅡ/CaMKⅡ and that of p-CREB/CREB were dropped (P<0.05). In comparison with the model group, in the EA group, the escape latency was shortened and the platform crossing times of rats rose (P<0.01), the arrangement was improved in the hippocampal CA1, the neuronal morphology was intact, the nucleoli were clear relatively and the pyknosis or dissolution were attenuated, the numbers of glial cells reduced relatively, the dilation of blood capillary was alleviated. The level of GLU in the serum and hippocampal tissue and the protein expression of NMDAR were reduced in the hippocampal tissue (P<0.01), the activity of Ca²⁺-ATP and the protein expression of CaMKⅡ, p-CaMKⅡ, CREB, p-CREB and BDNF were elevated (P<0.05, P<0.01); and the ratio of p-CaMKⅡ/CaMKⅡ and that of p-CREB/CREB increased (P<0.05). CONCLUSION EA at "Fengchi" (GB 20) and "Sishencong" (EX-HN 1) can attenuate learning and memory impairment in VD rats, which may be obtained by reducing GLU level in hippocampal tissue, inhibiting hippocampal excitotoxicity, mediating protein expression related to the NMDAR/CREB/BDNF signaling pathway, and maintaining neuronal survival and growth.
Electroacupuncture ; Male ; Animals ; Rats, Sprague-Dawley ; Learning ; Memory ; Signal Transduction ; Cyclic AMP Response Element-Binding Protein/metabolism* ; Memory Disorders/therapy* ; Brain-Derived Neurotrophic Factor/metabolism* ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Dementia, Vascular/therapy*

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

Objective: To investigate the automatic implicit attitude and explicit stigma of mental illness, and the intervention effectiveness on the stigma of mental illness in college students. Methods: Single category implicit association test(SC-IAT) and questionnaire survey were used to study the degree of implicit and explicit mental illness stigma among 30 college students of Peking University, and investigated the effect of two strategies, education and contact.Data were analyzed by SPSS 22.0 with t-test and variance analysis. Results: The D values of SC-IAT in the three dimensions of cognitive evaluation, emotional response and behavioral tendency of college students were 0.29±0.37, 0.24±0.43, and 0.10±0.43.There was a statistically significant difference between the cognitive evaluation dimension, the emotional response dimension and 0(t=4.069, P<0.01; t=2.925, P<0.01). There was no statistically significant difference between the implicit stigma and the 0 in the behavioral tendency dimension(t=1.423, P=0.167). In the explicit stigma, the mercy dimension score(1.94±0.61) was lower than the median, and the difference was statistically significant(t=-12.286, P<0.01), while the scores of anger dimension(4.62±0.44) and fear dimension (4.55±0.31) were higher than the median(t=13.243, 3.200, both P<0.01). There were no significant differences in the values of implicit and external stigma among pre-intervention, education intervention and after contact(P>0.05). The correct rates of questions "Which of the following situations do you think are considered mentally unhealthy? " and "Which of the following disorders are mental illnesses" (42±13)%, (54±13)%) increased after receiving educational intervention ((49±12)%, (64±13)%), the difference was statistically significant (F=3.682, P<0.05; F=3.576, P<0.05). Conclusion College students have implicit mental illness stigma, educational and contact intervention strategies can help improve college students' understanding of relevant knowledge, and cannot improve the level of implicit stigma of college students on mental illness.

Objective To grasp the current situation of drinking water-borne endemic fluorosis in Shandong Province,and provide a scientific basis for formulating preventive strategies.Methods In 2016,according to the "National Surveillance Scheme of Drinking Water-Borne Endemic Fluorosis" and "Shandong Provincial Surveillance Scheme of Drinking Water-Borne Endemic Fluorosis",10 counties (cities,districts) were selected in Shandong Province,3-5 villages were selected in each county (city,district),to investigate the operation of water improvement and fluorine reduction project and the water fluorine,and 1 tap water sample in each village was collected to detect water fluorine.At the same time,dental fluorosis examination was performed on all children aged 8-12 years old and fluorosis X-ray examination was performed on adults aged ≥25 years old.Water fluorine was detected by ion selective electrode method;the water fluorine was determined according to "Standards for Drinking Water Quality" (GB 5749-2006);criteria for diagnosis,grading and epidemic intensity of dental fluorosis were based on "Diagnosis of Dental Fluorosis" (WS/T 208-2011);the diagnostic and grading criteria for skeletal fluorosis were based on the "Diagnostic Criteria for Endemic Skeletal Fluorosis" (WS 192-2008).Results All the 32 villages in 10 counties (cities,districts) changed water,water improvement and fluorine reduction project ran normally,24 villages had qualified water fluorine (≤ 1.20 mg/L),and 8 villages had water fluorine exceeding the standard.The detection rate of dental fluorosis in children was 25.75％ (419/1 627),and the difference between 10 counties (cities,districts) was statistically significant (x2 =288.55,P ＜ 0.01);the dental fluorosis index was 0.48,and the defect rate was 2.77％ (45/1 627).The detection rate of skeletal fluorosis in adults was 4.72％ (72/1 525),and the difference between 10 counties (cities,districts) was statistically significant (x2 =18.83,P ＜ 0.01).Conclusions The problem of water fluorine exceeding the standard in water improvement and fluorine reduction project in Shandong Province is still serious.The condition of fluorosis has not been fully controlled,and the prevention and treatment measures need to be further strengthened.

Objective: To investigate the effects of different expression of monoacylglycerol lipase (MAGL) in tumor-associated macrophages (TAMs) with the proliferation of MHCC97H human liver cancer cells in vivo and its mechanism. Methods: Human peripheral blood-derived monocyte was induced to differentiate into M2-type TAMs and was identified by flow cytometry. The co-culture model of TAMs and MHCC97H human liver cancer cells was established, and the expression of MAGL in TAMs cells was detected by qRT-PCR. The expression of MAGL in TAMs cells was detected by plasmid transfection. ELISA and qRT-PCR was used to detect the mRNA expression levels and secretion levels of inflammatory factors in TAMs cells. The subcutaneous tumor model of MHCC97H mice was constructed to observe the effect of different expression of MAGL in TAMs cells with the proliferation of MHCC97H human liver cancer cells in vivo. F-test was used for the measurement of homogeneity of variance between two independent samples. A t-test was used for homogeneity of variance, and the corrected t-test was used for non-homogeneity of variance. Results: Human peripheral blood-derived monocytes were successfully induced to differentiate into M2-type TAMs. An in vitro co-culture model was established. qRT-PCR showed that MHCC97H human liver cancer cells significantly down-regulated the expressional level of MAGL in TAMs cells. The constructed subcutaneous tumor model of mice demonstrated that up-regulation up-regulation of MAGL expression in M2-type TAMs inhibited the proliferation of MHCC97H human liver cancer cells in vivo. Furthermore, the mechanistic study illustrated that the high expression of MAGL promoted the transcription and secretion of inflammatory factors such as interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha in M2-type TAMs cells. Conclusion The overexpression of MAGL inhibits the proliferation of MHCC97H hepatocellular carcinoma cells in vivo, and its mechanism may be associated to the release of inflammatory factors that from TAMs cells.

Tung tree (Vernicia fordii) is an economically important woody oil plant that produces tung oil rich in eleostearic acid. Here, we report a high-quality chromosome-scale genome sequence of tung tree. The genome sequence was assembled by combining Illumina short reads, Pacific Bio-sciences single-molecule real-time long reads, and Hi-C sequencing data. The size of tung tree gen-ome is 1.12 Gb, with 28,422 predicted genes and over 73％ repeat sequences. The V. fordii underwent an ancient genome triplication event shared by core eudicots but no further whole-genome duplication in the subsequent ca. 34.55 million years of evolutionary history of the tung tree lineage. Insertion time analysis revealed that repeat-driven genome expansion might have arisen as a result of long-standing long terminal repeat retrotransposon bursts and lack of efficient DNA deletion mechanisms. The genome harbors 88 resistance genes encoding nucleotide-binding sites;17 of these genes may be involved in early-infection stage of Fusarium wilt resistance. Further, 651 oil-related genes were identified, 88 of which are predicted to be directly involved in tung oil biosynthesis. Relatively few phosphoenolpyruvate carboxykinase genes, and synergistic effectsbetween transcription factors and oil biosynthesis-related genes might contribute to the high oil content of tung seed. The tung tree genome constitutes a valuable resource for understanding genome evolution, as well as for molecular breeding and genetic improvements for oil production.

Objective To understand the implementation effects of control measures and the dynamic prevalence of drinking water-borne endemic fluorosis in Shandong Province.Methods From 2013 to 2017 in Shandong Province drinking water-borne endemic fluorosis areas,in accordance with the method of simple random sampling,10 monitored counties were selected,10 water fluorine decreasing projects were investigated of its running effect,and water fluoride was detected.In each monitored county,3 villages in the diseased areas were selected as fixed monitored villages.If the monitored village had changed its water,the operation of the project would be investigated.If the monitored village had not changed the water,one water sample would be collected according to 5 directions of east,west,south,north and middle to determine the water fluorine.All children aged from 8 to 12 in the village were also examined for dental fluorosis.X-ray fluorosis and urinary fluorosis in adults aged over 25 were detected in 2013 and 2017.Results From 2013 to 2017,in monitored counties,the normal operation rate of improved-water defluoridation projects was 99.19％ (368/371),the qualified rate of water fluoride content was 66.85％ (248/371).In 128 improved water projects,the normal operation rate was 100.00％ (128/128),the qualified rate of water fluoride content was 67.19％ (86/128).The average detection rate of dental fluorosis and community fluorosis index (CFI) in children aged 8-12 were 33.92％ (2 608/7 689) and 0.68 in all monitored counties from 2013 to 2017.The detection rate presented a declining trend year by year (x2 =152.47 P ＜ 0.01).The average detection rate and CFI in the villages with normal operation projects and qualified fluoride content were 26.10％ (1 311/5 023) and 0.47.The detection rate presented a declining trend year by year (x2 =207.67 P ＜ 0.01).The detection rate and CFI in the villages with water improvement projects under abnormal operation or excessive fluoride were 48.65％ (1 297/2 666) and 0.90.The detection rate of dental fluorosis in the villages with normal operation projects and qualified fluoride content was lower than the rate of the villages with water improvement projects under abnormal operation or excessive fluoride (x2 =193.98,P ＜ 0.01).In 2013 and 2017,X-ray detection rates of skeletal fluorosis in adults aged over 25 were 8.04％ (119/1 481) and 6.04％ (81/1 342),respectively.The adult urinary fluoride geometric mean values (1.24,1.49 mg/L) were lower than the normal limit of 1.6 mg/L both in qualified villages of water ffuoride content and exceeding-standard villages in 2017.Conclusions In Shandong Province,the effective water improvement has acquired some effects in control of drinking water-borne endemic fluorosis.But the water fluoride content of improved water defluoridation projects exceeds the national standard seriously and fluorosis has not been effectively controlled.