OBJECTIVE To investigate ameliorative effects and mechanisms of two probiotics （Bacillus subtilis， Lactobacillus acidophilus） combined with Aurantii Fructus Immaturus （AFI） on functional dyspepsia （FD） in rats. METHODS Rats were randomly divided into blank group， model group， positive control group （domperidone group， 2.7 mg/kg）， AFI group （9 g/kg）， L. acidophilus group （5×107 cfu/kg）， B. subtilis group （5×107 cfu/kg）， L. acidophilus+ AFI group （L. acidophilus 5×107 cfu/kg+ AFI 9 g/kg）， and B. subtilis+AFI group （B. subtilis 5×107 cfu/kg+AFI 9 g/kg）， with 8 rats in each group. Except for the blank group， FD model was established by tail-clamping stimulation+hunger and satiety disorder+swimming exhaustion in other groups. After modeling， each group was given the corresponding drug/probiotic suspensions/physiological saline intragastrically， once a day， for 14 consecutive days. After the last medication， gastric emptying rate and the rate of propulsion of the small intestine in rats were measured； the levels of brain-gut peptide-related indicators [gastrin （GAS）， substance P （SP）， vasoactive intestinal peptide （VIP）， somatostatin （SS） and cholecystokinin （CCK）] in the serum of rats were measured. The pathological morphology of the gastric antrum tissue and duodenal tissue was observed. Cecal contents from the rats were collected for gut microbiota sequencing analysis. The protein expression levels of tyrosine kinase receptor c-Kit and stem cell factor （SCF） in the gastric antrum tissue， as well as Toll-like receptor 4 （TLR4）， myeloid differentiation factor 88 （MyD88）， and nuclear factor κB （NF-κB） in the duodenal tissue of the rats were detected. RESULTS Compared with the blank group， model group showed significantly lower gastric emptying rate， small intestinal propulsion rate， serum levels of GAS and SP， relative abundance of Firmicutes， Ace， Chao and Sobs indexes of the gut microbiota， and protein levels of SCF and c-Kit in gastric antrum （P＜0.05）， while serum levels of VIP， SS and CCK， relative abundance of Bacteroidetes， as well as protein expressions of TLR4， MyD88， and NF-κB， were significantly higher （P＜0.05）. The histological structure JZYC23S53） of the gastric antrum tissue appeared basically normal； however， abnormalities were observed in the duodenal structure， with a significant infiltration of inflammatory cells visible. Compared with the model group， all treatment groups significantly modulated most of the above indexes （P＜0.05）. The histological structure of the gastric antrum tissue was normal. Except for the B. subtilis group and the B. subtilis+AFI group， the pathological states of the duodenum in the remaining rats gradually recovered. Compared with each single drug group， most of above indexes in rats from each combination group showed further improvement （P＜0.05）. CONCLUSIONS The combination of AFI with two probiotics can improve gastrointestinal motility in FD rats， and the effect is superior to that of using the drugs alone. The specific underlying mechanisms may be related to the activation of the SCF/c-Kit signaling pathway and the inhibition of the TLR4/MyD88/NF-κB signaling pathway.

Objective:To analyze effects of tectorigenin on improving cognitive deficits in rats with vascular dementia(VD)by regulating Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)signaling pathway.Methods:A total of 72 rats were randomly divided into sham operation group,model group,low,medium and high doses[25,50,100 mg/(kg·d)]tectorigenin groups and positive control group[piracetam 324 mg/(kg·d)],with 12 rats in each group.Except for sham operation group,VD models were replicated in other groups.After successful modeling,different doses tectorigenin groups and positive control group were administered intragastrically with different doses of tectorigenin and piracetam,while other groups were administered intragastrically with same volume of normal saline for 28 d.Spatial learning and memory ability were detected by Morris water maze.Neurotransmitter levels in hippocampus interstitial fluid were detected by high performance liquid chromatography-electro-chemical.Brain-derived neurotrophic factor(BDNF)and tyrosine kinase receptor b(TrkB)expressions in hippocampus were detected by RT-qPCR and Western blot.TLR4/MyD88/NF-κB pathway-related proteins in hippocampus were detected by Western blot.Results:Compared with sham operation group,escape latency was longer,while stay time in target area and times of crossing platform were lower in model group(P<0.05).Compared with model group,escape latency was shorter,while stay time in target area and times of crossing platform were higher in medium and high doses tectorigenin groups(P<0.05).NE,DA,5-HT and 5-HIAA levels in model group were lower than those in sham operation group(P<0.05),which were higher in medium and high doses tectorigenin groups than model group(P<0.05).Compared with sham operation group,BDNF and TrkB mRNA and proteins levels were lower,while TLR4,MyD88 and p-NF-κB p65/NF-κB p65 proteins levels were higher in model group(P<0.05).Compared with model group,BDNF and TrkB mRNA and proteins levels were higher,while TLR4,MyD88 and p-NF-κB p65/NF-κB p65 proteins levels were lower in medium and high doses tectorigenin groups(P<0.05).Conclusion:Tectorigenin can improve cognitive deficits in VD rats,which may be related to regulating TLR4/MyD88/NF-κB signaling pathway.

With the progress of society,the global development of scientific and technical research activities,and the increasing number of medical Institutional Review Board(IRB)review projects,the construction and management of electronic informatization have become extremely important.In the process of electronic information construction in institutional ethics review,it is necessary to take into account the new policy of ethical governance of science and technology,consider the system and standard operating procedures of IRB,and develop reasonable processes based on practical work,simplify manual operation,improve the accuracy of project management,achieve refined management,and facilitate communication among researchers,ethics committee secretaries,and members.

Objective:Through the analysis of five cases of occupational heat illness caused by high temperature, we expounded the pathogenesis and summarized the clinical characteristics of heat cramp and heat exhaustion of the newly revised diagnostic criteria for occupational heat illness (GBZ41-2019), in order to prevent the occurrence of occupational heat illness to put forward controllable countermeasures.Methods:According to the occupational history, clinical diagnosis and treatment and the other relevant data submitted by five patients, the diagnosis process was analyzed and summarized.Results:Five patients developed symptoms from July to August in summer, belonging to high-temperature operation. They improved by timely treatment. The symptoms, signs and laboratory tests of the five patients were different, but they were diagnosed as occupational heat illness.Conclusion:Employers should pay attention to the high temperature protection and cooling work, and strengthen the labor protection. If patients with heat cramp and heat exhaustion were timely treated, they could basically recover. Occupational disease diagnosticians should seriously study the new diagnostic criteria of occupational disease and constantly improve their diagnostic ability.

Objective:Through the analysis of five cases of occupational heat illness caused by high temperature, we expounded the pathogenesis and summarized the clinical characteristics of heat cramp and heat exhaustion of the newly revised diagnostic criteria for occupational heat illness (GBZ41-2019), in order to prevent the occurrence of occupational heat illness to put forward controllable countermeasures.Methods:According to the occupational history, clinical diagnosis and treatment and the other relevant data submitted by five patients, the diagnosis process was analyzed and summarized.Results:Five patients developed symptoms from July to August in summer, belonging to high-temperature operation. They improved by timely treatment. The symptoms, signs and laboratory tests of the five patients were different, but they were diagnosed as occupational heat illness.Conclusion:Employers should pay attention to the high temperature protection and cooling work, and strengthen the labor protection. If patients with heat cramp and heat exhaustion were timely treated, they could basically recover. Occupational disease diagnosticians should seriously study the new diagnostic criteria of occupational disease and constantly improve their diagnostic ability.

Metformin is currently a strong candidate anti-tumor agent in multiple cancers. However, its anti-tumor effectiveness varies among different cancers or subpopulations, potentially due to tumor heterogeneity. It thus remains unclear which hepatocellular carcinoma (HCC) patient subpopulation(s) can benefit from metformin treatment. Here, through a genome-wide CRISPR-Cas9-based knockout screen, we find that DOCK1 levels determine the anti-tumor effects of metformin and that DOCK1 is a synthetic lethal target of metformin in HCC. Mechanistically, metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, leading to metformin resistance. The DOCK1-selective inhibitor, TBOPP, potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids, and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models. Notably, metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression. This study shows that metformin effectiveness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for metformin-resistant HCC patients.
Animals ; Antineoplastic Agents/therapeutic use* ; Carcinoma, Hepatocellular/metabolism* ; Cell Line, Tumor ; Clustered Regularly Interspaced Short Palindromic Repeats ; Genome ; Humans ; Liver Neoplasms/metabolism* ; Metformin/therapeutic use* ; Mice ; Phosphorylation ; Synthetic Lethal Mutations ; Transcription Factors/metabolism* ; rac GTP-Binding Proteins/metabolism*

Objective:To investigate the stability and feasibility of improved silent MRA technique based on hybrid-arterial spin labeling(ASL) for imaging intracranial arterial stenosis.Methods:From September 2019 to May 2020, totally 35 patients with suspected intracranial vascular stenosis in Department of Neurology of Northern Jiangsu People′s Hospital were enrolled in this study. Silent MRA and improved silent MRA based on hybrid-ASL technique were performed respectively. The acquisition noise (noise measurement and subjective score) of two kinds of MRA examination were evaluated respectively. Two neuroradiologists performed image quality scoring and signal-to-noise ratio (SNR) measurement of intracranial arteries (including internal carotid artery, vertebrobasilar artery, anterior cerebral artery, middle cerebral artery, and posterior cerebral artery) in the two kinds of MRA images using a double-blind, completely randomized method. Independent sample t-test was used to compare the image quality and SNR of two kinds of MRA images in each segment. Two experts assessed the degree of stenosis at the site of confirmed intracranial artery stenosis. Kappa test was used to assess interobserver and intermodel agreement. Results:There was no significant difference in acquisition noise between improved silent MRA and silent MRA ( P>0.05). In all five segments measured, the image quality scores of internal carotid artery [(4.40±0.49)scores], anterior cerebral artery[(4.30±0.33)scores] and middle cerebral artery [(4.46±0.34)scores] in improved silent MRA were higher than those in silent MRA images [(4.02±0.43)scores, (4.02±0.31)scores, (4.02±0.31)scores; t=2.825, 2.877, 1.683, all P<0.05)]. The SNR of internal carotid artery (9.11±1.23) and middle cerebral artery (8.77±1.87) in improved silent MRA images was higher than that in silent MRA images (7.83±1.33, 8.06±2.67, respectively; t=11.154, 3.268, both P<0.05). A total of 24 patients (38 lesions) with intracranial vascular stenosis were diagnosed by CTA. Improved silent MRA (Kappa=0.89, 95%CI 0.82-0.95) and silent MRA (Kappa=0.85, 95%CI 0.77-0.92) were highly consistent among observers in evaluating the degree of cerebrovascular stenosis.The results of improved silent MRA were highly consistent with those of CTA (Kappa=0.92, 95%CI 0.87-0.98), and those of silent MRA were highly consistent with those of CTA (Kappa=0.85, 95%CI 0.77-0.92). Conclusions:The improved silent MRA is feasible to improve the imaging quality and signal uniformity through efficient marking based on keeping the low noise features. In the diagnosis of intracranial stenosis and occlusive disease, the stability of improved silent MRA imaging improves the diagnostic efficiency of stenosis to a certain extent.

From providing funds for the global fight against infectious diseases,to actively participating in global health security actions,to strengthening mutual cooperation in the field of health,and providing medical treatment,training and scholarships to countries in need,China's foreign aid on global poverty alleviation is increasingly diversified and expanding in scale.Indeed,China is playing an increasingly important leading role in the global health agenda.It is worth mentioning that over the years,artemisinin compound have saved millions of lives all over the world,especially in poverty-stricken areas.China's work mode of malaria elimination has also been written into WHO's technical documents and recommended to other countries.Since 2007,Chinese medical staff has carried out the Artemisinin Compound Malaria Control Project in Comoros,bringing Chinese prevention and treatment programs to the local area.By 2014,Comoros had achieved zero deaths from malaria,and the number of cases had dropped by 98％.Now,this program is also extended to Togo,another African country.This article preliminarily summarizes the malaria profile in Togo and introduces China-Togo Cooperative Artemisinin Malaria Control Demonstration Project to provide a reference for better anti-malaria assistance in Togo,and also shows one of the substantive actions of China's participation in global health governance,which contributes Chinese wisdom and offers Chinese solutions to global poverty alleviation.

Malaria is one of the major diseases threatening the lives of people in Africa. Over the past decade, China has provided anti-malaria assistance to Africa. In November 2007, fast control malaria team of Guangzhou University of Chinese Medicine cooperated with the Comoros health authority. In Moheli Island of the Comoros, the anti-malaria team adopted a new strategy of Mass Drug Administration (MDA) and active intervention. They established an effective anti-malaria system and reporting system, as well as a local anti-malaria team. Furthermore, they treated patients with malaria in Moheli Island and implemended health education in local people. In a very short time, they have achieved remarkable results. This paper summarized the experiences of the project in order to provide useful reference for China to better carry out anti-malaria action in Africa and expand foreign health assistance.

Objective To determine the prevalence and treatment of chronic obstructive pulmonary diseases (COPD) among citizens in Ningbo. Methods A multi-stage stratified random sampling was applied to select 8 neighborhoods and 3 villages out of 7 districts in Ningbo, people who were older than or equal to 40 years were enrolled as subjects. Information on the prevalence rate and treatment conditions of COPD was collected through respiratory symptoms and treatment questionnaire and lung function screening. Results A total of 5865 people were screened, 5674 of them met inclusion criteria and completed questionnaire and lung function test. Among whom, 3044 people were men (53.6%, the average age is 55.7±11.4), 2630 women (46.4%, the average age was 55.3 ± 10.7);473 of them were diagnosed with COPD, the overall prevalence rate was 8.3%, including 354 cases who had never been diagnosed as COPD, accounted for 74.8% of the total cases diagnosed with COPD, mainly in stage ⅠandⅡof the disease. There were statistically significant differences between diagnosed and undiagnosed patients in the overall COPD group and among different gender groups ( stagesⅠandⅡ) and (stagesⅢandⅣ). Among the 473 COPD cases, 119 (diagnostic yield 25.2%) of whom had been diagnosed with bronchitis, only 48 (41.2%of the diagnosed) received drug treatment, only 13 patients were treated regularly with medication. Conclusion The overall prevalence rate of COPD among those over 40 years of age in Ningbo was quite high and mainly had stagesⅠandⅡof the disease. The number of the diagnostic yield and those who received regular treatment are quite low. The current situation of diagnosis and treatment are far from satisfaction, management of COPD should be strengthened to reduce the burden for family and society.