OBJECTIVES: To observe the therapeutic effect of spermine in neonatal mouse models of severe hand, foot and mouth disease (HFMD) caused by enterovirus 71 (EV71) infection and explore its therapeutic mechanism in light of regulation of macrophage GBP5/NLRP3 inflammasome pathway. METHODS: Neonatal BALB/c mice (3-5 days old) were divided into control group, EV71 infection group and Spermine treatment group. The mice in the latter two groups received an intraperitoneal injection of 50 μL EV71 suspension (1×10⁶ TCID50 of EV71), followed 3 days later by intraperitoneal injection of 50 μL PBS or 100 μmol/L spermine. GBP5, NLRP3, CXCL10, and TNFSF10 expressions in heart, liver, lung and kidney tissues of the mice were detected using Western blotting and qPCR, and tissue pathologies and macrophage infiltration were assessed with HE staining and immunohistochemistry. In cultured THP-1 and RAW264.7 cells, the effects of EV71 infection, GBP5 siRNA transfection and treatment with spermine or eflornithine on GBP5, NLRP3, CXCL10, and TNFSF10 mRNA expressions were investigated using qPCR. RESULTS: In the neonatal mice, EV71 infection resulted in multiple organ damage, macrophage infiltration and activation of the GBP5/NLRP3 pathway, and spermine treatment significantly improved tissue injuries, reduced macrophage infiltration, and down-regulated the expressions of GBP5, NLRP3 and the inflammatory factors in the infected mice. In THP-1 and RAW264.7 cells, EV71 infection caused significant upregulation of GBP5, NLRP3, CXCL10, and TNFSF10 expressions, which were obviously lowered by spermine treatment. In THP-1 cells, treatment with eflornithine significantly suppressed the reduction of GBP5, NLRP3, CXCL10, and TNFSF10 expressions induced by GBP5 siRNA transfection. CONCLUSIONS Spermine suppressed EV71 infection-induced inflammatory responses by inhibiting GBP5-mediated NLRP3 inflammasome activation, suggesting a new strategy for treatment of severe HFMD.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein ; Mice ; Macrophages/metabolism* ; Enterovirus A, Human ; Mice, Inbred BALB C ; Inflammasomes/metabolism* ; Spermine/therapeutic use* ; Animals, Newborn ; Humans ; Enterovirus Infections ; Hand, Foot and Mouth Disease/drug therapy* ; RAW 264.7 Cells ; Chemokine CXCL10/metabolism*

Objective To explore the effect of PCSK9 inhibitor combined with atorvastatin on carotid atherosclerosis and its anti-inflammatory effect in patients with hypertension complicated with type 2 diabetes mellitus.Methods A total of 100 patients with hypertension complicated with type 2 diabetes mellitus who were treated in Nanchang Third Hospital from October 2022 to August 2023 were selected as the research subjects.They were divided into the control group and the study group by the random number table method,with 50 cases in each group.Both groups of patients received conventional antihypertensive,hypoglycemic,and antiplatelet therapy.The control group took 20 mg of atorvastatin calcium tablets orally,once a night.On the basis of the control group,the study group was additionally given 150 mg of evolocumab injection(a PCSK9 inhibitor)by subcutaneous injection,once every two weeks.Both groups of patients were followed up for 24 weeks.The levels of blood lipids,blood glucose,inflammatory cytokines,carotid intima-media thickness(IMT),atherosclerotic plaque score and adverse reactions of the patients in the two groups before and after treatment were detected and compared.Results The levels of TC,TG and LDL-C in the study group after treatment were lower than those before treatment and those in the control group at the same period,and the differences were statistically significant(P＜0.05).The levels of IL-1,IL-6,TNF-α,hs-CRP,as well as the ca-rotid IMT and atherosclerotic plaque score in the study group after treatment were lower than those before treatment and those in the control group at the same period,and the differences were statistically significant(P＜O.05).During the treatment period,there was no significant difference in the occurrence of adverse reac-tions between the two groups(P＞0.05).Conclusion The combination of PCSK9 inhibitor and atorvastatin can effectively regulate the blood lipid levels of patients with hypertension complicated and type 2 diabetes mellitus,alleviate the inflammatory response,and improve the degree of carotid atherosclerosis in these pa-tients.

Liver fibrosis is a repair response to chronic liver injury caused by various etiologies. Its continuous progression can develop into liver cirrhosis or even hepatocellular carcinoma, eventually leading to liver failure. Currently, there is no effective treatment for liver fibrosis. Hepatic macrophages play a key role in intrahepatic inflammatory response, progression and resolution of fibrosis, and have emerged as an important therapeutic target for anti-hepatic fibrosis. The function of hepatic macrophages in the process of liver fibrosis was mainly reviewed and the mode of action of hepatic macrophages from various aspects was discussed to provide ideas for the treatment of liver fibrosis.

With the aging of the world's population,the incidence of Alzheimer's disease (AD) is continuously increasing.Currently,AD has become one of the most severe challenges faced by modern medicine.Genistein is a flavonoid phytoactive substance,whose structure is similar to that of estrogen,allowing it to mimic the effects of estrogen and possess various biological activities.Due to its multi-pathway targeting and low toxicity characteristics,it is considered to be an effective potential therapeutic source for AD.In this paper,the pharmacokinetics of genistein are introduced,and its neuroprotective effects and mechanisms in AD are reviewed from the aspects of its estrogen-like action,antioxidant,anti-inflammatory,anti-β-amyloid,regulation of cholinergic neurotransmission and inhibition of Tau protein phosphorylation.

Objective To investigate the effect of nasal mask on preventing respiratory depression and hypoxia during anesthesia under painless gastroscopy.Methods 246 patients underwent elective painless gastroscopy from September 2022 to March 2023 were selected and divided into nasal catheter oxygen group(group C)and nasal mask oxygen group(group M)according to random number table method.The group C was inhaled oxygen by conventional nasal cannula,and in group M,oxygen was inhaled by a nasal mask.Patients in both groups were given 5 L/min preoxygenation for 3 min.After induction of anesthesia,gastroscopy was performed when modified observer's assessment of alertness/sedation(MOAA/S)score≤1.During anesthesia,hypoxia interventions were performed in group C based on percutaneous arterial oxygen saturation(SpO2)and in group M based on partial pressure of end-tidal carbon dioxide(PetCO2)and SpO2.The incidence of subclinical respiratory depression,hypoxia and severe hypoxia during anesthesia was recorded.The minimum SpO2 value during anesthesia was recorded;Implementation of intervention measures of jaw lifting,mask pressure oxygen and tracheal intubation.Record the number of gastroscope withdrawal cases.Mean arterial pressure(MAP),heart rate(HR),and respiratory rate(RR)were recorded at the time of entry(T0),immediately after induction of anesthesia(T1),at the end of gastroscopy(T2),and 5 minutes after awakening(T3).The occurrence of perioperative adverse events and the satisfaction of anesthesiologists and endoscopists were recorded.Results Compared with group C,the incidence of subclinical respiratory depression,hypoxia and severe hypoxia in group M was significantly decreased(P<0.05).The minimum value of SpO2 during anesthesia in group M was higher than that in group C(P<0.05).The incidence of jaw-lifting and mask ventilation were lower in group M than that in group C(P<0.05).The incidence of gastroscope withdrawal due to airway intervention in group M was lower than that in group C(P<0.05).Compared with T0,MAP,HR and RR of the two groups were significant reduction at T1 and T2(P<0.05).There was no significant difference in the incidence of adverse events between the two groups(P>0.05).The satisfaction of endoscopists in group M was higher than that in group C(P<0.05).Conclusion Compared with nasal catheter oxygen inhalation,anesthesia nasal mask can timely detect hypopnea and respiratory depression during gastroscopy,reduce the occurrence of hypoxia,and improve the airway safety of painless gastroscopy patients.

Objective To systematically evaluate the relationship between the dietary inflammatory in-dex(DII)and the onset risk of gestational diabetes mellitus(GDM).Methods The databases such as PubMed,Web of Science,Embase,Cochrane Library,CNKI and Wanfang Data were retrieved.The retrieval time was from the database establishment to September 10,2023.Two researchers separately screened the lit-eratures,extracted the data and conducted the bias risk assessment.The meta analysis was conducted by the RevMan 5.4 software.Results A total of 8 observational studies were included,involving 96 904 pregnant women.The results of meta-analysis showed that in the classified DII,compared with the DII anti-inflammato-ry tendency group,the risk of GDM onset in the DII pro-inflammatory tendency group was increased(OR=1.27,95％CI:1.07-1.50,P=0.006).In the continuous DII,for every unit increase in DII,the risk of GDM was increased by 29％(OR=1.29,95％CI:1.13-1.48,P＜0.001).In the subgroup analysis,the most of the stratified analysis results were consistent with the main analysis results.Conclusion The current evidence suggests that the high DII scores will increase the risk of GDM onset,but the aforementioned conclusion re-quires the validation through more high quality,large samples and multicenter studies.

Ribosomal proteins (RP) are important components of ribosomes and play key roles in ribosome biogenesis and protein translation. In addition, ribosomal proteins also possess many extra-ribosomal functions, such as regulation of gene expression, cell proliferation, differentiation, apoptosis, DNA repair, and many other cellular processes. The dysfunction of RP is closely related to the occurrence and development of various diseases including blood, metabolism, cardiovascular diseases and tumors, and RP might become potential therapeutic targets for a variety of diseases. The research progress on RP, including the basic functions of RP, extra-ribosomal properties, and the connections with human diseases were reviewed and their potential as biomarkers and therapeutic targets in diseases were discussed in this paper.

Humans ; SARS-CoV-2 ; COVID-19 ; Antibodies ; Antibodies, Viral/therapeutic use* ; Antibodies, Neutralizing/therapeutic use*

Objective: To investigate the characteristics of visual motor integration in children with developmental dyslexia and ADHD, and to provide a reference for the diagnosis and treatment of these children. Methods: During July to November of 2020，students from grade 3 to grade 5 of 7 primary schools in Xinjiang were selected by using random cluster sampling method. A total of 56 dyslexia group (group DD), attention deficit hyperactivity disorder group (group ADHD), comorbidity group and normal control group were selected and compared the differences of their visual motor integration ability and related factors ability. Multiple linear regression analysis was used to explore the predictive effects of related factors on visual motor integration ability. Results: The scores of visual integration ability and visual perception in comorbidity group (95.05±14.01, 12.71±7.40) were lower than those in DD group (104.77±17.19，23.04±11.48), ADHD group (104.00±14.11，25.70±10.74) and normal control group (129.80±12.91, 44.05±16.56) ( F/Z =58.24,110.49, P <0.05). The visual working memory score of the comorbidity group ( 73.64 ±5.36) was lower than the normal control group (78.96±4.68) ( P <0.05)，and there was no significant difference between the DD group (74.48±7.06) and the ADHD group (75.98±7.36) ( P >0.05). The results of multiple regression showed that visual perception, age, IQ and visual working memory were associated with visual and motor integration ability of dyslexia children with ADHD ( R 2=0.32，0.17，0.11， 0.04 ， P <0.05). Conclusion Visual motor integration and visual perception among children with DD combined ADHD are more severely impaired than those with ADHD and DD alone. Visual perception, age, IQ and visual working memory could help predict the development of visual and motor integration ability in children with DD combined ADHD.

Objective:Placental pathology reflects the health condition of both mother and fetus during pregnancy, providing information about pathogenesis especially in adverse pregnancies, and may provide guidance on subsequent pregnancies. Description on the placental changes after long-term use of rivanol is lacking, and this evaluated the placental changes, with emphasis on the differential diagnosis from other primary placental lesions.Methods:A total of 85 placentas from rivanol induced abortion submitted to the Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University from Januaury 2017 to October 2019 were reviewed; and 81 gestational-age-matched cases of spontaneous abortion or preterm delivery during the same period were also included as the control group. Diagnoses were based on the consensus statement of 2016 Amsterdam Placental Workshop Group. Statistical differences were analyzed by individual diagnostic terms.Results:The maternal age in rivanol group was (30.5±4.1) (range 22-41) years, compared with (30.9±4.3) (range 22-44) years in the control group. Gestational age was (23.2±3.5) (range 17-35) weeks and (23.3±2.8) (range 17-33) weeks in the rivanol and control groups. The incidence of chorioamnionitis in rivanol group was 91.8%, significantly higher than the control (63.0%, P<0.05); and there were more stage 1 (subchorionic) maternal response in rivanol than in the control (61.0% vs.28.6%, P<0.05) groups. In addition, acute deciduitis was also more common in rivanol group (27.1% vs. 13.6%, P<0.05). No significant difference was observed in fetal inflammatory responses (vasculitis of vessels in chorion plate and umbilical cord); maternal malperfusion (narrowing of intervillous space, increased intervillous fibrin deposition, decidual arteriopathy, villous infarction and retroplacental hematoma); and fetal malperfusion (villous stromal hemorrhage and avascular villi). Conclusions:The chemical chorioamnionitis caused by rivanol is characterized by maternal inflammatory response of low stage and high grade. The use of rivanol has no obvious impact on the fetal inflammatory response, maternal malperfusion and fetal malperfusion. Such morphologic changes may reflect the original placental lesions.