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*

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.

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.

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.

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.

Objective To investigate the perinatal outcomes after elective neurosurgery in pregnant women complicated by space-occupying lesions in saddle area.Methods Clinical data were retrospectively collected and analyzed from five gravidas with space-occupying lesions in saddle area,who underwent neurosurgery at Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from June 2017 to February 2018,including gestational age,perioperative management,surgical procedures,postoperative complications,pregnancy outcomes and pathological results.Results (1) Progressively deteriorated impaired vision was the chief complaint of all five patients.Space-occupying lesions in saddle area were detected by cranial MRI (plain scan).The surgical indication was clear as there was compression on optic nerve and a risk of blindness due to optic nerve atrophy,Two patients were operated in the third trimester and three in the second trimester.Postoperative pathology showed there were two cases with meningioma,two with pituitary macro adenoma and one with abscess of pituitary.Only one patient had mild postoperative cerebrospinal fluid rhinorrhea,which was improved three months later,and no complications were reported in the other four cases.All five patients had obvious improvement of vision after surgical intervention and no relapse was reported during a follow-up of 4-12 months.(2) Four gravidas continued their pregnancies to full or nearly full term,among which three underwent cesarean section due to obstetrical indications (one breech pregnancy,one twin pregnancy with scarred uterus and one complicated by hypertensive diseases of pregnancy with poor blood pressure control) and one delivered vaginally.Postpartum involution of the uterus was well in all of the four cases 42 d after delivery.The women with pituitary abscess terminated the pregnancy due to intraamniotic injection of ethacridine lactate at 20 weeks of gestation.Five neonates were all born with Apgar scores of 10 at 1,5 and 10 min without any visible defects at birth and all grew and developed normally at 4-12 months after birth.Conclusions For gravidas with space-occupying lesions in saddle area,it is necessary to weigh the pros and cons and choose an individualized treatment plan.Resection of saddle area lesions in the second or third trimester backed by a multidisciplinary team is a safe and feasible procedure if postponing the operation until delivery may cause irreversible or even life-threatening consequences.

Objective: To study the relationship between STAT3 gene (rs2293152, rs957970) polymorphism and susceptibility to bronchial asthma in children, and to lay the foundation for search of the candidate pathogenic gene of asthma and early prevention of the disease. Methods: One hundred and thirty hospitalized asthmatic children or out-patients with asthma at Affiliated Hospital of Southwest Medical University from September 2013 to September 2017 were selected as asthmatic group, and at the same time 145 healthy children were selected from the Affiliated Hospital of Southwest Medical University as the healthy control group.Apply sequence specific primers-polymerase chain reaction (SSP-PCR) was applied to detect susceptibility single nucleotide polymorphism (SNP) of STAT3 gene (rs2293152, rs9579700). The statistical differences in distribution between genotype and allele were analyzed between the asthma group and the healthy control group. Results: The distribution frequency of CC genotype of rs2293152 in STAT3 gene was significantly higher in the asthmatic group (19.2%)than that in the healthy control group (9.0%) (χ²=6.065, P=0.014). C allele was significantly higher in asthmatic group (41.9% vs.33.8%) (χ²=3.861, P=0.049). There was no significant difference in the distribution of rs957970 in STAT3 gene between the asthma group and the healthy control group. Conclusions The SNP of rs2293152 in STAT3 gene is associated with susceptibility to asthma in children in South Sichuan.C allele may be the susceptible gene for childhood asthma, while the SNP of rs957970 in STAT3 gene has no significant correlation with childhood asthma in Southern Sichuan.