This article reported a case of generalized arterial calcification in infancy (GACI), which was suspected prenatally and confirmed postnatally. At 24 weeks of gestation, a systematic ultrasound revealed aortic wall thickening with hyperechogenicity, a thickened mitral valve accompanied by hyperechoic changes, thickened and calcified tricuspid valves, and multiple hyperechoic foci in both ventricles. A follow-up echocardiography at 28 weeks showed no significant progression. Emergency cesarean section was performed at 31 weeks due to fetal distress. Postnatal echocardiography confirmed generalized arterial calcification. Whole-exome trio sequencing identified two variants in the ENPP1 gene: c.1274-2A>G and c.1437+3(IVS14)_c.1437+6(IVS14)delGAGT. Based on imaging, laboratory results, and genetic testing, the infant was diagnosed with GACI type 1, concomitant with autosomal recessive hypophosphatemic rickets type 2. Given the poor prognosis, the family withdrew from further medical intervention.

AIM:To investigate the mechanism by which exosomes(EXOs)derived from neural stem cells(NSCs)pretreated with astragaloside IV(ASIV)alleviate brain damage in rats after ischemic stroke.METHODS:Rat NSCs were isolated from fetal rats within 24 h of birth,cultured for 3 d,and subsequently treated with ASIV for additional 5 d.The EXOs from untreated NSCs and ASIV-pretreated NSCs(ASIV-EXOs)were isolated via ultracentrifugation of the cell supernatant.These EXOs were characterized using Western blot to detect specific markers such as CD63,tumor sus-ceptibility gene 101(TSG101)and calnexin.Nanoparticle analysis was employed to determine the size,and the morpholo-gy of the EXOs was observed under electron microscope.Six to eight-week-old SD male rats were randomly assigned to 6 groups:sham group,middle cerebral artery occlusion/reperfusion(MCAO/R)model group,edaravone(EDA)treatment(MCAO/R+EDA)group,EXOs treatement(MCAO/R+EXOs)group and ASIV-EXOs treatment(MCAO/R+ASIV-EXOs)group.Tail vein injections were administered within 2 h following the successful establishment of the MCAO/R model.The Zea Longa method was utilized to evaluate neurological deficits,while the TTC method was employed to assess brain infarc-tion.Pathological changes were examined through HE staining,and TUNEL and caspase-1 immunofluorescence double staining were conducted to detect cellular pyroptosis.Serum levels of interleukin-1β(IL-1β)and IL-18 were measured us-ing ELISA,and Western blot was performed to evaluate the expression of caspase-1,nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),gasdermin D(GSDMD),and IL-18 proteins in the ischemic area of the rat cerebral cortex across all groups.RE-SULTS:The MCAO/R group exhibited significantly higher neurological deficit scores compared to the sham group(P＜0.01)and lower scores in the administered groups relative to the MCAO/R group(P＜0.05).Cerebral infarction was mark-edly increased in the MCAO/R group compared to the sham group(P＜0.01),whereas the infarction area was reduced in the administered groups compared to the MCAO/R group(P＜0.05).Serum levels of IL-1β and IL-18 were significantly el-evated in the MCAO/R group versus the sham group(P＜0.01)and were lower in the administered groups compared to the MCAO/R group(P＜0.01).Moreover,IL-1β and IL-18 levels in the MCAO/R+ASIV-EXOs group were lower than those in the MCAO/R+EXOs group(P＜0.05).HE staining revealed pronounced sieve-like infarction foci in the ischemic area of the rat cerebral cortex in MCAO/R group,characterized by disorganized neuronal arrangements,reduced or absent Nys-trom's vesicles,shrunken or fragmented nuclei,and numerous red neurons.In contrast,drug-treated groups exhibited milder pathological changes with clearer neuronal structures and a significant reduction in red neuron counts.Immunofluo-rescence double staining indicated a significant increase in double-positive cells in the MCAO/R group compared to the sham group(P＜0.01),with a decrease in double-positive cells in the administered groups relative to the MCAO/R group(P＜0.05)and a further reduction in the MCAO/R+ASIV-EXOs group compared to the MCAO/R+EXOs group(P＜0.05).The expression levels of caspase-1,NLRP3,ASC,IL-18 and GSDMD proteins in the ischemic region of the rat cerebral cortex were significantly reduced in the administered groups compared to the MCAO/R group(P＜0.01),with further re-duction observed in the MCAO/R+ASIV-EXOs group compared to the MCAO/R+EXOs group(P＜0.05).CONCLU-SION:Exosomes derived from ASIV-pretreated NSCs attenuate brain damage in ischemic stroke rats,potentially through a mechanism involving the inhibition of pyroptosis mediated by the NLRP3/caspase-1 pathway.

AIM:To investigate the mechanism by which exosomes(EXOs)derived from neural stem cells(NSCs)pretreated with astragaloside IV(ASIV)alleviate brain damage in rats after ischemic stroke.METHODS:Rat NSCs were isolated from fetal rats within 24 h of birth,cultured for 3 d,and subsequently treated with ASIV for additional 5 d.The EXOs from untreated NSCs and ASIV-pretreated NSCs(ASIV-EXOs)were isolated via ultracentrifugation of the cell supernatant.These EXOs were characterized using Western blot to detect specific markers such as CD63,tumor sus-ceptibility gene 101(TSG101)and calnexin.Nanoparticle analysis was employed to determine the size,and the morpholo-gy of the EXOs was observed under electron microscope.Six to eight-week-old SD male rats were randomly assigned to 6 groups:sham group,middle cerebral artery occlusion/reperfusion(MCAO/R)model group,edaravone(EDA)treatment(MCAO/R+EDA)group,EXOs treatement(MCAO/R+EXOs)group and ASIV-EXOs treatment(MCAO/R+ASIV-EXOs)group.Tail vein injections were administered within 2 h following the successful establishment of the MCAO/R model.The Zea Longa method was utilized to evaluate neurological deficits,while the TTC method was employed to assess brain infarc-tion.Pathological changes were examined through HE staining,and TUNEL and caspase-1 immunofluorescence double staining were conducted to detect cellular pyroptosis.Serum levels of interleukin-1β(IL-1β)and IL-18 were measured us-ing ELISA,and Western blot was performed to evaluate the expression of caspase-1,nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),gasdermin D(GSDMD),and IL-18 proteins in the ischemic area of the rat cerebral cortex across all groups.RE-SULTS:The MCAO/R group exhibited significantly higher neurological deficit scores compared to the sham group(P＜0.01)and lower scores in the administered groups relative to the MCAO/R group(P＜0.05).Cerebral infarction was mark-edly increased in the MCAO/R group compared to the sham group(P＜0.01),whereas the infarction area was reduced in the administered groups compared to the MCAO/R group(P＜0.05).Serum levels of IL-1β and IL-18 were significantly el-evated in the MCAO/R group versus the sham group(P＜0.01)and were lower in the administered groups compared to the MCAO/R group(P＜0.01).Moreover,IL-1β and IL-18 levels in the MCAO/R+ASIV-EXOs group were lower than those in the MCAO/R+EXOs group(P＜0.05).HE staining revealed pronounced sieve-like infarction foci in the ischemic area of the rat cerebral cortex in MCAO/R group,characterized by disorganized neuronal arrangements,reduced or absent Nys-trom's vesicles,shrunken or fragmented nuclei,and numerous red neurons.In contrast,drug-treated groups exhibited milder pathological changes with clearer neuronal structures and a significant reduction in red neuron counts.Immunofluo-rescence double staining indicated a significant increase in double-positive cells in the MCAO/R group compared to the sham group(P＜0.01),with a decrease in double-positive cells in the administered groups relative to the MCAO/R group(P＜0.05)and a further reduction in the MCAO/R+ASIV-EXOs group compared to the MCAO/R+EXOs group(P＜0.05).The expression levels of caspase-1,NLRP3,ASC,IL-18 and GSDMD proteins in the ischemic region of the rat cerebral cortex were significantly reduced in the administered groups compared to the MCAO/R group(P＜0.01),with further re-duction observed in the MCAO/R+ASIV-EXOs group compared to the MCAO/R+EXOs group(P＜0.05).CONCLU-SION:Exosomes derived from ASIV-pretreated NSCs attenuate brain damage in ischemic stroke rats,potentially through a mechanism involving the inhibition of pyroptosis mediated by the NLRP3/caspase-1 pathway.

This article reported a case of generalized arterial calcification in infancy (GACI), which was suspected prenatally and confirmed postnatally. At 24 weeks of gestation, a systematic ultrasound revealed aortic wall thickening with hyperechogenicity, a thickened mitral valve accompanied by hyperechoic changes, thickened and calcified tricuspid valves, and multiple hyperechoic foci in both ventricles. A follow-up echocardiography at 28 weeks showed no significant progression. Emergency cesarean section was performed at 31 weeks due to fetal distress. Postnatal echocardiography confirmed generalized arterial calcification. Whole-exome trio sequencing identified two variants in the ENPP1 gene: c.1274-2A>G and c.1437+3(IVS14)_c.1437+6(IVS14)delGAGT. Based on imaging, laboratory results, and genetic testing, the infant was diagnosed with GACI type 1, concomitant with autosomal recessive hypophosphatemic rickets type 2. Given the poor prognosis, the family withdrew from further medical intervention.

Objective:To evaluate myocardial microcirculation perfusion with myocardial contrast echocardiography (MCE) in patients with acute myocardial infarction after percutaneous coronary intervention (PCI), and to explore the prognostic value of different types of myocardial microcirculation perfusion.Methods:This is a prospective cohort study. Patients with acute myocardial infarction who underwent successful PCI in Nanfang Hospital of Southern Medical University and Kanghua Hospital of Dongguan City from October 2019 to June 2021 were selected. All the enrolled patients completed MCE examination within 72 hours after PCI. According to the examination results, the patients were divided into normal microcirculation perfusion group, delayed microcirculation perfusion group, and blocked microcirculation perfusion group. Adverse cardiovascular events including all-cause death, cardiovascular death, and angina re-hospitalization were followed up, and left ventricular ejection fraction (LVEF) review results were collected at six months to one year after surgery. Kaplan-Meier survival curve was used to investigate the difference in the incidence of adverse cardiovascular events in different myocardial perfusion groups, and Cox regression analysis was used to evaluate the effect of myocardial perfusion on adverse cardiovascular events.Results:A total of 113 patients with acute myocardial infarction were included, aged (56.3±11.5) years, with 88(78%) males. There were 31 cases in the normal microcirculation perfusion group, 43 cases in the delayed microcirculation perfusion group and 39 cases in the blocked microcirculation perfusion group. LVEF was reviewed in 49 patients, and LVEF in the delayed microcirculation perfusion group was significantly improved compared with baseline at follow-up ((63.3±1.2) % vs. (58.6±1.8) %, P=0.043), and there was no statistically significant difference between the other two groups (all P>0.05). The median follow-up time was 473 days, during follow-up period 30 adverse cardiovascular events occurred. Kaplan-Meier survival curve analysis showed that there was a statistically significant difference in the incidence of adverse cardiovascular events among the three groups ( Plog-rank=0.029). Cox regression analysis showed that abnormal microcirculation perfusion (defined as delayed and blocked microcirculation perfusion) was an independent predictor of adverse cardiovascular events in patients with acute myocardial infarction after PCI ( HR=1.90, 95% CI1.16-3.12, P=0.011). Conclusions:Microcirculatory perfusion decrease or lost is common in patients with acute myocardial infarction after PCI. Timely restoration of blood flow reconstruction can save heart function when microcirculatory perfusion decreases. Microcirculatory perfusion is a predictor of adverse cardiovascular events in patients with acute myocardial infarction, and patients with poor myocardial perfusion are more likely to experience adverse cardiovascular events.

Objective:To investigate the effects of erythropoietin producing hepatocyte receptor A2 (EphA2) gene silencing on the growth, migration and invasion of human ovarian cancer HeyA8-MDR cells.Methods:After stable screening by plasmid and liposome mediated transfection, the expression of EphA2 protein was detected by Western blot. The effects of EphA2 gene silencing on the biological characters of HeyA8-MDR cells of ovarian cancer were observed by CCK-8 and Transwell chamber invasion assay.Results:Compared with HeyA8-MDR (negative control group) and HeyA8-MDR+ blank control group, the expression level of EphA2 protein in HeyA8-MDR+ experimental group was significantly decreased ( P<0.01). Cell proliferation, migration and invasion were inhibited ( P<0.05). Conclusions:EphA2 gene silencing can inhibit the growth, migration and invasion of HeyA8-MDR cells of ovarian cancer, providing a new idea for the treatment of ovarian cancer.

There are many kinds of variabilities of fetal venous system tending to complicated with complex cardiovascular malformations.Prenatal ultrasound is of great importance for evaluation of fetal venous system.High-definition flow(HD-Flow)combined with spatiotemporal image correlation(STIC)could not only display micro blood flow in fetal venous system,but also show the spatial alignment and flow direction in real time.The research progresses of HD-Flow combined with STIC for evaluating fetal venous system abnormalities were reviewed in this article.

As a ligand-dependent transcription factor,retinoid-associated orphan receptor γt(RORyt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the pro-gression of several inflammatory and autoimmune conditions.An emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORyt to decrease Th17 cell development and IL-17 production.Several RORyt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORyt by binding to orthosteric-or allosteric-binding sites in the ligand-binding domain.Some of small-molecule inhibitors have entered clinical evaluations.Therefore,in current review,the role of RORyt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was highlighted.Notably,the recently developed RORyt inhibitors were summarized,with an emphasis on their optimization from lead compounds,ef-ficacy,toxicity,mechanisms of action,and clinical trials.The limitations of current development in this area were also discussed to facilitate future research.

We report the diagnosis and treatment of two cases of fetal intestinal volvulus. Case 1 presented to Gansu Provincial Maternity and Child-care Hospital due to reduced fetal movements at 33 +4 weeks of gestation. Case 2 was referred to our hospital from a local hospital because of fetal bowel dilatation by ultrasound at 32 +5 weeks. Both cases were found to have fetal bowel dilatation with typical "whirlpool" or "coffee bean" signs on ultrasound after admission. After multidisciplinary consultation and discussion, an emergency cesarean section was performed, during which the two neonates underwent surgical operation and resection of necrotic bowel loops after confirming the diagnosis of volvulus and intestinal necrosis. Case 2 suffered from pulmonary artery thrombosis after the bowel surgery, and underwent pulmonary artery incision and embolectomy within 24 hours. Both newborns recovered well after the operation, whose growth parameters and nervous system development was normal for follow-up.

Objective:To explore the feasibility and clinical results of absorbable antibacterial calcium sulfate combined with tissue flaps in the treatment of traumatic calcaneal osteomyelitis (CO) secondary to skin and soft tissue defects in children.Methods:From January 2007 to August 2020, 44 cases of children with heel skin and soft tissue defects associated with traumatic CO were treated and followed up effectively in the Third Affiliated Hospital of Xinxiang Medical University.Among them, 17 cases were treated with absorbable calcium sulfate cement combined with tissue flaps as the calcium sulfate group, and 27 cases were treated with antibiotic polymethylmethacrylate (PMMA) bead combined with tissue flaps as the membrane induction group.A comparison was drawn on the therapeutic effect, recurrence rate of postoperative infection, postoperative ankle mobility, number of operations, total length of hospital stays and hospitalization expenses between both groups.Results:The average follow-up time was 10.7 months in the calcium sulfate cement group and 9.3 months in the membrane induction group.All flaps were effective except for 3 cases who presented with small necrosis on the distal end of the sural neurovascular flaps.The recurrence rate of postoperative infection and the hospitalization expenses in the calcium sulfate group were lower than those in the membrane induction group, but the differences were not statically significant (all P>0.05). The postoperative ankle mobility [(63.6±9.3)°], number of operations [2(1.0, 2.0) times] and total length of hospital stay [6.1(4.5, 7.4) weeks] of the calcium sulfate group were significantly lower than those of the membrane induction group [(57.7±9.5)°, 2(2.0, 3.0) times, 7.0(5.0, 9.0) weeks], the difference were statistically significant (all P<0.05). Severe CO may cause structural damage to calcaneal tubercle or insertion site of achilles tendon, but the active plantar flexion function of ankles will be good despite the decrease in strength. Conclusions:The effect of absorbable antibacterial calcium sulfate cement combined with tissue flaps in the treatment of traumatic CO in children is favorable, and the number of operations, length of hospital stays and hospitalization expenses are relatively less compared with PMMA cement combined with tissue flaps.