In healthy individuals,there is a favourable balance between commensal and potentially patho-genic bacteria.When the balance is broken,the host might suffer from gastrointestinal cancer.Studies have shown that high-fat diet can alter the composition of gastrointestinal microbiota,gastrointestinal microbiota may promote gastrointestinal cancer by affecting metabolites of gastrointestinal microbiota,leading to loss of gastrointestinal barrier function,suppressing anti-tumor immunity,etc.In this work,we will summary the current knowledge on relations and possible mechanisms of high-fat diet-associated gastrointestinal microbiota and gastrointestinal cancer.To provide new ideas for the treatment of gastrointestinal cancer.

Objective:To analyze the clinical features, treatment, and outcomes of fetal/neonatal atrial flutter (AFL) at the onset of the perinatal period to improve the management of this condition.Methods:This retrospective study analyzed the clinical data, treatment, and follow-up results of fetal/neonatal AFL cases transferred to Shanghai Children's Medical Center from November 2013 to August 2021. Clinical characteristics, cardioversion procedures, and outcomes were summarized. Descriptive method was used for statistical analysis.Results:A total of 21 fetuses/neonates presenting with AFL in the perinatal period were involved in this study, including 17 males and four females. Ten of them were born at full term, and 11 were preterms. All of the patients were delivered by cesarean section at 32 to 41 gestational weeks [ (36.6±1.9) weeks] with a birth weight of 2 130 to 4 450g [ (3 059±528) g]. Increased fetal heart rate was all detected after 32 weeks of gestation, and three of them were diagnosed with AFL by fetal echocardiography before being born. The heart rate remained elevated in all cases after birth. All were diagnosed as AFL based on an electrocardiogram on the day of birth, which showed a 2 to 6 over one ratio of atrioventricular conduction. Among the six cases of cardiac insufficiency and low blood pressure complicated by dyspnea and cyanosis, the symptoms were relieved in four cases after mask oxygenation and two cases after ventilation. Among the 21 cases, one was converted spontaneously to normal sinus rhythm and the other 20 recovered after medication or electrical cardioversion. Seven cases were initially treated by drug conversion with a success rate of 5/7 and hospitalized for 23 d (13-25 d). There was one with cardiac insufficiency before treatment and three newly developed cardiac insufficiency during treatment among the seven cases. Thirteen cases were offered electrical cardioversion initially, and the success rate of cardioversion was 12/13. There were five cases of cardiac insufficiency before treatment, while no new cases of cardiac insufficiency was reported during treatment. The duration of hospitalization was 11 d (9-14 d). Apart from one case, the rest 20 infants were followed up from one month to eight years old, and no recurrence was reported.Conclusions:For fetal/neonatal AFL with the onset during the perinatal period, the symptoms mainly manifest in late pregnancy. Its diagnosis depends on fetal echocardiography before birth or electrocardiogram after birth, and electrical cardioversion is a fast and effective measure. While the prognosis of perinatal-onset AFL is generally good.

Objective:To study the clinical characteristics of neonatal community-acquired Novel Coronavirus (COVID-19) Omicron variant infection.Methods:From March 30 to May 15, 2022, the epidemiological characteristics, clinical manifestations and outcomes of neonatal cases of community-acquired COVID-19 Omicron variant infection admitted to the isolation ward of our hospital were analyzed.Results:A total of 7 neonates infected with community-acquired COVID-19 Omicron variant were treated, including 3 males and 4 females. All of them were term infants with clear epidemiological exposure history. The infection was originated from caregivers of close contact (parents or babysitters). The main clinical symptoms was upper respiratory tract infection, including fever (6 cases), nasal congestion (6 cases), cough (5 cases), runny nose (2 cases), poor appetite (2 cases) and diarrhea (1 case). On admission, no abnormalities were found in blood routine examination and C-reactive protein (CRP). All but one case had normal serum amyloid A (SAA). No obvious abnormalities were found on chest X-ray. All patients were isolated in single-patient rooms after admission. They received standard symptomatic treatment and regular nucleic acid tests. The first negative nucleic acid results came on median 17 d(8~26 d) after the onset of the disease. The patients were discharged after two consecutive (24 h apart) nucleic acid tests with CT value ≥35 and continued health-monitor at home. On discharge, 5 patients had nasal congestion and 2 of them had cough. During the follow-up 4~6 weeks after discharge, all patients gradually recovered without positive nucleic acid results.Conclusions:All 7 neonates with community-acquired COVID-19 Omicron variant infection have epidemiological exposure history. The main clinical symptoms are long-lasting upper respiratory tract infections. It takes a relatively long time for the nucleic acid to turn negative, however, the overall short-term prognosis is good.

Objective:To investigate the relationship between the single nucleotide polymorphism（SNP）of function genes and effective components of Salvia miltiorrhiza and the molecular mechanism of specific quality formation of S. miltiorrhiza. Method:The fingerprints of components in S. miltiorrhiza from eight different habitats and varieties were obtained by high-performance liquid chromatography （HPLC）. The full-length cDNA of three functional genes acetyl-CoA C-acetyltransferase（SmAACT），4-diphosphocytidyl-2-C-methyl-D-erythritol kinase（SmCMK） and isopentenyl diphosphate isomerase（SmIPPI） in tanshinone metabolic pathway were amplified by polymerase chain reaction（PCR），cloned， and sequenced，followed by bioinformatics analysis. Result:The full-length cDNA sequences of three functional genes SmAACT，SmCMK， and SmIPPI in tanshinone metabolic pathway were obtained from 23 strains of S. miltiorrhiza from eight different habitats and varieties. As revealed by the analysis of SNP and amino acid polymorphisms of three functional genes，18，16， and 14 SNP sites were found respectively. HPLC results showed the samples from Beijing，Hubei，Shandong （No. SDB），Shanxi，Henan， and Shandong （No. SDZ） were clustered into one branch，and those from Hebei and Inner Mongolia were clustered into another branch， which suggested that the variation trend of S. miltiorrhiza components had little correlation with geographical distance，but the variety was a critical factor for the quality. Conclusion:There was an obvious genetic differentiation trend in S. miltiorrhiza from different habitats，and different origin-specific genotypes were formed. The molecular mechanism of the formation of the specific quality of S. miltiorrhiza from different habitats was discussed，which laid a foundation for the stability and effectiveness of clinical medication，and guided the breeding of excellent varieties of S. miltiorrhiza.

Objective:To study the predictive value of hour-specific total serum bilirubin(TSB) nomogram combined with clinical risk factors in the risk of hyperbilirubinemia.Method:Perinatal clinical data of newborns born in Shanghai Pudong New Area Health Care Hospital for Women and Children, Shanghai Pudong New Area People's Hospital and Shanghai Pudong Hospital from August 2017 to July 2018 were collected in this prospective study. Transcutaneous bilirubin (TcB) was monitored before discharge from hospital. Enrolled neonates were followed up for 28 days. The patients were assigned to neonatal hyperbilirubinemia group (NHB) and non-hyperbilirubinemia group (Non-HB) according to the occurrence of hyperbilirubinemia. The predictive value of models for the risk of hyperbilirubinemia was evaluated by receiver operating characteristic (ROC) curves and Logistic regression analysis.Result:A total of 8 664 newborns were included in this study, with 1 196 cases of hyperbilirubinemia, with an incidence of 13.8%. Logistic regression analysis showed that maternal blood type O, premature rupture of membranes, male gender, gestational age 35~37 weeks, subcutaneous ecchymosis/cranial edema, and breastfeeding were independent risk factors for NHB ( P<0.05). The area under receiver operative characteristic curve (ROC) of predischarge bilirubin risk zone only was 0.874(95% CI 0.861~0.885, P<0.05)and for all independent risk factors was 0.664 (95% CI 0.647~0.680, P<0.05). The area under ROC curve was 0.891 (95% CI 0.880~0.902, P<0.05) by combining predischarge bilirubin risk zone with clinical risk factors. Conclusion:Predischarge bilirubin risk zone combined with clinical risk factors can reasonably predict neonatal hyperbilirubinemia well.

Objective:To investigate the expression of N-myc downstream regulated gene 2(NDRG2) in hippocampus of epileptic mice and its effect on glutamate and glucose uptake in astrocytes of mice.Methods:The epileptic mouse model was induced by lithium chloride and pilocarpine nitrate. The mice were sacrificed at 1 d, 7 d, 15 d and 6 weeks after model establishment and the brain tissues of hippocampus were taken. Western blot was used to detect the expression of NDRG2 protein in hippocampus.The primary astrocytes of wild-type, NDRG2 + /+ and NDRG2 -/- mice were cultured and the NDRG2 phenotype of astrocytes was identified after primary culture. Glutamate content in the supernatant of astrocyte culture was determined by glutamate assay kit and ultraviolet spectrophotometer. Flow cytometry was used to detect the positive rate of 2-NBDG fluorescently labeled astrocytes. Results:(1) Compared with the control group (0.25±0.07), the expression of NDRG2 in the hippocampus of mice increased significantly in the acute phase of epilepsy (1 d(0.45±0.06, t=-3.84, P<0.05), 7 d(0.54±0.09, t=-4.30, P<0.05), 15 d(1.04±0.06, t=-15.08, P<0.01)), and remained significantly high in the chronic phase of epilepsy( 6 weeks (1.30±0.16, t=-10.40, P<0.01)). (2) The content of residual glutamate in the supernatant fluid of primary cell culture medium was detected.It was found that the uptake of glutamate by astrocytes in the NDRG2 -/- group was significantly lower than that in the NDRG2 + /+ group ((689.03±101.78) μmol/L, (113.67±37.35) μmol/L; t=9.19, P<0.01). (3) Western blot results showed that the expression of EAAT1 protein in NDRG2 -/- primary astrocyte was significantly lower than that of NDRG2 + /+ primary astrocyte(0.34±0.03, 1.16±0.21), and the difference was statistically significant ( t=-6.59, P<0.01). (4) Flow cytometry results showed that the positive rate of astrocyte in NDRG2 -/- group cells was significantly lower than that in NDRG2 + /+ group cells ((17.60±5.72)%, (72.22±8.35)%), and the difference was statistically significant ( t=-13.22, P<0.01). Conclusion:NDGR2 is closely related to the occurrence and development of epileptic diseases. The expression of NDRG2 is beneficial to exert its physiological function of EAAT1 and promotes the uptake of glutamate and glucose by astrocyte. It may be a potential cell protective factor to promote nerve protection and repairment.

The progression of renal damage in diabetic nephropathy(DN)is closely related to Nod-like receptor protein3(NLRP3)inflammasome activation. The characteristics of NLRP3 inflammasome activation include the changed expression and combination levels of NLRP3, apoptosis-associated speck-like protein(ASC)and pro-caspase-1, the increased expression levels of caspase-1, interleukin(IL)-1β and IL-18 and the excessive release levels of the relative inflammatory mediators. Its molecular regulative mechanisms involve the activation of multiple signaling pathways including reactive oxygen species(ROS)/thioredoxin-interacting protein(TXNIP)pathway, nuclear factor(NF)-κB pathway, nuclear factor erythroid-related factor 2(Nrf2)pathway, long non-coding RNA(lncRNA)pathway and mitogen-activated protein kinases(MAPKs)pathway. In addition, more importantly, never in mitosis aspergillus-related kinase 7(Nek7), as a kinase regulator, could target-combine with NLRP3 at upstream to activate NLRP3 inflammasome. Some extracts of Chinese herbal medicines(CHMs)such as quercetin, curcumin, cepharanthine, piperine and salidroside, as well as Chinese herbal compound prescriptions such as Wumei Pills both could treat NLRP3 inflammasome to ameliorate inflammatory renal damage in DN. Therefore, accurately clarifying the targets of anti-inflammatory CHMs and Chinese herbal compound prescriptions delaying DN progression by targeting the molecular regulative mechanisms of NLRP3 inflammasome activation will be one of the development directions in the future.
Caspase 1/immunology* ; Diabetes Mellitus/drug therapy* ; Diabetic Nephropathies/immunology* ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Inflammasomes/immunology* ; Interleukin-18/immunology* ; Interleukin-1beta/immunology* ; NIMA-Related Kinases ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology*

Almost all organisms exhibit ~24-h rhythms, or circadian rhythms, in a plentitude of biological processes. These rhythms are driven by endogenous molecular clocks consisting of a series of transcriptional and translational feedback loops. Previously, we have shown that the inner nuclear membrane protein MAN1 regulates this clock and thus the locomotor rhythm in flies, but the mechanism remains unclear. Here, we further confirmed the previous findings and found that knocking down MAN1 in the pacemaker neurons of adult flies is sufficient to lengthen the period of the locomotor rhythm. Molecular analysis revealed that knocking down MAN1 led to reduced mRNA and protein levels of the core clock gene period (per), likely by reducing its transcription. Over-expressing per rescued the long period phenotype caused by MAN1 deficiency whereas per mutation had an epistatic effect on MAN1, indicating that MAN1 sets the pace of the clock by targeting per.

To explore the effects and molecular mechanisms of triptolide（TP）on improving podocyte epithelial-mesenchymal transition（EMT）induced by high dose of D-glucose（HG）, the immortalized podocytes of mice were divided into the normal group（N）, the high dose of D-glucose group（HG）, the low dose of TP group（L-TP）, the high dose of TP group（H-TP）and the mannitol group（MNT）, and treated by the different measures respectively. More specifically, the podocytes in each group were separately treated by D-glucose（DG, 5 mmol·L⁻¹）or HG（25 mmol·L⁻¹）or HG（25 mmol·L⁻¹）+ TP（3 μg·L⁻¹）or HG（25 mmol·L⁻¹）+ TP（10 μg·L⁻¹）or DG（5 mmol·L⁻¹）+ MNT（24.5 mmol·L⁻¹）. After the intervention for 24, 48 and 72 hours, firstly, the activation of podocyte proliferation was investigated. Secondly, the protein expression levels of the epithelial markers in podocytes such as nephrin and podocin, the mesenchymal markers such as desmin and collagen Ⅰ and the EMT-related mediators such as snail were detected respectively. Finally, the protein expression levels of Wnt3α and β-catenin as the key signaling molecules in Wnt3α/β-catenin pathway were examined severally. The results indicated that, HG could cause the low protein expression levels of nephrin and podocin and the high protein expression levels of desmin, collagen Ⅰ and snail in podocytes, and inducing podocyte EMT. On the other hand, HG could cause the high protein expression levels of Wnt3α and β-catenin in podocytes, and activating Wnt3α/β-catenin signaling pathway. In addition, L-TP had no effect on the activation of podocyte proliferation, the co-treatment of L-TP and HG could significantly recover the protein expression levels of nephrin and podocin, inhibit the protein expression levels of desmin, collagen I and snail in podocytes, thus, further improving podocyte EMT. And that, the co-treatment of L-TP and HG could obviously decrease the high protein expression levels of Wnt3α and β-catenin induced by HG in podocytes, and inhibit Wnt3α/β-catenin signaling pathway activation. On the whole, HG can induce podocyte EMT by activating Wnt3α/β-catenin signaling pathway; L-TP can ameliorate podocyte EMT through inhibiting Wnt3α/β-catenin signaling pathway activation, which may be one of the effects and molecular mechanisms .
Animals ; Cells, Cultured ; Diterpenes ; pharmacology ; Epithelial-Mesenchymal Transition ; Epoxy Compounds ; pharmacology ; Glucose ; Mice ; Phenanthrenes ; pharmacology ; Podocytes ; drug effects ; Wnt Signaling Pathway ; Wnt3A Protein ; metabolism ; beta Catenin ; metabolism

Objective To study the clinical features,diagnosis,genetic characteristics and treatment of congenital disorder of glycosylation type Ⅰg (CDG-Ⅰg) and to raise the awareness of CDG-Ⅰg among the clinicians.Method The data of one child with CDG-Ⅰg admitted to Shanghai Children's Medical Center affiliated to Shanghai Jiaotong University School of Medicine was studied retrospectively.Literatures were retrieved with key words including "congenital glycosylation disorder Ⅰg","ALG12","congenital glycosylation defect Ⅰg","CDG-Ⅰg" and "congenital disorder" in the Chinese knowledge network,VP database,Wanfang database,Biomedicine,PubMed and the Web of Science database from data established until January 2018.We summarized the clinical and genetic characteristics of CDG-Ⅰg.Result An one-day-old male infant admitted to the Hospital due to "poor response with hypoglycemia" manifested with facial deformity,hypotonia,inverted nipples,micropenis and undescended testes.He had intermittent hypoglycemia and recurrent infection,treated with antimicrobials,glucose rehydration and hormone therapy.Serum insulin,growth hormone level,blood and urine metabolic screening were normal.The patient was compound heterozygous for ALG12 mutations,c.432C ＞ A,p.Cys144 * and c.904T ＞ C,p.Tyr302His,each of his parents carried a pathogenic mutation.The patient died in follow-up for unknown reasons.No reported cases of CDG-Ⅰg from China have so far been reported yet.We reviewed the other 8 cases CDG-Ⅰg (4 males and 4 females) born in foreign countries,5 of them with neonatal onset.Common clinical manifestaions include facial deformity,hypotonia,hypogenitalism,coagulopathy,hypoimmunity,recurrent infection,electroyte imbalance etc.The ALG12 gene has 11 mutation sites.Conclusion CDG-Ⅰg is a rare autosomal recessive disorder.Most reported patients had onset in neonatal period.It seems that the association of facial deformity,psychomotor retardation,hypotonia,coagulopathy,male hypogenitalism and hypoglycemia might be a clue to the diagnosis of CDG-Ⅰg.Gene detection of ALG12 can confirm the diagnosis.This disorder has no specific treatment yet.