OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with Oral-facial-digital syndrome type Ⅰ(OFDSⅠ). METHODS: A child with OFDSⅠ who received treatment at the Women and Children's Hospital Affiliated to Ningbo University in March 2023 was selected as the study subject. A retrospective research method was used to collect the clinical data of the child. Peripheral venous blood samples were collected from the child, her parents and sister. Genomic DNA was extracted, and whole exome sequencing (WES) was performed. Candidate variants were validated using Sanger sequencing for familial verification. According to the Standards and Guidelines for the Interpretation of Sequence Variants developed by the American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the "ACMG Guidelines"), the pathogenicity of the candidate variant was rated. This study was approved by the Medical Ethics Committee of Ningbo University Affiliated Women and Children's Hospital (Ethic No.: EC 2024-063). RESULTS: The child was a prematurely born female with deformities of the oral cavity, fingers, and toes. She was admitted to the Neonatal Department of the Hospital where she was born due to shortness of breath 15 minutes after birth. The WES results indicated that the child has harbored a heterozygous c.710dup (p.Y238Vfs*2) frameshifting variant of the OFD1 gene. Sanger sequencing confirmed that neither of the child's parents nor her sister had carried the same variant. According to the ACMG guidelines, the variant was rated as pathogenic (PVS1+PS4_Moderate+PM2-Supporting+PM6_Supporting+PP4). CONCLUSION Children with OFDSⅠ have clinical features such as oral, finger, and toe deformities. The c.710dup (p.Y238Vfs*2) variant of the OFD1 gene probably underlay the OFDSⅠ in this child. Above result has enriched the mutational spectrum of the OFD1 gene.
Humans ; Female ; Orofaciodigital Syndromes/genetics* ; Exome Sequencing ; Retrospective Studies ; Mutation ; Child ; Proteins

Objective To analyze the clinical efficacy and its effect on immune function and cytokines of ω-3 polyunsaturated fatty acid (PUFA) in the treatment of preterm infants<32 weeks and birth weight<1500g.Methods The clinical data of preterm infants with birth gestational age<32 weeks and birth weight<1500g admitted to the neonatal intensive care unit of Ningbo Women and Children's Hospital from January 2018 to January 2023 were retrospectively analyzed,and divided into ω-3 group (n=80) and ω-6 group (n=80) according to the type of fatty acid used for treatment.ω-6 group of preterm infants were given nutritional support with ω-6PUFA,while ω-3 group of preterm infants were given nutritional support with ω-3PUFA.The efficacy,complication rate,immune function and cytokine level before and after treatment were compared between two groups.Results On the 7th day after birth,the levels of C-reactive protein,lactic acid (Lac),total bile acids,interleukin-8 (IL-8) and on the 14th day after birth,Lac,IL-8,tumor necrosis factor-α,retinopathy,and necrotizing enterocolitis complications in ω-3 group were lower than those in ω-6 group and the use of oxygen was shorter;The CD4/CD8 levels were higher in the ω-6 group.Conclusion ω-3PUFA have remarkable efficacy in nutritional support of preterm infants,which can effectively regulate immune function and inhibit the release of inflammatory factors,with fewer complications and higher safety.

Objective:To investigate the clinical characteristics of patients with malignant tumors and immune checkpoint inhibitors (ICI) related multisystem adverse events as well as therapeutic efficacy of ICI.Methods:The general data, immune-related adverse events (irAE) type, onset time, severity and ICI efficacy of patients with malignant tumors who developed irAE after receiving ICI in China-Japan Friendship Hospital between January 2019 and November 2021 were retrospectively analyzed. All patients were divided into multisystem irAE group and single system irAE group according to whether patients with more than 1 organ or system developed irAE for once. The occurrence of irAE was summarized, and the clinical characteristics of patients were compared. Progression-free survival analysis was not performed owing to the pause of immunotherapy caused by some irAE, so the efficacy of ICI was evaluated by using ICI treatment duration (TD).Results:A total of 47 patients with malignant tumors and irAE were included in this study, with 70 times of irAE in total. The median onset time was 90 d (35 d, 196 d). Among them, 12 patients (25.53%) developed multisystem irAE (32 times of irAE in total); the other 35 patients (74.47%) developed single system irAE (38 times of irAE in total). Cutaneous toxicity for 7 times, thyroid toxicity for 7 times and pulmonary toxicity for 5 times were the most frequent among multisystem irAE group; pulmonary toxicity for 13 times, thyroid toxicity for 12 times and cutaneous toxicity for 5 times were the most frequent among single system irAE group. There were no statistically significant differences in the proportion of patients stratified by age, gender, the combination of other treatments and different body mass between the two groups (all P > 0.05). The median follow-up time was 20 months (9-40 months). The median TD of ICI was 16.00 months (95% CI 3.62-31.22 months) in multisystem irAE group and 4.60 months (95% CI 4.12-11.30 months) in single system irAE group; TD in multisystem irAE group was longer than that in single system irAE group, and the difference was statistically significant ( HR = 0.413, 95% CI 0.202-0.844, P = 0.038). Conclusions:The efficacy of ICI in patients with malignant tumors and multisystem irAE is better than that in those with single system irAE. It suggests that the better efficacy of ICI may be associated with greater risk of irAE. There is no significant difference in the clinical features between multisystem irAE and single system irAE.

OBJECTIVE: To investigate the changes in gray matter volume in depressive-like mice and explore the possible mechanism. METHODS: Twenty-four 6-week-old C57 mice were randomized equally into control group and model group, and the mice in the model group were subjected to chronic unpredictable mild stimulation (CUMS) for 35 days. Magnetic resonance imaging was performed to examine structural changes of the grey matter volume in depressive-like mice. The expression of brain-derived neurotrophic factor (BDNF) in the grey matter of the mice was detected using Western blotting and immunofluorescence staining. RESULTS: Compared with the control mice, the mice with CUMS showed significantly decreased central walking distance in the open field test (P < 0.05) and increased immobile time in forced swimming test (P < 0.05). Magnetic resonance imaging showed that the volume of the frontal cortex was significantly decreased in CUMS mice (P < 0.001, when the mass level was greater than or equal to 10 756, the FDRc was corrected with P=0.05). Western blotting showed that the expression of mature BDNF in the frontal cortex was significantly decreased in CUMS mice (P < 0.05), and its expression began to decrease after the exposure to CUMS as shown by immunofluorescence staining. The volume of different clusters obtained by voxel-based morphometry (VBM) analysis was correlated with the expression level of mature BDNF detected by Western blotting (P < 0.05). CONCLUSION The decrease of frontal cortex volume after CUMS is related with the reduction of mature BDNF expression in the frontal cortex.
Animals ; Mice ; Blotting, Western ; Brain-Derived Neurotrophic Factor ; Cerebral Cortex ; Depression/physiopathology* ; Frontal Lobe/pathology*

Mammals exhibit limited heart regeneration ability, which can lead to heart failure after myocardial infarction. In contrast, zebrafish exhibit remarkable cardiac regeneration capacity. Several cell types and signaling pathways have been reported to participate in this process. However, a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is unavailable. We collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury regeneration. We revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes, and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during regeneration. Furthermore, we identified a regeneration-induced cell (RIC) population in the epicardium-derived cells (EPDC), and demonstrated Angiopoietin 4 (Angpt4) as a specific regulator of heart regeneration. angpt4 expression is specifically and transiently activated in RIC, which initiates a signaling cascade from EPDC to endocardium through the Tie2-MAPK pathway, and further induces activation of cathepsin K in cardiomyocytes through RA signaling. Loss of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation, while overexpression of angpt4 accelerates regeneration. Furthermore, we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes, and promote cardiac repair in mice after myocardial infarction, indicating that the function of Angpt4 is conserved in mammals. Our study provides a mechanistic understanding of heart regeneration at single-cell precision, identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration, and offers a novel therapeutic target for improved recovery after human heart injuries.
Humans ; Mice ; Rats ; Cell Proliferation ; Heart/physiology* ; Mammals ; Myocardial Infarction/metabolism* ; Myocytes, Cardiac/metabolism* ; Pericardium/metabolism* ; Single-Cell Analysis ; Zebrafish/metabolism*

Objective:To compare the clinical value of video laryngoscopy and conventional laryngoscopy for tracheal intubation in neonatal resuscitation.Methods:From July 2018, 100 cases of premature or asphyxia infants born in our hospital requiring tracheal intubation were enrolled. The infants were randomly assigned into video laryngoscopy group and conventional laryngoscopy group with 50 cases in each group. The time needed for intubation, the first time success rate and complications associated with intubation were compared between the two groups.Results:The time needed for intubation (21.7±2.7)s vs.(23.7±1.8)s and the first time success rate [98.0% (49/50) vs. 86.0% (43/50)] were significantly better in the video laryngoscopy group than the conventional laryngoscopy group ( P<0.05). The incidence of intubation complications showed no significant difference between the two groups ( P>0.05). Conclusions:Using video laryngoscopy, the time needed for tracheal intubation is shorter and the first time success rate is higher, without more complications. Video laryngoscopy can be safely used in tracheal intubation of neonatal resuscitation.

Objective To investigate the effect and mechanism of necrostatin-1 (Hec-1) on the level of HMGB-1 protein in liver of rats with hemorrhagic-traumatic shock.Methods A number of 96 male SD rats were divided into sham-operated group,dimethyl sulfoxide (DMSO) group and Nec-1 group (n=32in each) by randomized number method.Rat model of hemorrhagic-traumatic shock was made by fracture of femoral bone and tibia bone and exsanguination from femoral vein until 30 mmHg and maintained at 30-40 mmHg for 90 min,then the shed blood was transfused back with Ringer's solution.The rats in shamoperated group were only under anesthesia for separating and ligating blood vessels,without exsanguination to induce hemorrhagic shock and without replenishment with blood.Rats in Nec-1 group were given 1 mg/kg Nec-1 through femoral vein 5 min before replenishment with blood and Ringer' s solution,while the rats in DMSO group were given equal volume of DMSO solution instead.Eight rats in each group were sacrificed separately at 2 h,8 h,16 h and 24 h after replenishment.The serum and liver tissues of rats in each group were collected to detect serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST),and to observe the pathological changes in liver with hematoxylin-eosin (HE) staining.The level of HMGB-1 in serum was detected by using ELISA.The cytoplasm protein and total protein expressions of HMGB-1 were assessed by using western blot analysis.Results Compared with DMSO group,levels of serum ALT at 8 h (P ＜0.05),16 h (P ＜ 0.01) and 24 h (P ＜ 0.01) in Nec-1 group were significantly lower.Level of serum AST in Nec-1 group were lower compared with DMSO group at 8 h (P ＜ 0.01),16 h (P ＜ 0.01) and 24 h (P ＜0.01).Compared with DMSO group,levels of serum HMGB-1 at 8 h (P ＜ 0.05),16 h (P ＜0.01) and 24 h (P ＜ 0.01) in Nec-1 group were significantly lower.Under light microscopy and transmission electron microscope,hepatic lobule destroyed,the blood extravasated,the immunocyte infiltrated and cellular organelle destroyed were found.Compared with DMSO group,the level of HMGB-1 protein in cytoplasm protein in Nec-1 group were significantly decreased at 8 h (P ＜ 0.01),16 h (P ＜0.01) and 24 h (P ＜0.01).The level of HMGB-1 protein in total protein in Nec-1 group were significantly decreased 8 h (P ＜ 0.05) and 24 h (P ＜ 0.05).Conclusions Nec-1 can remarkably protect the liver of rats with hemorrhagic-traumatic shock,decrease the level of HMGB-1,and protect the hepatocyte effectively.

OBJECTIVEThis article aimed to review the incidence of Helicobacter pylori (H. pylori) infection and its therapy.

DATA SOURCESRelevant articles published in English were identified by searching in PubMed from 2000 to 2013, with keywords "H. pylori". Important references from selected articles were also retrieved from Elsevier, Wiley, EBSCO, and SPRINGER. The Chinese articles published were searched from China National Knowledge Infrastructure (CNKI).

STUDY SELECTIONArticles about "prevalence", "gastric carcinoma", "peptic ulcer", "gastroesophageal reflux disease", "functional dyspepsia", "pathogenic mechanism", "therapy", "eradication rate", "antibiotic resistance", and "gene polymorphisms" were selected.

RESULTSThe decreased infection rates of H. pylori could also be linked to the changed disease spectrum, such as the decreased morbidity and recurrence rate of H. pylori-related peptic ulcer, and the increased morbidity of gastroesophageal reflux. Although different treatment regimens have been used for H. pylori infection, the H. pylori eradication rate declined gradually. Due to primary resistance to antibiotics, the gene polymorphism of host and infected strain, and the therapy regimes, H. pylori eradication became even more difficult.

CONCLUSIONSThe prevalence of H. pylori infection had been decreasing, but the rate of eradication failure has dramatically risen in many countries due to resistance to antibiotic. H. pylori therapy in clinical practice is becoming progressively more difficult.

Drug Resistance, Bacterial ; genetics ; Helicobacter Infections ; drug therapy ; epidemiology ; Helicobacter pylori ; drug effects ; genetics ; pathogenicity ; Humans

BACKGROUNDHelicobacter pylori (Hp) is a common and potentially curable cause of gastric mucosa lesion. This study investigated the relationship of Hp infection with histological changes in gastric mucosa and gastric cancer in Hp-positive patients compared with Hp-eradication patients followed up for ten years.

METHODSFrom an initial group of 1 006 adults, 552 Hp-positive subjects were randomly assigned to a treatment group (T; n = 276) or a placebo group (P; n = 276). In the randomized, double-blind, placebo-controlled, parallel trial, T group subjects received oral doses of omeprazole, amoxicillin and clarithromycin for 1 week; those in the P group received a placebo. One month after treatment ended, a 13C urea breath test was performed, and Hp was undetectable in 88.89% of the T group. All subjects were followed at 1, 5, 8, and 10 years after treatment, with endoscopy and biopsies for histological examination.

RESULTSGastric mucosa inflammation was significantly milder in the T group than that in the P group one year after Hp eradication and this persisted for 10 years. Glandular atrophy and intestinal metaplasia (IM) had deteriorated in both groups during ten years. However, the increased score of glandular atrophy at both the gastric antrum and corpus, and IM only at the gastric antrum, in the P group was more obvious than that in the T group. During the 10 years, 9 patients were diagnosed with gastric cancer (2 in the T group; 7 in the P group; P = 0.176). When mucosal atrophy was absent at the gastric antrum and corpus when entering the study, the incidence of gastric cancer in the P group (n = 6) was much higher than that in the T group (n = 0, P = 0.013).

CONCLUSIONSHp eradication may significantly diminish and help halt progression of gastric mucosal inflammation and delay the development of IM and atrophy gastritis. Hp eradication is helpful for reducing the risk for gastric cancer, especially in the early stage of Hp infection.

Adult ; Aged ; Amoxicillin ; therapeutic use ; Anti-Bacterial Agents ; therapeutic use ; Clarithromycin ; therapeutic use ; Double-Blind Method ; Female ; Follow-Up Studies ; Gastric Mucosa ; drug effects ; pathology ; Gastritis, Atrophic ; diagnosis ; drug therapy ; Helicobacter Infections ; drug therapy ; Helicobacter pylori ; pathogenicity ; Humans ; Male ; Middle Aged ; Omeprazole ; therapeutic use ; Stomach Neoplasms ; diagnosis ; prevention & control

Objective To investigate the effects of necrostatin-1 (Nec-1) on the liver of rats with trauma induced hemorrhagic shock.Methods Trauma induced hemorrhagic shock model was produced by adopting the left femur,tibia fracture and soft tissue injury,bleeding and reperfusion in male Sprague-Dawley (SD) rats.A total of 22 rats were divided into model group and Nec-1 group with 11 rats in each group by randomized digital number method and the 72-hour mortality was observed.In addition,72 rats were randomly divided into sham group,model group,Nec-1 group with 24 rats in each group.Rats in sham group were only received anesthesia,separating and ligating blood vessels,without trauma induced hemorrhagic and reperfusion,and the rats in Nec-1 group were received 1 mg/kg Nec-1 through femoral vein 5 minutes before reperfusion,while the rats in model group were received the same amount of solvent.The serum and liver tissues of each group were collected at 2,4,8 hours after reperfusion.Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected by automatic biochemistry analyzer.The pathology changes in liver were observed by hematoxylin-eosin (HE) staining.The mRNA expressions of tumor necrosis factor-oα (TNF-α) and interleukin-1β (IL-1β) in the liver were detcrmined by reverse transcription-polymerase chain reaction (RT-PCR).The protein expressions of receptor interaction of protease 1/3 (RIP1/RIP3) were also assessed by Western Blot analysis.Results Compared with model group,Nec-1 significantly reduced the 72-hour mortality [18.18％ (2/11) vs.63.64％ (7/11),P=0.040].Two hours after trauma induced hemorrhagic shock and reperfusion,the expressions of ALT and AST in model group were significantly increased compared with those in sham group [ALT (U/L):110.21 ±22.32 vs.80.98 ± 19.94,AST (U/L):364.29 ±64.83 vs.279.76 ±70.64,both P＜0.05],and reached the peak at 8 hours [ALT (U/L):387.41 ± 47.11 vs.82.76 ± 22.44,AST (U/L):973.35 ± 77.51 vs.261.49 ±52.03,both P＜0.01].Levels of serum ALT and AST in Nec-1 group were significantly decreased compared with model group [ALT (U/L) 4 hours:144.64± 33.79 vs.213.96± 36.21,8 hours:159.48 ± 43.57 vs.387.41 ± 47.11; AST (U/L) 4 hours:398.78 ± 59.48 vs.630.61 ± 59.93,8 hours:427.38 ± 80.75 vs.973.35 ± 77.51,all P＜0.01].Under light microscopy,it was noted that the hepatic sinus expansion,liver cells degeneration,necrosis,as well as infiltration of abundant inflammatory cells were observed.But the pathology changes in hepatic tissues were significantly mitigated in Nec-1 group.Along with the time extension,the mRNA expressions of TNF-α and IL-1β and the protein expressions of RIP1 and RIP3 were markedly up-regulated.Compared with model group,difference in the mRNA expressions of TNF-α and IL-1β in hepatic tissues in Nec-1 group were statistically significant,and the most obvious difference was at 8 hours [TNF-α mRNA:1.457 ± 0.081 vs.2.317 ± 0.062,IL-1β mRNA:0.690 ± 0.087 vs.1.812 ± 0.112,both P＜0.01].But there was no statistically significant difference in RIP1 and RIP3 between Nec-1 group and model group [RIP1 protein 8 hours:0.561 ± 0.033 vs.0.587 ± 0.036,RIP3 protein 8 hours:0.976 ± 0.040 vs.1.044 ± 0.115,both P＞0.05].Conclusion Nec-1 may be remarkable protect effect on the liver of rats with trauma induced hemorrhage shock and reperfusion,and the intrinsic mechanisms need further investigation.