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Medical Oncology (Northwood, London,... Jul 2024Preclinical and clinical research showed that immune checkpoint blockade provides beneficial effects for many patients with liver cancer. This study aimed to assess the...
Preclinical and clinical research showed that immune checkpoint blockade provides beneficial effects for many patients with liver cancer. This study aimed to assess the effect of CTLA-4-specific siRNA on the proliferation, cell cycle, migration, and apoptosis of HePG2 cells. Transfection of siRNA was performed by electroporation. The viability of cells was determined through MTT assay. Flow cytometry was performed to investigate the cell cycle and apoptosis rate, and the wound-healing assay was used to determine HepG2 cells migration. The expression levels of CTLA-4, c-Myc, Ki-67, BCL-2, BAX, caspase-9 (CAS9), and MMP-2,9,13 were measured by qRT-PCR. Transfection of specific CTLA-4-siRNA significantly inhibited the expression of the CTLA-4 gene. Also, our results revealed that CTLA-4 silencing diminished the proliferation and migration as well as induced the apoptosis of HePG2 cells. CTLA-4-siRNA transfection induced the cell cycle arrest in G2 phase. Moreover, CTLA-4-siRNA transfection reduced the expression levels of c-Myc, Ki-67, BCL-2, MMP-2,9,13, and elevated the expression levels of BAX and caspase-9. Our results suggest that silencing CTLA-4 through specific siRNA may be a promising strategy for future therapeutic interventions for treating liver cancer.
Topics: Humans; Liver Neoplasms; Hep G2 Cells; Apoptosis; Carcinoma, Hepatocellular; Cell Proliferation; CTLA-4 Antigen; Cell Movement; RNA, Small Interfering; Gene Silencing
PubMed: 38955918
DOI: 10.1007/s12032-024-02361-1 -
Pediatric Surgery International Jul 2024The aim of this study was to find statistically valid criteria to preoperatively divide acute appendicitis into simple and complicated to enable surgeons to administer... (Review)
Review
INTRODUCTION
The aim of this study was to find statistically valid criteria to preoperatively divide acute appendicitis into simple and complicated to enable surgeons to administer the most appropriate antibiotic prophylaxis/therapy before surgery.
MATERIALS AND METHODS
We retrospectively reviewed a cohort of patients who underwent appendectomy from January 2022 to December 2023. Patients included were 0-14 years of age. Exclusion criteria included patients who underwent interval appendectomy or concurrent procedures at the same time of appendectomy. We divided patients into two groups: simple (group S) and complicated (group C) appendicitis according to intraoperative finding. Generalized linear model (GLM) with logit function was developed to identify the predictive variables of the type of appendicitis (S vs C) in terms of CRP value, neutrophils percentage and WBC count adjusted for age and sex of patients. Finally, principal component analysis (PCA) was carried out to identify the cutoff value of statistically significant variables found in the previous analysis.
RESULTS
One hundred and twenty patients were eligible (N female = 49, N male = 71) for the study. 74 and 46 patients were included in groups S and C, respectively. In a preliminary analysis using univariate and multivariate GLM, only CRP (p value = < 0.001) and neutrophils percentage (p value = 0.02) were predictive variables for the type of appendicitis. The GLM shows a statistical lower value of CRP (adjusted odds ratio [OR] per unit, 0.17 [95% CI, 0.08-0.39]) and neutrophil percentage (adjusted OR per unit, 0.37 [95% CI, 0.16-0.86]) in the S group compared to C adjusted to age and sex. PCA analysis revealed a P-ROC cutoff of 4.2 mg/dl and 80.1 of CRP value (AUC = 84%) and neutrophil percentage (AUC = 70%), respectively.
CONCLUSIONS
We will perform a prospective study giving preoperative prophylactic cefazolin to patients with a CRP value under 4.2 mg/dl and amoxicillin-clavulanate therapy to patient with CRP value over 4.2 mg/dl.
Topics: Humans; Appendicitis; Female; Male; Retrospective Studies; Child; Appendectomy; Adolescent; Antibiotic Prophylaxis; Child, Preschool; Anti-Bacterial Agents; Infant; Preoperative Care; Acute Disease
PubMed: 38955876
DOI: 10.1007/s00383-024-05753-6 -
Techniques in Coloproctology Jul 2024Laser hemorrhoidoplasty has demonstrated significant therapeutic effectiveness. To diminish postoperative bleeding and enhance overall outcomes, we have additionally...
BACKGROUND
Laser hemorrhoidoplasty has demonstrated significant therapeutic effectiveness. To diminish postoperative bleeding and enhance overall outcomes, we have additionally adopted suture ligating the feeding vessels. This study aimed to understand the treatment outcomes and any associated complications.
METHODS
This study comprised patients with symptomatic grade II-III hemorrhoids who underwent laser hemorrhoidoplasty with feeding vessel suture ligation and Milligan-Morgan hemorrhoidectomy between 1 September 2020, and 31 August 2022. Surgical-related details, postoperative pain, discomfort after discharge, hemorrhoid recurrence, and any complications were collected from inpatient records, outpatient follow-ups, and telephone interviews. Initially, we will analyze the distinctions between the laser group and the traditional group, followed by an investigation into complications and satisfaction within the laser surgery subgroup.
RESULTS
The study included 323 patients, with 173 undergoing laser hemorrhoidoplasty (LHP) and 150 undergoing Milligan-Morgan hemorrhoidectomy. Regarding pain assessment, the LHP group exhibited superior performance compared to traditional surgery at postoperative 4 h, before discharge, and during the first and second outpatient visits, with statistically significant differences. Additionally, the LHP group had a lower rate of urinary retention and experienced significantly less pain, with statistically significant differences.
CONCLUSIONS
Laser hemorrhoidoplasty with feeding vessels suture ligation has been shown to reduce postoperative pain and appears to be a promising minimally invasive treatment option for symptomatic grade II and III hemorrhoids.
Topics: Humans; Hemorrhoids; Ligation; Female; Retrospective Studies; Male; Hemorrhoidectomy; Middle Aged; Treatment Outcome; Adult; Pain, Postoperative; Laser Therapy; Suture Techniques; Aged; Recurrence; Postoperative Complications; Patient Satisfaction; Sutures
PubMed: 38955875
DOI: 10.1007/s10151-024-02940-4 -
Journal of Cancer Research and Clinical... Jul 2024To explore the effect and mechanism of relaxin (RLX) in the growth and metastasis of livercancer after combination treatment with transarterial chemoembolization (TACE).
OBJECTIVE
To explore the effect and mechanism of relaxin (RLX) in the growth and metastasis of livercancer after combination treatment with transarterial chemoembolization (TACE).
MATERIALS AND METHODS
HCCLM3 and Huh-7 cells were adopted to evaluate the effect of tumor proliferation, migration, and invasion after RLX administration in vitro. The rabbit VX2 model was used to evaluate the biosafety, doxorubicin penetration, local tumor response, tumor metastasis, and survival benefit of RLX combined with TACE treatment.
RESULTS
RLX did not affect the proliferation, migration, or invasion of HCCLM3 and Huh-7 cells, and the expression of E-cadherin and HIF-1α also remained unchanged while the MMP-9 protein was upregulated in vitro. In the rabbit VX2 model, compared to the normal saline group (NS), RLX group (RLX) and TACE mono-therapy group (TACE), the group that received TACE combined with RLX (TACE + RLX) showed an improved local tumor response and survival benefit. Furthermore, TACE combined with RLX was found to reduce tumor metastasis. This combination therapy reduced the fibrotic extracellular matrix in the tumor microenvironment, allowing for better penetration of doxorubicin, improved infiltration of CD8+ T cells and affected the secretion of cytokines. Additionally, RLX combined with TACE was able to decrease the expression of HIF-1α and PD-L1. The biosafety of TACE combined with RLX was also confirmed.
CONCLUSION
RLX synergized with TACE by mitigating the fibrotic extracellular matrix and tumor hypoxic microenvironment, improving the therapeutic effect and inhibiting metastasis during the treatment of liver cancer.
Topics: Animals; Chemoembolization, Therapeutic; Rabbits; Relaxin; Liver Neoplasms; Doxorubicin; Humans; Combined Modality Therapy; Cell Proliferation; Cell Line, Tumor; Disease Models, Animal; Carcinoma, Hepatocellular; Neoplasm Metastasis
PubMed: 38955827
DOI: 10.1007/s00432-024-05864-6 -
Zhonghua Er Ke Za Zhi = Chinese Journal... Jul 2024To summarize the clinical manifestations, diagnosis, treatment and prognosis of acute flaccid myelitis (AFM) in children. Clinical characteristics of 4 AFM cases from...
To summarize the clinical manifestations, diagnosis, treatment and prognosis of acute flaccid myelitis (AFM) in children. Clinical characteristics of 4 AFM cases from Department of Neurology, Children's Hospital Affiliated to Capital Institute of Pediatrics, from September 2018 to November 2022, were analyzed retrospectively. The age of 4 children with AFM was 7 years, 4 years and 3 months, 7 years and 1 month, 6 years and 5 months, respectively. There were 2 boys and 2 girls. Prodromal infection status showed 3 children of respiratory tract infection and 1 child of digestive tract infection. The main manifestation was asymmetrical limb weakness after infection, and the affected limb range was from monoplegia to quadriplegia. Cranial nerve injury was involved in 1 child, no encephalopathy. Magnetic resonance imaging in the spinal cord of all 4 children showed long T1 and T2 signals, mainly involving gray matter. Cerebrospinal fluid cell-protein separation was observed in 2 children. Pathogen detected in 1 child pharyngeal swab was enterovirus D68. Antibody IgM to adenovirus was positive in the blood of 1 child. Antibody IgG against Echo and Coxsackie B virus were positive in the blood of another child. After glucocorticoid, human immunoglobulin or simple symptomatic treatment and at the same time under later rehabilitation training, muscle strength recovered to different degrees, but there were disabilities left in 3 children. AFM should be considered in children with acute and asymmetrical flaccid paralysis accompanied by abnormal magnetic resonance imaging signal in the central region of spinal cord, especially post-infection. The effective treatment is limited and the prognosis is poor.
Topics: Humans; Myelitis; Male; Female; Child; Child, Preschool; Retrospective Studies; Magnetic Resonance Imaging; Central Nervous System Viral Diseases; Neuromuscular Diseases; Enterovirus D, Human; Prognosis; Spinal Cord; Enterovirus Infections; Quadriplegia; Respiratory Tract Infections
PubMed: 38955687
DOI: 10.3760/cma.j.cn112140-20240320-00191 -
Zhonghua Er Ke Za Zhi = Chinese Journal... Jul 2024To investigate the pathogenic mechanism and clinical characteristics of the novel splicing variant of ATP-binding cassette subfamily B member 4 (ABCB4) and provide a...
To investigate the pathogenic mechanism and clinical characteristics of the novel splicing variant of ATP-binding cassette subfamily B member 4 (ABCB4) and provide a basis for subsequent genetic diagnosis. The clinical data of a 5-year-old child with cholestatic liver disease admitted to the Beijing Children's Hospital of Capital Medical University was retrospectively analyzed. The pathogenic variations were detected by whole exome sequencing and verified by Sanger sequencing, and bioinformatics was used to predict the pathogenicity of the mutation sites. Possible pathogenic variations were verified in vitro by Minigene assay. The clinical outcome was followed after discharge from hospital. The 5-year-old boy had developed cholestasis at the age of 11 months. His physical examination showed obvious enlargement of the liver and spleen. Cholestatic cirrhosis was diagnosed by liver function tests, abdominal ultrasonography, liver biopsy and pathology. The results of genetic analysis showed that the patient was a complex heterozygote of the ABCB4 gene, with a pathogenic mutation c.2860G>A and a novel mutation c.2065-8T>G, derived from the mother and father respectively. The conservative prediction of the c.2065-8T>G site showed that this region was highly conserved and may affect splicing. Minigene assay results confirmed that the c.2065-8T>G mutation resulted in a 7 bp retention of intron 16 in the mature mRNA. In the absence of nonsense-mediated mRNA decay, the amino acid frameshift forms a truncated protein, which is represented by p.Glu689ValfsTer19. The patient was diagnosed as progressive familial intrahepatic cholestasis type 3 (PFIC3) and treated with ursodeoxycholic acid (UDCA). His clinical symptoms improved during 18 months of follow-up. The c.2065-8T>G variant is confirmed to affect the splicing process and exhibits complex heterozygosity with c.2860G>A, which is identified as the cause of the disease. PFIC3 children with this variant showed cholestatic liver disease as the main manifestation with a slow progression and was sensitive to treatment with UDCA.
Topics: Humans; Male; Cholestasis, Intrahepatic; Child, Preschool; ATP Binding Cassette Transporter, Subfamily B; Mutation; Phenotype; Exome Sequencing; Genotype; Heterozygote; Retrospective Studies; Ursodeoxycholic Acid; Liver
PubMed: 38955683
DOI: 10.3760/cma.j.cn112140-20240319-00190 -
Zhonghua Er Ke Za Zhi = Chinese Journal... Jul 2024To investigate the association between intestinal colonization of segmented filamentous bacteria (SFB) and the risk of rotavirus infection, and the possible mechanisms...
To investigate the association between intestinal colonization of segmented filamentous bacteria (SFB) and the risk of rotavirus infection, and the possible mechanisms by which SFB resist rotavirus infection. This case-control study enrolled 50 children aged 0 to 5 years who present to the outpatient Department of Children's Hospital, Zhejiang University School of Medicine with diarrhea and positive stool tests for rotavirus. The children were divided into rotavirus enteritis group and control group consisting of 55 children with non-gastrointestinal and non-infectious surgical diseases.The age and sex composition of the two groups was matched. The DNA of the fecal flora was extracted and SFB was detected by real-time fluorescence quantitative PCR analysis. The children in the rotavirus enteritis group and the control group were subgrouped by age and sex to analyze the differences in SFB positivity rates between different groups, and further compare and analyze the differences in SFB positivity rates between these two groups of children in the ≤2 years old subgroup and the >2-5 years old subgroup. Neutralization test was performed with p3340 protein and rotavirus to determine the relationship between rotavirus infection rate and p3340 concentration in Vero cells. test or Fisher's exact probability method was used for comparison between the two groups. There were 50 children in the rotavirus enteritis group with an age of (1.7±0.9) years, and 55 children in the control group with an age of (1.8±1.1) years. The positive rate of SFB in children with rotavirus enteritis showed a declining trend across ages groups, with the highest rate of 10/14 in the ≤1 year old group, followed by 67% (14/21) in the >1-2 years old group, 9/15 in the >2-5 years old group, and there was no statistically significant difference (=0.867). The positive rate of SFB in the control group was 12/15 in the ≤1 year old group, 95% (19/20) in the >1-2 years old group, 50% (10/20) in the >2-5 years old group, with statistical significance (=0.004). The positive rate of SFB in children with rotavirus enteritis was 74% (20/27) in males and 56% (13/23) in females (=1.71, =0.192). In the control group, it was 79% (22/28) in males and 70% (19/27) in females (=0.49, =0.485). The positive rate of SFB was 66% (33/50) in the rotavirus enteritis group and 75% (41/55) in the control group, with no statistically significant (=0.56, =0.454). In the children ≤2 years old, the SFB positivity rate was 69% (24/35) in the rotavirus enteritis group and 89% (31/35) in the control group, with a statistically significant difference (=4.16, =0.041). However, in the children >2-5 years old, no statistically significant difference was observed, with the positive rate of SFB being 9/15 in the rotavirus enteritis group and 50% (10/20) in the control group (=0.734). Pearson correlation analysis revealed a negative correlation between rotavirus infection and SFB positivity (=-0.87,<0.001). As the concentration of the p3340 specific protein increased, the luminescence intensity of the luciferase in the Vero cells, which were suitable for cultivating rotavirus, exhibited a decreasing trend (=4.17, =0.001). SFB colonization in infants less than 2 years old is associated with a reduced risk of rotavirus infection. Cloning of specific SFB functional protein p3340 neutralizes rotavirus infection of Vero cells, and this mechanism of targeting rotavirus infection differs from the common antiviral mechanism.
Topics: Humans; Rotavirus Infections; Infant; Male; Female; Case-Control Studies; Child, Preschool; Rotavirus; Feces; Diarrhea; Enteritis; Infant, Newborn; Intestines; Animals
PubMed: 38955682
DOI: 10.3760/cma.j.cn112140-20240321-00202 -
Zhonghua Er Ke Za Zhi = Chinese Journal... Jul 2024To investigate the effects of modified endoscopic retrograde appendicitis therapy (mERAT) on the treatment of children with different severities of acute appendicitis....
To investigate the effects of modified endoscopic retrograde appendicitis therapy (mERAT) on the treatment of children with different severities of acute appendicitis. This study was a case-control study. A total of 586 children with acute appendicitis, who were admitted to the Pediatric Department of Second Affiliated Hospital of Air Force Medical University between January 2019 and November 2023, were selected as the research subjects. According to the severity of the disease, the patients were divided into simple appendicitis group, suppurative appendicitis group and perforated appendicitis group. The baseline data, hospitalization treatment and costs, outcomes, and recurrence in each group were analyzed, and the difference in the effectiveness of mERAT between the groups were compared by Kruskal-Wallis test and test. Among 586 children, there were 338 males and 248 females. The age at onset was 7.0 (4.6, 9.4) years. There were 475 cases of simple appendicitis, 78 cases of suppurative appendicitis, and 33 cases of perforated appendicitis. There were no significant differences in age and gender among the three groups (=0.59, =3.31, both >0.05). However, there were statistically significant differences in body temperature, white blood cell counts, neutrophil percentage, lymphocyte percentage, nausea or vomiting, right lower abdominal pain, umbilical pain, right lower abdominal tenderness, and right lower abdominal rebound pain (=7.56, 161.52, 169.11, and 169.61, =12.05, 13.82, 12.05, 7.74, 20.35, and 94.61, all <0.05). Also, the treatment time, postoperative hospital stay, total hospital stay, and cost showed statistically significant differences (4.70, 33.66, 34.99, 30.37, all <0.05). There was no significant difference in the initial treatment success rate (98.1% (466/475) 98.7% (77/78) 90.9% (30/33), =0.057). During the 30 (23, 36) months of follow-up, the recurrence rate was 7.9% (35/433) in the simple appendicitis group, 20.8% (15/72) in the suppurative appendicitis group, and 30.0% (9/30) in the perforated appendicitis group, with a statistically significant difference (=23.56, 0.001). Among the children with recurrent appendicitis, 15 cases still chose mERAT, of them 11 cases (31.2%) had simple appendicitis, 2 cases (2/15) had suppurative appendicitis, and 2 cases (2/9) had perforated appendicitis.The latest time to recurrence in the 3 groups was 32, 35 and 10 months, respectively. Treatment with mERAT has a good effect in pediatric simple appendicitis, but has a higher recurrence rate despite a better initial treatment success rate in suppurative appendicitis and perforated appendicitis.
Topics: Humans; Appendicitis; Male; Female; Child; Case-Control Studies; Treatment Outcome; Child, Preschool; Appendectomy; Acute Disease; Endoscopy; Severity of Illness Index; Recurrence; Hospitalization; Length of Stay
PubMed: 38955681
DOI: 10.3760/cma.j.cn112140-20240408-00249 -
Zhonghua Er Ke Za Zhi = Chinese Journal... Jul 2024
Topics: Humans; Child; Eosinophilia; Eosinophilic Esophagitis; Enteritis; Practice Guidelines as Topic; Consensus; Gastritis; Gastrointestinal Diseases
PubMed: 38955679
DOI: 10.3760/cma.j.cn112140-20240322-00204 -
Zhonghua Er Ke Za Zhi = Chinese Journal... Jul 2024
Topics: Humans; Gastrointestinal Hemorrhage; Child; China
PubMed: 38955677
DOI: 10.3760/cma.j.cn112140-20240321-00198