[Clinical features and genetic analysis of a child with Central core disease due to compound heterozygous variants of RYR1 gene].

OBJECTIVE: To explore the clinical features and genetic etiology of a child with Central core disease (CCD). METHODS: A child with CCD who was treated at the Children's Hematology Department of the First Affiliated Hospital of Zhengzhou University in February 2022 was selected as the study subject. Muscle biopsy was performed. Peripheral blood samples were collected from the child and his parents for the extraction of genomic DNA. The child was subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing. RESULTS: The child, a 12-year-old boy, had manifested motor retardation, facial weakness, ptosis, pectus carinatum, scoliosis, etc. Muscle biopsy showed that the central nucleus muscle fibers and atrophic muscle fibers were mainly type I. WES revealed that the child has harbored c.10561G>A (p.G3521S) and c.3448T>C (p.C1150R) compound heterozygous variants of the RYR1 gene. Sanger sequencing confirmed that they were inherited from his mother and father, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were considered as likely pathogenic (PS4+PM1+PM2_Supporting+PP3；PM1+PM2_Supporting+PM3+PP3). CONCLUSION: By combining his clinical manifestation and results of muscle pathology and genetic testing, the child was diagnosed with CCD, which may be attributed to the c.10561G>A (p.G3521S) and c.3448T>C (p.C1150R) compound heterozygous variants of the RYR1 gene.

Foamy macrophages potentially inhibit tuberculous wound healing by inhibiting the TLRs/NF-κB signalling pathway.

To characterise the distribution, classification, and quantity of foamy macrophages (FMs) in tuberculous wound tissue and the relationship between FM and delayed healing of tuberculous wounds. Morphological studies were performed to explore the distribution of FM and Mycobacterium tuberculosis (Mtb) in tuberculous wounds, with acute and chronic wounds included for comparison. Phorbol-12-myristate-13-acetate stimulation-differentiated THP-1 cells were treated with Mtb to induce their differentiation into FM with oxidised low-density lipoprotein treatment serving as a control. Relative cytokine levels were determined by quantitative PCR and Western blotting. Varied co-culture combinations of Mtb, THP-1, FM, and fibroblasts were performed, and proliferation, migration, ability to contract collagen gel, and protein levels of the chemokines in the supernatants of the fibroblasts were assessed. The differentially expressed genes in human skin fibroblasts (HSFs) after co-culture with or without FM were identified using microarray. Many FM were found in the tissues of tuberculous wounds. The FM that did not engulf Mtb (NM-FM) were mainly distributed in tissues surrounding tuberculous wounds, whereas the FM that engulfed Mtb (M-FM) were dominantly located within granulomatous tissues. Co-culture experiments showed that, with the Mtb co-culture, the portions of NM-FM in the total FM grew over time. The migration, proliferation, chemokine secretion, and the ability of fibroblasts to contract collagen gel were inhibited when co-cultured with Mtb, FM, or a combination of the two. Further investigation showed that the TLRs/NF-κB signalling pathway is involved in fibroblast function under the stimulation of FM. TLRs and NF-κB agonists could reverse the phenotypic changes in HSFs after co-culture with FM. The tuberculous wound microenvironment composed of Mtb and FM may affect wound healing by inhibiting the functions of fibroblasts. FM potentially inhibit fibroblasts' function by inhibiting the TLRs/NF-κB signalling pathway in tuberculous wounds.

Allogeneic blood transfusion in 163 children with acute lymphocytic leukemia (a STROBE-compliant article).

Little research has been done about the effects of allogeneic blood transfusion (ABT) on the recurrence and prognosis in the cases with childhood acute lymphocytic leukemia (cALL). In order to provide a basis for clinical safe blood transfusion, the data of 163 cases with cALL were retrospectively analyzed to explore the issue.The data of 163 cases with cALL between 2006 and 2011 were retrospectively analyzed. According to the frequency of blood transfusion, the 163 cases were divided into 4 groups including non-transfusion group, 1 to 10-time transfusion group, 11 to 25-time transfusion group, and >25-time transfusion group. Survival rates were compared with Log-Rank test. Cox regression analysis was used in the effects of risk factors on recurrence and death.ABT was performed in 152 cases with cALL (93.25%). In low-risk and intermediate-and-high risk cALL, the survival rate significantly decreased in all transfusion groups compared with that in non-transfusion group (all P < .01). Cox regression analysis showed that >25-time transfusion was an independent prognosis index of recurrence (odds ratio [OR] = 3.015, 95% confidence interval [CI]: 1.368-6.646) and death (OR = 3.979, 95% CI: 1.930-8.207) in cALL.Frequency of ABT appears to affect the recurrence and death in cALL. We should be careful with blood transfusion and avoid unnecessary blood transfusion as far as possible in the cases with cALL.

Impact of different sarcopenia stages on the postoperative outcomes after radical gastrectomy for gastric cancer.

BACKGROUND: The association between sarcopenia and postoperative outcomes has been well reported. However, the impact of different sarcopenia stages on postoperative outcomes has never been investigated. METHODS: We conducted a large, prospective study of patients who underwent radical gastrectomy for gastric cancer from August 2014 to December 2015. Sarcopenia was staged as "presarcopenia," "sarcopenia," and "severe sarcopenia" according to the definition of the European Working Group on Sarcopenia in Older People. Univariate and multivariate analyses evaluating the risk factors for total, surgical, and medical complications were performed. RESULTS: A total of 470 patients were included, in which 20.6%, 10%, and 6.8% of the patients were identified as having "presarcopenia," "sarcopenia," and "severe sarcopenia," respectively. Postoperative complications, duration of hospital stays, and costs increased with advancing sarcopenia stages. Severe sarcopenia, visceral fat area to total abdominal muscle area ratio, American Society of Anesthesiologists grade III, and tumor located at the cardia were independent risk factors for total complications. Visceral fat area to total abdominal muscle area ratio and tumor located at the cardia were independent risk factors for operative complications. Presarcopenia, sarcopenia, and severe sarcopenia were all identified as independent risk factors for medical complications, as well as age ≥75 years and Charlson Comorbidity Index. CONCLUSION: Patients had worse postoperative outcomes after gastric cancer operation with advancing sarcopenia stages. Severe sarcopenia, but not presarcopenia or sarcopenia, was an independent risk factor for total postoperative complications. The 3 sarcopenia stages independently influence medical but not surgical complications. Recognizing sarcopenia stages is important for preoperative risk stratification.