OBJECTIVETo identify the mutations of iduronate-2-sulfatase (IDS) gene, to reveal its mutation features, and to establish a basis for genetic counseling and prenatal gene diagnosis of Hunter syndrome.

METHODSUrine glycosaminoglycans (GAGs) assay, PCR and DNA sequencing were performed to detect mutation of IDS gene of the patient and his parents.

RESULTSThe result showed that the patient was: DS(++), HS(++), KS(-), CS(-), and that both of his parents were negative. A frame-shift deletion mutation (1062 del 16) was identified in exon 7 of the patient's IDS gene. His parents' genotypes were normal.

CONCLUSIONThe patient's mutation was not inherited by his parents but a novel one. The mutation probably altered the primary structure and tertiary structure of IDS enzyme protein remarkably and lowered the activity of IDS enzyme greatly. Therefore it is supposed to be the direct cause of the disorder.

Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child, Preschool ; Female ; Glycoproteins ; genetics ; urine ; Humans ; Male ; Mucopolysaccharidosis II ; enzymology ; genetics ; urine ; Mutation ; genetics

McCune-Albright syndrome is a rare G proteins alpha disorder. The disorder is characterized by polyostotic fibrous dysplasia, sexual precocity and hyperpigmented macules. It is caused due to mutations in the gene Gsalpha that incodes the alpha subunit of the trimeric guanosine triphate-binding protein. There is no specific treatment for this syndrome. Treatment is generally symptomatic. This paper reported three cases of McCune-Albright syndrome and reviewed the relevant literatures regarding to the pathogenesis, pathological features, diagnosis and treatment. All three cases presented with a characteristic triad: polyostotic fibrous dysplasia, sexual precocity and hyperpigmented macules and were thus definitely diagnosed with McCune-Albright syndrome.
Child ; Child, Preschool ; Diagnosis, Differential ; Female ; Fibrous Dysplasia, Polyostotic ; diagnosis ; etiology ; pathology ; therapy ; Humans ; Prognosis

Extrachromosomal DNA (ecDNA) is a class of circular DNA that is found off the chromosomes, either inside or outside the nucleus. ecDNA is abundant in cancer, and plays an important role during the tumor development. ecDNA contains multiple complete genes and regulatory elements that regulate transcription, including promoters and enhancers. It can replicate independently. However, the origin and mechanism of ecDNA is still unknown. Most scholars believe that DNA damage can elicit ecDNA production. The chromosomal fragments produced by DNA double-strand breaks are rearranged and circularized to form ecDNA via the non-homologous end-joining repair way. The chromatin on ecDNA is highly accessible and active. It works with oncogenes and co-amplify with enhancers to promote the transcription of oncogenes. Additionally, there are ultra-long-range chromatin contacts on ecDNA, which increases distant interaction. These features amplify the transcription of oncogenes and promote the development of tumors. Due to lack of centromeres, ecDNA has a non-equal segregation to daughter cells. Daughter cells, containing different copy numbers of ecDNA, can rapidly increase oncogene copy numbers, which drives the genome heterogeneity of the tumors. ecDNA-driven copy number regulation leads drug resistance and enables tumors to adapt quickly to the environment. Here we review the classification, origin of ecDNA and its role in tumorigenesis and development. We discuss the mechanisms of ecDNA promoting the transcription of oncogenes and leading to heterogeneity and drug resistance, aiming to provide new ideas on the diagnosis, treatment, and prognosis of tumors.

OBJECTIVE: To investigate the synergistic interaction between the deltoid muscle and the rotator cuff muscle group in patients with rotator cuff tears (RCT), as well as the impact of the critical shoulder angle (CSA) on deltoid muscle strength. METHODS: A retrospective analysis was conducted on clinical data from 42 RCT patients who met the selection criteria and were treated between March 2022 and March 2023. There were 13 males and 29 females, with an age range of 42-77 years (mean, 60.5 years). Preoperative visual analogue scale (VAS) score was 6.0±1.6. CSA measurements were obtained from standard anteroposterior X-ray films before operation, and patients were divided into two groups based on CSA measurements: CSA>35° group (group A) and CSA≤35° group (group B). Handheld dynamometry was used to measure the muscle strength of various muscle group in the shoulder (including the supraspinatus, infraspinatus, subscapularis, and anterior, middle, and posterior bundles of the deltoid). The muscle strength of the unaffected side was compared to the affected side, and muscle imbalance indices were calculated. Muscle imbalance indices between male and female patients, dominant and non-dominant sides, and groups A and B were compared. Pearson correlation analysis was used to examine the relationship between muscle imbalance indices and CSA as well as VAS scores. RESULTS: Muscle strength in all muscle groups on the affected side was significantly lower than on the unaffected side ( P<0.05). The muscle imbalance indices for the supraspinatus, subscapularis, infraspinatus, and anterior, middle, and posterior bundles of the deltoid were 14.8%±24.4%, 5.9%±9.7%, 7.2% (0, 9.1%), 17.2% (5.9%, 26.9%), 8.3%±21.3%, and 10.2% (2.8%, 15.4%), respectively. The muscle imbalance indices of the anterior bundle of the deltoid, supraspinatus, and infraspinatus were significantly lower in male patients compared to female patients ( P<0.05); however, there was no significant difference in muscle imbalance indices among other muscle groups between male and female patients or between the dominant and non-dominant sides ( P>0.05). There was a positive correlation between the muscle imbalance indices of infraspinatus and VAS score ( P<0.05), and a positive correlation between CSA and the muscle imbalance indices of middle bundle of deltoid ( P<0.05). There was no correlation between the muscle imbalance indices of other muscle groups and VAS score or CSA ( P>0.05). Preoperative CSA ranged from 17.6° to 39.4°, with a mean of 31.1°. There were 9 cases in group A and 33 cases in group B. The muscle imbalance indices of the anterior bundle of the deltoid was significantly lower in group A compared to group B ( P<0.05), while there was no significant difference in muscle imbalance indices among other muscle groups between group A and group B ( P>0.05). CONCLUSION Patients with RCT have a phenomenon of deltoid muscle strength reduction, which is more pronounced in the population with a larger CSA.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Shoulder ; Rotator Cuff Injuries/surgery* ; Shoulder Joint/diagnostic imaging* ; Rotator Cuff/surgery* ; Muscle Strength ; Deltoid Muscle

【Objective】 To investigate whether mesenchymal stem cells （MSC）can alleviate acute lung injury by inducing alveolar macrophages to polarize to M2 phenotype. 【Methods】 Umbilical cord MSC was extracted by adherent method and cell phenotypes were analyzed by flow cytometry. The differentiation along osteogenic and adipogenic pathways were assessed by histological staining in vitro. Mouse alveolar macrophage cell line（MH- S cells）which was stimulated by LPS was isolated co-culture with MSC and MSC soluble factor inhibitor was added. We set up three groups （LPS， LPS+MSC ，and MSC inhibitor）. After being cultured for 48 hours ，the macrophage polarization was analyzed by flow cytometry and qPCR. Thirty balb/c male mice were randomly divided into control group（n = 10），ALI group（n = 10）， and ALI+MSC group（n = 10）. LPS was instilled intranasally to establish acute lung injury model in mice. After treatment with MSC for 48 hours ，HE staining of lung tissue was performed for damage assessment. The alveolar lavage fluid （BALF）was obtained and the cells in BALF were analyzed by flow cytometry and qPCR to detect the expression of M2-type macrophage markers including CD206，IL10 and Arg1. The concentration of M1-type macrophage marker TNF-α in the supernatant was measured by ELISA. 【Results】 MSC showed adherent growth and had the ability of osteogenic and adipogenic differentiation. MSC can induce MH- S cells to polarize to M2 type and with a significant increase of CD206 positive proportion cells （P<0.05）. Prostaglandin E2 （PGE2） inhibitors can reverse this effect. Mouse ALI model was successful. After treatment with MSC，the pathology and lung injury score was significantly improved. The proportion of CD206 positive macrophages in alveolar lavage fluid in ALI + MSC group was significantly higher than that in ALI group. The expression of CD206 and IL-10 in mRNA level was significantly higher in ALI+MSC group than that in ALI group. The concentration of inflammatory cytokine TNF- α in alveolar lavage fluid was significantly lower in the ALI+ MSC group than in the ALI group（P<0.05）.【Conclusion】Umbilical cord mesenchymal stem cells can effectively alleviate acute lung injury induced by LPS in mice via PEG2 to induce macrophage to polarize to M2 type.

ObjectiveTo analyze the risk factors of hemorrhage during cesarean section in multiparous women with advanced delivery age， and provide a theoretical basis for the prevention and treatment of hemorrhage during cesarean section. MethodsWe retrospectively analyzed the clinical data of 1 838 women with advanced maternal age undergoing cesarean section in the First Affiliated Hospital of Sun Yat-sen University from January 2015 to December 2019. According to whether the intraoperative blood loss of the parturient is ≥ 500 mL， they were divided into hemorrhage group and non-hemorrhage group. The correlations of various factors such as basic maternal data， intraoperative factors， placental factors and intraoperative hemorrhage， and obtain the results by multi-factor binary logistic regression analysis independent risk factors were analyzed. ResultsLogistic regression analysis showed that operation time ［OR=1.069， 95% CI： （1.050， 1.089）， P<0.001］， placenta delivery method ［OR=3.131， 95%CI： （1.259， 7.782）， P=0.014］， fetal distress ［OR=4.727， 95% CI： （1.191， 18.763）， P=0.027］， surgical grade ［OR=21.494， 95%CI： （6.031， 76.611）， P<0.001］， anesthesia method ［OR=2.904， 95%CI： （1.158， 7.281）， P=0.023］ and weak uterine contractions ［OR=7.255， 95%CI： （4.413， 11.927）， P<0.001］ were independent risk factors for intraoperative hemorrhage. ConclusionsOperation time， fetal distress， operation level， anesthesia， uterine weakness， and placental delivery are the main influencing factors for bleeding during cesarean section in elderly women who have undergone cesarean section. Clinical measures should be taken to reduce the risk of hemorrhage during cesarean section.

OBJECTIVETo summarize the management of anastomotic leak following surgery for esophageal carcinoma.

METHODSThe medical records of the patients developing digestive tract leak after surgery for esophageal carcinoma in our hospital from January 2003 to March 2011 were retrospectively analyzed.

RESULTSA total of 36 patients were included, in whom 13 developed cervical anastomotic leak, 18 had intra-thoracic anastomotic leak, and 5 had intra-thoracic gastric necrosis. Of these patients, 7 were treated with resurgery, 6 with esophageal stent implantation, and 23 with conservative treatment. Treatment lasted for 5 to 181 days, averagely 47.0 +/- 31.9 days. After management, 9 patients died (25.0%). Among seven patients with resurgery, four had deceased, two were cured, and one developed leak again and was switched to conservative treatment until discharged. All the 6 patients treated with stent implantation were cured. Of the 24 patients receiving conservative treatment (including one switched from resurgery), 18 (75.0%) were cured and 1 was not cured but survived.

CONCLUSIONSAnastomotic leak following surgery for esophageal carcinoma should be treated individually based on the onset time, location, size, and extent of the leakage. Conservative treatment is still a safe and effective method. The efficacy of stent implantation needs further investigation to confirm.

Adult ; Aged ; Anastomotic Leak ; therapy ; Esophageal Neoplasms ; surgery ; Humans ; Male ; Middle Aged ; Precision Medicine ; Treatment Outcome

ObjectiveTo investigate the value of contrast enhanced 3D STIR SPACE sequence and compare it with contrast enhanced 3D VIBE sequence in displaying the sacral nerve plexus abnormalities in pelvic endometriosis. MethodsAll the 30 patients with endometriosis and 20 healthy women received pelvic MRI examinations by contrast enhanced 3D STIR SPACE sequence and contrast enhanced 3D VIBE sequence. Then we evaluated and analyzed the image quality and diagnostic confidence of the two sequences in identifying the sacral nerve plexus abnormalities. ResultsSacral plexus nerve fibers were clearly revealed in both healthy controls and patients with endometriosis on 3D STIR SPACE sequence and 3D VIBE sequence. The consistency of diagnosis confidence by two readers using 3D-STIR-SPACE sequence was strong （Kappa=0.684，P<0.001）， using 3D-VIBE sequence was moderate（Kappa=0.130，P =0.386）. ConclusionsBoth 3D STIR SPACE sequence and 3D VIBE sequence can clearly display sacral plexus nerve fibers. 3D STIR SPACE sequence has more advantages in showing sacral plexus abnormalities in pelvic endometriosis.

Objective: To investigate the long-term outcomes and risk factors in children with steroid-sensitive nephrotic syndrome (SSNS). Methods: A retrospective cohort study was conducted on newly onset SSNS admitted to the Department of Pediatrics of the First Affiliated Hospital of Sun Yat-sen University from January 2006 to December 2010 and 105 cases with follow-up for more than 10 years were included. Clinical data including general characteristics, clinical manifestation, laboratory tests, treatment and prognosis. The primary outcome was the clinical cure, and the secondary outcomes were relapse or ongoing immunosuppressive treatment within the last 1 year of follow-up and complications at the last follow-up. According to the primary outcome, the patients were divided into clinical cured group and uncured group. Categorical variables were compared between 2 groups using the χ² or Fisher exact test, and continuous variables by t or Mann-Whitney U test. Multiple Logistic regression models were used for multivariate analysis. Results: Of the 105 children with SSNS, the age of onset was 3.0 (2.1, 5.0) years, and 82 (78.1%) were boys, 23(21.9%) were girls. The follow-up time was (13.1±1.4) years; 38 patients (36.2%) had frequently relapsing or steroid-dependent nephrotic syndrome (FRNS or SDNS) and no death or progression to end-stage kidney disease. Eighty-eight patients (83.8%) were clinically cured. Seventeen patients (16.2%) did not reach the clinical cure criteria, and 14 patients (13.3%) had relapsed or ongoing immunosuppressive treatment within the last year of follow-up. The proportion of FRNS or SDNS (12/17 vs. 29.5% (26/88), χ²=10.39), the proportion of treatment with second-line immunosuppressive therapy (13/17 vs. 18.2% (16/88), χ²=21.39), and the level of apolipoprotein A1 at onset ((2.0±0.5) vs. (1.7±0.6) g/L, t=2.02) in the uncured group were higher than those in the clinical cured group (all P<0.05). Multivariate Logistic regression analysis showed that patients treated with immunosuppressive therapy had an increased risk of not reaching clinical cure in the long term (OR=14.63, 95%CI 4.21-50.78, P<0.001). Of the 55 clinically cured patients who had relapsed, 48 patients (87.3%) did not relapse after 12 years of age. The age at last follow-up was 16.4 (14.6, 18.9) years, and 34 patients (32.4%) were ≥18 years of age. Among the 34 patients who had reached adulthood, 5 patients (14.7%) still relapsed or ongoing immunosuppressive treatment within the last year of follow-up. At the last follow-up, among the 105 patients, 13 still had long-term complications, and 8 patients were FRNS or SDNS. The proportion of FRNS or SDNS patients with short stature, obesity, cataracts, and osteoporotic bone fracture was 10.5% (4/38), 7.9% (3/38), 5.3% (2/38), and 2.6% (1/38), respectively. Conclusions: The majority of SSNS children were clinically cured, indicating a favorable long-term prognosis. History of treatment with second-line immunosuppressive therapy was the independent risk factor for patients not reaching the clinical cure criteria in the long term. While it is not uncommon for children with SSNS to persist into adulthood. The prevention and control of long-term complications of FRNS or SDNS patients should be strengthened.
Male ; Female ; Humans ; Child ; Nephrotic Syndrome/drug therapy* ; Retrospective Studies ; Hospitalization ; Hospitals ; Immunosuppressive Agents/therapeutic use*

OBJECTIVEThe pathophysiology of beta-thalassemia is the imbalance of the alpha and non-alpha globin chain which leads to a series of clinical symptoms of hemolytic anemia. Scientists continuously try to explore gene-activated drugs to increase the level of non-alpha globin chain or decrease the level of alpha globin chain in the treatment of beta-thalassemia. To probe into the effects on globin-gene expression of meisoindigo (Me) in cultured erythroid cells derived from peripheral blood, so as to provide the theoretical basis for applying Me in the treatment of beta-thalassemia.

METHODSBy using the two-step liquid culture of erythroid progenitor cells and reverse transcription polymerase chain reaction (RT-PCR), and by using alpha mRNA as an inner control, the level of gamma mRNA and beta mRNA in cultured erythroid cells derived from peripheral blood of 11 patients with severe beta-thalassemia and 6 normal volunteers were measured under the effect of different concentration (2.5 micro mol/L, 5 micro mol/L and 10 micro mol/L) of Me.

RESULTS(1) No statistic significance was found in the ratio of beta/alpha mRNA by Me in cultured cells from both normal individuals and beta-thalassemia. (2) Me can significantly increase the ratio of gamma/alpha mRNA and (beta + gamma)/alpha mRNA (that is non-alpha/alpha mRNA) in cultured cells from normal individuals and beta-thalassemia. The ratio of gamma/alpha mRNA was increased 0.31 - 0.45 times and the ratio of non-alpha mRNA/alpha mRNA increased 0.21 - 0.32 times in Me induced cells from normal individuals. No significant result was observed among the different concentrations of Me (2.5 micro mol/L, 5 micro mol/L and 10 micro mol/L) in normal individuals. With the increasing of Me concentrations, the ratios of gamma/alpha mRNA and alpha/alpha mRNA were increased in cultured cells from beta-thalassemia. The ratio of gamma/alpha mRNA was increased 0.33 - 1.17 times and the ratio of non-alpha/alpha mRNA increased 0.25 - 0.89 times in Me induced cells from beta-thalassemia. There was no significant difference between the concentrations of 2.5 micro mol/L and 5 micro mol/L concentration in beta-thalassemia. However, there was significant difference between the concentrations of 10 micro mol/L and the concentrations of 2.5 micro mol/L and 5 micro mol/L in beta-thalassemia. (3) The increase of the ratio of gamma/alpha mRNA and non-alpha/alpha mRNA in beta-thalassemia was higher than that in normal individual with induction by Me with a higher concentration (10 micro mol/L).

CONCLUSIONMe can raise the ratio of gamma/alpha mRNA and non-alpha/alpha mRNA in cultured erythroid cells derived from peripheral blood of both normal individual and beta-thalassemia in the level of transcription, which can improve the imbalance of the alpha and non-alpha globin chain. So Me has a latent value in the therapy of beta-thalassemia.

Cells, Cultured ; Child ; Child, Preschool ; Erythroid Precursor Cells ; drug effects ; metabolism ; Female ; Gene Expression ; drug effects ; Globins ; genetics ; Humans ; Indoles ; pharmacology ; Infant ; Male ; RNA, Messenger ; drug effects ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction