Objective:To explore the association between insulin resistance (IR) and genome-wide DNA methylation based on Shanghai twin study.Methods:Monozygotic twins (MZ) from Shanghai were recruited during 2012-2013, 2017-2018, and 2022-2023. Data were collected by questionnaire survey, physical examination and laboratory tests. Genome-wide DNA methylation was quantified. Generalized linear mixed effect model was applied to analyze the association between methylation level at each site and homeostatic model assessment 2-insulin resistance (HOMA2-IR). Non-paired and paired designs were used to assess the association between DNA methylation and phenotype of IR. Cluster analysis was conducted to identify the clusters of top significant sites. Generalized linear regression was performed to examine the differential methylation patterns from clusters.Results:A total of 100 MZ pairs were included in this study. Hypermethylated cg10535199-2q23.1 ( β=0.74%, P=1.51×10 -7, OR=1.06, 95% CI: 1.03-1.09) and ch.17.49619327- SPOP ( β=0.23%, P=7.54×10 -7, OR=1.17, 95% CI: 1.08-1.28) were identified with suggestive significance. After correcting for multiple testing, no sites reached genome-wide significance. There was no statistical significance in the paired analysis. Two clusters with hypomethylated ( β=-0.39%, P<0.001) and hypermethylated ( β=0.47%, P<0.001) patterns were observed for HOMA2-IR. Conclusions:IR was significantly associated with DNA methylation, and genetic factors might contribute to the association.

Objective: Sialidosis type 2 has variants that are both catalytically inactive (severe), while sialidosis type 1 has at least one catalytically active (mild) variant. This study aimed to discuss the structural changes associated with these variants in a newly reported family carrying N-acetyl-α-neuraminidase-1 (NEU1) variants and explore the clinical characteristics of different combinations of variants in sialidosis type 1. Methods: First, whole-exome sequencing and detailed clinical examinations were performed on the family. Second, structural analyses, including assessments of energy, flexibility and polar contacts, were conducted for several NEU1 variants, and a sialidase activity assay was performed. Third, previous NEU1 variants were systematically reviewed, and the clinical characteristics of patients in the severe-mild and mild-mild groups with sialidosis type 1 were analyzed. Results: We report a novel family with sialidosis type 1 and the compound heterozygous variants S182G and V143E. The newly identified V143E variant was predicted to be a mild variant through structural analysis and was confirmed by a sialidase activity assay. Cherry-red spots were more prevalent in the severe-mild group, and ataxia was more common in the mild-mild group. Impaired cognition was found only in the severe-mild group. Moreover, patients with cherry-red spots and abnormal electroencephalographies and visual evoked potentials had a relatively early age of onset, whereas patients with myoclonus had a late onset. Conclusion Changes in flexibility and local polar contacts may be indicators of NEU1 pathogenicity. Sialidosis type 1 can be divided into two subgroups according to the variant combinations, and patients with these two subtypes have different clinical characteristics.

Objective:To explore the status of quality of sexual life, self-acceptance and self-disclosure in patients with breast cancer undergoing chemotherapy after surgery, and analyze the mediating effect of self-disclosure between self-acceptance and quality of sexual life.Methods:Using convenience sampling, 209 female patients with breast cancer undergoing postoperative chemotherapy in a Class Ⅲ Grade A hospital in Zhuhai from January to October 2022 were selected for investigation by using the General Information Questionnaire, Sexual Quality of Life Questionnaire for Breast Cancer Survivors, Self-Acceptance Questionnaire (SAQ) and Distress Disclosure Index (DDI). Pearson correlation was used to analyze the correlation between quality of sexual life, self-acceptance and self-disclosure in breast cancer patients undergoing chemotherapy after surgery. Bootstrap mediating effect method was used to analyze the mediating effect of self-disclosure between self-acceptance and quality of sexual life in breast cancer patients undergoing chemotherapy after surgery.Results:The scores of the quality of sexual life (average score of items), self-acceptance and self-disclosure of breast cancer patients undergoing chemotherapy after surgery were (2.69±0.59), (38.61±5.32) and (35.90±5.73) respectively. The quality of sexual life of patients was positively correlated with self-acceptance and self-disclosure, and self-acceptance had a mediating effect on the quality of sexual life through self-disclosure ( P<0.05) . Conclusions:The quality of sexual life of breast cancer patients undergoing chemotherapy after surgery needs to be improved. Helping patients increase their self-acceptance and self-disclosure level will help them improve their quality of sexual life.

Objective:To report embryonic testicular regression syndrome(ETRS) caused by DHX37 heterozygous variant for the first time in China and summarize the clinical manifestations of ETRS as to improve the understanding of doctors for this disease.Methods:The clinical data and whole exome sequencing results of five cases of ETRS from Shenzhen Children′s Hospital were collected. The reported cases of DHX37 heterozygous variant were reviewed.Results:Five patients with ETRS visited the doctors at the age of 2 months to 5 years and 5 months. Three patients raised as males came to hospital due to virilition and 2 female patients visited a doctor due to clitoral hypertrophy. No uterus was detected by ultrasound in all patients. The gonadal pathologies from 4 cases displayed no testicular tissue or gonadal dysgenesis, complicated with gonadoblastoma in one case. The genetic testing revealed that the heterozygous variant(c.923G>A, p. R308Q) in DHX37 was found in 2 cases, without variant in other 3 cases. According to the review, ETRS and 46, XY gonadal dysgenesis due to DHX37 herozygous variant was firstly reported in 2019. A total of 40 cases, including 21 cases of ETRS, presented with the virilition or female phenotype, with the disappearance of testicular tissue as the main pathologies. There is no report in China.Conclusion:The article summarized the clinical manifestations and whole exome sequencing results of 5 patients with ETRS, among which two cases were caused by DHX37 variants and one was complicated with gonadoblastoma.

OBJECTIVE To study the effects of Shenfu yixin granule on mitochondrial autophagy of cardiomyocytes in rats with heart failure after acute myocardial infarction. METHODS The model of heart failure after acute myocardial infarction was established by ligaturing the anterior descending branch of the left coronary artery in rats. The model rats were divided into model group，Shenfu yixin granule low-dose and high-dose groups （1.76，8.8 g/kg），Fosinopril sodium tablets group （positive control ，4 mg/kg），sham operation group was set up （only threading without ligation at the same position ），with 8 rats in each group. After 4 weeks of drug intervention ，the hemodynamic indexes of rats in each group were measured by physiological recorder. The pathological changes of myocardial tissue were observed in each group. The level of oxidative stress in cardiomyocytes ， mitochondrial membrane potential ，protein expression of PTEN-induced putative kinase 1（PINK1），E3 ubiquitin ligase Parkin and ubiquitin binding protein P 62 in myocardial tissue of rats in each group were detected. RESULTS Compared with sham operation group ，the pathological injuries such as myocardial fiber morphology disorder and inflammatory cell infiltration were serious. The left ventricular end systolic pressure （LVESP），maximum rate of rise of left ventricular internal pressure （+dp/dtmax）， maximun rate of decrease of left ventricular internal pressure （－dp/dtmax），total antioxidant capacity ，mitochondrial membrane potential，PINK1，Parkin and P 62 protein expression were significantly decreased in model group （P＜0.01）. The left ventricular end diastolic pressure （LVEDP），the level of reactive oxygen species and the activity of reduced nicotinamide adenine dinucleotide phosphate in left ventricular ischemic cardiomyocytes were significantly increased （P＜0.01）. Compared with model group ，the pathological injuries of myocardial tissue in intervention groups were alleviated ，and above indexes were improved in varying degrees（P＜0.01 or P＜0.05）. CONCLUSIONS Shenfu y ixin granule can reduce the level of oxidative stress and alleviate heart failure after acute myocardial infarction ，which may be related to the activation of Parkin-dependent pathway to strengthen mitochondrial autophagy and reduce mitochondrial dysfunction.

Objective:Luminex NxTAG? RPP kit was used to detect respiratory tract infection samples in Guangzhou, and the pathogen spectrum of respiratory tract infection in Guangzhou in the past year was summarized to provide reference for clinical diagnosis, treatment and disease prevention and control of respiratory tract infection.Methods:A total of 484 respiratory infection samples were collected from December 2018 to November 2019 from Guangdong Maternal and Child Health Hospital and The Second People's Hospital of Guangdong Province. QIAamp MinElute Virus Spin Kit(50) was used to extract total nucleic acid, and Luminex NxTAG? RPP Kit was used to detect pathogens in the samples. Excel 2016 was used to draw the data and SPSS19.0 software was used for statistical analysis.Results:Among the 484 samples, 397 were found to be positive, with A total positive rate of 79.96%. Infection included Influenza A H1N1pdm09 virus (H1N1 2009), rhinoviruses (RhV), Metapneumovirus (MPV). In the age distribution, the positive rates of H1N1 2009, Respiratory syncytial virus (RSV), Parainfluenza virus (PIV), MPV, RhV and Bocavirus (BoV) were relatively high in the children group. The positive rate of Influenza B virus (FLuB) in adult group was relatively high. The positive rates of H1N1 2009, RSV, MPV and BoV were higher in outpatients. The positive rate of FLuB was relatively high in hospitalized patients. In the pathogen detection of patients with different symptoms, the RSV positive rate of samples from patients with cough and sputum symptoms was higher. The positive rates of Coronaviruses (CoV), MPV and RhV samples from patients with nasal obstruction were higher. The detection rate of most pathogens is high in winter and spring.Conclusions:H1N1 2009, RhV and MPV are the important pathogens of respiratory tract infections in Guangzhou in 2019. Strengthening the research and monitoring of these pathogens can be the focus of the prevention and control of respiratory tract infectious diseases in Guangzhou.

Objective: To study the clinicopathologic features of lymphoproliferative disease by lymph node core needle biopsy(CNB)and to evaluate the diagnostic significance of CNB for lymphoproliferative disease. Methods: The annual distribution, entity constitute, clinical finding, gross feature, morphologic change, affiliate study and repeat biopsy diagnosis of 1 013 cases of lymph node CNB diagnosed at West China Hospital of Sichuan University from January 2009 to December 2015 were investigated. Results: (1) Proportion of lymph node CNB in total amount of biopsy specimens increased from 0.2% in 2009 to 0.8% in 2015.(2) The study cohort included 471 lymphomas, 12 atypical lymphoid hyperplasia (ALH), 136 suspected lymphomas, 372 benign lesions, and 22 cases of descriptive diagnoses. The most common types were diffuse large B cell lymphoma and T-lymphoblastic lymphoma. (3) Majority of patients were adolescents and children younger than 20 years or the elderly older than 60 years. 53.1% CNB tumor specimen consisted of ≥4 tissue cores and 40.5% were >2 cm in length. (4) 104 CNB cases with previous history of excision biopsy was included 45 carcinomas(no metastatic carcinoma was found), 32 lymphomas for treatment observation.1/14 suspicious lymphomas, 1/1 ALH and 3/22 cases benign lesions were diagnosed as lymphoma by repeat biopsy respectively. (5) 217 CNB cases were diagnosed as lymphoma by subsequent CNB (70), or subsequent excision biopsy (147) including 78.5%(73/93) suspected lymphomas, 5/7 ALH and 32.3%(20/62)benign lesions. Conclusions Lymph node CNB has certain clinical indications, although limited for the diagnosis of lymphoproliferative disorders. Suspected lymphomas and ALH diagnosed by CNB should be followed by repeat tissue biopsy. For the benign lesions by CNB it does not rule out additional biopsy to further investigate the lesion.

The interventional treatment of ischemic cerebrovascular disease has developed rapidly, but it also faces some difficulties, such as restenosis after simple balloon dilatation, in-stent restenosis and bleeding risk caused by anti-platelet therapy after stent angioplasty. The good results and bright prospects of drug eluting balloon (DEB) in treatment of coronary intervention provide a nice reference for the treatment of cerebral vascular intervention. As a new technology, DEB has the advantages of easily operation, short time of postoperative dual anti-platelet treatment, low risk of postoperative bleeding and no foreign matter left in the body. At present, only a few studies have attempted to do the cerebral vascular interventional therapy with DEB, and the results are encouraging. In this paper, the mechanism, mature experience in coronary arteries and clinical application of DEB are summarized to provide a new idea for interventional treatment of ischemic cerebrovascular diseases.

OBJECTIVETo investigate the clinicopathological characteristics, diagnosis, treatment and prognosis of gastric hepatoid adenocarcinoma(HAS).

METHODSRetrospective analysis of clinicopathological data of 24 cases with gastric HAS diagnosed by surgery and pathology in Chinese PLA General Hospital from January 2013 to May 2016 were carried out. All the patients underwent preoperative serum alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), endoscopy and imaging examination (CT or B-mode ultrasonography), and those with elevated AFP were excluded from liver cancer, cirrhosis, endodermal sinus tumor and other diseases. The follow-up ended in June 2016 or the death of the patient. The survival was from the operation to the death of the patient or the end of follow-up.

RESULTSThere were a total of 24 cases with gastic HAS, accounting for 1.03%(24/2 326) of the total number of patients with gastric cancer diagnosed at the same time in our center. There were 19 males and 5 females, the ratio of male to female was 3.8:1.0, the mean age of the patients was 55.9 (31 to 72) years, and 2 of them had liver metastasis. The first symptom in 50% (12/24) patients was epigastric pain, in 25%(6/24) was abdominal distension with vomiting, and the rest included dysphagia (12.5%, 3/24), hematemesis (8.3%, 2/24) and melena (4.2%, 1/24). Preoperative serum levels of AFP and CEA were elevated in 10 (41.7%) and 5 patients (20.8%) respectively. All the patients underwent surgical treatment, including 23 cases with D2 radical resection of gastric cancer and R0 resection, and the other of palliative gastrojejunostomy. Lesions of HAS located in gastric antrum in 11 cases (45.8%), in cardia in 7 cases (29.2%), and in gastric body in 6 cases (25%). Tumor maximum diameter of 10 cases was larger than 5 cm, and the average diameter was 5.7(1.0 to 12.0) cm. Postoperative pathological TNM staging: stage I(b was in 1 cases, stage II( in 7 cases, stage III( in 14 cases, stage IIII( in 2 cases; lymph node metastasis in stage N1-3 in 20 cases (83.3%). Poorly-differentiated tumors were found in 21 cases (87.5%), and no well-differentiated tumors were found. There were 11 cases (45.8%) with formation of intravascular tumor thrombi. In immunohistochemistry, AFP positive expression was found in 11 cases(45.8%). Seventeen HAS cases (70.8%, 17/24) received postoperative SOX(oxaliplatin + S-1) or XELOX (oxaliplatin + capecitabine) as adjuvant chemotherapy, 5 cases postoperative immune therapy, and 2 cases postoperative traditional Chinese medicine. All the patients were followed up for 0.7 to 42.0 months (median 8 months). A total of 9 patients died, of whom, 1 case underwent gastrojejunostomy because of liver and peritoneal metastasis before operation, and died 20 days after surgery; 4 cases died of multiple liver metastases after 1.5 to 12.0 months with survival of 3 to 18 months; 3 cases presented local recurrence after 2 to 17 months with survival of 6 to 22 months; 1 cases had peritoneal metastasis after 12 month with survival of 26 months.

CONCLUSIONSHAS is a rare type of gastric cancer with poor prognosis. The diagnosis is mainly based on histopathology, and radical resection is the mainstay treatment.

PURPOSE: The incidence of allergen specific immunotherapy-related systemic reactions (SRs) varies among different studies, and many factors are likely to contribute to SRs. This study aims to investigate the incidence, characteristics, and risk factors of SRs to standardize dust mite-specific subcutaneous immunotherapy (SCIT) in Central China. METHODS: All patients receiving standardized dust mites (100-100,000 SQ-U/mL; Alutard SQ, Hørsholn, Denmark) immunotherapy were followed up. Recorded data included demographics, diagnosis, patient status, pulmonary function testing results before and after each injection, allergen dosage, and details of SRs. RESULTS: From June 2011 to August 2014, a total of 208 patients received 4,369 injections; 27 (13.0%) patients experienced 48 (1.1%) systemic reactions. Most of the SRs were grade 2 reactions (n=30, 62.5%), followed by grade 1 (n=11, 22.9%), grade 3 (n=7, 14.6%), and no fatal reactions occurred. Forty-six SRs (95.8%) occurred within 30 minutes. Higher SR rates were associated with high concentration extracts (100,000 SQ-U/mL), injections with concomitant local reactions (LRs), children, asthma and high sensitivity (skin prick test 3+/4+ and/or sIgE≥17.5 kUA/L) (P<0.05). The estimated odds of SRs increased in children (OR=6.57; 95% CI: 1.88-22.97, P=0.003), asthmatic patients (OR=4.10; 95% CI: 1.72-9.80, P=0.002), and injections with LRs (OR=2.41; 95% CI: 1.33-4.36, P=0.004). CONCLUSIONS: The incidence of SRs to dust mite SCIT was low, and multiple factors were associated with the increased incidence of SRs. Children, asthmatics and patients with concomitant LR may be prone to develop SRs.
Asthma ; Child ; China ; Demography ; Dermatophagoides pteronyssinus ; Diagnosis ; Dust* ; Follow-Up Studies* ; Humans ; Immunotherapy* ; Incidence ; Mites* ; Respiratory Function Tests ; Risk Factors