This article reports a child with cardioaciocutaneous syndrome (CFCS) caused by a rare microdeletion of chromosome 19p13.3, and a literature review is conducted. The child had unusual facies, short stature, delayed mental and motor development, macrocephaly, and cardiac abnormalities. Whole-exome sequencing identified a 1 040 kb heterozygous deletion in the 19p13.3 region of the child, which was rated as a "pathogenic variant". This is the first case of CFCS caused by a loss-of-function mutation reported in China, which enriches the genotype characteristics of CFCS. It is imperative to enhance the understanding of CFCS in children. Early identification based on its clinical manifestations should be pursued, and genetic testing should be performed to facilitate diagnosis.
Humans ; Chromosome Deletion ; Chromosomes, Human, Pair 19/genetics* ; Ectodermal Dysplasia/genetics* ; Facies ; Failure to Thrive/genetics* ; Heart Defects, Congenital/genetics*

Objective To understand the current situation of human brain donation in Hebei Province by analyzing the basic information of Human Brain Bank samples of Hebei Medical University in order to provide basic data support for subsequent scientific research.Methods The samples collected from the Human Brain Bank of Hebei Medical University were analyzed(from December 2019 to February 2024),including gender,age,cause of death,as well as quality control data such as postmortem delay time,pH value of cerebrospinal fluid and and RNA integrity number and result of neuropathological diagnosis.Results Until February 2024,30 human brain samples were collected and stored in the Human Brain Bank of Hebei Medical University,with a male to female ratio of 9∶1.Donors over 70 years old accounted for 53％.Cardiovascular and cerebrovascular diseases(36.67％)and nervous system diseases(23.33％)accounted for a high proportion of the death causes.The location of brain tissue donors in Shijiazhuang accounted for 90％donations,and the others were from outside the city.The postmortem delay time was relatively short,90％within 12 hours and 10％more than 12 hours.69.23％of the brain samples had RNA integrity values greater than 6.Cerebrospinal fluid pH values ranged from 5.8 to 7.5,with an average value of 6.60±0.45.Brain weights ranged from 906-1496 g,with an average value of(1210.78±197.84)g.Three apolipoprotein E(APOE)alleles were detected including five genotypes(ε2/ε3,ε2/ε4,ε3/ε3,ε3/ε4,ε4/ε4).Eleven staining methods related to neuropathological diagnosis had been established and used.A total of 12 cases were diagnosed as neurodegenerative diseases(including Alzheimer's disease,Parkinson's disease,multiple system atrophy,corticobasal degeneration and progressive supranuclear palsy,etc.),accounting for 40％donated brains.The comorbidity rate of samples over 80 years old was 100％.Conclusion The summary and analyses of the data of brain donors in the Human Brain Bank of Hebei Medical University can reflect the current situation of the construction and operation of the brain bank in Hebei Province,and it can also be more targeted to understand and identify potential donors.Our information can provide reference for the construction of brain bank and provides more reliable materials and data support for scientific research.

Humans ; Philadelphia Chromosome ; Neoplasms ; Myelodysplastic Syndromes/genetics* ; Disease Progression

ObjectiveTo study the effect of Jinlida granules on visceral fat accumulation and its induced inflammatory response in prediabetic rats. MethodMale SD rats were randomly divided into normal group， model group， Jinlida low-dose group （1.5 g·kg^-1）， Jinlida high-dose group （3.0 g·kg^-1） and atorvastatin group （10 mg·kg^-1）. Prediabetic rat model was established using high-carbohydrate， high-fat diet combined with low-dose streptozotocin （STZ） by multiple small-dose intraperitoneal injections. After 8 weeks of modeling and drug intervention for 13 consecutive weeks， body weight， oral glucose tolerance test（OGTT）， fasting blood glucose （FBG）， fasting insulin （FINS）， insulin resistance index （HOMA-IR）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C） and high-density lipoprotein cholesterol （HDL-C） were measured in each group of rats. The content of visceral fat was quantified by micro-computed tomography （Micro-CT）. Hematoxylin-eosin staining （HE） was used to observe the pathological changes of fat cells. The levels of tumor necrosis factor-α （TNF-α） and interleukin- 6 （IL-6） in rat visceral fat and serum were determined by enzyme linked immunosorbent assay （ELISA）. The expression of macrophage marker CD68 in visceral fat was detected by immunofluorescence and Western blot. ResultCompared with normal group， model group had increased oral glucose tolerance， FBG， FINS， HOMA-IR， TC， LDL-C （P<0.01）， elevated body weight and visceral fat accumulation （P<0.05， P<0.01）， enhanced CD68 protein expression and TNF-α and IL-6 levels （P<0.01）， decreased HDL-C （P<0.01）， and abnormal hypertrophy of adipocytes. Compared with model group， Jinlida high- and low-dose groups lowered oral glucose tolerance， HOMA-IR， TC and LDL-C （P<0.05， P<0.01）， body weight and visceral fat accumulation （P<0.05）， and CD68 protein expression and TNF-α and IL-6 levels （P<0.05， P<0.01） and lessened hypertrophy of fat cells. ConclusionJinlida can improve the insulin resistance in prediabetic rats by reducing visceral fat accumulation and its induced inflammatory response， which provides a new pharmacological basis for clinical treatment of prediabetes by Jinlida granules.

OBJECTIVE: To compare the safety of low-dose cyclophosphamide and high-dose cyclophosphamide in the treatment of systemic lupus erythematosus (SLE). METHODS: A total of 1 022 patients with systemic lupus erythematosus from 24 hospitals in China between March 2017 to July 2018 were enrolled. Their clinical manifestations, laboratory tests, adverse events, reasons for stopping receiving intravenous cyclophosphamide and comorbidities were collected. Among them, 506 SLE patients received short-interval low-dose intravenous cyclophosphamide therapy (SILD IV-CYC, 400 mg every two weeks), and 256 patients underwent high-dose cyclophosphamide therapy (HD IV-CYC, 500 mg/m² of body surface area every month), the side effects between the two groups were compared, the remaining 260 SLE patients were treated with IV-CYC irregularly. Moreover, a total of 377 patients in SILD IV-CYC group and 214 patients in HD IV-CYC group had medical records of the reasons for stopping recei-ving IV-CYC. The reasons for stopping receiving IV-CYC in these two groups were analyzed. RESULTS: In this study, only 40.27%(238/591)of the SLE patients stopped receiving intravenous cyclophosphamide for the causes of disease improvement, however, up to 33.67% (199/591) of the patients for the reason of drug-related side effects. There were 83 patients out of 214 (38.79%) with high-dose intravenous cyclophosphamide treatment who stopped receiving IV-CYC for the drug-related side effects, which was significantly higher than that in the low-dose cyclophosphamide group (30.77%, 116/337, P=0.048). Of theses 506 patients in SILD IV-CYC group, 88 (17.39%) patients experienced gastrointestinal reactions, 66 (13.04%) suffered from infections, 49 (9.68%) had myelosuppression and 68 (13.44%) had alopecia, respectively. Among the 256 patients in the HD IV-CYC group, 80 (31.25%) experienced gastrointestinal reactions, 57 (22.27%) suffered from infections, 51 (19.92%) had myelosuppression and 49 (19.14%) had alopecia. Moreover, 71 (25.18%) of 282 female patients with age between 16 to 45 years in SILD IV-CYC group had abnormal menstruation, while menstrual disorder occurred in 39.72% (56/141) patients of HD IV-CYC group. There was no difference of drug-induced hepatic injury, hemorrhagic cystitis and fatigue between the two groups. CONCLUSION Low-dose cyclophosphamide showed a lower prevalence of adverse events than high-dose cyclophosphamide in systemic lupus erythematosus patients.
Humans ; Female ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Immunosuppressive Agents/adverse effects* ; Cyclophosphamide/therapeutic use* ; Lupus Erythematosus, Systemic/drug therapy* ; Administration, Intravenous ; Alopecia/drug therapy*

BACKGROUND: TOSO, also named Fas inhibitory molecule 3 (FAIM3), has recently been identified as an immunoglobulin M (IgM) Fc receptor (FcμR). Previous studies have shown that TOSO is specifically over-expressed in chronic lymphocytic leukemia (CLL). However, the functions of TOSO in CLL remain unknown. The B-cell receptor (BCR) signaling pathway has been reported to be constitutively activated in CLL. Here, we aimed to investigate the functions of TOSO in the BCR signaling pathway and the pathogenesis of CLL. METHODS: We over-expressed TOSO in B-cell lymphoma cell lines (Granta-519 and Z138) by lentiviral transduction and knocked down TOSO by siRNA in primary CLL cells. The over-expression and knockdown of TOSO were confirmed at the RNA level by polymerase chain reaction and protein level by Western blotting. Co-immunoprecipitation with TOSO antibody followed by liquid chromatography coupled with tandem mass spectrometry (IP/LCMS) was used to identify TOSO interacting proteins. Western blotting was performed to detect the activation status of BCR signaling pathways as well as B-cell lymphoma 2 (BCL-2). Flow cytometry was used to examine the apoptosis of TOSO-over-expressing B lymphoma cell lines and TOSO-down-regulated CLL cells via the staining of Annexin V and 7-AAD. One-way analyses of variance were used for intergroup comparisons, while independent samples t tests were used for two-sample comparisons. RESULTS: From IP/LCMS, we identified spleen tyrosine kinase (SYK) as a crucial candidate of TOSO-interacting protein and confirmed it by co-immunoprecipitation. After stimulation with anti-IgM, TOSO over-expression increased the phosphorylation of SYK, and subsequently activated the BCR signaling pathway, which could be reversed by a SYK inhibitor. TOSO knockdown in primary CLL cells resulted in reduced SYK phosphorylation as well as attenuated BCR signaling pathway. The apoptosis rates of the Granta-519 and Z138 cells expressing TOSO were (8.46 ± 2.90)% and (4.20 ± 1.21)%, respectively, significantly lower than the rates of the control groups, which were (25.20 ± 4.60)% and (19.72 ± 1.10)%, respectively (P < 0.05 for both). The apoptosis rate was reduced after knocking down TOSO in the primary CLL cells. In addition, we also found that TOSO down-regulation in primary cells from CLL patients led to decreased expression of BCL-2 as well as lower apoptosis, and vice versa in the cell line. CONCLUSIONS TOSO might be involved in the pathogenesis of CLL by interacting with SYK, enhancing the BCR signaling pathway, and inducing apoptosis resistance.

Objective To examine the effect of rational emotive therapy on negative emotions among advanced schistosomiasis patients with repeated hospitalizations. Methods A total of 97 advanced schistosomiasis patients with anxiety and depressive emotions that were hospitalized in Xiangyue Hospital of Hunan Institute of Schistosomiasis Control for three times or more were enrolled, and given rational emotive therapy for 4 weeks in addition to routine nursing care. The scores for anxiety, depression and quality of life were estimated in patients before and after the rational emotive therapy using the Self-Rating Anxiety Scale (SRS), the Self-Rating Depression Scale (SDS) and WHOQOL-BREF Form. Results The SAS and SDS scores were significantly lower 4 weeks following rational emotive therapy than before the intervention (SAS score, 45.40 ± 7.77 vs. 59.25 ± 9.29, t = 14.021, P < 0.01; 51.48 ± 8.01 vs. 63.93 ± 9.59, t = 12.991, P < 0.01). The percentages of patients with moderate and severe anxiety and depression were significantly lower 4 weeks following rational emotive therapy than before the intervention (P < 0.01), and the scores for each item in the quality of life were all significantly greater 4 weeks following rational emotive therapy than before the intervention (P < 0.01). Conclusion Rational emotive therapy may improve the negative emotions and the quality of life of advanced schistosomiasis patients with repeated hospitalizations.

Objective: To investigate the level of intolerance of uncertainty (IU) and possible related factors in the patients with anxiety disorders. Methods: The patients' diagnosis was made according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM- ). Thirty-five cases of generalized anxiety disorder (GAD), 15 cases of panic disorder (PD) and 31 healthy controls (HC group) were recruited at the same time. IU level was assessed by using the Chinese version of Intolerance of Uncertainty Scale (IUS). The characteristics of anxiety symptoms, depressive symptoms and body perception were assessed by Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD) and Body Perception Questionaire (BPQ), respectively. Results: The IU levels of both GAD group and PD group were significantly higher than those of HC group (P=0.000). There was no significant difference in IU levels between GAD group and PD group (P=0.491). The IU levels of GAD patients were positively correlated with HAMA-somatic anxiety (r=0.377, P=0.025) and BPQ-awareness (r=0.342, P=0.044). Conclusion: The patients with anxiety disorders have elevated IU levels, compared with healthy people. Possibly, somatic anxiety and body perception-awareness are related factors to IU in GAD patients.

Objective:The effects of anemoside B₄ on endometritis rats were studied through in vivo and in vitro experiments. Method:Animal experiments used 25% phenol glue to prepare endometritis models. 60 female SD rats were randomly divided into blank group， model group， Kushen gel group（0.005 g·kg^-1），anemoside B₄ gel low，medium and high dose groups（0.005，0.01，0.02 g·kg^-1），10 rats in each group，except for the blank group，rats in each group were injected with 25% phenol glue into their vagina every 2 days，and the modeling continued for 30 days. Administration started on the day after modeling. Anemoside B₄ gel low， medium and high dose groups were administered rectal daily，Kushen gel group was given daily vaginal administration. The blank group and model group were given the same amount of normal saline in the same way for 30 consecutive days. After the last administration，the uterus and its attachments of each group of rats were taken to analyze the uterine morphology and index. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of rat uterus. Real-time PCR was used to detect tumor necrosis factor-α （TNF-α），interleukin-1β （IL-1β），and interleukin-6 （IL-6），signal transduction protein 130 （gp130），signal transduction and transcription activator 3 （STAT3）mRNA expression. Detection of IL-6 and STAT3 protein expression in rat uterus by Western blot. In cell experiments，lipopolysaccharide （LPS）was used to induce rat endometrial epithelial cells to prepare an in vitro inflammation model， and Real-time PCR was used to detect the expression of IL-6，gp130 and STAT3 mRNA in each group of rat endometrial epithelial cells. Result:The results of animal experiments showed that compared with the blank group， the model group had inadequate uterine cavity adhesions， endometrial edema and hyperemia. Compared with model group， there was no adhesion in the uterine cavity of the rats in the high dose anemoside B₄ gel group and the Kushen gel group. The uterine tissue was relatively complete， and the uterine pathological structure was significantly improved. Compared with the blank group， the uterine index of the model group was significantly increased（P<0.05）， the expression of IL-1β mRNA in the uterine tissue was significantly increased （P<0.05）， the expression of mRNA and protein of IL-6 and STAT3 in the uterine tissue significantly increased （P<0.05）. Compared with model group， the uterine index in anemoside B₄ gel high dose group was significantly reduced （P<0.05）， and the mRNA and protein expression levels of IL-6 and STAT3 in the uterine tissue were significantly reduced （P<0.05）. There was no statistically significant difference between the TNF-α and IL-1β mRNA expression compared with the model group. Cell experiment results showed that compared with the blank group， the mRNA expression of IL-6 and gp130 in model group endometrial epithelial cells was significantly increased （P<0.01）， STAT3 mRNA expression was significantly increased （P<0.05）. Compared with model group， the mRNA expression levels of IL-6， gp130 and STAT3 in anemoside B₄ high dose group decreased significantly （P<0.05）. Conclusion:Anemoside B₄ can improve the inflammatory response of chronic endometritis in rats and reduce the release of inflammatory factor IL-6. The mechanism may be related to the down-regulation of IL-6/STAT3 pathway.