BACKGROUND: Stress cardiomyopathy (SCM) currently has a high incidence in older adults, and the theories regarding its causes include "catecholamine myocardial toxicity" and "sympathetic hyperactivation". However, the role of the central nervous system in the pathogenesis of SCM remains unknown. We investigated the role of microglia activation in the paraventricular hypothalamic nucleus (PVN) in the development of SCM. METHODS: An SCM model was created using male Sprague-Dawley (SD) rats, immobilized for 6 h every day for a week. Electrocardiogram, cardiac electrophysiology, and echocardiography examinations were performed to verify the changes in cardiac structure and function in rats with SCM. RNA sequencing was used to explore the changes in the hypothalamus during SCM. In addition, brain and heart tissues were collected to detect microglial activation and sympathetic activity. RESULTS: The main findings were as follows: (1) immobilization stress successfully induced SCM in SD rats; (2) microglia were significantly activated in the hypothalamus, as evidenced by cytosol thickening, increases in the number of microglial branches, and microglia enriched in the PVN; (3) in SCM, the microglia in the PVN exhibited increased central and peripheral cardiac sympathetic activity and increased the expression of neuroinflammatory factors; and (4) it is possible that inhibiting microglial activation could suppress the sympathetic activity of the central nervous system and heart and increase cardiac electrical stability in SCM rats. CONCLUSIONS SCM was induced in SD rats by immobilization stress, acting through the activation of the hypothalamic microglia. The activated microglia were specifically enriched in the PVN, increasing the activity of the central and peripheral sympathetic nervous systems by regulating the expression of neuro-inflammatory factors, mediating dysfunction of the left ventricle, and increasing the susceptibility to ventricular arrhythmias.

Humans ; Melphalan/therapeutic use* ; Multiple Myeloma/therapy* ; Hematopoietic Stem Cell Transplantation ; Transplantation, Autologous ; Transplantation Conditioning

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

The value of the "touching-bone" acupuncture technique in clinical application was explained through the investigation on the origin of the theory of the "touching-bone" acupuncture technique, the analysis on the characteristics of acupoint selection, the introduction of clinical characteristics and the discussion on the mechanism of acupuncture in treatment. The "touching-bone" acupuncture technique refers to deep needling method, originated from the short needling and needling of the ancient needling methodslisted in the . The target points are the reaction sites on meridian near to bone and the attachments of soft tissues on bone. During the needle insertion, the needle tip is thrust deeply to the bone or the needle body is closely attached to the bone so as to stimulate periosteum specifically. This needling technique contributes to the satisfactory effect on spasmodic, deep-located and intractable pain disorder, motor system diseases, mental diseases and cerebral diseases, etc. Hence, this acupuncture technique deserves to be promoted in clinical application and explored in research.
Acupuncture Therapy ; Meridians ; Needles

Objective :To explore therapeutic effect of single Chinese medicine Bidens pilosa grain on hyperlipidemia and its influence on serum levels of matrix metalloproteinase‐9 (MMP‐9) and tissue inhibitor of metalloproteinases‐1 (TIMP‐1).Methods :A total of 186 hyperlipidemia patients treated in our hospital from Jan 2014 to Jun 2017 were randomly divid‐ed into Bidens pilosa group (n＝94 ,received Bidens pilosa grain based on routine treatment ) and Xuezhikang group (n＝92 ,received Xuezhikang based on routine treatment ).Both groups were treated for two months .Serum levels of total cho‐lesterol (TC) , triglyceride (TG ) ,low density lipoprptein cholesterol (LDL‐ C) , high density lipoprptein cholesterol (HDL‐C) ,MMP‐9 and TIMP‐1 before and after treatment ,and total effective rate were observed and compared between two groups.Results :Compared with before treatment ,after treatment ,there were significant reductions in serum levels of TC ,TG ,LDL‐C and MMP‐9 [ Bidens pilosa group : (24.46 ± 4.92) μg／L vs.(20.53 ± 2.69) μg／L ,Xuezhikang group :(23.40 ± 2.57) μg／L vs.(19.98 ± 2.02) μg／L] ,and significant rise in serum levels of HDL‐C [ Bidens pilosa group :(1.28 ± 0.45) mmol／L vs.(1.54 ± 0.52) mmol／L , Xuezhikang group : (1.28 ± 0.45) mmol／L vs.(1.55 ± 0.52) mmol／L] and TIMP‐1 [ Bidens pilosa group : (4.67 ± 1.26) μg／L vs.(6.02 ± 2.24) μg／L ,Xuezhikang group :(4.63 ± 1.30) μg／L vs.(6.01 ± 2.31) μg／L] in two groups , P＝0.001 all.After treatment ,there were no significant difference in serum levels of TC ,TG ,LDL‐C ,HDL‐C ,MMP‐9 and TIMP‐1 and total effective rate between two groups , P＞0.05 all.Conclusion :Bidens pilosa can significantly improve serum lipid level ,reduce serum level of MMP‐9 and increase serum level of TIMP‐1 in hyperlipidemia patients .It＇s no significant difference compared with Xuezhikang .

OBJECTIVES: To use virtual anatomy technique in the analysis of post-mortem characteristic changes of CT images in the experimental drowning rabbit model and the related parameters in 3D virtual model, so as to explore its application value in the diagnosis of drowning in forensic pathology. METHODS: A model of drowning rabbits was established, with animal models of hemorrhagic shock and mechanical asphyxia as the controls. CT scan was performed on the experimental animals, and the differences in imaging features between the groups were compared by morphological reading of the tomographic images. CT data were imported into Mimics 14.0 software for 3D modeling. The CT values and lung volumes were calculated by the software, and the differences on CT values and lung volumes brought by different causes of death were analyzed. RESULTS: The CT images of lungs in the drowning group showed characteristic ground-glass opacity （diffuse and uniform density increase）. There were no obvious abnormalities in hemorrhagic shock group, and only a few similar changes were found in the mechanical asphyxia group. Compared with the controls, the CT values and the lung volumes in the drowning group were significantly increased P<0.05. CONCLUSIONS Based on post-mortem lung imaging, the combination of CT value and lung volume changes can effectively reflect the virtual anatomical features in drowning, and provide a diagnostic basis for the forensic identification of drowning.
Animals ; Drowning ; Lung/diagnostic imaging* ; Rabbits ; Tomography, X-Ray Computed

INTRODUCTIONHepatitis B virus (HBV) reactivation has been reported in B-cell lymphoma patients with resolved hepatitis B (hepatitis B surface antigen [HBsAg]-negative and hepatitis B core antibody [HBcAb]-positive). This study aimed to assess HBV reactivation and hepatitis occurrence in diffuse large B-cell lymphoma (DLBCL) patients with resolved hepatitis B receiving rituximab-containing chemotherapy compared with HBsAg-negative/HBcAb-negative patients to identify risk factors for HBV reactivation and hepatitis occurrence and to analyze whether HBV reactivation and hepatitis affect the survival of DLBCL patients with resolved hepatitis B.

METHODSWe reviewed the clinical data of 278 patients with DLBCL treated with rituximab-containing therapy between January 2004 and May 2008 at Sun Yat-sen University Cancer Center, China. Predictive factors for HBV reactivation, hepatitis development, and survival were examined by univariate analysis using the chi-square or Fisher's exact test and by multivariate analysis using the Cox regression model.

RESULTSAmong the 278 patients, 165 were HBsAg-negative. Among these 165 patients, 6 (10.9%) of 55 HBcAb-positive (resolved HBV infection) patients experienced HBV reactivation compared with none (0%) of 110 HBcAb-negative patients (P = 0.001). Patients with resolved hepatitis B had a higher hepatitis occurrence rate than HBsAg-negative/HBcAb-negative patients (21.8% vs. 8.2%, P = 0.013). HBcAb positivity and elevated baseline alanine aminotransferase (ALT) levels were independent risk factors for hepatitis. Among the 55 patients with resolved hepatitis B, patients with elevated baseline serum ALT or aspartate aminotransferase (AST) levels were more likely to develop hepatitis than those with normal serum ALT or AST levels (P = 0.037, P = 0.005, respectively). An elevated baseline AST level was an independent risk factor for hepatitis in these patients. Six patients with HBV reactivation recovered after immediate antiviral therapy, and chemotherapy was continued. HBcAb positivity, HBV reactivation, or hepatitis did not negatively affect the survival of DLBCL patients.

CONCLUSIONSDLBCL patients with resolved hepatitis B may have a higher risk of developing HBV reactivation and hepatitis than HBsAg-negative/HBcAb-negative patients. Close monitoring and prompt antiviral therapy are required in these patients.

China ; Hepatitis B ; Hepatitis B Antibodies ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Humans ; Lymphoma, Large B-Cell, Diffuse ; Mortality ; Prognosis ; Risk Factors ; Rituximab ; Virus Activation

OBJECTIVETo explore the treatment options for younger than 60 years old adults with Ph /BCR-ABL positive acute lymphoblastic leukemia (Ph⁺ ALL).

METHODSFrom January 2001 to June 2012, 42 adult patients were enrolled in the study. All patients received standard VDCP±L ±imatinb (IM) as induction therapy followed by intensive consolidation of modified Hyper-CVAD/MA±IM. At complete remission 1 (CR1), patients with appropriate donor received allogeneic hematopoietic stem cell transplantation (allo-HSCT), the others sequentially received intensive consolidation ±IM and autologous HSCT (ASCT) at molecular CR (MCR), then MM±VP±IM as maintenance therapy. Overall survival (OS), disease free survival (DFS) and relapse rate (RR) were analyzed.

RESULTSCR rate after 1 cycle of induction chemotherapy was 83.3%. 39(92.9%) patients achieved CR. The median DFS and OS were (22.0±3.5) and (37.0±5.3) months respectively, with cumulative RR of (43.7±9.7)% during a median follow-up of 26.5(8-75) months. All 7 patients in CT group relapsed. Two patients received IM pre- and post-ASCT maintained MCR for 35 and 12 months after ASCT. But the other 3 ASCT recipients without IM died of relapse within 1 year. The transplant-related mortality rate in allo-HSCT group was 12.5%. The estimated 3-year OS in allo-HSCT (n=16), ASCT (n=5) and CT (n=7) groups were (66.7±12.2)%, (25.0±21.7)% and (16.7±15.2)%, respectively (P=0.014); meanwhile, the estimated 3-year DFS in those groups were of (56.3±12.4)%, (26.7±22.6)% and 0, respectively (P=0.002).

CONCLUSIONIM combined with intensive chemotherapy significantly increased the CR rate with the improved quality of CR, which highlighted the feasibility of SCT. Allo-HSCT could decrease relapse to produce favorable OS and DFS in CR1 of young adults with Ph⁺ ALL. ASCT combined IM might be the treatment of choice for those achieved MCR but without donors.

Adolescent ; Adult ; Disease-Free Survival ; Female ; Humans ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; therapy ; Prospective Studies ; Recurrence ; Remission Induction ; Survival Rate ; Treatment Outcome ; Young Adult

OBJECTIVETo explore the efficacy and prognosis of first-line autologous hematopoietic stem cell transplantation (ASCT) for newly diagnosed patients with multiple myeloma(MM).

METHODSFrom January 2005 to December 31, 2012, 60 patients with MM were enrolled. All patients received thalidomide or/and bortezomib-based induction therapy, then received high-dose melphalan (200 mg/m²) and autologous stem cell support to get a ≥ partial response (PR), and followed by thalidomide-dexamethasone (TD) ±bortezomib as consolidation or maintenance treatment. With the follow up to December 31, 2012, the overall survival (OS), progression free survival (PFS) and the prognostic factors, including ISS stage, response and fluorescent in situ hybridization (FISH) data of cytogenetics were analyzed.

RESULTSWith a median follow up of 36.8 (12.0-102.5) months, the median OS and PFS estimate were not reached and 86.5 months, respectively. After transplantation, all (100%) patients received very good partial response (VGPR), and 34 (56.7%) patients achieved complete response (CR) after consolidation or maintenance treatment. The patients that achieved CR resulted in long term PFS (P=0.030), with no difference in OS (P=0.942). The univariate analysis showed that the abnormalities, including 13q14 deletion, 1q21 gain, IgH location and p53 deletion had the prognostic impacts. If the t(4;14) or p53 deletion was excluded, there would be no correlation between 13q14 deletion or 1q21 gain with PFS and OS. The patients with p53 deletion had a worst survival.

CONCLUSIONThere has been significant improvement in the outcome for young MM patients by using ASCT and novel drugs. Cytogenetic abnormalities and response to therapy are the main factors affecting the survival of patients.

Adult ; Aged ; Chromosome Aberrations ; Female ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; diagnosis ; genetics ; therapy ; Prognosis ; Transplantation, Autologous ; Treatment Outcome