A new form of familial platelet disorder caused by germline mutations in RUNX1 in a pedigree / 中华内科杂志

Objective: To investigate the clinical and biological characteristics of familial platelet disorder (FPD) with germline Runt-related transcription factor (RUNX) 1 mutations. Methods: Patients diagnosed with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with RUNX1 mutations from February 2016 to December 2021 in Wuhan No.1 Hospital underwent pedigree analysis and were screened for gene mutations (somatic and germline). Patients diagnosed with FPD with germline RUNX1 mutations were enrolled and evaluated in terms of clinical characteristics and biological evolution. Bioinformatics analysis was used to assess the pathogenicity of mutations and to analyze the effect of mutated genes on the function of the corresponding protein. Results: Germline RUNX1 mutations were detected in three out of 34 patients suffering from MDS/AML who had RUNX1 mutations. A pedigree of FPD with RUNX1 (RUNX1-FPD) c.562A>C and RUNX1 c.1415T>C mutations was diagnosed, and the mutations were of patrilineal origin. Bioinformatics analysis indicated that the locus at positions 188 and 472 in the AML-1G type of RUNX1 was highly conserved across different species, and that variations might influence functions of the proteins. The mutations were evaluated to be highly pathogenic. Of the nine cases with germline RUNX1 mutations: two patients died due AML progression; one case with AML survived without leukemia after transplantation of hemopoietic stem cells; four patients showed mild-to-moderate thrombocytopenia; two cases had no thrombocytopenia. During the disease course of the proband and her son, mutations in RUNX1, NRAS and/or CEBPA and KIT appeared in succession, and expression of cluster of differentiation-7 on tumor cells was enhanced gradually. None of the gene mutations correlated with the tumor were detected in the four cases not suffering from MDS/AML, and they survived until the end of follow-up. Conclusions: RUNX1-FPD was rare. The mutations c.562A>C and c.1415T>C of RUNX1 could be the disease-causing genes for the family with RUNX1-FPD, and these mutations could promote malignant transformation. Biological monitoring should be carried out regularly to aid early intervention for family members with RUNX1-FPD.

Clinical Analysis of Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical characteristics, treatment, and prognosis of patients with blastic plasmacytoid dendritic cell neoplasm(BPDCN).@*METHODS@#Clinical data of 5 patients diagnosed with BPDCN in Wuhan First Hospital and Wuhan Tongji Hospital from June 2016 to November 2021 were retrospectively analyzed.@*RESULTS@#Among the 5 patients, 3 were male and 2 were female, with a median age of 28(10-52) years old. Four patients showed obvious skin damage at the initial diagnosis; the other one showed clinical manifestations of acute leukemia rather than obvious skin damage at the initial diagnosis, but infiltrated skin when the disease relapsed after treatment. Other infiltration sites of lesions included bone marrow (2/5), peripheral blood (2/5), lymph nodes (3/5), liver and spleen (2/5). All patients had no clinical manifestation of central nervous system infiltration. Tumor cell specific immune markers CD4, CD56, CD123 were all positive, and the median Ki-67 index was 70%. TET2, ASXL1 and NRAS gene mutations were found respectively in 3 patients by next-generation sequencing technique (NGS). ALL-like, AML-like and invasive NK/T cell lymphoma-like first-line induction chemotherapy regimens were used for the patients. One patient died of severe complications during the early stage of chemotherapy, 3 patients were evaluated as CR, and 1 patient was evaluated as PR. 2 patients were recurred and progressed after induction of chemotherapy, and one of them was evaluated as CR after re-treatment. One patient received autologous hematopoietic stem cell transplantation (auto-HSCT) and got long-term survival (OS 87 months). 3 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which one died of transplantation related complications, and 2 cases survived. The median follow-up time of 4 patients with evaluable efficacy was 28.5(9-84) months, the median OS time was 31.5(10-87) months.@*CONCLUSION@#BPDCN is a highly heterogeneous malignant tumor with a poor prognosis. HSCT, especially allo-HSCT can significantly improve the prognosis of BPDCN patients.

Ixazomib-Based Regimen Followed by Autologous Hematopoietic Stem Cell Transplantation in the Treatment of POEMS Syndrome / 中国实验血液学杂志

OBJECTIVE@#To investigate the safety and efficacy of a new proteasome inhibitor Ixazomib followed by autologous hematopoietic stem cell transplantation (AHSCT) in the treatment of POEMS syndrome.@*METHODS@#The clinical manifestations, diagnosis and treatment process and follow-up results of 4 patients with POEMS syndrome who were treated with Ixazomib-based regimen combined with AHSCT in Wuhan No.1 Hospital from February 2018 to July 2020 were analyzed retrospectively. All patients were male, aged from 37-54 years old, with varying degrees of peripheral neuropathy, organ enlargement (liver, spleen or lymph nodes), circulatory overload (peripheral edema and/or pleural effusion), osteosclerosis, endocrine diseases (thyroid, gonads, etc.), skin changes (pigmentation, hemangioma, white nails, etc.), M protein, papilledema and other clinical manifestations and characteristics at the time of initial treatment. Two patients were pathologically diagnosed as hyaline vascular Castleman disease by lymph node biopsy. Three patients underwent lumbar puncture examinations and all showed elevated cerebrospinal fluid protein. All patients received at least 2 cycles of sequential AHSCT after induction chemotherapy based on ixazomib. The follow-up time was 10-28 months, and the median follow-up time was 16 months.@*RESULTS@#All cases survived. The complications were controllable during the treatment. Moreover, the clinical symptoms related to the disease were improved to a certain extent after the treatment. The levels of vascular endothelial growth factor (VEGF) showed a gradual decline.@*CONCLUSION@#Ixazomib combined with AHSCT is safe and effective in the treatment of POEMS syndrome.

Effect of Expression Regulation of Mitotic Control Protein DIS3 on Proliferation of 3 Cell Lines of Human Myeloma / 中国实验血液学杂志

OBJECTIVE@#To explore the effect of the expression regulation of mitotic control protein DIS3 on the proliferation ability of 3 cell Lines of human myeloma.@*METHODS@#Human myeloma cell lines NCI-h929, RPMI 8226 and U266B1 were selected as study objects, and the over-expression vector of DIS3 gene and DIS3-siRNA were designed and constructed, respectively. The cell experiments were divided into 5 groups: control, DIS3 over-expression-empty vector, DIS3-siRNA negative control, DIS3 over-expression and DIS3-siRNA group. After culture for 24 h, 48 h and 72 h, the proliferation capacity of these three cell lines was measured by MTT assay. And cell samples were collected after culture for 72 h, the expression of proliferation cell nuclear antigen (PCNA) was detected by RT-qPCR and Western blot.@*RESULTS@#MTT assay results showed that the proliferation capacity of cells in DIS3 over-expression group was significantly reduced, as compared with the DIS3 over-expression-empty vector group at the same time point (24, 48 or 72 h) (P＜0.05, P＜0.01). Compared with DIS3-siRNA negative control group at the same time point (24, 48 or 72 h), the proliferation capacity of cells in the DIS3-siRNA group significantly increased (P＜0.05, P＜0.01). The results of RT-qPCR and Western blot showed that the mRNA and protein expression levels of PCNA in cells of DIS3 over-expression group were significantly reduced, as compared with DIS3 over-expression empty vector group (P＜0.01). Compared with the DIS3-siRNA negative control group, the mRNA and protein expression of PCNA in the cells of DIS3-siRNA group very significantly increased (P＜0.01).@*CONCLUSION@#Over expression of DIS3 can significantly reduce the proliferation ability of 3 cell lines of human myeloma, which may be closely related with reducing PCNA expression.

Investigation and analysis of the working status and development situation of psychotherapy in psychiatric hospitals / 上海交通大学学报（医学版）

Objective·To understand the current situation of psychotherapy applied and relevant personnel's working in psychiatric hospitals, and provide advice to facilitate and promote the integrated service team building of domestic mental health institutions and the industry development of psychological treatment. Methods·Ninety-six psychiatric hospitals in China were selected and self-compiled questionnaire was used during the investigation. The actual feedback was collected from 52 hospitals in 25 provinces. Results·① According to the classification criteria of ICD-10 mental disorder, patients mainly suffered from schizophrenia, schizotypal disorder and delusional disorder, followed by affective disorder, in the psychiatric hospitals. ② There were 50 (96.2％) hospitals with psychological outpatient clinics, and 37 (71.2％) hospitals were equipped with mental wards. ③ The main types of patients who came to the psychology department in the psychiatric hospitals were emotional disorders, neurosis, stress-related and physical form disorders. ④ The composition of psychotherapists was 6 physicians, 2 clinical psychologists, and 1 nurse. ⑤ The top five psychotherapy techniques used by the psychiatric hospitals were cognitive therapy, supportive psychotherapy, behavioral therapy, group therapy, and family therapy. ⑥ 44.2％ of the practitioners working in this filed thought that the income had been too low if they only engaged in psychological treatment. Conclusion·In the staffing of mental health agency, compared to previous studies, the number of the psychology specialists increases, but it still makes up a small percentage, which does not match the needs of outpatient and ward patients. Psychological practitioners who rely on psychological treatment alone are in a lower income, and the gap between the expected income and actual income is too large. Government, health administration departments and hospitals should provide more support to psychological services and promote the development of institutions and personnel.

Application value of procalcitonin and immune inflammatory factors for prediction of bacteraemia in patients with hematologic malignancy combined with febrile neutropenia / 中国实验血液学杂志

This study was purposed to evaluate the diagnostic value of procalcitonin (PCT), C-reactive protein, interleukin-6 (IL-6), serum amyloid A (SAA) for bacteremia in patients with hematologic malignancy combined with febrile neutropenia. The total of 297 patients with hematologic malignancy combined with febrile neutropenia were analyzed retrospectively from 1253 patients admitted to West China hospital of Sichuan University from March 2011 to October 2012. They were divided into sepsis group (n = 95) and non-sepsis group (n = 202) according to blood culture. The results showed that the levels of PCT, CRP, IL-6 and SAA in sepsis group were higher than those in non-sepsis group, and there was statistically significant difference between these two groups (P < 0.05). The PCT had an AUC value of 0.974 (P < 0.05), and obviously higher than that of CRP (AUC = 0.681, P < 0.05), IL-6 (AUC = 0.661, P < 0.05) and SAA (AUC = 0.605, P < 0.05). When PCT had cut-off value of 1.06 ng/ml, sensitivity of 95.8%, specificity of 92.1%, and the Youden indicator of 0.879, the negative and positive predictive values were 97.8% and 85.0% respectively, the negative and positive likelihood ratios were 0.05 and 12.5 respectively, and all significantly higher than that of CRP, IL-6 and SAA. It is concluded that for patients with hematologic malignancy combined with febrile neutropenia and bacterial infection, the diagnostic value of serum PCT is superior to that of immune inflammatory factors (CRP, IL-6 and SAA), the PCT can predict the bacterium infection, provide laboratory evidence for rational antimicrobial drug usage and mortality reduction.

GenoType MTBDRplus assay for rapid detection of rifampin and isoniazid resistance in Mycobacterium tuberculosis in Sichuan / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the molecular and epidemic characteristics of rifampin (RFP) and isoniazid (INH) resistance of mycobacterium tuberculosis (MTB) in Sichuan.</p><p><b>METHODS</b>GenoType reg; MTBDRplus Assay GTplus was used to examine 68 clinical isolates of MTB and 105 clinical specimens for mutations in rpoB, katG and inhA genes related to RFP and INH resistance.</p><p><b>RESULTS</b>Of the 151 valid tests obtained, 44 (29.14%) and 26 (17.22%) showed drug resistance and multidrug resistance, respectively. Resistance to RFP and INH was found in 21.85% (33/151) and 24.50% (37/151) of the samples, respectively. The most prevalent mutations were rpoB S531L, katG S315T1 and inhA C-15T. The multidrug resistance rate in the sputum specimens was significantly higher than that in the non-respiratory samples (19.35% vs 7.41%).</p><p><b>CONCLUSION</b>Drug-resistant, especially multidrug-resistant tuberculosis is highly prevalent in Sichuan. The multidrug-resistant bacteria most frequently show rpoB S531L combined with katG S315T1 mutations, suggesting the necessity of developing rapid clinical identification methods for drug-resistant MTB to control the spread of the resistant strains.</p>

Challenges for rear hospital care of Wenchuan earthquake casualties: experience from West China Hospital / 中华创伤杂志(英文版)

To review the challenges and countermeasures in the hospital care for Wenchuan earthquake casualties and draw lessons for the protective response in the future. Medical records and laboratory findings of the victims admitted in West China Hospital (WCH) were retrospectively analyzed. Related data were compared between beforemath and aftermath of the earthquake and between WCH and frontier county hospitals. One thousand and thirty-one earthquake survivors were hospitalized, 1 358 victims underwent surgery and 142 victims were transferred to intensive care unit. The incidence of infection, crush syndrome and multiple organ dysfunction syndrome (MODS) was 39.6%, 20.7% and 2.3% respectively. Wound classification showed that the incidence of extremity damage was 72%, while the incidence of chest trauma, abdominal trauma and brain trauma was less than 10% respectively. Isolating rates of environmental pathogens were increased in the aftermath of earthquake, and the spectrum of the pathogens and related antibiotic sensitivities were quite different from those in the beforemath of earthquake. The social economic and population conditions in the earthquake-stricken areas affected the composition of the victims and the geographic features restricted the efficiency of rescue. Trauma-induced MODS, crush syndrome and severe infections all constituted the dilemma for the hospital care, to resolve whether the multidiscipline team work was proved to be an optimizing choice. For a more effective disaster protective response in the future, the study on rescue plan and the ladder therapies for massive casualties should be potentiated.

A cross-sectional survey on personality disorder in mental disorder outpatients in Shanghai / 中华流行病学杂志

Objective To study the prevalence and risk factors for personality disorder (PD)outpatients attending in for psychiatric and psychological counseling in Shanghai. Methods 3075 subjects were sampled by systematic sampling method from outpatients in psycho-counseling clinics and psychiatric clinics in Shanghai Mental Health Center. Based on DSM- Ⅳ criteria, personality disorders were assessed by both questionnaires (personality diagnostic questionnaire, PDQ-4+) and interviews (structured clinical interview for DSM- Ⅳ Axis Ⅱ , SCID- Ⅱ ). Logistic regression analysis was performed to determine the significant independent contributor to PD. Results 71.3% of the outpatients were found having pathological personality by using questionnaire of self rating PD scale. 982 outpatients (31.9%) met criteria for at least one personality disorder by using structured clinical interview. Younger age (OR= 1.8, 95% CI: 1.5-2.1 ), single or divorced (OR = 1.6, 95%CI:1.4-1.9), psychological counseling outpatients (OR=1.2, 95%CI: 1.1-1.3), mood and outpatients with neurosis disorders (OR = 1.7, 95%CI: 1.4-2.0) were more frequently assigned as personality disorders. Data from logistic regression analysis showed that patients of tender age, not nurtured and raised by their parents, with introvert characters were related risk factors of PD. Conclusion High prevalence rate of PD was found in this sample of Chinese outpatients, especially in thosepsychological counseling outpatients with mood or neurosis disorders. More attention should be paid to the recognition and intervention of PD in outpatients with mental disorders.

Association of the Pro12Ala polymorphism in peroxisome proliferators activated receptor-gamma gene with rheumatoid arthritis in Sichuan Province of China / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association of the Pro12Ala variant in peroxisome proliferators-activated receptor gamma (PPAR gamma) gene with rheumatoid arthritis.</p><p><b>METHODS</b>The genotypes of the Pro12Ala variant in the PPAR gamma gene were determined by polymerase chain reaction-restriction fragment length polymorphism in 421 unrelated subjects of the Han population in the Sichuan Province of China, including 207 subjects with rheumatoid arthritis and 214 subjects without the disease. The clinical data were also collected and analyzed.</p><p><b>RESULTS</b>The allele frequencies in the case and control groups were 98.79%, 95.79% for allele P and 1.21%, 4.21% for allele A; the genotype frequencies were 97.58% and 91.59% for PP, 2.42% and 8.41% for PA, and 0 for AA. The A allele frequency was much lower in the RA group than that in the control group.</p><p><b>CONCLUSION</b>The above data showed that the Pro12Ala variant of the PPAR gamma was associated with rheumatoid arthritis. The A allele might be a protective factor for RA. The Pro12Ala polymorphism in the PPAR gamma gene in Sichuan Han population is similar to that in other populations in China, but different from that in European and American populations.</p>

Effects of ruthenium red on body temperature in rats with lipopolysaccharide-induced fever / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of ruthenium red (RR) on the body temperature of rats with lipopolysaccharide (LPS)-induced fever and investigate the possible mechanism.</p><p><b>METHODS</b>Rat models of fever were established with lipopolysaccharide and the effects of RR at different doses were observed on the body temperature of the rats and the content of TRPV4 in the hypothalamus.</p><p><b>RESULTS</b>Compared with those in LPS group, the rats with LPS-induced fever receiving RR treatment showed a dose-dependent lowering of the body temperature. The rats with RR treatment had lower body temperature than those with saline injection. The content of TRPV4 in the saline group was significantly higher than that in RR+LPS and RR group.</p><p><b>CONCLUSIONS</b>RR inhibits LPS-induced fever in rats and regulates the hypothalamal expression of TRPV4 channels, which may participate in the maintenance of normal body temperature.</p>

The action of Pseudomonas aeruginosa biofilms in intrinsic drug resistance / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>There is a growing interest in studying the relationship between intrinsic resistance and biofilms resistance to drugs. However, the relationship still remains unclear in the macroscopic bacterial growth. Our study is to illuminate the change of bacterial drug resistance of gyrA mutant and active efflux pump during the development of Pseudomonas aeruginosa (P. aeruginosa) biofilms.</p><p><b>METHODS</b>The strains of type II topoisomerase gene mutant (gyrA mutant) and multidrug resistance (MDR) efflux pump were clinical isolates and detected by polymerase chain reaction (PCR). The process of bacterial biofilms development was observed by scanning electron microscope. Triparental mating experiments were performed to transfer report gene of green fluorescent protein (GFP) into P. aeruginosa biofilms strains and followed by analysis of bacterial survival rate between intrinsic resistance and biofilms resistance.</p><p><b>RESULTS</b>The fluorescent strains with pGFPuv could develop mature biofilms on Teflon surface. Before a period of 72 hours, the survival rate of biofilms bacteria and intrinsic resistance strains in ciprofloxacin solution was significantly different (P < 0.05). The survival number of intrinsic resistance strains (gyrA mutation and active efflux pump) was illustriously higher than biofilm strain in the initial stage of biofilms development. After 72 hours incubation, there was no clearly difference between mutants and biofilms strains in the survival rate (P > 0.05). The carbonyl cyanide m-chlorophenylhydrazone and azithromycin could significantly reduce the drug resistance of biofilm strains and efflux pump strains.</p><p><b>CONCLUSIONS</b>In the development of P. aeruginosa biofilms, the strains of gyrA mutation and MDR efflux could be conferred with new level of drug resistance. When co-cultured mutated strains with biofilm strains, biofilms may play a major role in bacterial resistance. But after 72 hours incubation (a mature biofilms had been developed), there was no clearly difference between the number of mutant strains and biofilm strains.</p>

Comparison of different diagnostic tests for antinuclear antibodies / 中华风湿病学杂志

Objective To compare and evaluate the usefulness of diagnostic tests of IFA with HEp-2 cell substrate and ELISA coated with purified nuclear antigens for ANA in SLE.Methods Sera derived from 226 SLE cases and 183 healthy controls were tested for ANA and all parameters were compared such as sensi- tivity,specificity,accuracy,positive predictive value,negative predictive value,positive likelihood ratio,nega- tive likelihood ratio,result consistency,rank correlation coefficient and kappa of ANA detected by IFA and ELISA.Accuracy was evaluated by ROC for two methods.All 36 samples with different results from two meth- ods were detected for ENA.The correlation of titer to A ratio of different patterns as studied.Results The sensitivity of IFA and ELISA was 91.15% and 92.04% respectively for SLE patients,specificity was 96.17% and 92.90%,accuracy was 93.40% and 92.42%,positive predictive value was 96.71% and 94.12%,negative predictive value was 89.80% and 90.43%,no significant difference was found between the two methods (P＞0.05).No significant difference was found in accuracy of both methods by ROC (P=0.409).Good agreement was found between two methods with rank correlation coefficient (R=0.823) and kappa (k=0.825).All of 36 samples with different ANA results from two methods were detected for ENA.In 14 cases with IFA positive and ELISA negative,the titer of one case was up to 1:1000 and the pattern was Golgi by IFA,the titers of the rest were about cutoff level and the pattern were granular and nucleolus mostly.In 22 cases with IFA nega- tive and ELISA positive,11 cases of them had the A ratio ranged from 2.67～30.5.Positive rate of ENA was 14.29% in 14 cases with IFA positive and ELISA negative,68.18% in 22 eases with IFA negative and ELISA positive and the difference was significant (P＜0.01).Poor correlation of titer to A ratio for granular pattern samples (R=0.083),but good correlation for homogeneous pattern was found (R=0.595).Conclusion IFA as the recommended detecting method for ANA is intuitive and can provide more information by different pattem than ELISA but it needs fluorescence microscope and experienced technician.While ELISA is very simple and the concentration of ANA can be evaluated by A ratio value.ELISA can be a substitute method for ANA be- cause both IFA and ELISA have high sensitivity,specificity,accuracy,agreement rate,kappa and rank correla- tion coefficient.In addition,ELISA is more accessable for screen test because of low rate of false negative re- sult.Result of ELISA is more accurate if new and uncommon antigens are coated such as Golgi and nucleolus. The new work flow in which ELISA is used to screen out the positive ANA samples and IFA is used then to detect the nuclear pattern of ANA can save time,cost,and in turn improve work efficiency.

A systematic review of diagnostic value of different methods to antinuclear antibody for SLE / 中华检验医学杂志

Objective To evaluate the different methods,such as indirect immunefluorescence assay with HEp-2 cell substrate(HEp-2-IFA)or with liver substrate(Liver-IFA)and ELISA,for determining antinuclear antibody(ANA)as an indicator of SLE.Methods Medline,Embase and CBM were searched from 1990 to 2005.Thirteen articles that described ANA as an indicator of SLE were selected according to specified inclusion criteria.All data from these articles were evaluated systematically by RevMan software.Results The odds ratios(OR)of ANA detected by HEp-2-IFA or Liver-IFA or ELISA were 100.55(P