[Clinical Characteristics and Survival Analysis of Carbapenem-Resistant Pseudomonas Aeruginosa Colonized or Infected Patients with Hematological Disorders].

OBJECTIVE: To observe the clinical characteristics and impact on mortality of carbapenem-resistant Pseudomonas aeruginosa (CRPA) colonized or infected patients with hematological disorders in order to provide evidence for the prevention and treatment of CRPA. METHODS: The patients who were colonized or infected with CRPA in the Department of Hematology of The First Affiliated Hospital of Zhejiang Chinese Medical University from January 2020 to March 2021 were selected as the research subjects, the clinical data such as hospitalization time, primary disease treatment regimen, granulocyte count, previous infection and antibiotic regimen of these patients were analyzed, meanwhile, antibiotic regimen and efficacy during CRPA infection, 30-day and long-term survival were also analyzed. RESULTS: A total of 59 patients were included in this study, and divided into CRPA infection group (43 cases) and CRPA colonization group (16 cases). Univariate logistic regression analysis showed that ECOG score (P =0.003), agranulocytosis (P <0.001), and exposure to upper than 3rd generations of cephalosporins and tigecycline within 30 days (P =0.035, P =0.017) were the high-risk factors for CRPA infection. Multivariate logistic regression analysis showed that ECOG score of 3/4 ( OR=10.815, 95%CI: 1.260-92.820, P =0.030) and agranulocytosis ( OR=13.82, 95%CI: 2.243-85.176, P =0.005) were independent risk factors for CRPA infection. There was a statistically significant difference in cumulative survival rate between CRPA colonization group and CRPA infection group ( χ2=14.134, P < 0.001). Kaplan-Meier survival analysis showed that the influencing factors of 30-day survival in patients with CRPA infection were agranulocytosis (P =0.022), soft tissue infection (P =0.03), and time of hospitalization before CRPA infection (P =0.041). Cox regression analysis showed that agranulocytosis was an independent risk factor affecting 30-day survival of patients with CRPA infection (HR=3.229, 95%CI :1.093-3.548, P =0.034). CONCLUSIONS: Patients with hematological disorders have high mortality and poor prognosis after CRPA infection. Bloodstream infection and soft tissue infection are the main causes of death. Patients with high suspicion of CRPA infection and high-risk should be treated as soon as possible.

Multiple risks analysis for aplastic anemia in Zhejiang, China: A case-control study.

To understand the risks associated with aplastic anemia (AA) in 4 cities of Zhejiang Province, China, with special focus on the joint contributions of multiple risks.Based on an Electronic Data Capture (EDC), a case control study was carried out. Data regarding socio-demographic, diseases history, living habits, and exposures to toxic substances, etc., were collected through survey questionnaires. t Test, chi-square test, or non-parametric rank sum test, and univariate and multivariate Logistic regression analysis were conducted to analyze data.The univariate logistic regression analysis results indicated that among all study participants (n = 1802), AA was associated with over 30 risks, in terms of their individual behaviors, daily and environmental exposures, diseases history, and family history. Multivariate logistic regression analysis further confirmed that the independent risks related to AA included presence of chemical factory within 3 km of living residence (odds ratio [OR] = 8.73, 95% CI: 1.42-53.74, P = .019), living in a newly decorated house/apartment (OR = 25.37, 95% CI: 4.44-144.81, P < .001), vegetarian diet (OR = 131.60, 95% CI: 3.45-5020.16, P = .009), preference of sugar (OR = 89.38, 95% CI: 7.22-1106.44, P < .001), preference of oily food (OR = 55.68, 95% CI: 5.12-605.26, P = .001), drinking lake water or pond water (OR = 58.05, 95% CI: 3.21-1049.81, P < .001), habit of staying up late (OR = 11.87, 95% CI: 3.43-41.02, P < .001), infection history (OR = 10.08, 95% CI: 2.75-36.93, P < .001). Result of receiver operating characteristic curve (ROC) analysis on the joint contribution of multiple risks indicated that AA was 13.835 times likely to occur when exposed to ≥1 risks than those exposed to 0 risks (95% CI: 9.995-19.149).Our study results demonstrated a comprehensive epidemiological pattern, in which the joint contributions of individual inherited health status, environment exposure, and individual behaviors lead to the occurrence of AA.

[Endocrine and metabolic features of female children with Prader-Willi syndrome: an analysis of 4 cases].

This article reports the clinical features and endocrine and metabolic features of 4 children with Prader-Willi syndrome (PWS). All the patients were female and aged 6-12 years at diagnosis. All of them had clinical manifestations of obesity, unusual facies, developmental retardation, and intellectual disability. Genetic detection showed that 2 patients had paternal deletion of the 15q11.2-q13 region, one patient had maternal autodiploid in the 15q11.2-q13 region, and one patient had no abnormality in the 15q11.2-q13 region. All patients had varying degrees of endocrine and metabolic disorders: 2 patients had short stature, among whom one had delayed appearance of secondary sex characteristics and the other one had type 2 diabetes; one patient had insulin resistance and no mammary gland development; one patient had a body height of P3-P10 and precocious puberty. Patients with PWS have various endocrine disorders, so long-term endocrine follow-up and management is very important.

Successful use of rituximab in platelet transfusion refractoriness in a multi-transfused patient with myelodysplastic syndrome.

A 61-year-old man with newly diagnosed INT-1 risk myelodysplastic syndrome--refractory cytopenia with multilineage dysplasia (MDS-RCMD) was not responsive to treatment, such as androgen, thalidomide, granulocyte--colony stimulating factor (G-CSF) combined with erythropoietin (EPO), interleukin-11 (IL-11) and thrombopoietin (TPO), and became transfusion dependent. Due to repeated blood transfusions, he developed platelet transfusion refractoriness (PTR) to platelets from cross-matched donors as well as random donors. Anti-HLA class I antibodies were positive with enzyme-linked immunosorbent assay; however, HLA-compatible platelet products were unavailable. PTR was unresponsive to high-dose immunoglobulin and plasma exchange. The patient was then treated with rituximab 375 mg/m(2) on days 1 and 8, and 100 mg total dose on days 15 and 22. Already after the first dose of rituximab, the patient was able to received successful platelet transfusion from all donors. Therefore rituximab may be considered as a potential therapy for PTR.

Combined use of Chinese medicine with allogeneic hematopoietic stem cell transplantation for severe aplastic anemia patients.

OBJECTIVE: To determine the effect of combined treatment with Chinese medicine (CM) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) on patients with severe aplastic anemia (SAA). METHODS: Eleven patients were treated with CM plus allo-HSCT. Nine patients received a conditioning regimen consisting of fludarabine (Flu), anti-thymocyte globulin (pig ALG), or anti-lymphocyte globulin (Rabbit ATG) and cyclophosphamide (CY), and two patients received pig ALG and CY. All patients were treated with Kidney (Shen)-reinforcing, blood-activating, and stasis-removing (KBS) herbal preparation beginning at 1 week before transplantation and ending at 8 weeks after transplantation. Chimerism status was assessed by analyzing short tandem repeat (STR) polymorphisms. RESULTS: All patients recovered hematopoietic function and none had graft failure. The median number of days required for the absolute neutrophil count (ANC) increased to >0.5×10(9)/L was 15 days (12-22 days) and for spontaneous platelet recovery to >20×10(9)/L without post-transplantation transfusion was 17 days (15-27 days). Nine patients were long-term survivors and achieved full donor chimerism. The overall cumulative incidence of acute graft versus host disease (GVHD) grades I-II and III-IV was 18.2% (2/11) and 9.1% (1/11), respectively. The overall accumulated incidence of chronic GVHD was 27.3% and all patients had limited chronic GVHD. At a median follow-up time of 32 months (range: 12-97 months), 9 patients were still alive. The estimated 5-year overall survival (OS) rate was 81.8%. The incidence of treatment-related mortality, 2-year post-transplantation, was 18.2%. Two patients died from GVHD after transplantation. CONCLUSION: Treatment with the KBS formulation may reduce the rate of graft failure and treatment-related mortality and improve the rate of OS in SAA patients with allo-HSCT.

[Analysis of clinical features of traditional Chinese medicine symptoms and syndromes of 220 patients with chronic aplastic anemia].

OBJECTIVE: To study Chinese medicine (CM) syndrome types of chronic aplastic anemia (CAA) patients and the distribution laws of typical CM symptoms in different genders. METHODS: From June 2002 to June 2012, 220 CAA outpatients/inpatients at Department of Hematology, Zhejiang Chinese Medical Hospital were recruited. Patients' symptoms and signs, as well as four diagnostic information at the first onset were collected. CM syndrome differentiation was performed. The syndrome types and typical symptoms were analyzed. RESULTS: (1) In the 220 CAA patients, there were 121 cases of Shen yang deficiency syndrome (55.0%), 18 of Shen yin deficiency syndrome type (8.18%), 81 cases of Shen yin-yang deficiency syndrome (36.82%). (2) The distribution of typical symptoms: fatigue and shortness of breath (77.12% males and 73.53% females), pale complexion (64.41% males and 57.84% females), low temperature of four limbs (12.71% males and 26.47% females), spontaneous perspiration and night sweating (32.20% males and 26.47% females), dry mouth and throat (6.78% males and 6.86% females), feverish feelings in palms and soles (14.41% males and 20.59% females), loose stool (6.78% males and 2.94% females), petechiae and ecchymosis (42.37% males and 43.14% females). CONCLUSIONS: Shen yang deficiency syndrome was most often seen in CAA patients at the initial diagnosis, followed by Shen yin-yang deficiency syndrome. Shen yin deficiency syndrome was the least seen. In CM symptoms, fatigue and shortness of breath were most common seen, followed by pale complexion, skin petechia and ecchymosis.

Bone marrow angiogenesis in patients presenting with differential Chinese medicine syndrome: correlation with the clinico-pathological features of aplastic anemia.

OBJECTIVE: To explore differences in bone marrow angiogenesis seen in aplastic anemia (AA) patients presenting with differential Chinese medicine (CM) syndrome, and to correlate these differences with clinical pathology. METHODS: Thirty-five patients were enrolled, including 18 with "yang deficiency syndrome" and 17 with "yin deficiency syndrome." Bone marrow biopsies and serum were collected. Microvessel density (MVD) and positive expression of vascular endothelial-derived growth factor (VEGF) were detected by immunohistochemisty. Hypoxia inducible factor -1α (HIF-1α), and VEGF expression were assayed by enzyme-linked immunoabsorbent assay (ELISA), serum lactate dehydrogenase (LDH) was tested by enzyme method and liquid chip technology was used to detected the expression of interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-γ and tumor necrosis factor (TNF)-α. RESULTS: Counts for leukocytes, absolute neutrophils and platelets in "yin deficiency syndrome" were lower than those found in "yang deficiency syndrome" (P<0.05). MVD and VEGF expression, and the positive rate of CD34 and VEGF in bone marrow were lower in AA, especially in "yin deficiency syndrome" (P<0.01 or P<0.05). "Yin deficiency syndrome" displayed decreased VEGF and LDH expression, and enhanced expression of HIF-1α as compared to "yang deficiency syndrome" (P<0.05). Levels of IL-4 and IL-6 were higher in AA (P<0.01), but IL-10 was decreased (P<0.05). High TNF-α expression was seen in "yang deficiency syndrome" and IFN-γ expression was decreased in "yin deficiency syndrome" as compared with normals (P <0.01 and P<0.05, respectively). CONCLUSION: AA patients have lower MVD than normals, especially in "yin deficiency syndrome." MVD might differentially correlate to disease severity, and could be dependent on bone marrow or serum VEGF expression and LDH. Additionally, IL-2, IL-10, IL-4 and IFN-γ were negatively associated while IL-6 and TNF-α were positively associated with MVD.

Multi-central clinical research into treating 80 cases of chronic thrombocytopenia with qi-supplementing and yin-nourishing therapy and western medicine.

OBJECTIVE: To probe the effects of qi-supplementing and yin-nourishing therapy (blood-increasing decoction and blood generating powder) on chronic thrombocytopenia. METHODS: Two hundred patients with chronic thrombocytopenia were randomly divided into control (n = 100) and test groups (n = 100) with Amino-polypeptide as a basic treatment for both. Test group patients consumed a blood-increasing decoction and blood-generating powder for 1-3 months. Improvements in platelet counts and TCM syndrome were observed. RESULTS: One hundred and sixty-four (80 in the test group and 84 in the control group) of 189 total participants were treated for 3 months. The total effective rate in improving TCM syndrome was 95.00% in the test group and 79.76% in the control group (P < 0.05). There was significant difference (P < 0.05) in the accumulated score of TCM syndrome between the two groups treated at different time points. The total effective rate of platelet counts was 86.25% in the test group and 59.52% in the control group (P < 0.05). There was a significant difference in platelet counts before and after treatment in the two groups (P < 0.05). There was no significant differences in platelet count between the two groups treated for 1-2 months; however, a significant difference was found between the two groups after treatment for 3 months (P < 0.05). CONCLUSIONS: After a 3-month treatment of chronic thrombocytopenia patients with qi-supplementing and yin-nourishing therapy, TCM syndrome was improved and platelet counts increased with no obvious side effects, and the quality of life of the participants was enhanced with noticeable long-term curative effects.

Treatment of severe aplastic anemia by immunosuppressor anti-lymphocyte globulin/anti-thymus globulin as the chief medicine in combination with Chinese drugs.

OBJECTIVE: To study the therapeutic effect of combined therapy with Chinese drugs and immuno-suppressors, mainly anti-lymphocyte globulin/anti-thymus globulin (ALG/ATG), for the treatment of severe aplastic anemia (SAA), the efficacy associated factors and adverse effects as well. METHODS: A retrospective analysis was conducted on 65 patients with SAA treated by combined therapy which was supplemented with cyclosporin A, androgen, hematopoietic growth factor, etc. RESULTS: Of the 57 patients followed-up, 26 (45.6%) were basically cured, 15 (26.3%) remitted, and 8 (14.0%) improved markedly, the total effective rate being 85.9%. By separately comparing with a single item of clinical data, it was shown that the therapeutic effectiveness was correlated, to a certain extent, with age, illness duration, neutrophil count, and bone marrow proliferation in patients before treatment, as well as with infection that occurred in the follow-up period. It was obviously higher in patients with peripheral neutrophil count > 0.5 x 10 10(9)/L (P<0.05). Various degrees of serum sickness-like reactions occurred in the treatment of 36 patients, including fever in 36 (63.2%), skin rash in 8 (14.0%), and musculoskeletal pain in 5 (8.8%). CONCLUSIONS: The therapeutic effect of combined therapy with Chinese drugs and ALG/ATG in treating SAA could be affirmed, showing some superiority as compared with Western medicine alone. The patients' age, duration of illness, neutrophil count, and bone marrow proliferation before treatment, and degree of infection that occurred could affect the therapeutic efficacy to a certain extent. Adverse reactions resulting from the combined therapy are less, showing the toxicity reducing and effect enhancing action of Chinese drugs.

Effects of phytoestrogen on mitochondrial structure and function of hippocampal CA1 region of ovariectomized rats.

The present study was undertaken to evaluate whether estrogen deprivation might lead to mitochondrial alteration of hippocampal neurons of ovariectomized (OVX) rats, and to evaluate the protective effect of estrogen and phytoestrogen on the mitochondrial alteration. First, OVX rats were used to mimic the pathologic changes of neurodegeneration of postmenopausal female, and we looked into the alteration of the mitochondrial ultrastructure and ATP content of hippocampal CA1 region after ovariectomy on different phase by transmission electron microscope (TEM) and reversed-phase high-performance liquid chromatography (HPLC), and found the best phase points of the alteration of the mitochondrial ultrastructure and ATP content. Next, estrogen and phytoestrogen were administered to the OVX rats for the protective effects on the mitochondrial ultrastructure and ATP content. Meanwhile, the density, size, shape, and distribution parameters of mitochondrial ultrastructure were analyzed according to the morphometry principle. The experimental results presented that (1) The alteration of mitochondrial ultrastructure elicited by ovariectomy worsened with the days going on, and the changes were the most noteworthy in volume density (Vv), average surface area (S), specific surface area (delta), and particle dispersity (Clambdaz) on 12th day (P < 0.05 or P < 0.01). Moreover, there was no statistical significance of the numerical density (Nv) among the five groups in the first step experiment. (2) The treatment with estrogen, genistein (Gs), and ipriflavone (Ip) significantly reversed the effect elicited by ovariectomy on Vv, S, delta, Clambdaz, Nv, and particle average diameter (D) of mitochondria of hippocampal CA1 region (P < 0.05). (3) Furthermore, ATP content of hippocampal CA1 region after ovariectomy declined significantly on 7th day (P < 0.05), and estrogen and phytoestrogen could reverse the alteration (P < 0.05). Taken together, these results revealed that phytoestrogen may have a protective role against the neurodegeneration after menopause via protecting mitochondrial structure and functions. Phytoestrogen may be a good alternative as a novel therapeutic strategy for menopausal syndrome.

[Immune response of dendritic cells capturing antigens from apoptotic U937 cells induced by artesunate].

The objective of study was to investigate whether U937 cells-loaded dendritic cells (DCs) could induce anti-leukemic immune activity. The apoptosis of U937 cells was induced by artesunate (ART). DCs derived from peripheral blood mononuclear cells of health donors were loaded with apoptotic U937 cells, and induced to maturation in the presence of TNF-alpha. Matured DCs were cocultured with autologous T-lymphocytes, and combined with IL-2 in order to induce the leukemia-specific CTL. The phenotypes of DCs and T lymphocytes were tested by flow cytometry. The ability of DC capturing antigens was measured by Dextran-FITC endocytosis. The IL-12p70 level was assayed by ELISA kit. The proliferation of CTL and CTL activity were measured by MTT assay. The results showed that the apoptotic rate of the U937 cells was 51.2% when U937 cells were induced by 1 microg/ml ART for 48 hours in vitro. DCs had the most powerful ability of endocytosis in its immature phase. Apoptotic U937 cells could not induce the features of DC maturation, and apoptotic U937 cell-pulsed immature DCs could be matured with TNF-alpha. The IL-12p70 level secreded by apoptotic U937 cell-loaded mature DCs (mDC-(Apo)U937) was higher than that of non-loaded mDC. The proliferation of autologous T lymphocytes co-cultured with mDC-(Apo)U937 was significantly remarkable and the content of CD8(+) CTL was significantly higher in comparison with any other groups. CTL induced by mDC-(Apo)U937 had stronger killing effect on U937 cells than NB4 (p < 0.01). It is concluded that the mDC-(Apo)U937 can effectively generate T cell-mediated dendritic antileukemic responses in vitro.

Treatment of 37 patients with refractory idiopathic thrombocytopenic purpura by shengxueling.

OBJECTIVE: To explore the clinical effect and possible mechanism of Shengxueling (SXL), a Chinese medical preparation mainly consisting of ginseng saponins, in treating refractory idiopathic thrombocytopenic purpura (ITP). METHODS: The selected 69 patients with ITP were randomly assigned to two groups, the 37 patients in the treated group were treated orally by SXL with the dose for adult as 60 mg twice a day for two weeks. Then when no marked rise of platelet count after that, the dose would be doubled and administered for another two weeks. Then the dose could be gradually reduced to the initiative level in patients who responded to the treatment, and if they did not, the treatment was regarded as ineffective and be terminated. The 32 patients in the control group were treated with ampeptide elemente instead of SXL, 0.4 g each time three times a day in the first two weeks, and, if that was ineffective, 0.2 g would be added each time and 1.8 g would be administered a day for two more weeks. Four weeks' treatment was regarded as one therapeutic course for both groups and the observation lasted for two successive courses in patients showing positive reslonse. RESULTS: In the 37 patients in the treated group, markedly effective was obtained in 7 (19.0%), favorably effective in 15 (40.5%), improved in 5 (13.5%) and ineffective in 10 (27.0%), the total effective rate being 59.5%. The corresponding number in the 32 patients in the control group was 4 (12.5%), 6 (18.8%), 3 (9.4%), 19 (59.4%) and 31.3% respectively. Comparison showed the difference in therapeutic efficacy between the two groups was significant (P<0.05). CONCLUSION: SXL is a safe and effective preparation for treatment of ITP, showing an immediate effect which is obviously superior to that of ampeptide elemente with less adverse effect.

[Cystic degeneration in liver injury induced by CCl4 in SD rats].

OBJECTIVE: To explore the hepatic injury induced by CCl4in SD rat. METHOD: 40 SD rats were allocated to male and female group, consisting of 20 animals/sex/group. SD rats were given at 2 mL x kg(-1) of 10% CCl4 through celiac injection per 3 day for 12 days. All rats were killed by anaesthesia of ethyl ether and bleeding through abdominal aorta at 12th day. Liver tissue was fixed in 10% neutral formalin, embedded in paraffin, cut at a nominal thickness of 3 microm, stained with hematoxylin and eosin ( H&E) , evaluated at by microscopic examination. RESULT: 19 cases with local necrosis, 8 cases with fatty degeneration, 9 cases with cystic degeneration and 2 cases with fibrosis were seen in group male. 20 cases with local necrosis, 9 cases with fatty cases degeneration, 1 case with cystic degeneration and 1 case with fibrosis were seen in group female. The incidence of cystic degeneration in male group was found significantly higher than that in female group (P < 0. 05) , but the incidence of other lesions was no significant difference between male and female group. CONCLUSION: CCl4 induces local necrosis , fatty degeneration, fibrosis and cystic degeneration in SD rat. The incidences of local necrosis , fatty degeneration and fibrosis were no significantly difference between male and female rat, but the incidence of cystic degeneration in male rats was significant higher than that in female rats.

[Target chemotherapy of intestinal nematode infection in area with low endemicity].

OBJECTIVE: To evaluate the control measures for intestinal nematodiasis in endemic area with low prevalence and intensity of infection. METHODS: Target chemotherapy was carried out in high-risk population based on the epidemiological characteristics such as age and clinical findings. Albendazole and mebendazole were administered each 200 mg once daily every year for 3 or 5 years. Saturated brine floatation and Kato-Katz thick smear techniques were used for stool examination to evaluate the efficacy of treatment. RESULTS: Two hundred residents from each of the three investigation villages were selected for target chemotherapy once a year for three years. The prevalence of intestinal nematodes decreased from 6.2% in 1995 to 5.4% in 1996 and 3.2% in 1997, and remained at 2.3% after three years in 2000. One control village where only primary school students were treated once a year for 5 years, the prevalence of Ascaris and Trichuris infection also decreased from 1.4% and 4.2% in 1995 to 0.9% and 1.4% in 2000, respectively. The target chemotherapy on the predisposed population to hookworm infection showed that the prevalence in the population above 41 years old was declined from 19.4% to 10.9%. CONCLUSION: The target chemotherapy is an economical and effective approach for the control of intestinal nematode infection in endemic area with low prevalence and intensity of infection.