[Extracorporeal Membrane Oxygenation Combined With Interventional Thrombectomy for Treating High-Risk Pulmonary Embolism Caused by Protein C Deficiency:Report of One Case].

Hereditary protein C deficiency is a chromosomal genetic disease caused by mutations in the protein C gene,which can lead to venous thrombosis and is mostly related to mutations in exons 4-9 and intron 8.Fatal pulmonary embolism caused by mutations in the protein C gene is rare,and the treatment faces great challenges.This article reports a case of fatal pulmonary embolism caused by a frameshift mutation in exon 8 of the protein C gene and summarizes the treatment experience of combining extracorporeal membrane oxygenation (for respiratory and circulatory support) with interventional thrombectomy,providing a basis for the diagnosis and treatment of this disease.

Decreased lymphocyte count before conditioning is associated with BK virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: BK virus-associated hemorrhagic cystitis (BKV-HC) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). It can cause morbidity and may increase treatment-related mortality. Previous studies showed that the occurrence of BKV-HC was related to various factors. However, there are still many controversial factors. It is not clear whether BKV-HC will affect the long-term prognosis of patients. OBJECTIVE: We aimed to identify risk factors for BKV-HC after allo-HSCT and evaluate the effect of BKV-HC on overall survival (OS) and progression- free survival (PFS) of patients. STUDY DESIGN: We retrospectively analyzed the clinical data of 93 patients who underwent allo-HSCT. Univariate and multivariate analysis were used to identify risk factors for BKV-HC. The Kaplan-Meier method was used to estimate OS and PFS. A difference was considered statistically significant if P < 0.05. RESULTS: A total of 24 patients developed BKV-HC. The median occurrence time of BKV-HC was 30 (range:8-89) days after transplantation, and the median duration was 25.5 (range:6-50) days. Multivariate logistic regression analysis indicated that peripheral blood lymphocyte count <1 × 109/L before conditioning (OR = 4.705, P = 0.007) and haploidentical transplantation (OR = 13.161, P = 0.018) were independent risk factors for BKV-HC. The 3-year OS rate was 85.9% (95%CI:62.1%-95.2%) in the BKV-HC group and 73.1% (95%CI: 58.2%-88.0%) in the non-BKV-HC group. There was no significant difference between the two groups (P = 0.516). The 3-year PFS rate was 76.3% (95%CI: 57.9%-94.7%) in the BKV-HC group and 58.1% (95%CI: 39.5%-76.7%) in the non-BKV-HC group. There was no significant difference in the two groups (P = 0.459). The severity of BKV-HC was not related to the OS and PFS of the patients (P value was 0.816 and 0.501, respectively). CONCLUSION: Haploidentical transplantation and decreased peripheral blood lymphocyte count before conditioning increased the risk of BKV-HC after allo-HSCT. The occurrence of BKV-HC after allo-HSCT and the severity of which did not affect OS and PFS of the patients.

Effect of Selective Dorsal Neurectomy on Erectile Function in Rats.

OBJECTIVE: This study aimed to investigate the effect of penile selective dorsal neurectomy (SDN) on erectile function in rats. METHODS: Twelve adult male Sprague-Dawley rats (15 weeks old) were divided into three groups (n=4 per group): in control group, rats received no treatment; in sham group, rats underwent a sham operation; in SDN group, rats underwent SDN with half of the dorsal penile nerve severed. The mating test was performed, and the intracavernous pressure (ICP) assessed six weeks after the surgical treatment. RESULTS: At postoperative six weeks, the mating test revealed no significant difference in mounting latency and mounting frequency among the three groups (P>0.05), while the ejaculation latency (EL) was significantly longer and ejaculation frequency (EF) lower in the SDN group than in the control and sham groups (P<0.05). There were no significant differences in preoperative and postoperative ICP and ICP/mean arterial blood pressure (MAP) among the three groups (P>0.05). CONCLUSION: SDN does not adversely affect the erectile function and sexual desire of rats, and at the same time it can reduce EL and EF, providing an application basis for SDN in the clinical treatment of premature ejaculation.

The novel HLA-A*24:02:160 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-A*24:02:160 differs from HLA-A*24:02:01:01 by one nucleotide in exon 3.

Feasibility of therapeutic plasma exchange-based combination therapy in the treatment of acquired hemophilia A: A retrospective 6 case series.

ABSTRACT: Poor availability and a lack of affordability of bypassing agents (recombinant activated factor VII and activated prothrombin complex concentrate) in west China prompted us to investigate an alternative cost-effective combination therapy. We aimed to explore the feasibility of therapeutic plasma exchange (TPE)-based combination therapy in the treatment of acquired hemophilia A (AHA).We retrospectively investigated the clinical features of AHA in 6 patients who were treated with a combination of TPE, corticosteroids, and rituximab in our department for 9 years between January, 2011 and December, 2019.We examined 1 male and 5 female patients. The median age at diagnosis of AHA was 51 years (18-66 years). In all patients, FVIII activity levels were low (median: 1.5%; 1-3%), FVIII inhibitor titers were high (median: 24.5 BU/mL; 13.2-48.6 BU/mL), and activated partial thromboplastin time was markedly prolonged (median: 99.4 s; 60.9-110.1 s). They underwent 2 to 8 cycles of plasma exchange and were given varying combinations of dexamethasone, methylprednisolone, prednisone, and rituximab. After TPE bleeding gradually stopped, and activated partial thromboplastin time decreased. After 3 months of treatment, FVIII inhibitors completely disappeared.TPE when combined with corticosteroids and rituximab, as adjunctive immunosuppressive agents, may be an effective and reliable treatment for AHA. When there is no alternative, intensive first-line treatment including TPE may be lifesaving.

Influencing Factors for Erectile Dysfunction of Young Adults with No Response to PDE5i.

Erectile dysfunction (ED) is a common male disorder. Although orally-administered phosphodiesterase type 5 inhibitors (PDE5 inhibitors) are now recognized as the primary pharmacological treatment method for ED, 20%-30% of the patients treated with PDE5 inhibitors exhibit no significant effects. This study aims to investigate the influencing factors of ED in young adults with no response to PDE5 inhibitors. ED patients who would take PDE5 inhibitors were included and investigated with a questionnaire. Patients with no response to PDE5 inhibitors (tadalafil and sildenafil) served as study group, and those with response to PDE5 inhibitors as control group. Then Chi square test and logistic regression analysis were applied to find the potential influencing factors. In total, 378 ED patients were included. Ninety-three (24.6%) cases were non-responsive to PDE5 inhibitors, and the remaining 285 (75.4%) responded to PDE5 inhibitors. In multiple logistic regression analysis, we found that history of drinking (OR=3.152; 95%CI 1.672-6.975), spousal noncooperation (OR=2.994; 95%CI 1.589-5.638), number of fixed sex partners (OR=0.358; 95%CI 0.132-0.651), duration of ED (OR=3.356; 95%CI 1.352-8.333), and depression (OR=3.689; 95%CI 1.579-8.979) could be the influencing factors for ED patients' non-response to PDE5 inhibitors. In conclusion, history of drinking, spousal noncooperation, number of fixed sex partner, long duration of ED, and depression could be the influencing factors for ED patients' non-response to PDE5 inhibitors. Patients and doctors should pay attention to these factors.

NQO1 potentiates apoptosis evasion and upregulates XIAP via inhibiting proteasome-mediated degradation SIRT6 in hepatocellular carcinoma.

BACKGROUND: Our previous study has demonstrated that NAD(P)H: quinone oxidoreductase 1 (NQO1) is significantly upregulated in human liver cancer where it potentiates the apoptosis evasion of liver cancer cell. However, the underlying mechanisms of the oncogenic function of NQO1 in HCC have not been fully elucidated. METHODS: Expression of NQO1, SIRT6, AKT and X-linked inhibitor of apoptosis protein (XIAP) protein were measured by western blotting and immunohistochemistry. Additionally, the interaction between NQO1 and potential proteins were determined by immunoprecipitation assays. Furthermore, the effect of NQO1 and SIRT6 on tumor growth was determined in cell model and orthotopic tumor implantation model. RESULTS: We found that NQO1 overexpression in HCC enhanced SIRT6 protein stability via inhibiting ubiquitin-mediated 26S proteasome degradation. High level of SIRT6 reduced acetylation of AKT which resulted in increased phosphorylation and activity of AKT. Activated AKT subsequently phosphorylated anti-apoptotic protein XIAP at Ser87 which determined its protein stability. Reintroduction of SIRT6 or AKT efficiently rescued NQO1 knock-out-mediated inhibition of growth and induction of apoptosis. In orthotopic mouse model, NQO1 knock-out inhibited tumor growth and induced apoptosis while this effect was effectively rescued by SIRT6 overexpression or MG132 treatment partially. CONCLUSIONS: Collectively, these results reveal an oncogenic function of NQO1 in sustaining HCC cell proliferation through SIRT6/AKT/XIAP signaling pathway.

Allogeneic hematopoietic stem cell transplantation following donor CIK cell infusion: A phase I study in patients with relapsed/refractory hematologic malignancies.

Patients with relapsed/refractory hematologic malignancies after allogeneic stem cell transplantation have a poor prognosis due to the high rate of relapse. Techniques capable of decreasing post-transplantation relapse rates are urgently sought. This study aimed to explore the feasibility and safety of allogeneic hematopoietic stem cell transplantation (HSCT) following infusion of donor cytokine-induced killer (CIK) cells. CIK cells were generated in vitro from donor peripheral blood mononuclear cells, and were phenotyped using flow cytometric analysis. CIK cells were administered to 15 high-risk relapsed/refractory hematologic malignancy patients who were not in complete remission in multiple infusions. These patients also received allogeneic HSCT. The side effects and outcomes were recorded. All patients achieved engraftment and complete remission. After CIK cell infusion, two patients developed graft-versus-host disease (GvHD), which was controlled by additional immunosuppressant drugs. At the last follow-up, nine patients had died and six patients were surviving at a median follow-up of 1513days (range, 771-1655days). In conclusion, allogeneic HSCT combined with sequential infusion of donor CIK cells is well tolerated in salvage relapsed/refractory hematologic malignancy patients.

Ginsenoside Rg3 induces apoptosis in human multiple myeloma cells via the activation of Bcl-2-associated X protein.

Ginsenoside Rg3 is one of the main constituents isolated from Panax ginseng, and exhibits cytotoxic effects against cancer cells. The present study aimed to investigate the effects of ginsenoside Rg3 on human multiple myeloma cells, and determine the underlying molecular mechanisms. The cells were exposed to ginsenoside Rg3 at various concentrations (0­80 µM) for 48 h. A subsequent cell proliferation assay demonstrated that treatment with ginsenoside Rg3 resulted in a dose­dependent inhibition of the proliferation of U266 and RPMI8226 cells. Furthermore, exposure to ginsenoside Rg3 led to a marked increase in the rate of apoptosis in the U266 cells, coupled with increased caspase­3 activity. The ginsenoside Rg3­treated cells also exhibited an elevation in the expression of B­cell lymphoma 2­associated X protein (Bax), a pro­apoptotic protein. Notably, knockdown of Bax protected the U266 cells from Rg3­induced apoptosis. Overall, these findings suggested that ginsenoside Rg3 induced apoptosis in multiple myeloma cells, at least partially, through upregulation of the expression of Bax.

Focused ultrasound-induced blood-brain barrier disruption enhances the delivery of cytarabine to the rat brain.

To investigate the feasibility of using focused ultrasound (FUS) with microbubbles for targeted delivery of cytarabine to the brain. Sprague-Dawly rats (weighing 200-250 g) received focused ultrasound with intravenous injection microbubbles. At 0, 2, 4, 8, and 24 hours (n=5 for each time point) after sonication, animals received intravenous administration of cytarabine at a normal dose of 4 mg/kg body weight. Additional five rats were given with a high dose (50 mg/kg body weight) of cytarabine alone. Blood-brain barrier (BBB) permeability and cerebral cytarabine were determined. FUS in conjunction with microbubbles caused a transient BBB opening. Sonication exposure promoted cytarabine accumulation at the sonicated site. Animals injected with a normal dose of cytarabine 2 hours after sonication had similar concentrations of cerebral cytarabine compared to those with higher cytarabine without sonication. FUS can temporarily open the BBB and thus facilitate the penetration of systemic cytarabine into the brain.

Oral immunization with recombinant Mycobacterium smegmatis expressing the outer membrane protein 26-kilodalton antigen confers prophylactic protection against Helicobacter pylori infection.

Helicobacter pylori infection is prevalent worldwide and results in chronic gastritis, which may lead to gastric mucosa-associated lymphoid tissue lymphoma and gastric cancer. We have previously reported that oral immunization with recombinant Mycobacterium smegmatis expressing the H. pylori outer membrane protein 26-kilodalton (Omp26) antigen affords therapeutic protection against H. pylori infection in mice. In the present study, we investigated the prophylactic effects of this vaccine candidate on H. pylori challenge in mice. We found that oral immunization with recombinant Mycobacterium Omp26 significantly reduced H. pylori colonization in the stomach compared to inoculation with wild-type M. smegmatis in control mice. Six of the recombinant Mycobacterium-immunized mice (60%) were completely protected from H. pylori infection. The severity of H. pylori-associated chronic gastritis assessed histologically was significantly milder in mice vaccinated with recombinant Mycobacterium than in control animals. Mice immunized with recombinant Mycobacterium showed enhanced antigen-specific lymphocyte proliferation and antibody responses. Moreover, immunization with recombinant Mycobacterium resulted in an increased expression of interleukin-2 and gamma interferon in the stomach and spleen, as determined by reverse transcription-PCR analysis. Our results collectively suggest that vaccination with recombinant Mycobacterium Omp26 confers prophylactic protection against H. pylori infection. The inhibition of H. pylori colonization is associated with the induction of antigen-specific humoral and cell-mediated immune responses.

Recombinant Mycobacterium smegmatis mc(2)155 vaccine expressing outer membrane protein 26 kDa antigen affords therapeutic protection against Helicobacter pylori infection.

Orally administered recombinant Mycobacterium smegmatis (rM. smegmatis) vaccines represent an attractive option for mass vaccination programmes against various infectious diseases. Therefore, in the present study, we evaluated the capacity of the outer membrane protein 26kDa antigen (Omp26) of Helicobacter pylori (H. pylori) to induce therapeutic protection against H. pylori infection in mice. Omp26 was cloned and expressed in M. smegmatis mc(2)155 as a fusion with the Mycobacterium fortuitum beta-lactamase protein under the control of the up-regulated M. fortuitum beta-lactamase promoter, pBlaF. The rM. smegmatis strain was shown to be relatively stable in vitro in terms of plasmid stability and bacterial persistence. We found that oral immunization of H. pylori-infected mice with rM. smegmatis-Omp26 induced protection, i.e., significant reduction in bacterial colonization in the stomach. The protection was strongly related to serum specific antibodies with a Th(1) and Th(2) profile as well as to local cytokines in the stomach and spleen. These findings suggest that Omp26 is a promising vaccine candidate antigen for use in a therapeutic vaccine against H. pylori. The rM. smegmatis expressing Omp26 antigen could constitute an effective, low-cost combined vaccine against H. pylori.

[Psychological factors and erectile function in men with refractory chronic prostatitis].

OBJECTIVE: To study the psychological factors and erectile function in patients with refractory chronic prostatitis. METHODS: We obtained and compared the scores on the NIH scales of chronic prostatitis symptoms, anxiety, depression and erectile function among 232 refractory and medical chronic prostatitis patients who had never received any psychotherapy. RESULTS: No significant differences were observed in the scores on chronic prostatitis symptoms between the refractory and the medical chronic prostatitis groups, while the scores on anxiety and depression were significantly higher and that on erectile function significantly lower in the refractory than in the medical group (P < 0.01), with a negative correlation between the scores on the former two items and that on the latter. CONCLUSION: Obvious psychological factors exist in patients with refractory chronic prostatitis, which may affect their erectile function.