Incidence of deep venous thrombosis in patients with hemophilia undergoing bilateral simultaneous total knee arthroplasty: a retrospective cohort study.

BACKGROUND: Hemophilic arthropathy usually affects the knees bilaterally. In order to reduce costs and improve rehabilitation, bilateral simultaneous total knee arthroplasty (TKA) can be performed. However, pharmacological prophylaxis for deep venous thrombosis (DVT) remains controversial in patients with severe hemophilia. The purpose of this study was to establish the incidence of DVT in severe hemophilia A patients undergoing bilateral simultaneous TKA without pharmacological thromboprophylaxis. METHODS: Consecutive patients with severe hemophilia A undergoing bilateral simultaneous TKA at a single center between January 2015 and December 2020 were retrospectively reviewed. All patients received a modified coagulation factor substitution regimen. Tranexamic acid (TXA) was used for hemostasis in all patients during surgery. All patients followed a standardized postoperative protocol with routine mechanical thromboprophylaxis, and none received anticoagulation. D-dimer was measured preoperatively, on the day of the operation and on postoperative days 1, 7 and 14. Ultrasound (US) of the lower extremities was performed before (within 3 days of hospitalization) and after surgery (days 3 and 14) to detect asymptomatic DVT. Patients were followed up until 2 years after surgery for the development of symptomatic DVT or pulmonary embolism (PE). RESULTS: 38 male patients with severe hemophilia A underwent 76 simultaneous TKAs. Mean (± standard deviation) age at the time of operation was 41.7 (± 17.1) years. Overall, 47.3% of patients had D-dimer concentrations above the threshold 10 µg/mL on day 7 and 39.5% on day 14. However, none of the patients had DVT detected on postoperative US, nor developed symptomatic DVT or PE during the 2-year follow-up. CONCLUSIONS: The risk of DVT in patients with severe hemophilia A after bilateral simultaneous TKA is relatively low, and routine pharmacological thromboprophylaxis may not be needed.

Mutation detection and inhibitor analysis of 43 children with severe hemophilia A in a single center: three novel mutations.

To investigate the risk factors of FVIII inhibitors development in severe hemophilia A (HA) patients who were received on-demand therapy and were infused with plasma cryoprecipitate and multiple FVIII concentrates alternately. We collected clinical information from 43 severe HA children who were treated with plasma cryoprecipitate and multiple FVIII concentrates. The F8 mutation was detected by long-distance PCR for inversion and detected by all exons and their flanking sequencing for other mutations. The inhibitor detection was performed by Nijmegen-modified Bethesda assay. The impact of novel amino substitutions on FVIII protein was predicted by SIFT and PolyPhen-2. The 3D analysis of missense mutations was performed using Swiss-PdbViewer. FVIII inhibitors were detected in nine cases (20.9%). All of the inhibitor positive cases had high risk F8 gene mutations. In most of the positive cases (7/9), inhibitors were developed during the first 10 EDs, which was significantly higher than that in the 10-50 EDs group and 50 EDs group (p = 0.009). Three novel mutations were reported, including c.214G > T (E72X), c.218 T > C (F73S), and c.2690C > G (S840X). For severe HA patients who are treated with multiple products of replacement therapy, it is important to supervise inhibitor during the first 10EDs, especially for those with high risk F8 gene mutations. F8 gene mutation is one of the most important genetic factors for inhibitor development. It is essential to detect F8 gene for all severe HA patients. Three novel mutations were reported to expand the mutation spectrum of the F8 gene.

Numerical Simulation of Gas-Liquid Gravity Displacement in Vertical Fractures during Drilling of Carbonate Formations.

In petroleum drilling, carbonate formations characterized by natural fractures can result in troublesome gas-liquid gravity displacement, which refers to the phenomenon that the drilling mud leakage and gas kick are simultaneously triggered. This work focuses on clarifying the mechanism of gas-liquid displacement in vertical fractures during the drilling of carbonate formations and investigating the characteristics of gas-liquid displacement under various conditions. First, the bottom hole pressure allowing for gas-liquid gravity displacement is analyzed, which determines the coexistence condition of leakage and kick in vertical fractures. Then, a theoretical model of gas-liquid displacement flow in a vertical fracture is established. To verify the reliability and accuracy of the model, the results of numerical simulation are compared with those of a visualization experiment. The development process and flow characteristics of gas-liquid displacement in the fracture under different conditions are numerically simulated. The effects of pressure difference, drilling mud property, and fracture geometry on the gas-liquid displacement rate are analyzed. It is found that the drilling mud leakage rate increases with the increase of fracture width, fracture height, and drilling mud density, while it decreases with the increase of pressure difference and fracture length. The gas invasion rate increases with the increase of fracture width, fracture height, and pressure difference, while it decreases with the increase of drilling mud density and fracture length. The equations for leakage rate and gas invasion rate are derived by the response surface method, and the methods for mitigating gas-liquid gravity displacement are discussed. It is expected that the present work provides a better understanding of the gas-liquid gravity displacement in carbonate formations.

Efficacy of intra-articular injection of allogeneic platelet-rich plasma for knee osteoarthritis combined with hematologic blood dyscrasias with platelet dysfunction: protocol of a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Autologous platelet-rich plasma (PRP) has been shown to alleviate the symptoms of patients suffering from knee osteoarthritis (KOA), but for certain patients with hematologic diseases with platelet dysfunction and patients receiving anti-platelet medications, autologous PRP is not an optimum solution. Allogeneic PRP has been proven to be safe and effective in the treatment of osteoarthritis, rotator cuff disease, refractory wounds and other medical fields. However, a well-designed and long-term follow-up prospective randomized controlled trial (RCT) to evaluate the effect of allogeneic PRP intra-articular injections for KOA combined with hematologic blood dyscrasias has not yet been performed. METHODS/ DESIGN: We will conduct an allogeneic PRP injection for KOA combined with hematologic blood dyscrasias with platelet dysfunction study: a prospective, randomized, double-blind, placebo-controlled trial. One hundred participants with KOA combined with hematologic blood dyscrasias with platelet dysfunction will be randomly allocated to receive either one allogeneic PRP injection or one saline injection into the knee joint. The primary outcome will be a 12-month change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score. Secondary outcomes will be the 36-Item Short-Form General Health Survey (SF-36) score, Lysholm score, overall knee pain score and MRI assessment at 1-, 3-, 6- and 12-month. DISCUSSION: The results of this study will help determine whether allogeneic PRP could be used as a non-surgical intervention to treat patients with knee OA combined with hematologic blood dyscrasias with platelet dysfunction. TRIAL REGISTRATION: Chinese Clinical Trials Registry reference: ChiCTR2100048624. Prospectively registered 11th of July 2021.

Hepatoprotective effect of diallyl trisulfide against lipopolysaccharide and D-galactosamine induced acute liver failure in mice via suppressing inflammation and apoptosis.

Acute liver failure (ALF), characterized by the quick occurrence of disorder in liver, is a serious liver injury with extremely high mortality. Therefore, we investigated whether diallyl trisulfide (DATS), a natural product from garlic, protected against ALF in mice and studied underlying mechanisms. In the present study, lipopolysaccharide (LPS) (10 µg·kg-1)/D-galactosamine (D-gal) (500 mg·kg-1) was intraperitoneally injected to ICR mice to induce ALF. The mice were orally administered 20-, 40-, or 80-mg·kg-1 DATS) 1 h before LPS/D-gal exposure. Serum biochemical analyses and pathological study found that DATS pretreatment effectively prevented the ALF in LPS/D-gal-treated mice. Mechanistically, pretreatment of DATS inhibited the increase of the numbers of CD11b+ Kupffer cells and other macrophages in the liver, the release of tumor necrosis factor-α into the blood, and Caspase-1 activation induced by LPS/D-gal treatment in mice. Furthermore, DATS inhibited the activation of Caspase-3, downregulation of Bcl-2/Bax ratio, and increase of TUNEL positive staining. Altogether, our findings suggest that DATS exhibits hepatoprotective effects against ALF elicited by LPS/D-gal challenge, which probably associated with anti-inflammation and anti-apoptosis.

Intra-articular injections of platelet-rich plasma decrease pain and improve functional outcomes than sham saline in patients with knee osteoarthritis.

PURPOSE: To compare the long-term clinical efficacy provided by intra-articular injections of either Pure Platelet-rich Plasma (P-PRP) or sham saline to treat knee osteoarthritis (KOA). METHODS: This prospective, parallel-group, double-blind, multi-center, sham-controlled randomized clinical trial recruited participants with KOA from orthopedic departments at nine public hospitals (five tertiary medical centers, four secondary medical units) starting January 1, 2014, with follow-up completed on February 28, 2021. Participants were randomly allocated to interventions in a 1:1 ratio. Data were analyzed from March 1, 2021, to July 15, 2021. Three sessions (1 every week) of P-PRP or sham saline injected by physicians. The primary outcome was the Western Ontario and McMaster Universities Arthritis Index (WOMAC) at 3, 6, 12, 24, 60 months of follow-up. Secondary outcomes included the International Knee Documentation Committee (IKDC) subjective score, visual analogue scale (VAS) score, intra-articular biochemical marker concentrations, cartilage volume, and adverse events. Laboratory of each hospital analyzed the content and quality of P-PRP. RESULTS: 610 participants (59% women) with KOA who received three sessions of P-PRP (n = 308, mean age 53.91 years) or sham saline (n = 302, mean age 54.51 years) injections completed the trial. The mean platelet concentration in PRP is 4.3-fold (95% confidence interval 3.6-4.5) greater than that of whole blood. Both groups showed significant improvements in IKDC, WOMAC, and VAS scores at 1 month of follow-up. However, only the P-PRP group showed a sustained improvement in clinical outcome measurements at month 24 (P < 0.001). There were statistically significant differences between the P-PRP and sham saline groups in all clinical outcome measurements at each follow-up time point (P < 0.001). The benefit of P-PRP was clinically better in terms of WOMAC-pain, WOMAC-physical function and WOMAC-total at 6, 12, 24, and 60 months of follow-up. No clinically significant differences between treatments were documented in terms of WOMAC-stiffness at any follow-up. A clinically significant difference favoring P-PRP group against saline in terms of IKDC and VAS scores was documented at 6, 12, 24 and 60 months of follow-up. At 6 months after injection, TNF-α and IL-1ß levels in synovial fluid were lower in the P-PRP group (P < 0.001). Tibiofemoral cartilage volume decreased by a mean value of 1171 mm3 in the P-PRP group and 2311 mm3 in the saline group over 60 months and the difference between the group was statistically significant (intergroup difference, 1140 mm3, 95% CI - 79 to 1320 mm3; P < 0.001). CONCLUSIONS: In this randomized clinical trial of patients with KOA, P-PRP was superior to sham saline in treating KOA. P-PRP was effective for achieving at least 24 months of symptom relief and slowing the progress of KOA, with both P-PRP and saline being comparable in safety profiles.

Hydrocarbon stapling modification of peptide alyteserin-2a: Discovery of novel stapled peptide antitumor agents.

Alyteserin-2a (ILGKLLSTAAGLLSNLNH2 ) is isolated from the skin exudates of midwife toad and has a wide range of biological applications. However, the use of alyteserin-2a as an antitumor agent is limited due to its structural flexibility. In this study, a series of stapled peptides were prepared through hydrocarbon stapling modification without destroying the key residues, and their chemical and biological properties were further evaluated for enhancing the application potential of alyteserin-2a in the field of antitumor drugs development. Among them, alyteserin-2a-Sp3 displayed significant improvement in helicity levels, protease resistance, and antitumor activity compared to that of the template peptide alyteserin-2a, indicating that alyteserin-2a-Sp3 had a potential to become a lead compound for the development of novel antitumor drugs. This study confirms the important effect of hydrocarbon stapling strategy on the secondary structure, hydrolase stability, and biological activity of alyteserin-2a.

Efficacy and safety of eltrombopag in Chinese patients with chronic immune thrombocytopenia: stage 2 results from a multicenter phase III study.

This phase III, randomized, placebo-controlled study conducted in three stages (6-week, randomized, placebo-controlled stage 1; 24-week, open-label stage 2; and continuous extension stage 3) assessed the long-term efficacy and safety of eltrombopag use in Chinese patients with chronic immune thrombocytopenia (ITP). This article presents the results from stage 2. Overall, 150 patients (placebo-eltrombopag [P-E], 50; eltrombopag-eltrombopag [E-E], 100) received open-label eltrombopag. The median platelet count was maintained between 41 × 109/L and 80 × 109/L. Most patients in both groups (P-E, 90.0%; E-E, 81.8%) achieved platelet counts ≥30 × 109/L and ≥2 times the baseline platelet count at least once with eltrombopag treatment. Overall, 32% of patients achieved platelet counts ≥50 × 109/L in ≥75% of platelet count assessments. Both groups showed a decreased tendency to infrequent bleeding and clinically significant bleeding events during stage 2 compared with baseline. Among patients who received ≥1 ITP medication at baseline, 70.4% in the P-E group and 40.8% in the E-E group reduced or permanently stopped ≥1 of their ITP medications. The stage 2 results further demonstrated a sustainable long-term efficacy and good tolerability of eltrombopag with a favorable benefit-risk ratio in Chinese chronic ITP patients.Trial registration: Clinicaltrials.gov NCT01762761. Registered 8 January 2013, https://clinicaltrials.gov/ct2/show/NCT01762761.

Successful treatment of acquired amegakaryocytic thrombocytopenia with eltrombopag and immunosuppressant.

Acquired amegakaryocytic thrombocypenia (AAMT) is an extremely rare hematologic disorder and standard treatment strategy has not been established. We described herein two cases of AAMT who were fully responded to eltrombopag and immunosuppressant. Patient 1 was refractory to steroid, IVIG and recombinant human thrombopoietin (rhTPO). Patient 2 did not respond to high dosage of steroid, IVIG, rhTPO and rituximab. Moreover, his AAMT progressed to aplastic anemia in 5 months. Both patients took eltrombopag and immunosuppressant, then they achieved long-term remission without obvious side effects. Our findings suggest that this combination can be a valuable alternative in AAMT.

A novel BRD4 inhibitor suppresses osteoclastogenesis and ovariectomized osteoporosis by blocking RANKL-mediated MAPK and NF-κB pathways.

Bromodomain-containing protein 4 (BRD4) has emerged as a promising treatment target for bone-related disorders. (+)-JQ1, a thienotriazolodiazepine compound, has been shown to inhibit pro-osteoclastic activity in a BRD4-dependent approach and impede bone loss caused by ovariectomy (OVX) in vivo. However, clinical trials of (+)-JQ1 are limited because of its poor druggability. In this study, we synthesized a new (+)-JQ1 derivative differing in structure and chirality. One such derivative, (+)-ND, exhibited higher solubility and excellent inhibitory activity against BRD4 compared with its analogue (+)-JQ1. Interestingly, (-)-JQ1 and (-)-ND exhibited low anti-proliferative activity and had no significant inhibitory effect on RANKL-induced osteoclastogenesis as compared with (+)-JQ1 and (+)-ND, suggesting the importance of chirality in the biological activity of compounds. Among these compounds, (+)-ND displayed the most prominent inhibitory effect on RANKL-induced osteoclastogenesis. Moreover, (+)-ND could inhibit osteoclast-specific gene expression, F-actin ring generation, and bone resorption in vitro and prevent bone loss in OVX mice. Collectively, these findings indicated that (+)-ND represses RANKL-stimulated osteoclastogenesis and averts OVX-triggered osteoporosis by suppressing MAPK and NF-κB signalling cascades, suggesting that it may be a prospective candidate for osteoporosis treatment.

Diallyl trisulfide protects against concanavalin A-induced acute liver injury in mice by inhibiting inflammation, oxidative stress and apoptosis.

AIMS: To investigate the protective effects and underlying mechanisms of diallyl trisulfide (DATS) against acute liver injury induced by concanavalin A (Con A). MATERIALS AND METHODS: DATS (20, 40, 80 mg/kg) were gavaged to ICR mice 1 h before Con A (20 mg/kg) tail vein injection. The survival rate of mice, alterations of serum biochemical markers and liver histopathology were measured to evaluate the protective effects of DATS at 24 h after Con A exposure. The indexes of inflammation, oxidative stress and apoptosis were determined to explore the possible mechanisms. KEY FINDINGS: DATS pretreatment increased survival rate of mice in a dose-dependent manner, inhibited the increase of liver-to-spleen ratio and serum liver injury markers, and attenuated liver pathological damage induced by Con A. Further study showed that DATS pretreatment inhibited the activation of Kupffer cells/macrophages, release of tumor necrosis factor-α (TNF-α) and Caspase-1-dependent inflammation induced by Con A. Moreover, DATS pretreatment alleviated the oxidative stress induced by Con A, which was evidenced by increased superoxide dismutase (SOD) and catalase (CAT) activities and decreased malondialdehyde (MDA) content in DATS and Con A co-treated mice compared with Con A alone group. Finally, DATS pretreatment reduced eosinophilic body formation, TUNEL positive staining and increased Bcl-2/Bax ratio in liver of Con A-injected mice, indicating attenuated apoptosis. SIGNIFICANCE: Collectively, the results suggest that DATS displays potent protective effects against Con A-induced acute liver injury in mice possibly through inhibition of inflammation, oxidative stress and apoptosis.

Effect of Eriocalyxin B on prostatic inflammation and pelvic pain in a mouse model of experimental autoimmune prostatitis.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disease in males. Eriocalyxin B (EriB), a natural diterpenoid purified from Isodon eriocalyx var. laxiflora, was previously reported to have antitumor effects via multiple immune-related pathways. In this study, we investigated the effect of EriB on CP/CPPS using a mouse model of experimental autoimmune prostatitis (EAP) and explored its potential mechanisms. METHODS: The EAP model was established in nonobese diabetic mice by intradermal injecting a mixture of prostate antigens and Complete Freund's Adjuvant on days 0 and 28. Then, EAP mice received daily intraperitoneal injections of EriB (5 or 10 mg/kg/d) for 14 days, from days 28 to 42 (EAP+EriB5 or EAP+EriB10 groups). The histopathological appearance of the prostate tissues was evaluated. Chronic pelvic pain development was assessed by cutaneous allodynia. Inflammatory cytokines were measured by enzyme-linked immunosorbent assay tests. We then explored anti-inflammatory potential mechanisms of EriB by studying the effects of PI3K inhibitor wortmannin (EAP+EriB10+Wort group) and NF-κB inhibitor SC75741 (EAP+EriB10+SC group) on prostate inflammation and pelvic pain using this model. RESULTS: Histological analyses revealed significant prostate inflammation in EAP mice compared with control mice. Significantly increased pelvic pain was detected in EAP mice (P < .05). Compared with the EAP+Veh group, chronic pain development, histological appearance, and cytokine levels demonstrated that EriB could alleviate the severity of EAP in a dose-dependent manner though upregulation of the PI3K/Akt/mTOR pathway and downregulation of the NF-κB pathway. Further mechanism research demonstrated that the PI3K/AKT/mTOR pathway could be blocked by wortmannin, but was not affected by SC75741. In addition, the NF-κB pathway could be further inhibited by SC75741 compared with the EAP+EriB10+Veh group. However, wortmannin could reactivate the NF-κB pathway, indicating that the PI3K/AKT/mTOR pathway negatively regulates the NF-κB pathway during EriB treatment. CONCLUSIONS: The results of the present study suggested that EriB could alleviate the severity of prostatic inflammation and pelvic pain in an EAP mouse model. These findings may broaden the value of EriB as a promising candidate for the treatment of CP/CPPS.

CaMK4-dependent phosphorylation of Akt/mTOR underlies Th17 excessive activation in experimental autoimmune prostatitis.

Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) is a complicated syndrome characterized by genitourinary pain in the absence of bacterial infection. Th17 cell-driven autoimmunity has been proposed as a cause of CP/CPPS. However, the factors that promote Th17-driven autoimmunity in experimental autoimmune prostatitis (EAP) and the molecular mechanisms are still largely unknown. Here, we showed that Th17 cells were excessively activated, and blockade of IL-17A could effectively ameliorate various symptoms in EAP. Furthermore, we revealed that calcium/calmodulin-dependent kinase Ⅳ (CaMK4), especially Thr196 p-CaMK4 was increased in the Th17 cells of the EAP group, which were activated by intracellular cytosolic Ca2+ . Pharmacologic and genetic inhibition of CaMK4 decreased the proportion of Th17 cells, and the protein and mRNA level of IL-17A, IL-22, and RORγt. The phosphorylation of CaMK4 was dependent on the increase in intracellular cytosolic Ca2+ concentration in Th17 cells. A mechanistic study demonstrated that inhibition of CaMK4 reduced IL-17A production by decreasing the phosphorylation of Akt-mTOR, which was well accepted to positively regulate Th17 differentiation. Collectively, our results demonstrated that Ca2+ -CaMK4-Akt/mTOR-IL-17A axis inhibition may serve as a promising therapeutic strategy for CP/CPPS.

Germacrone Induces Apoptosis as Well as Protective Autophagy in Human Prostate Cancer Cells.

BACKGROUND: Germacrone, a natural product isolated from the traditional Chinese medicine Rhizoma Curcuma, has been reported to exhibit antitumor activities in vitro. To further understand the antitumor mechanism of germacrone, we investigated the growth inhibitory effect of germacrone on the human prostate cancer cell lines PC-3 (androgen independent) and 22RV1 (androgen dependent). MATERIALS AND METHODS: Prostate cancer cells were cultured with different concentrations of germacrone, and cell viability was measured by MTT assay. The levels of proteins were measured by Western blotting. Cell apoptosis was assessed by flow cytometry. Images of autophagy-related protein staining were captured by fluorescence microscopy. Autophagic flux was assessed by detecting the LC3B-II level. RESULTS: Our results indicated that germacrone treatment significantly inhibited cell proliferation by inducing apoptosis in a dose-dependent manner, with IC50 values of 259 µM for PC-3 cells and 396.9 µM for 22RV1 cells. Germacrone-treated cells also exhibited induction of autophagy, as evidenced by elevated LC3B-II protein expression levels and punctuate patterns. Additionally, an autophagy inhibitor enhanced the growth inhibitory effect of germacrone. Moreover, the phosphorylation of Akt and mTOR was inhibited in germacrone-treated prostate cancer cells. CONCLUSION: Germacrone induced apoptosis and autophagy in prostate cancer cells by inhibiting the Akt/mTOR signaling pathway. Germacrone treatment also led to the activation of protective autophagy. These findings suggest that germacrone may potentially contribute to the development of a new therapeutic agent for prostate cancer treatment.

Baicalin suppresses the cell cycle progression and proliferation of prostate cancer cells through the CDK6/FOXM1 axis.

The aim of this study was to investigate the effects and mechanisms of baicalin against prostate cancer cell growth and cell cycle progression. A human prostate cancer cell line LNCaP was engrafted into nude mice, and the oncogenicity of LNCaP cells was analyzed. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay was used to measure LNCaP and PC3 proliferation capability. CDK6 mRNA level was detected using qRT-PCR. Western blotting was performed to assess the levels of cell cycle-associated proteins. In addition, cell cycle and apoptosis were analyzed using flow cytometry. Baicalin significantly decreased the expression of cell cycle-associated proteins. Furthermore, baicalin showed an observable effect on proliferation, cell cycle progression and apoptosis in LNCaP and PC3 cells. Upregulation of CDK6 and FOXM1 reversed the effect of baicalin. CDK6- and FOXM1-mediated cell growth attenuated the protective effect of baicalin in prostate cancer. This study presented an understanding of the role and mechanism of baicalin in prostate cancer cells, providing a new target and therapies for the prevention and treatment of prostate cancer.

LncRNA-SNHG16 Silencing Inhibits Prostate Carcinoma Cell Growth, Downregulate GLUT1 Expression and Reduce Glucose Uptake.

BACKGROUND: lncRNA-SNHG16 was identified as an oncogene in many cancers, but its involvement in prostate carcinoma is unknown. MATERIAL AND METHOD: Expression of lncRNA-SNHG16 and glucose transporter 1 (GLUT-1) in 52 prostate carcinoma tissues and 36 normal prostate tissues was analyzed by RT-qPCR. Transfections were performed to analyze gene interactions. Cell proliferation was analyzed by cell proliferation assay. RESULTS: Overexpression of lncRNA-SNHG16 effectively distinguished prostate carcinoma patients from normal ones. Expression levels of lncRNA-SNHG16 and GLUT-1 mRNA were significantly and positively correlated across prostate carcinoma tissues. In vitro cancer cell experiments revealed that lncRNA-SNHG16 siRNA silencing downregulated the expressions of GLUT-1 and reduced glucose uptake. lncRNA-SNHG16 siRNA silencing also significantly inhibited prostate carcinoma cell proliferation. However, lncRNA-SNHG16 siRNA silencing did not affect the normal prostate. CONCLUSION: In conclusion, lncRNA-SNHG16 might be a possible treatment target for prostate cancer.

Eriocalyxin B Induces Apoptosis and Autophagy Involving Akt/Mammalian Target of Rapamycin (mTOR) Pathway in Prostate Cancer Cells.

BACKGROUND Eriocalyxin B (EriB), a diterpenoid isolated from the plant Isodon eriocalyx, has been shown to possess anti-tumor properties. However, few systematic studies of the mechanism underlying the anti-tumor activity of Eriocalyxin B in prostate cancer cells have been published. The aim of this study was to investigate the effect of Eriocalyxin B on prostate cancer cells. MATERIAL AND METHODS In the present study, the PC-3 (androgen-independent) and 22RV1 (androgen-dependent) human prostate cancer cell lines were cultured with and without increasing doses of Eriocalyxin B. MTT assay was used to measure cell viability. Western blotting was performed to measure levels of proteins associated with apoptosis and autophagy. Flow cytometry was used to assess changes in cell apoptosis and cycle. Fluorescence microscopy was used to capture images of autophagy-related proteins. RESULTS Treatment of human prostate cancer cells with Eriocalyxin B resulted in apoptosis in a dose- and time-dependent manner. Eriocalyxin B also induced autophagy, with elevated LC3B-II protein expression and punctuate patterns. Additionally, autophagy protected prostate cancer cells from apoptosis induced by Eriocalyxin B, which was demonstrated by addition of chloroquine (CQ). Moreover, the results indicated that Eriocalyxin B could inhibit the phosphorylation of Akt and mTOR. Eriocalyxin B induced apoptosis and autophagy by inhibition of the Akt/mTOR pathway. CONCLUSIONS Eriocalyxin B induces apoptosis and autophagy involving the Akt/mTOR pathway in prostate cancer cells in vitro. These findings provide evidence for Eriocalyxin B as a potent therapeutic for the treatment of prostate cancer.

Outcome of CARE: a 6-year national registry of acquired haemophilia A in China.

Acquired haemophilia A (AHA) is a rare haemorrhagic disorder caused by autoantibodies directed against the functional epitopes of coagulation factor VIII (FVIII). Its management relies on prompt diagnosis, control of bleeding and eradication of the inhibitor by immunosuppression. China Acquired Hemophilia Registry (CARE), a nationwide multicentre registry, was intended to survey the status of AHA and standardize its diagnosis and therapy in China. One hundred and eighty-seven registered patients had an average age of 52 years. Diagnosis was delayed in 46·5% patients. There was a significant delay from diagnosis to immunosuppressive therapy in 68·3% patients. Bleeding control was significantly higher in patients treated with prothrombin complex concentrate (PCC) versus FVIII replacement therapy (84·6% vs. 34·4%; P < 0·001). Inhibitor eradication with a combination of steroids and cyclophosphamide showed a higher partial remission (PR) rate (92·2% vs. 70·3%) and stable complete remission (CR) rate (82·8% vs. 48·6%) than with steroids alone. Logistic regression model showed age and malignancy were significantly related to survival at final follow-up. The mean age for the survivors [51 years (IQR, 35-65 years)] was significantly lower than that of the non-survivors [79 years (IQR, 67-86 years)] (P < 0·001). Overall survival was higher in non-malignancy group than malignancy group (94·9% vs. 70%) (OR = 1·313; 95% CI, 0·913-1·889, P = 0·015).

Aptamers in hematological malignancies and their potential therapeutic implications.

Aptamers are short DNA/RNA oligonucleotides selected by the process called Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Due to their functional similarity to monoclonal antibodies with some superior characters, such as high specificity and affinity, flexible modification and stability, and lack of toxicity and immunogenicity, they are promising alternative and complementary targeted therapy for hematologic malignancies. The trends in aptamer technology including production, selection, modifications are briefly discussed in this review. The key aspect is to illustrate aptamers against cancer cells in hematologic malignancies especially those that have entered clinical trials. We also discuss some challenges remain in the application of aptamers.