SCD1 inhibits HBV replication by regulating autophagy under high lipid conditions.

Chronic hepatitis B virus (HBV) infection remains a significant public health concern worldwide. Several metabolic processes regulate HBV DNA replication, including autophagy and lipid metabolism. In this study, we clarified the effect of lipids on HBV replication and elucidated possible mechanisms. We discovered that lipid metabolic gene expression levels were negatively correlated with the HBV DNA in plasma. Our data showed that fatty acid stimulation significantly reduced HBV DNA, hepatitis B surface antigen (HBsAg), and hepatitis B e antigen (HBeAg) levels in HepG2.2.15 cells, which are human hepatoma cell cultures transfected with HBV DNA. The Stearoyl coenzyme A desaturase 1 (SCD1)-autophagy pathway has also been implicated in inhibiting HBV replication by fatty acids stimulation. SCD1 knockdown deregulates the inhibitory effect of fatty acids on HBV by enhancing autophagy. When 3 methyladenine (3MA) was added, the inhibitory effects of specific autophagy inhibitors eliminated the positive effects of SCD1 knockdown on HBV replication. Our results indicate that SCD1 participates in the regulation of inhibition of HBV replication by fatty acids stimulation through regulating autophagy.

Comparison of Edge of Lamina Block with Thoracic Paravertebral Block and Retrolaminar Block for Analgesic Efficacy in Adult Patients Undergoing Video-Assisted Thoracic Surgery: A Prospective Randomized Study.

Background: A novel ultrasound-guided paravertebral block, the edge laminar block (ELB) was reported recently. However, it was unclear how effective ELB was in comparison with traditional blocking methods. We conducted a trial to compare the analgesic efficacy of ELB with the thoracic paravertebral block (TPVB) and the retrolaminar block (RLB) in patients undergoing video-assisted thoracic surgery (VATS). Methods: We identified 90 patients who were scheduled for VATS and randomly assigned them to three groups: ELB group (Group E), TPVB group (Group T), and RLB group (Group R). Each group underwent ELB, TPVB, and RLB, respectively, under ultrasound guidance before general anesthesia induction. All patients received post-operative routine analgesia protocol. Our primary outcome was the extent of dermatomal sensory loss on the midclavicular, midaxillary, and scapular lines, measured using a pinprick 15 minutes after the nerve block. Secondary outcomes included the intraoperative dose of sufentanil, the numerical rating scale (NRS) scores assessed in the post-anesthesia care unit (PACU) and at 6, 12, and 24 hours post-operatively, and pethidine administrated as analgesic rescue dose. Results: The percentages of nerve block range reaching the midclavicular line, midaxillary line, and scapular line in Group E were 96.7%, 93.3%, 93.3%, and 60% in Group T and 30%, 56.7%, and 96.7% in Group R, respectively. Group E had wider dermatomal sensory loss on the midclavicular line and midaxillary line compared to Group R (P < 0.001) and had a wider range compared to Group T on the scapular line (P < 0.001). There was no significant difference in the intraoperative use of sufentanil in the three groups. Post-operative NRS scores at each time point were significantly lower in Group E than those in the other two groups (P < 0.01). Conclusion: ELB had a wider nerve block range and applied better post-operative analgesia in comparison with TPVB and RLB.

Transfusion of stored autologous blood in patients with low-grade pseudomyxoma peritonei: A retrospective analysis of its safety and outcome.

Background: Pseudomyxoma peritonei is a rare disease that presents as a malignant tumor on the peritoneal surface. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is the standard treatment for this disease and frequently requires a red blood cell transfusion. However, due to the limited collection and supply of allogeneic blood, surgical treatment may be delayed due to inadequate preparation of allogeneic blood in the course of clinical treatment. This study aimed to evaluate the safety and efficacy of transfusion of stored autologous blood in patients with low-grade pseudomyxoma peritonei. Methods: Pseudomyxoma peritonei patients who received cytoreductive surgery combined with heat-infused peritoneal chemotherapy were divided into two groups: transfusion of allogeneic blood and transfusion of stored autologous blood. A comparison of the differences in multiple factors between the two groups was performed, including tumor recurrence, survival time, hemoglobin and hematocrit levels, coagulation function (prothrombin time, activated partial thromboplastin time, and fibrinogen), total hospital stay duration, and incidence of serious adverse events after surgery. Results: Propensity scores matching analysis yielded 34 patients with allogeneic blood transfusion and 34 patients with stored autologous blood transfusion. Comparison analysis did not show statistical differences in several factors, including age, tumor grade, tumor recurrence rate after surgery, etc., between the two groups. The cytoreductive degree was considered an independent risk factor for tumor recurrence. The pseudomyxoma peritonei patients in the autologous transfusion group had a higher 5-year survival rate and a longer survival time. Moreover, transfusion of stored autologous blood did not increase the rate of tumor recurrence, or the total hospital stay duration after surgery, the hemoglobin level and coagulation function were well stabilized within 24 h after surgery, and there was a low incidence of serious adverse events. Conclusion: The clinical application of transfusion of stored autologous blood in pseudomyxoma peritonei patients is safe and effective.

TM2, a novel semi-synthetic taxoid, exerts anti-MDR activity in NSCLC by inhibiting P-gp function and stabilizing microtubule polymerization.

Taxane agents are of particular interest in non-small cell lung carcinomas (NSCLC) treatment, while multidrug resistance (MDR) mediated by P-glycoprotein (P-gp) limits their clinical efficacy. TM2, a chemically semi-synthesized taxane derivative, exerted significant anti-cancer efficacy in vitro and in vivo, especially against vincristine-resistant and adriamycin-resistant cancer cells. In this study, the anti-cancer effect of TM2 on drug-resistant NSCLC was evaluated both in vitro and in vivo, and the mechanism underlying its anti-MDR activity was further clarified. It was found that TM2 was significantly cytotoxic to cisplatin- and paclitaxel-resistant A549 (human non-small cell lung cancer) cells that overexpressing P-gp, resulting in IC50 values of 0.19 µM and 0.12 µM. TM2 micelles (5 mg/kg, 10 mg/kg, 20 mg/kg, i.v., 21 days) inhibited the growth of MDR xenograft with the maximal inhibitory rate up to 80.4%. Moreover, TM2 caused cell cycle arrest in the G2-M phase and apoptosis in drug-resistant cells through promoting tubulin polymerization, which acted in a way similar to taxane agents. Notably, TM2 acted as a P-gp inhibitor with high binding affinity, which resulted in impaired efflux function through forming H-bonds and ATP hydrolysis to induce P-gp conformational alterations. These findings indicated that TM2 displays anti-MDR activity with the potential for the treatment of NSCLC, which can inhibit P-gp function and stabilize microtubule polymerization.

[Correlative Analysis between Production of Platelet HLA-â Antibody and HLA-A, B Genes in Patients with Malignant Hematological Diseases].

OBJECTIVE: To investigate the correlation between the production of platelet HLA-Ⅰ antibody and HLA-A, B genes in patients with malignant hematological diseases, and explore the susceptible gene for producing platelet HLA-Ⅰ antibody. METHODS: Patients with malignant hematological diseases who had received multiple platelet transfusion were selected as the research objects in the Department of Hematology of our hospital. Platelet HLA-I antibody were screened by ELISA, and the patients were divided into positive and negative groups according to the results. HLA-A and B genes were sequenced after genomic DNA was extracted, and the frequencies of them were compared between the two groups. RESULTS: The positive rate of platelet HLA-I antibody was 22.95%. A total of 13 HLA-A alleles and 14 HLA-B alleles were obtained after the HLA-A and B genes sequencing in 100 cases. The frequencies of HLA-A*24, HLA-A*30, and HLA-B*13 were significantly different between the two groups (P<0.05). Frequencies of HLA-A*30 and HLA-B*13 in the positive group were lower than those in the negative group (RR=0.107, 0.387), but HLA-A*24 was higher (RR=1.412). After high-resolution typing of HLA-A*24, HLA-A*30, and HLA-B*13, frequencies of HLA-A*24∶02, HLA-A*30∶01, and HLA-B*13∶02 were significantly different between the two groups, the RR value was 1.412, 0.107, and 0.125, 95%CI was 0.961-2.075, 0.016-0.721, and 0.300-0.515, respectively. CONCLUSION: HLA-A*24∶02 may be a susceptible gene for producing platelet HLA-Ⅰ antibody in patients with malignant hematological diseases, while HLA-A*30∶01 and HLA-B*13∶02 may be two protective genes.

Pseudoginsenoside-F11 promotes functional recovery after transient cerebral ischemia by regulating the microglia/macrophage polarization in rats.

The polarization of microglia/macrophages after cerebral ischemia is critical for post-stroke damage/recovery. Previously, we found that pseudoginsenoside-F11 (PF11), an ocotillol-type saponin, has neuroprotective effects on permanent and transient cerebral ischemia in rats. This study aimed to investigate the effects and potential mechanisms of PF11 on microglia/macrophage polarization following transient cerebral ischemia in rats. In vivo data showed that oral administration of PF11 (12 mg/kg) significantly attenuated cognitive deficits and sensorimotor dysfunction, infarct volume and brain edema in transient middle cerebral artery occlusion (tMCAO)-treated rats, as well as reduced the loss of neurons and the over-activation of microglia in penumbra of ipsilateral striatum and cortex. Notably, the proportion of M2 microglia/macrophages in the total activated microglia/macrophages peaked on day 14 after tMCAO in rats, while PF11 promoted its peak advancing to day 3 post-tMCAO, which allowing the damaged brain to enter the repair period more quickly. Furthermore, PF11 increased the expression of anti-inflammatory markers and decreased the expression of pro-inflammatory markers in ipsilateral striatum and cortex. In addition, in vitro data showed that PF11 inhibited the induction of M1 microglia by oxygen glucose deprivation/re-oxygenation (OGD/R)-induced neurons, and promoted the polarization of microglia to M2 phenotype in a Jumonji domain-containing protein 3 (Jmjd3)-dependent manner. Moreover, PF11 promoted the protection of M2 microglia and attenuated the exacerbation of M1 microglia on OGD/R-induced neuronal damage. Taken together, these results indicate that PF11 protects ischemic neurons by promoting M2 microglia/macrophage polarization in a Jmjd3-dependent manner, ultimately facilitating the functional recovery following transient cerebral ischemia.

[Clinical Characteristics and Survival Analysis of Patients with IgD Multiple Myeloma].

OBJECTIVE: To explore the clinical features, prognosis and survival of patients with IgD multiple myeloma (MM). METHODS: The clinical data of 20 patients with IgD MM was analyzed retrospectively. The prognostic factors and survival analysis was carried out. We summarized their clinical characteristics. The survival analysis was carried out by Kaplan-Meier method, and the prognostic factor were analyzed by using log-rank test for single factor analysis of observation index. Variables of P<0.15 in single factor analysis were enrolled in multifactor cox regression analysis. RESULTS: IgD MM patients accounted for 4.3% of all MM patients in the same period, among which 80% were male, the median age of patients was 57.5(35-77) years old, 90% of the patients belongs to λ light chain type. At the time of diagnosis, 18 patients (90%) were in DS-Ⅲ stages, while 10 patients were in ISS-Ⅲ stage. The first clinical manifestations were fatigue, bone pain, kidney function impairment, anemia (Hb<100 g/L) in 14 cases (70%), 12 cases (60%) with osteolytic bone destruction≥3, combined with renal impairment in 8 cases (40%), and elevated blood calcium in 11 cases (51.4%). In only 5 patients the ratio of albumin to globntin was inverted, hypoalbuminemia accounted for 40%, and globulin increase accounted for only 15%. FISH results showed that the positive rate of 1q21 amplification (50%) was the highest, and it was easy to occur at the same time as other cytogenetic abnormalities. Extramedullary infiltration occurred in 4 cases (20%). The analysis of prognostic factors showed that only the increase of lactate dehydrogenase (LDH) level was an independent poor prognostic factor for IgD MM patients. Extramedullary infiltration and various cytogenetic abnormalities were found in 2 IgD MM patients with primary drug resistance, suggesting that extramedullary infiltration and various cytogenetic abnormalities may be prognostic factors, but the difference was not statistically significant, Which maybe related to the small sample size. All 20 patients were treated with bortezomib-containing regimen, of which 19 patients were evaluated, 17 patients (89.4%) showed effective, including CR+VGPR (52.6%), PR (31.5%), MR (5.3%), 2 patients primary drug resistance. The median PFS and OS was 9.5 and 10.5 months, respectively. CONCLUSION: IgD MM is a rare and invasive disease. Increased LDH is an independent prognostic factor. Bortizomib-containing regimen can improve the prognosis of IgD MM patients.

Comparison of efficacy and safety of corticosteroid and vincristine in treating kaposiform hemangioendothelioma and tufted angioma: A multicenter prospective randomized controlled clinical trial.

Kaposiform haemangioendothelioma (KHE) and tufted angioma (TA) are rare vascular tumors that can cause life-threatening Kasabach-Merritt phenomenon. No evidence-based treatment strategies have yet been established, and its management is still a challenge. The purpose of this multicenter prospective randomized controlled study was to evaluate and compare the efficacy of corticosteroid and vincristine (VCR) in the treatment of KHE and TA. All patients with KHE/TA who met the diagnostic criteria were consecutively recruited. The patients were randomized into a methylprednisolone (MP) group and a VCR group. The primary outcome was the single main parameter effective rate and overall effective rate of corticosteroid and VCR over 1 month after treatment. The single main parameters included platelets, fibrinogen, tumor size, texture, and appearance. From May 2016 to April 2018, a total of 59 patients completed the clinical trial, including 29 in the MP group and 30 in the VCR group. The results showed that VCR was superior to corticosteroid in the improvement of platelet (80.0% vs 44.0%, P = 0.019) and tumor texture (68.9% vs 30.8%, P = 0.007). Although the efficacy of VCR on fibrinogen (23.3% vs 20.7%, P = 1.000), tumor size (23.3% vs 13.8%, P = 0.273), and appearance (65.5% vs 46.2%, P = 0.120) was higher than that of corticosteroid, there was no significant difference (P > 0.05). Meanwhile, the overall effective rate of VCR was higher than that of corticosteroid (56.7% vs 31.0%), but the difference was also not statistically significant (P = 0.067). In conclusion, the therapeutic effect of VCR was significantly better than that of corticosteroid with regard to treating thrombocytopenia and tumor texture. We recommend that VCR could be an option for first-line treatment in KHE/TA patients.

[Clinical Analysis of 46 Cases of Multiple Myeloma with Extramedullary Disease].

OBJECTIVE: To investigate the effect of clinical baseline data on prognosis in patients with multiple myeloma (MM) complicated by extramedullary disease (EMD). METHODS: The clinical data of 46 MM patients with EMD were retrospectively analyzed. The clinical data and survival prognosis of MM patients in primary EMD group and recurrent EMD group were analyzed. The classified baseline data were expressed by the number of cases (percentage), the χ2 test was used to compare the two classification data groups. The OS and PFS curves were drawn by multiplication positive limit method (Kaplan-Meier). Log-rank test was used for the univariate analysis of prognosis, and COX proportional risk regression model was used for the multiple factors of prognosis. RESULTS: ß 2 microglobulin≥2.7 g/L, lactic dehydrogenase≥250 U/L, serum calcium≥2.75 mmol/L, plasma cells in bone marrow≥60% were the poor prognostic factors for PFS. Serum calcium≥2.75 mmol/L and the plasma cells in bone marrow≥60% were the poor prognostic factors for OS. Multivariate regression analysis enroling the statistically significant factors in univariate analysis baseline date in factors in showed that plasma cell level≥60% in bone marrow was independent poor prognostic factors for PFS, and serum calcium≥2.75 mmol/L was an independent poor prognostic factor for OS. The IgG type is the most common type of MM complicated by EMD. The remission depth of primary EMD group≥VGPR was lower than that of recurrent EMD group, and there was significant difference between the two groups (P<0.05), and the median OS time of patients with primary EMD group was shorter than that of patients with recurrent EMD group, the difference was statistically significant (P<0.05). The 3-year survival rates of primary EMD group and recurrent EMD group were 10.0% and 34%, respectively, there was no significant difference between the two groups (P>0.05). The 5-year survival rate was 0 and 20%, respectively, there was significant difference between the two groups (P<0.05). CONCLUSION: The remission depth of primary EMD group≥VGPR is lower than that of recurrent EMD group，and the OS time of patients in primary EMD group is shorter than that in recurrent EMD group. Bortezomib-based chemotherapy could not improve the prognosis of patients with primary EMD and recurrent EMD, and the prognosis of patients with primary EMD is even worse.

[Clinical Characteristic, Prognosis and Treatment Outcome of Elderly Multiple Myeloma Patients with Impaired Renal Function].

OBJECTIVE: To explore the risk factors, prognosis and curative effect of elderly patients with MM renal damage. METHODS: 118 patients with primary elderly MM treated in our hospital from January 2011 to December 2018, were enrolled analyzed retrospectively. The clinical characteristics and prognosis of renal function impairment group (RI group) and normal renal function group (non-RI group) were compared. The difference of renal efficacy and survival benefit between the patients treated with bortezomib, thalidomide (combination group) and chemotherapy regimen containing only one of them (single drug group) in RI group was compared. RESULTS: Univariate analysis showed that DS stage, pulmonary infection, uric acid, ß 2 microglobulin and leukocyte in RI group were higher than those in non-RI group, but hemoglobin was lower than that in non-RI group (P<0.05). Multivariate logistic regression analysis showed that ß 2 microglobulin was the independent risk factor for renal damage in elderly patients with MM. Kaplan-Meier method showed that the OS and PFS in RI group were significantly lower than those in non-RI group (P<0.05). The renal efficacy in the combined treatment group was significantly better than that of the single drug group (P<0.05), and it could bring benefit to the PFS of the elderly patients with MM renal damage (P<0.05). CONCLUSION: The prognosis of elderly MM patients with impaired renal function is poor. The prognosis of these patients can be improved by selecting chemotherapy regimen containing bortezomib and thalidomide at the same time, and monitoring, controlling all kinds of risk factors actively.

Standards of care for Kasabach-Merritt phenomenon in China.

Kasabach-Merritt phenomenon (KMP) is a rare disease that is characterized by severe thrombocytopenia and consumptive coagulation dysfunction caused by kaposiform hemangioendothelioma or tufted hemangioma. This condition primarily occurs in infants and young children, usually with acute onset and rapid progression. This review article introduced standardized recommendations for the pathogenesis, clinical manifestation, diagnostic methods and treatment process of KMP in China, which can be used as a reference for clinical practice.

Feasibility of laryngeal mask anesthesia combined with nerve block in adult patients undergoing internal fixation of rib fractures: a prospective observational study.

BACKGROUND: The laryngeal mask airway (LMA) is occasionally used in internal fixation of rib fractures. We evaluated the feasibility of general anesthesia with an LMA associated to a thoracic paravertebral block (TPB) and/or an erector spinae plane block (ESPB) for internal fixation of rib fractures. METHODS: Twenty patients undergoing unilateral rib fracture fixation surgery were enrolled. Each patient received general anesthesia with an LMA combined with TPB and/or ESPB, which provided a successful blocking effect. All patients received postoperative continuous analgesia (PCA) with 500 mg of tramadol and 16 mg of lornoxicam, and intravenous injection of 50 mg of flurbiprofen twice a day. Our primary outcomes including the partial pressure of arterial oxygen (PaO2) and arterial carbon dioxide (PaCO2) were measured preoperatively and on the first day after surgery. Secondary outcomes including the vital signs, ventilation parameters, postoperative numerical rating scale (NRS) pain scores, the incidence of postoperative nausea and vomiting (PONV), perioperative reflux and aspiration, and nerve block-related complications were also evaluated. RESULTS: Thirteen men and seven women (age 35-70 years) were enrolled. Six (30%) had a flail chest, nine (45%) had hemothorax and/or pneumothorax, and two (10%) had pulmonary contusions. The postoperative PaO2 was higher than the preoperative value (91.2 ± 16.0 vs. 83.7 ± 15.9 mmHg, p = 0.004). The preoperative and postoperative PaCO2 were 42.1 ± 3.7 and 43.2 ± 3.7 mmHg (p = 0.165), respectively. Vital signs and spontaneous breathing were stable during the surgery. The end-tidal carbon dioxide concentrations (EtCO2) remained within an acceptable range (≤ 63 mmHg in all cases). NRS at T1, T2, and T3 were 3(2,4), 1(1,3), and 0(0,1), respectively. None had PONV, regurgitation, aspiration, and nerve block-related complications. CONCLUSIONS: The technique of laryngeal mask anesthesia combined with a nerve block was feasible for internal fixation of rib fractures. TRIAL REGISTRATION: Current Controlled Trials ChiCTR1900023763 . Registrated on June 11, 2019.

Neolignans from Aristolochia fordiana Prevent Oxidative Stress-Induced Neuronal Death through Maintaining the Nrf2/HO-1 Pathway in HT22 Cells.

Bioassay-guided fractionation of the ethanolic extract of the stems of Aristolochia fordiana led to the isolation of six new dihydrobenzofuran neolignans (1-3 and 7-9), three new 2-aryldihydrobenzofurans (4-6), a new 8-O-4' neolignan (10), and 14 known analogues (11-24). The structures of compounds 1-10 were established by spectroscopic methods, and their absolute configurations were determined by analyses of the specific rotation and electronic circular dichroism data. The neuroprotective effects of compounds 1-24 against glutamate-induced cell death were tested in hippocampal neuronal cell line HT22. Compounds 17 and 20-24 exhibited moderate neuroprotective activity by increasing the endogenous antioxidant defense system. In addition, the neolignans activated the Nrf2 (nuclear factor E2-related factor 2) pathway, resulting in the increase of the expression of endogenous antioxidant protein HO-1 (heme oxygenase-1). The active compounds also preserved the levels of antiapoptotic protein Bcl-2 (B cell lymphoma/leukemia-2), which was decreased by glutamate. Collectively, these results suggested that the active neolignans protect neurons against glutamate-induced cell death through maintaining the Nrf2/HO-1 signaling pathway as well as preserving the Bcl-2 protein and might be promising novel beneficial agents for oxidative stress-associated diseases.