[Research progress on neurotoxicity induced by metal pollutants through astrocytes].

Metal pollutants in the natural environment and industrial environment can enter organisms through the respiratory tract and digestive tract causing adverse health effects. Many kinds of literatures confirm that metal pollutants have neurotoxicity. Recent studies have showed that astrocytes play an important role in neurotoxicity induced by metal pollutants. In this review, the latest progress of neurotoxicity induced by lead, mercury, cadmium, antimony and copper through astrocytes in recent years is summarized, which provides a new clue for the neurotoxicity research of metal pollutants.

[Efficacy of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei].

Objective: To evaluate the efficacy and safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of pseudomyxoma peritonei (PMP). Methods: In this descriptive case series study, we retrospective analyzed the records of PMP patients treated with CRS and HIPEC between January 2013 and June 2023 at Affiliated Cancer Hospital and Institute of Guangzhou Medical University. The inclusion criteria were as follows: (1) Aged 18 to 75 years and nonpregnant women. (2) Histologically confirmed diagnosis of pseudomyxoma peritonei. (3) Karnofsky Performance Scale (KPS)>70. (4) The functions of major organs such as the heart, liver, lungs, and kidneys can tolerate major surgery for long periods of time. (5) No evidence of extra-abdominal metastasis. Patients with extensive intra-abdominal adhesions or severe infectious diseases were excluded. The main outcomes were overall survival (OS) and postoperative major complications. The postoperative major complications were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). We used the peritoneal cancer index (PCI) score to quantitatively assess the peritoneal metastases and the completeness of cytoreduction (CCR) score at the end of surgery (CCR-0 and CCR-1 considered to be complete CRS). Results: A total of the 186 PMP patients with a median age of 56 (interquartile range extremes (IQRE), 48-64) years were included, 65 (34.9%) males and 121 (65.1%) females. The median peritoneal cancer index (PCI) score was 28 (20-34). Appendiceal origin accounted for 91.4%. Histological types were low grade in 99 patients (53.2%), high grade in 57 patients (30.6%), and 55 patients (29.6%) received complete cytoreduction (CCR-0/1). The median operative duration was 300 (211-430) minutes for all patients. Treatment-related 30-day mortality was 2.7%; 90-day mortality 4.3%; reoperation 1.6%; and severe morbidity 43.0%. Within the entire series, anemia(27.4%), electrolyte disturbance(11.6%), and hypoalbuminemia(7.5%) were the most frequent major complications (grade 3-4). The incidences of gastrointestinal anastomotic leakage, abdominal bleeding, and abdominal infection were 2.2%, 2.2%, and 4.3%, respectively. After a median follow-up of 38.1 (95%CI:31.2-45.1) months, the 5-year OS was 50.3% (95%CI: 40.7%-59.9%) with a median survival time of 66.1 (95%CI: 43.1-89.1) months. The survival analysis showed that patients with pathological low grade, low PCI, and low CCR score had better survival with statistically significant differences (all P<0.05). Further stratified into complete and incomplete CRS subgroups, the 5-year OS of the CCR-0 and CCR-1 subgroups was 88.9% (95%CI: 68.3%-100.0%) and 77.6% (95%CI: 62.7%-92.5%), respectively; and 42.0% (95%CI: 29.5%-54.5%) in the CCR-2/3 subgroup. Conclusions: CRS and HIPEC may result in a long-term survival benefit for PMP patients with acceptable perioperative morbidity and mortality. This strategy, when complete CRS is possible, could significantly prolong survival for strictly selected patients at experienced centers.

Therapeutic Outcome of Stereotactic Body Radiotherapy for Small Hepatocellular Carcinoma Lesions - A Systematic Review and Network Meta-analysis.

Surgical resection, stereotactic body radiotherapy (SBRT) and radiofrequency ablation (RFA) have seldom been compared for small hepatocellular carcinoma (HCC). We explored the treatment outcomes of SBRT for small HCC by conducting a network meta-analysis (NMA). We compared the efficacy and safety of surgical resection, RFA and SBRT for liver-confined small HCC (three or fewer lesions with a diameter ≤5 cm). The study endpoint included the odds ratios of the 1-, 3- and 5-year progression/recurrence/disease-free survival (disease progression-free survival; DPFS) and overall survival rates, as well as severe complications. Forty-five studies included 21 468 patients. In the NMA with comparable data, SBRT had comparable 1-, 3- and 5-year DPFS but significantly worse pooled long-term overall survival (3- and 5-year overall survival) than surgical resection (odds ratio 1.39, 95% confidential interval 1.3-1.89; odds ratio 1.33, 95% confidence interval 1.06-1.69, respectively). SBRT was associated with significantly better pooled 1-year DPFS compared with RFA (odds ratio 0.39, 95% confidence interval 0.15-0.97), with the remaining outcomes being comparable. SBRT had significantly less incidence of severe complications compared with surgical resection (odds ratio 0.62, 95% confidence interval 0.42-0.88) and RFA (odds ratio 0.2, 95% confidence interval 0.03-0.94). In conclusion, for small HCCs (≤5 cm) with one to three nodules, SBRT may be favourable to reduce the risks of severe complications. In terms of DPFS, SBRT may be recommended as an alternative first-line therapy for RFA and surgical resection. The results regarding overall survival should be interpreted with caution, considering the potentially uneliminated bias. There is a clear need for well-designed randomised trials to conclusively identify real differences in efficacy between these treatments, especially SBRT and surgical resection.

The flavonoids induce the transcription of mRNA encoding erythropoietin in cultured embryonic stem cells via the accumulation of hypoxia-inducible factor-1α.

Flavonoids are the most common phytochemicals in vegetables and herbal products. The beneficial functions of flavonoids in the brain and erythropoietic system have been proposed. Erythropoietin (EPO) is a potent protective agent in the brain; but which has difficulty to cross the blood brain barrier (BBB). Here, about 60 flavonoids were screened for their potential activation on the transcription of EPO mRNA in the neuronal embryonic stem cell lines, NT2/D1 and PC12. Amongst the screened flavonoids, formononetin, calycosin, ononin, chrysin, baicalein and apigenin showed robust up regulation of EPO production via enhancement of hypoxia response element (HRE) activity in cultured embryonic stem cells. In addition, the flavonoids showed activation of HRE activity by having increased accumulation of HIF-1α, but not on level of HIF-1ß, in the cultures. The accumulation of HIF-1α was attributed to up regulation of HIF-1α mRNA and blockade of HIF-1α degradation upon treatment of the flavonoids. These results suggested a promising trend of developing commercial products of flavonoids as food supplements tailored for brain health.

[Long-term outcome of 48 unoperated adult patients with Ebstein's anomaly].

Objective: To analyze the long-term outcome of unoperated Ebstein's anomaly (EA) patients aged over 18 years, and to evaluate the related factor of outcomes. Methods: The data of 48 unoperated EA patients from March 2004 to December 2008 in the First Hospital of Tsinghua University, were analyzed. The clinical data of the patients were collected, and patients received regular echocardiography, ECG and chest X-ray examinations. Septal leaflet attachment ratio (SLAr) was calculated based on transthoracic echocardiography imagines. The patients were divided into 3 groups according to SLAr: SLAr<0.45 (n=18), 0.45≤SLAr≤0.60 (n=21) and SLAr>0.60 (n=9). Chest X-ray was used for measurement of cardiothoracic ratio (CTR). Kaplan Meier survival curve was used to calculate the long-term survival rate. Cox proportional hazards regression model was used to analyze the influencing factors of death. Results: There were 19 males, and the mean age at diagnosis was (21.3±11.1) years. Forty-two patients (87.5%) were complicated with arrhythmia, including W-P-W syndrome (n=4), supraventricular tachycardia (n=16), right bundle branch block (n=37), and atrial fibrillation (n=2). The mean duration of follow-up was (148.8±16.8) months, the follow-up rate was 100% with no loss-to-follow up. Nine cases (18.8%) died during follow-up: 6 cases (12.5%) died of cardiac origin, including 3 cases of heart failure, 1 case of arrhythmia, and 2 cases of sudden death; 1 case died of accident; 2 cases died from unknown causes. During the follow-up period, the survival rates were 17/18, 19/21 (90.5%) and 3/9 in the SLAr<0.45, 0.45≤SLAr≤0.60 and SLAr>0.60 group, respectively. According to Kaplan-Meier survival curve, the 5-year survival rates among the three groups were 100%, 100% and 78%, respectively. The 10-year survival rates among the three groups were 94%, 95% and 44%, respectively. Decreased activity tolerance and heart failure were found in 7 patients (6 patients in SLAr>0.60 group and 1 patient in 0.45≤SLAr≤0.60 group). Two patients had cerebrovascular embolism. There were 3 cases with tachyarrhythmia lasting more than 24 hours. Cox regression analysis showed that the risk of death was higher in patients with SLAr>0.60 than in patients with SLAr<0.45 (HR=12.375, 95%CI 1.692-22.146, P=0.015); the risk of death in patients with CTR≥0.65 was 1.306 times higher than that in patients with CTR<0.65 (HR=1.306, 95%CI 0.417-12.754, P=0.038). Conclusions: EA patients often combines with arrhythmia. For unoperated EA patients, SLAr>0.60 and CTR≥0.65 are risk factors of death. EA patients with arrhythmia should be actively treated with drugs or radiofrequency ablation.

Long non-coding RNA PVT1 functions as an oncogene in ovarian cancer via upregulating SOX2.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long non-coding RNA PVT1 functions as an oncogene in ovarian cancer via upregulating SOX2, by M.-F. Zou, J. Ling, Q.-Y. Wu, C.-X. Zhang, published in Eur Rev Med Pharmacol Sci 2018; 22 (21): 7183-7188-DOI: 10.26355/eurrev_201811_16251-PMID: 30468460" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/16251.

The efficacy and safety of valproate medications for migraine in adults: a meta-analysis.

OBJECTIVE: Many parallel-group studies of migraine prophylaxis using valproate medications were reported in recent decades. This meta-analysis assessed the efficacy and safety of valproate medications for migraine prophylaxis in adults. MATERIALS AND METHODS: Searches were conducted in five databases: PubMed, Wiley, ScienceDirect, Web of Science, and the Cochrane Library. The data were acquired through December 31, 2018. Two independent authors searched for controlled clinical trials involving the use of valproate medications in migraine prophylaxis. Studies that met the inclusion criteria were assessed, and their methodological quality was examined. RESULTS: Seven placebo-controlled studies (782 participants) and seven controlled trials against active comparators (554 participants) were included in the final analysis. The active treatment of valproate medications was significantly superior to placebo (OR, 4.02; 95% CI 2.17-7.44; I2 = 66%). Compared with the other active comparators, there were no significant differences between treatments in the proportion of responders. CONCLUSIONS: Valproate medications were more effective than placebo in migraine prevention, with statistically significant differences. Both valproate and the other active comparators were well-tolerated, and no significant difference was noted in efficacy and safety for the prophylaxis of migraine.

Improvac induces immunocastration by affecting testosterone levels and disrupting spermatogenesis in male broiler chickens.

Immunocastration (vaccination against Gonadotropin-releasing hormone (GnRH)) has been regarded as a friendly substitution to physical castration in animals. To date, a few studies have reported the use of Improvac for immunocastration in boar and one study in broiler chickens; however, there is an apparent dearth of scientific evidence regarding the application of Improvac for immunocastration in birds. In the present study, we evaluated the effects of Improvac-based immunocastration on testosterone levels and spermatogenesis in broiler chickens and the effects of Improvac on the expression of genes related to testosterone biosynthesis and metabolism as well as spermatogenesis. The birds were randomly divided into 4 groups (n = 30 each): Control group (non-immunized), Early group (immunized with Improvac at week 3), Late group (immunized with Improvac at week 6), and Early + Late group (immunized with Improvac at weeks 3 and 6). Immunization with Improvac significantly improved the average daily gain compared to the Control group. Of note, following Improvac vaccination, the reproductive efficiency was significantly decreased in male broiler chickens. Furthermore, parameters such as the serum testosterone concentration, spermatogenesis, and the expression levels of genes related to testosterone metabolism (Cyp17A1, Cyp19, HSD3B1, and HSD17B3) and spermatogenesis (Cyclin A1 and Cyclin A2) were significantly reduced in the immunized groups compared to the Control group. Taken together, these findings reveal that immunization against GnRH can be achieved, at least partially, in male broiler chickens. The results of our study also support the hypothesis of using Improvac as an alternative solution to caponization, with considerably improved animal welfare.

Long non-coding RNA PVT1 functions as an oncogene in ovarian cancer via upregulating SOX2.

OBJECTIVE: The aim of this study was to identify the role of long non-coding RNA PVT1 (lnc-PVT1) in the progression of ovarian cancer. PATIENTS AND METHODS: The expression of lnc-PVT1 in ovarian cancer cells and 50 paired tissue samples were detected by quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR). Moreover, cell proliferation assay and transwell assay were performed to identify the function of lnc-PVT1 in vitro. QRT-PCR and Western blot were utilized to explore the possible underlying mechanism. RESULTS: Compared with normal tissues, the expression of lnc-PVT1 T1 was remarkably upregulated in tumor tissues. Moreover, the proliferation and invasion of ovarian cancer were promoted after knockdown of lnc-PVT1 in vitro. Moreover, both the mRNA and protein levels of SOX2 were suppressed after knockdown of lnc-PVT1 in vitro. Besides, the expression of SOX2 in tumor tissues was positively correlated to lnc-PVT1. CONCLUSIONS: Lnc-PVT1 could enhance the invasion and proliferation of ovarian cancer cells through upregulating SOX2, which might serve as a new therapeutic target for the treatment of ovarian cancer.

[Construction and in vitro verification of a new humanized anti-CD19 CAR-T cells with high affinity].

Objective: To construct humanized anti-CD19 chimeric antigen receptor T cells and investigate its ability to kill leukemia cells in vitro and in vivo. Methods: Humanized anti-human CD19 antibody with a high affinity was obtained based on mouse anti-human CD19 antibody (FMC63). Humanized CD19 CAR-T cells (hCART19) were constructed through transfection of lentivirus carrying a CAR sequence of humanized anti-CD19 scFv into human peripheral CD3(+) T cells. The ability of hCART19 to kill leukemia cells and secrete cytokines was detected by LDH release assay and ELISA. The in vivo tumor-killing effect of hCART19 was evaluated in a leukemia mouse model. Results: Several different humanized CD19 single-chain antibodies which were constructed by IMGT database were expressed in the eukaryotic expression vector and purified followed by acquiring humanized CD19 antibody (Clone H3L2) with similar binding ability to FMC63. Humanized CD19 CAR lentivirus vector was constructed and transfected into T cells to obtain hCART19 cells. The LDH release experiment confirmed that the killing rate of target cells was increased gradually along with the increased E/T ratio. When the ratio of E/T was 10∶1, the killing rate of target cells by hCART19 reached a maximum. When Raji cells were used as target cells, the hCART19 cells group had a significantly higher kill rate [(87.56±1.99)%] than the untransduced T cells group [(19.31±1.16)%] and the control virus transduced T cells group [(21.35±1.19)%](P<0.001). ELISA analysis showed that the secretion of IL-2 [ (10.56±0.88) pg/ml] and IFN-γ [ (199.02±12.66) pg/ml] in the hCART19 cells group were significantly higher than those in the untransduced T cells group [IL-2: (3.55±0.26) pg/ml; IFN-γ: (37.63±0.85) pg/ml] and the control virus transduced T cells group [IL-2: (2.92±0.32) pg/ml; IFN-γ: (52.07±3.33) pg/ml](P<0.001). The above experiments also showed similar results when CHO-K1-CD19 cells were used as target cells. Moreover, in a human leukemia xenograft animal model, the results showed that mice in the untransduced T cells group and the control virus transduced T cells group all died within 20 to 30 days, and the hCART19 cell group survived >40 days, which was more than the survival time of the other two groups of mice. The difference was statistically significant (χ(2)=11.73, P=0.008). Conclusion: Humanized CD19 CAR-T cells with anti-leukemic activity have been successfully constructed, which will lay a foundation for clinical studies in the future.

[To promote the sustainable development of surgical treatment for congenital heart disease by innovation and practice].

Due to the tireless efforts of medical staff, we have made great progress in the surgical treatment of congenital heart disease in recent years. A lot of new experiences has been accumulated and many new methods have been created in the diagnosis and treatment of congenital heart disease in neonates, minimal invasive surgical technique, hybrid procedure and the surgical treatment of complicated congenital heart disease. It is proved that innovation and practice are the basis of the surgical treatment of congenital heart disease.

[The outcomes of operation for 237 patients with Ebstein anomaly].

Objective: To evaluate the early and long-term outcomes cardiac surgery of patients with Ebstein anomaly. Methods: The clinic data of 237 patients with Ebstein anomaly received surgical procedures from March 2004 to December 2017 at Department of Cardiac Surgery, First Hospital of Tsinghua University was analyzed retrospectively. There were 105 male and 132 female patients with age of (19.4±16.7) years (ranging from 3 months to 64 years). The surgical procedures include anatomical repair in 188 patients, one and a half ventricle repair in 37 patients, tricuspid valve repair in 4 patients, tricuspid valve replacement in 10 patients, and Fontan procedure in 3 patients (total cavopulmonary connection in 2 patients; Glenn procedure in 1 patient). Results: The early mortality was 2.1% (n=5). One case of atrioventricular (0.4%) newly occurred. There were 228 patients available to follow-up. The range of follow-up duration was 3 to 168 months. Late survival was 99.1% (2 cases of late death) at 10 years. Three patients received reoperation (1.3%), including tricuspid valve repair of 1 patient and one and a half ventricle repair of 2 patients). Indication of tricuspid valve regurgitation improved from 3.6±0.3 to 1.5±0.4. Survival rate at 5 and 10 years was 98.6% and 98.2%, respectively. Conclusions: The principle of the techniques is to reconstruct the tricuspid valve and right ventricle anatomically. For most cases, the anatomical repair was demonstrated with low mortality, less complications and excellent durability at long-term follow-up. If the tricuspid valve is severely hypoplastic, one and a half ventricle repair and valve replacement may be alternatie.

CXCR4 antagonist AMD3100 enhances the response of MDA-MB-231 triple-negative breast cancer cells to ionizing radiation.

Radiation therapy (RT) is one of the primary modalities for triple-negative breast cancer (TNBC) treatment. However, due to the pro-metastatic potential of radiation and the intrinsic radiation resistance of some tumors, many patients experience RT failure, which leads to cancer relapse and distant metastasis. This preclinical study evaluated the efficacy of the antagonist of the SDF-1 receptor CXCR4, AMD3100, as a radiosensitizer in TNBC models. The combined effect of ionizing radiation and AMD3100 was determined in vitro by surviving fraction, cell cycle distribution, Bax and Bcl-2 expression, and apoptosis assays in a TNBC cell line (MDA-MB-231). For in vivo studies, human xenograft athymic nude mice were used. Treatment of TNBC cells with AMD3100 significantly augmented cellular radiosensitivity. Radiosensitivity was enhanced specifically through increased Bax expression, reduced Bcl-2 expression, prolonged G2-M arrest, and increased apoptosis. Combined treatment with AMD3100 and irradiation also enhanced tumor growth delay, with an enhancement factor ranging from 1.5 to 1.8. These findings support the evaluation of antagonists of the SDF-1 receptor CXCR4, such as AMD3100, as potent radiosensitizers in TNBC.

[Therapeutic effect of miR-489 in a mouse model of silica-induced matured pulmonary fibrosis].

Objective: To explore the potential therapeutic role of miR-489 in silica-induced pulmonary fibrosis mouse models. Methods: A total of 32 C57BL/6 male mice were randomly divided into four groups: saline, silica, silica plus miRNA control and silica plus miR-489 agomir (n=8 in each group) . The mice were instilled with silica particles suspended in saline or sterile saline intratracheally. Subsequently, miR-489 agomir or miRNA control was injected via the tail vein into each mouse at days 28, 35, 42 and 49, the miR-489 levels, histological examination, collagen deposition, fibrotic biomarkers (E-cadherin, α-SMA, Vimentin, Fibronectin) and transforming growth factor-ß(1) (TGF-ß(1)) protein levels in mouse lung tissues were measured. Results: miR-489 levels in silica plus miR-489 group were significantly increased in lung tissues compared with silica plus miRNA control group (P<0.05) . Histological examination showed attenuated inflammation, less severe fibrotic foci and less destruction of alveolar architecture in the silica plus miR-489 group. Additionally, both the severity and distribution of lung lesions were ameliorated in silica plus miR-489 group compared with the silica plus miRNA control group (P<0.05) . The collagen deposition and hydroxyproline levels in silica plus miR-489 group were significantly decreased compared with the silica plus miRNA control group (P<0.05) . These changes were supported by decreased protein levels of α-SMA, Vimentin, Fibronectin, TGF-ß1 along with increased protein levels of E-cadherin in silica plus miR-489 group (P<0.05) . Conclusion: Our data indicate that the upregulation of miR-489 has potential therapeutic role in silica-induced pulmonary fibrosis in vivo, which may be associated with the depression of TGF-ß1 release.

[The effects of different tidal volume ventilation on right ventricular function in critical respiratory failure patients].

Objective: To observe and explore the effects of different tidal volume (VT) ventilation on right ventricular (RV) function in patients with critical respiratory failure. Methods: Consecutive respiratory failure patients who were treated with invasive ventilator over 24 h in the Department of Critical Care Medicine at the Fourth Hospital of Hebei Medical University from June to December in 2015 were enrolled in this study.Clinical data including patients' vital signs, ventilator parameters and RV echocardiography were collected within 6 h (D0), day1(D1), day2 (D2) and day3 (D3) after ventilation started.According to the VT, patients with acute respiratory distress syndrome (ARDS) were assigned to low VT group [S6, ≤6 ml/kg predicted body weight (PBW)] and high VT group (L6, >6 ml/kg PBW), while non-ARDS patients were also assigned to low VT group (S8, ≤8 ml/kg PBW) and high VT group (L8, >8 ml/kg PBW). Results: A total of 84 patients were enrolled in this study.44.2% ARDS patients and 58.5% non-ARDS patients were in low VT groups.After ventilation, tricuspid annulus plane systolic excursion(TAPSE)decreased progressively in S6 [from 18.30(16.70, 20.70) mm to 17.55(15.70, 19.50) mm, P=0.001], L6 [from 19.50(17.00, 21.00) mm to 16.30(15.00, 18.00) mm P=0.001], S8[from 18.00(16.00, 21.00) mm to 16.50(15.50, 18.00) mm, P=0.001] and L8 [from 19.00(17.50, 21.50) mm to 16.35(15.15, 17.00) mm, P=0.001] groups.However, TAPSE decreased less in small VT groups (S6 and S8) than those of in large VT groups (S8 and L8) without significant differences.There were not statistical differences between different VT groups in terms of ventilation days, including right ventricle area/left ventricle area (RV(area)/LV(area)), TAPSE, peak mitral flow velocity of the early rapid filling wave (E), peak mitral flow velocity of the late rapid filling wave (A), early diastolic velocity of the tricuspid annulus (e'), pulmonary artery systolic pressure, inferior vena cava diameter (all P>0.05). Compared to L6 group, low VT (S6 group) resulted in decreased mortality at 28 days [1/19 vs 37.5%(9/24), P=0.014]. There were not statistical differences between different VT groups in terms of ventilation days, length of intensive care unit stay, length of hospital stay (all P>0.05). Logistic regression analysis showed that VT could be the independent factor of TAPSE (OR=1.104, 95%CI 0.100-1.003, P=0.049). Conclusions: Positive pressure mechanical ventilation resulted in RV systolic dysfunction .Lower VT may have the protective effect on RV function. Trial registration: Chinese Clinical Trial Registry, ChiCTR-POC-15007563.

High-dose calcium channel blocker (CCB) monotherapy vs combination therapy of standard-dose CCBs and angiotensin receptor blockers for hypertension: a meta-analysis.

In this study, we evaluated the efficacy and safety of high-dose calcium channel blocker (CCB) monotherapy and standard-dose CCBs combined with angiotensin receptor blockers (ARBs) for patients with hypertension. A comprehensive search of PubMed, Embase and the Cochrane Central Register of Controlled Trials was performed in December 2015. Randomized controlled trials designed to identify the above goal were included. Thirteen trials including 2371 patients were identified. The standard-dose CCB/ARB combination resulted in a greater reduction of systolic blood pressure (WMD -2.52, 95% confidence interval (CI): -3.76 to -1.28) and diastolic blood pressure (weighted mean difference (WMD) -2.07, 95% CI: -3.73 to -0.42) compared to high-dose CCB monotherapy. The overall hypertension control rate for the CCB/ARB combination was higher than that for CCB monotherapy (relative risk (RR): 1.17, 95% CI: 1.08-1.26). Furthermore, the CCB/ARB combination treatment yielded significantly fewer overall adverse events (RR: 0.84, 95% CI: 0.74-0.95), oedema (RR: 0.31; 95% CI: 0.18-0.52) and rash (RR: 0.27, 95% CI: 0.08-0.96, P=0.04) than did CCB monotherapy. The standard-dose CCB/ARB combination is superior to high-dose CCB monotherapy for lowering blood pressure and reducing adverse events in hypertensive patients. Future research should focus on the cost-effectiveness and long-term effects of these two treatment strategies for patients with hypertension.

[Effects of PSMB5 on proliferation and bortezomib chemo-resistance in human myeloma cells and its related molecular mechanisms].

Objective: To investigate the effects of proteasome beta 5 subunit (PSMB5) on proliferation and bortezomib (BTZ) chemo-sensitivity of multiple myeloma (MM) and its related molecular mechanisms. Methods: We used two MM cell lines, RPMI 8226 and BTZ drug-resistant cell line RPMI 8226/BTZ100 (hereinafter referred to as BTZ100) , as the research object. PSMB5 was overexpressed or knocked down in two myeloma cell lines via lentivirus transfection. CCK8 assay was used to detect the impact of PSMB5 on cell viability and bortezomib sensitivity in human myeloma cells; Using flow cytometry to test the effects of PSMB5 on apoptosis rate of human myeloma cells under the treatment of bortezomib; Apoptosis-related gene expression of Bax, Bcl-2, p-Akt and cleaved caspase-3 were detected by Western blot. Results: ①PSMB5 overexpression and knockdown were successfully constructed in RPMI 8226 and BTZ100 cells. ②PSMB5 expression was positively correlated with cell proliferation of RPMI 8226 and BTZ100 cells (P<0.05) . ③The cell viability was lower after PSMB5 knockdown in RPMI 8226 cells than control cells under the same concentration of BTZ[IC(50) at 24 h: (7.01±0.47) and (9.64±0.55) nmol/L respectively, t=6.289, P=0.003]. The cell viability was higher after PSMB5 overexpression in RPMI 8226 cells than control cells under the same concentration of BTZ[IC(50) at 24 h: (10.99±0.58) and (9.51±0.37) nmol/L respectively, t=3.724, P=0.020) . PSMB5 expression was negatively correlated with the sensitivity of RPMI 8226 cells to BTZ. The results of BTZ100 cells were similar. ④The expression of PSMB5 was negatively correlated with the apoptosis of RPMI 8226 and BTZ100 under the treatment of BTZ. ⑤Meanwhile, PSMB5 knockdown could increase the expression of pro-apoptosis gene Bax and cleaved caspase-3 and decrease the expression of anti-apoptotic gene Bcl-2 and p-Akt. PSMB5 over-expression has the opposite results. Conclusion: PSMB5 knockdown could improve the bortezomib sensitivity of MM cells via activation of apoptosis signaling. PSMB5 may be a potential therapeutic target for MM.