Studies have investigated the effects of androgen deprivation therapy (ADT) use on the incidence and clinical outcomes of coronavirus disease 2019 (COVID-19); however, the results have been inconsistent. We searched the PubMed, Medline, Cochrane, Scopus, and Web of Science databases from inception to March 2022; 13 studies covering 84 003 prostate cancer (PCa) patients with or without ADT met the eligibility criteria and were included in the meta-analysis. We calculated the pooled risk ratios (RRs) with 95% confidence intervals (CIs) to explore the association between ADT use and the infection risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severity of COVID-19. After synthesizing the evidence, the pooled RR in the SARS-CoV-2 positive group was equal to 1.17, and the SARS-CoV-2 positive risk in PCa patients using ADT was not significantly different from that in those not using ADT (P = 0.544). Moreover, no significant results concerning the beneficial effect of ADT on the rate of intensive care unit admission (RR = 1.04, P = 0.872) or death risk (RR = 1.23, P = 0.53) were found. However, PCa patients with a history of ADT use had a markedly higher COVID-19 hospitalization rate (RR = 1.31, P = 0.015) than those with no history of ADT use. These findings indicate that ADT use by PCa patients is associated with a high risk of hospitalization during infection with SARS-CoV-2. A large number of high quality studies are needed to confirm these results.
Male ; Humans ; Prostatic Neoplasms/chemically induced* ; Androgen Antagonists/adverse effects* ; COVID-19 ; Androgens/therapeutic use* ; SARS-CoV-2

To explore the protective effect and mechanism of ethyl acetate extract from Bidens bipinnata on hepatocyte damage induced by endoplasmic reticulum stress. Tunicamycin was used to establish the damage model in L02 cells. Methyl thiazolyl tetrazolium(MTT) colorimetric assay was used to investigate the survival rate of ethyl acetate extract from B. bipinnata in L02 cells injury induced by endoplasmic reticulum stress; the protein expressions of endoplasmic reticulum stress-related molecule glucose regulated protein 78(GRP78), PKR-like ER kinase(PERK), eukaryotic initiation factor-2(eIF2α), activating transcription factor 4(ATF4), C/EBP homologous protein(CHOP), B-cell CLL/lymphoma 2(Bcl-2), Bal-2 associated X apoptosis regulator(Bax) were examined by Wes-tern blot. The expressions of the above proteins were also detected after endoplasmic reticulum stress inhibitor(4-phenyl butyric acid) and CHOP shRNA-mediated knockdowns were added. The expressions of GRP78, PERK, CHOP in L02 cells were observed by immunofluorescence method. The results showed that ethyl acetate extract from B. bipinnata could significantly increase the survival rate of L02 cell injury caused by endoplasmic reticulum stress in a dose and time-dependent manner(P<0.05 or P<0.01). The expression levels of GRP78, PERK, eIF2α, ATF4, CHOP and Bax in the drug treatment groups were significantly down-regulated(P<0.05 or P<0.01), while Bcl-2 was significantly up-regulated(P<0.01). After endoplasmic reticulum stress inhibitor and CHOP shRNA-mediated knockdowns were added, the expression levels of GRP78, PERK, eIF2α, ATF4, CHOP, Bax in the drug treatment groups were significantly down-regulated(P<0.01), whereas Bcl-2 was significantly up-regulated(P<0.01). Immunofluorescence results showed that the expressions of GRP78, PERK, CHOP were consistent with the Western blot method. In conclusion, ethyl acetate extract from B. bipinnata has a significant protective effect on the damage of L02 cells caused by endoplasmic reticulum stress. The mechanism may be related to the inhibition of endoplasmic reticulum stress and the down-regulation of apoptosis in cells through the PERK/eIF2α/ATF4/CHOP signaling pathway.
Acetates ; Apoptosis ; Bidens ; Endoplasmic Reticulum Stress ; Hepatocytes ; Transcription Factor CHOP/genetics* ; eIF-2 Kinase/genetics*

ObjectiveMild hypothermia was an effective way of cerebral resuscitation after cardiac arrest. The expression of cold-induced RNA binding protein (CIRP) was significantly enhanced when the temperature was lowered. This study was to evaluate the effects and the mechanisms of CIRP inhibition on hippocampal neurological and mitochondria function after mild hypothermia in a rat model of cardiac arrest.MethodsFive male Sprague-Dawley rats were injected with AAV9 in the hippocampus, 1 μL on each side, speeding 0.2 μL/min. The expression of GFP was observed by fluorescence microscopy after 2w. Sixty rats were randomly divided into 5 groups (n= 12 for each group): sham operation group, model group, mild hypothermia group, mild hypothermia + CIRP inhibition group and mild hypothermia + normal control group. Injection of AAV9 was performed on mild hypothermia + CIRP inhibition group, same amount of empty vector on mild hypothermia + normal control group, while normal saline on the other groups. Animal models of global cerebral IR were established by transesophageal cardiac pacing inducing cardiac arrest followed by cardiopulmonary resuscitation at 2w after injection. Cooling to 32-34℃ was initiated and the temperature was maintained for 6h on mild hypothermia groups. NDS score, HE staining and pyramidal cell counting on hippocampal CA1 area were performed at 72h after reperfusion. At 24h after reperfusion, mitochondrial structure of pyramidal cells in hippocampal CA1 was observed under electronic microscope and the expressions of CIRP, dynamin-related protein 1 (Drp1) and cytochrome C (Cyt-C) were detected by Western blot.ResultsThe NDS score of model group was decreased, the number of pyramidal cells was reduced, and the mitochondria were severely damaged. The NDS score of mild hypothermia group was increased, and the number of pyramidal cells was increased (all P<0.05), and mitochondrial damage was reduced compared with model group. In mild hypothermia + CIRP inhibition group, the NDS score was no significant difference compared with mild hypothermia + normal control group and model group, and the number of pyramidal cells was lower than that in mild hypothermia + normal control group [(27.2±4.9) vs (50.2±4.4), P<0.05], similar to model group (25.2±3.8), the damage of mitochondria was severe. After 2 weeks of AAV9 injection, GFP was widely expressed in the hippocampus. The expression of CIRP in mild hypothermia + CIRP inhibition group was respectively small compared with sham operation group [(0.14±0.03) vs (0.03±0.01),P<0.05], which was successfully inhibited by injection of AAV9. The expression of CIRP in model group (0.25±0.05) was significantly higher than that in sham operation group. The expression of CIRP in mild hypothermia group (0.37±0.08) and mild hypothermia + normal control group (0.39±0.04) were higher than that in model group (all P<0.05). The trends of Drp1 and Cyt-C expression were the same, in model group was higher than that in sham operation group, in mild hypothermia group was lower than that in model group, in mild hypothermia + CIRP inhibition group was higher than in mild hypothermia + normal control group (all P<0.05); There were no significant differences between model group and mild hypothermia + CIRP inhibition group, and between mild hypothermia group and mild hypothermia + normal control group.ConclusionInhibition of CIRP expression in hippocampus can weaken the protective effects of mild hypothermia on neurons in a rat model of cardiac arrest. The mechanism of those effects might be association with mitochondrial division.

This study aimed to investigate the effect and possible mechanism of Bidens pilosa decoction on non-alcoholic fatty liver disease(NAFLD) induced by high fat and high glucose in mice. Bald/c mice were randomly divided into normal group, model group, metformin(200 mg·kg~(-1)) treatment group, Bidens pilosa decoction(10 g·kg~(-1)) treatment group, metformin and B. pilosa decoction(100 mg·kg~(-1)+5 g·kg~(-1)) treatment group. Except for the normal group, mice in the other four groups were fed with high-fat and high-glucose diet for 8 weeks to establish the non-alcoholic fatty liver model. After 4 weeks of treatment, blood was collected from the eyeballs, the mice were sacrificed, and relevant indicators were detected. The results showed that compared with the model group, blood lipid and blood glucose levels of each treatment group were significantly lower(P<0.05); HE staining results showed that liver pathological damage in each treatment group was significantly improved; oil red O staining results showed fat distribution in each treatment group significantly reduced(P<0.01); immunohistochemical staining showed that glucose regulated the protein expression of protein 78(GRP78) in liver tissues of each treatment group was also significantly reduced(P<0.01); Western blot results showed that endoplasmic reticulum stress signal pathway-related factors GRP78, phosphorylated-protein kinase R-like ER kinase(p-PERK), eukaryotic translation-initiation factor 2α(eIF2α), activating transcription factor 4(ATF4), C/EBP homologous protein(Chop), inositol requiring 1α(IRE1α), and cleaved-cysteinyl aspartate specific proteinase 12(cleaved-caspase-12) were significantly reduced(P<0.01). The results of the combined drug treatment group were better than those of the single drug treatment group. These results showed that B. pilosa decoction had the effect in improving non-alcoholic fatty liver, and its mechanism may be related to the down-regulation of the expression of endoplasmic reticulum stress(ERS)-related factors, and the reduction of the apoptosis of hepatocytes caused by ERS and the down-regulation of blood lipid and blood glucose levels.
Animals ; Apoptosis ; Bidens ; Endoplasmic Reticulum Stress ; Endoribonucleases ; Glucose ; Mice ; Non-alcoholic Fatty Liver Disease ; Protein-Serine-Threonine Kinases

The aim of this study was to investigate the preventive and therapeutic effects of Erzhi Pills on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine( MPTP)-induced Parkinson's disease( PD) in mice,and explore its possible mechanism of action. Mice were intraperitoneally injected with MPTP( 30 mg·kg^-1,0. 01 m L·g^-1) once daily to induce PD for 8 days. In the treatment group,Erzhi Pills were given by intragastric administration( 2. 5 g·kg^-1,once daily for 30 days). The normal group received an equal volume of normalsaline. In terms of behavior,the limb movement coordination ability of the mice was detected by climbing,hanging and swimming experiments. The spatial learning and memory ability of the mice was detected by Morris water maze test. The content of MDA,as well as the activity of GSH-PX and SOD were determined in mice serum. Western blot was used to detect the protein expression levels of TH,MAOB and apoptosis-related factors CHOP and caspase-12 in brain tissues. Immunohistochemistry was used to detect the expression of TH in section of brain tissues in mice. The results showed that in behavioral aspects,as compared with the model group,the scores of limb movement ability as well as scores of spatial learning and memory ability were significantly improved in the treatment groups( P<0. 05). In terms of serological indicators,as compared with the model group,the activities of SOD and GSH-PX were significantly increased in the serum of treatment groups,and the content of MDA was significantly decreased( P<0. 05). The results of Western blot showed that as compared with the model group,the protein levels of TH in the brain tissues of the mice in treatment group were significantly up-regulated,while the protein levels of MAOB and apoptosis-related factors CHOP and caspase-12 were significantly down-regulated( P<0. 05). The results of immunohistochemistry showed that the number of TH positive cells in the brain tissues of the mice in the treatment group was significantly increased as compared with the model group( P<0. 05). In summary,Erzhi Pills have a certain preventive and therapeutic effect on MPTP-induced PD mice,which can significantly improve the limb motor coordination ability and spatial learning and memory ability of PD mice. Its mechanism may be related to down-regulating the expression of apoptosis-related factors CHOP and caspase-12,reducing the dopaminergic neuron damage and inhibiting dopaminergic neuronal apoptosis.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Animals ; Disease Models, Animal ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Mice, Inbred C57BL ; Neuroprotective Agents/pharmacology* ; Parkinson Disease ; Substantia Nigra

OBJECTIVETo investigate the presence of leukemia stem cells (LSC) in acute myeloid leukemia (AML) and find out the relative position of leukemia cells in the figures of flow cytometry, and to analyze the relationship between minimal residual diseases (MRD) and the level of LSC, so as to explore the correlation of LSC changes with the curative effect and the prognosis during chemical therapy.

METHODSA total of 85 samples were collected from 50 AML (except M3) patients, including 50 samples from the newly diagnosed patients, 7 samples of AML patients with non-remission and 28 samples of AML patients with complete remission. All samples were used for detection of LSC from immune phenotype of CD34/CD38/CD123 by flow cytometry. The detection of immune phenotypic of leukemia cells was performed in the newly diagnosed patients. The detection of leukemia- associated immune phenotypes (LAIP) was implemented in the non-newly diagnosed patients.

RESULTSThe LSC was identified in the CD34/ CD38/ CD123 in AML and consistent with the relative position of the leukemia cell in flow cytometry figures. Statistical analysis showed significant difference in LSC content between the newly diagnosed AML group and the post-chemotherapy complete remission group(P<0.01),but did not between the newly diagnosed AML group and the post-chemotherapy non-remission group(P>0.05).There was significant positive correlation between the LSC content and MRD level in 28 AML patients with complete remission (r=0.680,P<0.01).

CONCLUSIONLSC exist in AML and the relative position are consistent with the leukemia cells in flow cytometry figures, the size characteristics and weak expression of CD45 are also similar to leukemia cells. The proportion of LSC decreases after chemotherapy. Detecting and tracking the LSC changes in bone marrow and combination with detecting minimal resident disease(MRD) may contribute to evaluate the theraputic efficacy and prognosis of leukemia patients.

OBJECTIVETo explore role of MIER3 gene in the development and progression of human colorectal carcinoma (CRC) and analyze the proteins that interact with MIER3 using bioinformatic techniques.

METHODSMIER3 mRNA and protein expressions were detected in 8 CRC biopsy samples and paired adjacent tissues using real-time PCR and Western blotting. A recombinant eukaryotic expression vector pcDNA3-MIER3 was constructed and its effect on the proliferation and invasion of CRC cells were tested using CCK8 assay and Transwell migration assay. Bioinformatic methods were used to predict and analyze MIER3-interacting proteins.

RESULTSMIER3 was obviously down-regulated in the 8 CRC tissues as compared with the paired adjacent tissues. In human CRC cell line DLD1, MIER3 overexpression induced by transfection of the cells with pcDNA3-MIER3 significantly inhibited the cell proliferation and suppressed cell invasiveness in vitro. Bioinformatics analyses indicated that NAT9 was a potential MIER3-interacting protein and MIER3 was probably associated with tumor susceptibility.

CONCLUSIONMIER3, which is obviously down-regulated in CRC tissues, is closely associated with the proliferation and invasion of CRC, and NAT9 protein is a probable MIER3-interacting protein.

BACKGROUNDTherapeutic hypothermia has been recommended for the treatment of cardiac arrest patients who remain comatose after the return of spontaneous circulation. The aim of this study was to evaluate the effectiveness and safety of mild hypothermia on patients with cardiac arrest by conducting a meta-analysis.

METHODSThe relevant trials were searched in Cochrane Library, PubMed, Web of Science, Embase, CNKI and Wan Fang Data from the date of their establishment to October 2014. Thereafter, the studies retrieved were screened based on predefined inclusion and exclusion criteria. Data were extracted, and the quality of the included studies was evaluated. A meta-analysis was conducted using the Cochrane Collaboration Review Manager 5.2 software.

RESULTSSix randomized controlled trials involving 531 cases were included, among which 273 cases were assigned to the treatment group and the other 258 cases to the control group. The meta-analysis indicated that mild hypothermia therapy after cardiac arrest produced significant differences in survival rate (relative risk [RR] =1.23, 95% confidence interval [CI]: 1.02-1.48, P = 0.03) and neurological function (RR = 1.33, 95% CI: 1.08-1.65, P = 0.007) after 6 months compared with normothermia therapy. However, no significant differences were observed in the survival to the hospital discharge (RR = 1.35, 95% CI: 0.87-2.10, P = 0.18), favorable neurological outcome at hospital discharge (RR = 1.53, 95% CI: 0.95-2.45, P = 0.08) and adverse events.

CONCLUSIONSThe meta-analysis demonstrated that mild hypothermia can improve the survival rate and neurological function of patients with cardiac arrest after 6 months. On the other hand, regarding the survival to hospital discharge, favorable neurological outcome at hospital discharge, and adverse events, our meta-analysis produced nonsignificant results.

Objective To evaluate the effect of process management of laparoscopic apparatus in sterilization and supply center with operating room.Methods The process management of laparoscopic apparatus in sterilization and supply center with operating room (OR) included the use and the process after using the laparoscopic apparatus in OR,as well as the receiving,cleaning,quality determination,packaging,sterilization and sending process in SSC.Effect before and after process management was compared.Results The qualified rates of sterilization and equipment packaging of laparoscopic apparatus and the nursing satisfaction were respectively (99.60 ± 0.38) ％,(98.40 ± 0.64) ％,(98.90 ± 2.84) ％ after process management,and (97.80 ±0.86) ％,(92.80 ± 1.32) ％,(86.14 ± 3.26) ％ before,and the differences were statistically significant (t =32.83,65.92,20.02,respectively;P ＜0.01).The cycle time and fault rate of laparoscopic apparatus were (2.12 ± 0.34) h and (0.24 ± 0.11) ％ after process management,and (2.68 ± 0.66) h and (0.56 ± 0.47) ％before,and the differences were statistically significant (t =2.60,11.48,respectively;P ＜ 0.01).Conclusions Process management of laparoscopic apparatus in sterilization and supply center with operating room can not only assure the cleaning and sterilization quality,but also improve the working efficiency,job satisfaction and nursing quality in OR as well.

Semen-derived enhancer of viral infection(SEVI) is a peptide fragment (PAP248-286) from prostatic acid phosphatase(PAP), which can enhance human immunodeficiency virus infection. The mechanisms of SEVI include: (1) SEVI with several cationic amino acid residues reduced electrostatic repulsion between HIV virus and the target cells; (2) The disorder state of SEVI in the human body fluids was helpful to the interaction between virus and the target cell membranes; (3) SEVI could capture HIV particles directly and speed the velocity of virus on the surface of the target cells and improve adsorption and fusion. Currently, the substances of inhibiting SEVI activity include: EGCG from green tea, small molecule compound of aminoquinoline Surfen, ThT analogs BTA-EG6. Those compounds might block the combination of HIV and SEVI or prevent the formation of amyloid fibers, and then reduce the enhancement of SEVI. The studies on the biological characteristics and mechanisms of SEVI have a big benefit for the prevention and treatment of HIV infection.
HIV Infections ; etiology ; transmission ; Humans ; Male ; Semen ; physiology ; Sexually Transmitted Diseases, Viral ; etiology ; Static Electricity