PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

Association Analysis between Genotype and Phenotype of α,β-Thalassaemia Carriers in Huizhou Area of Guangdong Province / 中国实验血液学杂志

OBJECTIVE@#To analyze the prevalence, genotype distribution and hematological characteristics of α,β-thalassaemia carriers in Huizhou area of Guangdong Province.@*METHODS@#10 809 carriers of simple β-thalassaemia and 1 757 carriers of α,β-thalassaemia were enrolled as our study cohort. The hematological parameters were detected by automated blood cell counters and automatic capillary electrophoresis. Suspension array technology, gap-polymerase chain reaction (gap-PCR) and PCR-reverse dot blot were used for the genotyping of thalassaemia carriers.@*RESULTS@#The prevalence of α,β-thalassaemia in Huizhou area of Guangdong Province was 1.99%. A total of 62 genotypes were detected, and the most prevalent genotype was --SEA/ αα, βCD41-42/ βN (19.29%), the next was --SEA/ αα, βIVS-II-654/ βN (16.73%). Significant differences in mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were found between different genotype groups for simple β-thalassaemia and α,β-thalassaemia. Violin plots showed that carriers with co-inheritance of β-thalassaemia and mild α-thalassaemia expressed the lightest anemia, and carriers with co-inheritance of β-thalassaemia and hemoglobin H (Hb H) disease expressed the most severe anemia.@*CONCLUSION@#There is a high prevalence of α,β-thalassaemia in Huizhou area of Guangdong Province. Because of the lack of specific hematological makers for diagnosis of α,β-thalassaemia, it is necessary to distinguish it from simple β-thalassaemia by genotyping of α- and β-thalassaemia in order to correctly guide genetic counseling and prenatal disgnosis.

Inhibitory effects of formononetin on lipopolysaccharide-induced apoptosis and inflammatory response in alveolar epithelial cells / 中国药房

OBJECTIVE To investigate the inhibitory effects of formononetin on lipopolysaccharide （LPS）-induced apoptosis and inflammatory response in alveolar epithelial cells through phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. METHODS Human lung cancer alveolar basal epithelial cells A549 were cultured in vitro and divided into control group （no intervention）， model group （1 μg/mL LPS）， different concentrations of formononetin groups （1 μg/mL LPS+6.25， 12.5， 25， 50 μmol/L formononetin）. The levels of inflammatory factors （interleukin-8， tumor necrosis factor-α） and cell viability were detected in each group. Another A549 cells were divided into control group， model group （1 μg/mL LPS）， LPS+25 group （1 μg/mL LPS+25 μmol/L formononetin）， inhibitor group （1 μg/mL LPS+20 μmol/L LY294002）， formononetin+inhibitor group （1 μg/mL LPS+25 μmol/L formononetin+20 μmol/L LY294002） and formononetin+activator group （1 μg/mL LPS+25 μmol/L formononetin+ 10 μmol/L SC79）. The secretion levels and mRNA expressions of inflammatory factors， cell apoptosis， and expressions of the key proteins of PI3K/Akt signaling pathway were detected in each group. RESULTS Compared with model group， the levels of inflammatory factors were decreased significantly after the intervention of 25 μmol/L of formononetin， and the cell viability was increased significantly （P＜0.05）. Compared with the control group， the secretion levels and mRNA expressions of inflammatory factors， apoptotic rate， and relative expressions of phosphorylated Akt and phosphorylated PI3K of the model group were increased significantly （P＜0.05）. Compared with the model group， the above indexes of the LPS+25 group and the inhibitor group were decreased significantly （P＜0.05）. Compared with the LPS+25 group， the above indicators of formononetin+inhibitor group were further decreased， while those of formononetin+activator group were increased significantly （P＜0.05）. CONCLUSIONS Formononetin can inhibit LPS-induced epithelial cell apoptosis and improve inflammatory response， and the mechanism may be related to the inhibition of the PI3K/Akt signaling pathway.

Clinical analysis of children with pathological phimosis treated by circumcision / 中华泌尿外科杂志

Objective:To investigate the clinical characteristics of pathological phimosis and analyze the correlation between pathological phimosis and balanitis xerotica obliterans(BXO) in children.Methods:The clinical data of 45 children who underwent circumcision and histopathologic evaluation in our hospital from July 2018 to August 2022 were retrospectively analyzed. According to the results of the pathological examination, lichen sclerosis et atrophicus cases were classified as the BXO group, and other cases were classified as the non-BXO group. The two groups' age, history, and symptoms were recorded and compared. The management of meatal stenosis and the effect of topical steroids were described.Results:There were 33 patients in the BXO group, aged (7.42±2.46)years old, of which 91% (30/33) were 5-11 years old. There were 12 patients in the non-BXO group, aged (10.42±2.88) years old. The difference of age between the two groups was statistically significant ( P< 0.05). But there was no significant difference between the BXO group and non-BXO group in the history of balanoposthitis(28 cases vs. 7 cases), history of foreskin dilated(15 cases vs. 3 cases), frequent urination (18 cases vs. 10 cases), urgent urination(12 cases vs. 4 cases), urination pain(17 cases vs. 3 cases), dysuria(21 cases vs. 5 cases), pruritus(25 cases vs. 7 cases), penile pain(7 cases vs. 1 case), ballooning(7 cases vs. 6 cases), and spraying (14 cases vs. 2 cases)( P > 0.05). All 8 cases of meatal stenosis were in the BXO group. Three cases underwent meatal dilatation and indwelling catheter was left for 5-10 days, and topical steroid was used on the third day after surgery. The remaining cases were treated with topical steroids after a pathological diagnosis of BXO. Among the 4 cases with partial urethral meatus involvement, 3 had good results after treatment, and 1 had no significant improvement and underwent meatal dilatation twice later. In 1 case, meatal stenosis was found two weeks after surgery, but no meatal abnormality was found during operation. All patients recovered smoothly during a median follow-up of 12.2 (5.4, 21.8) months. Conclusions:BXO is the main cause of pathologic phimosis in boys, and the diagnosis is based on histopathology. The main complication of BXO is meatal stenosis, which should be detected as early as possible and treated in time.

Dynamic changes and clinical value of serum angiopoietin-2 and surfactant protein D in pediatric acute respiratory distress syndrome / 中国小儿急救医学

Objective:To study the relationship between the dynamic changes of angiopoietin-2 (Ang-2) and surfactant protein D (SP-D) in pediatric acute respiratory distress syndrome (pARDS) and the severity and prognosis of the disease.Methods:Using nested case-control study method, 80 children with pneumonia complicated with pARDS admitted to PICU at Fujian Maternal and Child Health Hospital from June 2018 to May 2021 were selected as pARDS group, and 19 healthy children with corresponding age were selected as control group.According to the oxygenation, the children in pARDS group were divided into three subgroups: mild group (23 cases), moderate group (32 cases) and severe group (25 cases). According to the prognosis at discharge, the children in pARDS group were divided into survival group (67 cases) and death group (13 cases). Ang-2 and SP-D were detected by enzyme-linked immunosorbent assay.The levels of Ang-2 and SP-D in children with pARDS of different severity on the first day were compared; The changes of Ang-2 and SP-D levels on the 1st, 3rd and 8th day of children in survival group and death group were compared, and the receiver operating characteristic (ROC) curve was plotted to compare the predictive value of Ang-2 and SP-D for pARDS prognosis.Results:(1) The levels of Ang-2 and SP-D on the first day in pARDS group were significantly higher than those in control group( P<0.001). (2) The levels of Ang-2 and SP-D on the first day in children with pARDS of different severity levels were significantly different ( P<0.001), and the levels of Ang-2 and SP-D increased gradually with the increase of disease severity.(3) The levels of Ang-2 and SP-D in death group were significantly higher than those in survival group on the 1st, 3rd and 8th day ( P<0.05). (4) Prognostic efficacy of Ang-2 and SP-D levels in pARDS group at different time points: when the areas under the ROC curve predicted by Ang-2 on the 1st, 3rd and 8th day for inpatient mortality in children with pARDS were 0.808, 0.981 and 0.989, respectively; the optimal cut-off values were 6 000 pg/mL, 6 971 pg/mL and 4 171 pg/mL, respectively; the sensitivity was 84.6%, 92.3% and 92.3%, respectively; and the specificity was 76.1%, 97.0% and 98.5%, respectively.The areas under the ROC curve predicted by SP-D on the 1st, 3rd and 8th day for inpatient mortality in children with pARDS were 0.689, 0.993 and 0.983, respectively; the optimal cut-off values were 13544 pg/mL, 16003 pg/mL and 12294 pg/mL, respectively; the sensitivity was 84.6%, 100.0% and 100.0%, respectively; and the specificity was 46.3%, 98.5% and 97.0%, respectively. Conclusion:Serum Ang-2 and SP-D levels in children with pARDS increase with the aggravation of the disease.The dynamic changes of Ang-2 and SP-D in children with pARDS with different prognosis are different during the course of disease, and monitoring serum Ang-2 and SP-D during the course of disease has a certain predictive value for clinical outcome.

Distribution of pathogenic bacteria of bloodstream infection after chemotherapy in patients with acute leukemia and risk factors analysis of the occurrence of adverse events and prediction model construction / 白血病·淋巴瘤

Objective:To investigate the distribution of pathogenic bacteria of bloodstream infection after chemotherapy in patients with acute leukemia (AL), to analyze the risk factors for the occurrence of adverse events and to construct a nomogram model to predict the occurrence of adverse events.Methods:The clinical data of 313 AL patients with bloodstream infection who were admitted to the First Hospital of Jilin University from January 2018 to December 2020 were retrospectively analyzed, and the incidence, fatality and distribution characteristics of pathogenic bacteria after chemotherapy in AL patients were analyzed; the occurrence of adverse events (death or infectious shock) in patients with different clinicopathological characteristics were compared. Unconditional logistic binary regression model multifactor analysis was used to screen independent risk factors for the occurrence of adverse events in AL patients with bloodstream infection after chemotherapy; the nomogram model for predicting the occurrence of adverse events was developed by using R software; the Hosmer-Lemeshow test was used to verify the predictive effect of the model.Results:Of the 313 AL patients, the overall fatality rate was 4.2% (13/313), the all-cause fatality rate of bloodstream infection was 3.5% (11/313). Of the 313 cases, 254 cases (81.1%) were Gram-negative bacteria infection, mainly including 115 cases (45.3%) of Escherichia coli, 80 cases (31.5%) of Klebsiella pneumoniae, and 29 cases (11.4%) of Pseudomonas aeruginosa, and 10 cases (3.9%) died; 51 cases (16.3%) were Gram-positive cocci infection, mainly including 22 cases (43.1%) of Streptococcus spp., 20 cases (39.2%) of Staphylococcus spp., 7 cases (13.7%) of Enterococcus faecalis, and 0 case died; 8 cases (2.6%) were fungal infection, including 4 cases (1.3%) of Candida tropicalis, 2 cases (0.6%) of Candida subsmoothis, 1 case (0.3%) of Candida smooth, 1 case (0.3%) of new Cryptococcus, and 3 cases (37.5%) died. The differences in the occurrence rates of adverse events were statistically significant when comparing different treatment stage, risk stratification, timing of sensitive antibiotic use, total duration of fever, and glucocorticoid use in chemotherapy regimen, infecting bacteria carbapenem resistance, and leukemia remission (all P < 0.05). The results of logistic binary regression analysis showed that the use of glucocorticoid in chemotherapy regimen, the total duration of fever ≥7 d, the timing of sensitive antibiotic use ≥24 h, and carbapenem resistance of the infecting bacteria were independent risk factors for the occurrence of adverse events in AL patients with bloodstream infection after chemotherapy (all P < 0.05). A nomogram prediction model for the occurrence of adverse events in AL patients with bloodstream infection was established, and the nomogram model was calibrated and validated with good calibration and discrimination. Conclusions:The pathogenic bacteria of bloodstream infection after chemotherapy in AL patients is mainly Gram-negative bacteria, and the presence of glucocorticoid in chemotherapy regimen, long total duration of fever, poor timing of sensitive antibiotics, and infecting bacteria carbapenem resistance are risk factors for the occurrence of adverse events in AL patients with bloodstream infection after chemotherapy, and the nomogram prediction model based on these factors has a reliable predictive ability for the occurrence of adverse events.

Meranzin Hydrate Improves Depression-Like Behaviors and Hypomotility via Ghrelin and Neurocircuitry / 中国结合医学杂志

OBJECTIVE@#To investigate whether meranzin hydrate (MH) can alleviate depression-like behavior and hypomotility similar to Chaihu Shugan Powder (CSP), and further explore the potential common mechanisms.@*METHODS@#Totally 120 Spraque-Dawley rats were randomly divided into 5-8 groups including sham, vehicle, fluoxetine (20 mg/kg), mosapride (10 mg/kg), CSP (30 g/kg), MH (9.18 mg/kg), [D-Lys3]-GHRP-6 (Dlys, 0.5 mg/kg), and MH+Dlys groups by a random number table, 8 rats in each group. And 32 mice were randomly divided into wild-type, MH (18 mg/kg), growth hormone secretagogue receptor-knockout (GHSR-KO), and GHSR+MH groups, 8 mice in each group. The forced swimming test (FST), open field test (OFT), tail suspension test (TST), gastric emptying (GE) test, and intestinal transit (IT) test were used to assess antidepressant and prokinetic (AP) effects after drug single administration for 30 min with absorbable identification in rats and mice, respectively. The protein expression levels of brain-derived neurotrophic factor (BDNF) and phosphorylated mammalian target of rapamycin (p-mTOR) in the hippocampus of rats were evaluated by Western blot. The differences in functional brain changes were determined via 7.0 T functional magnetic resonance imaging-blood oxygen level-dependent (fMRI-BOLD).@*RESULTS@#MH treatment improved depression-like behavior (FST, OFT) and hypomotility (GE, IT) in the acute forced swimming (FS) rats (all P<0.05), and the effects are similar to the parent formula CSP. The ghrelin antagonist [D-Lys3]-GHRP-6 inhibited the effect of MH on FST and GE (P<0.05). Similarly, MH treatment also alleviated depression-like behavior (FST, TST) in the wild-type mice, however, no effects were found in the GHSR KO mice. Additionally, administration of MH significantly stimulated BDNF and p-mTOR protein expressions in the hippocampus (both P<0.01), which were also prevented by [D-Lys3]-GHRP-6 (P<0.01). Besides, 3 main BOLD foci following acute FS rats implicated activity in hippocampus-thalamus-basal ganglia (HTB) circuits. The [D-Lys3]-GHRP-6 synchronously inhibited BOLD HTB foci. As expected, prokinetic mosapride only had effects on the thalamus and basal ganglia, but not on the hippocampus. Within the HTB, the hippocampus is implicated in depression and FD.@*CONCLUSIONS@#MH accounts for part of AP effects of parent formula CSP in acute FS rats, mainly via ghrelin-related shared regulation coupled to BOLD signals in brain areas. This novel functionally connection of HTB following acute stress, treatment, and regulation highlights anti-depression unified theory.

Factors Influencing and Adverse Reactions of Voriconazole Clearance in Patients with Hematological Diseases / 中国实验血液学杂志

OBJECTIVE@#To monitor the changes of voriconazole minimum concentration(Cmin) in patients with hematological diseases, and evaluate the factors influencing and adverse reactions of voriconazole clearance in patients with hematological diseases, so as to provide a theoretical basis for reasonable clinical use of voriconazole.@*METHODS@#136 patients with hematological diseases who used voriconazole in Wuhan NO.1 Hospital from May 2018 to December 2019 were selected. The correlation between C-reactive protein, albumin, creatinine and voriconazole Cmin were analyzed, and the changes of voriconazole Cmin after glucocorticoid treatment was also detected. In addition, stratified analysis was used to explore the adverse events of voriconazole.@*RESULTS@#Among 136 patients, 77 were male (56.62%) and 59 were female (43.38%). There were positive correlations between voriconazole Cmin and C-reactive protein and creatinine levels (r=0.277, r=0.208), while voriconazole Cmin was negatively correlated with albumin level (r=-2.673). Voriconazole Cmin in patients treated with glucocorticoid was decreased significantly (P<0.05). In addition, sratified analysis of voriconazole Cmin showed that compared with voriconazole Cmin 1.0-5.0 mg/L group, the incidence of adverse reactions of visual impairment in voriconazole Cmin> 5.0 mg/L group was increased (χ2=4.318, P=0.038).@*CONCLUSION@#The levels of C-reactive protein, albumin and creatinine are closely related to the voriconazole Cmin, which indicate that inflammation and hyponutrition may prevent the clearance of voriconazole in patients with hematological diseases. It is necessary to monitor the voriconazole Cmin of patients with hematological diseases, and adjust the dosage in time to reduce adverse reactions.

To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia / 中华血液学杂志

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

Acupoint compatibility effect: increasing "effect value" and expanding "effect domain" / 中国针灸

By summarizing and exploring the theoretic connotation, key of functions and effect mechanism of acupoint compatibility, the effect of acupoint compatibility is concluded as the increase of "effect value" and the expansion of "effect domain". The increase of "effect value" is the concrete embodiment by the value of medical assessment scale, the value of objective index detection in clinical trial and the value of index detection in experiment research. The expansion of "effect domain" is the increase of effect target and the extension of effect scope. The paper interprets the scientific connotation of acupoint compatibility therapy from a new perspective, and emphasizes the innovative approaches to research while bringing forth new ideas on the research method. It is anticipated that a novel breakthrough can be achieved in the study of acupoint compatibility and the improvement of acupuncture-moxibustion efficacy.

Analysis of pathogenic bacteria distribution and drug resistance characteristics of bloodstream infection in patients with neutrophilic deficiency after chemotherapy in acute leukemia / 中国热带医学

@#Abstract: Objective　To investigate the distribution and drug resistance characteristics of pathogenic bacteria in patients with neutropenic acute leukemia (AL) and bloodstream infections (BSI). Methods　The clinical data of 258 neutropenic acute leukemia patients with bloodstream infections, who admitted to Shengjing Hospital of China Medical University from January 2016 to December 2021, were collected and analyzed for pathogenic bacteria and drug resistance. Results A total of 268 strains of pathogenic bacteria were isolated from 258 patients, including 180 strains of gram-negative bacteria (67.16%), 61 strains of gram-positive bacteria (22.76%), and 27 strains of fungi (10.07%). Gram-negative bacteria were mainly Klebsiella pneumoniae (53/268, 19.78%), Escherichia coli (49/268, 18.28%) and Pseudomonas aeruginosa (41/268, 15.30%). Gram-positive bacteria were mainly coagulase negative Staphylococcus (31/268, 11.57%) and Staphylococcus aureus(17/268, 6.34%). The main fungi were Candida tropicalis (25/268, 9.33%). Escherichia coli (33/268, 12.31%) was the most common pathogen isolated from acute myeloid leukemia (AML), followed by Pseudomonas aeruginosa (25/268, 9.33%), coagulase-negative Staphylococcus (18/268, 6.72%) and Candida tropicalis (18/268, 6.72%). Klebsiella pneumoniae (35/268, 13.06%) was the most common pathogen isolated from acute lymphoblastic leukemia (ALL),followed by Pseudomonas aeruginosa (15/268, 5.60%) and Escherichia coli (14/268, 5.22%). The resistance of Gram-negative bacteria to piperacillin/tazobactam, cefoperazone/sulbactam, imipenem, meropenem, ertapenem, amikacin, cefoxitin, amoxicillin/clavulanic acid was low. Gram-positive bacteria were sensitive to linezolid and vancomycin. Candida was sensitive to flucytosine, amphotericin B and itraconazole. Conclusions　In patients with granulosa after AL chemotherapy combined with BSI, the pathogenic bacteria isolated from AML are diverse, and the pathogenic bacteria isolated from ALL are mainly gram-negative bacteria. Pathogenic bacteria have different degrees of drug resistance to commonly used antibacterial drugs, so it is important to strengthen the monitoring of the distribution of pathogenic bacteria and the change of drug resistance and rational use of antibacterial drugs to minimize the death of patients.

Antiviral effect of Fufang yinhua jiedu (FFYH) granules against coronavirus and its potential mechanism / 药学学报

To investigate the effect of Fufang yinhua jiedu (FFYH) granules against coronavirus and its potential mechanism, we used Huh7, Huh7.5, H460, and C3A cell lines as in vitro models to evaluate the cytotoxicity and antiviral activity of FFYH by observation of cell pathogenic effect (CPE); and then the inhibitory effect of FFYH on the transcription expression of coronavirus RNA and inflammatory factor mRNA were evaluated by quantitive reverse transcription PCR (qRT-PCR); finally, the inhibitory effect of FFYH on the expression of coronavirus protein and its underlying mechanism against coronavirus were investigated by Western blot and immunofluorescence. Our results indicated that 50% toxic concentration (TC50) FFYH on Huh7, Huh7.5, H460, and C3A cells were 2 035.21, 5 245.69, 2 935.28 and 520 µg·mL-1, respectively; 50% inhibitory concentration (IC50) of FFYH on HCoV-229E in Huh7 and Huh7.5 cells were 438.16 and 238.54 µg·mL-1 with safety index (SI) of 4.64 and 21.99, respectively; IC50 of FFYH on HCoV-OC43 in H460 cells was 165.13 µg·mL-1 with SI of 17.78. Moreover, FFYH not only could inhibit the replication of coronaviruses (HCoV-OC43 and HCoV-229E) through inhibiting the transcription of viral RNA and the expression of viral protein, but also effectively suppress the expression of inflammatory factors interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) and interleukin-8 (IL-8) at mRNA level caused by coronaviruses, which might be associated with the inhibitory effect of FFYH on mitogen-activated protein kinase (MAPK) pathway and the nuclear translocation of nuclear transcription factor-κB (NF-κB). In summary, our results demonstrated that FFYH exhibited a good in vitro anti-coronavirus effect, which provides a theoretical basis for its clinical use in the treatment of anti-coronavirus pneumonia.

Oxygen Metabolism-induced Stress Response Underlies Heart-brain Interaction Governing Human Consciousness-breaking and Attention / 神经科学通报·英文版

Neuroscientists have emphasized visceral influences on consciousness and attention, but the potential neurophysiological pathways remain under exploration. Here, we found two neurophysiological pathways of heart-brain interaction based on the relationship between oxygen-transport by red blood cells (RBCs) and consciousness/attention. To this end, we collected a dataset based on the routine physical examination, the breaking continuous flash suppression (b-CFS) paradigm, and an attention network test (ANT) in 140 immigrants under the hypoxic Tibetan environment. We combined electroencephalography and multilevel mediation analysis to investigate the relationship between RBC properties and consciousness/attention. The results showed that RBC function, via two independent neurophysiological pathways, not only triggered interoceptive re-representations in the insula and awareness connected to orienting attention but also induced an immune response corresponding to consciousness and executive control. Importantly, consciousness played a fundamental role in executive function which might be associated with the level of perceived stress. These results indicated the important role of oxygen-transport in heart-brain interactions, in which the related stress response affected consciousness and executive control. The findings provide new insights into the neurophysiological schema of heart-brain interactions.

The comparison of survival between active surveillance or watchful waiting and focal therapy for low-risk prostate cancer: a real-world study from the SEER database / 亚洲男科学杂志(英文版)

To reduce treatment-related side effects in low-risk prostate cancer (PCa), both focal therapy and deferred treatments, including active surveillance (AS) and watchful waiting (WW), are worth considering over radical prostatectomy (RP). Therefore, this study aimed to compare long-term survival outcomes between focal therapy and AS/WW. Data were obtained and analyzed from the Surveillance, Epidemiology, and End Results (SEER) database. Patients with low-risk PCa who received focal therapy or AS/WW from 2010 to 2016 were included. Focal therapy included cryotherapy and laser ablation. Multivariate Cox proportional hazards models were used to compare overall mortality (OM) and cancer-specific mortality (CSM) between AS/WW and focal therapy, and propensity score matching (PSM) was performed to reduce the influence of bias and unmeasured confounders. A total of 19 292 patients with low-risk PCa were included in this study. In multivariate Cox proportional hazards model analysis, the risk of OM was higher in patients receiving focal therapy than those receiving AS/WW (hazard ratio [HR] = 1.35, 95% confidence interval [CI]: 1.02-1.79, P = 0.037), whereas no significant difference was found in CSM (HR = 0.98, 95% CI: 0.23-4.11, P = 0.977). After PSM, the OM and CSM of focal therapy and AS/WW showed no significant differences (HR = 1.26, 95% CI: 0.92-1.74, P = 0.149; and HR = 1.26, 95% CI: 0.24-6.51, P = 0.782, respectively). For patients with low-risk PCa, focal therapy was no match for AS/WW in decreasing OM, suggesting that AS/WW could bring more overall survival benefits.

Effect analysis of trajectory screw technique in fragility fracture of pelvic ring / 中国骨伤

OBJECTIVE@#To assess the clinical efficacy of minimally invasive technology with trajectory screw fixation for fragility fractures of pelvic(FFP).@*METHODS@#A retrospective case control study was performed to analyze the clinical data of 35 patients with FFP who were treated and followed up between January 2016 and December 2019. There were 12 males and 23 females, aged from 65 to 99 years with an average of(75.4±7.8) years old. There were 13 cases of type Ⅱb, 7 cases of type Ⅱc, 8 cases of type Ⅲa, 2 cases of type Ⅲb, 2 cases of type Ⅲc, 1 case of type Ⅳb, and 2 cases of type Ⅳc according to Rommens FFP comprehensive classification. All patients received the treatment of minimally invasive technology with trajectory screws fixation. According to the different methods of anterior pelvic ring fixation, FFP patients were divided into two groups:12 cases were fixed with the pedicle screw rod system in the anterior pelvic subcutaneous internal fixator (INFIX) group;23 cases were fixed with hollow screws of the pubic symphysis, superior ramus of pubis or acetabular anterior column in the screw group. The operation time, intraoperative blood loss, intraoperative fluoroscopy times, length of hospital stay, cost of internal fixation, pre- and post-operative visual analogue scale(VAS) were compared between the two groups. The fracture reduction quality was evaluated according to the Matta criteria, and the clinical function was evaluated by the Majeed functional scoring system respectively.@*RESULTS@#All patients were followed up for 12 to 39(16.5±5.4) months after surgery. There was no statistically significant difference in the operation time, intraoperative blood loss, intraoperative fluoroscopy time, and length of hospital stay between the two groups(P>0.05). As for the cost of internal fixation, the cost of internal fixation in the screw group [2 914 (2 914, 4 371) yuan] was significantly lower than that of the INFIX group [6 205 (6 205, 6 205) yuan] (P<0.05). No significant difference was observed in the incidence of postoperative complications between the two groups (P>0.05). There was no significant difference in VAS assessment at admission, 1 week, and 3 months after surgery between the two groups(P>0.05). However, the VAS assessment at 1 week and 3 months after surgery of the two groups were significantly better than those at admission(P<0.05). There was no significant difference in the quality of fracture reduction after the operation and the efficacy evaluation at the last follow-up between the two groups(P>0.05).@*CONCLUSION@#For the treatment of fragility fractures, minimally invasive technology with trajectory screw fixation can achieve good clinical efficacy. It has the advantages of being relatively minimally invasive, less bleeding, relieving the pain. It deserves clinical application.

Analysis on incidence of occupational diseases in Guangzhou from 2010 to 2020 / 中华劳动卫生职业病杂志

Objective: To analyze the incidence characteristics of occupational diseases in Guangzhou from 2010 to 2020, provide scientific basis for formulating occupational disease prevention and control policies. Methods: In January 2021, based on the data of occupational diseases in Guangzhou reported in the Information Monitoring System of Occupational Diseases and Occupational Health, descriptive epidemiological method was used to analyze the types and characteristics of occupational diseases in Guangzhou from 2010 to 2020. Results: A total of 1341 cases of 38 kinds of occupational diseases in 9 categories were reported in the past 11 years. The incidence of occupational pneumoconiosis, occupational otolaryngology and oral diseases and occupational chemical poisoning ranked the top three, accounting for 38.1% (511/1341) , 30.5% (409/1341) and 16.2% (217/1341) of the total cases respectively. The cases of pneumoconiosis in welders and silicosis accounted for 47.7% (244/511) and 34.4% (176/511) of the cases of occupational pneumoconiosis respectively. The cases of noise deafness accounted for 99.8% (408/409) of occupational otorhinolaryngology oral diseases. Acute occupational chemical poisoning cases accounted for 26.7% (58/217) of the occupational chemical poisoning cases, in which dichloroethane poisoning cases ranked the first, accounting for 79.3% (46/58) . Chronic occupational chemical poisoning cases accounted for 73.3% (159/217) of the occupational poisoning cases, in which benzene and lead poisoning cases ranked the top two, accounting for 79.2% (126/159) and 17.6% (28/159) respectively. Conclusion: Pneumoconiosis, silicosis, noise deafness, benzene poisoning, lead poisoning, dichloroethane poisoning should be supervised and managed as key occupational diseases in Guangzhou.

Research on the mechanism of bufalin inhibiting migration and invasion of human prostate cancer PC3 cells / 药学学报

In this study, we investigated the inhibitory effects of bufalin on proliferation, migration and invasion of PC3 cells in vitro, and preliminarily explored the molecular mechanism of epithelial-mesenchymal transformation (EMT) inhibited by bufalin. The viability of PC3 cells was evaluated by MTT assay, and the migration and invasion abilities of PC3 cells were detected by wound healing and Transwell assay. Western blot was used to detect the expression of EMT and integrin family proteins. The results showed that the half maximal inhibitory concentration (IC50) value of bufalin against PC3 cells was 0.26 ± 0.03 μmol·L-1. After bufalin treatment, the migration rate of PC3 cells slowed down (P < 0.05), the number of PC3 cells passing through the microporous membrane decreased (P < 0.05), which indicated that bufalin could inhibit the proliferation, migration and invasion of PC3 cells in a concentration-dependent manner. We found that bufalin could affect the expression of EMT-related proteins,including up-regulation of E-cadherin and down-regulation of N-cadherin, β-catenin, matrix metalloproteinase 9 (MMP9), matrix metalloproteinase 2 (MMP2), c-myc and Snail. Bufalin also inhibited the expression of integrin family proteins, including integrin α2 (ITGA2), integrin β1 (ITGB1), integrin β3 (ITGB3), integrin β5 (ITGB5), Yes-associated protein/transcriptional coactivator with a PDZ-binding motif (YAP/TAZ) and integrin-linked kinase (ILK). In addition, bufalin could also inhibit the protein expression level of phospho-focal adhesion kinase (p-FAK)/FAK, phospho-steroid receptor coactivator (p-Src)/Src and phospho-protein kinase B (p-Akt)/Akt. These results suggested that bufalin might inhibit the proliferation, metastasis and invasion of prostate cancer PC3 cells through the FAK/Src/phosphoinositide 3-kinase (PI3K)/Akt pathway. Therefore, bufalin provides reference value for the development of therapeutic drugs for prostate cancer.

Clinical Efficacy of Gandou Fumu Granules on Wilson Disease with Liver-kidney Deficiency and Phlegm-blood Stasis / 中国实验方剂学杂志

ObjectiveTo observe the clinical efficacy of Gandou Fumu granules （GDFM） in the treatment of Wilson disease （WD） with liver-kidney deficiency and phlegm-blood stasis. MethodNinety WD patients in The First Affiliated Hospital of Anhui University of Chinese Medicine were randomly divided into a control group （45 cases） and a treatment group （45 cases）. All patients were treated with sodium 2，3-dimercaptopropane-1-sulfonate （DMPS）， while those in the treatment group received additional GDFM. All patients were treated for four courses （32 days）. The traditional Chinese medicine （TCM） syndrome scores，clinical effective rate，24 h urinary copper，ceruloplasmin （CER），tumor necrosis factor-α（TNF-α），interleukin-1β（IL-1β），interleukin-6 （IL-6），superoxide dismutase （SOD），glutathione peroxidase （GSH-Px） and malondialdehyde （MDA） levels of the two groups before and after treatment were observed. ResultAfter treatment， the TCM syndrome scores of the two groups decreased （P<0.01），and the score of TCM syndrome in the treatment group was lower than that of the control group （P<0.01）. The total effective rate of the treatment group was 82.22% （37/45）， higher than 57.78% （26/45） of the control group （χ2=6.402，P<0.05）. There was no significant difference in CER before and after treatment in both groups. The post-treatment 24 hour urinary copper increased （P<0.01）， which was higher in the treatment group than that in the control group （P<0.05）. The TNF-α，IL-1β， and IL-6 levels were significantly reduced in both groups after treatment（P<0.01），and the above indicators in the treatment group were significantly lower than those in the control group （P<0.01）. After treatment，the SOD level increased and the MDA level decreased in the control group （P<0.01）， while no significant difference in GSH-Px level was observed. The SOD and GSH-Px levels increased and the MDA level decreased in the treatment group （P<0.01）. After treatment， SOD and GSH-Px levels of the treatment group were higher than those in the control group， while the MDA level was lower than that in the control group（P<0.05，P<0.01）. ConclusionGDFM can improve the TCM syndrome score and clinical efficacy，enhance the copper removing effect，and inhibit the inflammatory response and antioxidative stress in the treatment of WD with liver and kidney deficiency and phlegm-blood stasis.

Acute myeloid leukemia with positive TLS-ERG fusion gene: report of 9 cases and review of literature / 白血病·淋巴瘤

Objective:To investigate the clinical characteristics and prognosis of acute myeloid leukemia (AML) patients with positive TLS-ERG fusion gene.Methods:The clinical data of 9 AML patients with positive TLS-ERG fusion gene in the First Hospital of Jilin University from June 2013 to August 2020 were retrospectively analyzed, and the relevant literature was reviewed.Results:Among 9 patients with positive TLS-ERG fusion gene, there were 5 males and 4 females, with a median age of 16 years old (6-40 years old). Five patients received chemotherapy alone, 3 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), and 1 patient did not receive systematic treatment. Among 8 patients with systematic treatment, 1 patient had complete remission after the first induction chemotherapy and 5 patients had complete remission after induction therapy. The median overall survival time of 5 patients with chemotherapy alone was 1.5 months (1-11 months), of which 3 patients did not respond to the first course of treatment and died of infection, and 2 patients died after relapse. The median overall survival time of 3 patients with allo-HSCT was 16 months (13-17 months), of which 2 patients died after relapse and 1 patient had sustained molecular complete remission by the end of follow-up.Conclusions:AML with positive TLS-ERG fusion gene has low incidence rate and poor induction efficacy. Hematopoietic stem cell transplantation may partially improve the survival prognosis of patients, but it cannot overcome the adverse effect of positive TLS-ERG fusion gene on prognosis.

Effect of Geniposide on Liver Injury and Bile Acid Profile in Serum, Liver and Excrement of Rats / 中国实验方剂学杂志

Objective:To investigate the hepatotoxicity of different doses of geniposide on the liver of rats and the effects on bile acid profile in serum， liver tissue and feces. Method:The 60 Sprague Dawley rats， half male and half female， were randomly divided into 5 groups according to body weight： blank group and four different doses （50， 100， 200， 400 mg·kg^-1） geniposide groups， 12 rats in each group. The rats were treated by gavage once a day for 7 consecutive days， and the serum， liver and cecal contents were collected on the 8^th day of treatment. The activities of alanine aminotransferase （ALT）， aspartate aminotransferase （AST） and alkaline phosphatase （ALP）， the contents of albumin （ALB）， total bilirubin （TBIL）， total bile acid （TBA）， creatinine （Crea） and carbamide （Urea） were detected in each group. The sections of liver tissue were stained with hematoxylin-eosin（HE）， and the protein expressions of cytokeratin 7（CK7） and cytokeratin 19（CK19） were detected by immunohistochemistry. The protein expressions of CK7 and CK19 in the liver tissue were detected by Western blot. And the mRNA expressions of cholesterol 7<italic>α</italic>-hydroxylase （CYP7A1）， cholesterol 27<italic>α</italic>-hydroxylase （ CYP27A1） and cholesterol 12<italic>α</italic>-hydroxylase （CYP8B1） were detected by real-time PCR. The contents of 18 kinds of bile acids in serum， liver and cecal contents were determined by ultra-performance liquid chromatography-mass spectrometry（UPLC-MS）. Result:Compared with the control group， TBIL level in each dose of geniposide group was increasesd significantly （<italic>P</italic><0.01）. ALT， AST activity and TBA content in 400 mg·kg^-1 geniposide group were increased significantly （<italic>P</italic><0.05， <italic>P</italic><0.01）. HE staining showed that， compared with control group， there was bile duct reaction in the portal area and inflammatory cells infiltrate around bile duct in 200 mg·kg^-1 and 400 mg·kg^-1 geniposide groups， especially 400 mg·kg^-1. The expressions of CK7 and CK19 in liver tissue of 400 mg·kg^-1 geniposide group were significantly higher than those in the control group （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the control group， the contents of glycoursodeoxycholic acid （GUDCA） and glycohyodeoxycholic acid （GHDCA） in liver tissue of 400 mg·kg^-1 geniposide group decreased significantly （<italic>P</italic><0.05， <italic>P</italic><0.01）， the contents of sodium taurochenodeoxycholate （TCDCA）， hyodeoxycholic acid （HDCA）， cholic acid （CA） and chenodeoxycholic acid （CDCA） in liver tissue increased significantly （<italic>P</italic><0.01）， the contents of glycocholic acid hydrate （GCA）， glycochenodeoxycholic acid （GCDCA）， glycodeoxycholic acid hydrate （GDCA）， glycocholic acid （GLCA）， tauroursodeoxycholic acid （TUDCA）， GUDCA， GHDCA， ursodeoxycholic （UDCA） and taurolithocholic acid （TLCA） decreased， the proportions of TCDCA， HDCA， CA， CDCA and deoxycholic acid （DCA） in liver tissue increased， the contents of GHDCA and lithocholic acid （LCA） in serum decreased significantly （<italic>P</italic><0.01）， while sodium taurohyodeoxycholate hydrate （THDCA）， taurocholic acid （TCA）， GCA， TCDCA， UDCA， CA， CDCA， DCA in serum decreased significantly （<italic>P</italic><0.05， <italic>P</italic><0.01）. The contents of CA， UDCA， CA， CDCA and DCA increased significantly （<italic>P</italic><0.05）， the ratio of CA/DCA increased significantly （<italic>P</italic><0.05）， and the ratio of CA and CDCA increased by 19.60% and 4.63%， respectively； Compared with the control group， the contents of all bile acids in cecal contents of 400 mg·kg^-1 were decreased， and the contents of GCA， UDCA， HDCA， GCDCA， GDCA， TLCA， GLCA， CDCA， DCA and LCA were decreased significantly （<italic>P</italic><0.05， <italic>P</italic><0.01）. In addition， real-time PCR results showed that the mRNA expressions of CYP7A1， CYP27A1 in the 400 mg·kg^-1 geniposide group were significantly higher than those in the control group （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:The 400 mg·kg^-1geniposide can cause obvious hepatotoxicity in rats， and the bile acid profile in liver， serum and excrement changes significantly， and the changes of the each bile acid in liver， serum and feces are different. However， the causal relationship between the gardenoside-induced liver injury and the changes in bile acid profile are<italic> </italic>not clear. It needs to be further studied.