Acyl-CoA synthetase long chain family member 5 (ACSL5), is a member of the acyl-CoA synthetases (ACSs) family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs. The dysregulation of ACSL5 has been reported in some cancers, such as glioma and colon cancers. However, little is known about the role of ACSL5 in acute myeloid leukemia (AML). We found that the expression of ACSL5 was higher in bone marrow cells from AML patients compared with that from healthy donors. ACSL5 level could serve as an independent prognostic predictor of the overall survival of AML patients. In AML cells, the ACSL5 knockdown inhibited cell growth both in vitro and in vivo. Mechanistically, the knockdown of ACSL5 suppressed the activation of the Wnt/β-catenin pathway by suppressing the palmitoylation modification of Wnt3a. Additionally, triacsin c, a pan-ACS family inhibitor, inhibited cell growth and robustly induced cell apoptosis when combined with ABT-199, the FDA approved BCL-2 inhibitor for AML therapy. Our results indicate that ACSL5 is a potential prognosis marker for AML and a promising pharmacological target for the treatment of molecularly stratified AML.
Humans ; Antineoplastic Agents/therapeutic use* ; Apoptosis ; beta Catenin/metabolism* ; Biomarkers, Tumor/metabolism* ; Cell Line, Tumor ; Coenzyme A Ligases/metabolism* ; Leukemia, Myeloid, Acute/metabolism* ; Lipoylation ; Prognosis ; Wnt Signaling Pathway

ABSTRACT: Meningiomas are the most common primary intracranial neoplasm with diverse pathological types and complicated clinical manifestations. The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), published in 2021, introduces major changes that advance the role of molecular diagnostics in meningiomas. To follow the revision of WHO CNS5, this expert consensus statement was formed jointly by the Group of Neuro-Oncology, Society of Neurosurgery, Chinese Medical Association together with neuropathologists and evidence-based experts. The consensus provides reference points to integrate key biomarkers into stratification and clinical decision making for meningioma patients. REGISTRATION Practice guideline REgistration for transPAREncy (PREPARE), IPGRP-2022CN234.
Humans ; Meningioma/pathology* ; Consensus ; Neurosurgical Procedures ; Meningeal Neoplasms/pathology*

Objective:To explore the clinical characteristics and establish a corresponding prognostic scoring model in patients with early-stage clinical features of hepatitis B-induced acute-on-chronic liver failure (HBV-ACLF).Methods:Clinical characteristics of 725 cases with hepatitis B-related acute-on-chronic hepatic dysfunction (HBV-ACHD) were retrospectively analyzed using Chinese group on the study of severe hepatitis B (COSSH). The independent risk factors associated with 90-day prognosis to establish a prognostic scoring model was analyzed by multivariate Cox regression, and was validated by 500 internal and 390 external HBV-ACHD patients.Results:Among 725 cases with HBV-ACHD, 76.8% were male, 96.8% had cirrhosis base,66.5% had complications of ascites, 4.1% had coagulation failure in respect to organ failure, and 9.2% had 90-day mortality rate. Multivariate Cox regression analysis showed that TBil, WBC and ALP were the best predictors of 90-day mortality rate in HBV-ACHD patients. The established scoring model was COSS-HACHADs = 0.75 × ln(WBC) + 0.57 × ln(TBil)-0.94 × ln(ALP) +10. The area under the receiver operating characteristic curve (AUROC) of subjects was significantly higher than MELD, MELD-Na, CTP and CLIF-C ADs( P < 0.05). An analysis of 500 and 390 cases of internal random selection group and external group had similar verified results. Conclusion:HBV-ACHD patients are a group of people with decompensated cirrhosis combined with small number of organ failure, and the 90-day mortality rate is 9.2%. COSSH-ACHDs have a higher predictive effect on HBV-ACHD patients' 90-day prognosis, and thus provide evidence-based medicine for early clinical diagnosis and treatment.

Objective To investigate the current situations of the frailty and the perceived social support and explore the influence of social support on the frailty in elderly maintenance hemodialysis patients.Methods The 237 elderly patients with maintenance hemodialysis were investigated by the Fried frailty phenotype and the perceived social support scale in this cross-sectional study.Results The prevalence of frailty was 163 (68.8％)in 237 patients.The level of perceived social support was low.The frailty was negatively correlated with the social supportscore,family support,friends support,and other support(r =-0.326,-0.129,-0.301 and-0.230,respectively,all P ＜0.05).Multiple logistic regression analysis showed that friends support,dialysis vintage,Charlson comorbidity index(CCI)score and activities of daily living(ADL)score were the main influential factors for frailty in elderly maintenance hemodialysis patients.Conclusions Medical staff should evaluate the frailty in elderly patients with maintenance hemodialysis,and the frailty can be alleviated by improving the support of friends.

Objective To investigate the effect of high-fat diet(HFD)on liver damage caused by autoimmune hepatitis(AIH)in mice.Methods Fifty C57BL/6 male mice were divided randomly into four groups:standard chow(SC)group,HFD group,AIH + SC group and AIH+ HFD group.AIH model was built after feeding for one week and all mice were sacrificed after four weeks.Liver and spleen tissues and serum were collected. Liver histopathology was detected by HE staining. Serum alanine aminotransperase(ALT)and aspartate aminotransferase(AST)levels were measured.Western blot analysis and real-time polymerase chain reaction(PCR)analysis were used to test the expressions of NLR pyrin domain containing 3(NLRP3)and cysteinyl aspartate specific proteinase 1(Caspase-1).The concentrations of interleukin(IL)-6,IL-1β and tumor necrosis factor(TNF)-α were analyzed using enzyme linked immunosorbent assay technology.The amount of Th17 cells in spleen was analyzed by FACS.Means among groups were analyzed with one-way ANOVA.SNK-q analysis was used for groups with homogeneity of variance, while nonparametric test was used for groups with variance nonhomogeneity.Results Histologically,the H&E staining of liver tissue from HFD group showed adipose degeneration,and there was inflammation around vessel in AIH+SC group.Moreover,in AIH+HFD group,the inflammation was more serious with mildly adipose degeneration.Compared with SC group,serum levels of ALT and AST increased in HFD group and AIH +SC group,and greatest increase was observed in AIH+ HFD group.The differences were statistically significant(F=57.12 and 37.58, both P<0.05).The proportions of Th17 cells in SC group,HFD group,AIH+ SC group and AIH+HFD group were(2.98 ± 0.90)%,(6.89 ± 0.99)%,(6.47 ± 1.08)% and(9.96 ± 0.83)%, respectively.The differences among all groups were statistically significant(F=54.05,P<0.05).The concentrations of IL-1β,IL-6 and TNF-α in each group were as follows:SC:IL-1β[(7.62 ± 2.81)ng/L],IL-6 [(106.54 ± 53.08)ng/L],T NF-α[(107.26 ± 36.20)ng/L];HFD:IL-1β[(25.06 ± 7.09)ng/L],IL-6 [(220.11 ± 47.41)ng/L],TNF-α[(273.77 ± 33.62)ng/L];AIH+SC:IL-1β[(17.49 ± 5.68)ng/L],IL-6 [(260.73 ± 50.29)ng/L],TNF-α[(250.49 ± 81.63)ng/L];AIH+ HFD:IL-1β[(52.04 ± 10.22)ng/L], IL-6[(785.93 ± 70.91)ng/L],TNF-α[(913.97 ± 64.57)ng/L].The differences were statistically significant(F=44.66,242.15 and 233.49,respectively,all P<0.05).The expressions of NLRP3 and Caspase-1 were significantly increased in AIH+ HFD group than the other three groups(all P<0.05). Conclusions High-fat diet potentiates liver damage induced by autoimmune hepatitis,which might relate to the secretion of pro-inflammatory cytokines,the activation of Th17 cells and the NLRP3 inflammasome as well as pyroptosis.

Objective To observe and investigate the efficacy and safety of combining with intrathecal injection of vancomycin and dexamethasone based on intravenous meropenem for treating refractory purulent meningitis in children.Methods Ninety children cases of refractory purulent meningitis from June 2014 to March 2015 were randomized into the observation group (45 cases) and control group (45 cases) according to the random number table method.The control group was given intravenous meropenem therapy,on this basis the observation group was added with intrathecal injection of vancomycin and dexamethasone.The changes of serum inflammatory markers and clinical efficacies after 7 d treatment were compared between the two groups,and the incidence rate of sequelae in the two groups were recorded after 3-months follow up.Results The descend ranges of TNF-a,CRP and PCT after 7 d treatment in the observation group were (87.3±21.8)pg/mL,(47.9±10.7)mg/L and (348.9J67.3)pg/mL,which were significantly higher than (61.5±18.5)pg/mL,(33.0± 7.9)mg/L,(263.7 ± 61.5)pg/mL in the control group(P＜0.05).There was statistically significant difference in clinical efficacy between the two groups (Z=2.086,P=0.037),the total effective rate in the observation group was 93.3 ％,which was higher than 82.2 ％ in the control group (x2 =2.589,P =0.108);the average treatment duration in the observation group was(12.8 ± 3.9)d,which was significantly less than (16.7 ± 4.7)d in the control group,the difference was statistically significant(t=4.216,P＜0.01).There were no statistically significant differences in the incidence rate of adverse drug reactions and sequelae between the two groups (P＞0.05).Conclusion With intrathecal injection of vancomycin and dexamethasone based on intravenous meropenem therapy for treating purulent meningitis,can further inhibit the inflammatory reaction,and increases clinical efficacy without significantly increasing adverse drug reactions.

BACKGROUND:Degenerative lumbar scoliosis often appeared in the elderly, who may combine with other diseases, which can cause poor repair tolerance. Degenerative lumbar scoliosis commonly has a responsible vertebral body, so local decompression and selective fusion should be conducted. This can achieve nerve decompression, spinal stability, and is relatively minimaly invasive. OBJECTIVE:To explore the efficacy of selective interbody fusion, limited neural decompression combined with pedicle screw system fixation for degenerative lumbar scoliosis. METHODS:Clinical characteristics of 53 patients with degenerative lumbar scoliosis were retrospectively analyzed, and the indication and contraindication were investigated. Selective interbody fusion, and limited neural decompression combined with pedicle screw system fixation were performed in the patients. Treatment effect and complication were analyzed. During folow-up, Suk standard was utilized to judge bone graft fusion. Before treatment and during final folow-up, lower back pain score system recommended by the Japanese Orthopaedic Association was used for assessment, and the excelent and good rate of curative effects was calculated. Cobb’s angle on the sagittal and coronal positions was compared and analyzed before and after treatment. RESULTS AND CONCLUSION:The patients were folowed up for 12 to 36 months. According to low back pain score of Japanese Orthopaedic Association Scores, the excelent and good rate of curative effect was 89% during the last folow-up. According to Suk standard, the fusion rate of vertebra was 94%. The last X-ray films revealed that Cobb’s angle was averagely (4.3±2.3)° (0°-13.5°) on the coronal plane after treatment, and the correction rate of scoliosis was 56%. The Cobb’s angle was averagely (45.1±12.5)° (10.4°-65.3°) after treatment, and the correction rate of lordosis was 36%. Complications after repair consisted of cerebrospinal fluid leakage in two cases, nerve injury in two cases, instrumental failure in one case, and pulmonary infection in one case, and symptomatic deep venous thrombosis in three cases. These findings suggest that selective interbody fusion, and limited neural decompression combined with pedicle screw system fixation were effective and safe for degenerative lumbar scoliosis. The sequence of the lumbar vertebra on the coronal and the sagittal planes received reconstruction to different degrees, and could realize the stability of the lumbar vertebrae in the scoliosis.

Objective To investigate the dynamic change and the clinical curative effect evaluation of plasma (1-3)-beta glucan D (BG) in the patients with pulmonary disease complicating fungal infection .Methods The MB-80 miroorganism dynamic rapid de-tection system and fungi BG detection kits were adopted to detect plasma BG content before and after treatment in 87 cases of pul-monary disease complicating fungal infection and the controls .The sputum culture in the patients was performed before and after treatment .Results Plasma BG levels before antifungal therapy ,at 1 ,2 weeks after treatment in 87 patients were (162 .81 ± 70 .03) , (15 .89 ± 30 .88) and (4 .58 ± 7 .87)pg/mL ,which in the control group was (5 .62 ± 1 .83)pg/mL ,plasma BG level had statistical differences between before treatment and at 1 ,2 weeks after treatment in the patients with the control group (P<0 .05);Plasma BG levels between at 1 week after treatment with at 2 weeks after treatment and the control group had statistically significant differ-ences (P<0 .05) .Among 87 patients ,66 cases were positive sputum culture at 1 week after antifungal drug treatment and 9 cases were positive sputum culture at 2 weeks after treatment .Conclusion Continuously monitoring the patient′s plasma BG level com-bined with the sputum fungal culture results ,clinical symptoms and lung shadow in X-ray has certain clinical value to judge the anti-fungal effect .

Objective To investigate the clinical application value of strong ion gap(SIG)generated by the third generation equa-tion following pH and the anion gap(AG)in critically ill patients.Methods On the basis of the determination results of blood gas and blood biochemistry,the equation in the Stewart-Figge methodology was adopted to calculate SIG.Results (1)There were sta-tistically significant differences in K+ ,Na+ ,HCO3 - ,AG,pH,PO4 3 - ,ALB,SIG and Cr between the critical illness groups and the control group(P <0.05).(2)The SIG mean value ratio the death group to non-death group was 3.04,the difference was the big-gest,P <0.05,AG and Cr took the second place.Conclusion SIG as a new indicator in combination with other biochemical and blood gas indicators,such as the HCO3 - ,AG,pH,PO4 3 - ,Cr and lactic acid can reflect the situation of the acid-base disorders in critically ill patients and plays a strong indicative role in predicting the disease development trends.

Objective To investigate the changes and clinical significance of the frequency of circulating CD4+ CD25+ regulatory T cells (Treg) in nonalcoholic fatty liver (NAFL) patients.Methods CD4+ CD25+ Treg in the peripheral blood from 50 NAFL patients and 50 healthy subjects were quantitatively analyzed using flow cytometry. Group t test or Mann-Whitney U test and Spearman's rank correlation test were used for statistical analysis.Results The proportion of circulating CD4+CD25+ Treg in NAFL patients was (5.39 ± 1.94)％,which was significantly higher than that in healthy controls [(4.21±1.52)％](t=3.385,P＜0.01).Further analysis revealed that the frequency of Treg was positively correlated with triglyceride (TG) level and body mass index (r=0.307 and 0.251,respectively; P=0.002 and 0.012,respectively),and negatively correlated with high density lipoproteincholesterol (HDL-C) (r=-0.306,P=0.002).Meanwhile,Treg in patients with high body mass index,high TG,low HDL-C,hypertension and metabolic syndrome (MS) were all higher than those in controls (t=2.294,2.533,3.154,2.010 and 4.454,respectively; all P＜0.05).But there was no significant difference between patients with high fasting blood glucose and controls (U=1143.500,P=0.471).Conclusion The increased frequency of peripheral Treg in NAFL patients may have some relations with the imbalance of proinflammation and anti-inflammation in NAFL patients who coexisting with MS.