ObjectiveHuman Ku70 protein mainly involves the non-homologous end joining (NHEJ) repair of double-stranded DNA breaks (DSB) through its DNA-binding properties, and it is recently reported having an RNA-binding ability. This paper is to explore whether Ku70 has RNA helicase activity and affects miRNA maturation. MethodsRNAs bound to Ku protein were analyzed by RNA immunoprecipitation sequencing (RIP-seq) and bioinfomatic anaylsis. The expression relationship between Ku protein and miRNAs was verified by Western blot (WB) and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assays. Binding ability of Ku protein to the RNAs was tested by biolayer interferometry (BLI) assay. RNA helicase activity of Ku protein was identified with EMSA assay. The effect of Ku70 regulated miR-124 on neuronal differentiation was performed by morphology analysis, WB and immunofluorescence assays with or without Zika virus (ZIKV) infection. ResultsWe revealed that the Ku70 protein had RNA helicase activity and affected miRNA maturation. Deficiency of Ku70 led to the up-regulation of a large number of mature miRNAs, especially neuronal specific miRNAs like miR-124. The knockdown of Ku70 promoted neuronal differentiation in human neural progenitor cells (hNPCs) and SH-SY5Y cells by boosting miR-124 maturation. Importantly, ZIKV infection reduced the expression of Ku70 whereas increased expression of miR-124 in hNPCs, and led to morphologically neuronal differentiation. ConclusionOur study revealed a novel function of Ku70 as an RNA helicase and regulating miRNA maturation. The reduced expression of Ku70 with ZIKV infection increased the expression of miR-124 and led to the premature differentiation of embryonic neural progenitor cells, which might be one of the causes of microcephaly.

Circular RNAs (circRNAs) are a kind of non-coding RNA (ncRNA) with covalent closed-loop structure. They have attracted more and more attention because of their high stability, evolutionary conservatism, and tissue expression specificity. It has shown that circRNAs are involved in the development of a variety of diseases including malignant tumors recently. Nasopharyngeal carcinoma (NPC) is a malignant tumor that occurs in the nasopharynx and has a unique ethnic and geographical distribution in South China and Southeast Asia. Epstein-Barr virus (EBV) infection is closely related to the development of NPC. Radiotherapy and chemotherapy are the mainstays of treatment for NPC. But tumor recurrence or distant metastasis is the leading cause of death in patients with NPC. Several studies have shown that circRNAs, as gene expression regulators, play an important role in NPC and affect the progression of NPC. This review mainly summarized the research status of abnormally expressed circRNAs in NPC and EBV-encoded circRNAs. We also discussed the possibility of circRNAs as a therapeutic target, diagnostic and prognostic marker for NPC.

Aim To study the effects of Taohong Siwu Tang(TSD)on serum lipid metabolites in rats with abnormal uterine bleeding(AUB),and to analyze the mechanism of action of TSD in improving lipid metabo-lism disorders in AUB.Methods The rat model of AUB was replicated by the method of incomplete abor-tion with drugs,and the lipid metabolites of serum were detected by applying UPLC-Q-Exactive Orbitrap/MS technology,and combined with the principal com-ponent analysis and orthogonal partial least squares-discriminant analysis to screen for differential lipids,the changes of lipids in serum before and after the in-tervention of TSD were clarified.Results A total of 11 differential lipids were screened,mainly phosphati-dyl inositol,phosphatidic acid,phosphatidyl ethanola-mine,phosphatidyl serine,sterol lipids,ceramide,acrylolipids and fatty acids.The screened differential lipids all tended to regress to normal after the adminis-tration of TSD intervention.Conclusion Improvement of AUB by TSD may be related to lipid metabolism such as phosphatidic acid,phosphatidyl inositol,phos-phatidyl ethanolamine,phosphatidyl serine,and ce-ramide.

Objective To investigate the therapeutic effect of segmental decompression combined with corrective short-segment fusion surgery for the treatment of degenerative lumbar scoliosis.Methods In total,124 patients with degenerative lumbar scoliosis were selected and divided into short-and long-segment fusion groups using the random number table method,with 62 patients in each group.Posterior short-segment decompression,fixation,and fusion were performed in the short-segment fusion group;the fusion segment was the adjacent lumbar vertebra.Posterior long-segment decompression,fixation,and fusion were performed in the long-segment fusion group;the fusion segments included multiple adjacent lumbar vertebrae.At the 6th month after surgery,the coronal Cobb angle of lumbar convexity,sagittal Cobb angle of lumbar lordosis,intervertebral foramen height,intervertebral space height,intervertebral foramen area,spinal canal area,spinal canal diameter,Japanese Orthopedic Association(JOA)score,Oswestry Disability Index(ODI),degree of pain in the lower back and lower limbs,and postoperative complications were compared between the groups.Results The Cobb angle of the coronal lumbar scoliosis in the short-and long-segment fusion groups was significantly higher than that before surgery(P<0.05).At the 6th month after surgery,the intervertebral foramen height,intervertebral space height,intervertebral foramen area,spinal canal area,and spinal canal diameter in both groups increased,and those in the short-segment fusion group were higher than those in the long-segment fusion group(P<0.05);at the 6th month after the operation,the JOA scores of the short-segment and long-segment fusion groups were higher than those before surgery,and the JOA score of the short-segment fusion group was higher than that of the long-segment fusion group(P<0.05).The ODI score was lower than that before surgery in the short-and long-segment fusion groups,and the ODI score in the short-segment fusion group was lower than that in the long-segment fusion group(P<0.05).At the 6th month after surgery,the pain scores of the lower back and lower limbs in the short-and long-segment fusion groups were significantly higher than those before surgery(P<0.05).There were two cases of dural tears during decompression caused by lamina dura adhesion in the long-segment fusion group,and no serious complications were observed in the short-segment fusion group.Conclusions Both short-and long-segment decompression fixation fusion using a posterior approach can achieve good therapeutic effects for treating degenerative lumbar scoliosis.However,compared to the long-segment fusion group,the short-segment fusion group undergoing short-segment decompression fixation fusion through a posterior approach had a shorter surgical period,lower intraoperative blood loss,better recovery of lumbar function,and a lower risk of postoperative complications.

Objective To investigate the effect and mechanism of tetramethylpyrazine(TMP)on cognitive function in mice with post-traumatic stress disorder(PTSD).Methods The mice were randomly divided into normal group,model group and experimental group.Except for the normal group,the PTSD mouse model was established by single prolonged stress(SPS).The experimental group was intraperitoneally injected with 10 mg·kg-1 TMP,and the normal group and the model group were intraperitoneally injected with an equal amount of 0.9％NaCl.The Morris water maze,open field and elevated plus maze tests were used to evaluate the cognitive behavior of the mice.The apoptosis of neurons was detected by Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL).The expression of ionized calcium binding adapter molecule-1(Iba-1)protein was detected by immunofluorescence(ICC).The content of oxidative stress inflammatory factors was detected by enzyme-linked immunosorbent assay(ELISA).Results The escape latency of the normal group,model group,and TMP group were(56.50±9.89),(87.16±10.48)and(68.63±10.19)s,respectively;the corner residence time of the open field were(190.37±40.64),(260.39±40.54)and(218.63±38.27)s,respectively;the apoptosis rates were(18.28±2.35)％,(39.36±3.65)％and(30.74±3.58)％,respectively;the fluorescence intensities of Iba-1 were(8.01±2.23)％,(50.87±7.31)％and(7.49±1.41)％;malondialdehyde contents were(5.46±0.95),(12.98±2.06)and(8.31±1.28)nmol·mg-1,respectively;tumor necrosis factor-α contents were(53.59±9.91),(115.46±11.53)and(74.38±10.77)pg·mL-1,respectively.The above indexes in the normal group and the experimental group were statistically significant compared with the model group(P＜0.05,P＜0.01).Conclusion TMP can improve the cognitive function of PTSD mice,and the mechanism may be related to the regulation of inflammation and oxidative stress.

MAGED4B belongs to the melanoma-associated antigen family; originally found in melanoma, it is expressed in various types of cancer, and is especially enriched in glioblastoma. However, the functional role and molecular mechanisms of MAGED4B in glioma are still unclear. In this study, we found that the MAGED4B level was higher in glioma tissue than that in non-cancer tissue, and the level was positively correlated with glioma grade, tumor diameter, Ki-67 level, and patient age. The patients with higher levels had a worse prognosis than those with lower MAGED4B levels. In glioma cells, MAGED4B overexpression promoted proliferation, invasion, and migration, as well as decreasing apoptosis and the chemosensitivity to cisplatin and temozolomide. On the contrary, MAGED4B knockdown in glioma cells inhibited proliferation, invasion, and migration, as well as increasing apoptosis and the chemosensitivity to cisplatin and temozolomide. MAGED4B knockdown also inhibited the growth of gliomas implanted into the rat brain. The interaction between MAGED4B and tripartite motif-containing 27 (TRIM27) in glioma cells was detected by co-immunoprecipitation assay, which showed that MAGED4B was co-localized with TRIM27. In addition, MAGED4B overexpression down-regulated the TRIM27 protein level, and this was blocked by carbobenzoxyl-L-leucyl-L-leucyl-L-leucine (MG132), an inhibitor of the proteasome. On the contrary, MAGED4B knockdown up-regulated the TRIM27 level. Furthermore, MAGED4B overexpression increased TRIM27 ubiquitination in the presence of MG132. Accordingly, MAGED4B down-regulated the protein levels of genes downstream of ubiquitin-specific protease 7 (USP7) involved in the tumor necrosis factor-alpha (TNF-α)-induced apoptotic pathway. These findings indicate that MAGED4B promotes glioma growth via a TRIM27/USP7/receptor-interacting serine/threonine-protein kinase 1 (RIP1)-dependent TNF-α-induced apoptotic pathway, which suggests that MAGED4B is a potential target for glioma diagnosis and treatment.
Humans ; Tumor Necrosis Factor-alpha ; DNA-Binding Proteins/metabolism* ; Ubiquitin-Specific Peptidase 7 ; Cisplatin ; Temozolomide ; Transcription Factors ; Glioma ; Cell Proliferation ; Melanoma ; Cell Line, Tumor ; Apoptosis ; Nuclear Proteins/genetics*

BACKGROUND: Familial hypercholesterolemia (FH) is a common autosomal dominant hereditary disease. Its early diagnosis and intervention significantly improve the patient's quality of life. However, there are few types of research on the FH pathogenic genes in China. METHODS: In this study, we recruited a family diagnosed with FH and used whole exome sequencing (WES) to analyze the proband variants. Intracellular cholesterol level, reactive oxygen species (ROS) level, and the expression of pyroptosis-related genes were detected after overexpression of wild-type or variant LDLR in L02 cells. RESULTS: A heterozygous missense variant predicted to be deleterious to LDLR (c.1879G > A, p.Ala627Thr) was identified in the proband. Mechanistically, intracellular cholesterol level, ROS level, and the expression of pyroptosis-related genes, nucleotide-binding oligomerization domain-like receptor family protein 3 (NLRP3) inflammasome and components (caspase 1, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and NLRP3), gasdermin D (GSDMD), interleukin (IL) -18, IL-1β was elevated in the variant LDLR group, which was attenuated by inhibition of ROS. CONCLUSIONS FH is associated with a variant (c.1879G>A, p.Ala627Thr) in the LDLR gene. Regarding the mechanism, the ROS/NLRP3-mediated pyroptosis in hepatic cells may contribute to the pathogenesis of the LDLR variant.

Objective: A Mendelian randomization (MR) analysis was performed to assess the relationship between tea consumption and cancer. Methods: There were 100 639 participants with the information of gene sequencing of whole genome in the China Kadoorie Biobank. After excluding those with cancer at baseline survey, a total of 100 218 participants were included in this study. The baseline information about tea consumption were analyzed, including daily tea consumption or not, cups of daily tea consumption, and grams of daily tea consumption. We used the two-stage least square method to evaluate the associations between three tea consumption variables and incidence of cancer and some subtypes, including stomach cancer, liver and intrahepatic bile ducts cancer, colorectal cancer, tracheobronchial and lung cancer, and female breast cancer. Multivariable MR and analysis only among nondrinkers were used to control the impact of alcohol consumption. Sensitivity analyses were also performed, including inverse variance weighting, weighted median, and MR-Egger. Results: We used 54, 42, and 28 SNPs to construct non-weighted genetic risk scores as instrumental variables for daily tea consumption or not, cups of daily tea consumption, and grams of daily tea consumption, respectively. During an average of (11.4±3.0) years of follow-up, 6 886 cases of cancer were recorded. After adjusting for age, age², sex, region, array type, and the first 12 genetic principal components, there were no significant associations of three tea consumption variables with the incidence of cancer and cancer subtypes. Compared with non-daily tea drinkers, the HR (95%CI) of daily tea drinkers for cancer and some subtypes, including stomach cancer, liver and intrahepatic bile ducts cancer, colorectal cancer, tracheobronchial and lung cancer, and female breast cancer, are respectively 0.99 (0.78-1.26), 1.17 (0.58-2.36), 0.86 (0.40-1.84), 0.85 (0.42-1.73), 1.39 (0.85-2.26) and 0.63 (0.28-1.38). After controlling the impact of alcohol consumption and performing multiple sensitivity analyses, the results were similar. Conclusion: There is no causal relationship between tea consumption and risk of cancer in population in China.
Humans ; Female ; Stomach Neoplasms/epidemiology* ; Mendelian Randomization Analysis/methods* ; Tea ; Breast Neoplasms ; Lung Neoplasms ; Colorectal Neoplasms ; Polymorphism, Single Nucleotide ; Genome-Wide Association Study

ObjectiveTo explore the improvement effect of Flos Puerariae， Hoveniae Semen， and their compatibility on acute alcoholic gastric mucosal injury， and lay a foundation for further development of Flos Puerariae， Hoveniae Semen， and their compatibility in the prevention and treatment of alcohol-induced multiple organ injury. MethodThe acute alcohol-induced gastric mucosal injury model of mice was established by multiple intragastric administration of 56% Hongxing Erguotou liquor （15 mL·kg^-1）. A total of 120 male ICR mice were randomly divided into 8 groups， namely， the blank group， model group， omeprazole group （0.026 g·kg^-1）， Flos Puerariae-Hoveniae Semen （compatibility） high， medium， and low-dose groups （29.2，14.6， 7.3 g·kg^-1）， Flos Puerariae group （19.5 g·kg^-1）， and Hoveniae Semen group （19.5 g·kg^-1）， with 15 mice in each group. After one week of adaptive feeding， the animals were pre-administrated with the corresponding drug at the rate of 10 mL·kg^-1 for 3 d. From the 4^th day， after 1 h of administration， Erguotou liquid was administrated at the rate of 15 mL·kg^-1 and the blank group was administrated with the same volume of deionized water to record the drunkenness and sober up time. The administration was lasted for 3 d. One hour after the last administration， the eyeballs were removed and the mice were sacrificed. The concentration of ethanol in serum was determined by gas chromatograph， and the activity of ethanol dehydrogenase （ADH） in gastric mucosa was determined by ultraviolet-vis spectrophotometer. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in gastric mucosa. Serum inflammatory factors were determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression of nuclear transcription factor-κB （NF-κB） p65 and NF-κB inhibitory protein α （IκBα） were detected by real-time polymerase chain reaction （Real-time PCR）. ResultAs compared with the normal group， the content of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in serum of mice in the model group was increased （P<0.05）， the mRNA expression of NF-κB p65 in gastric mucosa tissues was increased （P<0.01）， and the mRNA expression of IκBα was decreased （P<0.01）. As compared with the model group， the drunkenness time of the omeprazole group， high and medium-dose compatibility groups， and Flos Puerariae group was prolonged （P<0.05）， the sober up time of the high and medium-dose compatibility groups was shortened （P<0.05）， the ethanol concentration in the serum of the high-dose compatibility group was decreased （P<0.05）， the ADH activity in the gastric mucosa of the omeprazole group and high and medium-dose compatibility groups was increased （P<0.05）， the macroscopic injury score of the high， medium， and low-dose compatibility groups and Flos Puerariae group was decreased （P<0.05）， the score of pathological injury in the omeprazole group， high， medium， and low-dose compatibility groups， and Flos Puerariae group was decreased （P<0.01）， the expression of IL-6 in serum of all drug groups was decreased （P<0.05）， the expression of IL-1β in serum of the omeprazole group， high， medium， and low-dose Flos Puerariae groups， and Hoveniae Semen group was decreased （P<0.05）， the expression of TNF-α in serum of high and medium-dose groups was decreased （P<0.05）， the mRNA expression of NF-κB p65 in gastric mucosa tissues of all drug groups was decreased （P<0.05）， and the mRNA expression of IκBα in gastric mucosa tissues of the omeprazole group and high， medium， and low-dose compatibility groups was increased （P<0.05）. As compared with the high-dose compatibility group， the drunkenness time in the low-dose compatibility group and Hoveniae Semen group was shortened （P<0.01）， the sober up time in the Flos Puerariae and Hoveniae Semen groups was prolonged （P<0.01）， the concentration of ethanol in the serum of the medium and low-dose compatibility groups， Flos Puerariae group， and Hoveniae Semen group increased （P<0.05）， the macroscopic injury score of the medium and low-dose compatibility groups and Hoveniae Semen group was increased （P<0.05）， the pathological injury score of the medium and low-dose compatibility groups， Flos Puerariae group， and Hoveniae Semen group was increased （P<0.01）， the content of IL-1β in serum of low-dose compatibility group， Flos Puerariae group， and Hoveniae Semen group was increased （P<0.01）， and the mRNA expression of IκBα in gastric mucosa of the Flos Puerariae group and Hoveniae Semen group was decreased （P<0.05）. As compared with the medium-dose compatibility group， the drunkenness time in the Hoveniae Semen group was shortened （P<0.05）， the sober up time in the Flos Puerariae group was prolonged （P<0.05）， the pathological injury score in the Flos Puerariae group and Hoveniae Semen group was increased （P<0.01）， and the content of IL-1β in serum of the low-dose compatibility group， the Flos Puerariae group， and Hoveniae Semen group was increased （P<0.05）. As compared with the low-dose compatibility group， the pathological injury score of the Hoveniae Semen group was increased （P<0.05）. ConclusionFlos Puerariae， Hoveniae Semen， and their compatibility play a role in preventing and treating acute alcoholic gastric mucosal injury in mice， which may be related to the inhibition of the expression of NF-κB signal pathway in gastric mucosa， and the high-dose compatibility group has the optimal effect.

Objective:To compare the clinical efficacy of robot-assisted versus fluoroscopy-assisted sacroiliac screw internal fixation for posterior pelvic ring fractures.Methods:China National Knowledge Infrastructure (CNKI), Wanfang Data, Chinese Medical Journal Full-text Database, PubMed, Web of Science and ScienceDirect were searched for literature on robot-assisted versus fluoroscopy-assisted sacroiliac screw internal fixation for posterior pelvic ring fractures. The search time was from the establishment of each database to March 2023. Meta-analysis was performed on the included literature. The random-effects model was used when the heterogeneity between groups was large, and the fixed-effects model was used when the heterogeneity between groups was small.Results:A total of 15 studies were included in the meta-analysis, including 465 patients in the robot-assisted group and 396 patients in the fluoroscopy-assisted group. Meta-analysis showed that the number of fluoroscopies [ SMD=-3.12, 95% CI (-4.34, -1.89), P<0.001], the number of guide pin adjustments [ SMD=-3.75, 95% CI (-6.77, -0.72), P=0.015], intraoperative blood loss [ SMD=-0.83, 95% CI (-1.18, -0.49), P<0.001], and operative time [ SMD=-2.59, 95% CI (-4.11, -1.08), P<0.001] were smaller than those in the fluoroscopy-assisted group. The rate of excellent screw implantation [ OR=10.13, 95% CI (3.67,27.98), P<0.001] of the robot-assisted was larger than the fluoroscopy-assisted group. There was no significant difference in Majeed functional score [ SMD=0.28, 95% CI (-0.0003, 0.55), P=0.050] and fracture healing time [ SMD=-0.14, 95% CI (-0.46, 0.17), P=0.367] between the two groups. Conclusion:Robot-assisted percutaneous sacroiliac screw fixation for posterior pelvic ring fractures has the advantages of less fluoroscopy, less guide pin adjustment, less intraoperative blood loss, shorter operation time, and higher rate of excellent screw position. However, there is no difference in Majeed score and fracture healing time between robot-assisted percutaneous sacroiliac screw fixation and fluoroscopy-assisted percutaneous sacroiliac screw fixation.