ObjectiveTo investigate the optimal ratio of goat horn replacing antelope horn in Fufang Lingjiao Jiangya pills and the blood pressure-lowering mechanism of this medicine. MethodsThe blood pressure-lowering efficacy of Fufang Lingjiao Jiangya pills with varying proportions of goat horn replacing antelope horn was evaluated on spontaneous hypertensive rats （SHR）. In this experiment， 50 SHR rats were randomly grouped as follows： model （n=8）， captopril （0.01 g·kg^-1） （n=6）， low-dose blank Fufang Lingjiao Jiangya pills （0.342 g·kg^-1） （n=6）， high-dose blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1） （n=6）， low-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， high-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）， low-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， and high-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）. Additionally， 8 WKY rats were used as the normal group. Drugs were administered by gavage for 4 weeks while an equal volume of distilled water was administered for the normal and model groups. Blood pressure was measured before administration， 3 h post administration， and biweekly thereafter. In the experiment for Fufang Lingjiao Jiangya pills with goat horn replacing antelope horn in different proportions， 48 SHR rats were randomly grouped as follows： model， blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1）， antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1）， 2× goat horn-containing Fufang Lingjiao Jiangya pills （0.824 g·kg^-1）， 4× goat horn Fufang Lingjiao Jiangya pills （0.969 g·kg^-1）， and 6× goat horn Fufang Lingjiao Jiangya pills （1.112 g·kg^-1）. The normal group included 8 WKY rats， and the normal group and model group received an equal volume of distilled water. The treatment lasted for 2 weeks， and blood pressure was recorded at various time points （pre-administration， 3 h post administration， and on days 4， 7， 10， and 14 of administration）. Serum levels of angiotensin-converting enzyme （ACE）， angiotensin Ⅱ（Ang Ⅱ）， renin， and interleukin-6 （IL-6） were measured by enzyme-linked immunosorbent assay. Histopathological changes in the heart， kidney， and thoracic aorta were observed by hematoxylin-eosin staining. The protein levels of ACE2， angiotensin Ⅱ type 1 receptor （AT1R）， and angiotensinogen （AGT） in the kidney tissue were determined by Western blot， while the expression of nuclear factor （NF）-κB p65 and Toll-like receptor 4 （TLR4） in the thoracic aorta tissue was assessed by immunohistochemistry. ResultsCompared with the model group， all treatment groups showed lowered blood pressure （P<0.05， P<0.01）， and the 6× goat horn-containing Fufang Lingjiao Jiangya pills group showed consistent blood pressure-lowering effect with the antelope horn-containing Fufang Lingjiao Jiangya pills group. Compared with the normal group， the model group showed elevated serum levels of ACE， Ang Ⅱ， renin， and IL-6， while the elevations were declined in the Fufang Lingjiao Jiangya pills groups （P<0.05， P<0.01）. Pathological changes in the heart， kidney， and thoracic aorta were alleviated in all the treatment groups， with the 6× goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups exhibited the best effect. Western blot and immunohistochemistry results showed that all the treatment groups exhibited down-regulated protein levels of AT1R， AGT， NF-κB p65， and TLR4 and up-regulated protein levels of ACE2 （P<0.05， P<0.01） compared with model group， with the 6×goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups showcasing the best effect. ConclusionReplacing antelope horn with 6×goat horn in Fufang Lingjiao Jiangya pills can achieve consistent blood pressure-lowering effect with the original prescription. The prescription may exert the effect by inhibiting the renin-angiotensin-aldosterone system （RAAS） and TLR4/NF-κB signaling pathways.

OBJECTIVES: To investigate the effect of Scleromitrion diffusum on gastric mucosal epithelial-mesenchymal transition (EMT) in rats with gastric precancerous lesion. METHODS: Fifty SD rats were randomly divided into blank control group (n=11), model control group (n=13), Scleromitrion diffusum (SD) group (n=13) and vitase group (n=13). Gastric precancerous lesion animal model was prepared by 1-methyl-3-nitro-1-nitrosoguanidine complex polyfactor method, and the drugs were administrated by gavage once a day for 6 weeks. The pathological changes of gastric mucosa were observed with hematoxylin and eosin staining, the expression of EMT marker proteins were detected with immunohistochemical staining and Western blotting. RESULTS: Compared with the model control group, the gastric mucosal injury was significantly attenuated in the Scleromitrion diffusum group, the mucosal tissue structure gradually recovered, the saccular expansion area was reduced, and the inflammatory infiltration was ameliorated. The expression of epithelial cadherin was higher, and the expression of neural cadherin and vimentin in the Scleromitrion diffusum group were lower than those of model control group (all P<0.05). CONCLUSIONS Scleromitrion diffusum can ameliorate gastric mucosal injury in rats with gastric precancerous lesion by reversing the EMT.
Animals ; Rats ; Rats, Sprague-Dawley ; Epithelial-Mesenchymal Transition/drug effects* ; Precancerous Conditions/metabolism* ; Gastric Mucosa/metabolism* ; Stomach Neoplasms/drug therapy* ; Male ; Cadherins/metabolism*

Sjögren's syndrome (SS) is an autoimmune disease characterized primarily by oral and periocular dryness. Astragalus-Salvia (AS) and Ophiopogon-Dendrobium (OD) represent two frequently utilized herb pairs in SS treatment. While the combination of AS-OD herb pairs demonstrates clinical efficacy in alleviating SS symptoms, its underlying mechanism remains unclear. This investigation sought to assess the therapeutic effects and elucidate the potential mechanisms of AS-OD in non-obese diabetic (NOD)/Ltj mice with SS. The study utilized NOD/Ltj mice as SS models, administering AS-OD treatment for 10 weeks at doses of 113.1, 226.2, and 339.3 mg·d^-1·20 g^-1. Results demonstrated that AS-OD improved SS symptoms, evidenced by enhanced salivary flow rate, decreased anti-SSA/Ro and anti-SSB/La antibody levels, increased swimming duration, and reduced lactate (LA) and blood urea nitrogen (BUN) levels in NOD/Ltj mice. AS-OD reduced lymphocyte infiltration, enhanced Aquaporin-5 (AQP5) expression in the submandibular gland, decreased inflammatory cytokine levels in the submandibular gland, and reduced the T helper type 17/regulatory T lymphocyte (Th17/Treg) cell ratio in the spleen. Transcriptomic and proteomic analyses indicated AS-OD's involvement in regulating phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and Janus kinase 3/signal transducer and activator of transcription 3 (JAK1/STAT3) pathways, with inhibitory effects validated in both NOD/Ltj mice submandibular gland and A-253 cells. Furthermore, AS-OD enhanced cell viability and reduced A-253 cell apoptosis through the PI3K/AKT pathway. In A-253 cells, AS-OD reduced inflammatory cytokine levels, CXC chemokine ligand 9/10 (CXCL9/10), and T-cell chemotaxis by inhibiting the JAK1/STAT3 pathway. AS-OD mitigates SS by suppressing inflammation and immune responses through the PI3K/AKT and JAK1/STAT3 pathways.
Animals ; STAT3 Transcription Factor/genetics* ; Sjogren's Syndrome/immunology* ; Mice, Inbred NOD ; Proto-Oncogene Proteins c-akt/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Janus Kinase 1/genetics* ; Humans ; Female ; Astragalus Plant/chemistry* ; Male

Objective:To investigate the efficacy of color Doppler ultrasound-guided percutaneous nephrostomy in the treatment of anastomotic leakage after laparoscopic pyeloplasty.Methods:A retrospective analysis was performed for the data of 15 children with peritoneal irritation after LP who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2018 to January 2023, of which 10 cases were anastomotic leaks and 5 cases were with renal pelvic blood clots. There were 12 males and 3 females. Age (4.2±2.7) years. The lesions were located on the left side of 11 cases and on the right side of 4 cases. All 15 cases had varying degrees of nausea, vomiting, abdominal pain and other symptoms. Physical examination: the children all showed painful faces and tense abdominal muscles. 15 patients had a preoperative pain score of 9.5 (8, 10). Ultrasound examination showed that the anterior and posterior diameters of renal pelvis separation were (34.93±4.86) mm, the anterior and posterior diameter/renal parenchymal thickness of renal pelvis separation was 15.66±1.02, renal dynamic nuclear imaging shows the renal function of the affected side was (29.69±1.71)%. Thirteen cases had the above symptoms before the abdominal drainage tube was removed, and the time of symptom onset was (3.3±1.1) days after surgery, of which 8 cases had a large increase in abdominal drainage, and color Doppler ultrasonography showed a large amount of fluid in the intra-abdominal intestinal space (about 500 ml). In 5 cases, the intraperitoneal drainage volume did not increase, and color Doppler ultrasonography showed strong echo in the renal pelvis, and blood clots were considered. All 13 patients were placed in the prone position under local anesthesia and underwent color Doppler ultrasound-guided percutaneous nephrostomy. The remaining 2 cases had abdominal drainage tube removed on the 3rd day after surgery, and peritoneal irritation signs appeared on the 4th and 6th days after surgery, respectively. Color Doppler ultrasonography showed that there was a large amount of fluid in the intra-abdominal intestinal space, and color Doppler ultrasound-guided peritoneal puncture and drainage + prone percutaneous nephrostomy was performed in the supine position under local anesthesia, and the biochemical analysis of the peritoneal puncture drainage fluid was confirmed to be anastomotic urine leakage. The drainage volume and urine output of 15 cases of peritoneal puncture drainage and pyelostomy were recorded, and the relief of nausea and vomiting symptoms and the score of postoperative pain after percutaneous nephrostomy were recorded. The changes of hydronephrosis and renal function before and after percutaneous nephrostomy were compared.Results:In this study, 15 patients underwent percutaneous nephrostomy with a duration of (16.8±1.9) min. The symptoms of nausea and vomiting disappeared after operation, and the pain scores were 3.2(2, 4) and 0.4(0, 2) at 2 h and 12 h after operation, respectively, which were statistically significant compared with those before operation ( P<0.01). In 13 children with simple percutaneous nephrostomy, the abdominal drainage tube was removed on (3.6±0.8) days and (8.6±1.0) days after percutaneous nephrostomy. In 2 children with peritoneal puncture and drainage plus percutaneous nephrostomy, the abdominal drainage tube was removed 3 days after the fistula operation, and the pyelostomy tube was removed 8 days after the fistula operation. The anterior and posterior diameters of renal pelvis separation were (10.87±4.05), (10.13±3.50) and (9.13±3.11) mm by color Doppler ultrasound at 3, 6 and 12 months after LP operation, respectively, and there were statistically significant differences compared with preoperative comparisons ( P<0.01).The diameter before and after renal pelvis separation was (7.60±2.86) mm, the diameter before and after renal pelvic separation/renal parenchymal thickness was 1.97±0.22, and the renal function was (39.23±2.66)% at 24 months after operation, which was statistically significant compared with that before operation ( P<0.01). Conclusions:Color Doppler ultrasound-guided percutaneous nephrostomy can effectively alleviate symptoms in the early stage, which could help to the healing of ureteral anastomosis, and has less trauma and short operation course.

Objective:To construct a nomogram model for differentiating gastric schwannoma (GS) from gastric stromal tumor (GST) (diameters 2 to 5 cm) based on CT imaging features before surgery.Methods:The clinical and imaging data of 49 patients with GS and 240 patients with GST in the Affiliated Hospital of Jining Medical University from July 2009 to April 2023 and Guangdong Provincial People′s Hospital from June 2017 to September 2022 were analyzed retrospectively. The independent factors for differentiating GS from GST were obtained by multivariate Logistic regression analysis. The nomogram model was constructed by R4.3.1 software. The efficacy of the nomogram model for differentiating GS from GST was evaluated by the receiver operating characteristics (ROC) curve, and calibration curve and decision curve analysis were used to evaluate the predictive efficacy and clinical application value of the nomogram model.Results:There were no statistical differences in the clinical symptom rate, calcification rate, ulcer rate, tumor vessel rate, ratio of long diameter to short diameter and CT value difference during the arterial and nonenhanced phases (CTV A-N) between GS patients and GST patients ( P>0.05). The proportion of female, incidence of lesions located in central or lower part of stomach, extraluminal or mixed growth rate, tumor-associated lymph node rate, strong enhancement rate, CT value difference during the portal and nonenhanced phases (CTV P-N), CT value difference during the delayed and nonenhanced phases (CTV D-N), CT value difference during the portal and arterial phases (CTV P-A) and CT value difference during the delayed and portal phases (CTV D-P) in GS patients were significantly higher than those in GST patients: 75.51% (37/49) vs. 58.33% (140/240), 85.71% (42/49) vs. 54.17% (130/240), 75.51% (37/49) vs. 45.00% (108/240), 44.90% (22/49) vs. 5.42% (13/240), 51.02% (25/49) vs. 27.08% (65/240), 32.0 (26.0, 43.5) HU vs. 29.0 (22.0, 37.7) HU, (44.59 ± 13.46) HU vs. (32.94 ± 12.47) HU, 20.0 (11.5, 25.0) HU vs. 10.0 (5.0, 17.0) HU and 9.0 (6.0, 12.0) HU vs. 4.0 (-2.7, 7.0) HU, the age, irregular shape rate, cystic degeneration rate and heterogeneous enhancement rate were significantly lower than those in GST patients: (58.12 ± 12.59) years old vs. (62.05 ± 11.22) years old, 16.33% (8/49) vs. 38.33% (92/240), 18.37% (9/49) vs. 51.25% (123/240) and 34.69% (17/49) vs. 56.25% (135/240), and there were statistical differences ( P<0.05 or<0.01). Multivariate Logistic regression analysis result showed that location, cystic degeneration, tumor-associated lymph node, CTV P-A and CTV D-P were the independent factors for differentiating GS from GST ( OR= 3.599, 0.201, 19.031, 1.124 and 1.160; 95% CI 1.184 to 10.938, 0.070 to 0.578, 6.159 to 58.809, 1.066 to 1.185 and 1.094 to 1.231; P<0.05 or<0.01). The nomogram model for differentiating GS from GST was constructed based on location, cystic degeneration, tumor-associated lymph node, CTV P-A and CTV D-P. The area under curve of the nomogram model for differentiating GS from GST was 0.924 (95% CI 0.887 to 0.951). The calibration curve analysis result showed that there was a good agreement between the predicted GS curve and the actual GS curve (the mean absolute error was 0.033). The result of the Hosmer-Lemeshow goodness-of-fit test indicated that the calibration of the nomogram model was appropriate ( χ2 = 2.52, P = 0.961). The clinical decision curve analysis result showed that when the threshold for the nomogram model for differentiating the two tumors was>0.03, the nomogram yielded more net benefits than the "all patients treated as GS" or "all patients treated as GST" scenarios. Conclusions:The nomogram model based on CT imaging features can be used to differentiate GS from GST before surgery.

Rheumatoid arthritis (RA) is an autoimmune disease with a complex etiology. Monocyte-derived macrophages (MDMs) infiltration are associated with RA severity. We have reported the deletion of G-protein-coupled receptor kinase 2 (GRK2) reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor signaling. However, as more GRK2-interacting proteins were discovered, the GRK2 interactome mechanisms in RA have been understudied. Thus, in the collagen-induced arthritis mouse model, we performed genetic GRK2 deletion using GRK2^f/fLyz2-Cre^+/- mice. Synovial inflammation and M1 polarization were improved in GRK2^f/fLyz2-Cre^+/- mice. Supporting experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptor γ (PPARγ) as a new GRK2-interacting protein. We further confirmed that fms-related tyrosine kinase 1 (Flt-1), which promoted macrophage migration to induce angiogenesis, was inhibited by GRK2-PPARγ signaling. Mechanistically, excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγ ligand-binding domain and enhanced Flt-1 transcription. Furthermore, the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology, Flt-1⁺ macrophages induced-synovial inflammation, and angiogenesis. Altogether, we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular signaling. Targeting GRK2 activity is a viable strategy to inhibit MDMs infiltration, affording a distinct way to control joint inflammation and angiogenesis of RA.

Objective:To evaluate the value of CT for differentiating gastric leiomyoma (GLM) from gastric schwannoma (GS).Methods:The clinical and imaging data of 42 patients with GLM (GLM group) and 41 patients with GS (GS group) were analyzed retrospectively. The general information and CT features were compared between two groups. The independent factors for differentiating GLM from GS were obtained by multivariate Logistic regression analysis. The receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficiency of the model.Results:The proportion of female and age in GLM group were significantly lower than those in GS group: 59.52% (25/42) vs. 85.37% (35/41), (51.83 ± 10.52) years old vs. (58.80 ± 10.63) years old, and there were statistical differences ( P<0.01). The upper part of the stomach rate, irregular shape rate, intraluminal growth rate, ratio of long diameter to short diameter and mild to moderate enhancement rate in GLM group were significantly higher than those in GS group: 71.43% (30/42) vs. 14.63% (6/41), 52.38% (22/42) vs. 21.95% (9/41), 92.86% (39/42) vs. 19.51% (8/41), 1.90 ± 0.55 vs. 1.34 ± 0.28 and 92.86% (39/42) vs. 51.22% (21/41), the cystic degeneration rate, ulcer rate, incidence of tumor-associated lymph node, CT values of venous phase and delayed phase in GLM group were significantly lower than those in GS group: 2.38% (1/42) vs. 26.83% (11/41), 7.14% (3/42) vs. 24.39% (10/41), 2.38% (1/42) vs. 60.98% (25/41), (59.21 ± 9.75) HU vs. (66.22 ± 10.33) HU and (65.02 ± 8.62) HU vs. (76.85 ± 11.89) HU, and there were statistical differences ( P<0.01 or <0.05); there were no statistical difference in the rate of calcification and the CT values of plain scan and arterial phase between the two groups ( P>0.05). Multivariate Logistic regression analysis result showed that the tumor location, growth mode, tumor-associated lymph node and ratio of long diameter to short diameter were the independent factors for differentiating GLM from GS ( OR = 34.385, 25.314, 0.023 and 97.700; 95% CI 2.848 to 415.171, 2.674 to 239.670, 0.001 to 0.637 and 3.113 to 3 066.549; P<0.01 or <0.05); when the model threshold was >0.647, the area under the curve was 0.988 (95% CI 0.934 to 1.000), with a sensitivity of 92.9% and specificity of 97.6%. Conclusions:When the tumor is prone to the upper part of the stomach, intraluminal growth, ratio of long diameter to short diameter >1.28, and the absence of the tumor-associated lymph node, GLM tends to be considered, on the contrary, it tends to be GS. Therefore, CT imaging features have certain value in differentiating GLM from GS before surgery.

Objective:To explore the clinical and genetic characteristics of 5α-reductase 2 deficiency syndrome(5α-RD2).Methods:Retrospective analysis of three cases of 5α-RD2 to summarize clinical data. Genetic testing was conducted using chromosome karyotyping analysis, whole-exome sequencing(WES), Sanger sequencing, and bioinformatics analysis. The effect of the novel variant on the structure of the 5α-reductase was evaluated by studying the homology modeling structure using SWISSMODEL and PyMoL.Results:The patients of all three cases have social gender as female. In Case 1, a 6-year-old patient sought medical attention due to abnormal external genitalia development. In Cases 2 and 3, 15-year-old patients presented with primary amenorrhea, and they showed masculinization of secondary sexual characteristics during puberty. In all three cases, the external genitalia exhibited varying degrees of masculinization, with clitoromegaly resembling a small penis and accompanying cryptorchidism. In Case 2, an hCG stimulation test was performed, and the testosterone/dihydrotestosterone(DHT) ratio was found to be 17.4. The karyotype of all three patients was 46, XY. Whole-exome sequencing(WES) detected SRD5A2 gene variants in all cases, with genotypes being p. Gln6Ter/p.Arg227Gln, p. Gln6Ter/p.Pro250Ala, and p. Arg227Ter/p.His89Tyr, respectively. Parental validation confirmed compound heterozygous mutations in all cases. The novel variant p. Pro250Ala was identified and classified as a likely pathogenic variant according to ACMG guidelines. Protein modeling analysis indicated that this variant may affect the binding of 5α-reductase 2 to NADPH. In Case 1, male gender was chosen, and a laparoscopic bilateral orchiopexy was performed. In Case 2, female gender was chosen, and testectomy and vaginoplasty were performed. The gender selection for Case 3 has not been definitively determined yet.Conclusions:Abnormal external genitalia is a common phenotype of 5α-RD2. After hCG stimulation test, there is a significant increase in the testosterone/dihydrotestosterone(DHT) ratio, which indicates that Sanger sequencing of the SRD5A2 gene can be directly performed. 5α-RD2 exhibits significant clinical heterogeneity, and WES can facilitate the differential diagnosis of 46, XY disorders of sex development. The study also reported a novel variant, p. Pro250Ala, which enriches the SRD5A2 gene variant database.

Objective:To evaluate the myocardial work of patients with different degrees of coronary artery stenosis with normal left ventricular ejection fraction and no segmental ventricular wall motion abnormality by left ventricular pressure-strain ring (PSL), and to explore the clinical value of myocardial work parameters in predicting severe coronary artery stenosis.Methods:The data of 238 patients undergoing coronary angiography (CAG) in the Affiliated Hospital of Jining Medical University from December 2020 to August 2021 was prospectively collected. According to the results of CAG, the patients were divided into control group, moderate stenosis group, severe stenosis (1-2 branches) group, severe stenosis (complex multiple branches) group. Global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), global work waste (GWW) and global work efficiency (GWE) were measured by PSL. Univariate and multivariate logistics regression were used to analyze the influencing factors of severe coronary artery stenosis. The receiver operating characteristic (ROC) curve was constructed to analyze the predictive value of GLS, GWI, GCW, GWW and GWE for severe coronary artery stenosis.Results:The GLS, GWI, GCW and GWE in severe stenosis group were lower than those in control group and moderate stenosis group (all P<0.05), while GWW was higher than those in control group and moderate stenosis group (all P<0.05); the GWI, GCW and GWE in severe stenosis (complex multiple branches) group were lower than those in severe stenosis (1-2 branches) group (all P<0.05), while GWW was higher than those in severe stenosis (1-2 branches) group (all P<0.05). Multivariate logistic regression analysis showed that GWE was an independent influencing factor for severe coronary stenosis ( OR=0.266, P<0.05). Compared with GLS, GWI, GCW and GWW, GWE had the largest area under the curve (0.920) to predict severe coronary stenosis, with sensitivity of 92.24% and specificity of 73.77%. The intra observer and inter observer correlation coefficients of GWI, GCW, GWW and GWE analyzed by two ultrasound physicians were 0.916 and 0.907, 0.989 and 0.981, 0.932 and 0.955, 0.931 and 0.937, respectively, which showed good repeatability. Conclusions:PSL provides a new method for quantitative evaluation of left ventricular systolic function in patients with coronary artery stenosis. GWE can be used as a sensitive indicator to predict patients with severe coronary artery stenosis, and is worth to be popularized and applied in the clinical.

N6-Methyladenosine (m⁶A) is the most abundant internal modification in eukaryotic mRNA, playing critical role in various bioprocesses. Like other epigenetic modifications, m⁶A modification can be catalyzed by the methyltransferase complex and erased dynamically to maintain cells homeostasis. Up to now, only two m⁶A demethylases have been reported, fat mass and obesity-associated protein (FTO) and alkylation protein AlkB homolog 5 (ALKBH5), involving in a wide range of mRNA biological progress, including mRNA shearing, export, metabolism and stability. Furthermore, they participate in many significantly biological signaling pathway, and contribute to the progress and development of cancer along with other diseases. In this review, we focus on the studies about structure, inhibitors development and biological function of FTO and ALKBH5.