Ameloblastoma is a benign tumor characterized by locally invasive phenotypes,leading to facial bone destruction and a high recurrence rate.However,the mechanisms governing tumor initiation and recurrence are poorly understood.Here,we uncovered cellular landscapes and mechanisms that underlie tumor recurrence in ameloblastoma at single-cell resolution.Our results revealed that ameloblastoma exhibits five tumor subpopulations varying with respect to immune response(IR),bone remodeling(BR),tooth development(TD),epithelial development(ED),and cell cycle(CC)signatures.Of note,we found that CC ameloblastoma cells were endowed with stemness and contributed to tumor recurrence,which was dominated by the EZH2-mediated program.Targeting EZH2 effectively eliminated CC ameloblastoma cells and inhibited tumor growth in ameloblastoma patient-derived organoids.These data described the tumor subpopulation and clarified the identity,function,and regulatory mechanism of CC ameloblastoma cells,providing a potential therapeutic target for ameloblastoma.

Head and neck squamous cell carcinoma(HNSCC)is characterized by high recurrence or distant metastases rate and the prognosis is challenging.There is mounting evidence that tumor-infiltrating B cells(TIL-Bs)have a crucial,synergistic role in tumor control.However,little is known about the role TIL-Bs play in immune microenvironment and the way TIL-Bs affect the outcome of immune checkpoint blockade.Using single-cell RNA sequencing(scRNA-seq)data from the Gene Expression Omnibus(GEO)database,the study identified distinct gene expression patterns in TIL-Bs.HNSCC samples were categorized into TIL-Bs inhibition and TIL-Bs activation groups using unsupervised clustering.This classification was further validated with TCGA HNSCC data,correlating with patient prognosis,immune cell infiltration,and response to immunotherapy.We found that the B cells activation group exhibited a better prognosis,higher immune cell infiltration,and distinct immune checkpoint levels,including elevated PD-L1.A prognostic model was also developed and validated,highlighting four genes as potential biomarkers for predicting survival outcomes in HNSCC patients.Overall,this study provides a foundational approach for B cells-based tumor classification in HNSCC,offering insights into targeted treatment and immunotherapy strategies.

The article describes the involvement of a clinical pharmacist in the pharmacotherapeutic process of a patient with severe intrahepatic cholestasis of pregnancy concomitant severe hyperlipidemia.Upon admission,the patient presented with triglyceride levels as high as 37.47 mmol·L-1,cholesterol levels of 15.70 mmol·L-1,and total bile acid levels elevated to 64.30 μmol·L-1,indicating a significantly increased risk of complications such as acute pancreatitis and intrauterine fetal demise.How to ensure the safety and efficacy of the medication at the same time is a major challenge in the treatment of this patient.The clinical pharmacist recommended a treatment regimen comprising ursodeoxycholic acid in combination with ademetionine 1,4-butanedisulfonate to lower bile acid levels,alongside fenofibrate combined with ezetimibe to manage hyperlipidemia.After adjustment,triglycerides,cholesterol,and bile acid levels decreasing to 11.10 mmol·L-1,5.94 mmol·L-1,and 49.30 μmol·L-1,respectively.The patient's condition was stable,ultimately resulting in a favorable childbirth outcome.The clinical pharmacist provided personalized pharmaceutical care throughout the patient's treatment,and assisted the clinician to formulate a medication plan in a scientific and rational manner.This article can be served as a reference for the diagnosis and treatment of similar complex obstetric patients.

Objective:To investigate the effects of early Comfort using Analgesics, minimal Sedatives and maximum Humane care (eCASH) patterns on the risk of negative mood and continuous renal replacement therapy (CRRT)-related adverse events in patients with severe CRRT.Methods:A total of 90 patients with severe CRRT in Shenzhen Integrated Traditional Chinese and Western Medicine Hospital from October 2018 to October 2020 were selected as the study subjects, and they were divided into observation group and control group according to random number table method, with 45 patients in each group. The control group was given routine nursing program, and the observation group was given eCASH mode on the basis of the control group.Nursing satisfaction, CRRT-related adverse events and negative mood scores before and after nursing were compared between 2 groups.Results:The nursing satisfaction degree of the observation group was 86.67% (39/45), significantly higher than that of the control group (66.67%, 30/45), and the difference was statistically significant ( χ2=5.03, P<0.05). After nursing, the Hospital Anxiety and Depression Scale-Anxiety(HADS-A) and Hospital Anxiety and Depression Scale-Depression(HADS-D) scores of the observation group were 5.18 ± 0.67 and 5.27 ± 0.61, respectively, lower than 8.14 ± 1.18, 7.94 ± 1.07 before intervention, and 6.33 ± 0.72, 5.94 ± 0.49 of the control group. Barthel Index(BI) (65.17 ± 8.67) was significantly higher than that before nursing 41.56 ± 6.46 and control group 60.48 ± 6.47, the difference was statistically significant ( t values were 5.74-20.76, all P<0.05). The scores of Visual Analogue Scale(VAS), Present Pain Intensity(PPI), sensory total score and emotional total score of observation group after nursing were 3.24 ± 0.56, 1.18 ± 0.25, 6.38 ± 0.89, 2.68 ± 0.59 significantly lower than those before nursing 6.24 ± 0.87, 3.24 ± 0.56, 11.24 ± 1.81, 6.37 ± 1.04 and 4.36 ± 0.67, 1.31 ± 0.31, 7.26 ± 0.96, 2.98 ± 0.62 of the control group. The difference was statistically significant ( t values were 2.19-20.70, P<0.05). Conclusions:eCASH model can significantly improve the negative emotions of patients with severe CRRT, improve their comfort and reduce the risk of related adverse events, which is worthy of clinical promotion.

Objective:To investigate the composition of the renal disease spectrum and epidemiological characterisics for renal biopsy cases in Xinjiang Uygur Autonomous Region.Methods:The clinical and pathological data of 10 684 renal biopsy cases from 12 hospitals in Xinjiang Uygur Autonomous Region from August 1986 to December 2019 were collected and the composition of renal diseases and pathological types were analyzed retrospectively.Results:Among the 10 684 renal biopsy cases with 5 595 males and 5 089 females, 7 804 cases (73.04%) were Han nationality, 2 357 cases (22.06%) were Uygur nationality and 523 cases (4.90%) were other nationalities. Among the 10 684 cases of renal biopsy, primary glomerular disease, secondary glomerular disease, tubulointerstitial disease, end-stage renal disease, genetic and congenital disease and post transplant glomerular disease were 8 533 cases (79.87%), 1 740 cases (16.29%), 229 cases (2.14%), 121 cases (1.13%), 46 cases (0.43%) and 15 cases (0.14%), respectively. The distribution of kidney diseases in Han, Uygur and other nationalities (except Han and Uygur in this region) was the same as that in general. There was no significant difference in disease type composition between Han and Uygur, Han and other nationalities, and Uygur and other nationalities (all P>0.05). Among the 8 533 cases of primary glomerular diseases, the top five pathological types were IgA nephropathy (3 095 cases, 36.27%), mesangial proliferative glomerulonephritis (2 008 cases, 23.53%), membranous nephropathy (1 503 cases, 17.61%), minimal glomerulopathy (567 cases, 6.64%) and focal segmental glomerulosclerosis (494 cases, 5.79%). The top five pathological types of primary glomerular diseases were different between Han and Uygur, and Han and other nationalities (both P<0.01). There was no statistically significant difference between Uygur and other nationalities in the top five pathological types of primary glomerular diseases ( P=0.113). Among 1 740 cases of secondary glomerular diseases, the top five pathological types were lupus nephritis (517 cases, 29.71%), Henoch-Sch?nlein purpura nephritis (304 cases, 17.47%), diabetic glomerulosclerosis (285 cases, 16.38%), benign renal arteriosclerosis (196 cases, 11.26%) and systemic vasculitis (101 cases, 5.80%). It was different between Han and Uygur, Han and other nationalities, and Uygur and other nationalities in the top five pathological types of secondary glomerular diseases. Conclusions:Primary glomerular disease accounts for 79.87% of renal diseases in Xinjiang Uygur Autonomous Region. IgA nephropathy is the main pathological type, followed by mesangial proliferative glomerulonephritis and membranous nephropathy. The most common pathological type of secondary glomerular disease in this region is lupus nephritis, followed by Henoch-Sch?nlein purpura nephritis and diabetic glomerulosclerosis. The top five pathological types of primary glomerular diseases and secondary glomerular diseases are different in different ethnic groups in Xinjiang Uygur Autonomous Region.

Objective:To analyze the mutation sites and characteristics of phospholipase CE1( PLCE1) gene in children with primary nephrotic syndrome(PNS) in Zhuang, Guangxi, China, so as to explore the expression status of PLCE1 protein in peripheral blood of PNS patients. Methods:(1)Blood samples of 154 Zhuang children with PNS and 98 healthy children of Zhuang nationality from July 2015 to September 2017 in Affiliated Hospital of Youjiang Medical College for Nationalities were collected to sequence PLCE1 gene with FastTarget target gene capture method in the combination with next generation sequencing.Based on the comparison between mutation results and information from the database, the pathogenicity, phenotype and distribution characteristics of these mutation sites were discovered and appraised.(2)The concentration of PLCE1 protein in serum samples were measured by enzyme-linked immuno sorbent assay, then the data of PNS group and healthy control group were compared and analyzed statistically with SPSS 25.0. Results:(1)A total of 18 low-frequency mutations of PLCE1 were observed, 5 of them(c.670C>T, c.578T>C, c.923G>T, c.4916C>T, and c. 5927_5929del) were found only in the PNS group, and 3 of them occurred in both PNS group and healthy control group: c.176C>T, c.389T>C, and c. 4304C>T.Five newly discovered mutations (c.923G>T, c.958T>A, c.1151C>T, c.2341A>G, and c. 3592G>C)were discovered and only c. 923 G>T is pathogenic mutation of PLCE1.(2)The concentration of PLCE1 protein in healthy control group was 414.65 (231.20, 729.81) ng/L and the level of PLCE1 in PNS group was 237.84 (116.14, 535.85) ng/L, ( Z=-3.212, P<0.001), and the value of PNS group was lower than that in the healthy control group. Conclusions:(1)As a new pathogenic mutation of PLCE1, c.923G>T was found.(2)The phenotype of PLCE1 gene mutation in Zhuang children with PNS was diverse, and they may differ by race and region.(3) PLCE1 protein of serum may act as a protective protein to guarantee various life activities of cells by participating in multiple signal transduction pathways.

There is accumulating evidence that microRNAs are emerging as pivotal regulators in the development and progression of neuropathic pain. MicroRNA-15a/16 (miR-15a/16) have been reported to play an important role in various diseases and inflammation response processes. However, whether miR-15a/16 participates in the regulation of neuroinflammation and neuropathic pain development remains unknown. In this study, we established a mouse model of neuropathic pain by chronic constriction injury (CCI) of the sciatic nerves. Our results showed that both miR-15a and miR-16 expression was significantly upregulated in the spinal cord of CCI rats. Downregulation of the expression of miR-15a and miR-16 by intrathecal injection of a specific inhibitor significantly attenuated the mechanical allodynia and thermal hyperalgesia of CCI rats. Furthermore, inhibition of miR-15a and miR-16 downregulated the expression of interleukin-1β and tumor-necrosis factor-α in the spinal cord of CCI rats. Bioinformatic analysis predicted that G protein-coupled receptor kinase 2 (GRK2), an important regulator in neuropathic pain and inflammation, was a potential target gene of miR-15a and miR-16. Inhibition of miR-15a and miR-16 markedly increased the expression of GRK2 while downregulating the activation of p38 mitogen-activated protein kinase and NF-κB in CCI rats. Notably, the silencing of GRK2 significantly reversed the inhibitory effects of miR-15a/16 inhibition in neuropathic pain. In conclusion, our results suggest that inhibition of miR-15a/16 expression alleviates neuropathic pain development by targeting GRK2. These findings provide novel insights into the molecular pathogenesis of neuropathic pain and suggest potential therapeutic targets for preventing neuropathic pain development.
Animals ; Computational Biology ; Constriction ; Down-Regulation ; Hyperalgesia ; Inflammation ; Injections, Spinal ; Mice ; MicroRNAs ; Neuralgia ; p38 Mitogen-Activated Protein Kinases ; Phosphotransferases ; Protein Kinases ; Rats ; Sciatic Nerve ; Spinal Cord ; Up-Regulation

Objective To investigate the effect of sodium arsenite (NaAsO2) on the expression of miRNA-21 (miR-21) mediated by transcription factor ETS-1 in human normal hepatocytes (L-02).Methods Dose-effect study:The L-02 cells were treated with different doses of NaAsO2 [0.0 (control),2.5,5.0,10.0,20.0,40.0 μmol/L] for 24 h.Time-effect study:L-02 cells were exposed to 0 (control) and 20 μmol/L NaAsO2 for 12,24,36 and 48 h (n =6).ETS-1 and miR-21 were treated with ETS-1 shRNA and miR-21 inhibitor,respectively.The cells treated with ETS-1 shRNA (100 nmol/L) were divided into 4 groups:①ETS-1 shRNA NC treatment alone (control group);②ETS-1 shRNA NC combined with NaAsO2 (20 μ,mol/L) treatment group;③ETS-1 shRNA treatment alone group;④Treatment with ETS-1 shRNA and NaAsO2 (20 μmol/L) group.The MiR-21 inhibitor (100 nmol/L) treated cells were also divided into 4 groups:① miR-21 inhibitor NC treatment (control group);② miR-21 inhibitor NC combined with NaAsO2 (20 μmol/L);③miR-21 inhibitor group;④miR-21 inhibitor combined with NaAsO2 (20 μ mol/L) treatment group.The expression of ETS-1 mRNA and miR-21 were detected by quantitative real-time PCR (qRT-PCR);the protein expression of ETS-1 was detected by Western blotting.Results Dose-effect study:The expression of ETS-1 mRNA in the groups of 0.0 (control),2.5,5.0,10.0,20.0 and 40.0 μmol/L was 1.008 ± 0.028,1.552 ± 0.029,1.697 ± 0.050,1.842 ± 0.077,2.233 ± 0.096 and 2.235 ± 0.092;miR-21 expression was 1.025 ± 0.094,1.552 ± 0.072,1.683 ± 0.066,1.915 ± 0.171,2.337 ± 0.195 and 2.592 ± 0.177;the expression of ETS-1 protein was 1.060 ± 0.045,1.267 ± 0.160,1.386 ± 0.087,1.723 ± 0.196,2.208 ± 0.122 and 2.284 ± 0.224,respectively,and the differences were statistically significant (F =47.797,8.959,65.748,all P ＜ 0.05),the NaAsO2 dose groups were significantly higher than those of the control group (all P ＜ 0.05),and there was a dose-effect relationship.Time-effect study:The expression of ETS-1 mRNA in L-02 cells was 1.253 ± 0.175,1.623 ± 0.220,1.771 ± 0.324 and 1.913 ± 0.251,respectively at 12,24,36 and 48 h;the expression of miR-21 was 1.502 ± 0.111,1.716 ± 0.113,1.979 ± 0.186 and 2.452 ± 0.304;the expression of ETS-1 protein was 1.196 ± 0.105,1.502 ± 0.076,1.651 ± 0.074 and 1.839 ± 0.139,respectively,there were significant differences between the groups (F =14.936,39.180,39.441,all P ＜ 0.05).The expression of various time points of exposure to NaAsO2 was significantly higher than those in the control group (1.044 ± 0.115,1.044 ± 0.124,1.108 ± 0.088,1.053 ± 0.061;1.092 ± 0.061,1.096 ± 0.169,1.024 ± 0.111,1.057 ± 0.146;1.020 ± 0.017,1.049 ± 0.121,1.024 ± 0.089,1.031 ± 0.124,all P＜ 0.05),and there was a time-effect relationship.ETS-1 shRNA and miR-21 inhibitor treatment:compared with ETS-1 shRNA NC combined with NaAsO2 (20 μmol/L),ETS-1 shRNA and NaAsO2 (20 μmol/L) could significantly inhibit the expression of ETS-1 (0.912 ± 0.238 vs 1.641 ± 0.225,P ＜ 0.05),and down-regulated the expression of miR-21 (1.313 ± 0.334 vs 2.363 ± 0.252,P ＜ 0.05).There was no significant difference of ETS-1 mRNA expression between miR-21 inhibitor and NaAsO2 (20.μmol/L) group (1.580 ± 0.077 vs 1.576 ± 0.065,P ＞ 0.05) compared with miR-21 inhibitor NC and NaAsO2 (20 μmol/L).Conclusions The expression of ETS-1 and miR-21 in L-02 cells is significantly higher than those in control.The high expression of ETS-1 mediates NaAsO2-induced miR-21 overexpression,which may be an important molecular mechanism of arsenic-induced expression dysregulation of human hepatic miRNAs and liver damage.

Objective To investigate the effect of thyroxine replacement therapy with residual subclinical hypothyroidism on the success rate of catheter ablation in elderly patients with atrial fibrillation(AF).Methods Among the consecutive patients with AF who underwent a first AF ablation in our center between 2009 and 2012,we identified 56 patients(41 paroxysmal AF,15 persistent AF)with subclinical clinical hypothyroidism after receiving thyroid hormone replacement therapy as study group.The control group consisted of 56 patients with euthyroidism and no history of thyroid dysfunction.All patients underwent catheter ablation.Results At the end of follow up,37.5%(21/56)patients were AF free after the first procedure in the study group,in comparison to 64.3%(36/56)in control group(χ2=8.655,P=0.003).Last procedure was performed in 27 patients of study group and in 15 patients of control group.After the last performed ablation,62.5%(35/56)study group patients and 80.4%(45/56)controls group patients had no recurrence(χ2=4.653,P=0.031).The major complications rate did not differ between two groups(P=0.642).Conclusions Thyroid hormone replacement therapy with residual subclinical hypothyroidism reduces catheter ablation success rate in elderly patients with atrial fibrillation.

Objective To compare the clinical effects of different doses of methylprednisolone therapy for children with severe hand,foot and mouth disease (HFMD).Methods According to different dosage methods, 240 children with severe HFMD were divided into large dose group,medium dose group and small dose group,80 cases in each group.The three groups were given different doses of methylprednisolone infusion on the basis of conventional treatment:large dose group(5 ~10mg·kg· -1 d -1 ),medium dose group(3 ~5 mg·kg· -1 d -1 ),small dose group (1 ~2mg · kg · -1 d -1 ).Results The time of fever sustaining,panic ease,mechanical ventilation,duration of hypertension and heart rate recovery of the medium -dose group were (47.93 ±4.72)h,(45.54 ±2.42)h,(51.43 ± 6.85)h,(53.66 ±7.62)h,(52.45 ±7.84)h,which were significantly shorter than those of the small -dose and large -dose group(all P <0.05).The incidence of turning to critically ill and the rate of ventilator use of the medium-dose group were significantly lower than those of the small -dose and large -dose group (all P <0.05 ).The incidence of pulmonary edema and pulmonary hemorrhage of the medium -dose group were significantly lower than those of the small -dose and large -dose group(all P <0.05).The differences among three groups were not statistically significant in the complications such as hypokalemia,hypocalcemia and gastrointestinal bleeding (all P >0.05 ). Conclusion Medium dose of methylprednisolone in the treatment of children with severe HFMD has significant effect and less adverse reactions,which is worthy of promotion.