Objective: To investigate the expression and functional role of FK506 binding protein 10 (FKBP10) in oral squamous cell carcinoma (OSCC), and to provide a research basis for the estimated prognosis and targeted therapy of OSCC. Methods: A total of 284 OSCC samples and 19 normal samples were selected from the Cancer Genome Atlas (TCGA) database, and diagnostic analysis was performed to determine mRNA expression. Survival analysis for FKBP10 and OSCC was conducted on a gene expression profile interaction analysis website. Real-time fluorescence quantitative PCR and Western Blot were used to detect the mRNA and protein expression of FKBP10 in four OSCC cell lines and SAS and SCC9 cells transfected with siRNA. The cell proliferation ability of FKBP10-silenced cells was detected using the CCK8 method, and the cell cycle distribution and apoptosis were detected by flow cytometry. Cell migration and invasion ability were detected through wound healing and invasion experiments. The expression changes of total protein and phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinase (AKT) after FKBP10 silencing were analyzed by proteomics and Western Blot. Results: According to the analysis of gene expression levels, the mRNA expression level of FKBP10 in OSCC was significantly higher than that in normal tissues (P < 0.001). In terms of diagnosis, the expression level of FKBP10 has unique diagnostic value for OSCC (P < 0.05). The survival analysis of FKBP10 and OSCC showed that a high expression of FKBP10 led to a decrease in patient survival and poor prognosis (P < 0.05). The expression of FKBP10 mRNA and protein in OSCC cell lines was higher than that in normal oral keratinocytes (P < 0.001). Silencing FKBP10 can reduce the proliferation, invasion, and migration ability of SAS and SCC9 (P < 0.001), and also block their cell cycle in the G0/G1 phase (P < 0.001), with a significant increase in apoptosis (P < 0.05). Protein mass spectrometry and Western blot analysis revealed that FKBP10 silencing significantly downregulated the expression of multiple proteins in the RAP1 signaling pathway, mainly RAP guanine nucleotide exchange factor 1 (RAPGEF1) (P < 0.05) and the phosphorylation of PI3K-AKT proteins (P < 0.05). Conclusion FKBP10 is highly expressed in OSCC, leading to poor prognosis for patients. Downregulated FKBP10 expression can inhibit the proliferation, migration, and invasion ability of OSCC cells, hinder cell cycle progression, and promote apoptosis via the RAP1-PI3K-AKT axis. FKBP10 is a potential therapeutic target and prognostic biomarker for OSCC.

More and more studies suggest that targeting neuronal antibodies,particularly anti-Hu antibody,can cause various degrees of damage to central nervous system and/or enteric nervous system and affect the occurrence,progression,and prognosis of related diseases.Therefore,elucidating the mechanisms of anti-Hu antibody-induced nervous system injury and its relevance to diseases is of significant importance for individualized diagnosis and treatment.This article reviewed the associations between anti-Hu antibody and paraneoplastic gastrointestinal dysmotility,chronic intestinal pseudo-obstruction,and irritable bowel syndrome,as well as the mechanisms of neuronal damage caused by anti-Hu antibody.

Objective:To investigate the efficacy of 3D-printed quantitative bone implants assisting second-stage Masquelet technique for the treatment of long-segment bone defect following Gustilo type IIIB and IIIC tibial fractures.Methods:A retrospective case series analysis was made on 26 patients with long-segment bone defect following Gustilo type IIIB and IIIC tibial fractures treated in Wuxi Ninth People′s Hospital from July 2015 to December 2020, including 20 males and 6 females; aged 19-63 years [(46.5±4.5)years]. Gustilo classification was type IIIB in 23 patients and type IIIC in 3. In the first stage, all patients had thoroughly emergent debridement, removal of all free bone pieces, restoration of the length and force line plus externally fixion, and vacuum sealing drainage (VSD) of the residual wound. After 2-7 days, the external fixation was removed and replaced by internal fixation, with the bone cement filling in the defect area and the free flap covering the wound. The length of tibial bone defect was 5-14 cm [(6.3±0.4)cm], and the tibial defect volume was 12.2-73.1 cm 3 [(33.6±9.2)cm 3]. In the second stage (6-19 weeks after injury), the bone cement was removed, followed by autologous bone grafting. Prior to bone grafting, digital technology was used to accurately calculate the bone defect volume, and an equal volume of bone harvesting area was designe to produce the 3D printed osteotomy template. Bone grafting was conducted after bone removal according to the osteotomy template during operation. The success rate of one-time iliac bone extraction, bone harvesting time, and bleeding volume were recorded. Pain in the bone extraction area was evaluated by visual analogue score (VAS) at 1 day and 1 month after operation and at the last follow-up. Wound healing, complications, and bone healing were observed. Life quality was evaluated by health survey brief form (SF-36) including scores of physical component summary (PCS) and mental component summary (MCS) before bone grafting and at the last follow-up. Results:All the patients were followed up for 13-53 months [(32.3±12.5)months]. One-time iliac bone extraction was successful in all the patients. Bone harvesting time was 15-30 minutes [(21.0±2.5)minutes]. The bleeding volume was 50-120 ml [(62.3±29.0)ml]. The VAS was 1-4 points [(1.2±0.9)points] at 1 day after operation, higher than these (0.0±0.0)points at 1 month after operation and at the last follow-up (all P<0.01). Totally, 25 patients obtained wound healing after operation, except for 1 patient with superficial wound infection after bone grafting that was healed by dressing change. There was 1 patient with bone infection after 3 months of bone grafting that was healed by repeated surgery with Masquelet technique in the first and second stage. Besides, 2 patients had symptoms of cutaneous nerve injury in the iliac donor area. The time of bone healing was 4-7 months [(5.8±0.8)months]. The scores of PCS and MCS in SF-36 at the last follow-up were (73.6±12.8)points and (83.6±13.2)points, significantly higher than those before bone grafting [(46.8±0.5)points, (60.7±2.0)points] (all P<0.01). Conclusion:Second-stage Masquelet technique with 3D printed quantitative bone implants for the treatment of long-segment bone defect following Gustilo type IIIB and IIIC tibial fractures is associated with shortened bone harvesting time, attenuated pain, reduced complications, accelerated bone healing and improved function.

Coronary artery disease (CAD) is a chronic disease but causes the highest mortality and morbidity among the cardiovascular diseases worldwide. Correlations between CAD and gut microbiota have been observed. This suggests that the gut microbiota could become a vital diagnostic marker of CAD, and restoring the gut habitat may become a promising strategy for CAD therapy. The elevated level of trimethylamine-N-oxide (TMAO), a gut microbiota-derived metabolite, was found to be associated with the increased risk of cardiovascular disease and the all-cause mortality. Preclinical studies have shown that it has pro-arteriosclerosis properties. It is likely that regulating the production of TMAO by gut microbiota may become a promising strategy for anti-atherosclerosis therapy. This review summarizes the clinical and preclinical researches on the intervention of CAD by regulating the gut microbiota and the microbiota-derived metabolite TMAO, with the aim to provide new target for the therapy of CAD.
Coronary Artery Disease ; Gastrointestinal Microbiome ; Humans ; Methylamines ; Oxides

Objective: To analyze the incidence and mutation characteristics of FLT3 gene mutation and clinical efficacy of tyrosine kinase inhibitor (TKI) in patients with mixed phenotype acute leukemia (MPAL). Methods: A total of 48 patients with MPAL who were admitted to Hebei Yanda Lu Daopei Hospital from June 2015 to February 2018 were retrospectively analyzed. The common mutated 58 genes in hematologic malignancies were detected by using amplicon-targeted next generation sequencing, of which internal tandem duplication (ITD) and point mutation occurred in the hotspot region of exon 14, 15 and 20 in FLT3 gene. Multiplex polymerase chain reaction (PCR) analysis was used to detect 35 gene fusions in hematological neoplams. Results: There were 7 cases of FLT3 mutation in 48 MPAL patients, which were all ITD mutations. The median length of the inserts of FLT3-ITD was 48 bp, and one MPAL patient carried 2 multiple length inserts simultaneously, and the median variant allele frequency (VAF) was 40.5% (7.9%-84.7%). There were no statistically significant differences in clinical and genetic characteristics between FLT3 mutation-positive and FLT3 mutation-negative MPAL patients (both P > 0.05). Among 7 FLT3 mutation-positive MPAL patients, 4 cases were often accompanied with RUNX1 mutation. A total of 4 MPAL patients with FLT3-ITD-positive received sorafenib or sunitinib combined chemotherapy, and 3 of them achieved complete remission. Conclusions ITD mutation is the main part in the FLT3 mutation of MPAL patients. FLT3-ITD-positive MPAL patients are often accompanied with RUNX1 mutation, which may benefit from targeted therapy with FLT3 kinase inhibitor.

Objective To investigate the clinical and molecular biological characteristics of mixed_phenotypic acute leukemia (MPAL) with SET_NUP214 fusion gene positive and extramedullary infiltration. Methods The clinical characteristics, diagnosis and treatment of one MPAL patient with SET_NUP214 and extramedullary infiltration who was admitted to Hebei Yanda Ludaopei Hospital in November 2017 were analyzed, and the literature was reviewed. Results The patient was diagnosed as MPAL with extramedullary infiltration. Gene detection found SET exon7_NUP214 exon17 fusion positive accompanied with PHF6, SRSF2 and NRAS mutations. After intensive chemotherapy, the patient achieved complete remission, and then received hematopoietic stem cell transplantation (HSCT), followed by early extramedullary relapse after transplantation, and achieved secondary remission after consolidation chemotherapy. Conclusions MPAL with SET_NUP214 fusion gene positive and extramedullary infiltration has a poor prognosis, and it is easy to relapse. Currently, HSCT is the best available treatment strategy for such patients.

Objective: To observe and compare the effects of two standards on the overweight trend in urban Shanghai infants and young children. Methods: A cluster randomized controlled trial was conducted in 19 communities in two districts of Shanghai, and the subjects (n=15 019) were divided into S-group and W-group by sealed envelope randomization. The subjects were newborns born between November 2013 and December 2014. The 2005 Shanghai growth standard was applied in the S-group and the 2006 WHO growth standard was used in the W-group. At each follow-up time point age of 1, 2, 4, 6, 9, 12 and 18 months, the outpatient physician assessed the length and weight of the infants according to the standard adopted by each group and provided feeding guidance. The weight-for-age Z scores (WAZ), length-for-age Z scores (LAZ) and weight-for-length Z scores (WLZ) were calculated according to the WHO standard. Weight, length, WAZ, LAZ, WLZ and overweight ratio (WLZ≥2) were compared between the two groups using t test, Wilcoxon test and χ² test. Results: A total of 6 509 infants (3 391 were boys, 3 118 were girls) were in the W-group, and 8 510 infants (4 374 were boys, 4 136 were girls) were in the S-group. Among the boys, the weight values at the age of 4, 6, 9, 12, 18 months in the W-group were all lower than those in the S-group ((7.5±0.8) vs. (7.7±0.8) kg, (8.6±0.8) vs. (8.7±0.8) kg, (9.6±0.9) vs. (9.7±0.9) kg, (10.4±1.0) vs. (10.5±1.0) kg, (11.5±1.1) vs.(11.7±1.1) kg; t=4.329, 2.422, 3.739, 2.451, 2.736; P<0.01, 0.015,<0.01, 0.014, 0.009). The length had no significant difference between two groups at all months of age(all P>0.05). The overweight ratio in the W-group was lower than that in the S-group at the age of 9, 12, 18 months(3.3% (71/2 170) vs. 4.9% (143/2 927), 2.5% (51/2 037) vs. 4.5% (126/2 818), 0.8% (7/832) vs. 3.1% (39/1 266); χ²=6.520, 14.209, 12.350; P=0.011,<0.01,<0.01).Among the girls, except at the age of 2 months (W-group (5.6±0.6) vs. S-group (5.7±0.6), t=2.935, P=0.003), weight values had no significant difference between the two groups at other age months (all P>0.05).The length in the W-group was higher than that in the S-group at 12 and 18 months of age ((75.6±2.4) vs.(75.5±2.3)cm, (82.4±2.9) vs.(82.2±2.7) cm; t=2.351, 2.197; P=0.019, 0.028). The ratio of overweight in the W-group was lower than that of S-group at the age of 12 and 18 months (1.8% (33/1 871) vs.3.0% (80/2 658), 0.6% (5/790) vs.1.7% (20/1 178); χ²=6.764,4.276; P=0.009, 0.039). Conclusions The application of WHO growth standard can help to reduce the weight gain rate of boys, promote the linear growth of girls, and thus alleviate the overweight trend of infants within 18 months. It suggested that 2006 WHO growth standard should be applied to infants within 1 year of age in Shanghai.

This retrospective analysis aimed to investigate the mutation profile of 16 common mutated genes in de novo acute myeloid leukemia (AML) patients. A total of 259 patients who were diagnosed of de novo AML were enrolled in this study. Mutation profiling of 16 candidate genes were performed in bone marrow samples by using Sanger sequencing.We identified at least 1 mutation in 199 of the 259 samples (76.8%), and 2 or more mutations in 31.7% of samples. FLT3-ITD was the most common mutated gene (16.2%, 42/259), followed by CEBPA (15.1%, 39/259), NRAS (14.7%, 38/259), and NPM1 (13.5%, 35/259). Concurrence was observed in 97.1% of the NPM1 mutated cases and in 29.6% of the double mutated CEBPA cases. Distinct patterns of co-occurrence were observed for different hotspot mutations within the IDH2 gene: R140 mutations were associated with NPM1 and/or FLT3-ITD mutations, whereas R172 mutations co-occurred with DNMT3A mutations only. Concurrence was also observed in 86.6% of epigenetic regulation genes, most of which co-occurred with NPM1 mutations. The results showed certain rules in the mutation profiling and concurrence of AML patients, which was related to the function classification of genes. Defining the mutation spectrum and mutation pattern of AML will contribute to the comprehensive assessment of patients and identification of new therapeutic targets.
Adolescent ; Adult ; Aged ; CCAAT-Enhancer-Binding Proteins ; genetics ; Child ; Child, Preschool ; China ; DNA Mutational Analysis ; Female ; GTP Phosphohydrolases ; genetics ; Gene Expression Profiling ; Gene Frequency ; Genetic Predisposition to Disease ; Humans ; Kaplan-Meier Estimate ; Leukemia, Myeloid, Acute ; genetics ; Male ; Membrane Proteins ; genetics ; Middle Aged ; Mutation ; Nuclear Proteins ; genetics ; Phenotype ; Retrospective Studies ; Young Adult ; fms-Like Tyrosine Kinase 3 ; genetics

Objective To compare the effects of different anesthetics on the recovery of neurologi-cal function after intracranial aneurysm embolization. Methods One hundred patients of both sexes with aneurysmal subarachnoid hemorrhage, aged more than 18 yr, with body mass index of 18. 5-24. 0 kg∕m2 , of American Society of Anesthesiologists physical status Ⅱ or Ⅲ and WFNS grade Ⅰ-Ⅳ, with the thick-ness of subarachnoid hemorrhage more than 4 cm, were divided into 2 groups (n= 50 each) using a random number table: propofol group (group P) and sevoflurane group (group S). After anesthesia induction, group P received intravenous infusion of propofol 100-300 μg·kg-1 ·min-1 , while the end-tidal sevoflu-rane concentration was maintained at 1. 4％-3. 5％ in group S. Immediately before induction (T0 ), imme-diately after the end of induction (T1 ), immediately after successful embolization of aneurysm (T2 ) and at 1, 2, 3 and 5 days after surgery (T3-6 ), central venous blood samples were collected for determination of plasma neuron-specific enolase and S100β protein concentrations by enzyme-linked immunosorbent assay. The development of postoperative cerebral vasospasm and delayed ischemic neurological deficit was recorded. The patients were followed up, and the Glasgow outcome score and occurrence of newly developed cerebral infarction were recorded within 6 months after surgery. Results There was no significant difference in the concentrations of plasma neuron-specific enolase and S100β protein at each time point, incidence of postop-erative cerebral vasospasm and delayed ischemic neurological deficit, or Glasgow outcome score and inci-dence of newly developed cerebral infarction within 6 months after surgery between two groups (P>0. 05). Conclusion Propofol and sevoflurane exert no effect on the recovery of neurological function after intracra-nial aneurysm embolization.

Objective To evaluate the efficacy and safety of oxycodone in patients undergoing microvascular decompression in treating trigeminal neuralgia and oxycodone versus sufentanil on early recovery after microvascular decompression in treating trigeminal neuralgia.Methods Eighty-six patients (38 males, 48 females, aged 18-65 years, BMI 18-30 kg/m2, ASA physical status Ⅰ or Ⅱ) scheduled for microvascular decompression in treating trigeminal neuralgia, were randomly divided into either oxycodone group (group O) and sufentanil group (group S) using a random number table, n=43 in each group.All patients received combined intravenous-inhalational anesthesia, as well as oxycodone 0.3 mg/kg injected intravenously in group O, sufentanil 0.4 μg/kg injected intravenously in group S for anesthesia induced analgesia.When the epidural was closed, oxycodone 0.07 mg/kg was injected intravenously in group O, sufentanil 0.1 μg/kg was injected intravenously in group S.On preoperative day 1 and 4, 24, 48 hours after surgery, numeric rating scale (NRS) was used to assess the incision pain and facial pain.When NRS scores≥4, oxycodone 3 mg in group O and sufentanil 5 μg in group S was injected intravenously as rescue analgesic.On preoperative day 1 and 3 days after surgery, the global QoR-40 aggregating score was used to assess the quality of patients recovery.The requirement for rescue analgesics was recorded.The occurrences of nausea and vomiting were recorded.Extubation time and discharge were recorded.The other adverse events (bradycardia, dysuria, dizziness and pruritus) were recorded.Results Compared with group S, the physical comfort score, the emotional state score, the psychological support score, the pain score and the global QoR-40 scores were higher in group O 3 days after surgery (P<0.05).Compared with group S, the incidence of nausea and vomiting was significantly lower in group O (20.9% vs 37.2%) (P<0.05).Conclusion In surgery less than 5 hours of microvascular decompression on treating trigeminal neuralgia, oxycodone 0.3 mg/kg can be safely and effectively used for anesthesia induction, oxycodone 0.07 mg/kg and 3 mg can be respectively used for postoperative prophylactic analgesia and remedial analgesia.Compared with sufentanil, oxycodone can improve the quality of recovery during the early period after microvascular decompression on treating trigeminal neuralgia, and decrease the incidence of nausea and vomiting.