Objective To detect the expression of N-acetyltransferase 10(NAT10)and polyadenylate bind-ing protein cytoplasmic 1(PABPC1)in non muscle invasive bladder cancer(NMIBC),and analyze the correla-tion between them and epithelial mesenchymal transition(EMT)and prognosis.Methods A total of 122 pa-tients with NMIBC treated in the hospital from May 2019 to May 2021 were selected.Immunohistochemistry was used to detect the expression of NAT10 and PABPC1 proteins in NMIBC tissues.Real time fluorescence quantitative polymerase chain reaction(qPCR)was used to detect the expression of NAT10,PABPC1 mRNA,and EMT markers in NMIBC tissues.Pearson correlation analysis was conducted on the correlation between EMT indicators[Snail,N-cadherin(N-cad),vimentin(Vim)mRNA].Cox regression analysis was conducted on the relationship between NAT10,PABPC1 and prognosis of NMIBC.Results Compared with adjacent tis-sues,the expression of NAT10 mRNA,PABPC1 mRNA,Snail mRNA,N-cad mRNA,and Vim mRNA in NMIBC cancer tissues was higher,and the difference was statistically significant(P＜0.001).The expression of NAT10 mRNA,PABPC1 mRNA in NMIBC cancer tissues was positively correlated with Snail mRNA,N-cad mRNA,and Vim mRNA(r=0.678,0.702,0.711,0.754,0.788,0.663,P＜0.001).The positive rates of NAT10 and PABPC1 in NMIBC cancer tissues were 59.02％(72/122)and 60.66％(74/122),respectively,while those in adjacent tissues were 6.56％(8/122)and 4.92％(6/122),respectively(x2=76.176,85.995,P＜0.001).The positive rates of NAT10 and PABPC1 in NMIBC cancer tissues were higher than those in ad-jacent tissues,and the difference was statistically significant(x2=76.176,85.995,P＜0.001).The positivity rates of NAT10 and PABPC1 in cancer tissues of stage T1,high-grade NMIBC patients were higher than those in cancer tissues of Ta/Ti,low-grade patients,and the differences were statistically significant(P＜0.05).The 3-year overall progression free survival rates of NMIBC patients in the NAT10 positive and negative groups were 48.61％(35/72)and 80.00％(40/50),respectively,with a statistically significant difference(Log rank x2=13.780,P=0.000).The 3-year overall progression free survival rates of PABPC1 positive and negative patients were 47.30％(35/74)and 83.33％(40/48),respectively,with a statistically significant difference(Log rank x2=11.830,P=0.001).T1 stage,high-grade,NAT10 positive,and PABPC1 positive were risk fac-tors affecting the prognosis of NMIBC.Conclusion The expression of NAT10 and PABPC1 in NMIBC cancer tissue is significantly upregulated and positively correlated with EMT markers,which is correlated with poor prognosis of NMIBC.

Objective To identify the pathogenic mutations in a family with piebaldism.Methods Clinical infor-mation and peripheral blood were collected from the patient with piebaldism and their parents.Whole exome se-quencing was performed to identify the potential pathogenic mutations.QPCR was used to determine the deletion of the target gene,while gap-PCR and Sanger sequencing was used to determine the size and the specific deletion site.Results The proband had a heterozygous deletion mutation of approximately 1.74 Mb located at chromosome 4,in-cluding a full length of the pathogenic gene KIT for mottled disease and it was the smallest micro deletion causing isolated piebaldism due to the loss of the KIT.Conclusions The heterozygous deletion including the KIT is a poten-tial cause of the piebaldism phenotype found in this family.

Necrotizing enterocolitis (NEC) is one of the most frequent and severe gastrointestinal diseases among neonates,especially preterm newborns.Its incidence is inversely associated with birth weight and gestational age.NEC is characterized by widespread or localized necrosis of the small intestine and colon,and intestinal perforation,septic shock and other complications can occur in severe cases.The overall survival rate of NEC has been improved in recent years.However,there is no uniform standards for early diagnosis and surgical intervention.Several biomarkers have been proposed for the early diagnosis of NEC and for the prediction of disease progression and severity.This review summarized the progress on early diagnosis and surgical indications of NEC.

Objective:To compare the efficacy of closed-loop target-controlled deep versus moderate neuromuscular blockade in gynecological laparoscopic surgery.Methods:This was a prospective study. Fifty American Society of Anesthesiologists Physical Status classification I or Ⅱ patients, aged 18-64 yr, with body mass index of 18-30 kg/m 2, scheduled for elective gynecological laparoscopic surgery in the General Hospital of Tianjin Medical University from March 2020 to March 2021, were allocated into 2 groups ( n=25 each) using a random number table method: closed-loop target-controlled moderate neuromuscular blockade group (group TOF) and closed-loop target-controlled deep neuromuscular blockade group (group PTC). Rocuronium was given by closed-loop target-controlled infusion in both groups. In group TOF, the target muscle relaxation was considered as train-of-four stimulation (TOF) of 1 or 2. In group PTC, the target muscle relaxation was considered as post-titanic count of 1 or 2. The score for operator′s satisfaction with muscle relaxation, grading, satisfaction rate, mean pneumo-peritoneum pressure, consumption of rocuronium, recovery index, recovery time to a TOF ratio 0.9 and time to extubation were recorded. The postoperative visual analogue scale score for abdominal pain and use of rescue analgesics were recorded, and the occurrence of complications such as shoulder pain, arm pain, nausea, vomiting and hypoxemia was also recorded within 48 h after surgery. Results:Compared with group TOF, the score for operator′s satisfaction with muscle relaxation, grading and satisfaction rate were significantly increased, the mean pneumo-peritoneum pressure was decreased, the total and average consumption of rocuronium was increased, the recovery time of a TOF ratio 0.9 was prolonged, and the postoperative visual analogue scale score for abdominal pain and usage rate of flurbiprofenate were decreased in group PTC ( P<0.05). There were no significant differences in the recovery index, tracheal extubation time or postoperative incidence of hypoxemia, shoulder pain, arm pain and nausea and vomiting between the two groups ( P>0.05). Conclusions:Compared with the closed-loop target-controlled moderate neuromuscular blockade, the closed-loop target-controlled deep neuromuscular blockade provides more satisfactory surgical conditions for gynecological laparoscopic surgery, decreases pneumoperitoneum pressure and reduces related complications, without increasing the development of postoperative adverse reactions.

Objective To explore the expression and clinical significance of lysine oxidase (Lox) in primary lesion of esophageal carcinoma (ESCA) and bone metastasis lesion based on bioinformatics. Methods The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases were used to screen for differentially expressed genes between ESCA and normal esophageal tissues. Follow-up information of patients with surgery for esophageal cancer in the Fourth Hospital of Hebei Medical University from January 2016 to December 2020 were screened, and the clinical materials of patients diagnosed as bone metastasis during the follow-up period were collected. Western blot was used to verify the expression of Lox in ESCA and normal esophageal tissues; immunohistochemical staining was used to detect the expression of Lox in human ESCA tissue and normal tissue; the impact of Lox expression on survival was explored by Kaplan-Meier curve and Cox regression. Results Through the analysis of ESCA data in GEPIA and TCGA databases, it was found that the expression of Lox in ESCA lesions was significantly higher than that in normal tissues (P<0.05); the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses found that Lox may be involved in the information conduction of various signaling pathways; the Western blot result showed that the expression of Lox in cancer tissue was higher than that in adjacent normal tissue (P<0.05); the analysis of follow-up data found that patients with high expression of Lox were more likely to have multiple bone metastases; survival analysis revealed that patients with high Lox expression had significantly shorter bone metastasis free survival and overall survival compared to patients with low Lox expression (P<0.05); Cox regression found that Lox was an independent risk factor for prognosis of patients with esophageal cancer bone metastasis. Conclusion Lox is highly expressed in ESCA and significantly related to clinical prognosis, which can be used as an effective target for the diagnosis and treatment of ESCA.

Lung squamous cell carcinoma (LSCC) accounts for approximately 30% of non-small cell lung cancer (NSCLC) cases and is the second most common histological type of lung cancer. Anaplastic lymphoma kinase (ALK)-positive NSCLC accounts for only 2%-5% of all NSCLC cases, and is almost exclusively detected in patients with lung adenocarcinoma. Thus, ALK testing is not routinely performed in the LSCC population, and the efficacy of such treatment for ALK-rearranged LSCC remains unknown. Echinoderm microtubule associated protein like 4 (EML4)-ALK (V1) and TP53 co-mutations were identified by next generation sequencing (NGS) in this patient with advanced LSCC. On December 3, 2020, Ensatinib was taken orally and the efficacy was evaluated as partial response (PR). The progression-free survival (PFS) was 19 months. When the disease progressed, the medication was changed to Loratinib. To our knowledge, Enshatinib created the longest PFS of ALK-mutant LSCC patients treated with targeted therapy since literature review. Herein, we described one case treated by Enshatinib involving a patient with both EML4-ALK and TP53 positive LSCC, and the relevant literatures were reviewed for discussing the treatment of this rare disease.
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Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms/pathology* ; Anaplastic Lymphoma Kinase/metabolism* ; Carcinoma, Squamous Cell/genetics* ; Mutation ; Cytoskeletal Proteins/genetics* ; Lung/pathology* ; Oncogene Proteins, Fusion/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Tumor Suppressor Protein p53/genetics*

Objective:To investigate the correlations of β-catenin expression with the efficacy of tyrosine kinase inhibitor (TKI) and prognosis of patients with advanced lung adenocarcinoma harboring epidermal growth factor receptor (EGFR) mutations.Methods:The clinical data of 125 patients with stage Ⅲ B-Ⅳ lung adenocarcinoma who were treated with first-line EGFR-TKI treatment in the 901st Hospital of Joint Logistic Support Force of Chinese PLA from January 2016 to December 2019 were collected. The expression of β-catenin protein was detected by immunohistochemistry, and subtypes of EGFR mutations were detected by amplification refractory mutation system (ARMS). Correlations of β-catenin expression with clinicopathological features, efficacy of EGFR-TKI and prognosis were analyzed. Twenty-eight pairs of specimens were selected before EGFR-TKI treatment and after resistance to EGFR-TKI to observe the changes of β-catenin expression. Results:Among 125 advanced lung adenocarcinoma patients with EGFR mutations, there were 60 cases of EGFR 19 del, 55 cases of L858R mutation and 10 cases of rare sensitive mutation; 79 cases (63.2%) had reduced membranous expression of β-catenin, 66 cases (52.8%) had ectopic expression in cytoplasm and 28 cases (22.4%) had ectopic expression in nucleus. The positive rates of Napsin A protein in the groups with different abnormal expression patterns of β-catenin were lower than those in the corresponding normal expression groups (all P < 0.001). Patients with International Association for the Study of Lung Cancer (IASLC) grade Ⅲ showed more frequent translocation in cytoplasma and nucleus of β-catenin than patients with IASLC gradeⅠ-Ⅱ (ectopic expression in cytoplasm: χ2 = 3.99, P = 0.046,ectopic expression in nucleus: χ2 = 11.07, P = 0.001). The objective remission rate (ORR) in patients with reduced membranous expression of β-catenin and ectopic expression in nucleus was lower than that in patients with normal membranous expression ( χ2 = 4.66, P = 0.031) and negative ectopic expression in nucleus ( χ2 = 10.22, P = 0.001), and the disease control rate (DCR) in patients with ectopic expression in nucleus was lower than that in the corresponding normal expression group ( χ2 = 10.95, P = 0.001). Patients with ectopic expression of β-catenin in nucleus and cytoplasma had worse progression-free survival (PFS) and overall survival (OS) than the corresponding cytoplasmic and nuclear ectopic expression negative groups (both P < 0.05). Multivariate Cox regression analysis showed that nuclear β-catenin ectopic expression was an independent risk factor for both PFS and OS (PFS: HR = 2.088, 95% CI 1.331-3.274, P = 0.001; OS: HR = 3.656, 95% CI 1.795-7.444, P<0.001). β-catenin membranous expression was reduced in 11 of 28 tissue samples that underwent secondary biopsy compared with pre-treatment ( P = 0.049). Conclusions:β-catenin expression in advanced lung adenocarcinoma with EGFR-sensitive mutations can be used as a molecular marker to predict the efficacy of EGFR-TKI and prognosis of patients.

OBJECTIVE: To investigate the effect of lateral prone position ventilation in patients with acute respiratory distress syndrome (ARDS). METHODS: A prospective control study was conducted. A total of 75 patients with moderate to severe ARDS admitted to the department of critical care medicine of Jingxian Hospital in Anhui province from January 2020 to December 2022 were selected as the research objects. According to the envelope method, the patients were divided into the lateral prone position ventilation group (38 cases) and the traditional prone position ventilation (PPV) group (37 cases), using lateral prone position ventilation and traditional PPV, respectively. The mechanical ventilation parameters were set according to the ARDS treatment guidelines and lung protective ventilation requirements in both groups, and the time of prone position for the first 3 times was not less than 16 hours per day. General data of patients were recorded, including heart rate (HR), mean arterial pressure (MAP), airway resistance and lung static compliance (Cst) before prone position (T0), 1 hour (T1), 4 hours (T2), 8 hours (T3), and before the end of prone position (T4), oxygenation index (PaO₂/FiO₂) before the first prone position (t0) and 12 hours (t1), 24 hours (t2), 48 hours (t3), and 72 hours (t4) after the intensive care unit (ICU) admission, as well as the incidence of pressure injury (PI) and vomiting, tracheal intubation time, and mechanical ventilation time. Repeated measures analysis of variance was used to compare the effects of different prone positions on patients before and after the prone position. RESULTS: There were no significant differences in age, gender, body mass index (BMI), acute physiology and chronic health evaluation II (APACHE II), underlying diseases, HR, MAP, pH value, PaO₂/FiO₂, blood lactic acid (Lac), arterial blood pressure of carbon dioxide (PaCO₂) and other general information between the two groups. The HR (intergroup effect: F = 0.845, P = 0.361; time effect: F = 1.373, P = 0.247; interaction: F = 0.245, P = 0.894), MAP (intergroup effect: F = 1.519, P = 0.222; time effect: F = 0.169, P = 0.954; interaction: F = 0.449, P = 0.773) and airway resistance (intergroup effect: F = 0.252, P = 0.617; time effect: F = 0.578, P = 0.679; interaction: F = 1.467, P = 0.212) of T0-T4 between two groups showed no significant difference. The Cst of T0-T4 between the two groups showed no significant difference in the intergroup effect (F = 0.311, P = 0.579) and the interaction (F = 0.364, P = 0.834), while the difference in the time effect was statistically significant (F = 120.546, P < 0.001). The PaO₂/FiO₂ of t0-t4 between the two groups showed no significant difference in the intergroup effect (F = 0.104, P = 0.748) and the interaction (F = 0.147, P = 0.964), while the difference in the time effect was statistically significant (F = 17.638, P < 0.001). The group factors and time factors were tested separately, and there were no significant differences in the HR, MAP, airway resistance, Cst, PaO₂/FiO₂ between the two groups at different time points (all P > 0.05). The Cst at T1-T4 and PaO₂/FiO₂ at t1-t4 in the two groups were significantly higher than those at T0/t0 (all P < 0.05). There were no significant differences in the tracheal intubation time [days: 6.75 (5.78, 8.33) vs. 7.00 (6.30, 8.45)] and mechanical ventilation time [days: 8.30 (6.70, 9.20) vs. 7.40 (6.80, 8.75)] between the lateral prone position ventilation group and the traditional PPV group (both P > 0.05). However, the incidences of PI [7.9% (3/38) vs. 27.0% (10/37)] and vomiting [10.5% (4/38) vs. 29.7% (11/37)] in the lateral prone position ventilation group were significantly lower than those in the traditional PPV group (both P < 0.05). CONCLUSIONS Both lateral prone position ventilation and traditional PPV can improve Cst and oxygenation in patients with moderate to severe ARDS. The two types of prone position have little influence on HR, MAP and airway resistance of patients, and there is no difference in the influence on tracheal intubation time and mechanical ventilation time of patients. However, the lateral prone position ventilation mode can reduce the incidence of PI and vomiting, and is worthy of clinical promotion and application.
Humans ; Respiration, Artificial ; Prone Position ; Prospective Studies ; Lung ; Respiratory Distress Syndrome/therapy* ; Respiration ; Vomiting

Objective Observation of the anti-inflammatory and detumescence effects on experimental rheumatoid arthritis(RA)rabbits by moxibustion,With lentiviral vector mediated NLRP3 overexpression in RA animal models,to investigate the effect of moxibustion on anti-CCP/RF levels in synovial fluid of RA rabbit joints and its regulation mechanism of NLRP3.Methods Randomly divided thirty Japanese big-ear white rabbits into 5 groups:group of blank,group of model,group of moxibustion,NLRP3 overexpression group and NLRP3 overexpression negative group,with 6 rabbits in each group.Both joint of the model group,and the groups with moxibustion was injected into FCA(0.5 mL·kg-1),the blank group used the same method to inject sterile saline.On the 3rd day and the 10th day after treatment,10 μL of NLRP3 overexpression lentiviral vector was injected into the joint cavity of the NLRP3 overexpression group of rabbits.The rabbits in the NLRP3 overexpression negative group were injected with the same amount of LvGFP as Contrast.moxibustion bilateral"BL23","ST 36"of the groups with moxibustion(5 cones with one point in a day.6 days for 1 course,1 day for rest,3 courses of treatment in total.)After treatment,observe the circumference of each rabbit's left and right knee joints,the content of RF,anti-CCP,IL-18 in synovial fluid was detected by ELISA.Results Compared with the blank group,the left and right knee joint circumferences in the model group increased,and the anti-CCP,RF,and IL-18 contents in the synovial fluid of the knee joint increased significantly(P<0.01);compared with the modle group,The circumference of the knee joint decreased,and the content of anti-CCP,RF and IL-18 decreased significantly(P<0.01);compared with the moxibustion group,the circumference of the left and right knee joints in the NLRP3 overexpression group increased(P<0.05),the content of anti-CCP,RF and IL-18 increased(P<0.05).Conclusions Moxibustion has anti-inflammatory effects on experimental RA rabbits.Moxibustion at Shenshu(BL23)and Zusanli(ST36)can significantly reduce the level of anti-CCP,RF the immune effector,also IL-18,the in synovial fluid of RA rabbits knee joint,yet this effect can be declined significantly under NLRP3 overexpression,suggesting that moxibustion performed its anti-inflammatory regulation by suppressing abnormal immune function in experimental RA rabbits,which may be closely related to the NLRP3 expression.

Objective To observe the effects of moxibustion on the expression of Nucleotide binding oligomeric domain like receptor thermoprotein domain associated protein 3(Nod-like receptor protein 3,NLRP3)inflammasome and Cysteine aspartate protease 12(Caspase-12)in synovial tissue of experimental Rheumatoid Arthritis(RA)rabbits,and explore the anti-inflammatory mechanism of moxibustion on RA rabbits.Methods Twenty-four Japanese big-eared white rabbits were randomly divided into 3 groups according to body weight and sex:the control group,the model group and the moxibustion group.The Freund's Complete Adjuvant(FCA)was injected into the joint cavities of two knee joints of rabbits at the dose of 0.5 mL·kg-1 in the model group and the moxibustion group,and the control group was injected with the same amount of normal saline as control.For the moxibustion group,scar free moxibustion was operated at bilateral"BL 23"and"ST 36"acupoints,moxibustion for 3 times per acupoint per day,continuous treatment for 6 days,rest for 1 day,as a course of treatment,a total of 3 courses of treatment.The histological changes of synovium samples of rabbit knee joints were observed under light microscope,real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the expression of NLRP3,Cysteine aspartate protease 1(Caspase-1),Caspase-12 in synovial tissues and Enzyme-linked immuno sorbent assay(ELISA)was used to measure the change of Interleukin-1β(IL-1β)content in the synovial fluid of experimental animals.Results Compared with the control group,the degree of synovial lesions(inflammatory cell infiltration,synovial tissue hyperplasia,fibrous tissue hyperplasia,macrophage hyperplasia,etc.)and pathological score were increased(P<0.05),the expression of NLRP3,Caspase-1 mRNA were increased(P<0.05),the expression of Caspase-12 mRNA was significantly downregulated(P<0.01)and the expression content of IL-1β was significantly up-regulated(P<0.01)in the model group;Compared with the model group,the synovial lesion degree and pathological score were decreased(P<0.05),the expression of NLRP3,Caspase-1 mRNA were decreased(P<0.05),the expression of Caspase-12 mRNA was significantly increased(P<0.01)and the expression of IL-1β was decreased(P<0.05)in the moxibustion group.Conclusion Moxibustion can significantly inhibit the pathological process of knee synovitis in RA rabbits;Moxibustion at"Shenshu(BL 23)"and"Zusanli(ST 36)"acupoints can significantly up-regulate the expression of Caspase-12 and then inhibit the NLRP3 inflammasome,which may be one of mechanisms of moxibustion to reduce RA inflammatory response.