[Analysis on the efficacy of dual vein induction therapy of Ustekinumab in complex perianal fistulizing Crohn's disease].

Objectives: To analyze the efficacy of dual vein induction therapy of Ustekinumab (UST) in complex perianal fistulizing Crohn's disease (PFCD). Methods: Clinical data of patients diagnosed with complex PFCD in the Second Affiliated Hospital of Wenzhou Medical University from January 2022 to March 2023 were retrospectively analyzed. After sufficient single intravenous infusion of UST (6 mg/kg) at week 0 and 8, every patient received single subcutaneous injection of UST 90 mg every 8 weeks for maintenance treatment. At week 8, 16, and 22-26, clinical outcomes of anal fistula were evaluated using perianal disease activity index (PDAI), and overall activity of the patients was evaluated using Harvey Bradshaw index (HBI). At week 22-26, Van Assche Index (VAI) was used to evaluate imaging outcome of anal fistula, and simplified endoscopic score of Crohn's disease (SES-CD) was employed to assess intestinal outcome events. The above indexes were compared in the patients before and after UST treatment. PFCD patients were divided into first-line UST treatment group and non first-line UST treatment group according to whether first-line UST treatment was used, the differences in anal fistula response rate and remission rate, intestinal response rate and remission rate as well as overall activity response rate and remission rate were compared between the two groups. Results: A total of 60 PFCD patients were included, including 46 males and 14 females, aged [M (Q1, Q3)] 25.0 (20.8, 30.0) years old. The clinical response rates of anal fistula [41.7% (25/60), 55.0% (33/60) and 63.3% (38/60), respectively, P=0.056] and the clinical remission rates of anal fistula [21.7% (13/60), 31.7% (19/60) and 43.3% (26/60), respectively, P=0.002] gradually increased at week 8, 16, 22-26. The overall activity response rates [53.3% (32/60), 70.0% (42/60), 83.3% (50/60), respectively, P=0.040] and the overall activity response rates [41.7% (25/60), 61.7% (37/60), 75.0% (45/60), respectively, P=0.001] also gradually increased at week 8, 16, 22-26. At week 22-26, the partial response rate and fistula healing rate of anal fistula imaging were 45.0% (27/60) and 38.3% (23/60), respectively. The endoscopic response rate and endoscopic response rate were 73.7% (44/60) and 45.0% (27/60), respectively. The endoscopic response rate of patients receiving first-line UST treatment [23 males and 8 females, aged 22.0 (21.0, 39.0) years] was higher than that of patients receiving non first-line UST treatment[23 males and 6 females, aged 26.5 (20.0, 30.0) years,87.1% vs 58.6%, P=0.013]. Conclusion: The dual vein induction therapy of UST could effectively improve the clinical efficacy in patients with complex PFCD.

[Clinical management and prognosis for descending necrotizing mediastinitis].

Objective: To investigate the clinical characteristics, treatment experiences and prognostic factors for descending necrotizing mediastinitis (DNM). Methods: A retrospective analysis was performed on the data of 22 patients with DNM diagnosed and treated in Henan Provincial People's Hospital from January 2016 to August 2022, including 16 males and 6 females, aged 29-79 years. After admission, all patients underwent CT scanning of the maxillofacial, cervical, and thoracic regions to confirm their diagnoses. Emergency incision and drainage were performed. The neck incision was treated with continuous vacuum sealing drainage. According to the prognoses, the patients were divided into cure group and death group, and the prognostic factors were analyzed. SPSS 25.0 software was used to analyze the clinical data. Rusults: The main complaints were dysphagia (45.5%, 10/22) and dyspnea (50.0%, 11/22). Odontogenic infection accounted for 45.5% (10/22) and oropharyngeal infection accounted for 54.5% (12/22). There were 16 cases in the cured group and 6 cases in the death group, with a total mortality rate of 27.3%. The mortality rates of DNM typeⅠand typeⅡwere respectively 16.7% and 40%. Compared with the cured group, the death group had higher incidences for diabetes, coronary heart disease and septic shock (all P<0.05). There were statistically significant differences between the cure group and the death group in procalcitonin level (50.43 (137.64) ng/ml vs 2.92 (6.33) ng/ml, M(IQR), Z=3.023, P<0.05) and acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score (16.10±2.40 vs 6.75±3.19, t=6.524, P<0.05). Conclution: DNM is rare, with high mortality, high incidence of septic shock, and the increased procalcitonin level and APACHE Ⅱ score combined diabetes and coronary heart disease are the poor prognostic factors for DNM. Early incision and drainage combined with continuous vacuum sealing drainage technique is a better way to treat DNM.

[Proportion and role of CD45+ erythroid progenitor cells in patients with tongue cancer metastasis].

Objective: To investigate the proportion and role of CD45+ erythroid progenitor cells (EPC) in patients with tongue cancer metastasis. Methods: The initial treatment of tongue cancer patients (n=40) from January 2017 to June 2018 in He'nan Provincial People's Hospital was included in this study. According to the presence or absence of lymph node metastasis, they were divided into tumor group (no lymph node metastasis was found in imaging and pathology) and metastasis group (both imaging and pathology confirmed lymph node metastasis). The expression of Ki-67 was detected by immunohistochemistry and the proportion of CD45+CD71+TER119+EPC was detected by flow cytometry. EPC was sorted by flow cytometry, interleukin-10 (IL-10) and transforming growth factor-ß (TGF-ß) were detected by enzyme-linked immunosorbent assay (ELISA), and reactive oxygen species (ROS) was detected by flow cytometry. Transwell was used for tumor invasion test; methyl thiazolyltetrazolium (MTT) assay was used to detect proliferation level. Results: There were 20 cases in the tumor group and metastasis group. There was no significant difference between the two groups in terms of age, sex, time of onset and size of tumors. Flow cytometry showed that the ratio of CD45+EPC in peripheral blood of tumor group and metastasis group was (1.2±0.2)% and (3.1±0.2)% (t=7.823, P<0.001). Correlation analysis showed that the ratio of CD45+EPC was positively correlated with the proliferation index of Ki-67 cells (r=0.592, P=0.006). The results of flow cytometry showed that the mean fluorescence intensity (MFI) of ROS in EPC was 102.1±22.9 in tumor group and 530.0±67.2 in metastasis group (t=6.025,P<0.001). The results of ELISA showed that the mass concentrations of IL-10 and TGF-ß in EPC supernatant of tumor group were (10.8±1.6) and (3.2±0.8) µg/L, respectively. The mass concentrations of IL-10 and TGF-beta in EPC supernatant of metastasis group were (26.9±3.7) and (6.4±0.9) µg/L, respectively (t=3.956, P=0.003; t=2.595, P=0.027). Transwell results showed that the proportion of invasive cells in the CD45+EPC group [(40.3±4.4)%] was higher than that in the control group [(17.5±2.2)%] (t=4.607, P=0.001). MTT proliferation experiment showed that the proliferation rate of the CD45+EPC group [(52.0±3.3)%] was higher than that of the control group [(30.5±1.9)%] (t=5.656, P<0.001). Conclusions: The proportion of CD45+EPC in patients with tongue cancer metastasis is significantly increased. CD45+EPC can promote the proliferation and metastasis of tongue cancer by secreting immunosuppressive molecules and ROS.

[Impact of TRAIL deficiency on Th17 cells in the mice experimental colitis induced by dextran sodium sulphate].

Objective: To investigate the impact of TNF-related apoptosis-inducing ligand (TRAIL) gene knock-out (TRAIL(-/-)) on Th17 cells in the mice colitis induced by dextran sulphate sodium (DSS). Methods: Mice were randomly assigned to 4 subgroups: wild type (WT), TRAIL(-/-), WT colitis and TRAIL(-/-)colitis (n=6/group). Colitis was induced by oral administration of 3.5% DSS for 7 consecutive days. The severity of colitis in each mouse was scored both clinically and histopathologically. Flow cytometry was performed to assess Th17 cell population in peripheral blood mononuclear cells (PBMC) and mesenteric lymph nodes (MLN). The expression levels of Th17 cell markers interleukin (IL)-17A and retinoic acid-related orphan receptor (ROR)-γt in PBMC and MLN were also examined using a quantitative polymerase chain reaction method. Results: Compared with WT group, WT colitis group displayed elevated CD4(+)IL-17A(+) Th17 cells (0.29±0.07 vs 0.08±0.03, 1.20±0.36 vs 0.40±0.11, both P<0.05) and enhanced mRNA expression of IL-17A and ROR-γt in PBMC and MLN (IL-17A: 2.43±0.87 vs 0.37±0.19, 5.03±1.77 vs 1.05±0.48, both P<0.05; ROR-γt: 2.49±0.48 vs 0.93±0.47, 23.75±7.60 vs 1.31±0.90, both P<0.05). After the DSS administration, TRAIL(-/-) group developed more severe colitis than WT group, mainly manifesting higher disease activity index, reduction of colon length and increased infiltration of inflammatory cells. In addition, TRAIL(-/-) colitis group exhibited increased proportion of CD4(+) IL-17A(+) Th17 cells (0.57±0.22 vs 0.29±0.07, P<0.001; 2.92±0.98 vs 1.20±0.36, P<0.000 1) as well as enhanced mRNA expression of IL-17A and ROR-γt in PBMC and MLN when compared with WT colitis group (IL-17A: 4.10±1.96 vs 2.43±0.87, 15.88±2.86 vs 5.03±1.77, both P<0.05; ROR-γt: 4.05±0.62 vs 2.49±0.48, 69.61±10.48 vs 23.75±7.60, both P<0.05). Conclusions: TRAIL deficiency not only promots the number and activity of Th17 cells in PBMC and in MLN, but also aggravats DSS-induced colitis in mice.

An 8-week brain MRI follow-up analysis of rat eosinophilic meningitis caused by Angiostrongylus cantonensis infection.

Early differential diagnosis and timely follow-up are advantageous in the management of Angiostrongylus cantonensis infection. This study aimed to characterize angiostrongyliasis in the rat brain for an 8-week period using magnetic resonance imaging (MRI) with contrast-enhanced T1-weighted images (T1WI), T2-weighted imaging (T2WI), fluid attenuation inversion recovery (FLAIR) and R2 mapping sequences. The data were analysed with Mathematica and Matlab software programs for weekly changes in each brain following the infection of 20, 50, 100 and 300 third-stage larvae (L3), respectively. The results showed that the average subarachnoid space detected by T2WI technique was peaked up to 10% increase of original size on day 35 after 100 or 300 larvae infection, while those infected with 20 or 50 larvae showed less than 4% increase during the entire course of observation. This increase was relevant to the mortality of the infected rats, because those with 100 or 300 larvae infections showed a sharp decrease in survival rate before day 40. After day 40, the average subarachnoid space was decreased, but the average ventricle size was persistently increased, with the highest increase observed in the group infected with 300 larvae on day 56. Furthermore, the R2 mapping mean and R2 mapping size were significantly different between the brains with severe infection (100 and 300 larvae groups together) and those with mild infection (20 and 50 larvae groups together) on day 49, but not on day 35. Our results showed that diagnosis for different quantity of larvae infection using MRI is possible and follow-up characterization is informative in revealing the effects of angiostrongyliasis on different brain areas. In conclusion, our results support the use of MRI as a non-invasive diagnostic technique for eosinophilic meningitis caused by A. cantonensis infection.

AC conductivity of selectively located carbon nanotubes in poly(epsilon-caprolactone)/polylactide blend nanocomposites.

DC and AC electrical conductivity of bionanocomposites based on the immiscible polymer blend poly(epsilon-caprolactone)/polylactide (PCL/PLA, w/w 70/30), loaded with multiwall carbon nanotubes (CNT), were studied in a wide frequency range, 10(-3) < or = f < or = 10(7) Hz from 143 to 313 K. The nanofiller concentration ranged from 0 to 4 wt % and it was shown to be selectively located in the PCL phase. The PCL crystallinity degree was not affected by the presence of CNT. The variation of the DC conductivity allowed the determination of the percolation threshold, p(c) = 0.98 wt %, and the critical exponent t = 2.2 of the scaling law. The linear dependence of log (sigma(DC)) versus p(-1/3) showed the existence of tunneling conduction among CNT not yet in physical contact. The temperature independent results indicated a conventional tunnel effect. The AC conductivity of the nanocomposites followed the predictions of the universal dynamic response and the s exponents were determined at low concentrations. Master curves are presented showing the length and temperature-time superpositions.

Stored of Hsp72/Hsp73 in germinal vesicle-stage mouse oocytes.

Heat-shock proteins (hsps) Hsp72 and Hsp73 are the stored maternal proteins found in mouse oocytes. Both hsps appear in mouse oocytes at germinal vesicle (GV) and metaphase II (M-II)-stages as previously demonstrated by immunoblotting analysis. In this report, we further determined the presences of Hsp72/Hsp73 proteins in mouse embryos at stages of 2-pronucleus, arrested 1-cell, 2-cell, arrested 2-cell, 4-cell, arrested 4-cell, 8-cell to morula and blastocyst. Except for the blastocyst stage, the Hsp72/Hsp73 proteins were detectable in most embryo stages. The concentration of Hsp72/Hsp73 in GV-stage oocytes was higher than that in M-II-stage oocytes, and in any stages of embryos before implantation. A dramatical increase in Hsp72/Hsp73 expression was found at the 2-cell stage. Together with these findings, we speculated that hsps accumulated or stored earlier in the GV-stage mouse oocytes to protect the oocytes against environmental influences acting on ovary, and hsps may be required for zygotic gene activation and provided a protective effect against apoptosis.

Mouse models for human familial adenomatous polyposis.

Colorectal cancer (CRC) is the second most frequent type of cancer in the Western hemisphere. In the United States alone, it is estimated that 150 000 new cases are detected every year and more than 65 000 patients die from complications associated with this cancer. Identification of genes implicated in the initiation and progression of colorectal cancer in humans has prompted the generation of mouse models for this cancer. We will provide a brief overview of these mouse models for CRC and what they have contributed to our understanding of the events involved in the initiation and progression of this cancer.

Enterococcus faecalis endocarditis presenting as meningitis.

Although Enterococcus faecalis is a relatively common cause of infective endocarditis, it rarely causes meningitis. A case of Enterococcus faecalis endocarditis presenting as meningitis in a 74-year-old diabetic man on chronic hemodialysis is reported. A review of the literature showed that the association of enterococcal meningitis and endocarditis has rarely been reported. This clinical association may be more common than previously recognized and it is suggested that echocardiography be considered for all patients with enterococcal hematogenous meningitis in order to rule out endocarditis.

Fission yeast Slp1: an effector of the Mad2-dependent spindle checkpoint.

Mad2 is a component of the spindle checkpoint, which delays the onset of anaphase until all chromosomes are attached to the spindle. Mad2 formed a complex with Slp1, a WD (tryptophan-aspartic acid)-repeat protein essential for the onset of anaphase. When the physical interaction between the two proteins was disrupted, the spindle checkpoint was no longer functional. Post-anaphase events such as chromosome decondensation and the next round of DNA replication were not delayed even when the spindle assembly was incomplete. This relief of dependence appears to be a result of deregulation of ubiquitin-dependent proteolysis mediated by the anaphase-promoting complex.

[Pulmonary resection by dealing with pulmonary vessels inside pericardium: report of 104 cases].

During 1985-1993, the writer had performed 104 pulmonary resections, which was 10% of the same time pulmonary resections, to treat type III center lung carcinoma by dealing with pulmonary vessels inside pericardium. The results demonstrated: one-year survival rate was 35%, while three year survival rate was 10%. The writer also found that this kind of operative mode can raise the pulmonary resection rate by 8.75%, and reduce the exploratory thoracotomy rate by 33% compared with the traditionary pulmonary resection.

Use of a GC/MS/MS technique in determination of biomarkers in regional petroleum.

The optimum conditions of a GC/MS/MS operation based on the covariant scan of electrostatic-magnetic fields on the trisector double focusing mass spectrometer JMS-HX100 have been searched for and procured. The distribution of C(29) sterane biomarkers in Arabian Medium crude oil is obtained by utilizing the best acquired parameter settings.

[Research of the electrophysiological properties of isolated ventricular papillary muscle of rhesus].

The electrophysiological properties of cardiac muscle of rhesus (Macaca mulatta) by use of intracellular electrode technique has been described in this paper. Thirty papillary muscle from 8 rhesus were used for this research and 68 successful records had been obtained. The value of resting potential is -86.26 +/- 7.57 mV (M +/- SD). The configuration of the action potential is typical for the ventricular muscle of mammalian. The amplitude of action potential is 118.80 +/- 10.69 mV: over-shoot is 25.57 +/- 6.11mV. The APD20, APD50, APD80, APD100 is 184.33 +/- 64.04, 301.02 +/- 95.32, 382.17 +/- 125.81 and 436.33 +/- 122.39 ms, respectively. The maximum depolarization velocity of 0 phase is 101.20 +/- 17.59 V/s. The effective refractory period is 292.69 +/- 93.91ms. Comparing the results of the rhesus cardiac muscle with that of other mammalians, authors found that they were very similar. It is suggested that the results and analysis of its mechanism derived from investigation of other mammalian cardiac tissues are applicable to the human.

Identification of ventricular tachycardia using intracavitary ventricular electrograms: analysis of time and frequency domain patterns.

Tachycardia detection by implantable antitachycardia devices using rate alone has major limitations. Several alternative methods have been proposed to distinguish ventricular tachycardia or ventricular fibrillation from normal sinus rhythm using intracardiac electrograms. These methods have not been tested, however, for recognition of ventricular tachycardia in patients with abnormal surface QRS conduction during sinus rhythm or with antiarrhythmic drug therapy. In this study, three techniques for the identification of ventricular tachycardia from intracavitary bipolar ventricular electrograms were examined and compared: correlation waveform analysis, amplitude distribution analysis, and spectral analysis using Fast Fourier transformation. Thirty episodes of induced monomorphic ventricular tachycardia were analyzed and compared sinus rhythm in four groups of patients with: I. Normal surface QRS conduction during sinus rhythm without antiarrhythmic drug therapy (five episodes); II. Intraventricular conduction delay or bundle branch block during sinus rhythm without antiarrhythmic drug therapy (nine episodes); III. Normal surface QRS conduction during sinus rhythm with antiarrhythmic therapy (six episodes); and IV. Intraventricular conduction delay or bundle branch block during sinus rhythm with antiarrhythmic drug therapy (ten episodes). Correlation waveform analysis had 100% sensitivity and specificity in distinguishing ventricular tachycardia from sinus rhythm, even in the presence of an intraventricular conduction delay, bundle branch block, and antiarrhythmic drug therapy. In contrast, amplitude distribution analysis differentiated 15/30 episodes (50.0%) of ventricular tachycardia from sinus rhythm, and a maximum of 18/30 episodes (60.0%) of ventricular tachycardia were identified by special analysis using Fast Fourier transformation. Correlation waveform analysis appears to be a reliable technique to discriminate ventricular tachycardia from sinus rhythm using intracavitary ventricular electrograms. Its computational demands are modest, making it suitable for consideration in an implantable antitachycardia device.

Mutagenicity of the anticancer drug, caracemide, and related compounds for salmonella.

Caracemide, MeCON(CONHMe)(OCONHMe) (I), is a novel anticancer drug. Since it was derived from acetohydroxamic acid (II), a known mutagen, its potential metabolites and related compounds were synthesized and tested for mutagenicities in S. typhimurium TA98 and TA100. These compounds were: MeNHCONH(OCONHMe) (III), MeCONH(OCONHMe) (IV), MeCONOH(CONHMe) (V), MeNHCOONH2 X HCl (VI), MeNHCONHOH (VII), MeNHCOON(CONHMe)2 (VIII), and NOH(CONHMe)2 (IX). The mutagenicities in the absence of rat liver homogenate were: (VI) much greater than (IV) greater than (II), (III), (V). The other compounds were not mutagenic. (I) was mutagenic only in the presence of rat liver homogenate. The doses required to demonstrate mutagenicities of these compounds were from 0.05 to 5 mumoles/plate. The major hydrolytic products at 25 degrees C, pH 7, were (III), (IV), and (V) from (I); (II) and (III) from (IV); and (II), (III), (VII) and MeNHCONH(OCOMe) (X) from (V). (III) was stable at pH 7. Treatment of (IV) with HCl yielded (VI). Hydrolysis of (III) or (V) with ammonia yielded (VII). These results suggest that caracemide may be activated enzymatically or nonenzymatically by deacetylation or decarbamoylation, and its anticancer activity may be related to the reactivity of its metabolites with DNA. The synthetic procedures and characterizations of new compounds (IV), (V) and (X) are described.