[Efficacy of stent placement in treatment of malignant tracheoesophageal fistula and relevant factors of fistula closure].

Objective: To investigate the efficacy of stent placement in the treatment of malignant tracheoesophageal fistula (MTEF) and the factors affecting the closure of the fistula. Methods: Clinical, pathological, laboratory, and imaging data of 288 patients with MTEF admitted to Zhongda Hospital, Southeast University from 2015 to 2021were retrospectively analyzed. Among them, there were 208 males; the age was (63.6±10.5) years. A total of 94 patients received conservative treatment (conservative group), and 194 in the stent group (170 cases with esophageal stents and 24 cases with tracheal stents). Patients were followed-up at 2 weeks, 1 month, 3 months, and 6 months to evaluate the effect of stent implantation. Multivariable logistic regression was used to analyze factors affecting fistula closure. Results: Age, fistula size, leukocyte count before treatment, and fistula location were significantly different between the conservative group and the stent group (P<0.05). The Karnofsky functional status (KPS) score before treatment in the conservative group was lower than the stent group, (45.1±1.0) vs (51.8±0.7) scores, respectively (P<0.001). After 2 weeks and 1 month of treatment, improvement in KPS scores was significantly better in the stent group than in the conservative group (P<0.05). At 1 month, the pulmonary infection rate in the stent group was 33.5% (58/173), significantly lower than that in the conservative group [77.0% (47/61); P<0.001]. Among the 288 patients, the fistula was closed in 196 patients and unclosed in 92 patients. Fistula size (OR=3.429, 95%CI: 1.623-7.829, P=0.001), leukocyte count before treatment (OR=1.160, 95%CI: 1.027-1.317, P=0.018), KPS score before treatment (OR=0.898, 95%CI: 0.848-0.945, P<0.001) and the treatment method (conservative treatment as reference, esophageal stent OR=0.010, 95%CI: 0.004-0.030, P<0.001; tracheal stent OR=0.003, 95%CI: 0.000-0.042, P<0.001) were factors affecting fistula closure. In the 170 patients in the esophageal stent group, early complications (≤24 h) occurred in 71 patients, and late (>24 h) complications occurred in 11 patients. While in the 24 patients in the tracheal stent group, 9 had early complications and 2 had late complications. Conclusions: Stent placement is an effective treatment for MTEF compared to conservative treatment. Stent treatment, small fistula size, low pre-treatment leukocyte count, and high pre-treatment KPS score are beneficial to fistula closure.

Development and validation of a nomogram to predict poor short-term response to recombinant human growth hormone treatment in children with growth disorders.

PURPOSE: The purpose of this study was to develop and validate a clinical predictive model for predicting the likelihood of a poor therapeutic response during the first year of recombinant human growth hormone (rhGH) treatment in children with growth disorders. METHODS: A total of 627 pediatric patients with growth disorders (GHD, ISS, TS, SGA) from The LG Growth Study cohort were evaluated. Restricted cubic splines (RCS) were utilized to investigate the association between predictors and the risk of poor rhGH response. Variables were selected using LASSO regression, and multivariate logistics regression models were established. Receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and clinical impact curves (CIC) were used to assess the predictive model's accuracy and clinical value. The predictive accuracy of the model was validated on the testing set. RESULTS: Two predictive models containing 8 baseline predictors (diagnosis, age, height SDS, bone age minus chronological age, rhGH dosage, distance from mid-parental height in SDS, weight SDS, IGF-1 SDS) and 1 post-treatment predictor (height SDS gain at 6 months) were constructed by multivariate logistic regression analyses. The nomogram was built based on the multivariate predictive model and showed good discrimination and model fit effects in both the training set and the testing set. DCA and CIC analyses presented good clinical usability. CONCLUSION: The clinical predictive model for predicting the probability of poor short-term response of rhGH treatment in pediatric patients with growth disorders is useful and can assist physicians in making clinical decisions.

The multidrug resistant modulator HZ08 reverses multidrug resistance via P-glycoprotein inhibition and apoptosis sensitization in human epidermoid carcinoma cell line KBV200.

Previous studies have demonstrated that the multidrug resistance modulator HZ08 has a strong multidrug resistance reversal effect in vitro and in vivo by inhibiting P-glycoprotein and multidrug resistance-associated protein 1 in K562/A02 and MCF-7/ADM cells, respectively. However, there are many other mechanisms responsible for resistance. In this study, MTT assay was used to examine the cytotoxicity and multidrug resistance reversal of HZ08 in KBV200 cells. It was also used to detect Rh123 and adriamycin accumulation in the presence of HZ08 to assess the effect on P-glycoprotein. Caspase-3 activity was analyzed under the incubation of HZ08 per se and in combination with vincristine. Results showed that HZ08 could increase the activity of caspase-3 with P-glycoprotein inhibition. Further studies revealed that HZ08 increased vincristine-induced apoptosis, characterized as an intrinsic apoptosis pathway with enhanced G2/M phase arrest, since HZ08 had an effect on the intrinsic apoptotic regulator Bcl-2 and Bax. Therefore, the outstanding reversal effect of HZ08 occurs not only through suppressing the P-glycoprotein function but also through activating the intrinsic apoptosis pathway.

Are progenitor cells pre-programmed for sequential cell cycles not requiring cyclins D and E and activation of Cdk2?

OBJECTIVES: Based on studies of unicellular organisms or cultured mammalian cells, the generally accepted model of cell-cycle regulation has been developed in which sequential (scheduled) expression of cyclins D, E, A and B and activation of Cdk2 and Cdk1 takes place. It is assumed that the same model is applicable both in vivo and in vitro. MATERIALS AND METHODS: In the present study, we compared proliferating marrow cells freshly isolated from healthy individuals with proliferating lymphocytes in cultures. RESULTS: We demonstrate that during progression of freshly collected human bone marrow cells through G(1), S and G(2)/M, only Cdk1 combined with cyclins A and B(1) was distinctly present and active, and its activity gradually increased. In contrast, in vitro growing mitogen-stimulated lymphocytes had perfectly scheduled sequential expression of all four cyclins and Cdk1 and Cdk2 activities. CONCLUSION: Our findings demonstrate that the pattern of cyclin expression and Cdk activity in bone marrow in vivo is distinctly different from the one observed for normal cells in vitro. Because proliferating bone marrow cells are predominantly expanding populations of committed progenitors, it is likely that during the expansion phase their cell-cycle progression is pre-programmed, being driven solely by Cdk1 combined either with cyclin A or with cyclin B(1). Expansion of progenitor cells thus may not require the early steps of cell-cycle regulation, associated with triggering progression by availability of growth factors and mitogens.

Antibacterial and antifungal activity of Erigeron breviscapus.

The antibacterial and antifungal properties of the ethanol extract of Erigeron breviscapus whole plant was evaluated. The extract showed a moderate antibacterial activity and a high antifungal activity.

Determination of manganese in feedstuffs by flow injection spectrophotometry based on rapid formation of permanganate at room temperature.

A simple and rapid flow injection spectrophotometric procedure was developed for determination of manganese. In the presence of pyrophosphate and acetate, manganese was immediately oxidized to permanganate by periodate at room temperature in slightly alkaline medium. Under optimized conditions, the determination was made with a sampling rate of 120/h, a linear range of 0-30 mg/L Mn(II), a detection limit (S/N = 3) of 0.08 mg/L, and a relative standard deviation of 0.6% (n = 11) at 10 mg/L Mn(II). The proposed method was used to determine manganese in trace mineral premixes and feedstuffs. Results agreed well with those obtained by the standard atomic absorption spectroscopy method.

Identical flow injection spectrophotometric manifold for determination of protein, phosphorus, calcium, chloride, copper, manganese, iron, and zinc in feeds or premixes.

A simple procedure using an identical manifold was developed for determination of nitrogen (protein) phosphorus, calcium, chloride, copper, manganese, iron, and zinc in feeds and feedstuffs. By changing appropriate reagents and detection wavelength, these 8 elements were determined successively with a simple identical double-line flow injection (FI) manifold. Fl spectrophotometric determinations were made by the blue indophenol reaction for ammonium, the molybdenum blue method for phosphate, the cresolphthalein complexone procedure for calcium, and the mercuric thiocyanate procedure for chloride. The chromogenic reagents for copper, iron, manganese, and zinc determination were bis(cyclohexanone)oxalydihydrazone (Cuprizone), 1,10-phenanthroline, formaldoxime, and xylenol orange, respectively. Sample digestion catalyst, Fl manifold, and some chemical parameters were optimized. The proposed procedure had a sampling rate of 90/h for each analyte. The determination ranges (mg/L) were 10-60 for N, 1-15 for P and Ca, 540 for Cl, and 0.5-15 for Cu, Fe, Mn, and Zn, respectively. Results of the analyses of animal feed and feedstuff samples by this procedure did not differ significantly from those obtained by proven manual methods.

Cloning and characterization of a novel Krüppel-like zinc finger gene, ZNF268, expressed in early human embryo.

With the aim of identifying genes involved in early human embryonic development, we have isolated a cDNA clone representing a novel human zinc finger gene ZNF268 from 3 week old human embryo cDNA library using a differential hybridization strategy. The complete cDNA sequence of ZNF268 contained an open reading frame of 2841 nucleotides that encodes a 947 amino acid protein with an N-terminal Krüppel-associated box (KRAB) domain and 24 C-terminal zinc fingers. Northern blot analysis showed that ZNF268 mRNA is mainly expressed in 3-5 week old human embryos suggesting it could play certain roles in the embryogenesis. The gene consists of six exons spanning about 22 kb of genomic DNA. According to the genomic sequence from the HTGS database, the ZNF268 gene is assigned to human chromosome 5.

Flow injection spectrophotometric determination of copper, iron, manganese, and zinc in animal feeds using a common manifold.

A rapid and simple procedure was developed for the determination of copper, iron, manganese, and zinc in animal feeds using an identical flow injection spectrophotometric manifold but different chromogenic reagents and different detection wavelengths. Bis(cyclohexanone)oxalydihydrazone, formaldoxime, 1,10-phenanthroline, and xylenol orange were adopted as chromogenic reagents for Cu, Mn, Fe, and Zn, respectively. Detection conditions such as manifold parameters, buffer pH, reagent concentration, temperature, and acidity of sample solution were optimized. Analytical characteristics of the method and interference of metal ions commonly present in feeds were studied. By changing the reagents and detection wavelengths, which can be done quickly, the proposed low cost flow injection system can determine Cu, Fe, Mn, or Zn in the range of 0.5-10 mg/L with a sampling throughput of 120/h.

[Cloning and identification of a new telomeric-associated zinc finger protein cDNA].

In order to isolate novel genes related to early human embryo development and differentiation, a directional cDNA library was constructed from 3-week-old human embryo. Single-pass DNA sequence analysis was used to sequence 47 randomly picked low-abundance cDNA clones. This approach led us to select a clone, L30, showing significant homology with the telomeric-associated DNA and zinc finger protein genes. It is about 3.8 kb in length and contains an open reading frame of notable length within 5'-region, and a tailing signal of AAUAAA and poly (A+) with 39 A in 3'-region. The gene was transcribed in human embryo by Northern blot hybridization and assigned to human chromosome 12 by in situ hybridization.