Reduced-toxicity conditioning regimen with low dose post-transplantation cyclophosphamide and low-dose anti-thymocyte globulin as graft-versus-host disease prophylaxis for haploidentical stem cell transplantation in older patients.

Reduced-toxicity conditioning (RIC) regimens are used for allogeneic hematopoietic stem cell transplantation in older patients. However, successful outcomes are hindered by graft-versus-host disease (GVHD), treatment-related mortality, and relapse, particularly after haploidentical donor hematopoietic stem cell transplantation (HID-HSCT). The aim of this study was to evaluate the effectiveness of an RIC conditioning regimen that included a combination of cyclosporin A, methotrexate (on day + 1), mycophenolate, lower doses of post-transplantation PTCy (40 mg/kg on day + 3), and ATG (7.5 mg/kg) as GVHD prophylaxis prior to haplo-stem cell transplantation (haplo-SCT) in older patients. METHODS: We retrospectively analyzed outcomes in 55 patients ≥ 55 years of age with hematologic malignancies treated with fludarabine, cytarabine, busulfan, and low-dose cyclophosphamide as the conditioning regimen between January 1, 2019, and November 30, 2023. RESULTS: Neutrophil engraftment was successful in all patients within 28 days, with 54 patients (98.2%) achieving complete donor chimerism. The cumulative incidence of non-relapse mortality was 0% at 30 days, 7.5% at 100 days, and 19% at 1 year. The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was 25% (95%CI, 15-38%), whereas that of grade III-IV aGVHD was 9.1% (95% CI, 3.3-19%). The cumulative incidence of extensive chronic graft-versus-host disease at 1 year was 3.6% (95%CI, 0.66-11%). The cumulative incidences of relapse, overall survival, and GVHD-free/relapse-free survival at 1 year were 9.0%, 71.6%, and 67.1%, respectively. CONCLUSIONS: An RIC conditioning regimen, including a combination of lower PTCy/ATG as GVHD prophylaxis, followed by haplo-SCT, might be a promising option for appropriately selected older patients.

Higher efficacy of Etoposide + Cytarabine Plus Pegfilgrastim in poorly mobilizing Multiple Myeloma and lymphoma Patients.

BACKGROUND AIMS: An optimal strategy for mobilizing hematopoietic stem cells in poorly mobilizing patients with multiple myeloma (MM) and lymphoma has not yet been determined. METHODS: We retrospectively analyzed the efficacy and safety of etoposide combined with cytarabine (etoposide 75 mg/m2, daily d1∼2; Ara-C 300 mg/m2, every 12 h d1∼2), plus pegfilgrastim (6 mg d6) in 32 patients with MM or lymphoma, among whom 53.1% were defined as "proven poor mobilizers." RESULTS: This approach resulted in adequate mobilization (≥2.0 × 106 CD34+ cells/kg) in 93.8% of patients and optimal mobilization (≥5.0 × 106 CD34+ cells/kg) in 71.9% of patients. A total of 100% of patients with MM reached at least 5 × 106 CD34+ cells/kg collected, the amount required for double autologous stem cell transplant. In total, 88.2% of patients with lymphoma reached at least 2 × 106 CD34+ cells/kg collected, the amount required for a single autologous stem cell transplant. This was achieved with a single leukapheresis in 78.1% of cases. A median peak number of 42.0/µL circulating CD34+ cells and a median number of blood CD34+ cells counts in 6.7 × 106/L were collected among 30 successful mobilizers. Approximately 6.3% of patients required plerixafor rescue, which was successful. Nine (28.1%) of the 32 patients suffered grade 2∼3 infections, and 50% required platelet transfusions. CONCLUSIONS: We conclude that chemo-mobilization with etoposide, Ara-C and pegfilgrastim in poorly mobilizing patients with MM or lymphoma is very effective and has acceptable toxicity.

Loss of IRF8 inhibits the growth of acute myeloid leukemia cells.

The transcription factor interferon regulatory factor 8 (IRF8), as a member of the IRF family, is essential for myeloid cell differentiation. However, the precise role of IRF8 in the pathogenesis of acute myeloid leukemia (AML) remains unknown. By using multivariate analysis, we discovered that high IRF8 expression was an independent poor predictor of overall survival (OS) in AML patients from our clinical follow-up study. The proliferation of three AML cell lines was significantly inhibited by shRNA-mediated knockdown of IRF8, owing to cell cycle S-phase arrest. Furthermore, we demonstrated that knocking down IRF8 could suppress the expression of CyclinA and CyclinB1, resulting in a shift in cell cycle distribution. Loss of IRF8 in AML cells decreased the expression of STAT3 and phosphor-STAT3 (pSTAT3), which are key factors in JAK/STAT signal pathway and are important for AML progression. Using a xenograft mouse model, we discovered the antiproliferative effect of losing IRF8 in vivo. In conclusion, this study found that IRF8 may play a prognostic factor and therapeutic target in AML.

Identification of blood-based key biomarker and immune infiltration in Immunoglobulin A nephropathy by comprehensive bioinformatics analysis and a cohort validation.

BACKGROUND: To identify the critical genes in the onset and progression of Immunoglobulin A nephropathy (IgAN) and to explore its immune cell infiltration feature. METHODS: Differentially expressed genes (DEGs) were firstly screened from 1 blood-derived dataset GSE73953 and a glomerulus derived dataset GSE93798 through limma analysis, overlap genes omitting and weighted gene correlation network analysis (WGCNA) and further reduced according to expression pattern and correlation with the clinical features: eGFR and proteinuria, followed by external validation using the GSE37460 dataset and an IgAN cohort. In addition, the CIBERSORT tool for immune cell infiltration analysis, ceRNA network construction and Connectivity Map (CMAP) were also performed. RESULTS: A total of 195 DEGs were found, and among them, 3 upregulated (ORMDL2, NRP1, and COL4A1) and 3 downregulated genes (ST13, HSPA8 and PKP4) are verified to correlate clinically, and finally ORMDL2, NRP1 and COL4A1 were validated in patient cohort and with the ability of IgAN discrimination (highest AUC was COL4A1: 97.14%). The immune cell infiltration results revealed that significant differences could be found on resting memory CD4 T cells, activated NK cells, and M2 macrophages between control and IgAN. CONCLUSIONS: Our results demonstrated here that significantly upregulated DEGs: ORMDL2, NRP1 and COL4A1, could be served as the diagnostic marker for IgAN, and dysregulated immune cell infiltration hinted possible the immune system intervention point in the setting of IgAN.

Comparative efficacy and safety of thirteen biologic therapies for patients with moderate or severe psoriasis: A network meta-analysis.

PURPOSE: This network meta-analysis was aimed to enhance the corresponding evidence with respect to the efficacy and safety of biologic treatments. METHODS: PubMed and EMBASE database searches were conducted. Odds ratios were used to evaluate multi-aspect comparisons. SUCRA was used to analyze the ranking of treatments in each endpoint. Psoriasis Area and Severity Index 50%, 75%, 90%, 100%, PGA, dermatology quality of life index were considered as outcomes while adverse events and discontinuation were adopted to evaluate safety. RESULTS: For safety issues, briakinumab was associated with least headache and itolizumab had the lowest risk of infection. Ustekinumab performed best in discontinuation. SUCRA ranked briakinumab, brodalumab, Infliximab and ixekizumab as the favorable efficacy therapies, while briakinumab and brodalumab seemed to have mild side effects. No heterogeneity was observed between these comparisons. CONCLUSIONS: Briakinumab performed relatively stable under efficacy and safety outcome. Infliximab can be a good choice for its lower risk of infection. Brodalumab present very good potential in efficacy outcome like PASI and PGA. More clinical trials are required to supply more data about discontinuation of infliximab and infection of brodalumab and larger RCT for assessment of briakinumab.

A cytogenetic analysis of male meiosis in Asparagus officinalis.

Asparagus (Asparagus officinalis) has several traits that make it a useful model for cytogenetic studies, however, few studies of the meiosis process have been made in asparagus. Here, we present in detail an atlas of male meiosis in asparagus, from preleptotene to telophase II. The meiosis process in asparagus is largely similar to those of the well-characterized model plants Arabidopsis thaliana, Zea mays, and Oryza sativa. However, most asparagus prophase I meiotic chromosomes show a strongly aggregated morphology, and this phenotype persists through the pachytene stage, highlighting a property in the control of chromosome migration and distribution in asparagus. Further, we observed no obvious banding of autofluorescent dots between divided nuclei of asparagus meiocytes, as one would expect in Arabidopsis. This description of wild-type asparagus meiosis will serve as a reference for the analyses of meiotic mutants, as well as for comparative studies among difference species. Abbreviations: DAPI: 4',6-diamidino-2-phenylindole; FISH: fluorescence in situ hybridization; PBS: phosphate-buffered saline; PMC: pollen mother cell; SEM: Scanning Electron Microscope.

Thermal Decomposition Behavior of Hydroxytyrosol (HT) in Nitrogen Atmosphere Based on TG-FTIR Methods.

The thermal decomposition behavior of olive hydroxytyrosol (HT) was first studied using thermogravimetry (TG). Cracked chemical bond and evolved gas analysis during the thermal decomposition process of HT were also investigated using thermogravimetry coupled with infrared spectroscopy (TG-FTIR). Thermogravimetry-Differential thermogravimetry (TG-DTG) curves revealed that the thermal decomposition of HT began at 262.8 °C and ended at 409.7 °C with a main mass loss. It was demonstrated that a high heating rate (over 20 K·min-1) restrained the thermal decomposition of HT, resulting in an obvious thermal hysteresis. Furthermore, a thermal decomposition kinetics investigation of HT indicated that the non-isothermal decomposition mechanism was one-dimensional diffusion (D1), integral form g(x) = x², and differential form f(x) = 1/(2x). The four combined approaches were employed to calculate the activation energy (E = 128.50 kJ·mol-1) and Arrhenius preexponential factor (ln A = 24.39 min-1). In addition, a tentative mechanism of HT thermal decomposition was further developed. The results provide a theoretical reference for the potential thermal stability of HT.

Preparation, Characterization, and Antioxidant Activity Evaluation of Liposomes Containing Water-Soluble Hydroxytyrosol from Olive.

Due to the multiple hydroxyl groups in its structure, hydroxytyrosol (HT) is very sensitive to air and light and has very strong instability and hydrophilicity that affect its biological activity. This study attempted to prepare liposomes containing water-soluble HT to improve the bioavailability and biocompatibility of the target drug. The preparation process factors (temperature, mass ratio of phospholipid (PL) and cholesterol (CH), Tween-80 volume, HT mass) were studied and response surface methodology (RSM) was applied to optimize the conditions. The results demonstrated that by using a temperature of 63 °C, mass ratio of PL and CH 4.5:1, HT mass 5 mg and Tween-80 volume of 6 mL, HT liposomes with an encapsulation efficiency (EE) of 45.08% were prepared. It was found that the particle sizes of the HT liposomes were well distributed in the range of 100-400 nm. Compared to free HT, prepared HT liposomes had better stability and a distinct slow release effect in vitro. Besides, HT liposomes presented better DPPH radical scavenging activity than free HT, which could be due to the fact that HT was encapsulated fully inside the liposomes. In addition, the encapsulation mechanism of HT was evaluated. In summary, the results indicated that HT liposome could enhance the antioxidant activity and was a promising formulation for prolonging the biological activity time of the target drug.

[Clinical features and prognosis of acute myeloid leukemia with acquired trisomy 21].

OBJECTIVE: To delineate the clinical features and prognostic significance of acquired trisomy 21 (+21) in 31 patients with acute myeloid leukemia (AML). METHODS: Chromosome specimen was prepared from bone marrow samples using a direct method and (or) cultivation, and their karyotypes were analyzed with R banding. The clinical features, chemotherapeutic effect and survival status of patients with acquired +21 were evaluated. RESULTS: Cytogenetic studies were successfully performed on 3 329 patients with newly diagnosed AML, among which 31 (0.93%) had acquired +21. And 16 (0.48%) of the 31 patients had +21 as the sole abnormality. The most frequent subgroup of bone marrow morphology was AML-M5b, and its total number was 12 (38.7%) of the total. Thirty patients among those with +21 received standard chemotherapy. The complete remission (CR) rate (63% vs. 80%, P< 0.05) and median overall survival (OS) (7 months vs. 15 months, P< 0.01) of AML patients with acquired +21 were both lower than those without. Age (60 years or older) was associated with a significantly lower CR rate (30% vs. 80%, P< 0.05) and shorter median OS (4 months vs. 12 months, P< 0.01). Comparing to acquired +21 with other additional abnormalities, acquired +21 solely was associated with a lower median OS (6 months vs. 12 months, P< 0.05), but did not affect the CR rate (60% vs. 67%, P> 0.05). Three patients undergoing allogenetic hematopoietic stem cell transplantation (allo-HSCT) were still alive at the end of follow-up. Their survival time have reached 56, 36 and 105 months, respectively, which were remarkably longer than those only received chemotherapy (P< 0.01). CONCLUSION: The presence of acquired +21 in patients with AML has a adverse prognosis with or without other additional abnormalities. Older age (60 years or older) and +21 alone predicted relatively poorer outcome. Allo-HSCT was expected to prolong the survival time of AML patients with acquired +21.

In Vivo and In Vitro Toxicity Evaluation of Polyprenols Extracted from Ginkgo biloba L. Leaves.

Polyprenols of Ginkgo biloba L. leaves (GBP) are a new type of lipid with 14-24 isoprenyl units, which in humans have strong bioactivity like the dolichols. A large amount of work showed that GBP had good antibacterial activity and powerful protective effects against acute hepatic injury induced by carbon tetrachloride and alcohol, as well as antitumor activity, but the safety of GBP was not considered. The current study was designed to evaluate the toxicity of these polyprenols. Acute toxicity in mice was observed for 14 days after GBP oral dosing with 5, 7.5, 10, 15 and 21.5 g/kg body weight (b. wt.) Further, an Ames toxicity assessment was carried out by plate incorporation assay on spontaneous revertant colonies of TA97, TA98, TA100 and TA102, with GBP doses designed as 8, 40, 200, 1000 and 5000 µg/dish, and subchronic toxicity was evaluated in rats for 91 days at GBP doses of 500, 1000 and 2000 mg/kg b. wt./day. The weight, food intake, hematological and biochemical indexes, the ratio of viscera/body weight, and histopathological examinations of tissue slices of organs were all investigated. The results showed that no animal behavior and appearance changes and mortality were seen during the observation period with 21.5 g/kg GBP dose in the acute toxicity test. Also, no mutagenicity effects were produced by GBP (mutation rate < 2) on the four standard Salmonella strains (p > 0.05) in the Ames toxicity test. Furthermore, the no observed adverse effect level (NOAEL) of GBP was 2000 mg/kg for 91 days feeding of rats in the subchronic toxicity tests. Results also showed the hematological and biochemical indexes as well as histopathological examination changed within a small range, and all clinical observation indexes were normal. No other distinct impacts on cumulative growth of body weight, food intake and food utilization rate were discovered with GBP. No significant difference was discovered for the rats' organ weight and the ratio of viscera to body weight (p > 0.05). Reversible pathological changes in the histopathological examinations of tissue slices of organs were not observed. GBP could therefore be considered as a safe material with minor side effects.

Enzymatic hydrolysis of oleuropein from Olea europea (olive) leaf extract and antioxidant activities.

Oleuropein (OE), the main polyphenol in olive leaf extract, is likely to decompose into hydroxytyrosol (HT) and elenolic acid under the action of light, acid, base, high temperature. In the enzymatic process, the content of OE in olive leaf extract and enzyme are key factors that affect the yield of HT. A selective enzyme was screened from among 10 enzymes with a high OE degradation rate. A single factor (pH, temperature, time, enzyme quantity) optimization process and a Box-Behnken design were studied for the enzymatic hydrolysis of 81.04% OE olive leaf extract. Additionally, enzymatic hydrolysis results with different substrates (38.6% and 81.04% OE) were compared and the DPPH antioxidant properties were also evaluated. The result showed that the performance of hydrolysis treatments was best using hemicellulase as a bio-catalyst, and the high purity of OE in olive extract was beneficial to biotransform OE into HT. The optimal enzymatic conditions for achieving a maximal yield of HT content obtained by the regression were as follows: pH 5, temperature 55 °C and enzyme quantity 55 mg. The experimental result was 11.31% ± 0.15%, and the degradation rate of OE was 98.54%. From the present investigation of the antioxidant activity determined by the DPPH method, the phenol content and radical scavenging effect were both decreased after enzymatic hydrolysis by hemicellulase. However, a high antioxidant activity of the ethyl acetate extract enzymatic hydrolysate (IC50 = 41.82 µg/mL) was demonstated. The results presented in this work suggested that hemicellulase has promising and attractive properties for industrial production of HT, and indicated that HT might be a valuable biological component for use in pharmaceutical products and functional foods.

A new combined technology: Macroporous adsorption resin and high speed counter current chromatography for hydroxytyrosol separation from olive leaf enzymatic hydrolysate.

Due to three free hydroxyl groups, hydroxytyrosol (HT) presents strong bioactivity and has broad food and drug application prospects. However, there is no good separation and purification technology. In this study, separation and purification technology of HT from the ethyl acetate extraction of enzymatic hydrolysate from olive leaf (EEEH) was investigated with macroporous adsorption resin (MAR) and high-speed counter-current chromatography (HSCCC) and the separation factors were optimized. First, the adsorption properties of eight MARs (AB-8, S-8, D-101, X-5, XAD-1, XAD-5, NKA-Ⅱ, H-103) for HT enrichment were studied. The results showed that H-103 macroporous resin was adsorbent, sample concentration was 1.5 mg/mL, eluent was 30 % ethanol solution, sample loading rate was 3.0 BV/h, elution velocity was 2.0 BV/h, and HT purity of EEEH was increased from 10.23 % to 40.78 %. Then, solvent systems were examined according to partition coefficients of target component and petroleum ether: ethyl acetate: methanol: water (4:6:4:6, v/v) system was chosen. The critical experimental parameters of HSCCC were optimized as following: revolution speed was 1200 rpm and flow rate was 3 mL/min. The HT purity of macroporous resin purified EEEH was increased from 40.78 % to 85.7 %. Therefore, MAR-HSCCC combined technology could be a very effective approach to separate and purify HT from EEEH.

Effects of Low Temperature-Ultrasound-Papain (LTUP) Combined Treatments on Purine Removal from Pork Loin and Its Influence on Meat Quality and Nutritional Value.

A combined pretreatment method of "low temperature-ultrasound-papain" (LTUP) was proposed to remove the purine of pork loins. Compared with untreated pork loin, under optimal conditions (temperature 58 °C, ultrasound density 100 W/cm2, and papain concentration 0.085%), the purine removal rate of treated pork loin could reach 59.29 ± 1.39%. The meat quality of pork loin treated with the LTUP method such as hardness and chewiness decreased by 58.37% and 64.38%, respectively, and the in vitro protein digestibility was increased by 19.64%; the cooking loss was decreased by 15.45%, compared with the simulated household blanching process (HT). In view of the high purine removal rate, the losses of free amino acids and soluble peptides were acceptable and reasonable. SEM and LF-NMR results showed that low temperature and ultrasound combined with papain treatment opened a channel for purine transfer and promoted purine dissolution by affecting the protein structure of pork loin. In addition, the migration of water within the muscle tissue was also related to purine removal. In summary, LTUP is recommended as an efficient and green way for the meat industry to remove purine.

Borderline personality disorder and thyroid diseases: a Mendelian randomization study.

Background: Previous studies have shown that there is a correlation between diseases of the thyroid gland and mental illnesses; however, any causal relationship between them remains unclear. This study aimed to evaluate the causal relationship between borderline personality disorder and four thyroid diseases. Methods: The causal relationship was inferred using double-sample Mendelian randomization analysis of appropriate instrumental variables from genome-wide association studies. We calculated the estimated value of the effect using various statistical methods. Results: Borderline personality disorder was a risk factor for non-toxic single thyroid nodules with each increase in standard deviation increasing the risk of a non-toxic single thyroid nodule by 1.13 times (odds ratio = 1.131; 95% confidence interval, 1.006-1.270; P=0.039). There was no evidence of a correlation between borderline personality disorder and hyperthyroidism/thyrotoxicosis, hypothyroidism, and autoimmune thyroiditis. Conclusion: This study showed that there is a positive causal correlation between borderline personality disorder and non-toxic single thyroid nodules but not with other thyroid diseases. This means that thyroid status should be monitored in patients with borderline personality disorder. However, the possibility of a causal relationship between other mental illnesses and thyroid diseases requires further research.

Enhanced antihypertensive potential of fermented pomegranate juice: The contribution of phenolic compounds biotransformation and the resultant angiotensin-I-converting enzyme inhibition mechanism.

Current research on plant food-derived phenolic compounds as angiotensin-I-converting enzyme (ACE) inhibitors has been well documented. Pomegranate juice (PJ) has been reported positively contributed to ACE inhibition. Microbial fermentation is a preferable technique to regulate the biotransformation of phenolic compounds and their bioaccessibility, therefore promoting the ACE inhibitory activity in plant food with antihypertension potential. In this study, the remarkable improvements of ACE inhibitory activity and antioxidant capacity in Lactobacillus plantarum fermented PJ were observed. A consecutive study of phenolic compounds biotransformation, ACE inhibition kinetics and structure-activity relationship were performed. This study firstly highlights the relationship between the enhanced ACE inhibitory activity in fermented PJ and the biotransformation of phenolic compounds, providing a new way to reinforce plant food ACE inhibition potential by microbial fermentation.

[Preparation and Application of Monoclonal Antibody Against Human von Willebrand Factor Propeptide].

OBJECTIVE: To develop monoclonal antibodies that can specifically recognize human von Willebrand factor (VWF) propeptide (VWFpp) in plasma, and establish a rapid and reliable method for the detection of VWFpp antigen in plasma by using the double-antibody sandwich ELISA with the obtained anti-VWFpp monoclonal antibody. METHODS: The recombinant human VWFpp (D1 and D2 regions) protein expressed in eukaryotic cells was used as immunogen to immunize BALB/c mice with routine method, so as to obtain clones of fusion cells. After screening and identification, hybridoma cell lines secreting monoclonal antibodies against VWFpp were selected, and then double-antibody sandwich ELISA assay was used to construct VWFpp antigen detection kit for the determination of VWFpp in human plasma. The levels of VWFpp antigen in plasma of 12 leukemia patients who underwent bone marrow transplantation were dynamically detected. RESULTS: Two hybridoma cell lines that can be subcultured continuously and secrete monoclonal antibodies against VWFpp were obtained and named SZ175 and SZ176 respectively. Identified by ELISA and Western blot, the antibodies could both specifically recognize VWFpp but couldn't recognize mature VWF (without propeptide). Based on the principle of double-antibody sandwich ELISA, monoclonal antibodies SZ175 and SZ176 were successfully made into a kit for detecting VWFpp antigen. The plasma VWFpp levels of leukemia patients before and after bone marrow transplantation were dynamically detected. The results showed that the plasma VWFpp levels of the patients after transplantation were significantly higher than those before transplantation. CONCLUSION: Two monoclonal antibodies against VWFpp were successfully prepared, and a double-antibody sandwich ELISA detection kit for VWFpp antigen was constructed, which provides a powerful tool for further study on the biological function of VWFpp, the clinical diagnosis and classification of von Willebrand disease (VWD), and the prognostic monitoring of endothelial injury-related diseases.

The first complete mitogenome of skin beetles Omorgus chinensis (Coleoptera: Trogidae) with the phylogenetic implications.

The first complete mitogenome of Trogidae, Omorgus chinensis (Coleoptera: Trogidae) is sequenced using the next generation sequencing. The genomic structure is a circular molecule with 18682 bp in length, comprising 13 protein-coding genes, 22 transfer RNA genes (tRNAs), 2 ribosomal RNAs (rRNAs) and a control region. The nucleotide composition is A (39.44%), C (13.82%), T (36.78%), and G (9.96%) with an AT content of 76.22%. The phylogenetic analysis of 18 insects in Scarabaeoidae show that Omorgus chinensis shares a close ancestry with Lucanidae and Geotrupidae.

Numerical solution for circular tunnel excavated in strain-softening rock masses considering damaged zone.

Despite the extensive investigation on the stress and displacement distributions in tunnels, few have considered the influences of the damaged zone around a tunnel on the strength and stiffness parameters of the surrounding rock, including the gradual variation in the damaged factor D and dimensionless damaged radius [Formula: see text], under the effect of excavation disturbance. In this paper, a numerical solution is presented for the stresses and displacement of a circular tunnel excavated in a Hoek-Brown rock mass considering the progressive destruction of the damaged zone. First, the results obtained using the proposed algorithm are compared with those obtained using other numerical solutions, demonstrating a high degree of accuracy through some examples. Second, the influences of the damaged factor [Formula: see text] and dimensionless damaged radius [Formula: see text] on the stresses, radial displacement, plastic radii, and ground response curve are investigated. The results show that, as the damaged factor D increases, the radial displacement and plastic radius increase, whereas the tangential stress decreases. Both the plastic radius and displacement decrease with decreasing [Formula: see text]. This shows that the damaged factor D has a significant effect on tunnel convergence.

Hematopoiesis reconstitution and anti-tumor effectiveness of Pai-Neng-Da capsule in acute leukemia patients with haploidentical hematopoietic stem cell transplantation.

BACKGROUND: With the rapid development of haploidentical hematopoietic stem cell transplantation (haplo-HSCT), primary poor graft function (PGF) has become a life-threatening complication. Effective therapies for PGF are inconclusive. New Chinese patent medicine Pai-Neng-Da (PND) Capsule exerts dual effect in promoting hematopoiesis recovery and regulating immunity. Still, the application of PND capsule in hematopoietic stem cell transplantation, especially in the haplo-HSCT setting, has not yet been reported. AIM: To evaluate the role of PND capsule in acute leukemia patients with haplo-HSCT. METHODS: We retrospectively collected data of acute leukemia patients who underwent haplo-HSCT at the Affiliated People's Hospital of Ningbo University between April 1, 2015 and June 30, 2020. Twenty-nine consecutive patients received oral PND capsule from the sixth day to the first month after haplo-HSCT were included in the PND group. In addition, 31 patients who did not receive PND capsule during haplo-HSCT were included in the non-PND group. Subsequently, we compared the therapeutic efficacy according to the western medical evaluation indexes and Chinese medical symptom scores, and the survival between the PND group and the non-PND group, using the chi-square test, Fisher's exact test, and the Kaplan-Meier method. RESULTS: The duration of platelet engraftment was shorter in the PND group than in the non-PND group (P = 0.039). The PND group received a lower frequency of red blood cells and platelet transfusions than the non-PND group (P = 0.033 and P = 0.035, respectively). In addition, PND capsule marginally reduced the rate of PGF (P = 0.027) and relapse (P = 0.043). After 33 (range, 4-106) months of follow-up, the 3-year relapse-free survival (P = 0.046) and progression-free survival (P = 0.049) were improved in the PND group than in the non-PND group. Also, the therapeutic efficacy of the PND group according to Chinese medical symptom scores was significantly better than that of the non-PND group (P = 0.022). Moreover, the adverse events caused by PND capsule were mild. Nevertheless, there were no significant differences in the duration of neutrophil engraftment, the risk of infection within 100 days after haplo-HSCT, the acute graft-versus-host disease, or the 3-year overall survival between the two groups. CONCLUSION: PND capsule could promote hematopoiesis reconstitution, improve the therapeutic efficacy of Chinese medical symptom scores, present anti-tumor effectiveness, and prolong the survival of acute leukemia patients with haplo-HSCT.

Local symptoms of Hashimoto's thyroiditis: A systematic review.

Objective: Hashimoto's thyroiditis (HT) is the most common type of thyroid disease and can cause many different manifestations. The local symptoms of HT are an under-studied area of research. Therefore, the purpose of this study was to investigate the local symptoms of HT and their prevalence. Methods: A systematic review was performed to find articles in PubMed that discuss the local symptoms of HT. Relevant vocabulary terms and key terms included: autoimmune thyroid disease (AITD), hyperthyroidism, hypothyroidism, neck, throat, pharynx, airway, esophagus, breathe, swallow, globus, sleep apnea, symptoms, and quality of life. Two investigators independently screened the eligible studies. Results: A total of 54 articles fulfilled the inclusion criteria. Of these, 25 were clinical studies, 24 were case reports, and five were reviews. These clinical studies and case reports included a total of 2660 HT patients. There were eight local symptoms related to HT: neck pain (0.02%~16%), voice changes (7%~30%), throat discomfort (20%~43.7%), shortness of breath (28%~50%), dysphagia (29%), goiter-related symptoms (69.44%), sleep apnea, and generally defined compressive symptoms. Due to the use of different outcome measures among all the studies, a meta-analysis of the data could not be performed. Conclusion: Goiter symptoms, which are an item on the ThyPRO scales, are the most frequent local symptoms in HT patients, and include neck pain, voice changes, throat discomfort, and dysphagia. These local symptoms should be identified in the clinic and included in the early diagnosis and management of HT, as well as evaluated further to understand their relevance in the pathogenesis of HT.