Objective: To observe the efficacy and adverse reactions of a combination therapy regimen based on bortezomib and glucocorticoids in recurrent/refractory immune thrombocytopenic purpura (iTTP) . Methods: Six patients with recurrent/refractory TTP were included and treated with a glucocorticoid and two courses of bortezomib-based regimen. The clinical remission status of patients, changes in ADAMTS13 activity/ADAMTS13 inhibitor, and the occurrence of treatment-related adverse reactions were observed. Results: Of the 6 patients, 2 were males and 4 were females, with a median age of 21.5 (18-68) years. Refractory TTP was found in 1 case and recurrent TTP in 5 cases. Glucocorticoids were administered with reference to prednisone at 1 mg·kg(-1)·d(-1), and gradually reduced in dosage after achieving clinical remission. Bortezomib is subcutaneously administered at 1.3 mg/m(2) on days 1, 4, 8, and 11 with a 28-day treatment course consisting of 2 courses. Six patients achieved clinical remission after receiving bortezomib as the main treatment. ADMATS13 activity returned to normal in all patients with TTP after treatment, and the ADAMTS13 inhibitor turned negative. Thrombocytopenia is the most common adverse reaction after treatment, with other adverse reactions, including peripheral neuritis and abdominal pain, but ultimately all patients returned to normal. In a median follow-up of 26 (9-41) months, 5 patients maintained sustained remission, and 1 patient relapsed after 16 months of bortezomib treatment. Conclusion: Combination therapy of bortezomib and glucocorticoids has a satisfactory therapeutic effect and controllable adverse reactions for recurrent/refractory iTTP.
Male ; Female ; Humans ; Young Adult ; Adult ; Middle Aged ; Aged ; Bortezomib/therapeutic use* ; Glucocorticoids/therapeutic use* ; Rituximab/therapeutic use* ; Purpura, Thrombotic Thrombocytopenic/drug therapy* ; Purpura, Thrombocytopenic, Idiopathic/drug therapy* ; ADAMTS13 Protein/therapeutic use*

Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.
Humans ; Polymyxin B/adverse effects* ; Retrospective Studies ; Gram-Negative Bacterial Infections/complications* ; Fever/drug therapy* ; Sepsis/drug therapy* ; Anti-Bacterial Agents/therapeutic use* ; Bacteremia/complications*

Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.
Male ; Humans ; Middle Aged ; Atorvastatin/therapeutic use* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Hypercholesterolemia/drug therapy* ; Cholesterol, LDL/therapeutic use* ; Anticholesteremic Agents/therapeutic use* ; Treatment Outcome ; Triglycerides ; Apolipoproteins B/therapeutic use* ; Double-Blind Method ; Pyrroles/therapeutic use*

ObjectiveTo preliminarily predict the active components， targets， and signaling pathways of modified Shengjiangsan in the treatment of immunoglobulin A nephropathy （IgAN） based on network pharmacology， and to explore its underlying mechanism through molecular docking and experimental verification on animals. MethodThe active ingredients and related targets of modified Shengjiangsan were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP）， UniProt， SwissTargetPrediction， and literature review. IgAN-related targets were obtained from GeneCards and Online Mendelian Inheritance in Man （OMIM）. Cytoscape 3.9.0 was used to construct the regulation network of the related targets of Shengjiangsan and IgAN， and the protein-protein interaction （PPI） network was plotted by STRING. The common genes were analyzed for gene ontology （GO） functional annotation and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment by Metascape. Key targets and main active ingredients were selected for molecular docking by AutoDockTools 1.5.6. The experimental model of IgAN was induced by bovine serum albumin（BSA， ig） combined with lipopolysaccharide （LPS， iv） and the complex of CCl₄ and castor oil （sc） in rats. The model rats were treated with modified Shengjiangsan and benazepril hydrochloride for four weeks. The rats were sacrificed after drug administration. The levels of transforming growth factor-β₁ （TGF-β₁） and interleukin-6 （IL-6） in the serum and kidney tissues were detected by enzyme-linked immunosorbent assay（ELISA）， immunohistochemistry， Real-time quantitative polymerase chain reaction （Real-time PCR）， and Western blot. ResultA total of 105 active ingredients were obtained according to oral bioavailability（OB）， drug-likeness（DL）， and literature screening. There were 124 common genes and 59 core targets. Neurotrophic tyrosine receptor kinase 1 （NTRK1）， cullin-3 （CUL3）， tumor protein 53 （TP53）， epidermal growth factor receptor （EGFR）， exportin 1 （XPO1）， and other targets might be closely related to IgAN. As predicted by KEGG enrichment analysis， the treatment of IgAN with modified Shengjiangsan mainly involved the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， nuclear transcription factor-kappa B （NF-κB） signaling pathway， and cytokine-cytokine receptor interaction signaling pathway. As revealed by molecular docking， the main active ingredients in modified Shengjiangsan showed stable binding activities with NTRK1， CUL3， TP53， EGFR， and XPO1 in the core targets， indicating that it presumedly regulated inflammatory responses by affecting NTRK1， CUL3， TP53， EGFR， and XPO1 target proteins. The results of experimental verification on animals showed that the expression levels of cytokines TGF-β₁ and IL-6 in the serum and kidney tissues of IgAN rats were significantly decreased by modified Shengjiangsan， suggesting that Shengjiangsan might inhibit excessive fibrosis， and inflammatory and immune responses by regulating signaling pathways such as cytokine-cytokine receptor interaction， PI3K/Akt， and NF-κB. ConclusionModified Shengjiangsan may treat IgAN through multiple targets and pathways. Its mechanism may be related to the inhibition of excessive fibrosis， and inflammatory and immune responses by affecting the expression of NTRK1， CUL3， TP53， EGFR， and XPO1 and the regulation of the cytokine-cytokine receptor interaction， PI3K/Akt， NF-κB， and other signaling pathways.

OBJECTIVE: To investigate the expression of WTAP gene in acute myeloid leukemia (AML) and its clinical significance. METHODS: 74 acute myeloid leukemia patients with non-M3 type and 19 normal donors were selected, and real-time quantitative polymerase chain reaction was used to detect the mRNA expression level of WTAP gene in their bone marrow cells. The relationship between the mRNA expression level of WTAP gene and the clinical characteristics was analyzed. RESULTS: The relative mRNA expression of WTAP gene in the non-M3 AML group was significantly higher than that in the healthy control group, and the difference showed statistically significant (P<0.01). There showed no statistically significant difference in WTAP gene expression among each subtypes (all P>0.05) according to the classification of FAB. The mRNA expression level of WTAP gene in FLT3-ITD mutated AML patients was higher than that in FLT3-ITD unmutated group (P=0.016), and the mRNA expression level of WTAP gene in AML patients with CEBPα mutation was lower than that in CEBPα unmutated group (P=0.016). The expression level of WTAP mRNA was positively correlated with WT1 expression (r=0.6866, P<0.01). There was no relationship between WTAP mRNA expression level and other clinical parameters, such as age, gender, white blood cell count, hemoglobin level, platelet count, bone marrow original proportion of immature cells, chromosome karyotype, and NPM1, DNMT3A, ASXL1, NRAS, TET2 genes mutation status (P>0.05). The expression level of WTAP mRNA showed no obvious effect on the complete remission of patients after first treatment. The different expression level of WTAP gene at initial diagnosis showed also no effect on the overall survival time of patients. CONCLUSION The expression level of WTAP gene is increasing in new diagnosed non-M3 acute myeloid leukemia. There is a positive correlation between the expression level of WTAP gene and the expression level of WT1 fusion gene. WTAP mRNA always shows higher expression in patients with FLT3-ITD mutation than that in patients without FLT3-ITD mutation, and shows lower expression in patients with CEBPα mutation than that in unmutated group.
Cell Cycle Proteins ; Humans ; Karyotype ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Prognosis ; RNA Splicing Factors ; Remission Induction ; fms-Like Tyrosine Kinase 3/genetics*

Objective To detect chromosomal aberrations in two fetuses with multiple malformation.Methods The two fetuses were subjected to chromosomal microarray analysis (CMA) by using Affymetrix CytoScan 750K arrays.The results were analyzed by bioinformatic software.Results CMA analysis suggested that both fetuses harbored pathogenic copy number variations (CNVs) in the 2p15-16.1 region,which ranged from 255 kb to 257 kb and encompassed the XPO1 and USP34 genes.Conclusion Deletion of the chr2 (61 659 957-61 733 075,hg19) encompassing the XPO1 and USP34 genes may underlie the multiple malformations in the two fetuses.

Objective To study the influences of mental disorders on female systemic lupus erythematosus(SLE)and analyze the factors. Methods We used symptom check list -90 (SCL-90) as a basis for judging mental disorders disease activity. Disease activity, social support and depreciation - discrimination were used as possible influencing factors. Social support and discomfort – discrimination were possible influencing factors. Multivariate unconditional logistic regression model was used to analyze the influencing factors of mental disorders. Results The total score of SCL-90 of patients with female SLE was significantly higher than that of norm models ［(136.39±48.66) vs (129.96±38.76)］ (P<0.05), in 289 SLE patients, the number of patients with mental disorders was 128 (44.3%). High monthly income(OR=0.770, 95% CI:0.604-0.981, P=0.034) was a protective factor for mental disorders. High disease activity (OR=1.792, 95% CI:1.023-3.138, P=0.042)and high discomfort–discrimination (OR=1.100, 95% CI:1.035-1.169, P=0.002)were risk factors for mental disorders. Conclusions Female SLE patients have a higher risk of mental disorders than the general population. And eliminating self-depreciation, reducing social discrimination, active employment, increasing monthly income, standardizing treatment and reducing disease activity may effectively alleviate mental disorders in SLE patients.

As an usually occurs in athletes, iliotibial band syndrome is payed more attention for people, the disease is diagnosed mainly by clinical symptoms, physical examination and MRI, but there is no uniform diagnostic criteria. The pathogenesis of iliotibial band syndrome is considered to be related to pressure and friction factors. As for the treatment, manipulation, muscle exercise, mainly drugs and physical therapy and so on both at home and abroad are recognized to use to achieve desired effect. For conservative failure, refractory iliotibial band syndrome patients, arthroscopy, or release of iliotibial band syndrome surgery are performed. While conservative local drug injection combined with muscle exercise could play a role in pain management besides, arthroscopic as operation method is more advanced, and applicable to all types of patients without absolute contraindication, so it is helpful for patients with early activity. At present, there is still a great deal of controversy about its pathogenesis, and there is no obvious limit for the specific indications of its various therapies in clinic, so it needs further specification.

Objective To investigate the feasibility of prophylactic cranial irradiation with hippocampal avoidance (HA-PCI) in non-small cell lung cancer (NSCLC).Methods The clinical data of 56 patients with brain metastases of NSCLC who were treated from 2011 to 2014 were collected.Brain metastases and the hippocampus were delineated on T1 W1 contrast-enhanced MRI,and the distance between brain metastases and the hippocampus was analyzed;an HA-PCI regimen was also developed,and the distribution of the metastases in planning target volume (PTV) low-dose regions around the hippocampus was analyzed.Results None of the 139 metastases involved the hippocampus.There were 6(4.3％) and 18 (12.9％) metastases within 5 mm and 10 mm,respectively,outside the hippocampus.In the HA-PCI regimen,the D50％ and D2％ of PTV were 25.6 Gy and 27.1 Gy,respectively.Dmean and D2％ for the hippocampus were 7.4 Gy and 9.9 Gy,respectively;D50％ within 0-5.0 mm,5.1-10.0 mm,and 10.1-15.0 mm outside the hippocampus was 10.3 Gy,15.1 Gy,and 20.5 Gy,respectively.Conclusions HA-PCI may be feasible theoretically,but this needs to be confirmed by the intracranial failure pattern in patients with long-term survival.

OBJECTIVETo investigate the neuroprotective effects of glycyrrhizin (Gly) as well as its effect on expression of high-mobility group box 1 (HMGB1) in rats after traumatic brain injury (TBI).

METHODSMale Sprague-Dawley rats were randomly divided into three groups: sham group, TBI group, and TBI+Gly group (n=36 per group). Rat TBI model was made by using the modified Feeney's method. In TBI+Gly group, Gly was administered intravenously at a dosage of 10 mg/kg 30 min after TBI. At 24 h after TBI, motor function and brain water content were evaluated. Meanwhile, HMGB1/HMGB1 receptors including toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE)/nuclear factor-κB(NF-κB) signaling pathway and inflammatory cytokines in the injured brain tissues were detected using quantitative real-time polymerase chain reaction, western blot, electrophoretic mobility shift assay and enzyme-linked immunosorbent assay. Furthermore, HMGB1, RAGE and TLR4 immunohistochemistry and apoptosis were analyzed.

RESULTSBeam walking performance impairment and brain edema were significantly reduced in TBI+Gly group compared with TBI group; meanwhile, the over-expressions of HMGB1/HMGB1 receptors (TLR4 and RAGE)/NF-κB DNA-binding activity and inflammatory cytokines were inhibited. The percentages of HMGB1, RAGE and TLR4-positive cells and apoptotic cells were respectively 58.37% ± 5.06%, 54.15% ± 4.65%, 65.50% ± 4.83%, 52.02% ± 4.63% in TBI group and 39.99% ± 4.99%, 34.87% ± 5.02%, 43.33% ± 4.54%, 37.84% ± 5.16% in TBI+Gly group (all P<0.01 compared with TBI group).

CONCLUSIONGly can reduce secondary brain injury and improve outcomes in rat following TBI by down-regulation of HMGB1/HMGB1 receptors (TLR4 and RAGE)/NF-κB-mediated inflammatory responses in the injured rat brain.

Animals ; Brain Injuries ; drug therapy ; Glycyrrhizic Acid ; pharmacology ; therapeutic use ; HMGB1 Protein ; metabolism ; Male ; Neuroprotective Agents ; therapeutic use ; Rats ; Rats, Sprague-Dawley