Emerging biologic frontiers for Sjogren's syndrome: Unveiling novel approaches with emphasis on extra glandular pathology.

Primary Sjögren's Syndrome (pSS) is a complex autoimmune disorder characterized by exocrine gland dysfunction, leading to dry eyes and mouth. Despite growing interest in biologic therapies for pSS, FDA approval has proven challenging due to trial complications. This review addresses the absence of a molecular-target-based approach to biologic therapy development and highlights novel research on drug targets and clinical trials. A literature search identified potential pSS treatment targets and recent advances in molecular understanding. Overlooking extraglandular symptoms like fatigue and depression is a notable gap in trials. Emerging biologic agents targeting cytokines, signal pathways, and immune responses have proven efficacy. These novel therapies could complement existing methods for symptom alleviation. Improved grading systems accounting for extraglandular symptoms are needed. The future of pSS treatment may involve gene, stem-cell, and tissue-engineering therapies. This narrative review offers insights into advancing pSS management through innovative biologic interventions.

Potential Implications of the Lung Microbiota in Patients with Chronic Obstruction Pulmonary Disease and Non-Small Cell Lung Cancer.

Recently, chronic obstructive pulmonary disease (COPD) has been considered as a common risk factor of non-small cell lung cancer (NSCLC). However, very few studies have been conducted on the effects of COPD on the lung microbiota in patients with NSCLC. To identify the lung microbiota in patients with COPD and NSCLC (CN), the microbiome of the induced sputa of 90 patients was analyzed using 16S rDNA sequencing. The results showed no significant differences in the bacterial diversities of induced sputa among patients with COPD, NSCLC, and CN and no intrinsic differences among patients with different pathological types of lung cancer. After surgical operation, the diversities of the induced sputa in patients with CN significantly decreased. More remarkably, both the microbial community phenotypes and the components of the induced sputa in patients with CN obviously differed from those in patients with COPD or NSCLC. The relative abundances of Streptococcus, Veillonella, Moraxella, and Actinomyces significantly decreased, but those of Neisseria and Acinetobacter significantly increased in patients with CN compared with those in patients with COPD or NSCLC alone, resulting in increased Gram-negative microbiota and, therefore, in potential pathogenicity and stress tolerance, as well as in enhancement of microbial glycolipid metabolism, amino acid metabolism, and oxidative stress. Although COPD did not affect the number of pulmonary flora species in patients with NSCLC, these significant alterations in the microbial populations, phenotypes, and functions of induced sputa due to COPD would contribute to inflammation-derived cancer progression in patients with CN.

Validation of the KANG KC-2850 oscillometric upper-arm ambulatory blood pressure monitor in general population according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization universal standard.

OBJECTIVE: To evaluate the accuracy of the KANG KC-2850 ambulatory blood pressure monitor (ABPM) for clinical blood pressure (BP) measurement according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO) universal standard (ISO 81060-2:2018). METHODS: BP was sequentially measured and compared with a standard mercury sphygmomanometer in 85 eligible participants. A standard adult cuff (22-3232 cm) was used for test device measurements. A total of 255 comparison pairs were obtained and analyzed according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO universal standard. RESULTS: The standard requirements were followed precisely. For the validation Criterion 1, the mean ± SD of the differences between the test device and reference BP readings was -1.12 ± 5.01 and -0.33 ± 4.52 mmHg for SBP and DBP, respectively. For Criterion 2, the SD of the averaged BP differences between the test device and reference BP per subject was 3.59 and 3.60 mmHg for SBP and DBP, respectively. CONCLUSION: The KANG KC-2850 ABPM met all the requirements for validation by the AAMI/ESH/ISO universal standard and can be recommended for clinical use in general population.

Nicotine-induced miR-21-3p promotes chemoresistance in lung cancer by negatively regulating FOXO3a.

Lung cancer is the leading cause of cancer-related mortality worldwide and cigarette smoking is reported to contribute to the lung cancer-related mortality. The present study aimed to investigate the molecular mechanism underlying nicotine-induced chemoresistance in lung cancer. The expression of microRNA (miR)-21-3p and its predicted target FOXO3a in lung cancer cells was detected via reverse transcription-quantitative PCR, in the presence or absence of nicotine. The regulatory effect of miR-21-3p and FOXO3a on lung cancer cell proliferation and apoptosis induced by docetaxel or cisplatin treatment was evaluated by performing Cell Counting Kit-8 and Annexin V/PI staining assays, respectively. The interaction between miR-21-3p and FOXO3a was analyzed by performing luciferase reporter assays and western blotting. FOXO3a overexpression rescue experiments were conducted in vitro and in vivo using a xenograft mouse model to assess the function of miR-21-3p/FOXO3a in lung cancer. Nicotine induced miR-21-3p expression in lung cancer cells in a dose-dependent manner. miR-21-3p downregulated FOXO3a expression by directly binding to the 3'-untranslated region of FOXO3a. Moreover, miR-21-3p knockdown sensitized lung cancer cells to docetaxel or cisplatin treatment. Mechanistically, FOXO3a was predicted as a direct target of miR-21-3p. FOXO3a overexpression promoted the chemosensitivity of lung cancer cells to docetaxel or cisplatin treatment. Furthermore, FOXO3a overexpression antagonized the regulatory function of miR-21-3p on docetaxel- or cisplatin-treated lung cancer cells. In the docetaxel- or cisplatin-treated lung cancer xenograft mouse model, miR-21-3p promoted chemoresistance via negatively regulating FOXO3a. Therefore, the present study demonstrated that nicotine-induced miR-21-3p promoted chemoresistance to docetaxel or cisplatin treatment via negatively regulating FOXO3a, which may serve as a novel therapeutic strategy for the treatment of patients with chemoresistant lung cancer.

Polysaccharides from Platycodonis Radix ameliorated respiratory syncytial virus-induced epithelial cell apoptosis and inflammation through activation of miR-181a-mediated Hippo and SIRT1 pathways.

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis in young children, but there are few safe and effective treatments for this disease. Platycodonis Radix is widely used as an antitussive and expectorant drug for preventing various diseases in lower respiratory tract, in which the polysaccharides are one of the main bioactivity constituents. In this study, the protective effects of the P. Radix polysaccharides (PRP) against RSV-induced bronchiolitis in juvenile mice and RSV-induced apoptosis of epithelial HEp-2 cells were investigated. The results showed that PRP obviously decreased the levels of IL-1ß, IL-4, IL-6, TNF-α, IFN-γ and TSLP in lung tissues, and reduced the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) of RSV-infected mice. Furthermore, it reduced the apoptosis of RSV-infected HEp-2 cells and remarkably inhibited the mRNA expressions of RSV L gene, which indicated that PRP affected transcription and replication of RSV in host cells. Compared with that in RSV-infected group, miR-181a-5p in the PRP-treated group presented the highest relative abundance and its expression was violently reduced by approximately 30%. Mechanistically, PRP had the similar effects as miR-181a-5p antagomir on RSV-induced apoptosis and inflammation in HEp-2 cells via upregulating BCL2, MLL3 and SIRT1, which could be reversed by miR-181a-5p mimic. Therefore, it demonstrated that PRP not only protected against RSV-induced lung inflammation in mice but also inhibited apoptosis of RSV-infected HEp-2 cells via suppressing miR-181a-5p and transcriptionally activating Hippo and SIRT1 pathways.

Effect of Early Enteral Nutrition on Serum Inflammatory Factors and Intestinal Mucosal Permeability in Patients with Severe Acute Pancreatitis.

BACKGROUND: To analyze the effect of early enteral nutrition on serum inflammatory factors and intestinal mucosal permeability in patients with severe acute pancreatitis. METHODS: A total of 55 patients with severe acute pancreatitis were divided into 2 groups: the control group (n = 27), who received routine treatment and the observation group (n = 28), who received early enteral nutrition. The expression of serum inflammatory factors and the permeability of the intestinal mucosa were compared between the 2 groups before and after treatment, and rates of infection and mortality within 30 days were statistically analyzed. RESULTS: The recovery duration of serum and urine amylase and the length of hospital stay in the observation group were shorter than those in the control group. The white blood cell counts, levels of procalcitonin, and the expression of interleukin-6 (IL-6) in the observation group were lower than those in the control group 7 days after the treatment was commenced, and the differences were statistically significant (P < .05). The concentration of diamine oxidase in the serum and the urinary lactulose to mannitol (L/M) ratio in the observation group were lower than those in the control group 7 days after treatment was commenced. The infection rate in the observation group (21.43%) was lower than that in the control group (51.85%) (P < .05). There was no difference in the 30-day mortality between the 2 groups (P > .05). CONCLUSION: Early enteral nutrition may reduce the expression of serum inflammatory factors, decrease the permeability of the intestinal mucosa, and improve the prognosis of patients with severe acute pancreatitis.

[Pharmacodynamics and intestinal flora research on different processed products of Puerariae Lobatae Radix and Puerariae Thomsonii Radix].

This study aims to explore the pharmacodynamic differences of Puerariae Lobatae Radix(PLR), Puerariae Thomsonii Radix(PTR) and their different processed products and the influences of these medical materials on the diversity of intestinal flora. The Sennae Folium-induced diarrhea model, streptozotocin(STZ)-induced diabetes model and L-nitro-arginine methyl ester(L-NAME)-induced hypertension model were used to compare the pharmacodynamic differences in anti-diarrhea, blood glucose reduction and blood pressure lowering among raw, roasted and vinegar-processed PLR and PTR. The effects of raw and processed PLR and PTR on intestinal flora diversity of rats were evaluated by 16 S rDNA high-throughput sequencing. The roasted PLR and PTR performed better in anti-diarrhea, especially the former. PLR and its processed products all presented the efficacy of reducing blood glucose, and the vinegar-processed PLR was the most outstanding. The raw PTR was not that effective in reducing blood glucose, whereas its efficacy was improved after roasting and vinegar processing. Both PLR and PTR were capable of lowering blood pressure to a certain extent, and PLR is superior to PTR in this aspect. Further, the vinegar-processed PLR showed the best effect. The diversity of intestinal flora was different among rats to which different products of PLR and PTR were administered. The roasted PLR led to the highest abundance of Lactobacillus, which was closely related to its best antidiarrheal effect. The highest abilities of vinegar-processed PLR to lower blood glucose and blood pressure were associated with the high abundance of Blautia and Prevotella_9. This study lays a foundation for elucidating the processing mechanisms of PLR and PTR and provides a basis for their further development and application.

The value of the exertional heat stroke score for the prognosis of patients with exertional heat stroke.

OBJECTIVE: This study aims to evaluate the exertional heat stroke score (EHSS) system for the prognosis of exertional heat stroke (EHS) patients. METHODS: Forty-two EHS patients who had been treated in our hospital between January 2017 and December 2019 were divided into two groups according to their prognosis, a survival group and a non-survival group. All the patients had received comprehensive EHS treatment after admission, and their EHSS parameters were collected within 24 h of admission, including body temperature, hepatorenal function, and coagulation function. A retrospective comparative evaluation was made of the effectiveness of the EHSS, the Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) in making an EHS prognosis. RESULTS: Among 42 patients, 28 patients were treated successfully and discharged from the hospital, 5 were given a poor prognosis, and 9 died, amounting to a fatality rate of 21.42%. Univariate analysis showed that within 24 h of admission, the differences were statistically significant (p < 0.05) in the comparison of the following factors: lactate concentration, platelets, prothrombin time, fibrinogen, troponin, aspartate aminotransferase, total bilirubin, urinary creatinine, acute gastrointestinal injury, temperature, and Glasgow coma score. However, no statistically significant difference in blood pH was observed between the two groups of patients (p = 0.117). The EHSS, APACHE II, and SOFA scores of the survival group were significantly lower than those of the non-survival group (p < 0.001). The area under the receiver operating characteristic curve of the EHSS, APACHE II and SOFA scores were the area under the curve (AUC) EHSS = 0.96 (0.901, 0.990), AUC Apache II = 0.895 (0.802, 0.950), and AUC SOFA = 0.884 (0.837, 0.964), respectively. Thus, the EHSS diagnostic efficacy of the survival group was significantly higher than that of the other two scores. In addition, the sensitivity and specificity of EHSS were higher than those of the APACHE II and SOFA scores. CONCLUSION: The EHSS has a good diagnostic efficacy for the prognosis of EHS patients and is significantly higher than that of the APACHE II and SOFA scores. This finding provides a theoretical basis for further increasing the rescue success rate of EHS patients and improving their prognostic quality of life.

Isovitexin potentiated the antitumor activity of cisplatin by inhibiting the glucose metabolism of lung cancer cells and reduced cisplatin-induced immunotoxicity in mice.

The increased resistance and toxicity have become the main causes of chemotherapy failure for treating lung cancer. The combination of chemotherapeutic drugs with other agents has been recognized as a promising strategy to overcome these difficulties. Isovitexin (IVT) is a well-known flavone C-glycoside found in many plants and has attracted wide attention due to its obvious antitumor and antioxidant effects. In this study, we investigated the synergistic effects of IVX and cisplatin (DDP) in non-small cell lung cancer (NSCLC) A549 and H1975 cells. The results showed that the combined treatment with IVT and DDP markedly inhibited proliferation and induced apoptosis of the two NSCLC cells. Using a mouse model of A549 xenograft, IVT potentiated the inhibition of DDP on tumor growth, but reduced DDP-induced hepatotoxicity and nephrotoxicity in mice. Remarkedly, IVT promoted lipopolysaccharide (LPS)- and lectin- stimulated splenocyte proliferation, and enhance cytotoxic T lymphocyte (CTL) and natural killer (NK) cell activities as well as the production of IL-2 and TNF-α. Furthermore, IVT significantly reduced glucose uptake, lactate production, and ATP production, and downregulated the protein expressions of pyruvate kinase M2 (PKM2)-mediated pathway in both A549 and H1975 cells. After the over-expression of PKM2 in the NSCLC cells, the synergistic antitumor effect of IVT and DDP was markedly weakened. Therefore, IVT not only inhibited cell proliferation and glucose metabolism via downregulating the expression of PKM2 to enhance the antitumor activity of DDP against lung cancer cells, and improved DDP-induced immunotoxicity in mice. It also presented a novel strategy to enhance the anti-tumor effect of platinum-based chemotherapy against NSCLC.

STIM1 mediates IAV-induced inflammation of lung epithelial cells by regulating NLRP3 and inflammasome activation via targeting miR-223.

AIMS: Influenza A virus (IAV) infection accelerates the inflammatory injury of lung epithelial cells that contributes to pulmonary lesion. Recently, stromal interaction molecule 1 (STIM1) was found to mediate cellular immune response and participated in lung tumorigenesis. Our study aimed to illustrate the function and mechanism of STIM1 in IAV-induced inflammation injury and oxidative stress of lung epithelial cells. MAIN METHODS: We evaluated the levels of STIM1 in IAV-infected patients' serum and BEAS-2B cells using RT-qPCR, Elisa and western blotting methods. MTT and Elisa were performed to measure cell viability and cytokine contents. Besides, ROS intensity, SOD contents and cell apoptosis were detected based on DCFH-DA probe, colorimetry and cell death kits. A luciferase assay and Pearson's correlation analysis evaluated the associations between target genes. KEY FINDINGS: STIM1 was dramatically up-regulated in IAV-infected patients' serum and BEAS-2B cells. Silencing STIM1 in vitro inhibited oxidative stress and inflammatory responses induced by IAV, and reversed cell viability and suppressed apoptosis. Moreover, miR-223 and NLRP3 were negatively and positively correlated with STIM1. STIM1 was found to regulate NLRP3 expression by binding the AACUGAC motif in miR-223. STIM1/miR-223/NLRP3 axis modulated IAV-induced inflammation injury of lung epithelial cells. SIGNIFICANCE: Our evidence indicated that silencing STIM1 alleviated IAV-induced inflammation injury of lung epithelial cells by inactivating NLRP3 and inflammasome via promoting miR-223 expression. These findings may contribute to understand the mechanism of IAV-induced lung injury and help for therapy of IAV infection.

Diagnostic value of medical thoracoscopy for undiagnosed pleural effusions.

To investigate the diagnostic value of medical thoracoscopy for the diagnosis of undiagnosed pleural effusions, a retrospective study was performed on the clinical data of 86 patients with undiagnosed pleural effusions who had medical thoracoscopy at Shaanxi Provincial People's Hospital (Xi'an, China) between May 2012 and November 2013. Of the 86 patients, 79 cases of pleural effusions were confirmed by medical thoracoscopic biopsy with a diagnosis rate of 91.9%. In these 79 confirmed patients, 37 had pleura cancer metastasis (43.0%) and 20 had tuberculous pleuritis (23.3%). The most common type of malignant tumor was lung cancer, accounting for 86.5% of the patients with pleural metastasis. Tuberculosis was often observed in the 16-35 years of age patient group, while malignant tumors were typically detected in the 36-65 year and 65 years and above patient groups. Notably, the overall diagnosis distribution had little connection with sex or smoking-history. Neither mortality nor major complications were observed in patients who received medical thoracoscopy examination. In conclusion, medical thoracoscopy is a safe and effective examination method and has an important diagnostic value for unidentified pleural effusion in patients.

[Varieties textual research, resource investigation and identification of commercial drugs on Cuscutae Semen].

Through the textual research, resource investigation, literature reviews (including Flora of China, municipal Flora, pharmacopoeia of China and municipal drug standards) and identification of commercial drugs on Cuscutae Semen, it was found the species described in the herbal textual was Cuscuta chinensis, with good quality from Shandong and Henan Province. The identification of commodities showed the majority drugs were from C. australis, varied from the ancient herbal textuals .Mordern literature reviews indicate that it was necessary to strengthen the research on Cuscutae Semen from C. australis, C. chinensis and C. japonica because of their differences in resources, macroscopical and microscopical characters, while wrong descriptions in some literatures. It was suggested that the two species (C. australis and C. chinensis) should be separated in pharmacopoeia of China. The study provides scientific basis for the development and utilization of Cuscutae Semen.

[Effect of Polydatin on Epithelial-Mesenchymal Transition of Human Alveolar Epithelium A549 Cells Induced by TGF-ß1].

OBJECTIVE: To explore the effect of polydatin on the growth of TGF-ß1induced humanalveolar epithelium A549 cells and the mechanism of polydatin for inhibiting the process of epithelial-mesenchymal transition (EMT). METHODS: A549 cells in vitro cultured were randomly divided into five groups, i.e., the blank group, the control group, the low dose polydatin group, the middle dose polydatin group, the high dose polydatin group. Common culture fluid was added in A549 cells of the blank group. Five ng/mLTGF-ß1contained culture fluid was added in A549 cells of the control group. 50, 100, and 150 µmol/mL of polydatin plus 5 ng/mL TGF-ß1contained culture fluid was added in A549 cells of low, middle, and high dosepolydatin groups, respectively. Morphological changes were observed and recorded at different time points. The optimal concentration of polydatin was determined by MTT method. Protein and mRNA expressions of E-cad epithelial cell marker) and Vimentin (mesenchymal cell marker) were detected by Western blot and Real-time PCR. RESULTS: Under inverted phase contrast microscope, A549 cells turned from previous pebble shape to fusiform shape after intervened by polydatin and TGF-ß1. The intercellular space was enlargedand the intercellular connection became loose. These phenomena were more obviously seen in the control group. A549 cells were more satiated in low, middle, and high dose polydatin groups than in the control group. The EMT inhibition was most obviously seen in the middle dose polydatin group at 48 h. Protein and mRNA expressions of E-cad showed an overall descending tendency after intervened by polydatin and TGF-ß1 (P < 0.05). But compared with the control group, protein and mRNA expressions of E-cad were down-regulated in a lesser amplitude in each intervened group. Besides, the tendency was more obviously seen at 48 h than at 24 h. Protein and mRNA expressions of Vimentin showed an overall up-regulating tendency. But compared with the control group, protein and mRNA expressions of Vimentin were down-regulated in a lesser amplitude in each intervened group. Besides, the tendency was more obviously seen at 48 h than at 24 h (P < 0.05). CONCLUSIONS Polydatin could inhibit TGF-ß1 induced EMT process of A549 cells time- and dose-dependently. It also played roles in inhibiting pulmonary fibrosis.

Significance of Trask protein interactions in brain metastatic cohorts of lung cancers.

A class of adhesion protein that occurs in the membrane with both extracellular and intracellular domain and play vital role in maintaining multicellularity is TRASK, also called CUB-domain containing protein1, CD318 (CDCP1). Specifically, in the current study, documented aggressive grades of lung cancers and distant metastatic tissues were examined for protein interactions of Trask and compared with lung cancer variants in situ. The intracellular domain of Trask has the ability to undergo tyrosine phosphorylation and thereafter undergo increased genomic expression, as well as interact with cytoskeletal proteins in the cell periphery and other local signal transduction machinery to induce invadopodia formation and distant metastasis. We incorporated proximity ligation assay to examine protein interactions of Trask in metastatic lung cancer tissues and compare with advanced and low-grade lung cancers restricted to the primary site of origins. Here, we provide direct evidence that activated Trask, which is a phosphorylated form, binds with cytoskeletal proteins actin and spectrin. These interactions were not seen in locally growing lung cancer and cancer in situ. These interactions may be responsible for invadopodia formation and breaking free from a multicellular environment. Functional studies demonstrated interaction between Trask and the STOCs Orai1 and Stim1. Calcium release from internal stores was highest in metastatic lung cancers, suggesting this mechanism as an initial stimulus for the cells to respond chaotically to external growth factor stimulation, especially in aggressive metastatic variants of lung cancers. Recently, inhibitors of STOCs have been identified, and preclinical evidence may be obtained whether these drugs may be of benefit in preventing the deadly consequences of lung cancer.

Decitabine plus thalidomide yields more sustained survival rates than decitabine monotherapy for risk-tailored elderly patients with myelodysplastic syndrome.

OBJECTIVE: The open-label, prospective, observational study aimed to evaluate whether decitabine (DAC) plus thalidomide versus DAC monotherapy improved progression-free (PFS), overall survival (OS) and acute myeloid leukemia-free survival (AML-FS) for risk-tailored elderly patients with myelodysplastic syndromes (MDS). METHOD: Enrolled 107 patients (age: 65-82 years) received DAC (52/107) or DAC plus thalidomide (55/107) therapy for MDS. RESULTS: 35/52 patients (67.3%) with DAC therapy reached overall response (OR), compared with 36/55 patients (65.5%) in DAC+thalidomide regimen (P>0.05). DAC+thalidomide administered did not gain more profits of PFS and OS than DAC monotherapy. Risk-tailored analysis showed that DAC+thalidomide therapy did not enhance PFS (48.9% versus 42.8%, P>0.05) and OS (78.6% versus 71.2%, P>0.05) when compared with simple DAC regimen. Nevertheless, DAC+thalidomide markedly improved OS over DAC monotherapy (50.6% versus 40.2%, P<0.05) in high risk profile. Meanwhile, low risk group was superior to high risk group in AML-FS (57.2% versus 21.3%, P<0.01), but DAC+thalidomide still did not prolong 2-year AML-FS when compared with DAC (32.4% versus 27.8%, P<0.05). Moreover, thalidomide had a favorable toxicity profile as a single agent. In comparison with DAC monotherapy, the DAC+thalidomide regimen was relatively well tolerated. There was no severe non-hematological toxicity appearing in elderly patients with MDS. CONCLUSIONS: The study demonstrated that DAC+thalidomide improved 2-year OS for high risk patients. Thalidomide's proven activity and low toxicity profile made it an alternative treatment option for risk-tailored elderly patients with MDS.

A prospective, observational study of added medium-dose cytosine arabinoside versus As2O3 for elderly patients with acute promyelocytic leukemia.

This open-label, prospective, observational study aimed to evaluate disease-free survival (DFS), overall survival (OS), PML-RARα polymerase chain reaction (PCR) monitoring and safety in elderly patients with de novo acute promyelocytic leukemia (APL) who were treated with either arsenic trioxide (As2O3) or medium-dose cytosine arabinoside (MiDAC) as frontline consolidation regimens. A total of 167 patients (age≥65 years old) received all-trans retinoic acid + daunorubicin as induction therapy. Of these patients, 22 died before attaining complete remission; the remaining 145 subjects received MiDAC- or As2O3-based consolidation therapy. As2O3 was superior to MiDAC for improving DFS and OS. This benefit appeared to result from the longer 5-year DFS (92.0 vs. 69.1%, P<0.01) and OS (94.5 vs. 79.7%, P<0.05) of As2O3 compared to MiDAC. PCR monitoring demonstrated that As2O3 promoted a lower positive rate than MiDAC (21.7 vs. 4.5%, P<0.05), but this treatment had no advantage for maintaining a low positive rate in the high-risk group. The most common life-threatening adverse drug effects in patients with MiDAC were platelet counts<25×10(9)/L (85.7%), leukocyte counts<1.0×10(9)/L (81.4%) and severe infection (84.3%). In contrast, the As2O3 regimen rarely caused leukocyte counts<1.0×10(9)/L (22.7%, P<0.01), platelet counts<25×10(9)/L (37.3%, P<0.01) or severe infection (21.3%, P<0.01). These data confirm that MiDAC should not be added during the initial consolidation of patients with APL because this treatment is far less effective, particularly in patients with a low-risk profile, and far more toxic than As2O3.

Interferon α-2b gains high sustained response therapy for advanced essential thrombocythemia and polycythemia vera with JAK2V617F positive mutation.

OBJECTIVE: This open-label, prospective, observational study aimed to evaluate treatment response, efficacy therapy and safety to IFN α-2b for the essential thrombocythemia (ET) and polycythemia vera (PV) with JAK2V617F positive mutation. METHOD: A total of 123 ET patients received IFNα-2b therapy with JAK2V617F positive or negative mutation; and 136 PV patients with JAK2V617F(+) received IFNα-2b or hydroxyurea (HU) therapy according to random number assignment (ages 18-65 years old). RESULT: ET patients receiving IFN α-2b with JAK2V617F(+) had a greater advantage in overall hematologic response (OHR) than JAK2V617F(-) (83.3% versus 61.4%, P<0.01). For PV patients with JAK2V617F(+), IFN had no OHR superiority to HU (70.3% versus 70.8%, P>0.05), but which gained a greater satisfactory molecular response than HU (54.7% versus 19.4%, P<0.01). IFN significantly decreased the phlebotomy rate, which was better than HU for MPDs patients with OHR than HU (3.6% versus 65.7%, P<0.01). Furthermore, ET patients with JAK2V617F(+) demonstrated a definite advantage over JAK2V617F(-) in five-year PFS (75.9% versus 47.6%, P<0.05). For PV patients with JAK2V617F(+), IFN α-2b was superior to HU in five-year PFS (66.3% versus 46.7%, P<0.01). Moreover, IFN α-2b also contributed to improved vasomotor symptoms in MPDs, and especially significantly decreased the incidence of distal paresthesias (14.1% versus 37.5%) and erythromelalgia (9.4% versus 29.2%) better than HU (P<0.01). Meanwhile, IFN did not observe the severe hematological adverse events in patients with PV or ET. CONCLUSION: The data confirmed that IFN α-2b benefited the patients with ET or PV, particularly for JAK2V617F(+) mutation.

How to determine post-FCR therapy for cytogenetic risk-tailored elderly patients with chronic lymphocytic leukemia, maintenance rituximab or observation.

The open-label, prospective, observational study aimed to evaluate whether the addition of maintenance rituximab (MR) improved progression-free survival (PFS) and overall survival (OS), after fludarabine, cyclophosphamide, and rituximab (FCR) for cytogenetic risk-tailored elderly patients with chronic lymphocytic leukemia (CLL). Enrolled 201 patients (ages 65-84 years) who received FCR and gained an overall response. One hundred and four of 201 patients were in the observation (OBS) arm while 97/201 patients continued to receive MR therapy. After FCR, no more benefits were provided by MR versus OBS in cytogenetic better intermediate-risk cohort. PFS at 10 years reached 68.6 versus 58.1 % (P > 0.05). Ten-year OS was 81.8 versus 74.6 % (P > 0.05). However, the improvement of PFS and OS were as dramatic as the improvements of being MR treating versus OBS mainly in the poor-risk cohort. PFS at 10 years reached 57.1 versus 22.7 % (P < 0.01), and 10-year OS was 71.2 versus 41.7 % (P < 0.01). Compared with OBS, no severe hematologic adverse events (AEs) (Grades 3-4) appeared in patients with MR; only some mild non-hematologic AEs incurred (nausea-vomiting 0.96 %, allergy 1.9 % and infection 1.9 %) during the maintenance treatment. The study showed that MR improved 10-year RFS and OS for cytogenetic poor-risk patients with CLL.

Standard intensive chemotherapy is less effective and far more toxic than attenuated induction and post-induction regimen in elderly patients with acute myeloid leukemia.

The open-label, prospective study aimed to evaluate the efficacy and safety for standard intensive chemotherapy compared with attenuated therapy in elderly patients with acute myeloid leukemia (AML). A total of 297 patients between 65 and 82 years were enrolled in the study. The 141 patients received standard-dose therapy (daunorubicin 45 mg/m(2) × 3 days with cytarabine 100 mg/m(2) × 7 days for induction therapy, while post-induction therapy consisted of high-dose cytarabine 1.5 g/m(2) × 4 days), and the attenuated treatment (daunorubicin 30 mg/m(2) × 3 days with cytarabine 75 mg/m(2) × 7 days for induction therapy, while post-induction therapy consisted of attenuated high-dose Ara-C 1.0 g/m(2) × 3 days) was administered to the remaining 156 patients, based on a random number assigned. Total 168 patients (56.6%) achieved complete remission with an incomplete blood recovery (CR)/CRi. No significant differences were observed between the two treatments (P = 0.60). Attenuated chemotherapy improved overall survival (OS) and progression-free survival (PFS) compared to standard-dose therapy; 5-year OS values for these two groups were 39 and 24 months, respectively (P < 0.001), and the PFS values for these two groups were 35 versus 23 months (P < 0.001). In addition, the attenuated treatment with a poor risk profile overcame the negative impact and yielded OS and PFS values similar to those of the standard-dose chemotherapy with a better-to-intermediate risk profile. Five-year OS values for these two groups were 28 versus 28 months (P = 0.89), and the 5-year PFS values were 27 and 28 months, respectively (P = 0.89). The most common adverse drug effect for chemotherapy was agranulocytosis (98.3%). There was a significant difference in early mortality between the attenuated and standard-dose treatment groups (0.64% vs. 7.1%, respectively, P < 0.01). Standard intensive chemotherapy is less effective and far more toxic than attenuated induction and post-induction regimen in elderly patients with AML.

How to determine bortezomib-based regimen for elderly patients with multiple myeloma: PAD versus CBd, an observational study.

BACKGROUND: This was an open-label, observational, prospective assessment. We conducted an analysis of the impact of bortezomib-based therapy (PAD: bortezomib, doxorubicin, high-dose dexamethasone vs. CBd: cyclophosphamide bortezomib, low-dose dexamethasone) on the survival rates and adverse events in elderly patients with newly diagnosed multiple myeloma (MM). METHODS: Out of 303 patients, 128 received the PAD regimen and the other 175 patients received the CBd induction therapy (age 65-89 years). Baseline patient characteristics between the two cohorts were balanced in age (P = 0.69), international staging system (ISS) prognostic stages (P = 0.90), serum calcium (P = 0.70), and serum creatinine (P = 0.52). RESULTS: Overall response (OS) after the induction chemotherapy was achieved in 214 of 303 patients (70.6 %), with no significant differences observed between the two treatment groups (71.9 vs. 69.7 %, P = 0.68). Patients with ISS stage 2 reached the same 5-year OS advantages compared to patients with ISS stage 1, because they received bortezomib-based PAD or CBd treatments. Patients receiving CBd protocol gained similar satisfactory progression-free survival (PFS) results when compared to the PAD regimen group: PFS at 5 years reached 58.2 versus 58.9 % (P = 0.85). Five-year OS in the CBd arm had significant advantages compared to the PAD group, 79.9 versus 49.9 % (P < 0.05). The overall safety profiles showed that 26 of 128 (20.3 %) patients died in the PAD arm, while 13 of 175 patients died (7.4 %) in the CBd group (P < 0.01). Similarly, the PAD arm had a higher serious infection rate than that of the CBd arm (39.2 vs. 13.1 %, P < 0.01). CONCLUSIONS: Bortezomib benefits elderly patients with newly diagnosed MM; they achieve satisfactory treatment responses and survival advantages. Further, patients treated with CBd have superior treatment advantages, with a predictable safety profile, when compared to the PAD regimen.