Research progress in mechanism of anticancer action of shikonin targeting reactive oxygen species.

Excessive buildup of highly reactive molecules can occur due to the generation and dysregulation of reactive oxygen species (ROS) and their associated signaling pathways. ROS have a dual function in cancer development, either leading to DNA mutations that promote the growth and dissemination of cancer cells, or triggering the death of cancer cells. Cancer cells strategically balance their fate by modulating ROS levels, activating pro-cancer signaling pathways, and suppressing antioxidant defenses. Consequently, targeting ROS has emerged as a promising strategy in cancer therapy. Shikonin and its derivatives, along with related drug carriers, can impact several signaling pathways by targeting components involved with oxidative stress to induce processes such as apoptosis, necroptosis, cell cycle arrest, autophagy, as well as modulation of ferroptosis. Moreover, they can increase the responsiveness of drug-resistant cells to chemotherapy drugs, based on the specific characteristics of ROS, as well as the kind and stage of cancer. This research explores the pro-cancer and anti-cancer impacts of ROS, summarize the mechanisms and research achievements of shikonin-targeted ROS in anti-cancer effects and provide suggestions for designing further anti-tumor experiments and undertaking further experimental and practical research.

Feasibility Analysis of Individualized Low Flow Rate Abdominal Contrast-Enhanced Computed Tomography in Chemotherapy Patients: Dual-Source Computed Tomography With Low Tube Voltage.

PURPOSE: The aim of the study is to investigate the feasibility of using dual-source computed tomography (CT) combined with low flow rate and low tube voltage for postchemotherapy image assessment in cancer patients. METHODS: Ninety patients undergoing contrast-enhanced CT scans of the upper abdomen were prospectively enrolled and randomly assigned to groups A, B, and C (n = 30 each). In group A, patients underwent scans at 120 kVp with 448 mgI/kg. Patients in group B underwent scans at 100 kVp with 336 mgI/kg. Patient in group C underwent scans at 70 kVp with of 224 mgI/kg. Quantitative measurements including the CT number, standard deviation of CT number, signal-to-noise ratio, contrast-to-noise ratio, subjective reader scores, and the volume and flow rate of contrast agent were evaluated for each group. RESULTS: There was no statistically significant difference in the subjective image scores within the three groups except for the kidney (all P > 0.05). Group C showed significantly higher CT values, lower noise levels, and higher signal-to-noise ratio and contrast-to-noise ratio values in the majority of the regions of interest compared to the other groups (P < 0.05). In group C, the contrast agent dose was decreased by 46% compared to group A (79.48 ± 12.24 vs 42.7 ± 8.6, P < 0.01), and the contrast agent injection rate was reduced by 22% (2.7 ± 0.41 vs 2.1 ± 0.4, P < 0.01). CONCLUSIONS: The use of 70 kVp tube voltage combined with low iodine flow rates prove to be a more effective approach in solving the challenge of compromised blood vessels in postchemotherapy tumor patients, without reducing image quality and diagnostic confidence.

[Clinical Features and Prognostic Analysis of Newly Diagnosed Diffuse Large B-cell Lymphoma Combined with Hemophagocytic Syndrome].

OBJECTIVE: To compare the clinical features and prognosis between newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients with and without hemophagocytic syndrome (HPS). METHODS: The clinical data of 45 DLBCL patients in Gansu Provincial Hospital from January 2012 to December 2021 were retrospectively analyzed. The patients were divided into HPS group (15 cases) and non-HPS group (30 cases). The clinical features and prognosis of the two groups were compared, and survival analysis was performed using Kaplan-Meier method. RESULTS: Patients with HSP were mostly characterized by fever, cytopenia and splenomegaly. The levels of ferritin and soluble CD25 increased in all patients. The level of fibrinogen decreased in 66.67% patients, while triglyceride increased in 53.33% patients, and bone marrow hemophagocytosis occurred in 80.00% patients. Compared with non-HSP group, the proportions of patients with advanced stage (Ann Arbor stage III/IV) and lactate dehydrogenase (LDH) ≥240 U/L were higher in HSP group (both P < 0.05). The median survival time of HSP group was 8.0 months, which was significantly shorter than 45.5 months of non-HSP group (P < 0.001). CONCLUSION: The DLBCL patients with HPS have later Ann Arbor stage, higher LDH and shorter overall survival time compared with patients without HPS.

[Effects of Different Nutritional Scoring Systems on Prognosis of Elderly Patients with Multiple Myeloma].

OBJECTIVE: To analyze the prognostic nutritional index (PNI), controlling nutritional status (CONUT) and fibrinogen/albumin ratio (FAR) levels in elderly patients with multiple myeloma (MM) and their prognostic impact. METHODS: The clinical data of 74 elderly MM patients diagnosed in Gansu Provincial Hospital from January 2020 to July 2022 were retrospectively analyzed. The optimal cut-off values for PNI, CONUT score and FAR were obtained by receiver operating characteristic (ROC) curve, which were used for grouping patients. The correlation of above three indexes with clinical parameters such as sex, serum calcium (Ca), ß2-microglobulin (ß2-MG), serum creatinine (Cr) in elderly MM patients were analyzed. The survival rates of patients with different levels of each index were compared. Univariate and multivariate analysis of the impact of clinical indicators on the prognosis of patients were performed. RESULTS: The optimal cut-off values for PNI, CONUT score and FAR were 39.775, 3.5 and 0.175, respectively, according to which the patients were divided into high and low group. Statistical analysis showed that there were significant differences in albumin level among different groups (all P < 0.05). In addition, there was a significant difference in hemoglobin between high-PNI group and low-PNI group (P < 0.05), while in sex distribution between high-FAR and low-FAR group (P < 0.05). The survival rate of elderly MM patients with increased PNI, decreased CONUT score and FAR was higher (all P < 0.05). Univariate and multivariate analysis showed that ß2-MG, Cr, PNI, CONUT score and FAR were independent prognostic factors for elderly MM patients. CONCLUSION: PNI, CONUT score and FAR are related to some clinical indicators of elderly MM patients, and have an impact on the prognosis.

Modified endoscopic retrograde appendicitis therapy vs. laparoscopic appendectomy for uncomplicated acute appendicitis in children.

OBJECTIVES: Modified endoscopic retrograde appendicitis therapy (mERAT) has been proposed as an alternative to laparoscopic appendectomy for the treatment of appendicitis. However, data from children in large samples are lacking. The aim of this article is to evaluate the efficacy between mERAT and laparoscopic appendectomy (LA) in children with uncomplicated appendicitis. METHOD: We retrospectively analyzed 594 patients with suspected uncomplicated appendicitis from October 2018 to May 2021. A pool of 294 consecutive patients who met the inclusion criteria were ultimately enrolled in this study (228 and 66 patients in mERAT and LA, respectively). Given the differences in baseline clinical data (gender, age), the regression equation including differences in clinical baseline, grouping factor, and white blood cell count was established to address the influence of potential confounding factors. RESULT: The initial success rate of mERAT management was 96.9%, and the recurrence rate was 6.9% in the mERAT group and 1.7% in the LA group within 1 year, which was no significant difference. But the mERAT group had a lower rate of adverse events. Finally, those results indicated that the treatment modalities, LA or mERAT, had no significant effect on initial success rate (P = 0.99) or recurrence rate (P = 0.17) within 1 year, but a significant effect on the adverse events rate during hospitalization (P = 0.01) in the multivariate regression analysis. CONCLUSION: Among children with uncomplicated appendicitis, an initial mERAT management strategy had a success rate of 96.9%, which was similar to the LA group at 1 year. This follow-up supports the feasibility of mERAT alone as an alternative to surgery for uncomplicated appendicitis.

[Clinical Anslysis of TAFRO Syndrome].

OBJECTIVE: To investigate the clinical characteristics, diagnosis, and treatment of one patient with TAFRO syndrome, and to strengthen the understanding of this rare type. METHODS: The clinical manifestations, diagnosis and treatment process, and prognosis of the patient admitted in Gansu Provincial People's Hospital were retrospectively analyzed. RESULTS: Combined with laboratory tests, bone marrow examination, imaging, pathology, etc, the patient was diagnosed with TAFRO syndrome. After three cycles of treatment with pomalidomide (2-3 mg/d, d1-21), cyclophosphamide (300 mg/m2, 0.54 g once a week) and dexamethasone (20 mg/d, two days a week), platelet count, serum creatinine and procalcitonin returned to normal, the systemic edema disappeared, and the patient's condition was alleviated. The therapeutic effect was good. CONCLUSION: TAFRO syndrome is rare, involves multiple systems, progresses rapidly, and has a worse prognosis. The choice of the "Pomalidomide+cyclophosphamide+dexamethasone" regimen is help to improve the survival prognosis of patient with TAFRO syndrome.

Outcome and characteristics of nonsecretory multiple myeloma compared with secretory multiple myeloma: a retrospective multicenter study from China.

BACKGROUND: Nonsecretory multiple myeloma (NSMM) is a rare type of multiple myeloma (MM). Few studies have described the clinical features and outcomes of NSMM in novel agents. Additionally, the prognostic characteristics have remained controversial in recent years. PURPOSE: To investigate the clinical and prognostic features of NSMM and explore the prognostic value of involved free light chain (FLC) levels in NSMM patients in the Chinese population. METHODS: We retrospectively enrolled 176 newly diagnosed NSMM cases between January 2005 and December 2021 from 19 clinical centers in China. The control group was selected using a 1:4 propensity score matching technique of newly diagnosed secretory MM, with age, sex and diagnosis time as the matching variables. RESULTS: The median age of NSMM patients was 60 years, and 22.6% of patients were classified as ISS stage 3. The ORR of the NSMM patients was 87.4%, and the CR was 65.8%. Compared to the matched secretory MM patients, more NSMM patients achieved CR after first-line treatment (65.8% vs. 36%, p = 0.000). The ORR of first-line treatment was not significantly different between NSMM and secretory MM (89.45% vs. 84.7%, p = 0.196). The first-line PFS was 27.5 m and 23 m (p = 0.063), and the median OS was 81 m and 70 months (p = 0.401). However, for CR-achieved NSMM and CR-not-achieved NSMM patients, the median PFS was 37 m vs. 16 m (p = 0.021), while the median OS showed no difference (107 m vs. 87 m, p = 0.290). In multivariate analysis, the significant factors for PFS were age ≥ 65 and ISS-3. ISS-3 was the only independent prognostic factor of OS. The iFLC ≥ 50 mg/L group had a high ORR of 97.3%, and the median PFS and OS were 48 m and NR, respectively. Compared to the matched secretory MM, the iFLC ≥ 50 mg/L group also showed more CR and longer OS (NR vs. 70 m, p = 0.006) and PFS (48 m vs. 23 m, p = 0.003). CONCLUSIONS: Our results revealed that Chinese NSMM patients are younger and have a higher CR but not superior survival. The subgroup of NSMM patients with iFLC ≥ 50 mg/L had better outcomes than secretory MM.

[Efficacy and Safety of Bendamustine in the Conditioning Regiment for Autologous Hematopoietic Stem Cell Transplantation in Patients with Lymphoma].

OBJECTIVE: To investigate the clinical efficacy and safety of bendamustine in the conditioning regimen for autologous stem cell transplantation in patients with lymphoma. METHODS: The clinical data of 35 patients with lymphoma, including 5 patients of Hodgkin lymphoma and 30 patients of non-Hodgkin lymphoma, who underwent autologous stem cell transplantation after pretreatment with BeEAM regimen from January 2020 to June 2022 in Gansu Provincial Hospital were retrospectively analyzed. Hematopoietic reconstitution, disease outcome after transplantation and the side effects were analyzed. RESULTS: All 35 patients achieved hematopoietic reconstitution after AHSCT，the median time to neutrophil engraftment was 11 (8-15) days, and the median time to platelet engraftment was 12 (9-17) days. Among the 35 patients, 4 patients died at the end of follow-up, including 3 patients died of lymphoma recurrence or progression and 1 patient died of cerebral hemorrhage. Among 34 patients, 30 had no disease progression at the end of follow-up. The OS rates of patients at 12 and 24 months after transplantation were 90.97% and 90.97%, respectively. The 12 and 24 months PFS rates were 89.64% and 84.92%, respectively. Thiry-five patients underwent grade 3-4 bone marrow suppression. The non-hematological toxicity of BeEAM pretreatment regimen mainly included nausea, vomiting, diarrhea, and oral mucositis, 35 patients experienced nausea and vomiting, but only 4 patients had grade 3-4 nausea and vomiting. Eight patients experienced Grade 1-2 diarrhea. Oral mucositis occurred in 12 patients, including 1 patient of grade 3 oral mucositis. One patient with grade 3 oral mucositis also had grade 3-4 hypokalemia and hypon atremia. 8.6% of patients experienced Grade 1-2 abnormal liver and kidney function. An addition, infectious fever occurred in 18 patients during neutropenia. All patients improved after symptomatic treatment, and there were no transplant-related death. CONCLUSION: Bendamustine as a pretreatment regimen for autologous stem cell transplantation in lymphoma is effective, and the side effects are tolerable.

[Clinical Features and Prognosis of Patients with Castleman's Disease].

OBJECTIVE: To analyze the clinical features and prognosis of patients with Castleman's disease (CD) and improve the diagnosis and treatment of CD. METHODS: Clinical data of patients diagnosed with CD by pathological biopsy in Gansu Provincial Hospital from January 2009 to November 2020 were retrospectively analyzed. According to clinical classification, the patients were divided into two groups: UCD (unicentric CD) group (n=20) and MCD (multicentric CD) group (n=9). The clinical manifestations, laboratory examination, treatment regimens, pathological examination and follow-up data were statistically analyzed. RESULTS: There were no significant differences in average age and gender ratio between UCD group and MCD group. In UCD patients, 80.0% were hyaline vascular type, and 20.0% were plasma cell type. In MCD patients, 33.3% were hyaline vascular type, 55.6% were plasma cell type, and 11.1% were mixed type. There was significant difference in pathological classification between the two groups (P=0.039). The UCD patients usually presented asymptomatic single lymph node enlargement with mild clinical symptoms, while the MCD patients were characterized by multiple superficial and deep lymph node enlargement throughout the body. The incidences of asthenia, splenomegaly, serous effusion in MCD group were higher than those in UCD group (P<0.05). Meanwhile, the incidences of anemia, hypoproteinemia, increased ESR, elevated serum globulin and elevated ß2-microglobulin were significantly higher than those in UCD group too (P<0.05). There was no significant difference in the incidences of abnormal WBC, PLT and elevated LDH between the two groups (P>0.05). Among 20 patients with UCD, 13 cases reached complete remission (CR), 1 case achieved partial remission (PR). Among 9 patients with MCD, 3 cases received CR and 4 cases received PR. CONCLUSION: Patients with CD requires pathological examination for diagnosis. Patients with UCD show mild clinical symptoms, good surgical treatment effect and good prognosis. Patients with MCD have diversified clinical manifestations and relatively poor prognosis, and these patients require comprehensive treatment.

Bone Marrow Mesenchymal Stem Cell Exosome Attenuates Inflammasome-Related Pyroptosis via Delivering circ_003564 to Improve the Recovery of Spinal Cord Injury.

Bone marrow mesenchymal stem cell (BMSC) is previously reported to present a certain effect on treating spinal cord injury (SCI), while the underlying mechanism is largely uncovered. Therefore, the current study aimed to investigate the involvement of exosome-delivered circRNA profile in the BMSC's effect on pyroptosis for SCI treatment. H2O2 treated rat primary neurons were cultured with normal medium, BMSC, BMSC plus GW4869, and BMSC-derived exosome, respectively, then inflammasome-related pyroptosis markers, and circRNA profiles were detected. Subsequently, circ_003564-knockdown BMSC exosome was transfected into H2O2 treated rat primary neurons and NGF-stimulated PC-12 cells. Furthermore, in vivo validation was conducted. BMSC and BMSC-derived exosome both decreased inflammasome-related pyroptosis markers including cleaved caspase-1, GSDMD, NLRP3, IL-1ß, and IL-18 in H2O2-treated neurons, while exosome-free BMSC (BMSC plus GW4869) did not obviously reduce these factors. Microarray assay revealed that BMSC (vs. exosome-free BMSC) and BMSC-derived exosome (vs. normal medium) greatly regulated circRNA profiles, which were enriched in neuroinflammation pathways (such as neurotrophin, apoptosis, and TNF). Among three functional candidate circRNAs (circ_015525, circ_008876, and circ_003564), circ_003564 was most effective to regulate inflammasome-related pyroptosis. Interestingly, circ_003564-knockdown BMSC exosome showed higher expression of inflammasome-related pyroptosis markers compared to negative-control-knockdown BMSC exosome in H2O2 treated primary neurons/NGF-stimulated PC-12 cells. In vivo, BMSC exosome improved the function recovery and decreased tissue injury and inflammasome-related pyroptosis in SCI rats, whose effect was attenuated by circ_003564 knockdown transfection. BMSC exosome attenuates inflammasome-related pyroptosis via delivering circ_003564, contributing to its treatment efficacy for SCI.

Association between sedation and small neoplasm detection during diagnostic esophagogastroduodenoscopy: a propensity score-matched retrospective study.

BACKGROUND: Esophagogastroduodenoscopy (EGD) is fundamental for detecting upper gastrointestinal (GI) neoplasms. However, the impact of sedation on small neoplasm detection during EGD has not been evaluated. The aim of this study was to investigate whether EGD with sedation could improve small upper GI neoplasm detection. METHODS: This propensity score-matched retrospective study analyzed the medical records of outpatients undergoing diagnostic EGD at a large tertiary center between January 2013 and December 2018. The primary outcome was the detection rate of small upper GI neoplasms (≤10 mm). The secondary outcomes were biopsy rate and small neoplasms in different anatomic subsites. RESULTS: After propensity score matching, 20,052 patients undergoing diagnostic EGD with or without propofol sedation were identified. A higher detection rate of small upper GI neoplasms was observed in the sedation group (2.80% vs. 2.02%; p < .001). In particular, the detection rate of small cancers in the sedation group was 3-fold higher than that in the no-sedation group (0.16% vs. 0.05%; p = .023). Small neoplasms were more likely identified at the gastric antrum (1.60% vs. 1.09%; p = .002) and angulus (0.66% vs. 0.45%; p = .044) in the sedation group. In addition, endoscopists were more likely to take biopsies when performing sedated EGD (41.4% vs. 36.4%, p < .001), and a higher biopsy rate was associated with an increased detection rate of small neoplasms. CONCLUSIONS: Sedation was significantly associated with a higher detection rate of small upper GI neoplasms and might be recommended for improving the quality of EGD.

Biomass-Based Carbon-Supported Sulfate Catalyst for Efficient Synthesis of Dimethoxymethane from Direct Oxidation of Dimethyl Ether.

The synthesis of dimethoxymethane (DMM) from direct oxidation of dimethyl ether (DME) is a green and competitive route with good atomic economy and low carbon emission and is also an urgent need. In this work, biomass-based carbon-supported sulfate catalysts were designed and prepared for the efficient synthesis of DMM from DME oxidation. The prepared carbon support from cellulose displayed much larger specific surface area and a developed microporous structure, which effectively benefited a high dispersion of sulfate components, leading to mainly weak acid sites and more oxygen functional groups on the catalyst surface. The Ti(SO4)2/PC-H2SO4 catalyst exhibits excellent performance for DME oxidation with DMM1-2 selectivity up to 96.7%, and DMM selectivity reaches 89.1%, notably higher than that of previously reported results. The distinctive surface structure and chemical properties of the carbon support have important impacts on the dispersion state of sulfate species, affecting the acidic and redox properties of the catalysts.

[Clinical Characteristics and Prognosis of Patients with Primary Bone Diffuse Large B-Cell Lymphoma].

AbstractObjective: To investigate the clinical characteristics and prognosis of patients with primary bone diffuse large B-cell lymphoma. METHODS: The clinical data of 15 patients with primary diffuse large B-cell lymphoma treated in our hospital from January 2013 to December 2020 were collected, the clinical data and prognosis of the patients were analyzed retrospectively. RESULTS: The median age of the 15 patients was 59 (19-89) years old; among the patients, 7 were males and 8 were females, ostealgia was the initial symptom. The pathological types of the 15 patients were diffuse large B-cell lymphoma (DLBCL), 5 cases of Has type GCB subtype (5/15), and 10 cases of Non-GCB subtype (10/15). After 15 patients were diagnosed, 11 patients (11/15) received chemotherapy, 3 patients (3/15) received surgery, and 1 patient was untreated (1/15), median chemotherapy courses was 5 (1-9). 8 patients have achieved complete remission (8/15), 3 patients achieved partial remission (3/15), and 1 patient achieved stable disease (1/15), 1 patient was lost to follow-up (1/15), 1 patient was untreated (1/15), and 1 patient was progression of disease (1/15). Age, pathological subtype, sex, stage, ß2-MG level, LDH level, and the using of rituximab were not correlated with the complete remission rate of the patients(P>0.05), while the IPI score was correlated with the recent complete remission rate (P<0.05). The median follow-up time was 19 (1-38) months, 10 patients survived, in which 6 cases were still in complete remission, and the median time to progression-free survival was 15 (1-38) months. CONCLUSION: The first symptom of primary bone diffuse large B-cell lymphoma is bone pain, the main pathological subtype is Non-GCB, the optimal treatment is combined chemotherapy, and the IPI score is related to the prognosis of the treatment.

Treatment and outcome patterns of patients with Waldenström's macroglobulinemia: a large, multicenter retrospective review in China.

In this study, we aimed to investigate treatment options and the prognosis of patients with WM in China. This retrospective study included 1141 patients diagnosed with symptomatic WM between January 2003 and December 2019 at 35 tertiary hospitals in 22 provinces of China. Fifty-four patients (7.3%) received monotherapy, 264 (36.0%) received chemoimmunotherapy, 395 (53.8%) received other combination regimens without rituximab, and 21 (2.9%) received ibrutinib. Using a multivariable Cox regression model, age > 65 years old, platelets <100 × 109/L, serum albumin <3.5 g/dl, ß2 microglobulin concentration ≥4 mg/L and LDH ≥250 IU/L predicted poor OS. In summary, our study showed that frontline treatment choices for WM are widely heterogeneous. We validated most of the established prognostic factors in the rIPSS (age >65 years, LDH ≥250 IU/L, ALB <3.5 g/dl and ß2 microglobulin ≥4 mg/L) together with PLT ≤ 100 × 109/L indicate a poor prognosis for patients with WM.

[Coagulation Indexes and Their Prognostic Significance in Patients with Multiple Myeloma].

OBJECTIVE: To analyze the relationship between coagulation indexes and prognosis of patients with multiple myeloma (MM). METHODS: A total of 99 newly diagnosed MM patients treated in Gansu Provincial Hospital from October 2017 to October 2019 were enrolled. Plasma thromboplastin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-dimer (D-D), platelet (PLT), and other laboratory indexes were detected. The relationship between coagulation indexes and clinical characteristics of MM patients was analyzed. The differences in survival rates among MM patients with different levels of coagulation indexes were compared, and the effect of each clinical index on the prognosis of MM patients was analyzed by univariate and multivariate. RESULTS: Each coagulation index was correlated to sex, disease classification and stage, and ß2-MG level of MM patients. Disease stage and ß2-MG level were positively correlated with coagulation indexes, which means that patients with late-stage disease or high ß2-MG, IgA and IgG levels were more likely to develop into coagulation disorders (P<0.05). The survival rate of patients with MM exhibiting elevated PT, FIB, and D-D levels was significantly lower (P<0.05). Univariate and multivariate analysis showed that each coagulation index was the influencing factor on the follow-up outcomes of MM patients, in which FIB was an independent prognostic factor. CONCLUSION: Coagulation function is correlated with multiple clinical indicators of patients with MM and plays an important role in their prognosis.

[The Influence of Serum Homocysteine Level to the Prognosis of Newly Diagnosed Multiple Myeloma Patients and Analysis of Related Factors].

OBJECTIVE: To analyze the influence of serum homocysteine (Hcy) levels to the prognosis of newly diagnosed multiple myeloma (MM) patients, and to explore related factors affecting the prognosis of the patients. METHODS: The clinical pathological data of 180 newly diagnosed MM patients treated in our hospital from March 2013 to February 2015 were collected, and the patients were divided into high and low Hcy groups based on the median Hcy. The survival curves of the patients in the two groups were drawn to compare the differences of the survival; univariate and multivariate survival analysis was used to observe the influence of serum cysteine to the prognosis of newly diagnosed MM patients; the clinicopathological data of the patients with high and low Hcy in the two groups was compared, Pearson test was used to further analyzes the relationship between Hcy and different factors, and explores the related factors of Hcy affecting the prognosis of the patients. RESULTS: The median survival times of patients in the high and low Hcy groups were 32 (5-59) and 41 (7-71) months, respectively. The 3-year survival rate of the patients in high Hcy group was significantly lower than those in low Hcy group, and the difference shows statistically significant (P<0.05). The results of univariate survival analysis showed that the OS of newly diagnosed MM patients whom with advanced age, high bone disease grade, high-level bone marrow plasma cell count, LDH, C-reactive protein, Cr, ß2-MG, Hcy, low-level Hb, and ALB was significantly shortened (all P<0.05). The results of multivariate survival analysis showed that old age, high levels of bone marrow plasma cells, Cr, ß2-MG, low levels of Hb, and ALB were the independent risk factors shorting the overall survival (OS) time of newly diagnosed MM patients (all P<0.05), while Hcy showed no independent relation for the OS of patients (P>0.05). The Hb level of the patients in high Hcy group was significantly lower than those in low-Hcy group, while the LDH level was significantly higher than those in low Hcy group (all P<0.05). Pearson test results showed that serum Hcy and Hb showed negative correlation (r=-0.813, P<0.05), but it shows positive correlation with LDH (r=0.726, P<0.05). CONCLUSION: Serum Hcy level has a correlation trend with the survival of newly diagnosed MM, which is affected by factors such as Hb.

[Value of Neutrophil/Lymphocyte Ratio and Monocyte/Lymphocyte Ratio in the Prognosis of Patients with Multiple Myeloma].

OBJECTIVE: To investigate the effect of neutrophil/lymphocyte ratio (NLR) and monocyte/lymphocyte ratio (MLR) in the valuation prognosis of patients with multiple myeloma (MM). METHODS: The clinical data of 82 patients with initially diagnosed MM admitted to Gansu Provincial People's Hospital was analyzed retrospectively. NLR and MLR were calculated based on blood routine results respectively. The optimal cut-off point of NLR and MLR was determined according to the ROC curve, and the patients were divided into the high NLR/MLR group and the low NLR/MLR group. The general data, biochemical indicators and prognosis of the patients in each groups were compared respectively. The prognostic significance of the high NLR/MLR group and the low NLR/MLR group in patients between different treatment regimens and different clinical characteristics were analyzed. Risk stratification was designed based on NLR and high MLR as two risk factors, and the effect of risk factors, on the prognosis of MM patients were compared. RESULTS: ROC curve analysis determined that the optimal cut-off point of NLR was 3.1 (sensitivity 75%, specificity 70.7%) and the optimal cut-off point of MLR was 0.34 (sensitivity 83.3%, specificity 53.4%). The lactate dehydrogenase (LDH) and mean platelet volume (MPV) were correlated to NLR and MLR (P<0.05). There were no significant difference in age, sex, serum calcium (Ca), ß 2-microglobulin (ß 2-MG), albumin (Alb), hemoglobin (Hb), platelet (PLT), serum creatinine (Cr), bone marrow plasma cell ratio and ISS stage between the two groups (P>0.05). The OS rate of patients with higher NLR and MLR was lower than those with low NLR and MLR and showed poor prognosis; Further analysis showed that there were statistically significant differences in OS time among patients with different MLR and NLR in the new drug treatment group and the traditional chemotherapy group, as well as patients in different age stratification groups, different ß 2-MG stratification groups and different serum creatinine stratification groups. Patients with 2 risk factors showed a poorer prognosis than those with 0-1 risk factor. CONCLUSION: Elevated NLR and MLR are associated with poor prognosis in MM patients and may serve as the cost-effective and readily available prognostic biomarkers.

[Analysis on Related Factors of Pulmonary Infection in Patients with Multiple Myeloma Treated with Bortezomib].

OBJECTIVE: To analyze the risk factors, distribution of pathogenic strains and tolerance of pulmonary infection in patients with multiple myeloma(MM) during bortezomib chemotherapy. METHODS: The clinical data of 85 patients with multiple myeloma treated by bortezomib in our hospital from January 2015 to January 2019 was analyzed. The patients were divided into infection group and control group according to whether they were infected. The tolerance, pathogen distribution, and related risk factors were retrospectively analyzed. RESULTS: Pulmonary infection rate was 55.29% in 85 MM patients. The proportions of the patients with anemia, neutropenia, and ECOG score ≥2 points in the infection group were significantly higher than those in the control group (P<0.05). In this study, 30 strains of pathogenic bacteria were detected, with gram-negative bacteria accounting for 60%, gram-positive bacteria for 33.33%, fungi for 3.3% and tuberculosis bacteria for 3.3%. Pseudomonas aeruginosa, klebsiella pneumoniae, streptococcus pneumoniae, staphylococcus aureus accounted showed the highest proportion. Most of MM patients with pulmonary infection showed a heterprognosis after two weeks antibiotic treatment, while 3 patients died. About 30 percent of early deaths were due to pulmonary infections. CONCLUSION: Anemia, neutropenia, ECOG score ≥2 points are the major clinical characteristics of the multiple myeloma patients with pulmonary infections. Pulmonary infection is an important cause of early death in patients with multiple myeloma. Pathogenic bacteria are mainly composed of gram-negative bacteria. Beta-lacta/ beta-lactamase inhibitor combinations or Carbapenems are effective empiric treatment for controlling the progression of pulmonary infection.

[Analysis of Risk Factors of Herpes Zoster in Patients with Multiple Myeloma Treated with Bortezomib].

OBJECTIVE: To explore and analyze the risk factors of herpes zoster in patients with multiple myeloma (MM) during the chemotherapy with bortezomib. METHODS: Clinical data of 85 MM patients treated with bontizomib from January 2015 to January 2019 were selected and divided into case group and control group accroding to the occurred of herpes zoster. The clinical characteristic, treatment outcome and related factor of herpes zoster were retrospective analyzed. RESULTS: Twenty of the 85 patients with MM treated with bortezomib developed herpes zoster occurred (23.5%). Single-factor analysis showed that age≥65 years, lymphocytopenia occurred before treatment, neutropenia occurred before treatment, ECOG score≥2, application of cyclophosphamide, absence of preventive antiviral therapy were associated with the genesis of herpes zoster (P＜0.05). Multivariate logistic regression analysis showed that lymphocytopenia occurred before treatment, the application of cyclophosphamide and the absence of preventive antiviral therapy were the independent risk factors for herpes zoster (P＜0.05). CONCLUSION: The incidence of herpes zoster is high in the multiple myeloma patients treated with bortezomib. Lymphocytopenia occurred before treatment, the application of cyclophosphamide, and the absence of prophylactic antiviral therapy are the important risk factors for herpes zoster, for which the clinicians should attach great importance.

The involvement of hsa_circ_0000417 in the development of hypospadias by regulating AR.

BACKGROUND: Congenital hypospadias is a common congenital malformation of the urinary system in male children. However, the role of circRNA in congenital hypospadias remains unknown. METHODS: Differentially expressed circRNAs and mRNAs were identified by RNA sequencing. GO and KEEG analysis were performed to uncover the key function and pathways. The interaction networks were constructed and analyzed by competing endogenous (ce)RNA analysis. Immunohistochemistry (IHC) and qRT-PCR were used to detect the expressions of androgen receptor (AR) and hsa_circ_0000417 in normal and hypospadias tissues. Further, the correlation between hsa_circ_0000417 and other clinical indicators were calculated. RESULTS: Compared with normal foreskin tissues, 1329 circRNAs and 978 mRNAs were significantly upregulated, 3176 circRNAs and 614 mRNAs were significantly downregulated in hypospadias tissues, respectively. MAPK and PI3K-Akt signaling pathways play important roles in congenital hypospadias. The expression of AR and hsa_circ_0000417 in 68 hypospadias tissues was significantly lower than that in 68 normal foreskin tissues (P < 0.05). The expression of the AR, as analyzed using IHC, was consistent with the qPCR results. A significant correlation was noted between the expression of AR and hsa_circ_0000417 in 68 clinical samples (P < 0.05). Furthermore, the expression level of hsa_circ_0000417 was associated with the incidence of other diseases and the location of the hypospadias site (P < 0.05). Expression of hsa_circ_0000417 was significantly downregulated in hypospadias patients without other diseases (P < 0.05). CONCLUSION: Hsa_circ_0000417 may regulate the expression of AR, and the expression of hsa_circ_0000417 in normal foreskin tissues is associated with the occurrence of hypospadias.