[Treatment status of tyrosine kinase inhibitor for newly-diagnosed chronic myeloid leukemia: a domestic multi-centre retrospective real-world study].

Objective: To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China. Methods: Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed. Results: 6 893 patients in CP (n=6 453, 93.6%) or AP (n=440, 6.4%) receiving initial imatinib (n=4 906, 71.2%), nilotinib (n=1 157, 16.8%), dasatinib (n=298, 4.3%) or flumatinib (n=532, 7.2%) -therapy. With the median follow-up of 43 (IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance (n=1 055, 15.3%), intolerance (n=248, 3.6%), pursuit of better efficacy (n=168, 2.4%), economic or other reasons (n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph(+) ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph(+) ACA, poorer TFS; Ph(+) ACA, poorer OS. Conclusion: At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Clinical characteristics and risk factors of diabetic foot ulcers with PAD.

OBJECTIVE: This study aimed to analyze the clinical characteristics of patients with diabetic foot ulcers combined with peripheral arterial disease (PAD) and the risk factors. PATIENTS AND METHODS: A retrospective study was conducted on 120 patients with diabetic foot ulcers in the Second Affiliated Hospital of Dalian Medical University from October 2018 to February 2021. The patients were divided into uncombined with the PAD group (42 cases) and combined with the PAD group (78 cases). The baseline information and clinical indicators were measured from two groups. Univariate and binary logistic regression was used to analyze the risk factors of PAD in patients with diabetic foot ulcers. RESULTS: The proportion of patients with age ≥ 60 years, Wagner grade 4-5 and smoking history in the combined group was higher than that in the uncombined group (p < 0.05). The diastolic blood pressure (DBP) of the combined group was lower than that of the uncombined group, while the C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and glycated hemoglobin (HbA1c) levels of the combined group were higher than those of the uncombined group (p < 0.05). Binary logistic regression analysis showed that age ≥ 60 years, high Wagner grade, smoking, elevated CRP, NLR and HbA1c levels were risk factors for patients with diabetic foot ulcer combined with PAD (OR > 1, p < 0.05). An elevated DBP level was the protective factor for PAD in patients with diabetic foot ulcer (OR < 1, p < 0.05). CONCLUSIONS: Patients with diabetic foot ulcer combined with PAD have the clinical characteristics of poor blood pressure control, long course of disease, and low ABI value. Age ≥ 60 years, high Wagner grade, smoking history, elevated CRP, NLR and HbA1c levels are the risk factors of PAD in patients with diabetic foot ulcer. Increased DBP is protective for PAD in patients with diabetic foot ulcer.

[To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia].

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

[Construction and validation of a nomogram model of early related factors for hepatic insufficiency after hemihepatectomy].

Objectives: To investigate the early related factors for hepatic insufficiency after hemihepatectomy and to construct and validate a nomogram model. Methods: This was a retrospective cohort study.There were 207 patients with liver tumor who underwent hemihepatectomy in the Department of Hepatobiliary Surgery,Cancer Hospital,Chinese Academy of Medical Sciences from October 2016 to December 2022. Using the random number method,patients were randomly divided into a model group(n=166) and a validation group(n=41) according to an 4︰1 ratio. There were 118 males and 48 females in the modeling group,with an age (M(IQR)) of 59.0(13.3) years (range: 22.0 to 81.0 years),42 patients in the group with postoperative liver insufficiency and 124 patients in the group without postoperative liver insufficiency. There were 32 males and 9 females in the validation group, with an age of 54.0(19.0) years (rang: 25.0~81.0 years). The first results of the peripheral blood test of patients within 24 hours after surgery were collected,and the independent related factors for incomplete postoperative liver function were determined by multivariate Logistic regression analysis,and related factors of postoperative incomplete liver function were screened by best subset selection. A nomogram model of the risk of postoperative hepatic insufficiency after hemihepatectomy was constructed using R software,followed by internal and external validation of the model. Results: Multivariate logistic regression analysis showed that elevated D-dimer level and decreased antithrombin Ⅲ (AT-Ⅲ) activity within 24 hours after surgery were independent related factors for the development of postoperative hepatic insufficiency in hemihepatectomized patients. The results of the best subset selection showed that ALT,D-dimer, and AT-Ⅲ activity levels within 24 hours postoperatively were the most relevant factors for postoperative hepatic insufficiency. The R software was applied to build a nomogram prediction model based on the above three indicators in the model set,and the receiver operating characteristic(ROC) curve of the model showed an area under the curve of 0.803 and the calibration curve showed a U-index of -0.012 for the model(P=0.977). The results of the clinical decision analysis and the clinical impact curve indicated that the model had good clinical utility. The internal validation results of the Bootstrap method suggested that the model had reasonable consistency. The area under the ROC curve of the validation group model was 0.806,suggesting that the model had a good generalization prediction ability. Conclusions: The levels of ALT,D-dimer,and AT-Ⅲ activity within 24 hours after hemihepatectomy are valuable indicators for predicting liver insufficiency after hemihepatectomy. The nomogram model is reliable and can be used as an indicator for close postoperative monitoring.

TLR4-MyD88-NF-κB signaling imbalances Th17 and Treg cells in thymoma with myasthenia gravis.

OBJECTIVE: Thymus is an immune organ in which pathological changes may cause autoimmune diseases, including myasthenia gravis (MG). Recent studies have focused on Toll-like receptor 4 (TLR4) signaling as the cause of such changes. In our previous study, an imbalance of T helper 17 (Th17) cells and T regulatory (Treg) cells was found in MG thymoma. These results suggest the involvement of TLR4 in the pathogenesis of thymoma MG via an alteration of the Th17/Treg balance. Here, we aimed to assess whether the TLR4-MyD88-NF-κB pathway is upregulated in MG thymoma and its relationship with Th17/Treg cells. PATIENTS AND METHODS: We collect thymoma samples from 54 patients with or without MG, detecting the expression level of TLR4, MyD88, and NF-κB in thymoma tissues. Next, we established an in vitro experiment of coculturing thymoma cells with CD4+ T cells and detected the differentiation of Th17 cells and Treg cells and their marker protein, retinoid-related orphan receptor gamma t (RORγt) and forkhead transcription factor 3 (Foxp3). RESULTS: We found TLR4, MyD88, and NF-κB expressed more in MG thymoma compared with simple thymoma. After the transwell coculturing, we observed an imbalance of Th17/Treg cells after TLR4 stimulation. CONCLUSIONS: TLR4 is stimulated in thymoma, causing an increase of Th17 cells and a decrease of Treg cells, namely an imbalance of Th17/Treg cells, resulting in MG.

[Factors influencing severe cytopenia in chronic phase chronic myeloid leukemia patients receiving initial second generation tyrosine kinase inhibitors and its impact on treatment responses and outcomes].

Objective: To explore the influencing covariates of severe neutrophils and/or thrombocytopenia and their effect on treatment response and outcome in patients with chronic-phase chronic myeloid leukemia (CP-CML) receiving initial second-generation tyrosine kinase inhibitors (2G-TKI) . Methods: Data from consecutive patients aged ≥18 years with newly diagnosed CP-CML who received initial 2G-TKI at Peking University People's Hospital from September 2008 to November 2021 were interrogated. Binary logistic regression models and Fine-Gray and Cox regression models were applied. Results: Data from 267 patients who received initial 2G-TKI, including nilotinib (n=239, 89.5% ) and dasatinib (n=28, 10.5% ) , were interrogated. The median age was 36 (range, 18-73) years, and 156 (58.4% ) patients were male. At a median treatment period of 1.0 (0.1-3.0) month, 43 (16.1% ) patients developed grade ≥3 neutrophils and/or thrombocytopenia and recovered within 1.0 (0.1-24.6) month. Male (OR=2.9, 95% CI 1.2-6.8; P=0.018) , age of ≥36 years (OR=3.2, 95% CI 1.4-7.2, P=0.005) , a spleen below a costal margin of ≥7 cm (OR=2.8, 95% CI 1.2-6.6, P=0.020) , and a hemoglobin (HGB) level of <100 g/L (OR=2.9, 95% CI 1.3-6.8, P=0.012) at diagnosis were significantly associated with grade ≥ 3 neutrophils and/or thrombocytopenia. Based on their regression coefficients, male, age of ≥36 years, a spleen below a costal margin of ≥7 cm, and an HGB level of <100 g/L were given 1 point to form a predictive system. All patients were divided into three risk subgroups, and the incidence of severe cytopenia significantly differed among the three groups (P < 0.001) . Grade ≥3 neutrophils and/or thrombocytopenia for >2 weeks was significantly associated with lower cumulative incidences of complete cytogenetic response (CCyR, HR=0.5, 95% CI 0.3-0.7, P<0.001) and major molecular response (MMR, HR=0.4, 95% CI 0.3-0.8, P=0.004) and was not significantly associated with failure, progression, and survival. Conclusion: Male, advanced age, a large spleen, and a low HGB level were significantly associated with severe cytopenia. The four covariates were used to establish a prediction model, in which the incidence of severe cytopenia among different risk groups was significantly different. Severe cytopenia for >2 weeks was a negative factor for responses but not for outcomes.

[Incidence and prognosis of olfactory and gustatory dysfunctions related to infection of SARS-CoV-2 Omicron strain: a national multi-center survey of 35 566 population].

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.

[A brief discussion on the inspiration and thinking of the Metaverse concept to promote the innovative development of intelligent medicine in China].

Created by digital technology,the Metaverse is a digital platform where the digital virtual world and the actual real world can coexist to some extent. Based on the integration of Metaverse and medical science,this article describes the great development of intelligent medicine in the fields of medical practice,medical education and medical research,especially in the field of surgery. First,the technical source of the Metaverse concept in the field of intelligent medicine can be traced back to technology to generate actual digital data sets from human anatomy. Second,the successful industrial practice of Metaverse in the field of intelligent medicine conforms to the authentic and credible fundamental purpose of "taking people as the first priority and serving people"， that is， "virtual" must be based on "actual" for "actual".

[A scoring system to predict molecular responses in patients with chronic myeloid leukemia in the chronic phase receiving initial imatinib therapy].

Objective: To develop a scoring system to predict molecular responses in patients with chronic myeloid leukemia in the chronic phase (CML-CP) receiving initial imatinib therapy. Methods: Data from consecutive adults with newly diagnosed CML-CP treated by initial imatinib was interrogated and subjects were distributed randomly into training and validation cohort, in a ratio of 2∶1. Fine-gray models were applied in the training cohort to identify co-variates of predictive value for major molecular response (MMR) and MR4. A predictive system was built using significant co-variates. The predictive system was then tested in the validation cohort and the area under the receiver-operator characteristic curve (AUROC) was used to estimate accuracy of the predictive system. Results: 1 364 CML-CP subjects receiving initial imatinib were included in this study. Subjects were distributed randomly into training cohort (n=909) and validation cohort (n=455) . In the training cohort, the male gender, European Treatment and Outcome Study for CML (EUTOS) Long-Term Survival (ELTS) intermediate-risk, ELTS high-risk, high WBC (≥130×10(9)/L or 120×10(9)/L, MMR or MR4) and low HGB (<110 g/L) at diagnosis were significantly related with poor molecular responses and were given points based on their regression coefficients. For MMR, male gender, ELTS intermediate-risk and low HGB (<110 g/L) were given 1 point; ELTS high-risk and high WBC (≥130×10(9)/L) , 2 points. For MR4, male gender was given 1 point; ELTS intermediate-risk and low HGB (<110 g/L) were given 2 points; high WBC (≥120×10(9)/L) , 3 points; ELTS high-risk, 4 points. We divided all subjects into 3 risk subgroups according to the predictive system above. Cumulative incidence of achieving MMR and MR4 in 3 risk subgroups was significantly different in both training and validation cohort (all P values <0.001) . In the training and validation cohorts, the time-dependent AUROC ranges of MMR and MR4 predictive systems were 0.70-0.84 and 0.64-0.81, respectively. Conclusions: A scoring system combining gender, WBC, HGB level and ELTS risk was built to predict MMR and MR4 in CML-CP patients receiving initial imatinib therapy. This system had good discrimination and accuracy, which could help phsicians optimize the selsction of initial TKI-therapy.

[Comparison of follow-up treatment regimens for colorectal cancer liver metastases without objective response to neoadjuvant chemotherapy: direct surgery or surgery after second-line chemotherapy].

Objective: To compare the effect of direct surgery or surgery after second-line chemotherapy for colorectal cancer patients with liver metastases who did not achieve objective remission after neoadjuvant chemotherapy. Methods: A retrospective case cohort study was used. The clinical and pathological data of 107 patients with colorectal cancer liver metastases who did not achieve objective response to neoadjuvant chemotherapy at Department of Hepatobiliary Surgery,Cancer Hospital,Chinese Academy of Medical Sciences from December 2008 to December 2016 were retrospectively collected. There were 71 males and 36 females, median age was 57 years (range: 28 to 79 years). According to the different treatment regimens after neoadjuvant chemotherapy,107 cases were divided into a direct surgery group (direct group,n=65) and an operation after receiving second-line chemotherapy group (second-line group,n=42). The propensity score matching(PSM) of the Logistic regression model was used to match the bilobar distribution of liver metastases and the number of first-line chemotherapy cycles in the two groups of patients. The caliper value was set to 0.10 and the matching ratio was 1∶2. T test, Mann-Whitney U test, χ2 test or Fisher's exat test was used to analyzed the data between the tuo groups, respectively. Survival analysis design was used to investigate the difference in prognosis between the two groups of patients. Results: The follow-up time(M(IQR)) was 56.3(34.3) months (range: 2.1 to 95.0 months),and all patients were followed up. After PSM,there were 28 cases in the direct group and 42 cases in the second-line group, there were no significant differences in whether R0 resection was feasible,blood loss,blood transfusion,postoperative complications and postoperative hospital stay between the two groups (all P>0.05). The 1,3,and 5-year progression-free survival(PFS) rates of the direct group were 40.0%,16.5%,and 11.0%,and the 1,3,and 5-year overall survival(OS) rates were 98.5%,61.2%,and 41.4%,respectively, the second-line group 1,3,5 years PFS rates were 35.7%,14.3%,14.3%,1,3,5-year OS rate were 95.2%,55.1%,44.4%,respectively. The median PFS time of the direct group and the second-line group was 8.5 months and 7.5 months,respectively,and the difference was not statistically significant (P=0.826). The median OS time of the direct group and the second-line group were 33.8 months and 46.9 months,respectively. The difference was not statistically significant(P=0.646).The median PFS time of the direct group and second-line chemotherapy complete remission and partial remission group(CR/PR group) was 10.2 months and 9.1 months,respectively,and the difference was not statistically significant(P=0.669). The median OS time of the direct group and the second-line CR/PR group was 51.0 months and 46.9 months,respectively,and the difference was not statistically significant(P=0.427). The results of survival analysis suggested that major liver resection was an independent prognosis factor for PFS (HR=1.809,95%CI: 1.067 to 3.067,P=0.028) and OS(HR=2.751,95%CI: 1.317 to 5.747,P=0.007). Second-line chemotherapy was not an independent prognostic factor for PFS (HR=0.945, 95%CI:0.570 to 1.567,P=0.828) and OS (HR=0.866,95%CI: 0.468 to 1.602,P=0.646). Conclusions: There is no significant difference in the short-term outcome and long-term prognosis between direct surgery patients and second-line chemotherapy followed by surgery. Second-line chemotherapy is not an independent prognostic factor for colorectal cancer liver metastases patients who fail to achieve objective response after neoadjuvant chemotherapy.

[Combination of socio-demographic and clinical co-variates for predicting treatment responses and outcomes in patients with chronic myeloid leukemia in the chronic phase].

Objective: To explore the impacts of socio-demographic and clinical co-variates on treatment responses and outcomes in patients with chronic myeloid leukemia in the chronic phase (CML-CP) receiving tyrosine kinase inhibitor (TKI) and identified the predictive models for them. Methods: Data of newly diagnosed adult patients with CML-CP receiving first-line TKI and having complete socio-demographic data and clinical information were reviewed. Cox model was used to identify the independent variables associated with complete cytogenetic response (CCyR) , major molecular response (MMR) , molecular response 4 (MR(4)) and molecular response 4.5 (MR(4.5)) , as well as failure-free survival (FFS) , progression-free survival (PFS) , overall survival (OS) and CML-related OS. Results: A total of 1414 CML-CP patients treated with first-line imatinib (n=1176) , nilotinib (n=170) or dasatinib (n=68) were reviewed. Median age was 40 (18-83) years and 873 patients (61.7% ) were males. Result of the multivariate analysis showed that lower educational level (P<0.001-0.070) and EUTOS long-term survival intermediate or high-risk (P<0.001-0.009) were significantly associated with lower cumulative incidences of CCyR, MMR, MR(4) and MR(4.5), as well as the inferior FFS, PFS, OS and CML-related OS. In addition, those who were males, from rural households, had white blood cells (WBC) ≥120×10(9)/L, hemoglobin (HGB) <115 g/L and treated with first-line imatinib had significantly lower cumulative incidences of cytogenetic and/or molecular responses. Being single, divorced or widowed, having, rural household registration, WBC≥120×10(9)/L, HGB<15 g/L, and comorbidity (ies) was significantly associated with inferior FFS, PFS, OS, and/or CML-related OS. Thereafter, the patients were classified into several subgroups using the socio-demographic characteristics and clinical variables by cytogenetic and molecular responses, treatment failure and disease progression, as well as overall survival and CML-related OS, respectively. There were significant differences in treatment responses and outcomes among the subgroups (P<0.001) . Conclusion: Except for clinical co-variates, socio-demographic co-variates significantly correlated with TKI treatment responses and outcomes in CML-CP patients. Models established by the combination of independent socio-demographic and clinical co-variates could effectively predict the responses and outcome.

[Survey and analysis of the concerns of patients with chronic myeloid leukemia in China in 2021].

Objective: To investigate the concerns of adult patients with chronic myeloid leukemia (CML) in the chronic phase receiving tyrosine kinase inhibitor (TKI) therapy in China. Methods: A cross-sectional questionnaire including 23 issues of concern was filled by patients with CML nationwide from August to September 2021. The results were compared with those from 2015 to 2016. Results: Data from 952 questionnaires were analyzed. The five most concerned issues were "TKI-related adverse effects and management" (66%) , "stopping TKI therapy" (46%) , "CML risk assessment" (46%) , "TKI dose reduction" (42%) , and "restrictions in daily life activities" (41%) . Compared with the results from 2015 to 2016, patients paid more attention to "TKI-related adverse effects and management" , "monitoring" , and "interpretation of laboratory reports" (all P<0.01) . Concerns of "TKI reimbursement policies" , "price reduction of TKIs" , and issues related to generic TKIs decreased significantly (all P<0.01) . Multivariate analysis showed that female patients (OR=1.8, 95% CI 1.4-2.5, P<0.001) , elderly patients (OR=1.0, 95% CI 1.0-1.0, P<0.001) , or patients with bachelor's degree or higher (OR=1.8, 95% CI 1.3-2.4, P<0.001) were more concerned with "TKI dose reduction" than others. Patients with a bachelor's degree or higher (OR=1.6, 95% CI 1.2-2.2, P=0.002) paid more attention to "CML risk assessment" , whereas those currently receiving a second- or third-generation TKI therapy (OR=1.9, 95% CI 1.3-2.6, P<0.001) were more concerned about "TKI resistance" . Conclusion: Patients with CML paid the most attention to "TKI-related adverse effects and management" , "stopping TKI therapy" , "CML risk assessment" , "TKI dose reduction" , and "restrictions in daily life activities" . Patients' sociodemographic covariates and treatment status were associated with their concerns.

[Efficacy analysis of the radiotherapy and chemotherapy in patients with stage â £ esophageal squamous carcinoma: a multicenter retrospective study of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG R-01F)].

Objective: To evaluate the survival and prognostic factors of radiotherapy in patient with Ⅳ stage esophageal squamous carcinoma treated with radiation or chemoradiation. Methods: The medical records of 608 patients with stage Ⅳ esophageal squamous cell carcinoma who met the inclusion criteria in 10 medical centers in China from 2002 to 2016 were retrospectively analyzed. The overall survival and prognostic factors of all patients at 1, 3 and 5 years were analyzed. Results: The 1-, 3-, 5- year overall survival (OS) rates was 66.7%, 29.5% and 24.3% in stage ⅣA patients, and 58.8%, 29.0% and 23.5% in stage ⅣB patients. There was no statistical difference between the two groups (P=0.255). Univariate analysis demonstrated that the length of lesion, treatment plan, planned tumor target volume (PGTV) dose, subsequent chemotherapy, and degrees of anemia, radiation esophagitis, radiation pneumonia were related to the prognoses of patients with Ⅳ stage esophageal carcinomas after radiotherapy and chemotherapy (P<0.05). Multivariate analysis demonstrated that PGTV dose (OR=0.693, P=0.004), radiation esophagitis (OR=0.867, P=0.038), and radiation pneumonia (OR=1.181, P=0.004) were independent prognostic factors for OS. Conclusions: For patients with stage Ⅳ esophageal squamous cell carcinoma, chemoradiotherapy followed by sequential chemotherapy is recommended, which can extend the total survival and improve the prognosis of the patients. PGTV dose more than 60 Gy has better efficacy.

The natural history and patterns of metastases from mucosal melanoma: an analysis of 706 prospectively-followed patients.

Background: We examined whether mucosal melanomas are different in their clinical course and patterns of metastases when arising from different anatomic sites. Our hypothesis was that metastatic behavior would differ from primary mucosal melanomas at different anatomical sites. Patients and methods: Clinical and pathological data from 706 patients were compared for their stage distribution, patterns of metastases, CKIT/BRAF mutation status, and overall survival for different anatomical sites. Results: The anatomic sites of the primary mucosal melanomas were from the lower GI tract (26.5%), nasal cavity and paranasal sinuses (23%), gynecological sites (22.5%), oral cavity (15%), urological sites (5%), upper GI tract (5%), and other sites (3.0%). At initial diagnosis, 14.5% were stage I disease, 41% Stage II, 21.5% Stage III, and 23.0% stage IV. Predominant metastatic sites were regional lymph nodes (21.5%), lung (21%), liver (18.5%), and distant nodes (9%). Oral cavity mucosal melanoma had a higher incidence of regional nodal metastases (31.7% versus 19.8%, P = 0.009), and a higher incidence of lung metastases (32.5% versus 18.5%, P = 0.007) compared to other primary mucosal melanomas. There was a 10% incidence of CKIT mutation and 12% BRAF mutation. Mucosal melanomas from nasal pharyngeal and oral, gastrointestinal, gynecological, and urological had a similar survival with a 1-year survival rate (88%, 83%, 86%), 2-year survival rate (66%, 57%, 61%), 5-year survival rate (27%, 16%, 20%), respectively. Conclusions: The largest sample size allows, for the first time, a comparison of primary melanoma stage and patterns of metastases across anatomical sites. With few exceptions, the presenting stages, incidence of nodal and distant metastases, the site of predilection of distant metastases, or overall survival were similar despite different primary anatomic sites. These findings suggest that clinical trials involving mucosal melanomas and the administration of systemic therapy can be applied equally to mucosal melanomas regardless of their primary anatomic site.

[Phonological assessment and voice analysis of thyroid surgery patients].

Objective:To investigate the changes of speech and voice acoustics in patients with thyroid disease before and after operation, get objective values, and conducive to guiding the clinical diagnosis and treatment and recurrent laryngeal nerve protection. Method:A total of 216 patients undergoing thyroid surgery from October 2015 to October 2016 were treated with TVQ and GRBAS at 1 day before surgery, 1 week, 1 month, and 3 months postoperatively to phonological assessment, and Praat software was used to collect and analyze the acoustic acoustics index for preoperative and postoperative comparative analysis. Result:All patients did not damage the recurrent laryngeal nerve, unilateral or bilateral thyroid subtotal resection (no exploration of recurrent laryngeal nerve) in patients with postoperative speech and voice index F0 was decreased at 1 week after surgery (P<0.05), the other indicators did not change significantly; difference was found out in single-sided total thyroidectomy+ipsilateral central area lymph node dissection, bilateral thyroidectomy+unilateral central area lymph node dissection (exploration of unilateral recurrent laryngeal nerve) in patients with TVQ, GRBAS and F0, HNR after surgery 1 week compared with preoperative (P<0.05), However, there was no significant difference 3 months; TVQ, GRBAS and F0, HNR were significantly changed in patients with bilateral thyroidectomy+bilateral central lymph node dissection (revealed bilateral recurrent laryngeal nerve) at 1 week after operation (P>0.05). F0 and HNR were lower than those before operation, and the patients were treated with Jitter and Shimmer. The patients were treated with TVQ, GRBAS, Jitter and Shimmer before operation, however, the majority of patients' TVQ, GRBAS, Jitter, Shimmer can be restored to preoperative level after surgery 3 months (P>0.05). Conclusion:The appearance of speech and voice problems in patients after thyroid surgery may increase with the expansion of the surgical range, the change in speech and voice after neck lymph node dissection is reversible.

[A comparative study of therapy effects between esomeprazole plus mosapride citrate and botulinum toxin injection on vocal process granuloma].

Objective:Anti-reflux medications or botulinum toxin A injections are the main current therapies for the definite vocal process granuloma. This studies is focusing on comparing the effects of proton pump inhibitors plus prokinetic agents with botulinum toxin A injections on vocal process granuloma. Method:Adult patients in our outpatient department (from December 2014 to June 2016) complaining of trachyphonia and/or abnormal pharyngeal sensations who were found to have contact granulomas (38 cases) were included. Patients were divided into two groups according to the treatment selected by themselves: esomeprazole with mosapride citrate (n=28) or botulinum toxin A injection (n=20). The reflux symptom index and reflux finding score determined by electronic fibrolaryngoscopy were utilized to assess efficacy. Result:There was no statistical difference on age, sex and reflux symptom index and reflux finding score before treatment between the two groups. Total effective rate in the esomeprazole with mosapride citrate group and the botulinum toxin A group were 96.43% and 45.00%, separately. The recorded symptoms after therapy resolved with a statistically significant improvement in the esomeprazole with mosapride citrate group. Conclusion:Combined proton pump inhibitor plus prokinetic drug therapy plays a significant role in the treatment of vocal process granulomas.

CXCL2/MIF-CXCR2 signaling promotes the recruitment of myeloid-derived suppressor cells and is correlated with prognosis in bladder cancer.

The accumulation of myeloid-derived suppressor cells (MDSCs) has been observed in solid tumors and is correlated with tumor progression; however, the underlying mechanism is still poorly understood. In this study, we identified a mechanism by which tumor cells induce MDSC accumulation and expansion in the bladder cancer (BC) microenvironment via CXCL2/MIF-CXCR2 signaling. Elevated expression of CXCL2 and MIF and an increased number of CD33+ MDSCs were detected in BC tissues, and these increases were significantly associated with advanced disease stage and poor patient prognosis (P<0.01). A positive association was observed between CXCL2 or MIF expression and the number of tumor-infiltrating CD33+ MDSCs (P<0.01). Subsequently, we demonstrated that CD45+CD33+CD11b+HLA-DR- MDSCs from fresh BC tissues displayed high levels of suppressive molecules, including Arg1, iNOS, ROS, PDL-1 and P-STAT3, and stronger suppression of T-cell proliferation. Interestingly, these CD45+CD33+CD11b+HLA-DR- MDSCs exhibited increased CXCR2 expression compared with that in peripheral blood from BC patients or healthy controls (P<0.05). Chemotaxis assay revealed that bladder cancer cell line J82 induced MDSC migration via CXCL2/MIF-CXCR2 signaling in vitro. Mechanistic studies demonstrated that J82-induced MDSC trafficking and CXCR2 expression were associated with increased phosphorylation of p38, ERK and p65. Conversely, inhibition of the phosphorylation of p38, ERK or p65 decreased J82-induced MDSC trafficking and CXCR2 expression. CXCL2/MIF-stimulated activation of the mitogen-activated protein kinase and nuclear factor kappa B pathways in MDSCs was MyD88 dependent. Overall, our results identify the CXCL2/MIF-CXCR2 axis as an important mediator in MDSC recruitment and as predictors and potential therapeutic targets in BC patients.

Impact of Protein Nutritional Status on Plasma BNP in Elderly Patients.

BACKGROUND: Previous studies have demonstrated that the levels of B-type natriuretic peptide (BNP) in plasma are negatively correlated with Body Mass Index (BMI) whereas lean body mass is also closely related to plasma BNP. The purpose of this study is to determine the effect of protein nutritional status on plasma BNP in aged patients. METHODS AND RESULTS: The cross-sectional study was applied and the anthropometric measurement and nutritional biochemical test was performed in 1118 elderly inpatients in a stable condition were enrolled in the study (mean age, 75 years; 54% women). The partial correlation and multivariate regression analysis were conducted to analyze the relation of plasma BNP with covariates. After adjustment for confounding factors such as age, smoking and coexisting diseases, we found that the concentrations of BNP were independently associated with serum albumin (ß=-0.065, P<0.001), serum total cholesterol (ß=-0.097, P<0.012) and calf circumference (ß=-0.032, P<0.014) in female patients, and associated with the serum albumin (ß=-0.051, P<0.001), prealbumin (ß=-2.177, P<0.026), mid-arm circumference (ß=-0.062, P<0.001) and grip strength (ß=-0.100, P<0.048) in male patients. Every 1 gram per liter of increased serum albumin corresponded to the reduced plasma BNP in male patients by 13.9% (OR 0.861, 95% CI 0.817, 0.909) and in female patients by 13.4% (OR 0.866, 95% CI 0.819, 0.916). CONCLUSIONS: Our study suggests that plasma BNP is negatively correlated with muscle mass, and it is also related to muscle force in male patients. The serum albumin is an independent determinant factor of BNP in both men and women. These findings suggest that good protein nutritional status could be beneficial in maintaining the cardiac function in elder population.

Predictor of massive bleeding following stent placement for malignant oesophageal stricture/fistulae: a multicentre study.

AIM: To evaluate retrospectively the incidence and predictors of massive bleeding after stent placement for malignant oesophageal stricture/fistulae. MATERIALS AND METHODS: This retrospective study comprised 519 patients with malignant oesophageal stricture/fistulae that were successfully treated with stent placement at three hospitals. The patients were divided into two groups based on the occurrence of massive bleeding. Univariate and multivariate analysis was performed to evaluate predictive factors of massive bleeding. RESULTS: Massive bleeding occurred in 54 of 519 patients 1-37 days following stent placement. All of the patients who developed massive bleeding died within 24 hours of the event. Univariate analysis showed massive bleeding was associated with the presence of a concomitant tracheal stent (p<0.001), the existence of concomitant oesophageal fistulae (p<0.001), and prior radiotherapy (p<0.001). Multivariate analysis exhibited that concomitant tracheal stent insertion (odds ratio [OR], 23.134; 95% confidence interval [CI], 9.523-56.199; p<0.001), the presence of oesophageal fistulae (OR, 3.724; 95% CI, 1.677-8.269; p=0.001), and prior radiotherapy (OR, 13.310; 95% CI, 5.464-32.421; p<0.001) were predictors of massive bleeding following stenting. CONCLUSIONS: The presence of oesophageal fistulae, prior radiotherapy, and concomitant tracheal stent are important factors contributing to bleeding after stenting.