Refractory hypothyroidism.

INTRODUCTION: Persistently elevated thyroid stimulating hormone (TSH) despite levothyroxine (LT4) treatment that exceeds the standard weight-adjusted dose is a common clinical presentation. This may lead to additional testing for LT4 malabsorption or poor LT4 adherence, the latter of which is challenging to confirm because it is predicated on accurate patient accountability. CASE REPORT: A 35-year-old lady, post-radioactive iodine therapy for Graves' disease remained euthyroid for a year on oral LT4. Two years later, she was clinically and biochemically hypothyroid despite claiming LT4 compliance. As all laboratory investigations were within the reference range, pseudomalabsorption was suspected and a LT4 absorption test was done. During the test, her free thyroxine increased significantly at 4 hours, reaching a peak of more than 50% from baseline while TSH decreased appropriately from 0 minute to 360 minutes. This was followed by normalisation of TSH with LT4 treatment under direct observation. DISCUSSION: The LT4 absorption test is a prompt and economical means to rule out true malabsorption, decrease unwarranted subspecialty referrals and validate the weight-adjusted LT4 dose reduction.

[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.

[Clinical efficacy of 585 nm Q-switched laser treatment on inflammatory lesion and postinflammatory erythema of acne vulgaris].

OBJECTIVE: To evaluate the efficacy and safety of 585 nm Q-switched laser in the treatment of acne inflammatory lesions and postinflammatory erythema. METHODS: A total of 25 patients with moderate facial acne, symmetrical distribution of inflammatory lesions and postinflammatory erythema on both sides of the face, were enrolled. Among the 25 patients, 22 patients completed all the treatment and evaluation, and 3 patients were lost to follow-up. 585 nm Q-switched laser was used on a randomly selected side of the face for three times of treatment at a 2 week interval. The evaluations were made before each treatment, 2 and 4 weeks after the last treatment, therefore the evaluation time points were before the treatment, weeks 2, 4, 6, and 8, respectively, for a total of 5 times. Acne severity was assessed using the investigator' s global assessment (IGA) score, and erythema severity was assessed using the investigator' s subjective erythema score and narrow-spectrum reflectance spectrophotometer at each follow-up. RESULTS: After 3 times of treatment, there was statistically significant difference between the IGA score in week 8 and before treatment on both sides(Z=2.64, P < 0.01; Z=2.67, P < 0.01). There was no significant difference in IGA score between the treatment side and the control side before treatment and in week 8 (P=0.59, P=0.26). There was statistically significant difference between the investiga-tor' s subjective erythema score in week 8 and before treatment on the treatment side(Z=4.24, P < 0.01), while no significant difference was showed on the control side(Z=1.73, P=0.08). In week 8, the investigator's subjective erythema score of the treatment side was lower than that of the control side (Z=3.61, P < 0.01). The erythema index of the treatment side was significantly decreased at 5 time points (P < 0.01), and the index decreased significantly in week 8 compared with the index before treatment (P < 0.01), while the erythema index of the control side was not significantly different at 5 time points. The treatment related adverse events included erythema and edema after treatment and pain during treatment, the severity was mild to moderate, which resolved spontaneously within 1 to 3 days. Nine patients were very satisfied with the treatment, 7 patients were satisfied, and 6 patients considered average. CONCLUSION: 585 nm Q-switched laser has some effect in the treatment of postinflammatory erythema, and it ensures good tolerance and safety. There was no statistically significant difference between the treatment side and the control side on the improvement of acne inflammatory lesions.

[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.

[The efficacy and safety of low-dose chemotherapy combined with tyrosine kinase inhibitors in the treatment of Philadelphia-chromosomal-positive acute lymphoblastic leukemia].

Objective: The study aims to explore the efficacy and safety of low-dose chemotherapy combined with tyrosine kinase inhibitor (TKI) as an induction therapy for Philadelphia-chromosomal-positive acute lymphoblastic leukemia (Ph(+) ALL) . Methods: The data of the consecutive newly diagnosed patients with Ph(+) ALL were reviewed. The efficacy and safety of low-dose chemotherapy and conventional-dose chemotherapy combined with TKI were compared. Results: A total of 217 patients with a median age of 38 (10-69) years old were included in this study. 78 patients were in the low-dose chemotherapy group, and 139 patients were in the conventional-dose chemotherapy group. There were no significant differences in the 4-week complete remission (CR) rate (98.7% vs 97.0%, P=0.766) and overall CR rate (100% vs 100%, P=1.000) between the two groups. Multivariate analyses showed that the chemotherapy intensity was not related to the disease-free survival rate and overall survival rate. However, the lower incidence of infection (P=0.017) , the shorter duration of neutropenia (P=0.001) and PLT<20 × 10(9)/L (P=0.057) , and the lower red blood cell transfusion volume (P=0.002) were more common in the low-dose chemotherapy group than in the conventional-dose chemotherapy group. Conclusions: The low-dose chemotherapy is superior to the conventional-dose chemotherapy combined with TKI as induction therapy in Ph(+) ALL with similar efficacy but is safer.

[Concordant systemic and local eosinophilia relates to poorer disease control in patients with nasal polyps].

Objective: To explore whether blood and polyp tissue eosinophil numbers are independent risk factors for poor disease control in patients with nasal polyp. Methods: By using the electronic medical records database and manual evaluation, 183 nasal polyp patients who had undergone endoscopic sinus surgery at least one year prior to the study with complete data of tissue specimens, baseline blood routine test, nasal endoscopy and sinus computed tomography, were identified and recruited to assess disease control based on the criteria of a European Position Paper on Rhinosinusitis and Nasal Polyps 2012 (EPOS 2012). Multiple logistic regression model was used to determine the association between blood and tissue eosinophil numbers and risk of poor disease control by adjusting for demographics and comorbidities. Results: We broke down the cohort into 4 groups according to blood (0.3×109/L) and tissue (10%) eosinophils. The patients without eosinophilic inflammation represented the largest group (41.5%). The group with concordant blood and tissue eosinophilia represented the second largest (31.2%), and the patients with isolated tissue (15.3%) or blood (12.0%) eosinophilia were relatively rare. Multiple logistic regression models found blood eosinophil count and tissue eosinophil percentage were independently associated with increased risk for poor disease control after adjustments for covariates related to poor treatment outcome. Furthermore, subjects with concordant blood and tissue eosinophilia had a higher risk for poor disease control than those with isolated blood or tissue eosinophilia. Conclusion: Concordant blood and tissue eosinophilia relates to a higher likelihood of poor disease control than isolated blood or tissue eosinophilia after adjustment of potential confounders in nasal polyp patients.

[Primary experience and discussion on the treatment of esthesioneuroblastoma].

Objective: To summarize the preliminary experience in the treatment of esthesioneuroblastoma (ENB) and to explore the effect of age, chemotherapy, modified Kadish stage and pathological grade on the prognosis of ENB. Methods: The clinical data of 87 ENB patients from the First Affiliated Hospital of Sun Yat-sen University and Sun Yat-sen University Cancer Center between June 2002 and November 2017 were retrospectively analyzed. The modified Kadish stage was used to evaluate the extent of the lesions, and the Hyams grading system was used for pathological grading. The patients were followed up regularly to evaluate the recurrence and metastasis of the tumor. Cox proportional hazard model was used for univariate and multivariate analyses. Prognostic factors with P<0.05 in univariate analysis were included in multivariate analysis. After controlling the confounding factors, the model coefficients were used to calculate the hazard ratio (HR) and 95% confidence interval (CI). Results: The median follow-up time of ENB patients was 29 months, and the 5-year overall survival rate was 39.3%. In univariate analysis, age, chemotherapy, modified Kadish stage and pathology grade were independent predictors of overall survival, while gender, radiotherapy and surgery were not prognostic factors. Multivariate analysis showed that modified Kadish stage and pathology grade were independent predictors of overall survival rate after excluding confounding factors. Conclusions: Age, chemotherapy, modified Kadish stage and pathological grade are taking important role in the overall survival rate of patients with ENB. Modified Kadish stage and pathological grade are independent predictors of overall survival rate.

[Analysis of the clinical characteristics of 24 cases of hematological malignancies with SET-NUP214 fusion gene].

Objective: To investigate the expression of SET-NUP214 fusion gene in hematological malignancies and to analyze its related clinical biological characteristics. Methods: The clinical data of 24 patients with SET-NUP214 fusion gene-positive hematological malignancies were retrospectively analyzed, and the Kaplan-Meier method was used for survival analysis. Results: Among the 24 patients with SET-NUP214 fusion gene, 15 cases of acute lymphoblastic leukemia (ALL) (13 cases of T-ALL and 2 cases of B-ALL) , 7 cases of acute myeloid leukemia (AML) , and 2 cases of T/myeloid mixed acute leukemia have been identified. The immunophenotype of 13 cases of T-ALL was mainly characterized by CD3(+)CD2(-), 73.3% of ALL was characterized by myeloid marker expression, and 85.7% of AML was characterized by CD7 expression. Complete remission (CR) was achieved in 22 patients (91.7%) after induction chemotherapy. All 24 patients received allogeneic hematopoietic stem cell transplantation (HSCT) . With a median follow-up of 24 months, the 3-year relapse free survival (RFS) of AML and ALL was 85.7% and 33.3%, respectively (P=0.128) . Comparing 13 cases of SET-NUP214-positive and 62 cases of SET-NUP214-negative T-ALL, the CR rates of induction chemotherapy were 92.3% and 93.5% (P=0.445) , and the 4-week CR rates of induction chemotherapy were 69.2% and 72.6%, respectively (P=0.187) ; the differences were not statistically significant. After HSCT, the 3-year RFS of SET-NUP214(+)T-ALL and SET-NUP214(-)T-ALL was 38.5% and 66.4%, respectively (P=0.028) , and the difference was statistically significant. Conclusion: The SET-NUP214 fusion gene is mainly detected in T cell-derived hematological malignancies, and the prognosis of SET-NUP214 positive T-ALL is relatively poor.

[Clinical characteristics, treatment pattern, and outcomes in newly diagnosed patients with chronic myeloid leukemia in the chronic phase by age].

Objective: To explore the clinical characteristics, treatment patterns, and outcomes in newly diagnosed patients with chronic myeloid leukemia in the chronic phase (CML-CP) by age. Methods: Clinical data of consecutive ≥14 years old newly diagnosed CML-CP patients were retrospectively analyzed. Results: This study included 957 patients. Of the patients, 597 (62.4%) were male. The median age was 40 years (range, 14-83 years) . The patients were stratified into three age groups: <40 years (n=470; 49.1%) , 40-59 years (n=371; 38.8%) , and ≥60 years (n=116; 12.1%) . The proportions of the patients who had splenomegaly (P<0.001) , WBC ≥100 × 10(9)/L (P<0.001) , anemia (P<0.001) , PLT<450 × 10(9)/L (P=0.022) , more blasts in the blood (P=0.010) , and clonal chromosome abnormalities in Philadelphia chromosome-positive cells (P=0.006) at diagnosis significantly decreased with age. However, the proportions of those with comorbidities (P<0.001) , intermediate or high Sokal risk (P<0.001) , and receiving imatinib as front-line therapy (P<0.001) significantly increased with age. No significant differences in gender and the EUTOS Long-Term Survival risks were noted across the three age groups. The multivariate analysis showed that ≥60 years was an adverse predictor for overall survival. However, age was not significantly associated with tyrosine kinase inhibitor (TKI) therapy responses and other outcomes. The incidences of nonhematological toxicity were significantly increased with age during TKI therapy (P<0.001) . However, those of hematological toxicity was similar across the three age groups. The proportions of the patients maintaining imatinib therapy (P=0.026) and receiving low-dose TKI therapy (P<0.001) significantly increased with age at the end of follow-up. Conclusions: Significant differences exist in clinical characteristics, TKI response, overall survival rates, and nonhematological toxicity among newly diagnosed CML-CP patients of different ages.

Oral health care and service utilisation in individuals with Rett syndrome: an international cross-sectional study.

BACKGROUND: There is a dearth of literature available on the comparative oral health status of those with Rett syndrome (RTT) despite diurnal bruxism being a supportive diagnostic criterion for the disorder. This study was designed to investigate the dental experiences of individuals with RTT in terms of perceived at-home and professional dental care. METHODS: Using data in the InterRett database, provided by English-speaking families of individuals with a confirmed MECP2 genetic mutation, the study investigated relationships between dental problems, oral care, child factors including bruxism and use of gastrostomy, and socioeconomic indicators. The study also explored relationships between dental presentations and socioeconomic, child, and family-related factors. RESULTS: Individuals with RTT exhibiting bruxism were more likely to access dental treatment. Those who had full oral feeding had a higher incidence rate of dental treatment than those with full tube feeding. A conservative (under) estimation of the overall dental caries progression rate revealed that this may be similar to that of the normal population. CONCLUSIONS: Drivers for dental treatment in RTT include bruxism as well as dental caries. Those who have full oral feeding experience more dental treatment than those with full tube feeding. A higher maternal education level may confer a protective effect for oral health outcomes in those with RTT. Nevertheless, families generally tended to value the importance of oral health despite reported difficulties in day-to-day mouth care.

[Two cases of hypoxic encephalopathy caused by simple asphyxial gas poisoning].

This article analyzes the clinical manifestations and magnetic resonance imaging (MRI) data of 2 patients with hypoxic encephalopathy after simple asphyxia gas poisoning. Both patients were in a moderate coma after being poisoned, and the arterial blood lactic acid level and carbon dioxide partial pressure were higher than the normal range within 1 week after poisoning. Two patients were cured and discharged after being treated with oxygen therapy and glucocorticoids. The prognosis was good.

The body fat distribution and fatty acid composition of muscles and adipose tissues in geese.

In this study, we evaluated the body fat distribution and fatty acid composition of muscles and adipose tissues of Yangzhou geese, including thirty 60-day-old goslings (15 males and 15 females) and 20 320-day-old geese (10 males and 10 females). Adipose tissues of Yangzhou geese were distributed widely and could be divided into 5 types: subcutaneous fat, abdominal fat, sartorial fat, neck fat, and mesenteric fat. Higher contents of abdominal fat, sartorial fat, neck fat, and mesenteric fat but a lower content of subcutaneous fat were found in adult geese than in goslings (P ≤ 0.05). Adult female geese deposited more fat than adult male geese (P ≤ 0.05). No difference was found in the fat distribution and fat content between male and female goslings (P > 0.05). The breast muscle of adult geese was characterized by a higher content of total monounsaturated fatty acids (ΣMUFAs) and a lower content of n-6 polyunsaturated fatty acids (ΣPUFAs n-6) than that of goslings (P ≤ 0.05). Lower concentrations of total saturated fatty acids and ΣPUFA were found in adult female geese than in female goslings (P ≤ 0.05). In comparison with adult female geese, the breast muscle of adult male geese had higher total saturated fatty acids and stearic acid (P ≤ 0.05). For the thigh muscle, adult female geese had a higher ΣMUFAs content than adult male geese (P ≤ 0.05). In adipose tissues, adult geese had a higher Σn-6/Σn-3 ratio but had lower contents of erucic acid, linolenic acid, arachidonic acid, docosatetraenoic acid, and ΣPUFA n-3 than goslings, and adult female geese had a higher ΣMUFAs content than adult male geese (P ≤ 0.05). In conclusion, adult geese, especially adult female geese, accumulated more fat than goslings. Both age and sex affected the fatty acid composition of muscles and adipose tissues in geese. This research provides essential information not only for the nutritional evaluation of geese but also for the consumption and processing of goose products.

[Variables associated with BCR-ABL kinase domain mutation in TKI-resistant patients with chronic myeloid leukemia].

Objectives: To explore BCR-ABL kinase domain mutation profiles and clinical variables associated with them in tyrosine kinase inhibitor (TKI) -resistant patients with chronic myeloid leukemia (CML) . Methods: Imatinib-, nilotinib-, and/or dasatinib-resistant patients with CML who screened BCR-ABL mutation (s) in Peking University People's Hospital between June 2001 and September 2019 were retrospectively reviewed. BCR-ABL mutation was analyzed by Sanger sequencing. Binary logistic regression model was built to identify independent clinical variables associated with developing BCR-ABL mutation (s) . Results: Data of 1 093 TKI-resistant cases in 804 patients who experienced resistance to imatinib (n=576, 52.7%) , nilotinib (n=238, 21.8%) , and dasatinib (n=279, 25.5%) were analyzed. In total, 291 (50.5%) imatinib-, 152 (63.9%) nilotinib-, and 160 (57.3%) dasatinib-resistant cases developed BCR-ABL mutation (s) . T315I mutation was the most frequent mutation detected in imatinib-, nilotinib-, and dasatinib-resistant cases, accounting for 12.3%, 27.3%, and 34.1%, respectively. Y253F/H (7.5%) and F359V/C/I (5.6%) were the mutation detected in ≥5% imatinib-resistant cases; F359V/C/I (12.2%) , Y253F/H (11.8%) , and E255K/V (10.5%) in nilotinib-resistant cases; and F317L/V/I/C (11.5%) and E255K/V (5.4%) in dasatinib-resistant cases. In multivariate analyses, no TKI dose reduction or discontinuation of TKI therapy was the common variable associated with developing BCR-ABL mutation (s) . Other variables associated with developing BCR-ABL mutation (s) in imatinib-, nilotinib-, or dasatinib-resistant cases included male gender, younger age, no comorbidity, advanced phase before starting current TKI therapy, longer interval from diagnosis to starting current TKI therapy, acquired resistance, and TKI resistance due to progression to advanced phase or hematologic failure. In addition, interval from TKI failure to BCR-ABL mutation detection, starting initial TKI therapy to TKI failure, and starting current TKI therapy to TKI failure were associated with the frequency of developing BCR-ABL mutation. Dasatinib and nilotinib use and acquired resistance were identified to be associated with the development of T315I mutation in multivariate analyses. Conclusions: More than half of TKI-resistant CML patients developed BCR-ABL mutation (s) by Sanger sequencing. T315I mutation was the most frequently detected. Clinical variables significantly associated with developing BCR-ABL mutation (s) should be used not only as basis for the choice of subsequent TKIs but also the understanding of TKI-resistant mechanisms.

[Analysis of the efficacy and influencing factors of nilotinib or dasatinib as second- or third-line treatment in patients with chronic myeloid leukemia in the chronic phase and accelerated phase].

Objective: To explore the efficacy and prognosis of nilotinib or dasatinib as second- or third-line treatment in patients with chronic myeloid leukemia (CML) in the chronic phase (CP) and accelerated phase (AP) . Methods: From January 2008 to November 2018, the data of CML patients who failed first- or second-line tyrosine kinase inhibitor (TKI) -therapy received nilotinib or dasatinib as second-line and third-line therapy were retrospectively reviewed. Results: A total of 226 patients receiving nilotinib or dastinib as second-line (n=183) and third-line (n=43) therapy were included in this study. With a median follow-up of 21 (range, 1-135) months, the cumulative rates of complete hematological response (CHR) , complete cytogenetic response (CCyR) and major molecular response (MMR) were 80.4%, 56.3%and 38.3%, respectively in those receiving TKI as second-line TKI therapy. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 78.7%and 93.1%, respectively. Multivariate analyses showed that Sokal high risk, female gender, the best response achieved

[Dasatinib-related pulmonary adverse events in patients with chronic myeloid leukemia].

Objective: To explore dasatinib-related pulmonary adverse events in patients with chronic myeloid leukemia (CML) . Methods: We retrospectively analyzed the incidence of pleural effusion (PE) and pulmonary arterial hypertension (PAH) in patients with CML treated with dasatinib at Peking University People's Hospital from April 2008 to January 2020. Results: A total of 280 patients were collected. The median dasatinib treatment time was 26 (1-142) months. Ninety (32.1%) patients developed PE, including 40 (44.4%) in grade 1, 44 (48.9%) in grade 2, and 6 (6.7%) in grade 3. The incidence of PE increased gradually with the prolongation of treatment. The multivariate analysis showed that increasing age (every 10 years, HR=1.6; P<0.001) , advanced phase when starting dasatinib therapy (HR=2.2; P=0.008) , and cardiovascular comorbidity (ies) (HR=1.9; P=0.018) were significantly associated with developing PE. The advanced phase when starting dasatinib therapy (HR=3.4; P=0.001) , interval from diagnosis to taking TKI for ≤6 months (HR=2.2; P=0.015) , and dose < 100 mg/d when PE was found (HR=3.1; P=0.001) were associated with more severe PE. PE relieved or disappeared after intervention in half of the patients. Among 60 patients with symptoms of cough, chest tightness, and shortness of breath, 49 underwent ultrasonic cardiography; 8 (16.3%) had high probability of PAH, approximately 3.5% in all patients; and 6 (75.0%) of them had PE. PAH was reversible. There was no difference in the incidences of PE and PAH between branded and Chinese generic dasatinib. Conclusion: PE is a common dasatinib-related pulmonary adverse event, and PAH is rare in patients with CML. The identification of individuals with high risk, close monitoring, and timely intervention may help to alleviate PE and PAH.

Silica-based colloid centrifugation enhances sperm quality in cockerel semen.

1. PercollTM is one of the most widely used colloid for animal sperm preparation. The aim of this study was to evaluate whether PercollTM colloid centrifugation could be practical to improve cockerel sperm quality, and to compare the effects of PercollTM single layer centrifugation (SLC) and density gradient centrifugation (DGC) in order to obtain the most optimal protocol for cockerel semen.2. In the experiment with PercollTM SLC for fresh semen, an increase of motile sperm was seen after PercollTM 80% SLC and 90% SLC was conducted, at levels of 28.8% and 30.2% respectively (P < 0.01). The increase of progressively motile sperm after PercollTM 80% SLC and 90% SLC was 177.2% and 202.4% respectively (P < 0.01). Meanwhile, for semen stored at 4°C for 24 h, the increase of motile sperm after PercollTM 70% SLC and 80% SLC was 41.2% and 44.0% (P < 0.01), and the increase of progressive sperm after PercollTM 70% SLC and 80% SLC was 71.3% and 83.1% respectively (P < 0.01). Both the percentage of motile sperm and progressive sperm of the fresh and stored cockerel semen after appropriate PercollTM SLC was significantly enhanced.3. Sperm membrane integrity did not show any decrease after PercollTM centrifugation compared with non-centrifuged semen, which suggested that the PercollTM centrifugation treatment in this study did not cause damage to cockerel sperm membranes.4. In the experiment regarding the comparison of PercollTM SLC and DGC with fresh semen, the increase of motile sperm after PercollTM 80% SLC, 90% SLC and 40%/80% DGC was 29.5%, 36.4%, and 25.0% respectively; and the increase of progressive sperm was 44.7%, 58.5%, and 54.7%, respectively. For semen stored at 4°C for 24 h, the increase of motile sperm after PercollTM 70% SLC, 80% SLC and 35%/70% DGC were 41.2%, 44.0%, and 26.4%; and the increase of progressive sperm was 71.3%, 83.1%, and 43.7%, respectively. There were no significant differences between the increase of sperm motility after PercollTM 80%, 90% SLC or PercollTM 40%/80% DGC in fresh cockerel semen. There was no significant difference between PercollTM 70%, 80% SLC and PercollTM 35%/70% in stored cockerel semen. There was a tendency for sperm recovery rates with PercollTM SLC to be higher than PercollTM DGC, although this did not reach statistical significance in this study.5. It was concluded that PercollTM SLC was more suitable for cockerel sperm separation than PercollTM DGC. The results suggested that PercollTM 80% SLC was the most optimal procedure to separate fresh cockerel sperm and PercollTM 70% SLC was the most optimal procedure to separate stored cockerel sperm. PercollTM SLC is more simple, user-friendly and economical and less time-consuming than DGC for cockerel semen processing.

[Comparison of the efficacy and safety of Chinese generic imatinib and branded imatinib in patients with chronic myeloid leukemia in consideration of demographic characteristics].

Objectives: To compare the efficacy and safety of Chinese generic imatinib with branded imatinib as frontline therapy in adults with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) (Frontline group) , and to explore the efficacy and safety of Chinese generic imatinib in CML-CP patients switching from branded imatinib (Switching group) . Methods: Frontline group: Data of adults with newly diagnosed CML-CP receiving Chinese generic imatinib (Xinwei(®)) or branded imatinib (Glivec(®)) between October 2013 and August 2018 were retrospectively collected and analyzed. Switching group: Data of adults diagnosed with CML-CP who received branded imatinib and then switched to Chinese generic imatinib after achieving at least complete cytogenetic response (CCyR) were retrospectively collected and analyzed. Results: Frontline group: In total, 409 adult patients receiving Chinese generic imatinib (n=201) or Glivec (n=208) were included in this study. Median age was 42 years (range, 18-83 years) . Comparison of baseline showed significant difference on demographic characteristics among two cohorts: lower education level (P<0.001) , and divorced or widowed status (P=0.004) and rural household registration (P<0.001) were more common in the generic imatinib cohort than those in the Glivec cohort. There was no significant difference on age, gender, Sokal risk score, WBC and HGB between the 2 cohorts. With a median follow-up of 25 months (range, 3-62 months) , there was no significant difference on the 3-year cumulative incidence of achieving CCyR (97.5% vs 94.5%, P=0.592) , major molecular response (MMR) (84.3% vs 93.1%, P=0.208) , molecular response(4.0) (MR(4.0)) (42.7% vs 41.7%, P=0.277) , molecular response(4.5) (MR(4.5)) (25.4% vs 33.0%, P=0.306) as well as the 3-year probabilities of failure free survival (FFS) (76.7% vs 81.0%, P=0.448) , progression free survival (PFS) (91.8% vs 96.3%, P=0.325) and overall survival (OS) (95.8% vs 98.5%, P=0.167) between the generic and branded imatinib cohorts. Multivariate analysis showed the type of imatinib was not associated with treatment responses and outcomes. The incidences of adverse effects were comparable in the 2 cohorts. Switching group: In total, 39 patients switching from branded imatinib to Chinese generic imatinib after achieving at least CCyR were included in this study. Median age was 42 years (range, 23-80 years) . With a median follow-up of 39 months (range, 6-63 months) , molecular responses were maintained in 23 (58.9%) patients and improved in 12 (39.8%) patients. Adverse effects were tolerable. Conclusion: Demographic characteristics might influence the choice of the type of TKI used in CML-CP patients. There was a comparable efficacy and safety between the Chinese generic imatinib and the branded imatinib in adults with newly diagnosed CML-CP under standard management and closely monitoring. Patients could safely switch from the branded imatinib to the Chinese generic imatinib.

[Observation on the efficacy of consolidation chemotherapy combined with allogeneic natural killer cell infusion in the treatment of low and moderate risk acute myeloid leukemia].

Objective: To evaluate the efficacy of consolidation chemotherapy combined with allogeneic natural killer (NK) cell infusion in the treatment of low or intermediate-risk (LIR) acute myeloid leukemia (AML) . Methods: A cohort of 23 LIR AML patients at hematologic complete remission (CR) received NK cell transfusion combined with consolidation chemotherapy after 3 consolidation courses from January 2014 to June 2019 were reviewed. Control group cases were concurrent patients from Department of Hematology, and their gender, age, diagnosis, risk stratification of prognosis, CR and the number of courses of consolidate chemotherapy before NK cell transfusion were matched with LIR AML patients. Results: A total of 45 times of NK cells were injected into 23 LIR AML patients during 4 to 7 courses of chemotherapy. The median NK cell infusion quantity was 7.5 (6.6-8.6) ×10(9)/L, and the median survival rate of NK cells was 95.4% (93.9%-96.9%) . Among them, the median CD3(-)CD56(+) cell number was 5.0 (1.4-6.4) ×10(9)/L, accounting for 76.8% (30.8%-82.9%) ; The number of CD3(+) CD56(+) cells was 0.55 (0.24-1.74) ×10(9)/L, accounting for 8.8% (4.9%-20.9%) . Before NK cell infusion, the number of patients with positive MRD in the treatment and control groups were 9/23 (39.1%) and 19/46 (41.3%) (χ(2)=0.030, P=0.862) respectively. After NK infusion, There was no significant difference in terms of MRD that went from negative to positive between the treatment and the control groups (14.3% vs 22.2%, χ(2)=0.037, P=0.847) . In the treatment group, 66.7% (6/9) of the MRD were converted from positive to negative, which was significantly higher than that in the control group (10.5%, 2/19) (χ(2)=6.811, P=0.009) . Morphological recurrence occurred in 1 case of MRD negative in the treatment group and 2 cases of MRD positive in the control group. By the end of follow-up, the median follow-up was 35 (10-59) months, the number of patients with morphological recurrence in the treatment group was 30.4% (7/23) , which was significantly lower than that in the control group (50.2%, 24/46) (χ(2)=2.929, P=0.087) , although there was no statistically significant difference between the two groups. There was no significant difference on MRD-negative between the treatment and the control groups (43.5% vs 43.5%, χ(2)=1.045, P=0.307) . The 3-year leukemia-free survival was better in the treatment group [ (65.1±11.1) %] than that in the control group [ (50.0±7.4) %] (P=0.047) . The 3-year overall survival in the treatment and control groups were (78.1±10.2) % and (65.8±8.0) % (P=0.212) , respectively. Conclusion: The consolidation of chemotherapy combined with allogeneic NK cell infusion contributed to the further remission of patients with LMR AML and the reduction of long-term recurrence.

[New system combining Hyams grading system and modified Kadish stage to evaluate the progress of esthesioneuroblastoma].

Objective:Esthesioneuroblastoma(ENB) is a sinonasal rare tumor, and the assessment on the prognosis have not been used with on consensus, our study aims to set an accuracy indicator to predict the outcomes of ENB.Method:A retrospective review was performed on 31 ENB patients. We collected 31 patients with ENB and reviewed the clinical data and pathological slides; modified Kadish stages were evaluated by otolaryngologist and imaging specialist; Hyams grading system were confirmed by two pathologists, who reviewed and paid attention to the pathological characteristics of Hyams grading system. Finally, the relation among the clinical data, pathological features and clinical outcome of these 31 ENB were analyzed by Kaplan-Meier method.Result: The Hyams grading system and modified Kadish stage were considered together seemed to evaluate the prognosis of ENB more accurately, when the scores over 6 points, the patients had the poor prognosis with the mean median survival months of 24.67±32.22, compared with the scores under 6 and the final scores reached at 4, 5, 6, 7, 8, the tumor metastasis rates were 14.3%, 16.7%, 33.3%, 50.0%, 100.0% respectively.Conclusion:Taking the Hyams grading system and modified Kadish stage into consideration, which may evaluate the prognosis of ENB more accurately.