[Analysis of the factors influencing the severity of coronavirus disease 2019 in patients with myeloproliferative neoplasms based on an online questionnaire].

Objective: To explore the variables associated with the severity of coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 omicron variant during the epidemic in patients with myeloproliferative neoplasms (MPN). Methods: A cross-sectional study. During the SARS-CoV-2 omicron variant pandemic from December 15, 2022, to March 15, 2023, COVID-19 related data for patients with MPN who were treated at Peking University People's Hospital were collected through an online questionnaire-based survey. All questionnaires and clinical data were checked by medical assistants. Logistic multivariate analysis was used to explore the prevalence and variables associated with the severity of COVID-19 in patients with MPN. Results: A total of 239 patients with MPN, including 90 (37.7%) presenting with essential thrombocythemia (ET), 50 (20.9%) with polycythemia vera (PV), and 99 (41.4%) with myelofibrosis (MF), were enrolled in the study. The 99 patients with MF included 87 (87.9%) with primary MF, 5 (5.1%) with post-PV MF, and 7 (7.1%) with post-ET MF. Overall, 239 (100%) patients reported that they experienced COVID-19 during the pandemic. Of these, 226 (94.6%) had mild disease, 4 (1.7%) had moderate disease, 7 (2.9%) had severe disease, and 2 (0.8%) had critical disease. Two (0.8%) patients with severe COVID-19 died, one of which suffered from MT and the other from PV. Multivariate analysis showed that older age (OR=2.36, 95%CI 1.24-4.49), MF (OR=10.22, 95%CI 1.13-92.80), or comorbidity (OR=5.25, 95%CI 1.25-22.03) were associated with a significantly higher risk of developing moderate, severe, or critical COVID-19. Among patients with MF, higher risk stratification reflected an increased risk of developing moderate, severe, or critical COVID-19 (P=0.034). Conclusion: During the omicron pandemic, older age, MF (especially higher-risk categories), and comorbidity were associated with a higher risk of developing moderate, severe, or critical COVID-19.

[Research progress in N6-methyladenosine modification in the field of stomatology].

N6-methyladenosine (m6A) is the most abundant and widely distributed internal RNA modification in eukaryotic cells, and it is involved in the regulation of gene expression and biological processes in many cells. In recent years, studies on the role of m6A modification in oral cavity have emerged gradually. Existing researches show that m6A-related proteins are involved in the regulation of oral squamous cell carcinoma and its resistance to therapy. Methyltransferase-like 3 regulates apoptosis and autophagy of chondrocytes in inflammation, the angiogenesis and osteogenesis during distraction osteogenesis of endothelial progenitor cells, inflammatory response of dental pulp cells, the differentiation and osteogenesis of dental pulp stem cells, the development of tooth roots and the differentiation of bone marrow mesenchymal stem cells and so on. Moreover, m6A modification may also be related to the occurrence and development of periodontitis, oral ulcers and oral submucosal fibrosis. These studies have provided new ideas for the pathogenesis of various oral diseases and the diagnosis and treatment of oral bone tissue repair and regeneration. This paper reviews the recent research progress on the role of m6A modification in the field of stomatology and summarize the current research status of m6A in the field of stomatology, in order to provide reference for the further research of m6A function and mechanism in the field of stomatology.

Efficacy and safety of intrathecal pemetrexed for TKI-failed leptomeningeal metastases from EGFR+ NSCLC: an expanded, single-arm, phase II clinical trial.

BACKGROUND: This study aimed to evaluate the efficacy and safety of intrathecal pemetrexed (IP) for treating patients with leptomeningeal metastases (LM) from non-small-cell lung cancer (NSCLC) who progressed from epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment in an expanded, prospective, single-arm, phase II clinical study (ChiCTR1800016615). PATIENTS AND METHODS: Patients with confirmed NSCLC-LM who progressed from TKI received IP (50 mg, day 1/day 5 for 1 week, then every 3 weeks for four cycles, and then once monthly) until disease progression or intolerance. Objectives were to assess overall survival (OS), response rate, and safety. Measurable lesions were assessed by investigator according to RECIST version 1.1. LM were assessed according to the Response Assessment in Neuro-Oncology (RANO) criteria. RESULTS: The study included 132 patients; 68% were female and median age was 52 years (31-74 years). The median OS was 12 months (95% confidence interval 10.4-13.6 months), RANO-assessed response rate was 80.3% (106/132), and the most common adverse event was myelosuppression (n = 42; 31.8%), which reversed after symptomatic treatment. The results of subgroup analysis showed that absence of brain parenchymal metastasis, good Eastern Cooperative Oncology Group score, good response to IP treatment, negative cytology after treatment, and patients without neck/back pain/difficult defecation had longer survival. Gender, age, previous intrathecal methotrexate/cytarabine, and whole-brain radiotherapy had no significant influence on OS. CONCLUSIONS: This study further showed that IP is an effective and safe treatment method for the EGFR-TKI-failed NSCLC-LM, and should be recommended for these patients in clinical practice and guidelines.

Age-specific characteristics of head and neck second primary malignancies in patients treated for nasopharyngeal carcinoma: a retrospective study.

This study was performed to analyse the age-specific characteristics of head and neck second primary malignancies (SPMs) in patients treated for nasopharyngeal carcinoma (NPC). The medical records of 56 NPC patients diagnosed with head and neck SPMs were reviewed retrospectively. Patients < 45 years old at NPC diagnosis were assigned to the younger group and those ≥ 45 years of age were assigned to the older group. The treatment of the index NPC, latency period, pathological TNM stage, survival status, and SPM subsite were analysed. Patients in the older group were found to have a shorter median latency period than those in the younger group: 8.5 years (range 3-20 years) versus 11 years (range 1-30 years) (P = 0.015). The proportion of SPMs in the jaw was significantly higher in the younger group (P = 0.002). Patients in the younger group receiving radiotherapy with chemotherapy had a shorter latency period (P = 0.003) and higher risk of developing SPMs in the jaw (P = 0.036) than those receiving radiotherapy alone. A long-term and age-dependent regular customised follow-up strategy for NPC is necessary for the prevention and early detection of head and neck second primary malignancies.

[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.

[Spatial distribution characteristics of the prevalence of advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody in Hunan Province in 2020].

OBJECTIVE: To investigate the spatial distribution characteristics of the prevalence of advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody, and to examine the correlation between the prevalence of advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody in Hunan Province in 2020, so as to provide insights into advanced schistosomiais control in the province. METHODS: The epidemiological data of schistosomiasis in Hunan Province in 2020 were collected, including number of permanent residents in survey villages, number of advanced schistosomiasis patients, number of residents receiving serological tests and number of residents seropositive for anti-Schistosoma antibody, and the prevalence advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody were descriptively analyzed. Village-based spatial distribution characteristics of prevalence advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody were identified in Hunan Province in 2020, and the correlation between the revalence advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody was examined using Spearman correlation analysis. RESULTS: The prevalence of advanced schistosomiasis was 0 to 2.72% and the seroprevalence of anti-Schistosoma antibody was 0 to 20.25% in 1 153 schistosomiasis-endemic villages in Hunan Province in 2020. Spatial clusters were identified in both the prevalence of advanced schistosomiasis (global Moran's I = 0.416, P < 0.01) and the seroprevalence of anti-Schistosoma antibody (global Moran's I = 0.711, P < 0.01) in Hunan Province. Local spatial autocorrelation analysis identified 98 schistosomiasis-endemic villages with high-high clusters of the prevalence of advanced schistosomiasis, 134 endemic villages with high-high clusters of the seroprevalence of anti-Schistosoma antibody and 36 endemic villages with high-high clusters of both the prevalence of advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody in Hunan Province. In addition, spearman correlation analysis showed a positive correlation between the prevalence of advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody (rs = 0.235, P < 0.05). CONCLUSIONS: There were spatial clusters of the prevalence of advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody in Hunan Province in 2020, which were predominantly located in areas neighboring the Dongting Lake. These clusters should be given a high priority in the schistosomiasis control programs.

Progressive plasticity during colorectal cancer metastasis.

Metastasis is the principal cause of cancer death, yet we lack an understanding of metastatic cell states, their relationship to primary tumor states, and the mechanisms by which they transition. In a cohort of biospecimen trios from same-patient normal colon, primary and metastatic colorectal cancer, we show that while primary tumors largely adopt LGR5 + intestinal stem-like states, metastases display progressive plasticity. Loss of intestinal cell states is accompanied by reprogramming into a highly conserved fetal progenitor state, followed by non-canonical differentiation into divergent squamous and neuroendocrine-like states, which is exacerbated by chemotherapy and associated with poor patient survival. Using matched patient-derived organoids, we demonstrate that metastatic cancer cells exhibit greater cell-autonomous multilineage differentiation potential in response to microenvironment cues than their intestinal lineage-restricted primary tumor counterparts. We identify PROX1 as a stabilizer of intestinal lineage in the fetal progenitor state, whose downregulation licenses non-canonical reprogramming.

[Association between sedentary behavior and force expiratory volume in 1 second reduction in middle-aged and elderly adults in communities].

Objective: To analyze the relationship between sedentary behavior and the force expiratory volume in 1 second (FEV1) reduction in middle-aged and elderly people in communities. Methods: The participants aged ≥40 years were randomly selected from a natural population cohort in Songjiang District, Shanghai, for pulmonary function tests and survey by using international physical activity questionnaire, a generalized additive model was used to analyze the association between sedentary behavior and FEV1 reduction in the study population and different sex-age subgroups. Results: A total of 3 121 study subjects aged ≥40 years were included. The prevalence of FEV1 reduction was 14.8%, which was higher in men than in women. There were 24.8% participants were completely sedentary. The prevalence of FEV1 reduction in women aged <60 years in complete sedentary group was 2.04 (95%CI: 1.11-3.72) times higher than that in non-complete sedentary group. In men aged <60 years, the prevalence of FEV1 reduction increased with daily sedentary time (OR=1.16, 95%CI: 1.04-1.29), and the prevalence of FEV1 reduction was also higher in those with sedentary time >5 hours/day than those with sedentary time ≤5 hours/day (OR=3.02, 95%CI: 1.28-7.16). The sensitivity analysis also found such associations. Conclusions: FEV1 reduction rate in age group <60 years was associated with sedentary behavior. Complete sedentary behavior or absence of moderate to vigorous physical activity played important roles in FEV1 reduction in women, while men were more likely to be affected by increased sedentary time, which had no association with physical activity. Reducing sedentary time to avoid complete sedentary behavior, along with increased physical activity, should be encouraged in middle-aged and elderly adults in communities to improve their pulmonary function.

Prophylactic therapy for prevention of surgical site infection after extraction of third molar: An overview of reviews.

BACKGROUND: To compare the effect of different prophylactic therapies on prevention of surgical site infection after extraction of third molars with different degree of impaction. MATERIAL AND METHODS: Systematic reviews and meta-analyses evaluating the effect of different prophylactic therapies on prevention of surgical site infection after extraction of third molars were included. An electronic search was performed in PubMed, EMBASE, and the Cochrane Database of Systematic reviews. AMSTAR 2 tool was used to evaluate the confidence in results from the included reviews. Descriptive analyses were performed. RESULTS: Six reviews were included. A significant benefit of different antibiotics to the prevention of site infection after extraction of third molars was reported. Amoxicillin/amoxicillin clavulanic acid could significantly reduce the rate of surgical site infection versus placebo. Chlorhexidine gel could significantly reduce the frequency of alveolar osteitis versus placebo. CONCLUSIONS: Based on the limited evidence, there is a significant benefit of prophylactic therapy while the comparative effect of different types of prophylactic regimes are controversial.

[Clinical and genetic characteristics of young patients with myeloproliferative neoplasms].

Objectives: To investigate the clinical and genetic features of young Chinese patients with myeloproliferative neoplasms (MPN). Methods: In this cross-sectional study, anonymous questionnaires were distributed to patients with MPN patients nationwide. The respondents were divided into 3 groups based on their age at diagnosis: young (≤40 years) , middle-aged (41-60 years) , and elderly (>60 years) . We compared the clinical and genetic characteristics of three groups of MPN patients. Results: 1727 assessable questionnaires were collected. There were 453 (26.2%) young respondents with MPNs, including 274 with essential thrombocythemia (ET) , 80 with polycythemia vera (PV) , and 99 with myelofibrosis. Among the young group, 178 (39.3%) were male, and the median age was 31 (18-40) years. In comparison to middle-aged and elderly respondents, young respondents with MPN were more likely to present with a higher proportion of unmarried status (all P<0.001) , a higher education level (all P<0.001) , less comorbidity (ies) , fewer medications (all P<0.001) , and low-risk stratification (all P<0.001) . Younger respondents experienced headache (ET, P<0.001; PV, P=0.007; MF, P=0.001) at diagnosis, had splenomegaly at diagnosis (PV, P<0.001) , and survey (ET, P=0.052; PV, P=0.063) . Younger respondents had fewer thrombotic events at diagnosis (ET, P<0.001; PV, P=0.011) and during the survey (ET, P<0.001; PV, P=0.003) . JAK2 mutations were found in fewer young people (ET, P<0.001; PV, P<0.001; MF, P=0.013) ; however, CALR mutations were found in more young people (ET, P<0.001; MF, P=0.015) . Furthermore, mutations in non-driver genes (ET, P=0.042; PV, P=0.043; MF, P=0.004) and high-molecular risk mutations (ET, P=0.024; PV, P=0.023; MF, P=0.001) were found in fewer young respondents. Conclusion: Compared with middle-aged and elderly patients, young patients with MPN had unique clinical and genetic characteristics.

[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.

[Exposure level of neonicotinoid pesticides and their metabolites in pregnant women in the suburb of Shanghai].

In 2021, a total of 151 pregnant women were selected from the suburb of Shanghai. A questionnaire survey was conducted to obtain data about maternal age, gestational week, total annual household income, education level and passive smoking among pregnant women and one spot urine was collected. The concentrations of eight neonicotinoid pesticides and four metabolites in urine were measured by ultra-high performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry. The differences in detection frequencies and concentrations of neonicotinoid pesticides and their metabolites among pregnant women with different characteristics were compared, and the influencing factors of the detection of neonicotinoid pesticides in urine were analyzed. The results showed that at least one neonicotinoid pesticide was detected in 93.4% (141 samples) of urine samples. The detection frequencies of N-desmethyl-acetamiprid, clothianidin, thiamethoxam, and N-desmethyl-clothianidin were high, about 78.1% (118 samples), 75.5% (114 samples), 68.9% (104 samples), and 44.4% (67 samples), respectively. The median concentration of the sum of all neonicotinoid pesticides was 2.66 µg/g. N-desmethyl-acetamiprid had the highest detection concentration with a median concentration of 1.04 µg/g. A lower urinary detection frequency of imidacloprid and its metabolites was seen in pregnant women aged 30-44 years [OR (95%CI): 0.23 (0.07-0.77)]. A higher detection frequency of clothianidin and its metabolites was seen in pregnant women with per capita annual household income≥100 000 yuan [OR (95%CI): 6.15 (1.56-24.28)]. There was widespread exposure to neonicotinoid pesticides and their metabolites in pregnant women from the suburb of Shanghai, which might pose potential health risks to pregnant women, and maternal age and household income were potential influencing factors of the exposure to neonicotinoid pesticides.

[Optimization of the medium and fermentation condition for the Penicillium aurantiocandidum Z12 strain with molluscicidal actions against Oncomelania hupensis].

OBJECTIVE: To optimize the culture and fermentation conditions of the Penicillium aurantiocandidum Z12 strain, a fungal strain with molluscicidal actions against Oncomelania hupensis, so as to provide the basis for the research and development of molluscicidal active substances from the P. aurantiocandidum Z12 strain and its fermentation broth and large-scale fermentation. METHODS: The carbon source, nitrogen source and mineral salts were identified in the optimal culture medium for the P. aurantiocandidum Z12 strain with a single-factor experiment to determine the best fermentation condition for the P. aurantiocandidum Z12 strain. Factors that significantly affected the growth of the P. aurantiocandidum Z12 strain were identified using the Plackett-Burman design, and the best range of each factor was determined using the steepest climb test. Response surface analyses of temperature, pH value, seeding amount and liquid-filling quantity were performed using the Box-Behnken design to create a regression model for fermentation of the P. aurantiocandidum Z12 strain to identify the optimal culture medium. RESULTS: Single-factor experiment preliminarily identified the best culture medium and conditions for the P. aurantiocandidum Z12 strain as follows: sucrose as the carbon source at approximately 20 g/L, tryptone as the nitrogen source at approximately 5 g/L, K2HPO4 as the mineral salt at approximately 5 g/L, initial pH at approximately 8, temperature at approximately 28 °C, seeding amount at approximately 6%, and liquid-filling quantity at approximately 50 mL/100 mL. Plackett-Burman design showed that factors that significantly affected the growth of the P. aurantiocandidum Z12 strain included temperature (t = -5.28, P < 0.05), seeding amount (t = 5.22, P < 0.05), pH (t = -4.30, P < 0.05) and liquid-filling quantity (t = -4.39, P < 0.05). Steepest climb test showed the highest mycelial growth at pH of 7.5, seeding amount of 8%, and liquid-filling quantity of 40 mL/100 mL, and this condition was selected as the central point of response surface analysis for the subsequent optimization of fermentation conditions. Response surface analyses using the Box-Behnken design showed that the optimal conditions for fermentation of the P. aurantiocandidum Z12 strain included sucrose at 15 g/L, tryptone at 5 g/L, K2HPO4 at 5 g/L, temperature at 28.2 °C, pH at 7.5, seeding amount at 10%, and liquid-filling quantity at 35.8 mL/100.0 mL, resulting in 0.132 g yield of the P. aurantiocandidum Z12 strain. CONCLUSIONS: The optimal culture condition for the P. aurantiocandidum Z12 strain has been identified, and the optimized culture medium and fermentation condition may effectively improve the fermentation yield of the P. aurantiocandidum Z12 strain.

[Dose-response association between fluid overload and hospital mortality in patients with sepsis].

Objective: To investigate dose-response associations between fluid overload (FO) and hospital mortality in patients with sepsis. Methods: The current cohort study was prospective and multicenter. Data were derived from the China Critical Care Sepsis Trial, which was conducted from January 2013 to August 2014. Patients aged≥18 years who were admitted to intensive care units (ICUs) for at least 3 days were included. Fluid input/output, fluid balance, fluid overload (FO), and maximum FO (MFO) were calculated during the first 3 days of ICU admission. The patients were divided into three groups based on MFO values: MFO<5%L/kg, MFO 5%-10%L/kg, and MFO≥10% L/kg. Kaplan-Meier analysis was used to predict time to death in hospital in the three groups. Associations between MFO and in-hospital mortality were evaluated via multivariable Cox regression models with restricted cubic splines. Results: A total of 2 070 patients were included in the study, of which 1 339 were male and 731 were female, and the mean age was (62.6±17.9) years. Of 696 (33.6%) who died in hospital, 968 (46.8%) were in the MFO<5%L/kg group, 530 (25.6%) were in the MFO 5%-10%L/kg group, and 572 (27.6%) were in the MFO≥10%L/kg group. Deceased patients had significantly higher fluid input than surviving patients during the first 3 days [7 642.0 (2 874.3, 13 639.5) ml vs. 5 738.0 (1 489.0, 7 153.5)ml], and lower fluid output [4 086.0 (1 367.0, 6 354.5) ml vs. 6 130.0 (2 046.0, 11 762.0) ml]. The cumulative survival rates in the three groups gradually decreased with length of ICU stay, and they were 74.9% (725/968) in the MFO<5% L/kg group, 67.7% (359/530) in the MFO 5%-10%L/kg group, and 51.6% (295/572) in the MFO≥10%L/kg group. Compared with the MFO<5%L/kg group, the MFO≥10%L/kg group had a 49% increased risk of inhospital mortality (HR=1.49, 95%CI 1.28-1.73). For each 1% L/kg increase in MFO, the risk of in-hospital mortality increased by 7% (HR=1.07, 95% CI 1.05-1.09). There was a"J-shaped"non-linear association between MFO and in-hospital mortality with a nadir of 4.1% L/kg. Conclusion: Higher and lower optimum fluid balance levels were associated with an increased risk of in-hospital mortality, as reflected by the observed J-shaped non-linear association between fluid overload and inhospital mortality.

[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.

[Treatment responses, outcomes, and prognostic factors associated with them in patients with secondary acute myeloid leukemia].

Objective: To evaluate treatment responses, outcomes, and prognostic factors in adults with secondary acute myeloid leukemia (sAML) . Methods: Between January 2008 and February 2021, date of consecutive cases of younger than 65 years of adults with sAML were assessed retrospectively. Clinical characteristics at diagnosis, treatment responses, recurrence, and survival were evaluated. Logistic regression and Cox proportional hazards model were employed to determine significant prognostic indicators for treatment response and survival. Results: 155 patients were recruited, including 38, 46, 57, 14 patients belonging to t-AML, and AML with unexplained cytopenia, post-MDS-AML, and post-MPN-AML, respectively. In the 152 evaluable patients, the rate of MLFS after the initial induction regimen was 47.4%, 57.9%, 54.3%, 40.0%, and 23.1% in the four groups (P=0.076) . The total rate of MLFS after the induction regimen was 63.8%, 73.3%, 69.6%, 58.2%, and 38.5% (P=0.084) , respectively. Multivariate analysis demonstrated that male gender (OR=0.4, 95% CI 0.2-0.9, P=0.038 and OR=0.3, 95% CI 0.1-0.8, P=0.015) , SWOG cytogenetic classification into unfavorable or intermediate (OR=0.1, 95% CI 0.1-0.6, P=0.014 and OR=0.1, 95% CI 0.1-0.3, P=0.004) and receiving low-intensity regimen as induction regimen (OR=0.1, 95% CI 0.1-0.3, P=0.003 and OR=0.1, 95%CI 0.1-0.2, P=0.001) were typical adverse factors impacting the first CR and the final CR; PLT<45 × 10(9)/L (OR=0.4, 95%CI 0.2-0.9, P=0.038) and LDH ≥258 U/L (OR=0.3, 95%CI 0.1-0.7, P=0.005) were independent factors for CR. Among the 94 patients with achieving MLFS, 46 cases had allogeneic hematopoietic stem cell transplantation. With a median follow-up period of 18.6 months, the probabilities of relapse-free survival (RFS) and overall survival (OS) at 3 years were 25.4% and 37.3% in patients with transplantation, and in patients with chemotherapy, the probabilities of RFS and OS at 3-year were 58.2% and 64.3%, respectively. At the time of achieving MLFS, multivariate analysis revealed that age ≥46 years (HR=3.4, 95%CI 1.6-7.2, P=0.002 and HR=2.5, 95%CI 1.1-6.0, P=0.037) , peripheral blasts ≥17.5% at diagnosis (HR=2.5, 95%CI 1.2-4.9, P=0.010 and HR=4.1, 95%CI 1.7-9.7, P=0.002) , monosomal karyotypes (HR=4.9, 95%CI 1.2-19.9, P=0.027 and HR=28.3, 95%CI 4.2-189.5, P=0.001) were typical adverse factors influencing RFS and OS. Furthermore, CR after induction chemotherapy (HR=0.4, 95%CI 0.2-0.8, P=0.015) and transplantation (HR=0.4, 95%CI 0.2-0.9, P=0.028) were substantially linked to longer RFS. Conclusion: Post-MDS-AML and post-MPN-AML had lower response rates and poorer prognoses than t-AML and AML with unexplained cytopenia. In adults with male gender, low platelet count, high LDH, and SWOG cytogenetic classification into unfavorable or intermediate at diagnosis, and receiving low-intensity regimen as the induction regimen predicted a low response rate. Age ≥46 years, a higher proportion of peripheral blasts and monosomal karyotype had a negative effect on the overall outcome. Transplantation and CR after induction chemotherapy were greatly linked to longer RFS.

[Revision rate of periprosthetic joint infection post total hip or knee arthroplasty of 34 hospitals in China between 2015 and 2017: a multi-center survey].

Objective: To investigate the rate of periprosthetic joint infection (PJI) revision surgeries and clinical information of hip-/knee- PJI cases nationwide from 2015 to 2017 in China. Methods: An epidemiological investigation. A self-designed questionnaire and convenience sampling were used to survey 41 regional joint replacement centers nationwide from November 2018 to December 2019 in China. The PJI was diagnosed according to the Musculoskeletal Infection Association criteria. Data of PJI patients were obtained by searching the inpatient database of each hospital. Questionnaire entries were extracted from the clinical records by specialist. Then the differences in rate of PJI revision surgery between hip- and knee- PJI revision cases were calculated and compared. Results: Total of 36 hospitals (87.8%) nationwide reported data on 99 791 hip and knee arthroplasties performed from 2015 to 2017, with 946 revisions due to PJI (0.96%). The overall hip-PJI revision rate was 0.99% (481/48 574), and it was 0.97% (135/13 963), 0.97% (153/15 730) and 1.07% (193/17 881) in of 2015, 2016, 2017, respectively. The overall knee-PJI revision rate was 0.91% (465/51 271), and it was 0.90% (131/14 650), 0.88% (155/17 693) and 0.94% (179/18 982) in 2015, 2016, 2017, respectively. Heilongjiang (2.2%, 40/1 805), Fujian (2.2%, 45/2 017), Jiangsu (2.1%, 85/3 899), Gansu (2.1%, 29/1 377), Chongqing (1.8%, 64/3 523) reported relatively high revision rates. Conclusions: The overall PJI revision rate in 34 hospitals nationwide from 2015 to 2017 is 0.96%. The hip-PJI revision rate is slightly higher than that in the knee-PJI. There are differences in revision rates among hospitals in different regions.

Promotional Effect and Molecular Mechanism of Synthesized Zinc Oxide Nanocrystal on Zirconia Abutment Surface for Soft Tissue Sealing.

Studies have confirmed that tooth loss is closely related to systemic diseases, such as obesity, diabetes, cardiovascular diseases, some types of tumors, and Alzheimer's disease. Among many methods for tooth restoration, implant restoration is the most commonly used method. After implantation, long-term stability of implants requires not only good bone bonding but also good soft tissue sealing between implants and surrounding soft tissues. The zirconia abutment is used in clinical implant restoration treatment, but due to the strong biological inertia of zirconia, it is difficult to form stable chemical or biological bonds with surrounding tissues. In this study, we investigated synthesized zinc oxide (ZnO) nanocrystal on the zirconia abutment surface by the hydrothermal method to make it more beneficial for soft tissue early sealing and the molecular mechanism. In vitro experiments found that different hydrothermal treatment temperatures affect the formation of ZnO crystals. The crystal diameter of ZnO changes from micron to nanometer at different temperatures, and the crystal morphology also changes. In vitro, scanning electron microscopy, energy dispersive spectrometry, and real-time polymerase chain reaction results show that ZnO nanocrystal can promote the attachment and proliferation of oral epithelial cells on the surface of zirconia by promoting the binding of laminin 332 and integrin ß4, regulating the PI3K/AKT pathway. In vivo, ZnO nanocrystal ultimately promotes the formation of soft tissue seals. Collectively, ZnO nanocrystal can be synthesized on a zirconia surface by hydrothermal treatment. It can help to form a seal between the implant abutment and surrounding soft tissue. This method is beneficial to the long-term stability of the implant and also can be applied to other medical fields.