Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

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.
Humans ; Male ; Female ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Hospital Mortality ; Cohort Studies ; Prospective Studies ; Water-Electrolyte Imbalance ; Sepsis ; Intensive Care Units ; Retrospective Studies

The massive loss of oligodendrocytes caused by various pathological factors is a basic feature of many demyelinating diseases of the central nervous system (CNS). Based on a variety of studies, it is now well established that impairment of oligodendrocyte precursor cells (OPCs) to differentiate and remyelinate axons is a vital event in the failed treatment of demyelinating diseases. Recent evidence suggests that Foxg1 is essential for the proliferation of certain precursors and inhibits premature neurogenesis during brain development. To date, very little attention has been paid to the role of Foxg1 in the proliferation and differentiation of OPCs in demyelinating diseases of the CNS. Here, for the first time, we examined the effects of Foxg1 on demyelination and remyelination in the brain using a cuprizone (CPZ)-induced mouse model. In this work, 7-week-old Foxg1 conditional knockout and wild-type (WT) mice were fed a diet containing 0.2% CPZ w/w for 5 weeks, after which CPZ was withdrawn to enable remyelination. Our results demonstrated that, compared with WT mice, Foxg1-knockout mice exhibited not only alleviated demyelination but also accelerated remyelination of the demyelinated corpus callosum. Furthermore, we found that Foxg1 knockout decreased the proliferation of OPCs and accelerated their differentiation into mature oligodendrocytes both in vivo and in vitro. Wnt signaling plays a critical role in development and in a variety of diseases. GSK-3β, a key regulatory kinase in the Wnt pathway, regulates the ability of β-catenin to enter nuclei, where it activates the expression of Wnt target genes. We then used SB216763, a selective inhibitor of GSK-3β activity, to further demonstrate the regulatory mechanism by which Foxg1 affects OPCs in vitro. The results showed that SB216763 clearly inhibited the expression of GSK-3β, which abolished the effect of the proliferation and differentiation of OPCs caused by the knockdown of Foxg1. These results suggest that Foxg1 is involved in the proliferation and differentiation of OPCs through the Wnt signaling pathway. The present experimental results are some of the first to suggest that Foxg1 is a new therapeutic target for the treatment of demyelinating diseases of the CNS.

Objective: To evaluate the feasibility and potential value of comprehensive geriatric assessment (CGA) in elderly (≥60 years) patients with newly diagnosed acute myeloid leukemia (AML) in China. Methods: The CGA results of 83 newly diagnosed AML (non-APL) patients from 16 hospitals in Beijing and Tianjin between March 2016 and December 2017 were prospectively collected and analyzed. The clinical data, treatment and follow-up information were also collected. Results: Of 83 newly diagnosed elderly AML patients, 81 patients (97.6%) completed all designated CGA assessment. The median number of impaired scales of the CGA assessment in the studied population was 2(0-6). Sixteen patients (19.3%) showed no impairments according to the geriatric assessment scales implem ented by this study. The distributions of impaired scales were as follows: impairment in ADL, 55.4%; IADL impairment, 42.2%; MNA-SF impairment, 48.2%; cognitive impairment, 15.7%; GDS impairment, 31.7%; HCT-CI impairment, 19.5%, respectively. In patients with "good" ECOG (n=46), the proportion of impairment for each CGA scale ranged from 6.5% to 37.0% and 32 patients (68.9%) had at least one impaired CGA scale. Survival analysis showed that the number of impaired scales of the CGA was significantly correlated with median overall survival (P=0.050). Conclusions CGA was a tool with feasibility for the comprehensive evaluation in elderly AML patients in China. Combined with age and ECOG, CGA may be more comprehensive in assessing patients’ physical condition.

OBJECTIVE: To observe the incidence of intensive care unit-acquired weakness (ICU-AW) of mechanically ventilated patients, and to identify the relevant risk factors. METHODS: A prospective cohort study was conducted. The patients admitted to intensive care unit (ICU) of Fuxing Hospital, Capital Medical University, aged 18 years old or older, with the duration of mechanical ventilation ≥ 24 hours and expected to stay in ICU for ≥ 7 days from May 2015 to January 2016 were enrolled. From the 7th day after ICU admission, the patients were evaluated for consciousness every day. If the patient was awake and could cooperate with muscle strength measurement, the day was recorded as T1, and the patient's muscle strength was measured using the Medical Research Council scale (MRC) and recorded, then all patients were divided into two groups according to MRC score, ICU-AW group (MRC score < 48) and non-ICU-AW group (MRC score ≥ 48). The death, transfer or the 28th day of ICU admission were regarded as the end of observation. The data from the first day of ICU admission to T1 (before T1), including metabolic factors (the lowest value of blood sodium, blood potassium, blood calcium, albumin, and the highest value of blood glucose), mechanical ventilation factors (mode and duration of mechanical ventilation), organ dysfunction factors [occurrence and duration of sepsis, multiple organ dysfunction syndrome (MODS)], and drug factors (whether the patients used aminoglycoside, sedative, muscle relaxant or glucocorticoids, etc., the time of these drugs usage and the cumulative dose) of the patients were observed, recorded and analyzed, as well as the data from T1 to the end of the observation period, including the duration of mechanical ventilation, incidence of ventilator associated pneumonia (VAP), 28-day mortality, the length of ICU stay, and the cost of ICU and hospitalization. The relevant factors with statistical significance in univariate analysis were enrolled in multivariate analysis, and Logistic regression equation was established to screen the independent risk factors that might lead to ICU-AW. RESULTS: 486 patients with mechanical ventilation were enrolled in this study, and 37 patients were enrolled according to the inclusion and exclusion criteria, including 15 patients with ICU-AW (with ICU-AW incidence of 40.5%) and 22 patients without ICU-AW. In the univariate analysis, ICU-AW group patients showed statistical differences in following factors as compared with the non-ICU-AW group: age, and the duration of invasive ventilation and the total duration of mechanical ventilation, braking time, sepsis, MODS and duration of them, the usage days and dosage of sedative and glucocorticoid before T1. The total duration of mechanical ventilation from T1 to the end of the observation period, total duration of mechanical ventilation during the observation period, and length of ICU stay of the ICU-AW group were significantly longer than those of the non-ICU-AW group [hours: 190 (110, 274) vs. 4 (0, 57), hours: 337 (237, 477) vs. 78 (43, 170), days: 20±7 vs. 14±7, all P < 0.05], the incidence of VAP, 28-day mortality and total hospitalization expenses were significantly higher than those of the non-ICU-AW group [26.7% (4/15) vs. 0% (0/22), 53.3% (8/15) vs. 9.1% (2/22), 10 thousands Yuan: 18.7±7.7 vs. 12.1±10.8, all P < 0.05]. Multivariate Logistic regression analysis showed that the total duration of mechanical ventilation between the patient awake and ICU admission [odds ratio (OR) = 1.03, 95% confidence interval (95%CI) was 1.01-1.05, P = 0.011] and the duration of MODS (OR = 1.79, 95%CI was 1.17-2.72, P = 0.007) were the independent risk factors for ICU-AW in mechanically ventilated patients. CONCLUSIONS ICU-AW is quite common in patients with mechanical ventilation and has a higher incidence. The risk factors associated with ICU-AW were the total duration of mechanical ventilation and duration of MODS.
Adult ; Humans ; Intensive Care Units ; Muscle Weakness/epidemiology* ; Prevalence ; Prospective Studies ; Respiration, Artificial ; Risk Factors

Objective: To observe the incidence of intensive care unit-acquired weakness (ICU-AW) of mechanically ventilated patients, and to identify the relevant risk factors. Methods: A prospective cohort study was conducted. The patients admitted to intensive care unit (ICU) of Fuxing Hospital, Capital Medical University, aged 18 years old or older, with the duration of mechanical ventilation ≥ 24 hours and expected to stay in ICU for ≥ 7 days from May 2015 to January 2016 were enrolled. From the 7th day after ICU admission, the patients were evaluated for consciousness every day. If the patient was awake and could cooperate with muscle strength measurement, the day was recorded as T1, and the patient's muscle strength was measured using the Medical Research Council scale (MRC) and recorded, then all patients were divided into two groups according to MRC score, ICU-AW group (MRC score < 48) and non-ICU-AW group (MRC score ≥ 48). The death, transfer or the 28th day of ICU admission were regarded as the end of observation. The data from the first day of ICU admission to T1 (before T1), including metabolic factors (the lowest value of blood sodium, blood potassium, blood calcium, albumin, and the highest value of blood glucose), mechanical ventilation factors (mode and duration of mechanical ventilation), organ dysfunction factors [occurrence and duration of sepsis, multiple organ dysfunction syndrome (MODS)], and drug factors (whether the patients used aminoglycoside, sedative, muscle relaxant or glucocorticoids, etc., the time of these drugs usage and the cumulative dose) of the patients were observed, recorded and analyzed, as well as the data from T1 to the end of the observation period, including the duration of mechanical ventilation, incidence of ventilator associated pneumonia (VAP), 28-day mortality, the length of ICU stay, and the cost of ICU and hospitalization. The relevant factors with statistical significance in univariate analysis were enrolled in multivariate analysis, and Logistic regression equation was established to screen the independent risk factors that might lead to ICU-AW. Results: 486 patients with mechanical ventilation were enrolled in this study, and 37 patients were enrolled according to the inclusion and exclusion criteria, including 15 patients with ICU-AW (with ICU-AW incidence of 40.5%) and 22 patients without ICU-AW. In the univariate analysis, ICU-AW group patients showed statistical differences in following factors as compared with the non-ICU-AW group: age, and the duration of invasive ventilation and the total duration of mechanical ventilation, braking time, sepsis, MODS and duration of them, the usage days and dosage of sedative and glucocorticoid before T1. The total duration of mechanical ventilation from T1 to the end of the observation period, total duration of mechanical ventilation during the observation period, and length of ICU stay of the ICU-AW group were significantly longer than those of the non-ICU-AW group [hours: 190 (110, 274) vs. 4 (0, 57), hours: 337 (237, 477) vs. 78 (43, 170), days: 20±7 vs. 14±7, all P < 0.05], the incidence of VAP, 28-day mortality and total hospitalization expenses were significantly higher than those of the non-ICU-AW group [26.7% (4/15) vs. 0% (0/22), 53.3% (8/15) vs. 9.1% (2/22), 10 thousands Yuan: 18.7±7.7 vs. 12.1±10.8, all P < 0.05]. Multivariate Logistic regression analysis showed that the total duration of mechanical ventilation between the patient awake and ICU admission [odds ratio (OR) = 1.03, 95% confidence interval (95%CI) was 1.01-1.05, P = 0.011] and the duration of MODS (OR = 1.79, 95%CI was 1.17-2.72, P = 0.007) were the independent risk factors for ICU-AW in mechanically ventilated patients. Conclusions ICU-AW is quite common in patients with mechanical ventilation and has a higher incidence. The risk factors associated with ICU-AW were the total duration of mechanical ventilation and duration of MODS.

Background: With the publication of Sepsis-3 definition, epidemiological data based on Sepsis-3 definition from middle-income countries including China are scarce, which prohibits understanding of the disease burden of this newly defined syndrome in these settings. The purpose of this study was to describe incidence and outcome of Sepsis-3 in Yuetan sub-district of Beijing and to estimate the incidence rate of Sepsis-3 in China. Methods: The medical records of all adult residents hospitalized from July 1, 2012 to June 30, 2014 in Yuetan sub-district of Beijing were reviewed. Patients with sepsis-3 and severe sepsis/septic shock were identified. The incidence rates and mortality rate of sepsis-3 and sepsis/septic shock were calculated, incidence rates and in-hospital mortality rates were normalized to the population distribution in the 2010 National Census. Population incidence rate and case fatality rate between sexes were compared with the Z test, as the data conformed to Poisson distribution. Results: Of the 21,191 hospitalized patients, 935 patients were diagnosed with Sepsis-3, and 498 cases met severe sepsis/septic shock criteria. The crude annual incidence rate of Sepsis-3 in Yuetan sub-district was 363 cases per 100,000 population, corresponding to standardized incidence rates of 236 cases per 100,000 population per year, respectively. The overall case fatality rate of Sepsis-3 was 32.0%, the crude population mortality rates of Sepsis-3 was 116 cases per 100,000 population per year, the standardized mortality rate was 67 cases per 100,000 population per year, corresponding to a speculative extrapolation of 700,437 deaths in China. The incidence rate and mortality rate of Sepsis-3 were significantly higher in males, elderly people, and patients with more comorbidities. The 62.1% of patients with Sepsis-3 had community-acquired infections, compared with 75.3% of infected patients without Sepsis-3 (P < 0.001). The most common infection in patients with Sepsis-3 was lower respiratory tract infection. When compared with patients with Sepsis-3, patients diagnosed as severe sepsis/septic shock were more likely to have higher case fatality rate (53.4% vs. 32.0%, P < 0.001) Conclusions: This study found the standardized incidence rate of 236 cases per 100,000 person-year for Sepsis-3, which was more common in males and elderly population. This corresponded to about 2.5 million new cases of Sepsis-3 per year, resulting in more than 700,000 deaths in China. Clinical trial registration NCT02285257, https://clinicaltrials.gov/ct2/show/record/NCT02285257.

Objective: To evaluate the feasibility and potential value of comprehensive geriatric assessment (CGA) in elderly (≥60 years) patients with newly diagnosed acute myeloid leukemia (AML) in China. Methods: The CGA results of 83 newly diagnosed AML (non-APL) patients from 16 hospitals in Beijing and Tianjin between March 2016 and December 2017 were prospectively collected and analyzed. The clinical data, treatment and follow-up information were also collected. Results: Of 83 newly diagnosed elderly AML patients, 81 patients (97.6%) completed all designated CGA assessment. The median number of impaired scales of the CGA assessment in the studied population was 2(0-6). Sixteen patients (19.3%) showed no impairments according to the geriatric assessment scales implem ented by this study. The distributions of impaired scales were as follows: impairment in ADL, 55.4%; IADL impairment, 42.2%; MNA-SF impairment, 48.2%; cognitive impairment, 15.7%; GDS impairment, 31.7%; HCT-CI impairment, 19.5%, respectively. In patients with "good" ECOG (n=46), the proportion of impairment for each CGA scale ranged from 6.5% to 37.0% and 32 patients (68.9%) had at least one impaired CGA scale. Survival analysis showed that the number of impaired scales of the CGA was significantly correlated with median overall survival (P=0.050). Conclusions: CGA was a tool with feasibility for the comprehensive evaluation in elderly AML patients in China. Combined with age and ECOG, CGA may be more comprehensive in assessing patients' physical condition.
Activities of Daily Living ; Aged ; China ; Geriatric Assessment ; Humans ; Leukemia, Myeloid, Acute ; Prospective Studies

Objective To study the clinicopathological features and differential diagnosis of bizarre parosteal osteochondromatous proliferation (BPOP). Methods The clinicopathological features of 3 patients with BPOP were analyzed , and related literature was reviewed. Results 3 patients included 2 males and 1 female with an average age 40 years old (24-53 years old). The lesions in three patients were located in the left side of the distal radius, the left side of the little finger inside and the right side of ulna coracoid, respectively. Histologically, characterized by unusual mineralized cartilaginous matrix (`blue bone'), the lesion was composed of a heterogeneous mixture of bone, cartilage and fibrous tissue. Conclusion BPOP is a rare benign surface osteocartilaginous lesion, and its diagnosis and differential diagnosis mainly depend on radiographic and histopathologic features.