Acetaminophen(AAP)-induced hepatic injury is one of the common causes of drug-induced hepatic injury.Up to date,the mechanisms of AAP-induced hepatic injury are still incompletely understood.Recent advances suggest that reactive metabolite formation,glutathione depletion,alkylation of proteins,especially mitochondrial proteins and peroxynitrite formation are critical initiating events for the toxicity.This review will focus on more recent advances in mitochondrial dysfunction after AAP overdose.Additional,oxidative stress and inflammatory mediators are also important for the overall outcome.

Objective To investigate the predictive value of clinical and radiographic features in fungal pathogen identification in immunocompromised patients with pulmonary invasive fungal infection (IFI).Methods All consecutive immunocompromised adult patients with pulmonary IFI in respiratory intensive care unit (ICU)in the First Affiliated Hospital of Xinjiang Medical University were recruited during a 2 year period.All patients met the 2008 European Organization for Research and Treatment of Cancer and Mycoses Study Group (EORTC /MSG) criteria were studied for proved or probable IFI responding to antifungal agents.The data of demographic,clinical and radiographic features,as well as serological test results of the patients were collected.Differences in the clinical and radiographic features of pulmonary IFIs caused by yeasts and molds were compared by χ2 test.A logistic regression model was used to perform discriminant analysis,and the effect of discrimination was assessed for accuracy.Results The study included 143 patients with a probable diagnosis of IFI who had the following risk factors:diabetes mellitus (43.4%),chronic lung disease (32.2%),broad-spectrum antibiotics administration (≥14 days;35.7%),malignancy (23.1%),corticosteroid therapy (≥14 days;23.1%),chronic renal failure and renal replacement therapy (16.1%),and immunological disease (10.5%).Frequent broad-spectrum antibiotics administration was associated with yeast infection (P <0.05 ),while mold infection was associated with chronic lung disease (P <0.05 ) .Yeast was more often isolated from patients with concurrent bacterial infection and on mechanical ventilation (P <0.05 ) . Thoracic high-resolution computed tomography (HRCT)showed the following images:bronchial pneumonia/pulmonary consolidation (53.1%),massive shadowing (29.4%),small nodules (24.5%),large nodules (18.9%),pleural effusion (18.9%),halo sign (14%),and cavity (9.8%).Imaging showed that mold was more common than yeast in patients with pleural and pericardial effusions (P <0.05).Logistic regression modeling showed that broad-spectrum antibiotics administration,prolonged mechanical ventilation,and pleural and pericardial effusions were statistically significant in fungal identification (P <0.05 ),with a predictive accuracy of 77.6%.Conclusions For immunocompromised patients with pulmonary IFI,most of the risk factors ,the main clinical and chest HRCT features did not help to predict the type of fungal pathogen,and yeast but not cryptococcus may be accompanied or colonized.

Objective:To investigate the expression of fibroblast growth factor 7 (FGF7) and related inflammatory factors in the serum of patients with acute exacerbation of chronic obstructive pulmonary disease (COPD).Methods:A case control study was conducted. The patients with AECOPD admitted to the First Affiliated Hospital of Xinjiang Medical University from November 2016 to January 2020 were enrolled. The patients were divided into mild group [forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio (FEV1/FVC) < 0.70, FEV1 percentage in predicted value (FEV1%) ≥ 80%], moderate group (FEV1/FVC < 0.70, 50% ≤ FEV1% < 80%), and severe group (FEV1/FVC < 0.70, 30% ≤ FEV1% < 50%) based on their lung function test results, with 20 patients in each group, and 20 patients with normal pulmonary function who underwent elective non-thoracic surgery such as gastrointestinal surgery and orthopedics surgery in the same period were selected as controls. The demographic data, FEV1/FVC, FEV1%, FVC, maximum mid-expiratory flow percentage in predicted value (MMEF%), 6-minute walking test (6MWT), and St George Respiratory Questionnaire (SGRQ) score were recorded respectively. Serum levels of FGF7, interleukins (IL-6, IL-1β) and tumor necrosis factor-α (TNF-α) were determined by enzyme linked immunosorbent assay (ELISA). Pearson correlation was used to analyze the correlation between TNF-α and lung function.Results:Compared with the normal pulmonary function group, the levels of FEV1/FVC, FEV1%, MMEF% and 6MWT in the mild, moderate and severe groups were significantly decreased, and the SGRQ scores were increased, the indicators continued to deteriorate with the aggravation of the disease, the statistical differences were found between severe group and normal pulmonary function group [FEV1/FVC: 0.39±0.09 vs. 0.81±0.04, FEV1%: (38.80±6.28)% vs. (109.58±13.80)%, MMEF%: (0.34±0.14)% vs. (2.69±0.99)%, 6MWT (m): 279.00±41.61 vs. 402.85±53.97, SGRQ scores: 34.95±6.71 vs. 2.60±2.06, all P < 0.05]. Compared with the normal pulmonary function group, the levels of FGF7 in the mild, moderate and severe groups were significantly lowered (ng/L: 6.31±2.65, 6.10±1.39, 6.64±1.77 vs. 8.29±3.51, all P < 0.05), but no significant difference was found among the mild, moderate and severe groups (all P > 0.05). Compared with the normal pulmonary function group, IL-6 and TNF-α levels were significantly increased in the mild, moderate and severe groups, and TNF-α increased with the aggravation of the disease, the statistical difference was found between severe group and normal pulmonary function group (ng/L: 7.42±2.28 vs. 3.83±0.92, P < 0.05). There was no significant difference in IL-1β level between the normal pulmonary function group and the mild, moderate, severe groups. Correlation analysis showed that TNF-α was negatively correlated with FEV1/FVC and FEV1% ( r values were -0.350 and -0.527, respectively, both P < 0.01). Conclusion:In AECOPD patients, serum FGF7 was decreased, while IL-6 and TNF-α were increased; however, with the aggravation of the disease, there was no significant change in the level of FGF7 in the peripheral blood, but the TNF-α level might be increased, accompanied by severe damage of small airway function.

Objective To evaluate the predictive factors for failure of non-invasive positive pressure ventilation (NIPPV) in immunosuppressed patients with acute respiratory failure (ARF). Methods The clinical data of 118 immuno-deficient patients treated with NIPPV in the respiratory and intensive care unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University from January 2012 to August 2017 were retrospectively analyzed. The patients were divided into a non-endotracheal intubation (ETI) group (n = 62) and ETI group (n = 56) according to whether ETI was performed during the hospitalization period or not. Each observed indicator was analyzed by univariate analysis, and factors leading to failure of NIPPV were further analyzed by Logistic regression. Receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of risk factors for failure of NIPPV in immunosuppressed patients with ARF. Results The non-intubation rate for NIPPV in immunosuppressed patients was 50.8% (60/118). Compared with the non-ETI group, the body temperature, pH value in the ETI group were significantly increased, the partial pressure of arterial carbon dioxide (PaCO2) was significantly decreased, the ratio of oxygenation index (PaO2/FiO2) < 100 mmHg (1 mmHg = 0.133 kPa), acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ) score ≥ 20, and the number of cases requiring catecholamine were significantly increased, the mortality was significantly increased. Multivariate Logistic regression analysis showed that the APACHE Ⅱ score ≥ 20 [odds ratio (OR) = 15.274, 95% confidence internal (95%CI) = 2.175-107.252, χ2= 7.516, 1 = 0.006], PaO2/FiO2< 100 mmHg (OR = 0.075, 95%CI = 0.014-0.408, χ2= 8.968, 1 = 0.003), and need for catecholamine (OR = 35.736, 95%CI = 6.974-183.124, χ2= 18.400, 1 < 0.001) were independent risk factors for failure of NIPPV. ROC curve analysis showed that the APACHE Ⅱ score ≥ 20 and PaO2/FiO2< 100 mmHg could predict failure of NIPPV, the area under ROC curve (AUC) of the APACHE Ⅱ score ≥ 20 was 0.787, the sensitivity was 83.93%, the specificity was 69.35%, the positive predict value (PPV) was 71.21%, the negative predict value (NPV) was 82.69%, the positive likelihood ratio (PLR) was 2.74, the negative likelihood ratio (NLR) was 0.23, and Youden index was 0.53; the AUC of PaO2/FiO2< 100 mmHg was 0.757, the sensitivity was 80.65%, the specificity was 66.07%, the PPV was 68.18%, the NPV was 78.85%, the PLR was 2.38, the NLR was 0.29, and Youden index was 0.47. Conclusions 50.8% of immunocompromised and ARF patients treated with NIPPV did not require ETI, which is independent of the etiology of ARF. APACHE Ⅱ score ≥ 20, PaO2/FiO2<100 mmHg, and the need for catecholamine are predictive factors for failure of NIPPV in immunocompromised patients.

Objective:To explore the pros and cons of sequential high-flow nasal cannula (HFNC) and non-invasive positive pressure ventilation (NIPPV) immediately following early extubated patients with severe respiratory failure (SRF) due to acute exacerbations of chronic obstructive pulmonary disease (AECOPD), so as to provide evidence for clinical selection of optimal scheme.Methods:Consecutive AECOPD patients admitted to the respiratory intensive care unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University from January 2019 to September 2020 were screened for enrollment. Patients were between 40 years old and 85 years old with acute exacerbation of bronchial-pulmonary infection, who received endotracheal intubation mechanical ventilation (ETI-MV) as the initial respiratory support method. The pattern of synchronous intermittent mandatory ventilation (SIMV) was used in the study. The parameters were set as follows: tidal volume (VT) 8 mL/kg, support pressure 10-15 cmH 2O (1 cmH 2O = 0.098 kPa), positive end-expiratory pressure (PEEP) 4-6 cmH 2O and the ratio of inspiratory to expiratory time 1.5-2.5∶1. Under these conditions, the plateau pressure (Pplat) was maintained less than 30 cmH 2O. The minimum fraction of inspired oxygen was adjusted to keep the pulse oxygen saturation no less than 0.92. When the pulmonary infection control window (PIC window) occurred, the subjects were extubated immediately and randomly divided into two groups, with one group receiving HFNC (called HFNC group), the other group receiving NIPPV (called NIPPV group). Patients with failed sequential HFNC or NIPPV underwent tracheal re-intubation. The rate of tracheal re-intubation within 7 days of extubation, complications (such as nose and face crush injury and gastric distension), in-hospital mortality, duration of ETI before PIC window, length of RICU stay and length of hospital stay were compared, respectively. Results:Forty-four patients were enrolled in the study, 20 in the HFNC group and 24 in the NIPPV group. There was no significant difference in the duration of ETI before PIC window between HFNC and NIPPV groups (hours: 95.9±13.1 vs. 91.8±20.4, P > 0.05). The rate of tracheal re-intubation within 7 days in the HFNC group was significantly higher than that in the NIPPV group [35.0% (7/20) vs. 4.2 % (1/24), P < 0.05]. However, the incidence of complication in the HFNC group was significantly lower than that in the NIPPV group [0% (0/20) vs. 25.0% (6/24), P < 0.05]. Compared with the NIPPV group, the in-hospital mortality in the HFNC group was slightly higher [5.0% (1/20) vs. 4.2% (1/24)], the length of RICU stay (days: 19.5±10.8 vs. 15.5±7.2) and the length of hospital stay (days: 27.4±12.2 vs. 23.3±10.9) were slightly longer, without statistical differences (all P > 0.05). Conclusion:For early extubated patients with SRF due to AECOPD, the compliance of sequential HFNC increased and the complications decreased significantly, but the final effect may be worse than sequential NIPPV.

Objectives: To investigate the influence of duration of antibiotic therapy on the prognosis of patients with AML who had Gram-negative bloodstream infection during consolidation chemotherapy. Methods: Data were collected retrospectively from 591 patients enrolled from the registered "A Phase III study on optimizing treatment based on risk stratification for acute myeloid leukemia, ChiCTR-TRC-10001202" treatment protocol between September 2010 and January 2016 in different treatment cycles. Results: A total of 119 episodes of Gram-negative bloodstream infection occurred during consolidation chemotherapy. Excluding the 5 episodes in which fever lasted longer than 7 days, 114 episodes of infection were analyzed. The median neutrophil count was 0 (0-5.62)×10⁹/L, median neutropenia duration was 9 (3-26) days, median interval of antibiotics administration was 7 (4-14) days. Logistic regression analysis showed that there is no significant difference on 3-day recurrent fever rate and reinfection by the same type bacteria between antibiotics administration ≤7 days or >7 days (1.2% vs 3.0%, P=0.522, OR=0.400, 95% CI 0.024-6.591; 18.5% vs 21.2%, P=0.741, OR=0.844, 95% CI 0.309-2.307). Propensity score analysis confirmed there was no significant difference on same pathogen infection rate between antibiotics application time ≤ 7 days or >7 days (P=0.525, OR=0.663, 95% CI 0.187-2.352). No infection associated death occurred within 7 or 30 days in both groups. Conclusion Discontinuation of therapy until sensitive antibiotics treated for 7 days does not increase the recurrent fever rate and the infection associated death rate. Indicating that, for AML who had Gram-negative bloodstream infection during consolidation chemotherapy, short courses of antibiotic therapy is a reasonable treatment option when the infection is controlled.

Objective: To analyze the clinical, laboratory characteristics and prognosis of adult early T-cell precursor acute lymphoblastic leukemia (ETP-ALL). Methods: The clinical data of 13 adult ETP-ALL patients from January 2009 to March 2017 were retrospectively analyzed and compared with non-ETP ALL patients. Results: 13 ETP-ALL patients (17.3%) were identified in 75 adult T-ALL patients, the median age of the patients was 35 years old (15 to 49 years) and 10 patients were male (76.9%). ETP-ALL patients had lower WBC count, LDH level, blasts in peripheral blood, lower incidence of thymic mass and higher PLT count compared to non-ETP ALL patients. The CR rate after one course induction chemotherapy for ETP-ALL and non-ETP ALL patients was 33.3% and 90.1%, respectively (χ²=26.521, P<0.001). The median overall survival(OS) was 11.33 (95%CI 0-28.46) and 25.69 (95%CI 11.98-39.41) months, respectively. The 3-year OS was 41.7% and 40.7%, respectively (P=0.699). The median event free survival (EFS) was 1.51 (95%CI 1.23-1.79) and 21.36 (95%CI 4.67-38.04) months, respectively. The 3-year EFS was 16.7% and 39.5%, respectively (P=0.002). The 3-year relapse free survival (RFS) was 53.0% and 52.0%, respectively (P=0.797). Multivariate analysis revealed that CNSL and allo-HSCT were independent risk factors affecting OS of T-ALL and ETP-ALL didn’t affect the prognosis of T-ALL. Conclusion To our knowledge, this study is the first report on characteristics and prognosis of adult ETP-ALL patients in China. At total of 13 T-ALL patients (17.3%) were classified as having ETP-ALL. These patients had a lower leukemia burden and lower CR rate after one course induction compared to non-ETP ALL patients. Allo-HSCT can improve the prognosis of ETP-ALL.

Objective: To analyze the clinical features and prognosis of acute lymphoblastic leukemia patients with immunophenotype of CD10^-pre-B (CD10^- pre B-ALL) . Methods: 6 adult cases with CD10^- pre B-ALL immunophenotypes were analyzed retrospectively, related literatures were reviewed to clarify these kind of patients’ clinical features and prognosis. Results: CD10^- pre B-ALL occurred in 1.5% of ALL, 1.8% of B-ALL and 11.5% of pre B-ALL respectively. All the 6 patients were male with the median age as 33.5 years old, the median white blood cells was 101.78×10⁹/L, MLL-AF4 fusion transcripts were evident in all cases. Complete remission (CR) was achieved in 5 patients after first induction chemotherapy, 1 patient failed to respond to induction therapy, and got CR after 3 courses of chemotherapy. 2 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in CR₁, 1 patient relapsed in the short term and underwent allo-HSCT in CR₂. 1 patient was still waiting for allo-HSCT. Of the 2 patients who didn’t receive transplantation, 1 died following a relapse, the other remained to be in CR. Conclusions CD10^- pre B-ALL was a rare but distinct subtype in adult ALL characterized by male dominance, high onset white blood cells and MLL rearrangement rate. Conventional chemotherapy produced a high response rate but more likely relapse, allo-HSCT may have the potential to improve the prognosis of these patients.

Objective:To investigate the influencing factors of endotracheal intubation and mechanical ventilation (ETI-MV) in patients with acute respiratory distress syndrome (ARDS) caused by viral pneumonia, and to provide evidence for individualized use of ETI-MV.Methods:Patients with ARDS due to viral pneumonia admitted to the respiratory intensive care unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University were retrospectively analyzed from November 2017 to March 2022. The gender, age, concomitant diseases, clinical symptoms and signs, complications, lab results, ARDS severity, infectious virus type, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ), respiratory support methods and prognosis-related variables were collected. Univariate analysis was performed on each factor, and the variables with statistical significance in the univariate analysis were subjected multivariate logistic regression analysis. The receiver operating characteristic curve (ROC curve) was drawn to evaluate the predictive value of each index for the implementation of ETI-MV.Results:A total of 117 patients were enrolled in the study, including 61 patients in the ETI-MV group, and 3 patients (4.9%), 39 patients (63.9%) and 19 patients (31.1%) with mild, moderate and severe ARDS, respectively. There were 56 patients in non-ETI-MV group, and the mild, moderate and severe ARDS cases were 16 cases (28.6%), 38 cases (67.8%) and 2 cases (3.6%), respectively. There was significant difference between the two groups ( P < 0.05). Univariate analysis showed that during 24 hours admitted to RICU, the levels of interleukin-6 [IL-6 (ng/L): 104.0±90.0 vs. 62.4±76.0], oxygenation index [PaO 2/FiO 2 (mmHg, 1 mmHg≈0.133 kPa): 123.9±30.9 vs. 173.6±28.5], the proportion of cases with pulmonary infiltrating opacity distribution range ≥ 3/4 lung fields [85.3% (52/61) vs. 21.5% (12/56)], APACHE Ⅱ score ≥ 16.5 [67.2% (41/61) vs. 42.9% (24/56)], the rate of nosocomial invasive aspergillus infection [14.8% (9/61) vs. 3.6% (2/56)], the percentage of nosocomial bacterial infection [16.4% (10/61) vs. 3.6% (2/56)], and the lowest CD4 + T lymphocyte count in the course of the disease [cells/mm 3: 192.2±35.8 vs. 215.0±58.3] had significant differences between ETI-MV and non-ETI-MV group (all P < 0.05). Multivariate Logistic regression analysis showed that during 24 hours admitted to RICU the distribution range of pulmonary infiltrating opacity ≥ 3/4 the lung fields [odds ratio ( OR) = 12.527, 95% confidence interval (95% CI) = 3.279-47.859, P < 0.001], APACHE Ⅱ score ≥ 16.5 ( OR = 30.604, 95% CI = 4.318-216.932, P = 0.001), PaO 2/FiO 2 ( OR = 0.948, 95% CI = 0.925-0.972, P < 0.001), CD4 + T lymphocytes cell count ( OR = 0.975, 95% CI = 0.955-0.995, P = 0.015), and nosocomial bacterial infection ( OR = 38.338, 95% CI = 1.638-897.158, P = 0.023) were independent risk factors for ETI-MV. The area under the ROC curve (AUC) of ROC showed that PaO 2/FiO 2 had the greatest predictive value for ETI-MV, with AUC of 0.903, sensitivity of 91.1% and specificity of 95.1% in case of cutoff value of 151 mmHg. The AUC of pulmonary infiltrating opacity distribution range was 0.809, the sensitivity of 85.2%, specificity of 78.6% when the cutoff value was ≥ 3/4 lung field. APACHE Ⅱ scores had the lowest predictive value for selecting ETI-MV, with AUC of 0.704, sensitivity of 83.6% and specificity of 57.1% under the cutoff value was 16.5. Conclusions:For patients with ARDS caused by viral pneumonia, PaO 2/FiO 2 is still the classic reference for selecting ETI-MV, however, the distribution range of pulmonary infiltrating opacity and the systemic severity of the disease during 24 hours admitted to the RICU may provide supplemental helpful information to determine whether the patients choose ETI-MV, especially for moderate ARDS.

Objective:To investigate the combination of internal fixation for periprosthetic fractures of the proximal femur (PFFF) after hip arthroplasty.Methods:The data of 58 patients with periprosthetic fractures after hip arthroplasty from May 2008 to March 2022 were retrospectively analyzed, including 31 males and 27 females. The average age was 75.5±18.2 years (range, 35-95 years). There were 39 total hip arthroplasty and 19 hemiarthroplasty; 37 biological prosthesis and 21 cemented prosthesis. Intraoperative periprosthetic fractures occurred in 6 cases and 52 cases postoperatively. Unified classification system (UCS): UCS IV.3A1 type 2 cases, 3A2 type 1 case, 3B1.1 type 19 cases, 3B2.1 type 25 cases, 3B3 type 2 cases, 3C type 9 cases. Fracture site: 3 cases in zone A (greater trochanter), 46 cases in zone B (around the femoral stem), and 9 cases in zone C (distal to the tip of the femoral stem. Internal fixation is composed of primary and secondary fixation, the main fixation method was the cerclage of steel wire or titanium cable, locking compression plate, and locking attachment plate fixation. The secondary fixation method was the cerclage of titanium cable, which was required to cover three zones A, B and C to form an overall balanced fixation. The modified Harris hip scores (mHHS), plate length, working length and screw number of different internal fixation combinations were compared.Results:The follow-up time was 54.2±21.6 months (range, 11-86 months). All patients showed signs of fracture healing at 10.2±1.5 weeks (range, 7-13 weeks) after operation, and bony union was observed at 19.6±1.3 weeks (range, 17-22 weeks) after operation. No delayed union or nonunion was observed. After operation, one case had a stress fracture and was revised with double-plate internal fixation; one case had a failed internal fixation and was revised with double-plate internal fixation and a large allograft bone graft. The mHHS score of UCSIV.3B2.1 group (80.3±4.6) was the lowest at 6 months after operation, and the difference between the groups of different types was statistically significant ( F=256.72, P<0.001). The score of simple internal fixation group (91.6±4.2) was higher than that of revision combined with internal fixation group (81.9±4.1), and the difference was statistically significant ( t=8.32, P<0.001). The plate length and working length were 24.9±2.5 cm and 12.6±1.7 cm for UCS IV.3B1.1, 25.4±2.6 cm and 13.6±1.8 cm for 3B2.1 and 28.1±2.5 cm and 4.9±1.9 cm for 3C, respectively ( F=5.33, P=0.005; F=6.78, P<0.001). The number of screws in zone A was significant difference among different UCS types ( F=52.67, P<0.001); UCS IV.3B1.1 (6.5±2.3) and 3B2.1 (6.7±2.2) were more than 3B3 (3.5±1.5) and 3C (3.7±1.6). The number of screws in zone B was significant difference among different UCS types ( F=42.15, P<0.001); The number of UCS IV.3B1.1 (2.3±1.6) and 3B2.1 (2.8±1.9) were significantly more than that of 3B3 (1.0±0.5) and 3C (1.2±0.6). The number of screws in zone C was significant differences among different UCS types ( F=39.62, P<0.001); The number of UCS IV.3B1.1 (3.8±1.9) and 3B2.1 (3.9±1.7) were more than that of 3B3 (2.0±0.5), the difference was statistically significant ( P<0.05). Conclusion:The function of hip after simple internal fixation of proximal femoral periprosthetic fractures was better than that of those who underwent revision at the same time; the number of screws of UCSIV.B1 and B2 is more than that of B3.