Objective To study the effect of TLR4 activation with LPS on BMP9-induced osteogenic differentiation of immortalized mouse embryonic fibroblasts ( iMEFs).Methods The activation of TLR4/NF-κB signaling path-way was detected by ICC.iMEFs were treated with LPS,BAY11-7082,Adnovirus GFP and BMP9.The early osteo-genic differentiation capability of iMEFs was detected by ALP staining and quantitative assay .The later osteogenic differentiation capability was detected by alizarin red S staining .The expression of later osteogenic differentiation marker gene OCN and OPN were detected by PCR and Western blot .The change of p-Smad1/5/8 was detected by Western blot.The expression of Runx2 and Dlx5 were detected by PCR and Western blot .Results LPS can effec-tively stimulate TLR4/NF-κB signaling pathway .TLR4 activation inhibited BMP 9-induced osteogenic differentiation . BMP9-induced osteogenic differentiation related gene and Smad 1/5/8 signaling activation were inhibited by TLR4 activation .The inhibition effect was partly reversed by BAY 11-7082 ( P<0.05 ) .Conclusions TLR4 activation with LPS can inhibit BMP9-induced osteogenic differentiation of iMEFs cells via NF-κB signaling pathway .

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 explore the diagnostic yield of bronchoscopic rapid on-site evaluation (B-ROSE) in patients with severe invasive bronchopulmonary aspergillosis (IBPA) and provide evidence for starting antifungal treatment before microbiological results were available. METHODS: A prospective cohort study was conducted to select patients with severe pneumonia suspected of IBPA admitted to the respiratory intensive care unit (RICU) in the First Affiliated Hospital of Xinjiang Medical University from June 2014 to June 2022, and those who were primarily infected with other pathogens (such as bacteria, Mycobacterium tuberculosis) at admission were excluded. Whether the antifungal treatment was initiated or not on the basis of the bedside B-ROSE, the B-ROSE was administered as soon as possible within 24 hours after admission to RICU. The current international definition of invasive aspergillosis was used as the gold diagnostic standard, the diagnostic accordance rate, the sensitivity and specificity of B-ROSE were calculated respectively, and the receiver operator characteristic curve (ROC curve) was also plotted, to evaluate the predictive value in diagnosing IBPA. RESULTS: A total of 176 patients with severe pneumonia suspected of IBPA were included in the study. According to international diagnostic standards, there were 81 cases of IBPA and 95 cases of non-IBPA. According to the early diagnosis of B-ROSE, there were 89 cases of IBPA and 87 cases of non-IBPA. The diagnostic accordance rate of B-ROSE was 84.09% (148/176), the area under the ROC curve for B-ROSE in diagnosing severe IBPA was 0.844, the 95% confidence interval (95%CI) was 0.782-0.905, the sensitivity was 87.65%, the specificity was 81.05%, the positive predictive value was 79.78%, the negative predictive value was 88.51%, the rate of underdiagnosis was 12.35% (10/81), and the rate of misdiagnosis was 18.95% (18/95). Compared with the true negative group, the proportion of long-term (≥ 14 days) use of glucocorticoid [70.0% (7/10) vs. 9.1% (7/77), P < 0.01] and the proportion of cases with diabetes [40.0% (4/10) vs. 10.4% (8/77), P < 0.05] were significantly higher in the false negative group (underdiagnosis group). However, B-ROSE of both groups showed mucosal bleeding, congestion and edema [100.0% (10/10) vs. 94.8% (73/77), P > 0.05], indicating that acute mucosal inflammation was non-characteristic. Compared with the true positive group, the proportion of long-term (≥ 14 days) use of glucocorticoid in the false positive group (misdiagnosis group) was significantly reduced [33.3% (6/18) vs. 60.6% (43/71), P < 0.05]. The B-ROSE results showed the proportion of cases with mucosal white spots, black plaques and pseudomembrane was significantly reduced [16.7% (3/18) vs. 52.1% (37/71), P < 0.01] in the misdiagnosed group, which suggest that cases of long-term use of glucocorticoid and cases with B-ROSE showing mucosal white spots, black plaques and pseudomembrane were less likely to be misdiagnosed. The main diseases that were easily misdiagnosed as IBPA included pulmonary tuberculosis (38.9%, 7/18), inflammatory lung adenocarcinoma (27.8%, 5/18) and pulmonary vasculitis (16.7%, 3/18). CONCLUSIONS Before obtaining microbiological evidence, B-ROSE can assist in decision-making of early anti-aspergillus treatment for severe IBPA. This method is prompt, simple, and has high accuracy and reliability. If B-ROSE lacks characteristic manifestations, especially for severe pneumonia in patients with long-term use of glucocorticoid or diabetes, attention should be paid to the underdiagnosis of IBPA. Diseases such as lung tuberculosis, inflammatory lung adenocarcinoma and lung vasculitis should be vigilant against misdiagnosis as IBPA.
Humans ; Prospective Studies ; Antifungal Agents ; Glucocorticoids ; Rapid On-site Evaluation ; Reproducibility of Results ; Pulmonary Aspergillosis ; Pneumonia ; Diabetes Mellitus ; Adenocarcinoma of Lung ; Vasculitis ; Retrospective Studies

Objective:To explore the timing of sequential noninvasive positive pressure ventilation (NIPPV) following endotracheal intubation mechanical ventilation (ETI-MV) in aged patients with severe community-acquired pneumonia (SCAP).Methods:A prospective cohort study was conducted. The SCAP patients aged ≥ 75 years old admitted to respiratory intensive care unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University from July 2017 to August 2019 were enrolled. SCAP was diagnosed according to the criteria of Guidelines for the diagnosis and treatment of community-acquired pneumonia in adults in China (2016) published by Chinese Thoracic Society. ETI-MV was initially performed as respiratory support after RICU admission. Sequential NIPPV was performed immediately following extubation when the patients exhibited pulmonary infection abated (PIA) window. The gender, age, underlying diseases, and body temperature, heart rate (HR), respiratory rate (RR), oxygenation index (PaO 2/FiO 2) after RICU admission, as well as acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, improved pneumonia score of British Thoracic Society (confusion, uremia, respiratory, blood pressure, age 65 years, CURB-65), and pneumonia severity index (PSI) score within 24 hours after RICU admission were recorded. The duration and times of ETI, the incidences of ventilator associated pneumonia (VAP) and aspiration, the duration of mechanical ventilation (MV), the length of RICU and hospital stay and RICU prognosis were also recorded. The patients were divided into the ETI ≤ 7 days group and the ETI > 7 days group according to the duration of ETI, and the clinical data were compared between the two groups. Multivariate Logistic regression analysis was used to screen the risk factors of aged patients with SCAP whose ETI was more than 7 days, and receiver operator characteristic (ROC) curve was drawn to evaluate the predictive value of risk factors. Results:Fifty aged patients with SCAP were enrolled, with 24 patients in the ETI ≤ 7 days group and 26 in the ETI > 7 days group. Univariate analysis showed that compared with the patients with ETI ≤ 7 days, the incidences of concurrent cerebrovascular diseases [46.2% (12/26) vs. 16.7% (4/24)], VAP [61.5% (16/26) vs. 16.7% (4/24)] and aspiration [69.2% (18/26) vs. 25.0% (6/24)] were significantly increased in patients with ETI > 7 days (all P < 0.05). Multivariate Logistic regression analysis indicated that VAP and aspiration were independent risk factors of ETI > 7 days in the aged SCAP patients [VAP: odds ratio ( OR) = 4.852, 95% confidence interval (95% CI) was 1.076-21.877, P = 0.040; aspiration: OR = 5.903, 95% CI was 1.474-23.635, P = 0.012]. ROC curve analysis showed that the area under ROC curve (AUC) of VAP for predicting ETI > 7 days in aged patients with SCAP was 0.724, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and Youden index were 61.54%, 83.33%, 80.00%, 66.67%, 3.69, 0.46 and 0.45, respectively. Similarly, the AUC of aspiration was 0.721, the sensitivity, specificity, PPV, NPV, PLR, NLR and Youden index were 69.23%, 75.00%, 75.00%, 69.23%, 2.77, 0.41 and 0.44, respectively. Analysis of prognostic indicators showed that compared with patients with ETI ≤ 7 days, the reintubation rate and RICU mortality were significantly increased in patients with ETI > 7 days [53.8% (14/26) vs. 4.2% (1/24), 38.5% (10/26) vs. 12.5% (3/24), both P < 0.05]. Moreover, the patients with ETI > 7 days had significantly prolonged total duration of MV, the length of RICU stay and total hospital stay as compared with the patients with ETI ≤ 7 days [total duration of MV (days): 23.8±11.8 vs. 11.3±3.1, length of RICU stay (days): 30.6±14.1 vs. 16.0±5.1, total length of hospital stay (days): 33.0±14.9 vs. 20.2±6.1, all P < 0.01]. Conclusions:Sequential NIPPV performed immediately following extubation within 7 days in the aged SCAP patients might reduce the mortality and shorten the duration of MV. The prolonged ETI duration because of the VAP or aspiration would lead to a reduced function of sequential NIPPV and an increased mortality of the aged patients with SCAP.

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.

Objective:To explore the efficacy and case selection of non-invasive positive pressure ventilation (NIPPV) in the treatment of acute respiratory distress syndrome (ARDS) caused by viral pneumonia.Methods:These patients who were continuously admitted in the Respiratory Intensive Care Unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University from December 2017 to June 2019 and met the inclusion and exclusion criteria were enrolled in this prospective cohort study. All subjects accepted NIPPV as the initial intervention and they were divided into the NIPPV failure group and NIPPV success group according to the requirement of endotracheal intubation (ETI). Univariate analysis and multivariate logistic regression analysis were used to identify the risk factors for NIPPV failure. Receiver operating characteristic (ROC) was plotted to evaluate the predictive value of risk factors for NIPPV failure in these patients.Results:Forty-three patients were studied in this experiment. The success rate of NIPPV was 62.8% (27/43), and the failure rate was 37.2% (16/43). Compared with the NIPPV success group, the incidence of nosocomial infection [44% (7/16) vs 0 (0/27), χ 2 =11.082, P<0.05] and mortality rate [50% (8/16) vs 7% (2/27), χ 2 =7.965, P<0.05] were significantly increased in the NIPPV failure group. The univariate analysis indicated that the acute physiology and chronic health evaluation II (APACHEⅡ) score, the ratio of early concurrent bacterial or fungal infections, and the proportion of patients with insufficient NIPPV at the early 72 h were significantly higher in the NIPPV failure group (all P<0.05). Meanwhile, multivariate logistic regression analysis identified that the baseline APACHEⅡ score ( OR=1.941, 95% CI:1.159-3.249, P=0.012), the rate of early concurrent bacterial or fungal infections ( OR=8.602, 95% CI:1.267-58.416, P=0.028), and insufficient use of NIPPV at the early 72 h ( OR=10.06, 95% CI:1.592-63.527, P=0.014) were independent risk factors associated with NIPPV failure. The ROC curve showed the area under curve (AUC), the sensitivity, and the specificity was 0.748, 62.5%, and 74.1% respectively, which demonstrates that that APACHE Ⅱ score at admission was the most predictive factor of NIPPV failure. For the observed indicator without enough NIPPV treatment within 72 h, the AUC, the sensitivity, and the specificity was 0.714, 68.8%, and 74.1%, respectively. And for the observed indicator with concurrent bacterial or fungal infections, the AUC, the sensitivity and the specificity is 0.707, 56.3% and 85.2%, respectively. Conclusions:Early use of enough NIPPV in patients with ARDS caused by viral pneumonia can significantly decrease ETI and mortality rates. However, NIPPV should not be conducted in patients suffered from severe ARDS or early concurrent bacterial or fungal infections.

Synthetic electroactive microbial consortia, which include exoelectrogenic and electrotrophic communities, catalyze the exchange of chemical and electrical energy in cascade metabolic reactions among different microbial strains. In comparison to a single strain, a community-based organisation that assigns tasks to multiple strains enables a broader feedstock spectrum, faster bi-directional electron transfer, and greater robustness. Therefore, the electroactive microbial consortia held great promise for a variety of applications such as bioelectricity and biohydrogen production, wastewater treatment, bioremediation, carbon and nitrogen fixation, and synthesis of biofuels, inorganic nanomaterials, and polymers. This review firstly summarized the mechanisms of biotic-abiotic interfacial electron transfer as well as biotic-biotic interspecific electron transfer in synthetic electroactive microbial consortia. This was followed by introducing the network of substance and energy metabolism in a synthetic electroactive microbial consortia designed by using the "division-of-labor" principle. Then, the strategies for engineering synthetic electroactive microbial consortiums were explored, which included intercellular communications optimization and ecological niche optimization. We further discussed the specific applications of synthetic electroactive microbial consortia. For instance, the synthetic exoelectrogenic communities were applied to biomass generation power technology, biophotovoltaics for the generation of renewable energy and the fixation of CO₂. Moreover, the synthetic electrotrophic communities were applied to light-driven N₂ fixation. Finally, this review prospected future research of the synthetic electroactive microbial consortia.
Microbial Consortia ; Synthetic Biology ; Electron Transport ; Electricity ; Biodegradation, Environmental

Tetrandrine(TET),a natural bisbenzyl isoquinoline alkaloid extracted from Stephania tetrandra S.Moore,has diverse pharmacological effects.However,its effects on melanoma remain unclear.Cellular prolif-eration assays,multi-omics analyses,and xenograft models were used to determine the effect of TET on melanoma.The direct target of TET was identified using biotin-TET pull-down liquid chromatograph-mass spectrometry(LC-MS),cellular thermal shift assays,and isothermal titration calorimetry(ITC)analysis.Our findings revealed that TET treatment induced robust cellular autophagy depending on activating transcription factor 6(ATF6)-mediated endoplasmic reticulum(ER)stress.Simultaneously,it hindered autophagic flux by inducing cytoskeletal protein depolymerization in melanoma cells.TET treatment resulted in excessive accumulation of reactive oxygen species(ROS)and simultaneously triggered mitophagy.Sirtuin 5(SIRT5)was ultimately found to be a direct target of TET.Mechanistically,TET led to the degradation of SIRT5 via the ubiquitin(Ub)-26S proteasome system.SIRT5 knockdown induced ROS accumulation,whereas SIRT5 overexpression attenuated the TET-induced ROS accumula-tion and autophagy.Importantly,TET exhibited anti-cancer effects in xenograft models depending on SIRT5 expression.This study highlights the potential of TET as an antimelanoma agent that targets SIRT5.These findings provide a promising avenue for the use of TET in melanoma treatment and underscore its potential as a therapeutic candidate.

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.