High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

Objective: To investigate the hygienic status of the central air conditioner ventilation system in public places in urban areas of Ma'anshan City, Anhui Province, so as to provide insights into formulation of supervision and management interventions. Methods: A total of 15 public places with the central air conditioner ventilation system were randomly sampled from main urban areas in Ma'anshan City in 2022. Sampling and detection were performed following the standard GB/T 18204.5—2013 Examination methods for public places Part 5: Central air conditioning ventilation system, including total number of bacteria and total number of fungus on the inner surface of wind pipes, total number of bacteria and fungus, particulate matter (PM10) and β-hemolytic streptococci in the air supply system, and Legionella pneumophila in the cooling water, and the detection indicators were assessed following the WS 394—2012 Guideline for hygiene of the central air conditioner ventilation system in public places. The eligible rate of samples, the detection rate of L. pneumophila were analyzed. Results: A total of 368 samples were collected from 15 public places, and the qualified rate was 50.54%, no places had all eligible measurement indicators. The qualified rates of total bacteria and fungus numbers on the inner surface of wind pipes were 52.67% and 59.33%. The qualified rates of total bacterium number, total fungus number, PM10 and β-hemolytic streptococci were 12.00%, 28.00%, 90.00% and 96.00% in the air supply system. The qualified rates of samples in administrative workplaces, hotels, bathing places and malls (supermarkets) were 32.50%, 59.24%, 61.09% and 68.92%, the qualified rates of total bacteria on the inner surface of air ducts were 8.33%, 72.46%, 66.67% and 61.90%, and the qualified rates of total fungus numbers in air supply were 0, 21.70%, 33.30% and 71.40%, respectively, with statistical significance (P<0.05). A total of 18 cooling water samples were collected, and L. pneumophila was detected in three samples (16.67%). Conclusions Poor hygiene is seen in the central air conditioning ventilation systems in public places in main urban areas of Ma'anshan City. High attention needs to be paid to contamination of bacterium, fungus and L. pneumophila, and expansion of supervision coverage and improved supervision intensity are recommended.

Objective:To evaluate the clinical outcome of Robot-assisted sacroiliac screw fixation in the treatment of fragility fracture of the sacrum in the elderly.Methods:From March 2016 to June 2022, a retrospective analysis was performed on 30 patients with fragility fractures of the sacrum in the elderly who accepted robot-assisted sacroiliac screw to treat fragility fractures of the sacrum in our hospital. There were 12 males and 18 females with average age 71.03±8.25 years (range, 60-89 years). According to the classification of fragility fractures of the pelvis (FFP) in the elderly, there were 22 patients with FFP II, 2 patients with FFP III, and 6 patients with FFP IV. Surgical planning was based on the average CT value of S 1 channel and whether there is a transsacral screw channel. Robot-assisted sacroiliac screw fixation was performed during surgery. The pain of pre-operation and post-operation was evaluated using the visual analogue scale (VAS), the position of sacroiliac screws was evaluated by Gras grading, and the degree of functional recovery after surgery was evaluated using the Majeed function score. Results:All 30 patients successfully completed the operation. The mean operation time was 27.00±6.68 min (range, 18-35 min), the mean fluoroscopy times were 27.13±5.16 (range, 18-34), and the mean blood loss was 30.53±6.61 ml (range, 23-38 ml). All patients were followed up, and the mean follow-up time was 19.03±7.8 months (range, 8-25 months). The VAS was 5(5, 6), 4(3, 4), 3(2, 3), 0(0, 1) points before surgery, 1 week, 2 months and 6 months after surgery, respectively, and the difference was statistically significant ( H=103.26, P<0.001). After the surgery of 2 months, 6 months and the last follow-up time, the Majeed function scores were 88(83, 90), 91(87, 92), 92(90, 93) points, respectively, and the difference was statistically significant ( H=19.59, P<0.001). Screw position was evaluated according to Gras grading at 3 days after surgery, including 28 cases of level I, 2 cases of level II, and no screw penetrated the cortical bone or entered the sacral canal or sacral foramen. No vascular or nerve injury occured during the operation. 28 patients with FFS met the fracture healing criteria, and the healing time was 4.54±1.57 months (range, 3-7 months). Two patients had bone nonunion, one of whom underwent anterior ring plate removal due to infection of the pelvic anterior wound, and one month later, pelvic CT scan revealed loosening of the sacroiliac screw; the other one is considered to be related to too early weight bearing. Conclusion:For fragility fractures of the sacrum in elderly, Robot-assisted sacroiliac screw is an effective minimally invasive treatment, with high accuracy of screw placement, effective pain reduction, improved fracture healing rate, and achieve the satisfactory clinical efficacy.

ObjectiveTo explore the improvement and mechanism of the water extract of Lonicerae Japonicae Flos （FL） on nonalcoholic steatohepatitis （NASH）. MethodC57BL/6 mice were fed with methionine-choline-deficient （MCD） diet for 6 weeks. From the 3^rd week， the mice were continuously orally given with FL （0.2 and 0.4 g·kg^-1） until the end of the experiment. Serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） activities of mice were detected， and the liver pathology was analyzed by hematoxylin-eosin （HE） staining. The content of triglyceride （TG） and non-esterified fatty acids （NEFA）， and the activity of myeloperoxidase （MPO） in the liver tissue were determined. Hepatic collagen deposition was observed by Sirius Red and Masson staining assays， and the hepatic hydroxyproline （HYP） content was measured. Network pharmacology combined with following experimental verifications were used to analyze the potential mechanism of FL in the improvement of NASH. Real time polymerase Chain reaction （Real-time PCR） was used to detect hepatic mRNA expression of inflammation-related factors and fibrosis-related factors. The release of heat shock protein （HSP60） in the serum and α-smooth muscle actin （α-SMA） in the liver were detected by Western blot. ResultFL （0.2 and 0.4 g·kg^-1） reduced serum ALT and AST， hepatic MPO activity， and HYP content in the MCD-induced NASH mice. The results of network pharmacology suggested that FL presumably improved NASH by influencing biological processes related to extracellular matrix and inflammation， and signal pathways such as nuclear factor kappa-B （NF-κB）， hypoxia inducible factor-1α （HIF-1α）， and heat shock proteins were possibly involved. FL （0.2 and 0.4 g·kg^-1） reduced the increase of mRNA expression of inflammation-related and fibrosis-related factors， and FL （0.4 g·kg^-1） decreased the release of HSP60 in serum and reduced the protein expression of α-SMA in liver. ConclusionFL improves NASH by reducing inflammation， decreasing collagen deposition， and inhibiting HSC activation.

Objective:To evaluate the efficacy and safety of combination therapy of eltrombopag, recombinant human thrombopoietin (rhTPO) , and standard immunosuppressive therapy (IST) for severe aplastic anemia (SAA) .Methods:A total of 16 cases with SAA treated with IST combined with eltrombopag and rhTPO were retrospectively analyzed.Results:At 3 months, the total response rate was 81.3%, and the complete hematological response rate was 37.5%. At 6 months, the total response rate was 87.5%, and the complete hematological response rate was 50.0%. The median time of platelet transfusion independence was 35 (16-78) days, the median time of red blood cell transfusion independence was 47.5 (15-105) days, the median platelet transfusion was 5.5 (3-20) U, and the median red blood cell transfusion was 6.5 (2-16) U.Conclusion:The combination of eltrombopag and rhTPO can improve the hematological response rate of IST for SAA and the quality of hematological remission with minimal toxic effects.

Objective To explore the clinical efficacy and safety of low﹣dose decitabine subcutaneous injection combined with arsenicals in the treatment of medium﹣ and high﹣risk myelodysplastic syndromes (MDS). Methods Eight cases of medium﹣ and high﹣risk MDS without allogeneic hematopoietic stem cell transplantation in the Affiliated Cancer Hospital of Zhengzhou University and Xinhua Area Hospital of Pingdingshan City from January 2015 to August 2018 were retrospectively analyzed. The patients were given subcutaneous injection of low﹣dose decitabine combined with arsenicals. The specific regimen was as follow:0.1-0.2 mg/kg of decitabine, subcutaneous injection 2 times/week, 4 weeks in total; arsenic injection 10 mg/time or 0.16 mg/kg, intravenous administration, 1 time/d, 4 weeks; compound Huangdai tablets 60 mg/kg per day, 3 times orally. The efficacy and adverse reactions were observed. Results In 8 patients, there were 5 male and 3 female, with an average age of 61.4 years old (44-80 years old) Eleven cases were refractory anemia with excess blasts (RAEB), 6 cases were RAEB﹣2, 1 case was refractory cytopenia with multilineage dysplasia (RCMD) with bone marrow fibrosis (MF). Three of the patients had previously received treatment with decitabine. All patients completed the treatment successfully and no treatment﹣related deaths occurred. By the end of follow﹣up, 2 patients had complete remission, 4 patients had complete bone marrow remission with hematologic improvement, 1 patient had stable disease, and 1 patient had disease progression. For 2 patients who had been treated with decitabine regimen, the regimen of re﹣administered decitabine plus arsenic was still effective. Eight patients had more than level 2 of myelosuppression, except for one patient with intestinal infection due to unclean diet and one patient with mild pulmonary infection. The remaining 6 patients had no associated infection and heart, liver, kidney and other adverse reactions. Conclusion Low﹣dose decitabine subcutaneous injection combined with arsenicals is safe and could be a new treatment for the medium﹣ and high﹣risk MDS.

Objective To explore the difference in efficacy between multiparametric MRI (Mp-MRI) based on prostate imaging reporting and data system version 2 (PI-RADS v2) and abbreviated biparametric MRI (Bp-MRI) in detecting prostate cancer (PCa) and clinically significant prostate cancer (csPCa), and to evaluate the consistency of image interpretation between different readers. Methods The imaging, pathological and clinical data of patients with prostatic Mp-MRI in our hospital from February 2015 to June 2018 were retrospectively analyzed. At the beginning, 250 patients were randomly selected. Two radiologists visually evaluated the images of those patients using two 5-point scoring schemes based on Mp-MRI and Bp-MRI. The remaining cases were independently proceeded by one of the radiologists using two schemes respectively. Weighted Kappa test was used to assess the consistency of the results interpreted by the two radiologists. The receiver operating characteristic (ROC) curve was used to evaluate the efficiency of the two scoring schemes in detecting PCa and csPCa, and with Z test to investigate whether there was any difference in detection efficiency between the two schemes. Results Nine hundred and seventy eight patients were eventually enrolled in the study. The results of the consistency assessment showed that there was good agreement between the two radiologists, whether using Mp-MRI or Bp-MRI, with the weighted Kappa coefficient of 0.800 and 0.812, respectively. The ROC curve analysis showed that the area under the curve (AUC) of PCa detected by Mp-MRI and Bp-MRI was 0.873 and 0.879, respectively, and the AUC of csPCa detected was 0.922 and 0.932, respectively. In addition, there was no statistically significant difference between the AUC of PCa and csPCa detected by the two schemes (P>0.05). Conclusion The Bp-MRI scoring scheme has good stability in the evaluation of benign and malignant prostate, and its detection efficiency of PCa or csPCa is not lower than that of standard Mp-MRI based on PI-RADS v2.

Objective: To explore the effect of combination regimen of interferon alpha-1b, interleukin-2 and thalidomide (ITI regimen) on minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) who were in hematologic remission but MRD-positive. Methods: Eighteen patients (17 from Tumor Hospital of Zhengzhou University and 1 from the First People's Hospital of Pingdingshan City) with AML admitted from July 2016 to June 2018, who were in hematologic remission but MRD-positive were treated with different doses of ITI regimen, and the MRD levels were monitored. Results: Among 18 patients who received a conventional dose of ITI regimen for 1 to 2 months, 7 patients had undetectable MRD, 3 had significant decrease in MRD levels, 3 had elevated MRD level and had hematologic recurrence. Three patients with elevated MRD level received a higher dose of ITI regimen, 2 of them turned to MRD negative and the other 1 patient had decreased MRD level. The total response rate was 72.2%, and the response rate in patients with MRD > 1.0% was 57.1% (4/7) , and that of patients with MRD < 1.0% was 81.8% (9/11) , respectively. Conclusion The ITI regimen can reduce the MRD level of patient with AML who are in hematologic remission but MRD-positive. The therapeutic effect could be improved by a higher dose administration of ITI regimen, and therapeutic effect may be negatively correlated with MRD level before treatment.

Objective: To improve the knowledge and experience of ibrutinib combined with CAR-T cells in the treatment of high-risk chronic lymphoblastic leukemia (CLL) patients or small lymphocytic lymphoma (SLL) with TP53 gene aberration. Methods: One case of del (17p) CLL patients with BCL-2 inhibitor resistance was treated with ibrutinib combined with CAR-T cells, successfully bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT) , and the relative literatures were reviewed. Results: The patient was a young female with superficial lymph node enlarging at the beginning of the onset. Lymph node biopsy was confirmed as small lymphocytic lymphoma (SLL) without del (17p) . The disease progressed rapidly to CLL/SLL with del (17p) and bone marrow hematopoietic failure 2 years later. Firstly, the patient was treated with BCL-2 inhibitor (Venetoclax) , and the enlarged lymph nodes shrank significantly 2 months later. After 3 months, the disease progressed rapidly. The spleen was enlarged to 16 cm below the ribs, the neck lymph nodes was rapidly enlarged, and the superior vena cava syndrome appeared, which were mainly attributed to venetoclax resistance; so BTK inhibitor (ibrutinib) was used continuously after venetoclax discontinuation. Partial remission (PR) was achieved without lymphocytosis after 2 months, then ibrutinib was combined with CAR-T cells targeting CD19 antigen. Grade 1 of cytokine release syndrome (CRS) appeared after CAR-T cells infusion, and the complete remission (CR) was achieved after 1 month both in bone marrow and peripheral blood, with minimal residual disease (MRD) negative, then bridging allo-HSCT after 2 months of combined therapy. Conclusion CLL/SLL patients with TP53 aberration have poor prognosis because of rapid progression, drug resistance, etc. Ibrutinib combined with CAR-T cell therapy can quickly achieved complete remission.

OBJECTIVE: To verify the accuracy of oxygen concentration (FiO₂) of modified oxygen treatment with Venturi and humidity system. METHODS: Patients just after ventilator weaning and before the removal of tracheal intubation/tracheotomy tube, who admitted to the intensive care unit (ICU) of Henan Provincial People's Hospital from May 1st to December 15th in 2017, were enrolled. All patients were given a modified oxygen treatment with Venturi and humidity system, and the oxygen flow rate (Flow) of the Venturi device and the oretical value of FiO₂ were adjusted according to the patient's condition. Patients were divided into five groups based on doctor's orders: Flow 3 L/min FiO₂ 0.24, Flow 3 L/min FiO₂ 0.26, Flow 6 L/min FiO₂ 0.28, Flow 6 L/min FiO₂ 0.30, Flow 9 L/min FiO₂ 0.35. The value of FiO₂ at the inhalation end of patients of each group was measured by TSI airflow analyzer, and the consistency between the measured value of FiO₂ at the inhalation end and the FiO₂ marked value of Venturi was compared and analyzed. RESULTS: When the FiO₂ theoretical value of Venturi were adjusted to 0.24, 0.26, 0.28, 0.30, and 0.35, the measured values of FiO₂ at the inhalation end of patients were 0.38±0.05, 0.38±0.05, 0.40±0.04, 0.41±0.04, and 0.77±0.11, respectively, which were all significantly higher than the theoretical value of FiO₂ (all P < 0.01). The difference between the measured value of FiO₂ at the inhalation side and the FiO₂ value of the Venturi annotated and the difference rate were both "V"-shaped, both of which decreased with the increase in theoretical value of FiO₂ to a Flow of 9 L/min and a theoretical value of FiO₂ 0.35, the accuracy was the worst, with the FiO₂ difference of 0.42±0.11, and the FiO₂ difference rate of (121.6±36.5)%. CONCLUSIONS There is a difference between the measured value and the theoretical value of FiO₂ at the inhalation end of the modified Venturi oxygen therapy humidification system, which needs to be paid attention to during clinical oxygen therapy.
Humans ; Humidity ; Oxygen/analysis* ; Oxygen Inhalation Therapy ; Respiration, Artificial ; Ventilator Weaning