Objective:To establish a determination method for sodium hyaluronate injection.Methods:Sodium hyaluronate was specifically hydrolyzed by hyaluronidase,and the optimal enzymolysis conditions were enzymolysis at 37 ℃ for 4 h at 100 IU·mg-1 of enzyme reaction concentration.The analysis was performed on a of Shodex sug-ar SH1011 column(300 mm ×8 mm,6 μm)with a mobile phase of 1％H3PO4 at a flow rate of 0.6 mL·min-1.The eluent was detected at 230 nm.Results:Linear ranges were 101.38-1 013.76 μg·mL-1(r=0.999 5),RSDs of precision,stability and repeatability tests were lower than 1％,and average recovery was 100.4％,RSD=2.0％(n=9).The RAD of determination results of this method and colorimetric was 0.1％-1.2％.Conclusions:The method is accurate and reproducible,and can be used for the determination of sodium hyalur-onate injection.

Objective To compare the differences in the levels of lactate dehydrogenase(LDH),creatine kinase(CK),and neuron-specific enolase(NSE)in the cerebrospinal fluid(CSF)between the patients with purulent meningitis(PM)and those with tuberculous meningitis(TBM)and evaluate the utility of the three biomarkers in the differentiation of PM and TBM.Methods Thirty-five PM patients and 45 TBM patients who attended the Department of Neurology from December 2019 to December 2021 were enrolled in this study.The CSF samples were collected from the patients before treatment.The levels of LDH,CK,NSE,and glucose,protein,and chloride in CSF were measured and compared between PM and TBM patients.The correlation between the biomarkers in CSF was analyzed by Pearson correlation coefficient.Linear regression analysis was performed to analyze the risk factors for the occurrence of TBM.Receiver operating characteristic(ROC)curves were plotted to evaluate the discriminative value of CSF LDH,CK,NSE alone or in combination in differential diagnosis of PM and TBM.Results Patient age,gender,clinical features such as fever,pathological signs,vomiting,limb twitching,and CSF levels of glucose and protein did not show significant difference between TBM patients and PM patients(P＞0.05).TBM was associated with significantly higher LDH and NSE levels in CSF and significantly lower CK level and chloride in CSF compared to PM(P＜0.05).Pearson correlation analysis showed that LDH level in CSF was negatively correlated with CK and chloride(r＜0,P＜0.05),and positively correlated with NSE(r＞0,P＜0.05).CK was negatively correlated with NSE(r＜0,P＜0.05),and positively correlated with chloride(r＞0,P＜0.05).NSE was negatively correlated with chloride(r＜0,P＜0.05).Linear regression analysis showed that LDH,CK,NSE,and chloride levels in CSF were all associated with the occurrence of TBM(P＜0.05).ROC curves demonstrated that the AUCs of CSF levels of LDH,CK,NSE alone and in combination for differentiation between PM and TBM were 0.849(95％CI:0.768-0.930),0.858(95％CI:0.779-0.937),0.851(95％CI:0.771-0.931),and 0.954(95％CI:0.911-0.996),respectively.Conclusions The clinical features are similar for PM and TBM patients.However,the levels of LDH,CK,and NSE in CSF are different between PM and TBM.LDH,CK,NSE in combination may improve the differential diagnosis between PM and TBM.

Objective:To systematically evaluate the incidence of psychological dysfunction in critically ill patients with post-intensive care syndrome (PICS) .Methods:Computer search was conducted on CNKI, Wanfang Database, VIP, SinoMed, PubMed, Embase, Cochrane Library, Web of Science, CINAHL and Scopus for literature related to the incidence of psychological dysfunction in critically ill PICS patients, and the search period was from establishment of the databases to April 2023. Data extraction and quality evaluation were carried out for the included literatures and Stata 17.0 software was used for meta-analysis.Results:A total of 32 articles were included, with a total of 496 399 patients. Meta-analysis results showed that the incidence of psychological dysfunction in critically ill PICS patients was 31.0% (95% CI: 26%-35%). Subgroup analysis results showed that the incidence of psychological dysfunction in PICS patients was higher in foreign literature, literature on virus-infected ICU patients, and literature published from 2017 to 2023, with incidence of 32.5% (95% CI: 25%-40%), 34.0% (95% CI: 29%-39%), and 32.8% (95% CI: 28%-38%), respectively. Conclusions:The incidence of psychological dysfunction in critically ill patients with post-intensive care syndrome is relatively high. Medical staff should pay more attention to the psychological health of post-ICU patients, strengthen screening of psychological dysfunction in critically ill patients with post-intensive care syndrome and give timely targeted intervention measures.

Objective Study on mechanism of Xuanfei Jiedu Formula in treating multi-drug resistant Pseudomonas aeruginosa pneumonia.Methods Except the Control group,the MDR-PA(9×108 CFU/mL,0.5 mL)pneumonia rat model was established by tracheal intubation,and an un-modeled control group was used.After successful modeling,rats were randomly divided into model group,XFJDF-low dose group,XFJDF-medium dose group,XFJDF-high dose group and IPM group,with 12 animals in each group;In addition to the blank group and the model group,the remaining drug administration groups were collectively referred to as the intervention treatment group.One day after modeling,the XFJDF-low dose,XFJDF-medium dose,and XFJDF-high dose groups were given the corresponding doses by gavage.The imipenem and cilastatin group was given Imipenem intraperitoneal injection,and the control and model groups were given saline gavage twice a day for 7 days.The rats'general status,body weight changes,and wet-dry weight ratio(W/D)of the lung tissue were observed.Hematoxylin-eosin staining was used to observe the pathological changes to the lung tissue of rats in each group under a light microscope.The serum levels of IL-1β,TGF-β,TNF-α,and IL-6 were detected by enzyme immunosorbent assay.Serum GSH content and MPO activity of rats were detected by colorimetry.The serum content of MDA was detected by TBA method.The total antioxidant capacity(T-AOC)was detected by kit method.The protein levels of TLR4,Myd88,and NF-κBp65 in lung tissues were determined by immunohistochemistry.The mRNA and protein levels of TLR4,Myd88,and NF-κBp65 in the lung tissues of each group were detected by qPCR and Western Blot.Results Compared with the control group,the model groups had delayed responses,increased respiratory frequency,increased respiratory noise,and appeared to have different degrees of chills,as well as decreased diet and water intake and decreased body weight.The W/D of lung tissue was significantly increased(P＜0.01),and a large number of inflammatory cells had infiltrated the alveolar cavity and around the lung bronchus.Some alveolar walls were fractured and fused to form air cavities,with inflammatory exudation,pulmonary interstitial thickening,and local lung fiber formation.The serum levels of IL-1β,TNF-α,TGF-β,and IL-6 were significantly increased(P＜0.01),MDA content was increased,MPO activity was enhanced,GSH content and T-AOC capacity were decreased(P＜0.01),and the mRNA and protein levels of TLR4,Myd88,and NF-κBp65 in lung tissue were significantly increased(P＜0.01).Compared with the model groups,the intervention group and the treatment group showed improvements in the above indexes(P＜0.05,P＜0.01),and the Xuanfei Jiedu Formula high-dose group and IPM group had the most significant improvements(P＜0.05,P＜0.01).Conclusions Xuanfei Jiedu can significantly improve the general state,body weight,lung tissue W/D,and lung tissue pathology,and the reduce inflammation and oxidative stress,of MDR-PA rats.The mechanism may be related to its inhibition of the expression of TLR4/Myd88/NF-κB pathway proteins in lung tissue.

Objective To explore the action of Bufei Jianpi formula(BJF)on mitochondrial damage to skeletal muscle in chronic obstructive pulmonary disease(COPD)rats via its regulation of the IRS-1/PI3K signaling axis.Methods 60 SPF SD rats were randomly divided into Control group,Model group(COPD stable stage group),aminophylline(Am)group,BJF group,pioglitazone(PIO)group and BJF+PIO group,with 10 rats per group.A stable COPD rat model was established via forced smoking and Klebsiella pneumoniae nasal drip method.Samples were taken from the 9th week to the end of the 20th week,and the weight of the rats was measured every week.Routine sectioning and HE staining were performed on lung and skeletal muscle tissue,and corresponding pathological changes were observed under a light microscope.The lung function of the rats was observed by whole-body plethysmography in weeks 0,8,and 20,including tidal VT,PEF,and EF50.The mRNA expression of IRS-1,leptin,PGC1-α,and PI3K in rat skeletal muscle was detected by qPCR.The expression of PGC-1α,TFAM,IRS-1,PI3K,AKT,p-AKT,and leptin in rat skeletal muscle tissue was detected by Western blot.Results The Model group,but not the Control group,showed a large number of inflammatory cells infiltrating the alveolar interstitium and bronchus,indicative of lung disease;some alveolar walls had broken and fused to form air cavities,and fiber networks were destroyed.After drug treatment,the rats showed improved alveolar wall and fiber network integrity and reduced inflammatory cell infiltration in the bronchus,especially those in the BJF and Am groups.In the drug treatment groups,the skeletal muscle pathology of each group showed improved spatial arrangement,the atrophy and fracturing of muscle fibers were ameliorated to different degrees,and cytoplasmic staining of muscle cells was uneven,and the BJF group showed the most significant effects.Compared with the Control group,the Model group's PEF,VT,and EF50 significantly decreased from week 8(P＜0.01),while the BJF,BJF+PIO and Am groups had significantly increased PEF and EF50(P＜0.01).Compared with Control group,the Model group's mRNA and protein expression levels of IRS-1,PGC-1α,and PI3K were significantly decreased(P＜0.05,P＜0.01),the level of leptin was significantly increased(P＜0.01).Compared with the Model group,the mRNA and protein expressions of IRS-1,PGC-1α and PI3K in the BJF group were significantly increased(P＜0.05,P＜0.01),and the mRNA expression of IRS-1 in the PIO group was significantly increased(P＜0.01).The BJF+PIO group's mRNA levels of PGC-1α(P＜0.01)and mRNA and protein levels of IRS-1 and PI3K were significantly increased(P＜0.05,P＜0.01).The mRNA and protein expression levels of PI3K in the Am group were significantly increased(P＜0.01).The expression levels of leptin mRNA were significantly decreased in the four treatment groups(P＜0.01),and the expression of leptin protein was significantly decreased in all treatment groups except the Am group(P＜0.01).Compared with the Control group,the Model group's quadriceps femoris tissue showed a significant decrease in TFAM and p-AKT expression.TFAM and p-AKT expression in all the treatment groups showed an increasing trend,but the difference was not statistically significant(P＞0.05).Conclusions By regulating the IRS-1/PI3K signaling axis,Bufei Jiempi reduces mitochondrial damage to skeletal muscle,increases the expression of PGC-1α and mitochondrial transcription factor TFAM,enhances mitochondrial biosynthesis,and reduces pathological damage to lung and skeletal muscle tissue.

Objective:Exploring the role and mechanism of gremlin-1 in lipotoxicity-mediated pancreatic β-cell dysfunction.Methods:The model of lipid toxicity-mediated pancreatic β-cell dysfunction was constructed using palmitic acid(PA) to treat mouse pancreatic β-cells(MIN6). Initially, to clarify the effects of lipotoxicity on islet β-cells, the cellular lipid deposition and changes in the levels of insulin caused by PA were detected. The effects of PA on gremlin-1 expression and its downstream signaling pathway BMPs/Smads were further investigated using qPCR and Western Blot assay. Subsequently, recombinant mouse gremlin-1 protein and BMP signaling pathway inhibitor LDN193189 were used to intervene the cells to explore the effects of gremlin-1 and its downstream signaling pathway BMPs/Smads on pancreatic islet β-cells.Results:PA could reduce pancreatic β-cell viability and insulin secretion capacity( P<0.05). Meanwhile, PA inhibited the expression and secretion of cell gremlin-1 and upregulated BMP-4 and its downstream Smad-1 and Smad-5( P<0.05). Intervention of cells with recombinant mouse gremlin-1 protein resulted in a significant elevation of insulin secretion and a concomitant decrease in the expression of key molecules in the BMP4/Smads signaling pathway( P<0.05). And inhibition of the BMP4/Smads signaling pathway ameliorated PA-induced pancreatic β-cell dysfunction. Conclusion:Gremlin-1 is involved in the regulation of lipotoxicity-mediated pancreatic islet β-cell dysfunction, and this effect may be associated with activation of BMP4/Smads signaling pathway.

Objective:To evaluate the efficacy and safety of matched sibling donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of myelofibrosis (MF).Methods:In this case series, the clinical data of 18 patients with MF who received allo-HSCT in the Department of Hematology, Peking University People′s Hospital from December 2008 to December 2023 were retrospectively studied. Kaplan-Meier survival analysis and competitive risk model were used to evaluate the probabilities of 3-year overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR), and transplant related mortality (TRM). The transplant related complications were also analyzed.Results:Among the 18 patients included, there were 12 males and 6 females, with a median age of 50 (range: 28-64) years. All 18 patients achieved neutrophil engraftment, and the time of neutrophil engraftment [ M ( Q1, Q3)] was 16.0 (11.8, 18.0) days. Twelve patients achieved platelet engraftment, and the platelet engraftment time was 21.0 (16.2, 43.2) days. Six patients had grade Ⅱ to Ⅳ acute graft-versus-host disease (GVHD), and six patients had chronic GVHD. The 3-year OS rate and DFS rate after transplantation were 62.2% and 52.2%, respectively. The 3-year CIR and TRM were 29.7% and 24.6%, respectively. Four patients died during follow-up, with the main cause of death being infections. Conclusion:Matched sibling allo-HSCT is a feasible option for the treatment of MF.

Objective:To delineate the clinical characteristics and outcomes associated with severe cardiac toxicity during the preconditioning phase of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with aplastic anemia (AA).Methods:This retrospective case series study included 31 patients with severe AA who underwent allo-HSCT and were diagnosed with severe cardiac toxicity at the Hematology Department of Peking University People′s Hospital from August 2012 to June 2022. The clinical manifestations of severe cardiac toxicity observed during the preconditioning process were assessed. Patient survival was assessed using the Kaplan-Meier method.Results:In this cohort of 31 patients, the median follow-up period was 9 days (range: 4-365 days). Severe cardiac toxicity manifested within 6 days after the initial cyclophosphamide (Cy) administration. Twenty patients died within 30 days of initiating Cy preconditioning, of which 16 patients died due to severe cardiac toxicity within 25 days. Patients whose cardiac function improved within 30 days post-preconditioning showed a median survival duration of 222 days ( n=11). Troponin I (TNI) levels in patients who died within 30 days of initiating Cy preconditioning began increasing on day 5 post-Cy, peaking sharply by day 9 after a notable rise on day 8. B-type natriuretic peptide (BNP) levels in patients who died within 30 days of initiating Cy preconditioning started to rise from day 1, stabilized between days 2 and 5, and then doubled daily from days 6 to 8, remaining elevated thereafter. Notably, the initial increases in BNP and TNI correlated with electrocardiogram (ECG) signs of low voltage and T-wave inversion in 83.87% of cases ( n=26). Most patients ( n=28, 90.32%) were administered corticosteroid therapy. In those with restored cardiac function, the ejection fraction returned to >50% within 30 days of initiating Cy preconditioning. Conclusions:Patients with severe cardiac toxicity during the preconditioning phase of allo-HSCT typically exhibit early, sustained, and marked elevations in myocardial damage markers, including BNP and TNI, accompanied by ECG abnormalities following Cy administration, with BNP often increasing first. These indicators are associated with rapid disease progression and high mortality. Prompt initiation of treatment upon clinical diagnosis is critical for improving survival outcomes.

Chronic skin diseases have complex pathogeneses and prolonged courses, and have long adverse impacts on the physical and mental health, as well as the normal life of patients. It is necessary to develop evidence-based strategies and measures for effective prevention and control of chronic skin diseases. However, related studies are limited in China. This article proposes a population medicine research plan for health promotion and equity, and disease prevention, diagnosis, control, treatment, and rehabilitation to establish a collaborative platform for strengthening research on the prevention and treatment of chronic skin diseases in China.

Objective:To analyze the clinical characteristics and outcomes of patients with invasive fungal sinusitis (invasive fungal rhinosinusitis, IFR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and explored the risk factors for IFR after allo-HSCT.Methods:Nineteen patients with IFR after allo-HSCT at Peking University People’s Hospital from January 2012 to December 2021 were selected as the study group, and 95 patients without IFR after allo-HSCT during this period were randomly selected as the control group (1:5 ratio) .Results:Nineteen patients, including 10 males and 9 females, had IFR after allo-HSCT. The median age was 36 (10–59) years. The median IFR onset time was 68 (9–880) days after allo-HSCT. There were seven patients with acute myeloid leukemia, five with acute lymphoblastic leukemia, two with myelodysplastic syndrome, two with chronic myeloid leukemia, one with acute mixed-cell leukemia, one with multiple myeloma, and one with T-lymphoblastic lymph node tumor. There were 13 confirmed cases and 6 clinically diagnosed cases. The responsible fungus was Mucor in two cases, Rhizopus in four, Aspergillus in four, and Candida in three. Five patients received combined treatment comprising amphotericin B and posaconazole, one patient received combined treatment comprising voriconazole and posaconazole, nine patients received voriconazole, and four patients received amphotericin B. In addition to antifungal treatment, 10 patients underwent surgery. After antifungal treatment and surgery, 15 patients achieved a response, including 13 patients with a complete response and 2 patients with a partial response. Multivariate analysis revealed that neutropenia before transplantation ( P=0.021) , hemorrhagic cystitis after transplantation ( P=0.012) , delayed platelet engraftment ( P=0.008) , and lower transplant mononuclear cell count ( P=0.012) were independent risk factors for IFR after allo-HSCT. The 5-year overall survival rates in the IFR and control groups after transplantation were 29.00%±0.12% and 91.00%±0.03%, respectively ( P<0.01) . Conclusion:Although IFR is rare, it is associated with poor outcomes in patients undergoing allo-HSCT. The combination of antifungal treatment and surgery might be effective.